cssi/SciSciGPT-SciSciNet huggingface dataset:
Analysis of 2,440 human exomes highlights the evolution and functional impact of rare coding variation

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations. We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute’s Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders. Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation. We identified more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), reflecting the recent dramatic increase in the size of the human population. The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of protein-coding variation and the differential signatures of population structure from rare and common variation. This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
Understanding the Past: Statistical Analysis of Causal Attribution

Would the third-wave democracies have been democratized without prior modernization? What proportion of the past militarized disputes between nondemocracies would have been prevented had those dyads been democratic? Although political scientists often ask these questions of causal attribution, existing quantitative methods fail to address them. This article proposes an alternative statistical methodology based on the widely accepted counterfactual framework of causal inference. The contribution of this article is threefold. First, it clarifies differences between causal attribution and causal effects by specifying the type of research questions to which each quantity is relevant. Second, it provides a clear resolution of the long-standing methodological debate on “selection on the dependent variable.” Third, the article derives new nonparametric identification results, showing that the complier probability of causal attribution can be identified using an instrumental variable. The proposed framework is illustrated via empirical examples from three subfields of political science.
Trajectory estimation of transmission line zero sequence impedance using relay records

In this paper, a new trajectory estimation method is proposed to better measure and calculate zero sequence impedance of transmission lines. Compared with currently used methods, the new method is more accurate and capable of online estimation without taking transmission line out of operation.
Bravest Girl in the World: Exploring Social Justice through Adolescents' Lens.

As professors of education in an urban community, we wanted to identify mechanisms that would allow young people in the urban core the opportunity to share their unique voices with the world and for us to better understand their views on social justice and social change. The purpose of this paper is to discuss adolescent student perspectives on social justice. Data was gathered from narratives written by students in which they identified the “Dreamkeepers” in their worlds, and how they would define a social justice advocate. Findings suggest that these young writers had deep thoughts about the policies and practices that create socially just environments; were able to recognize, identify, and label characteristics and behaviors of social justice advocates— Dreamkeepers—both in peers and adults; and they strive to emulate these ideals and have a deep desire not only to achieve their dreams but also to enable others.
Abstract W P296: Care Trajectories and Costs after Ischemic Stroke for Patients in the Veterans Health Administration

Background: Patients vary greatly in their use of care after hospitalization for stroke. We classified stroke patients according to their care trajectories and associated costs in the 12-month period after hospital discharge. Methods: We followed a cohort of 3,811 veterans for one year after hospitalization with ischemic stroke in Veterans Health Administration facilities in 2007. Three discharge outcomes -- nursing home care, home care, and mortality -- were modeled jointly with Latent Class Growth Analysis. VA and Medicare costs were obtained for use of institutional care (inpatient acute, rehabilitation facility, and nursing home) and home care (home health, other home care, and outpatient rehabilitation). Covariates included patient age, NIHSS stroke severity and FIM scores measured at hospital discharge. Results: Members of the cohort had one of five care trajectories: 49% had a Rapid Recovery with little or no use of care in the 12 months after discharge, 15% had a Gradual Recovery with initially high nursing or home care use that tapered off over time, 9% had consistent use of Long-Term Home Care (HC), 13% had consistent use of Long-Term Nursing Home Care (NH), and 14% had an Unstable trajectory with multiple transitions between long-term and acute care. Patients with Long-Term NH and Unstable trajectories had the highest average total costs (greater than $60,000 per person) and patients with the Rapid Recovery trajectory had the lowest cost (less than $11,000 per person). Medicare accounted for 23% of total costs. In a multinomial regression model, the likelihood of a Long-Term NH, Long-Term HC or an Unstable Trajectory was greatest for persons with more severe strokes (higher NIHSS score), more disability (lower FIM score), and age 65 or older. About half of the veterans received rehabilitation services. Most rehabilitation was delivered in the NH. There was no clear association between use of rehabilitation and subsequent care trajectory. Conclusions: Care trajectories were explained partly by veteran health and functional status. However, we need a better understanding of system factors shaping care trajectories, particularly access to and use of rehabilitation services.
Truth, Understanding, and High-Cost Consumer Credit: The Historical Context of the Truth in Lending Act

Since the inception of human civilization consumer credit has provided a paradoxically useful and dangerous social institution. Each civilization has attempted to strike the right balance between protecting vulnerable members of society and facilitating socially useful debt. Most policy strategies for addressing the harmful aspects of consumer credit can be classified into a handful of categories: debtor amnesty, contract restrictions, selective protection, self-help free markets, charitable lending, and cooperative lending. Historical case studies exploring each of these strategies are presented. During its history the United States has imported and now continues to use variations on each of these strategies, plus one more. Credit disclosure rules, such as those found in the Truth in Lending Act, are from a historical perspective a relatively new innovation. The Truth in Lending Act was possible because it sounds in a relatively rare ideological overlap shared by those tending to advocate free markets and those tending to advocate government regulation. Nevertheless, Truth in Lending has failed to live up to its theoretical promise. For disclosure law to evolve into a more meaningful consumer protection, it must be reoriented toward promoting consumer understanding of credit price and terms, rather than the current accurate but often unheeded descriptions.
Consequences of Enlightenment

