NMR software

Role Reversal

2012-01-30T08:59:00.002+01:00

In the beginning computers were computational tools with no graphic interface. From the user's point of view CW-NMR and FT-NMR were equivalent, because both of them plotted the results on paper and the analysis only began after printing. People ignored that FT spectrometers contained a computer and a program. Things changed with the structural determinations of biopolymers by Wüthrich and others. The 80s were a period of economical growth, protein NMR was a promising new field, Bill Gates was becoming the richest man in the world with his software company, so combining NMR with software was a risky but potentially lucrative investment. There was money and there were people looking for it. Not forgetting that you really needed a good software to process 2-D NMR. The first generation of stand-alone NMR software (separated from a spectrometer) was written with biopolymers in mind: Felix, Triad, etc…
In the 90s personal computers became moderately fast and were finally able to complete a FT operation in a matter of seconds or minutes, instead of hours. A new concept was possible: off-line processing. Basically it means working far from the spectrometer. Gates had already created Windows, and Bruker created a program for it, called Win-NMR. In theory it was a good idea, because Windows offered a graphic interface that was unknown on the spectrometers of the epoch. In practice it didn't work too much, for a number of reasons. Computers weren't so widely available as today, chemists didn't want to come out of the spectrometer room without a plot (and after having it, they didn't ask for more), writing software was not something Bruker was celebrated for, the price was absurdly high.
A few years later the web arrived everywhere and with it free software: RMN, SwaN-MR, Mestre-C, SpinWorks for the small molecules; NMRPipe, PROSA and Gifa for the big molecules; never the twain shall meet. Free software is not forever: the organizations that fund the projects gets soon tired of spending money, in a matter of years. Computers evolve in the meanwhile, old software doesn't run on new machines and it needs to be recompiled. The source code is often non available but, even when it is, a lot of hard work is required. See for example how long it took for the Vespa team to revive PyGAMMA. Eventually people understood that freedom comes from money: you pay for your copy and the programmer keeps working on the product, no dependance from big sponsors. Gifa became NMRNoteBook, Mestre-C became MestreNova, SwaN-MR became iNMR.
While free software was going commercial, commercial software became free. Jeol began giving away Jeol Delta. That was quite natural too. In theory the company makes money with the hardware, so they can afford to renounce to the revenues from software, if this helps to make them more popular and Jeol always needs because they are, historically, the no. 3. For similar reasons I suppose, ACD did not ask money for their drawing program ChemSketch. For every person that knows the name "ChemSketch" there are probably 1000 that know "ChemDraw"… So you may think that Bruker and Agilent should do the same: give the software for free and make money with the hardware, because you can duplicate software at no cost and, in their case, the program was born as a part of the spectrometer, it has already been paid for. I have the impression that the contrary is true. It's like with printers and cartridges, or with razors and blades, or with espresso machines and coffee, etc… Bruker and Agilent compete with each other, they must keep the price of the spectrometers as low as possible and make the revenues with service and accessories, like software.
Things changed again two years ago, when ACD decided to give away the NMR Processor for free (for non commercial use). Apparently, the rationale is: they sell many products. In the field where they have a monopoly, they can keep the price absurdly high. In the field where there is competition, they lower the price to zero, so the competitors will soon starve to death and a new monopoly is created. Another possible rationale is: they have lost their battle against the competition and this is their revenge. Whatever the reason, it unleashed a chain reaction. After another year the Notebook became free too (for non commercial use, etc…). To tell the truth, I remember that, many years ago, searching with Google, I landed on a page where they hosted a beta version of the program, which was freely available. When, after a few months, the expiration date arrived, the "expired" tag appeared, but the program was still full-functional.
The model is common nowadays: the basic subscription is free, the premium subscription is so expensive that compensates. The equivalent of the premium subscription are the additional modules that add functionality to the basic program. Around the same time, last summer I received an invitation from Bruker: "Come visit our booth and we'll install TopSpin for free on your Mac. The program will last for 3 years". After another week, Agilent invited me saying: "We'll give you our program not just for the Mac, but for any OS and it will never expire". This is really a bad thing to see. First they ask you 10 thousands euro. After a few years, when people realize that other programs, which cost 30 times less, are actually better, they lower the price to zero but never admit the defeat nor apologize with the old customers (or give them the 10 thousands euro back…).
There's a difference between free and commercial software. When you need help, in the latter case you know whom to call. In the former case you write into a forum and the chances that you receive the proper answer are rather small. With the multitude of available programs it's rare to find an expert into any of them. NMR is just a technique that is used in conjunction with other ones. Most of the users of NMR software are expert in other fields. The number of people who needs explanations is much higher than the number of people who can provide them. It happens that, when a feature is only available in free software, people desire it to be included into commercial software. Can't you believe it? Here is a case.

Passing of Time

2011-12-22T08:53:00.005+01:00

In 2005 David Martineau drew the iNMR palette.
In 2011 Pascal Fricke has drawn it again.

Spinach

2011-11-14T16:33:00.003+01:00

A picture can be worth a thousands words. You can find many interesting and self-explanatory pictures here:
http://spindynamics.org/Spinach-examples.php
In a nutshell: Spinach is not a program, but an open source library; it's something for programmers, not for end users. The language is, once again, Matlab. When the language is Matlab, usually that the programmer and the end user are the same person.
The purpose of Spinach is, once again, to simulate NMR experiments and spectra, of all kinds. With this latest arrival, I am even more convinced that the vast majority of NMR software belongs to the class of simulation software. The mole of published material (in the sense that you can find an article in literature) is inversely proportional to the number of users. It is a fascinating field nonetheless. You can freely download Spinach and read it. Installing it is a different story.

Screencast #1

2011-10-03T16:15:00.000+02:00

This is my first screencast. It is a true waste of bandwidth and nothing else. I made it in high definition and added a beautiful soundtrack, but Blogger (the host of my blog) has decided to spoil it.
The visual effect you see in the movie is necessary: when you duplicate a page, the new page is identical to the old one. Without an animated effect it would be hard to understand if the command was executed or not. What was not necessary was the movie itself...

Changes

2011-09-13T16:02:00.003+02:00

After many happy experiments in the field of manual phase correction, after many years and many different solutions, this is what I like now, the perfect phase correction module for 2012:

At first it is confusing, because of the so many controls and because of its asymmetry. The two important elements are the circular slider for the zero-order phase correction and the long vertical slider for first-order correction. This module works in connection with a pivot marker, which can be either horizontal or vertical.Some people don't understand the idea behind the pivot marker. It is not a third parameter. It's simply an interface element which frees the user from the task of adjusting the zero-order correction. Without the pivot, the correction is a two-parameter optimization (iterative, non intuitive and tedious). With the pivot, it becomes a single parameter optimization (intuitive, natural, easy and instantaneous).This new module is so thin, that it let you see the whole spectrum behind it. When the thumb reaches the end of the run on the vertical slider, the value for the end of the run changes, so the visual effect is that the thumb returns to the center.If you aren't a purist, the button "auto" performs automatic phase correction.

nmrglue

2011-08-22T16:47:00.007+02:00

NMR glue is based on the same libraries on which VeSPA is built. The installation of nmrglue is similar. Different is the result. After the installation is complete, there is no icon to click. The instructions say nothing about what to do after installation. While the purpose of the program is clearly described, I can't add anything of my own, because I can't use it. The program is somewhere on my computer, but I don't know how to launch it.
Who feels the need of another NMR program? I still haven't found the answer to the question: "Who felt the need of inventing Python?".

cute NMR

2011-07-23T12:38:00.005+02:00

Among the many unfinished open source projects, cuteNMR is worth of some attention. It is not usable, but at least it works. One of the high points is the dialog for manual phase correction. Though nothing spectacular or innovative, it is much better than the one you can find inside NPNMR.

The Pleasure of Writing the Truth

2011-07-21T17:12:00.003+02:00

We chemists can publish hundreds of figures. Just think at the experimental section of an average article and the part of that section that describes NMR data.
How many times you find the symbol "m" for multiplet? It's a lot of times. Sometimes really there was no viable alternative, other times, however, it was possible to describe that multiplet (or rationalize it) as "ddd" or something similar. It does not happen because of laziness. The values of the coupling constants are not reported in such a case.
Other times the J values are reported, but under the first order approximation. We know that this approximation is often valid. We also know, however, that many times it is not accurate. Modern NMR programs includes analyzers of first-order multiplet. It's unfortunate that their marketing always forgets that second order spectra exist in abundance! Obviously people begin to believe that this ignorance is forgivable ("Everybody is using that pretty multiplet analyzer…").
Methods to simulate a spin system and fit it against a complex experimental spectrum have been available for decades. They aren't completely automatic and require a little of attention and time by the part of the user. This small investment is balanced by the fun of fitting (because normally it's funny).
Last, but not least, when it's time to write your articles you know your figures are as true and accurate as they can be!
Strangely I don't remember any cross-platform program that performs both simulation and fitting. I remember SpinWorks, WinDNMR and Perch for Windows and iNMR for the Mac. Three general methods (algorithms) are known: LAOCOON, Total Line Shape Fitting and manual fitting. The latter is not an algorithm and has no mathematical basis, yet it's often the most practical one. It is very useful to have all the three methods inside the same program, and it should be an all-purpose processing program (you save the effort of moving data between applications).
I have gathered a few links in case you want to practice the art of simulation on your Mac:

http://www.inmr.net/articles/nmrdb.html
http://www.inmr.net/articles/fitab.html
http://www.inmr.net/articles/hobut.html
http://www.inmr.net/articles/dipolar.html
http://www.inmr.net/articles/DNMR.html

Glassy Contours

2011-07-19T13:49:00.004+02:00

This is a new concept in the art of plotting. Only one color is used for positive peaks and another color for negative peaks. The difference among the levels is a different value of the alpha channel. Click the picture to enlarge.
This option is featured in iNMR reader 4.1.5 and iNMR 4.1.6.

iPad

2011-07-02T10:30:00.002+02:00

There are too many reasons why any wise guy will never write a program to process or visualize NMR spectra on the iPad. What's the iPad? A small, light-weight device that you can use to read books and newspapers, watch pictures and movies, hear music, play games. It's a machine to enjoy contents created by some other means. If you realize this, you conclude that the iPad comes ready to watch NMR spectra as well, provided that those spectra are saved as PDF.
I think that one day tablets will substitute the PC as we know it today. That day tablets will have evolved from the iPad to something bigger, less closed, backward compatible with the PC. Then you will see NMR applications for the iPad, but the iPad will be a complete different thing from what it is today.
The iPad is closed system. The programs are sold through a single store. Only the owner of the store decides what will be sold (or freely distributed) and when it will be released. If your program is accepted, your problem aren't finished yet. Soon or later a user will discover a bug, and you will want to release a new version. You and the users will continue suffering for another week or two, until Apple decides to release the new version.
The NMR market is composed by two sectors: the industry and the academy. The App store is composed by one sector: the consumer market. Do you see any intersection? I see none. Actually, many industries refuse the idea of buying software on the App store.
The main problem is that writing a program requires time and time has a cost. Many people would say: "We don't need anything sophisticated. Give us the simplest thing", forgetting that the simple software has never been successfully, especially in the NMR field. Do you think that SpinWorks has been more successful than XWin-NMR? The former was simple, free and relatively unknown. The latter was big, complicated, expensive… and famous! Even if we try to forget this history lesson, writing a small program is still very very costly. For most programmers, and for all NMR programmers, the OS of the iPad is a foreign language. You can learn it, but it takes 1 or 2 years of study and practice before you become productive. You need a sound reason before spending 2 years of your life. This sound reason can be the project of writing 100 small programs or 1 big program. No wise man will spend 2 years of his life to write a single stupid program.
With a few exceptions, today's NMR programs are cross-platform. From the point of view of the customer, a cross-platform product is a safer investment. The same is true for the makers. Actually it will be hard to survive for single-platform software. Putting our issue into this context, the question becomes: "Which of the existing NMR software is easier to port to the iPad?". MestreNova is based on QT, which permits "the creation of applications for Symbian and Maemo, MeeGo (Nokia N9) in addition to desktop platforms, such as Microsoft Windows, Mac OS X, and Linux". No mention of iOs. No chances to see MNova on the iPad. Other NMR programs are based on Java, an established standard. Do you know that the iPad does NOT support Java? In other words, the iPad was designed to be incompatible. If you buy it, you should know it. After examining all the existent NMR software, the best candidate for a port is iNMR, because it is written for Mac OS X, therefore many pieces of code can be recycled unchanged or with minimal change. A lot of work is still required, though. Will it be remunerated?
That's the sad part of the App store, and of the software market in general. People don't understand the difference between a game and NMR software. The former can sell 1000 copies in a single day. If the cost of making the game was 50 thousands dollars, you can sell it at 3 dollars. You have covered the cost in 1 month. The public feels that 3 dollar is the fair price for any kind of software. Making an NMR software can cost the double: 100 thousands dollars. Just because we are optimistic, let's assume it will sell a copy per day, for a period of 2 years. Calculating the percentage that Apple takes for itself, the correct price would be 200 dollars. At this price, alas, it can no more sell a copy per day, maybe 2 copies per week (we are over-optimistic). The price for sustainability would then become 700 dollars, more than the iPad itself! At this price nobody would buy it. And we haven't counted the cost for after-sale support, an essential ingredient of a respectable NMR software.
My impression, however, is that NMR software and the App Store are two distant worlds. Before becoming reliable, usable, comfortable, NMR software requires several years of growth. The App Store, instead, favors games of fast success and fast decline.
The last chance is to find an hobbyist who will write this program for pure pleasure. The chemists I know barely have the time to read the manual of a program. Will they find the time to read the documentation of Apple's iOS and to write a program?

Spinus and nmrdb.org

2011-06-17T11:41:00.003+02:00

I don't remember how many years ago I discovered the web. I was excited by how many things were available for free. There were a lot of curious and interesting things but, I was the first to admit, nothing really serious that could substitute a true book, or a true CD or a true computer program. The great thing about the internet was that I could easily read the opinions of other people around the world. I mean: ordinary people just like me.
Things began to change with the appearance of SDBS 14 years ago. It was the first really useful thing I found on the web.
The last discoveries are Spinus and nmrdb.org.
SPINUS-WEB

SPINUS (Structure-based Predictions In NUclear magnetic resonance Spectroscopy) is an on-going project for the development of structure-based tools for fast prediction of NMR spectra. SPINUS - WEB currently accepts molecular structures via a Java molecular editor, and estimates 1H NMR chemical shifts. The predictions are obtained from ensembles of previously trained feed-forward neural networks, and corrected with data from an additional memory.
SPINUS - WEB predictions are restricted to:
CHn protons (no predictions for hydrogen atoms bonded to heteroatoms are made),
compounds containing elements C, H, N, O, S (some oxidation states), F, Cl, Br, or I.
For a data set of 100 independent structures representing a wide variety of structural features, SPINUS gave the following average errors for chemical shifts: 0.16 ppm for aliphatic class, 0.23 ppm for aromatic class, 0.35 ppm for non-aromatic pi class, and 0.29 ppm for rigid aliphatic class. A global average error of 0.23 ppm was obtained for the 952 predictions. A global error of ca. 0.6 Hz was observed for coupling constants.

This service depends on a number of Java applets that apparently do not work on my computer. Who cares, an alternative interface is available at nmrdb.org. In practice you can forget about Spinus and just connect to the latter. Spinus will be called in the background.
When you arrive at the home page of nmrdb.org, you find 4 applications: Simulator, Resurrector, Assigner, Predictor. The latter lets you draw a formula, from which a H-1 spectrum is generated. No alternative is given: if you already have the ChemDraw formula, it's of no use. You have to draw the formula again, which is easy and funny, I have to say.
The Simulator allows to simulate a second-order H-1 spectrum, so it's nothing really new. The required input are the values of chemical shifts and Js. Every time you change a value, a new FID is generated and FTed. Too slow for running it on the web, in my opinion.
The Resurrector transforms a list of peaks (copied from a PDF paper, for example) into the picture of the corresponding H-1 spectrum. How many formats are recognized? As you know, different journals may require different styles for reporting the NMR values. The ACS style is of course recognized. They have described nmrdb.org on a scientific paper, which probably contains all the details; I have not found them on the web page for the Resurrector.
The Assigner is something that does not work but suggests you to move to another site, called mylims.org:

The principe of mylims.org is very simple:
You upload a jcamp file
You process your spectrum
You save the result of the processing
You retrieve the ACS assignment for publication
Using mylims.org you will be able to make fourier transform, phase correction, baseline correction, “smart” peak picking, auto peak picking and even be able to assign 2D nmr !

The NMR Predictor brings us back to our starting point. This picture gives you an idea of how it works:

You hover the mouse over an atom in the formula or over a peak in the spectrum. Two yellow squares appear, that hilights the correponding spots into the formula and into the spectrum. Just what you expect, because the similar programs all work in this way.

VeSPA

2011-06-01T08:49:00.004+02:00

VeSPA is an open source software funded with public money. They are investing time, money and expertise into it. Something good is going to happen. Here is what the software manual says:

The Vespa package enhances and extends three previously developed magnetic resonance spectroscopy (MRS) software tools by migrating them into an integrated, open source, open development platform. Vespa stands for Versatile Simulation, Pulses and Analysis. The original tools that have been migrated into this package include:
- GAVA/Gamma - software for spectral simulation
- MatPulse – software for RF pulse design
- IDL_Vespa – a package for spectral data processing and analysis
The new Vespa project addresses current software limitations, including:
non-standard data access, closed source multiple language software that complicates algorithm extension and comparison, lack of integration between programs for sharing prior information, and incomplete or missing documentation and educational content.

I am interested into the spectral simulation module only, because pulse design is not my field (yet) and because there are already too many programs for processing.
Installing VeSPA is not an easy task. VeSPA depends on a lot of other software, which in turn depends on other software, etc.. You need a guide, which is this page:
http://scion.duhs.duke.edu/vespa/project/wiki/Installation
Install the 8 packages in the listed order. For some of these packages you will be prompted to install an outdated version. Resist to the temptation of installing the latest version, because this will break the inter-dependencies of the other packages. Installing the first packages of the list is a merely mechanical process: click to download, click to accept the license agreement, etc.. The last packages, instead, are written in Python and are a little more complicated to install. In my case, it was necessary to use the unix commands cd, su, sudo and exit repeatedly. Renounce if you don't know these commands. Such a complicated installation is quite discouraging. I see no reason, for example, why anybody should try to install the processing part of VeSPA, while other software is available that can be installed with a single click. I can see the other side of the coin, however, and it brights.
Instead that reinventing the wheel once again, they put together many bricks, old and new ones, that were already available. Do you remember this old article of mine?
There has been the terrible tradition, in our field, that every newcomer reinvents the wheel. We have seen a lot of simulation programs and nothing is available or working and supported. Now I welcome the VeSPA team because they have apparently embraced the opposite philosophy.
The big problem I see, after the installation, is that, at this writing moment, VeSPA is not a complete substitute for Gamma. The new program is devoted to in-vivo metabolomics. In theory there is space to grow and include what is left outside, yet this will not be easy in practice. Who is going to do it? Who is going to pay for it? I bet nobody will do.
The VeSPA web site is:

http://scion.duhs.duke.edu/vespa/

My current situation is: I have VeSPA installed but it's not what I wanted. I wanted Gamma. I have also installed Gamma in the process, but it does not work. If I try running gamma, I get the error message:

Apparently You Do Not Have A Proper Path Set To GAMMA......
Please Set The Variable GAMMA_PATH To Reflect The Base GAMMA
Directory, The One Off Of Which The Subdirectory share Exists.
This Change Can Be Done In The gamma Script You Are Running
Or You Can Set GAMMA_PATH As An Environment Variable.

