cssi/SciSciGPT-SciSciNet huggingface dataset:
Adaptive subdomain modeling: A multi-analysis technique for ocean circulation models

Abstract Many coastal and ocean processes of interest operate over large temporal and geographical scales and require a substantial amount of computational resources, particularly when engineering design and failure scenarios are also considered. This study presents an adaptive multi-analysis technique that improves the efficiency of these computations when multiple alternatives are being simulated. The technique, called adaptive subdomain modeling, concurrently analyzes any number of child domains, with each instance corresponding to a unique design or failure scenario, in addition to a full-scale parent domain providing the boundary conditions for its children. To contain the altered hydrodynamics originating from the modifications, the spatial extent of each child domain is adaptively adjusted during runtime depending on the response of the model. The technique is incorporated in ADCIRC++, a re-implementation of the popular ADCIRC ocean circulation model with an updated software architecture designed to facilitate this adaptive behavior and to utilize concurrent executions of multiple domains. The results of our case studies confirm that the method substantially reduces computational effort while maintaining accuracy.
Fall risk and function in older women after gynecologic surgery.

Abstract Purpose of study To examine change in balance-related fall risk and daily functional abilities in the first 2 post-operative weeks and up to 6 weeks after gynecologic surgery. Materials and methods Prospective cohort study in gynecologic surgery patients age 65 and older. Balance confidence (Activities-specific Balance Confidence Scale) and functional status (basic and instrumental activities of daily living) were recorded pre- and post-operatively daily for 1 week and twice the second week. Physical performance balance and functional mobility were measured pre- and 1 week post-operatively using the Tinetti Fall Risk Scale, Timed Up and Go, and 6-Minute Walk test. Measures were repeated 6 weeks after surgery. Non-parametric tests for paired data were used comparing scores baseline to post-operative (POD) 7 and to POD 42. Results Median age was 72 years (range 65–88). Fall risk was elevated during the first 2 post-operative weeks, greatest on the median discharge day, POD 2 (p Conclusions After gynecologic surgery, older women’s fall risk is highest on POD 2 and remains elevated from baseline for 2 weeks. Functional limitations in the early home recovery period include the anticipated (bathing, cooking, etc.) and some unanticipated (medication management) ones. This information may help with post-operative discharge planning.
Treatment of Bladder Carcinoma with Concomitant Infusion Chemotherapy and Irradiation

In 1983 carcinoma of the urinary bladder was responsible for over 10,000 deaths in the United States1. Despite advances in treatment and detection of the disease, this death rate has remained virtually unchanged for the last 30 years. Transurethral resection, partial cystectomy and interstitial implant are appropriate treatments for low grade, low stage tumors, while pre-operative irradiation followed by planned cystectomy is the accepted modality of treatment for high stage, deeply invasive carcinomas. Patients who demonstrate complete response in the surgical cystectomy specimen carry a better prognosis2,3,4,5. Blandy in 1980, showed that patients achieving complete response within 6 months of curative irradiation had a 5 year survival rate of 56%2. Therefore, if the complete response rate can be improved then hopefully this will translate into prolonged survival.
Randomized Trial of Smartphone-Based Evaluation for an Obstetrics and Gynecology Clerkship

Objective We hypothesized that compared to paper evaluations, a smartphone-based quick response (QR) evaluation tool would improve timeliness of feedback, enhance efficacy of giving and receiving feedback, and be as easy to use. Design We performed a randomized controlled trial of student and instructor experience with two evaluation tools in the OB/GYN clerkship at University of Washington School of Medicine (UWSOM). Sites were randomized to the QR or paper tool; students at QR sites received individualized QR codes at the beginning of the clerkship. Instructors and students completed postintervention surveys regarding the evaluation tool and associated feedback. We compared responses between groups using chi-squared tests. Setting Participating clerkship sites included primary, tertiary, private practice and institutional settings affiliated with the University of Washington in the Washington, Wyoming, Alaska, Montana and Idaho region. Participants Of the 29 OB/GYN UWSOM clerkship sites, 18 agreed to participate and were randomized. Of 29 eligible instructors, 25 (86%) completed the survey, with n = 18 using QR and n = 7 using paper. Of 161 eligible students, 102 (63%) completed the survey, with n = 54 using QR and n = 48 using paper. Results Compared to those using paper evaluations, instructors using QR evaluations were significantly more likely to agree that the evaluation tool was easy to understand (100% QR vs 43% paper, p = 0.002), the tool was effective in providing feedback (78% QR vs 29% paper, p = 0.002), and they felt comfortable approaching students with the tool (89% QR vs 43% paper, p = 0.002). Compared to those using paper evaluations, students using QR evaluations were less likely to agree the tool was effective in eliciting feedback (QR 43% vs paper 55%, p = 0.042). Conclusion Instructors found QR evaluations superior to paper evaluations for providing feedback to medical students, whereas students found QR evaluations less effective for feedback.
Towards regeneration: the evolution of medicine from fighting to building