Acknowledgements 1. The consequences of enlightenment 2. Aesthetics as critique 3. The difficulty of art 4. Communication and transformation: aesthetics and politics in Habermas and Arendt 5. The role of aesthetics in the radicalisation of democracy 6. Infinite reflection and the shape of praxis 7. Feeling and/as force.
The Cyber Threat Landscape

Spies have been damaging U.S. interests since the American Revolution. But today's world makes it easier to commit espionage because of the increase in the number of people who now have access to sensitive information, the ease of transmitting information, and the growing demand for sensitive information from end users. This chapter highlights some of the high-profile adversaries who have crossed the lines to perpetrate the most damaging U.S. counterintelligence and business failures. Actual case histories are offered throughout the narrative to emphasize the degree of importance these actions have on the threat landscape.
Epic Hero and Epic Fable

HE EPIC HERO occupies a secure niche in modern criticism. His reassuring presence guarantees the unity of an epic poem and directs our scrutiny when we search for theme. If he is not easy to pick out, there ensues a quarrel over his identity, with a list of candidates for the post; the poem in question, especially if it is an ancient epic, is either disparaged as formless and episodic, or else praised for bold independence, held together on other and more interesting principles. Modern critics evidently see it as the norm for ancient and modern epics alike to be organized around an individual, who will embody the meaning of the poem. Scholes and Kellogg describe the nucleus of the epic as "the chronicle of the deeds of the hero"; by their account, "the epic plot is to a certain extent bespoken by epic characterization. The plot is inherent in the concept of the protagonist."' According to Northrop Frye, "In literary fictions the plot consists of somebody doing something. The somebody, if an individual, is the hero ... Fictions ... may be classified, not morally, but by the hero's power of action, which may be greater than ours, less, or roughly the same."" Of Frye's five classifications, the epic hero belongs to number three, the hero of the "high mimetic mode," "superior in degree to other men but not to his natural environment" (pp. 33-34). Morton W. Bloomfield, after a careful discussion of the meaning of the word "hero," asserts: "Whatever term be used for the major personage or personages of narrative or drama, that these genres have always been presented around such figures cannot be doubted."3
Rice Plant Density Effect on Rice Water Weevil (Coleoptera: Curculionidae) Infestation

Field research was conducted during 1990, 1991, and 1992 to examine effects of plant density on rice water weevil, Lissorhoptrus oryzophilus Kuschel, oviposition in rice, Oryza sativa L. Results of the plant density study showed that there was a trend for more eggs per plant at lower densities, but a trend toward more eggs per unit area with higher plant densities. Plant densities influenced rice water weevil oviposition during the first 3 wk of permanent flooding. However, plant spacing cannot be manipulated to control rice water weevil infestation because recommended optimum plant densities do not differ significantly in their effect on oviposition.
pH dependence of the renin reaction: a modification of commercial renin activity radioimmunoassay kits.

The commercially available renin activity radioimmunoassay kits contain materials of high quality, but the procedures recommended by the manufacturers are based on false assumptions and are incapable of producing satisfactory results. A simple modified procedure which can be used with the commercially available materials to produce highly reliable and consistent measurements of renin activity is presented. These modifications consist of a simple one-step adjustment of the pH and a shortening of the incubation period. A general discussion of the reactions and data to support the modification are presented.
Writing for Publication in Nursing by Marilyn H. Oermann and Judith C. Hays: (2011). Second Edition. New York, NY: Springer, 361 pages, $55.00, softcover, ISBN: 978-082611802-8.

Nurses who feel the professional need or the personal desire (or both!) to write for publication but who feel intimidated or fazed by the prospect, fear not! Oermann and Hays have written a seeming...
241 ORAL ALKALI REDUCES URINE ENDOTHELIN EXCRETION IN CHRONIC KIDNEY DISEASE ASSOCIATED WITH PRIMARY HYPERTENSION.