Currently GAMMA_PATH is Set To /E/gamma/gamma-4.2.1

which means absolutely nothing to me, because there is no "share" subdirectory. I have tried to set the variable:

GAMMA_PATH='~/gamma'

and the error persists unchanged. The last chance was to use pygamma. Not exactly what I want, but they say it's equivalent to gamma and I remember having installed it in the process of installing VeSPA. My first attempt was:
pygamma
The answer: command not found.
Then I have tried something more... detailed:
python "/Library/Frameworks/Python.framework/Versions/2.6/lib/python2.6/site-packages/pygamma/pygamma.py"
The answer was:

Traceback (most recent call last):
File "/Library/Frameworks/Python.framework/Versions/2.6/lib/python2.6/site-packages/pygamma/pygamma.py", line 7, in
import _pygamma
ImportError: dlopen(/Library/Frameworks/Python.framework/Versions/2.6/lib/python2.6/site-packages/pygamma/_pygamma.so, 2): no suitable image found. Did find:
/Library/Frameworks/Python.framework/Versions/2.6/lib/python2.6/site-packages/pygamma/_pygamma.so: mach-o, but wrong architecture

What kind of joke is this? They really have no idea of what a user is.
I have my theory why everybody writes his own simulation software: it's because nobody is able to install somebody else's software.

VirtualBox

2011-05-25T08:47:00.007+02:00

This piece of open source software is worth trying. It is not an application; it does nothing by itself. All it does is to create a virtual computer. Instead of buying a computer, you start a virtual machine. Think at the enviromental impact. You can even start many virtual machines simultaneously.
In my case, I own a Mac but have found some interesting games that require Windows. I have already tried BootCamp, that is perfect, yet I also liked the possibility of keeping my game open while I was working. It made no sense to buy a commercial software to run a free game, but Virtual Box is different, because it is free.
Advantages:

Is free

Is backed by a big company like Oracle

Easy to install

Many things work without the need of configuring them, for example when I install an operating system on a virtual machine, it is already connected to the internet

Limitations:

I have found a program (Chessmaster) that does not run on the virtual machine. Maybe you will find other programs that won't run.

Though the manual says it is possible to share a folder between the host system and the guest system I have not been able of sharing anything.

If I really need to exchange files between my real computer and the virtual machine, I send emails to myself. For this reason, I use the virtual box only for playing. Using it for real work is not practical, and probably it's not even safe. Anyway, for the average Mac user, there is no reason to use Windows for work. Maybe the the contrary is true, that is Windows users might need to install Mac OS on their machines. This is impossible, or at least not permitted.
Oracle is actively working on the VirtualBox and it may become a planetary success in the future.

Cyberduck

2011-05-04T16:19:00.005+02:00

Though you can easily move your spectra with a USB memory stick, the ancient FTP protocol is still the most popular way to transfer data from the spectrometer to the PC (or laptop) where processing is performed.
When I started my first NMR experimentations, FTP was not available: local networks were extremely rare and the spectrometers didn't even contain an operating system. So you can guess I have used many FTP clients in my life. During the last 6 years, however, I have been using Cyberduck exclusively, not just because it's free (actually I donated my shareware fee long ago), but because it never fails. It's also very easy to use: the icon gives the exact idea of the complexity of this program.
Over the decades I have always received the question: "Why can't I open my spectra on my PC/Mac?". The last time it happened was this morning. The first thing I say is: "Check your FTP client", because this is the most common cause of the trouble. The second thing I say is "Switch to a SERIOUS program like Cyberduck" (I wonder what they think about the icon). Most of the times I discover that the other guy is using "Filezilla", something that I have never seen but must be a terrible piece of crap, considering the countless troubles it has caused along the years. Nobody ever thinks about the FTP client; the innocent NMR program is the one the receives the blame, instead.
When you are using the wrong client, or the right client with the wrong settings, your files arrive with a different size (this fact alone should ring a bell) or with some bytes changed. One of the great things about Cyberduck is that you don't have to care about settings. It just works out of the box.

Fighting the Pirate

2011-04-11T09:20:00.001+02:00

Six years ago I took the decision of investing my efforts into the creation of a software application. It was a complex project that potentially required thousands of hours of work. I had to make it financially viable. No sponsor was in sight, so the only solution was to make a commercial program and sell it. I was extremely lucky, because the facilities to sell it were readily available and convenient too.
The difference between a normal application and a commercial one is that the latter must be copy-protected in some way.
I had complete freedom about how which technology to choose to protect the program. It was clear to me, and still it is, that no money had to be spent for the protection. First, I was not sure that the product could sell enough to invest part of the money into its protection. Second, it's a non-sense to spend money to protect software by piracy. I think that those who steal a copy of a program are inherently thieves. They can't be convinced to buy a regular copy. Stopping the theft does not increase the volume of sales, therefore it is not the case of investing money for the protection.
On the other hand, I had discovered since a long time that:
- writing a program is easy;
- selling it is hard;
- convincing people to use it, after buying, is even harder.
Have you read all the books you have bought? Are you still using all the programs you have bought? We are subsidizing the software industry with this kind of unhappy purchases. I want my share of this cash flow and copy-protection is the way of keeping this little share intact.
I invented my own home-made protection, which was based on a simple but effective encryption. I don't know, however, who were the pirates and how they worked. I believed that a pirate was somebody interested into directly using the program. Nothing was farther from truth. After a couple of years I found the first pirated copy of my program. It had been cracked by someone who only wanted to demonstrate how smart he was (or how dumb I was), but had no idea about whose was the program and what it was for. There was no intent of stealing my money or saving their money. It merely was a kind of illegal hobby. The pirate thinks he is a gentleman, because he never cracks the latest version of a commercial program, but the version of yesteryear. Unfortunately, not all the customers need or asks for the latest version, so piracy is still a danger.
When I discovered the first successful crack, I was not terribly worried. First of all, beige worried could not have helped in any case. Second reason: the particular version they had cracked was probably the buggiest version I had ever released. Third reason: the program was still relatively unknown, up to the point that having illegal copies around was a cheap publicity.
Fast forward another two years and I was seriously worried. This time they had cracked one of the finest version I remembered having made, virtually flawless. Multiple copies of the cracked version had already been uploaded on Rapidshare and were relatively easy to find with Google. I realized had to fight and I fought. On the prevention side I studied how the crack had been executed. Then I implemented a different protection mechanism. All my future versions became more difficult to crack. But what about the copies around? I simply wrote a single email to Rapidshare. I explained that they were violating a copyright, but I didn't threaten anything. With my great surprise, all the files were removed within 24 hours. I accomplished two great results: all the copies had disappeared from the web and a lot of broken links had remained around. Anybody who was going to search for the crack, he was going for a frustrating experience.
Today things are quite different, because there are a lot of parasite sites that promise you, in change of a registration, to disclose the links for the download. No link is published, but probably no link exists in reality. I can't believe that somebody can risk a virus infection, a robbery of their bank account or simply a ton of porn spam, only for getting a dubious link to a cracked program, and not the most recent version of it. The parasite sites are the worst enemies of the pirates.
I had discovered the main weakness of my protection mechanism: the bottleneck design. This is an important and wise design in normal programming. Instead of disseminating the code with duplications, I concentrate the important instructions into a single routine, that is called several times by the rest of the program. If I want to change the mechanism, it is enough to change the internal code of the bottleneck routine, I don't need to care for the rest of the program. Alas, it was too easy for the pirate to find the bottleneck and modify it. Instead of verifying the key code, the cracked routine simply returned "yes" every time, even if no key was present at all.
At the same time, I had discovered the weakness of the pirate. He was not using the program, he had no time to verify if the program was functional (he doesn't even know what the program is about). He has too many applications to unprotect, because he is in competition with other pirates. It's not important, for them, to demonstrate they can unprotect a single program. Their goal is to unprotect as many programs as possible. Quantity does not mean quality and accuracy, this is a piece of information I can exploit.
I have found two solutions that can be combined together. First, I have duplicated the code that verifies the key. The pirate will find the first occurrence, he will bypass it and the program will be apparently unprotected. Five minutes later the second version of the code will be called. By that time, the pirate has already quit the program, so he will never know there is another verification. The second solution that I have found is to put some important action into my bottleneck. Apart from returning "yes", the routine must do something necessary for the rest of the program. If the pirates bypasses the routine, a hole will remain into the memory. Soon or later, the program will fall into it and crash.
Last month a friend of mine, who lives into another continent, discovered a new cracked copy of my program into a lab nearby his. My friend sent me the cracked copy. I launched it and waited. After five minutes, without doing anything, the program crashed by himself! At least in this last battle I have been the winner. The war will go on forever.

Lotus Symphony

2011-03-04T08:32:00.004+01:00

Even spectroscopists needs an Office suite. Just because I need it infrequently, and there are many free options available, I have chosen one of them. Initially I adopted OpenOffice, then switched to NeoOffice because of its more appealing and sensible graphic interface. The main problem with both of them was that the documents looked different when seen with MS Office. Now I have switched to IBM Lotus Symphony and that problem is solved. Maybe the latest versions of the other programs have improved, but I am so happy with my Symphony that I don't see any reason for trying something different again.
This is a product nobody writes or talk about, so most people confuse it with the original Lotus Symphony suite. The two products have nothing in common but the name. Probably this arguable choice by IBM to recycle the brand was unfortunate: people refuse to even try the new Symphony because they think they already know it.
The new Lotus Symphony is a blend of OpenOffice and Eclipse, topped with a stylish interface. The result is a rare combination of elegance, simplicity and, mainly, intuitiveness: the best virtue of Symphony. Other sure pros are the perfect compatibility with MS Office and the absence of a price.
The main con is the time it takes to start. It really takes an incredible amount of time, about 20 seconds. Afterwards, however, the program seems fast enough for all the things I do. Another limitation is that the suite is not complete. There are four components (word-processor, spreadsheet, presentation program, web browser) and they are very well done, but I need other two programs at least (one for drawing and one for keeping a database). The first three components, however, are really rich in features and this is what really matters. It is far better to have three great programs than to have five not-so-great programs.
There is a problem that I hope will be solved with future releases. If a file contains accented chars in its name (or in the name of any surrounding folder), that file can't be opened. It is necessary to change the name of the file and of its surrounding folders.
Need I tell you that I will never consider the option of using a web-based service instead of a classic desktop application like this? Lotus Symphony does not ignore the web, to tell the truth; it can (optionally) connect to its home servers to let you choose more templates/clip arts or to give you more information. I really like the idea, though I never used those resources, because I find the program extremely intuitive and very easy to use. I have recommended Symphony to my relatives and they all agree with me.

Bell Bell

2011-02-05T13:50:00.004+01:00

Our friends working in the field of biopolymers can study a single molecules for months and can afford to spend a lot of time with their NMR spectra, if the time invested translates into higher accuracy of their results.
Software makers are more interested in creating automatic tools that work without human intervention, day and night, because of the higher appeal of any push-button solution. Is anybody helping our friends? Yes! One month ago a simple and effective tool appeared for measuring the volume of a 2-D cross peak, courtesy of iNMR. Let's see, with a practical example, what it does and how it works.

We start from the normal contour map. Here you click on a single peak and optionally enter two labels to assign it. In the picture we have selected the peak at the bottom right. Many things automatically happen, if you like: the program can locate the maximum of the peak and fit the overall shape with a gaussian bell. Why a Gaussian instead of a Lorentzian? As you know, 2-D spectra are premultiplied with cosine bells before the FT, and the purpose of this weight is just to transform the shape. The tails of the gaussian are much shorter, so we avoid the lorentzian as far as possible. The additional problem, in this particular case and in many other cases, is the presence of unresolved J-couplings. When they are resolved, you can fit the peak with a combination (sum) of bells. In our case, we could try to fit the peak with a doublet, but for simplicity we'll approximate it to a singlet.
My pictures do not show the moving cross-sections around the border of the contour plot. The cross-sections, that exist into the program, give a graphic idea of the goodness of the fit. Up to now, cross-sections included, there is nothing new. Everything has been copied from more ancient programs (read: Sparky). But now, a single click brings us into the Manual Fitting module, which is the novelty.

We have two orthogonal cross-sections: the yz section at the top and the xz section at the bottom. The experimental spectrum is black, the model (gaussian curve) is red. We can change the 5 parameters that describe the model. The simpler way to change them is by dragging the little square handles. Alternatively, we have the numerical fields or the little arrows. When you change the x frequency in the lower panel, the programs show a different vertical cross-section in the upper panel, corresponding to the new x. When you change the y frequency in the upper panel, a different horizontal section is selected.
The final picture shows my best result, that is the way I would measure the volume of this particular peak. Higher accuracy can likely be obtained with a model comprising two gaussians (something you can also do with this module), yet the present result is accurate enough for many practical applications.

All the values are automatically stored into a bigger module called "Cross Peaks Manager" (CPM in the following; actually you need to create a CPM before starting any volume-fitting operation). The CPM stores things of different kinds: chemical shifts, assignments, integrated volumes, fitted volumes, etc. A real-life problem where a CPM can be precious is the measure of relaxation times of very large molecules, like proteins. These molecules are so large that very few signals are resolved in the 1-D proton spectrum, while the sensitivity of other nuclei is not enough. You collect a series of HSQC spectra, a 2-D experiment that resolves all the signals (or almost all of them). A single CPM can manage the whole series of experiment. When you have processed all of them, you can ask the CPM to create a table with the integrals. The table combines volumes measured by integration and volumes measured by fitting (manual or automatic). You are not confined to a single solution. You are free to integrate each single peak with the most appropriate technique for it. If this is not enough, you have the time-saving option of simultaneous automatic integration.

Free for 1 Year

2011-01-17T22:40:00.002+01:00

I said to myself: "What if I return to the original concept of the blog, that is to write reviews of existing NMR software"?
I remembered there was one I had never tried. It's called NPNMR (where NP stays for: "Natural Products") and the web site has been in existence for a number of years, though I only heard about it from Google. The NMR wiki ignores it. I remembered there was a freeware version; I wanted to try it. The installation was successful. License was more problematic. The free license is not forever. It only lasts one year, starting from January 1, 2010. In practice it has already expired. "If you use the software on a regular basis, you should purchase a regular (commercial) license." I am waiting day after day, now I am a little tired of waiting and here is the review (without having tried the program!).
From the little I have read of the manual, it could be a fine product, with all the functions that today are considered the bare minimum. The author copied the right ideas from the right sources. The final result looks personal and tasteful. Some interface choices are arguable, like the multitude of different tools to perform correlated actions. For example, there are three integration modes and they are all necessary: the "integration" mode, the "remove" mode and the "edit" mode. Easy to learn but awkward for repetitive work.
The commercial price is reasonable. 500 euro for a professional program was a convenient price 10 years ago. I appreciate this kind of commercial policy: rounded figures that never change, the same price for everybody, no special deals, no promotions. Maybe the recent trend of the market made you think that a software can cost an order of magnitude less, but this is wrong. The software industry is not sustainable at low prices.
NPNMR is a Java program, with the limitations and the advantages of the language.
My impression about the NPNMR story is that the market is saturated. It's not enough to have a good product. It's not enough if the product is also free. A lot of hard work is required to make it popular. And NPNMR is not popular yet (otherwise I would have already found a license valid for 2011). A free product that requires a lot of hard work is an absurdity that can't last. We have already seen what happened in the past with other programs: Mestre-C is the most famous example, with NMRPipe representing a different illustration of the same basic concept.

Video is a Latin word

2011-01-15T10:12:00.002+01:00

Few weeks ago I was with Giuseppe "Jimmy" Tarascio, a kind and nice guy who deserves to be a celebrity. To my eyes, he is a celebrity. We were alone and we didn't know where to start a discussion from, so I said: "This morning I have received your newsletter". "Glad to know it", he replied, "I never know if it arrives or not". "I am receiving all the issues", I confirmed. Then he narrated how difficult it is to manage his newsletter, mainly because he wants to send PDF attachments with it. In practice, Jimmy painfully compiles by hand the list of recipients each time he broadcasts an issue. As soon as I heard this, I felt guilty and promised I was going to unsubscribe. I did it when I got back home.
For the same reason I am not giving here the link to the beautiful web site that Jimmy is slowly building up, enriched by exercises, articles and videos. His site is not dedicated to NMR and it is not written in English, so 99% of my readers can't find any pleasure in visiting it.
Why can't you find videos on my blog? Apart from the fact that I haven't learned to make them yet, I don't like videos (unless they are Tarascio's, of course). Why?
1. Slowness. Only in the morning my ADSL connection is fast enough to watch a video without interruptions (or with few of them). Podcasts represented the solution to this problem (first you download, then you watch). Unfortunately, podcasts are already out of fashion.
2. Language. It's not easy to translate an unknown word without spelling. Language is still a barrier, like in Babel's time.
3. Voice. The synthetic voice can be clear and funny, but not very funny. Very few can afford to hire a professional speaker.
4. Speed. Just like with live demonstrations, it is difficult to follow and learn the operations shown by the screencast. Live demonstrations are possibly worse, because you don't have the pause and backwards controls.
5. Resolution. I don't like slow resolution pictures and movies. Do you?
6. Screencasts are not interactive. I remember that years ago (probably in the age of system 8 or even before), Apple introduced a rich help system. The manual for an application contained pictures, movies and scripts. Not only the manual told you which menu commands to select, it selected the command for you, after drawing a red circle to show its position inside the menu. Really impressive, but probably too expensive because bulky and annoying PDF books are the norm today.
What's Tarascio's secret? His videos are neither about software, nor about NMR, but about "winning moves". What's my advise? I think that HTML is really a wonderful solution for presentations. A little of Java Scripts can help, but not Flash!

Routine Prediction

2010-12-01T11:08:00.015+01:00

Not everybody remembers how easy it is and how effective it can be to add (or correct) a few points at the beginning of the FID. Two years ago I explained how Linear Prediction works and how we can extrapolate the FID in both directions. This time I will show a simple practical application.
I have observed that, in recent years, C-13 spectra acquired on Varian instruments require a much-larger-then-it-used-to-be phase correction. When I say correction, I mean first-order phase correction, because the zero-order correction is merely a different way of representing the same thing (a different perspective).
A large first-order phase correction can be substituted with linear prediction. I will show the advantage with a F-19 example, yet the concept is general.

The spectrum, after FT and before phase correction, looks well acquired. Now we apply the needed correction, which amounts to no less than 1073 degrees.

