cssi/SciSciGPT-SciSciNet huggingface dataset:
Islet Architecture Controls Synchronous β Cell Response to Glucose in the Intact Mouse Pancreas in vivo

The spatial architecture of the islets of Langerhans is hypothesized to facilitate synchronized insulin secretion between β cells, yet testing this in vivo in the intact pancreas is challenging. Robo βKO mice, in which the genes Robo1 and Robo2 are deleted selectively in β cells, provide a unique model of altered islet architecture without loss of β cell differentiation or islet damage from diabetes. Combining Robo βKO mice with intravital microscopy, we show here that Robo βKO islets lose synchronized intra-islet Ca2+ oscillations between β cells in vivo. We provide evidence that this loss is not due to a β cell-intrinsic function of Robo, loss of Connexin36 gap junctions, or changes in islet vascularization, suggesting that the islet architecture itself is required for synchronized Ca2+ oscillations. These results will have implications for understanding structure-function relationships in the islets during progression to diabetes as well as engineering islets from stem cells.
Efficacy of Office Ergonomics Education

The incidence of musculoskeletal injuries associated with computer use is increasing. Education has been advocated as a prevention method for reducing the incidence and severity of these injuries. Although the inclusion of education in prevention programs has become a popular practice, its efficacy is poorly defined. The present study was designed to investigate the efficacy of worker education programs in preventing musculoskeletal injuries in a population of reservation center employees who spend the majority of their workdays, using the computer. Participants were randomly assigned to one of three study groups (control, traditional education, or participatory education). Data collection utilized self-report surveys and observational checklists to collect data prior to intervention and at approximately 3, 6, and 12 months post intervention. Those who received education reported less pain/discomfort and psychosocial work stress following the intervention than those who did not receive education. There was no indication that the differences in reported pain/discomfort or psychosocial work stress were related to better work area configuration or improved worker postures. Those workers in the participatory education intervention group reported a significantly better perception of their health status than those in the control group or the traditional education group. It is unclear if the method of intervention was solely responsible for the higher rating.
Individual sensitivity preprocessing for data privacy

The sensitivity metric in differential privacy, which is informally defined as the largest marginal change in output between neighboring databases, is of substantial significance in determining the accuracy of private data analyses. Techniques for improving accuracy when the average sensitivity is much smaller than the worst-case sensitivity have been developed within the differential privacy literature, including tools such as smooth sensitivity, Sample-and-Aggregate, Propose-Test-Release, and Lipschitz extensions. In this work, we provide a new and general Sensitivity-Preprocessing framework for reducing sensitivity, where efficient application gives state-of-the-art accuracy for privately outputting the important statistical metrics median and mean when no underlying assumptions are made about the database. In particular, our framework compares favorably to smooth sensitivity for privately outputting median, in terms of both running time and accuracy. Furthermore, because our framework is a preprocessing step, it can also be complementary to smooth sensitivity and any other private mechanism, where applying both can achieve further gains in accuracy. We additionally introduce a new notion of individual sensitivity and show that it is an important metric in the variant definition of personalized differential privacy. We show that our algorithm can extend to this context and serve as a useful tool for this variant definition and its applications in markets for privacy. Given the effectiveness of our framework in these important statistical metrics, we further investigate its properties and show that: (1) Our construction is conducive to efficient implementation with strong accuracy guarantees, evidenced by an O(n) implementation for median (with presorted data), and O(n2) implementation for more complicated functions such as mean, α-trimmed mean, and variance. (2) Our construction is both NP-hard and also optimal in the general setting (3) Our construction can be extended to higher dimensions, although it incurs accuracy loss that is linear in the dimension.
Cycle intersection graphs and minimum decycling sets of even graphs

We introduce the cycle intersection graph of a graph, an adaptation of the cycle graph of a graph, and use the structure of these graphs to prove an upper bound for the decycling number of all even...
Heterogeneous Integration Using Omni-Directional Interconnect Packaging

We present a new packaging building block for 3D integrated circuits: Omni Directional Interconnect (ODI). It adds a new degree of freedom in packaging that enables combining the high bandwidth benefit of standard 3D stacking with the minimal die area, thermal performance and direct power delivery of 2D packaging. ODI performance and cost benefits in high-performance computing are summarized. It is shown that by using careful assembly strategy, the required tolerances can be made the same as other 2.5/3D technologies. The fabrication results for two of the architectures are included and show good repeatability and robust assembly.
Experimental observation of coupled valley and spin Hall effect in p‐doped WSe2 devices