Purpose Renal endothelin 1 (ET-1) production is increased in the 5/6 nephrectomy experimental model of chronic kidney disease (CKD) and in rats with normal GFR ingesting mineral acid or acid-producing dietary protein. Unpublished data from our laboratory support that amelioration of the acid retention in experimental CKD with dietary alkali decreases renal ET-1 production as measured by urine excretion of endothelin 1 (UET-1V). We hypothesized that the same is true in human CKD. Methods We recruited 18 healthy controls, 21 subjects with primary hypertension without CKD, and 19 subjects with CKD (plasma creatinine 1.5-6.0 mg/dL) and primary hypertension without diabetes, evidence of glomerulonephritis, or history of renal replacement therapy. We reduced systolic blood pressure (SBP) in the latter 2 groups toward 130 mm Hg over 6 months. We then prescribed oral Na+ citrate to CKD subjects with TCO2 Summary UET-1V was higher than healthy controls (3.1 6 0.4 ng/g Cr) in hypertensives without CKD (5.9 6 1.1 ng/g Cr, p Conclusions The data show that primary hypertensives with compared to those without CKD have higher UET-1V despite improved BP control that is decreased by oral Na+ citrate. These studies support the contention that subjects with CKD have increased renal ET-1 production that is mediated by the associated positive acid balance.
Painted Lady: Aspasia in Nineteenth-Century European Art

Despite pioneering reclamation efforts, feminist rhetoricians have only scratched the surface of the multilayered historical reception and representation of Aspasia, a fifth-century BCE Milesian woman famous for the company she kept. Aspasia’s penchant for historical perseverance means that her recovery must extend far beyond the ancient world. Throughout the centuries roused by the so-called Woman Question, she was on the lips and brush-tips of many on the lookout for antecedent and analogous women to serve as models or antimodels. Focusing on nineteenth-century Europe, we illustrate her powerful presence in art. Our discussion showcases Aspasia conversing (Nicolas-Andre Monsiau), instructing (Honore Daumier), and contemplating (Henry Holiday). In their work Aspasia resists attempts to mute her colors and reemerges as a painted lady.
Biology of vascularized bone grafts

Vascularized canine fibular autografts demonstrated improved biologic and mechanical characteristics 3 months after surgery when compared with nonvascularized controls. The vascularized proximal fibula maintained its overall architecture without bony collapse or significant bone turnover. The strength and stiffness of these grafts were approximately 40 per cent and 56 per cent more than nonvascularized grafts, respectively.
FASP: A machine learning approach to functional astrocyte phenotyping from time-lapse calcium imaging data

We propose a machine learning approach to characterize the functional status of astrocytes, the most abundant cells in human brain, based on time-lapse Ca2+ imaging data. The interest in analyzing astrocyte Ca2+ dynamics is evoked by recent discoveries that astrocytes play proactive regulatory roles in neural information processing, and is enabled by recent technical advances in modern microscopy and ultrasensitive genetically encoded Ca2+ indicators. However, current analysis relies on eyeballing the time-lapse imaging data and manually drawing regions of interest, which not only limits the analysis throughput but also at risk to miss important information encoded in the big complex dynamic data. Thus, there is an increased demand to develop sophisticated tools to dissect Ca2+ signaling in astrocytes, which is challenging due to the complex nature of Ca2+ signaling and low signal to noise ratio. We develop Functional AStrocyte Phenotyping (FASP) to automatically detect functionally independent units (FIUs) and extract the corresponding characteristic curves in an integrated way. FASP is data-driven and probabilistically principled, flexibly accounts for complex patterns and accurately controls false discovery rates. We demonstrate the effectiveness of FASP on both synthetic and real data sets.
There Is a Problem: The Defeat of Neo-Cartesianism

In the last chapter, I stated my methodology of endoxa: starting from the assumption that common sense and learned opinion get the benefit of the doubt. Because this is defeasible epistemic support, the support could be lost if there were some reason to think that the endoxa were misguided. The methodology was applied thusly: (i) it is simply a datum of common sense that (a significant number of) animals experience morally significant pain and (ii) that they do so is also the consensus of concerned scientists. Neo-Cartesianism serves as a potential defeater for this defeasible justification. I then delineated some forms of neo-Cartesianism and canvassed some reasons to accept neo-Cartesianism from both philosophy and science.
Quinacrine in endometrial cancer: Repurposing an old antimalarial drug.

Abstract Objective Generate preclinical data on the effect of quinacrine (QC) in inhibiting tumorigenesis in endometrial cancer (EC) in vitro and explore its role as an adjunct to standard chemotherapy in an EC mouse model. Methods Five different EC cell lines (Ishikawa, Hec-1B, KLE, ARK-2, and SPEC-2) representing different histologies, grades of EC, sensitivity to cisplatin and p53 status were used for the in vitro studies. MTT and colony formation assays were used to examine QC's ability to inhibit cell viability in vitro . The Chou-Talalay methodology was used to examine synergism between QC and cisplatin, carboplatin or paclitaxel. A cisplatin-resistant EC subcutaneous mouse model (Hec-1B) was used to examine QC's role as maintenance therapy. Results QC exhibited strong synergism in vitro when combined with cisplatin, carboplatin or paclitaxel with the highest level of synergism in the most chemo-resistant cell line. Neither QC monotherapy nor carboplatin/paclitaxel significantly delayed tumor growth in xenografts. Combination treatment (QC plus carboplatin/paclitaxel) significantly augmented the antiproliferative ability of these agents and was associated with a 14-week survival prolongation compared to carboplatin/paclitaxel. Maintenance with QC resulted in further delay in tumor progression and survival prolongation compared to carboplatin/paclitaxel. QC was not associated with weight loss and the yellow skin discoloration noted during treatment was reversible upon discontinuation. Conclusions QC exhibited significant antitumor activity against EC in vitro and was successful as maintenance therapy in chemo-resistant EC mouse xenografts. This preclinical data suggest that QC may be an important adjunct to standard chemotherapy for patients with chemo-resistant EC.
Using Sound to Influence the Behavior of Free-Ranging Marine Animals

