cssi/SciSciGPT-SciSciNet huggingface dataset:
The relationship between relative solvent accessibility and evolutionary rate in protein evolution

Recent work with Saccharomyces cerevisiae shows a linear relationship between the evolutionary rate of sites and the relative solvent accessibility (RSA) of the corresponding residues in the folded protein. Here, we aim to develop a mathematical model that can reproduce this linear relationship. We first demonstrate that two models that both seem reasonable choices (a simple model in which selection strength correlates with RSA and a more complex model based on RSA-dependent amino acid distributions) fail to reproduce the observed relationship. We then develop a model on the basis of observed site-specific amino acid distributions and show that this model behaves appropriately. We conclude that evolutionary rates are directly linked to the distribution of amino acids at individual sites. Because of this link, any future insight into the biophysical mechanisms that determine amino acid distributions will improve our understanding of evolutionary rates.
Effect of cell-free ascites containing mitochondrial DNA (mtDNA) from ovarian cancer (OC) patients on human neutrophils and neutrophil extracellular traps (NETs).

e22087 Background: Mitochondrial damage-associated molecular patterns, made of mtDNA and formylated peptides, are released after cellular injury and recruit/activate neutrophils. NETs made of stret...
Marine fishes of Florida, by David B. Snyder and George H. Burgess

Marine fishes of Florida represents the first comprehensive text covering marine fish diversity within state waters. As Florida contains among the highest levels of aquatic biodiversity in the USA,...
An allosteric site in the T-cell receptor Cβ domain plays a critical signalling role

The molecular mechanism through which the interaction of a clonotypic αβ T-cell receptor (TCR) with a peptide-loaded major histocompatibility complex (p/MHC) leads to T-cell activation is not yet fully understood. Here we exploit a high-affinity TCR (B4.2.3) to examine the structural changes that accompany binding to its p/MHC ligand (P18-I10/H2-Dd). In addition to conformational changes in complementarity-determining regions (CDRs) of the TCR seen in comparison of unliganded and bound X-ray structures, NMR characterization of the TCR β-chain dynamics reveals significant chemical shift effects in sites removed from the MHC-binding site. Remodelling of electrostatic interactions near the Cβ H3 helix at the membrane-proximal face of the TCR, a region implicated in interactions with the CD3 co-receptor, suggests a possible role for an allosteric mechanism in TCR signalling. The contribution of these TCR residues to signal transduction is supported by mutagenesis and T-cell functional assays.
Tools and Strategies for Continuous Quality Improvement and Patient Safety

The healthcare delivery system is overly complex, nontransparent, and inefficient. Stakeholders are searching for effective remedies to insure that high-quality care is readily available to all no matter their socioeconomic standing and their location. High-performing healthcare organizations differentiate themselves by focusing relentlessly on attention to detail, and continuously on process-improvement initiatives to advance patient care. The science of continuous quality improvement offers a powerful way of thinking about how to transform clinical operations and healthcare teams to this end. In this chapter, we focus on the five quality improvement tools that we recommend every provider to master—checklists, process maps, Ishikawa diagrams, run charts, and control charts—to improve the process and outcomes of surgical care. The tools help visualize, analyze, and track process and outcome data for both individual and groups of patients and should be used routinely by clinicians and healthcare systems to evaluate and improve care. The tools can be used to achieve measurable improvements in the efficiency, effectiveness, performance, accountability, and outcomes of quality in services or processes of care.
Can we use pyroxene weathering textures to interpret aqueous alteration conditions? Yes and No

Pyroxene minerals are a significant component of Shergottite-Nakhlite-Chassignite (SNC) meteorites (e.g., Velbel 2012) and detected across large areas of Mars’ surface (e.g., Mustard et al. 2005). These minerals are associated with chloride, sulfate, and perchlorate salts that may represent briny waters present in Mars’ history. Previous textural analyses by Velbel and Losiak (2010) comparing pyroxenes and amphiboles from various natural weathering environments showed no correlation between apparent apical angles (describing the morphology of denticular weathering textures) and mineralogy or aqueous alteration history in relatively dilute solutions. However, high-salinity brines preferentially dissolve surface species, potentially leading to different textures dependent on the brine chemistry. In this study, we performed controlled pyroxene dissolution experiments in the laboratory on a well-characterized diopside to determine if aqueous alteration in different high-salinity brines, representative of potential weathering fluids on Mars, produce unique textural signatures. Following two months of dissolution in batch reactors, we observed denticles on etch pit margins and pyroxene chip boundaries in all of the solutions investigated: ultrapure water (18 MΩ cm −1 ; a H 2 O = 1); low-salinity solutions containing 0.35 M NaCl ( a H 2 O = 0.99), 0.35 M Na 2 SO 4 ( a H 2 O = 0.98), and 2 M NaClO 4 ( a H 2 O = 0.9); and near-saturated brines containing 1.7 M Na 2 SO 4 ( a H 2 O = 0.95), 3 M NaCl ( a H 2 O = 0.75), and 4.5 M CaCl 2 ( a H 2 O = 0.35). No systematic change in denticle length or apical angle was observed between any of the solutions investigated, even when altered in brines with significantly different salinity, activity of water, and anion composition. Based on these and previous results from natural systems, apical angle measurements are not a useful proxy for determining the extent or nature of aqueous alteration. However, since denticles form relatively slowly during weathering at circum-neutral pH, denticle length may be a useful proxy for chemical weathering duration. All of the experimental solutions produced median denticle lengths ≤1 μm, likely due to the brief weathering experiments. However, perchlorate brines produced a significantly wider range of denticle lengths than those observed in all the other experimental solutions tested. Since perchlorate is likely a common constituent in martian soils (Glotch et al. 2016), denticle length measurements should be used cautiously as proxies for extent of aqueous alteration on Mars, particularly in samples that also contain perchlorate.
Development of a novel mouse tk+/- embryonic stem cell line for use in mutagenicity studies.

