cssi/SciSciGPT-SciSciNet huggingface dataset:
Attention Narrows Position Tuning of Population Responses in V1

Summary When attention is directed to a region of space, visual resolution at that location flexibly adapts, becoming sharper to resolve fine-scale details or coarser to reflect large-scale texture and surface properties [1]. By what mechanism does attention improve spatial resolution? An improved signal-to-noise ratio (SNR) at the attended location contributes [2], because of retinotopically specific signal gain [3–10]. Additionally, attention could sharpen position tuning at the neural population level, so that adjacent objects activate more distinct regions of the visual cortex. A dual mechanism involving both signal gain and sharpened position tuning would be highly efficient at improving visual resolution, but there is no direct evidence that attention can narrow the position tuning of population responses. Here, we compared the spatial spread of the fMRI BOLD response for attended versus ignored stimuli. The activity produced by adjacent stimuli overlapped less when subjects were attending at their locations versus attending elsewhere, despite a stronger peak response with attention. Our results show that even as early as primary visual cortex (V1), spatially directed attention narrows the tuning of population-coded position representations.
Systems-based medicine approaches to understand and treat complex diseases. The example of multiple sclerosis

Systems medicine is an emerging concept that acknowledges the complexity of a multitude of non-linear interactions among molecular and physiological variables. Under this new paradigm, rather than a collection of symptoms, diseases are seen as the product of deviations from a robust steady state compatible with life. This concept requires the incorporation of mathematics and physics to the more classical arsenal of physiology and molecular biology with which physicians are trained today. This review explores the diverse types of information that can be accumulated towards the understanding of multiple sclerosis (MS), a complex autoimmune disease that targets the central nervous system (CNS). The challenge of data integration and modeling of dynamical systems is discussed in the context of disease susceptibility and response to treatment. A theoretical framework that supports the use of combination therapy is also presented.
Measurement of the lifetime of hadrons containing the b-quark☆

Data collected with the High Resolution Spectrometer at PEP, corresponding to an integrated luminosity of 200 pb- 1 ofe+e annihilation at 29 GeV, were used to measure the mean hfetlme of hadrons containing the bottom quark. The hfetlme was determined using the impact parameter method on events containing a high-transverse-momentum electron The result, based on a sample of 301 events, is vB = 102~039042 ps, where the Indicated errors include both statistics and systematlcs In the context of the standard model, the lifetime of hadrons containing a bottom quark is determined by the electroweak coupling between the b and the c and u quarks. In the Kobayashi-Maskaw a scheme, the lifetime constrains the values of the matrix elements [ Vbc [ and ] Vbu [ [ 11. This letter presents a measurement of the lifetime of a mixture of hadrons containing the b-quark. The data sample consists of e+e---}bb annihilations at x/~=29 GeV, tagged by a high-PT electron coming from the semileptonic decay of the b-quark. Two different analysis techniques are used, but the quoted result is based on a maximum likelihood fit to the measured impact parameter distribution. A detailed description of the High Resolution Spectrometer can be found elsewhere [2]. For this analysis, the tracking system is essential. It consists
Condorcet — a man of the avant‐garde

In 1785 Condorcet proposed a method to aggregate qualitative data, but until very recently this method was attributed to contemporary authors and its importance completely neglected.
Effects of iron depletion on Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) and trophozoite growth: implications for antiamoebic therapy

Objectives The purpose of this study was to determine the mechanism by which iron chelation affects the trophozoite survival of Entamoeba histolytica. Fe2+ is a cofactor for E. histolytica alcohol dehydrogenase 2 (EhADH2), an essential bifunctional enzyme [alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] in the glycolytic pathway of E. histolytica.
Role of pK(a) of nucleobases in the origins of chemical evolution.

The formation of canonical base pairs through Watson–Crick hydrogen bonding sits at the heart of the genetic apparatus. The specificity of the base pairing of adenine with thymine/uracil and guanine with cytosine preserves accurate information for the biochemical blueprint and replicates the instructions necessary for carrying out biological function. The chemical evolution question of how these five canonical nucleobases were selected over various other possibilities remains intriguing. Since these and alternative nucleobases would have been available for chemical evolution, the reasons for the emergence of this system appear to be primarily functional.While investigating the base-pairing properties of structural nucleic acid analogs, we encountered a relationship between the pKa of a series of nonstandard (and canonical) nucleobases and the pH of the aqueous medium. This relationship appeared to correspond with the propensity of these molecules to self-assemble via Watson–Crick-type base-pairing interac...
Experience with a transfusion recipient education program about hepatitis C.

