Is there an easy way to actually find an article for Nature Communications without a title if you know its article number? Nature's search has the same problem - if you look for article 1, you find all the other articles: www.nature.com/search/advan...

This is the work of Grace Luettgen, a very talented @jhu.edu Physics + Biophysics undergraduate - so keep an eye out for her!

Lots of other predictions, tests. We are hoping this stimulates some further experiments to try to prove us wrong! In particular, our model would predict that cells should be attracted to a particular point in the device - and we don't see this immediately in the data (but can't rule it out).

Why does internalization matter for chemorepulsion? Internalization decreases the amount of bound receptor. If you inhibit it, you get more bound receptor - and you get attraction again!

We then propagate error from the noise in the ligand-receptor binding to the noise in the response, and work out the signal-to-noise. The triangle is the 0-500 ng/mL experiment - repelled! The square is the 0-100 ng/mL experiment - attracted!

Why does response switch from increasing to decreasing as you go toward larger chemoattractant (larger probability of bound receptor)? If A and I are nonlinear functions of the bound receptor, the ratio of the two R = A/I can easily switch between being increasing and decreasing- chemorepulsion!

Then we take an idea from earlier work on growth cones and assume bound receptor regulates the eventual response of the cell via a nonlinear feedforward loop.

Because we know internalization is important, we start with the simplest possible model for ligand-dependent internalization, which does reasonably at capturing the timescale for the experiments.

Malet-Engra et al. find chemorepulsion depends on endocytosis doi.org/10.1016/j.cu... - so maybe cells take in CCL19, shaping the gradient around them, somehow reversing it, akin to self-generated gradients? We don't rule this out, but think the data can be explained at a single-cell level.

Fair!

Yes, those of us who aren't playing in that league have to show productivity in other ways. I had ~4 first author postdoc papers published when I got my offer- but I still think the preprints are valuable because they let you talk in more detail about the stuff you're most excited about.

Preprints are clearly doing well at helping life move forward despite unreasonable review times [we preprint everything!], but the risk is that search committees start to overvalue prestige.

This is the right perspective IMO. Research gets accelerated by finding a new starting place - great if that can be catalyzed! If a conversation with an expert goes, "Didn't Prof. Jones or someone at University X use a similar approach in 1995?" it's still useful even if it's Prof. Johnson in 1997.

I was curious about the numbers. This claims that ~17% of postdocs are H1B holders: www.cupahr.org/resource/dat... - so this would be a de facto exclusion of those 17%. Probably more worrying is the difficulty hiring international faculty, who would mostly have to start on H1B

I think that's a pretty analogous case! Award given for early work that may not be the most influential of their career - but possibly the award wouldn't have been given without the later work. I guess Hinton for Boltzmann machines also fits - though that was also the most "physics" topic.

Conflict of interest note: really, I'm just cheering for grad school classmates who did some of the cool quantum computing work to get recognized.