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A.I. and Gene Regulation December 27, 2019

Posted by stuffilikenet in Applications, Brain, Geek Stuff, Mutants, Science.
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Understanding gene regulation is a bitch. Seriously, this is one of the thornier problems of science today and it is because the complexities of living cells, with the thousands of proteins in each cell, make tracing a single protein’s regulation just as complex as hell. Smart guys Tareen and Kinney have figured out a way for AI to interpret (some) interactions using massively-parallel reporter assays to figure out the biophysical basis for (some) gene regulation…which is more than we have had heretofore. They did this by assigning nodes and weights with explicit physiochemical interpretations. This last is the important bit; many AI algorithms are very difficult to interpret, so the underlying “logic” is impenetrable to humans.  The smart guys made many of the decisions explicit, so they would be better able to understand the “logic” by which the characterizations were derived.

 

 

Homework: Biophysical models of cis-regulation as interpretable neural networks, Ammar Tareen, Justin B. Kinney BioRxiv,

Nanowired Brain-like Functions December 25, 2019

Posted by stuffilikenet in Awesome, Brain, Mutants, Science.
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Nation Institute of Material Science geeks have created a complex metallic nanowire structure that mimics brain-like functions, such as memorization, learning, forgetting, becoming alert and returning to calm.

"figure: (a) Micrograph of the neuromorphic network fabricated by this research team. The network contains of numerous junctions between nanowires, which operate as synaptic elements. (b) A Human brain and one of its neuronal networks." Image

This indicates that self-organizing structures can be built from random arrangements of conducting fibers. This suggests that many different types of brain-like activity can be induced from stuff other than the kind of materials from which you and I are made.
Intelligent life on other worlds might be made of very different stuff indeed.

 

Homework: “Emergent dynamics of neuromorphic nanowire networks” by Adrian Diaz-Alvarez, Rintaro Higuchi, Paula Sanz-Leon, Ido Marcus, Yoshitaka Shingaya, Adam Z. Stieg, James K. Gimzewski, Zdenka Kuncic and Tomonobu Nakayama, 17 October 2019, Scientific Reports.
DOI: 10.1038/s41598-019-51330-6

Multi-dimensional Blood Testing and A.I. December 23, 2019

Posted by stuffilikenet in Applications, Awesome, Brain, Brilliant words, Geek Stuff, Science, Star Trek Technology.
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I suggested long ago that sufficiently-comprehensive blood tests could effectively predict a person’s risk of developing a broad array of different diseases. We would use artificial intelligence to find patterns of varying concentrations of blood proteins to predict and/or diagnose disease. Someone much better funded than me has a newly developed platform called SomaScan which can scan five thousand individual proteins from a single blood sample.

In a new study testing the efficacy of predicting 11 different health indicators using these protein expression patterns some models were much more effective than others, such as the protein expression model predicting percentage body fat. The cardiovascular risk model was cited as only modestly predictive, however, the researchers do suggest the protein-pattern-based system is generally more convenient, and cheaper, than many traditional tests currently available for evaluating health conditions.

The study in Nature Medicine was funded by SomaLogic which owns SomaScan, so grain of salt, people. But it’s exciting to see that someone is actually looking into what I feel will be the method of the future for maximizing health…also, the study used ~85 million protein measurements in 16,894 participants, which is a pretty damn good sample size.  Plenty of data there for an A.I. to examine for hidden relationships.

