cssi/SciSciGPT-SciSciNet huggingface dataset:
Tunable cell-surface mimetics as engineered cell substrates.

Abstract Most recent breakthroughs in understanding cell adhesion, cell migration, and cellular mechanosensitivity have been made possible by the development of engineered cell substrates of well-defined surface properties. Traditionally, these substrates mimic the extracellular matrix (ECM) environment by the use of ligand-functionalized polymeric gels of adjustable stiffness. However, such ECM mimetics are limited in their ability to replicate the rich dynamics found at cell-cell contacts. This review focuses on the application of cell surface mimetics, which are better suited for the analysis of cell adhesion, cell migration, and cellular mechanosensitivity across cell-cell interfaces. Functionalized supported lipid bilayer systems were first introduced as biomembrane-mimicking substrates to study processes of adhesion maturation during adhesion of functionalized vesicles (cell-free assay) and plated cells. However, while able to capture adhesion processes, the fluid lipid bilayer of such a relatively simple planar model membrane prevents adhering cells from transducing contractile forces to the underlying solid, making studies of cell migration and cellular mechanosensitivity largely impractical. Therefore, the main focus of this review is on polymer-tethered lipid bilayer architectures as biomembrane-mimicking cell substrate. Unlike supported lipid bilayers, these polymer-lipid composite materials enable the free assembly of linkers into linker clusters at cellular contacts without hindering cell spreading and migration and allow the controlled regulation of mechanical properties, enabling studies of cellular mechanosensitivity. The various polymer-tethered lipid bilayer architectures and their complementary properties as cell substrates are discussed.
Parametric Instability Driven by Weakly Trapped Particles in Nonlinear Plasma Waves.

This Letter describes a new parametric instability mechanism caused by a distribution ${f}_{T}$ of particles trapped in the potential wells of a wave train. The mechanism explains a nonlinear instability in Trivelpiece-Gould (TG) waves, and it could also be a destabilizing factor in a range of nearly collisionless nonlinear plasma waves. The theory is compared to particle in cell simulations of TG waves.
Prophylactic vaccination protects against the development of oxycodone self-administration.

Abuse of prescription opioids is a growing public health crisis in the United States, with drug overdose deaths increasing dramatically over the past 15 years. Few preclinical studies exist on the reinforcing effects of oxycodone or on the development of therapies for oxycodone abuse. This study was conducted to determine if immunopharmacotherapy directed against oxycodone would be capable of altering oxycodone-induced antinociception and intravenous self-administration. Male Wistar rats were administered a small-molecule immunoconjugate vaccine (Oxy-TT) or the control carrier protein, tetanus toxoid (TT), and trained to intravenously self-administer oxycodone (0.06 or 0.15 mg/kg/infusion). Brain oxycodone concentrations were 50% lower in Oxy-TT rats compared to TT rats 30 min after injection (1 mg/kg, s.c.) whereas plasma oxycodone was 15-fold higher from drug sequestration by circulating antibodies. Oxy-TT rats were also less sensitive to 1-2 mg/kg, s.c. oxycodone on a hot water nociception assay. Half of the Oxy-TT rats failed to acquire intravenous self-administration under the 0.06 mg/kg/infusion training dose. Oxycodone self-administration of Oxy-TT rats trained on 0.15 mg/kg/infusion was higher than controls; however under progressive ratio (PR) conditions the Oxy-TT rats decreased their oxycodone intake, unlike TT controls. These data demonstrate that active vaccination provides protection against the reinforcing effects of oxycodone. Anti-oxycodone vaccines may entirely prevent repeated use in some individuals who otherwise would become addicted. Vaccination may also reduce dependence in those who become addicted and therefore facilitate the effects of other therapeutic interventions which either increase the difficulty of drug use or incentivize other behaviors.
Cerebrovascular Injury After Serial Exposure to Chronic Stress and Abstinence from Methamphetamine Self-Administration

Cerebrovascular damage caused by either exposure to stress or the widely abused drug, methamphetamine (Meth) is known but stress and drug abuse frequently occur in tandem that may impact their individual cerebrovascular effects. This study examined their co-morbid cerebrovascular effects during abstinence from self-administered Meth after the exposure to chronic unpredictable stress (CUS). Exposure to CUS prior to unrestricted Meth self-administration had no effect on Meth intake in rats; however, the pro-inflammatory mediator cyclooxygenase-2 (COX-2) and the breakdown of cell-matrix adhesion protein β-dystroglycan in isolated cerebral cortical capillaries were increased after 3 days of abstinence and persisted for 7 days. These changes preceded decreases in occludin, a key structural protein component of the blood-brain barrier. The decrease in occludin was blocked by the COX-2 specific inhibitor nimesulide treatment during abstinence from Meth. The changes in COX-2, β-dystroglycan, and occludin were only evident following the serial exposure to stress and Meth but not after either one alone. These results suggest that stress and voluntary Meth intake can synergize and disrupt cerebrovasculature in a time-dependent manner during abstinence from chronic stress and Meth. Furthermore, COX-2 inhibition may be a viable pharmacological intervention to block vascular changes after Meth exposure.
Round-Optimal Secure Multiparty Computation with Honest Majority.

