gebhart/patrepeval huggingface dataset:
Multi-scale approaches for high-speed imaging and analysis of large neural populations (2016)

Abstract Progress in modern neuroscience critically depends on our ability to observe the activity of large neuronal populations with cellular spatial and high temporal resolution. However, two bottlenecks constrain efforts towards fast imaging of large populations. First, the resulting large video data is challenging to analyze. Second, there is an explicit tradeoff between imaging speed, signal-to-noise, and field of view: with current recording technology we cannot image very large neuronal populations with simultaneously high spatial and temporal resolution. Here we describe multi-scale approaches for alleviating both of these bottlenecks. First, we show that spatial and temporal decimation techniques provide order-of-magnitude speedups in spatiotemporally demixing calcium video data into estimates of single-cell neural activity. Second, once the shapes of individual neurons have been identified (e.g., after an initial phase of conventional imaging with standard temporal and spatial resolution), we find that the spatial/temporal resolution tradeoff shifts dramatically: after demixing we can accurately recover neural activity from data that has been spatially decimated by an order of magnitude. This offers a cheap method for compressing this large video data, and also implies that it is possible to either speed up imaging significantly, or to “zoom out” by a corresponding factor to image order-of-magnitude larger neuronal populations with minimal loss in accuracy or temporal resolution. Author Summary The voxel rate of imaging systems ultimately sets the limit on the speed of data acquisition. These limits often mean that only a small fraction of the activity of large neuronal populations can be observed at high spatio-temporal resolution. For imaging of very large populations with single cell resolution, temporal resolution is typically sacrificed. Here we propose a multi-scale approach to achieve single cell precision using fast imaging at reduced spatial resolution. In the first phase the spatial location and shape of each neuron is obtained at standard spatial resolution; in the second phase imaging is performed at much lower spatial resolution. We show that we can apply a demixing algorithm to accurately recover each neuron’s activity from the low-resolution data by exploiting the high-resolution cellular maps estimated in the first imaging phase. Thus by decreasing the spatial resolution in the second phase, we can compress the video data significantly, and potentially acquire images over an order-of-magnitude larger area, or image at significantly higher temporal resolution, with minimal loss in accuracy of the recovered neuronal activity. We evaluate this approach on real data from light-sheet and 2-photon calcium imaging.
Targeting acetyl-CoA metabolism attenuates the formation of fear memories through reduced activity-dependent histone acetylation (2022)

ABSTRACT Histone acetylation is a key component in the consolidation of long-term fear memories. Epigenetic enzymes involved in histone acetylation, including histone acetyltransferases and deacetylases, have been put forward as potential pharmacological targets in the treatment of pathological fear memories, such as those that underlie post-traumatic stress disorder (PTSD). However, these enzymes typically play a ubiquitous role in gene regulation, which precludes the clinical use of systemic manipulations. Recently, we have found that a nuclear-localized metabolic enzyme, Acetyl-coA synthetase 2 (Acss2), modulates histone acetylation during learning and memory. Loss of Acss2 is well-tolerated in mice, with no impact on general health or baseline behavior. Here, we show that an Acss2 null mouse model shows reduced acquisition of long-term fear memories in assays of contextual and cued fear conditioning. We find that loss of Acss2 leads to consolidation-specific reductions in both histone acetylation and the expression of critical learning and memory-related genes in the dorsal hippocampus. Further, we show that systemic administration of blood-brain-barrier (BBB)-permeable Acss2 inhibitors during the consolidation window reduces fear memory formation in mice and rats, and also reduces anxiety in a predator-scent-stress (PSS) paradigm. Our findings suggest that Acss2 plays a critical role in the formation of fear memories, and represents a potential pharmacological target in the treatment of PTSD.
Discovery and characterisation of novel asexual Epichloë endophytes from perennial ryegrass (Lolium perenne L.) (2015)