Homework:

Plasma protein patterns as comprehensive indicators of health, Nature Medicine, Stephen A. Williams, Mika Kivimaki, Claudia Langenberg, Aroon D. Hingorani, J. P. Casas, Claude Bouchard, Christian Jonasson, Mark A. Sarzynski, Martin J. Shipley, Leigh Alexander, Jessica Ash, Tim Bauer, Jessica Chadwick, Gargi Datta, Robert Kirk DeLisle, Yolanda Hagar, Michael Hinterberg, Rachel Ostroff, Sophie Weiss, Peter Ganz & Nicholas J. Wareham

40Hz Light Pulses Stop Alzheimer’s May 10, 2019

Posted by stuffilikenet in Awesome, Brain, Geek Stuff, Science, Star Trek Technology.
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Neuroscientists at MIT have published a paper which demonstrates that 40Hz pulses of light can somehow inhibit the progress of neurodegeneration in mouse model. This study is designed to figure out how a flickering light could stifle cognitive decline, using two unique mouse models engineered to overproduced the toxic proteins that contribute to neurodegeneration. The animals were exposed to light flickering at 40 Hz for one hour every day for between three and six weeks. It worked a treat;  mice engineered to overproduce tau proteins (that usually cause neurodegeneration) displayed no neuronal degeneration after three weeks of treatment compared to a control group that displayed nearly 20 percent total neuronal loss. The other mouse model, engineered to produce a neurodegenerative protein called p25, displayed no neurodegeneration whatsoever during the entire six weeks of treatment.

 

mousebrains.jpeg

The researchers then zoomed in on the light-treated animal’s neurons and microglia to study whether the treatment induced any unusual changes in gene expression. The light-treated mice revealed increased neuronal expression of genes associated with synaptic function and DNA repair. In microglia, the brain’s immune cells, there was a decrease in genes associated with inflammation.

Nobody understands how a 40 Hz flickering light can trigger these specific changes to gene expression deep in the brain, but human trials testing the sound and light treatment in Alzheimer’s patients have already begun.

Note: Adding a 40 Hz auditory tone to the process improved the efficacy of this treatment.  Your elderly parents can benefit from this by using gnuaural, an open-source generator of binaural beats for meditation and other psychological effects.

Homework: https://www.cell.com/neuron/fulltext/S0896-6273(19)30346-0

Manufactured Human Organs November 20, 2018

Posted by stuffilikenet in 3D Printing, Awesome, Brain, Science, Star Trek Technology.
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Scientists at Tel Aviv University have created human organs (little ones but, hey) from a bit of biopsied tissues.  They separated the cells from the rest, induced pluripotency and built up organs in differentiated cell layers on a gel scaffolding.  They were able to grow cardiac, spinal and cortical cells from the biopsy sample.

This is critical to success: the cells are the patient’s own cells, with little chance of immune system rejection.  These guys (Tal Dvir, Reuven Edri, NAdav Noor, Idan Gal, Dan Peer and Irit Gat Viks) are currently engaged in regenerating an injured spinal cord and an infarcted heart with spinal cord and cardiac implants. They have also begun to investigate the potential of human dopaminergic implants to treat Parkinson’s disease in animal models.

They have big plans for this technology: “We believe that the technology of engineering fully personalized tissue implants of any type will allow us to regenerate any organ with a minimal risk of immune response,” Prof. Dvir concludes.

Homework: Reuven Edri et al, Personalized Hydrogels for Engineering Diverse Fully Autologous Tissue Implants, Advanced Materials (2018). DOI: 10.1002/adma.201803895

Diagnosing Alzheimer’s with AI November 12, 2018

Posted by stuffilikenet in Applications, Awesome, Brain, Science.
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This is pretty good news if you think Alzheimer’s can be slowed or halted in some way (unproven, but a good idea): researchers funded by NIH have developed a (so far) 100% accurate method of diagnosing Alzheimer’s before any clinical symptoms appear.  The study seems pretty bullet-proof, too: Prospective 18F-FDG PET brain images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (2109 imaging studies from 2005 to 2017, 1002 patients) and retrospective independent test set (40 imaging studies from 2006 to 2016, 40 patients) were collected. 90% of the images were used as training data and the rest used as test data.  The learning algorithm developed for early prediction of Alzheimer disease achieving 82% specificity at 100% sensitivity, an average of 75.8 months prior to the final diagnosis.

