cssi/SciSciGPT-SciSciNet huggingface dataset:
Altered pHi regulation in 3T3/CFTR clones and their chemotherapeutic drug-selected derivatives.

Recently (L. Y. Wei, M. J. Stutts, M. M. Hoffman, and P. D. Roepe. Biophys. J. 69: 883-895, 1996), 3T3 cells overexpressing the cystic fibrosis transmembrane conductance regulator (CFTR) were found to exhibit chemotherapeutic drug resistance and other traits of multidrug resistant (MDR) cells. In the present work, NIH 3T3/CFTR clones were selected with either doxorubicin or vincristine in incremental fashion to generate series of stable MDR cell lines that exhibit increasing levels of drug resistance. Thus C3D6 (grown in the presence of 600 nM doxorubicin) was selected from C3D4 (grown in the presence of 400 nM doxorubicin), which was selected from C3D1 (grown in the presence of 100 nM doxorubicin), which was in turn selected from the original 3T3/CFTR clone C3 (M. J. Stutts, S. E. Gabriel, J. C. Olsen, J. T. Gatzy, T. L. O'Connell, E. M. Price, and R. C. Boucher. J. Biol. Chem. 268: 20653-20658, 1993), which was not grown in the presence of chemotherapeutic drug. A similar series was generated via select...
Preliminary Investigation of an Anaerobic Membrane Separation Process for Treatment of Low-Strength Wastewaters

As a result of an evaluation of biomass reduction technologies, anaerobic treatment was found to have potential for the lowest level of biomass production in the treatment of municipal and industrial wastewaters. A limitation of anaerobic wastewater treatment processes for dilute wastewaters and at cold temperatures is the ability to maintain a significant level of methanogenic organisms in the reactor to sustain efficient treatment. A process consisting of an anaerobic baffled reactor followed by membrane separation was proposed for the treatment of low strength wastewaters at colder temperatures. A 4 gpm pilot plant facility was assembled and installed at the West Point wastewater treatment plant in Seattle, to test the feasibility of the anaerobic/membrane separation treatment system. During a 7 month period, 3 different attempts were made for system start up with the result of little methanogenic activity in the anaerobic baffled reactor system. The temperatures during the start up ranged from 10 to 15°C and may have been a significant factor in the inability to generate a significant methanogenic population within the time available. Another aspect of this continuing study to investigate biomass reduction was a cost analysis to evaluate the potential for an anaerobic/membrane process for biomass reduction. The cost analysis showed that the significant capital expenditure for adding a membrane reactor to retrofit an existing secondary treatment system resulted in a greater annual amortization costs than the significant operational cost savings realized by less sludge production, less aeration hp, and excess methane gas production. Because the membrane separation system represented about 90% of the retrofit costs, the cost analysis suggests that a less expensive method be pursued for liquid solids separation after anaerobic treatment of low strength wastewaters. This title belongs to WERF Research Report Series ISBN: 9781843397298 (eBook)
Water and Ion Balance, Hormonal Control of

Publisher Summary This chapter focuses on the water and ion balance control by hormones in insects. Insects are found in habitats ranging from the driest deserts to aquatic habitats of diverse ionic composition. In many species, the environment changes dramatically during metamorphosis. Insects respond to perturbations in body water composition by using a combination of hormonal and autonomous mechanisms to vary the amount and composition of fluid excreted by the excretory system. Hormones acting on the hindgut appear to stimulate recovery of fluid and ions from the primary urine, leading to cycling of materials through the excretory system and hemolymph, and clearance of wastes. The majority of information about regulation of hindgut transport comes from studies on the locust. The locust hindgut consists of two distinct regions, a more anterior ileum and a more posterior rectum. Two peptide factors isolated from the corpus cardiacum are ion transport peptide, acting on the ileum, and chloride transport-stimulating hormone, acting on the rectum. The amino acid sequence of these peptides has been determined. Other factors that stimulate water reabsorption by the hindgut include neuroparsins A and B. In addition, a number of factors modulate contractions by the hindgut musculature.
Scanning Electron Microscopy Study of Endothelial Injury and Thrombus Formation in WT and VWF Deficient Mice.