The study of animal behavior holds many fascinations, but probably no aspect is more rewarding to its students than controlling, by appropriate stimuli, specific activities of free-ranging animals. The excitement that such work brings with it, especially when dealing with animals in the sea, stems in large part from the feeling that one has “tuned in” on an important line of communication with an animal on its terms—in an environment far different from that experienced by the researcher working under controlled laboratory conditions. It certainly is not my intent here to belittle laboratory studies; in fact, such studies often form the basis for work undertaken in the field. I am certain that much of our present knowledge about controlling the behavior of certain cetaceans and fishes rests, in large part, on the many hours of observation and experimentation that have been carried out on captive animals, held either in aquaria or in large enclosures. This will, I hope, become evident later in this chapter. Yet such results are not ends in themselves, although they may appear so at times. The control of overt behavior under field conditions will often serve to demonstrate that a hypothesis—set forth by preliminary observations, correlative analyses, and models of predictability—can increase our understanding of the activities of a given species in its natural environment, be it a coral reef, a grass flat, or a wide expanse of open sea.
Predicting the Cloud Patterns for the Boreal Summer Intraseasonal Oscillation Through a Low-Order Stochastic Model

Abstract: We assess the limits of predictability of the large-scale cloud patterns in the boreal summer intraseasonal variability (BSISO) as a measure of outgoing longwave radiation (OLR), a proxy for convective activity. A recent developed nonlinear data analysis technique, nonlinear Laplacian spectrum analysis (NLSA), is applied to the OLR data, defining two spatial modes with high intermittency associated with the BSISO time series. Then a recent developed data-driven physics-constrained low-order modeling strategy is applied to these time series. The result is a four dimensional system with two observed BSISO variables and two hidden variables involving correlated multiplicative noise through the nonlinear energy-conserving interaction. With the optimal parameters calibrated by information theory, the non-Gaussian fat tailed probability distribution functions (PDFs), the autocorrelations and the power spectrum of the model signals almost perfectly match those of the observed data. An ensemble prediction scheme incorporating an effective online data assimilation algorithm for determining the initial ensemble of the hidden variables shows the useful prediction skill in the non-El Nino years is at least 30 days and even reaches 55 days in those years with regular oscillations and the skillful prediction lasts for 18 days in the strong El Nino year (year 1998). Furthermore, the ensemble spread succeeds in indicating the forecast uncertainty. Although the reduced linear model with time-periodic stableunstable damping is able to capture the non-Gaussian fat tailed PDFs, it is less skillful in forecasting the BSISO in the years with irregular oscillations. The failure of the ensemble spread to include the truth also indicates failure in quantification of the uncertainty. In addition, without the energy-conserving nonlinear interactions, the linear model is sensitive with parameter variations.
Inspection Frequency, Sociodemographic Factors, and Food Safety Violations in Chain and Nonchain Restaurants, Philadelphia, Pennsylvania, 2013-2014.

Objectives:We explored how restaurant inspection frequency and restaurant neighborhood sociodemographic characteristics are related to food safety inspection outcomes in chain and nonchain restaura...
Glyphosate resistance in common ragweed (Ambrosia artemisiifolia L.) from Mississippi, USA.

Glyphosate is one of the most commonly used broad-spectrum herbicides over the last 40 years. Due to the widespread adoption of glyphosate-resistant (GR) crop technology, especially corn, cotton and soybean, several weed species have evolved resistance to this herbicide. Research was conducted to confirm and characterize the magnitude and mechanism of glyphosate resistance in two GR common ragweed ( A mbrosia artemisiifolia L.) biotypes from Mississippi, USA. A glyphosate-susceptible (GS) biotype was included for comparison. The effective glyphosate dose to reduce the growth of the treated plants by 50% for the GR1, GR2 and GS biotypes was 0.58, 0.46 and 0.11 kg ae ha−1, respectively, indicating that the level of resistance was five and fourfold that of the GS biotype for GR1 and GR2, respectively. Studies using 14 C-glyphosate have not indicated any difference in its absorption between the biotypes, but the GR1 and GR2 biotypes translocated more 14 C-glyphosate, compared to the GS biotype. This difference in translocation within resistant biotypes is unique. There was no amino acid substitution at codon 106 that was detected by the 5-enolpyruvylshikimate-3-phosphate synthase gene sequence analysis of the resistant and susceptible biotypes. Therefore, the mechanism of resistance to glyphosate in common ragweed biotypes from Mississippi is not related to a target site mutation or reduced absorption and/or translocation of glyphosate.
Pathology of esophageal cancer and Barrett's esophagus.