: Shortly after test kits for antibodies to the hepatitis C virus (HCV) were licensed in May of 1990, our medical community undertook a public education program encouraging previous transfusion recipients to see their physicians about the wisdom of being tested for anti-HCV. In response, 1034 samples were received for testing. All samples repeatably reactive (RR) with anti-HCV enzyme-linked immunoassay (EIA) were tested further with a research recombinant immunoblot assay (RIBA). Overall, 76 of the 1034 (7.4%) recipient samples were RR and 64 of these (84.2%) were reactive with RIBA. Recipients transfused prior to surrogate testing (alanine aminotransferase [ALT] and anti-hepatitis B core [anti-HBc]) in 1986 showed a 8.6 percent reactivity with RIBA and those transfused after surrogate testing showed a 4.8 percent reactivity, a 44 percent reduction. Of the 57 recipient samples reactive with RIBA and suitable for assay, 11 (19.3%) had an elevated ALT. Among 76 randomly selected blood donors with RR EIAs studied for comparison with recipients, 20 (26.3%) were reactive with RIBA, 9 of which had an abnormal surrogate test that would have disqualified them. ALT concentrations were abnormal in 6 (30%) of the donors who were reactive on RIBA. We conclude that an education program that encourages previous transfusion recipients to seek medical advice about anti-HCV testing is practical from the standpoint of the blood center. We believe more widespread implementation of similar programs should be considered. The findings also suggest that, when available, supplemental testing should be offered to blood donors with RR EIAs before they are counseled about permanent deferral because of anti-HCV testing and to transfusion recipients identified by programs such as the one described.
Effects of Syndepositional Faulting and Folding on Early Cretaceous Rivers and Alluvial Architecture (Lakota and Cloverly Formations, Wyoming, U.S.A.)

ABSTRACT Quantitatively reconstructed paleochannel hydraulics (e.g., channel discharges, slopes, velocities), geometries (e.g., widths, depths, sinuosities, channel patterns), and alluvial architecture record the local effects of syndepositional faults and folds. These effects are evaluated from Lower Cretaceous rocks in three areas: (1) the northern Black Hills, where the axes of syndepositional folds trend roughly perpendicular to paleoflow, (2) the northwestern Black Hills, where the trend of a syndepositional fault is oblique to paleoflow, and (3) the Wind River basin, where the trends of syndepositional faults are nearly parallel to paleoflow. In each area, channel-belt deposits are laterally and vertically connected where local subsidence rates were high, producing thick, laterally extensive sandstones. Areas of lower subsidence rates are characterized by isolated or laterally connected channel-belt deposits, and thinner sandstones. Surface deformation controlled the positions of some rivers because of the development of antecedent drainages, or by directing rivers toward areas of maximum subsidence. Some reconstructed channel slopes, which range from 0.62 10-4 to 5.43 10-4, record surface deformation. The three-dimensional alluvial architecture was simulated using the model of Mackey and Bridge (1995), together with quantitatively reconstructed paleochannel parameters, in order to provide quantitative insight as to possible conditions and processes that produced the observed alluvial architecture. The effects of deformation on channel slopes, together with depositional topography, were important in controlling avulsion and resultant alluvial architecture. The most important condition that governed the alluvial architecture was comparable rates of local subsidence and sediment accumulation. Paleochannel reconstructions indicate that the rivers were 48-180 m wide and 4.4-13.6 m deep, and had discharges of 64-1073 m3s-1. Channel deposits all appear to represent point bars and associated channel fills of meandering rivers. Sinuosities were comparable, ranging from 1.1 to 1.4, and show no consistent trends with other channel parameters. Hence, with the exception of two paleochannels (out of the thirteen that were reconstructed) differences in hydraulic parameters such as slope and sediment transport rate had no discernible effect on channel pattern or sinuosity.
Permeability of the Zona Pellucida to Protein Tracers

Penetration of the zona pellucida of the rat, mouse, and individual representatives of other species, as well as the extracellular coats of the rabbit, by exogenous protein was studied using horseradish peroxidase and ferritin as tracers. In addition, possible variation in penetration in relationship to time of exposure and preimplantation stage of development was studied in the rat and rabbit. In all species studied, both peroxidase (mol wt 40,000) and ferritin (mol wt at least 500,000) had penetrated when examined by electron microscopy whether the exposure was 10 mm or longer and regardless of stage of development. It is concluded that the zona pellucida does not exclude molecules on the basis of size within the normal range of individual protein molecules. Despite considerable literature bearing on the subject, there is still confusion concerning the permeability of the zona pellucida. Experiments relevant to this topic have been basically of two designs: investigations that measured the permeability of the zona pellucida itself, and those that dealt with the passage of materials into the cells or the cavity of the blastocyst at preimplantation stages. In the latter case it is clear that passage of material into the cytoplasm or cavity of the preimplantation stages also means prior passage through the zona pellucida. However, failure to demonstrate incorporation of the material into the cells or in the cavity of the blastocyst does not mean that the material has failed to traverse the zona pellucida. It is partly this dual basis of acquiring information that has led to the confusion that exists concerning the permeability of the zona pellucida. Preliminary observation from this laboratory indicated that the zona pellucida is readily penetrated by large molecular-weight
On the use of time series and search based software engineering for refactoring recommendation