Figure 2:

Example of fluorine 18 fluorodeoxyglucose PET images from Alzheimer’s Disease Neuroimaging Initiative set preprocessed with the grid method for patients with Alzheimer disease (AD). One representative zoomed-in section was provided for each of three example patients: A, 76-year-old man with AD, B, 83-year-old woman with mild cognitive impairment (MCI), and, C, 80-year-old man with non-AD/MCI. In this example, the patient with AD presented slightly less gray matter than did the patient with non-AD/MCI. The difference between the patient with MCI and the patient with non-AD/MCI appeared minimal to the naked eye.

I do recommend doing your homework (below), since the paper is pretty digestible for the alert layman, and the study itself well structured.

Homework:

  1. Yiming Ding, Jae Ho Sohn, Michael G. Kawczynski, Hari Trivedi, Roy Harnish, Nathaniel W. Jenkins, Dmytro Lituiev, Timothy P. Copeland, Mariam S. Aboian, Carina Mari Aparici, Spencer C. Behr, Robert R. Flavell, Shih-Ying Huang, Kelly A. Zalocusky, Lorenzo Nardo, Youngho Seo, Randall A. Hawkins, Miguel Hernandez Pampaloni, Dexter Hadley, Benjamin L. Franc. A Deep Learning Model to Predict a Diagnosis of Alzheimer Disease by Using 18F-FDG PET of the BrainRadiology, 2018; 180958 DOI: 10.1148/radiol.2018180958

 

Training Neural Networks to Write Bach in a Day! March 24, 2017

Posted by stuffilikenet in Applications, Awesome, Brain, Geek Stuff, Toys, Video.
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Fascinating bit of video here as Our Hero (not me, in this case) takes Bach (and later Mozart) MIDI files, creates an 88-character ASCII-character alphabet from them and trains a Recurrent Neural Network to output similar sequences.

The results (and a lot of the process) is shown in the video above.  Take your time and watch the whole thing; I wonder how long he would have to train the RNN to start outputting Baroque Muzak continually?

Drawing the Wrong Conclusion March 6, 2017

Posted by stuffilikenet in Brain, Brilliant words, Science.
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…or, how we got to now.

Too Much Science to Read, Let Alone Review November 15, 2016

Posted by stuffilikenet in Awesome, Brain, Brilliant words, Geek Stuff, Science, Star Trek Technology, Toys, Uncategorizable.
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It’s been a banner week for science geeks, nerds, and squints. The locked-in lady gets to at least shout from her prison quietlyGoogle has radar sensitive enough to not only find objects but identify them by their radar signature and perovskite is once again breaking solar-conversion efficiency records.

Ordinarily I would give you a breakdown of each of these nifty developments, but more are coming and I may want to return to these later when I am not pressed for time.  Follow the links above; there are others as well that you will find more well constructed than my chicken scratchings, I’m sure.

Brain-Computer Interface Now in Use at Home!!! November 15, 2016

Posted by stuffilikenet in Applications, Awesome, Brain, Geek Stuff, Science, Star Trek Technology, Toys, Uncategorizable.
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A 58-year-old woman (“HB”) with ALS has had a functioning brain-computer interface (BCI) for a while now, and is able to communicate (slowly) with the outside world. She was facing total lock-in Real Soon Now, so any device which offers communication ability is welcome.

What it is:

A diagram illustrating the setup and use of the ECoG implant.

Electrode strips at the top laid across her brain like band-aids read faint electrical signals.  With training HB was able to “type” fairly quickly (words per minute, but still).  More work remains to be done on the interfacing software (I am imagining more inputs and a neural network to interpret her thoughts more and more efficiently), and HB is ecstatic to have a way t live in the world.  She would like to use the interface to control a wheelchair, for example, but that is a ways off.

 

Homework:  Vansteensel, Mariska J. et. al., Fully Implanted Brain–Computer Interface in a Locked-In Patient with ALS, New England Journal of Medicine November 12, 2016 DOI: 10.1056/NEJMoa1608085

Update: New Scientist has an excellent writeup as well.