Giant spin Hall effect (GSHE) has been observed in heavy metal materials such as Ta, Pt, and W, where spins are polarized in the surface plane and perpendicular to the charge current direction. Spins generated in these materials have successfully switched magnets with in-plane magnetic anisotropy (IMA) and perpendicular magnetic anisotropy (PMA) through spin orbit torque (SOT) mechanism. It is generally accepted that PMA magnets are preferred over IMA magnets in data storage applications owing to their large thermal stability even at ultra scaled dimensions. However, SOT switching of PMA magnets by conventional GSHE materials requires either a small external magnetic field, a local dipolar field, or introducing tilted anisotropy to break the symmetry with respect to the magnetization. To deterministically switch a PMA without any additional assistance, nonconventional GSHE materials that can generate spins with polarization perpendicular to the surfaces are needed. Several monolayer transition metal dichalcogenides (TMDs) have been predicted to generate such out of plane spins due to their 2D nature and unique band structures. Interestingly, opposite spins are locked to their respective sub-band in each K valley of the TMD valence band with substantially large energy splitting, which enables polarized spins to be accessible through electrical gating and spatially separated by electric field through the valley Hall effect (VHE). Therefore, spatial separation and accumulation of spins in these 2D TMDs are uniquely referred to as coupled valley and spin Hall effect. Here, we report an experiment of electrical generation of spin current with out of plane polarization in monolayer WSe2 and detection of spin signals through a nonlocal spin valve structure built on a lateral graphene spin diffusion channel that partially overlaps with WSe2.
Relationship between Laboratory Abrasion Tests and Service Performance

Abstract In development work on GR-S commercial recapping compounds originated in 1943 by the Directorate of Mechanical Engineering, Department of National Defence, Ottawa, Canada, in which an attempt was made to correlate road performance with physical properties as determined in the laboratory, it was found that no relationship whatever existed between the results of road tests carried out under the supervision of that directorate and standard laboratory abrasion resistance tests carried out in the Canadian National Research Council Rubber Laboratory at Ottawa. In the laboratory test the sandpaper in the abrasion machine became coated with a smear of tacky viscous material which the air jet was unable to remove. Under these conditions the rubber tends to slide over the sandpaper surface, with relatively little actual abrasion of the rubber. The effect remains even after a considerable overcure of the sample. It was felt that the removal of the tacky viscous material from vulcanized GR-S by extraction mi...
New Proof of the Cheeger–Müller Theorem

We present a short analytic proof of the equality between the analytic and combinatorialtorsion. We use the same approach as in the proof given by Burghelea, Friedlander andKappeler, but avoid using the difficult Mayer-Vietoris type formula for the determinantsof elliptic operators. Instead, we provide a direct way of analyzing the behaviour of thedeterminant of the Witten deformation of the Laplacian. In particular, we show that thisdeterminant can be written as a sum of two terms, one of which has an asymptoticexpansion with computable coefficients and the other is very simple (no zeta-functionregularization is involved in its definition).
Full-length transcript characterization of SF3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns

While splicing changes caused by somatic mutations in SF3B1 are known, identifying full-length isoform changes may better elucidate the functional consequences of these mutations. We report nanopore sequencing of full-length cDNA from CLL samples with and without SF3B1 mutation, as well as normal B cell samples, giving a total of 149 million pass reads. We present FLAIR (Full-Length Alternative Isoform analysis of RNA), a computational workflow to identify high-confidence transcripts, perform differential splicing event analysis, and differential isoform analysis. Using nanopore reads, we demonstrate differential 3' splice site changes associated with SF3B1 mutation, agreeing with previous studies. We also observe a strong downregulation of intron retention events associated with SF3B1 mutation. Full-length transcript analysis links multiple alternative splicing events together and allows for better estimates of the abundance of productive versus unproductive isoforms. Our work demonstrates the potential utility of nanopore sequencing for cancer and splicing research.
Characterizing Sources of Uncertainty to Proxy Calibration and Disambiguate Annotator and Data Bias

Supporting model interpretability for complex phenomena where annotators can legitimately disagree, such as emotion recognition, is a challenging machine learning task. In this work, we show that explicitly quantifying the uncertainty in such settings has interpretability benefits. We use a simple modification of a classical network inference using Monte Carlo dropout to give measures of epistemic and aleatoric uncertainty. We identify a significant correlation between aleatoric uncertainty and human annotator disagreement (r ≈ .3). Additionally, we demonstrate how difficult and subjective training samples can be identified using aleatoric uncertainty and how epistemic uncertainty can reveal data bias that could result in unfair predictions. We identify the total uncertainty as a suitable surrogate for model calibration, i.e. the degree we can trust model’s predicted confidence. In addition to explainability benefits, we observe modest performance boosts from incorporating model uncertainty.
An Empirical Examination of Sell-Side Brokerage Analysts' Published Research, Concierge Services, and High-Touch Services

This paper uses a proprietary panel dataset to categorize and quantify the activities that sell-side brokerage analysts use to build and sustain their network of buy-side client relations. We then ...
Frequency-Dependent Squeezing for Advanced LIGO.