Esophageal cancer is a serious malignancy with high mortality. The two common distinctive pathologic subtypes of esophageal cancer are squamous cell carcinoma and adenocarcinoma. These differ with regards to etiology, ethnic distribution, pathogenesis, and location in the esophagus. The precursor lesions are also unique to each subtype. Squamous cell carcinoma is more common in East Asia, is linked to smoking and tobacco use, more commonly involves the middle esophagus, and the precursor lesion is squamous dysplasia. Adenocarcinoma is more common in the United States and certain European countries, associated with obesity and gastroesophageal reflux disease (GERD), more commonly involves the distal esophagus, and the precursor lesion is Barrett’s esophagus. Endoscopic surveillance with biopsy evaluation is the standard of care in high-risk groups. Endoscopic ablative therapies for early cancers have lower morbidity than surgery. Despite increased awareness, identification of high-risk groups and endoscopic surveillance, a large proportion of patients present with advanced cancers. Surgery and chemoradiation, either in neo-adjuvant or adjuvant setting, is the usual treatment for patients with advanced but resectable esophageal cancers. The prognosis and further management largely depends upon the pathologic tumor-node-metastasis (TNM) staging provided by the American Joint Committee on Cancer (AJCC) and the International Union against Cancer. Currently, the 7th edition of TNM staging system is being applied for prognostication and this is more focused on pathologic evaluation. Eighth edition of AJCC/UICC TNM staging has been introduced and will be implemented for clinical use in 2018.
The effect of rare earth element segregation on grain boundary energy and mobility in magnesium and ensuing texture weakening

Abstract This paper elucidates a key puzzle related to texture randomization - effect of rare earth on grain boundaries. We use electron back-scatter diffraction and molecular dynamics to compare recrystallization between pure Mg and a Y-containing alloy. The alloy's texture components were initially similar, but the large ⟨a⟩ fiber grains in pure Mg overtook all other components. Y segregation homogenized the energies of ⟨a⟩ fiber grain boundaries, curtailing conventional recrystallization. Grain boundary mobilities were reduced proportionally to the energy stabilization, reducing the dominance of 10 1 ¯ 0 extrusion texture. This allows other grain orientations to stabilize thus producing a more randomized texture.
The effect of stents in cerebral aneurysms: A review

The etiology of up to 95% of cerebral aneurysms may be accounted for by hemodynamically-induced factors that create vascular injury. The purpose of this review is to describe key physical properties that stents have and how they affect cerebral aneurysms. We performed a two-step screening process. First, a structured search was performed using the PubMed database. The following search terms and keywords were used: "Hemodynamics," "wall shear stress (WSS)," "velocity," "viscosity," "cerebral aneurysm," "intracranial aneurysm," "stent," "flow diverter," "stent porosity," "stent geometry," "stent configuration," and "stent design." Reports were considered if they included original data, discussed hemodynamic changes after stent-based treatment of cerebral aneurysms, examined the hemodynamic effects of stent deployment, and/or described the geometric characteristics of both stents and the aneurysms they were used to treat. The search strategy yielded a total of 122 articles, 61 were excluded after screening the titles and abstracts. Additional articles were then identified by cross-checking reference lists. The final collection of 97 articles demonstrates that the geometric characteristics and configurations of deployed stents influenced hemodynamic parameters such as aneurysmal WSS, inflow, and pressure. The geometric characteristics of the aneurysm and its position also had significant influences on intra-aneurysmal hemodynamics after treatment. In conclusion, changes in specific aneurysmal hemodynamic parameters that result from stenting relate to a number of factors including the geometric properties and configurations of deployed stents, the geometric properties of the aneurysm, and the pretreatment hemodynamics.
Ultrastructure of the Egg Envelopes of a Uropodid Mite

During the course of a continuing investigation relating to the effects of environmental factors upon hatching in the eggs of a mite prey and its mite predator, an examination of the microscopic and ultra structure of the membranes surrounding the developing embryo of the predator was undertaken. The purpose was to determine the nature of these membranes and the changes in them during the period of incubation.
A Single-Chip Remotely Powered Transceiver with an Embedded Temperature Sensor

A single-chip remotely-powered wireless transceiver with an embedded temperature sensor and a miniature antenna is implemented in the 950 MHz UHF frequency band using GlobalFoundries' 45 nm CMOS SOI technology. With antenna, temperature sensor, ADC, modulator and demodulator integrated on a single chip, the system consumes only $\pmb{120\ \mu \mathrm{W}}$ of harvested power with an area of $\pmb{0.7\ \mathrm{mm} \times 0.8\ \mathrm{mm}}$ , which makes it one of the smallest wireless temperature sensing transceiver. The uplink data rate is 312.5 kbps with a 10 MHz system clock generated using an on-chip digitally controlled oscillator. The temperature sensor is measured over a range of 20°C to 100°C with a sensing accuracy of +0.7 to −1°C.
Dusp6 is a genetic modifier of growth through enhanced ERK activity

