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Comment: Re:and yet, the GOP blocks private space. (Score 3, Informative) 96

by the gnat (#49706419) Attached to: Russian Rocket Crashes In Siberia

It goes against every instinct in my body to defend the GOP, but it's a bit unfair to attack the party for "block[ing] private space" when just below this article was another article about Congress making policy to suit the private space industry, mainly on the Republican side:

The commercial space industry had a great day on Capitol Hill on Wednesday, with the Republican-controlled House Science Committee giving it most of what it wanted while swatting away proposed changes from the minority Democrats.

Among the goodies approved by the committee: a decade-long extension of the moratorium on regulating commercial human spaceflight; a nine-year extension of industry-government cost sharing for damages caused by launch accidents; and an act that would give companies property rights to materials they mine from asteroids.

Comment: Re:Lies! Lies! All lies! (Score 1) 284

by the gnat (#49683841) Attached to: Third Bangladeshi Blogger Murdered In As Many Months

You can't say the same about Muslims when they commit acts like this, because they are expressly commanded by Muhammed either in the Quran or the Hadith (honor killings, killing apostates, drawing images of the "prophet", etc.).

Honor killings are definitely not prescribed by Islamic law. They tend to be most common in Islamic societies because these societies are - let's face it - relatively primitive and more family-oriented (not in a good way). But I've read about Hindus doing the same thing, and I suspect that was even more common when the caste system held sway. (It's the same deal with female genital mutilation - not at all Islamic, but mostly-but-not-entirely practiced by certain Islamic societies.)

Comment: Re:Nice but... (Score 2) 55

by the gnat (#49647277) Attached to: Electron Microscopes Close To Imaging Individual Atoms

Other than the obvious loss of information, I'd be interested in knowing what pitfalls come up that are specific to this case. To make things a little more concrete, take the case of a GPCR dopamine receptor. Supposedly dopamine (or one of a variety of drugs) interacts with this receptor in such a way that a different region changes conformation which in turn alters the conformation of a G-protein so that it binds GTP. This all seems to require very specific protein conformations and I can see how observing the average of many could be misleading.

Well, the main pitfall is what I already mentioned - if the conformations being averaged really are very different, this will decrease the effective resolution of the reconstruction, which will be very obvious even to an untrained eye. EM used to be notorious for producing vague blobs, in part because of the limitations of the technology (before they had direct electron detectors and had to use film), but also because the software tools (and users) weren't as good about picking out different conformations. And when the individual protein domains (often of known structure) resemble spheres in the reconstruction, it's difficult to tell that something isn't working. So it was indeed possible to generate a map that was a misleading average, and there are probably structures like that out there. But that's why everyone relied on crystallography for detailed structural information.

The good news is that at the resolution range people are using now, it should be possible to build individual structural components, but only if the particles are nearly homogeneous. So the ability to build (or dock) atomic models that clearly fit the map on the level of individual amino acids becomes a test for whether the averaging is justified.

The case you mentioned isn't really applicable, because the GPCR only assumes that conformation when bound to dopamine, and tends to work like a molecular switch. And of course if we did have a range of conformations being looked at, the reconstruction would resemble a soup can, without any atomic detail, which isn't really a publishable result. GPCRs are so small that it's currently better to use crystallography, but there are indeed structures of GPCRs in various static states at high resolution.

The remaining problems are that a) proteins aren't really static and b) the experimental methods for structural studies may induce non-physiological artifacts. I don't think (a) is that much of a problem because we have plenty of ways of studying protein dynamics and everyone is implicitly aware of this limitation anyway. The second problem is potentially worse: purification can sometimes have weird effects, crystallization packs molecules into a lattice that may not represent the native conformation, both crystallography and EM typically work at cryogenic temperatures which is known to change the structure in various ways (mostly but not always subtle), radiation damage can have side effects too. Much worse are the older "negative stain" EM structures where the proteins were covered with uranium or something similarly massive and sandwiched between thin sheets of carbon. Fortunately this is much less common now that cryo-EM has gotten so much better.

Ultimately the value of any model is determined by its ability to explain biochemical data and suggest new testable hypotheses. That's ultimately the most important way to validate their accuracy, and researchers ignore it at their peril.

Comment: Re:Nice but... (Score 4, Informative) 55

by the gnat (#49643233) Attached to: Electron Microscopes Close To Imaging Individual Atoms

I really do hope the people doing this have examined and discussed the possible pitfalls of drawing conclusions from averages of this type of data.

Yes, the pitfalls are well known, mostly because this has always been an issue with crystallography as well - it is impossible at present to determine the 3D molecular structure from a single molecule, so we are always dependent on either crystalline diffraction or averaging thousands of images to obtain the density map. (NMR has its own, well-understood problems.) The good news is that we known enough about macromolecular structure to be able to make subjective judgements very quickly based on the level of detail in the maps. (There are also plenty of higher-resolution structures of many smaller components, so we can calibrate our expectations based on known parts.) If the molecules are very heterogeneous, or the averaging is done poorly, the maps will not display known high-resolution features such as secondary structure or amino acid sidechains. For crystallography, there are also ways to calculate the deviation from the average (and I presume EM either has something analogous, or will soon). It is also common for some regions to have higher "local resolution" than others, and this can be quantified in various ways.