To improve the quality of software systems, one of the widely used techniques is refactoring, defined as the process of improving the design of an existing system by changing its internal structure without altering the external behavior. The majority of existing refactoring works do not consider the impact of recommended refactorings on the quality of future releases of a system. In this paper, we propose to combine the use of search-based software engineering with time series to recommend good refactoring strategies in order to manage technical debt. We used a multi-objective algorithm to generate refactoring solutions that maximize the correction of important quality issues and minimize the effort. For these two fitness functions, we adapted time series forecasting to estimate the impact of the generated refactorings solution on future next releases of the system by predicting the evolution of the remaining code smells in the system, after refactoring, using different quality metrics. We evaluated our approach on one industrial project and a benchmark of 4 open source systems. The results confirm the efficiency of our technique to provide better refactoring management comparing to several existing refactoring techniques.
Simulating flows in solid rockets

As part of the DOE ASAP program, the Center for Simulation of Advanced Rockets is pursuing. the simulation of solid propellant rockets. In this paper, the challenges inherent in simulating the fluid flow in such a rocket are discussed. Among the complications that must be accommodated are: complex geometry, turbulence, two phase flow with chemically reacting dispersed phase, and radiative heat transfer. Various simulation and modeling techniques are being pursued to handle thesecomplications, including: a multi-block compressible flow code, large eddy simulation (LES) of turbulence, particle dynamics and tracking and radiation hydrodynamics., The details of these modeling and simulation techniques in the context of the solid rocket problem are discussed., :-
Macroergonomic Tools & Strategies: An International Overview

Macroergonomic tools and intervention strategies that have been developed internationally to solve complex, organizational and technical systems problems are reviewed in this paper. These tools are loosely grouped into three categories: 1) systems tools/simulation and modeling, 2) technology transfer, and 3) participatory ergonomics. The features that characterize and define the tools are discussed and a description of their use and implementation within organizations are examined in detail. The strengths and weaknesses of each macroergonomic tool are also presented. Some of the commonalities among the various macroergonomic tools and strategies are enumerated along with future recommendations for developing and expanding macroergonomic tools. The issue of developing a potentially robust and generalized international macroergonomic database is analyzed.
Structural Reliability and Stability of Nonmetric Conjoint Analysis

Structural reliability and stability of nonmetric conjoint analysis are examined under conditions of severe structural perturbation and substantial variation in the number of stimulus profiles. The...
Systematics of the Northern Grasshopper Mouse (Onychomys leucogaster) on the Central Great Plains

This assessment of the systematic relationships of populations of the northern grasshopper mouse, Onychomys leucogaster , on the central Great Plains is based on study of molts and pelages and on analyses of measurements. Variation in color of a population of O. leucogaster on the central plains reflects differences in three developmental pelages, with two intervening, maturational molts, and one annual molt and pelage. Geographic variation in color of pelage is clinal, the dorsum gradually shifting from pale on the western plains to dark in the east. Variation in mensural characters is slight and not entirely coincident with that of pelage. Two nominal subspecies of O. leucogaster, O. l. arcticeps Rhoads to the west and O. l. breviauritus Hollister to the east, have been recognized on the central Great Plains. We regard these taxa as indistinguishable; the name O. l. arcticeps has priority.
Discussion of Managing the key problem in the Course of Design Plane Link Mechanisms the Optimization Technology

Through summarying for the machinery optimization design principle and process, the management method for the key questions in the course of optimization design plane - link mechanisms is discussed.
A review of nonalcoholic fatty liver disease - genetics and animal models

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from simple NAFL to nonalcoholic steatohepatitis, to irreversible cirrhosis. NAFLD is the most common chronic liver disease in developed countries and is considered as the hepatic manifestation of cardiovascular disease and metabolic syndrome. In the pathogenesis of NAFLD, hepatic lipid accumulation results from an imbalance between lipid synthesis, storage, oxidation, and/or secretion, and eventually triggers hepatic inflammation and injury. The increasing incidence of NAFLD etiological studies has shown that obesity, hepatitis C, and cryptogenic cirrhosis are associated with NAFLD. Here, we provide a comprehensive NAFLD review that covers the population genetics, genome-wide associated study, epidemiology, pathophysiology of the disease progression, and current existing animal models.
Nonprescription Analgesic Anti-inflammatory Drugs: Efficacy and Safety