Have you noticed what happened to the baseline? It's all predictable. When you increase the phase correction, the baseline starts rolling. The higher the phase correction, the shorter the waves. With modern method for correcting the baseline we eliminate all the waves, yet there are two potential problems: 1) The common methods for automatic phase correction will have an hard time. 2) If you prefer manual phase correction, you need an expert eye to assess the symmetry of the peaks over such a rolling baseline. Anyway, just to show you that linear prediciton is not a necessity, here is the spectrum after applying standard baseline correction:

Now let's start from the FID again, this time applying linear prediction. one way to use it is to add the 3 missing points at the beginning. The result, after a mild phase correction (<10°) and before the baseline correction is:

The lesson is: by adding the missing points we correct the phase.
Alternatively we can both add the 3 missing points and recalculate the next 4 points. In this way the baseline improves a lot:

The lesson is: by recalculating the first few points of the FID we can correct the baseline of the frequency domain spectrum.

2011

2010-11-04T15:00:00.001+01:00

Promotional Sale

2010-10-27T16:25:00.003+02:00

There are three possible reasons why you can be tempted by iNMR.
First reason: it's for research. It happens that they are not using iNMR in the industry, not because they don't like it, but because they don't buy Macs anymore in the industry. So, the majority of iNMR users are not doing repetitive activities. They don't ask to process 20 spectra in 20 seconds. Maybe they want to estimate the concentrations by time-consuming line-fitting or they want to monitor the phosphorylation of a protein by a series of thirty H-N HSQC, or they want to simulate the effect of a slow rotation, as they used to do with DNMR in the '70s. iNMR users asked for such things years ago and now you find them already into the program.
Second reason: students learn the program by themselves. Nowadays few research groups are pure-NMR-groups. When a new PhD students joins the lab, he has many techniques to learn, not just NMR processing. Luckily, iNMR has many things in common with the other applications he daily works with on his/her Mac. iNMR also helps novices to understand NMR processing because spectra are clearly depicted at every stage. A lot of things become natural after the first day of use.
Third reason: today Mestrelab has started a promotional sale, a sort of end-of-the-year clearance.
You can buy a disposable license at €90 instead of €150. You can download and try the program before buying.

Oh, Sugar

2010-09-03T17:31:00.007+02:00

I have good news! With a minimal simplification of my INADEQUATE filter I have been able to rescue the last cross-peak of cholesterol. It had been rejected because too near to the diagonal. I changed the code saying: "if it's on the diagonal, it is bad; if it's just near, let's accept it". So it is possible to have the perfect INADEQUATE of cholesterol, with all the expected cross-peaks IN and everything else OUT.
Yesterday I received another INADEQUATE spectrum, this time of sucrose. The S/N is still high enough to make my filter unnecessary. If I play with the contour plot all the noise disappears while the 12 carbon atoms and their 10 bonds remain. Only a spurious peak remains at the coordinates 103.7;-22.9. I have not received the 1-D external projection, so I created it artificially. The spectral width is the same in both dimension (instead of being doubled for the DQF axis). The consequence is that two cross-peaks fall just on the boundary and are partially folded. This is the spectrum:

I have applied the filter with the same parameters used for the cholesterol (C-C coupling; linewidths in the two dimensions) while the threshold corresponds to the above plot. The result is perfect. All the cross-peaks are resolved and they are all present. Nothing else survives.

This time all the peaks are regular anti-phase doublets. The Js are generally larger than in cholesterol.
Click on the thumbnails to see the full-size pictures. There is an expansion to help counting the correct number of cross-peaks.
Do you want to send another spectrum? I can clean it for free. Remember to enclose the 13-C of the same sample.

Interstellar Space

2010-09-01T23:09:00.008+02:00

One of the most ancient 2-D experiments has always been more talked about than practiced. The INADEQUATE was invented 30 years ago (an era in which many chemists were still using CW-NMR) and has always been regarded as a the future thing, like travels to the Moon. Everybody agrees it is useful, but the experimental difficulties are discouraging.
The information that can be extracted by this experiment is a formidable aid to unveil the structure of unknown natural compounds. For a long time, however, the experiment has been nearly impossible. You needed a powerful transmitter, because the nominal 180° pulse must be a true 180° pulse over a large spectral width. You also needed a sensitive probe. A cryo-probe is the best. Today we can have both things.
I am not mentioning here the many attempts to increase the actual sensitivity with experimental tricks, because this is a blog about software. 19 years ago the S/N limit was overcome by a pure numerical method, see this paper, commercialized as CCBond (also sold under the trademark FRED). I understand that the same program is now part of the larger NMRanalyst (™). No software that I know has ever changed the world. Having never personally used this particular product, I take for granted what the paper says while observing, at the same time, that its popularity is limited.
From the cited paper I read that the program failed to detect a few bonds in the INADEQUATE spectrum of cholesterol; the authors also explained why (the presence of second order effects). I think this is a serious issue. You can't use such a tool with confidence. A user has no way to verify if these second order effects are present or not, then he cannot verify if his spectrum can or cannot be handled by this particular program.
A few months ago I received a nice INADEQUATE spectrum. Guess which compound it was? Cholesterol! This is the first time I see this particular spectrum, so I can't tell if it was acquired correctly or not. I can see ALL the bonds with possibly one exception. I see the peaks corresponding to the bond between C20 and C22, yet it's not clear if they fall at the correct frequency or, instead, at the frequencies of C10 and C20. It is amazing, however, to see all the bonds without the aid of any special software. It is like discovering that we can go to the Moon with RyanAir.
A bitter surprise came from the observation that not all the peaks have the same shape. The very few articles I have read on the subject say that every cross peak is an anti-phase doublet (one peak goes up, the other peak goes down). Here, instead, I can see several different deviations from this simple model. This means that all the numerical methods previously described cannot be applied to this example. Should I try to improve this spectrum, I am going to lose one or more peaks, which would be a pity since I can already see all the peaks in the untreated spectrum. Maybe all the other INADEQUATE spectra ever acquired only have doublets and mine is the worst INADEQUATE ever. Maybe my spectrum is OK and the model is too simplistic. I hope some reader can solve this fundament doubt.
For the moment being I assume that my spectrum is perfect, simply because it's the only spectrum I have got. I have devised a new numerical method to improve it. It works like a filter and can clean the spectrum. I start from the known frequencies of the carbon atoms. They are easy to get from the standard 13-C spectrum reported at the top in my pictures. Everybody knows that a genuine peak can only fall at the frequency of an existing carbon. The cross-peaks also come in horizontal pairs. The vertical position (DQ frequency) of a pair is given by the sum of the two chemical shifts. Anything that does not fall at these predictable frequencies cannot be a genuine signal. My method filters it out. The signal/noise remains the same, but the plot is much easier to read.
My method, in theory, requires 4 parameter, provided by the user:
- A threshold level. This is the lowest contour level.
- The approximate width of a generic multiplet in the X dimension.
- The width in the Y dimension.
- The C-C coupling constant.
The method is not dumb, though. If nothing is found using the user's parameters, it will automatically try with different starting values. The last 3 parameters are easy to set, either by observation or by mining the literature. The most critical parameter is the threshold. Fortunately, it's not very critical.
I am going to show how tolerant my method can be. The previous picture shows the optimal threshold. [Click on the thumbnails to see the full-size pictures]. When I start from this value of threshold (1620), no cross-peak is lost and no false positive is created (spectrum not shown).
In the next picture the threshold has been reduced to less than the half, quite far from the optimal value. The threshold is now 620.

My method yields this:

The only difference between this and the spectrum processed with the optimal threshold, is the additional presence of the two cross-peaks labeled 22->20. This is good to know, because it means that the threshold is not critical. You can enter a wrong value and the result will almost be the same. This bond C20-C22 actually exists, but the cross-peaks on the left falls at the wrong frequency. It makes you think that C20 is bonded with C10 instead. As you can see, the column of C-10 now contains 5 cross-peaks (5 bonds??).
C-22 falls at 36.2 ppm. C-10 falls at 36.5. C-20 falls at 35.8. It is difficult to demonstrate if two atoms are bonded when their chemical shifts are so near.
I am very glad to see the cross peaks 5-10, 5-4, 3-4, 3-2 because they deviate from the simple doublet model. A simplistic model would never recognize these peaks, but my filter assumes a more generic model.
If I raise the threshold to 2620, the following cross-peaks disappear: 5-10, 1-10, 14-13 and 25-27. They are not so many, yet the basic lesson is: it is better to underestimate the threshold than to overestimate it.
I need more examples to test this method against. I feel it is promising indeed. The algorithm is simple and fast, which are always good qualities. It is amazing how far you can go with very little math.

Student Price

2010-08-26T12:17:00.009+02:00

It was 40 days ago when I mentioned the student license of TopSpin and other products, once pricey, that are now free for academic users. Knowing that many students prefer the MacBook and would like to run authentic Mac applications on it, I am going to write about the student promotion of iNMR. It is not free, but it is as cheap as it can possibly be. It's 39 euro (equivalent to 49 USD or 32 British pounds or 4200 Yens). What's so special about this license is that it is... perfectly normal! I mean: it INCLUDES direct customer support and this is quite valuable for a student that is learning NMR and a new software at the same time. Is this program difficult to learn? As for every NMR program, it CAN be hard if you are so familiar with TopSpin (or VNMR, or Jeol Delta) that you can't adapt yourself to anything else. The learning curve of iNMR is actually incredibly smooth if you start processing easy examples (1-D spectra or well acquired 2-D like TOCSY, HSQC...) before moving on to the esoteric.
Today you find video tutorials everywhere. The iNMR site offers "visual guides" instead. I feel more comfortable with the latter, first of all because English is not my native language; second of all because I can keep both the program and the guide open at the same time; third of all because I can read the guide at my own pace.
The iNMR manual is also worth of a mention. Actually I dedicated a whole post to it a few years ago. It is not the usual bulky PDF file. It looks like coming directly from Apple, because it closely resembles the manuals of Mail, Safari and iTunes for Mac OS X. Technically speaking, all these manuals are task-oriented. In simpler terms, every chapter answers to a question in the form: "I want to perform the operation X. I can I do it?". Here is an example. As you can see each chapter is just one page long.
In which cases would a student need help, then? An example is when she needs to write a script (a macro command); another extreme case is when she needs a modification to the program itself. Anyway, support also means giving a fast answer to people who can't find the time to read the manual. When you are a paying customer, you have your privileges.
For those who prefer freeware, there is the trial version of the same product (printing is disabled). iNMR has been around for 5 years by now, therefore there's plenty of reviews, short and long ones.

Can Zero-Filling Correct the Baseline?

2010-08-18T12:04:00.008+02:00

I want to show you a proton spectrum that has puzzled me during the last weeks. It contains something that's quite typical and something that I can't explain. I have processed the spectrum in two different ways, with zero-filling and without it. The spectrum without zero-filling is black, the spectrum with zero-filling is green (the number of points is doubled).
This detail is the bottom part of the TMS signal (magnified to show the ringing effect). Where does the ringing come from? TMS is a small symmetric molecule and its protons have a long relaxation time. Their signal persists at the end of the FID. When we add the zeroes after the signal, a step is created. The FT of the step is the ringing that we see. The spectrum without zero-filling doesn't contain the step, so there is no ringing. The period of the ringing is exactly 1 point. In simpler words: odd points are positive, even points are negative. Things are not so simple, actually, because the rule is reversed on the two sides of the peak. This is something I have always seen, I don't know if it's a constant rule or something that's merely more probable than its opposite.
Without zero-filling, we have only half of the points. They correspond to the maxima on the left of the peak and to the minima on the right of it. Any program for automatic phase correction is fooled by asymmetric peaks like this. Even humans are often fooled. They think that the spectrum is "difficult to phase" and don't recognize that the peak is asymmetric. Asymmetry and ringing are two sides of the same coin. Without zero-filling we have asymmetry, with zero-filling we have ringing. In the first case it is difficult to recognize that the signal is truncated, because it appears much larger than it actually is.
Up to this point I can explain everything. It's all familiar to me. There is another effect that I can't explain at all and appears when I observe the whole spectral range. The baseline of the normal spectrum is wavy.
The baseline is perfectly flat in the other case. This is the first time I see such an effect: can zero-filling correct the baseline?
This spectrum was acquired on a recent Jeol 400 MHz instrument. I wonder if the digital filter has anything to do with the latter effect.

The Barrier

2010-07-17T12:17:00.001+02:00

In the last two years NMR software has kept evolving slowly, but the world around it is changing more rapidly. From a technical point of view nothing important happened; while from a commercial point of view we are in the middle of a revolution. Prices have dropped down considerably. The false categories, the so-called "professional", "industry-standard" programs on a side and "low-budget", "alternative" programs on the other side, have disappeared. The companies that were selling the products in the first category have realized that the true values were actually reversed and adjusted the prices accordingly.
Consider TopSpin, for example. I remember its original price was in the range € 4000-5000. At the beginning of the month, I have visited an industrial lab where they had recently purchased a license for off-line processing. They told me they had paid € 3000 for TopSpin. They had also considered a solution by ACDlabs, but after receiving a quote of € 10,000 they renounced with disgust. The main reason why they prefer TopSpin is that it is possible to process the spectra directly on the spectrometer, with great saving of time. When back into the lab, they simply print the already processed spectra.
Less than 24 hours later I had a pleasant talk with Angelo Ripamonti, from Bruker Italy. He gave me different figures. The price of a license is € 2,000, complete with box, cartaceous manual and CD. They also have an electronic edition, called "Topspin Student Edition". It is the same product, the license expires after 3 years and costs € 99 (as far as I understand, there is no after-sale support; I am not sure, though). With my great surprise, Angelo said that they hope the students will familiarize with TopSpin during their PhD period and remain faithful to it. I used to think that TopSpin was by far the most famous of all the NMR programs; evidently they are not so sure and fear the competition.
On one thing we agreed all along the line: the chemical industry has completely disappeared from Italy (if we are allowed to measure it by the number of magnets being sold). If I could, I would also close the Italian universities (what's its purpose, if there is no industry? the local job market wants nurses, not chemists), but that's another story (Angelo hopes the Universities will grow and buy more magnets).
I told Angelo that I had noticed that ACD had their own "academic edition", which is completely free. I myself have received a copy, though never used yet. I asked for his opinion: could the ACD move be a reply to Bruker's Student Edition? "No", he said, "they are making a lot of money from their NMR database". Translation: ACD is the only competitor in the field of NMR database and they want to monetize as much as they can while the favorable situation persists. Indeed, the "price" I paid for the NMR processor was my email address, which they have already used to advertise the database.
Bruker is also lured by this segment of the market. They bought Perch and are working on it to make a new product that will predict the chemical shifts from the structure. Not the same thing as a database, but with the same purpose.
As my readers know, I had long waited to try the ACD program, because I started this blog with the intention of writing reviews for all the software in existence. Time passed and I have different pastimes today. If I haven't found the time yet to study the Processor and write a review, there are very few chances I can do it in future. The mere length of the manual discourages me. I want however to comment on their commercial move.
(1) It is not correct to first sell a program to several universities and then to give it for free to the rest of the world. Unless they give the database for free to those universities that paid for the processor. That would be a fair compensation. What about, however, the universities who already have bought both products? What about those who never bought anything? After this precedent, how can ACD convince somebody to pay for one of their products, when there's the risk that it becomes free after a few years?
(2) People see with different eyes a program that is free starting from version 1 and a program that is free starting from version 12. Consider, for example, Internet Explorer. It was born as a freeware and it was a huge success, actually a monopoly. It still accounts for 45% of the market. Firefox accounts for the 32%. Opera, instead, started as a commercial product before becoming free. Its share of the market is a disappointing 2%. What people feel is that if the former commercial product was not good enough to sell copies, it is not good enough to bother with.
(3) I don't know exactly why, but ACD has not been lucky, so far, with free programs. Consider their ChemSketch, for example. I have never found a bad review, while I always hear people complaining about ChemDraw. Somehow the latter remains the undisputed no. 1 in the field. Why?
(4) If you want your product to become popular, making it free is a good move, but giving it a catchy name is as much as important. People at ACD have always lacked in inspiration. "ACD NMR Processor Academic Edition" is the less memorable of the names. Even a distasteful name like "BottomSpin" would have proved more effective.
(5) If you analyze the situation in detail, this product is still far from being "free". Whenever you print, the program adds a red line reminding it's not to be used for commercial purposes. The file format is proprietary and not recognized by all the programs (you are locked-in). There is a potential risk that the program becomes commercial again in future.
The battle has reached the first result. It has created a barrier. If a new competitor wants to enter into the arena, its product must be at least as good as today's free programs (and there are at least 3 formerly commercial programs that are available for free today). Given that it costs a lot of time and money to create a new NMR program, while the prices keep falling, the barrier is very high. We are not going to see any novel program in the next decade, neither free nor commercial. If all the investments are made in the field of databases and predictors, even existing processing programs are not going to be revamped, but simply refreshed.
Do not think that users are happy and programmers are sad. Not at all! After 4 years, the most read page of this blog remains "TopSpin Free Download" and readers who comments there are angry as before (the page exists, but there is nothing to download!). All the programmers I am talking with, on the other hand, are quite glad: their programs are selling and nobody went in bankrupt in the last few years, despite the financial crises. Apparently a point of contact has been found between the two sides. The prices are more reasonable than they used to be a decade ago, the programs are better and many customers prefer to pay if they can receive a good service in addition to the product.

Universal Hole

2010-07-01T16:36:00.010+02:00

Earlier in this week I cited a paper by Kobzar and Luy. It contains the statement:

The coupling extraction procedure is not yet implemented in any available software.

that confirms and enforces what I have always being saying:

Any NMR program contains some hole and by the time it's filled another hole appears.

What they have found is a kind of super-hole that is common to every program. My first thought would normally be: "If nobody cares, why should I?", but this time I was intrigued by a figure just above the cited statement. That figure resembles a picture of mine I published here a few months ago. Despite the apparent similarity, however, the two methods have little in common.
Driven by curiosity, I looked on the web for anything more recent on the same subject and found this page that describes the very same "long range J" procedure. Does it mean that somebody has already filled the hole?
I have contacted the PR man at nucleomatica and he explained that the procedure is not commercial yet. It is a very simple data manipulation, there is no secret about it, but neither there is demand for it by the market. In conclusion, there is no hurry to make it available (to a distracted public).
Finally he gave me this picture, which is a world-exclusive of my blog:
Believe it or not, what you see is the same multiplet shown into the JMR figure (page 133, fig. 3d). Same molecule, same kind of experiment, another sample, another instrument.
The two experimental multiplets in black differ for the absence (top) or presence (bottom) of an anti-phase coupling. Both traces come from 2-D experiments and the resolution can never be enough to directly measure the size of the coupling.
The green circle hilights a slider. When you move the slider, the program adds an artificial coupling to the upper trace. The result is shown in red. When the red multiplet is like the black multiplet at the bottom we have succesfully simulated the missing coupling AND NOW WE KNOW HOW LARGE IT IS. That's what it's all about.
If you remember, I have gone much further with my unbeatable simulator, because it is able to extract all the couplings with a single experiments.
The strenght of my method is, alas, also its drawback: even when you are interested into a single J value, you are forced to measure them all. It can be very hard in cases like this.
Despite the external similarities the two methods are very different inside, serve two different purposes and can live side by side very well into the same program.

