cssi/SciSciGPT-SciSciNet huggingface dataset:
Sensing Cooperativity in ATP Hydrolysis for Single Multisubunit Enzymes in Solution

Cooperative interactions are critical for multisubunit enzymes to fulfill their enzymatic cycle in a coordinated fashion. To study this poorly understood process in the mammalian double-ring 16-subunit chaperonin TRiC/CCT, ATP number distributions in various hydrolyzed states are measured for single copies of the enzyme as each of the subunits can bind and hydrolyze ATP. Fluorescent-nucleotide-bound chaperonins are localized in free solution by closed-loop feedback provided by an Anti-Brownian ELectrokinetic trap (ABEL trap), producing fluorescence emission traces which allow determination of the number of nucleotides on each enzyme. As ADP molecules are dissociating from the chaperonin, the single peak at eight ADP bound simply falls in height over time, indicating a highly cooperative ADP release process difficult to observe by ensemble-averaged methods (figure).By adding AlFx during ATP incubation, ATP transition state mimics (ADP•AlFx) are locked to the complex and show a dominant peak at 8 nucleotides for all incubation concentrations above 25 μM. Although ensemble averages of the single-molecule data can be matched with standard cooperativity models, surprisingly, the observed number distributions depart significantly from standard models and reveal stronger cooperativity, illustrating the power of the single-molecule distribution-based approach.View Large Image | View Hi-Res Image | Download PowerPoint Slide
Optical Activation of TrkA Signaling

Nerve growth factor/tropomyosin receptor kinase A (NGF/TrkA) signaling plays a key role in neuronal development, function, survival, and growth. The pathway is implicated in neurodegenerative disorders including Alzheimer’s disease, chronic pain, inflammation, and cancer. NGF binds the extracellular domain of TrkA, leading to the activation of the receptor’s intracellular kinase domain. As TrkA signaling is highly dynamic, mechanistic studies would benefit from a tool with high spatial and temporal resolution. Here we present the design and evaluation of four strategies for light-inducible activation of TrkA in the absence of NGF. Our strategies involve the light-sensitive protein Arabidopsis cryptochrome 2 and its binding partner CIB1. We demonstrate successful recapitulation of native NGF/TrkA functions by optical induction of plasma membrane recruitment and homo-interaction of the intracellular domain of TrkA. This approach activates PI3K/AKT and Raf/ERK signaling pathways, promotes neurite growth in P...
Emotional Intelligence, Information Elaboration, and Performance: The Moderating Role of Informational Diversity

This article explores the effects of emotional intelligence (EI) in a team setting. Informational diversity is theorized to moderate the relationship between team EI and performance. I propose that...
Equilibrium existence in global games with general payoff structures

We consider global games with general payoff structures and prove existence of equilibrium. This shows that the global games’ method is well defined with arbitrary strategic interaction among players, thus providing a foundation for the study of more general equilibrium behavior, especially as research in global games moves beyond the case of strategic complements. We also show that, in every global game, even though the information of each player is correlated, the joint information measure is absolutely continuous with respect to the product of its marginals. As one application, the result here can be used to show the existence of equilibrium in global games with both complementarity and congestion. This proves existence of equilibrium in a finite-player version of the model in Karp et al. (Games Econ Behav 60:155–175, 2007), thus addressing a gap in the proof of equilibrium existence documented in Hoffmann and Sabarwal (Games Econ Behav 94:188–190, 2015).
Information technologies that facilitate care coordination: provider and patient perspectives

Health information technology is a core infrastructure for the chronic care model, integrated care, and other organized care delivery models. From the provider perspective, health information exchange (HIE) helps aggregate and share information about a patient or population from several sources. HIE technologies include direct messages, transfer of care, and event notification services. From the patient perspective, personal health records, secure messaging, text messages, and other mHealth applications may coordinate patients and providers. Patient-reported outcomes and social media technologies enable patients to share health information with many stakeholders, including providers, caregivers, and other patients. An information architecture that integrates personal health record and mHealth applications, with HIEs that combine the electronic health records of multiple healthcare systems will create a rich, dynamic ecosystem for patient collaboration.
Surprising properties of dropout in deep networks

