cssi/SciSciGPT-SciSciNet huggingface dataset:
Pre- and postnatal inflammatory mechanisms in chronic lung disease of preterm infants

Epidemiological data suggest a strong association between chorioamnionitis and the development of chronic lung disease in preterm infants. Increased concentrations of proinflammatory cytokines present in the amniotic fluid and the systemic fetal circulation seem to be important mediators in the early inflammatory response by recruiting and activating inflammatory cells and by inducing pathways of lung injury. As a consequence vascular cell adhesion molecules are upregulated and a marked infiltration of neutrophils and macrophages as well as an increased expression of interleukin-8 mRNA in the bronchoalveolar epithelium and in the interstitial tissue takes place. These antenatal events may prime the lungs such that various injurious factors in the postnatal period provoke an excessive inflammatory response: oxygen toxicity, mechanical ventilation, inappropriate resuscitation, pulmonary and systemic infections, persistent ductus arteriosus. Besides proinflammatory cytokines, toxic oxygen radicals, lipid mediators and potent proteases may be responsible for acute and chronic lung injury. In general, an imbalance between pro- and anti-inflammatory factors can be considered as a hallmark of lung injury, and may considerably affect normal alveolarisation and pulmonary vascular development by inducing growth arrest of the immature lung.
Collagen biosynthesis; tissue culture experiments to ascertain the role of ascorbic acid in collagen formation

Quantitative studies of collagen formation by chick embryonic lung tissue grown in media deficient in, or completely lacking, ascorbic acid have been carried out. Cell growth and collagen formation in such cultures can proceed almost normally in media lacking ascorbic acid. Ascorbic acid in combination with whole embryo extract, dialyzed media, or synthetic mixture number 703 was found to have no appreciable effect on cell growth or total collagen formation. This is in marked contrast to the almost total failure of collagen formation in scorbutic animals and suggests that for slow collagen biosynthesis as distinct from more prolific collagen-producing systems, ascorbic acid plays an indirect role.
Maintaining Accurate Math Responses in Elementary School Students: The Effects of Delayed Intermittent Reinforcement and Programming Common Stimuli.

This study examined the effect of delayed reinforcement on digits completed by elementary school children and the effect of programming stimuli common to reinforcement conditions on the maintenance of their performance. Participants exhibited similar levels of responding during intermittent and continuous reinforcement. Responding continued for a number of sessions at similar levels during a maintenance phase that included stimuli present during delayed reinforcement.
Student Preference for Case Studies: Enhanced Learning in a Human Physiology Course

Case studies offered in lecture sessions as an active learning strategy seek to engage students in critical thinking and facilitate guided inquiry. With large class sizes, it can be challenging to conduct in-depth critical thinking and cover the many topics in the syllabus. We have realized that long lectures can be boring while processoriented inquiry using case studies can encourage critical thinking and enhance student learning and complement shorter lectures. In this research, we demonstrate that, even with large class sizes, introducing case studies can increase understanding of a physiological concept. We also conclude that offering case studies in an early phase of the curriculum could promote students’ mastery in physiology.
Perfect light trapping in mid-IR using patterned ZnO structures (Presentation Recording)

Plasmonic assisted mid-IR light trapping using 1D grating structures patterned in Ga-ZnO is demonstrated. FDTD simulations of these structures with proper grating period and depth show the light trapping into a resonant mode resulting in a close to 100% reflection dip in the 4-8 µm wavelength regime. The 1D grating structures of different periods are fabricated using standard photolithography followed by etching. The resonant reflection dips in the experimentally measured spectra well agree with the FDTD simulation, exhibiting light trapping in the mid-IR as predicted.
Tyrosine Kinase-Deficient EphB6 Receptor-dependent Alterations in Proteomic Profiles of Invasive Breast Carcinoma Cells as Determined by Difference Gel Electrophoresis