Like other single-gene disorders, muscular dystrophy displays a range of phenotypic heterogeneity even with the same primary mutation. Identifying genetic modifiers capable of altering the course of muscular dystrophy is one approach to deciphering gene-gene interactions that can be exploited for therapy development. To this end, we used an intercross strategy in mice to map modifiers of muscular dystrophy. We interrogated genes of interest in an interval on mouse chromosome 10 associated with body mass in muscular dystrophy as skeletal muscle contributes significantly to total body mass. Using whole-genome sequencing of the two parental mouse strains combined with deep RNA sequencing, we identified the Met62Ile substitution in the dual-specificity phosphatase 6 (Dusp6) gene from the DBA/2 J (D2) mouse strain. DUSP6 is a broadly expressed dual-specificity phosphatase protein, which binds and dephosphorylates extracellular-signal-regulated kinase (ERK), leading to decreased ERK activity. We found that the Met62Ile substitution reduced the interaction between DUSP6 and ERK resulting in increased ERK phosphorylation and ERK activity. In dystrophic muscle, DUSP6 Met62Ile is strongly upregulated to counteract its reduced activity. We found that myoblasts from the D2 background were insensitive to a specific small molecule inhibitor of DUSP6, while myoblasts expressing the canonical DUSP6 displayed enhanced proliferation after exposure to DUSP6 inhibition. These data identify DUSP6 as an important regulator of ERK activity in the setting of muscle growth and muscular dystrophy.
The Art of the 5-Minute Talk

Medical students are expected to be educators as well as learners in their clinical clerkships. Clear and concise 5-minute talks addressing questions that arise on rounds can help to educate the team, improve patient care, and build students’ confidence in their teaching skills. It is important to narrow the scope of these talks to cover a specific clinical question and dig deep to fully understand the context of the question and any areas of debate or uncertainty. Key studies should be cited and discussed as they pertain to the clinical question. All talks should address the specific context of the patient’s case and respect the uniqueness of each patient. Preparation of an outline with the main teaching points can help to keep the talk organized and concise and avoid the pitfalls of excessive detail and digression. A one-page handout that summarizes the main points of the talk can be created from the outline plus any key tables or figures from the articles cited in the talk.
Rational Approximation of Scientific Data

Scientific datasets are becoming increasingly challenging to transfer, analyze, and store. There is a need for methods to transform these datasets into compact representations that facilitate their downstream management and analysis, and ideally model the underlying scientific phenomena with defined numerical fidelity. To address this need, we propose nonuniform rational B-splines (NURBS) for modeling discrete scientific datasets; not only to compress input data points, but also to enable further analysis directly on the continuous fitted model, without the need for decompression. First, we evaluate three different methods for NURBS fitting, and compare their performance relative to unweighted least squares approximation (B-splines). We then extend current state-of-the-art B-spline adaptive approximation to NURBS; that is, adaptively determining optimal rational basis functions and weighted control point locations that approximate given input data points to prespecified accuracy. Additionally, we present a novel local adaptive algorithm to iteratively approximate large data input domains. This method takes advantage of NURBS local support to refine regions of the approximated model, acting locally on both input and model subdomains, without affecting other regions of the global approximation. We evaluate our methods in terms of approximated model compactness, achieved accuracy, and computational cost on both synthetic smooth functions and real-world scientific data.
Insights into the Role of P-Bodies and Stress Granules in Protein Quality Control

The eukaryotic cell is highly compartmentalized, and contains a variety of both membrane-bound and membraneless organelles. The latter include the cytoplasmic ribonucleoprotein (RNP) granules, known as the processing body (P-body) and the stress granule. These RNP structures are thought to be involved in the storage of particular mRNAs during periods of stress. Here, we find that a mutant lacking both P-bodies and stress granules exhibits phenotypes suggesting that these structures also have a role in the maintenance of protein homeostasis. In particular, there was an increased occurrence of specific protein quality control (PQC) compartments in this mutant, an observation that is consistent with there being an elevated level of protein misfolding. These compartments normally house soluble misfolded proteins and allow the cell to sequester these polypeptides away from the remaining cellular milieu. Moreover, specific proteins that are normally targeted to both P-bodies and stress granules were found to instead associate with these PQC compartments in this granuleless mutant. This observation is interesting as our data indicate that this association occurs specifically in cells that have been subjected to an elevated level of proteotoxic stress. Altogether, the results here are consistent with P-bodies and stress granules having a role in normal protein homeostasis in eukaryotic cells.
Iterative combinatorial auctions for managing product transitions in semiconductor manufacturing

AbstractSuccessful management of product transitions in the semiconductor industry requires effective coordination of manufacturing and product development activities. Manufacturing units must meet...
One Versus Two Doses of Intravenous Tranexamic Acid in Total Knee Arthroplasty.