The first detection of gravitational waves by the Laser Interferometer Gravitational-Wave Observatory (LIGO) in 2015 launched the era of gravitational-wave astronomy. The quest for gravitational-wave signals from objects that are fainter or farther away impels technological advances to realize ever more sensitive detectors. Since 2019, one advanced technique, the injection of squeezed states of light, is being used to improve the shot-noise limit to the sensitivity of the Advanced LIGO detectors, at frequencies above ∼50 Hz. Below this frequency, quantum backaction, in the form of radiation pressure induced motion of the mirrors, degrades the sensitivity. To simultaneously reduce shot noise at high frequencies and quantum radiation pressure noise at low frequencies requires a quantum noise filter cavity with low optical losses to rotate the squeezed quadrature as a function of frequency. We report on the observation of frequency-dependent squeezed quadrature rotation with rotation frequency of 30 Hz, using a 16-m-long filter cavity. A novel control scheme is developed for this frequency-dependent squeezed vacuum source, and the results presented here demonstrate that a low-loss filter cavity can achieve the squeezed quadrature rotation necessary for the next planned upgrade to Advanced LIGO, known as "A+."
Coseismic damage runs deep in continental strike-slip faults

Abstract Coseismic off-fault damage and pulverization significantly influence the mechanical and transport properties, and in turn the rupture dynamics of faults. Although field-based, laboratory, and numerical studies help elucidate the structure of damage zones adjacent to modern strike-slip faults, the vertical extent of these zones remains an open question. To address this question, we analyzed particle size distribution and microfracture density of fragmented garnets from the Sandhill Corner shear zone, a strand of an ancient, seismogenic, strike-slip fault system exhumed from frictional-to-viscous transition depths (400–500 °C). The shear zone has mutually overprinting pseudotachylyte and mylonite, and juxtaposes quartzofeldspathic and schist units. The inner parts of the quartzofeldspathic and schist units (∼63 m and ∼5 m wide from the lithologic contact, respectively) have two-dimensional D-values ≥1.5, which indicates dynamic fragmentation during rupture propagation. Similar to the particle size distribution analysis, microfracture density data from the garnets show progressive but asymmetric increase toward the core in each unit. Our results suggest that coseismic damage extends down to the base of the seismogenic zone in mature strike-slip faults, and the asymmetric distribution of damage may indicate preferred rupture directivity as proposed for some modern strike-slip faults.
Enhancing the Detonation Properties of Liquid Nitromethane by Adding Nitro-Rich Molecule Nitryl Cyanide

Nitromethane (NM) is widely used in a variety of industrial applications because of its simple molecular structure and its good combustion and detonation properties. We propose to improve the deton...
SIR Analysis Via Signal Fractions

The analysis of signal-to-interference ratios (SIRs) in wireless networks is instrumental to derive important performance metrics, including reliability, throughput, and delay. While a host of results on SIR distributions are now available, they are often not straightforward to interpret, bound, visualize, and compare. In this letter, we offer an alternative path towards the analysis and visualization of the SIR distribution. The quantity at the core of this approach is the signal fraction (SF), which is the ratio of the received signal power to the total received power. A key advantage is that the SF is constrained to [0, 1]. We exemplify the benefits of the SF-based approach by reviewing known results for Poisson cellular networks. In the process, we derive new approximation and bounding techniques that are generally applicable.
DNN-Chip Predictor: An Analytical Performance Predictor for DNN Accelerators with Various Dataflows and Hardware Architectures

The recent breakthroughs in deep neural networks (DNNs) have spurred a tremendously increased demand for DNN accelerators. However, designing DNN accelerators is non-trivial as it often takes months/years and requires cross-disciplinary knowledge. To enable fast and effective DNN accelerator development, we propose DNN-Chip Predictor, an analytical performance predictor which can accurately predict DNN accelerators’ energy, throughput, and latency prior to their actual implementation. Our Predictor features two highlights: (1) its analytical performance formulation of DNN ASIC/FPGA accelerators facilitates fast design space exploration and optimization; and (2) it supports DNN accelerators with different algorithm-to-hardware mapping methods (i.e., dataflows) and hardware architectures. Experiment results based on 2 DNN models and 3 different ASIC/FPGA implementations show that our DNN-Chip Predictor’s predicted performance differs from those of chip measurements of FPGA/ASIC implementation by no more than 17.66% when using different DNN models, hardware architectures, and dataflows. We will release code upon acceptance.
Horseshoe-based Bayesian nonparametric estimation of effective population size trajectories.

