cssi/SciSciGPT-SciSciNet huggingface dataset:
Fate of microglia during HIV-1 infection: From activation to senescence?

Microglia support productive human immunodeficiency virus type 1 (HIV-1) infection and disturbed microglial function could contribute to the development of HIV-associated neurocognitive disorders (HAND). Better understanding of how HIV-1 infection and viral protein exposure modulate microglial function during the course of infection could lead to the identification of novel therapeutic targets for both the eradication of HIV-1 reservoir and treatment of neurocognitive deficits. This review first describes microglial origins and function in the normal central nervous system (CNS), and the changes that occur during aging. We then critically discuss how HIV-1 infection and exposure to viral proteins such as Tat and gp120 affect various aspects of microglial homeostasis including activation, cellular metabolism and cell cycle regulation, through pathways implicated in cellular stress responses including p38 mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB). We thus propose that the functions of human microglia evolve during both healthy and pathological aging. Aging-associated dysfunction of microglia comprises phenotypes resembling cellular senescence, which could contribute to cognitive impairments observed in various neurodegenerative diseases. In addition, microglia seems to develop characteristics that could be related to cellular senescence post-HIV-1 infection and after exposure to HIV-1 viral proteins. However, despite its potential role as a component of HAND and likely other neurocognitive disorders, microglia senescence has not been well characterized and should be the focus of future studies, which could have high translational relevance. GLIA 2016
Investigating Ca2+-Dependent Regulation of Sodium Channels via Thermodynamic and Structural Analysis of Nav1.4 and Nav1.5 Carboxy Tail Interactions with Calmodulin

Voltage-gated sodium channels (Nav) are essential for cardiac and skeletal muscle function. Channelopathic mutations in cardiac sodium channel (Nav1.5) and skeletal muscle sodium channel (Nav1.4), particularly in their cytoplasmic carboxy tails (CTNav), give rise to numerous arrhythmias and myotonias. In Nav regulation, CTNav partners with the Ca2+-sensing protein calmodulin (CaM). We aim to understand how CaM regulates channel function. Ca2+-free CaM (apoCaM) is a regulatory modulator of Nav, and apoCaM bound to the CTNav increases the channel's open probability. CaM also participates in the Ca2+-dependent inactivation (CDI) of Nav1.4. In contrast, Nav1.5 does not show CDI and no role of Ca2+-CaM is known in Nav1.5. To understand the Ca2+-control of CaM regulation of these sodium channels we have collected binding data of CTNavs with CaM, in the presence and absence of Ca2+. Binding data of CTNavs with CaM mutants with Ca2+-binding knocked out in either of CaM's functional domains (lobes) have also been collected to understand the distinct roles of CaM's lobes. Collectively, these binding data have allowed us to predict CTNav and CaM populations as a function of Ca2+ concentration. To gain information on the structural changes induced by Ca2+ on the CTNav-CaM complexes, we conducted small angle scattering (SAXS) experiments on CTNav1.4-CaM and CTNav1.5-CaM in the presence and absence of Ca2+. The distance distribution function, P(r), shows changes in both complexes upon addition of Ca2+. Computational modeling of flexible forms of the complexes reveals conformations of CTNav-CaM, in the presence and absence of Ca2+, that are compatible with our SAXS data. The molecular envelope of the CTNav1.5-apoCaM matches well with the apoCaM-CTNav1.5 crystal structure previously determined by our lab.
A Case Study in Computational Psychiatry: Addiction as Failure Modes of the Decision-Making System

Abstract We review a new perspective on addiction as due to failure modes of decision-making networks. In a sense, this suggests that addiction is a symptom that can arise from any of a number of potential underlying vulnerabilities. We identify four primary action-selection systems and review how multiple deficits (or “failure modes”) of these systems can lead to continued harmful dysfunction typically identified as addiction. These methods have shaped a new generation of tools for studying the etiology of neuropsychiatric dysfunction. These tools are aimed at identifying specific failure modes so that treatments can be individualized for specific patients. Moving beyond dysfunction, we also review how a computational understanding of treatment paradigms can reveal their interaction with these multiple decision systems, which can suggest ways to identify the patients most likely to be helped by treatments and ways to improve the treatments themselves.
Mutational Analysis in Cultured Human-Hamster Hybrid Cells

A convincing body of evidence has now accrued that a large proportion of human developmental disease, including cancer, is caused by environmental agents acting directly or after metabolic activation to produce damage in the genome of affected somatic cells. (1−6) This concept has led to attempts to develop short-term in vitro tests that will provide reliable and scientifically sound means of assessing the mutagenic and carcinogenic potential of environmental agents so as to reduce harmful exposure to humans.
Flexural strength reduction of cement pastes exposed to CaCl2 solutions

