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ref: work-0 tags: distilling free-form natural laws from experimental data Schmidt Cornell automatic programming genetic algorithms date: 09-14-2018 01:34 gmt revision:5 [4] [3] [2] [1] [0] [head]

Distilling free-form natural laws from experimental data

  • There critical step was to use partial derivatives to evaluate the search for invariants. Even yet, with a 4D data set the search for natural laws took ~ 30 hours.
    • Then again, how long did it take humans to figure out these invariants? (Went about it in a decidedly different way..)
    • Further, how long did it take for biology to discover similar invariants?
      • They claim elsewhere that the same algorithm has been applied to biological data - a metabolic pathway - with some success.
      • Of course evolution had to explore a much larger space - proteins and reculatory pathways, not simpler mathematical expressions / linkages.

{1409}
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ref: -0 tags: coevolution fitness prediction schmidt genetic algorithm date: 09-14-2018 01:34 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

Coevolution of Fitness Predictors

  • Michael D. Schmidt and Hod Lipson, Member, IEEE
  • Fitness prediction is a technique to replace fitness evaluation in evolutionary algorithms with a light-weight approximation that adapts with the solution population.
    • Cannot approximate the full landscape, but shift focus during evolution.
    • Aka local caching.
    • Or adversarial techniques.
  • Instead use coevolution, with three populations:
    • 1) solutions to the original problem, evaluated using only fitness predictors;
    • 2) fitness predictors of the problem; and
    • 3) fitness trainers, whose exact fitness is used to train predictors.
      • Trainers are selected high variance solutions across the predictors, and predictors are trained on this subset.
  • Lightweight fitness predictors evolve faster than the solution population, so they cap the computational effort on that at 5% overall effort.
    • These fitness predictors are basically an array of integers which index the full training set -- very simple and linear. Maybe boring, but the simplest solution that works ...
    • They only sample 8 training examples for even complex 30-node solution functions (!!).
    • I guess, because the information introduced into the solution set is relatively small per generation, it makes little sense to over-sample or over-specify this; all that matters is that, on average, it's directionally correct and unbiased.
  • Used deterministic crowding selection as the evolutionary algorithm.
    • Similar individuals have to compete in tournaments for space.
  • Showed that the coevolution algorithm is capable of inferring even highly complex many-term functions
    • And, it uses function evaluations more efficiently than the 'exact' (each solution evaluated exactly) algorithm.
  • Coevolution algorithm seems to induce less 'bloat' in the complexity of the solutions.
  • See also {842}

{1408}
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ref: -2018 tags: machine learning manifold deep neural net geometry regularization date: 08-29-2018 14:30 gmt revision:0 [head]

LDMNet: Low dimensional manifold regularized neural nets.

  • Synopsis of the math:
    • Fit a manifold formed from the concatenated input ‘’and’’ output variables, and use this set the loss of (hence, train) a deep convolutional neural network.
      • Manifold is fit via point integral method.
      • This requires both SGD and variational steps -- alternate between fitting the parameters, and fitting the manifold.
      • Uses a standard deep neural network.
    • Measure the dimensionality of this manifold to regularize the network. Using a 'elegant trick', whatever that means.
  • Still yet he results, in terms of error, seem not very significantly better than previous work (compared to weight decay, which is weak sauce, and dropout)
    • That said, the results in terms of feature projection, figures 1 and 2, ‘’do’’ look clearly better.
    • Of course, they apply the regularizer to same image recognition / classification problems (MNIST), and this might well be better adapted to something else.
  • Not completely thorough analysis, perhaps due to space and deadlines.

{1407}
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ref: -0 tags: tissue probe neural insertion force damage wound speed date: 06-02-2018 00:03 gmt revision:0 [head]

PMID-21896383 Effect of Insertion Speed on Tissue Response and Insertion Mechanics of a Chronically Implanted Silicon-Based Neural Probe

  • Two speeds, 10um/sec and 100um/sec, monitored out to 6 weeks.
  • Once the probes were fully advanced into the brain, we observed a decline in the compression force over time.
    • However, the compression force never decreased to zero.
    • This may indicate that chronically implanted probes experience a constant compression force when inserted in the brain, which may push the probe out of the brain over time if there is nothing to keep it in a fixed position.
      • Yet ... the Utah probe seems fine, up to many months in humans.
    • This may be a drawback for flexible probes [24], [25]. The approach to reduce tissue damage by reducing micromotion by not tethering the probe to the skull can also have this disadvantage [26]. Furthermore, the upward movement may lead to the inability of the contacts to record signals from the same neurons over long periods of time.
  • We did not observe a difference in initial insertion force, amount of dimpling, or the rest force after a 3-min rest period, but the force at the end of the insertion was significantly higher when inserting at 100 μm/s compared to 10 μm/s.
  • No significant difference in histological response observed between the two speeds.