We should retreat from metaphors of war in medicine and look to regenerative medicine in its broadest sense, say Ian Hargraves and colleagues with a focus on rebuilding both bodies and lives
Red Wine Retards Abeta Deposition and Neuroinflammation in Alzheimer’s Disease

Abstract Moderate consumption of red wine has been known to protect from age-related neurodegenerative changes, including Alzheimer’s disease (AD). The pathophysiology of AD is complex and involves multiple factors, including abeta accumulation, abnormal hyperphosphorylation of tau proteins, neuroinflammation, and oxidative stress. Red Wine is rich in many polyphenols, including resveratrol and quercetin, that are found to possess antioxidant, antiinflammatory, and neuroprotective properties. The polyphenols derived from red wine could prevent the generation and assembly of β-amyloid peptides into oligomeric form and also prevent the aggregation of tau protein complex and thus impede AD progression. Red wine has also shown to increase the activity of antioxidant enzymes, such as superoxide dismutase and catalase enzymes. The present book chapter summarizes the effect of red wine, its polyphenolic constituents in prevention or treatment of AD.
On caustics associated with the linearized vorticity equation

The linearized vorticity equation serves to model a number of wave phenomena in geophysical fluid dynamics. One technique that has been applied to this equation is the geometrical optics, or multi-dimensional WKB technique. Near caustics, this technique does not apply. A related technique that does apply near caustics is the Lagrange Manifold Formalism. Here we apply the Lagrange Manifold Formalism to determine an asymptotic solution of the linearized vorticity equation and to study associated wave phenomena on the caustic curve.
Fibromyalgia: A Central Sensitivity Syndrome

Fibromyalgia syndrome (FMS) is a clinically recognizable chronic disease with widespread pain, fatigue, poor sleep and other symptoms, as well as multiple tender points. FMS involves documented neurological, biochemical and endocrine abnormalities. Central sensitization develops from multiple factors, including genetics, poor sleep, trauma, psychosocial stress and autonomic dysfunction. Both the 1990 and 2010 American Academy of Rheumatology (ACR) classification criteria may be used for diagnosis of FMS in the clinical setting. Management includes both non-pharmacological and pharmacological approaches. Physician support, education, treatment of sleep difficulties, physical exercise and cognitive behavioral therapy are important non-pharmacological modalities. Several drugs have been found to be efficacious through randomized double-blind trials. Of these, pregabalin, duloxetine and milnacipran are approved by the FDA. Research in the past few decades has helped to advance a better understanding of the mechanisms and better treatment of FMS.
Dihydropyridine-Sensitive and -Insensitive Ca2+ Channels in Normal and Transformed Fibroblasts

The importance of voltage-sensitive Ca2+ channels in the surface membrane of excitable cells is undisputed and well studied. Ca2+ ions entering the cytoplasm through Ca2+ channels provide the message which leads to neurotransmitter release, contraction in cardiac and smooth muscle, and secretion in many endocrine and exocrine cells. More recently, it has become clear that intracellular Ca2+ ions are also involved in the control of a variety of cellular functions which are not restricted to electrically excitable cells, such as cell adherence, cytoskeletal organization, motility, phagocytosis, and even control of cell growth.
Evaluation of VEGF-Induced Vascular Permeability in Mice

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and vascular leak involved in development, wound healing, tumor growth, macular degeneration, and ischemia. Studying the effects of VEGF in vitro is not always sufficient to approximate the complex in vivo response that involves multiple cell types within functioning tissues. Treating mice with an intravenous injection of recombinant VEGF produces a rapid and transient biochemical response that is accompanied by a series of ultrastructural changes. Similar events are induced by hypoxia-induced VEGF in the heart following myocardial infarction or by tumor cell-released VEGF during metastasis. Studying how intact blood vessels respond to VEGF will augment the further development of antipermeability strategies to improve disease progression in a number of pathologies.
Spectral Characteristics of Semiconductor Diode Lasers

The spectral linewidth and phase noise characteristics of single-frequency semiconductor diode lasers have become quite important for application to such areas as frequency standards, fiber optical sensors, laser gyros, and optical communications. This work describes the spectral broadening mechanisms which have been observed for monolithic (GaAl)As and lead-salt diode lasers as well as the spectral characteristics of external-cavity controlled (GaAl)As diode lasers.
Chapter 33 - Intricate tactile sensitivity: a key variable in western integrative bodywork

During the past 150 years throughout the US and Western Europe, there have been a widespread development and rapid proliferation of experiential approaches to the human body involving highly sophisticated methods of touch, body movement, and body awareness. Outside investigators mistakenly lump these bodyworks together with other qualitatively different practices, massage, physical therapy, “laying on of hands” - leading to deficiencies in the design of studies to investigate them. The family of bodyworks analyzed in the chapter differs from these other kinds of practices in significant ways, one of which is the focus of this chapter. Another common mistake on the part of outside investigators is to isolate an individual “move” or technique from the rich complex of a given method. The application of that atomistic piece is subjected to outcome studies, for example, use of the pelvic lift in the treatment of chronic back pain. If successful, the atomized piece is investigated as to how it might be integrated into clinical medical practice. The problem with this approach is that, it is constrained to an understanding of the narrowest range of efficacies. The focus on an isolated practice loses the wholeness of the method, and by doing so distorts the meaning and efficacy of the practice itself.
Human Skin Explants Recapitulate Key Features of HSV-1 Infections.