Phylodynamics is an area of population genetics that uses genetic sequence data to estimate past population dynamics. Modern state-of-the-art Bayesian nonparametric methods for recovering population size trajectories of unknown form use either change-point models or Gaussian process priors. Change-point models suffer from computational issues when the number of change-points is unknown and needs to be estimated. Gaussian process-based methods lack local adaptivity and cannot accurately recover trajectories that exhibit features such as abrupt changes in trend or varying levels of smoothness. We propose a novel, locally adaptive approach to Bayesian nonparametric phylodynamic inference that has the flexibility to accommodate a large class of functional behaviors. Local adaptivity results from modeling the log-transformed effective population size a priori as a horseshoe Markov random field, a recently proposed statistical model that blends together the best properties of the change-point and Gaussian process modeling paradigms. We use simulated data to assess model performance, and find that our proposed method results in reduced bias and increased precision when compared to contemporary methods. We also use our models to reconstruct past changes in genetic diversity of human hepatitis C virus in Egypt and to estimate population size changes of ancient and modern steppe bison. These analyses show that our new method captures features of the population size trajectories that were missed by the state-of-the-art methods.
Differential network analysis: A statistical perspective

Networks effectively capture interactions among components of complex systems, and have thus become a mainstay in many scientific disciplines. Growing evidence, especially from biology, suggest that networks undergo changes over time, and in response to external stimuli. In biology and medicine, these changes have been found to be predictive of complex diseases. They have also been used to gain insight into mechanisms of disease initiation and progression. Primarily motivated by biological applications, this article provides a review of recent statistical machine learning methods for inferring networks and identifying changes in their structures.
Histone acetyltransferase inhibition rescues differentiation of emerin‐deficient myogenic progenitors

Introduction Emery-Dreifuss muscular dystrophy (EDMD) is a disease characterized by skeletal muscle wasting, major tendon contractures, and cardiac conduction defects. Mutations in the gene encoding emerin cause EDMD1. Our previous studies suggested that emerin activation of histone deacetylase 3 (HDAC3) to reduce histone 4-lysine 5 (H4K5) acetylation (ac) is important for myogenic differentiation. Methods Pharmacological inhibitors (Nu9056, L002) of histone acetyltransferases targeting acetylated H4K5 were used to test whether increased acetylated H4K5 was responsible for the impaired differentiation seen in emerin-deficient myogenic progenitors. Results Nu9056 and L002 rescued impaired differentiation in emerin deficiency. SRT1720, which inhibits the nicotinamide adenine dinucleotide (NAD)+ -dependent deacetylase sirtuin 1 (SIRT1), failed to rescue myotube formation. Discussion We conclude that emerin regulation of HDAC3 activity to affect H4K5 acetylation dynamics is important for myogenic differentiation. Targeting H4K5ac dynamics represents a potential new strategy for ameliorating the skeletal muscle wasting seen in EDMD1.
BR-Bodies Provide Selectively Permeable Condensates that Stimulate mRNA Decay and Prevent Release of Decay Intermediates

Biomolecular condensates play a key role in organizing RNAs and proteins into membraneless organelles. Bacterial RNP-bodies (BR-bodies) are a biomolecular condensate containing the RNA degradosome mRNA decay machinery, but the biochemical function of such organization remains poorly defined. Here, we define the RNA substrates of BR-bodies through enrichment of the bodies followed by RNA sequencing (RNA-seq). We find that long, poorly translated mRNAs, small RNAs, and antisense RNAs are the main substrates, while rRNA, tRNA, and other conserved non-coding RNAs (ncRNAs) are excluded from these bodies. BR-bodies stimulate the mRNA decay rate of enriched mRNAs, helping to reshape the cellular mRNA pool. We also observe that BR-body formation promotes complete mRNA decay, avoiding the buildup of toxic endo-cleaved mRNA decay intermediates. The combined selective permeability of BR-bodies for both enzymes and substrates together with the stimulation of the sub-steps of mRNA decay provide an effective organization strategy for bacterial mRNA decay.
Measurement of velocities in gas-liquid two-phase flow using laser Doppler velocimetry

Measurements of bubble and liquid velocities in two-phase flow have been made using a new forward/backward scattering Laser Doppler Velocimetry (LDV) technique. A standard LDV fiber optic probe was used to measure the bubble velocity using direct backscattered light. A novel retro-reflector and lens assembly permitted the same probe to measure the liquid velocity with direct forward-scattered light. Preliminary results show the usefulness of the technique in a duct of narrow thickness dimension.
Chapter 1 – Introduction to the Scientific Projects

The projects are an important part of calculus course. Calculus is a coherent subject in its own right, but even if one is interested in studying mathematics for its own sake, one should be aware of the fact that calculus has important things to say about science and the world. The projects are not easy. They require a lot of work and time to think. The goal of the projects is to write a technical report or term paper on the subject. The projects have “exercises” aimed at helping one get started and posing the right questions.
Cadillac Contracts and Up-front Payments: Efficient Investment under Expectation Damages

This article shows that up-front payments can eliminate the overinvestment effect identified by Shavell (1980), by controlling which party breaches a contract. At the same time, "Cadillac" contracts (contracts for a very high quality or quantity) can protect against underinvestment due to Williamsonian holdups. This combination provides efficient investment incentives when courts use expectation damages as a remedy for breach. The expectation damages remedy is therefore well-suited to multidimensional but one-sided investment problems, in contrast to specific performance, which is well-suited to two-sided but unidimensional investment problems. Copyright 1996 by Oxford University Press.
Self-Organized Superlattices in GaInAsSb Grown on Vicinal Substrates