Tranexamic acid (TXA) has been shown to reduce blood loss and postoperative transfusions in total knee arthroplasty (TKA). There is no consensus on the ideal dosing regimen in the literature, although there is a growing body of literature stating there is little benefit to additional doses. Our study compared one versus two doses of TXA in primary TKA and its effect on postoperative transfusion rate. We retrospectively reviewed patients undergoing primary TKA at our two high-volume arthroplasty centers between 2013 and 2016. Patients were included if they underwent unilateral primary TKA, and received one or two doses of intravenous TXA. Patients receiving therapeutic anticoagulation were excluded. Our primary outcome was postoperative transfusion rate. Secondary outcomes included blood loss, length of stay, rate of deep vein thrombosis or pulmonary embolism (DVT/PE), readmission and reoperation.A total of 1,191 patients were included: 891 received one dose and 300 received two doses. There was no significant difference in rate of transfusion, deep vein thrombosis or pulmonary embolism (DVT/PE), blood volume loss, and reoperation. There was a significantly higher risk of readmission (6.7 vs. 2.4%, odds ratio [OR] 2.96, p < 0.001) and reoperation (2.0 vs. 0.6%, OR 3.61, p = 0.024) in patients receiving two doses. These findings were similar with subgroup analysis of patients receiving only aspirin prophylaxis.In unilateral TKA, there is no difference in transfusion rate with one or two doses of perioperative TXA. There was no increased risk of thromboembolic events between groups, although the two-dose group had a higher rate of readmission and reoperation. Given the added cost without clear benefit, these findings may support administration of one rather than two doses of TXA during primary TKA.
Impact of Hearing Loss on Patient Falls in the Inpatient Setting

Introduction The objectives of this study were to investigate an association between the risk of patient falls and self-reported hearing loss and to examine whether self-reported hearing loss with versus without hearing aids predicts patient falls in an inpatient setting. Methods This retrospective cohort analysis was conducted in 2018 in a large, urban, academic medical center. Participants included unique inpatients (N=52,805) of adults aged >18 years between February 1, 2017, and February 1, 2018. Outcome measures were falls in the inpatient setting and hearing loss with versus without hearing aids as predictors for patient falls. Results Self-reported hearing loss was associated with falls in the inpatient setting (OR=1.74, 95% CI=1.46, 2.07, p Conclusions In the inpatient setting, there was a positive association between hearing loss and falls. However, among patients with hearing loss, only those without hearing aids were significantly more likely to fall, accounting for the Morse Fall Scale score and demographics characteristics. These findings support adding hearing loss as a modifiable risk factor in risk assessment tools for falls and exploring the use of amplification devices as an intervention.
Inhibition of fungal spore germination by Nasutitermes: evidence for a possible antiseptic role of soldier defensive secretions.

The antifungal property of two of the principal components of the terpenoid frontal gland secretions of nasute termite soldiers was studied by incubating spore suspensions of the fungus Metarhizium anisopliae with α-pinene and limonene singly or in combination at different concentrations. In vitro assays showed that these substances reduced spore germination through direct and indirect (vapor) contact. To determine if the frontal gland secretions protected termites from fungal infection in vivo, the effect of M. anisopliae on the time course of survival of Nasutitermes costalis and N. nigriceps was studied by exposing termites to either a 4.3 × 107 spores/ml or a control sporeless suspension. The caste composition of experimental groups was manipulated to create mixed-caste subcolonies and monocaste groups. Relative to Coptotermes formosanus, a species that relies on the mechanical defenses of soldiers, N. costalis and N. nigriceps were less susceptible to fungal infection. Spore-exposed N. costalis and N. nigriceps termites had 1.2 times the hazard ratio of death of controls, while the hazard ratio of death of spore-exposed C. formosanus was 11.4 times that of controls. Although the lower susceptibility to infection in Nasutitermes may be explained in part by the antifungal properties of α-pinene and limonene, group composition also played a major role in the survival of spore-exposed termites. Mixed-caste and soldier monocaste groups had 3.4 and 4.7 times the hazard ratio of death, respectively, relative to the worker monocaste treatment. These results suggest that although Nasutitermes terpenoid secretions may have antifungal properties, the caste composition of groups and the social interactions of termites also play a role in determining susceptibility to fungal infection.
Power Amplifier Nonlinearities Effects on Massive MIMO Uplink Channel Estimation