The expression profiles of the erythropoietin producing hepatocellular carcinoma (Eph) receptor family of tyrosine kinases have been previously shown to provide molecular signatures of normal breast cells, breast tumor cells and invasive breast carcinoma cells. In particular, the expression of EphB6 receptor is lost in invasive breast carcinoma cell line MDA-MB-231. The comparative proteomic profiles of native and EphB6-expressing MDA-MB-231 cells using difference gel electrophoresis (DIGE) and liquid chromatography-mass spectrometry of selected proteins are presented in this study. The expression of more than 70 proteins was significantly altered in EphB6-transfected MDA-MB-231 cells. These altered proteins are involved in glycolysis, cell cycle regulation, tumor suppression, cell proliferation, mitochondrial metabolism, mRNA splicing, DNA replication and repair. Although the majority of these proteins have been implicated in tumorigenesis, the impairment of energy homeostasis and altered regulation of signaling pathways appear to be noteworthy targets of EphB6. Based on the identities of altered proteins and the pathways regulated by these proteins, this study suggests that the interactions of EphB6 with a wide variety of proteins lead to altered proteomic profile of EphB6-transfected MDA-MB-231 cells. The erythropoietin producing hepatocellular carcinoma (Eph) receptors are the largest family of receptor tyrosine kinases (1). These receptors are activated by their cognate ephrin ligands. Eph receptors and ephrin ligands are classified into A and B classes based on their sequence similarities. There are 14 Eph receptors and 9 ephrin ligands known in mammalian cells. These receptors have been well characterized for their involvement in brain development, axon guidance and angiogenesis (2). The role of these receptors and ligands is becoming increasingly important in cancer initiation and progression. While Eph receptors and ephrin ligands are known to be up-regulated in some cancers (3-5), EphB6 is lost in more aggressive/invasive breast cancers, melanomas and neuroblastomas (4, 6, 7). It has been previously shown that down-regulation of EphB6 is related to epigenetic silencing of this gene by promoter methylation (8), as confirmed by detection of the methylated promoter using methylation sensitive PCR (8, 9). It is interesting to note that, unlike other members of the Eph receptor family, EphA10 and EphB6 are kinase-deficient. To address the biological role of EphB6, its interacting partners were characterized by using a yeast two- hybrid system. The results of that study indicated the interaction of its cytoplasmic domain with intracellular proteins such as aldolaseA, dynactin, clusterin and plekstrin homology
The role of mycobacterial cell wall nucleic acid complex in the treatment of bacillus Calmette-Guerin failures for non-muscle-invasive bladder cancer.

Introduction:The treatment of high-risk non-muscle-invasive bladder cancer (NMIBC) utilizes transurethral resection followed by adjuvant intravesical immunotherapy or chemotherapy. Intravesical bacillus Calmette–Guerin (BCG) is the mainstay of adjuvant immunotherapy, but there are limited nonsurgical options for patients that fail this treatment. Mycobacterial cell wall nucleic acid complex (MCNA) is an immunotherapeutic agent utilized primarily after failure of intravesical BCG. The purpose of this paper is to provide a comprehensive review of the published literature regarding MCNA.Methods:A literature review was performed and identified studies indexed in MEDLINE® related to utilization of MCNA for patients with NMIBC.Results:Two trials assessed the efficacy of MCNA in patients with NMIBC, comprising a total of 184 patients. Most patients had carcinoma in situ (CIS) with (26%) or without (52%) concomitant papillary tumors. A minority of patients had only papillary tumors (22%). Most patients (95%) prev...
The Ethical Judgment of Private Club Senior Executives

ABSTRACTThe purpose of this study is to investigate effects of working experience and organization size on ethical judgments on ethical issues among senior private club executives. Senior club executives at small and large private clubs were given five vignettes, representing ethical dilemmas in five categories of ethical behavior identified by previous researchers. They were asked to determine whether each issue was a question of ethics or not (N = 413). The multivariate analysis of variance results indicate that senior executives working in the large-sized club with more than 20 years’ hospitality working experience tend to make higher ethical judgments on ethical issues.
Introduction to the Symposium on Wrongful Convictions: Issues of Science, Evidence and Innocence

It is hard to imagine an injustice greater than the incarceration or, worse yet, execution of an innocent. Especially in our system of justice, which purports to accept as a basic premise that it is better that ten guilty go free than that one innocent person be imprisoned, the incarceration of an innocent is simply intolerable. Yet it happens--and much more often than we would like to believe. Questions abound as to why and what can be done about it. The problem of wrongful convictions has been discussed for some time, but it has often been rejected or downplayed. It was only the advent of DNA technology, which makes it possible to definitively demonstrate that a person did not commit the crime for which he or she is incarcerated, that has forced doubters to acknowledge that wrongful convictions actually do occur. Unfortunately, the incidence of wrongful conviction is almost impossible to determine, because DNA evidence is not available in a large majority of cases. There is reason to believe, however, that the number of wrongfully convicted individuals should cause us to have real concern about how the criminal justice system is functioning. The problem of wrongful convictions must be addressed on several fronts. First, we must get a better understanding of what leads to such convictions in order to determine what can be done to remedy them. Next, we must find ways to identify those cases in which wrongful convictions have occurred and means by which to prove innocence and secure the inmate's release. Finally, it is crucially important that we focus as well on the larger, systemic issues to prevent such injustices from occurring. The articles in this Symposium cover many facets of wrongful convictions and do so in an interdisciplinary fashion. They span the geographic spectrum as well, with articles focusing on Missouri issues, as well as issues of national and international significance.
Inflatable penile prosthesis (IPP): diagnosis of complications