The development of novel antiviral compounds is hindered by the lack of model systems that recapitulate the pathophysiology of human infections. Tajpara et al. developed an ex vivo human abdominal skin model of HSV-1 infection to examine host-pathogen interactions and test the efficacy of antiviral compounds. This approach provides a platform for future development and testing of antiviral drugs.
Are awe-prone people more curious? The relationship between dispositional awe, curiosity, and academic outcomes.

Objective Guided by a functional account of awe, we aimed to test the hypothesis that people who often feel awe are also more curious (Studies 1 and 2), and that this relationship in turn relates to academic outcomes (Study 3). Method In Study 1 (n = 1,005), we used a self-report approach to test the relationship between dispositional awe and curiosity. In Study 2 (n = 100), we used a peer-report approach to test if participants' dispositional awe related to how curious they were rated by their friends. In Study 3, in a sample of 447 high school adolescents we tested if dispositional awe related to academic outcomes via curiosity. Results We found that dispositional awe was positively related to people's self-rated curiosity (Study 1) and how curious they were rated by their friends (Study 2). In Study 3, we found that dispositional awe was related to academic outcomes via curiosity. Conclusions We conclude that among the seven positive emotion dispositions tested, awe was related to unique variance in curiosity, and this link in turn predicted academic outcomes. This work further characterizes awe as an epistemic emotion and suggests that activities that inspire awe may improve academic outcomes.
Building Trust and Cooperation in Weak States: Persuasion and Source Accountability in Liberia during the 2014-2015 Ebola Crisis

How do governments in weak states persuade suspicious citizens to trust them and comply with emergency measures during crises? To answer this question, we study the effectiveness of the Liberian government’s door-to-door canvassing campaign during the 2014-2015 Ebola epidemic by combining data from an original, representative survey of Monrovia conducted during the crisis with plausibly as-if random variation in where the campaign was and was not able to reach. We find that the campaign was remarkably effective at increasing adherence to safety precautions, support for contentious control policies, and general trust in government. To uncover the pathways through which the campaign proved so effective, we conducted over 100 in-depth qualitative interviews in 38 randomly sampled communities. Analysis of these interviews suggests that local intermediaries were effective because their embeddedness in communities subjected them to monitoring and sanctioning, thereby assuring their fellow residents that they were accountable and thus credible.
Accelerated and Robust Analytical Target Cascading for Distributed Optimal Power Flow

Augmented Lagrangian-based distributed algorithms, such as analytical target cascading (ATC), may converge slowly, oscillate around the optimal point, or diverge if penalty multipliers are not selected appropriately or the level of importance of objective terms is not balanced. This article presents accelerated, robust ATC (AR-ATC) to solve the optimal power flow (OPF) distributedly. A function is designed to determine a balancing coefficient whose incorporation into ATC makes a balance between the important level of terms of objective functions. If penalty multipliers are initialized to large values, the proposed function creates a balancing coefficient to avoid the premature convergence or divergence. A balancing coefficient will be created to reduce the number of iterations if penalty multipliers are set to small values. Mathematical justifications and simulation studies are performed to analyze the effectiveness of AR-ATC. Potential applications of the proposed method on auxiliary problem principle, alternating direction method of multipliers (ADMM), and Nesterov-based ADMM are also studied numerically. Simulations are performed for direct current optimal power flow and alternating current optimal power flow problems.
Exposure therapy for eating disorders: A systematic review.

Abstract Exposure therapy is a potential method for the treatment of eating disorders. The current paper reviews the literature on exposure interventions for eating disorders, including studies (N = 60) on exposure and response prevention (ERP), in vivo feared food exposure, mirror exposure, family-based treatment with exposure, and virtual reality exposure therapy. Mirror exposure alone or in the context of cognitive-behavioral therapy (CBT) can decrease body dissatisfaction. The few controlled trials on ERP for binge and purge cues show only marginal benefit of ERP for binge or purge cues over and above other treatment methods such as CBT. In vivo exposure to feared foods may decrease state anxiety and increase caloric intake and body mass index, but research is limited. Virtual reality exposure could improve accessibility and feasibility of exposures in the clinical setting. A significant portion of the trials incorporated exposures into an overarching treatment such as CBT, body image therapy, or inpatient treatment, so the effects of exposure itself are difficult to parse apart. We discuss the state of the current literature in the context of learning theory and offer insights into new approaches to the application of exposure therapy in an eating disordered population.
Imaging depth limit analysis in multiphoton microscopy using the beam propagation method

We apply our recently developed beam propagation model to simulate wave propagation in scattering biological tissue. The imaging depth limit is estimated for two-photon, three-photon, and non-degenerate two-photon microscopy.
Observations on the life history and ecology of Clubiona pacifica Banks in Washington State (Araneae: Clubionidae)