{1406}
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ref: -0 tags: insertion speed needle neural electrodes force damage injury cassanova date: 06-01-2018 23:51 gmt revision:0 [head]

Effect of Needle Insertion Speed on Tissue Injury, Stress, and Backflow Distribution for Convection-Enhanced Delivery in the Rat Brain

  • Tissue damage, evaluated as the size of the hole left by the needle after retraction, bleeding, and tissue fracturing, was found to increase for increasing insertion speeds and was higher within white matter regions.
    • A statistically significant difference in hole areas with respect to insertion speed was found.
  • While there are no previous needle insertion speed studies with which to directly compare, previous electrode insertion studies have noted greater brain surface dimpling and insertion forces with increasing insertion speed [43–45]. These higher deformation and force measures may indicate greater brain tissue damage which is in agreement with the present study.
  • There are also studies which have found that fast insertion of sharp tip electrodes produced less blood vessel rupture and bleeding [28,29].
    • These differences in rate dependent damage may be due to differences in tip geometry (diameter and tip) or tissue region, since these electrode studies focus mainly on the cortex [28,29].
    • In the present study, hole measurements were small in the cortex, and no substantial bleeding was observed in the cortex except when it was produced during dura mater removal.
    • Any hemorrhage was observed primarily in white matter regions of the external capsule and the CPu.

{1405}
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ref: -0 tags: insertion speed neural electrodes force damage date: 06-01-2018 23:38 gmt revision:2 [1] [0] [head]

In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain

  • Targeted at CED procedures, but probably applicable elsewhere.
  • Used a blunted 32ga CA glue filled hypodermic needle.
  • Sprague-dawley rats.
  • Increased insertion speed corresponds with increased force, unlike cardiac tissue.
  • Greatuer surface dimpling before failure results in larger regions of deformed tissue and more energy storage before needle penetration.
  • In this study (blunt needle) dimpling increased with insertion speed, indicating that more energy was transferred over a larger region and increasing the potential for injury.
  • However, friction stresses likely decrease with insertion speed since larger tissue holes were measured with increasing insertion speeds indicating lower frictional stresses.
    • Rapid deformation results in greater pressurization of fluid filled spaces if fluid does not have time to redistribute, making the tissue effectively stiffer. This may occur in compacted tissues below or surrounding the needle and result in increasing needle forces with increasing needle speed.

{1327}
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ref: -2015 tags: ice charles lieber silicon nanowire probes su-8 microwire extracellular date: 05-30-2018 23:40 gmt revision:3 [2] [1] [0] [head]

PMID-26436341 Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes.

  • Xie C1, Liu J1, Fu TM1, Dai X1, Zhou W1, Lieber CM1,2.
  • Again, use silicon nanowire transistors as sensing elements. These seem rather good; can increase the signal, and do not suffer from shunt resistance / capacitance like wires.
    • They're getting a lot of mileage out of the technology; initial pub back in 2006.
  • Su-8, Cr/Pd/Cr (stress elements) and Cr/Au/Cr (conductor) spontaneously rolled into a ball, then the froze in LN2. Devices seemed robust to freezing in LN2.
  • 300-500nm Su-8 passivation layers, as with the syringe injectable electrodes.
  • 3um trace / 7um insulation (better than us!)
  • Used 100nm Ni release layer; thin / stiff enough Su-8 with rigid Si support chip permitted wirebonding a connector (!!)
    • Might want to use this as well for our electrodes -- of course, then we'd have to use the dicing saw, and free-etch away a Ni (or Al?) polyimide adhesion layer -- or use Su-8 like them. See figure S-4
  • See also {1352}

{1404}
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ref: -0 tags: tissue response indwelling implants dialysis kozai date: 04-04-2018 00:28 gmt revision:1 [0] [head]

PMID-25546652 Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

  • (Interesting): eight identical electrode arrays implanted into the same region of different animals have shown that half the arrays continue to record neural signals for >14 weeks while in the other half of the arrays, single-unit yield rapidly degraded and ultimately failed over the same timescale.
  • In another study, aimed at uncovering the time course of insertion-related bleeding and coagulation, electrodes were implanted into the cortex of rats at varying time intervals (−120, −90, −60, −30, −15, and 0 min) using a micromanipulator and linear motor with an insertion speed of 2 mm/s.40 The results showed dramatic variability in BBB leakage that washed out any trend (Figure 3), suggesting that a separate underlying cause was responsible for the large inter- and intra-animal variability.