Inflatable penile prostheses are a common treatment for erectile dysfunction that is unresponsive to less-invasive measures. Complications can arise at the time of the placement of the prosthesis or at a later date. Complications may be related to infection and/or mechanical failure of one or more of the prosthesis components including cylinder, reservoir, pump, and tubing. Mechanical failure includes kinking, migration, and aneurysmal dilation of the cylinder, erosion of the tunica albuginea of the corpora cavernosum by the cylinder, disconnection of the tubing, and migration of the reservoir. MRI of the entire components with the cylinders in both flaccid and inflated states is the best imaging modality available to image patients with suspected implant complications.
Weights of Adult Gray Squirrels

Checking stations on West Virginia's state-owned forests offered technicians the opportunity to weigh 10,973 gray squirrels, Sciurus carolinensis Gmelin, during the October hunting seasons of 1949 through 1952. A total of 4050 squirrels were classified as adults and these are discussed in this paper. Age classifications were based on the examination of sexual organs as outlined by Allen (1943). Squirrel weights were obtained from specimens brought into the checking stations by hunters. Multilated and gutted squirrels were eliminated from the sample. The state-wide sample indicated little difference between the sexes; the males averaged 523 grams and the females 518 grams (Table 1). The results indicated that squirrels from the …
Studies on the mechanism of sodium excretion in uraemia.

1. A group of eight patients with advanced renal failure, and a creatinine clearance of 3·8–24 ml/min, were subjected to sodium loading and sodium depletion. 2. With sodium loading there was a consistent increase in blood pressure (0·01 3. Fractional reabsorption of filtered sodium was proportional to creatinine clearance both in the sodium-loaded (r = +0·86, 0·001 4. Urinary aldosterone excretion and plasma renin activity consistently increased with sodium depletion, the percentage increases of the two being significantly related (r = +0·95, P 5. The results suggest that excretion of a sodium load in uraemia may be effected in part as the result of a raised blood pressure that elevates the glomerular filtration rate; by increasing the peritubular capillary pressure this may be responsible for the observed decrease in reabsorption of filtered sodium. The responsiveness of glomerular filtration rate to blood pressure changes suggests a decrease in afferent arteriolar tone that may account for the increased sodium excretion per nephron which occurs even in uraemic patients without hypertension. 6. It is suggested that aldosterone may continue to play an important regulatory role in sodium homeostasis in uraemia and that renin concentrations are the major determinants of aldosterone production in uraemia.
An ultra-wideband millimeter-wave phased array

Wideband millimeter-wave arrays are of increasing importance due to their growing use in high data rate systems, including 5G communication networks. In this paper, we present a new class of ultra-wideband millimeter wave arrays that operate from nearly 20 GHz to 90 GHz. The array is based on tightly coupled dipoles. Feeding designs and fabrication challenges are presented, and a method for suppressing feed resonances is provided.
Research on the Practical Technique of State Estimation for Power System Dispatching and Its Application

State estimation( SE) is one of the basic functional modules for power dispatching control center. Making a summary of the technologies and application of SE in the preceding decades,this paper proposes practical techniques with parameter management,system debug and indicator analysis to further improve the practicality of SE. A case study on the 220 kV and above power grids of CSG demonstrates the effectiveness and feasibility of the proposed method.
Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord

Circuit function in the CNS relies on the balanced interplay of excitatory and inhibitory synaptic signaling. How neuronal activity influences synaptic differentiation to maintain such balance remains unclear. In the mouse spinal cord, a population of GABAergic interneurons, GABApre, forms synapses with the terminals of proprioceptive sensory neurons and controls information transfer at sensory-motor connections through presynaptic inhibition. We show that reducing sensory glutamate release results in decreased expression of GABA-synthesizing enzymes GAD65 and GAD67 in GABApre terminals and decreased presynaptic inhibition. Glutamate directs GAD67 expression via the metabotropic glutamate receptor mGluR1β on GABApre terminals and regulates GAD65 expression via autocrine influence on sensory terminal BDNF. We demonstrate that dual retrograde signals from sensory terminals operate hierarchically to direct the molecular differentiation of GABApre terminals and the efficacy of presynaptic inhibition. These retrograde signals comprise a feedback mechanism by which excitatory sensory activity drives GABAergic inhibition to maintain circuit homeostasis.
Evaluation of the Catalytic Contribution from a Positioned General Base in Ketosteroid Isomerase

Proton transfer reactions are ubiquitous in enzymes and utilize active site residues as general acids and bases. Crystal structures and site-directed mutagenesis are routinely used to identify these residues, but assessment of their catalytic contribution remains a major challenge. In principle, effective molarity measurements, in which exogenous acids/bases rescue the reaction in mutants lacking these residues, can estimate these catalytic contributions. However, these exogenous moieties can be restricted in reactivity by steric hindrance or enhanced by binding interactions with nearby residues, thereby resulting in over- or underestimation of the catalytic contribution, respectively. With these challenges in mind, we investigated the catalytic contribution of an aspartate general base in ketosteroid isomerase (KSI) by exogenous rescue. In addition to removing the general base, we systematically mutated nearby residues and probed each mutant with a series of carboxylate bases of similar pKa but varying s...
Abstract 15: Metabolomic profiling of cell death in human lung cancer cells by a novel digitoxin analog