Clubiona pacifica Banks, 1896 is a common secondary occupant of lepidopteran leafrolls on alders (Alnus spp.). We collected rolled alder leaves at riparian sites in Washington State to determine seasonal phenology of C. pacifica and to examine egg laying and predatory activity. All stages of the spider occurred in rolled leaves, and spiders were found in rolled leaves throughout the season. Rolled alder leaves were used by C. pacifica as protected sites in which to molt and spend inactive periods and possibly to seek prey. Field observations and greenhouse experiments indicated that C. pacifica is capable of preying upon leafroller larvae. Occasionally, lepidopteran leafrolls were used by C. pacifica as ready-made chambers in which to oviposit, but more commonly the female spider herself folded an alder leaf to form a protective retreat for oviposition. These egg sac retreats and the associated egg sac are described and illustrated. After eclosion C. pacifica passes through a prelarval stage, a larval stage, and six nymphal stages before reaching adulthood. The principal period of reproduction and egg deposition is June and July, and most post-larval stages of C. pacifica appear to overwinter. We postulate that some individuals require two years to complete their life cycle although others may do so in a shorter time. Three ichneumonid wasps parasitized C. pacifica: Gelis sp. attacked the eggs; Schizopyga frigida and Zaglyptus varipes parasitized immature and adult spiders.
AIM2 in health and disease: inflammasome and beyond

Nucleic acid sensing is a critical mechanism by which the immune system monitors for pathogen invasion. A set of germline-encoded innate immune receptors detect microbial DNA in various compartments of the cell, such as endosomes, the cytosol, and the nucleus. Sensing of microbial DNA through these receptors stimulates, in most cases, interferon regulatory factor-dependent type I IFN synthesis followed by JAK/STAT-dependent interferon-stimulated gene expression. In contrast, the detection of DNA in the cytosol by AIM2 assembles a macromolecular complex called the inflammasome, which unleashes the proteolytic activity of a cysteine protease caspase-1. Caspase-1 cleaves and activates the pro-inflammatory cytokines such as IL-1β and IL-18 and a pore-forming protein, gasdermin D, which triggers pyroptosis, an inflammatory form of cell death. Research over the past decade has revealed that AIM2 plays essential roles not only in host defense against pathogens but also in inflammatory diseases, autoimmunity, and cancer in inflammasome-dependent and inflammasome-independent manners. This review discusses the latest advancements in our understanding of AIM2 biology and its functions in health and disease.
Abstract 6474: FAT1 and CASP8 co-mutations are associated with poor prognosis in HPV negative head and neck squamous cell carcinoma

INTRODUCTION: FAT1 alterations with somatic mutations or deletions are observed in head and neck squamous cell carcinomas (HNSCC). These alterations lead to loss of function of FAT1. FAT1 loss of function was known to be associated with aberrant Wnt activation, cell migration and invasion. In this study, we present analysis and outcomes of co-mutations seen in FAT1-mutation positive HNSCC. METHODS: TCGA data were analyzed for mutation, gene expression data and overall survival. We examined mutation data in 415 HPV negative samples and 72 HPV positive samples. The Fisher9s Exact test was used to determine if differences in mutation frequency existed between the different cohorts. Mantel-Cox method was used for overall survival (OS) comparison between the cohorts. RESULTS: FAT1 somatic mutation was the third most commonly mutated gene in HPV-negative HNSCC while it was not common in HPV-positive HNSCC. FAT1 mutation was seen in 25.8% of HPV negative HNSCC (107/415), while 4.2% (3/72) HPV positive HNSCC had FAT1 mutation. We then analyzed the frequency of co-mutations in FAT1-mutated HPV-negative HNSCC. CDKN2A, NOTCH1, CASP8, FBXW7, ZFHX4, HRAS, DCC, ATR mutations were more common in FAT1-mutated cancers. CASP8 mutation was seen in 24.30% (26 out of 107 samples) of FAT1-mutations positive HPV negative HNSCC, while it was less common in FAT1-mutation negative HNSCC (9.08% 28/308) (P=0.002). The patients with FAT1 and CASP8 co-mutation were associated with shorter overall survival when compared with patients with FAT1-mutation (19.8 months vs 52.3 months P=0.02). FAT1 only or CASP8 only mutation without co-mutation did not affect survival. To determine the mutation impact of the FAT1 and CASP8 mutations in HNSCC, differentially expressed genes between mutated and non-mutated genes were analyzed in HNSCC. CASP8 mutation was the top gene among the genes with somatic mutation in HNSCC and associated with gene expression changes in more than 6000 genes. FAT1 was ranked 11th resulting in differential gene expression in more than 1000 genes. DISCUSSION: FAT1 somatic mutations are commonly seen in HPV negative HNSCC. We have demonstrated for the first time that CASP8 and FAT1 co-mutations are associated with poor prognosis with decreased overall survival in HPV negative HNSCC. Both CASP8 and FAT1 mutations are among the top genes with mutation impact on differential gene expression in HNSCC suggesting significance of these mutations in HNSCC. Citation Format: Emrullah Yilmaz, David Lee, Andrew Cowan, Gregory Gan, Michelle Ozbun, Yan Guo. FAT1 and CASP8 co-mutations are associated with poor prognosis in HPV negative head and neck squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6474.
Examining the Gap Between Medical School Matriculation and Graduation Rates Amongst Self-Identified Minorities.

