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siyer

258 karma · joined October 7, 2013

I'm a PhD student in Bioengineering at Stanford University. I do neuroscience research on using optogenetics to control pain.

http://stanford.edu/~smiyer/

submissionscomments
siyer··on Optogenetics Hardware Setup
Specifically in the peripheral nervous system, there's been some work along these lines, primarily in anesthetized experiments, using ChR2-expressing stem cells, which integrate into denervated nerves, and enable optogenetic control of the previously denervated muscles. See here: http://www.ncbi.nlm.nih.gov/pubmed/24700859

We wrote a review recently about what's been happening in optogenetics in the peripheral nervous system/spinal cord. That's here: http://www.ncbi.nlm.nih.gov/pubmed/27147590

siyer··on The Curse of Culture
Within pharma, Derek Lowe has been blogging for many years, with a mix of posts focusing on new developments as well as broader strategic questions. http://blogs.sciencemag.org/pipeline/ The comment section there is also typically informed.
siyer··on This Biology Book Blew Me Away
And you feel every ounce of those when reading them. Most good versions of this class of book are this heavy (typically prescribed for the late 'undergrad'/first year grad introductory class reading). The neuroscience equivalent (Kandel, Schwartz, Jessell) is 8.7 pounds, with very thin pages.
siyer··on The Facebook Papers, Part 1: The great unbundling
It refers to the Graham Holdings Company which used to own The Washington Post, still owns Slate, and also owns Kaplan.
siyer··on “Heroes of CRISPR” Disputed
See: http://www.ipscell.com/2016/01/patent-expert-weighs-in-on-cr... and https://law.stanford.edu/2015/12/29/the-crispr-patent-interf... They're mostly specific to Cas9.
siyer··on Scientists bust myth that our bodies have more bacteria than human cells
See also: Ed Yong in The Atlantic, who has a nice story on this that includes some rather fun sentences [1]: http://www.theatlantic.com/science/archive/2016/01/youre-pro...

[1] Such as: "In 2014, Judah Rosner from the National Institutes of Health drew attention to this “fake fact” in a letter to Microbe magazine. More recent estimates, he noted, put the total number of human cells at anywhere from 15 trillion to 724 trillion, and the number of gut microbes at anywhere between 30 trillion and 400 trillion. Which gives a ratio that can best be expressed as ¯\_(ツ)_/¯."

siyer··on Ketamine’s effect bolsters a new theory of mental illness
On the mechanistic side of things, http://www.pnas.org/content/112/26/8106.short is one of the more interesting papers to come out recently on ketamine's mode of action.
siyer··on Thoughts Can Fuel Some Deadly Brain Cancers
Stanford's release on this goes into more scientific detail, and has a nice interview with the senior author in which she discusses the background behind the work.

http://med.stanford.edu/news/all-news/2015/04/brain-tumor-gr...

siyer··on Ultrasound Restores Memory to Mice with Alzheimer’s
The first author of that paper did an AMA on reddit.com/r/science that you may find interesting as an update on where things stand: http://www.reddit.com/r/science/comments/2tykiu/
siyer··on Ultrasound Restores Memory to Mice with Alzheimer’s
The article is here (the link in the popsci article doesn't work for me): http://stm.sciencemag.org/content/7/278/278ra33.full

There's a news article about the paper that Science wrote up, which goes into some of the history of the work and has a broad sampling of views on the relevance of this paper within the broader context. http://news.sciencemag.org/biology/2015/03/ultrasound-therap...

siyer··on The Martian started as a self-published blog, and became a major motion picture
Andy Weir gave a fun talk at Google about his experiences writing the book/some of the software he used to help him in his planning. You can find it here: https://www.youtube.com/watch?v=gMfuLtjgzA8
siyer··on How Reddit Sparked a Dialogue Between Scientists and the General Public
I did an AMA on /r/science early in 2014 when the paper I'd been working on for most of my PhD came out [1], and it was a very fun experience - lots of great questions, good back-and-forth, and it meant that massively more people read my paper than would have otherwise. (It drove about 60% of the overall views to the linked Stanford press-release, and the comment thread itself had about 60,000 unique visitors).