Wireless communication systems have known a huge evolution in the past ten years. At every second, many wireless communication devices transmit signals which need a desirable power level to ensure a better quality for transmission. High Power amplifiers (HPA) are the responsible elements for increasing the power of signals to the desired levels to reach the destination. However, these amplifiers generate nonlinear distortions due to their saturation property which degrade the quality of the transmitted signal. This paper studies the impact of the nonlinear distortions of HPA on our previous proposed channel estimation algorithms Adaptive Orthogonal Matching Pursuit (AOMP) and Block Orthogonal Matching Pursuit (BOMP) over massive Multiple Input Multiple Output (MIMO) system. We focused especially on the impact of Saleh, SSPA and Clipping models on AOMP and B-OMP. As a simulation result, it has been shown that B-OMP outperforms AOMP even in the presence of the nonlinearities distortions of HPA. However, in terms of Bit Error Rate (BER), both of them proved a good performance with Saleh model with BER of $6x 10^{-3}$ compared to SSPA and Clipping with a BER of ${1.4x10}^{-2}$ and ${2x10}^{-2}$ respectively.
Elsie M. Pinkston (1937–2012)

Elsie May Pinkston, a colleague, mentor, and friend to many in the behavior analysis community, died on May 31, 2012, in Chicago, at age 74. Elsie was a true original—a down-home Kansas farm girl with sophisticated tastes, steely resolve, impish irreverence, brainy insight and creativity, and a huge heart. She also played a leading role in the expansion of behavior analysis from science into practice.
Judging Parents, Judging Place: Poverty, Rurality, and Termination of Parental Rights

Parents are judged constantly, by fellow parents and by wider society. But the consequences of judging parents may extend beyond community reputation and social status. One of the harshest potential consequences is the state’s termination of parental rights. In such legal contexts, the state assesses parents’ merits as parents in relation to a wide array of their characteristics, decisions and actions, including where the parents live. Among those parents judged harshly in relation to geography are impoverished parents who live in rural places. We argue that such judgments are unjust because poor rural parents often do not have ready access to state support in the form of programs that would permit them to be better parents. That is, spatial obstacles may prevent these parents from meeting their children’s first order needs by gaining access to public benefits. Rural parents are often similarly without reasonable access to the types of services and programs that would enhance their parenting skills, either because such programs are not offered in rural places or because the transportation obstacles to reach the programs are too great. We thus highlight the state’s hypocrisy in judging rural parents, including these parents’ failure to avail themselves of public services, even as the state fails to make meaningfully available the very assistance and services that would enable them to be better parents. In considering termination of parental rights in rural contexts, we survey cases that have used rural residence as a strike against a parent in termination proceedings. Our critiques based on these cases fall into three cate
How the wisdom of crowds, and of the crowd within, are affected by expertise

We investigated the effect of expertise on the wisdom of crowds. Participants completed 60 trials of a numerical estimation task, during which they saw 50–100 asterisks and were asked to estimate how many stars they had just seen. Experiment 1 established that both inner- and outer-crowd wisdom extended to our novel task: Single responses alone were less accurate than responses aggregated across a single participant (showing inner-crowd wisdom) and responses aggregated across different participants were even more accurate (showing outer-crowd wisdom). In Experiment 2, prior to beginning the critical trials, participants did 12 practice trials with feedback, which greatly increased their accuracy. There was a benefit of outer-crowd wisdom relative to a single estimate. There was no inner-crowd wisdom effect, however; with high accuracy came highly restricted variance, and aggregating insufficiently varying responses is not beneficial. Our data suggest that experts give almost the same answer every time they are asked and so they should consult the outer crowd rather than solicit multiple estimates from themselves.
What Works to Address Violence Against Children (VAC) in and Around Schools

Violence against children (VAC) is a pervasive, global issue with both short- and long-term health, social, and economic consequences. This systematic review sought to identify best practices for d...
Why Do Some Americans Resist COVID-19 Prevention Behavior? An Analysis of Issue Importance, Message Fatigue, and Reactance Regarding COVID-19 Messaging.

Despite the rapid transmission of and death toll claimed by COVID-19, there is evidence of resistance toward behaviors shown to effectively prevent and slow the spread of the disease, such as mask wearing and social distancing. This study applies psychological reactance theory to examine COVID-19 message factors (i.e., message fatigue, issue importance) that may be linked to nonadherence to CDC recommendations via the experience of reactance. Participants (N = 268) were current U.S. residents over the age of 18 who completed an online survey about their perceptions of COVID-19 messaging in general as well as toward a specific COVID-19 message they recalled. Results of structural equation modeling indicated that perceived freedom threat toward a COVID-19 message was predicted positively by message fatigue and negatively by issue importance. Greater perceived freedom threat was linked to greater reactance, which in turn was associated with lower levels of adherence to hygiene- and social-related COVID-19 preventive behavior. Notably, the negative association between reactance and social-related adherence was stronger than that between reactance and hygiene-related adherence. Implications for the role of reactance in risk and crisis communication as well as for public health messaging during the COVID-19 pandemic are discussed.