Self-organized superlattices are observed in GaInAsSb epilayers grown lattice matched to vicinal GaSb substrates. The natural superlattice (NSL) is oriented at a slight angle of about 4{sup o} with respect to the vicinal (001) GaSb substrate. This vertical composition modulation is detected at the onset of growth. Layers in the NSL are continuous over the lateral extent of the substrate. Furthermore, the NSL persists throughout several microns of deposition. The NSLs have a period ranging from 10 to 30 nm, which is dependent on deposition temperature and GaInAsSb alloy composition. While the principle driving force for this type of phase separation is chemical, the mechanism for the self-organized microstructure is related to local strains associated with surface undulations. By using a substrate with surface undulations, the tilted NSL can be induced in layers with alloy compositions that normally do not exhibit this self-organized microstructure under typical growth conditions. These results underscore the complex interactions between compositional and morphological perturbations.
Fixed-Term Employment Contracts in an Equilibrium Search Model

Abstract We develop a theoretical model of firm dynamics and unemployment and characterize equilibria with tenure dependent separation taxes. The model is a version of the Lucas and Prescott island model with undirected search. Two equivalent decentralizations are considered: one with spot labor markets and one with long-term employment relations. We model “temporary contracts” as the special case of a separation tax that only applies to workers with tenure higher than J. While in principle these contracts require a J-dimensional state space, equilibrium allocations solve a simple dynamic programming problem characterized by two-dimensional inaction set(s).
Progress in the pumping of a gamma-ray laser

A decade ago the difficulties in realizing a gamma-ray laser were considered almost insurmountable. However, in 1982 we began to emphasize an interdisciplinary concept of upconversion which ultimately launched a renaissance in the field.1 The essential concept was the “optical” pumping of nuclei. In this case optical meant x rays, but the fundamentals were the same. Useful, resonant absorption of pump power would occur over short distances to produce high concentrations of excited nuclei while wasted wavelengths would be degraded to heat in much large volumes. Of all the cases considered, the nuclear analog of the ruby laser embodied the simplest concepts for a gamma-ray laser. Not surprisingly, the greatest rate of achievement has been realized in that direction.
Chapter 16 – Miravalles Power Station, Guanacaste Province, Costa Rica

Publisher Summary The drive from San Jose, Costa Rica's capital, to its geothermal power complex at Miravalles is best attempted during the dry season and in daylight. It is a spectacular trip. This chapter examines the details of the various power plants at Miravalles, and sees how the Costa Ricans overcame two serious obstacles that could have blocked the development of the field. In 1975, ICE began identifying geothermal areas worthy of further exploration. The geoscientific studies together with data acquired by drilling have led to a fairly clear picture of the reservoir and a good working model of the field. A problem encountered by ICE with the Miravalles wells is that the wells in the northeast sector of the field, closest to the volcano, produce highly acidic geofluid. ICE has devised a method for neutralizing the acidic geofluid using a downwell injection scheme similar to the one used to inhibit calcite scaling. ICE is working on developing a new chemical inhibition process to counteract these adverse side effects of the neutralization process. Throughout the development of geothermal resources at Miravalles, ICE has been sensitive to preserving the environment from any harmful effects. There are several aspects of geothermal power development that might adversely affect the environment, but at each step ICE took action to mitigate these effects.
QCD physics in atlas at the Large Hadron Collider

Abstract The LHC will provide a unique opportunity to test the predictive power of QCD, probing regions in x and Q 2 well beyond those studied to date. Almost any process one can think of will contribute to this understanding: from a measurement of the total cross section and inclusive cross sections of b's, t's, and W's to searches for physics beyond the Standard Model. In addition, a measurement of α s (E t ) out to E t ∼3TeV with a precision of ∼10% should be possible.
A relative Segre zeta function

Abstract The choice of a homogeneous ideal in a polynomial ring defines a closed subscheme Z in a projective space as well as an infinite sequence of cones over Z in progressively higher dimension projective spaces. Recent work of Aluffi introduces the Segre zeta function, a rational power series with integer coefficients which captures the relationship between the Segre class of Z and those of its cones. The goal of this note is to define a relative version of this construction for closed subschemes of projective bundles over a smooth variety. If Z is a closed subscheme of such a projective bundle P ( E ) , this relative Segre zeta function will be a rational power series which describes the Segre class of the cone over Z in every projective bundle “dominating” P ( E ) . When the base variety is a point we recover the absolute Segre zeta function for projective spaces. Part of our construction requires Z to be the zero scheme of a section of a bundle on P ( E ) of rank smaller than that of E that is able to extend to larger projective bundles. The question of what bundles may extend in this sense seems independently interesting and we discuss some related results, showing that at a minimum one can always count on direct sums of line bundles to extend. Furthermore, the relative Segre zeta function depends only on the Segre class of Z and the total Chern class of the bundle defining Z, and the basic forms of the numerator and denominator can be described. As an application of our work we derive a Segre zeta function for products of projective spaces and prove its key properties.
ipcoal: an interactive Python package for simulating and analyzing genealogies and sequences on a species tree or network.