We analyze dropout in deep networks with rectified linear units and the quadratic loss. Our results expose surprising differences between the behavior of dropout and more traditional regularizers like weight decay. For example, on some simple data sets dropout training produces negative weights even though the output is the sum of the inputs. This provides a counterpoint to the suggestion that dropout discourages co-adaptation of weights. We also show that the dropout penalty can grow exponentially in the depth of the network while the weight-decay penalty remains essentially linear, and that dropout is insensitive to various re-scalings of the input features, outputs, and network weights. This last insensitivity implies that there are no isolated local minima of the dropout training criterion. Our work uncovers new properties of dropout, extends our understanding of why dropout succeeds, and lays the foundation for further progress.
Financial Crises, Dollarization, and Lending of Last Resort in Open Economies

Foreign currency debt is considered a source of financial instability in emerging markets. We propose a theory in which liability dollarization arises from an insurance motive of domestic savers. Since financial crises are associated to depreciations, savers ask for a risk premium when saving in local currency. This force makes domestic currency debt expensive, and incentivizes borrowers to issue foreign currency debt. Providing ex post support to borrowers can alleviate the effect of the crisis on savers' income, lowering their demand for insurance, and, surprisingly, it can reduce ex ante incentives to borrow in foreign currency.
Autoregulation of the Streptococcus mutans SloR Metalloregulator Is Constitutive and Driven by an Independent Promoter.

ABSTRACT Streptococcus mutans, one of ∼600 bacterial species in the human oral cavity, is among the most acidogenic constituents of the plaque biofilm. Considered to be the primary causative agent of dental caries, S. mutans harbors a 25-kDa SloR metalloregulatory protein which controls metal ion transport across the bacterial cell membrane to maintain essential metal ion homeostasis. The expression of SloR derives in part from transcriptional readthrough of the sloABC operon, which encodes a Mn2+/Fe2+ ABC transport system. Here we describe the details of the sloABC promoter that drives this transcription as well as those for a novel independent promoter in an intergenic region (IGR) that contributes to downstream sloR expression. Reverse transcriptase PCR (RT-PCR) studies support the occurrence of sloR transcription that is independent of sloABC expression, and the results of 5′ rapid amplification of cDNA ends (5′ RACE) revealed a sloR transcription start site in the IGR, from which the −10 and −35 promoter regions were predicted. The results of gel mobility shift assays support direct SloR binding to the IGR, albeit with a lower affinity than that for SloR binding to the sloABCR promoter. The function of the sloR promoter was validated by semiquantitative real-time PCR (qRT-PCR) experiments. Interestingly, sloR expression was not significantly affected when bacteria were grown in the presence of a high manganese concentration, whereas expression of the sloABC operon was repressed under these conditions. The results of in vitro transcription studies support the occurrence of SloR-mediated transcriptional activation of sloR and repression of sloABC. Taken together, these findings implicate SloR as a bifunctional regulator that represses sloABC promoter activity and encourages sloR transcription from an independent promoter. IMPORTANCE Tooth decay is a ubiquitous infectious disease that is especially pervasive in underserved communities worldwide. S. mutans-induced carious lesions cause functional, physical, and/or esthetic impairment in the vast majority of adults and in 60 to 90% of schoolchildren in industrialized countries. Billions of dollars are spent annually on caries treatment, and productivity losses due to absenteeism from the workplace are significant. Research aimed at alleviating S. mutans-induced tooth decay is important because it can address the socioeconomic disparity that is associated with dental cavities and improve overall general health, which is inextricably linked to oral health. Research focused on the S. mutans SloR metalloregulatory protein can guide the development of novel therapeutics and thus alleviate the burden of dental cavities.
Permutation-Invariant Consensus over Crowdsourced Labels

This paper introduces a novel crowdsourcing consensus model and inference algorithm — which we call PICA (Permutation-Invariant Crowdsourcing Aggregation) — that is designed to recover the ground-truth labels of a dataset while being invariant to the class permutations enacted by the different annotators. This is particularly useful for settings in which annotators may have systematic confusions about the meanings of different classes, as well as clustering problems (e.g., dense pixel-wise image segmentation) in which the names/numbers assigned to each cluster have no inherent meaning.The PICA model is constructed by endowing each annotator with a doubly-stochastic matrix (DSM), which models the probabilities that an annotator will perceive one class and transcribe it into another. We conduct simulations and experiments to show the advantage of PICA compared to two baselines (Majority Vote, and an "unpermutation" heuristic) for three different clustering/labeling tasks. We also explore the conditions under which PICA provides better inference accuracy compared to a simpler but related model based on right-stochastic matrices. Finally, we show that PICA can be used to crowdsource responses for dense image segmentation tasks, and provide a proof-of-concept that aggregating responses in this way could improve the accuracy of this labor-intensive task.
Subset Source Coding