We study the exact round complexity of secure multiparty computation (MPC) in the honest majority setting. We construct several round-optimal n-party protocols, tolerating any \(t<\frac{n}{2}\) corruptions.
Large girth approximate Steiner triple systems

In 1973 Erdos asked whether there are n-vertex partial Steiner triple systems with arbitrary high girth and quadratically many triples. (Here girth is defined as the smallest integer g \ge 4 for which some g-element vertex-set contains at least g-2 triples.) We answer this question, by showing existence of approximate Steiner triple systems with arbitrary high girth. More concretely, for any fixed \ell \ge 4 we show that a natural constrained random process typically produces a partial Steiner triple system with (1/6-o(1))n^2 triples and girth larger than \ell. The process iteratively adds random triples subject to the constraint that the girth remains larger than \ell. Our result is best possible up to the o(1)-term, which is a negative power of n.
HiGlass: web-based visual exploration and analysis of genome interaction maps

We present HiGlass, an open source visualization tool built on web technologies that provides a rich interface for rapid, multiplex, and multiscale navigation of 2D genomic maps alongside 1D genomic tracks, allowing users to combine various data types, synchronize multiple visualization modalities, and share fully customizable views with others. We demonstrate its utility in exploring different experimental conditions, comparing the results of analyses, and creating interactive snapshots to share with collaborators and the broader public. HiGlass is accessible online at http://higlass.io and is also available as a containerized application that can be run on any platform.
Green Rust: The Simple Organizing 'Seed' of All Life?

Korenaga and coworkers presented evidence to suggest that the Earth’s mantle was dry and water filled the ocean to twice its present volume 4.3 billion years ago. Carbon dioxide was constantly exhaled during the mafic to ultramafic volcanic activity associated with magmatic plumes that produced the thick, dense, and relatively stable oceanic crust. In that setting, two distinct and major types of sub-marine hydrothermal vents were active: ~400 °C acidic springs, whose effluents bore vast quantities of iron into the ocean, and ~120 °C, highly alkaline, and reduced vents exhaling from the cooler, serpentinizing crust some distance from the heads of the plumes. When encountering the alkaline effluents, the iron from the plume head vents precipitated out, forming mounds likely surrounded by voluminous exhalative deposits similar to the banded iron formations known from the Archean. These mounds and the surrounding sediments, comprised micro or nano-crysts of the variable valence FeII/FeIII oxyhydroxide known as green rust. The precipitation of green rust, along with subsidiary iron sulfides and minor concentrations of nickel, cobalt, and molybdenum in the environment at the alkaline springs, may have established both the key bio-syntonic disequilibria and the means to properly make use of them—the elements needed to effect the essential inanimate-to-animate transitions that launched life. Specifically, in the submarine alkaline vent model for the emergence of life, it is first suggested that the redox-flexible green rust micro- and nano-crysts spontaneously precipitated to form barriers to the complete mixing of carbonic ocean and alkaline hydrothermal fluids. These barriers created and maintained steep ionic disequilibria. Second, the hydrous interlayers of green rust acted as engines that were powered by those ionic disequilibria and drove essential endergonic reactions. There, aided by sulfides and trace elements acting as catalytic promoters and electron transfer agents, nitrate could be reduced to ammonia and carbon dioxide to formate, while methane may have been oxidized to methyl and formyl groups. Acetate and higher carboxylic acids could then have been produced from these C1 molecules and aminated to amino acids, and thence oligomerized to offer peptide nests to phosphate and iron sulfides, and secreted to form primitive amyloid-bounded structures, leading conceivably to protocells.
Embedding Covert Information in Broadcast Communications

We analyze a two-receiver binary-input discrete memoryless broadcast channel, in which the transmitter communicates a common message simultaneously to both receivers and a covert message to only one of them. The unintended recipient of the covert message is treated as an adversary who attempts to detect the covert transmission. This model captures the problem of embedding covert messages in an innocent codebook and generalizes previous covert communication models in which innocent behavior corresponds to the absence of communication between legitimate users. We identify the exact asymptotic behavior of the number of covert bits that can be transmitted when the rate of the innocent codebook is close to the capacity of the channel to the adversary. Our results also identify the dependence of the number of covert bits on the channel parameters and the characteristics of the innocent codebook.
Nuclear Transcriptomes of the Seven Neuronal Cell Types That Constitute the Drosophila Mushroom Bodies