{1402}
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ref: -0 tags: recurrent cortical model adaptation gain V1 LTD date: 03-27-2018 17:48 gmt revision:1 [0] [head]

PMID-18336081 Adaptive integration in the visual cortex by depressing recurrent cortical circuits.

  • Mainly focused on the experimental observation that decreasing contrast increases latency to both behavioral and neural response (latter in the later visual areas..)
  • Idea is that synaptic depression in recurrent cortical connections mediates this 'adaptive integration' time-constant to maintain reliability.
  • Model also explains persistent activity after a flashed stimulus.
  • No plasticity or learning, though.
  • Rather elegant and well explained.

{1401}
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ref: -2016 tags: somatostatin interneurons review date: 02-11-2018 18:08 gmt revision:0 [head]

PMID-27225074 Somatostatin-expressing neurons in cortical networks.

  • Urban-Ciecko J1, Barth AL1.
  • High (~ 10hz) tonic (constitutive) firing rate. All GABA.
  • Somatostatin, a neuropeptide, is of ill-defined role. Unknown when it is released.
  • SST interneurons receive diffuse input from cortical pyramidal cells, but each synapse is of low strength.
  • SST intererneurons are frequently electrically connected through gap junctions, but almost never through electrical synapses. The resulting network can extend for hundreds of microns, and has been shown to cause synchronized firing when cells are active.
  • Common anesthetics (isoflurane, urethane) profoundly silence the SSTs.
  • Wide diversity of axonal and dendritic branching patterns, targeting both apical (20%) and distal pyramidal cell dendrites.
  • SST neuron activity is reduced in Dravet syndrome.
  • SST neurons have also been implicated in schizophrenia; affected individuals show decreased SST mRNA and mislocalization of SST interneurons.

{1384}
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ref: -0 tags: NET probes SU-8 microfabrication sewing machine carbon fiber electrode insertion mice histology 2p date: 12-29-2017 04:38 gmt revision:1 [0] [head]

PMID-28246640 Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration

  • SU-8 asymptotic H2O absorption is 3.3% in PBS -- quite a bit higher than I expected, and higher than PI.
  • Faced yield problems with contact litho at 2-3um trace/space.
  • Good recordings out to 4 months!
  • 3 minutes / probe insertion.
  • Fab:
    • Ni release layer, Su-8 2000.5. "excellent tensile strength" --
      • Tensile strength 60 MPa
      • Youngs modulus 2.0 GPa
      • Elongation at break 6.5%
      • Water absorption, per spec sheet, 0.65% (but not PBS)
    • 500nm dielectric; < 1% crosstalk; see figure S12.
    • Pt or Au rec sites, 10um x 20um or 30 x 30um.
    • FFC connector, with Si substrate remaining.
  • Used transgenic mice, YFP expressed in neurons.
  • CA glue used before metabond, followed by Kwik-sil silicone.
  • Neuron yield not so great -- they need to plate the electrodes down to acceptable impedance. (figure S5)
    • Measured impedance ~ 1M at 1khz.
  • Unclear if 50um x 1um is really that much worse than 10um x 1.5um.
  • Histology looks realyl great, (figure S10).
  • Manuscript did not mention (though the did at the poster) problems with electrode pull-out; they deal with it in the same way, application of ACSF.

{1062}
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ref: Kim-2008.01 tags: PEDOT review soft date: 12-29-2017 04:34 gmt revision:4 [3] [2] [1] [0] [head]

PMID-21204405 Soft, Fuzzy, and Bioactive Conducting Polymers for Improving the Chronic Performance of Neural Prosthetic Devices.

  • lays out the soft electrode approach (obviously).
  • Extensive discussion of conductive polymer plating methods for neural electrodes.

