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February 9, 2012

The Elsevier Boycott and the Research Works Act

Perhaps you’ve heard about the Elsevier Boycott aka the Cost of Knowledge. I’m not going to rehash the problem we all know so well. But here are a few links I wanted to share. Just fyi, Elsevier’s take home (EBITDA) is about $500 million/year. That’s about a quarter of what Starbucks makes. Or about 7-fold more than Newport Corporation makes. And as the graph above shows, a good chunk of the revenue is from their scientific publications. Making money is great. I only bring it up to highlight the magnitude of money that is being made. It’s not peanuts.

I’m inclined to believe that most publishers are well aware that their business model needs to evolve. I think most of them know that although their contribution to the scientific process is important, it is only a small part of the entire process now that distribution (and even basic typesetting) is quite trivial. I have this positive view because I’ve spoken personally with editors at top tier journals and this is the impression they left me with. They seemed very interested in finding new ways to contribute to the scientific process and increase the value of their services.

Apparently not all of the commercial scientific publishing world is so reasonable.

A DrugMonkey post pointed to this article by a UK publishing industry representative named Graham Taylor. He dissects it quite well. Here’s an excerpt:

From Graham Taylor’s article: “Public funds have not paid for the peer-reviewed articles that are based on research supported by agencies such as the National Institutes of Health (NIH). They have only paid for the research itself and whatever reports the researchers are required to submit to the agency.”

DrugMonkey: Another falsehood, wrapped up with a disingenuous misdirecting belittlement. “Only” for the research? ONLY????? These publishers seem universally unaware that the VAST, VAST majority of the value of an academic article is the bloody research. The damn content. That is what has value. The fancy layout? That’s nice and all but we can do without that. The science is the thing. Trying to dismiss this as a minor contribution is…well…..that takes some serious chutzpah.

If publishers fail to adapt to the changes in technology that threaten their business model, then that’s a problem that scientists don’t necessarily have to worry about. There are plenty of new journals with excellent editorial oversight that are more than capable of taking up the slack. However, the big problem we all need to pay attention to is when publishers try to change laws to prevent the free distribution of research results. The current effort is a bill called the “Research Works Act”. As Michael Eisen describes in his blog, the bill is written to outlaw the free dissimination of taxpayer-funded research in order to protect the anachronistic business model of publishers like Elsevier.

The bill reads:

No Federal agency may adopt, implement, maintain, continue, or otherwise engage in any policy, program, or other activity that:
(1) causes, permits, or authorizes network dissemination of any private-sector research work without the prior consent of the publisher of such work; or
(2) requires that any actual or prospective author, or the employer of such an actual or prospective author, assent to network dissemination of a private-sector research work.

And the bill’s definition of “private sector” includes all NIH-funded research carried out at universities.

They are using intentionally misleading language to distinguish works funded by the government but carried out by a non-governmental agency as “private sector research”. Thus, under this bill, works funded by the NIH but carried at a University would be “private sector research”.

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February 8, 2012

Predatory open science funding

There are some open access journals that seem to have relativley loose editorial standards. And by “editorial” I mean “ethical”, and by “relatively loose”, I mean “no”. These publishers have been called “predatory” open access publishers. The idea is simple: solicit submissions via spam email, accept submissions, and then charge publication fees that more than cover the cost of your spamming operation. Here’s a list of predatory open access publishers. Richard Poynder did a very in depth story on this phenomenon. If you’re interested to know more, read the PDF linked to on this blog post. The bottom line is, it works. At least some people send papers to predatory open access journals and pay to have them published. And that’s why any email address you’ve used as a corresponding author will get inundated with spam from these outfits.

What’s new– to me at least– is what seems to be predatory micro funding for scientific research. Microfinance has been used for many years to get enterprises off the ground. More recently, groups like Kickstarter have developed web sites to finance proposed creative and technology projects. Kickstarter is cool. It’s all above the table, as far as I can tell, and has many success stories.

By contrast, the Open Source Science Project is sketchy as hell. Here’s the model: researchers post project proposals and funders browse and decide what they want to fund. This is very similar to Kickstarter. However, the business makes money by charging the researchers monthly subscription fees. At this point, I’m gone. That’s the only red flag I need. But there are other red flags too: zero success stories, endless attempts to look legit by association (a bunch of university and industry logos all over their site), the “Privacy Policy” and “Terms of Use” do not actually link to anything, and the identity of the people running the organization is not revealed anywhere. There is no evidence that anyone has ever had a project funded through their system.

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January 26, 2012

BCG Matrix

Here’s a BCG Matrix for scientific papers. One paper is plotted on the graph. At Nature’s Action Potential blog, the editor explains why they accepted it. This is an interesting step towards greater transparency. Where do other papers you like lie on this graph?
(Hat tip to JT)

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January 17, 2012

NIH stats

Success rate for all grants at NIH in 2011 = 18 %
Success rate for New Investigators = 15%

More stats at Sally Rockey’s blog.

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December 31, 2011

Optimizing pulse frequency for 2p imaging

The lasers used in multiphoton imaging deliver their photons in pulses. Many commonly used systems pulse at 80 MHz. However, there are good reasons to try different frequencies.

In 2007, Donnert, Eggeling, and Hell published a Nature Methods paper where they used low frequency pulses to get more fluorescence signal out of the preparation. The idea was that many molecules get excited into triplet states that are long-lived. By having a long time between pulses, there is time for the molecules to fall back down into the ground state so that the next pulse will have a large population of molecules available to be excited.

The next year, Ji, Magee, and Betzig published a Nature Methods paper where they used high frequency, low power pulses to get an increase in signal-to-noise ratio with two-photon imaging.

Several people have been confused by these apparently contradictory results. Recently there was a discussion on the Confocal Listserv about this topic, again pointing out the differences between the two papers.