This paper studies the fundamental limits of storage for structured data, where statistics and structure are both critical to the application. Accordingly, a framework is proposed for optimal lossless and lossy compression of subsets of the possible realizations of a discrete memoryless source (DMS). For the lossless subset-compression problem, it turns out that the optimal source code may not index the conventional source-typical sequences, but rather index certain subset-typical sequences consistent with the subset of interest. Building upon an achievability and a strong converse, an analytic expression is given, based on the Shannon entropy, relative entropy, and subset entropy, which identifies such subset-typical sequences for a broad class of subsets of a DMS. Intuitively, subset-typical sequences belong to those typical sets which highly intersect the subset of interest but are still closest to the source distribution in the sense of relative entropy. For the lossy subset-compression problem, an upper bound is derived on the subset rate-distortion function in terms of the subset mutual information optimized over the set of conditional distributions that satisfy the expected distortion constraint with respect to the subset-typical distribution and over a set of certain auxiliary subsets. By proving a strong converse result, this upper bound is shown to be tight for a class of symmetric subsets. As shown in our numerical examples, more often than not, one achieves a gain in the fundamental limits, in that the optimal compression rate for the subset in both the lossless and lossy settings can be strictly smaller than the source entropy and the source rate-distortion function, respectively, although exceptions are also possible.
Computerized Residency Interview Scheduling: A Randomized Controlled Trial of Categorical General Surgery Applicants.

Objective Scheduling interviews can be stressful and time-intensive for general surgery applicants and program coordinators. The objectives of this study were to determine whether computerized scheduling program (CSP) would decrease time to schedule interviews, reduce workload for residency coordinators, and improve applicant satisfaction. Design A prospective randomized controlled trial of 2 interview-scheduling methods was conducted. All categorical general surgery applicants selected to interview for the 2017 match were randomized to either standard e-mail/phone scheduling or CSP using InterviewBroker. Time required to schedule an interview, number of communications, reschedules, withdrawals, and cancellations were all recorded. Additionally, applicants completed a voluntary, anonymous 9-question paper survey on their interview date. The program director and interviewers were blinded to the experimental groups. Setting A single general surgery residency program. Participants Participants in the study included all categorical general surgery applicants selected for an interview in the 2017 match cycle (N = 62 standard group, N = 62 CSP group). Results The CSP group took less time to schedule interviews (9 minutes vs. 80 minutes; p Conclusions CSPs expedited interview scheduling, decreased workload for program coordinators, and improved general surgery applicant satisfaction. However, despite the benefits of CSPs for programs and applicants, CSP use is not widespread among general surgery residency programs. Adoption of CSPs by all programs could greatly improve interview-scheduling processes for applicants and programs.
The Latarjet Procedure for Anterior Shoulder Instability in Pediatric and Adolescent Athletes

Objectives:To investigate surgical outcomes of the Latarjet procedure in the pediatric and adolescent athletic population compared to alternative techniques used to treat anterior shoulder instabil...
Symmetry properties for solutions of nonlocal equations involving nonlinear operators

Abstract We pursue the study of one-dimensional symmetry of solutions to nonlinear equations involving nonlocal operators. We consider a vast class of nonlinear operators and in a particular case it covers the fractional p-Laplacian operator. Just like the classical De Giorgi's conjecture, we establish a Poincare inequality and a linear Liouville theorem to provide two different proofs of the one-dimensional symmetry results in two dimensions. Both approaches are of independent interests. In addition, we provide certain energy estimates for layer solutions and Liouville theorems for stable solutions. Most of the methods and ideas applied in the current article are applicable to nonlocal operators with general kernels where the famous extension problem, given by Caffarelli and Silvestre, is not necessarily known.
A Structural Characterization of Market Power in Electric Power Networks