Abstract Calcium chloride (CaCl2) can react with calcium hydroxide (Ca(OH)2) to form calcium oxychloride which can reduce flexural strength and damage concrete. This paper aims to characterize the reduction in flexural strength of cement pastes exposed to CaCl2 solutions using the ball-on-three-balls test. The amounts of Ca(OH)2 and calcium oxychloride in the cement paste are measured using thermogravimetric analysis and low-temperature differential scanning calorimetry, respectively. The volume change that occurs as a result of the reactions between the cement paste and CaCl2 is also measured. The reduction in flexural strength increases as the concentration of the CaCl2 solution increases and the exposure temperature decreases. The flexural strength reduction can be mitigated by increasing the amount of supplementary cementitious materials (fly ash) in the cement pastes. Lowering the water-cementitious materials ratio also reduces the flexural strength reduction. The flexural strength reduction is correlated with the amount of calcium oxychloride and the volume change in the cement pastes exposed to the CaCl2 solution. While the flexural strength reduction is believed to be primarily due to the formation of calcium oxychloride, the formation of Friedel's salt and Kuzel's salt also contributes to the flexural strength reduction.
Inferential characterization of the dose-response relationships of neurohormonal antagonists in chronic heart failure: A novel approach based on large-scale trials with active comparators.

Abstract Background Current guidelines for the treatment of heart failure strongly recommend the use of inhibitors of the renin-angiotensin system and sympathetic nervous system in all patients with a reduced ejection fraction who can tolerate these drugs. Yet, there is no consensus about the efficacy of low doses of these drugs or the likely shape of the dose-response relationship for these agents. Methods Inferences were made by examining the effects of drugs in placebo-controlled trials before the protocol-specified opportunity for uptitration and by reassessing the results of large-scale trials with active comparators that inadvertently produced different intensities of neurohormonal blockade. Results In the case of inhibitors of the renin-angiotensin system, low starting doses appear to be effective in many patients, and 3–5 fold increases in dose do not have a mortality advantage over low doses. By contrast, in the case of beta-adrenergic blockers, although low starting doses appear effective in improving outcomes, achievement of target doses may yield substantial incremental mortality benefits, even such doses are accompanied by only small additional decreases in heart rate. Conclusion When treating patients with heart failure to reduce mortality, the totality of evidence supports a relatively flat dose-response relationship for inhibitors of the renin-angiotensin system but a steep dose-response relationship for beta-adrenergic receptor blockers.
Dissociation of force production from MHC and actin contents in muscles injured by eccentric contractions.

The primary purpose of this study was to determine the relationship between myosin heavy chain (MHC) and actin contents and maximum isometric tetanic force (Po) in mouse extensor digitorum longus (EDL) muscles following eccentric contraction-induced injury. Po and protein contents were measured in injured (n=80) and contralateral control (n = 80) EDL muscles at the following time points after in vivo injury: sham, 0, 0.25, 1, 3, 5, 14, and 28 days. Po was reduced by 37 ± 2.3% to 49 ± 3.8% (p ≤ 0.05), while MHC and actin contents were unaltered from 0 to 3 days after injury. Whereas Po partially recovered between 3 and 5 days (from −49 ± 3.8% to −35 ± 3.6%), MHC and actin contents in the injured muscles declined by 19 ± 4.9% and 20 ± 5.3%, respectively, by 5 days compared with control muscles. Decrements in Po were similar to the reductions in MHC and actin contents at 14 (∼24%) and 28 (∼11%) days. Evaluation of myofibrillar and soluble protein fractions indicated significant reductions in the content of major proteins at 5 and 14 days. Immunoblots of heat shock protein 72 revealed elevations starting at 0.25 days, peaking during 1–3 days, and declining after 5days. These findings indicate that decreased contractile protein content is not related to the initial decrease in Po. However, decreased MHC and actin contents could account for 58% of the Po reduction at 5 days, and for nearly all the decrements in Po from 14 to 28 days.
After #Charlottesville: Interrogating our Racist Past in the Trump Era

In wake of the violent and deadly events in Charlottesville and President Donald Trump’s response in which he effectively defended the Neo-Nazis and Confederate monuments, it’s important that college students understand the Lost Cause movement, the building of Confederate monuments and how college campuses are affected. In preparation for the fall 2017 semester, I revised my AFS 310 African Americans and U.S. Education syllabus in which I devoted the first five weeks of the semester to interrogating the aftermath of Charlottesville and this nation’s Confederate legacies on college campuses. Centering the unit’s theme on “The Lost Cause and the Collegiate Idea,” this article will discuss in depth the unit I taught as well as student assessment and outcomes upon completion of the unit.
Influence of Antimicrobial Agents on the Thermal Sensitivity of Foodborne Pathogens: A Review.

