cssi/SciSciGPT-SciSciNet huggingface dataset:
It's never too early to look: subclinical disease in sarcomeric dilated cardiomyopathy.

The observation that ≈30% of nonischemic dilated cardiomyopathy (DCM) is genetic in origin represents one of the most important advances in modern cardiology and has transformed our view of this common disorder.1 Equally surprising is the more recent finding that sarcomeric genes previously linked to the development of hypertrophic cardiomyopathy (HCM) were also causative in the pathogenesis of DCM.2 Mutations in most of the protein components of the cardiac sarcomere have now been linked to DCM, many of them arising in close proximity to known HCM mutations, and provide a unique challenge: how can such divergent patterns of ventricular remodeling arise from such closely related structural changes? Although it may appear to be straightforward that discrete alterations in sarcomeric function caused by gene mutations could eventually lead to either left ventricular (LV) dilation or hypertrophy, our lack of understanding regarding the earliest clinical stages of DCM before the effects of secondary changes are manifest have precluded mechanistic insight. In this issue of Circulation Genetics , Lakdawala et al used a unique and well-characterized sarcomeric DCM cohort to directly determine whether abnormal systolic function can be detected in genotype-positive patients with normal LV ejection fraction and size. Their robust approach, including determination of echo strain and systolic myocardial tissue velocity and comparisons among sublinical DCM, overt DCM, and control (genotype-negative) family members across 4 independent mutation groups, revealed a significant decrease in systolic function in the subclinical group. These results complement their previous findings that gene mutations linked to HCM cause diastolic dysfunction in subclinical cohorts and fully establish that the primary mechanisms driving diverse ventricular remodeling in sarcomeric cardiomyopathies are tightly coupled to the underlying changes in sarcomere dynamics.4 Article see p 503 Since the publication of the first linkage studies in 1990, >1000 mutations in genes …
Assembly of a Complex Containing Cdc45p, Replication Protein A, and Mcm2p at Replication Origins Controlled by S-Phase Cyclin-Dependent Kinases and Cdc7p-Dbf4p Kinase

In Saccharomyces cerevisiae, replication origins are activated with characteristic timing during S phase. S-phase cyclin-dependent kinases (S-CDKs) and Cdc7p-Dbf4p kinase are required for origin activation throughout S phase. The activation of S-CDKs leads to association of Cdc45p with chromatin, raising the possibility that Cdc45p defines the assembly of a new complex at each origin. Here we show that both Cdc45p and replication protein A (RPA) bind to Mcm2p at the G1-S transition in an S-CDK-dependent manner. During S phase, Cdc45p associates with different replication origins at specific times. The origin associations of Cdc45p and RPA are mutually dependent, and both S-CDKs and Cdc7p-Dbf4p are required for efficient binding of Cdc45p to origins. These findings suggest that S-CDKs and Cdc7p-Dbf4p promote loading of Cdc45p and RPA onto a preformed prereplication complex at each origin with preprogrammed timing. The ARS1 association of Mcm2p, but not that of the origin recognition complex, is diminished by disruption of the B2 element of ARS1, a potential origin DNA-unwinding element. Cdc45p is required for recruiting DNA polymerase a onto chromatin, and it associates with Mcm2p, RPA, and DNA polymerase « only during S phase. These results suggest that the complex containing Cdc45p, RPA, and MCMs is involved in origin unwinding and assembly of replication forks at each origin.
The influence of disuse on bone microstructure and mechanics assessed by HR-pQCT

Numerous clinical cohorts are exposed to reduced skeletal loading and associated bone loss, including surgical patients, stroke and spinal cord injury victims, and women on bed rest during pregnancy. In this context, understanding disuse-related bone loss is critical to developing interventions to prevent fractures and the associated morbidity, mortality, and cost to the health care system. The aim of this pilot study was to use high-resolution peripheral QCT (HR-pQCT) to examine changes in trabecular and cortical microstructure and biomechanics during a period of non weight bearing (WB) and during recovery following return to normal WB. Surgical patients requiring a 6-week non WB period (n=12, 34.8±7.7 yrs) were scanned at the affected and contralateral tibia prior to surgery, after the 6-week non WB period, and 6 and 13 weeks after returning to full WB. At the affected ultradistal tibia, integral vBMD (including both trabecular and cortical compartments) decreased with respect to baseline (-1.2%), trabecular number increased (+5.6%), while trabecular thickness (-5.4%), separation (-4.6%), and heterogeneity (-7.2%) decreased (all p<0.05). Six weeks after return to full WB, trabecular structure measures reverted to baseline levels. In contrast, integral vBMD continued to decrease after 6 (-2.0%, p<0.05) and 13 weeks (-2.5%, p=0.07) of full WB. At the affected distal site, the disuse period resulted in increased porosity (+16.1%, p<0.005), which remained elevated after 6 weeks (+16.8%, p<0.01) and after 13 weeks (+16.2%, p<0.05). A novel topological analysis applied to the distal tibia cortex demonstrated increased number of canals with surface topology ("slabs" +21.7%, p<0.01) and curve topology ("tubes" +15.0%, p<0.05) as well as increased number of canal junctions (+21.4%, p<0.05) following the disuse period. Porosity increased uniformly through increases in both pore size and number. Finite element analysis at the ultradistal tibia showed decreased stiffness and failure load (-2.8% and -2.4%, p<0.01) following non WB. These biomechanical predictions remained depressed following 6 and 13 weeks of full WB. Finite element analysis at the distal site followed similar trends. Our results suggest that detectable microstructural and biomechanical degradation occurs--particularly within the cortical compartment--as a result of non WB and persists following return to normal loading. A better understanding of these microstructural changes and their short- and long-term influence on biomechanics may have clinical relevance in the context of disuse-related fracture prevention.
THE YDJ1 MOLECULAR CHAPERONE FACILITATES FORMATION OF ACTIVE P60V-SRC IN YEAST