The insect mushroom body (MB) is a conserved brain structure that plays key roles in a diverse array of behaviors. The Drosophila melanogaster MB is the primary invertebrate model of neural circuits related to memory formation and storage, and its development, morphology, wiring, and function has been extensively studied. MBs consist of intrinsic Kenyon Cells that are divided into three major neuron classes (γ, α′/β′ and α/β) and 7 cell subtypes (γd, γm, α′/β′ap, α′/β′m, α/βp, α/βs and α/βc) based on their birth order, morphology, and connectivity. These subtypes play distinct roles in memory processing, however the underlying transcriptional differences are unknown. Here, we used RNA sequencing (RNA-seq) to profile the nuclear transcriptomes of each MB neuronal cell subtypes. We identified 350 MB class- or subtype-specific genes, including the widely used α/β class marker Fas2 and the α′/β′ class marker trio. Immunostaining corroborates the RNA-seq measurements at the protein level for several cases. Importantly, our data provide a full accounting of the neurotransmitter receptors, transporters, neurotransmitter biosynthetic enzymes, neuropeptides, and neuropeptide receptors expressed within each of these cell types. This high-quality, cell type-level transcriptome catalog for the Drosophila MB provides a valuable resource for the fly neuroscience community.
Characterization of thin film evaporation in micropillar wicks using micro-Raman spectroscopy

Thin film evaporation on microstructured surfaces is a promising strategy for high heat flux thermal management. To enhance fundamental understanding and optimize the overall heat transfer performance across a few microns thick liquid film, however, requires detailed thermal characterizations. Existing characterization techniques using infrared thermometry or contact-mode temperature sensors such as thermocouples and resistance temperature detectors cannot accurately measure the temperature of the thin liquid film near the three-phase contact line due to the restriction of low spatial resolution or temperature sensitivity. In this work, we developed a non-contact, in situ temperature measurement approach using a custom micro-Raman spectroscopy platform which has a spatial resolution of 1.5 μm and temperature sensitivity within 0.5 °C. We utilized this method to characterize thin film evaporation from fabricated silicon micropillar arrays. We showed that we can accurately measure the local thin film temperature and map the overall temperature distribution on the structured surfaces at different heat fluxes. We investigated the effects of micropillar array geometries and showed that the temperature rise of the liquid was reduced with the decreasing micropillar pitch due to the increased fraction of the thin film area. This work offers a promising method with micro-Raman to quantify phase change heat transfer on microstructured surfaces. This characterization technique can significantly aid mechanistic understanding and wick structure optimization for various phase-change based thermal management devices.
Job polarization and the natural rate of unemployment in the United States

Abstract I present a new estimate of the natural rate of unemployment in the United States that accounts for changes in the age, gender, and skill composition of the labor force. Using micro-level data from the Current Population Survey for the period 1994–2017, I find that the natural rate of unemployment has declined by 0.5 percentage point since 1994 and was 4.5% at the end of 2017. My projections show that ongoing demographic and technological changes could lower the trend rate further to 4.4% by the end of 2022.
Teacher Performance Ratings and Professional Improvement

Like other public workers, teachers typically receive high and compressed ratings that do little to differentiate them based on performance. Motivated by empirical evidence of substantial variation...
Active Gate Driver for SiC-MOSFET-Based PV Inverter With Enhanced Operating Range

For photovoltaic (PV) inverter applications, the grid code mandates reactive power support to the grid, and the amount of reactive power injection may be limited by the voltage overshoot during the switching transients of a power device. For SiC- mosfet -based PV inverters, this problem is more pronounced since the voltage and current gradient during switching transitions are much higher than a Si-based power converters. During a cloudy day when the inverter has to operate at PV panels open-circuit voltage, it becomes harder to push higher reactive power support to the grid due to the current derating of the SiC-devices at the operating dc bus voltages to keep the device within its safe operating limits with low switching losses at all operating conditions. Slowing down the switching transient could be a remedy but this also increases the converter losses. This paper demonstrates an application of a dynamic gate resistance modulation technique to keep the SiC-device within its safe operating limits while maintaining a low switching loss with minimum voltage and current overshoots. This helps to inject more power to the grid with at higher dc bus voltages without enhancement of the thermal management system. The proposed implementation also works equally well at high junction temperatures (up to $T_j = 150$ °C), which further increases the operating range of the PV inverter.
MAVBench: micro aerial vehicle benchmarking

Unmanned Aerial Vehicles (UAVs) are getting closer to becoming ubiquitous in everyday life. Among them, Micro Aerial Vehicles (MAVs) have seen an outburst of attention recently, specifically in the area with a demand for autonomy. A key challenge standing in the way of making MAVs autonomous is that researchers lack the comprehensive understanding of how performance, power, and computational bottlenecks affect MAV applications. MAVs must operate under a stringent power budget, which severely limits their flight endurance time. As such, there is a need for new tools, benchmarks, and methodologies to foster the systematic development of autonomous MAVs. In this paper, we introduce the "MAVBench" framework which consists of a closed-loop simulator and an end-to-end application benchmark suite. A closed-loop simulation platform is needed to probe and understand the intra-system (application data flow) and inter-system (system and environment) interactions in MAV applications to pinpoint bottlenecks and identify opportunities for hardware and software co-design and optimization. In addition to the simulator, MAVBench provides a benchmark suite, the first of its kind, consisting of a variety of MAV applications designed to enable computer architects to perform characterization and develop future aerial computing systems. Using our open source, end-to-end experimental platform, we uncover a hidden, and thus far unexpected compute to total system energy relationship in MAVs. Furthermore, we explore the role of compute by presenting three case studies targeting performance, energy and reliability. These studies confirm that an efficient system design can improve MAV's battery consumption by up to 1.8X.
Antibody-mediated immunosuppression can result from RBC antigen loss independent of Fcγ receptors in mice.