Background: Digitoxin, a cardiac glycoside had shown considerable promise as an anti-cancer therapeutic. However, doses of digitoxin required to inhibit cancer cell proliferation lead to cardiotoxic side effects. We have previously shown that a novel analog of digitoxin, MonoD, activates apoptosis in human lung cancer cells at much lower concentrations as compared to digitoxin. We postulate that treatment with MonoD leads to distinct metabolic signatures on lung cancer cells as compared to digitoxin, which will help delineate the pathways that dictate MonoD action. Experimental Approach: NCI-H460 cells from identical passages were used for metabolite analysis using an optimized version of the methanol/water (80:20) protocol for metabolite extraction. The supernatant containing metabolites were suspended in 0.1% formic acid spiked with an internal standard for Q-Exactive analysis. The data was analyzed using SIEVETM 2.0 software with the component extraction algorithm that has been specifically designed for optimal data analysis in untargeted metabolomics experiments. Metabolites that were found to be significantly different between treatment groups were detected via Chemspider/HMDB database search. Results: We observed several metabolites along the prostaglandin synthesis pathway which were downregulated in MonoD treated lung cancer cells. Prostaglandins play a key role in the generation of the inflammatory response. Chronic inflammation has been shown to be a causative factor in a variety of cancers. Cyclooxygenase‐2 (COX-2) derived prostaglandin has been previously shown to promote tumor growth by binding its receptors and activating signaling pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Using the metabolite profiling data, we posited that COX-2, a key enzyme involved in prostaglandin synthesis, in addition to NFκB, a key transcription factor of proinflammatory signaling pathway are downregulated with MonoD treatment. Immunoblotting confirmed the downregulation of COX-2 and NFκB in MonoD-treated cells. Conclusion: Using metabolite profiling, we have elucidated an important mode of action for MonoD in lung cancer cells, and shown that MonoD exerts its anti-tumorigenic properties by downregulating key factors involved in inflammatory response. Citation Format: Yogesh Kulkarni, Neelam Azad, Vivek Kaushik, Juan Sebastian Yakisich, Rajkumar Venkatadri, Clayton Wright, Yon Rojanasakul, George O’Doherty, Anand Krishnan V Iyer. Metabolomic profiling of cell death in human lung cancer cells by a novel digitoxin analog. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 15.
Mitochondrial Disorders Causing Cardioskeletal Myopathies in Childhood

Abstract Mitochondria are important organelles that are found in all nucleated human cells. They perform a variety of essential functions, including hosting pathways of intermediary metabolism, generating cellular energy in a form of adenosine trinucleotide phosphate, maintaining calcium homeostasis in excitable cell types, charging the creatine kinase circuit in muscle and brain, regulating cell death programs such as apoptosis, and participating in cell cycle control through retrograde signaling. Genetic mitochondrial disorders can result in deleterious effects on tissues that have high energy demands such as skeletal muscle, brain, and heart, but can also lead to disorders of virtually any organ or cell type. Defects in mitochondrial DNA can give rise to mitochondrial respiratory chain disorders, as can a large number of nuclear gene defects, often manifesting as skeletal and cardiac muscle disease. In addition, given the dependence of muscle on fatty acids for energy, certain long chain fatty acid oxidation disorders can mimic respiratory chain disorders. In this chapter, we will review a variety of mitochondrial disorders and their impact on cardiac function.
Evaluation of transimpedance amplifiers for readout of a position sensitive avalanche photodiode

BetaBox, a direct detection beta camera utilizing a 13.5×13.5mm2 active area position sensitive avalanche photodiode (PSAPD) (Radiation Monitoring Devices) is currently being developed to image distributions of charged particles in microfluidic chips. The previously reported signal processing chain incorporated charge sensitive amplifiers (Cremat Inc., CR-110) in the frontend readout design. Charge sensitive amplifiers, particularly the CR-110 product, are commonly used as preamplifiers when reading out PSAPDs. However, the 140µs pulse decay of this device suggests a possible count rate limitation in the performance of the beta camera. To address this limitation, the frontend readout was redesigned to replace the charge sensitive amplifiers with op-amps configured as transimpedance amplifiers. We hypothesize that, since the equivalent circuit of the PSAPD appears more like a charge division network loaded by a large semiconductor junction capacitance (∼150 pF) than an APD, this signal source can be optimally processed using the transimpedance amplifier approach. Results show that the designed signal processing chain using a transimpedance amplifier with 100ns RC time constant displays not only comparable image quality to the previous signal chain using the CR-110 but also reduced image distortion at high count rates.
Designing Well-Structured Cyclic Pentapeptides Based on Sequence–Structure Relationships