Brain-Computer Interface Restores Locomotion November 9, 2016

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You heard me. Watch the video and be amazed.

The researchers think it could be ready for human trials by the end of the decade.

If it sounds familiar, it might be because Star Trek thought of it first:

Image result for spock's brain

Homework: Capogrosso, Marco, Milekovic, Tomislav, et. al, A brain–spine interface alleviating gait deficits after spinal cord injury in primates, Nature

Experimental Design Review—Before Results September 25, 2016

Posted by stuffilikenet in Awesome, Brain, Brilliant words, Geek Stuff, Science.
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BMC Psychology has taken a novel (actually, a scorched earth) approach to the problem of irreproducible results in psych studies. Peer reviews of submitted studies will be checked for experimental methods only, until the end of the review process.  The thinking is, reviewers may be unconsciously biased by seeing results they agree with (or disagree with), rather than the value of the methods by which they were derived.

Given that as many as one-third of psych studies in a recent review (of a thousand studies) could not be reproduced, I think this is an excellent first step to cleaning house of cognitive biases.

Sadly, BMC Psychology is not one of the larger players in this field; it may be that this will enhance their prestige.

Graphene Nanoribbons in Spinal Recovery September 20, 2016

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Researchers at Rice University have caused rats with severed spinal columns to pass electrical signals 24 hours after “reapposition of the two sharply severed cords…re-establishes contact by regrowth.” There was a magic ingredient, however: polyethylene glycolated graphene nanoribbons, which were applied during the apposition. Two weeks later [ Video ], the rat could walk without losing balance, stand up on his hind limbs and use his forelimbs to feed himself with pellets. No recovery was observed in controls.

Christopher Reeves died a little too soon, apparently.

 

Homework:  Kim C, Sikkema WKA, Hwang I, Oh H, Kim UJ, Lee BH, Tour JM. Spinal cord fusion with PEG-GNRs (TexasPEG): Neurophysiological recovery in 24 hours in rats. Surg Neurol Int 13-Sep-2016;7:

The Madness of Crowds September 18, 2016

Posted by stuffilikenet in Awesome, Brain, Brilliant words.
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A thoughtful dissection of crowd psychology is currently running in one of my feeds (ribbonfarm.com), which answers my questions about how persecuted folk end up in cultish groups.  It’s another long-form essay (and uh, book report : ) ), so only go there when you have time.

Why Your Life is Not a Journey August 25, 2016

Posted by stuffilikenet in Brain, Brilliant words, Uncategorizable, Video.
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Snippets from the film “Tree of Life”.  .

Science News Roundup August 12, 2016

Posted by stuffilikenet in Awesome, Brain, Geek Stuff, Science, Star Trek Technology, Uncategorizable.
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I haven’t had a lot of free time for stuff I like lately, but I didn’t want a few items from my science newsfeeds to go unnoticed by you, my adoring public. I expect most people don’t follow this kind of stuff closely, so pay attention:

First off, a team from the UK has found that a commonly available drug Fenamate can reduce the inflammation in a particular pathway to protect against a Alzheimer’s disease model in rodents. A mouse is not a man, but the results are intriguing enough (protected all rats in the study) that trials with humans are being strongly considered.  Because the drug is already approved for pain relief, the difficulty in getting into trials in the first place is enormously reduced. “In the USA, wholesale price of a week’s supply of generic mefenamic acid has been quoted as $426.90 in 2014. Brand-name Ponstel is $571.70. In contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan. In the Philippines, 10 tablets of 500 mg generic mefenamic acid cost PHP39.00 (or the equivalent of $0.88USD) as of October 25, 2014.”—Wikipedia.

Evil bastards? Well, sure. What do you expect from companies who can buy or sell legislators?