Background Anti-RhD administration can prevent de novo anti-RhD formation following RhD+ red blood cell (RBC) exposure, termed antibody-mediated immunosuppression (AMIS). Recent studies suggest that AMIS may occur through target antigen alterations, known as antigen modulation. However, studies suggest that AMIS may occur independent of antigen modulation. In particular, AMIS to RBCs that transgenically express the fusion hen egg lysozyme-ovalbumin-Duffy (HOD) antigen have been shown to occur independent of activating Fcγ receptors (FcγRs) thought to be required for antigen modulation. Therefore, we sought to determine the mechanism behind AMIS following HOD RBC exposure. Study design and methods Following transfer of HOD RBCs into wild-type or FcγR-chain knockout recipients in the presence or absence of monoclonal anti-hen egg lysozyme (HEL) antibody, individually or in combination, HOD antigen levels and anti-HOD antibody formation were examined. Results Our results demonstrate that anti-HEL antibodies individually or in combination suppressed anti-HOD IgM, which correlated with the rate of detectable decrease in HEL on HOD RBCs. Furthermore, exposure to anti-HEL antibodies alone or in combination equally suppressed anti-HOD IgG formation. Unexpectedly, combination or individual anti-HEL antibodies induced AMIS and antigen modulation in an FcγR-independent manner. Pre-exposure of HOD RBCs to anti-HEL antibodies reduced antigen levels and suppressed anti-HOD antibody formation following HOD RBC exposure. Conclusion These results suggest that antibody-mediated antigen modulation may reflect a mechanism of AMIS that can occur independent of activating FcγRs and may provide a surrogate to identify antibodies capable of inducing AMIS against different RBC antigens.
SUSAN: segment unannotated image structure using adversarial network.

PURPOSE To describe and evaluate a segmentation method using joint adversarial and segmentation convolutional neural network to achieve accurate segmentation using unannotated MR image datasets. THEORY AND METHODS A segmentation pipeline was built using joint adversarial and segmentation network. A convolutional neural network technique called cycle-consistent generative adversarial network (CycleGAN) was applied as the core of the method to perform unpaired image-to-image translation between different MR image datasets. A joint segmentation network was incorporated into the adversarial network to obtain additional functionality for semantic segmentation. The fully automated segmentation method termed as SUSAN was tested for segmenting bone and cartilage on 2 clinical knee MR image datasets using images and annotated segmentation masks from an online publicly available knee MR image dataset. The segmentation results were compared using quantitative segmentation metrics with the results from a supervised U-Net segmentation method and 2 registration methods. The Wilcoxon signed-rank test was used to evaluate the value difference of quantitative metrics between different methods. RESULTS The proposed method SUSAN provided high segmentation accuracy with results comparable to the supervised U-Net segmentation method (most quantitative metrics having P > 0.05) and significantly better than a multiatlas registration method (all quantitative metrics having P < 0.001) and a direct registration method (all quantitative metrics having P< 0.0001) for the clinical knee image datasets. SUSAN also demonstrated the applicability for segmenting knee MR images with different tissue contrasts. CONCLUSION SUSAN performed rapid and accurate tissue segmentation for multiple MR image datasets without the need for sequence specific segmentation annotation. The joint adversarial and segmentation network and training strategy have promising potential applications in medical image segmentation.
Response of a Liquid Jet in a Multiple-Detonation Driven Crossflow

A bench-scale experiment was developed to investigate the response of a liquid injector site to the passage of multiple-detonation-type events with application to rotating detonation engines. The e...
Comparison of the Kansas City Cardiomyopathy Questionnaire and Minnesota Living With Heart Failure Questionnaire in Predicting Heart Failure Outcomes

Patient-reported outcome measures (PROMs) are relevant independent outcomes in heart failure (HF) care and are predictive of subsequent hospitalization and death in HF. The Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) are the 2 most widely adopted PROMs specific to HF. We compared their prognostic abilities in a prospective cohort of HF patients. A prospective cohort of subjects from a single-center registry was analyzed with regard to baseline KCCQ and MLHFQ scores and the outcomes of death, transplant, or left ventricular assist device implantation and hospitalization. A total of 516 subjects with reduced left ventricular ejection fraction (HFrEF) and 151 subjects with preserved left ventricular ejection fraction (HFpEF) were included. Discrimination was assessed using c-statistics based on time-to-event analyses and receiver-operator curves. The additive contribution of MLHFQ was assessed through the change in c-statistic, incremental discrimination index, and category-free net reclassification index. Overall, KCCQ was superior to MLHFQ for predicting death/transplant/ventricular assist device (c-statistic 0.702 [0.666 to 0.738] and 0.658 [0.621 to 0.695] respectively, p value for difference <0.001) and hospitalization (c-statistic 0.640 [0.613 to 0.666] and 0.624 [0.597 to 0.651], respectively, p value for difference 0.022). However, this difference was statistically nonsignificant in the HFpEF group alone. When analyzing the additional prognostic information afforded by adding MLHFQ to KCCQ in the overall, HFrEF, and HFpEF groups there was no significant improvement, although adding KCCQ to MLHFQ did significantly improve risk stratification. Scoring based upon the abbreviated KCCQ-12 did not reduce the prognostic accuracy of KCCQ. In conclusion, KCCQ is more prognostic of death/transplant/left ventricular assist device and hospitalization than MLHFQ in a combined cohort of patients with HFrEF and HFpEF, although the effect in HFpEF was less pronounced. KCCQ should be the preferred PROM for patients with HF if prognostication is a desired goal of using the PROMs.
Market-oriented programming (abstract)