Asexual fungal endophytes of the genus Epichloë form mutually beneficial associations with cool-season pasture grasses such as ryegrasses (Lolium spp.). Alkaloid production by the fungus confers both beneficial (deterrence of invertebrate herbivory) and detrimental (toxicity to mammalian livestock) attributes. A few novel strains with desirable metabolite profiles have been advanced into commercial production by inoculation of perennial ryegrass cultivars. In the present study, an integrated process for discovery of novel endophytes based on exploitation of genotypic information has been designed and implemented. A survey of genetic diversity was performed on a large-scale, customised germplasm collection (containing 244 accessions) in order to identify previously uncharacterised endophyte genotypes. Preliminary qualitative metabolic profiling in the endogenous genetic background permitted elimination of undesirable combinations, and definition of a subset of priority candidates. A novel method was developed for inoculation of endophytes into meristem-culture-derived callus tissue of single genotypes from multiple perennial ryegrass cultivars, in order to allow isogenic comparisons with respect to both host and endophyte genotype. Beneficial toxin profiles were confirmed for associations formed with the grass genotypic panel, and semi-quantitative metabolite analysis provided evidence for genotype-specific effects of both host and genotype on levels of alkaloid production. Vegetative stability was also assessed over both shorter and longer terms. A final set of three prioritised candidates was obtained, two of which (belonging to the known taxa E. festucae var. lolii and LpTG-2) produce the alkaloids ergovaline and peramine. The third candidate endophyte, belonging to a putative novel taxon, solely produces representatives of an additional alkaloid class, the epoxy-janthitrems.
State switched acoustic source (1994)

To produce high amplitude low-frequency signals, an underwater transducer must generate a relatively large volume displacement. Since water exerts a large reaction force back on the transducer, ‘‘conventional wisdom’’ dictates that such a transducer would have to be a high Q resonant device and thus not be broadband as seemingly required for many applications. However, a transducer does not have to be broadband in the conventional sense to work in communication and SONAR systems. A transducer capable of switching between two discrete frequencies is adequate for communication and one capable of switching among several frequencies could produce chirp signals for active sonars. Ordinarily, a broadband transducer is needed to switch frequencies rapidly. It is theoretically possible, however, to instantaneously switch frequencies with a high Q resonant system provided that the system’s resonant and drive frequencies are altered simultaneously. Such a ‘‘state-switched’’ transducer [Munk, Webb, Birdsall, unpublished (1980), (1981)] would retain the advantages (high power, high efficiency, and large displacements) of a high Q resonant transducer without the accompanying disadvantage of slow response time. A state-switched acoustic source with an active spring of PZT has been built to demonstrate the state switching concept. [Research supported by ONR 334.]
Dynamic expressivity with static optimization for streaming languages (2013)

Developers increasingly use streaming languages to write applications that process large volumes of data with high throughput. Unfortunately, when picking which streaming language to use, they face a difficult choice. On the one hand, dynamically scheduled languages allow developers to write a wider range of applications, but cannot take advantage of many crucial optimizations. On the other hand, statically scheduled languages are extremely performant, but have difficulty expressing many important streaming applications.
Chlamydia psittaci and ocular adnexal lymphomas (2009)

Infectious agents, including bacteria, have been variously associated with lymphomagenesis and, in some cases, regarded as targets for new therapeutic approaches. Several lines of evidence indicates that ocular adnexal lymphomas (OAL) may be antigen-driven disorders, although the source of the putative antigen(s) is still unknown. Chlamydiae infection is responsible for inflammatory ocular diseases including chronic follicular conjunctivitis, which could provide persistent antigenic stimulation. On these grounds, we have carried out a study aimed to assess whether infection by Chlamydiae is associated with the development of OAL.
Expression of the Klebsiella pneumoniae CG21 acetoin reductase gene in Clostridium acetobutylicum ATCC 824 (2001)