I can testify to the /r/science mods doing a great job at making the AMAs possible, but it's still by no means a perfect process. Some things that helped make ours work were 1) downvoting trolls early - threads that could have been derailed were instead kept pretty vibrant. 2) setting aside enough time to do it - we basically wrote off a day of lab work and typed furiously instead. 3) Responding to the more critical comments - ignoring comments _really_ doesn't work. It's much better to wade in with your point of view.

[1] http://www.reddit.com/r/science/comments/1ycd0l?sort=confide...

siyer··on The Growth of Administrative Staff in Universities
Polices tend to be lab and department specific. Most everyone I know if reimbursed for flights and hotels (though they are typically required to apply for internal travel grants that exist for this purpose). Food reimbursement varies from lab to lab.
siyer··on A 19th Century Scientist Who Thought 22 Trillion Aliens Live in Our Solar System
"[T]he New York Sun dropped a bombshell of a story: Astronomer Sir John Herschel had erected an enormous telescope in South Africa that could magnify celestial bodies an astounding 42,000 times. And when he pointed it at the moon he saw a field of poppies."

In case anyone would like to read more about this fantastical hoax, I highly recommend Matthew Goodman's excellent book about 19th century newspaper hoaxes, The Sun and the Moon. It's a pretty fun book that tackles topics that range from the relationship between religion and science in pre-Civil War America, through to the relationship between P.T. Barnum and Edgar Allan Poe, and the rise of cheap newspapers targeted to the mass public (perhaps the antecedents of Buzzfeed, etc.) http://www.amazon.com/gp/product/B0023RSZPA

siyer··on Ask HN: What book changed your life in 2014?
It's perhaps more precise to say that some biologists disagree (as is perhaps inevitable). Alon's book is was the required textbook for the Systems Bioengineering (III) class at Johns Hopkins as of 5 years ago (which is when I took it). It's definitely well within the mainstream of the field.
siyer··on My Great-Great-Aunt Discovered Francium, and It Killed Her
I thought this article was one of the best descriptions I've seen of the perils (both personal and teleological) of the scientific process.

"We should celebrate scientists not solely for their accomplishments but also for their courage and the tenacity required to discover anything at all. There are brave people out there working right now. They are brave not because they are killing themselves slowly or leaping from airplanes or catching rare tropical diseases, although scientists have done all those things. They are brave because of the intense emotional risks of trying to do something no one has done before by following your own lead. Radiation is a potent allegory for human life. Everything is always, inevitably falling apart; we are all in arrested decay. Our greatest achievements may become at best footnotes; few people remember us; we can’t know what will eventually come of our work."

siyer··on Giant leap against Diabetes
The authors have uploaded a copy of the paper which can be accessed here: http://hsci.harvard.edu/files/hsci/files/pagliuca_et_al_cell...

(I'd actually recommend giving the paper a skim even if you're not trained in biology. The Introduction and Discussion should still be very comprehensible, and while the Results do suffer from the alphabet soup problem (as do most biological papers), the overall structure of the evidence should be clear - pay particularly close attention to Figure 5A and Figure 6A-C).

Commentary from a very well regarded stem cell scientist (and prolific blogger, Paul Knoepfler) here: http://www.ipscell.com/2014/10/top-10-takeaways-from-harvard...

The key next challenge appears to be the creation and testing of appropriate delivery device that can enable persistent survival of the differentiated cells while still enabling them to sense blood glucose levels.

siyer··on Artificial arms get closer to the real thing
I work in the field, so I thought I'd chime in here. Our lab (and others) have published a few papers on using optogenetics to control peripheral nervous system targets, but as some of the other commenters have mentioned, it's very much in the early stages right now, and is likely to be a long way away from human trials.

A few points:

1. There are two relevant ways to make motor neurons light sensitive. As another commenter mentioned, you can create a transgenic line of animals (this is necessarily restricted to mice/rats). That's been done, and it's been shown that you can control muscle movement in such mice [1]. In that work, a rather interesting, and now replicated [2] observation was made, which is that if you use optogenetics to do this (muscle control) you actually induce less fatigue than if you use electrical stimulation to do this. Why this is the case is not yet understood.