Market-oriented programming is the construction of computational economies, where agents interact through a price system. Markets can provide effective allocation of resources for a variety of distributed environments, and economic analysis a powerful design tool for interaction mechanisms. The spread of electronic commerce puts a premium on market-aware agents, and presents a case for market awareness on the part of agent developers and AI researchers as well.
The efficiency of regulatory arbitrage

Classic public choice skepticism about the regulatory state, based on theories of rent-seeking, rent extraction and regulatory capture, is based on the unrealistic, and usually unstated, assumption of a monopolist regulator. In practice, the regulatory state is polycentric, involving numerous quasi-independent agencies with overlapping responsibilities. This has led to a more optimistic picture based on the idea of regulatory arbitrage: when firms can, to some extent, pick and choose their preferred regulator, regulatory agencies are constrained to deliver relatively efficient regulatory policies. In our view, this optimism is also unrealistic. We build a family of models that explores the possible regulatory outcomes, and use some aspects of Gordon Tullock’s critique of the common law as a conceptual foundation for the analysis of the efficiency of a polycentric regulatory system.
The impression management benefits of humorous self-disclosures: How humor influences perceptions of veracity

Abstract Across five studies, we identify humor as a powerful impression management tool that influences perceptions of veracity. In many domains, such as negotiations and interviews, individuals face a challenge with respect to disclosing negative information and managing impressions. For example, an interviewer may ask an applicant to name their greatest weakness. In these settings, disclosures that reveal negative information (e.g., “I am not good at math.”) can harm perceptions of warmth and competence. We demonstrate that pairing a humorous statement with a disclosure (e.g., “I am not good at math. Geometry is where I draw the line.”) changes perceptions of the veracity of the disclosure; disclosures are less likely to be judged as true when they are accompanied by a humorous statement than when they are not. We introduce the Speaker's Inferred Motive (SIM) Model and consider the possibility that (a) speakers pursue different motives, such as a transmission-of-ideas motive (to convey information) or an entertainment motive (to amuse an audience), (b) audience members infer the speaker’s motive, and (c) these inferences influence perceptions of the veracity of proximal disclosures. As a result, by using humor, a speaker may signal a shift in motive and diminish perceptions of the veracity of both the humorous statement and proximal claims. Taken together, when a target discloses negative information, including information that is highly relevant to the conversational partner, the use of humor can boost perceptions of warmth and competence. We discuss implications of our findings with respect to communication, interpersonal perception, and impression management.
A Teensy microcontroller-based interface for optical imaging camera control during behavioral experiments.

Abstract Background Systems neuroscience experiments often require the integration of precisely timed data acquisition and behavioral monitoring. While specialized commercial systems have been designed to meet various needs of data acquisition and device control, they often fail to offer flexibility to interface with new instruments and variable behavioral experimental designs. New method We developed a Teensy 3.2 microcontroller-based interface that is easily programmable, and offers high-speed, precisely timed behavioral data acquisition and digital and analog outputs for controlling sCMOS cameras and other devices. Results We demonstrate the flexibility and the temporal precision of the Teensy interface in two experimental settings. In one example, we used the Teensy interface to record an animal’s directional movement on a spherical treadmill, while delivering repeated digital pulses that can be used to control image acquisition from a sCMOS camera. In another example, we used the Teensy interface to deliver an auditory stimulus and a gentle eye puff at precise times in a trace conditioning eye blink behavioral paradigm, while delivering repeated digital pulses to trigger camera image acquisition. Comparison with existing methods This interface allows high-speed and temporally precise digital data acquisition and device control during diverse behavioral experiments. Conclusion The Teensy interface, consisting of a Teensy 3.2 and custom software functions, provides a temporally precise, low-cost, and flexible platform to integrate sCMOS camera control into behavioral experiments.
Game networks

