--- Log opened Wed Nov 25 00:00:35 2015
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03:31 < chris_99> .tell nmz787 http://www.aliexpress.com/item/3D-priter-control-board-MKS-SBase-V1-0-32-s-Motherboard-compatible-Smoothieware-open-source-firmware/32410815670.html
03:31 < yoleaux> chris_99: I'll pass your message to nmz787.
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04:02 < ebowden> Does anyone here know of any 3D printable micropipettes that actually have accuracy and precision comparable to commercial ones? The best I can find is this one: http://www.thingiverse.com/thing:255519
04:07 < ebowden> Well, and this one, but it's a bit sketchy: http://www.thingiverse.com/thing:159052
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04:31 < kanzure> vitrification and devitrification selection can happen before cryopreservation
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05:12 < streety> the second link looks like the better pipette to me, the volume control on the first just doesn't look very stable
05:14 < ebowden> Sadly, the second looks less well tested.
05:16 < streety> Although I agree with that I'd prefer to test the second
05:16 < streety> both leave a lot to be desired
05:20 < ebowden> I really want a printable option that has the numerical markings, that's able to be set anywhere between 1 and 200 microlitres. We even have those in undergrad labs, it can't be that hard.
05:20 < ebowden> I'm talking first year here.
05:21 < streety> Yeah, regardless of the design you would probably need to calibrate it to get accurate volumes
05:21 < streety> would be interesting to see how these compare with the cheap pipettes now available from China
05:22 < ebowden> How good are the cheap chinese ones?
05:22 < streety> I've no idea, never used them
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05:24 < ebowden> I wonder if there will ever be an OS, partially printed machine for screening small molecules.
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05:28 < streety> are you looking for a liquid handling robot or should a "machine for screening small molecules" be more than just that
05:28 < streety> the readout is going to be very assay dependent
05:33 < ebowden> Yup.
05:34 < kanzure> i don't think that's a yes/no question
05:35 < ebowden> The "Yup" was in agreement to "the readout is going to be very assay dependent"
05:35 < ebowden> streety, probably things that involve photographing a pre-stained culture plate.
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05:39 < ebowden> I know a mathematician that works for a scientific instruments company which is developing an automatic cell culturing machine.
05:41 < streety> The liquid handling portion shouldn't be that difficult to build utilizing 3d printing. For imaging I think we're limited to the case and positioning the optical elements
05:41 < streety> actually printing the lenses would be quite transformative
05:42 < ebowden> Do we have standard sizes of cell culture well?
05:42 < streety> any automated means of cheaply producing lenses would be great
05:43 < streety> there are slight variations but until you get down to the 1536 range they're relatively standard
05:44 < streety> some of the newer plate readers can actually scan a plate to define where the wells are and then go and image/read the contents of the wells
05:44 < streety> that's mainly for PCR type assays during which there may have been some plate warping
05:46 < ebowden> I wonder what we'd get it we tested caffeine derivatives.
05:47 < streety> something closer to whatever you were looking for
05:47 < streety> maybe
05:48 < streety> what would you be looking for?
05:51 < streety> http://www.engineering.com/3DPrinting/3DPrintingArticles/ArticleID/6268/3D-Printed-Lenses-Coming-Soon.aspx & http://3dprint.com/16561/formlabs-3d-printed-lens/ <- 3d printed lenses
05:52 < streety> not optical quality but not with a little processing they aren't too bad
05:53 < ebowden> Oh, derrrrp. Testing for activity against cancer cell lines and safety in healthy cell lines.
05:53 < ebowden> No idea why I didn't mention what I'd be testing the derivatives for.
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05:55 < ebowden> Maybe try melatonin derivatives as well.
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05:59 < streety> no worries, if you test enough compounds you will likely find something. Whether that something is good enough your guess is as good as mine
06:00 < streety> has there been any work on high throughput screening in organoids and 3d cultures?
06:00 < ebowden> That'd be awesome.
06:00 < streety> perhaps a better chance of any hits identified working in vivo
06:00 < ebowden> I think some people worked out how to grow a sort of proto-brain organoid from skin stem cells.
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06:04 < ebowden> Imagine an assay for assays that works by screening a bunch of molecules with well-known activity in animal models in each of them, and seeing which of them is most concordant.
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06:08 < ebowden> A method of finding an assay that best models in-vivo responses.
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06:10 < ebowden> Streety, has anyone used concordance screen to find better assays before?
06:21 < streety> not in a systematic way as far as I know
06:21 < streety> the general approach is, x happens in vivo, x happens in our assay therefore our assay is good
06:22 < streety> sometimes, x doesn't happen in this alternative assay, therefore our assay is better
06:23 < ebowden> Why not just screen a whole bunch of molecules of known in vivo response?
06:24 < ebowden> Get an assay that is acceptably concordant.