Abstract Molecular chaperones have been implicated in the formation of active p60v-src tyrosine kinase. In Saccharomyces cerevisiae, expression of p60v-src causes cell death, a phenomenon that requires functional Hsp90. We show here that mutations in a member of a second class of chaperones, the yeast dnaJ homologue YDJ1, suppress the lethality caused by p60v-src. One p60v-src-resistant ydj1 mutant, ydj1-39, which has two point mutations in the highly conserved "J" domain, has reduced levels of v-src mRNA and protein. However, a ydj1 null mutant produces normal quantities of active p60v-src, indicating that Ydj1p facilitates, but is not essential for, the formation of active p60v-src. We also report p60v-src-resistance in a previously identified temperature-sensitive ydj1 mutant, ydj1-151. In this mutant, the level of p60v-src remains unaltered, but the protein is much less active in vivo. In addition, p60v-src immunoprecipitates from the ydj1-151 strain contained Hsp90 and Hsp70 in greater amounts than in wild-type strains. Ydj1 protein was also detected in p60v-src immunoprecipitates from both wild-type and ydj1-151 strains. These results indicate that Ydj1p participates in the formation of active p60v-src via molecular chaperone complexes.
Regulation of bHLH-PAS protein subcellular localization during Drosophila embryogenesis

The Drosophila Single-minded and Tango basic-helix-loop-helix-PAS protein heterodimer controls transcription and embryonic development of the CNS midline cells, while the Trachealess and Tango heterodimer controls tracheal cell and salivary duct transcription and development. Expression of both single-minded and trachealess is highly restricted to their respective cell lineages, however tango is broadly expressed. The developmental control of subcellular localization of these proteins is investigated because of their similarity to the mammalian basic-helix-loop-helix-PAS Aromatic hydrocarbon receptor whose nuclear localization is dependent on ligand binding. Confocal imaging of Single-minded and Trachealess protein localization indicate that they accumulate in cell nuclei when initially synthesized in their respective cell lineages and remain nuclear throughout embryogenesis. Ectopic expression experiments show that Single-minded and Trachealess are localized to nuclei in cells throughout the ectoderm and mesoderm, indicating that nuclear accumulation is not regulated in a cell-specific fashion and unlikely to be ligand dependent. In contrast, nuclear localization of Tango is developmentally regulated; it is localized to the cytoplasm in most cells except the CNS midline, salivary duct, and tracheal cells where it accumulates in nuclei. Genetic and ectopic expression experiments indicate that Tango nuclear localization is dependent on the presence of a basic-helix-loop-helix-PAS protein such as Single-minded or Trachealess. Conversely, Drosophila cell culture experiments show that Single-minded and Trachealess nuclear localization is dependent on Tango since they are cytoplasmic in the absence of Tango. These results suggest a model in which Single-minded and Trachealess dimerize with Tango in the cytoplasm of the CNS midline cells and trachea, respectively, and the dimeric complex accumulates in nuclei in a ligand-independent mode and regulates lineage-specific transcription. The lineage-specific action of Single-minded and Trachealess derives from transcriptional activation of their genes in their respective lineages, not from extracellular signaling.
Local Scale Economies, Mortgage Loan Sales, and Access to Credit: 1994-2008

Although most studies argue that expansive secondary markets for loan sales tend to enhance opportunities to manage risk, lower loan rates, and improve access to credit, other studies point to situations in which locally based credit providers remain important (e.g. relationship lending in the small business loan market). We consider a related set of issues in the context of home mortgage markets. Using census tract data from HMDA for 1994-2008, we estimate (i) the extent to which locally as opposed to globally active secondary markets increase access to credit, (ii) how this relationship differs for low versus high-risk segments of the market, and (iii) how these relationships have changed over time as information technology has become more advanced. Throughout, we measure access to credit using origination rates, and also median loan size requested which is assumed to be inversely related to loan rates. Our primary models are estimated separately for each sample year both by OLS and two-stage least squares. For the later, lagged county population is used to instrument for the local scale of secondary market activity. Findings for the conforming sized sector indicate that locally active secondary markets increased access to credit in the 1990s, but evidence of such effects largely disappears in the 2000s. Moreover, these patterns were most pronounced in high-unemployment and low income communities, locations likely perceived as high risk and also targeted by the 1992 GSE Act as underserved. In the non-conforming jumbo loan sized sector, the influence of the local scale of secondary market activity appears mixed: in no sample year are origination rates affected, but median loan size requested is substantively higher in markets with locally active secondary markets, and especially in the latter part of the 2000s. Based on these results, we argue that secondary markets (i) do mitigate risk and expand access to credit for the bulk of the mortgage market, (ii) that this is especially true in the highest risk segments of the market, and (iii) for the most idiosyncratic portions of the market, locally based credit providers remain important, analogous to behavior in the market for small business financing.
Efficient Investment via Assortative Matching