We introduce Game networks (G nets), a novel representation for multi-agent decision problems. Compared to other game-theoretic representations, such as strategic or extensive forms, G nets are more structured and more compact; more fundamentally, G nets constitute a computationally advantageous framework for strategic inference, as both probability and utility independencies are captured in the structure of the network and can be exploited in order to simplify the inference process. An important aspect of multiagent reasoning is the identification of some or all of the strategic equilibria in a game; we present original convergence methods for strategic equilibrium which can take advantage of strategic separabilities in the G net structure in order to simplify the computations. Specifically, we describe a method which identifies a unique equilibrium as a function of the game payoffs, and one which identifies all equilibria.
Split equilibrium problems for related games and applications to economic theory

ABSTRACTIn this paper we introduce the concept of split Nash equilibrium problems associated with two related noncooperative strategic games. Then we apply the Fan-KKM theorem to prove the existenc...
Mice Against Ticks: an experimental community-guided effort to prevent tick-borne disease by altering the shared environment

Mice Against Ticks is a community-guided ecological engineering project that aims to prevent tick-borne disease by using CRISPR-based genome editing to heritably immunize the white-footed mice ( Peromyscus leucopus) responsible for infecting many ticks in eastern North America. Introducing antibody-encoding resistance alleles into the local mouse population is anticipated to disrupt the disease transmission cycle for decades. Technology development is shaped by engagement with community members and visitors to the islands of Nantucket and Martha's Vineyard, including decisions at project inception about which types of disease resistance to pursue. This engagement process has prompted the researchers to use only white-footed mouse DNA if possible, meaning the current project will not involve gene drive. Instead, engineered mice would be released in the spring when the natural population is low, a plan unlikely to increase total numbers above the normal maximum in autumn. Community members are continually asked to share their suggestions and concerns, a process that has already identified potential ecological consequences unanticipated by the research team that will likely affect implementation. As an early example of CRISPR-based ecological engineering, Mice Against Ticks aims to start small and simple by working with island communities whose mouse populations can be lastingly immunized without gene drive. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.
The Effects of Information Systems Compatibility on Firm Performance following Mergers and Acquisitions

This study investigates the consequences of information systems compatibility between the target and acquirer firms in the context of mergers and acquisitions (M&A). Using a unique data set of ERP ...
The Role of Pregnancy Concerns in the Relationship between Substance Use and Unprotected Sex among Adolescents

Background: Substance use and unprotected sex are prevalent among adolescents. The link between substance use and unprotected sex is well-established. Research has also highlighted how adolescents’...
A Class I Haemophilus ducreyi Strain Containing a Class II hgbA Allele Is Partially Attenuated in Humans: Implications for HgbA Vaccine Efficacy Trials.

ABSTRACT Haemophilus ducreyi causes chancroid and is a major cause of cutaneous ulcers in children. Due to environmental reservoirs, both class I and class II H. ducreyi strains persist in cutaneous ulcer regions of endemicity following mass drug administration of azithromycin, suggesting the need for a vaccine. The hemoglobin receptor (HgbA) is a leading vaccine candidate, but its efficacy in animal models is class specific. Controlled human infection models can be used to evaluate vaccines, but only a class I strain (35000HP) has been characterized in this model. As a prelude to evaluating HgbA vaccines in the human model, we tested here whether a derivative of 35000HP containing a class II hgbA allele (FX548) is as virulent as 35000HP in humans. In eight volunteers infected at three sites with each strain, the papule formation rate was 95.8% for 35000HP versus 62.5% for FX548 (P = 0.021). Excluding doses of FX548 that were ≥2-fold higher than those of 35000HP, the pustule formation rate was 25% for 35000HP versus 11.7% for FX548 (P = 0.0053). By Western blot analysis, FX548 and 35000HP expressed equivalent amounts of HgbA in whole-cell lysates and outer membranes. The growth of FX548 and 35000HP was similar in media containing hemoglobin or hemin. By whole-genome sequencing and single-nucleotide polymorphism analysis, FX548 contained no mutations in open reading frames other than hgbA. We conclude that by an unknown mechanism, FX548 is partially attenuated in humans and is not a suitable strain for HgbA vaccine efficacy trials in the model.
Variability in weed biological control: Effects of foliar nitrogen on larval development and dispersal of the alligatorweed flea beetle, Agasicles hygrophila