We consider a market in which capacity-constrained generators compete in scalar-parameterized supply functions to serve an inelastic demand spread throughout a transmission constrained power network. The market clears according to a locational marginal pricing mechanism, in which the independent system operator (ISO) determines the generators’ production quantities to minimize the revealed cost of meeting demand, while ensuring that network transmission and generator capacity constraints are met. Under the stylizing assumption that both the ISO and generators choose their strategies simultaneously, we establish the existence of Nash equilibria for the underlying market, and derive an upper bound on the allocative efficiency loss at Nash equilibrium relative to the socially optimal outcome. We also characterize an upper bound on the markup of locational marginal prices at Nash equilibrium above their perfectly competitive levels. Of particular relevance to ex ante market power monitoring, these bounds reveal the role of certain market structures—specifically, the market share and the residual supply index of a producer—in predicting the degree to which that producer is able to exercise market power to influence the market outcome to its advantage. Finally, restricting our attention to the simpler setting of a two-node power network, we provide a characterization of market structures under which a Braess-like paradox occurs due to the exercise of market power. Speficically, we provide a necessary and sufficient condition on market structure under which the strengthening of the network's transmission line capacity results in the (counterintuitive) increase in the total cost of generation at Nash equilibrium.
A Multi-Scale Analysis of 27,000 Urban Street Networks: Every US City, Town, Urbanized Area, and Zillow Neighborhood

OpenStreetMap offers a valuable source of worldwide geospatial data useful to urban researchers. This study uses the OSMnx software to automatically download and analyze 27,000 US street networks f...
The Reappearing Masterpiece: Ranking American Artists and Art Works of the Late Twentieth Century

A survey of the illustrations in textbooks of modern art produces the startling finding that art scholars consider Robert Smithson's Spiral Jetty to be the most important individual work made by an American artist during the past 150 years. More generally, quantifying the evidence of the textbooks reveals the source of the pluralism, or stylistic incoherence, of American art since the late 1960s. A persistently high demand for artistic innovation has produced a regime in which conceptual approaches have predominated. The art world has consequently been flooded by a series of new ideas, often embodied in individual works, usually made by young artists who have failed to make more than one significant contribution in their careers. The monumental Spiral Jetty, made in 1970 by a young artist who was killed soon thereafter while in the process of making his art, brought together a remarkable number of the central themes of the advanced art of the time and has become a symbol for that art.
An integrated silicon bipolar receiver subsystem for 900-MHz ISM band applications

A wide-band dual conversion receiver subsystem is presented which is suitable for 900-MHz portable wireless applications including cordless telephony. The circuit features 118 dB of dynamic range and is operable from 6.5 V down through 2.7 V while consuming 26 mA. The receiver utilizes the MOSAIC V radio frequency (RF) silicon bipolar process and features an LNA, two mixers, two oscillators, second LO amplifier, dual modulus prescaler, LF amplifier, RSSI, coilless demodulator, and power down control.
Normative inference in efficient markets

This paper develops a nonparametric method to infer social preferences over policies from prices of securities when agents have non-stationary heterogeneous preferences. We allow for arbitrary efficient risk-sharing mechanisms, formal and informal, and consider a large class of policies. We present a condition on the distribution of aggregate wealth that is necessary and sufficient for the revelation of social preferences over a universal set of policies. We also provide a weaker condition that is sufficient for revelation of social preferences for an arbitrary finite collection of policies.
The Contradictory Expressive Functions of the Americans with Disabilities Act and Physician-assisted Suicide Laws

Certain laws, such as civil rights laws and criminal laws, are considered to have powerful expressive functions. The expressive functions may be directed at shifting social norms, or at articulatin...
Graph Convolution over Pruned Dependency Trees Improves Relation Extraction.

Dependency trees help relation extraction models capture long-range relations between words. However, existing dependency-based models either neglect crucial information (e.g., negation) by pruning the dependency trees too aggressively, or are computationally inefficient because it is difficult to parallelize over different tree structures. We propose an extension of graph convolutional networks that is tailored for relation extraction, which pools information over arbitrary dependency structures efficiently in parallel. To incorporate relevant information while maximally removing irrelevant content, we further apply a novel pruning strategy to the input trees by keeping words immediately around the shortest path between the two entities among which a relation might hold. The resulting model achieves state-of-the-art performance on the large-scale TACRED dataset, outperforming existing sequence and dependency-based neural models. We also show through detailed analysis that this model has complementary strengths to sequence models, and combining them further improves the state of the art.
Learning consumer and producer embeddings for user-generated content recommendation

User-Generated Content (UGC) is at the core of web applications where users can both produce and consume content. This differs from traditional e-Commerce domains where content producers and consumers are usually from two separate groups. In this work, we propose a method CPRec (consumer and producer based recommendation), for recommending content on UGC-based platforms. Specifically, we learn a core embedding for each user and two transformation matrices to project the user's core embedding into two 'role' embeddings (i.e., a producer and consumer role). We model each interaction by the ternary relation between the consumer, the consumed item, and its producer. Empirical studies on two large-scale UGC applications show that our method outperforms standard collaborative filtering methods as well as recent methods that model producer information via item features.
Local News and National Politics