Next, paraplegic patients have had nerve and muscle function partially restored using a three-step training regimen in Brazil. Starting with VR to give them the sensation of walking through haptic feedback during brain-controlled maneuvering through a VR landscape, the patients then proceeded to move using a robotic walker on a treadmill with full support, also run through the brain-machine interface. Finally, they practiced walking with the robosuit used in that World Cup game a couple of years ago.  This took months, but the eight fully paralyzed patients who completed (one moved away) ALL showed some improvement.

This is a big deal.  None of these guys were ever supposed to get any sensation or control back.

This program is on-going, so we don’t know how much improvement will ultimately result from this innovative program, but I for one am pretty excited. Isn’t this why we work in computer science in the first place?

10% Happier, by Dan Harris July 10, 2015

Posted by stuffilikenet in Awesome, Books, Brain, Brilliant words, Science.
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10% Happier, by Dan Harris is the story of ABS anchorman Dan Harris’ journey through Buddhism to mindfulness in the most torturous of routes: trial and error from Eckhard Tolle, Deepak Chopra and a host of what he calls affectionately “Jew-Bus”, Jewish people who have come to embrace Buddhist practices (Harris is Jewish).  In his guise of newsman he cheats his way into getting real answers to the deep mystery: how do you meditate, and why (he even got face time with the Dalai Lama along the way, which is not that easy).

The real juicy part of this book is not so much who he met or how he learned this or that thing, but his blow-by-blow account of his thoughts and reactions as he began learning meditation.  Especially interesting was his reaction to a ten-day Zen retreat of six-hour daily meditation, wherein he finally felt he “got it” and later the emotional outpouring he experience when meditating upon compassion for the first time.

The reason I loved this book is that his story resonates closely with my own, especially the embarrassing awareness of the banality of my own thoughts, the ease of distraction and the lack of rigor in focus or awareness of anything but the voice in my head.  That, and I’m hoping to get a little guidance on my own practice, and I think this book helped.

The link above goes to the Audible audiobook version, but it is also available at sfpl.org.  I do recommend the audiobook, as it is read by him and guarantees his nuances will not be misunderstood (c.f., “Jew-Bus”, above).

The Antibody by Christopher Lukas June 28, 2015

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I haven’t been able to find it on Amazon1, but The Antibody by Christopher Lukas is a gripping tale of a man’s struggle with suicide, depression, cancer and loss.  Written, directed and starring only himself, it is hilarious, tragic and real. I cried at the end, and I don’t cry for much. Watch it at the link above; no telling how long it will last.

—-

1. Seriously, Amazon?

The Singularity Started With the Wheel March 16, 2015

Posted by stuffilikenet in 3D Printing, Applications, Awesome, Brain, Brilliant words, Mutants, Science, Star Trek Technology.
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As difficult as it may be to comprehend, the wheel is the basic unit of technology. It made the repetitive business of carrying stuff easier. When tasks can be easily repeated (preferably automated), they can also be tweaked to do them better, maybe each time.

With computer controls, these tweaking steps can be automated, and the results don’t even have to be seen by a human.  These results can be used to produce new methods to experiment, ad infinitum. This is precisely why we should not allow AIs any autonomy whatever in creating new AIs.

But I digress.

The tools of automation are now cheaply available, giving everyone who wants it access to finely-controlled stepper motors which can be used in the trial and error methods heretofore mentioned.  Cheap microcontroller systems to run them combined with said stepper motors give us robotic assemblers, 3D printers and molecular assemblers.

Yeah, you heard me.

Usually, small-molecule synthesis usually relies on procedures that are highly customized for each target. Martin Burke, a Howard Hughes Medical Institute (HHMI) early career scientist at the University of Illinois at Urbana-Champaign, used a single, fully-automated process to synthesize fourteen distinct classes of small molecules from a common set of building blocks.