This paper compares pre-commitment investment strategy in a linear public goods game using two different matching protocols: assortative and random matching. We express the payoff function as an investment decision in which players pre-commit to an investment level and then a third party (the experimenter) matches subjects into pairs after having observed the investment decisions. After ruling out a mixed NE, we adopt the asymmetric equilibrium suggested by Gunnthorsdottir et al. (2010) and we (surprisingly) find that subject behavior is in line with the predictions. The mean investment level under the assortative matching treatment is remarkably high and is close to 90 percent of the initial endowment, when compared to the random matching treatment (50 percent of the initial endowment).
Investigation of Oxide Bifilms in Investment Cast Superalloy IN100: Part I. Mechanical Properties

Oxide bifilms are a proposed casting inclusion reported to have been observed in vacuum investment cast polycrystalline Ni-based superalloys. Ongoing research seeks to determine if current superalloy casting practices can result in the formation of oxide bifilms, and subsequently if it is possible to observe and characterize this phenomenon. The effects of casting atmosphere, turbulence, filtering, hot isostatic pressing (HIP), and heat treatment have been investigated to identify the critical parameters that have been reported to result in bifilm formation in Ni-based superalloys. Room temperature tensile and room temperature fatigue testing are used to identify the effects of each casting and processing parameter on casting defect formation and the resultant effects on mechanical properties. Characterization of mechanical test specimens seeks to identify the role of casting defects and microstructural features on the fracture mechanisms of the specimen conditions analyzed, and in particular, evidence of bifilm formation and the chemical composition(s) of oxide bifilms. Analyzed tensile and fatigue data did not indicate an influence of bifilms on the tensile or fatigue strength of vacuum processed IN100. Bifilms were not observed, via the characterization methods utilized, to be an active mechanism in tensile or fatigue fracture.
Diabetes Among United States-Bound Adult Refugees, 2009–2014

We reported diabetes prevalence among all US-bound adult refugees and assessed factors associated with disease. We analyzed overseas medical evaluations of US-bound refugees from 2009 through 2014 by using CDC’s Electronic Disease Notification System. We identified refugees with diabetes by searching for diabetes-related keywords and medications in examination forms with text-parsing techniques. Age-adjusted prevalence rates were reported and factors associated with diabetes were assessed by using logistic regression. Of 248,850 refugees aged ≥18 years examined over 5 years, 5767 (2.3 %) had diabetes. Iraqis had the highest crude (5.1 %) and age-adjusted (8.9 %) prevalence of disease. Higher age group and body mass index were associated with diabetes in all regions. Diabetes prevalence varied by refugee nationality. Although the absolute rates were lower than rates in the United States, the prevalence is still concerning given the younger age of the population and their need for health services upon resettlement.
From empathy to denial: Arab responses to the Holocaust

The result of a collaborative effort between historians Meir Litvak and Esther Webman, From Empathy to Denial represents the first scholarly exploration of Arab attitudes toward the Holocaust. Both...
Computerized neurocognitive assessments and detection of the malingering athlete.

BACKGROUND Healthcare professionals are concerned that athletes have the capability to intentionally underperform on baseline computerized neurocognitive assessments in an effort to expedite their return to the field of play following a concussion. The purpose of this study was to determine if the use of overlapping validity measures will provide better sensitivity for detecting malingering athletes on a baseline computerized neurocognitive assessment. METHODS Twenty male, collegiate rugby players (mean age 23±4 years) participated in this study. Subjects completed 2 Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) assessments within a 7-day interval. The initial test, non-malingering baseline (NM), was performed adhering to ImPACT's normal sequence of instructions. Immediately prior to the second assessment, the malingering attempt (MA), each participant was instructed to "underperform on the test" in such a way that it was not obvious they were trying to score poorly. RESULTS ImPACT detected 70% (N.=14) of the malingerers using internal validation measures, whereas the trained physician identified 80% of the malingerers (N.=16) including all of the malingerers detected by ImPACT. The Schatz Word Memory Check identified 100% of malingering tests. CONCLUSIONS These data indicate that the combination of a trained physician review and ImPACT test measures are more successful at recognizing possible malingers than use of the ImPACT validity measures alone. The Schatz Word Memory Check was highly effective at identifying invalid baseline tests and should be considered a valid test measure for future clinical reviews.
Going Too Far: Sexual Assault on Campus

This case involves the alleged sexual assault of a college athlete by her professor. Rather than report the incident, the athletes turns to social media to cryptically share her story. Her messages...
Reaction Sites on the Al2O3 Support of Pd/Al2O3

