cssi/SciSciGPT-SciSciNet huggingface dataset:
Purine Analogs as Potential Anticytomegalovirus Agents

SummaryThe activity of 25 purine analogs was determined against human cytomegalovirus in vitro. Nineteen compounds were considered to have a degree of antiviral activity with seven of them markedly inhibiting both virus-induced cytopathogenic effects in WI-38 cells and the development of detectable virus. These seven compounds were 2-amino-9-β-d-ribofuranosyl-9H-purine-6-thiol, 2-aminopurine-6-thiol, 9-β-d-arabinofuranosyladenine, purine-6-thiol hydrate, purine-6-carboxaldehyde thiosemicarbazone, 2-amino-6-[(1-methyl-4-nitroimidazol-5-yl) thio] purine, and 9-β-d-ribofuranosyl-9H-purine-6-thiol. The active thiopurines protected the cells from virus infection if allowed to incubate with the cells 1 hr prior to addition of the virus. None of the compounds had demonstrable virucidal activity.
The effects of short sleep duration on proteinuria and chronic kidney disease: a systematic review and meta-analysis.

Background The risks of proteinuria and chronic kidney disease (CKD) in adults who regularly have short sleep duration (short sleepers) are controversial. The aim of this meta-analysis was to assess the effects of short sleep duration on proteinuria and CKD. Methods A literature search was conducted using MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from the inception of the databases through November 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risks of proteinuria and CKD in short sleepers were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed utilizing a random-effect, generic inverse variance method. Results Six observational studies with 252 075 individuals and three observational studies with 37 197 individuals were included in the analyses to assess the risks of CKD and proteinuria in short sleepers, respectively. The pooled RR of CKD in short sleepers was 1.51 (95% CI, 0.99-2.55). When meta-analysis was restricted only to studies with adjusted analysis for confounders assessing the risk of CKD in short sleepers, the pooled RR of CKD was 1.54 (95% CI, 0.80-2.95). The pooled RR of proteinuria in short sleepers was 1.47 (95% CI, 1.26-1.72). Conclusions Despite the lack of significant association between short sleep duration and CKD, our meta-analysis suggests a potential association between short sleep duration and proteinuria, a surrogate marker for kidney disease progression. Future study is required to investigate if reversal of short sleep helps reduce proteinuria.
Strength statistics of single crystals and metallic glasses under small stressed volumes

Abstract It has been well documented that plastic deformation of crystalline and amorphous metals/alloys shows a general trend of “smaller is stronger”. The majority of the experimental and modeling studies along this line have been focused on finding and reasoning the scaling slope or exponent in the logarithmic plot of strength versus size. In contrast to this view, here we show that the universal picture should be the thermally activated nucleation mechanisms in small stressed volume, the stochastic behavior as to find the weakest links in intermediate sizes of the stressed volume, and the convolution of these two mechanisms with respect to variables such as indenter radius in nanoindentation pop-in, crystallographic orientation, pre-strain level, sample length as in uniaxial tests, and others. Experiments that cover the entire spectrum of length scales and a unified model that treats both thermal activation and spatial stochasticity have discovered new perspectives in understanding and correlating the strength statistics in a vast of observations in nanoindentation, micro-pillar compression, and fiber/whisker tension tests of single crystals and metallic glasses.
Abstract 14866: Athletic Heart Screening: Usefulness of Echocardiography and Economic Impact

Background: The athletic heart screen (AS) for sudden cardiac death (SD) detection is controversial in the USA. EKG use is common in AS programs but ECHO is uncommon. Our study aims to determine th...
Revisiting the God of the Gaps: On the Tempestuous Experience of Overwhelming Presence