Abstract Abstract 3062 Poster Board II-1038 VWF is a large plasma glycoprotein required for normal hemostasis, and performs its function through binding to coagulation Factor VIII, and via interactions with both platelet surface glycoproteins and the activated and/or damaged vascular surface. We have developed a scanning electron microscopy (SEM) protocol to visualize endothelial damage and thrombus formation in wild-type and VWF-deficient mice. Thrombus formation is initiated by ferric chloride, and subsequently at defined time points, the circulation is rapidly flushed and aldehyde fixed. The carotid artery is removed, externally fixed, sectioned (both longitudinally and in cross-section), processed for SEM, and visualized. With this protocol we have obtained high-quality images (exceeding 100,000x) of FeCl3-induced endothelial damage and thrombus formation in C57BL/6 and VWF-deficient mice at baseline, and at 30, 60, 90, 120, 240, and 300 seconds post-injury (please access http://sites.google.com/site/mottolab/ to view images). Interestingly, we find that FeCl3 induces little, if any, endothelial denudation and collagen exposure at these time points, with the endothelium clearly appearing changed from baseline, but not damaged. Thus, initial platelet adhesion seems to be occurring in the absence of collagen exposure in this model. In wild-type mice, platelets adhere rapidly to the endothelial surface and assume a cross-linked appearance by 90 seconds, with continual inward growth of the thrombus through the 300 second time point. In VWF-deficient mice, platelets also adhere rapidly to the endothelial surface, but in contrast, remain recognizable longer without assuming a highly-activated phenotype. Compared with wild-type, at all time points examined the VWF-deficient thrombus appears smaller with considerably less cross-linking and platelet activation. Interestingly, during the course of these experiments we also have identified what appears to be red blood cells (RBCs) participating in thrombus formation. Similar to platelets, RBCs interact directly with the endothelial surface, and subsequently become elongated in the direction of blood flow. These elongated RBCs are often observed to cluster and bind platelets, with the subsequent formation of large platelet-erythrocyte complexes. Further characterization of these complexes and the role they may play in thrombus formation is currently in progress. Additionally, similar SEM studies are underway with both ADAMTS13-deficient and GPIb alpha-deficient mice, and with mice transiently expressing in vivo biotinylated VWF for visualization of this molecule at high magnification and resolution. These studies should help better define the mechanisms of endothelial activation and thrombus formation as they occur in situ. Disclosures No relevant conflicts of interest to declare.
Abstract 296: Decreased Hepatic Avpr1a Gene Expression and Elevated Serum Bile Acid in Mouse Model of Metabolic Syndrome

The KK/HIJ mouse has been demonstrated to have polygenic obesity and insulin resistance and serve as a model of metabolic syndrome. From microarray studies in this mouse strain, we observed hepatic gene expression of arginine vasopressin receptor 1A (Avpr1a) as the most differentially elevated gene in the liver following 3-week of voluntary wheel running activity. Subsequent studies validated that hepatic Avpr1a gene expression is significantly upregulated following voluntary activity and also highly suppressed (4 to 8-fold) in 2 independent models of insulin resistance (including obesity and lipoatrophic models). Although Avpr1a is highly abundant in the liver, its physiologic role is not well described. One proposed role for hepatic Avpr1a is mediation of vasopressin-induced bile acid secretion. To further evaluate the relationship between hepatic Avpr1a and bile acid homeostasis, we determined the age-related change in these variables in female KK mice. To investigate, adipose tissue, liver and serum were collected from female KK mice from before sexual maturity (PRE: 4.5 weeks old, n=9) and after sexual maturation (POST: 6 to 30 weeks old, n=12). Consistent with previous studies using this obesity-prone strain, we observed a robust increase in adiposity with age despite a standard rodent chow diet. RT-PCR studies of hepatic gene expression revealed a 53% lower Avpr1a in POST compared to PRE mice (p
Permanent magnet motor operating mechanism with 40.5kV vacuum circuit breaker

A novel motor operating mechanism is presented which applied in the high voltage circuit breaker. The new motor is a permanent magnet motor with limited angle and only working in the starting stage. Based on the requirement of high voltage circuit breaker, the structure and parameters of motor are designed. The dynamic simulation of permanent magnet motor are achieved by employing the finite element method. The prototype of motor and drive control system are developed, established the performance testing system, and completed the dynamic characteristics testing. Finally, the winding current and angle of driving motor are obtained through the performance testing with the circuit breaker. The results indicate that the permanent magnet motor have a good mechanical characteristics and reach the operation of high voltage circuit breaker.
Thrombolytic therapy: pre- and post-GISSI-2, ISIS-3, and GUSTO-1.

At present, data are available from three large-scale randomized trials of mortality that directly compared different thrombolytic regimens, namely, GISSI-2, ISIS-3, and GUS-T0-1. These trials randomized over 100,000 patients worldwide. When examined individually as well as in aggregate, these trials demonstrate at most only small absolute differences between thrombolytic agents both in terms of lives saved and major complications, including hemorrhagic stroke. Specifically, TPA produces more strokes and cerebral bleeds, but whether or not there is a small incremental mortality benefit is not yet clear. All three trials indicate that the choice of thrombolytic agent is much less important to ultimate survival than is the delay time between onset of symptoms and initiation of treatment
Enhancing the resolution of a near-eye display with a Pancharatnam-Berry phase deflector.