06:24 < streety> Often there are not many, or any, compounds with known in vivo response. At least not if you restrict yourself to pathways relevant to the disease being studied
06:26 < ebowden> With alzheimer's, most of the ones of known human response are one for which the response was: "complete failure".
06:26 < ebowden> *With alzheimer's, most of the ones of known human response are one for which the response was "complete failure".
06:27 < ebowden> *With alzheimer's, most of the ones of known human response are ones for which the response was "complete failure".
06:29 < streety> the usual response to that would be developing a new model in which the old compound also fails. Little exploration is done on why the compound failed in vivo and whether it is the same mechanism in vitro though
06:30 < streety> at least when the failure can't be attributed to other causes
06:30 < streety> wrong patient group, wrong/inactive compound, wrong dose etc
06:31 < ebowden> I'd find ones in which a shitload of molecules that fail in humans fail in it.
06:33 < ebowden> For many disease there is no shortage of them.
06:33 < ebowden> For many diseases there is no shortage of them.
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09:57 < kanzure> reason@fightaging.org comments about "young blood rejuvenation" stuff https://news.ycombinator.com/item?id=10628040
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11:06 < kanzure> .wik vladimir demikhov
11:06 < yoleaux> "Vladimir Petrovich Demikhov (Russian: Влади́мир Петро́вич Де́михов; Kulini Farm, July 18, 1916 – Moscow, November 22, 1998) was a Soviet scientist and organ transplant pioneer, who performed several transplantations in the 1930s and 1950s, such as the transplantation of a heart into an animal and a lung-heart replacement in an animal." — https://en.wikipedia.org/wiki/Vladimir_Demikhov
11:06 < kanzure> "In 2015, Italian neurosurgeon Sergio Canavero has said the procedure (head anastomosis venture) might be feasible – with improved technology and more accurate ability to keep neural tissue perfused – before end of 2017, which is when he intends to perform the procedure in either the United States or China.[12][13] A 30-year-old Russian with Werdnig–Hoffmann disease (type I spinal muscular atrophy) and rapidly declining health has ...
11:06 < kanzure> ... volunteered to offer his head for the study.[14]"
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13:23 < pompolic>  /n
13:23 < pompolic> oops
13:32 < kanzure> "The scientists at Sooam, led by Dr. Hwang, used Missy’s cells to successfully produce three Missy clones. After 10 years of research and effort, the quest to clone Missy had finally succeeded. Three identical clones of Missy were returned to the original owners. The clones are named Mira (after a Korean myth of an all-powerful benevolent dragon), Chingu (which means "friend" in Korean) and Sarang ("love")."
13:32 < kanzure> .wik missyplicity
13:32 < yoleaux> "The Missyplicity Project was a project devoted to cloning Joan Hawthorne and John Sperling's dog, a border collie and husky mix. Missy died on July 6, 2002 at the age of 15 years." — https://en.wikipedia.org/wiki/Missyplicity
13:32 < kanzure> oh look they have public marketing https://www.facebook.com/sooambiotech/
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13:49 < kanzure> "Junctional Blockade Stochastically Induces Different Species-Specific Head Anatomies in Genetically Wild-Type Girardia dorotocephala Flatworms" http://www.mdpi.com/1422-0067/16/11/26065
13:50 < kanzure> "Planarian flatworms are a popular system for exploring body plan patterning due to their regenerative capacity, but despite considerable molecular information regarding stem cell differentiation and basic axial patterning, very little is known about how distinct head shapes are produced. Here, we show that after decapitation in G. dorotocephala, a transient perturbation of physiological connectivity among cells (using the gap junction ...
13:50 < kanzure> ... blocker octanol) can result in regenerated heads with quite different shapes, stochastically matching other known species of planaria (S. mediterranea, D. japonica, and P. felina). We use morphometric analysis to quantify the ability of physiological network perturbations to induce different species-specific head shapes from the same genome. Moreover, we present a computational agent-based model of cell and physical dynamics during ...
13:50 < kanzure> ... regeneration that quantitatively reproduces the observed shape changes."
13:50 < kanzure> "Morphological alterations induced in a genomically wild-type G. dorotocephala during regeneration include not only the shape of the head but also the morphology of the brain, the characteristic distribution of adult stem cells (neoblasts), and the bioelectric gradients of resting potential within the anterior tissues. Interestingly, the shape change is not permanent; after regeneration is complete, intact animals remodel back to G. ...
13:50 < kanzure> ... dorotocephala-appropriate head shape within several weeks in a secondary phase of remodeling following initial complete regeneration."