____References____

[0] Kim DH, Richardson-Burns S, Povlich L, Abidian MR, Spanninga S, Hendricks JL, Martin DC, Soft, Fuzzy, and Bioactive Conducting Polymers for Improving the Chronic Performance of Neural Prosthetic Devicesno Source no Volume no Issue no Pages (2008)

{1010}
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ref: Salcman-1973.07 tags: Salcman MEA microelectrodes chronic recording glass cyanocrylate date: 12-29-2017 04:33 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-4708761 Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes

  • Teflon-coated 25um Pt-Ir (90/10)
  • Heat fuse this with a glass micropipette & backfill with cyanoacrylate. {1011}
    • Isobutyl acrylate is hydrolysed more slowly and hence is less toxic to the surronding tissue
    • cyanoacrylate is apparently biodegradable.
  • Durable, stable: one electrode displayed a single cortical spike (though not necessarily the same one) for more than 90 consecutive days.
  • unacceptably low impedance = 100K or less
  • Unit activity was present only 10-24H after surgery.
  • formal review of even older microelectrode studies.
  • 10nA should be 100x too small to have any effect on a platinum tip [17]
  • A seperable cell with a SNR of 3:1 would become lost if the electrode tip moved 15um away from a 20um soma.
    • "It becomes clear that the problem of holding single units for prolonged periods in the unrestrained animal is not achieved without considerable difficulty". Yet they think they have solved it.

____References____

Salcman, Michael and Bak, Martin J. Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes Biomedical Engineering, IEEE Transactions on BME-20 4 253 -260 (1973)

{1400}
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ref: -0 tags: robinson pasquali carbon nanotube fiber fluidic injection dextran neural electrode date: 12-28-2017 04:20 gmt revision:0 [head]

PMID-29220192 Fluidic Microactuation of Flexible Electrodes for Neural Recording.

  • Use viscous dextran solution + PDMS channel system
  • Durotomy (of course)
  • Parylene-C insulated carbon fiber electrodes, cut with FIB or razor blade
  • Used silver ink to electrically / mechanically attach for recordings.
  • Tested in hydra, rat brain slice (reticular formation of thalamus), and in-vivo rat.
  • Electrodes, at 12um diameter, E=120GPa, are approximately 127x stiffer than one 4x20um PI (E=9GPa) probe. Less damage though.

{1368}
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ref: -0 tags: Lieber nanoFET review silicon neural recording intracellular date: 12-28-2017 04:04 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-23451719 Synthetic Nanoelectronic Probes for Biological Cells and Tissue

  • Review of nanowireFETS for biological sensing
  • Silicon nanowires can be grown via vapor-liquid-solid or vapor-solid-solid, 1D catalyzed growth, usually with a Au nanoparticle.
  • Interestingly, kinks can be introduced via "iterative control over nucleation and growth", 'allowing the synthesis of complex 2D and 3D structures akin to organic chemistry"
    • Doping can similarly be introduced in highly localized areas.
    • This bottom-up synthesis is adaptable to flexible and organic substrates.
  • Initial tests used polylysine patterning to encourage axonal and dendritic growth across a nanoFET.
    • Positively charged amino group interacts with negative surface charge phospholipid
    • Lieber's group coats their SU-8 electrodes in poly-d-lysine as well {1352}
  • Have tested multiple configurations of the nanowire FET, including kinked, one with a SiO2 nanopipette channel for integration with the cell membrane, and one where the cell-attached fluid membrane functions as the semiconductor; see figure 4.
    • Were able to show recordings as one of the electrodes was endovascularized.
  • It's not entirely clear how stable and scalable these are; Si and SiO2 gradually dissolve in physiological fluid, and no mention was made of longevity.

{1176}
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ref: Gilgunn-2012 tags: kozai neural recording electrodes compliant parylene flexible dissolve date: 12-28-2017 03:50 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-6170092 (pdf) An ultra-compliant, scalable neural probe with molded biodissolvable delivery vehicle

    • Optical coherence tomography is cool.
  • Large footprint - 150 or 300um, 135um thick (13500 or 40500 um^2; c.f. tungsten needle 1963 (50um) or 490 (25um) um^2.)
  • Delivery vehicle is fabricated from biodissolvable carboxy-methylcellulose (CMC).
    • Device dissolves within three minutes of implantation.
    • Yet stiff enough to penetrate the dura of rats (with what degree of dimpling?)
    • Lithographic patterning process pretty clever, actually.
    • Parylene-X is ~ 1.1 um thick.
    • 500nm Pt is patterned via ion milling with a photoresist mask.
    • Use thin 20nm Cr etch mask for both DRIE (STS ICP) and parylene etch.
  • Probes are tiny -- 10um wide, 2.7um thick, coated in parylene-X.
  • CMC polymer tends to bend and warp due to stress -- must be clamped in a special jig.
  • No histology. Follow-up: {1399}

{1236}
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ref: -0 tags: optogenetics micro LED flexible electrodes PET rogers date: 12-28-2017 03:24 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-23580530 Injectable, cellular-scale optoelectronics with applications for wireless optogenetics.