We report an electro-optic image shifter to enhance the resolution of display devices with a Pancharatnam–Berry phase deflector (PBD). The switching time of our PBD is less than 1 ms. Through synchronizing and computational factorization, we are able to double the display resolution for reducing the screen door effect. Such a thin and lightweight PBD image shifter can be easily integrated into wearable display devices. Its potential application for virtual reality and augmented reality is emphasized.
Perceived Value of an Online Interactive Learning Tool and Its Critical Antecedents: An Abstract

With the rapid advancement of information technology, students show increasing interest in technology-enhanced pedagogies (Jackson et al., 2011; Sun et al., 2017), and experiential learning can be promoted by interactive online teaching. Previous study reveals that online courses with great levels of interactivity combine higher levels of student motivation, enhanced learning outcomes, and satisfaction over interactive learning environments (Espasa & Meneses, 2010). LearnSmart is an adaptive learning tool that evaluates students’ knowledge levels by tracking the topics students have mastered and thus identifies the areas that need further instruction and practice (Norman, 2011). Based on constructivism theory (Leidner & Jarvenpaa, 2006), it is important for marketing professors to emphasize the engaging learning experience among college students. This study extends the literature on interactive learning and teaching and empirically evaluates the perceived value of LearnSmart as a subjective evaluation measure of student learning effectiveness, with respect to several relevant factors in the literature such as perceived competence, perceived challenge, satisfaction with LearnSmart, semesters, instructors, course delivery format, and devices to access the course.
Serological, genetic and clinical associations with increased health-care resource utilization in inflammatory bowel disease

OBJECTIVE Inflammatory bowel diseases (IBD) are associated with significant morbidity and economic burden. The variable course of IBD creates a need for predictors of clinical outcomes and health resource utilization (HRU) to guide treatment decisions. We aimed to identify clinical, serological or genetic markers associated with inpatient resource utilization in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS Patients with IBD with available genetic and serological data who had at least one emergency department visit or hospitalization in a 3-year period were included. The primary outcome measure was HRU, as measured by the All Patient Refined Diagnosis Related Group classification system. Univariate and multivariate linear and logistic regression models were used to identify the associations with HRU. RESULTS Altogether 858 (562 CD and 296 UC) patients were included. Anti-CBir1 seropositivity (P = 0.002, effect size [ES]: 0.762, 95% confidence interval [CI] 0.512-1.012) and low socioeconomic status (P = 0.005, ES: 1.620 [95% CI 1.091-2.149]) were independently associated with a high HRU. CD diagnosis (P = 0.006, ES: -0.701 [95% CI -0.959 to -0.443]) was independently associated with a low inpatient HRU. CONCLUSION In patients with IBD who required at least one emergency department visit or hospitalization, anti-CBir1 antibody status may be a useful biomarker of HRU when formulating management strategies to reduce disease complications and resource utilization.
Effect of Bifidobacterium infantis 35624 (Align) on the Lactulose Breath Test for Small Intestinal Bacterial Overgrowth

Small intestinal bacterial overgrowth (SIBO) may cause symptoms in patients with abdominal bloating, distension, and gas. SIBO can be assessed using the lactulose breath test (LBT). A commonly used probiotic supplement is Align containing Bifidobacterium infantis 35624. The aim of this study was to determine the effect of B. infantis 35624 on hydrogen and methane excretion during LBT. Healthy subjects underwent LBT before and after 2 weeks of daily Align administration. Hydrogen and methane concentrations were measured for each breath sample. Results are expressed as mean ± SE and analyzed using repeated measures ANCOVA. A breath test was considered positive if hydrogen and/or methane increased > 20 ppm above baseline by 90 min of the test or if a dual hydrogen peak was present. Nineteen healthy subjects were studied. Hydrogen levels were similar pre- and post-probiotic across the 3-h study (p = 0.768). In contrast, methane levels were significantly higher with probiotic administration (p = 0.012). A rise in methane > 20 ppm was seen in three subjects pre-probiotic but six post-probiotic. Of the 19 subjects, an “abnormal” LBT pre-probiotic was present in ten subjects and during the probiotic, 13 were abnormal. This study found that 2 weeks of B. infantis 35624 (Align) supplementation affects LBT assessment for SIBO by significantly increasing methane, but not hydrogen, excretion after lactulose administration. Methane levels reached values that would be considered positive for SIBO patients. This study suggests that patients undergoing LBT should discontinue probiotics prior to the test as these supplements may alter the test results.
The aleu207-->arg mutation in F1F0-ATP synthase from Escherichia coli. A model for human mitochondrial disease.

Abstract The mitochondrial ATPase 6 gene encodes a subunit of F1F0 adenosine triphosphate (ATP) synthase. A mutation in the ATPase 6 gene has been genetically linked to two maternally inherited genetic diseases: neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP) and certain cases of subacute necrotizing encephalopathy (SNE). Although the severity of both NARP and SNE disease were correlated with the quantity of the ATPase 6leu156-->arg mutation in each patient, the mutation could not be shown to alter F1F0-ATP synthase activity. To investigate the biochemical effects of the ATPase 6leu156-->arg mutation on F1F0-ATP synthase, the aleu207-->arg mutation was constructed in the F1F0-ATP synthase from Escherichia coli to serve as a model for the disease mutation. Characterization of the model bacterial enzyme revealed that the mutation abolishes detectable ATP synthesis via oxidative phosphorylation. The aleu207-->arg mutation results in a structural perturbation blocking proton translocation through F1F0-ATP synthase. The results suggest that a structural defect in human F1F0-ATP synthase is the biochemical basis for NARP and SNE.
Exposure of fibrinogen receptors on fresh and stored platelets by ADP and epinephrine as single agents and as a pair