Rudolf Otto, commenting on the famous thesis of Johannes Weiss and Albert Schweitzer that the message of Jesus, according to the NT, was fundamentally eschatological, calls attention to an apparent contradiction, namely, that a radical eschatology with apocalyptic effects as attributed to Jesus is ill-disposed to what Schweitzer also found in Jesus, a “marvelous ethic.” The problem is how the imminent breaking in of eternity may be reconciled with strict responsibility toward things that endure in time. This is the problem that Antje Jackelen addresses in her work, particularly in Time & Eternity. Her proposal to bring back the partnership of time and eternity that modernity has split asunder suggests a revisiting of the infamous and vilified argument for the “god of the gap.” The latter is a symptom of modernity’s diagnosed alienation of eternity from time confining eternity to the flickering epiphanies in the presumed ever closing fissures in the scientific attempt to account for the cosmos in a seamless narration. Even as Jackelen dismisses the disparaged “arguments” for an ever retreating god of the gap, the argument of this essay is that the derision is in the fact that the more the gap seems to be mended by science the more the texture of narrated time rips apart, heralding the perennial return of the sacred salvage. Some of the critiques of modernity in the works of historians, anthropologists, philosophers, and literary critics may show the way out of the maze and aid the efforts of theologians to reclaim their discourses in the interstices of the received dominant narrative of this age.
A Chronic Disease State Simulation in an Ambulatory Care Elective Course.

Objective. To implement a chronic disease state simulation in an ambulatory care elective course and to assess the simulation’s impact on students’ perceptions of their empathy toward patients and of their counseling skills.Design. The chronic disease state simulation occurred over 2 weeks. Students alternated playing the role of patient and pharmacist. As patients, students adhered to medication regimens, lifestyle modifications, and blood glucose or blood pressure monitoring. As pharmacists, students conducted patient interviews, and provided education and counseling. Empathy and counseling skills were assessed through course surveys, written reflections, and SOAP notes.Assessment. Results from a cohort of 130 students indicated the simulation enhanced students’ perceptions of their abilities to empathize with and counsel patients with chronic diseases.Conclusion. The chronic disease state simulation provides a novel approach to develop skills needed for working with complex patient cases in ambulatory ...
Transluminal Balloon Dilation of Ureteral Strictures

AbstractUreteral strictures are uncommon problems in urological practice. The nonvascular application of the Gruntzig balloon catheter is proposed as an alternative to surgery in some of these patients. We treated 6 ureteral strictures in 5 patients by balloon dilation with an 83 per cent success rate.
Molecular genetic analysis of the primary immunodeficiency disorders.

Rapid progress in the application of molecular genetics to the primary immune deficiency disorders is adding to our knowledge of how the immune system functions in health and disease. Currently, the molecular genetic causes have been found for 7 of the 17 World Health Organization recognized immune deficiency disorders.
Survey of Ant Species in Rockwall County, Texas

Abstract. The myrmecofauna of Rockwall County, TX are undersampled. A survey from March to November 2015 resulted in collection and identification of twelve species of ants. Solenopsis invicta Buren, Monomorium minimum Buckley, and Forelius pruinosus Roger were the species collected most often on the ground, while Crematogaster laeviuscula Mayr was the dominant arboreal species. We believe our identification of Aphaenogaster huachucana Creighton to be the first record of this species in the state.
Law as a Means to an End: Instrumentalism in the legal profession

The first sentence of the rules governing the legal profession declares that the core of lawyering is a means (lawyer)–ends (client) relationship: “a lawyer, as a member of the legal profession, is a representative of clients.” It mandates that “a lawyer shall abide by a client's decisions concerning the objectives of representation.” Confirming this avowedly instrumental connection, the rules caution that “A lawyer's representation of a client … does not constitute an endorsement of the client's political, economic, social or moral views or activities.” The implicit point is that serving as a tool to advance a client's perhaps immoral ends does not make the lawyer immoral. Legal practice is infused with an additional sense of instrumentalism: lawyers take an instrumental attitude toward law itself, wielding and manipulating legal rules and processes to advance their clients' goals. Legal rules and mechanisms are the tools of their craft, what they operate with to get things done. Furthermore, many lawyers see the practice of law instrumentally as a means to their own enrichment and wield and manipulate legal rules and processes to further their personal ends. Practicing lawyers have long acted instrumentally in the three respects just mentioned. The shift away from non-instrumental views of law chronicled in earlier chapters relates specifically to views expressed the legal elite: leaders of the bar, prominent judges, and legal academics. That does not mean these developments had no effect on legal practice.
SplitThreader: Exploration and analysis of rearrangements in cancer genomes