Abstract Purpose Despite increasing diversity, data indicates that there is a gap between the matriculation or admission of and graduation rates amongst medical students who identify with racial or ethnic minority groups. The purpose of this study was to identify barriers experienced by minority medical students that may account for this gap. Methods An IRB approved online survey was created, and distributed electronically to minority medical students, residents, and practicing physicians. Information on demographics, family dynamics, academic struggles, health issues, financial difficulties and faculty diversity was collected via self-report. Results Participants (n = 167) who completed the survey identified as Black/African/African American (60%), Hispanic/Latinx (26%), Asian (8%), and as Other racial or ethnic minority (6%). The majority of survey participants graduated within the traditional 4 years of medical school (83%) and 17% did not. The most frequently reported reason was to pursue academic advancement (42%) which included completing a research year, dual degree, or PhD. The second reason was due to academic deficiencies (38%), either course failure or failure of a board exam. The majority of respondents (59%) also reported not having enough faculty members who were members of racial or ethnic minority groups at their medical school. Conclusions Our data suggests the majority of racial and ethnic minority medical students graduate within the traditional 4 years of medical school. However, if they do not, it is either due to academic advancement to become a more successful residency applicant, or due to academic issues. The majority of respondents reported that they perceive a lack of racial and ethnic minority faculty members in academics.
AN INTEGRATED PERSPECTIVE: APPLYING TEAM LEARNING AND KNOWLEDGE CREATION THROUGH TEAM LEARNER STYLES

Research in the field of organizational and team learning is well documented with several notable theories explaining the components and process. However, after thorough examination of the literature, there is an obvious disconnect between theoretical understanding and organizational application. The focus of this research is to develop an applied framework for team learning and knowledge creation by integrating three currently recognized theoretical models. The three models incorporated are Boisot’s Social Learning Cycle Model (SLC), Kolb’s Learning Style Inventory Model (LSI) and Lee’s Modes of Learning Progression Model (MLP). These three models are selected because they provide the primary dimensions, in tandem, required for the construction of the newly applied framework. This resulting Team Learner Style Quadrant (TLSQ) framework suggests that specific learning styles suits the various stages in the learning process of teams that are charged with different roles for team learning and knowledge creation and can be easily applied to any organization. Finally, propositions of knowledge diffusion are provided for framework validity, providing researchers with a direction for future hypotheses and model development. Keywords: team learning, organizational learning, learning progression, learner style, knowledge creation, knowledge diffusion.
Heartbeat: is postmenopausal hormone therapy a risk factor or preventative therapy for cardiovascular disease in women?

Cardiovascular disease (CVD) is the leading cause of death in women in high-income countries. Most CVD events in women occur after menopause and there is a clear relationship between earlier age at menopause and increased CVD risk. Thus, it seems biologically plausible that the decrease in hormone levels after menopause might be related to CVD risk (figure 1). Yet, the potential role of post-menopausal hormone therapy (MHT) in reducing CVD risk in women remains controversial. In this issue of Heart , Gersh et al 1 summarise the pros and cons of MHT and provide a historical overview of MHT studies, highlighting limitations such as inclusion of women with pre-existing heart disease, and the type, dose and timing of MHT. They argue that ‘Human-identical hormones initiated early in menopause appear safe to be continued indefinitely, under close supervision, offering post-menopausal women greater potential for long-term CV health and improved quality of life.’ Of course, ‘Individualised decision-making is a key component of all MHT conversations; standard CVD risk reduction must be included in all therapeutic plans.’ Figure 1 Age-dependent shift in oestrogen levels. Levels of oestrogen decline with age and result in increased visceral fat, higher rates of insulin resistance and an increase in cardiovascular disease. In an editorial counterpoint, Thamman2 disagrees with this …
Time-to-Collision Estimations in Young Drivers with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder

Individuals with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) may exhibit driving difficulties due to cognitive impairments such as time perception difficulties, a construct related to the perception of time-to-collision (TTC). This study examined the timing abilities of drivers with ASD and ADHD. Sixty participants (nADHD = 20, nASD = 20, nTD = 20) completed a time reproduction task and a TTC estimation task in a driving simulator. Results indicated drivers with ASD were less precise in time reproduction across all time intervals and over-reproduced time at shorter intervals. Drivers with ASD produced larger TTC estimates when driving at a faster speed compared to typically developing drivers. Drivers with ASD, but not ADHD, appear to present difficulties in time estimation abilities.
Book review: Wazhmah Osman, Television and the Afghan Culture Wars: Brought to You by Foreigners, Warlords, and Activists:

Wazhmah Osman, Television and the Afghan Culture Wars: Brought to You by Foreigners, Warlords, and Activists. Champaign: University of Illinois Press, 2020, 288 pp., $28.00 (Paperback). ISBN: 978-0...
Depression readmission risk is elevated in multiple sclerosis compared to other chronic illnesses.