In the face of widening demand and increased use of nonprescription drugs, there has been increasing attention focused on the efficacy and safety of over-the-counter (OTC) analgesic anti-inflammatory medicines and risks attending their use. The approved dose varies from country to country, but worldwide the major compounds are paracetamol (acetaminophen), aspirin, ibuprofen, diclofenac, and naproxen: these are the focus of the present review; other less widely used or combination medications are not evaluated. The efficacy and safety of each drug is reviewed: what emerges is that, used as recommended at purchase, all of these compounds are effective and safe. Risk/benefit considerations should not govern the choice of compound. However, once sold, they may be misused in higher doses, and for longer durations than recommended, and risks increase, especially if used in combination with similar prescribed compounds that increase the effective dose. In these circumstances, other risk factors also apply, including the user’s age, gender, comorbid illnesses, and co-use of other medications. The adverse events (AEs), seen when OTC compounds are used long term or in higher-than-recommended doses, cannot validly be used to estimate the risks attending correct OTC use, but many observational studies fail to distinguish between AEs associated with prescription and OTC uses. The small number of studies which have evaluated risks associated with excessive use of drugs purchased OTC finds a small but statistically significant increase in the same AEs that are known to be associated with their prescription use. Correct use of OTC compounds is the key to safety.
Affective decision-making moderates the effects of automatic associations on alcohol use among drug offenders

ABSTRACTBackground: This study used a dual-process model of cognition in order to investigate the possible influence of automatic and deliberative processes on lifetime alcohol use in a sample of drug offenders. Objective: The objective was to determine if automatic/implicit associations in memory can exert an influence over an individual’s alcohol use and if decision-making ability could potentially modify the influence of these associations. Methods: 168 participants completed a battery of cognitive tests measuring implicit alcohol associations in memory (verb generation) as well as their affective decision-making ability (Iowa Gambling Task). Structural equation modeling procedures were used to test the relationship between implicit associations, decision-making, and lifetime alcohol use. Results: Results revealed that among participants with lower levels of decision-making, implicit alcohol associations more strongly predicted higher lifetime alcohol use. Conclusion: These findings provide further sup...
The effects of Ricean fading channel on microcellular mobile radio systems

The user capacity and spectrum efficiency of a microcellular mobile radio system using a fast frequency-hopped (FFH) spread-spectrum modulation technique are evaluated. Additive white Gaussian noise (AWGN) and a Rice distribution with random-to-specular ratio (K) are used to model the microcellular environment. The probability of bit error for noncoherent detection of on-off-keying (OOK) modulation operating in a Ricean fading channel is derived as a closed-form expression. At an average bit error rate 10/sup -3/ and considering only the degradation due to mutual interference, the system capacity and the spectrum efficiency are found to be 209 users and 33.44%, respectively. With K=-7 dB and a mean signal-to-noise ratio of 20 dB, the system capacity and spectrum efficiency are found to be 169 and 27.2%, respectively, at the same error rate. This capacity is roughly 1.21 times that of a cellular system. >
Intergenerational Relationships and Psychological Well-Being of Chinese Older Adults With Migrant Children: Does Internal or International Migration Make a Difference?:

Relying on a purposive sample of 550 Chinese older adults in Beijing, China, this study examined the potential influence of children’s out-migration, internally or internationally, on intergenerati...
Improving the Parent–Adolescent Relationship With Adventure-Based Counseling: An Adlerian Perspective

This article offers a model for enhancing parent–adolescent relationships by using adventure-based counseling (ABC) activities through the conceptual lens of Adlerian theory. A case study is provided to demonstrate the application of an adventure-based activity to address the goal of misbehavior and enhance the characteristics necessary for a healthy parent–adolescent relationship with connectedness, communication, awareness, and support. Specific instructions are offered to enrich counselor development of ABC application in clinical practice.
"Red, Blue, and Purple Firms: On the Coherence and Implications of Organizational Ideology"

Building on the premise that many organizations have deeply embedded ideologies, we examine the influence of these ideologies on adoption of socially progressive practices by profit-seeking firms. ...
Incorporation of Physics-Based Machining Models in Real-Time Decision Making via Metamodels

Abstract Physics-based machining models typically require significant computational resources and time which makes them impractical for quick process optimization calculations in an industrial shop-floor setting. In this paper, we demonstrate the use of metamodeling to help overcome the inefficiency of traditional engineering modeling tools. Metamodels are surrogate models of an existing model that provide an approximate relationship between a set of input process variables and output response variables. Using 2D orthogonal machining as a case study, we utilize the Response Surface Methodology to develop surrogate models which provide approximate relationships between machining variables such as cutting tool speed, depth of cut, rake angle, and tool and workpiece materials, and response variables such as maximum residual stress, residual stress transition depth, surface hardness, tool wear, and wear depth. The Kriging interpolation method is used to generate response surface maps. Finally, we develop the idea of a mobile application which can be easily deployed in an industrial setting to efficiently use such metamodels for physics-based decision making during the initial manufacturing process development phase.
Post-Intensive Care Syndrome in Family Decision Makers of Long-term Acute Care Hospital Patients.