Genomic rearrangements and associated copy number changes are important drivers in cancer as they can alter the expression of oncogenes and tumor suppressors, create gene fusions, and misregulate gene expression. Here we present SplitThreader (http://splitthreader.com), an open- source interactive web application for analysis and visualization of genomic rearrangements and copy number variation in cancer genomes. SplitThreader constructs a sequence graph of genomic rearrangements in the sample and uses a priority queue breadth-first search algorithm on the graph to search for novel interactions. This is applied to detect gene fusions and other novel sequences, as well as to evaluate distances in the rearranged genome between any genomic regions of interest, especially the repositioning of regulatory elements and their target genes. SplitThreader also analyzes each variant to categorize it by its relation to other variants and by its copy number concordance. This identifies balanced translocations, identifies simple and complex variants, and suggests likely false positives when copy number is not concordant across a candidate breakpoint. It also provides explanations when multiple variants affect the copy number state and obscure the contribution of a single variant, such as a deletion within a region that is overall amplified. Together, these categories triage the variants into groups and provide a starting point for further systematic analysis and manual curation. To demonstrate its utility, we apply SplitThreader to three cancer cell lines, MCF-7 and A549 with Illumina paired- end sequencing, and SK-BR-3, with long-read PacBio sequencing. Using SplitThreader, we examine the genomic rearrangements responsible for previously observed gene fusions in SK-BR-3 and MCF-7, and discover many of the fusions involved a complex series of multiple genomic rearrangements. We also find notable differences in the types of variants between the three cell lines, in particular a much higher proportion of reciprocal variants in SK-BR-3 and a distinct clustering of interchromosomal variants in SK-BR-3 and MCF-7 that is absent in A549.
Public Reason, Convergence Discourse, and the Well-Ordered Society Under Crisis

A well-ordered society faces a crisis whenever non-compliers intrude society. This has a potential to destabilize political order. This paper provides a formal analysis of two competing solutions to the problem of political stability offered in the public reason liberalism literature – namely, using public reason or using convergence discourse to restore political stability in the well-ordered society. The formal analyses offered in this paper show that using public reason fails completely, while using convergent discourse, although doing better, has its own limitations.
PREVALENCE OF MONOCLONAL GAMMOPATHY OF UNKNOWN SIGNIFICANCE IN WILD TYPE TRANSTHYRETIN AMYLOIDOSIS PATIENTS

Background: Monoclonal gammopathy (MG) is a diagnostic feature of light chain amyloidosis (AL). MG of unknown significance (MGUS) in the general population increases with increasing age. Wild type transthyretin amyloidosis (ATTRwt) is a disease of elderly men and MGUS would be expected to co-exist
The coccidian parasites Toxoplasma and Neospora dysregulate mammalian lipid droplet biogenesis

Upon infection, the intracellular parasite Toxoplasma gondii co-opts critical functions of its host cell to avoid immune clearance and gain access to nutritional resources. One route by which Toxoplasma co-opts its host cell is through hijacking host organelles, many of which have roles in immunomodulation. Here we demonstrate that Toxoplasma infection results in increased biogenesis of host lipid droplets through rewiring of multiple components of host neutral lipid metabolism. These metabolic changes cause increased responsiveness of host cells to free fatty acid, leading to a radical increase in the esterification of free fatty acids into triacylglycerol. We identified c-Jun kinase and mammalian target of rapamycin (mTOR) as components of two distinct host signaling pathways that modulate the parasite-induced lipid droplet accumulation. We also found that, unlike many host processes dysregulated during Toxoplasma infection, the induction of lipid droplet generation is conserved not only during infection with genetically diverse Toxoplasma strains but also with Neospora caninum, which is closely related to Toxoplasma but has a restricted host range and uses different effector proteins to alter host signaling. Finally, by showing that a Toxoplasma strain deficient in exporting a specific class of effectors is unable to induce lipid droplet accumulation, we demonstrate that the parasite plays an active role in this process. These results indicate that, despite their different host ranges, Toxoplasma and Neospora use a conserved mechanism to co-opt these host organelles, which suggests that lipid droplets play a critical role at the coccidian host-pathogen interface.
Abstract 023: Mission Lifeline Regional Reports Impact Performance in Two Major Metropolitan EMS Regions