Platelet concentrates stored at 22 degrees C have a marked decrease in their aggregation response to adenosine diphosphate (ADP) or epinephrine but a normal response to these agents when used as a pair. Since platelet stimulation involves exposure of receptors for fibrinogen, we studied fibrinogen binding to platelets from fresh and stored concentrates. Following stimulation with 10 microM ADP or 20 microM epinephrine, platelet suspensions from fresh concentrates bound 125I-fibrinogen in a reaction that reached completion within 30 min. Significantly less binding occurred in suspensions from platelet concentrates that had been stored for 5 days at 22 degrees C. When stimulated by ADP and epinephrine as a pair (2 microM each), binding of fibrinogen to platelets was complete within 10–15 min and was not significantly decreased in suspensions from stored concentrates. We also investigated the effect of storage on the glycoprotein IIb-IIa complex, thought to be a specific receptor for fibrinogen on the platelet surface. Binding of a monoclonal antibody specific for this complex (B59.2) to platelet suspensions was unaffected by 5 days of storage. Furthermore, B59.2 inhibited aggregation, secretion, and fibrinogen binding of fresh and stored platelets stimulated with the pair of agents just as it did with single agents. We conclude that storage for 5 days at 22 degrees C impairs the exposure of fibrinogen receptors on platelets in response to ADP or epinephrine when used as single agents, without affecting the glycoprotein IIb-IIIa complex quantitatively. The function of the receptor is normal in response to the pair of agents.
Constructive Logic Versus Algebraization I

The Introduction explains the issues raised by constructive logic for different traditions; principally, for mainstream constructive mathematics treated here, and for the foundational tradition, the subject of Part II. The material is arranged under the following headings. 1. Flashy metatheorems and some neglected implications . For example, classical proofs of Π 0 2 theorems are essentially no harder to unwind than corresponding constructive, more precisely, intuitionistic proofs. In short, intuitionistic restrictions tend to be too weak in practice, incidentally despite the (little known) elegance of their metatheory documented in a digression. 2. Weakness of the constructive meaning of Π 0 3 → Π 0 3 . This is illustrated by reference to various elementary implications of this form between familiar finiteness theorems in arithmetic. A proviso is formulated which corrects that weakness, and is often satisfied in practice. 3. Metamathematics of classical systems : modern variants of Hubert's program without detour via constructive logic. For example, some recalcitrant proofs of Π 0 2 theorems have in fact been unwound by suitable functional interpretations such as the n.c.i.; cut elimination is generally less efficient. 4. Applying the n.c.i.: reassurances (about additional skills needed for successful applications, beyond knowing the metatheory of the n.c.i.). Attention is drawn to proof strategies used in ordinary mathematics, of comparable generality to logical metatheorems, where similar additional skills are needed, and have proved to be available. Much the same applies to successful applications of model theory which, contrary to superficial impressions, are shown to involve operations on proof's, and not only on the theorem proved. 5. Algebraization: reminders and surprises (principal section). By reference mainly to recent literature, the potential of algebraization and a couple of other general mathematical strategies in the sense of 4. above is documented, and contrasted with logical contributions to the constructive tradition in mathematics. Remarkably many significant and general points are illustrated by work on sums of squares and by the Appendix . The latter supplements section 2. by reference to the most sophisticated implication between finiteness theorems in the number-theoretic literature. Particular attention is given to realizing the 'proviso' mentioned in 2., or, equivalently, to making a proper choice between various meanings of the popular phrase: from a counterexample to the conclusion we get one to the premise. - The Appendix can be read independently of the main text.
Flood Control through Engineered Avulsions and Floodways in the Lower Yellow River

AbstractDue to high in-channel sedimentation rates, the Yellow River Delta of China has changed course frequently in its history, with huge socioeconomic impacts. The following questions are addres...
Validation of an automated-ETDRS near and intermediate visual acuity measurement.

BACKGROUND The aim of this study was to determine the repeatability of an automated-ETDRS (Early Treatment Diabetic Retinopathy Study) near and intermediate visual acuity measurement in subjects with normal visual acuity and subjects with reduced visual acuity. The agreement of automated-ETDRS with gold standard chart-based visual acuity measurement was also studied. METHODS Fifty-one subjects were tested (aged 23 to 91 years; 33 subjects with normal visual acuity: 6/7.5 or better; 18 subjects with reduced visual acuity: 6/9 to 6/30). Near and intermediate visual acuity of one eye from each subject was measured with an automated tablet-computer system (M&S Technologies, Inc.) and Precision Vision paper chart in a random sequence. Subjects were retested one week later. Repeatability was evaluated using the 95 per cent limits of agreement (LoA) between the two visits. RESULTS Average difference between automated-ETDRS near visual acuity and near visual acuity by paper chart was 0.02 ± 0.10 logMAR (p > 0.05). Agreement of near visual acuity between automated-ETDRS and paper chart was good, with 95 per cent LoA of ±0.19 logMAR. Furthermore, automated-ETDRS near visual acuity showed good repeatability (95 per cent LoA of ±0.20). Mean difference between automated-ETDRS intermediate visual acuity and intermediate visual acuity by paper chart was 0.02 ± 0.10 logMAR (p > 0.05). Agreement of intermediate visual acuity between automated-ETDRS and paper chart was good, with 95 per cent LoA of ±0.20 logMAR. In addition, automated-ETDRS intermediate visual acuity had good repeatability (95 per cent LoA of ±0.16). CONCLUSION Automated-ETDRS near and intermediate visual acuity measurement showed good repeatability and agreement with the gold standard chart-based visual acuity measurement. The findings of this study indicate the automated visual acuity measurement system may have potential for use in both patient care and clinical trials.
Recent advances in understanding inherited deficiencies in immunity to infections