Objective:Assess readmissions for depression or suicide attempt (SA) after MS admission versus other chronic inflammatory illnesses.Methods:This retrospective cohort study identified MS, asthma, rh...
GAPDH cooperativity mediates drug resistance and metabolism in Plasmodium fal-ciparum malaria parasites

Efforts to control the global malaria health crisis are undermined by antimalarial resistance. Identifying mechanisms of resistance will uncover the underlying biology of the Plasmodium falciparum malaria parasites that allow evasion of our most promising therapeutics and may reveal new drug targets. We utilized fosmidomycin (FSM) as a chemical inhibitor of plastidial isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway. We have thus identified an unusual metabolic regulation scheme in the malaria parasite through the essential glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Two parallel genetic screens converged on independent but functionally analogous resistance alleles in GAPDH. Metabolic profiling of FSM-resistant gapdh mutant parasites indicates that neither of these mutations disrupt overall glycolytic output. While FSM-resistant GAPDH variant proteins are catalytically active, they have reduced assembly into the homotetrameric state favored by wild-type GAPDH. Disrupted oligomerization of FSM-resistant GAPDH variant proteins is accompanied by altered enzymatic cooperativity and reduced susceptibility to inhibition by free heme. Together, our data identifies a new genetic biomarker of FSM-resistance and reveals the central role of GAPDH cooperativity in MEP pathway control and antimalarial sensitivity.
Suppressors of Cytokine Signaling Proteins Are Differentially Expressed in Th1 and Th2 Cells: Implications for Th Cell Lineage Commitment and Maintenance

Positive regulatory factors induced by IL-12/STAT4 and IL-4/STAT6 signaling during T cell development contribute to polarized patterns of cytokine expression manifested by differentiated Th cells. These two critical and antagonistic signaling pathways are under negative feedback regulation by a multimember family of intracellular proteins called suppressor of cytokine signaling (SOCS). However, it is not known whether these negative regulatory factors also modulate Th1/Th2 lineage commitment and maintenance. We show here that CD4(+) naive T cells constitutively express low levels of SOCS1, SOCS2, and SOCS3 mRNAs. These mRNAs and their proteins increase significantly in nonpolarized Th cells after activation by TCR signaling. We further show that differentiation into Th1 or Th2 phenotype is accompanied by preferential expression of distinct SOCS mRNA transcripts and proteins. SOCS1 expression is 5-fold higher in Th1 than in Th2 cells, whereas Th2 cells contain 23-fold higher levels of SOCS3. We also demonstrate that IL-12-induced STAT4 activation is inhibited in Th2 cells that express high levels of SOCS3 whereas IL-4/STAT6 signaling is constitutively activated in Th2 cells, but not Th1 cells, with high SOCS1 expression. These results suggest that mutually exclusive use of STAT4 and STAT6 signaling pathways by differentiated Th cells may derive in part, from SOCS3- or SOCS1-mediated repression of IL-12/STAT4- or IL-4/STAT6 signaling in Th2 and Th1 cells, respectively. Given the strong correlation between distinct patterns of SOCS expression and differentiation into the Th1 or Th2 phenotype, SOCS1 and SOCS3 proteins are therefore Th lineage markers that can serve as therapeutic targets for immune modulation therapy.
Duplex Ultrasound Velocity Criteria for Carotid Stenting Patients

Stroke is the third leading cause of death in the United States with over 783,000 strokes reported annually.1 Over one-third of patients die and another one-third are severely disabled. The annual economic cost exceeds $30 billion.2 Randomized trials have established the efficacy of carotid endarterectomy (CEA) in the prevention of stroke for patients with high-grade carotid stenosis (CS).3, 4, 5, 6, 7 The advent of newer technologies and a desire for less invasive treatment have encouraged investigators to propose carotid artery stenting (CAS) as an alternative to CEA.1,8, 9, 10 Our institution1, 8,11, 12, 13, 14, 15, 16, 17 (Figure 13-1), along with others,18, 19, 20, 21, 22 has demonstrated that CAS is technically feasible and safe in patients with restenosis after CEA, surgically inaccessible lesions, previous radiation, or significant medical comorbidities. The 30-day stroke and death rate in 190 CAS procedures at our institution was 4.15%, indicating a competitive alternative to CEA.14 However, due to the proven efficacy of CEA, current indications for CAS have been limited to situations where CEA yields suboptimal results.13,23
1H NMR structure of the heme pocket of HNO-myoglobin.