A broadly applicable automated process could greatly increase the accessibility of [this class of compounds] to enable investigations of their practical potential. More broadly, these findings illuminate an actionable roadmap to a more general and automated approach for small-molecule synthesis (he used Csp3-rich polycyclic natural product frameworks and developed a catch-and-release chromatographic purification method).

As a former chemist, I must say this is plenty difficult and detailed…but it only has to be done once and this genie is not going back into the bottle.  This will step up the pace of novel moiety experimentation, especially now that we have computational chemistry on a sound footing.  Picture this: computer cranks out theoretical molecule families for research.  Magic chemistry machine makes them.  Another automated machine tests them.  Potential drug candidates can be screened without human intervention, for conditions that currently have no treatment, but do have a good theoretical model.

Honestly, I have been thinking of this for thirty-five years, when one of my classmates described the room-temperature chemistry that was just being used for automated peptide synthesis, a hot subject in my college years1.

Now, with  automated synthesis producing testable quantities of continuously-varying drugs, we can start continuously comparing them with standard drugs for, say, antibiotic activity in a Petri-like environment (I hope it is no surprise that this technology exists already, although it is not in concert with the aforementioned molecular assembler), quickly finding optimal candidates in what could be an entirely automated process.  Promising candidates’ structures can be continuously varied by the molecular assembler under the watchful eye of an expert system (it is fun to imagine the expert system eventually deciding that chlorine bleach is the optimal antibiotic; obviously safety trials against mammalian cell lines need to run in parallel).

Aha, I hear you cry, what about diagnosis?  I’m pretty sure I covered this already2, when I  talked about brute-force cracking the human medical condition through big data: thousands of tests administered cheaply, regularly through millions of peoples’ lifetimes.  This data would be trawled for correlations between medical conditions and test results, telling us things clinicians would miss just because human heads can’t hold that kind of data well enough to draw statistical conclusions, or even reasonable inferences…but computers can.  Frustratingly, the legal problems here are beyond human comprehension as well; the intellectual property costs to create this many tests would be astronomical, although once acquired it could be quite cheap to administer (this is already possible, just not done for greed’s sake).  This will require a revolution in thinking which is not, alas, forthcoming soon3.

Other science can be brute-forced in a similar fashion by automation in other chemical reactions; I picked drug discovery for illustration since that’s where the most money can be found currently.

These are delightful speculations and become even more possible as long as things continue the way they are going, at least in terms of physical possibility.  Cheaper, faster processors make it possible to control all manner of laboratory  and industrial devices, not just your toaster, son.

It all makes me wish I were a better writer, because these ideas deserve better advocacy than I can bring to bear.

 

Homework:

Synthesis of many different types of organic small molecules using one automated process Junqi Li, Steven G. Ballmer, Eric P. Gillis, Seiko Fujii, Michael J. Schmidt, Andrea M. E. Palazzolo, Jonathan W. Lehmann, Greg F. Morehouse, Martin D. Burke

 

EDIT: Somebody did it: “As proof of concept, we have demonstrated its capacity by optimizing the lycopene biosynthetic pathway. This fully-automated robotic platform, BioAutomata, evaluates less than 1% of possible variants while outperforming random screening by 77%. “–Mohammad HamediRad et al. Towards a fully automated algorithm driven platform for biosystems design, Nature Communications (2019). DOI: 10.1038/s41467-019-13189-z

 

______

1 We’re getting there, fellas.  Keep up the good work.

2 Please try to keep up.

3 If ever.

No Mud, No Lotus, by Thich Nhat Hanh February 23, 2015

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No Mud, No Lotus  is pretty much a simple manual for transforming suffering into mindfulness and perhaps joy by ancient (but not mysterious) practices: stopping, mindful breathing, and deep concentration.

The devil is in the details, and I urge readers to stop after this book.  Tibetan Buddhism is very, very busy with details which are (probably) unnecessary to enjoy a peaceful, enlightened life, or at least slow down and appreciate the life you have now.

Still, this particular book seems to me to strike a balance I can appreciate.  I do recommend it.