Summary ipcoal is a free and open source Python package for simulating and analyzing genealogies and sequences. It automates the task of describing complex demographic models (e.g. with divergence times, effective population sizes, migration events) to the msprime coalescent simulator by parsing a user-supplied species tree or network. Genealogies, sequences and metadata are returned in tabular format allowing for easy downstream analyses. ipcoal includes phylogenetic inference tools to automate gene tree inference from simulated sequence data, and visualization tools for analyzing results and verifying model accuracy. The ipcoal package is a powerful tool for posterior predictive data analysis, for methods validation and for teaching coalescent methods in an interactive and visual environment. Availability and implementation Source code is available from the GitHub repository (https://github.com/pmckenz1/ipcoal/) and is distributed for packaged installation with conda. Complete documentation and interactive notebooks prepared for teaching purposes, including an empirical example, are available at https://ipcoal.readthedocs.io/. Contact p.mckenzie@columbia.edu.
Randomized allocation with nonparametric estimation for contextual multi-armed bandits with delayed rewards

Abstract We study a multi-armed bandit problem with covariates in a setting where there is a possible delay in observing the rewards. Under some reasonable assumptions on the probability distributions for the delays and using an appropriate randomization to select the arms, the proposed strategy is shown to be strongly consistent.
Feedback generates a second receptive field in neurons of the visual cortex

Animals sense the environment through pathways that link sensory organs to the brain. In the visual system, these feedforward pathways define the classical feedforward receptive field (ffRF), the area in space in which visual stimuli excite a neuron1. The visual system also uses visual context-the visual scene surrounding a stimulus-to predict the content of the stimulus2, and accordingly, neurons have been identified that are excited by stimuli outside their ffRF3-8. However, the mechanisms that generate excitation to stimuli outside the ffRF are unclear. Here we show that feedback projections onto excitatory neurons in the mouse primary visual cortex generate a second receptive field that is driven by stimuli outside the ffRF. The stimulation of this feedback receptive field (fbRF) elicits responses that are slower and are delayed in comparison with those resulting from the stimulation of the ffRF. These responses are preferentially reduced by anaesthesia and by silencing higher visual areas. Feedback inputs from higher visual areas have scattered receptive fields relative to their putative targets in the primary visual cortex, which enables the generation of the fbRF. Neurons with fbRFs are located in cortical layers that receive strong feedback projections and are absent in the main input layer, which is consistent with a laminar processing hierarchy. The observation that large, uniform stimuli-which cover both the fbRF and the ffRF-suppress these responses indicates that the fbRF and the ffRF are mutually antagonistic. Whereas somatostatin-expressing inhibitory neurons are driven by these large stimuli, inhibitory neurons that express parvalbumin and vasoactive intestinal peptide have mutually antagonistic fbRF and ffRF, similar to excitatory neurons. Feedback projections may therefore enable neurons to use context to estimate information that is missing from the ffRF and to report differences in stimulus features across visual space, regardless of whether excitation occurs inside or outside the ffRF. By complementing the ffRF, the fbRF that we identify here could contribute to predictive processing.
Phagocytic glia are obligatory intermediates in transmission of mutant huntingtin aggregates across neuronal synapses

Emerging evidence supports the hypothesis that pathogenic protein aggregates associated with neurodegenerative diseases spread from cell to cell through the brain in a manner akin to infectious prions. Here, we show that mutant huntingtin (mHtt) aggregates associated with Huntington disease transfer anterogradely from presynaptic to postsynaptic neurons in the adult Drosophila olfactory system. Trans-synaptic transmission of mHtt aggregates is inversely correlated with neuronal activity and blocked by inhibiting caspases in presynaptic neurons, implicating synaptic dysfunction and cell death in aggregate spreading. Remarkably, mHtt aggregate transmission across synapses requires the glial scavenger receptor Draper and involves a transient visit to the glial cytoplasm, indicating that phagocytic glia act as obligatory intermediates in aggregate spreading between synaptically-connected neurons. These findings expand our understanding of phagocytic glia as double-edged players in neurodegeneration-by clearing neurotoxic protein aggregates, but also providing an opportunity for prion-like seeds to evade phagolysosomal degradation and propagate further in the brain.
Prevalence of SARS-CoV-2 Antibodies Among Healthcare Workers at a Tertiary Academic Hospital in New York City.