A tk{sup +/-} mouse embryonic stem (ES) cell line, designated 1G2, has been created in which one allele of the thymidine kinase (tk) gene was inactivated by targeted homologous recombination. This line is an analog of the mouse lymphoma tk{sup +/-} L5178Y cell line, which is used widely to assess the mutagenicity of chemical agents. Treatment of 1G2 cells with the alkylating agent N-ethyl-N-nitrosourea (ENU) resulted in a dose-related increase in tribluorothymidine-resistant colonies. Mutant frequencies of 152 and 296 per 10{sup 6} cells were determined for 0.1 and 0.3 mg/ml doses of ENU, compared with a spontaneous mutant frequency of 15 per 10{sup 6} cells. The data indicate that tk{sup +/-} 1G2 ES cells may be useful for the creation of a transgenic mouse model for assessing in vivo mutation using an endogenous autosomal gene. 45 refs., 2 figs., 1 tab.
Bacterial Translocation in Polytrauma Patients

Long before the era of scientific medicine, physicians considered the gut to be a reservoir of “evil toxins” which could lead to illness or abet existing illnesses. Violent purging with strong chathartics as well as enemas were frequently recommended for a host of major illnesses. The patients of that era were often reduced to a state of major dehydration and then bled as well in the course of their treatment (Rush 1812). As a more enlightened era of medicine dawned, these practices were abandoned. Although bleeding for certain illnesses such as pneumonia were still recommended in the early 20th century.
Health-related quality of life and economic burden of vestibular loss in older adults.

Objectives Vestibular loss is a debilitating condition, and despite its high prevalence in older adults, the quality of life (QoL) burden of vestibular loss in older individuals has not been well-studied. This report quantifies the impact on overall QoL and identifies domains of health most affected. We hypothesize vestibular loss will be associated with impairment in diverse domains of health-related QoL. Study Design Prospective, case-control study. Methods A convenience sample of 27 patients age ≥60 years with vestibular physiologic loss was recruited from an academic neurotology clinic. The patients did not have any identifiable cause of their vestibular loss other than aging. The convenience sample was compared to an age-matched cross-sectional sample of the general US population (n = 1266). The main outcome was QoL measured by the Ontario Health Utilities Index Mark III (HUI3). Results Compared to the general population, patients with vestibular loss had significantly lower overall unadjusted HUI3 scores (-0.32, p < 0.001). Multivariate regression analysis showed vestibular loss was significantly associated with poorer performance in vision (-0.11 p < 0.0001), speech (-0.15, p < 0.0001), dexterity (-0.13, p < 0.0001), and emotion (-0.07, p = 0.0065). Adjusted aggregate HUI3 was also significantly lower for vestibular loss (-0.15, p = 0.0105). These QoL decrements resulted in an average loss of 1.30 Quality-Adjusted Life Years (QALYs). When using a $50,000/QALY willingness-to-pay threshold, vestibular loss was associated with a $64,929 lifetime economic burden per affected older adult, resulting in a total lifetime societal burden of $227 billion for the US population ≥60 years of age. Conclusions Loss of vestibular function with aging significantly decreases quality of life across multiple domains of well-being. These QoL reductions are responsible for heavy societal economic burdens of vestibular loss, which reveal potential benefits of prompt diagnosis and treatment of this condition. Level of Evidence 3.
An ultra high endurance and thermally stable selector based on TeAsGeSiSe chalcogenides compatible with BEOL IC Integration for cross-point PCM

We present the results of a primary study on an OTS chalcogenide material system (TeAsGeSi) that incorporates Se and an extra dopant. Vth and Ioff are trade-off parameters that can be tuned by modification of OTS composition, thickness and process temperature. The resulting new selector material demonstrated excellent endurance (>1010 with 50ns-pulsed 400uA On-current) and robust OTS characteristics after 350°C/30 mins annealing. The thin film could withstand 500 °C annealing.
DECOMPOSING ANALYTIC SURFACES