The immune system is central to our interactions with the world in which we live and importantly dictates our response to potential allergens, toxins, and pathogens to which we are constantly exposed. Understanding the mechanisms that underlie protective host immune responses against microbial pathogens is vital for the development of improved treatment and vaccination strategies against infections. To that end, inherited immunodeficiencies that manifest with susceptibility to bacterial, viral, and/or fungal infections have provided fundamental insights into the indispensable contribution of key immune pathways in host defense against various pathogens. In this mini-review, we summarize the findings from a series of recent publications in which inherited immunodeficiencies have helped illuminate the interplay of human immunity and resistance to infection.
2121-P: Proinflammatory Cytokines Alter Beta-Cell Exosome Cargo and Function to Enhance Activation of the CXCL10-CXCR3 Axis in Diabetes

Coordinated activity among islet cells is necessary for glucose homeostasis. Chronic exposure to diabetogenic factors such as pro-inflammatory cytokines, perturbs islet cell crosstalk and β-cell function in diabetes. Secretory nanovesicles - exosomes (EXO) derived from cytokine exposed β-cells modulate physiological and pathological responses to β-cell stress. However, the mechanisms governing this process remain unknown. We tested the hypothesis that β-cell failure in diabetes is mediated in part through β-cell autocrine release of pro-inflammatory EXO to promote inflammation and inhibit β-cell function. Assessment of EXO concentrations from Min6 β-cells exposed to diabetogenic cytokines (IL-1β, TNF-α, and IFNγ, cytoEXO) revealed a 2-fold increase in EXO secretion (p Disclosure N. Javeed: None. T.K. Her: None. M. Brown: None. P.M. Vanderboom: None. A.M. Egan: None. A. Vella: Advisory Panel; Self; vTv Therapeutics, Zealand Pharma A/S. Research Support; Self; Novo Nordisk A/S, Xeris Pharmaceuticals, Inc. I.R. Lanza: None. T. Patel: None. A. Matveyenko: None.
Mechanisms Underlying the Development of Cardiac Arrhythmias

Normal cardiac rhythm is fairly regular and typically ranges between 50 and 90 beats per minute in adults at rest and up to 220 beats per minute during physical activity and/or emotional stress. A cardiac arrhythmia simply defined is a variation from the normal heart rhythm that is not physiologically justified. Arrhythmia can be regular or irregular (such as tachycardia and fibrillation, respectively) as well as slower or faster than the normal resting rate (brady- and tachyarrhythmias, respectively). In this chapter, our principal focus is on mechanisms underlying the development of tachyarrhythmias. These are generally divided into two major categories: (1) enhanced or abnormal impulse formation (i.e., focal activity) and (2) abnormal conduction leading to reentry
A Meta-Analysis of Cue Reactivity in Tobacco Cigarette Smokers

INTRODUCTION The cue reactivity paradigm allows for systematic evaluation of motivational responses to drug-related cues that may elicit drug use. The literature on this topic has grown substantially in recent decades, and the methodology used to study cue reactivity has varied widely across studies. The present research provided a meta-analytic investigation of variables that have an impact on cue reactivity effects to enhance our understanding of this key feature of tobacco use disorders. METHODS A total of 128 publications yielded 249 effect sizes, which were analyzed to investigate the magnitude of the cue reactivity effect and potential moderators. RESULTS Craving generated a moderate-to-large effect size (Hedges' g = 0.71, p < .001), indicating that drug cues produced significantly greater craving than neutral cues. However, physiological variables yielded significantly lower or nonsignificant effect sizes. Analyses of a variety of empirically and theoretically relevant moderator variables showed that cue modality, cue personalization, cue reactivity environment, and the use of multiple assessments of cue reactivity were significantly associated with the magnitude of cue-specific craving effects (ps < .001). Effect sizes were not significantly related to abstinence status, gender, cigarettes per day, and treatment-seeking status. CONCLUSIONS The results underscored the strength of self-reported craving as an index of cue reactivity across studies, which support theories that posit cue reactivity is core to the addictive process for daily tobacco cigarette smokers. The present research further elucidates the variables that alter the cue reactivity effects across studies and provides recommendations for future cue reactivity research. IMPLICATIONS A core feature of addiction is that drug-related cues can have a major impact on motivational responses across multiple substance use disorders, including tobacco cigarettes. This paper describes a meta-analysis updating and synthesizing cue reactivity research with tobacco cigarette smokers over the last 20 years, a time of rapid growth for this literature. The study leads to a better understanding of the cue reactivity paradigm across different self-report and physiological variables and identifies factors that may modulate addictive motivation for tobacco cigarettes.
ModelMine: a tool to facilitate mining models from open source repositories