The level of journalistic resources dedicated to coverage of local politics is in a long-term decline in the US news media, with readership shifting to national outlets. We investigate whether this trend is demand- or supply-driven, exploiting a recent wave of local television station acquisitions by a conglomerate owner. Using extensive data on local news programming and viewership, we find that the ownership change led to (1) substantial increases in coverage of national politics at the expense of local politics, (2) a significant rightward shift in the ideological slant of coverage, and (3) a small decrease in viewership, all relative to the changes at other news programs airing in the same media markets. These results suggest a substantial supply-side role in the trends toward nationalization and polarization of politics news, with negative implications for accountability of local elected officials and mass polarization.
Methodology for a World Bank Human Capital Index

This paper describes the methodology for a new World Bank Human Capital Index (HCI). The HCI combines indicators of health and education into a measure of the human capital that a child born today can expect to obtain by her 18th birthday, given the risks of poor education and health that prevail in the country where she lives. The HCI is measured in units of productivity relative to a benchmark of complete education and full health, and ranges from 0 to 1. A value of x on the HCI indicates that a child born today can expect to be only x x100 percent as productive as a future worker as she would be if she enjoyed complete education and full health. The methodology of the HCI is anchored in the extensive literature on development accounting.
On the pitfalls of applying isotropic mobility spectrum analysis to conductors with weak anisotropy

It is shown that applying isotropic quantitative mobility analysis to anisotropic materials can lead to drastic qualitative errors, even in the case of modest anisotropy. The procedure may provide not only wrong values for carrier mobilities and concentrations but even a wrong number of carrier species.It is shown that applying isotropic quantitative mobility analysis to anisotropic materials can lead to drastic qualitative errors, even in the case of modest anisotropy. The procedure may provide not only wrong values for carrier mobilities and concentrations but even a wrong number of carrier species.
Polynomial Time Decodable Codes for the Binary Deletion Channel

In the random deletion channel, each bit is deleted independently with probability $p$ . For the random deletion channel, the existence of codes of rate $(1-p)/9$ , and thus bounded away from 0 for any $p , has been known. We give an explicit construction with polynomial time encoding and deletion correction algorithms with rate $c_{0} (1-p)$ for an absolute constant $c_{0} > 0$ .
Forecasting Bond Risk Premia with Unspanned Macroeconomic Information

I provide evidence on the existence of unspanned macro risk. I investigate the usefulness of unspanned macro information for forecasting bond risk premia in a macro-finance term structure model fro...
Farewell Downton Abbey, Adieu Primogeniture and Entail: Britain’s Brief Encounter with Forced Heirship

This article observes a little-noted proposal (the Landed Property of Intestates Bill) introduced into the British Parliament in 1836. It considers the debate upon it that ensued, and the accompanying pamphlet literature. The Bill proposed to alter the inheritance custom of primogeniture that directed the pattern of descent of freehold land in the absence of directions by settlement or will, and the dialogue is used as a lens to view the nexus between inheritance customs and broader political, economic and social concerns. The intensity of the dispute over primogeniture suggests that more was at stake than simply the devolution of land. The controversy in the Commons over the proposed legislation encompassed a discussion on the variety of purposes that succession law should serve. Lurking in the background in the debate over the proposed bill was a more abstract conundrum: should succession laws primarily be crafted to serve political ends, the constitution; or was it more appropriate to calibrate them to foster desirable social, economic or familial goals? In short, the debate put into sharp focus the question of what interests drive inheritance law, and how attempts can be made to modify it, if and when such concerns alter over time. The bill failed, and it would be for another century for Parliament to abolish primogeniture.
Do patent rights matter? 40 years of innovation, complexity and productivity

Abstract Does the rigorous protection of patents advance or retard economic development? Two decades ago, a new global standard of intellectual property swept across developing and industrialized nations through the implementation of the WTO’s TRIPS Agreement. Many years later, the issue of patent rights remains contentious. In this paper, we focus on the effects of patent rights systems on total factor productivity growth, using dynamic panel regression analysis for 70 countries from 1965 to 2009. We show that the effects of stronger or more rigorous patent systems are insignificant for productivity growth in both developing and industrialized countries. Why does the strength of patents appear to have no impact on productivity? Classic economic theory suggests that stronger patent systems incentive innovative output with important spill-over effects for productivity and growth. We offer an alternative explanation using data from the Economic Complexity Index. We find that while patents rights are increasingly irrelevant to productivity, the relationship between economic complexity and productivity is highly positive and significant. Our results are consistent with the contributions of the absorptive capacity theory in that they suggest it is not the discovery and ownership of novel products and processes at the innovative frontier that induces productive growth, but the ability to adapt, replicate and diffuse along the international productive chain.
High-Capacity Donors’ Preferences for Charitable Giving:

How can charities solicit high-capacity donors to provide the funds for matching grants and leadership gifts? In conjunction with Texas A&M University’s fundraising organizations, we conducted a fi...
Exploiting Data Sensitivity on Partitioned Data

Several researchers have proposed solutions for secure data outsourcing on the public clouds based on encryption, secret-sharing, and trusted hardware. Existing approaches, however, exhibit many limitations including high computational complexity, imperfect security, and information leakage. This chapter describes an emerging trend in secure data processing that recognizes that an entire dataset may not be sensitive, and hence, non-sensitivity of data can be exploited to overcome some of the limitations of existing encryption-based approaches. In particular, data and computation can be partitioned into sensitive or non-sensitive datasets – sensitive data can either be encrypted prior to outsourcing or stored/processed locally on trusted servers. The non-sensitive dataset, on the other hand, can be outsourced and processed in the cleartext. While partitioned computing can bring new efficiencies since it does not incur (expensive) encrypted data processing costs on non-sensitive data, it can lead to information leakage. We study partitioned computing in two contexts - first, in the context of the hybrid cloud where local resources are integrated with public cloud resources to form a effective and secure storage and computational platform for enterprise data. In the hybrid cloud, sensitive data is stored on the private cloud to prevent leakage and a computation is partitioned between private and public clouds. Care must be taken that the public cloud cannot infer any information about sensitive data from inter-cloud data access during query processing. We then consider partitioned computing in a public cloud only setting, where sensitive data is encrypted before outsourcing. We formally define a partitioned security criterion that any approach to partitioned computing on public clouds must ensure in order to not introduce any new vulnerabilities to the existing secure solution. We sketch out an approach to secure partitioned computing that we refer to as query binning (QB) and show how QB can be used to support selection queries. We evaluate conditions under which partitioned computing approaches such as QB can improve the performance of cryptographic approaches that are prone to size, frequency-count, and workload attacks.
Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora

Bystander selection—the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment—is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic–species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen (“proportion of bystander exposures”). Data sources include the 2010–2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for eight of nine organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.
Cellular multifunctionality in the muscle activity of Hydra vulgaris

As a cnidarian, Hydra has an anatomically simple neuromuscular system likely similar to those of ancestral species, and its study could provide insights on the design logic and function of animal body plans throughout evolution. Here we have used calcium imaging to map the activity of the entire epitheliomuscular system of living Hydra in mounted preparations. We find seven basic spatiotemporal patterns of activation, with fast and slow kinetics of initiation and propagation. Contrary to previous assumptions, both endodermal and ectodermal epitheliomuscular tissues are systematically activated jointly during contractions, in spite of their muscle fibers being orthogonally arranged. We also find that individual cells surprisingly participate in multiple patterns, using different kinetics of activation. Our results reveal that Hydras epitheliomuscular tissue is a multifunctional system that can be flexibly reconfigured to generate different spatiotemporal activity patterns, enabling a structurally simple design to implement a varied behavior output.
Creating Structured Linked Data to Generate Scholarly Profiles: A Pilot Project using Wikidata and Scholia

INTRODUCTION Wikidata, a knowledge base for structured linked data, provides an open platform for curating scholarly communication data. Because all elements in a Wikidata entry are linked to defining elements and metadata, other web systems can harvest and display the data in meaningful ways. Thus, Wikidata has the capacity to serve as the data source for faculty profiles. Scholia is an example of how third-party tools can leverage the power of Wikidata to provide faculty profiles and bibliographic, data-driven visualizations. DESCRIPTION OF PROGRAM In this article, we share our methods for contributing to Wikidata and displaying the data with Scholia. We deployed these methods as part of a pilot project in which we contributed data about a small but unique school on the Indiana University-Purdue University Indianapolis (IUPUI) campus, the IU Lilly Family School of Philanthropy. NEXT STEPS Following the completion of our pilot project, we aim to find additional methods for contributing large data collections to Wikidata. Specifically, we seek to contribute scholarly communication data that the library already maintains in other systems. We are also facilitating Wikidata edit-a-thons to increase the library’s familiarity with the knowledge base and our capacity to contribute to the site.
Deep Learning With Asymmetric Connections and Hebbian Updates.