Abstract The hydrogenation of CO adsorbed on Pd/Al 2 O 3 can proceed through the formation of a methoxy species on the Al 2 O 3 support by spillover. The rate of formation of the methoxy species and the effect of coadsorbed water on CH 3 O hydrogenation are presented. Methoxy hydrogenates faster than CO adsorbed on Pd, and though H 2 O decreases the rate of spillover, methoxy hydrogenation may contribute to the high rate of steady state methanation observed on Pd/Al 2 O 3 .
Student Success: Identifying High‐Impact Practices

This chapter discusses the work of the Center for Community College Student Engagement, highlighting institutes the Center hosts and work that comes from these meetings. Examples of interventions that evolved from the High-Impact Practices Institutes conducted by the Center are provided. The chapter concludes with a discussion about implementation and evaluation practices important to the interpretation of intervention success.
Privacy and Fear in the Drone Era: Preserving Privacy Expectations Through Technology

The increasing use of unmanned aerial vehicles (i.e. drones) is raising a number of privacy issues. The high-resolution cameras that drones can carry may pose serious privacy hazards to the general public. Numerous media stories highlight incidents of drones spying on people, often with negative consequences (e.g. lawsuits and arrests). Our research seeks to understand how incorporating privacy-preserving technologies in drone design can mitigate privacy fears. We identify several classes of privacy-preserving technological solutions and evaluate their potential efficacy across a variety of situations through a Mechanical Turk survey of 7,200 respondents. Our results inform both drone designers and regulators who wish to develop, operate, and/or regulate novel drone services while assuaging public fears of privacy violations.
Ps four-wave mixing measurements of electric field in a ns pulse discharge in a hydrogen diffusion flame

Abstract Time-resolved electric field in ns pulse discharge plasmas generated in room air and in an atmospheric pressure hydrogen diffusion flame has been measured by ps four-wave mixing, for plane-to-plane electrode geometry. Electric field is put on the absolute scale using the Laplacian field measured before breakdown. The results show that peak electric field during breakdown in the flame, approximately 40 kV/cm, is significantly lower compared to that in room air, 75 kV/cm, due to higher temperature of combustion products. In both cases, peak electric field is higher compared to DC breakdown field. Both in air and in the flame, the electric field follows the applied voltage before breakdown and decreases rapidly after breakdown, due to charge separation and plasma self-shielding. The electric field in air is compared with the predictions of an analytic model of ns pulse breakdown, showing good agreement between the predicted and the measured breakdown field. The model also predicts earlier breakdown as well as breakdown voltage reduction as the temperature is increased, in qualitative agreement with the experimental data. The use of the present ps four-wave mixing diagnostics for measurements of electric fields below ∼20 kV/cm in atmospheric pressure flames is challenging, due to low signal-to-noise. The sensitivity of the present diagnostics is controlled by the high temperature and low N2 fraction in the combustion product mixture, as well as by the limited bandwidth of the Stokes beam generated by the stimulated Raman cell, which provides access only to several rotational levels of nitrogen molecules. The present diagnostics will have much better sensitivity in high-pressure flames, since the four-wave mixing signal scales as the squared number density of nitrogen.
Human Nature and Mind in Martin Heidegger

When Professor Tymieniecka asked me to present a brief paper at this Third Symposium on Phenomenology and Oriental Philosophy, she said that what was needed for the occasion was a straightforward presentation of some of the central ideas of Heidegger on the questions of human nature and mind. The reason for her request, no doubt, is her experience that too frequently discussions of the thought of Heidegger quickly reach a point where argument about what a particular text means pushes aside fruitful dialogue. I shall make every attempt to respond to the request of Professor Tymieniecka. However, the thought ]of Heidegger is itself not always as straightforward as it is hermeneu- tical. Moreover, I cannot claim to have mastered Heidegger’s thought to the extent that I can claim to be able to give a definitive interpretation of his meaning of human nature and mind. With these two caveats in mind I will make my presentation as clear as I am able; I hope it will be suitable to enable us to carry on a fruitful dialogue.
Five Assumptions Academics Make About Public Deliberation, And Why They Deserve Rethinking

Academic research on public dialogue and deliberation is abundant and sophisticated. This body of multi-disciplinary scholarship draws on the insights of political theory and case studies, such that much is known about the promise and practical nuances of designing engagement processes with authentically deliberative outcomes. The socio-historical and institutional contexts in which public deliberation is organized and practitioners make their living are less well-studied. This article uses a multi-method study of deliberation as a strategic action field (SAF) in order to reconsider common assumptions about deliberation practice. Based on practitioners’ shared experiences and everyday struggles, I challenge researchers to develop deeper analyses of 1) change and power, 2) reproduction of inequality, 3) stability and settlement, 4) markets and politics, and 5) crises and opportunities in the field. Given expanding demand for deliberative remedies and converging strategies and discourses across related SAFs, this new research agenda is a timely addition to both deliberation scholarship and comparative historical sociology.
Building Qualitative Research Capacity Among Interdisciplinary Teams to Investigate Girls’ Challenges With Menstruation: Process and Lessons Learned From a 14-Country E-Course:

Public health–related decisions are influenced by a variety of actors operating on local to global levels, including community leaders, educators, nongovernment organizations, government officials,...
Cancer-Specific Biomarker hNQO1-Activatable Fluorescent Probe for Imaging Cancer Cells In Vitro and In Vivo

Human NAD(P)H quinone oxidoreductase-1 (hNQO1) is an important cancer-related biomarker, which shows significant overexpression in malignant cells. Developing an effective method for detecting NQO1 activity with high sensitivity and selectivity in tumors holds a great potential for cancer diagnosis, treatment, and management. In the present study, we report a new dicyanoisophorone (DCP) based fluorescent probe (NQ-DCP) capable of monitoring hNQO1 activity in vitro and in vivo in both ratiometric and turn-on model. NQ-DCP was prepared by conjugating dicyanoisophorone fluoroprobe with hNQO1 activatable quinone propionic acid (QPA), which remain non-fluorescent until activation by tumor-specific hNQO1. NQ-DCP featured a large Stokes shift (145 nm), excellent biocompatibility, cell permeability, and selectivity towards hNQO1 allowed to differentiate cancer cells from healthy cells. We have successfully employed NQ-DCP to monitor non-invasive endogenous hNQO1 activity in brain tumor cells in vitro and in xenografted tumors developed in nude mice.
Activation of the hypothalamic paraventricular nucleus by acute intermittent hypoxia: Implications for sympathetic long-term facilitation neuroplasticity

Abstract Exposure to acute intermittent hypoxia (AIH) induces a progressive increase of sympathetic nerve activity (SNA) that reflects a form of neuroplasticity known as sympathetic long-term facilitation (sLTF). Our recent findings indicate that activity of neurons in the hypothalamic paraventricular nucleus (PVN) contributes to AIH-induced sLTF, but neither the intra-PVN distribution nor the neurochemical identity of AIH responsive neurons has been determined. Here, awake rats were exposed to 10 cycles of AIH and c-Fos immunohistochemistry was performed to identify transcriptionally activated neurons in rostral, middle and caudal planes of the PVN. Effects of graded intensities of AIH were investigated in separate groups of rats (n = 6/group) in which inspired oxygen (O2) was reduced every 6 min from 21% to nadirs of 10%, 8% or 6%. All intensities of AIH failed to increase c-Fos counts in the caudally located lateral parvocellular region of the PVN. c-Fos counts increased in the dorsal parvocellular and central magnocellular regions, but significance was achieved only with AIH to 6% O2 (P
Wenn das Immunsystem verrückt spielt

Eine 36-jahrige Patientin mit bekannter schubformiger Mutipler Sklerose stellte sich mit Fieber und Schuttelfrost seit dem Vortag sowie einem Exanthem auf der Notfallstation vor.
Effectiveness of a Seed Plate Assay for Evaluating Charcoal Rot Resistance in Soybean and the Relationship to Field Performance

Charcoal rot of soybean, caused by Macrophomina phaseolina, is a disease of economic significance in the United States. Although there are soybean cultivars with moderate resistance, identifying and quantifying resistance is challenging. Existing assays are time consuming, and results are often highly variable. The objectives of this research were to (i) create a reproducible seed plate assay (SPA) for charcoal rot resistance and (ii) correlate field-based disease assessments with SPA results on diverse soybean accessions. To develop the SPA, surface-disinfected seeds from eight soybean genotypes (representing three susceptible and five resistant cultivars) were placed on water agar plates inoculated with M. phaseolina. After incubation at room temperature in darkness for 7 days, percent germination was determined for each cultivar relative to the germination on noninoculated plates. Results from SPA were in general agreement with published responses. None of the soybean genotypes showed complete resistance to M. phaseolina. For the second objective, charcoal rot resistance in 18 soybean accessions was assayed with SPA, and results were analyzed for correlation with field disease assessments from Stuttgart, AR, from 2011 to 2014 and from Rohwer, AR, in 2011 and 2012. SPA consistently categorized soybean genotype resistance compared with field disease assessment averages, and results were consistent with previously published resistance determinations. SPA was significantly correlated with percent height of internal stem discoloration (PHSD) at Stuttgart from 2011 to 2013 and in 2012 at Rohwer, with root and stem severity (RSS) at Rohwer in 2012, and with tap root colonization (CFU) at Stuttgart in 2012. SPA was significantly correlated to yield at Stuttgart in 2011, 2013, and 2014, and in 2011 and 2012 at Rohwer. Yield was not correlated to RSS, PHSD, or CFU at either location or in any year. Therefore, SPA is a reproducible and rapid assay for charcoal rot resistance in soybean and is significantly associated to field performance.
What Is Urban Ecology and Why Should We Study It

This chapter introduces urban ecology as an analytical approach to understand how our cities work as ecosystems and to assess trade-offs associated with proposals intended to make our cities more sustainable. We present the concept of social-ecological metabolism and review the fundamentals of systems ecology that we can employ to quantify flows of materials, nutrients, and energy upon which our cities, and thus the majority of the world’s population, depend. We make the case that predicted population growth, climate uncertainties, and natural resource declines will present difficult challenges to urban citizens and their leaders, making the study of urban ecology very important to securing more resilient cities in the years to come.
Mineralogy dictates the initial mechanism of microbial necromass association