Mining Software Repositories (MSR) has opened up new pathways and rich sources of data for research and practical purposes. This research discipline facilitates mining data from open source repositories and analyzing software defects, development activities, processes, patterns, and more. Contemporary mining tools are geared towards data extraction, analysis primarily from textual artifacts and have limitations in representation, ranking and availability. This paper presents ModelMine, a novel mining tool focuses on mining model-based artifacts and designs from open source repositories. ModelMine is designed particularly to mine software repositories, artifacts and commit history to uncover information about software designs and practices in open-source communities. ModelMine supports features that include identification and ranking of open source repositories based on the extent of presence of model-based artifacts and querying repositories to extract models and design artifacts based on customizable criteria. It supports phase-by-phase caching of intermediate results to speed up the processing to enable efficient mining of data. We compare ModelMine against a state-of-the-art tool named PyDriller in terms of performance and usability. The results show that ModelMine has the potential to become instrumental for cross-disciplinary research that combines modeling and design with repository mining and artifacts extraction. URL: https://www.smreza.com/projects/modelmine/
Dual inhibition of DNA-PK and DNA polymerase theta overcomes radiation resistance induced by p53 deficiency.

TP53 deficiency in cancer is associated with poor patient outcomes and resistance to DNA damaging therapies. However, the mechanisms underlying treatment resistance in p53-deficient cells remain poorly characterized. Using live cell imaging of DNA double-strand breaks (DSBs) and cell cycle state transitions, we show that p53-deficient cells exhibit accelerated repair of radiomimetic-induced DSBs arising in S phase. Low-dose DNA-dependent protein kinase (DNA-PK) inhibition increases the S-phase DSB burden in p53-deficient cells, resulting in elevated rates of mitotic catastrophe. However, a subset of p53-deficient cells exhibits intrinsic resistance to radiomimetic-induced DSBs despite DNA-PK inhibition. We show that p53-deficient cells under DNA-PK inhibition utilize DNA polymerase theta (Pol θ)-mediated end joining repair to promote their viability in response to therapy-induced DSBs. Pol θ inhibition selectively increases S-phase DSB burden after radiomimetic therapy and promotes prolonged G2 arrest. Dual inhibition of DNA-PK and Pol θ restores radiation sensitivity in p53-deficient cells as well as in p53-mutant breast cancer cell lines. Thus, combination targeting of DNA-PK- and Pol θ-dependent end joining repair represents a promising strategy for overcoming resistance to DNA damaging therapies in p53-deficient cancers.
Topological analysis of type 3 secretion translocons in native membranes

Abstract PFPs (Pore-forming proteins) perforate cellular membranes to create an aqueous pore and allow the passage of ions and polar molecules. The molecular mechanisms for many of these PFPs have been elucidated by combining high resolution structural information of these proteins with biochemical and biophysical approaches. However, some PFPs do not adopt stable conformations and are difficult to study in vitro. An example of these proteins are the bacterial Type 3 Secretion (T3S) translocators. The translocators are secreted by the bacterium and insert into the target cell membrane to form a translocon pore providing a portal for the passage of T3S toxins into eukaryotic cells. Given the important role that the T3S systems play in pathogenesis, methods to study these translocon pores in cellular membranes are needed. Using a combination of protein modifications and methods to selectively permeate and solubilized eukaryotic membranes, we have established an experimental procedure to analyze the topology of the Pseudomonas aeruginosa T3S translocon using P. aeruginosa strain variants and HeLa cell lines.
Self-rated mental and physical health are prospectively associated with psychosocial and academic adjustment to college

To examine prospective associations between physical and mental self-rated health (SRH), college generation status and college adjustment among first-year college students. Participants and methods...
Flipping the Script About the Rio Grande Valley and the Border During Turbulent Times

This chapter concludes the book with attention to how Rio Grande Valley organizations and individuals continue to push for a productive, forward-thinking vision of the region and U.S.–Mexico borderlands. From a region-wide lobbying effort in the state capitol to national speeches and open letters to President Trump to grassroots social media campaigns, borderlanders tell a different story. Their discursive practice of debordering extends the term to encompass strategic place-making from within borderlands. Production of knowledge about the border should be a conversation with borderland communities, especially when national policies and politics about our borderlands and its communities exacerbate racial violence and suffering, such as unequipped and overcrowded detention centers and declining funding for public services for the disenfranchised.
Telehealth for Dialectical Behavioral Therapy: A Commentary on the Experience of a Rapid Transition to Virtual Delivery of DBT