Faster Faster Faster

2010-06-29T09:24:00.011+02:00

Our machines, even when hitting an apparent performance peak, only run at one small fraction of their true potential speed. I feel that today's computers and their software are OK for routine spectra. I couldn't ask for more. Other spectra are quite large, however, and I must wait a few seconds during processing. Without going into the third dimension, consider these novel experiments to measure long range heteronuclear Js. Each row contains at least 4096 points. Quite likely we are going to see larger rows in the next few years. The time required to compute the FFT is in the order of the seconds. It would be great if we could half this time. The solution is public since 2008 and freely available. It must also be well-know, because I have initially found it on Wikipedia.
What they say, in practice, is that if you use the GPU (the graphic chip) instead of the CPU (the main brain of the computer)...

In this work we present a novel implementation of FFT on GeForce 8800GTX that achieves 144 Gflop/s that is nearly 3x faster than best rate achieved in the current vendor’s numerical libraries.

Another paper says:

We implemented our algorithms using the NVIDIA CUDA API and compared their performance with NVIDIA's CUFFT library and an optimized CPU-implementation (Intel's MKL) on a high-end quad-core CPU. On an NVIDIA GPU, we obtained performance of up to 300 GFlops, with typical performance improvements of 2--4x over CUFFT and 8--40x improvement over MKL for large sizes.

The source code (to be compiled), is available on another site. What upsets me is the ReadMe file:

Currently there are a few known performance issues (bug) that this sample has discovered in rumtime and code generation that are being actively fixed. Hence, for sizes >= 1024, performance is much below the expected peak for any particular size. However, we have internally verified that once these bugs are fixed, performance should be on par with expected peak. Note that these are bugs in OpenCL runtime/compiler and not in this sample.

Maybe they have already found the solution to this problem.
There's another issue, however: how long does it take to move the matrix from the main memory to the GPU and back? I presume that loading the columns will take much more time than loading the rows. In this case it is better to transpose the matrix between the two FFTs (just like when we use the CPU). Eventually, the bottleneck will the the transposition, not the FT.

Meet me in Florence this summer!

2010-05-28T09:02:00.003+02:00

Have you already decided which conference to attend this year? Is it perhaps the Euromar?
Of all the people I know, nobody will be attending this event. I have examined the list of sponsors and exhibitors and there will be no representative of the software industry.
They used to attend the past Euromars and were unhappy. I myself have no intention of registering...
A Worldwide Magnetic Resonance Conference ???
Why have I chosen this apparently ignored occasion? I will not attend any conference at all this year, but I will try to be in town during that week (from July 4 to 10), so this could be a unique opportunity to meet me in person.
How can you contact me? Try adding a comment to this post. Your comment will be submitted to my moderation and will not appear (automatically) in public. If you insert your email address, I will contact you. If you have submitted a poster, write here the title, so I can find you directly at the conference.
Weather info: July can be very hot in Florence, but the "PalaCongressi" that helds the conference is quite comfortable. It is a sort of huge underground bunker, shielded from the heat.

Street View

2010-04-12T21:43:00.003+02:00

I have discovered that my room is on Street View. The room from where I am writing now, from where I have written all my posts, where I have been working for the last 44 months is this one:
The next window at right leads to my bedroom.

Cold War

2010-03-27T09:46:00.009+01:00

Please find the similarities:

http://www.ansa.it/web/notizie/rubriche/english/2010/03/26/visualizza_new.html_1737522932.html

http://acdlabs.typepad.com/freenmrblog/

http://www.telegraph.co.uk/sport/football/leagues/premierleague/chelsea/7457982/Chelsea-v-Inter-Milan-as-it-happened.html

To tell the truth, I will always like Russian people because of Čajkovskij, Botvinnik, Tolstoj, Kramnik, Puškin, Šostakovič and I also like the Ucranians Lobanovs'kyj and Prokof'ev, the Latvian Tal', the Azerbaijani Kasparov... I even respect Putin more than Obama (without even mentioning our shameful and unpresentable Mr. B., of course). It is not in my nature to fight. Russians are free to do whatever they like with their own money. Sometime it looks obscene, sometime they find a Samuel Eto'o.

Two Promises

2010-03-12T14:10:00.003+01:00

I promised a review on the DOSY Toolbox and the program itself is a promise too. It has only arrived at version 0.8, which is an explicit declaration: it is not completed yet. What could be missing? From my personal point of view, the documentation is largely incomplete. I can easily find out by myself how to perform the basic NMR processing (FT, phase and baseline correction, correction of the frequency scale, and so on), because I have continuously been doing these operations for 25 years with countless different computers. I feel lost when doing the specific DOSY processing. The meaning of the buttons looks clear. I have also read a few papers describing the scopes and the internal details of each method, but I still miss the general picture.
The ideal solution for a user like me would be a set of test spectra with detailed step-by-step instructions on how to process them to get the best results and, for the lengthy calculations, the time required. In this way I would have a tool to test if the version I have installed is free of bug (and properly installed) and at the same time a collection of tutorials.
What makes the toolbox rather unusual is the language used to write it, which is not C++ or Java or Python, but MATLAB. The consequences are that many operations are a little harder than usual. Examples are: starting the program, opening and saving a file, selecting a region, understanding if the program is idle or busy. These nuisances are mitigated by the facts that the program:
1) is free;
2) is cross-platform;
3) is the only alternative I can find in this price range;
3) can import and export the spectrum at any processing stage, so you are still free to use your preferred program for generic manipulations.
The one thing you'd better get used, if you launch the program from a unix shell, to is to look frequently at the contents of this shell during the execution of the toolbox, because many important messages are reported there. They can signal a situation of error, or explain why a command can't be executed, or simply inform you about the current status of the program.
The main window contains all the buttons for all the available processing functions. In practice the space allocated for the controls is larger than the area containing the plot. The latter can show only one selected row of the experiment (after FT). After the DOSY processing a second window appears with a contour plot of the complete DOSY map. The new window contains additional controls, most of them containing the word "plot" into their titles.
Nowadays I have a very large monitor, yet I can only work with the windows at their maximum sizes. I am a little worried about what can happen if you install the program on a laptop, because when I make the windows smaller I can't read the numerical values anymore (the fields are scaled down proportionally to the window, while the text size remains large, so I can only see the bottom parts of the digits).

It seems that, up to this moment, I have described MATLAB more than the DOSY toolbox itself, right? For the reasons I have reported, I could only try the simplest algorithm (HR-DOSY, mono-exponential) and the results are really great. The components of the (difficult) test that comes with the program are resolved. It is a mixture of sucrose, isopentanol and n-propanol. It is the same mixture shown on Journal of Magnetic Resonance (DOI).
During the last two months I have exchanged hundreds of messages with the author. It has been a painful and continuously interrupted work, because we had different computers and, more importantly, I have no copy of MATLAB. Each of us also had the usual urgent chores to deal with in the same period. I must admit I have been boring and annoying, often asking questions I could have found an answer to by myself. This slow torture has come to an happy end when we have created and successfully tested a file format (called DOSY Toolbox ASCII) to exchange data with other NMR programs, both in input and in output. It's enough that the other program is scriptable, and that you can read/write text files with a script. If these conditions are met, you can de facto use the toolbox as an external module of your preferred traditional NMR program.
Apart from the happiness for this extremely useful achievement, I have been the witness of the dedication and the kindness of Mathias Nilsson. I will remember with joy this collaboration, despite the several frustrating moments. We never met in person, so I identify the name Nilsson with the interface of the program and not with the face of the man. It is rather strange, even for someone like me that spends whole days in front of a computer. When the main window of the DOSY toolbox appears on the monitor, I feel like I am visiting a new friend of mine.

Men at Work

2010-01-14T21:24:00.004+01:00

As soon as I began experimenting with the DOSY toolbox I was surprised to discover an unexpected hole, which is just a novel proof of my old theory on NMR imprinting.
If your first spectrometer is a Varian, you will become a certain kind of spectroscopist and a certain kind of programmer. If your first instrument is a Bruker, you will become a different spectroscopist and a different programmer.
If a brukerist programmer had written this toolbox, he would have imported the frequency domain spectrum and started from there. Mathias Nilsson is instead a Varianist and he imports the FID only. We talked about it and now he agrees with me on the importance of importing and exporting the data to and from as many programs as possible. For example, I might prefer using an external software for the preliminary processing (FT, phase and baseline correction), then the DOSY toolbox for the separation of components, eventually a third software (or the first one again) for printing, visualizing, creating slides, etc...
This is not really efficient, because in many real cases I probably want to try with different preliminary processing (e.g.: apply or remove a line broadening), and this is already easily done with the toolbox, but becomes cumbersome if I move data from an application to another at each stage. The principle is, however, to let the user choose whatever he prefers.
This kind of transfer is the less problematic one: the information is not to be stored, not to be transmitted, is consumed on the spot on the same machine that generates it. I and Mathias have already started collaborating on this and, if only we were better programmers, we had already finished by now, but this is not the case.
Unfortunately, we are equipped with two different brains, and it has a price: countless emails to explain each other what we need, what we can do, how we would solve a given problem. It's really a case where it takes more to explain a thing than to do it.
In practice, we have created a simple, highly readable, redundant file format that consists into a text file, like JCAMP-DX, but without compressions of any kind. At the same time, we are testing this format on the field. I am writing two scripts (the language is Lua) to export data from iNMR to the DOSY toolbox and to import data back again.
We have chosen this approach because I am the prototype of the average ignorant. If I am able to write these scripts for at least one external program, this can be categorized as an easy task, whichever other program you want to use in combination with the DOSY toolbox, the only requisite being that the program must be scriptable.
Now you know what I have been doing during these days and why the promised review is not ready yet. To tell the truth, I don't know why I should write a review in a case like this, where the source is open and the author is so collaborative. I mean: if I find something that I don't like, it's more productive to talk about it directly with Mathias Nillson than to spend a day to write a review.
Generally speaking, I don't believe in open source, I don't see how it might work. Pick any example of a moderately large project: how many people can safely modify it? Normally, it's only the original author. In practice, it makes little difference if the source is open or not.
In this particular case, the software is written with MATLAB, which I haven't, but it would be the same if it was written in a language I am familiar with.

To be continued...

Installing the DOSY toolbox on a Mac

2010-01-07T20:16:00.008+01:00

The DOSY toolbox is an open source program written by Dr. Mathias Nilsson that runs on Windows, Linux, Mac and on any other platform covered by MATLAB. I am going to review it next week, while today I am giving a few practical tips that I prefer to leave out of the review, for the sake of readability and tidiness.
I know that 14% of my readers have a Mac, and I have verified that the original installation instructions of the toolbox are inaccurate and unclear (for the average Mac user at least), so today I will simply explain how you can install the DOSY toolbox on your Mac.
Download the file called DOSYToolbox06_MAC_13May09_pkg from the address:
http://personalpages.manchester.ac.uk/staff/mathias.nilsson/software.htm
With a double click this archive generates a folder called: "DOSYToolbox06_MAC_13May09_pkg 2". This name is actually too long and useless, therefore I have shortened it into "DOSYToolbox06" and moved the folder inside my home directory. This is not strictly necessary but is a safe and sensible move. Inside the folder there is an installer called "MCRInstaller.dmg". It installs the runtime of MATLAB, which is necessary (unless you already own MATLAB itself). The difference is... technically speaking... to make it short... well the difference is $2,000 that you save if you install the runtime instead of buying matlab itself. Got it? A little slower but much cheaper.
The installer works like any other installer: you must always say "yes", you can't be wrong, eventually you will read it's all OK but you have no clue of what it has done and this is terribly bad because you absolutely need to know where the files have been installed, otherwise you can't run the DOSY toolbox at all. Fortunately I have discovered where the files have gone:
/Applications/MATLAB/MATLAB_Compiler_Runtime/v710
(this is valid, of course, for version 7.1 of the runtime).
The downloaded folder also contains a script called: "run_DOSYToolbox06_MAC.sh". This is the command that starts the program, and it needs an argument and this argument is the path to the matlab runtime that you have already installed. In other words, the canonical way to start the toolbox would be to type a command like this into the Terminal:
/path/to/run_DOSYToolbox06_MAC.sh /path/to/MATLAB_Compiler_Runtime/v710
for example:
/Users/your_name/DOSYToolbox06/run_DOSYToolbox06_MAC.sh /Applications/MATLAB/MATLAB_Compiler_Runtime/v710
This is highly impractical, but you can easily create a double-clickable shortcut:
- open the Automator application
- choose the template called "workflow"
- into the leftmost column, click on "Utilities"
- into the second column, double click on "Run Shell Script"
- from the pop-up menu "Shell" choose "/bin/bash"
- fill the main field with our command:
Run this workflow. If, in a few seconds, the DOSY toolbox window appears, it means that the workflow works. Quit the DOSY toolbox and save the workflow. Be careful and select the proper File Format: it should be "Application" and not "Workflow".
Finally you have created a double-clickable application (you can paste a different icon)
and you can forget Terminal, shell, bash and the likes...
At the time of this writing, though, it seems that the DOSY toolbox is fully functional only if launched from a shell. It is a puzzling and unwelcome incident, I hope it's going to find a solution soon.
Has anybody the compiler for the Mac? Would this person be so kind to compile version 0.7 for the rest of us Mac users? "Open source" means that some times you should also give, not always take.

Jake Bundy

2009-12-03T07:46:00.003+01:00

What's your position and where are you working?
For the past 5 years I have worked as a lecturer in Biological Chemistry in the section of Biomolecular Medicine at Imperial College London.

Where have you been working before?
Before this, I post-doc’ed at Cambridge; before that, UC Davis; and before that, for my first post-doc, at Imperial College again.

Briefly describe your research.
I am interested in metabolism in invertebrate and microbial species, and how this is involved in several different biological questions. Some of the projects I currently work on include microbial virulence and pathogenesis; how metabolism is affected by problems with recombinant protein folding in the bioprocessing yeast Pichia pastoris; and using earthworms as biomonitors of environmental pollution.

What do you use NMR for?
Together with mass spectrometry, I use NMR for metabolite profiling, as part of the technology for metabolomic studies. Although it’s generally less sensitive than mass spec, NMR still has a very useful role – as a near-universal and robust detector, it can give a quick and information-rich spectral profile. Most of the work we do, we just use 1D NMR for profiling; particularly useful for studies where you want to process as many samples as possible. However there are also other cases where more in-depth NMR experiments are needed, for example for isotopomer analysis to investigate metabolic fluxes; or to assign novel metabolites (essentially a natural products chemistry problem).

Which NMR software are you using?
XWIN-NMR and Topspin for data acquisition; iNMR for all NMR processing. I also use Chenomx NMR Suite for helping assign and quantitate metabolites in NMR spectra.

Which other NMR software have you used in the past?
I’ve also used VNMR and ACDLabs NMR software, and MestreC (before it was released as a commercial product).

How do you rate iNMR?
iNMR is not only my favourite NMR software for Mac OS (I’m not sure how many competitors there are at the moment), but it’s easily my favourite NMR software full stop. It’s one of a handful of Mac-only packages that I use all the time as part of my regular working day (others include Papers, Aabel, and Bookends). Features that I particularly like include the Overlay Manager (which makes it by far the quickest and easiest NMR software to use for comparing multiple spectra, in my opinion), and also the overall simplicity of using it to produce quality spectral images that can go straight into a paper or presentation without having to use multiple machines or virtualization. I admit I wasn’t really bothered by lack of anti-aliasing on spectra before using iNMR, but now I’m used to it, I do find it genuinely annoys me when looking at spectra in Topspin, say – it’s distinctly harder to see fine detail without zooming in. It’s also elegant and quick – not essential properties for software, but makes it more enjoyable to use on a regular basis.

Is it enough for your needs?
Well, it’s certainly enough for my needs in the sense that all of the spectra that I acquire are processed with iNMR – so in one sense, yes, almost by definition. It’s not 100% perfect though, there are still some small issues that could be ironed out in future releases – and as I’ve already said, I do use Chenomx software for some complementary uses which iNMR isn’t primarily designed for. I definitely see it as a crucial part of my workflow for the foreseeable future though, and expect it will keep improving (although by now it’s a relatively mature product).

Hands on 3-D Processing

2009-12-02T09:12:00.005+01:00

A measure of the computing power available today with a desktop computer is the possibility of processing huge spectra in real time. For example: is it possible to correct the phase of a 3-D matrix interactively, in real time? The answer is: yes and you don't even have to employ more than a single core nor to buy an high-end graphic card. When I mean interactive processing I mean that:
- you see a graphic representation of the matrix at each processing stage.
- you can play with it, for example change a parameter just to see the effect it has on the matrix.
It is always necessary to know and understand the mathematical rules that govern NMR processing. The more you know them the more you enjoy their visual representations. The more you play with the graphics, the more you understand the maths behind. The two things go together.
You can find a self-teaching course on basic 3-D processing on the iNMR web site. There is no theory, only a lot of examples and a good measure of practical tips.

Open Source NMR freeware

2009-11-26T17:40:00.012+01:00

Most of the readers arrive here using Google, without knowing me and my blog. Usually they get very angry because they arrive... on the trapping post I wrote 3 years ago! I want to do something to keep them glad...
So you want "open source" stuff? Do you know what it really means? Are you ready to compile, test, debug it and add a graphic interface to it?
Just because you asked for it, here is a list of available projects. If you know other links, add them into a comment.

CCPN
NPK
matNMR
ProSpectND
Connjur
Newton-NMR
nmrproc
DOSY Toolbox
list of 30+ projects

Tips

2009-11-16T16:55:00.004+01:00

It rarely happens to find valuable tips about processing on the web. When it happens, it's probably not enough to bookmark the page (it may disappear), copying it is a better idea. Here is the link:
http://spin.niddk.nih.gov/NMRPipe/embo/
When you arrive there, scroll down until you find the chapter Some General Tips About Spectral Processing.
The focus is on multi-dimensional processing with NMRPipe, but a few concepts are generally applicable indeed.
The brief discussion about first-point pre-multiplication is something to bear in mind. You can also find clearly expressed opinions on zero-filling, linear prediction and baseline correction.