Publisher Summary This chapter explains the concept of decomposing analytic surfaces. One of the basic problems of topology is the characterization of manifolds by means of algebraic invariants. In the case of compact manifolds of dimension less than three, there exists a complete classification. In fact, such manifolds are completely determined by their fundamental groups. In high, dimensions the undecidability of the word problem for finitely presented groups preclude any complete algebraic classification. The theorem of Enriques–Kodaira for the simply connected case states that if M is a simply connected compact complex surface, there exists nonsingular projective algebraic surface V such that V is diffeomorphic to M and one of the following three possibilities hold: (1) V is rational, (2) V is elliptic, and (3) V is of general type.
New method to determine restrained-shrinkage stresses in propellant-grain models

This paper deals with the photoelastic determination of restrained-shrinkage stresses which may be produced by curing or by thermal effects in models of solid propellant grains bonded to the case. Use is made of the birefringence exhibited in the curing process of a restrained polyurethane rubber. The techniques developed to take advantage of this property are shown in detail. The method can also be applied to the determination of the residual stresses produced in the curing process of a propellant cast around a rigid insert. An example of this application is also given. The extension of the method, using epoxies, to three-dimensional analyses is pointed out.
Differentiation and Proliferation of CD8+ Suppressor T Lymphocytes

Analysis of cellular interactions involved in the generation of immune responses has been greatly enhanced by characterization of molecules required for the induction and up-regulation of T cell functions. In contrast, signals that lead preferentially to down-regulation of T cell-mediated immunity and antibody synthesis are less clearly understood. Similarly, whereas technologies for propagation and cloning of T cell subsets with helper cell function and with cytolytic activity are well-established, progress in long-term culture of T cell subsets with suppressor function has been remarkably slower. We hypothesize that these two impediments to clearer understanding of suppressor cells are directly related. That is, development of the technology for culture of nontransformed T suppressor cell (Ts) clones is likely to depend upon substantive advances in our understanding of the hormonal requirements of Ts precursors for differentiation and/or proliferation.
Graph-Theoretic Analysis of Estimators for Stochastically-Driven Diffusive Network Processes

Monitoring of a linear diffusive network dynamics that is subject to a stationary stochastic input is considered, from a graph-theoretic perspective. Specifically, the performance of minimum mean square error (MMSE) estimators of the stochastic input and network state, based on remote noisy measurements, is studied. Using a graph-theoretic characterization of frequency responses in the diffusive network model, we show that the performance of an off-line (noncausal) estimator exhibits an exact topological pattern, which is related to vertex cuts and paths in the network's graph. For on-line (causal) estimation, graph-theoretic results are obtained for the case where the measurement noise is small.
A Model of the Baroreceptor Reflex Neural Network

The baroreceptor vagal reflex is an important part of the cardiovascular control system. It may be defined as the biological neural control system responsible for the short-term blood pressure regulation. A simplified scheme of the baroreceptor vagal reflex circuit is the following. Baroreceptors located in the great arteries provide the sensory information to second-order neurons located in the nucleus tractus solitarii (NTS) in the lower brainstem [5]. Via a network of intemeurons, the second-order neurons affect motor neurons which in turn control heart rate and total peripheral resistance and thus blood pressure [3]. The firstorder neurons (baroreceptors) encode each pressUre pulse with a frequencyadapting train of spikes [1]. One of the mysteries of the identiiied baroreflex related second-order neurons in NTS is that in spite of receiving direct monosynaptic inputs from the first-order neurons, they do not show any pulse-rhythmic activity that contains the frequency Component corresponding to cardiac frequency.
Identifying disruptions to the ecological balance of nature: a foraminiferal example across the initiation of the Paleocene–Eocene thermal maximum

Deriving ecological and evolutionary descriptions of, and implications from, faunal assemblage patterns is commonly addressed by observation and a variety of exploratory techniques (scaling and clustering), along with qualitative evaluations of species occurrences and relative abundances. We argue that interpretations of faunal patterns, especially those documented by the fossil record, should be based upon the composition and structure of entire communities to provide strong conclusions and replicable results.As an example, we use benthic foraminiferal data at high resolution (1–2 cm, corresponding to 300–1400 yr) over a section corresponding to about 20 kyr across the beginning of the Paleocene–Eocene thermal maximum (PETM). The PETM was an episode of rapid global warming about 55.5 Ma, associated with ocean acidification and lowered open oceanic productivity and deoxygenation and marked by severe turnover in benthic foraminiferal assemblages. Here we provide a stand-alone approach applicable to any dynamic faunal system, perturbation detection analysis (PDA), to recognize and identify community disruption evidenced as either positive growth or negative decline, and we use this methodical approach to obtain new information on foraminiferal communities before, during, and after the initiation of the PETM.We conclude that the late Paleocene benthic foraminiferal community (FCOM1) was in a growth stage of positive increasing diversity, suggestive of favorable environmental conditions. This stage continued through the initial changes at the onset of the PETM, when disruption through environmental stress led to this community's termination. A second community (FCOM2) formed with declining diversity and high variability, showing a lack of adaptation to changing conditions. Knowledge of total assemblage status under both adverse and advantageous conditions is necessary, but not recognized by methods that rely upon analysis of single samples only: individual samples cannot be used to recognize disruptive changes in a community's structure, but these are easily identified using PDA.
Thermomechanical Modeling of High-Temperature Bonded Interface Materials