Acetoin reductase catalyzes the production of 2,3-butanediol from acetoin. The gene encoding the acetoin reductase of Klebsiella pneumoniae CG21 was cloned and expressed in Escherichia coli and Clostridium acetobutylicum ATCC 824. The nucleotide sequence of the gene encoding the enzyme was determined to be 768 bp long. Expression of the K. pneumoniae acetoin reductase gene in E. coli revealed that the enzyme has a molecular mass of about 31,000 Da based on sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis. The K. pneumoniae acetoin reductase gene was cloned into a clostridial/E. coli shuttle vector, and expression of the gene resulted in detectable levels of acetoin reductase activity in both E. coli and C. acetobutylicum. While acetoin, the natural substrate of acetoin reductase, is a typical product of fermentation by C. acetobutylicum, 2,3-butanediol is not. Analysis of culture supernatants by gas chromatography revealed that introduction of the K. pneumoniae acetoin reductase gene into C. acetobutylicum was not sufficient for 2,3-butanediol production even though the cultures were producing acetoin. 2,3-Butanediol was produced by cultures of C. acetobutylicum containing the gene only when commercial acetoin was added.
Negative‐working photoresist of methacrylate polymers based on the transesterification of the 2‐hydroxyethyl group in the presence of an acid (2002)

Abstract This article reports a novel crosslinking functionality of the 2‐hydroxyethyl methacrylate unit (HEMA) in the presence of an acid. The polymeric compositions, consisting of a polymer containing the HEMA unit and a photoacid generator, were insolubilized in an aqueous base developer on exposure to UV light and a successive baking process to provide a negative‐working photoresist. A series of poly(benzyl methacrylate‐ co ‐methacrylic acid‐ co ‐2‐hydroxyethyl methacrylate) terpolymers with various contents of HEMA were prepared to elucidate the photopolymeric characteristics. The polymer behavior in films was examined by a comparison of the photosensitivity and IR spectroscopic method. Experiments with a model compound were also carried out. On the basis of the results, we found that the resist was insolubilized by crosslinking through the transesterification of HEMA segments due to acid generated from the photoacid generator and subsequent heating. The advantage of using the 2‐hydroxyethyl group is that in the terpolymer, the HEMA unit is transparent at a short‐wavelength region and is a promising crosslinking unit for ArF lithographic photoresists. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1858–1867, 2002
Local Composition of Cycled Silicon Negative Electrodes (2009)

Abstract not Available.
Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial (2019)

A dose-response relationship was observed for upadacitinib efficacy; the 30-mg once-daily dose showed the greatest clinical benefit. Dose-limiting toxicity was not observed.
Online Deep Equilibrium Learning for Regularization by Denoising (2022)

Plug-and-Play Priors (PnP) and Regularization by Denoising (RED) are widely-used frameworks for solving imaging inverse problems by computing fixed-points of operators combining physical measurement models and learned image priors. While traditional PnP/RED formulations have focused on priors specified using image denoisers, there is a growing interest in learning PnP/RED priors that are end-to-end optimal. The recent Deep Equilibrium Models (DEQ) framework has enabled memory-efficient end-to-end learning of PnP/RED priors by implicitly differentiating through the fixed-point equations without storing intermediate activation values. However, the dependence of the computational/memory complexity of the measurement models in PnP/RED on the total number of measurements leaves DEQ impractical for many imaging applications. We propose ODER as a new strategy for improving the efficiency of DEQ through stochastic approximations of the measurement models. We theoretically analyze ODER giving insights into its convergence and ability to approximate the traditional DEQ approach. Our numerical results suggest the potential improvements in training/testing complexity due to ODER on three distinct imaging applications.
Gap junction density in human myometrium at term revealed by an anti-peptide antibody and laser scanning confocal microscopy. (1993)

The concept that the progesterone-estrogen ratio determines gap junction abundance in myometrium has developed from studies in laboratory animals. In the humans, however, gap junctions form in abundance at term despite a high progesterone-estrogen ratio. We have therefore examined the relationship between contractile activity, progesterone and estrogen levels and gap junction abundance in human myometrium at term. Myometrial tissue obtained from women who had an elective or emergency Cesarean operation at the 38th or 39th week of pregnancy was immunohistochemically examined using a polyclonal antiserum raised against a synthetic peptide matching part of the sequence of connexin43, the principal component of myometrial gap junctions. The concentration of progesterone and estradiol in the maternal blood was measured by means of radio-immunoassay. The number of gap junctions was estimated by counting of punctate staining patterns obtained in myometrial tissue as viewed by laser confocal microscopy and calculated per 1 microns 3 of tissue. The number of gap junctions measured was found to be related to the presence or absence of labor. In the myometrium of women in labor (active phase), the number of gap junctions was highest (45.25 +/- 35). When the myometrium was not contracting (non-labor) and when contractions were weak (pre-labor) the number of gap junctions was low (15.16 +/- 10-5.75 +/- 5). In the pre-and active phase of labor, the concentration of progesterone in maternal blood was significantly higher (P < 0.025 and 0.03, respectively) than in women who were not in labor. The present study shows the potential of using optical section series obtained by laser confocal microscopy for the quantification and mapping of the three-dimensional distribution of gap junctions in human myometrium at term.
Real-time slit scanning microscopy in the meridional plane (2009)