Cyclic peptides are a promising class of molecules for unique applications. Unfortunately, cyclic peptide design is severely limited by the difficulty in predicting the conformations they will adopt in solution. In this work, we use explicit-solvent molecular dynamics simulations to design well-structured cyclic peptides by studying their sequence–structure relationships. Critical to our approach is an enhanced sampling method that exploits the essential transitional motions of cyclic peptides to efficiently sample their conformational space. We simulated a range of cyclic pentapeptides from all-glycine to a library of cyclo-(X1X2AAA) peptides to map their conformational space and determine cooperative effects of neighboring residues. By combining the results from all cyclo-(X1X2AAA) peptides, we developed a scoring function to predict the structural preferences for X1–X2 residues within cyclic pentapeptides. Using this scoring function, we designed a cyclic pentapeptide, cyclo-(GNSRV), predicted to be we...
Acoustic Microscopy of Advanced Aerospace Materials

Ultrasonic Scanning Acoustic Microscopy (SAM) is useful for material elastic property quantification, surface and subsurface crack initiation detection and growth estimation, and fiber-matrix interfacial damage assessment [1–5]. The advantage of the method is that the imaging technique can provide the crack sizing information while helping in the detection of interface degradation and early crack initiation so that their growth can be monitored during interrupted fatigue tests. The scanning acoustic microscope technique has been applied in the past to metal matrix composites subjected to both room temperature and elevated temperature fatigue cycling in addition to thermomechanical fatigue (in-phase and out-of-phase) conditions. In this paper, we present results obtained from an in-house developed acoustic microscope operating in the frequency range of 25–200 MHz. Results of characterization of many aerospace materials such as metal matrix and ceramic matrix composites and titanium alloys are provided to demonstrate the versatility of the system.
Mechanistic Insights into the Polyglutamine Ataxias

Several hypotheses have been advanced in order to explain the molecular mechanisms by which expanded polyglutamine (polyQ) triggers neurodegeneration. In this chapter, we discuss the experimental evidence supporting the leading hypotheses in the field. In particular, we focus on the mechanisms by which abnormal protein folding, oligomerization, and aggregation may impair neuronal function and survival in the dominant spinocerebellar ataxias (SCAs) caused by polyQ expansion.
An in-depth characterization of a large cohort of adult patients with eosinophilic esophagitis.

Abstract Background Eosinophilic esophagitis (EoE) is a chronic, allergic, immune-mediated disease associated with increased risk of comorbid atopic conditions. Objective To perform an in-depth characterization of a large cohort of manually verified adult patients with EoE, including evaluation of less studied associations, such as pollen food allergy syndrome, anaphylaxis, autoimmunity, and psychiatric comorbidities. Methods We performed a manual retrospective electronic medical record review of 1,218 patients with EoE identified by International Classification of Diseases, Ninth Revision and International Classification of Disease, 10th Revision codes from the University of Pennsylvania Health Systems. Through manual medical record review, we evaluated patient demographics, family and smoking history, laboratory and endoscopic findings, treatment, and comorbid atopic, autoimmune, and psychiatric conditions. Results A total of 950 of the 1,218 patients had biopsy-proven EoE. This cohort was predominantly male, white, and never-smokers who presented most commonly with dysphagia, with an initial biopsy results showing 49 eosinophils per high-powered field, a serum absolute eosinophilic count of 446,000/µL, and mean total IgE level of 243 IU/mL. Of the patients, 55% had impaction (of which 38% required endoscopic removal), and 56% had strictures or fibrosis (of which 56% underwent dilatation). Therapy used was predominantly (77%) medical only. Comorbid atopy, pollen food allergy syndrome, drug allergy, anaphylaxis, autoimmunity, and psychiatric illnesses were higher in the EoE cohort compared with the general University of Pennsylvania Health Systems population. Conclusion Our adult cohort of manually verified, biopsy-proven EoE had an increased risk of pollen food allergy syndrome, anaphylaxis, and comorbid autoimmune and psychiatric conditions compared with the University of Pennsylvania Health Systems population. There was also an increased prevalence of impaction and stricture or fibrosis requiring endoscopic intervention compared with the pediatric population.
Educational Competitions to Boost the Cyber Workforce-Development

Cyber Defense Competitions are widely known throughout collegiate institutions. The Department of Energy and Argonne National Laboratory set out to develop a more extensive educational competition that would build up cyber workforcedevelopment for the Energy Sector. Utilizing hands-on training, the Department of Energy and the national laboratories seek to increase the effectiveness and interest in cybersecurity careers for the Energy Sector.
Physiological Actions and Receptors

Prolactin has become highly specialized in mammals to play important roles in reproduction. The core physiological actions of prolactin in mammals are antigonadotropic and pro-lactogenic. These core physiological functions drive the most obvious pathological consequences of excess prolactin secretion (hyperprolactinemia). The few known examples of isolated prolactin deficiency have been characterized by alactogenesis without other discernable consequences.
Sport as a tool for community leaders of people with disabilities: exploring an innovative, immersive exchange training program

Research question: The purpose of this study was to explore how an immersive mentorship and cultural exchange program may be structured to empower disability sport community leaders to face barrier...
Rabbit Annulus Fibrosus Cells Express Neuropeptide Y, Which Is Influenced by Mechanical and Inflammatory Stress.