Abstract Host quality can have dramatic effects on performance of biological control agents but its importance is understudied. We used a combination of field measurements and laboratory experiments to determine the range of foliar nitrogen (FN) that larvae of the alligatorweed flea beetle (Agasicles hygrophila) are exposed to in the field and its importance to larval development and dispersal. Seasonal variability in FN was assessed at field sites spanning southern to northern Louisiana every 2–3 weeks during the growing season for four years. In a series of laboratory experiments, alligatorweed FN was manipulated to examine its influence on larval development and survival (under different temperature regimes), adult biomass, and dispersal of the biological control agent, A. hygrophila. There was strong seasonality of FN in field sites with peak levels (4–8% dry weight nitrogen; DW N) recorded early during each year, declining during summer, and slightly increasing again in the fall which coincides with flea beetle activity. Foliar nitrogen and rearing temperature had strong independent effects on larval development rate. High FN increased survival by 40%, decreased developmental time by 15%, and resulted in 11% larger adults. Increasing temperature reduced survival by 43%, shortened developmental time by 28%, and led to 15% smaller adults. In the dispersal experiment we were unable to detect an interaction between FN and conspecific density on larval dispersal, though results suggested that FN may lessen effects at moderate densities. Mean dispersal was more than double in the low versus high FN treatment (51% vs. 23%). Larval density and nitrogen both affected larval weight; high nitrogen plants produced 33% larger larvae over the duration of the experiment and larval fresh weight decreased by 38% from low (one larva plant−1) to high (twenty larvae plant−1) density treatments. We demonstrated that increasing nitrogen in leaf tissues shortens larval A. hygrophila developmental time and increases survival to adulthood, regardless of exposure temperature during development. It also suggests that foliar nitrogen may have important effects on biological control of alligatorweed, particularly as a result of seasonal variation in temperature and plant nutrition at field sites, and could contribute to observed variation in A. hygrophila efficacy in the field.
ON TESTING CONDITIONAL QUALITATIVE TREATMENT EFFECTS.

Precision medicine is an emerging medical paradigm that focuses on finding the most effective treatment strategy tailored for individual patients. In the literature, most of the existing works focused on estimating the optimal treatment regime. However, there has been less attention devoted to hypothesis testing regarding the optimal treatment regime. In this paper, we first introduce the notion of conditional qualitative treatment effects (CQTE) of a set of variables given another set of variables and provide a class of equivalent representations for the null hypothesis of no CQTE. The proposed definition of CQTE does not assume any parametric form for the optimal treatment rule and plays an important role for assessing the incremental value of a set of new variables in optimal treatment decision making conditional on an existing set of prescriptive variables. We then propose novel testing procedures for no CQTE based on kernel estimation of the conditional contrast functions. We show that our test statistics have asymptotically correct size and nonnegligible power against some nonstandard local alternatives. The empirical performance of the proposed tests are evaluated by simulations and an application to an AIDS data set.
Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule

The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest.
Stereoselective synthesis of E,Z-1,3-dienes via tandem nucleophile addition to a dienylphosphonium salt followed by wittig reaction

Abstract 1,3-Dienes of E,Z configuration were synthesized by addition of nucleophilic anions to butadienyltriphenylphosphonium bromide followed by in situ Wittig reaction of the derived E allylic phosphorane to an aldehyde.
Carbene cascades for the formation of bridged polycyclic rings

Abstract A general strategy to synthesize bridged polycyclic molecules is presented. The synthesis is accomplished via a cascade reaction initiated by rhodium carbene formation. Subsequent intramolecular reaction with an alkyne is then followed by a transannular C–H bond insertion. A rationale for prediction of the major structural isomer that is formed is described and applied to a wide variety of substrates. This rationale is based on conformational and stereoelectronic considerations for the ring system in the substrate.
A New, Lipophilic p-Alkoxybenzyl Ether Protecting Group and Its Use in the Synthesis of a Disaccharide

In contrast to major advances in the chemical synthesis of oligosaccharides, the methods of purification of the intermediates are essentially the same as they were decades ago. Here, the synthesis of p-(dodecyloxy)benzyl chloride is described and it is demonstrated that the new p-(dodecyloxy)benzyl ether protecting group can render a protected disaccharide sufficiently lipophilic for selective adsorption on C18 silica, thus sidestepping the expensive silica gel chromatography traditionally used for the isolation of protected oligosaccharides.
Preparation and crystal structure of Sr6TiNb4O18

Abstract The crystal structure of newly prepared Sr6TiNb4O18 was determined by single-crystal X-ray diffraction and is described here. This compound crystallizes in space group R3m (No. 160; a=5.6437(5), c=41.347(3)A, Z=3). The structure consists of infinite perovskite-type slabs, five octahedra in thickness, extending parallel to (111)perovskite. All Sr ions are 12-coordinated; Nb5+ and Ti4+ are distributed among the octahedral M sites. The cation coordination spheres in and bordering the gaps between the perovskite-type slabs are highly distorted with bond valence sums indicative of residual chemical strain: SrO bonds are stretched, MO bonds compressed. Nb5+ preferentially occupies the distorted octahedral sites that border the gaps; the least amount of the higher valent metal is found in octahedral sites embedded in the center of the slabs. Similar crystal-chemical effects were reported for isostructural Ba6TiNb4O18 and for Sr5TiNb4O17, also a perovskite-slab-type structure but with slices cut parallel to (110)perovskite.
Overriding effect of temperature over reagent and substrate size for boron-mediated aldol reaction of methyl phenylacetate

Abstract The enolization temperature overrides all other aspects, including the sterics of the alkyl group of the boron reagent and the alkoxy group of the ester during the enolboration–aldolization of phenylacetates. This study has led to the first n -Bu 2 BOTf-mediated anti -selective aldol reaction of an ester.
Hospital treatment and patient outcomes: Evidence from capacity constraints