ABSTRACT Consumers are driving food production toward the use of more organic antimicrobial agents such as essential oils (EOs) by demanding more natural and clean-label food products. Due to the s...
Bio-inspired design for robust power grid networks

Abstract Technological advances have created a world where humans are highly dependent on an uninterrupted electric power supply, yet extreme weather events and deliberate attacks continue to disrupt power systems. Inherently robust ecological networks present a rich source of robust design guidelines for modern power grids. Analyses of ecosystem networks in literature suggest that this robustness is a consequence of a unique preference for redundant pathways over efficient ones. The structural similarity between these two system-types is exploited here through the application of ecological properties and analysis techniques to long-term power grid design. The level of biological similarity between these two system-types is quantitatively investigated and compared by computing ecological network metrics for a set of synthetic power systems and food webs. The comparison substantiates the use of the ecological robustness metric for optimizing the design of power grid networks. A bio-inspired optimization model is implemented, which restructures the synthetic power systems to mimic ecosystem robustness. The bio-inspired optimal networks are evaluated using N-1, N-2, and N-3 contingency analyses to assess system performance under the loss of 1, 2, and 3 components respectively. The bio-inspired grids all experienced significantly fewer violations in each loss scenario compared to traditional configurations, further supporting the application of the ecological robustness metric for power system robustness. The results provide insights into how ecological robustness can guide the design of power systems for improved infrastructural resilience to better survive disturbances.
Diagnosis of “Sweat-Chloride Negative” Cystic Fibrosis

Common variable immunodeficiency (CVID) is a multigenic disorder and one needs to have a priori hypothesis on which genes to sequence to identify the cause Many of the patients with CVID will present with an initial IgA deficiency as an isolated finding and later progress with a decrease in IgG and later IgM levels
The Development and Influence of Parasocial Relationships With Television Characters: A Longitudinal Experimental Test of Prejudice Reduction Through Parasocial Contact:

The current study investigates parasocial relationships as the underlying mechanism explaining prejudice reduction following extended exposure to mediated outgroups. Heterosexual participants viewe...
Family Therapy with Adolescents

There has been a dramatic increase in the number of adolescents admitted to psychiatric facilities since the early 1980s (AAPPH, 1980–1985). The prevalence of depression, attempted suicide, aggressive behavior, and drug and alcohol abuse among adolescents, as well as the breakdown of traditional family and community supports, appears to be contributing to this disturbing phenomenon. At the time of admission, most adolescents are accompanied to the hospital by their families, many of whom are in crisis and overwhelmed. Even though the vast majority of adolescents return home after brief inpatient treatment, relatively little attention has been paid to family therapy approaches within the psychiatric setting, and treatment in many adolescent units continues to be oriented primarily toward the individual patient (Anderson, 1977; Hanrahan, 1986; Singh, 1987).
The Association of Airflow Obstruction with Occupational Exposures in a Sample of Rural Adults in Iowa

A recent article reported that occupational exposure to vapor-gas, dust, and fumes (VGDF) was more common in a sample of rural adults than in a sample of adults in urban settings. In another study ...
Measuring the resilience of health systems in low- and middle-income countries: a focus on community resilience

The concept of community resilience has gained considerable attention in the global health discussions since the Ebola outbreak of West Africa in 2014–2015. However, there are no measurement models to quantify community resilience. Without measurement models, it is unclear how to test strategies for building community resilience or to describe their likely intended and unintended results and their impact on health outcomes. We propose a measurement model for community resilience with relevant constructs and indicators to measure these constructs. We conducted a scoping review, systematically searching, screening and selecting relevant articles from two bibliographic databases (PUBMED and Google Scholar) for literature using search terms such as “resilience”, “community resilience” and “health systems resilience”. We screened 500 papers, then completed a full text review of 112 identified as relevant based on their title and abstract. A total of 27 papers and reports were retained for analysis. We then aggregated and synthesised the various definitions of community resilience and the frameworks for understanding these definitions. We identified key constructs from these frameworks and organised these constructs into domains and sub-domains. We proposed indicators to capture aspects of these domains and sub-domains and operationalised these indicators as a measurement model for quantifying community resilience in health systems. We propose a model with 20 indicators to assess community resilience. These indicators tap into various constructs from different theoretical frameworks of community resilience and are useful for assessing the level of knowledge, financial resources, and human, social and physical capital that are needed (or lacking) to respond to any types of shock, including health shock at the community level. This is an initial attempt to describe a multilevel measurement model for quantifying community resilience. This model will help to guide the development and testing of strategies for strengthening community resilience and will require further work to assess its relevance, reliability and validity in different LMIC settings.
How Standard Are Standard Precautions? Knowledge and Attitudes Towards Standard Precautions at an Academic Medical Center

Background Standard precautions (SP) are the basis of infection prevention and include a set of common sense infection control practices that prevent transmission of diseases that can be acquired by contact with blood, body fluids, non-intact skin, and mucous membranes. Standard Precautions require that the risk for exposure be assessed and appropriate precautions be applied based on risk (e.g. hand hygiene, personal protective equipment, sharps safety, disinfection, respiratory etiquette). Observations and anecdotal evidence led us to believe there was a lack of understanding of standard precautions among healthcare personnel. Methods A survey was conducted at a large health system to assess knowledge and practices related to specific elements of standard precautions. Results There were over 3000 respondents that included healthcare workers from inpatient (41%), outpatient (37%) and both settings (22%). Nurses comprised the majority of respondents (54%) and others included physicians (9%), respiratory therapists, as well as physical and occupational therapists. The vast majority (96%) of respondents agreed SP were required in the care of all patients, but a large proportion (34%) interpreted that to mean SP always involves wearing gloves and over one-fifth (22.5%) thought PPE was always required. Hand hygiene and sharps safety were identified as the most understood elements of SP. Whereas, respiratory etiquette and cleaning and disinfection were reported as the least understood elements, with PPE, waste disposal and linen handling also being reported as inadequately understood components of SP. Conclusions In an era of increasing drug resistance, fewer antibiotics, SP are our best defense against the spread of infections in the health care setting. Our survey showed that there is room for improvement in healthcare workers understanding of the elements of SP. We plan to use the survey to craft a targeted education campaign on improving understanding of and adherence to SP.
PaletteStarViz: a visualization method for multi-criteria decision making from high-dimensional pareto-optimal front

Visual representation of a many-objective Pareto-optimal front in four or more dimensional objective space requires a large number of data points. Moreover, choosing a single point from a large set even with certain preference information is problematic, as it causes a large cognitive burden on the part of the decision-makers. Therefore, many-objective optimization and decision-making practitioners have been interested in effective visualization methods to enable them to filter down a large set to a few critical points for further analysis. Most existing visualization methods are borrowed from other data analytic domains and they are too generic to be effective for many-criteria decision making. In this paper, we propose an alternative visualization method, following an earlier concept, using star-coordinate plots for effectively visualizing many-objective trade-off solutions. The proposed PaletteStarViz respects some basic topological, geometric, and functional decision-making properties of high-dimensional trade-off points mapped to a "two-and-a-half" dimensional space. We demonstrate the use of PaletteStarViz to a number high-dimensional Pareto-optimal fronts.
Few-Shot Learning with Intra-Class Knowledge Transfer

We consider the few-shot classification task with an unbalanced dataset, in which some classes have sufficient training samples while other classes only have limited training samples. Recent works have proposed to solve this task by augmenting the training data of the few-shot classes using generative models with the few-shot training samples as the seeds. However, due to the limited number of the few-shot seeds, the generated samples usually have small diversity, making it difficult to train a discriminative classifier for the few-shot classes. To enrich the diversity of the generated samples, we propose to leverage the intra-class knowledge from the neighbor many-shot classes with the intuition that neighbor classes share similar statistical information. Such intra-class information is obtained with a two-step mechanism. First, a regressor trained only on the many-shot classes is used to evaluate the few-shot class means from only a few samples. Second, superclasses are clustered, and the statistical mean and feature variance of each superclass are used as transferable knowledge inherited by the children few-shot classes. Such knowledge is then used by a generator to augment the sparse training data to help the downstream classification tasks. Extensive experiments show that our method achieves state-of-the-art across different datasets and $n$-shot settings.
Gene amplification, laboratory evolution, and biosensor screening reveal MucK as a terephthalic acid transporter in Acinetobacter baylyi ADP1.

Microbial terephthalic acid (TPA) catabolic pathways are conserved among the few bacteria known to turnover this xenobiotic aromatic compound. However, to date there are few reported cases in which this pathway has been successfully expressed in heterologous hosts to impart efficient utilization of TPA as a sole carbon source. In this work, we aimed to engineer TPA conversion in Acinetobacter baylyi ADP1 via the heterologous expression of catabolic and transporter genes from a native TPA-utilizing bacterium. Specifically, we obtained ADP1-derived strains capable of growing on TPA as the sole carbon source using chromosomal insertion and targeted amplification of the tph catabolic operon from Comamonas sp. E6. Adaptive laboratory evolution was then used to improve growth on this substrate. TPA consumption rates of the evolved strains, which retained multiple copies of the tph genes, were ~0.2 g/L/h (or ~1 g TPA/g cells/h), similar to that of Comamonas sp. E6 and almost 2-fold higher than that of Rhodococcus jostii RHA1, another native TPA-utilizing strain. To evaluate TPA transport in the evolved ADP1 strains, we engineered a TPA biosensor consisting of the transcription factor TphR and a fluorescent reporter. In combination with whole-genome sequencing, the TPA biosensor revealed that transport of TPA was not mediated by the heterologous proteins from Comamonas sp. E6. Instead, the endogenous ADP1 muconate transporter MucK, a member of the major facilitator superfamily, was responsible for TPA transport in several evolved strains in which MucK variants were found to enhance TPA uptake. Furthermore, the IclR-type transcriptional regulator DcaS was identified as a repressor of mucK expression. Overall, this work presents an unexpected function of a native protein identified through gene amplification, adaptive laboratory evolution, and a combination of screening methods. This study also provides a TPA biosensor for application in ADP1 and identifies transporter variants for use in metabolic engineering applications focused on plastic upcycling of polyesters.
Self-regulation in optometry

This study provides an empirical analysis of the effects of advertising and commercial practice on the price and quality of optometrists' services. Data were collected by actually purchasing eye examinations and eyeglasses from optometrists in cities with and without restrictions on advertising and commercial practice. Analysis of the data supports the view that advertising and commercial practice lower prices but do not lower the quality of professional care available in the market. The implications of these findings are discussed.
Interim Measures in the Practice of the International Court of Justice and the International Criminal Court

Comparative international jurisprudence is a precious tool in the hands of international lawyers to examine the increasing, and increasingly important, phenomenon of cross-fertilization among international courts and tribunals. From this perspective, this chapter reviews the practice of the International Court of Justice and the International Criminal Court with regard to the issuance of provisional measures by considering their nature, form, modalities and efficacy. In light of the comparative exercise carried out herein, this chapter contends that interim measures granted by the ICJ and the ICC—despite the existing differences due to the framework of their statutory norms—share some remarkable common features.
Predictors of Tracheostomy Decannulation in Adult Laryngotracheal Stenosis.

ObjectivePredictors of tracheostomy decannulation in patients with laryngotracheal stenosis are not fully known, making prognosis difficult. The aim was to identify predictors of tracheostomy decan...
Comparisons of Graph Neural Networks on Cancer Classification Leveraging a Joint of Phenotypic and Genetic Features.

Cancer is responsible for millions of deaths worldwide every year. Although significant progress hasbeen achieved in cancer medicine, many issues remain to be addressed for improving cancer therapy.Appropriate cancer patient stratification is the prerequisite for selecting appropriate treatment plan, ascancer patients are of known heterogeneous genetic make-ups and phenotypic differences. In thisstudy, built upon deep phenotypic characterizations extractable from Mayo Clinic electronic healthrecords (EHRs) and genetic test reports for a collection of cancer patients, we evaluated variousgraph neural networks (GNNs) leveraging a joint of phenotypic and genetic features for cancer typeclassification. Models were applied and fine-tuned on the Mayo Clinic cancer disease dataset. Theassessment was done through the reported accuracy, precision, recall, and F1 values as well as throughF1 scores based on the disease class. Per our evaluation results, GNNs on average outperformed thebaseline models with mean statistics always being higher that those of the baseline models (0.849 vs0.772 for accuracy, 0.858 vs 0.794 for precision, 0.843 vs 0.759 for recall, and 0.843 vs 0.855 for F1score). Among GNNs, ChebNet, GraphSAGE, and TAGCN showed the best performance, while GATshowed the worst. We applied and compared eight GNN models including AGNN, ChebNet, GAT,GCN, GIN, GraphSAGE, SGC, and TAGCN on the Mayo Clinic cancer disease dataset and assessedtheir performance as well as compared them with each other and with more conventional machinelearning models such as decision tree, gradient boosting, multi-layer perceptron, naive bayes, andrandom forest which we used as the baselines.
Recent advances in understanding the Th1/Th2 effector choice.

For over 35 years since Mosmann and Coffman proposed the seminal "type 1 T helper (Th1)/type 2 T helper (Th2)" hypothesis in 1986, the immunological community has appreciated that naive CD4 T cells need to make important decisions upon their activation, namely to differentiate towards a Th1, Th2, Th17 (interleukin-17-producing T helper), follicular T helper (Tfh), or regulatory T cell (Treg) fate to orchestrate a variety of adaptive immune responses. The major molecular underpinnings of the Th1/Th2 effector fate choice had been initially characterized using excellent reductionist in vitro culture systems, through which the transcription factors T-bet and GATA3 were identified as the master regulators for the differentiation of Th1 and Th2 cells, respectively. However, Th1/Th2 cell differentiation and their cellular heterogeneity are usually determined by a combinatorial expression of multiple transcription factors, particularly in vivo, where dendritic cell (DC) and innate lymphoid cell (ILC) subsets can also influence T helper lineage choices. In addition, inflammatory cytokines that are capable of inducing Th17 cell differentiation are also found to be induced during typical Th1- or Th2-related immune responses, resulting in an alternative differentiation pathway, transiting from a Th17 cell phenotype towards Th1 or Th2 cells. In this review, we will discuss the recent advances in the field, focusing on some new players in the transcriptional network, contributions of DCs and ILCs, and alternative differentiation pathways towards understanding the Th1/Th2 effector choice in vivo.
ECOA-10. Integrated genomic and clinical analysis of BRAF-mutated glioma in adults

BRAF alterations are recognized as a significant driver of disease in pediatric low-grade glioma (pLGG) but the implications of BRAF alterations on the natural history and response to treatment are unclear in adult glioma. We characterized the molecular and clinical features of a multi-institutional cohort of adults with BRAF-mutated gliomas. We identified patients with glioma containing BRAF alterations on sequencing in multi-institutional cohorts (Dana-Farber/Brigham Cancer Center, Johns Hopkins Hospital, GENIE, TCGA). BRAF alterations were grouped into previously defined classes: I (V600E; RAS-independent/dimerization-independent), II (RAS-independent/dimerization-dependent), III (RAS-dependent/dimerization-dependent) in addition to BRAF copy number gains, fusions, and other. We interrogated 289 BRAF-altered gliomas (199 patients >=18yrs, 90 patients <18yrs; range 0-85yrs), and observed histopathologic and molecular differences between BRAF-altered gliomas in adults versus pediatric patients. Amongst adults, the most common BRAF alterations were Class I followed by copy number gains, with glioblastoma (GBM) the most prevalent histology. In comparison, pediatric gliomas in our cohort frequently harbored Class I mutations followed by BRAF fusions, with primarily pilocytic astrocytoma and pLGG histologies. Principal component analysis and correlation analysis revealed molecular features associated with gliomas of different BRAF alterations and histologies, including mutation of NF1, a negative regulator of RAS, which was significantly associated with class II/III BRAF alterations (64.3%) and not observed in BRAFV600E-mutated gliomas (0%, n=62) (p<0.0001). Demographic and molecular features were evaluated for correlates for adult glioma risk stratification. Comparative survival analysis showed no significant difference between adult GBM harboring Class I compared to other BRAF alterations, whereas young adult age (18-35yrs) was associated with improved outcomes (p<0.05). Among 86 GBM patients with detailed clinicopathologic data, 7 received RAF-targeted therapy, with variable clinical response. This cohort of BRAF-altered adult gliomas demonstrates a broad range of molecular alterations with implications for treatment sensitivity and patient risk stratification.
Defining R-loop classes and their contributions to genome instability

R-loops are non-B DNA structures that form during transcription when the nascent RNA anneals to the template DNA strand forming a RNA:DNA hybrid. Understanding the genomic distribution and function of R-loops is an important goal, since R-loops have been implicated in a number of adaptive and maladaptive processes under physiological and pathological conditions. Based on R-loop mapping datasets, we propose the existence of two main classes of R-loops, each associated with unique characteristics. Promoter-paused R-loops (Class I) are short R-loops that form at high frequency during promoter-proximal pausing by RNA polymerase II. Elongation-associated R-loops (Class II) are long structures that occur throughout gene bodies at modest frequencies. We further discuss the relationships between each R-loop class with instances of genome instability and suggest that increased class I R-loops, resulting from enhanced promoter-proximal pausing, represent the main culprits for R-loop mediated genome instability under pathological conditions.
Cutaneous Pathology of COVID-19 as a Window into Immunologic Mechanisms of Disease

Many skin manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection reflect activation of cutaneous and systemic immune responses involving effector pathways of both the innate and adaptive arms of the immune system. This article reviews evidence from the recent clinical and scientific literature that informs the current understanding of the consequences of coronavirus disease 2019 (COVID-19)-induced immune cell activation, as relevant to dermatology. Topics include the clinical consequences of autoantibody production in patients with COVID-19, immunologic evidence for chilblains as a manifestation of SARS-CoV-2 infection, and the relationship between type I interferons and COVID-19 disease severity.
On the Stability of Parametrically Excited Standing Waves

A recent theoretical analysis of parametrically excited standing waves has shown that in systems with large aspect ratio they can exhibit very interesting spatial as well as dynamical behavior1. Under suitable conditions spatially periodic waves were found to be unstable with respect to spatial modulations of the wave number which do not induce the well-known Eckhaus instability. Thus the eventual number of cells in the system does not change, instead the instability leads to the formation of coexisting patches with different wave numbers (“wave-number kinks”). For other parameter values the band of stable wave numbers is found to disappear above a critical value of the external driving. This gives access to a well-controlled transition to a dynamic state which presumably shows chaotic behavior. In the present communication the conditions for the appearance of these two phenomena are discussed in more detail. In particular, the dependence of the phase diffusion coefficient on external as well as internal parameters is presented.
Percutaneous Coronary Intervention and Stable Angina

Interventional cardiology has revolutionized modern cardiovascular care. Its effect is felt on medical therapy, as well as in cardiovascular surgery, by allowing patients with myocardial ischemia to be treated less invasively and avoiding an operative approach. Interventional cardiology has also spurred interest in specific aspects of preventive cardiology in attempts to identify vulnerable regions or even vulnerable plaques/lesions in the coronary arteries, which could be treated or passivated in some way early, prior to the onset of symptom development such as unstable angina, acute infarction, or sudden death. As originally developed and then applied in September 1977,1,2 the technique was described to treat focal, subtotal concentric, nontortuous proximal stenoses in patients with single-vessel disease. This lesion group was not selected so much because it would uniquely benefit the most in terms of improved morbidity or mortality compared to other subsets of disease, but more because it was this lesion group that could be accessed with the technology available at that time which was large, inflexible, rigid, and not very deliverable.3
A CMOS wideband LNA for DCS1800 PCS1900 and WCDMA

A wideband CMOS LNA for PCS 1900 and WCDMA is presented. The design circuit uses conventional configuration with an additional capacitance. This method is mainly used to optimize the noise performance of LNA. This paper explored the method's application in 3/sup rd/ generation receiver, which is capable of adapting to the various communications standards in a low-cost CMOS technology. One of the advantages of the method is the simplicity of the circuit compared to other wideband LNA implementation. The design is implemented in a 0.18/spl mu/m TSMC CMOS technology. In the simulation, the 200MHz bandwidth of interest and a total 560 MHz bandwidth are well matched. Additionally, the power consumption of the circuit is less than 7mW from a supply voltage of 1.8V.
Immunization and diagnosis in bovine reproductive tract infections.

This chapter discusses immunization and diagnosis in bovine reproductive tract infections. Bovine genital tract infections that result in pregnancy loss are large economic problems in the cattle industry. Such infections can occur by either a hematogenous or an ascending route. Because the diseases acquired by the former route are primarily septicemic whereas local ascending infections are primarily sexually transmitted diseases (STDs), diagnosis and control may differ between these two categories. Systemic infection with localization in the gravid uterus occurs in leptospirosis, systemic campylobacteriosis (caused by Campylobacter fetus subsp, fetus), listeriosis, brucellosis, neosporosis, and Haemophilus sommus infection. In these syndromes, systemic immunity and serologic diagnosis are often reliable. Brucellosis is a good example of hematogenous infection with localization in the gravid uterus because systemic vaccination and serologic assays for diagnosis have been practiced for decades. Haemophilus sommus infection is also presented because it is a septicemic disease causing abortion and many other sequelae, thus immunity is complex.
Tracking in Urban Environments Using Sensor Networks Based on Audio-Video Fusion

Heterogeneous sensor networks (HSNs) are gaining popularity in diverse fields, such as military surveillance, equipment monitoring, and target tracking yarvis:2005:infocom. They are natural steps in the evolution of wireless sensor networks wireless sensor network (WSNs) driven by several factors. Increasingly, WSNs will need to support multiple, although not necessarily concurrent, applications. Different applications may require different resources. Some applications can make use of nodes with different capabilities. As the technology matures, new types of nodes will become available and existing deployments will be refreshed. Diverse nodes will need to coexist and support old and new applications.
Abstract 4547: Enhanced anti-tumor effect of WNT pathway antagonists in combination with taxanes

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The Wnt/beta-catenin pathway, which signals through the Frizzled (FZD) receptor family and several co-receptors, has long been implicated in cancer. We have previously demonstrated that inhibition of WNT/beta-catenin signaling by vantictumab (anti-FZD) or OMP-54F28 (FZD8-Fc) inhibits tumor growth, decreases tumorigenicity and induces differentiation in solid tumors. The anti-tumor effect of our Wnt antagonists is most evident in combination with chemotherapeutic agents. We sought to determine if the anti-tumor effect of Wnt pathway inhibitors varied with different chemotherapeutic agents. We compared the growth inhibitory effect of vantictumab and OMP-54F28 with either taxanes (paclitaxel and nab-paclitaxel) or with DNA synthesis inhibitors (gemcitabine and carboplatin) in patient-derived tumor xenografts. In a model for pancreatic ductal carcinoma, vantictumab with nab-paclitaxel was more efficacious than vantictumab with gemcitabine in inhibiting tumor growth and Wnt target gene expression (at doses of nab-paclitaxel and gemcitabine that were equivalent in their single-agent growth-inhibitory effects). Histologic analysis indicated that nab-paclitaxel increased mitotic cells and beta-catenin levels. Importantly, the addition of vantictumab to nab-paclitaxel reversed the nab-paclitaxel-induced increase in mitotic cells and beta-catenin expression. An independent experiment in a serous ovarian cancer xenograft model also showed enhanced anti-tumor activity when combining OMP-54F28 with either paclitaxel or nab-paclitaxel compared to the combination with carboplatin. A potential mechanism to account for these results involves on the observation that Wnt/beta-catenin signaling is under cell cycle control and peaks at the G2/M phase. Taxanes inhibit microtubule function and block the cell cycle at G2/M. In contrast, other chemotherapeutic agents, such as platinum compounds and nucleoside analogs, inhibit DNA synthesis and block cell proliferation at S phase. We hypothesize that combination of Wnt blockade with chemotherapeutic agents, such as taxanes, that induce G2/M arrest may result in optimal anti-tumor activity. Citation Format: Wan-Ching Yen, Marcus M. Fischer, John Lewicki, Austin Gurney, Timothy Hoey. Enhanced anti-tumor effect of WNT pathway antagonists in combination with taxanes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4547. doi:10.1158/1538-7445.AM2014-4547
Geometric morphometric and phylogenetic analyses of Arizona Sky Island populations of Scaphinotus petersi Roeschke (Coleoptera: Carabidae)

Scaphinotus petersi Roeschke, 1907 (Carabidae) is a ground beetle endemic to Sky Islands in south-eastern Arizona. Previous taxonomic studies described several subspecies with morphological differences inhabiting geographically isolated mountain ranges. We combined molecular sequence data and morphometric data, especially head and pronotum shape analyses, to examine the variation and divergence in subspecies and isolated montane populations. In this study, we employ a combination of distance morphometrics as well as geometric morphometrics to quantify the level of morphological variation, and to test the hypothesis that geographically distinct populations of S. petersi are phenotypically distinct. Results suggest that these isolated populations have diverged morphologically and genetically. Phylogenetic analyses identified two monophyletic lineages within the species that correspond generally to pronotum shape. We observed significant morphological variation among most montane populations in of S. petersi, with the pronotum shape as the clearest delimiting trait. © 2015 The Linnean Society of London
An Analytical Study of Transmission Modifications as Related to Vehicle Performance and Economy