  • Supplementary materials
  • 21 authors, University Illinois at Urbana-Champaign, Tufts, China, Northwestern, Miami ..
  • GaN blue and green LEDs fabricated on a flexible substrate with stiff inserter.
    • Inserter is released in 15 min with a dissolving silk fibrin.
    • made of 250um thick SU-8 epoxy, reverse photocured on a glass slide.
  • GaN LEDS fabricated on a sapphire substrate & transfer printed via modified Karl-Suss mask aligner.
    • See supplemental materials for the intricate steps.
    • LEDs are 50um x 50um x 6.75um
  • Have integrated:
    • Temperature sensor (Pt serpentine resistor) / heater.
    • inorganic photodetector (IPD)
      • ultrathin silicon photodiode 1.25um thick, 200 x 200um^2, made on a SOI wafer
    • Pt extracellular recording electrode.
        • This insulated via 2um thick more SU-8.
  • Layers are precisely aligned and assembled via 500nm layer of epoxy.
    • Layers made of 6um or 2.5um thick mylar (polyethylene terephthalate (PET))
    • Layers joined with SU-8.
    • Wiring patterned via lift-off.
  • Powered via RF scavenging at 910 Mhz.
    • appeared to be simple, power in = light out; no data connection.
  • Tested vs control and fiber optic stimulation, staining for:
    • Tyrosine hydroxylase (makes l-DOPA)
    • c-fos, a neural activity marker
    • u-LEDs show significant activation.
  • Also tested for GFAP (astrocytes) and Iba1 (activated microglia); flexible & smaller devices had lower gliosis.
  • Next tested for behavior using a self-stimulation protocol; mice learned to self-stimulate to release DA.
  • Devices are somewhat reliable to 250 days!

{1399}
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ref: -0 tags: kozai CMC dissolving insertion shuttle parylene date: 12-28-2017 03:19 gmt revision:1 [0] [head]

PMID-25128375 Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes.

  • CMC = carboxymethyl cellulose, commonly used as a food additive, in toothpaste, etc.
  • To address CMC dissolution, we developed a sophisticated targeting, high speed insertion (∼80 mm/s), and release system to implant shuttles.
  • Cross section of the probes are large, 300 x 125um and 100 x 125um.
  • Beautiful histology: the wound does gradually close up as the CMC dissolves, but no e-phys.

{1057}
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ref: Kozai-2009.11 tags: electrodes insertion Kozai flexible polymer momolayer date: 12-28-2017 02:59 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

PMID-19666051[0] Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain.

  • This study investigated the use of an electronegative (hydrophillic) self-assembled monolayer (SAM) as a coating on a stiff insertion shuttle to carry a polymer probe into the cerebral cortex, and then the detachment of the shuttle from the probe by altering the shuttle's hydrophobicity.
    • Used 11-mercaptoundecanoic acid.
    • Cr/Au (of course) evaporated on 15um thick Si shuttle.
    • SAM attracts water once inserted, causing the hydrophobic polymer to move away.
      • Why not make the polymer hydrophillic?
      • Is this just soap?
  • Used agarose brain model.
  • Good list of references for the justification of soft electrodes, and researched means for addressing this, mostly usnig polymer stiffeners.
    • "Computer models and experimental studies of the probe–tissue interface suggest that flexible and soft probes that approach the brain’s bulk material characteristics may help to minimize micromotion between the probe and surrounding tissue ({737}; {1203}; {1102}; {1200}; LaPlaca et al., 2005; {1216}; Neary et al., 2003 PMID-12657694; {1198})"
  • "However, polymer probes stick to metallic and silicon surfaces through hydrophobic interactions, causing the polymer probe to be carried out of the brain when the insertion shuttle is removed. The solution is to use a highly hydrophillic, electronegative, self-assembled monolayer coating on the shuttle.
  • Biran et al 2005 suggests that incremental damage due to stab wounds from the shuttle (needle) should be minor.
  • Probes: 12.5 um thick, 196 um wide, and 1.2cm long, polymide substrate and custom designed lithographed PDMS probes.
  • Polymer probes were inserted deep - 8.5 mm.
  • PDMS probes inserted with non-coated insertion shuttle resulted in explantation of the PDMS probe.

____References____

[0] Kozai TD, Kipke DR, Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain.J Neurosci Methods 184:2, 199-205 (2009 Nov 15)