Background Family members of critically ill patients experience indications of post-intensive care syndrome, including anxiety, depression, and posttraumatic stress disorder. Despite increased use of long-term acute care hospitals for critically ill patients, little is known about the impact of long-term hospitalization on patients' family members. Objectives To examine indications of post-intensive care syndrome, coping strategies, and health-related quality of life among family decision makers during and after patients' long-term hospitalization. Methods A single-center, prospective, longitudinal descriptive study was undertaken of family decision makers of adult patients admitted to long-term acute care hospitals. Indications of post-intensive care syndrome and coping strategies were measured on the day of hospital admission and 30 and 60 days later. Health-related quality of life was measured by using the Short Form-36, version 2, at admission and 60 days later. Results The sample consisted of 30 family decision makers. On admission, 27% reported moderate to severe anxiety, and 20% reported moderate to severe depression. Among the decision makers, 10% met criteria for a provisional diagnosis of posttraumatic stress disorder. At admission, the mean physical summary score for quality of life was 47.8 (SD, 9.91) and the mean mental summary score was 48.00 (SD, 10.28). No significant changes occurred during the study period. Problem-focused coping was the most frequently used coping strategy at all time points. Conclusion Family decision makers of patients in long-term acute care hospitals have a significant prevalence of indications of post-intensive care syndrome.
Global Screening of Salmonella enterica Serovar Typhimurium Genes for Desiccation Survival.

Salmonella spp., one of the most common foodborne bacterial pathogens, has the ability to survive under desiccation conditions in foods and food processing facilities for years. This raises the concerns of Salmonella infection in humans associated with low water activity foods. Salmonella responds to desiccation stress via complex pathways involving immediate physiological actions as well as coordinated genetic responses. However, the exact mechanisms of Salmonella to resist desiccation stress remain to be fully elucidated. In this study, we screened a genome-saturating transposon (Tn5) library of Salmonella Typhimurium (S. Typhimurium) 14028s under the in vitro desiccation stress using transposon sequencing (Tn-seq). We identified 61 genes and 6 intergenic regions required to overcome desiccation stress. Salmonella desiccation resistance genes were mostly related to energy production and conversion; cell wall/membrane/envelope biogenesis; inorganic ion transport and metabolism; regulation of biological process; DNA metabolic process; ABC transporters; and two component system. More than 20% of the Salmonella desiccation resistance genes encode either putative or hypothetical proteins. Phenotypic evaluation of 12 single gene knockout mutants showed 3 mutants (atpH, atpG, and corA) had significantly (p<0.02) reduced survival as compared to the wild type during desiccation survival. Thus, our study provided new insights into the molecular mechanisms utilized by Salmonella for survival against desiccation stress. The findings might be further exploited to develop effective control strategies against Salmonella contamination in low water activity foods and food processing facilities.
Relationship between lymphopenia and objective response rate with programmed death-1 (PD-1) inhibitor therapy: A single-center retrospective analysis.

e14512Background: Lymphopenia is frequent in advanced cancers, but the impact of absolute lymphocyte count (ALC) on clinical responses with PD-1 immune checkpoint inhibitors is unknown. Methods: We performed a retrospective chart review of adult solid tumor patients treated with a PD-1 inhibitor (nivolumab or pembrolizumab) at Johns Hopkins from 2015-2016. Patients receiving PD-1 inhibitors concurrently with investigational immunotherapies, on unreported clinical trials or for cancers in which the activity of immune checkpoint inhibitors is unclear, or for whom response information is not available, were excluded. Data were collected on patient treatment history, objective response to PD-1 therapy by RECIST 1.1, and ALC at treatment initiation and one and three months after treatment initiation. Results: 172 patients met the inclusion criteria (lung n = 54; melanoma n = 61; kidney n = 25; other tumors n = 32). Lymphopenia (ALC < 1000) was present in 30.2%, 26.7%, and 34.3%, at 0, 1, and 3 months after tre...
Technological Advances in Stent Therapies: a Year in Review

Stent technology has rapidly evolved since the first stainless steel bare metal stents with substantial developments in scaffolding, polymer, drug choice, drug delivery, and elution mechanisms. Most recently, there has been the evolution of bioabsorbable vascular scaffolds, potentially eliminating the need for long-term foreign object retention. These rapid developments have led to an ever-expanding selection of new stents, making the choice of which to use in which patient challenging. Operators must balance potential short- and long-term clinical ramifications, namely stent thrombosis, in-stent restenosis, target lesion revascularization, and target lesion failure. In this review, we hope to provide insight for interventional cardiologists on the details of stent technology and how this impacts outcomes, stent selection, and duration of dual-antiplatelet therapy duration post drug-eluting stent implantation.
Validation of the K6 and its depression and anxiety subscales for detecting nonspecific psychological distress and need for treatment

The present study sought to validate cutoff scores for the K6 denoting clinically significant nonspecific psychological distress and need for treatment. One thousand sixty (1060) adults (M age = 36.27) participated online via Amazon’s Mechanical Turk, and completed the K6, IPIP-NEO-120, and demographic information. Results revealed that a two-factor solution (Depression and Anxiety) for the K6 fit data statistically significantly better than a single-factor model. Results also revealed good concurrent validity for the K6 and its two identified subscales: K6-Dep and K6-Anx. Cutoff scores denoting clinically significant distress and need for treatment for the K6 (10), K6-Dep (4) and K6-Anx (4) were identified and each yielded total classification accuracy of approximately 71%. The findings of the present study suggested that the K6 and its two subscales may have clinical utility in discerning between those who are experiencing enough psychological distress to currently need psychological treatment and those who have never received treatment. Future research should validate the K6’ subscales against diagnostic measures of depressive and anxious disorders, and compare them to other epidemiological measures of psychological distress and need for treatment with appropriate methodological considerations.
Patching of the Left Main Coronary Artery