In an automotive power electronics package, bonded interface materials play a critical role in providing a smooth heat dissipation path from the device to the coolant. However, these materials are susceptible to failure when the package gets exposed to repeated changes in its thermal environment and internal temperature variations. Under these thermal conditions, the coefficient of thermal expansion mismatch between the different component layers results in thermally induced stresses and consequently the delamination of the material from its adjoining surfaces or crack initiation and propagation within the material. Thermomechanical modeling offers a path to study the complex nature of these bonded materials, guides their design and selection, and, in conjunction with experimental results, plays an important role in predicting their lifetime. In this chapter, two modeling strategies—similar in approach and implementation but different in the underlying theory—are discussed in the context of high-temperature bonded materials. In addition, a short review of sintered silver is provided, as it is widely seen as a potentially promising and reliable bonded material for high-temperature applications.
Generation of an induced pluripotent stem cell line (TRNDi004-I) from a Niemann-Pick disease type B patient carrying a heterozygous mutation of p.L43_A44delLA in the SMPD1 gene.

Abstract Niemann-Pick disease type B (NPB) is a rare autosomal recessive lysosomal storage disease caused by mutations in the SMPD1 gene, which encodes for acid sphingomyelinase. A human induced pluripotent stem cell (iPSC) line was generated from dermal fibroblasts of a 1-year old male patient with NPB that has a heterozygous mutation of a p.L43_A44delLA of SMPD1 using non-integrating Sendai virus technique. This iPSC line offers a useful resource to study the disease pathophysiology and as a cell-based model for drug development to treat NPB.
Short implants: are they a viable option in implant dentistry?

Abstract Short-length implants (<10 mm) can be used effectively in atrophic maxillae or mandibles even with crown/implant ratios that previously would have been considered excessive. Short implants can support either single or multiple units and can be used for fixed prostheses or overdentures. The use of short-length implants may avoid the need for complicated bone augmentation procedures, thus allowing patients who were either unwilling or unable for financial or medical reasons to undergo these advanced grafting techniques to be adequately treated.
The Clumsy Horse: A Professional Development Tool for Facilitators of Self-Directed, Case-Based Learning.

Introduction With the constant evolution of science and advancing technology, future physicians must learn to navigate an ever-changing health care environment by continuous learning throughout the...
Rare Disaster Concerns Everywhere

We propose an empirical framework of disaster concerns to explain cross-sectional return variation both within and across asset classes. Using a large set of out-of-the-money options on international equity indices, foreign currencies, and global government bonds, we measure the global …nancial market’s rare disaster concerns under only no-arbitrage conditions. Assets that have low return covariations with such concerns earn high excess returns in the future. The return predictability driven by rare disaster concerns is distinct from that driven by exposures to realized disaster shocks such as macroeconomic downturns and liquidity crunches, and is not
A non-contacting system for rail neutral temperature and stress measurements: Concept development:

Continuous welded rail has become the standard in modern railway track construction around the world because it alleviates well-documented disadvantages of rail joints in a track. Continuous welded...
Performance of an advanced heat recovery ventilation system in the Canadian Arctic

A demonstration house was previously built and commissioned in Iqaluit, Nunavut, Canada. The purpose of the overall effort is to develop and integrate technologies and evaluate the performance of a...
Developing Criteria and Associated Instructions for Consistent and Useful Quality Improvement Study Data Extraction for Health Systems.

The Agency for Healthcare Research and Quality (AHRQ) could devote resources to collate and assess quality improvement studies to support learning health systems (LHS) but there is no reliable data on the consistency of data extraction for important criteria. We identified quality improvement studies and evaluated the consistency of data extraction from two experienced independent reviewers at three time points: baseline, first revision (where explicit instructions for each criterion were created), and final revision (where the instructions were revised). Six investigators looked at the data extracted by the two systematic reviewers and determined the extent of similarity on a scale of 0 to 10 (where 0 represented no similarity and 10 perfect similarity). There were 42 assessments for baseline, 42 assessments for the first revision, and 42 assessments for the final revision. We asked two LHS participants to assess the relative value of our criteria. The consistency of extraction improved from 1.17 ± 1.85 at baseline to 6.07 ± 2.76 after revision 1 (P < 0.001) and to 6.81 ± 1.94 out of 10 for the final revision (P < 0.001). However, the final revision was not significantly improved over the first revision (P = 0.14). One key informant rated the difficulty in finding and using quality improvement studies a 6 (moderately difficult) while the other a 4 (moderately difficult). When asked how valuable it would be if AHRQ found and collated the demographic information about the health systems and the interventions used in published quality improvement studies, they rated it a 9 (highly valuable) and a 6 (moderately valuable). Creating explicit instructions for extracting data for quality improvement studies helps enhance the consistency of data extraction. This is important because it is difficult for LHS to vet these quality improvement studies on their own and they would value AHRQ’s support in that regard.
Clinical Perspectives: Breast Cancer Brain Metastasis