Abstract Soil organic matter (SOM) improves soil fertility and mitigates disturbance related to climate and land use change. Microbial necromass (the accumulated cellular residues of microorganisms) comprises the majority of soil C, yet the formation and persistence of necromass in relation to mineralogy is poorly understood. We tested whether soil minerals had different microbial necromass association mechanisms. Specifically, we tested whether microbial necromass directly sorbed to mineral surfaces or was consumed by live microorganisms prior to mineral association. Applying Raman microspectroscopy with 13C enriched microbial necromass to quantify microbe-mineral interactions, we show that mineralogy alters the initial mechanism of microbial necromass association. In the presence of K-feldspar (lower abiotic C preservation potential), microbial necromass required assimilation by live microorganisms for mineral retention. In contrast, with amorphous aluminum hydroxide (higher abiotic C preservation potential) microbial necromass was retained predominately through abiotic sorption, and was subsequently protected from microbial decomposition. Despite different mechanisms, both minerals retained similar quantities of microbial necromass under biotic conditions. Mineralogy determined not only the quantity of mineral-associated C, but the distinct pathway of microbial necromass association. These findings show the utility of Raman microspectroscopy as a technique to study microbe-mineral interactions, and imply that heterogeneity in mineral-organic interactions could result in gradients of organic matter stability.
The Cation Diffusion Facilitator Family Protein EmfA Confers Resistance to Manganese Toxicity in Brucella abortus 2308 and Is an Essential Virulence Determinant in Mice.

Brucella abortus is a Gram-negative bacterium that causes abortion and infertility in food animals and a chronic debilitating febrile disease in humans known as brucellosis. As with all pathogenic bacteria , the Brucella spp. require sufficient metal nutrition during the course of an infection. Host-mediated 'metal withdrawal' defenses actively restrict the bioavailability of metals which requires invading bacteria to employ high affinity metal acquisition systems to overcome these metal-limiting conditions. While obtaining sufficient metals during host infection is critical to the survival of these bacteria , avoiding metal toxicity is equally important. Excess accumulation of one metal relative to others can lead to protein mis-metallation when surplus metal ions outcompete other metal species for their native binding sites. To prevent metal toxicity , bacteria respond to high intracellular metal concentrations by means of metal-responsive transcriptional regulators that downregulate metal import systems , and exporters that remove excess intracellular metal. Manganese (Mn) is an essential micronutrient for Brucella strains , and the purpose of this study was to better define the cellular components that maintain Mn homeostasis and prevent Mn toxicity in these bacteria. The Mn-responsive repressor Mur downregulates the expression of mntH , the gene encoding the sole high affinity Mn importer in Brucella in response to increased intracellular levels of Mn. But phenotypic analysis of a B. abortus mur mutant suggests that Mur plays a minimal role in preventing Mn toxicity. Instead , an ortholog of the cation diffusion facilitator (CDF) type metal exporter EmfA , which prevents Mn toxicity in the close phylogenetic relative Rhizobium etli , is critical for preventing Mn toxicity in Brucella. The experimental findings of this study indicate that EmfA-mediated resistance to Mn toxicity plays a critical role in the virulence of Brucella strains , and suggests that the primary function of EmfA may be to maintain the proper intracellular balance of Mn in these bacteria during the course of infection.
Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study.

Interventions that relieve vasomotor symptoms while reducing risk for breast cancer would likely improve uptake of chemoprevention for perimenopausal and postmenopausal women. We conducted a pilot study with 6 months of the tissue selective estrogen complex bazedoxifene (20 mg) and conjugated estrogen (0.45 mg; Duavee) to assess feasibility and effects on risk biomarkers for postmenopausal breast cancer. Risk biomarkers included fully automated mammographic volumetric density (Volpara), benign breast tissue Ki-67 (MIB-1 immunochemistry), and serum levels of progesterone, IGF-1, and IGFBP3, bioavailable estradiol and testosterone. Twenty-eight perimenopausal and postmenopausal women at increased risk for breast cancer were enrolled: 13 in cohort A with baseline Ki-67 85% drug adherence. Significant changes in biomarkers, uncorrected for multiple comparisons, were a decrease in mammographic fibroglandular volume (P = 0.043); decreases in serum progesterone, bioavailable testosterone, and IGF-1 (P < 0.01), an increase in serum bioavailable estradiol (P < 0.001), and for women from cohort B a reduction in Ki-67 (P = 0.017). An improvement in median hot flash score from 15 at baseline to 0 at 6 months, and menopause-specific quality-of-life total, vasomotor, and sexual domain scores were also observed (P < 0.001). Given the favorable effects on risk biomarkers and patient reported outcomes, a placebo-controlled phase IIB trial is warranted.
EFFECTS OF COLD STRATIFICATION AND HORMONES ON SEED GERMINATION OF SARRACENIA ALATA

Abstract Seed germination requirements for S. alata were investigated using cold stratification and phytohormones. Treatments included no stratification (control), two week, three week, four week, ...
What are Academic Subreddits Talking About?: A Comparative Analysis of r/academia and r/gradschool