Background: SARS-CoV-2 antibody testing is important for understanding immunity prevalence, and may have implications for healthcare workers (HCW) during the SARS-CoV-2 pandemic. Methods: We conducted immunologic testing of healthcare workers to determine the prevalence of SARS-CoV-2 IgG in this population. HCW were advised to wait at least two weeks from time of symptom onset or suspected exposure before undergoing testing. All participants were self-reported asymptomatic for at least three days at the time of testing. Results: Two hundred eighty-five samples were collected from March 24, 2020 to April 4, 2020. The average age of participants was 38 years (range 18-84), and 54% were male. Thirty-three percept tested IgG positive, 3% tested weakly positive, and 64% tested negative. Neither age nor sex was associated with antibody development. Conclusion: Thirty-six percent of HCW had IgG antibodies to SARS-CoV-2, reflecting the high exposure of inpatient and ambulatory frontline staff to this viral illness, most of whom had minimal symptoms and were working in the weeks preceding testing. While we continue to recommend standard protective precautions per CDC guidelines for all HCW, HCW with SARS-CoV-2 IgG may become our safest frontline providers as we learn if our IgG antibodies confer immunity. Knowing IgG antibody status may ease concerns regarding personal risk as this pandemic continues.
A critical comparison of turbulence models for homogeneous shear flows in a rotating frame

A variety of turbulence models, including five second‐order closures and four two‐equation models, are tested for the problem of homogeneous turbulent shear flow in a rotating frame. The model predictions for the time evolution of the turbulent kinetic energy and dissipation rate, as well as those for the equilibrium states, are compared with the results of physical and numerical experiments. Most of the two‐equation models predict the same results for all rotation rates, in which there is an exponential time growth of the turbulent kinetic energy and dissipation rate. The second‐order closures are qualitatively superior since, consistent with physical and numerical experiments, they only predict this type of unstable flow for intermediate rotation rates in the range −0.1≤Ω/S≤0.6. For rotation rates outside this range, there is an exchange of stabilities with a solution whose kinetic energy and dissipation rate decay with time. Although the second‐order closures are superior to the two‐equation models, there are still problems with the quantitative accuracy of their predictions.
Purinergic Receptors of the Central Nervous System: Biology, PET Ligands, and Their Applications.

Purinergic receptors play important roles in central nervous system (CNS). These receptors are involved in cellular neuroinflammatory responses that regulate functions of neurons, microglial and as...
Weighted ensemble milestoning (WEM): A combined approach for rare event simulations

To directly simulate rare events using atomistic molecular dynamics is a significant challenge in computational biophysics. Well-established enhanced-sampling techniques do exist to obtain the thermodynamic functions for such systems. However, developing methods for obtaining the kinetics of long timescale processes from simulation at atomic detail is comparatively less developed an area. Milestoning and the weighted ensemble (WE) method are two different stratification strategies; both have shown promise for computing long timescales of complex biomolecular processes. Nevertheless, both require a significant investment of computational resources. We have combined WE and milestoning to calculate observables in orders-of-magnitude less central processing unit and wall-clock time. Our weighted ensemble milestoning method (WEM) uses WE simulation to converge the transition probability and first passage times between milestones, followed by the utilization of the theoretical framework of milestoning to extract thermodynamic and kinetic properties of the entire process. We tested our method for a simple one-dimensional double-well potential, for an eleven-dimensional potential energy surface with energy barrier, and on the biomolecular model system alanine dipeptide. We were able to recover the free energy profiles, time correlation functions, and mean first passage times for barrier crossing events at a significantly small computational cost. WEM promises to extend the applicability of molecular dynamics simulation to slow dynamics of large systems that are well beyond the scope of present day brute-force computations.
Structure of MlaFB uncovers novel mechanisms of ABC transporter regulation

ABC transporters facilitate the movement of diverse molecules across cellular membranes, but how their activity is regulated post-translationally is not well understood. Here we report the crystal structure of MlaFB from E. coli, the cytoplasmic portion of the larger MlaFEDB ABC transporter complex, which drives phospholipid trafficking across the bacterial envelope to maintain outer membrane integrity. MlaB, a STAS domain protein, binds the ABC nucleotide binding domain, MlaF, and is required for its stability. Our structure also implicates a unique C-terminal tail of MlaF in self-dimerization. Both the C-terminal tail of MlaF and the interaction with MlaB are required for the proper assembly of the MlaFEDB complex and its function in cells. This work leads to a new model for how an important bacterial lipid transporter may be regulated by small proteins, and raises the possibility that similar regulatory mechanisms may exist more broadly across the ABC transporter family.
Restricted Spatial Regression Methods: Implications for Inference

The issue of spatial confounding between the spatial random effect and the fixed effects in regression analyses has been identified as a concern in the statistical literature. Multiple authors have...
Hospitalized COVID-19 Patients treated with Convalescent Plasma in a Mid-size City in the Midwest