2. The other (more relevant) way to do this would be to use viral vectors to transduce the motor neurons you want to control with the light-sensitive ion channels. We published a paper last year showing this was possible in rats [3]. The advantage here is that you can get control over individual muscles without any effect on unwanted muscles, through a subtlety of the injection method used. There are naturally many caveats here, the most important being that human gene therapy is still in its infancy, and is typically used only for very life-threatening disorders. It's also important to note that in both these cases, you still needed a way to deliver light to the relevant nerve. While there's lots of work going on to make light-sensitive ion channels even more light-sensitive, it's likely that preliminary optogenetic control of muscle will still require implants.

3. One of the applications talked about in the link here goes the other way - it's focused on delivering touch information back to the brain. There's less published here with optogenetics than there is in motor control. We've published a paper using viral methods to control sensation earlier this year (in mice) [4], but the type of sensation we were trying to control was pain, not simple touch.

That said, I know that many groups are trying to develop ways to specifically make touch-transducing neurons light sensitive - I'd be surprised if we didn't see quite a few papers on this over the next year or two.

[1] http://www.nature.com/nm/journal/v16/n10/abs/nm.2228.html [2] http://www.sciencemag.org/content/344/6179/94.short [3] http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourna... [4] http://www.nature.com/nbt/journal/v32/n3/full/nbt.2834.html

siyer··on Aspirin could dramatically cut cancer risk, according to biggest study yet
No one should be using mercola.com as a source for information on anything. It's one of the most well-known dens of harmful and dangerous pseudoscience on the internet (see: http://www.sciencebasedmedicine.org/joe-mercola-quackery-pay... for one of many articles the excellent folks over at Science Based Medicine have written about the site).
siyer··on Male Scent May Compromise Biomedical Research
My point is more that there are differing levels of the prior probability of a study being true. Yes, 'xxx affected by cell phones' stories are bunk, however, those stories tend not to be published in Nature Methods, tend not to come out of highly respected laboratories, and tend not to have voluminous documentation and results, with 9 Supplementary Figures.

I've been reading this paper closely over the past 30 minutes, it's important enough that I'm sure it'll be heavily discussed at conferences and meetings this year. I can't think of a single thing that these researchers could have done that they haven't done. They've approached the question carefully, looked into a ton of second-order explanations and effects, and provided a plausible discussion of how and why they see their effects.

siyer··on Male Scent May Compromise Biomedical Research
"and the mechanism is likely keyed off of testosterone in general rather than mouse smells in particular, which seems reasonable."

Yes, this is what Figure 1c and 1d of the paper demonstrate. (To be precise, not testosterone, but adrostenone, androstadienone, and 3M2H).

"My head isn't going to explode if this is established by further experiment. But it's suspicious to me."

Supplementary Fig. 1 and Supplementary Fig. 3 describe replications performed in two other laboratories, one at the University of Alabama, Birmingham, and the other at another laboratory at McGill.

Look, I'm all for scientific skepticism, and it's true that there's a lot of low-powered stuff out there. However, papers are best evaluated on what they actually say (which, incidentally, is why open-access/archiving is important), rather than on a filtered impression of what a press release says. If you'd like a copy of the paper, let me know, I'd be happy to send you a pdf.

siyer··on Male Scent May Compromise Biomedical Research
The current changed title is overbroad, it's certainly not shown by this study that experimenter sex is an issue in all animal research. I would simply suggest the title of the paper itself: "Olfactory exposure to males, including men, causes stress and related analgesia in rodents". It's fairly straightforward, and not as jargon-filled as scientific titles go.
siyer··on Male Scent May Compromise Biomedical Research
This is just reflexive HN negativity. As a pain researcher who's completely unaffiliated with the group that did this work, I find this to be an excellent paper - carefully done, with good controls, standard sample sizes for the field, and sensible assays.

People interested in more of the details can read the Nature Methods article here: http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth...

It also fits into a long history of work out of the Mogil lab about the limitations in our current assays for pain. It's worth noting that this is by no means an easy problem. Pain is inherently subjective, and measuring and quantifying it in humans is difficult, let alone in rodents. The only way forward is more work like this - that carefully quantifies the sources of potential bias and error in our assays, and proposes solutions for how to get around them.

Edited to add: Vox has a good interview with Mogil that goes more into this. You can read it here: http://www.vox.com/2014/4/28/5653444/mice-get-stressed-out-f...

siyer··on LyX 2.1.0 released
The keyboard shortcuts are completely editable if you go into the various .bind files (When similar things happened to me in the past, I made a couple of quick fixes to those and got keyboard shortcuts working beautifully again).