Graduate school and academia can often be challenging and hard to navigate. This work explores how people are using Reddit to reach out to others in academic subreddits to talk about issues one might face in their academic journey. We also explore how such discussion differs between subreddits by comparing two popularly used academic subreddits: r/gradschool and r/academia. For each subreddit, we investigated 300 posts and 500 comments. Using topic modelling, we identify and distinguish the main emergent types of posts and comments we find in these two subreddits. We find that posts in r/academia center more on the challenging aspects of academia such as plagiarism, working in academia, and mental health, whereas r/gradschool posts deal with more generic issues on graduate school life. However, we find that the way the community reacts and provides support via comments is similar in both subreddits, mostly by providing moral support and solidarity.
Stakeholder engagement in methodological research: Development of a clinical decision support tool.

Introduction Shared patient-clinician decision-making is central to choosing between medical treatments. Decision support tools can have an important role to play in these decisions. We developed a decision support tool for deciding between nonsurgical treatment and surgical total knee replacement for patients with severe knee osteoarthritis. The tool aims to provide likely outcomes of alternative treatments based on predictive models using patient-specific characteristics. To make those models relevant to patients with knee osteoarthritis and their clinicians, we involved patients, family members, patient advocates, clinicians, and researchers as stakeholders in creating the models. Methods Stakeholders were recruited through local arthritis research, advocacy, and clinical organizations. After being provided with brief methodological education sessions, stakeholder views were solicited through quarterly patient or clinician stakeholder panel meetings and incorporated into all aspects of the project. Results Participating in each aspect of the research from determining the outcomes of interest to providing input on the design of the user interface displaying outcome predications, 86% (12/14) of stakeholders remained engaged throughout the project. Stakeholder engagement ensured that the prediction models that form the basis of the Knee Osteoarthritis Mathematical Equipoise Tool and its user interface were relevant for patient-clinician shared decision-making. Conclusions Methodological research has the opportunity to benefit from stakeholder engagement by ensuring that the perspectives of those most impacted by the results are involved in study design and conduct. While additional planning and investments in maintaining stakeholder knowledge and trust may be needed, they are offset by the valuable insights gained.
Minimally Invasive Surgery is Associated with an Increased Risk of Postoperative Venous Thromboembolism After Distal Pancreatectomy

Venous thromboembolism (VTE) is a major cause of morbidity and mortality following distal pancreatectomy (DP). However, the influence of operative technique on VTE risk after DP is unknown. The purpose of this study was to examine the association between the MIS technique versus the open technique and the development of postoperative VTE after DP. Patients who underwent DP from 2014 to 2015 were identified in the American College of Surgeons National Surgical Quality Improvement Program pancreas-specific database. Multivariable logistic regression was then used to identify independent associations with the development of postoperative VTE after DP. A total of 3558 patients underwent DP during this time period. Of these cases, 47.8% (n = 1702) were performed via the MIS approach. After adjusting for significant covariates, the MIS approach was independently associated with the development of any VTE (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.06–2.40; p = 0.025), as well as increasing the risk of developing a postdischarge VTE (OR 1.80, 95% CI 1.05–3.08; p = 0.033) when compared with the open approach. There was an association between VTE and the development of numerous postoperative complications, including pneumonia, unplanned intubation, need for prolonged mechanical ventilation, and cardiac arrest. Compared with the open approach, the MIS approach is associated with higher rates of postoperative VTE in patients undergoing DP. The majority of these events are diagnosed after hospital discharge.
Assessing Stretched-Vortex Subgrid-Scale Models in Finite Volume Methods for Unbounded Turbulent Flows

Simulations of complex, compressible, high-Reynolds-number flows require high-fidelity physics and turbulence models to be appropriately coupled with strong numerical regularization methods. Obtaining grid-independent and scheme-independent solutions of these flows when using both explicit turbulence models and additional numerical regularization is especially important for further testing and development of accurate physics models. To this end, the current study investigates the interaction between the stretched-vortex subgrid-scale model and both the fourth-order piecewise parabolic limiter and a fifth-order upwinding interpolation (or hyperviscosity). It is demonstrated that computing the subgrid-scale kinetic energy estimate for the stretched-vortex model at a coarser resolution than the base mesh provides results which are independent of the use of numerical regularization techniques. This is shown to be the case for a temporally-evolving shear-layer, the inviscid Taylor–Green vortex problem, and a decaying, homogeneous turbulent flow.
Remote patient monitoring sustains reductions of hemoglobin A1c in underserved patients to 12 months.