13:53 < kanzure> other papers from that group http://lobolab.umbc.edu/publications/
13:53 < kanzure> including "Evolutionary development of tensegrity structures"
13:55 < kanzure> ( http://www.sciencedirect.com/science/article/pii/S0303264710001000 )
13:56 < kanzure> "A bioinformatics expert system linking functional data to anatomical outcomes in limb regeneration" http://dx.doi.org/10.1002/reg2.13
13:56 < kanzure> "Limbform: a functional ontology-based database of limb regeneration experiments" http://bioinformatics.oxfordjournals.org/content/30/24/3598 http://lobolab.umbc.edu/limbform/
13:56 < fenn> ebowden streety you can easily calibrate a micropipette by dispensing onto a milligram scale. also, curcumin/turmeric supposedly prevents alzheimers but has low bioavailability, so maybe increasing the bioavailability would be a good thing to work on
13:57 < kanzure> last two screenshots over here... hm. http://lobolab.umbc.edu/limbform/screenshots/
13:58 < fenn> should be a "creature constructor" video game
13:58 < kanzure> didn't spore do that at some point?
13:59 < kanzure> https://www.youtube.com/watch?v=dRovPCiBBTw&t=55s
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14:09 < fenn> that praying mantis thought it was a monkey
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14:22 < nmz787_i> fenn, piperidine in black pepper is supposed to potentiate turmeric
14:22 < nmz787_i> maybe that should be for ebowden and streety
14:23 < nmz787_i> or maybe it was piperine
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14:31 < nmz787_i> the 'daily mirror' article image on sooam's facebook page shows that the 'experiment' cost 60k-pounds (or whatever that curly L thing for that euro money is)
14:31 < kanzure> $100k/clone
14:32 < nmz787_i> also I heard that england might secessede from the EU... so I guess this confusion about what their currency is might go away sometime
14:33 < nmz787_i> "The clones’ weights have consistently been within one pound of each other and have developed like Melvin did. The major physical differences between clones are that Henry (middle) has a white stripe between his eyes and a smaller head than Ken (right). Please refer to previous Facebook posting including July 6, 2013 for comparison and more information."
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14:57 < nmz787_i> hmm, $300 3D printer on monoprice.com
14:57 < nmz787_i> I really shouldn't be as interested as I am, since the local public library has a free 3D printer of some sort
14:57 < chris_99> nmz787_i, did you see that smoothieboard clone link i posted earlier btw
14:57 < nmz787_i> and I think some guy who runs it
14:58 < nmz787_i> oh, no, I haven't been reading the logs this past week or so
14:58 < chris_99> http://www.aliexpress.com/item/3D-priter-control-board-MKS-SBase-V1-0-32-s-Motherboard-compatible-Smoothieware-open-source-firmware/32410815670.html
14:59 < nmz787_i> huh, says the microstepping can go below the level of the Allegro chips
14:59 < nmz787_i> I like that idea
15:00 < chris_99> yeah 1/32
15:00 < chris_99> i've got some of those stepper drivers
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15:37 < streety> fenn, nmz787_i thanks, yes I would use a scale to calibrate a 3d printed pipette. Nice and simple.
15:37 < streety> just need some way to calibrate a 3 printed scale
15:37 < streety> *3d
15:38 < streety> I think the UK will stay in the EU for a while yet.
15:39 < streety> The reason may be the same as why Scotland stayed with the UK but the outcome will be the same
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16:17 < nmz787_i> ah, so the UK is a superset of England, huh... and the UK, not England, was thinking of secceding ?
16:21 < kanzure> "Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans" http://www.icemanwimhof.com/files/pnas.pdf
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17:32 < fenn> increased epinephrine (adrenaline) isn't something i would recommend to people with autoimmune diseases
17:39 < fenn> breathing exercise instructions are cheaper to transmit than anti-inflammatory drugs though
17:40 < ebowden> I wonder how the side-effects and efficacy compare.
17:41 < ebowden> What could both used together do?
17:41 < fenn> it's probably difficult to get a constant enough flow of adrenaline to completely suppress the immune system the way corticosteroids do
17:43 < ebowden> We need to figgure out better NSAIs.
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17:44 < ebowden> Because corticosteriods can be ever so slightly horrifying.
17:44 < fenn> well something that isn't targeting COX-1 or COX-2 would be a good start
17:45 < ebowden> Safe NRF2 activators?
17:47 < fenn> i haven't heard of Nrf2, seems to be some sort of antioxidant system?
17:47 < fenn> something about multiple sclerosis
17:48 < ebowden> Yes, you'd think small molecule NRF2 activators would be great for promoting tumor growth, but Curcumin and Berberine both have in vitro and in-vivo anti-cancer activity, though likely through other mechanisms.
17:49 < fenn> are curcumin and berberine Nrf2 activators?
17:49 < ebowden> Though curcumin is even more of a pain to get absorbed than berberine.
17:49 < ebowden> Yes.
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17:50 < ebowden> Also, berberine was as effective as metformin in a phase 3 clinical trial for type 2 diabetes for some reason.