The unique 1H NMR signal of nitrosyl hydride at 14.8 ppm is used to obtain a solution structure of the distal pocket of Mb-HNO, a rare nitroxyl adduct with a half-life of several months at room temperature. 1H NMR, NOESY and TOCSY data were obtained under identical experimental conditions on solutions of the diamagnetic HNO and CO complexes of equine Mb, allowing direct comparison of NMR data to a crystallographically characterized structure. Twenty NOEs between the nitrosyl hydride and protein and heme-based signals were observed. The HNO orientation obtained by modeling the experimental 1H NMR NOESY data yielded an orientation of ca. –104° referenced to the N-Fe-N vector between α and β meso protons. An essentially identical orientation was obtained by simple energy minimization of the HNO adduct using ESFF potentials, suggesting steric control of the orientation. Differences in chemical shifts are seen for protons on residues Phe43(CD1) and Val68(E11), but both exhibit virtually identical NOESY contacts to other residues, and thus are attributed to small movements of ca. 0.1 A within the strong ring current. The most significant differences are seen in the NOESY peak intensities and chemical shifts for the ring non-labile protons of the distal His64(E7). The orientation of the His64(E7) in Mb-HNO was analyzed on the basis of the NOESY cross-peak changes and chemical shift changes, predicting a ca. 20° rotation about the β-γ bond. The deduced HNO and His64(E7) orientations result in geometry where the His64(E7) ring can serve as the donor for a significant H-bond to the oxygen atom of the bound HNO.
Modulation of ecotropic murine retroviruses by N-linked glycosylation of the cell surface receptor/amino acid transporter.

The cell surface receptor for ecotropic host-range (infection limited to mice or rats) murine leukemia viruses (MuLVs) is the widely expressed system y+ transporter for cationic amino acids (CAT-1). Like other retroviruses, ecotropic MuLV infection eliminates virus-binding sites from cell surfaces and results in complete interference to superinfection. Surprisingly, infection causes only partial (ca 40 to 60%) loss of mouse CAT-1 transporter activity. The NIH/Swiss mouse CAT-1 (mCAT-1) contains 622 amino acids with 14 hydrophobic potential membrane-spanning sequences, and it is known that the third extracellular loop from the amino terminus is required for virus binding. Although loop 3 is hypervariable in different species and mouse strains, consistent with its proposed role in virus-host coevolution, loop 3 sequences of both susceptible and resistant species contain consensus sites for N-linked glycosylation. Both of the consensus sites in loop 3 of mCAT-1 are known to be glycosylated and to contain oligosaccharides with diverse sizes (J. W. Kim and J. M. Cunningham, J. Biol. Chem. 268:16316-16320, 1993). We confirmed by several lines of evidence that N-linked glycosylation occludes a potentially functional virus-binding site in the CAT-1 protein of hamsters, thus contributing to resistance of that species. To study the role of receptor glycosylation in animals susceptible to infection, we eliminated loop 3 glycosylation sites by mutagenesis of an mCAT-1 cDNA clone, and we expressed wild-type and mutant receptors in mink fibroblasts and Xenopus oocytes. These receptors had indistinguishable transport properties, as determined by kinetic and voltage-jump electrophysiological studies of arginine uptake in oocytes and by analyses Of L-[3H]arginine uptake in mink cells. Bindings of ecotropic envelope glycoprotein gp7O to the accessible receptor sites on surfaces of mink cells expressing wild-type or mutant mCAT-1 were not significantly different in kinetics or in equilibrium affinities (i.e., K(D) approximately 3.7 X 10(-10) to 7.5 X 10(-10) M). However, when values were normalized to the same levels of mCAT-1 transporter expression, cells with wild-type glycosylated mCAT-1 had only approximately 50% as many sites for gp70 binding as cells with unglycosylated mCAT-1. Although infection with ecotropic MuLV had no effect on activity of the mink CAT-1 transporter that does not bind virus, it caused partial down-modulation of wild-type mCAT-1 and complete down-modulation of unglycosylated mutant mCAT-1. These results suggest that N-linked glycosylation causes wild-type mCAT-1 heterogeneity and that a significant proportion is inaccessible to virus. In part because only the interactive fraction of mCAT-1 can be down-modulated, infected murine cells conserve an amino acid transport capability that supports their viability.
Clinical comparison of the isolator and BacT/Alert aerobic blood culture systems.

The performance characteristics of the Isolator (Wampole Laboratories, Cranbury, N.J.) and the BacT/Alert (Organon Teknika Corporation, Durham, N.C.) aerobic blood culture systems were compared for 6,009 blood culture sets obtained from patients with suspected bloodstream infections. The BacT/Alert aerobic bottle [BTA(O2)] was continuously agitated while it was incubated in 5% CO2 at 36 degrees C; culture plates prepared from the Isolator tube [I(O2)] were incubated in 5% CO2 at 37 degrees C. From 394 blood cultures, 416 clinically significant isolates of bacteria and yeasts were recovered. The overall yields for BTA(O2) and I(O2) were not significantly different (319 versus 336; P = 0.20). I(O2) recovered significantly more staphylococcus (P < 0.05) and yeast isolates (P < 0.01). BTA(O2) recovered significantly more aerobic and facultatively anaerobic gram-negative bacilli (P < 0.05). In blood culture sets which produced growth of the same organisms in both the BTA(O2) and I(O2) systems, the BTA(O2) system detected growth sooner, but more rapid identification was possible with the I(O2) system by virtue of earlier isolation of colonies on solid media.
Failed Searches: How the choice set of job applicants affects an employer’s likelihood of making an offer