Abstract Aims We sought to determine whether underserved patients enrolled in a statewide remote patient monitoring (RPM) program for diabetes achieve sustained improvements in hemoglobin A1c at 6 and 12 months and whether those improvements are affected by demographic and clinical variables. Methods Demographic and clinical variables were obtained at baseline, 6 months and 12 months. Baseline HbA1c values were compared with those obtained at 6 and 12 months via paired t-tests. A multivariable regression model was developed to identify patient-level variables associated with HbA1c change at 12 months. Results HbA1c values were obtained for 302 participants at 6 months and 125 participants at 12 months. Compared to baseline, HbA1c values were 1.8% (19 mmol/mol) lower at 6 months (p Conclusions Patients enrolled in RPM had improved diabetes control at 6 and 12 months. Neither clinic type nor sociodemographic variables significantly altered the likelihood that patients would benefit from this type of technology. These results suggest the promise of RPM for delivering care to underserved populations.
Design Considerations for Fast Mechanical Switches Using Piezoelectric Actuators

Hybrid circuit breakers (HCB) have been proposed as protection devices for multi-terminal DC power systems. The HCB consists of a fast mechanical switch (FMS), which carries the nominal current, in parallel with a semiconductor switch, which breaks the fault current. While most of the proposed FMS prototypes are based on Thomson coil actuators, FMS based on piezoelectric actuators have a faster response time and better stroke control. However, the contact separation and contact forces in piezoelectric FMS are an order of magnitude lower than Thomson coil-based FMS. This paper investigates the design considerations for FMS using piezoelectric actuators, i.e. the trade-offs between the blocked force, stroke, response time, and dimensions of the actuator using finite element model and spring mass damper models. The results are expected to guide the development of future versions of piezoelectrically actuated FMS.
Improvement to Nem SP3 Modelling and Simulation

Accurate reactor core steady state safety analysis requires coupling between thermal-hydraulics and three dimensional multigroup pin by pin neutronics. Concerning the neutronics modeling, the Nodal Expansion Method (NEM) code is developed at North Carolina State University in the framework of high fidelity multiphysics coupling with CTF. NEM includes a simplified third-order Spherical Harmonic (SP3) solver. In this work, the solver has been improved by incorporating higher order scattering matrix library. The boundary conditions were corrected with one dimensional P 3 theory and a consistent coupling coupling between zeroth- and second-order flux moments was established. Two methods for generating second order discontinuity factors (DFs) has ben developed, one based on the Generalized Equivalence Theory (GET) and one based on Parial Current Equivalence Theory (PCET). DFs were generated with three lattice sizes: single pin, 2 pins and assembly level. These developments were tested using the C5G7 benchmark. The results of the SP3 solver improvement, by using P 2 and P 3 scattering cross sections, show a 50% decrease in the eigenvalue (k eff ) prediction error compared to the reference transport solution. The GET DFs are applied in the C5G7 core pin by pin calculation and are compared with PCET DFs. The results show that PCET have a better performance in global results (eigenvalue). Concerning the different lattice sizes studies, the results show that DFs generated in smalll colorsets can improve local solutions. However, in order to reveal strong global trends, DFs should be generated in a larger corloset representative of the whole core. For the core calculations, DFs generated with the three colorsets together with an additional mixed type DFs were tested. For the mixed type, DFs generated from assembly size lattice were used for the internal interfaces and DFs generated from 2 pins size lattice were used for the assemblies boundary interfaces. These mixed DFs outperformed all the other configurations indicating that they manage to accomplish a satisfying compromise between global and local trends.
Protecting P-glycoprotein at the blood–brain barrier from degradation in an Alzheimer’s disease mouse model

Failure to clear Aβ from the brain is partly responsible for Aβ brain accumulation in Alzheimer’s disease (AD). A critical protein for clearing Aβ across the blood-brain barrier is the efflux transporter P-glycoprotein (P-gp). In AD, P-gp levels are reduced, which contributes to impaired Aβ brain clearance. However, the mechanism responsible for decreased P-gp levels is poorly understood and there are no strategies available to protect P-gp. We previously demonstrated in isolated brain capillaries ex vivo that human Aβ40 (hAβ40) triggers P-gp degradation by activating the ubiquitin-proteasome pathway. In this pathway, hAβ40 initiates P-gp ubiquitination, leading to internalization and proteasomal degradation of P-gp, which then results in decreased P-gp protein expression and transport activity levels. Here, we extend this line of research and present results from an in vivo study using a transgenic mouse model of AD (human amyloid precursor protein (hAPP)-overexpressing mice; Tg2576). In our study, hAPP mice were treated with vehicle, nocodazole (NCZ, microtubule inhibitor to block P-gp internalization), or a combination of NCZ and the P-gp inhibitor cyclosporin A (CSA). We determined P-gp protein expression and transport activity levels in isolated mouse brain capillaries and Aβ levels in plasma and brain tissue. Treating hAPP mice with 5 mg/kg NCZ for 14 days increased P-gp levels to levels found in WT mice. Consistent with this, P-gp-mediated hAβ42 transport in brain capillaries was increased in NCZ-treated hAPP mice compared to untreated hAPP mice. Importantly, NCZ treatment significantly lowered hAβ40 and hAβ42 brain levels in hAPP mice, whereas hAβ40 and hAβ42 levels in plasma remained unchanged. These findings provide in vivo evidence that microtubule inhibition maintains P-gp protein expression and transport activity levels, which in turn helps to lower hAβ brain levels in hAPP mice. Thus, protecting P-gp at the blood-brain barrier may provide a novel therapeutic strategy for AD and other Aβ-based pathologies.