Objective Rabbit annulus fibrosus (AF) cells were exposed to isolated or combined mechanical and inflammatory stress to examine the expression of neuropeptide Y (NPY). This study aims to explore the ability of AF cells to produce NPY in response to mechanical and inflammatory stress. Methods Lumbar AF cells of 6- to 8-month-old female New Zealand white rabbits were harvested and exposed to combinations of inflammatory (interleukin-1β) and mechanical (6% or 18%) tensile stress using the Flexcell System. NPY concentrations were measured in the media via enzyme-linked immunosorbent assay. The presence of NPY receptor-type 1 (NPY-1R) in AF cells of rabbit intervertebral discs was also analyzed via immunohistochemistry and immunofluorescence. Results Exposure to inflammatory stimuli showed a significant increase in the amount of NPY expression compared to control AF cells. Mechanical strain alone did not result in a significant difference in NPY expression. While combined inflammatory and mechanical stress did not demonstrate an increase in NPY expression at low (6%) levels of strain, at 18% strain, there was a large-though not statistically significant-increase in NPY expression under conditions of inflammatory stress. Lastly, immunofluorescence and immunohistochemistry of AF cells and tissue, respectively, demonstrated the presence of NPY-1R. Conclusion These findings demonstrate that rabbit AF cells are capable of expressing NPY, and expression is enhanced in response to inflammatory and mechanical stress. Because both inflammatory and mechanical stress contribute to intervertebral disc degeneration (IDD), this observation raises the potential of a mechanistic link between low back pain and IDD.
Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 at a Tertiary Care Medical Center in New York City.

Objective To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with coronavirus disease 2019 (COVID-19). Study design Children 1 month to 21 years of age with COVID-19 from a single tertiary care children's hospital between March 15 and April 13, 2020 were included. Demographic and clinical data were collected. Results In total, 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (P = .99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (P Conclusions We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.
Constant observation of pediatric patients at risk for self-harm and suicide: An evidence-based practice inquiry

Suicide is a leading cause of death for pediatric patients in the United States. The utilization of protective observation strategies, namely constant observation, is a regulatory recommendation as part of a comprehensive suicide prevention plan for hospitalized behavioral health patients. Constant observation is the increased level of observation and supervision with continuous one-to-one monitoring techniques, taken to assure the safety and well-being of a patient and others in the patient care environment (Moore et al., 1995). This evidence-based practice inquiry describes a search for the best evidence on constant observation practices ensuring the safe care of pediatric patients at risk for self-harm or suicide. The findings included no high-level evidence, however four literary themes related to the challenges of constant observation emerged: confusing language and definitions, untested models of care, important privacy issues and lack of pediatric observation strategies for patients at risk for self-harm and suicide. Impaired communication underscored each of the themes.
Development and application of a decision tree to determine appropriate handling of gene therapies

Background & Aim Executives at the Food and Drug Administration (FDA) state that by the year 2025, there will be 10 to 20 cell and gene therapy (GT) product approvals per year. Current infrastructure is not sufficient to accommodate the spike in GT at most healthcare facilities. Furthermore, few healthcare providers (HCP) are trained to assess the risk of GT, or to implement safe handling strategies. Containment of GT, from entry to exit, requires a customized approach dictated by the construct of the vector. The risk of hazardous exposure to a novel therapy is amplified when containment procedures are undefined. Uncertainty regarding GT handling is due to a lack of relevant contemporary information and training. The outdated guidance's are drafted for pre-clinical laboratories, and many HCP are forced to extrapolate them to alternate settings. Recent papers have attempted to bridge the gap, but there is much work to be done with GT risk level identification, infrastructure establishment, and policy development. This presentation aims to describe a decision tree that sends the HCP on a rational path toward safe handling, by taking precautions that match the risk level of the GT vector. Methods, Results & Conclusion The method to eliminate vector exposure is by careful consideration of its replication status, integration ability, carcinogenicity, and toxicity. Vectors that are replication deficient, do not integrate into the host genome, and are otherwise not hazardous, are routed toward minimal handling precautions on the decision tree. However, if any of these factors, or a combination of them are present in a vector, the routing process dictates a more cautious approach. Importantly, influences such as capsid size and seroconversion are being added to the current body of knowledge to form the decision tree. Escalated handling precautions involves moving from Biosafety Level 1 (BSL1) to Biosafety Level 2 (BSL2) or 3. Two vectors, one using Adeno-associated virus (AAV), and the other incorporating the Herpes Simplex Virus (HSV-1) are routed through the decision tree. Because AAV is non-replicating, does not integrate into the host genome, and is non-toxic, it is reasonable to infer that handling can be performed in a BSL1 environment. However, since HSV-1 is replication competent and integrates into the host genome, BSL2 is a prudent recommendation. The decision tree provides a safety tool for HCP tasked with GT handling. Its application depends on modern infrastructure, focused training, and clear policy.
Runoff inflow volumes to the Highland Lakes in Central Texas: temporal trends in volumes, and relations between volumes and selected climatic indices