Extant hiring research has generally focused on understanding outcomes for employees and not on outcomes for employers. I theorize on how employer cognitive hiring decision processes affect their likelihood of extending an offer of employment. I argue that greater variety in the job experiences of candidates in the applicant pool complicates employer comparison processes. Hiring is a two-stage process and I predict that comparison difficulties materialize among a winnowed down consideration set of candidates in this second stage. More experienced employers have less difficulty with variety because they have better constructed preferences. Regression analyses from an online market for contract labor on over 640,000 job postings by over 170,000 employers support my contentions. Greater variety in job experiences among job candidates in the applicant pool leads to a lower likelihood a job offer will be extended to any of them. This relationship is completely mediated by the variety in job candidates in the second stage consideration set. The more experience an employer has in hiring in a domain, the less of an issue variety becomes. Results utilizing an instrumental variable and several supporting analyses are also reported. Contributions to the study of evaluation in markets, hiring, and cognitive processes of categorization are discussed.
Uninducible Mutants in the gal i Locus of Saccharomyces cerevisiae

Uninducible galactose nonfermenter mutants of Saccharomyces cerevisiae have been isolated and mapped in the gal i locus. They appear to be analogous to the is mutations found in the regulatory genes of the Escherichia coli lactose and galactose systems. The susceptibility to suppression by an ochre suppressor of an i allele in an isi− double mutant suggests that the i locus in S. cerevisiae codes for a protein.
Regulation of tissue factor coagulant activity on cell surfaces

Tissue factor (TF) is a transmembrane glycoprotein and an essential component of the factor VIIa-TF enzymatic complex that triggers activation of the coagulation cascade. Formation of TF-FVIIa complexes on cell surfaces not only trigger the coagulation cascade but also transduce cell signaling via activation of protease-activated receptors. Tissue factor is expressed constitutively on cell surfaces of a variety of extravascular cell types, including fibroblasts and pericytes in and surrounding blood vessel walls and epithelial cells, but is generally absent on cells that come into contact with blood directly. However, TF expression could be induced in some blood cells, such as monocytes and endothelial cells, following an injury or pathological stimuli. Tissue factor is essential for hemostasis, but aberrant expression of TF leads to thrombosis. Therefore, a proper regulation of TF activity is critical for the maintenance of hemostatic balance and health in general. TF-FVIIa coagulant activity at the cell surface is influenced not only by TF protein expression levels but also independently by a variety of mechanisms, including alterations in membrane phospholipid composition and cholesterol content, thiol-dependent modifications of TF allosteric disulfide bonds, and other post-translational modifications of TF. In this article, we critically review the key literature on mechanisms by which TF coagulant activity is regulated at the cell surface in the absence of changes in TF protein levels with specific emphasis on recently published data and provide the authors' perspective on the subject.
Intranet-Based Quality Improvement Documentation at the Veterans Affairs Maryland Health Care System

The Pathology and Laboratory Medicine Service of the Veterans Affairs Maryland Health Care System is inspected biannually by the College of American Pathologists (CAP). As of the year 2000, all documentation in the Anatomic Pathology Section is available to all staff through the VA Intranet. Signed, supporting paper documents are on file in the office of the department chair. For the year 2000 CAP inspection, inspectors conducted their document review by use of these Web-based documents, in which each CAP question had a hyperlink to the corresponding section of the procedure manual. Thus inspectors were able to locate the documents relevant to each question quickly and efficiently. The procedure manuals consist of 87 procedures for surgical pathology, 52 procedures for cytopathology, and 25 procedures for autopsy pathology. Each CAP question requiring documentation had from one to three hyperlinks to the corresponding section of the procedure manual. Intranet documentation allows for easier sharing among decentralized institutions and for centralized updates of the laboratory documentation. These documents can be upgraded to allow for multimedia presentations, including text search for key words, hyperlinks to other documents, and images, audio, and video. Use of Web-based documents can improve the efficiency of the inspection process.
Special connotations of "quadra," "penta," and "hexa" in descriptive terminology of dinoflagellates

Abstract The meanings of three terms applied originally to tabulation patterns in thecae of modern peridinoid dinoflagellates are reviewed and the need for caution in extending them to paratabulation patterns of dinoflagellate cysts is emphasized. Two new terms are proposed.
Thermomechanical modelling of dry contacts in automotive disc brake

Abstract The objective of this study is to analyze the thermal behavior of the full and ventilated brake discs of the vehicles using computing code ANSYS. The modeling of the temperature distribution in the disc brake is used to identify all the factors and the entering parameters concerned at the time of the braking operation such as the type of braking, the geometric design of the disc and the used material. The numerical simulation for the coupled transient thermal field and stress field is carried out by sequentially thermal-structural coupled method based on ANSYS to evaluate the stress fields and deformations which are established in the disc with the pressure on the pads. The results obtained by the simulation are satisfactory when compared with those of the specialized literature.