Shadow

2009-11-14T23:06:00.003+01:00

Here is a picture I have found on the internet. I have never been in this place, if this is what you want to hear. Suppose, instead, that I live just in front of this tower and tomorrow I take a photo of it immediately after dawn, then another photo after 25 hours and so on for a week, with regular intervals of 25h between pictures. Eventually I print all the pictures in order and ask you:
"This pictures have been taken in this exact order at regular intervals. Can you tell me how long the intervals were?".
Somebody will answer: "1 hour" and the answer would be partially correct. A more correct answer would be 1 + 24 n hours, with n = 0, 1, 2, 3….
The world of FT-NMR is similar. The difference is that the regular interval between consecutive observation is known in advance while the speed of the hands and of the shadow is unknown. In other words, it is the opposite of my example of the tower.
The equivalent of a day, in the world of FT-NMR, is very very short and is called dwell time. It forms a Fourier pair, so to speak, with the spectral width. The spectroscopist sets the former, the latter is a mere mathematical consequence.
The ignorant says that the spectral width is the distance from the first point of the spectrum to the last one. This statement is as incorrect as saying that a day is made of 23 hours! The spectral width, actually, is the distance from the first point to the first point after the last one!
Let's verify it with a numerical example. Let's say we have a spectrum of 1024 points, separated by 2 Hz. If we zero-fill the FID up to 2048 points, the distance should decreases to 1 Hz. The spectral width is 2048 Hz in both cases, and this is OK. If you measure it the other way, then you have a spectral width of 2046 Hz that grows up to 2047 Hz. This is absurd, because the value is fixed at acquisition time and can't be changed by processing.
The relation is Spectral_width = 1 / Dwell_time.
Many books report another formula: Spectral_width = 1 / (2 * Dwell_time). This assumes an instrument without quadrature detection, in other words with a single detector. I have never used such an instrument.
To be exact, my whole description is dated, because today's instruments work in oversampling, the actual dwell times are shorter than what the spectroscopist sets (4 or 8 times the value reported), the FID that we see is already the result of a couple of FT (first direct, then inverse), et cetera. Seems complicated but it is not. We see what we need to see, the complications are hidden.
The important concept to remember is that the components of a digital spectrum, even if they are called "points", should be treated and conceptualized as tiles. There is no room in between. This idea will help you when you'll try to save a spectrum as a table of intensity vs. frequency. You will get the correct frequency value of each "point".

Trigonometry for Dummies

2009-10-21T16:18:00.004+02:00

This is a doublet of doublets. If you move one doublet towards the other, for example by increasing the smaller J, the central peaks will coalesce into a single peak of double intensity (the algebraic sum of the central peaks).

A triplet is a special case of doublet of doublets (the Js are identical).

Another doublet of doublets. This time the smaller coupling is anti-phase.
If we increase the small J, we'll see another algebraic addition.

This is a triplet. Right?

NMR for Dummies

2009-10-20T18:33:00.004+02:00

Here is where the real fun begins. I was not joking with my previous post. You can really do these things at home. The simple instructions are available on another site, and they are illustrated. After completing the tutorial (it takes 5 minutes in total) a working application will remain in your hard disc, and you will be free to apply the same treatment to your own spectra.
iNMR has always been available as a free download (since 2005). Access is unlimited and the program never expires. Other specialized simulation modules are included to cover most of the needs of an advanced spectroscopist (the few exceptions are motivated by the fact that other needs were already covered by existing freeware).
My blog is three years old. Half of the comments have been dedicated to a single post, which is clearly (and purposely) the least representative of the blog. When people find something useful (and this is certainly the case today) and free, they don't comment.
If you are not going to comment, I will comment by myself.
COMMENT: although it's a serious work, although it contains a lot of maths (and maybe just for this reason) it's funny too.

Try this at home

2009-10-16T22:25:00.003+02:00

Returning to the DQF-COSY of taxole, I have found this challenge:

I couldn't tell which kind of multiplet it was. I have extracted the section corresponding to the red line and moved it into my novel simulator. Then I have introduced 3 couplings and pushed the "Fit" button.

That's all. The goodness of the fit is convincing. It is a doublet of doublets of doublets and the Js are: 14.7, 6.4 and 9.9 Hz. The latter corresponds to an antiphase coupling. Not only I know which kind of multiplet it is, I have also measured the Js!
You might feel it's funny, I find it amazing, perhaps somebody will say it is useful. "The coupling constants were extracted from the DQF-COSY by the blogger's simulator".

Digitization

2009-10-16T09:53:00.005+02:00

I am continuing my explorations on board of my new multiplet simulator. It has been easy to simulate an asymmetric doublet. Here the asymmetry is only apparent and is due to the limited digitization.

As explained yesterday, the black line belongs to an experimental 2-D spectrum (today I have chosen a TOCSY), the red line is a theoretical doublet acquired and processed under the same conditions.
My simulator allows me to change the frequency by dragging the blue label at the bottom.

In this way the coupling remains constant. It turns out that my spectrum was a middle-range case. With a slight increase of the chemical shift I can obtain a symmetric doublet, or even a singlet!

Natural Products

2009-10-15T22:58:00.005+02:00

A reader asked me: "What is the shape of a 2-D peak?" and my answer was: "Exponential! (in time domain)". This is all you need to know, I think. The picture should help, as always. If you are reading this blog, it means that you have something like a computer. Even the iPhone is a computer (you can run programs on it) and can display my blog. I suspect, however, that you have a better computer, like I do.
You can use your computer to run simulations and more: you can ask it to fit a model spectrum to an experimental spectrum. This is what I have done. The black line is a (fragment of a projection of a) DQF-COSY. The red line is a model generated by the computer. All I said was:
1) the signal has an exponential decay;
2) it's an anti-phase doublet;
3) here is an experimental spectrum and here are its processing parameters;
4) please fit the model to my spectrum!
The goal was a better estimate of the coupling constant. The distance between the two peaks is 7.3 Hz, while the model contains a J = 8.88 Hz. My impression is that the model is more accurate by 1.6 Hz.
The calculation involved is very little (the whole process was faster than the blinking of an eye). The job of programming was more time-consuming. If you don't like spending time, find someone else that can do the job for you. They ask 0.99$ (0.79€) for an application (for the iPhone). Calculating the Js with more accuracy is certainly worth the price.
There is no secret, no new theory, should you need more explanations please ask.
If you want to know more, I can try to explain what was behind the question of the reader. It's not necessary, it's an un-necessary complication, but it's also well-know theory. If you submit to FT a function (e.g.: an exponential decay) you get a different function (in the example, a Lorentzian). They form a "Fourier pair". Being that most 2-D spectra are weighted with a squared cosine-bell my friend probably wanted to know which other function it makes a pair with.
Now you can realize that it is more a theoretical question than a practical one: if the final goal is to simulate an NMR spectrum, it's enough to know that the signal decays exponentially (and everybody knows it).
The program shown by the picture can simulate a multiplet (with 3 different J values). The multiplicities that can be chosen from the menus are:
but it's trivial to extent the menu and handle quintets and so on. Even without further modifications, you can already simulate a quartet of triplets of doublets."R" is the inverse of the transversal relaxation time. This kind of program can't simulate second-order spectra, but nothing prevents you from writing a program that simulates second-order spectra in time domain.
What happens when the user pushes the "Fit" button? The computer runs a Levenberg-Marquardt optimization, based on first derivatives. How have I found the derivatives without knowing the function that describes a peak? You know: life is simpler when you have a computer...

interviews

2009-09-28T21:54:00.007+02:00

Here is the complete list of my interviews:
Kevin Theisen
Stefano Antoniutti
Arthur Roberts
Antonio Randazzo
Bernhard Jaun
Daniel J. Weix
Jacek Stawinski
Stefano Ciurli
Jake Bundy
If you like to be interviewed, please send both questions and answers via email (or as a comment here).
The next Euromar conference will be held in Florence from July 4 to July 9 2010. I have no intention to attend but I want to be there. If you plan to attend, contact me via email or phone and let's arrange a meeting. I would be delighted to know you in person.

Stefano Ciurli

2009-08-18T11:44:00.002+02:00

Q. Please introduce yourself to the readers of the blog.
A. I am a full professor of general and inorganic chemistry at the University of Bologna (Italy).
I received my M.Sc. from the University of Pisa with a thesis done at Columbia University (NY), received my Ph.D. in chemistry from Harvard University, and done a post-doctoral work at the NMR center in Florence.
I work on the structural biology and biological chemistry of metalloproteins. After several years of work on electron transfer proteins containing Fe and Cu, I have been spending the last ten years working on the biochemistry of nickel.
I use NMR mainly for processing and visualization of 1D, 2D, and 3D NMR spectra of proteins prior to go on and use other programs for more dedicated tasks of spectral signal assignment.

Q. Which NMR software are you using?
A. The first choice is iNMR, for its amazing speed and flexibility, especially for 3D spectra. Easy to use and great performance. I use MestreNova for teaching purposes (mainly because of lack of Mac computers among the students, otherwise that would be perfect, considering the simulation modules etc.), and NMRPipe for other different tasks more dedicated to protein NMR.

Q. Is iNMR enough for your needs?
A. I like to use both iNMR and NMRPipe, having iNMR as the first choice and leaving NMRPipe for more specialized work.

QR-DOSY

2009-07-24T16:41:00.007+02:00

At the beginning of the month we saw that there are cases where the diffusion coefficients can be measured with the same mathematical tools used to measure relaxation. We have seen DOSY spectra of pure compounds where each signal decays as a pure exponential. Even a mixture can behave in the same way, if the signals don't overlap. In summary, calculating the diffusion coefficients is often easy.
What I was curious to discover was: is it possible to recalculate the components of a mixture if the diffusion coeffients are known? From a pure mathematical point of view the answer was already: "yes", but I wanted to verify it in practice.
As far as I know, something like: "QR-DOSY" has never been mentioned. So many DOSY methods already exist and I don't mind to increase the Babel with yet another acronym. Do you?

THEORY
If we know the diffusion coefficient D(j) we can calculate that the NMR signal in the spectrum i will be proportional to a value A(i,j) = exp(-D(j)F(i)) where F is a function of the gyromagnetic ratio, the gradient strength, the diffusion delay, etc.. but not a function of the chemical shift nor of the diffusion coefficient.
For each column of the DOSY spectrum we have a system of equations: Ax = b.
x = intensity of the spectrum of the pure compounds at the chemical shift that coresponds to the given column.
b = intensity of the DOSY along the same column.
We know A and b, therefore we can calculate x. A is the same for all the columns and this is a great advantage. We can apply a well known decomposition: Rx = Qb.
Calculating Q and R from A takes time, but we need to do it only once. Then then computer can swiftly solve all the systems in the form Rx = Qb.

METHODS
Obviously, we will find that some values of the x will be negative. In such a case, we can choose a subset of A (omitting the component with negative intensity) and solve the reduced problem. This simplifying mechanism can be applied iteratively, even when the value of x is positive yet small.

RESULTS

This is the same old spectrum we are familiar with, processed with the new QR-DOSY.

DISCUSSION
Two components are completely separated. The third component is not, although at this point it becomes easy to recognize its peaks. Other cases I have studied yield similar results, maybe not as nice. Advantages of the QR-DOSY method:
- easy to understand;
- easy to use WITH THE ASSISTANCE of a software for the book-keeping activity (like measuring the diffusion coefficients);
- fast;
- the user can play with a few parameters, trying to improve the results;
- the final spectra are clean from artifacts.
Cons:
- not all the components are always resolved;
- it's a problem if two diffusion coefficients are similar (of course the program itself can easily detect this circumstance).

Jacek Stawinski

2009-07-14T13:03:00.006+02:00

Q. What's your position and where are you working?
A. I am Professor of Organic Chemistry at Stockholm University, Stockholm, Sweden, and at the Institute of Bioorganic Chemistry, Polish Academy of Science, Poznan, Poland.
Q. Where have you been working before?
A. Adam Mickiewicz University, Poznan, Poland, and Institute of Organic Chemistry, Polish Academy of Science, Warsaw, Poland
Q. Briefly describe your research.
A. My field of expertise is bioorganic phosphorus chemistry, nucleic acids chemistry, and lipid and phospholipid chemistry (http://www.organ.su.se/js).
Q. What do you use NMR for?
A. Characterization of synthetic intermediates, structure determination, spin simulations, NMR dynamic processes.
Q. Which NMR software are you using now?
iNMR, the latest version.
Q. Which other NMR software have you used in the past?
A. Swan NMR, Topspin, MestreC, MNOVA
Q. How do you rate iNMR?
A. iNMR is superior, by far, to all NMR software I have used. It provides a powerful, intuitive and professional environment for processing and plotting NMR data. The software is very fast, has scripting ability, and a lot of keyboard shortcuts and useful extras. No doubts, iNMR is right on the cutting edge on the NMR processing software development. Due to simple interface, iNMR is a user friendly application, but it hides a lot of powerful tools for advanced tasks. And last, but not least, the support from the programmer is prompt, competent, and friendly.
Q. Is it enough for your needs?
A. I have never faced a situation when iNMR could not do, what other software can. For me, it is the tool of choice for dynamic NMR. Also very useful during teaching NMR courses.

Bull's-Eyes

2009-07-09T18:20:00.008+02:00

Here are some caffeine peaks (below) and EthoxyEthanol peaks (above). The display is DOSY-like, yet the numerical treatment is a simpler and faster mono-exponential fit. Each column has been processed independently from the rest, and each column yields a different result:

Now let's apply a Whittaker Smoother, with a small value of lambda (100), along each ROW:

or a big lambda (500):

or a huge value (8000):

The smoother averages the results obtained from the different columns. The peaks are perfectly aligned.

Wandering

2009-07-09T17:00:00.008+02:00

Jean Marc Nuzillard writes:

The example that is provided by Carlos in his blog would benefit from a processing trick I use when there is no multiplet superimposition:
I simply integrate the multiplets that are recorded at different gradient intensities and I perform a monoexponential fit on integral values.
I suspect the noise on integral values is lower than the one in individual columns of the 1D spectra set, thus making D values more accurate.
Bye bye butterflies. This idea is absolutely trivial but maybe it would be interesting
to implement it.

I agree with the idea. Actually I had arrived at the same conclusion for a different reason. Look at this spectrum (a DOSY after FT):
The signal/noise ratio is low yet acceptable, the compound is pure, the decay mono-exponential. No concern about phase and baseline. Alas, this peak is too nasty for my tastes. The frequency is not constant over time. The "trivial" trick by Jean-Marc should work. I give my preference to binning, because the output of binning is not a numerical table (like with integration) but a new spectrum, so the same NMR program can be used for the subsequent exponential fit.
Before Carlos corrects me, let me stress a few details. We have processed the same experiment with two different algorithms. I got the butterflies and I am not proud of it. Carlos' pictures are a little smaller and cannot be compared:
(taken from his blog). Anyway, we are really confusing the matter here. From what I understand, the purpose of Carlos was to show how Bayesian DOSY can effectively separate the components of a mixture. I can't express any opinion, because as I said I only have two experiments to work with. In both cases there is no superposition of peaks, therefore there is nothing to separate. I normally like simple examples like these, yet I acknowledge they are not enough.
Today I could repeat the same processing of Carlos, because he himself has very kindly given me both the raw data and the software. But 1) I am not terribly interested into this comparison 2) He doesn't give me these things for free for me to criticize him 3) If I really want to do such a thing I'll post a comment directly on his blog.
Now let's go on: ho to make the butterflies go away? The next post shows how to transform a butterfly into bull's-eyes.

Pictures

2009-07-09T16:27:00.004+02:00

In my fourth year of blogging I have started publishing pictures of spectra. I like my pictures, yet this is not the point. I don't want to convince you that my pictures are beautiful. I want to convince you that I am a spectroscopist and not a programmer.
The programmers have always stated that "in the near future" it will be possible to obtain a completely automatic analysis: from the sample directly to the response (meaning a chemical formula or a list of values), by-passing the plotted spectrum. I have found the same concept and expression "near future", scattered in the literature of all the decades, from the 60s onward.
I really believe it: someday in the future we'll arrive at the completely automatic analysis.
Being that, at this writing time, I am working as a programmer and not as a spectroscopist, I should adhere to this belief and be happy. It happens, instead, that I always think like a spectroscopist scared of remaining unemployed. I really hate to design and write programs for automatic processing and reporting. I like creating programs to display the spectra.
Here comes the difference between "diffusion" and "DOSY". The mere idea of DOSY is to make a troble-free program: push this button and you'll have everything, the diffusion coefficients and the individual components of the mixture. This is what I have understood up to now. In my whole life I have only worked with 2 DOSY experiments, which have not been carried out by me. I have already shown the first one and today I am going to show the second one (please wait a few minutes..).

Ghost of a Butterfly

2009-07-04T17:11:00.004+02:00

Sometimes the butterfly disappears when the picture is scaled down, like into this web page. Click it!

Butterflies

2009-07-04T11:10:00.005+02:00

Carlos kindly gave me a copy of the DOSY spectrum he showed on his blog last year.
I am experimenting alternative processing routes. Here is a detail of the caffeine peaks, after applying the rudest (and probably simplest) treatment. The decays have been linearized (by taking the logarithm). The slope of the line is proportional to the diffusion coefficient. The final results are reported as a normal DOSY spectrum.
Click on the thumbnail to see the image at natural scale.

There is less signal/noise in the tails of the peaks, obviously, therefore the error increases: graphically we see the wings of a butterfly.
Being that it's impossible to correct the phase perfectly, some butterflies are asymmetric.

Daniel J. Weix

2009-06-12T10:38:00.005+02:00

Q. What's your position and where are you working?
A. Assistant Professor, University of Rochester.
Q. Briefly describe your research.
A. Synthetic organic methodology, especially catalysis.
Q. What do you use NMR for?
A. Assaying purity of synthesized materials and identification of products (both organic and inorganic).
Q. Which NMR software are you using?
A. We use iNMR, latest version.
Q. Which other NMR software have you used in the past?
A. I have used MestreC, Bruker XWIN-PLOT, NUTS, MacNUTS (new version), and MestreNOVA.
Q. How do you rate iNMR?
A. I like iNMR better than all of the other software that I have used. The workflow is good and I'm already almost as fast as I was under NUTS (the fastest software of those mentioned above). It seems superior to MestreNOVA, with better keyboard shortcuts (MestreNOVA involved a lot of clicking) and a better user interface. New features are discoverable vs. having to dig into the manual. Importantly, my students like the software very much and they can be taught to use it in very short order.
Q. Is it enough for your needs?
A. More important to me than a list of features is the usability of the program. What good are features that sound nice, but are buggy or so round-about to use that they take more time than the result is worth? Can I get the results I need easily? Can we produce publication quality images? Is it fast? Two features that are often overlooked are the quality of the manual and the customer service of the company behind the software. In these areas iNMR excels. For us, iNMR is more than adequate!

Bernhard Jaun

2009-06-10T17:05:00.003+02:00

Q. What's your position and where are you working?
A. Professor in Organic Chemistry at ETH Zurich (Swiss Federal Institute of Technology). Head of the NMR labs.

Q. Where have you been working before?
A. Columbia University New York, then ETH Zurich for the last 29 years.

Q. Briefly describe your research.
A. Physical organic chemistry, in particular its application to biological questions.

Q. What do you use NMR for?
A. I am the head of NMR operations in an institute with more than 200 scientists. Most of them use NMR. The applications go from 3D solution structures of biopolymers to physical organic applications of NMR (such as host guest complexation, dynamic processes, thermodynamics and kinetics) to structure elucidation of novel natural compounds and (for the majority) characterization of synthetic intermediates.