The incidence of central nervous system metastasis from primary breast cancer has steadily increased with aggressive chemotherapy resulting in improved long-term survival. Brain metastases are more common among those with more aggressive histological subtypes of breast cancer such as triple negative and HER2-positive subtypes. Effectiveness of pharmacological treatment for brain metastases is hindered by the blood–brain barrier. As such, current standard-of-care treatment modalities for CNS metastases include microsurgical resection, whole-brain radiation therapy, and stereotactic radiosurgery, either alone or in combination. Despite providing good local control, involvement of the CNS remains a devastating complication of breast cancer significantly limiting patient survival and quality of life. Leptomeningeal disease is a particularly devastating neurological complication of breast cancer and has limited treatment options. Overall prognosis of breast cancer brain metastasis remains dismal with 1- and 2-year survival rates of 20 % and 2 %, respectively. Clearly, there is a dire need to identify biomarkers permitting earlier and accurate diagnosis of CNS metastases, development of prevention strategies in high-risk individuals, and establishing more effective treatment options such as targeted systemic and intrathecal therapies.
Functional and Structural Aging of the Vestibular System

Purpose Aging is ubiquitous and the elderly population (aged 65 years and older) will continue to grow, reaching an estimated 25% of the U.S. population by 2060. Symptoms of dizziness and imbalance...
Prediction of Suicide-Related Events by Analyzing Electronic Medical Records from PTSD Patients with Bipolar Disorder.

Around 800,000 people worldwide die from suicide every year and it’s the 10th leading cause of death in the US. It is of great value to build a mathematic model that can accurately predict suicide especially in high-risk populations. Several different ML-based models were trained and evaluated using features obtained from electronic medical records (EMRs). The contribution of each feature was calculated to determine how it impacted the model predictions. The best-performing model was selected for analysis and decomposition. Random forest showed the best performance with true positive rates (TPR) and positive predictive values (PPV) of greater than 80%. The use of Aripiprazole, Levomilnacipran, Sertraline, Tramadol, Fentanyl, or Fluoxetine, a diagnosis of autistic disorder, schizophrenic disorder, or substance use disorder at the time of a diagnosis of both PTSD and bipolar disorder, were strong indicators for no SREs within one year. The use of Trazodone and Citalopram at baseline predicted the onset of SREs within one year. Additional features with potential protective or hazardous effects for SREs were identified by the model. We constructed an ML-based model that was successful in identifying patients in a subpopulation at high-risk for SREs within a year of diagnosis of both PTSD and bipolar disorder. The model also provides feature decompositions to guide mechanism studies. The validation of this model with additional EMR datasets will be of great value in resource allocation and clinical decision making.
The Sizes of the X-ray and Optical Emission Regions of RXJ1131-1231

We use gravitational microlensing of the four images of the z=0.658 quasar RXJ1131-1231 to measure the sizes of the optical and X-ray emission regions of the quasar. The (face-on) scale length of the optical disk at rest frame 400 nm is 1.3 10^15cm, while the half-light radius of the rest frame 0.3-17 keV X-ray emission is 2.3 10^14cm. The formal uncertainties are factors of 1.6 and 2.0, respectively. With the exception of the lower limit on the X-ray size, the results are very stable against any changes in the priors used in the analysis. Based on the Hbeta line-width, we estimate that the black hole mass is ~10^8 Msun, which corresponds to a gravitational radius of r_g~2 10^13 cm. Thus, the X-ray emission is emerging on scales of ~10r_g and the 400 nm emission on scales of ~70 r_g. A standard thin disk of this size should be significantly brighter than observed. Possible solutions are to have a flatter temperature profile or to scatter a large fraction of the optical flux on larger scales after it is emitted. While our calculations were not optimized to constrain the dark matter fraction in the lens galaxy, dark matter dominated models are favored. With well-sampled optical and X-ray light curves over a broad range of frequencies there will be no difficulty in extending our analysis to completely map the structure of the accretion disk as a function of wavelength.
Hypertrophic cardiomyopathy ß-cardiac myosin mutation (P710R) leads to hypercontractility by disrupting super-relaxed state: multiscale measurements and computational modeling