Abstract Telehealth has been rapidly adopted to provide continuity of delivery of mental health services in light of COVID-19. However, the remote implementation of intensive treatments like dialectical behavioral therapy (DBT) has been vastly understudied. The aim of the current commentary is to describe potential obstacles, propose solutions, and discuss advantages of transitioning from traditional in-person to a virtual delivery format for full model DBT. We speak to these points at multiple levels of relevance to clinical scientists and practitioners: (1) considerations about the virtual delivery format, (2) considerations for the virtual delivery of DBT specifically, and (3) person-level considerations (e.g., client, clinician). We illustrate the commentary using examples of obstacles encountered and solutions identified during our DBT team’s rapid transition to telehealth in response to COVID-19-related shut-downs and discuss considerations for the extension of telehealth delivery of DBT going forward. We are hopeful that the rapid transition to telehealth delivery of mental health services in response to COVID-19 serves as a call to action for clinicians to adapt and leverage technology to deliver DBT on a broader scale to improve patient health outcomes.
Cobamide sharing drives skin microbiome dynamics

The human skin microbiome is a key player in human health, with diverse functions ranging from defense against pathogens to education of the immune system. While recent studies have begun to shed light on the valuable role that skin microorganisms have in maintaining a healthy skin barrier, a detailed understanding of the complex interactions that shape healthy skin microbial communities is limited. Cobamides, the vitamin B12 class of cofactor, are essential for organisms across the tree of life. Because this vitamin is only produced by a limited fraction of prokaryotes, cobamide sharing has been shown to mediate community dynamics within microbial communities. Here, we provide the first large-scale unbiased metagenomic assessment of cobamide biosynthesis and utilization in the skin microbiome. We show that while numerous and diverse taxa across the major bacterial phyla on the skin are cobamide dependent, relatively few species encode for de novo cobamide biosynthesis. We find that cobamide sharing shapes the network structure in microbial communities across the different microenvironments of the skin and that changes in community structure and microbiome diversity are driven by the abundance of cobamide producers in the Corynebacterium genus, in both healthy and disease skin states. Lastly, we find that de novo cobamide biosynthesis is enriched only in host-associated Corynebacterium species, including those prevalent on human skin. We confirm that the cofactor is produced in excess through quantification of cobamide production by skin-associated species isolated in the laboratory. Taken together, our results support a role for cobamide sharing within skin microbial communities, which we predict stabilizes the microbiome and mediates host interactions.
Threshold estimation in single photon emission computed tomography and planar imaging for clinical radioimmunotherapy.

Thresholding is the most widely used organ or tumor segmentation technique used in single photon emission computed tomography (SPECT) and planar imaging for monoclonal antibodies. Selecting the optimal threshold requires a priori knowledge (volumes from CT or magnetic resonance) for the size and contrast level of the organ in question. Failure to select an optimal threshold leads to overestimation or underestimation of the volume and, subsequently, the organ-absorbed dose value in radio-immunotherapy. To investigate this threshold selection problem, we performed a phantom experiment using six lucite spheres ranging from 1 to 117 ml and filled with a uniform activity of 1 microCi/ml Tc-99m. These spheres were placed at the center and off-center locations of a Jasczsak phantom and scanned with a three-headed gamma camera in SPECT and planar modes. Target-nontarget (T:NT) ratios were changed by adding the appropriate activity to the background. A threshold search algorithm with an interpolative background correction was applied to sphere images. This algorithm selects a threshold that minimizes the difference between the true and measured volumes (SPECT) or areas (planar). It was found that for spheres equal to or larger than 20 ml [diameter (D) > 38 mm] and T:NT ratios higher than 5:1, mean thresholds at 42% for SPECT and 38% for planar imaging yielded minimum image segmentation errors, which is in agreement with current literature. However, for small T:NT ratios ( 38 mm). Hence, the use of fixed thresholds in low contrasts and with tumor and organ sizes of clinical interest (25 < or = D < or = 50 mm) may result in limited volume estimation accuracy. Therefore, we have provided the investigator a method to obtain the threshold values in which the proper threshold can be selected based on the organ and tumor size and image contrast. By measuring and calibrating the proper threshold value derived through machine-specific phantom measurements, a more accurate volume and activity quantitation can be performed. This, in turn, will provide tumor-absorbed dose optimization and greater accuracy in the measurement of potentially subacute, toxic absorbed doses to normal organs for patients undergoing radioimmunotherapy.
Crystalline silicon on silicon nitride hybrid platform for integrated photonic applications

We demonstrate a hybrid material platform, in which a layer of crystalline silicon is placed on top of a silicon nitride on a silicon dioxide die. We also report an efficient interlayer coupling structure with 0.02 dB insertion loss. Using this hybrid platform, high-Q resonators are demonstrated.
Higher prevalence of bipolar I disorder among Asian and Latino compared to Caucasian patients receiving treatment

