Friday, January 23, 2015

Overselling cross disciplinarity

I wrote a post How (not) to break into a field. Some of those ideas where supported when I recently started reading Paul Krugman's nice little book, The Self-Organizing Economy

Early in the book he notes:
the authors of articles and books on complexity almost never talk to serious economists or read what serious economists write; as a result, claims about the applicability of the new ideas to economics are usually coupled with statements about how economies work (and what economists know) that are so ill-informed as to make any economist who happens to encounter them dismiss the whole enterprise. 
But it does not have to be that way.
Unfortunately, you could replace "complexity" with quantum information theory and "economics" with chemistry, biology, or condensed matter physics.
Or,  astrophysicists and cancer, ... physicists and the origin of life .... string theorists and condensed matter ....

On the positive side, Krugman then discusses some nice simple "economic" models that produce spatial or temporal organisation, and power laws. He also briefly relates what he is doing to ideas of emergence and Phil Anderson.

My only disappointment is that there is no real data in the book. However, if you want to see some real data for scaling laws in economics and finance see this helpful review which contains curves such as the one below.

Thursday, January 22, 2015

Quantum protons in enzymes

A number of proteins involve short strong hydrogen bonds [also known as low-barrier bonds] and there is considerable debate about how important or relevant they are for functionality. A particularly interesting enzyme is KetoSteroid Isomerase (KSI) which features such bonds. Its structure and mechanism has recently been elucidated by some beautiful experiments using mutants near the active site.

There is a nice paper
Quantum delocalization of protons in the hydrogen-bond network of an enzyme active site
Lu Wang, Stephen D. Fried, Steven G. Boxer, and Thomas E. Markland

This is a combined experimental and theoretical study of isotope substitution effects where the protons are replaced with deuterium. This allows one to probe the effects of the zero-point motion of the protons in hydrogen bonds. You can see zero-point energy with a pH meter.

The authors measure the change in the pKa [acidity] with H/D substitution of the different amino acid residues in the active site of KSI. Significantly, they find that for one of the KSI tyrosine's the pKa change is much larger than the change in water. Furthermore, they calculate this change using an ab initio path integral molecular dynamics simulation, obtaining a value in reasonable agreement with experiment.

The large isotope effect arises because of the significant quantum delocalisation of the protons in the H-bond network near the tyrosine's. This is illustrated in the figure below, showing the probability of finding a proton along the co-ordinate associated with proton transfer between the two different tyrosine's [when nu_16=0 the proton is equidistant between the Tyr16 and Tyr57 residues].


The simulation is a real tour de force. It uses a "force field" calculated "on the fly" from density functional theory with the B3LYP-D3 functional.
These simulations treat both the nuclear and electronic degrees of freedom quantum mechanically in the active-site QM region and also incorporate the fluctuations of the protein and solvent environment in the MM region. The simulations consisted of between 47 and 68 QM atoms and more than 52,000 MM atoms describing the rest of the protein and solvent. 
These simulations, which until recently would have been computationally prohibitive, were made possible by 
accelerating the path integral molecular dynamics convergence using a generalized Langevin equation, 
using new methods to accelerate the extraction of isotope effects, and 
exploiting graphical processing units (GPUs) to perform efficient electronic structure theory evaluations through an interface to the TeraChem code. 
Such a combination yielded almost three orders of magnitude speedup compared with existing AI-PIMD approaches.
Being able to perform such detailed stimulations will allow critical examination of controversial claims that short hydrogen bonds and proton tunnelling is a key ingredient in the functionality of specific enzymes.

Wednesday, January 21, 2015

Where is all this blog traffic coming from?

Normally this blog attracts about 700 page views per day, according to blogspot. However, yesterday it got 5000! I have no idea why. Presumably someone with a significant following Tweeted it.
If you know the answer, please let me know, even if you are a robot!


I have not seen a traffic increase like that this since I pointed out that Greg Scholes' "quantum biology" paper in Nature involved fitting 20 data points to a curve with 17 parameters.

Tuesday, January 20, 2015

The baby Natures: exclusivity for the masses

The Economist recently ran a report, entitled Exclusivity for everybody with the subtitle "The modern luxury industry rests on a paradox, but is booming nonetheless."
The paradox is that luxury/status brands such as Gucci, Cartier, Louis Vutton got their name because they were so exclusive [expensive]. But now they are mass produced and mass marketed to middle classes, even in the Majority World.

I realised that this is just what the mother of luxury journals, Nature Publishing Group, has done too. Now everyone can have a Nature paper too!

Monday, January 19, 2015

How does your audience feel?

Last year Physics Today had an interesting article
Psychological insights for improved physics teaching
Lauren Aguilar, Greg Walton and Carl Wieman

It generated a lot of letters in last months issue.
I think it raises some issues that are not thought or talked about enough. Here, I just want to suggest that psychology does play a role in research seminars and conference seminars too. Speakers and their messages are not just judged on their scientific merits. In particular, our views are sometimes influenced by our emotions, positive or negative.

Over the past year I think I have heard talks that have evoked in me responses such as

negative- boredom, confusion, frustration, anger, feeling inadequate, ....

positive- excitement, intellectual stimulation, curiousity, feeling clever, ....

The former can come from talks that are obscure, too technical, poorly prepared, patronising, or full of hype...

I have to confess, that as much a I try to be objective, I think my negative evaluations are amplified by the emotions.

Positive emotions can come from actually learning or understanding something new. Here I have an anecdotal observation. I think I have noticed that some of my colleagues evaluations of speakers, job candidates, and Ph.D candidates is greatly embellished when they learn just one thing from a talk, even if it is something really basic, that they did not know or understand before.

Friday, January 16, 2015

Should funding agencies spread the money around?

Yes.

The whole process of applying for [and mostly not getting] funding can be very frustrating. Generally, I am empathetic to colleagues who share their disappointments with me. However, there are two situations I am not particularly sympathetic too.

Professor A is well funded and applies for an extra grant and does not get it.

Professor B's grant application is successful but does not receive the full requested amount.

I am even less sympathetic when A or B's spouse complains to me about this.

These decisions need to be considered in a broader context. Funding agencies do have limited budgets and they need to consider what is going to be for institutions and a country in the long term.

Consider the following vignettes of different faculty.

John Smith is 45 and holds multiple grants. He has 3 postdocs and 11 Ph.D students. He publishes in luxury journals.

Sue Jones has been an assistant professor for 3 years and has one Ph.D student, funded with start up funds. She is yet to get an external grant.

Jane Doe is 60 and a member of the National Academy of Sciences. She does not have enough money to hire a postdoc. She often publishes PRLs based on international collaborations.

Joe Blogs is 50, but has not had an external grant for one year. Next year he won't be able to even pay for liquid helium for his lab or travel to conferences.

Steve Sun has tenure, one grant, and two Ph.D students. Occasionally he gets postdocs on external fellowships.

If I honestly look at the quality of the science these faculty are doing it is comparable, particularly if I factor out the hype, luxury journals, and factor in output relative to resources and opportunity. Saying one is better, or more strategic, or promising, is really subjective.

So, who should I fund if I have enough money for only 2 or 3 grants?
It is a hard call.
Consider what would be best for the country and field as a whole.
John will probably just do more of the same, and will power on regardless of whether he gets another grant. It may actually better for everyone if he got more focussed, both on topics and people.
Sue not getting a grant may mean she does not get tenure, which could mean a big waste of her and her universities time and resources. If she limps through, her career may never really take off and she will be a burden.
Given Jane's career experience and wisdom, an investment in a postdoc for her could be a strategic one.
If Joe does not get a grant, his research program may shut down and he will spend the last 15-20 years of his career, not doing any research, but still costing the university a lot of money.
Although an extra grant for Steve would be nice it is not essential to his survival.
If I was making the final call I would probably not give two grants but three smaller grants to Sue, Jane, and Joe.
What would you do?

I hope this illustrates the complexity of distributing funding. On the one hand you want to reward excellence and dot want to promote equity. You want to allow people to expand in to new areas. But you also need to consider things from a broad perspective.

Different countries handle this quite differently. 
In the USA there is a significantly different success rate for "renewals" and new applications. In Australia, there is no such distinction. Traditionally, Canada has given out a lot of small grants, so the success rate is high and most faculty have one grant so they can survive. Most faculty cannot afford to hire postdocs. Yet Canada is moving towards a more "elite" system. In contrast, in Australia, just a few faculty have grants and they are substantial compared to North America. But, funding is becoming even more concentrated among those associated with "Centres of Excellence". In Europe many faculty have a guaranteed level of funding that is associated with their position, until they retire.

My main point is that I think the money should be spread around more than it is most countries. However, to what extent and how I am not sure.

I welcome discussion.

Thursday, January 15, 2015

Satire of reductionism run amok

The "cartoon" below appeared at CERN.
I learnt about it from a commenter on Peter Woit's excellent blog, Not even wrong.


Note, "The problem of condensed matter: they still don't get it".