We show that deep networks can be trained using Hebbian updates yielding similar performance to ordinary back-propagation on challenging image datasets. To overcome the unrealistic symmetry in connections between layers, implicit in back-propagation, the feedback weights are separate from the feedforward weights. The feedback weights are also updated with a local rule, the same as the feedforward weights - a weight is updated solely based on the product of activity of the units it connects. With fixed feedback weights as proposed in [17] performance degrades quickly as the depth of the network increases. If the feedforward and feedback weights are initialized with the same values, as proposed in [30], they remain the same throughout training thus precisely implementing back-propagation. We show that even when the weights are initialized differently and at random, and the algorithm is no longer performing back- propagation, performance is comparable on challenging datasets. We also propose a cost function whose derivative can be represented as a local Hebbian update on the last layer. Convolutional layers are updated with tied weights across space, which is not biologically plausible. We show that similar performance is achieved with untied layers, also known as locally connected layers, corresponding to the connectivity implied by the convolutional layers, but where weights are untied and updated separately. In the linear case we show theoretically that the convergence of the error to zero is accelerated by the update of the feedback weights.
Structural Perspective on Revealing and Altering Molecular Functions of Genetic Variants Linked with Diseases

Structural information of biological macromolecules is crucial and necessary to deliver predictions about the effects of mutations—whether polymorphic or deleterious (i.e., disease causing), wherein, thermodynamic parameters, namely, folding and binding free energies potentially serve as effective biomarkers. It may be emphasized that the effect of a mutation depends on various factors, including the type of protein (globular, membrane or intrinsically disordered protein) and the structural context in which it occurs. Such information may positively aid drug-design. Furthermore, due to the intrinsic plasticity of proteins, even mutations involving radical change of the structural and physico–chemical properties of the amino acids (native vs. mutant) can still have minimal effects on protein thermodynamics. However, if a mutation causes significant perturbation by either folding or binding free energies, it is quite likely to be deleterious. Mitigating such effects is a promising alternative to the traditional approaches of designing inhibitors. This can be done by structure-based in silico screening of small molecules for which binding to the dysfunctional protein restores its wild type thermodynamics. In this review we emphasize the effects of mutations on two important biophysical properties, stability and binding affinity, and how structures can be used for structure-based drug design to mitigate the effects of disease-causing variants on the above biophysical properties.
Transcriptional Circuit Fragility Influences HIV Proviral Fate

Transcriptional circuit architectures in several organisms have been evolutionarily selected to dictate precise given responses. Unlike these cellular systems, HIV is regulated through a complex circuit composed of two successive phases (host and viral), which create a positive feedback loop facilitating viral replication. However, it has long remained unclear whether both phases operate identically and to what extent the host phase influences the entire circuit. Here, we report that, although the host phase is regulated by a checkpoint whereby KAP1 mediates transcription activation, the virus evolved a minimalist system bypassing KAP1. Given the complex circuit's architecture, cell-to-cell KAP1 fluctuations impart heterogeneity in the host transcriptional responses, thus affecting the feedback loop. Mathematical modeling of a complete circuit reveals how these oscillations ultimately influence homogeneous reactivation potential of a latent virus. Thus, although HIV drives molecular innovation to fuel robust gene activation, it experiences transcriptional fragility, thereby influencing viral fate and cure efforts.
Observations of Radio Magnetars with the Deep Space Network

The Deep Space Network (DSN) is a worldwide array of radio telescopes which supports NASA’s interplanetary spacecraft missions. When the DSN antennas are not communicating with spacecraft, they provide a valuable resource for performing observations of radio magnetars, searches for new pulsars at the Galactic Center, and additional pulsar-related studies. We describe the DSN’s capabilities for carrying out these types of observations. We also present results from observations of three radio magnetars, PSR J1745–2900, PSR J1622–4950, and XTE J1810–197, and the transitional magnetar candidate, PSR J1119–6127, using the DSN radio telescopes near Canberra, Australia.
Structural Supervision Improves Learning of Non-Local Grammatical Dependencies