The standard microscope architecture around which confocal microscopes are built imposes fundamental restrictions on the speed with which images (three-dimensional data sets) can be obtained. Commercially available slit scanning confocal microscopes are able to produce optically sectioned images at frame rates well in excess of 100 Hz. However only the focal (x-y) plane can be imaged at this speed. To image a volume specimen it is necessary to physically change the distance between the objective lens and the specimen. This refocusing process is often necessarily slow and represents a bottleneck to the speed of image acquisition. We describe the construction of a slit scanning confocal microscope based on what we know to be a novel microscope architecture, which permits images of other planes and, particular, the meridional (x-z) plane to be acquired in real time.
Crystal structures of the barium salts of isonitroso- and of NN′-dimethyl-isonitroso-malonamide (1976)

The structures of (I) 2Ba[NH2·CO·C(NO)·CO·NH2]2·7H2O, and (II) Ba[MeNH·CO·C(NO)·CO·NHMe]2 have been determined by X-ray (heavy-atom) methods from diffractometer data and refined by least squares to R 0.10 and 0.038 respectively. Crystals of (I) are tetragonal, space group P41212,a= 10.718(3), c= 51.12 (3)Å, Z= 8. Crystals of (II) are trigonal, space group R, a= 10.966(2)Å, α= 73.34(2)°. Z= 3. (I) comprises pairs of barium atoms 4.763 Å apart and bridged in an infinite polymeric array in the ab plane by the ligands, the resulting layers normal to c being hydrogen-bonded by interleaving water molecules. The barium atoms are nine- and ten-co-ordinated by an assortment of ligand nitrogen and oxygen atoms and water molecules. (II) comprises centro-symmetric triads of barium atoms disposed in the three-fold axis [Ba ⋯ Ba, 4.2414(7)Å] and bridged by the oxygen atoms of the ligands, the centrosymmetric barium being six-co-ordinate, and the others nine-co-ordinate. A three-dimensional polymer is formed by oxygen bridges.
Simulation of surface charge effect on impulse flashover characteristics of outdoor polymeric insulators (2010)

Effect of pre-deposited surface charges on impulse flashover characteristics of a polymeric insulator is studied by means of computer simulations utilizing a model based on criteria for streamer inception, propagation and sustenance. A parametric study is performed to investigate the influences imposed by magnitude and polarity of the charge, its location on insulator surface and properties of insulator material on its flashover voltages. The obtained results are analyzed in terms of electric field distributions in the vicinity of the insulator surface and are compared with experimental data available in the literature.
Phase Morphology, Thermal and Mechanical Properties of Compatibilized Nylon12/Natural Rubber Blends Using PS/MNR (2013)