Introduction: There are limited data regarding relationships between race/ethnicity and bipolar disorder. This study assessed such relationships in patients receiving treatment in a university clinic. Methods: Demographic, illness characteristics, symptom severity, treatment, and care utilization data were collected from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation, Mini-International Neuropsychiatric Interview, and the STEP-BD Clinician Rated Packet. Data were compared among 51 Asian, 35 Latino, and 86 Caucasian patients in treatment at the Stanford University Bipolar Disorders Clinic. χ2 tests and analyses of variance were used to assess between-group differences. Results: Asian and Latino compared to Caucasian patients had significantly higher prevalence of bipolar I disorder (58.8% and 60.0% versus 37.2%, respectively). Asian and Latino patients also had a higher prevalence of history of psychosis, but this was related to the excess of bipolar I disorder, becoming non-significant after controlling for bipolar subtype. The racial/ethnic difference in bipolar subtype prevalence did not appear to be secondary to demographic or socioeconomic differences. Discussion: The higher prevalence of bipolar I disorder and thus lower prevalence of bipolar II disorder and bipolar disorder not otherwise specified in Asian and Latino patients may be related to under-diagnosis, misdiagnosis, or care underutilization of patients with milder forms of bipolar disorders. Additional research and public health efforts are warranted to further understand the effects of race and ethnicity on the management of bipolar disorders and to enhance timely and accurate diagnosis, culturally sensitive treatment, and optimal care utilization.
Redefining terrorism under the Mubarak regime : towards a new definition of terrorism in Egypt

In the fight against terrorism, many states have overreacted to its threat and have adopted overbroad definitions of terrorism that forfeited fundamental rights in the name of protecting national security. Egypt, under President Mubarak's regime, was one of those states that have exceedingly abused its terrorism definition to restrain many Egyptians' fundamental rights and freedoms. The following article provides a comprehensive analysis of the Egyptian definitional approach by highlighting the various deficiencies in the Egyptian definition of terrorism. Moreover, the paper underscores the harmful implication that such ambiguous and vague a definition may pose for the legal system and emphasises how easily this definition lends itself to manipulation by unscrupulous political regimes. To provide more insight, the article compares the Egyptian definition of terrorism to a number of international law definitions and underscores the various dissimilarities between them in the light of international law norms and standards for defining terrorism. It is further claimed that there are core elements of an objective definition that can be distilled from the various international definitions in order to prevent any potential abuse of power or undue interference with fundamental rights and freedoms. The article concludes with legal recommendations derived from the analysis of international law approaches for the prospective Egyptian legislator to consider when amending the anti-terrorism law of Egypt.
SHARAD soundings and surface roughness at past, present, and proposed landing sites on Mars: Reflections at Phoenix may be attributable to deep ground ice

We use the Shallow Radar (SHARAD) on the Mars Reconnaissance Orbiter to search for subsurface interfaces and characterize surface roughness at the landing sites of Viking Landers 1 and 2, Mars Pathfinder, the Mars Exploration Rovers Spirit and Opportunity, the Phoenix Mars lander, the Mars Science Laboratory Curiosity rover, and three other sites proposed for Curiosity. Only at the Phoenix site do we find clear evidence of subsurface radar returns, mapping out an interface that may be the base of ground ice at depths of ~15–66 m across 2900 km2 in the depression where the lander resides. At the Opportunity, Spirit, and candidate Curiosity sites, images and altimetry show layered materials tens to hundreds of meters thick extending tens to hundreds of kilometers laterally. These scales are well within SHARAD's resolution limits, so the lack of detections is attributable either to low density contrasts in layers of similar composition and internal structure or to signal attenuation within the shallowest layers. At each site, we use the radar return power to estimate surface roughness at scales of 10–100 m, a measure that is important for assessing physical properties, landing safety, and site trafficability. The strongest returns are found at the Opportunity site, indicating that Meridiani Planum is exceptionally smooth. Returns of moderate strength at the Spirit site reflect roughness more typical of Mars. Gale crater, Curiosity's ultimate destination, is the smoothest of the four proposed sites we examined, with Holden crater, Eberswalde crater, and Mawrth Vallis exhibiting progressively greater roughness.
Sense of place: inquiry and application

‘Sense of place’ is a fundamental, yet presumptive concept within the planning and design disciplines. Professional theories have largely remained focused on the physical aspects of place, as this is their primary mode of production. However, the academic literature suggests that sense of place is a multidimensional concept that extends beyond the physical attributes of a given location. A thorough literature review reveals that sense of place is influenced by four primary dimensions. It is argued that this theoretical perspective can better inform the transformation of space into place by linking each dimension with specific design processes.
A new algorithm for linear and integer feasibility in horn constraints

In this paper, we detail a new algorithm for the problem of checking linear and integer feasibility of a system of Horn constraints. For certain special cases, the new algorithm is faster than the "Lifting Algorithm" described in [1]. Moreover, the new approach is based on different ideas and in fact exploits several properties of Horn constraint systems (HCS) which are not known to be part of the literature. In the case of constraints of bounded width (corresponding to "loosely coupled" systems), our algorithm can be modified to run in O(n3+mċn+ mċn2/log(max(m,n))) time. Our main result establishes that checking the feasibility of an HCS can be reduced to three subproblems: negative-cost cycle detection in networks (NCCD), matrix-vector multiplication (MV), and the conversion of an HCS to a non-redundant set of difference constraints (H2D). The MV and NCCD problems have been extremely well-studied, and specialized, fast algorithms exist for relevant special cases. We have identified a new problem, H2D, which warrants future research, since improved algorithms for H2D could be implemented in our algorithm to decrease the running time.