State-of-the-art LSTM language models trained on large corpora learn sequential contingencies in impressive detail, and have been shown to acquire a number of non-local grammatical dependencies with some success. Here we investigate whether supervision with hierarchical structure enhances learning of a range of grammatical dependencies, a question that has previously been addressed only for subject-verb agreement. Using controlled experimental methods from psycholinguistics, we compare the performance of word-based LSTM models versus Recurrent Neural Network Grammars (RNNGs) (Dyer et al. 2016) which represent hierarchical syntactic structure and use neural control to deploy it in left-to-right processing, on two classes of non-local grammatical dependencies in English—Negative Polarity licensing and Filler-Gap Dependencies—tested in a range of configurations. Using the same training data for both models, we find that the RNNG outperforms the LSTM on both types of grammatical dependencies and even learns many of the Island Constraints on the filler-gap dependency. Structural supervision thus provides data efficiency advantages over purely string-based training of neural language models in acquiring human-like generalizations about non-local grammatical dependencies.
Salvage therapy with lomustine for temozolomide refractory recurrent anaplastic astrocytoma: A retrospective study.

e13023 Background: There is no standard therapy for recurrent anaplastic astrocytoma (AA). Assess response and toxicity of lomustine (CCNU) in recurrent AA following prior surgery, radiotherapy and...
Modeling of the interaction of rigid wheels with dry granular media

Abstract We analyze the capabilities of various recently developed techniques, namely granular Resistive Force Theory (RFT) and continuum plasticity implemented with the Material Point Method (MPM), in capturing dynamics of wheel-dry granular media interactions. We compare results to more conventionally accepted methods of modeling wheel locomotion. While RFT is an empirical force model for arbitrarily-shaped bodies moving through granular media, MPM-based continuum modeling allows the simulation of full granular flow and stress fields. RFT allows for rapid evaluation of interaction forces on arbitrary shaped intruders based on a local surface stress formulation depending on depth, orientation, and movement of surface elements. We perform forced-slip experiments for three different wheel types and three different granular materials, and results are compared with RFT, continuum modeling, and a traditional terramechanics semi-empirical method. Results show that for the range of inputs considered, RFT can be reliably used to predict rigid wheel granular media interactions with accuracy exceeding that of traditional terramechanics methodology in several circumstances. Results also indicate that plasticity-based continuum modeling provides an accurate tool for wheel-soil interaction while providing more information to study the physical processes giving rise to resistive stresses in granular media.
Mendelian randomization analysis using mixture models for robust and efficient estimation of causal effects

Mendelian randomization (MR) has emerged as a major tool for the investigation of causal relationship among traits, utilizing results from large-scale genome-wide association studies. Bias due to horizontal pleiotropy, however, remains a major concern. We propose a novel approach for robust and efficient MR analysis using large number of genetic instruments, based on a novel spike-detection algorithm under a normal-mixture model for underlying effect-size distributions. Simulations show that the new method, MRMix, provides nearly unbiased or/and less biased estimates of causal effects compared to alternative methods and can achieve higher efficiency than comparably robust estimators. Application of MRMix to publicly available datasets leads to notable observations, including identification of causal effects of BMI and age-at-menarche on the risk of breast cancer; no causal effect of HDL and triglycerides on the risk of coronary artery disease; a strong detrimental effect of BMI on the risk of major depressive disorder.
Exploiting parallelism in the ME calculus

We present some parallelization techniques for the Model Evolution (ME) calculus, an instantiation-based calculus that lifts the DPLL procedure to rst-order clause logic. Specically, we consider a restriction of ME to the EPR fragment of clause logic for which the calculus is a decision procedure. The main operations in ME’s proof procedures, namely clause instantiation and candidate literal generation, oer opportunities for MapReducestyle parallelization. This term/clause-level parallelization is largely orthogonal to the sort of search-level parallelization performed by portfolio approaches. We describe a hybrid parallel proof procedure for the restricted calculus that exploits parallelism at both levels to synergistic eect. The calculus and the proof procedure have been implemented in a new solver for EPR formulas. Our initial experimental results show that our term/clauselevel parallelization alone is eective in reducing runtime and can be combined with a portfolio-based approach to maximize performance.
Exploring the Landscape of Spatial Robustness

The study of adversarial robustness has so far largely focused on perturbations bound in p-norms. However, state-of-the-art models turn out to be also vulnerable to other, more natural classes of perturbations such as translations and rotations. In this work, we thoroughly investigate the vulnerability of neural network--based classifiers to rotations and translations. While data augmentation offers relatively small robustness, we use ideas from robust optimization and test-time input aggregation to significantly improve robustness. Finally we find that, in contrast to the p-norm case, first-order methods cannot reliably find worst-case perturbations. This highlights spatial robustness as a fundamentally different setting requiring additional study. Code available at this https URL and this https URL.