Inflow to the Highland Lakes has substantially decreased from 1942–2013, likely due to increased evapotranspiration from the proliferation of 19 major upstream reservoirs and about 69,500 minor reservoirs and water bodies. Increased evapotranspiration from land surfaces and stream channels also probably represent major causes for inflow reduction. Eight climatic indices were evaluated with respect to correlations with inflow volumes to the lakes. A combination of the indices for the Atlantic Multidecadal Oscillation and Oceanic Nino Index (Nino 3.4 region) was found to be, up to three months in advance, a fair indicator for the wettest three-month inflow periods, and a good indicator, up to nine months in advance, of the driest three-month inflow periods. The single best index indicator of dry periods is the Pacific Decadal Oscillation—a good indicator of the driest three-month periods up to a year in advance. Citation: Slade RM Jr. 2020. Runoff inflow volumes to the Highland Lakes in Central Texas: temporal trends in volumes and relations between volumes and selected climatic indices. Texas Water Journal. 11(1):32-60. Available from: https://doi.org/10.21423/twj.v11i1.7025.
Law and Religion: Reimagining the Entanglement of Two Universals

In the last few decades, the study of law and religion has undergone considerable reconstruction. Less and less constrained by modern statist construals of rights talk or tied to confessional conte...
The NCA-1 and NCA-2 ion channels function downstream of Gq and Rho to regulate locomotion in C. elegans

The heterotrimeric G protein Gq positively regulates neuronal activity and synaptic transmission. Previously, the Rho guanine nucleotide exchange factor Trio was identified as a direct effector of Gq that acts in parallel to the canonical Gq effector phospholipase C. Here we examine how Trio and Rho act to stimulate neuronal activity downstream of Gq in the nematode Caenorhabditis elegans. Through two forward genetic screens, we identify the cation channels NCA-1 and NCA-2, orthologs of mammalian NALCN, as downstream targets of the Gq/Rho pathway. By performing genetic epistasis analysis using dominant activating mutations and recessive loss-of-function mutations in the members of this pathway, we show that NCA-1 and NCA-2 act downstream of Gq in a linear pathway. Through cell-specific rescue experiments, we show that function of these channels in head acetylcholine neurons is sufficient for normal locomotion in C. elegans. Our results suggest that NCA-1 and NCA-2 are physiologically relevant targets of neuronal Gq-Rho signaling in C. elegans.
Physician leadership during the COVID-19 pandemic: An emphasis on the team, well-being and leadership reasoning

Background The COVID-19 pandemic impacted many aspects of normal operations in academic medicine. While effective leadership is always important, the intensity and urgency of COVID-19 challenged academic medicine leaders to find new ways to lead their institutions and manage their own experiences of the pandemic. Methods Sixteen physician leaders from Michigan Medicine took part in semistructured interviews during April and May 2020. Participants were asked open-ended questions about the attributes and techniques that were important to effectively lead during a crisis. The authors analysed the interviews using thematic analysis. Results Participants described three overarching themes of leadership during the COVID-19 pandemic: (1) bringing together a diverse team with clear, shared goals; (2) using a range of strategies to tend to their teams’—as well as their own—well-being; and (3) engaging in leadership reasoning as a way of learning from others and reflecting on their own actions to inform their future leadership practice. Conclusion The results of this study reveal several salient themes of crisis leadership during the COVID-19 pandemic. The findings also highlight the role of leadership reasoning, a reflective practice employed by leaders to understand and improve their leadership skills. This finding presents leadership skill development as part of lifelong learning in medicine. Findings may be incorporated into best practices and preparations to inform future healthcare leaders.
Competition for Talent: The Impact of Venture Capital Investments on Incumbent Firms

This paper identifies a new channel, competition for talent, through which venture capital (VC) investments affect incumbent firms. Using a unique payroll dataset, I find that VC investments increase the wage growth of high-skilled workers at local incumbents, while there is no effect for low-skilled workers. This impact is particularly strong in regions with inelastic labor supply. Establishment-level high-skilled employment growth at incumbents is negatively correlated with local VC investments, but it is positively correlated with VC investments in other areas where the parent firm operates, highlighting the spillover effects of competition for talent through firms’ internal network of establishments.
Blue Ridge Bike and Hike