Q. Which NMR software are you using now?
A. Topspin, VNMR, Mnova, iNMR, plus specialized software for 3D solution structure calculation such as XPLOR, SPARKY, CNS, DYANA, MARDIGRAS etc.
We have quite a large percentage of people using Macs (ca. 50%) in our institute.

Q. Which other NMR software have you used in the past?
A. SwaNMR for Mac OS9 and most of the software used for NMR over the last thirty years.

Q. How do you rate iNMR?
A. iNMR is a good and fast program which can do practically all of the work an NMR spectroscopist will ever need. Its strength lies in the flexibility and its more mathematical/physical approach to NMR such as beeing able to do all kinds of transforms, simulating dynamic exchange problems, analyzing spin systems etc. Clearly, the program is written by an NMR specialist for NMR spectroscopists.

The "weaknesses" are in the fact that iNMR is not as easy to learn as some other programs by people who do not know much about NMR and are only interested in getting "nice" plots and listings for their synthetic papers etc. Compared to other programs, iNMR uses only a fraction of icons and palettes but insiders can work very efficiently because of all the keyboard shortcuts and the scripting ability. The current versions still have a few bugs or inconveniences in the field of graphics, e.g. when it comes to plot 1D spectra at the border of 2Ds etc., axis adjustments when changing the window size etc. [Editor's note: this interview refers to the old version 3; the current version 4, made with the collaboration of prof. Jaun himself, solved all the above mentioned problems].

Maybe the best point about iNMR is that according to my experience, there is no other software where the programmer is so fast in responding to either bug reports or demands for new features. So, if I still sometimes get angry about a bug (or something I want to do but cant find out how) in iNMR, it is usually my own fault because I did'nt take the time to write to the author about it. If I had contacted the author, the problem would long be solved by now. Compare that to MS Office or the spectrometer manufacturers NMR programs!

Q. Is it enough for your needs?
A. We NMR spectroscopists have to accept that for a majority of the scientists in todays chemistry/biology research, NMR is a black box that's neverless - and "unfortunately"- absolutely necessary. They like to use software that seems to generate listings and plots without requiring knowledge by the operator. We still try to teach our own students about the innards of NMR-experiments. But the reality is that black-box attitude and the trend for automation are increasing all the time.

I think that in my domain of responsability with 200 scientists using NMR, it might actually be a good idea to start to write some scripts for iNMR that do all the standard processing for routine spectra. This might make iNMR more poular for all those, who are not really interested in the inner workings and just need a nice plot to show to their supervisor and who now rather use MNOVA for Mac because they think it is easier to use.

Also, I think that iNMR could become the tool of choice for all special and more physical things that can be done by NMR. In particular, there is only a very limited number of still living programs that can iteratively fit dynamic spectra from complicated exchanging spin systems. Other things I could think of are extracting coupling constants from 2Ds by simulation of cross peaks, analysing relaxation data, measuring residual dipolar couplings from heteronuclear 2D spectra, diffusion etc. etc.

Antonio Randazzo

2009-06-09T22:21:00.002+02:00

Q. What's your position and where are you working?
A. I am an Associate Professor at the Faculty of Pharmacy - University of Naples "Federico II"- Italy

Q. Where have you been working before?
A. I have worked also at The Scripps Research Institute (San Diego - California - USA) and at the Vanderbilt University (Nashville - Tennessee - USA)

Q. Briefly describe your research.
A. I have worked in the field of Bioactive Natural Product. I was in charge of the isolation and structural elucidation of new secondary metabolites from marine organisms. The characterization of the new compounds has been accomplished mainly by NMR. Then I moved to the structural study of protein by NMR. Currently I study unusual structures of DNA. In particular I study the structure of modified DNA quadruplex structures....always by means of NMR. I had the occasion to use NMR also in the field of food science.

Q. Which NMR software are you using now?
A. Currently I am using iNMR on two different machines: an iMAC and a brand new MAC PRO both running Leopard OS and both equipped with two monitors. I find really cool to display 2-3-4 spectra distributed between the two screens and using the recently developed "global cross" feature to display a synchronized cursor simultaneously in all spectra. In this way the assignment of whatever molecule become very simple even in the case of complex and overlapped spectra.

Q. Which other NMR software have you used in the past?
A. I have used many NMR softwares. However, I have used extensively Xeasy and Felix (Accelrys, San Diego USA).

Q. How do you rate iNMR?
A. Top score!

Q. Is it enough for your needs?
A. I find it an EXCELLENT software. I am impressed on the very high quality processing features and the very easy way to use it. It is fast and very user friendly. It satisfies completely all my needs and it is also affordable. Furthermore, It is great in commenting the spectra in order to get a nice pictures for scientific work or didactics. Moreover, the after sale assistance to the software is absolutely incomparable with other softwares. Each improvement I have asked for the software, it has been realized in hours!!!! The assistance is the best ever. I have not found anything like the iNMR assistance before in all my carrier. I definitively give to iNMR my strongest recommendation.

Arthur Roberts

2009-06-08T23:59:00.004+02:00

Q. Please introduce yourself to the readers of the NMR software blog.
A. I am a project scientist at the School of Pharmacy at the University of California San Diego (UCSD). I was hired to bring some novel NMR technology that I developed at the University of Washington to UCSD.
I worked as a postdoctoral fellow at the Department of Medicinal Chemistry at the University of Washington and at Washington State University. I started my career as an EPR spectroscopist, where we built instruments. I have been doing NMR, since 2003.
Currently I study the process of drug metabolism, which happens to be the main road block for drug development. We hope that our research will lead to drugs of higher efficacy and fewer side effects. We are developing NMR technology that will allow us to rapidly determine drug bound structures and will speed drug development. We have developed a variety of NMR pulse programs for this purpose.
We do Paramagnetic protein NMR. We also do NMR simulations and write NMR pulse programs.

Q. Which NMR software are you using now?
A. Topspin 2.1 and iNMR 3.15.

Q. Which other NMR software have you used in the past?
A. VNMRJ, Spinworks, Sparky, NMRpipe, MestreC, xwinnmr, and MestreNova

Q. How do you rate iNMR?
A. In terms of NMR software, it is the best in terms of ease of use and power.

iNMR
It can process 1D, 2D, and 3D. Easy to use and powerful. It can read multiple formats and can convert files to ascii. The graphics are also very nice. No apparent bugs.
Topspin
It can process 1D, 2D, and 3D. Also powerful, but not very easy to use. I need my data converted to ascii for analysis with other programs and I could not find a way to do it with this software. It can only read Bruker formats.
Mestre-C
It can process 1D and 2D data. Powerful and easy to use, but a little buggy. For 2D, the conversion to ascii is not ideal.
NMRpipe
It can process 1D and 2D data. Not as powerful as the above programs and very clumsy to use. No easy way to convert data to ascii. It is also very slow.
MestreNova
It can process at least 1D and 2D. Powerful and easy to use, but slow, very slow. I found no easy way to convert my 2D spectra to ascii. Also, several useful features were removed from MestreC for this version.
VNMRJ
It can process 1D and 2D. Not as good as Topspin, but equally difficult. This software can not convert to ascii or read other file formats.
Spinworks
It can process 1D and 2D. It is fairly easy to use, but not as powerful as the software above. It is also quite buggy.

This is how I rate all the software and I tested a lot of NMR software:
iNMR > Topspin > Mestre-C > xwinnmr > MestreNova > Spinworks > Sparky > NMRpipe

Q. Is iNMR enough for your needs?
A. Yes, it does everything that I need including processing 3D data sets and it does it fast. It allows me to read files that I produced at the University of Washington on a Varian Unity Inova and the Bruker Avance III at the University of California San Diego. It allows me to convert files to ascii, so that I can do singular value decomposition of it with a scientific analysis program that we use. It produces publication-quality graphics. It is also very easy to use, so I don't need to spend a lot of time training graduate students or other postdocs on how to use it. I also didn't have to spend a lot of time learning it myself. I can't imagine a lab without it.

Stefano Antoniutti

2009-06-08T10:09:00.005+02:00

Q. Please introduce yourself to the readers of the NMR software blog.
A. My position is Associate Professor in General and Inorganic Chemistry since year 2000 at the Dept. of Chemistry, Università di Venezia Ca' Foscari, Italy. I am responsible for Dept. NMR instrumentation and services since Year 1992. I entered the Department in 1983 as a researcher. Since 1983 I have my name in more than 80 scientific papers on ISI classified journals in the field.
My research area is in the field of Inorganic and Organometallic transition metal complexes. The research group I belong to is involved mainly in synthesis and characterization of new complexes.
NMR is the main way of characterization of our new compounds. I began using permanent magnet-pen plotter-1H CW instruments in the early '80s; moved to monodimensional FT NMR in the '80s; today use of multidimensional, multinuclear NMR (1H, 31P, 13C, 15N, 119Sn etc) is my daily routine.
Since 1995 in our Dept. we separated acquisition of spectra from spectral data elaboration, exporting NMR spectra from our Bruker AC instrument to our personal computers, mainly Macintosh machines.
Luckily, after the demise of Bruker from the Mac software area, we discovered the SwaN-MR package (free !!!) which became quickly the workhorse of our daily NMR duties. Today, our Mac users have switched to iNMR, the Wintel users to MNova.

Q. Which other NMR software have you used?
A. Apart from the built-in software of our instruments (Varian and Bruker NMRs) we began in the '90 with WINNMR, a Bruker software written for both PCs and Macs, in two versions. Some day, Buker decided not to develop any more the Mac version, concentrating their efforts only on the PC side. More or less in the same period I discovered SwaN-MR and Giuseppe Balacco, starting a brand new era for our work: you should remember that Bruker software was very expensive (any license was about €500, in those years, and used a hardware key!), and sadly far from complete, at least initially. For example, only 1H and 13C nuclei were supposed to be used; only after some request to the developers' team it was possible to obtain an improved version, really multinuclear!
In a sense, SwaN-MR (which I still use sometime today on a G5 machine) was a complete breakthrough, having a revolutionary impact on our work!
Giuseppe was very cooperative, so everytime some bug was evident, I obtained in a short time (from hours to minutes !) an improved and corrected version. He introduced the simulation routine on my request, and tailored it exactly as a chemist, in my opinion, needed it, not like a software engineer thinks a chemist should use it: a real dream. The same approach he maintained, and improved, when he wrote iNMR.
I find the latter a very high quality software, almost unbeatable for his price/performance ratio. Surely it can be that a more complete software package exists, but at least at ten or more times the price! (If I remember, current Bruker PC software is in the Thousands € range for a license, and only or PC or Linux boxes).

Q. Is iNMR enough for your needs?
A. As usual, you use only a small fraction of the opportunities offered by a software; even after having been host of Giuseppe for a couple of times in the last years, to make him to teach us how to use the program, I think that an usage of more than 20% of the opportunity it offers (and are continuously improved) is to be considered unrealistc. Everyday I discover something new, and with more or less the same frequency, new options are offered by new versions of the software, which Giuseppe considers really a commitment to do.
Anyway, iNMR never failed to offer me a solution to any need in my research work, and I always cite it in my papers, hoping to extend the number of its user. I evaluated other software, but none fulfilled my needs like iNMR (and, in the times of Mac OS 7/8/9, SwaN-MR). For instance, its baseline correction routine in bidimensional spectra is outstanding, far better in results than the Winnmr one, letting you extract correlations you would have missed otherwise.

Testing the Razors

2009-05-31T18:00:00.011+02:00

As I wrote initially, I like the razors because they are easy to learn and use.
I have simulated two molecules only, because they are the standard (minimal) test I perform on simulation software. I come from the old school, where simulation means generating a plot from chemical shift values (while the razors mainly estimate the chemical shifts from the structure).
The first test is N,N-dimethylformamide.


1-H
exp.  calc.  diff.
8.019 1.609 -6.41
2.970 3.001 0.031
2.883 3.001 0.118

13-C
exp.  calc.  diff.
162.6 198.7 36.1
36.4 34.568 -1.9
31.3 34.568 3.3

The second test is ortho-dichloro-benzene.
Simulated by iNMR:
Simulated by HNMRazor:

Interview with Kevin Theisen

2009-05-31T12:13:00.004+02:00

Kevin already told his story on the offcial website of iChemLabs. I was curious to know more details... Here is the first offical interview of my blog.
OS: How much accurate are the predictions of the NMRazors?
KT: The NMRazors are fairly accurate for most molecules. They will handle any molecule encountered in an undergraduate organic chemistry course. The NMRazors will be less accurate for molecules where complex anisotropic and 3D effects are present. I used several published references when developing the algorithms in the NMRazors and they are cited on the NMRazor website.
OS: Programming is similar to chemical synthesis: there are starting materials and finished products. What were the staring material for the NMRazors?
KT: When I first began programming chemistry applications, I started with a graph based depth-first search traversal of a database of reactions in order to optimize synthetic routes. A credible synthetic database was too expensive for me to obtain as an undergraduate, so I moved on to other applications in chemistry. I quickly discovered that the graph data structure is really integral to computational chemistry, as most chemical entities are efficiently modeled with them, especially structures. I was and still am a huge fan of spectroscopy, so I began to work on algorithms to traverse molecules and find functional groups for nuclear magnetic resonance simulations. It was originally a text based application, and I remember showing some of my favorite professors connection table inputs with ppm table outputs. It was very unattractive, so I taught myself Swing and the NMRazor GUI was created.
OS: Why do you prefer Java? Because of the language itself, the available frameworks, the platform independence or any other reason?
KT: Java is a wonderful programming language for several reasons. Mainly, it's object oriented and the graphical capabilities available with Java Swing are really unparalleled in other languages. The other reason was that I used a Mac, my friends usually used PCs and a few had Linux, so I needed a programming language that I could use on Mac and then deploy on other operating systems. Java was really the only choice for me at the time, given my minimal experience. The only downside to Java is that it is interpreted, so it may be slower if the program is carelessly written, and the JREs on different operating systems are not always consistent, so I still need to test on all three systems before I am sure a program actually works.
OS: How much work was required? What was the most difficult part: the algorithm or the interface?
KT: The interface was the most difficult part of the NMRazors because I was just starting to learn Java Swing. Now that I have pretty much mastered Java Swing, perfecting the algorithms is more difficult and takes far more time. But this is a good thing, because this saved time I can devote to truly perfecting the algorithms.
OS: Can you briefly describe the algorithms?
KT: There are two main ways to predict spectra, quantum mechanics and chemoinformatics. Quantum mechanics approaches calculate electron densities and then predict chemical shifts based on shielding. The NMRazors use a chemoinformatics approach, which takes a large database of spectra, defines similarity between the structures, and then interpolates to predict the chemical shifts of unknown species. Both can be very accurate if done properly, but quantum approaches take several hours. Since I couldn't afford a database of spectra, I went one level of abstraction further and used incremental constants to predict shifts. So the algorithm is similar to how a spectroscopist would predict a chemical shift in their head: they would look at the functional groups surrounding the nucleus of interest and add together the deshielding effects. There are other approximations for solvent effects, and splitting needs to be calculated, as well as second order interactions and more. These considerations make sure the simulated spectrum is as close to the real spectrum as possible.
OS: How do you manage to study and lead iChemlabs at the same time?
KT: There are days where it gets a little difficult. But fortunately, I have help with all the backend servers and services, web design, software testing, and of course accountants to do all the financials. Also, we were careful when we set up the company to put the appropriate infrastructure in place to manage our growth. Because we made sure to have redundant servers and source code control and bug reporting systems and product build processes in place, adding new products has become routine. Furthermore we outsource email and payment services so we just don't have to deal with those headaches. The bottom line, though, is I am very passionate about my company and my research. Currently, my research has become very exciting. It is a mix of chemical informatics and theory, which provide daily puzzles for me to solve. Both iChemLabs and my research push me to different edges of technology. Since I really enjoy both jobs it is not that hard to keep them both going. Every day I simply have fun with this stuff.
OS: You are marketing the razors for educational use. Could there be any practical use for them?
KT: My goal in my work is to provide quality software to students and scientists that is both accessible and affordable. The NMRazors were released for free for educational use because I knew it would be useful for students like myself that were working hard trying to interpret spectra for the first time. I also price our other software affordably so that I can continue to fund their development, without requiring customers to spend half of their savings. The NMRazors are used at several universities around the world now, and I am very happy with how this project developed.
In terms of practicality, as the algorithms mature over time, they will certainly be very useful to industry.
OS: Let's talk about ChemDoodle. How do you compare it against IsisDraw, ACD ChemSketch and Marvin?
KT: Firstly, I created ChemDoodle because I needed a very robust set of features, I could not afford ChemDraw, and ACD Labs would not respond to my emails when I requested pricing information.
Regardless, the chemical drawing software that was available was built on 10-20 year old systems that are severely out of date. ChemDoodle takes a new approach to drawing molecules, making the interface aesthetic and the controls more intuitive, providing functionality that takes advantage of current technology such as connections to online databases, and providing a more artistic approach to drawing figures by allowing users to completely control the look of structures including using different bond stroke styles for truly stunning graphics. ChemDoodle also contains many widgets, or mini-applications, which are added bonuses that perform very powerful and specific tasks. All these reasons are why I refer to ChemDoodle as a chemical structure environment, rather than just a chemical drawing tool like the ones mentioned.
Two years later, and we have succeeded in solving many of the issues other programs suffer from, and we work wonderfully on all operating systems. We receive emails almost daily complimenting us on our work and for creating a superior chemical drawing program, and we proudly agree.
OS: Are you going to write software for the iPhone? It seems like half of the world is doing it...
KT: That was a very attractive idea a year ago, when Brad Larson created Molecules. However, we are really focused on perfecting our desktop software and pushing ChemDoodle to be the best chemical drawing program in everyone's mind. We also have a couple secret projects that are under development, though not for the iPhone. These are brand new ideas, very different from current software, and we are sure chemists will love to use them.

Unusual Solution

2009-05-24T23:47:00.002+02:00

This is how I solved the problem of the razor.
1- I described the bug on my (this) blog.
2- It rang a bell into Kevin's mind;
3- Kevin recompiled both programs (1-H and 13-C).
It may sound difficult for you, yet recompiling a program is very easy (provided you are the author, it can be a nightmare in other cases!).
The new versions work and produce the desired plots.
I will return on the subject with more articles.
Thank you, Kevin!

We Insist!

2009-05-24T12:13:00.005+02:00

Maybe there is an error into the drawing module, or I haven't understood how to use it.
Today I am going to bypass drawing with a clever trick. You can follow me step by step.
1) I open NHMRazor.
2) Command: Find Molecule.
3) I insert a molecular formula: C6H12.
4) I find 30 result: great! I scroll down the list and select 2-methyl-2-ene.
5) I click the button "Load". This loads the structure:
We have almost done it! Next step:
6) A click on the triplet icon.
7) This time I don't select any solvent (who knows?) and assume that the default settings are OK. Final step: button OK...
I am not showing the result because nothing has changed since yesterday ("The server has an error that is currently being fixed. Sorry for any inconvenience").
Have you ever played Myst? You know the feeling.