17:51 < ebowden> Which of course was jumped on by altmed nuts.
17:51 < fenn> well, good
17:51 < ebowden> It's not alternative medicine anymore, now it's just medicine.
17:52 < ebowden> And for love of god don't give it to kids.
17:52 < fenn> as long as nobody gets a patent on it i'm fine with "real medicine" validating "alternative medicine"
17:53 < ebowden> What I don't like is people pretending that berberine working means that homeopathy and bleach cure cancer.
17:53 < fenn> "One study reports that it is superior to metformin in treating polycystic ovary syndrome"
17:54 < fenn> heh but bleach does cure cancer
17:54 < fenn> very aggressive treatment
17:54 < ebowden> Never heard of the pco thing.
17:54 < ebowden> lol
17:54 < ebowden> Yeah, bullets kill cancer cells.
17:55 < ebowden> Shoot out the tumors!
17:56 < fenn> apparently cancer cells are under lots of oxidative stress from their malfunctioning mitochondria and high rate of growth, so just a little bit more oxidative stress is enough to push them over the edge and die. someone at berkeley was wondering if breathing oxygen cold-plasma would be a good cancer treatment...
17:57 < ebowden> Why not ozone therapy?
17:57 < ebowden> And other things without credible evidence of efficacy?
17:58 < fenn> ozone damages the lungs at relatively low concentrations
17:59 < fenn> i get what you are saying, but in order to get anything beyond neat idea stage someone has to actually do the experiment
17:59 < ebowden> Have we even seen it in animal models?
18:00 < fenn> dunno much about cancer treatment to be honest
18:00 < fenn> .title http://www.nature.com/articles/srep06638
18:00 < yoleaux> Effect of additive oxygen gas on cellular response of lung cancer cells induced by atmospheric pressure helium plasma jet : Scientific Reports
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18:00 < ebowden> I wonder if we could find a small molecule that up-regulates Nrf2 in healthy cell lines and down-regulates it in cancer cell lines.
18:01 < ebowden> That might be a decent start.
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20:14 < kanzure> "In the new OSU research, the engineers developed a mathematical model to simulate the freezing process in the presence of cryoprotectants, and identified a way to minimize damage. They found that if cells are initially exposed to a low concentration of cryoprotectant and time is allowed for the cells to swell, then the sample can be vitrified after rapidly adding a high concentration of cryoprotectants. The end result is much less ...
20:14 < kanzure> ... overall toxicity, Higgins said."
20:14 < kanzure> .title http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142828
20:14 < yoleaux> PLOS ONE: Toxicity Minimized Cryoprotectant Addition and Removal Procedures for Adherent Endothelial Cells
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20:21 < kanzure> "Ice-free cryopreservation, known as vitrification, is an appealing approach for banking of adherent cells and tissues because it prevents dissociation and morphological damage that may result from ice crystal formation. However, current vitrification methods are often limited by the cytotoxicity of the concentrated cryoprotective agent (CPA) solutions that are required to suppress ice formation. Recently, we described a mathematical ...
20:21 < kanzure> ... strategy for identifying minimally toxic CPA equilibration procedures based on the minimization of a toxicity cost function. Here we provide direct experimental support for the feasibility of these methods when applied to adherent endothelial cells. We first developed a concentration- and temperature-dependent toxicity cost function by exposing the cells to a range of glycerol concentrations at 21°C and 37°C, and fitting the ...
20:21 < kanzure> ... resulting viability data to a first order cell death model. This cost function was then numerically minimized in our state constrained optimization routine to determine addition and removal procedures for 17 molal (mol/kg water) glycerol solutions. Using these predicted optimal procedures, we obtained 81% recovery after exposure to vitrification solutions, as well as successful vitrification with the relatively slow cooling and ...
20:21 < kanzure> ... warming rates of 50°C/min and 130°C/min. In comparison, conventional multistep CPA equilibration procedures resulted in much lower cell yields of about 10%. Our results demonstrate the potential for rational design of minimally toxic vitrification procedures and pave the way for extension of our optimization approach to other adherent cell types as well as more complex systems such as tissues and organs."
20:21 < kanzure> yeah so.... 10% sounds pretty good to me.
20:22 < ebowden> 81% sounds better.
20:23 < kanzure> pfft what's a little cell death ever done to you
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23:01 < kanzure> what counts as "recovery after exposure to vitrification solutions"
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23:32 -!- Topic for ##hplusroadmap: biohacking, nootropics, transhumanism, open hardware | sponsored by lobsters everywhere, banned by the Federal Death Administration (5 times) | this channel is LOGGED: http://gnusha.org/logs | http://diyhpl.us/wiki | "ray kurzweil is a pessimist" - george church
23:32 -!- Topic set by kanzure [~kanzure@unaffiliated/kanzure] [Wed May 20 12:46:25 2015]
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