Abstract Hypertrophic cardiomyopathy (HCM) is the most common inherited form of heart disease, associated with over 1000 mutations, many in β-cardiac myosin (MYH7). Molecular studies of myosin with different HCM mutations have revealed a diversity of effects on ATPase and load-sensitive rate of detachment from actin. It has been difficult to predict how such diverse molecular effects combine to influence forces at the cellular level and further influence cellular phenotypes. This study focused on the P710R mutation that dramatically decreases in vitro motility and actin-activated ATPase, in contrast to other MYH7 mutations. Optical trap measurements of single myosin molecules revealed that this mutation reduced the step size of the myosin motor and the load-sensitivity of the actin detachment rate. Conversely, this mutation destabilized the super-relaxed state in larger, two-headed myosin constructs, freeing more heads to generate force. Micropatterned hiPSC-cardiomyocytes CRISPR-edited with the P710R mutation produced significantly increased force (measured by traction force microscopy) compared with isogenic control cells. The P710R mutation also caused cardiomyocyte hypertrophy and cytoskeletal remodeling, as measured by immunostaining and electron microscopy. Cellular hypertrophy was prevented in the P710R cells by inhibition of ERK or Akt. Finally, we used a computational model that integrates measured molecular changes to demonstrate that closely predict the measured traction forces. These results confirm a key role for regulation of the super-relaxed state in driving hypercontractility in HCM and demonstrate the value of a multiscale approach in revealing key mechanisms of disease. Significance Statement Heart disease is the leading cause of death world wide, and hypertrophic cardiomyopathy (HCM) is the most common inherited form of heart disease, affecting over 1 in 200 people. Mutations in myosin, the motor protein responsible for contraction of the heart, are a common cause of HCM but have diverse effects on the biomechanics of the myosin protein that can make it difficult to predict the combined effects of each mutation. We demonstrate that complex biomechanical effects of mutations associated with heart disease can be effectively studied and understood using a multi-scale experimental and computational modeling approach. This work can be extended to aid in the development of new targeted therapies for patients with different mutations.
Community Health Behaviors and Geographic Variation in Early-Onset Colorectal Cancer Survival Among Women.

INTRODUCTION Despite overall reductions in colorectal cancer (CRC) morbidity and mortality, survival disparities by sex persist among young patients (age <50 years). Our study sought to quantify variance in early-onset CRC survival accounted for by individual/community-level characteristics among a population-based cohort of US women. METHODS Geographic hot spots-counties with high early-onset CRC mortality rates among women-were derived using 3 geospatial autocorrelation approaches with Centers for Disease Control and Prevention national mortality data. We identified women (age: 15-49 years) diagnosed with CRC from 1999 to 2016 in the National Institutes of Health/National Cancer Institute's Surveillance, Epidemiology, and End Results program. Patterns of community health behaviors by hot spot classification were assessed by Spearman correlation (ρ). Generalized R values were used to evaluate variance in survival attributed to individual/community-level features. RESULTS Approximately 1 in every 16 contiguous US counties identified as hot spots (191 of 3,108), and 52.9% of hot spot counties (n = 101) were located in the South. Among 28,790 women with early-onset CRC, 13.7% of cases (n = 3,954) resided in hot spot counties. Physical inactivity and fertility were community health behaviors that modestly correlated with hot spot residence among women with early-onset CRC (ρ = 0.21 and ρ = -0.23, respectively; P < 0.01). Together, individual/community-level features accounted for distinct variance patterns in early-onset CRC survival among women (hot spot counties: 33.8%; non-hot spot counties: 34.1%). DISCUSSION Individual/community-level features accounted for approximately one-third of variation in early-onset CRC survival among women and differed between hot spot vs non-hot spot counties. Understanding the impact of community health behaviors-particularly in regions with high early-onset CRC mortality rates-is critical for tailoring strategies to reduce early-onset CRC disparities.
The Potential of Artificial Intelligence in Higher Education

Artificial Intelligence (AI) is seeping into many aspects of our everyday lives, with common internet applications, smartphones and even household appliances. Within education, AI is a rapidly emerging field and there is a strong potential for AI to greatly extend and enhance teaching and learning in higher education (Crompton et al., 2020). AI is defined as “computing systems that are able to engage in human-like processes such as learning, adapting, synthesizing, self-correction and use of data for complex processing tasks” (Popenici & Kerr, 2017). In the Horizon Report 2020 report (Brown et al., 2020), AI is listed as one of six technologies with the potential for high impact in higher education. The Horizon Report (2020), is an annual publication that examines the major trends in educational technology that are shaping global higher education. This paper will highlight some of the ways AI is supporting both students and faculty members including bespoke learning, intelligent tutoring systems, facilitating collaboration, and automated grading. This is followed by a section on ethical implications.
The New Landsat Global Land Survey (GLS) DEM

The Landsat project, for its Collection 2 distribution, is going to introduce a new global Digital Elevation Model (DEM) for scene orthorectification. The new global DEM is a composite of the latest and greatest available DEM sources and will include reprocessed SRTM (called NASADEM), hi-resolution stereo optical data (ArcticDEM), and various nationally produced datasets. With exception of a few places, most of the world will have the updated DEM, with improvements in absolute vertical accuracy and horizontal improvements of up to 360 meters (12 Landsat 30m pixels). This new DEM will be used to process all the scenes from Landsat 1–8 in Collection 2 processing and will be made available to public in Summer 2020.
Post-Recall Stock Market Signals: The Impact of Ad Spending on Sales Performance

This research proposes and empirically tests whether adjustments to post-recall advertising spending strategy can be used as an effective tool to create a competitive advantage in resources, thus i...
Molecular Signatures of Chromosomal Instability Correlate With Copy Number Variation Patterns and Patient Outcome in IDH-Mutant and IDH-Wildtype Astrocytomas