A Picture from Kevin Theisen

2009-05-24T08:43:00.002+02:00

Shaving with a new HNMRazor

2009-05-23T22:06:00.004+02:00

The NMR razors are simple and (probably) powerful applications that can simulate a spectrum directly from the molecular formula. For the user's point of view it works like a (very) simplified version of ChemDraw. When you have finished drawing the structure, you hit a button to simulate the spectrum. When you hit the button, the program asks you such spectroscopic details like solvent, temperature, magnetic field, etc.. When you have finished this further step, the razor calls home. Yes, because all you have downloaded is a graphic interface, the true program is running into a remote and ultra-secret location.
I like this program because I have understood everything in 5 minutes.
To start with, I have simulated the 1-H spectrum of ethyl acetate in CDCl3, at 200 MHz.
Here it is:
Well, you know, I am not a lucky guy! Enough for today. If you want to try by yourself:
http://www.ichemlabs.com/content/nmrazors
This morning I shaved my face with a Gillette blue II. It is as good as a Gillette can be and it is much cheaper than the other models of the same brand. Officially it is disposable, yet I don't remember when I bought it. Quite likely I have been using the same razor for 3 or 4 months. As long as it works... Two complete reviews in a single post, I am very productive...

Off-Topic

2009-05-08T19:02:00.005+02:00

I am not particularly inclined to blog in May.
Do you want to play with me?

Cool

2009-04-20T09:42:00.002+02:00

Sweet J 2.1 sports sound and cool animation effects.

one look

2009-04-07T21:20:00.005+02:00

My software always shows me the FID when I open a new spectrum. Then I transform it. Some people find this ritual annoying and prefer to see the transformed spectrum directly, because all the FIDs look the same. Sometimes it happens, however, that a FID looks different:
It merely means that something wrong happened during the acquisition. No matter what went wrong, no matter why this particular FID looks different. It is enough to recognize that it is very unusual.
Having a look at the FID is not a waste of time. Processing this particular FID and trying in all ways to compensate for its defects can potentially be a waste of time.
My software always shows me the FID because I want it so.

Sweet J

2009-04-01T11:30:00.010+02:00

It took 14 years for Sweet J to grow.
When only a few hard-die fans could remember the name, version 2.0 appeared. The new interface resembles the old one, yet the differences are noteworthy. Version 1 included 4 modal dialogs. Now only the preferences dialog has survived. The other three have been fused, instead, into the main window. The interface updates immediately, therefore there is no "OK" button. The purpose of Sweet J is limited. The implementation, instead, is rather sophisticated. I say it because the source code is freely available.
When I say "sophisticated" I mean that it's not trivial to connect all the pieces of the interface to a chemistry logic. For example, if you change one of the skeleton atoms, the equation by Haasnoot et al. is no more applicable, therefore the whole interface needs to be updated (some controls disappear, for example).
The picture below has already appeared on the Apple site, on Macupdate and on Macs in Chemistry.
My blog is the official sponsor of this effort. Or is it the opposite? (Sweet J sponsoring the NMR software blog?)... There's also a theory going around which says that Lou Reed wrote a song inspired by it, which is unbelievable: "Sweet Jane" the song predates "Sweet J" the program. Maybe it's the opposite...

Prima Cala

2009-03-22T17:50:00.004+01:00

This beach is near to my home (a 5 minutes walk). I come here whenever I need a little of fresh hair. The place is often windy, like today.

Equinox

2009-03-20T15:41:00.003+01:00

Spring

2009-03-19T23:02:00.002+01:00

SDBS beautified

2009-03-13T10:47:00.008+01:00

The Spectral Database for Organic Compounds is very popular
and deserves all my praise: is straightforward to use, easy to access, rich of data, void of advertisement and completely free. Everybody has used it at least once, what else should I say?
Jaume Farràs Soler sent me a shell script to import a list of peaks, copied from SDBS, into iNMR. He said that the pictures of SDBS were not clear enough, while in this way he could generate much better ones. The address of this script is now:
http://www.inmr.net/library/sdbs2inmr
Later on we'll see why it can be useful. Let's start with a more immediate approach. First thing first: if you have a Mac, download the latest version (3.1.4) of iNMR passion (freeware). Now, the next time you find a 1-H spectrum on SDBS, scroll down the page, until you find this button:Clicking the button leads you to a list like:



  Hz     ppm   Int.

   1367.55   3.422    485
   1360.72   3.405    942
   1353.88   3.388    515
    755.00   1.890    118
.......................

Copy the list, including the header: "Hz ppm Int.", into the clipboard. Open iNMR passion and choose, from the menu, "Simulate List of Peaks". You will instantly see the spectrum, synthesized, as large as your monitor, ready to be explored (or printed) and, it goes without saying, anti-aliased.

Caveat: I guess that SDBS reports the apparent eight of the peaks, which is given by the proper height of a peak plus the contribute of any overlapping peaks. iNMR interprets this value, instead, as the natural height. The result is that all the peaks of a multiplet will become taller, while the singlets will be OK.
The areas will be a little distorted. What's also missing from the SDBS list is the width of each peak. In the synthetic spectrum all lines appear equal and narrow (1 Hz wide). The areas of broad peaks will be strongly underestimated. Add to this the effect above (for overlapping peaks).

If you want something more realistic, you can use the script by Jaume. It will generate a list with widths. Import the list into the deconvolution module of iNMR, where you'll be able to modify individual line-widths and intensities. The spectrum will look more realistic, yet don't ask me where to get the correct values from.

If, instead, you know about another database, with a different list format, send me the address. I'll write another version of iNMR passion that will recognize your format too.

Evgeny wants you

2009-03-10T08:22:00.007+01:00

Last year he opened the NMR wiki. This month Evgeny Fadeev has started a discussion group. Synthetic description: "All about magnetic resonance, summaries go to NMR Wiki". Evgeny also says: "Send invitations to your friends and ask them to invite their friends. Then we'll make it work!!!".
You are in time to become one of the first 100 members.

Making the Headlines

2009-03-08T21:50:00.005+01:00

The NMR discovery of the month, according to spectroscopynow, is the whitening method. When this humble blog introduced the method in October, I didn't believe it was SO important. I am still pinching myself.

Split Plot Splats

2009-03-08T09:35:00.001+01:00

ini386

2009-03-06T22:21:00.001+01:00

The reader ini386 compared the ease of use of iNMR with that of the Adobe reader. Such a comparison is impossible. Both products and their histories are under the eyes of every one. You should know them! Today I am trying to expose a few facts that are never been secret, they have been just ignored. In other words: nobody really cares about what I am going to write.
iNMR has arrived to version 3.1.1, with 3.1.3 ready to appear next week, through an incredible number of changes and upgrades. In the beginning, the process could be explained in two ways: either the preliminary versions were not satisfactory or the users were impossible to satisfy (does it make any difference?). Afterwards the process became a little different. Once you know that it's so easy to release a new version, it's impossible to stop. You are happy with the program not because it's perfect, but because you know that any defect you find can be eliminated.
While there is a single author, iNMR is the product of many minds. Two hands only; many minds. The clear separation of roles is a winning strategy. The users are in command: their desiderata are normally satisfied. The exception is when they ask another application or a companion application; these requests are difficult to satisfy. If, instead, they ask for a new functionality or a single modification, they are the kings. The user, however, don't the internal mechanism of the program and can't imagine them. It was relatively easy in the case of SwaN-MR, where the data structures were the same (in RAM, on disc and into the dialogs). It's impossible in the case of iNMR: the data structures (which contain the same data) changes at each level and there's a great work of translation under the surface. For this reason the user/king can't tell to the servant how to do his job.
When it's working time, the servant is the king. He can decide, for example, to spend a week to finish a job that could have been done in a couple of hours. The fun is in trying all the possible variations (and not having a deadline). Misunderstandings are frequent (and funny too): the user asks for a certain function, the programmer understands a different thing. Eventually both things are done (and remain; and the program grows...).
The opposite situation (democracy) is dull and stressing. In this case there are the meetings, boring and time-consuming, where there's always people who need to speak even when they have no (useful) idea to communicate. Often you can also encounter their historical enemies, and the psychodrama is on the show. Now, if you know that a new proposal for a change or for an experiment must be approved by a meeting of this kind, you'll be scared of proposing anything (and you'll never desire to experiment).
Don't get me wrong. I know very well that the concentration of resources (energies, capital, skills, everything) is the road to success. I am convinced that I go nowhere if I am alone. What's difficult (and probably never required) is to find an agreement between the coworkers. That's impossible while you are inventing something new. When a problem has already been studied very well, when several books have already been dedicated to the subject, then it becomes possible to work as a team.
Programming is becoming more and more similar to chemistry. When intermediate structures become important and popular, they are prepared commercially. Teams of programmers work together to create general-purpose libraries. Individual programmers can assemble the ready-made pieces to create the final applications. When the closest intermediate can't be found, we can still copy (recycle) the ideas, as we do in chemistry.
I couldn't have written this post 20 years ago. I was a different man. I used to say to the users: "This is the program. Learn it." And they kept saying: "Have you ever though about adding...? Why don't you imitate that other program...?". We have kept saying the same things over and over until today (and tomorrow). What is changed is that now I pay more attention of what they say, while they understand more of what I am saying. In the past I was happy if I could change their minds. Today I am happy when they have changed mine. It's not a virtue, it's my beard that's becoming grey. When I had a whole life in front of me, I tried to make the world a better place where to spend this apparently unlimited existence. I tried to make people think just like me. Today I enjoy to learn new things, to embrace new ideas. It's not as having another chance in life, it doesn't even come close, but it has a flavor of it.

Limited Undo

2009-02-26T22:16:00.005+01:00

It's great when you can undo after you have already saved a document and go back, back, back... It would be even greater if everything could be really undoable. Take for example Adobe(R) Acrobat(R) Reader 9.0.0. I was reading a book of 1200 pages. I was reading one of the internal pages (don't remember which) and had arrived to the bottom of the window. I moved my hand to press the key "Page Down", but I pressed the wrong (nearby) key, which happens to be the "End" key. Ok, I said, there's the Undo command. No way, said Acrobat Reader, you can't undo. The rationale is probably: "The user has not edited the document, there is nothing to undo". Why not adopting the rationale: "Every time a key is pressed, chances are it was a mistake"???
Dear reader, don't think that, just because today's software allow for unlimited undoing, you can really undo everything. Actually there are a lot of important and common things that can't be undone, or can be remedied to, but only using a command different from Undo. Try for example to click a link in this page and to return here with an Undo. Does it work? Try typing a long sentence with your word processor and to remove the last word only with Undo. What happens?
Luckily, everybody knows how to jump back to the previous page with the command go back and to delete the last word by selecting it and cutting it away. How do you find the page you were reading with Acrobat?
Adobe Reader takes 172.6 MB on my hard disk. It's larger than many historical operative systems (combined). It's also much larger than my first hard disc (40 MB), yet it can't undo. It's really a mystery what's hidden inside. There is potential room for a million of viruses.
I have an assignment for you. I mean you guys who haven't the least idea of what NMR means but nonetheless try to post comments into my blog only to link to your web sites. I have always deleted your posts. This time I want to give you a chance.
Read the credits of Adobe Reader (they appear after you open the "about" box). If you can write the exact number of people who appear into the credits, I will not delete your comment.

New Millennium

2009-02-06T09:56:00.004+01:00

What's the difference between the old and the new millenium? Do you remember when I described the whitening method? Now it has been published, as a peer-reviewd article, on Magnetic Resonance in Chemistry:
Automatic phase correction of 2D NMR spectra by a whitening method
Giuseppe Balacco, Carlos Cobas
Published Online: Feb 3 2009 10:57AM
DOI: 10.1002/mrc.2394
If you have followed this blog, you know that many other papers have appeared on a similar subject (automatic phase correction of 1-D spectra). In the past, to discover that the method didn't actually work, you had to write a program by yourself (apart a few lucky exceptions). If you want to verify the whitening method in practice, you have plenty of simpler and faster alternatives.
You can download iNMR Passion (freeware) or you can download the freely accessible iNMR (or iNMR reader: they don't allow printing, in demo mode, which is irrelevant in our context). If you have a generic operative system you can ask for a demo copy of MestreNova.
Please don't complain if some of these products are commercial. FTF: where do you publish your results? On your own blog? Second thing: we haven't patented our method and anybody is free to include the algorithm into her/his own program (free or commercial); citing the source would be fair.
A final disclaimer: the whitening method works nicely in 2-D spectroscopy. It's not yet applicable in 3-D cases. When, however, the phase of a 2-D spectrum is impossible to correct manually, it's also impossible to correct it automatically. Obvious!

N as FID

2009-02-02T08:23:00.002+01:00

A bidimensional Free Induction Decay of an aqueous solution.

mosaic

2009-02-01T17:44:00.002+01:00

do you recognize it? can you do the same?

Desktop Pictures

2009-02-01T12:56:00.004+01:00

These images are 1680x1050 JPEGs because these are the dimension of my screen. It's a C-H HSQC of ubiquitine at 500 MHz, fully processed.

Crystal

2009-02-01T09:44:00.004+01:00

The above image has been generated without shades and 3-D effects: it's a plain flat map. All the optical effects come from the spectrum itself. Positive points are black, negative points are red. Click the image to see it larger.

Bullets

2009-01-31T21:55:00.003+01:00

A rarely seen combination of colors, which I find refreshing and relaxing at the same time; it combines very well with a gray grid.

Roses and Strawberries

2009-01-31T19:02:00.002+01:00

This ROESY requires a little of baseline correction.

Explosion

2009-01-31T18:28:00.001+01:00

This is what happens when the phase of a ROESY is not correct.

Stars or Gold?

2009-01-31T18:14:00.002+01:00

...it's only a COSY.

NM-art

2009-01-30T20:10:00.002+01:00

This picture is dedicated to Antonio Triolo (who conied the term NM-art) and Antonio Guidi (who believes this art should be exploited to make money).
What you see is a fragment of a TOCSY, very out-of-phase.

Writing an Help Book

2009-01-20T23:33:00.009+01:00

I don't consider myself an expert in software documentation. I have written hundreds of manual pages for the programs that I have written in the last 20 years, but I did it reluctantly, just because nobody else was going to do it.
Having dedicated the last two months of my life to write another manual (which is not finished yet), I like to share with you my thoughts and my personal rules.
The source of inspiration, this time, has been the Apple Help Programming Guide. Sounds obvious? They certainly have more experience than myself, so why not exploiting it? First doubt: many third party applications deliver their documentation in other forms, for example as PDF files. Second exception: Apple itself, when a program is more professional, like in the case of XCode, avoids its own Help Viewer. Third doubt: it's normally good to follow Apple guidelines, because users already know how the interface works, but is this theory still valid in this particular case? Do they read the manuals of, let's say, Mail or Safari?
While the Help Viewer has its drawbacks, the advantages are too many: it's searchable from the menu-bar and this fact alone makes it the best choice. It makes no difference if you are writing the manual for a simple unprofessional application or for a complex one (a scientific one, in our case). It's true that we should expect a little more sacrifice from researchers (they can't say they don't like studying!), yet their situation really requires simplified manuals. Speaking for myself, there are applications that I rarely use, until I need them to solve some specific tasks. It would be great to find the answers I need, explained in plain terms, easy to understand even without reading the rest of the manual.
That's exactly the main principle of the the Apple Help. Apple says: don't write a feature-oriented manual. That would be, for example, an orderly description of what each menu command does. What they say, instead, is: identify the typical tasks (workflows) the user is faced to and write a page for each of these workflows. The approach is more popular than it might appear. Consider, for example, the case of a department buying a site license for a new program, that nobody knows and that is accompanied by a 1,000 pages manual. The boss can't tolerate that all his employees study 1,000 pages of manual. He will ask one of them to study it and write down a condensed (2-pages!) "how-to", with sequential, step-by-step instructions for the most common tasks. Now, if the manual already comes with many of these "how-to" to choose from, all the boss has to do is to photocopy one of them. Isn't it a time-saving?
Also consider the usual job of an help desk. They are asked by the user: "I want to do this but the program doesn't allow me to". Here again, the answer usually comes either as a list of steps to repeat or a list of conditions to verify.
The third reason why a task-oriented manual saves time is that it's more readable. Why? Because it's outlined, schematic, consistent. The reader can swiftly identify which paragraphs to skip (because he's already familiar with a particular command, for example, or because they treat special cases) and which paragraphs to pay attention to.
I am speaking about saving time, but actually I have lost a lot of my time to write my last "opus", mainly because of a non appropriated strategy and probably also because of non appropriated tools. What I have been doing lately has been to rewrite a manual that I had initially written in 2005, and incrementally updated to reflect the evolution of the program described. The original sin was my decision to put everything into the manual, like short lessons of NMR processing, the promotion of the product itself (who doesn't it?) and personal comments. All these things were motivated but, in the end, it had become difficult to search the manual, because there was too much information and it was not uniform. Hence my new rule: "The manual must be nothing but a comprehensive collection of answers". Tutorials, articles, hands-on lessons, podcasts, etc... are all precious items, but their place, today, is on the web site. When I want to express my opinions and compare alternative programs I have my blog. The manual needn't to be more than a reminder. At the same time, however, any single page should be easy to understand even for a beginner. That's why I don't mind repeating the same advices in many places.
As Apple itself suggests, however, there must also be a few propaedeutic pages. If you browse the guide of the operative system ("Mac help") you can actually recognize four kinds of pages. To take the examples from my own work, they are:

.
Before writing a page you have to choose the right format, and the corresponding style. An overview page is explicative; it defines the concepts of the program. A reference page is descriptive. A task page gives straight instructions. A navigation page normally contains links only, into a suggested order for learning. All the navigation pages must be reachable from the entry point (home) of the help book and, taken together, they must provide links to all the other pages.
It's important not to mix two styles into the same page. For the same subject, for example, I have written a reference page, an overview page, and a task page. They used to be a single page in the old edition of the manual. There is, however, a partial and important exception, that I will explain later.
Here is, in practice, how I have proceeded. I have identified those areas of the program that fit well into reference tables, for example the preferences dialog and the keyboard shortcuts, and have written those pages first. They are feature-oriented, therefore relatively easy to write (it's enough to describe the individual options in the order that they appear inside the dialog). To describe the other modules, the first choice is always a task-oriented page. It can be a list of the many available ways to accomplish a given task, or the sequential list of steps (sometimes with ramifications). In practice, I have invented many variations. It's a fact that task pages are more schematic and therefore easier to consult. Deciding which pages to write and their titles is a little more complicated, because there's no ready scheme to follow. In theory you should observe the users at work (with other programs too), hear their FAQ, etc... The titles of the chapters should correspond to the expectations of the users, not to the menus of the program.
In practice, it's still possible to start from the features! For example, I try to remember why I added a certain command, what problem I had in mind, etc.. and I find the typical workflow that incorporates that command. If I identify two or more typical workflows, I write a page for each of them. Their description goes into the central box of the page. Yes, it's not necessary to start from the beginning. It's more convenient to write down only the skeleton of the workflow, then to explain the concepts or what's happening inside the program or the available alternatives, adding these things between the lines. The first sentence of each paragraph contains an instruction to follow, the rest of the paragraph contains the explanations (for the interested reader only). When an important note can't find a place inside the workflow box, it will go either into the introduction or into the conclusion. Here I disagree with Apple's guidelines, because they neglect the most important concept. I think that the manual should give the answers, it shouldn't force the reader to stop and think. A mistake that I try to avoid is to start a chapter with a formal definition that refers to concepts that will be explained in the body below. What's good for a textbook can be bad for an help book. When the reader arrives to a chapter he still doesn't know if he has found what he needs, therefore it's not ready to concentrate on the topic. He needs to be reassured first. The introduction should just refresh a few basic concepts that set the context for what follows. The difficult notions will find their space below the central box. Here is the exception that I was referring earlier. While the overview and the reference pages are more unitary, a task page, being graphically divided into three regions (introduction, workflow-box and conclusion), can contain all things. The introduction can become, if necessary, an overview section and the conclusion a reference section (it can describe rare cases and special usages). Obviously, if I see that any of these sections becomes too long I will move it into its own page. More often than not, however, it's possible to cover a whole subject with one or two task-pages, using the described technique of writing between the lines. In practice my manual contains 13 overviews, 15 reference tables and 44 task pages. The last group is destined to grow: as new questions arrive from the users, I am going to add new workflows.
While Apple encourages to add pictures, actions (scripts) and multimedia content into an help book, I see a clear trend, by their side, toward text-only manuals (and I have followed suit). While it's true that the right picture can be an ace, and sometimes it is really necessary, I agree that they should be added only in such a case. To say which command to use, for example, I prefer mentioning the menu and the name of the command, rather than showing the icon to click. The icons are just shortcuts and the user should discover these shortcuts by herself. Adding a picture has a drawback: the page exceeds the limits of the screen and it's no more possible to see the whole workflow with a glance. Apple really succeeds into containing each page into a small size. I am not as good. Anyway, when each element of the program interface clearly shows its name, there's no difficulty in describing it without the aid of pictures.
Don't you think it's better to follow the inverse approach, namely to add a short explicatory message into a window instead than to reproduce the window itself into the manual? Actually, having deliberated to write a task-oriented manual, which doesn't list each and every command, it's useful to design a self-explicatory interface. Indeed I have renounced to write pages to describe some commands that were sufficiently covered by their yellow help tips.
Another thing that Apple uses sparingly are the internal links, which instead I use extensively (they are the main reason, after all, why I prefer HTML manuals).
Things that they use a lot but I would discourage are several Apple extensions to the HTML tags (for example, all the lists of links in their help books are created dynamically). The Help Viewer, for those who ignore it, recognizes a few special instructions which are not as good as they seem at first sight. I have so many reasons to prefer standard XHTML: the manual looks the same into a normal browser, so there's no need to test it with the Help Viewer (not an easy thing) and the user is free to read the manual with the browser of her choice. The whole manual can be uploaded on the web (it becomes easier to give a link to a specific page, as I have done inside this article). Last but not least, the Help Viewer, which is normally so sluggish, becomes much faster when the HTML files do not contain the special tags! Anyway, the meta "description" tag is a necessity, like the tag: meta name="robots" content="noindex" in the index pages (you don't want an index page to appear as a result of a search).
You may be curious to know which tools I have used. Actually I have simply duplicated a few files from the Apple's help books installed on my iMac and substituted their text with mine. By inspecting the XHTML code I got the impression it was generated by a computer, but I haven't investigated further. I have used Smultron, by Peter Borg, because it's what I am currently using to edit my HTML and CSS files, and I admit that it's less than ideal, yet I haven't felt the need for anything more refined. For the sake of your curiousity, the manual of Smultron is a PDF file!
If you have to document your own program, and can describe it in a few pages, than you don't have to ponder your strategy too much. You can just unleash your ingenuity and the manual will likely be a masterpiece. If, instead, the program to describe is complex, and you still want to follow Apple's guidelines, be prepared to spend a considerable amount of time. I don't know if my rules can work for you, maybe you'll find better strategies or stick strictly to the official guidelines. I have just enjoyed to share my experience, for what it's worth.
Don't be disappointed if my story ends with a sad note. Whenever my manual will be finished, I am not expecting any particular feedback from its readers. Half of the users of the program don't read the manuals and the rest have no time to write a line. I'll remain my only judge. That's probably why so many guys like programming and so few like writing technical documentation. I have tried both and let me say that they are arts of the same level of difficulty.

goodbye 2008

2008-12-28T15:37:00.002+01:00

Wrap Up

2008-11-26T08:48:00.005+01:00

When you split an article in pieces on a blog, they appear in reversed order, so it's not a great idea. A summary helps:

To be honest, I have not described all the details. I feel I have been pedant enough. There is another trick yet. If you select multiple items, the preview window shows additional controls. Without explaining everything, here is the picture:

Coda

2008-11-18T14:24:00.009+01:00

In this fourth and final part of the article, we'll discover the flexibility of the metadata system. For example, let's say you don't like the slideshow. A single picture is enough. You want, however, to inspect the metada. In the second part we learned that the command "Get Info" satisfies this need. The new command "Quick Look" can generate a different representation. It shows the same information (more or less), with an HTML layout and much larger fonts. In other words, it's more readable:

There is also the opposite way of doing things. Let's say that you want to see your list of files in text form, without icons and thumbnails, without the coverflow effect, but you want to see the preview of your files nonetheless. Here again the "Quick Look" command comes to the rescue. It opens a glassy, dark-grey window, that acts as an ispector. When you select a file, the preview window shows the internal pages. You can use the scrollbar (or the keys PageUp and PageDown) to move through the pages. If you select a different file, its contents are automatically shown.

The preview also includes an optional Full-Screen mode, when all the other windows are hidden and the background is black. You activate this mode by clicking the symbol with two white arrows. The full screen-mode is too large to be shown here.
None of things described in my article will help you to make a discovery. That's normal. Do you ask to the computer hardware to increase the number of your publications? I think not. Why, then, should we ask such a thing to the software?

Slideshow

2008-11-18T13:07:00.004+01:00

In the second part of this article we saw the coverflow effect. In this third part we'll see what happens when we move the mouse near to one of the thumbnails.

Two arrow controls appear. They let us browse the internal pages of a document. In the case of a spectrum, the pages can correspond to some important details or to user comments. Alternatively the user may choose to change the display mode. In our example, the integrals are shown on the first page only, the peak frequencies on the second page only.

In practice, the computer has automatically generated a slideshow presentation for you. This becomes very useful indeed when you want to browse your spectra of yesteryear, or when your boss asks you how are things going and you obviously have no time to prepare a PowerPoint presentation.

If you click the above pictures you can see them at their natural size.

Metadata

2008-11-18T11:26:00.008+01:00

It's not easy to obtain the permission to show a nice spectrum. For this article I have downloaded a collection of spectra of a standard compound from the Biological Magnetic Resonance Data Bank. They are not very nice but can serve my purpose. I have also processed the spectra to highlight the relevant information.
Now I'll show you what is visible after you close the processing application. All the snapshot are taken while working with the operative system. I have uploaded very large pictures, so you don't lose too much (you'll only lose the animation effects). The blog shows them at a reduced size, but if you click a picture, the full-size original appears.
As a starting point, I have selected a file, without opening it; the command "Get Info" shows this panel:
This is only moderately useful, because selecting a file is already a time-consuming operation (you have to navigate through the folder hierarchy). The good news is that the computer can find the spectra for you, if you specify the same properties. This is the job of the command "Find". For example, we can ask the list of all the files relating to substances of general formula C5H7NO3:
Yes, the computer understand a chemical formula! Such a search is not restricted to NMR documents. We can however add more conditions to restrict the search, how many conditions we like. For example:
Every time I type a single character the list of results is updated (live). There is also the option of displaying an animated list. It's a cinematic effect that's very characteristic. If you have ever seen iTunes or the iPhone you know what I mean. On my blog I am limiting myself to displaying static pictures, however. Here is how my spectra look like:
And this is only the appetizer! [continues...]

What's New

2008-11-17T17:57:00.002+01:00

For more than two years I have been describing application software ("the programs"), and not the operative systems. Sounds obvious? It isn't. I had noticed, in the past, the attempt of a couple of programs (namely the ACD suite and the "NMRnotebook") to substitute the operative system. What they do is to put all your NMR data into a monolithic archive. From that moment on you can't search your files into the normal directory tree: the application program manages everything, substituting for the system. Can they do it better?
I have also seen the opposite phenomenon, that is the appearance of new operative systems that do every kind of things, up to the point to make you feeling that application programs are no more necessary. My preference goes to the latter trend, for a practical reason. When you are in troubles with an operative system, you can find a neighbor or relative that knows it well and that can help you. If you are at work, you can call the IT department. If your troubles arise from the application software, instead, you don't know whom you can turn to. That's why I prefer doing more things than possible with the operative system, if I am allowed.
While I will be describing a specific OS, I am writing for everybody: it's the idea that counts, not the implementation.
Now, in my life I have studied only two OS. The first one was called "IBM-DOS" and the second one "MS-DOS". It happened in an era when the computers included heavy and bulky printed manuals. I have been commuting for half of my life, so I had plenty of opportunities to read paper manuals (over and over again). I am not using those OS any more and I have forgotten what I had learned. I have come in touch with the modern systems, but still feel like a stranger (I haven't found the new manuals yet!). Last week I have begun working with Mac OS 10.5.5. It resembles the old version 7 that I was using in the early 90s, so it looks familiar to me. I have tried to read the installation manual, which shows a few things you can do but doesn't tell how to do them. It only explains how to install the system. I am learning by practice.
The rationale is that customers don't know what to do during the endless installation process, so they are given a manual to spend their time with. Unfortunately, you can read as slowly as you possibly can, but the installation will always be slower than you. To give you an idea, the whole manual, including the unreadable license agreement, weights 94 g.
What has this to do with NMR? Well, this OS seems to be almost ready to handle NMR data out of the box. I want to show you the technologies that I have explored so far, and they are enough to write posts for a week. Mainly I will describe two commands: "Get File Info" and "Find...", that are so ancient I believe they have always been there, with the same keyboard shortcuts (maybe under a different menu). What's new? Now you can install custom plug-ins for those commands. The operative system will instantly become NMR-savvy. Writing a plug-in is not terribly complicated. The Apple site gives you all the tools, libraries, instructions, examples and templates you need. You can write a plug-in in an afternoon. If you have more time, with the same tools you can even write a complete NMR program. No need to look around for the FFT algorithm, it's already a component of the OS. Of course, it has been put there to manipulate sounds, not to process NMR spectra. If you can't write a line of code and want everything ready and free... then you are lucky! What I will be showing during this week can be done with freely available plug-ins. You don't need to know how to write them.
Let me clarify my intent. It's not that I am supporting Apple. I think it's a greedy corporation, no better than Microsoft or IBM. Their products are over-priced in the U.S. and sold at an outrageous price elsewhere. I would rather encourage you to stick to your old hardware and software. (Beware that programs written for System 7 are not compatible with 10.5). Nonetheless, it's nice to be curious about the new technologies. What I have discovered last week sounded new to me, probably is well known to you, surely will become normal practice in the near future. Enough said, for today [continues...].

ProSpect

2008-10-26T10:30:00.004+01:00

A rare event: I have found an NMR program that's been a pleasure to inspect. It comes with an HTML manual (with pictures) and sample data. These two ingredients remove the usual obstacle for learning (you rarely guess right how to arrive to a frequency domain spectrum). In this case, instead, I could easily open one of the included sample spectra, because they come with their own processing scripts, and experiment with the buttons (relying on the help of the yellow tips). It's clear that they spent their time and money in making this program. It's well done.
The program is called ProSpect ND and comes from Utrecth. It's completely free. In theory, it's cross-platform. I have tested the Windows version.
Why isn't it more famous? Well, to start with the name, it is focused on multi-dimensional spectroscopy and favors serious processing and flexibility over simplicity of use. You realize this fact from the very beginning. To open a spectrum (Bruker or Varian, no other format is recognized) you must first convert it into the ProSpect format with a script; it's not trivial.
The program also includes all the routines to process and analyze a 1D spectrum. The graphical layout is, well, arguable. For example, the peak-picking labels tend to overlap with each other.
Speaking of 1D, LAOCOON is also included. Forgive my personal reminiscence: the manual doesn't refer to the first version, as everybody else has always been doing, but to the the last version by Cassidei and Sciacovelli, who happen to be the ones who teached me how to use a spectrometer (and some theory too, in the case of Sciacovelli).
My first impression: they have written a program the way they like it. If you need to print your 1D spectra, I bet you'll have diverging opinions. If you like to spend much time in 2D processing to obtain the optimal results, and the other free alternatives don't satisfy you, chances are that ProSpect ND will.
This product confirms the rule: it takes time and money to make NMR software. If you want it free, you must find a sponsor with large shoulders. There's an important difference that puts ProSpect apart from more famous free programs like the original Mestre-C, NMRPipe, SpinWorks, NPK. Prospect is open source. In the case of NPK I may be wrong. Anyway, you can directly download all the source code of ProSpectND without asking any permission, without registering, without logging in. Guess the language? Phyton? Noo! Java? Noo! C++? Noo! OK, here's an hint: the first date on many source files says 1997.
C? Yes, I like it!

Students

2008-10-24T11:13:00.004+02:00

They say that students buy Macs. Is it true? If it is so, and you are a student, be sure to check this promotion out. It's a full-fledged, up-to-date application, offered at a price that's certainly affordable for any student. It's possible to test the product before buying it, of course.
...and you can even leave your comment here below!

End of the World

2008-10-10T13:57:00.004+02:00

Il mercato ormai di questo ritmo sta scontando la fine del mondo, altro che recessione! Se per caso avete perso del denaro in questi giorni, potete consolarvi in fondo era solo carta straccia. Presto torneremo al baratto, torneremo ad essere agricoltori, due galline, una capretta per il latte, ci potremo sedere intorno ad un focolare e stringerci con i nostri familiari e le persone più care, il pianeta non sarà più inquinato, sarà un luogo più vivibile,niente stress, niente lavoro forzato, il capo che rompe le palle, niente più calcio e calciatori fighette, niente più auto, Briatore e cocainomani del billionaire, niente più grande fratello e isola dei coglioni...che spettacolo forse stiamo andando verso un mondo migliore e allora forza S&P 500 ancora 900 punti verso lo zero! Hahahaha!
taken from Ferro Azzurro
Will all the NMR programs resist to this crisis?

Whitening

2008-10-02T23:24:00.003+02:00

In 2007 Carlos proposed to me a joint project to invent a new algorithm for 2D automatic phase correction. There were two reasons why I replied negatively. First thing first, I am doing research with no grants and no salary. Although there was the certainty of making some money in case the algorithm had been invented, I was doubtful that I could invent this thing any time soon. The second reason was that I have fun correcting the phase manually and I didn't want to spoil my fun. Instead of admitting that any normal person would benefit from an automatic procedure, I am still tempted to teach manual phase correction to everybody, guessing that they can have the same fun that I have. Carlos accepted my answers, at least the first reason. The story seemed to end there, but it was not forever.
This summer I wrote to Carlos that I really couldn't find anything interesting to do during my holidays and that it was better to do some work. He said he had an idea to keep me busy. Guess what? Inventing the automatic 2D phase correction. This time I agreed. I proposed a three-steps roadmap. The first step consisted into trying to correct the phase of a single isolated peak, adjusting simultaneously the 4 parameters involved. The second step was a semi-automatic method in which the user was required to select any number of peaks, even of different sign, and the computer had to do the rest. The preliminary method invented at the first stage would have been the main ingredient. The third stage was the completely automated method.
I liked this roadmap because the first stage looked feasible (I hate wasting time on hopeless research). The other stages were challenging, but, in my heart, I was hoping to find an escape route before arriving there. I was glad enough to have something to do for the first week.
Carlos asked me if I wanted any 2D spectrum to test my ideas. He had already mentally created a list of different cases with different characteristics. An important case was the edited HSQC, containing both positive and negative peaks (and more noise; and no diagonal). It looked more difficult then the other cases. I said: "I have never acquired this kind of spectrum; send me a specimen". When the file arrived I was already working on my project, but not making any progress because my code was infested by bugs (I was out of shape). I suspended my activity to inspect the edited HSQC. Processing it was a relaxing activity, which I did on autopilot. When I saw the 2D plot in front of me, I said to myself: "What have you done? You have corrected the phase without paying the least attention to which peaks are positive and which are negative. Actually you haven't even paid the least attention to where the peaks are located, but the phase is perfectly corrected! What does it mean?"
There was an explanation. Manual phase correction is ALWAYS so easy, at least the coarse correction is easy. I know that if I am moving the slider into the good direction, peaks become narrower and take less space into the map. Because my background is usually white, I know that if the white regions are growing, that is a sign that I am going into the right direction. I stop when the white regions start shrinking again. I immediately realized that my mental process could be easily translated into a computer algorithm. I also noted that the correction along the X axis is independent from the correction along the Y axis. The four-dimensional problem could be factorized into two bi-dimensional problems, easier and faster. I suspended the original project and began to write the new algorithm. In 24 hours I verified that it worked and worked very well. I also debugged the old code (belonging to the original project) and discovered that it was quite unstable: it only worked under ideal conditions.
I was forced to abort the first project, but very happy of having invented something really useful and really new (in a single stage). The weakness of the aborted project was that it had to observe a limited number of points at each time. The whitening method, instead, looks at one million points simultaneously. It's a statistic measure and it's reliable just because it condenses one million of observations.
Today the whitening method is a component of 3 commercial products. It has been already presented at a meeting and (in the form of poster) at a conference. We have written an article and submitted it to Magnetic Resonance in Chemistry. You may be wondering what the hell we could have written into that article, if six words are enough to state the method: "maximize the number of white pixels". Wait and see. I am convinced that the article will be accepted just because the principle is clear (have you noticed the pun?). If they have published (in many cases of 1-D automatic correction) the articles that describe algorithms that nobody has never seen in practice, why shouldn't they publish ours? Our products can be freely downloaded and you too can test the algorithm!
The natural question is: if this method is so obvious and simple, why nobody else had invented it before? The answer can be found inside Carlos' blog. While I have been performing REAL 2D phase correction for years, there are people that even ignore that such a thing is possible. What they are doing is the correction of selected rows and columns (traces) or their sum. Actually it's a mono-dimensional correction, but they believe it's a 2D correction. A pertaining example can be found on Glenn's Bruker-oriented blog. I have had the privilege of performing true 2-D manual correction and it helped me.
Finally, I must confess: I am having a lot of fun with automatic phase correction and after I have invented it I don't want to go back!

Commuting

2008-10-01T14:47:00.004+02:00

The canonical sequence is:
Rance -> FT -> shuffle -> FT -> shuffle -> FT
This is the result:
The following sequence also arrives there:
FT -> Rance -> shuffle -> FT -> shuffle -> FT
which proves the commutability between FT and Rance. When I try this:
FT -> shuffle -> FT -> Rance -> shuffle -> FT
the result is: