How to finish your Ph.D thesis

Just write it!
Stop procrastinating. Take responsibility.
Don't wait for permission, guidance, or feedback from your supervisor, advisor, committee, or anyone else.
The more you have written and "complete" the greater the pressure on the supervisor, department, and university, to o.k. submission of the thesis.

With supervisors who are tardy/slack/lazy/negligent/disorganised about feedback make sure meetings, submissions of drafts, and requests for feedback are documented in emails.

Another crazy metric?

I have been looking at some books about better writing since next year I am going to be giving a couple of workshops on this. 

I was really intrigued that one book mentioned the Flesch Reading Ease Score which is defined by the equation:

A sign that this is a "widely accepted" metric is that it is incorporated in Microsoft Word.

The main thing that bothers me is the number of significant figures in the coefficients.

But also, surely you could devise the metric so that it actually does give values in the range 0-100, like most guides claim. Pathological text can produces negative values or values greater than 100.

Correlation or causation?

This xkcd cartoon features in an interesting article in the Economist Triumph of the nerds about how the internet has changed the world of cartoons.

Deconstructing excited state dynamics in a solvent

What determines the excited state lifetime of a chromophore in a solvent?
What are the relative importance of the polarity of the solvent [dielectric relaxation time] and the viscosity?

The key physics associated with the solvent polarity is that the dipole moment in the ground and excited states are usually different and so the solvent relaxes and there is an associated redshift of the emission. The viscosity is particularly relevant when there is intramolecular twisting and this motion is usually overdamped.

This problem is of fundamental interest because it concerns overdamped quantum dynamics.
It is of applied interest because significant biomolecular sensors make use of the sensitivity of specific chromophores [e.g. Thioflavin-T binding to amyloid fybrils].

Two recent papers from Dan Huppert's group raise three important questions for me.

An Accounts in Chemical Research
Molecular Rotors: What Lies Behind the High Sensitivity of the Thioflavin-T Fluorescent Marker?
raises the question:
1. What is unique about Thioflavin-T? 
How are the photophysical properties fine tuned?

The authors give convincing arguments as to why Thioflavin-T works. Some of these are reviewed in this earlier post.

However, given there are lots of other chromophores which undergo excited state twisting to dark states [see e.g., this review] it is not clear to me why all these other molecules don't work just as well as Thioflavin-T?

The excited state dynamics is interpreted in terms of the figure below where there are two distinct excited singlet states:

A local excited state (LE) and a twisted intramolecular charge-transfer (TICT) state.

2. Are the LE and TICT states distinct? 

In the simplest two-diabatic state picture there is a single excited state and as the chromophore twists this smoothly evolves from a bright state at the Franck-Condon point to a dark TICT state. This is what Seth Olsen and I found for the chromophore of the Green Fluorescent Protein [see our recent J. Chem. Phys. paper].

The paper
Temperature and Viscosity Dependence of the Nonradiative Decay Rates of Auramine-O and Thioflavin-T in Glass-Forming Solvents
reports that over more than three orders of magnitude the excited state lifetime is proportional to the viscosity and to the dielectric relaxation time.

This raises a subtle issue: causality vs. correlation. The authors point out that in the simple theory of a dielectric liquid the viscosity and the dielectric relaxation time are proportional to one another.

3. Can one separate out the respective contribution of the polarity of the solvent and of the viscosity?

There are two distinct reaction co-ordinates here: the motion associated with each is overdamped. One co-ordinate is the intra-molecular twisting of the solute and which couples to the viscosity of the solvent. The other co-ordinate is the local electric polarisation of the solvent which couples to the dipole moment of the excited state.

Rocket science for children

Yesterday I did some science demos at a kids holiday club, using the Coke-Mentos fountain. Previous efforts led to the post Developing science demonstrations that actually teach science. It is fun and cool to do spectacular demonstrations that cause kids to go "Wow!" and think that science is "fun". But these also need to be a vehicle to teach something about critical thinking and the process of doing science.

Small initiatives can help. For example, I had one child record the height of each of the fountain, that was estimated by the group. This emphasized that measurement, error estimation, record keeping, and comparisons are key parts of doing science.

Aside: Yesterday I thought the Coke-Mentos fountain was higher than last time, particularly for diet Coke. I suspect the fact that is was a hot day helped, increasing the solubility of the carbon dioxide?

We also did Film canister rockets which the kids always enjoy.
I found it amusing that the kids ran off and told their friends they were doing "rocket science".

My questions about condensed phase photochemistry?

For the excited state dynamics of a specific chromophore in a solvent what are the essential degrees of freedom (electronic, vibrational, and solvent) that must be included in a model Hamiltonian?

What determines if the excited state dynamics is classical, semi-classical, or fully quantum? Under what conditions does the Born-Oppenheimer approximation break down?

For a specific photochemical reaction what are the relevant vibrational degrees of freedom? What determines the relative importance of stretching, torsional, and pyramidal vibrations?

What determines the branching ratio for passage through a conical intersection? Relevant parameters may be the slope at the intersection, slanting, size of the wavepacket, and the distance of closest approach (impact parameter)

What is the interplay of the electronic, vibrational and solvent degrees of freedom in excited state dynamics?

What determines the relative importance of the viscosity and the polarity of the solvent for the dynamics? What is the role of the spatial inhomogeneity of the solvent?

In the presence of a solvent what are respective criteria for the localization/delocalization of electronic and/or vibrational excitations over different parts of the chromophore?

What are definitive experimental signatures of delocalization?

What are definitive experimental signatures of breakdown of the Born-Oppenheimer approximation?

What is the role of the solvent in non-adiabatic processes?

Questions about protein folding

What is the physical code that relates the amino acid sequence to a proteins native structure?
How do proteins fold so fast?
Can protein structure be computationally predicted?

These are highlighted as key questions in a nice readable review in Science The Protein Folding problem, 50 years on by Ken Dill and Justin MacCallum.

The article gives a sober assessment of limited but significant achievements and the substantial challenges ahead.