A small chain of retail stores selling outdoors equipment, Blue Ridge Bike and Hike (Blue Ridge) was expanding rapidly. The finance manager had to develop a financial plan for accommodating this growth and the investment it required. Clearly, the business was growing faster than could be financed from internal sources--it had been increasing a long-term loan and had just ended the year with a higher-than-usual balance on its bank line of credit. Excerpt UVA-F-1749 Rev. Dec. 23, 2019 Blue Ridge Bike and Hike Blue Ridge Bike and Hike (Blue Ridge) was expanding. In the mid-Atlantic region, the chain of outdoor equipment focused on bike touring and backpack camping had increased sales by 25% for each of the last two years and was expecting about 20% growth in 2015. Blue Ridge had achieved this sales growth through carefully designed store expansions and one new store opening that together leveraged the store's reputation for helpful and knowledgeable staff. Financing the recent growth had been accomplished with little planning. Blue Ridge had increased long-term borrowing to cover some needed investments in store infrastructure (display structures and leasehold improvements), and annual income was able to finance much of the needed investment in inventory (a major commitment of resources). However, financing the anticipated growth in 2015 was going to require careful thought. Blue Ridge would need significant leasehold investments in 2015, some of which were needed to fully absorb past growth, and there was no opportunity for additional long-term borrowing. Furthermore, management was concerned that the cash balance in the company's account had not kept pace with the expansion and, in fact, was slightly below the 2012 level. Finally, as of the end of 2014, Blue Ridge had an outstanding balance on its bank line of credit equal to $ 101,000. While this was below the $ 200,000 maximum Blue Ridge could borrow against the line, this was an unusually high level for the end of the year. Pedro Morales, Blue Ridge's financial manager, had joined Blue Ridge right out of college four years before as an accountant. He took over the top finance job just two years later. Now Morales was asked to put together a financial plan. Given the company's profitability, it was possible Blue Ridge might squeak by on internally generated funds. Yet it could also be the case that the company would have to seek other sources of funds or renegotiate its line of credit with National Bank, the bank that provided the credit line and had handled all Blue Ridge banking needs since its founding 11 years before. . . .
3DE Appearance of the Different Types of Normal Mechanical and Biological Valves

A comprehensive understanding of normal prosthetic valve anatomy and function is essential to identify and evaluate pathologic states. Three dimensional echocardiography (3DE) and in particular 3D transesophageal echocardiography (3DTEE) provides exceptional enface atrial and ventricular views of mitral prostheses from a single acoustic window. By providing a panoramic view of mitral valve prostheses and surrounding bed, the sewing ring of surgical prostheses can be readily imaged, and prosthesis morphology including subtle findings that cannot be seen on two-dimensional echocardiography (2DE) can be better appreciated. Moreover, mechanical prosthesis occluder mechanism including spatial orientation of the occluder leaflets, and normal leaflet excursion can be ascertained. The added depth provided by 3D imaging allows visualization of mechanical aortic prosthesis occluder motion when not seen on 2D imaging, and a better appreciation of aortic and mitral bioprostheses cusp morphology. For patients who undergo, mitral valve repair, the annuloplasty band or ring can also be readily appreciated in the 3D space
Television, Power, and the Public in Russia

The Russian media are widely seen to be increasingly controlled by the government. Leaders buy up dissenting television channels and pour money in as fast as it haemorrhages out. As a result, TV news has become narrower in scope and in the range of viewpoints which it reflects: leaders demand assimilation and shut down dissenting stations. Using original and extensive focus group research and new developments in cognitive theory, Ellen Mickiewicz unveils a profound mismatch between the complacent assumption of Russian leaders that the country will absorb their messages, and the viewers on the other side of the screen. This is the first book to reveal what the Russian audience really thinks of its news and the mental strategies they use to process it. The focus on ordinary people, rather than elites, makes a strong contribution to the study of post-communist societies and the individual's relationship to the media.
Amyloid Fibril Formation of Natively Unfolded Proteins

Originally published in: Amyloid Proteins. Edited by Jean D. Sipe. Copyright © 2005 Wiley-VCH Verlag GmbH & Co. KGaA Weinheim. Print ISBN: 3-527-31072-X The sections in this article are Introduction Molecular Mechanisms of Amyloid Fibril Formation by a Natively Unfolded Protein: α-Synuclein α-Synuclein in Parkinson's Disease and other Neurodegenerative Disorders Key Structural Properties of α-Synuclein: A Natively Unfolded Protein Major Structural Characteristics of Partially Folded α-Synuclein Fibril Formation by α-Synuclein and the Partially Folded Amyloidogenic Conformation Fibrillogenesis of Natively Unfolded Proteins Requires Partial Folding Fibril Formation by Proteins Involved in Conformational Disorders Amyloid β protein (Aβ) Tau protein Islet Amyloid Polypeptide (IAPP) or Amylin Prion Protein Polyglutamine Repeat Diseases Fibrillation of Proteins Unrelated to Conformational Disease Yeast Prions Prothymosin α Apolipoprotein CII (ApoCII) Histones Conclusions Acknowledgments Keywords: intrinsically disordered proteins; amyloid formation; protein; fibrils; alpha-synuclein