BackgroundSARS-CoV-2 and its associated disease, COVID-19, has infected over seven million people world-wide, including two million people in the United States. While many people recover from the virus uneventfully, a subset of patients will require hospital admission, some with intensive care needs including intubation, and mechanical ventilation. To date there is no cure and no vaccine is available. Passive immunotherapy by the transfusion of convalescent plasma donated by COVID-19 recovered patients might be an effective option to combat the virus, especially if used early in the course of disease. Here we report our experience of using convalescent plasma at a tertiary care center in a mid-size, midwestern city that did not experience an overwhelming patient surge.MethodsHospitalized COVID-19 patients categorized as having Severe or Life-Threatening disease according to the Mayo Clinic Emergency Access Protocol were screened, consented, and treated with convalescent plasma collected from local donors recovered from COVID-19 infection. Clinical data and outcomes were collected retrospectively.Results31 patients were treated, 16 severe patients and 15 life-threatened patients. Overall mortality was 27% (4/31) but only patients with life-threatening disease died. 94% of transfused patients with severe disease avoided escalation to ICU care and mechanical ventilation. 67% of patients with life-threatening disease were able to be extubated. Most transfused patients had a rapid decrease in their respiratory support requirements on or about day 7 following convalescent plasma transfusion.ConclusionOur results demonstrate that convalescent plasma is associated with reducing ventilatory requirements in patients with both severe and life-threatening disease, but appears to be most beneficial when administered early in the course of disease when patients meet the criteria for severe illness.
Visuo-Proprioceptive Control of the Hand in Older Adults

To control hand movement, we have both vision and proprioception, or position sense. The brain is known to integrate these to reduce variance. Here we ask whether older adults integrate vision and proprioception in a way that minimizes variance as young adults do, and whether older subjects compensate for an imposed visuo-proprioceptive mismatch as young adults do. Ten healthy older adults (mean age 69) and 10 healthy younger adults (mean age 19) participated. Subjects were asked to estimate the position of visual, proprioceptive, and combined targets, with no direct vision of either hand. After a veridical baseline block, a spatial visuo-proprioceptive misalignment was gradually imposed by shifting the visual component forward from the proprioceptive component without the subject's awareness. Older subjects were more variable than young subjects at estimating both visual and proprioceptive target positions. Older subjects tended to rely more heavily on vision than proprioception compared to younger subjects. However, the weighting of vision vs. proprioception was correlated with minimum variance predictions for both older and younger adults, suggesting that variance-minimizing mechanisms are present to some degree in older adults. Visual and proprioceptive realignment were similar for young and older subjects in the misalignment block, suggesting older subjects are able to realign as much as young subjects. These results suggest that intact multisensory processing in older adults should be explored as a potential means of mitigating degradation in individual sensory systems.
On-The-Fly Information Retrieval Augmentation for Language Models

Here we experiment with the use of information retrieval as an augmentation for pre-trained language models. The text corpus used in information retrieval can be viewed as form of episodic memory which grows over time. By augmenting GPT 2.0 with information retrieval we achieve a zero shot 15% relative reduction in perplexity on Gigaword corpus without any re-training. We also validate our IR augmentation on an event co-reference task.
Systematic determination of the mitochondrial proportion in human and mice tissues for single-cell RNA-sequencing data quality control

MOTIVATION Quality control (QC) is a critical step in single-cell RNA-seq (scRNA-seq) data analysis. Low-quality cells are removed from the analysis during the QC process to avoid misinterpretation of the data. An important QC metric is the mitochondrial proportion (mtDNA%), which is used as a threshold to filter out low-quality cells. Early publications in the field established a threshold of 5% and since then, it has been used as a default in several software packages for scRNA-seq data analysis, and adopted as a standard in many scRNA-seq studies. However, the validity of using a uniform threshold across different species, single-cell technologies, tissues and cell types has not been adequately assessed. RESULTS We systematically analyzed 5 530 106 cells reported in 1349 annotated datasets available in the PanglaoDB database and found that the average mtDNA% in scRNA-seq data across human tissues is significantly higher than in mouse tissues. This difference is not confounded by the platform used to generate the data. Based on this finding, we propose new reference values of the mtDNA% for 121 tissues of mouse and 44 tissues of humans. In general, for mouse tissues, the 5% threshold performs well to distinguish between healthy and low-quality cells. However, for human tissues, the 5% threshold should be reconsidered as it fails to accurately discriminate between healthy and low-quality cells in 29.5% (13 of 44) tissues analyzed. We conclude that omitting the mtDNA% QC filter or adopting a suboptimal mtDNA% threshold may lead to erroneous biological interpretations of scRNA-seq data. AVAILABILITYAND IMPLEMENTATION The code used to download datasets, perform the analyzes and produce the figures is available at https://github.com/dosorio/mtProportion. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Realizing ergodic properties in zero entropy subshifts

A subshift with linear block complexity has at most countably many ergodic measures, and we continue the study of the relation between such complexity and the invariant measures. By constructing minimal subshifts whose block complexity is arbitrarily close to linear but have uncountably many ergodic measures, we show that this behavior fails as soon as the block complexity is superlinear. With a different construction, we show that there exists a minimal subshift with an ergodic measure such that the liminf of the slow entropy grows slower than any given rate tending to infinitely but the limsup grows faster than any other rate majorizing this one yet still growing subexponentially. These constructions lead to obstructions in using subshifts in applications to properties of the prime numbers and in finding a measurable version of the complexity gap that arises for shifts of sublinear complexity.