These methods still lose information - if, say, 10% of copies of a particular loop or sidechain are in a different conformation, this will probably not be captured. But EM experts have gotten much better about identifying clusters of similar conformations, at least on a larger scale. And in the end, the static average structure is still vastly more useful than no structure at all. Scientists can and do still publish spectacularly stupid interpretations occasionally, but these aren't due to the misuse of averaging, but rather to pure incompetence and wishful thinking.

Comment: Re:Nice but... (Score 4, Informative) 55

by the gnat (#49642015) Attached to: Electron Microscopes Close To Imaging Individual Atoms

There's another technical objection to the summary: "atomic resolution" in this context isn't the same thing as "imaging individual atoms". The actual cryo-EM images themselves are much noisier and do not have nearly this effective resolution - it is the average of many thousands of images that gives you atomic resolution electron density maps. (The same is true for X-ray crystallography, although you start with just Fourier amplitudes there, not images.) That's not a slam on the paper, which is an impressive technical achievement, but as the authors note, many conformationally homogeneous single particles (i.e. protein complexes) are required to get a map of this quality. Any differences between particles will simply be averaged out, and the more different they are, the worse the resolution.

Comment: Re:Sad state of research in the West (Score 1) 182

by the gnat (#49539035) Attached to: Chinese Scientists Claim To Have Genetically Modified Human Embryos

We've been hindered by what is basically a cult ideology about unborn life that we cannot do experiments like this (legally) in the west.

The fact that this experiment was done in China rather than "the West" has nothing to do with religion. The application of the CRISPR-Cas system for genetic modification was only discovered in 2012, and molecular analyses and proof-of-concept experiments - performed in the US and Europe, mostly - are being published in high-profile journals almost every month. There are, at last count, at least three companies (two in the US, one in Europe) founded by the scientists who elucidated the mechanism that have the explicit goal of human gene therapy. In fact, one group (in the US) just demonstrated in vivo genome editing (in an animal model, because only a lunatic would try this experiment in humans first).

There is no legal barrier to performing these experiments on human embryos in the US or Europe. In the US, I believe researchers are still prohibited from using NIH funding for such experiments, but that would not stop them from using private funding (and at this point, VCs and private donors are practically flinging sacks of money at this system). Their hesitation is based on concerns about the ethics of potentially lethal experimentation on unwilling test subjects. No, not the embryos, but the hypothetical live births that would result from implantation. If they're really, really lucky, the off-target effects will be silent or embryonic lethal. If they're unlucky - and given how new the system is, it's very difficult to guess what would happen - they'll wind up creating new genetic afflictions. Everyone working on the system is very excited about the potential applications to human health; no one wants to bring the field to a premature halt by rushing into human experimentation and accidentally causing severe birth defects because they didn't understand how it worked well enough.

There is a secondary issue, which is that China is almost pathetically desperate to prove it can do the same caliber of science as the West, to the extent that it's starting to throw money at non-Chinese researchers to set up labs in China, and offers large bounties for high-profile publications. (They're also known to be desperate for a Nobel prize in the sciences.) So far they've tended to just cherry-pick relatively easy, unimaginative projects following up on research done in the West (to be fair, Western scientists have done this among themselves for decades), rather than making entirely novel discoveries. Thus there is an enormous financial (and social) incentive to jump into a fast-moving field and try the obvious - but ethically dubious - application to human health.

Comment: Re:Darwin by proxy (Score 1) 616

by the gnat (#49532241) Attached to: Bill To Require Vaccination of Children Advances In California

If only it were that simple. Unfortunately, the classroom full of unvaccinated children may contain one of the few unlucky ones who have legitimate medical reasons for not being vaccinated. The fact that there are a small fraction of people like this, dependent on herd immunity for their protection, is one of the reasons for compulsory vaccination.

Comment: Re:The Chinese advantage (Score 1) 226

by the gnat (#49372183) Attached to: Chinese Scientists Plan Solar Power Station In Space

When your government is full of engineers, not lawyers, and when you can just ignore the flat-earth lobby instead of wasting half your funding fighting their just-because-we-can delays, you can test ideas like this.

Also useful: when your government is full of unelected bureaucrats who aren't held accountable by voters, completely dominate the news media, and stomp on any popular organization or sentiment that they don't control, and thus are free to ignore the interests of their citizens and instead spend money on wasteful, thinly-disguised military projects.

(Except, of course, that's not what's actually happening in this case - the article summary makes it sound like "OMG China will dominate space", because of course that's more interesting than "superannuated Chinese scientist spouts nonsense".)

Comment: Re:Simplr math ... (Score 1) 353

by the gnat (#49367445) Attached to: Former HP CEO Carly Fiorina Near Launching Presidential Bid

I think her target market is Republicans who want a viable female challenger to Hilary. Realistically, she's setting herself up for Sec. of Commerce, or maybe, if she's extremely lucky and does moderately well in the primaries, VP. I am no fan of hers for all of the obvious reasons, but she is a rocket scientist compared to Bachmann and Palin.

Comment: Re:Cowards! (Score 1) 299

by the gnat (#49303245) Attached to: Scientists: It's Time To Resolve the Ethics of Editing Human Genome

These people want to put a stop to progress because they think humans are some kind of holy ground that must not be tred upon.

Actually, those people are involved in (at current count) at least two companies that have targeted therapeutic modification of humans as their primary business goal.

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