This operation would substitute the implant of double- or triple-bypass grafts when the distal vessels are free of disease.
β-Cell Dysfunction, Glucose Intolerance, and Diabetes in the Polycystic Ovary Syndrome

Among women with polycystic ovary syndrome (PCOS), the prevalence of impaired glucose tolerance is estimated to be between 30 and 40%, whereas that of type 2 diabetes mellitus has been placed at 5–10%. These prevalences are among the highest known among women of reproductive age. The predisposition to glucose intolerance in PCOS may be influenced by antenatal events, including the rate of in utero growth and development as well as exposure to excess androgen concentrations from the maternal circulation. Once defects in insulin secretion develop in the setting of the characteristic insulin resistance of PCOS, glucose intolerance becomes evident. Provocative testing of pancreatic β-cell function may provide insights into the future risk for glucose intolerance among women with PCOS.
Strategies for Modeling, Approximation, and Decomposition in Genetic Algorithms Based Multidisciplinary Design

This chapter discusses the applicability of new computational paradigms motivated by biological processes, in the realm of multidisciplinary engineering design, and particularly, in the context of using formal methods of design optimization. The computational models considered in this discussion include genetic algorithms, neural networks, and a modeling of the biological immune system. The focus of the chapter is two-fold. First, it introduces the reader to the implementation of these newly emergent methods. Second, it describes how the use of these methods alleviates some of the difficulties associated with the application of formal optimization methods in practical design problems. Such problems are typically characterized by the presence of a large number of design variables and constraints, the need to consider multiple objective criterion, and, in some cases, a fuzzy description of design specifications. The analysis associated with the multidisciplinary design problem is both complex and computationally expensive. The discussion focuses on methods to reduce the computational effort through development of efficient optimal search algorithms, and in the efficient management of couplings in the analysis problem.
THE TIME DIMENSION OF PROTEIN SYSTEMS

Publisher Summary This chapter explores the time dimension of protein systems. Proteins are systems that can exist in a large number of conformations. The complete characterization of these conformations is a very important step in understanding the protein structure and function and generally involves the study of the positions of all the atoms at a given time. There are time events dealing with more than one atom of the protein. It is possible to divide the protein into many parts, each of which behaves as a rigid body during the time scale of interest. It is useful to divide the time events with respect to the molecular process involved. Division can be made in terms of the biologically significant time events. It is possible now to map the different time events in a protein system specifying their time, the part of the protein involved, the molecular process, and their biological significance, if any.
A Systematic Network of Autism Primary Care Services (SYNAPSE): A Model of Coproduction for the Management of Autism Spectrum Disorder.

The prevalence of Autism Spectrum Disorder (ASD) is growing rapidly, affecting 1 in 59 children in the United States in 2018. Individuals with ASD currently receive fragmented care that threatens their health and well-being. Challenges of autism care include disconnections between the medical system and school supports, poor care coordination between primary care and specialists, and saturation of neuropsychiatry-based centers’ capacity to care for the ASD population. ASD treatment also lacks of a coordinated system of care for patients’ multi-system comorbidities. Families are calling for an ASD care delivery system to meet their needs and the needs of their children. To serve people with ASD and their medical and other providers, we propose a coordinated approach to care grounded in primary care. We call the model the “Systematic Network of Autism Primary Care Services (SYNAPSE).” We develop the model by applying the frameworks of “coproduction” of care and chronic disease management. In this Commentary we discuss the model’s rationale, underpinnings, and the implications for clinical practice. We advance these ideas to align with policy makers’ recognition of the importance of primary care for ASD, as reflected by the most recent Interagency Autism Coordinating Committee (IACC) meeting at the National Institute of Mental Health.
Induction of phase II drug metabolizing enzymes in rat liver by various agents: Is there a coordinate response?