To produce a tough material for application demanding high impact resistance and low moisture absorption, melt blending of Nylon12 (Polyamide 12, PA12) and natural rubber (NR) was carried out in a brabender plasticorder at 210 °C with rotor speed of 70 rpm in the presence of polystyrene/maleated natural rubber (PS/MNR) blend as a compatibilizer. The effect of compatibilizer content (1, 3, 5, 7 and 10 phr) on phase morphology, thermal, and mechanical properties of [Nylon12/NR]/[PS/MNR] blends was investigated by using SEM, DSC, and Izod impact tester, respectively. The result revealed that PS/MNR blend improved the compatibility of Nylon12/NR blends efficiently due to the presence of amide linkage at the interfaces from the reaction between the reactive groups of MNR and the NH 2 end groups of Nylon12 during mixing. A fine phase morphology (good dispersion and small dispersed phase size of NR domains in Nylon12 matrix) of [Nylon12/NR]/[PS/MNR] blends was observed at the optimum compatibilizer content of 7 phr, relating to the improvement of mechanical property. The impact energy of [Nylon12/NR]/[PS/MNR] blends was 503 J/m higher than that of neat Nylon12 (115 J/m) and Nylon12/NR binary blend (241 J/m) due to the toughening effect of rubber and proper morphology. The melting temperature of all blends did not change obviously from thermal analysis. However, the presence of rubber particle obstructed the crystallization of Nylon12 phase, leading to the decreasing of %crystallinity from 93% to around 70%.
Platelet phospholipases A2 (2002)

The major physiological role of platelets is in the cessation of bleeding following damage to the vasculature. Ordinarily, platelets circulate within intact blood vessels in a quiescent state, but undergo extremely rapid and powerful activation upon exposure to the subendothelial matrix leading to formation of a platelet aggregate or vascular plug. This rapid response is achieved by the stimulatory action of a range of diverse agonists including extracellular matrix proteins, e.g. collagen, and products of the coagulation cascade, e.g. thrombin. Activation is reinforced through release of agonists from platelet granules, notably ADP, and liberation of thromboxane A2 (TxA2), the major product of the metabolism of arachidonic acid (AA) in the platelet. The positive feedback action of ADP and TxA2 is of direct clinical relevance. The Antiplatelet Trialists' Collaboration published a summary of 20 randomized trials in 1988, concluding that antiplatelet therapy significantly reduces (by ∼ 25%) the risk of cardiovascular death, non-fatal myocardial infarction and nonfatal stroke in patients with unstable angina or a past history of heart attack, transient ischemic attack, or stroke. A follow-up report by the same group, confirmed the efficacy of platelet inhibition in a broader spectrum of pathological conditions. More recently, the CAPRIE study has shown that the ADP receptor antagonist, clopidogrel, and aspirin have a similar therapeutic benefit in individuals with a history of thrombotic disease. Aspirin, however, remains the drug of choice in the majority of cases primarily for reasons of cost.
Prediction of the Water Content in Protein Binding Sites (2009)

An efficient molecular simulation methodology has been developed to determine the positioning of water molecules in the binding site of a protein or protein-ligand complex. Occupancies and absolute binding free energies of water molecules are computed using a statistical thermodynamics approach. The methodology, referred to as Just Add Water Molecules (JAWS), features "theta-water" molecules that can appear and disappear on a binding-site grid. Key approximations render the technique far more efficient than conventional free energy simulations. Testing of JAWS on five diverse examples (neuraminidase, scytalone dehydratase, major urinary protein 1, beta-lactoglobulin, and COX-2) demonstrates its accuracy in locating hydration sites in comparison to results from high-resolution crystal structures. Possible applications include aid in refinement of protein crystal structures, drug lead optimization, setup of docking calculations, and simulations of protein-ligand complexes.
Integrated high quality factor lithium niobate microdisk resonators (2014)

Lithium Niobate (LN) is an important nonlinear optical material. Here we demonstrate LN microdisk resonators that feature optical quality factor ~10(5), realized using robust and scalable fabrication techniques, that operate over a wide wavelength range spanning visible and near infrared. Using our resonators, and leveraging LN's large second order optical nonlinearity, we demonstrate on-chip second harmonic generation with a conversion efficiency of 0.109 W(-1).
The Cilk++ concurrency platform (2009)

The availability of multicore processors across a wide range of computing platforms has created a strong demand for software frameworks that can harness these resources. This paper overviews the Cilk++ programming environment, which incorporates a compiler, a runtime system, and a race-detection tool. The Cilk++ runtime system guarantees to load-balance computations effectively. To cope with legacy codes containing global variables, Cilk++ provides a "hyperobject" library which allows races on nonlocal variables to be mitigated without lock contention or substantial code restructuring.