Abstract Understanding the relationship between health care service provision and patient outcomes has become more important as providers are increasingly evaluated on the efficacy of their care delivery. This study examines this relationship using an approach that recognizes the role that capacity constraints at hospitals within a local area serve in patient allocation. Hourly data on hospital patient censuses over a 12-year period show that hospital assignment is influenced by supply-side, hospital-level constraints on the number of empty beds available for the period during which treatment is sought. Using this as a source of variation, the estimates indicate that treatment at a more procedure-intensive hospital lowers readmission rates, and that the effect is particularly pronounced for unplanned hospital readmissions. The results reinforce the importance of identifying the relationship between treatment intensity and outcomes in a causal framework and indicate that these hospitals are providing higher quality care.
High-Temperature Raman Investigation of Concentrated Sulfuric Acid Mixtures: Measurement of H-Bond ΔH Values between H3O+ or H5O2+ and HSO4-

Forty-two mol percent sulfuric acid is a room-temperature molten salt composed of H-bonded ion pairs H3O+−HSO4- (8.2 M) and H5O2+−HSO4- (5.4 M), the former breaking primarily below ∼360 °C and the latter, mainly between ∼360 °C and the critical point. These ruptures produce H2SO4 and H2O. Iterative van't Hoff thermodynamic analysis of Raman spectra to 360 °C employing peak height or component area ratios at ∼905 and ∼1035 cm-1 or at ∼1165 and ∼1035 cm-1 yielded an average ΔH of 3.2 ± 0.2 kcal/mol corresponding to H-bond breakage between H3O+ and HSO4-. A Raman ΔH of 5.9 ± 0.3 kcal/mol was measured for the rupture of H5O2+−HSO4- H-bonds between 360 and 513 °C versus ∼5.7 kcal/mol calculated. H-bonds exist between species other than the two hydronium−bisulfate ion pairs but are not measured by the Raman H2SO4/HSO4- intensity ratios. Hydrogen bonding wanes near the critical point, ∼665 °C, at which only neutral species, H2SO4 and H2O (plus some SO3), remain. A ΔH of 3.5 ± 0.4 kcal/mol was also measured from ...
On the scope of the Pt-catalyzed Srebnik diborylation of diazoalkanes. An efficient approach to chiral tertiary boronic esters and alcohols via B-stabilized carbanions

Abstract Conditions milder than those previously reported are shown to be generally applicable to the Pt-catalyzed insertion of non-carbonyl-stabilized diazoalkanes into B 2 pin 2 . Selective transformation of one (pinacolato)boryl unit in the products is enabled by rapid, low-temperature deboronation in the presence of a Lewis base and genesis of a highly reactive B-stabilized carbanion.
Quantitative Real-Time Imaging of Glutathione with Subcellular Resolution.

Abstract Aims: Quantitative imaging of glutathione (GSH) with high spatial and temporal resolution is essential for studying the roles of GSH in redox biology. To study the long-standing question o...
Equilibrium Acidities and Homolytic Bond Dissociation Energies (BDEs) of the Acidic H−N Bonds in Hydrazines and Hydrazides

The equilibrium acidities in DMSO for phenylhydrazine, five of its p-substituted derivatives, 1,2-diphenylhydrazine, and 1,1,2-triphenylhydrazine were measured and the BDEs of their acidic N−H bonds were estimated by using the following equation: BDE = 1.37pKHA + 23.06Eox(A-) + 73.3 kcal/mol. The α-N−H bonds in the hydrazides CH3CONHNH2, PhCONHNH2, NH2NHCO2Et, and PhSO2NHNH2 were found to be 2 to 4 pKHA units more acidic than the α-N−H bonds in the corresponding amides, and the BDEs were estimated to be 23−27 kcal/mol weaker. Similarly, the BDE of a N−H bond in hydrazine was estimated to be 26 kcal/mol weaker than that of an N−H bond in NH3. Introduction of a RCO group into hydrazine had little or no effect on the BDE, but introduction of RCO into the β-position of PhCONHNH2 caused about an 8 kcal/mol increase in BDE. An increase in BDE was also observed for introduction of an RCO group into aniline. Here the carbonyl group is effectively destabilizing a nitrogen-centered radical by virtue of its strong ...
Complex Polycyclic Lactams from Pericyclic Cascade Reactions of Zincke Aldehydes

In the course of a simple mechanistic study on the rearrangement of Zincke aldehydes to Z-α,β,γ,δ-unsaturated amides, a thermally induced pericyclic cascade rearrangement that converts Zincke aldehydes derived from allylic and homoallylic amines into polycyclic lactams was discovered. The key reaction involves an E-Z alkene isomerization, a 6π electrocyclic ring closure, a [1,5]-sigmatropic shift of hydrogen, a 6π electrocyclic ring-opening, and a Diels—Alder cycloaddition, and proceeds with excellent stereoselectivity. The unusual observation that furans and an indole serve as dienophiles in this cascade reaction permitted the synthesis of complex, functional group-rich tri- and tetracyclic lactams. In all cases, the rigid polycyclic products are available in only two steps from pyridinium salts and the allylic or homoallylic secondary amines.