2913 Female Sprague Dawley rats were treated for seven days with various agents administered either in the diet or by daily gavage. The compounds evaluated were 5, 6-benzoflavone (BF, 500 mg/kg diet), diallyl sulfide (DAS, 500 mg/kg BW/day), ethoxyquin (EXO, 3.0 gms/kg diet), phenobarbital (PB, 500 mg/kg diet), and cyclopenta-1,2-dithiol-3-thione (CPDTT, 150 mg/kg BW/day). BF, DAS, EXO, and PB are mixed Phase I/II inducers, while CPDTT is a “pure” Phase II inducer. After seven days of treatment, rats were sacrificed and liver RNA expression was analyzed employing an Affymatrix oligonucleotide microarray. Induction ratios (Expression Levels of Treated/Expression Levels of Controls) were determined for four genes with known antioxidant response elements (AREs). Quinone Oxidoreductase: BF, 8:1; DAS, 6:1; EXO, 5.5:1; CPDTT, 4:1; PB, 1.2:1 Glutathione Transferase (GST) Pi: BF, 3:1; DAS, 25:1, EXO, 15:1; CPDTT, 70:1; PB, 1.2:1 Glutathione Transferase (GST) Yc2 (Aflatoxin Epoxide): BF, 1.9:1; DAS, 5:1; EXO, 4:1; CPDTT, 3:1; PB, 2.5:1 Aldehyde Keto Reductase 7A3 (AFAR): BF, 1.2:1; DAS, 8:1; EXO, 4:8; CPDTT, 14:8; PB, 1.5:1 BF was the strongest inducer of quinone reductase, but minimally induced GST Pi and AFAR. In contrast, the CPDTT profoundly induced GST Pi and AFAR while having more limited effects on GST Yc2 or quinone oxidoreductase. Finally, DAS was a relatively strong inducer of all four genes. However, it was much weaker than CPDTT at induction of GST Pi or AFAR. This pattern implied specificity of Phase II induction even within the genes which have ARE elements and are known to be mediated via the ARE NFR2-Keap pathway. Similar varied agent specific patterns were observed with additional Phase II enzymes (GST, epoxide hydrolase, UDPG A6). In contrast, the induction of various Phase I genes cytochromes P450 (1A1, 1B1, 2B1, and 3A) appear to be more closely coordinated with DAS, EXO, and PB inducing CYPs2B and CYP 3A. Only BF significantly induces CYP1A1 and 1B1. Thus, it appears that there is not a clear coordinate induction of the widest range of Phase II drug metabolizing enzymes.
BCL6 Regulates Diffuse Large B-Cell Lymphoma Cell Cycle and Apoptosis Checkpoints through Direct Repression of the p300 Histone Acetyl-Transferase.

The BCL6 oncogenic transcriptional repressor protein is frequently constitutively expressed in Diffuse Large B-cell Lymphomas (DLBCLs). A BCL6 peptidomimetic inhibitor (BPI) that specifically inhibits the repressor activity of BCL6 can induce cell death in DLBCL cell lines and primary tumor tissue, both in vitro and in vivo. Many genes involved in DNA damage, cell cycle and others are targets of BCL6. Among these is the p53 tumor suppressor gene. However, we find that p53 mRNA levels are actually higher in the subset of DLBCL patients with higher BCL6 expression (n=176 cases). Overall, we could readily detect p53 protein expression by immunohistochemistry in 50% of BCL6 positive DLBCL samples (n=350 cases). By studying expression levels of p53 target genes, we show that even in DLBCLs expressing wild-type p53, the protein is not fully active, and a p53 activating peptide was required to trigger p53 activity and execute cellular checkpoints. Accordingly, even though p53 was already present, BCL6 blockade by BPI could still induce a p53 response in DLBCL cells (with only small changes in p53 levels). Based on these results we speculated that BCL6 might inhibit p53 activity through an alternative mechanism such as regulating its activity through post-translational modifications. In accordance with this prediction, we found that BPI can strongly induce expression of the p300 histone acetyl-transferase, which can activate p53 by acetylation. The p300 promoter has two BCL6 binding sites and by chromatin immunoprecipitation (ChIP) assays we show that BCL6 directly binds to these sites. We found that 80% of DLBCL (n=70) express low protein levels of p300 (compared with other B-lymphomas) and the same is apparent from mRNA studies. By performing kinetic studies in DLBCL cells with multiple time points, we show that after BPI treatment, p300 mRNA and then protein levels are induced, after which p53 becomes acetylated and after which p53 target genes (p21, PUMA, NOXA, GADD45 and PIG3) are upregulated. These changes are partially or totally overcome by expression of either a p53-dominant negative or p300-dominant negative construct. In DLBCL cells with p53 mutations, this program is preferentially executed trough p73 and/or p63, which in turn become acetylated by p300. Interestingly, after BPI treatment p300 acetylates BCL6 itself, which further reduces BCL6 activity. This leads to higher BCL6 inhibition and triggering of a signal amplification loop. These findings have significant therapeutic implications, since co-treatment of DLBCL cells with BPI plus histone deacetylase inhibitors such as Trichostatin A or SAHA (i.e. that hyperacetylate p53 and BCL6) resulted in a synergistic effect in killing DLBCL cells. Our studies demonstrated that p300 is a direct target gene of BCL6 with a critical role in determining DLBCL response to treatments that require activation of p53 and/or p53-family members. This can be capitalized on to develop powerful biological therapeutic regiments for DLBCL.
The Effect of a No-Cost Contraceptive Initiative on Method Selection by Women with Housing Insecurity.