Chromosomal instability due to mutations in genes guarding the stability of the genome is a well-known mechanism underlying tumorigenesis and malignant progression in numerous cancers. The effect of this process in gliomas is mostly unknown with relatively little research examining the effects of chromosomal instability on patient outcome and therapeutic efficacy, although studies have shown that overall/total copy number variation (CNV) is elevated in higher histologic grades and in cases with more rapid progression and shorter patient survival. Herein, we examine a 70-gene mRNA expression signature (CIN70), which has been previously shown to correlate tightly with chromosomal instability, in 2 independent cohorts of IDH-mutant astrocytomas (total n = 241), IDH-wildtype astrocytomas (n = 228), and oligodendrogliomas (n = 128). Our results show that CIN70 expression levels correlate with total CNV, as well as higher grade, progression-free survival, and overall survival in both IDH-mutant and IDH-wildtype astrocytomas. In oligodendrogliomas, these mRNA signatures correlate with total CNV but not consistently with clinical outcome. These data suggest that chromosomal instability is an underlying factor in aggressive behavior and progression of a subset of diffuse astrocytomas. In addition, chromosomal instability may in part explain the poor response of diffuse gliomas to treatment and may serve as a future therapeutic target.
Plant legacies and soil microbial community dynamics control soil respiration

Abstract Through litter and root inputs, plants modulate soil properties and the soil microbial communities around them. In turn, these changes in soil properties and microbial community composition can impact plant performance (i.e., plant-soil feedbacks). Many studies have focused on how plant-soil feedbacks affect plant performance and successional patterns, but studies on the impact of plant-soil feedbacks on ecosystem processes are rare. Our research focused on the potential of species-specific plant-soil feedbacks to affect rates of soil organic matter (SOM) decomposition. We conducted a “home vs. away” plant-soil feedback greenhouse experiment using two C3 grass species (Bromus inermis and Pascopyrum smithii) grown in C4 tallgrass prairie soil. We used a closed-circuit CO2 trapping method and isotopic analysis to differentiate between root-derived and SOM-derived CO2 production. Contrary to our predictions, plant-soil feedbacks on plant biomass were independent of the effects of plant-soil interactions on SOM-derived CO2 production, but we did detect a significant legacy of conditioning by B. inermis on subsequent total belowground respiration (i.e., total belowground respiration was higher in soils originally conditioned by B. inermis regardless of which plant species was currently growing in those soils). We attribute these results to the differential effects of these plant species on soil chemistry and soil microbes during the original conditioning phase. This is supported by the observation that differences in soil chemistry and bacterial community composition persisted in soils conditioned by different plant species throughout the entire experiment. Together these results suggest that plant-soil history is important for soil respiration and that differences in soil microbial communities induced by conditioning with different plant species may have lasting effects on ecosystem processes.
Medicare and Medicaid: An Anniversary to Remember

![Figure][1] President Lyndon B. Johnson signed legislation creating the Medicare and Medicaid programs on July 30, 1965. Although Medicare and Medicaid have not been without their critics—even at the time of enactment—there is no denying the effects of the program on the American
Open government initiatives in North America

The Obama Administration has initiated an open government policy for the United States to increase transparency, citizen participation and collaboration; the Mexican and Canadian governments have been pursuing similar efforts of their own. This panel will review the status of these initiatives with representatives from government agencies in the US and Mexico, as well as academic researchers who have been studying their progress and strategies. The panelists will discuss their experiences and insights into the process of making government more open and participatory, not only through conventional broadcast style website information, but also through increased citizen interaction through social media and Web 2.0 technologies, including twitter, Facebook, YouTube, tagging, and social bookmarking. Research on crowd sourcing, young voters and citizen-generated content will provide scholarly perspective on these initiatives.
Boundary Nevanlinna—Pick Interpolation Problems for Generalized Schur Functions

Three boundary multipoint Nevanlinna-Pick interpolation problems are formulated for generalized Schur functions. For each problem, the set of all solutions is parametrized in terms of a linear fractional transformation with a Schur class parameter.
A Diradical Route to Bioactive Natural Products and Their Analogs

Abstract In this chapter we describe the development and application of the intramolecular diyl trapping reaction (cycloaddition) to the total synthesis of hirsutene, capnellene, coriolin, and hypnophilin, as well as its application toward the synthesis of aphidicolin and dan analog of taxol®
Relations among suicidality, recent/frequent alcohol use, and gender in a Black American adolescent sample: a longitudinal investigation

OBJECTIVE: Examine longitudinally select factors that may contribute to suicide ideations and attempts in adolescents. METHOD: Using a multiple cohort research design, surveys were administered to a longitudinal sample of Black American adolescents aged 11-18 years. RESULTS: Two logistic growth models were tested with the probability of a suicide ideation (n = 977) and identified suicide attempt (n = 457) as the outcome variables and the recency and frequency of alcohol use and gender as the predictor variables. The recency and frequency of alcohol use was significantly related to suicide ideations and identified attempts in both females and males. These findings were differentiated based on the age effects for recency and frequency of alcohol use. More recent and frequent alcohol use among younger adolescents exacerbated probabilities of suicide ideations and identified suicide attempts compared to older adolescents. CONCLUSION: Results indicate that early systematic assessment of suicidal behavior and alcohol use in Black American adolescents can inform developmentally and culturally responsive prevention and intervention efforts. Language: en
The effect of water subcooling on film boiling heat transfer from vertical cylinders