Andrew Ridsdale chimed in with his thoughts (link to post). One of his points is that n different experiments, different factors are limiting the signal.

In Hell’s experiments with low pulse rates, they were imaging cell-free molecules– a very bright signal. Bleaching (triplet-state occupancy) was the limiting factor, rather than damage. Because there weren’t even any cells around to be damaged, other than E. coli cells in the last figure. So allowing for relaxation time and maximum occupancy of the ground state gave the best results. All of the relevant processes were governed by 2p excitation and thus were second order.

In the Ji, Magee, and Betzig experiments, the signals were very dim and the limiting factor was damage to the preparation. Andrew’s point seems to be that in this case, the signal is coming from second order processes and the damage is from higher order processes, maybe even as high as 5th order, though they estimate it to be on average about 2.4 order. So in this case, it’s best to use pulses that are just barely effective for 2p excitation and completely ineffective for higher order processes (damage), and then blast the prep with as many pulses as possible. Since the likelihood of a 2p event is already low, bleaching isn’t as much of a factor.

(btw, Brain Windows did a very nice post on the Ji and Donnert papers)

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December 11, 2011

Teaching MATLAB

In a previous post, I gave the two line MATLAB code to generate a Gabor patch. At the other end of the spectrum, this web page spends an entire MATLAB tutorial on making a Gabor patch. It’s a great neuroscience example for someone learning the methods of MATLAB programming.

If you’re interested in stuff like this, it’s from UCL’s Institute of Cognitive Neuroscience’s MATLAB tutorial class. A lot of their class materials are online. (link) Also, this book isn’t a bad place for a beginner to start.

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November 30, 2011

An Arch-based voltage sensor

The newest voltage sensor is from Adam Cohen’s lab and based on a microbial rhodopsin, a class of light sensitive proteins already being put to use in optogenetics.

In this case, they’ve take Archaerhodopsin 3 (a related protein to Arch, which has been used to hyperpolarize neurons and silence activity) and removed it’s ion fluxing ability. But since it still senses voltage and light, its optical characteristics change with voltage.

How does it compare with existing voltage sensors? It has a relatively large change in fluorescence over a physiological voltage range (about 50%), but it’s very slow (41 ms onset). They can nicely see APs in single sweeps in cultured cells. In slices and in vivo, the signals will be smaller. One of the best voltage imaging schemes around, DiO+DPA, has a similar fluorescence change and is way faster (<1 ms). Note that signals from Arch(D95N) in culture (top picture below) don’t look massively better than DiO+DPA in slice (bottom picture below). Hopefully Arch(D95N)’s signals will still be usable in slices and in vivo.

Arch(D95N) in culture

DiO+DPA in slice

But of course, having a genetically targettable construct is a huge advantage. So a fairer comparison would be to other voltage sensing proteins. In that case, Arch(D95N)’s fluorescence change is excellent, but its slow speed is a handicap and makes that big fluorescence change less useful. Perhaps the biggest problem with Arch(D95N) is that it’s dim. The quantum yield is 9e-4 and an EMCCD was required for these experiments. For comparison, many GFP based proteins have quantum yields over 5e-1. It’s extiction coefficient is decent– it absorbs light– it’s just really unlikely to emit a fluorescence photon.

Maybe the protein engineers will follow up and make a brighter and faster version, the authors themselves report that they’re actively working on speed. For what it’s worth, the native protein (with it’s fluxing capability intact) is much faster, so there’s hope on that front.

Knopfel has taken perhaps the most rigorous and deliberate approach to voltage sensing protein design. The first big problem is that the sensor has to be at the membrane, so unlike calcium sensors, the signal-generating ROI is pretty small. The second big problem is that the sensor adds an unnatural capacitance to the membrane, so when expression levels increase to improve S:N, the capacitance also increases and messes up excitability. They have a nice analysis in this paper.

Nevertheless, there’s a lot to do with voltage sensors and I don’t think people have really started to fully explore what they’re capable of. These systems don’t need to be perfect, there is a huge amount of physiology to explore even using the existing voltage sensors.

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Arrests likely in Olympus case

If you live in Japan, then you’ve already been updated by the nightly news over the past few weeks. For those of you for whom this has slipped under the radar: Olympus, the 92-year-old company which includes the microscope business, is likely going to be dismantled due to massive fraud that may involve upcoming arrests.

Olympus, Tokyo Police, and Japan’s version of the SEC have all worked to piece together what former management did to cover losses in the 90s and 00s. It’s at least on the order of 100s of millions. Currently there is talk that yakuza may be involved in some of the shady financial dealings. Olympus is probably going to be delisted, but could still avoid that fate.

The short version is that Olympus hid losses in the 90s, then covered it up for quite a while. Recently they hired a new CEO, that guy questioned the former dealings, Olympus fired him, the scandal broke, the stock plummetted, and so they fired some more people and are trying to come clean. The stock rebounded a bit now that it seems that Olympus is trying to sort stuff out. But they’re still in a heap of trouble and could be ripe for a takeover.

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October 1, 2011

Sense of scale

The vast majority of the time, I buy what I intend to. Like the old maxim from construction: “Measure twice, cut once”, I always take care to ensure I’m ordering the right thing. At least when things are expensive. When they’re cheap, I’m less careful. Check out the photo above. I thought, “Sure, that’s the bench vice I’m looking for.” It was so inexpensive, that I went ahead and ordered it without much thought.

I don’t know how big that vice looks to you, but I was surprised when it arrived. Click through to get the sense of scale…
Read the rest of this entry »

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September 26, 2011

Art – Neurobiology art by Greg Dunn

Greg Dunn, a grad student at Penn, is a gifted artist. His work combines the geometry of neuronal arbors with the spare aesthetics of east Asian watercolor art.

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