Abstract Objectives To compare the sociodemographic characteristics of participants in a contraceptive initiative by housing security and determine the association between housing insecurity on contraceptive method selection before and after the removal of cost. Study design This cross-sectional assessment includes 4,327 reproductive-aged participants in the HER Salt Lake Contraceptive Initiative who sought new contraceptive services and reported housing status at enrollment. HER Salt Lake prospectively explored the impact of improved contraceptive access on socioeconomic outcomes in Salt Lake County (USA). For six months (September 2015–March 2016) we collected control data, which included clinic standard-of-care cost-sharing. The intervention started March 2016, and provided no-cost contraception services and unlimited opportunities for method switching over the subsequent three years. Results There were 964 (22%) housing-insecure participants. Compared to those with stable housing, housing-insecure individuals more commonly identified as a sexual minority, received public assistance and lacked health insurance. Housing-insecure women preferentially selected long-acting reversible contraception during the control period (aOR 1.60; 95%CI 1.01–2.56), but method selection equalized across housing status during the intervention. Conclusions When cost is not a barrier, all women desire a comprehensive selection of contraceptive methods, regardless of housing security. Contraceptive clients in this vulnerable population need interventions which address access barriers to all methods to support reproductive planning. Implications Unintended pregnancy during housing insecurity may result in homelessness. This study found housing-insecure women desire access to all contraceptive methods, not just long acting reversible contraception. Integration of comprehensive family planning initiatives into efforts to address homelessness is essential to support this vulnerable population in their reproductive planning.
Elevated sorbitol underlies a heritable neuropathy.

A new study identifies sorbitol dehydrogenase (SORD) deficiency as a slowly progressive hereditary motor axonopathy caused by a genetic defect in the second step of the polyol pathway, thus leading to elevated tissue and blood sorbitol. SORD deficiency is the most common recessive cause of neuropathy, for which therapeutic intervention with aldose reductase inhibitors may have potential.
Flipped Learning at the University Level

The common conception (possibly a misconception) of teaching at the university level in America (among other Western countries) is that of the quintessential “Sage on the Stage.” In essence, this preconceived view takes the form of the wise and learned professor standing in front of over two hundred students sitting in an auditorium, and lecturing to them about whatever topic is on the agenda for that particular day.
Friend, Foe, or Food: What Influences Students’ Attitudes Toward Animals?

Animals play a large role in society, yet attitudes about animals vary widely depending on individual differences in age, gender, experience with animals, and culture. The purpose of this study was...
IEEE education society awards and frontiers in education conference awards

The IEEE Education Society and the Frontiers in Education (FIE) Conference annually recognize many outstanding leaders in engineering education. The IEEE Education Society hosted the Awards Banquet on Saturday, November 8, 2003, and Saturday, October 23, 2004, in honor of the recipients at the two most recent FIE Conferences held in Boulder, Colorado, and in Savannah, Georgia, respectively. The IEEE Computer Society and the Educational Research and Methods (ERM) Division of the American Society for Engineering Education (ASEE) also presented several awards at each banquet.
Public views about COVID-19 'Immunity Passports'

Importance Discovery of effective vaccines and increased confidence that infection confers extended protection against coronavirus disease (COVID-19) have renewed discussion of using immunity certificates or 'passports' to selectively reduce ongoing public health restrictions. Objective To determine public views regarding government and private conferral of immunity privileges. Design and setting National on-line survey fielded in June 2020. Participants were randomly asked about either government 'passports' or private 'certificates' for COVID-19 immunity. Participants Adults from a standing panel maintained for academic research, selected to approximate national demographics. Main outcomes/measures Level of support/opposition to immunity privileges, and whether views vary based on: government vs. private adoption; demographics; political affiliation or views; or various COVID19-related attitudes and experiences. Results Of 1315 respondents, 45.2% supported immunity privileges, with slightly more favoring private certificates than government passports (48.1% vs 42.6%, p = 0.04). Support was greater for using passports or certificates to enable returns to high-risk jobs or attendance at large recreational events than for returning to work generally. Levels of support did not vary significantly according to age groups, socioeconomic or employment status, urbanicity, political affiliation or views, or whether the respondent had chronic disease(s). However, estimates from adjusted analyses showed less support among women (odds ratio, 0.64; 95% confidence interval, 0.51 to 0.80), and among Hispanics (0.56; 0.40 to 0.78) and other minorities (0.58; 0.40 to 0.85) compared with whites, but not among blacks (0.83; 0.60 to 1.15). Support was much higher among those who personally wanted a passport or certificate (75.6% vs 24.4%) and much lower among those who believed this would harm the social fabric of their community (22.9% vs 77.1%). Conclusions and relevance Public views are divided on both government or private uses of immunity certificates, but, prior to any efforts to politicize the issues, these views did not vary along usual political lines or by characteristics that indicate individual vulnerability to infection. Social consensus on the desirability of an immunity privileges programs may be difficult to achieve.