A method of vehicle performance measurement has been developed so that selection of optimum fuel-economy-performance trade-offs can be made for a vehicle having various powertrain components. This method was utilized in an analytical study of drivetrain component features such as--overall ratio range, number of ratio steps, locked converters, continuously variable drives, etc. Both manual and automatic type transmissions are considered. Indications are that ratio range is an important consideration in the selection of transmission design parameters and also conventional transmission concepts can be competitive with the more exotic continuously variable type units.
Civil Society and Participatory Governance: Municipal Councils and Social Housing Programs in Brazil

1: Introduction 2: Housing Policy as Critical Challenge for Development and Democracy 3: The Effect of Municipal Housing Councils on Policy Outcomes 4: Civil Society Density, Participatory Governance, and Policy Outcomes 5: Pathways to Participatory Governance: Policy-Making in Brazil's Municipal Housing Councils 6: The Creation Effect: Evaluating Commitment in Participatory Governance Institutions 7: Longevity in Participatory Governance Institutions: Sao Paulo's Municipal Housing Council at 10 8: Conclusion: Can Democracy Remedy Social Challenges? Findings on the Effect of Participatory Governance Institutions
Pop-rock music as precipitating cause in youth suicide

The plaintiffs in a law suit alleged that the heavy metal rock band Judas Priest, and its publisher CBS, were liable for damages to two youths who shot themselves after listening to the band's album. Crucial issues included “proximate cause” and “precipitating cause” in suicide, and the alleged role of subliminal messages. The judge ruled that although the “heavy metal” music might have had a toxic influence, the sounds and words are protected by the free speech first amendment. The influence of subliminal messages on behavior is unproven. There were many other elements in the personalities and situations of the victims to account for their self-destructive behavior.
The Art of Writing a Test: A Skill Never Learned

(1987). The Art of Writing a Test. The Clearing House: A Journal of Educational Strategies, Issues and Ideas: Vol. 61, No. 4, pp. 175-178.
Stability of sterile aqueous lidocaine hydrochloride and epinephrine injections submitted by U.S. hospitals.

The stability of lidocaine hydrochloride and epinephrine injections that had been stored in hospital pharmacies across the United States was studied. Through a voluntary drug stability program, the Food and Drug Administration selected 220 samples (representing four manufacturers) from hospital pharmacies representing an adequate cross section of the country. The samples were analyzed for strength, identification, pH, and physical condition. Six samples failed to meet USP requirements for strength of epinephrine, but all six of these samples had passed the expiration dates. Of the 62 samples that were analyzed for the presence of the d-isomer of epinephrine, approximately 95% had less than 5% d-isomer present. Only one sample had greater than 10% d-isomer present, and this sample had a low epinephrine content (26%) and had passed the expiration date. Lidocaine hydrochloride and epinephrine injections appear to be stable after storage under actual marketplace conditions.
Effect of a low calcium diet on bone crystallinity and skeletal uptake of Ca45 in rats.

SummaryChemical and X-ray diffraction analyses were performed on femurs of rats receiving a low (0.1%) and high (0.8%) calcium diet with (50 ppm) and without (0 ppm) fluoride supplementaton in the water. In addition, uptake of Ca45 by the ends and shafts of tibia was determined. Bone crystal-linity (i.e., crystal size and/or perfection) was not affected by calcium intake, and the improvement in crystal texture produced by fluoride was the same for the high and low calcium groups. Skeletal uptake of radiocalcium was approximately 20 times higher in calcium deficient animals. Fluoride decreased slightly the uptake of radiocalcium.
New constraints on the provenance of hopanoids in the marine geologic record: Bacteriohopanepolyols in marine suboxic and anoxic environments

Abstract The abundance and structural diversity of bacteriohopanepolyols (BHPs) was examined in three marine pelagic environments that are characterized by strong vertical redox gradients and water column suboxia or anoxia. The abundance and, in most instances, structural diversity of BHPs was highest at depths where conditions were suboxic or anoxic. However, the majority of the BHP structures that were identified are environmentally cosmopolitan and their biological sources are presently not well constrained. An isomer of bacteriohopanetetrol (denoted BHT II) was observed at all three study sites in association with anoxic and suboxic conditions within the water column. Based on the absence of BHT II from terrigenous and oxic marine environments studied to date, and its strong association with suboxic and anoxic marine pelagic environments, we propose that BHT II is a promising candidate biomarker for water column suboxia and anoxia in the marine geologic record. The molecular fingerprint of BHPs in suspended and sinking particles and core-top sediments indicates that hopanoids produced within the water column are exported to marine sediments and that their biological source is most likely associated with settling particles and not the free-water phase. Based on our observations, BHPs likely represent an important input to the sedimentary hopanoid inventory, particularly in upwelling environments characterized by pelagic oxygen minimum zones (OMZ) and anoxic marine basins.