The effect of subcooling on the film boiling heat transfer of water from vertical copper cylinders has been investigated experimentally using a transient quench technique. A lumped parameter model was utilized since the Blot numbers were always less than 0.05. The amount of subcooling varied from 0 K to 70 K and the initial cylinder wall temperatures were of the order of 1100 K. Heat transfer coefficient were measured at the midpoint of the cylinders and were obtained over quench times in which they were verified to be constant. Subcooling had a significant effect on both the film boiling heat transfer coefficient and the minimum film boiling temperature. As the subcooling varied from 0 K to 70 K, the h transfer coefficient increased by a factor of five. As the subcooling varied from 0 K to 60 K, the minimum film boiling temperature increased from approximately 600 K to 1000 K. An attempt to correlate the heat transfer coefficient data with a method recently proposed by Sakurai et al. was only successful at subcooled temperature differences less than 10 K. A modified correlation is presented using the Sakurai et al. parameters which better represents the data over the complete subcoolingmore » range.« less
A Review of “Investigative Journalism in China: Eight Cases in Watchdog Journalism”

What could be more timely in the wake of the WikiLeaks scandal than a book on the state of watchdog journalism in China, a country whose officials have studiously avoided commenting on any of the l...
Apicoplast targeting of a Toxoplasma gondii transmembrane protein requires a cytosolic tyrosine-based motif.

Toxoplasma gondii, like most apicomplexan parasites, possesses an essential relict chloroplast, the apicoplast. Several apicoplast membrane proteins lack the bipartite targeting sequences of luminal proteins. Vesicles bearing these membrane proteins are detected during apicoplast enlargement, but the means of cargo selection remains obscure. We used a combination of deletion mutagenesis, point mutations and protein chimeras to identify a short motif prior to the first transmembrane domain of the T. gondii apicoplast phosphate transporter 1 (APT1) that is necessary for apicoplast trafficking. Tyrosine 16 was essential for proper localization; any substitution resulted in misdirection of APT1 to the Golgi body. Glycine 17 was also important, with significant Golgi body accumulation in the alanine mutant. Separation of at least eight amino acids from the transmembrane domain was required for full motif function. Similarly placed YG motifs are present in apicomplexan APT1 orthologs and the corresponding N-terminal domain from Plasmodium vivax was able to route T. gondiiAPT1 to the apicoplast. Differential permeabilization showed that both the N- and C-termini of APT1 are exposed to the cytosol. We propose that this YG motif facilitates APT1 trafficking via interactions that occur on the cytosolic face of nascent vesicles destined for the apicoplast.
Costa Rica's Chinatown: The Art of Being Global in the Age of China

Inaugurated in its capital city of San Jose in 2012, Costa Rica's Chinatown represents the newest addition to a list of over 100 Chinatowns worldwide. Through ethnographic research on the project's construction, public debates, and fall-out, this paper analyzes how municipal efforts to enact urban revitalization were tied to a changing global landscape increasingly defined by China. In particular, I examine how planners, urban citizens, and ethnic Chinese community members use Chinatown as a space in which to debate and deploy competing visions of “the art of being global” based on their diverse valuations of China's significance to national identity and future development. The project's ultimate failure highlights how “world conjuring” efforts of this kind can undermine the multicultural histories and cosmopolitan ties that cities claim as the very source of their global difference and value.
FATAL MALARIA INFECTION IN TRAVELERS: NOVEL IMMUNOHISTOCHEMICAL ASSAYS FOR THE DETECTION OF PLASMODIUM FALCIPARUM IN TISSUES AND IMPLICATIONS FOR PATHOGENESIS

Plasmodium falciparum is a significant cause of morbidity and mortality in travelers to areas where the parasite is endemic. Non-specific clinical manifestations may result in failure to recognize malaria until autopsy, when it is often too late to obtain whole blood for microscopic evaluation. The use of immunohistochemical (IHC) assays in the detection of three P. falciparum antigens, histidine rich protein-2 (HRP-2), aldolase, and Plasmodium lactate dehydrogenase (pLDH), was evaluated in formalin-fixed paraffin-embedded autopsy tissues from five travelers to malaria-endemic areas, whose deaths were initially suspected to have been caused by other bacterial or viral hemorrhagic fevers. The HRP-2 assay was specific for P. falciparum, whereas the aldolase and pLDH assays also reacted with P. vivax. Immunostaining patterns were predominately cytoplasmic and membranous. P. falciparum antigens were detected in a variety of organs but were most abundant in the blood vessels of brain, heart, and lung tissues.