The American Heart Association launched Mission: Lifeline (M:L) in 2007 with a goal of reducing system barriers to prompt treatment for heart attacks, beginning with the 911 call and continuing thr...
Saddle vs Nonsaddle Pulmonary Embolism: Clinical Presentation, Hemodynamics, Management, and Outcomes

Abstract Objective To understand the clinical significance, hemodynamic presentation, management, and outcomes of patients presenting with saddle pulmonary embolism (PE). Methods All patients with saddle PE diagnosed at Mayo Clinic in Rochester, Minnesota, from January 1, 1999, through December 31, 2014, were included in this study. These patients were age and simplified Pulmonary Embolism Severity Index (sPESI) matched (1:1) to a nonsaddle PE cohort. Both groups were then classified into massive, submassive, and low-risk PE based on established criteria and compared for clinical presentation, management, and outcomes. Results A total of 187 consecutive patients with saddle PE were identified. The saddle PE group presented more frequently with massive PE (31% vs 20%) and submassive PE (49% vs 32%), whereas low-risk PE was more common in the nonsaddle PE group (48% vs 20%). Systemic thrombolysis was used more frequently in the saddle PE group on admission (10% vs 4%; P=.04) and later during hospitalization (3.2% vs 0%; P=.03). Late major adverse events were similar in both groups except for mechanical ventilation (6% in saddle PE vs 1% in nonsaddle PE; P=.02). Overall in-hospital mortality did not differ between the 2 groups (4.3% in saddle PE vs 5.4% in nonsaddle PE; P=.81). Conclusion Although patients with saddle PE presented with higher rates of hemodynamic compromise and need for thrombolysis and mechanical ventilation, we found no difference in short-term outcomes compared with an age- and severity-matched nonsaddle PE cohort. Overall, in-hospital mortality was low in both groups.
Preservation Strategies that Support the Scale-up and Automation of Tissue Biomanufacturing

Tissue engineering strategies to repair or replace tissues and organs that have been damaged by disease, trauma, or congenital issues usually require many weeks of production during which time patients are incapacitated or reliant on temporary devices. In order to fully meet the rising clinical demand of transplantable tissues/organs, various preservation technologies need to be implemented to create “off-the-shelf” availability of biological components and products. This review will focus on the preservation methods used for biological resources (cells, growth factors, and biological scaffolds) and also for the finished tissue-engineered constructs. Recent studies have demonstrated that conventional cryopreservation and vitrification preservation methods can maintain functionality and properties of cells and cell-seeded scaffolds during long-term storage. Lyophilization can also be used as an alternative strategy for engineered tissues that are devoid of cells. Additionally, fabrication technologies combined with freezing/thawing processes will likely emerge as the preferred strategy to better control the physical and biological properties of engineered tissues while simultaneously providing a shelf life for the product. The development of preservation methodologies for tissue engineering would minimize the shortage of tissues/organs and offer an effective and commercialized strategy for improved automation of tissue biomanufacturing.
Sphingolipids as Regulators of Autophagy and Endocytic Trafficking

Abstract Macroautophagy (herein referred to as autophagy) is a highly conserved stress response that engulfs damaged proteins, lipids, and/or organelles within double-membrane vesicles called autophagosomes for lysosomal degradation. Dysregulated autophagy is a hallmark of cancer; and thus, there is great interest in modulating autophagy for cancer therapy. Sphingolipids regulate each step of autophagosome biogenesis with roles for sphingolipid metabolites and enzymes spanning from the initial step of de novo ceramide synthesis to the sphingosine-1-phosphate lyase 1–mediated exit from the sphingolipid pathway. Notably, sphingolipid metabolism occurs at several of the organelles that contribute to autophagosome biogenesis to suggest that local changes in sphingolipids may regulate autophagy. As sphingolipid metabolism is frequently dysregulated in cancer, a molecular understanding of sphingolipids in stress-induced autophagy may provide insight into the mechanisms driving tumor development and progression. On the contrary, modulation of sphingolipid metabolites and/or enzymes can induce autophagy-dependent cell death for cancer therapy. This chapter will overview the major steps in mammalian autophagy, discuss the regulation of each step by sphingolipid metabolites, and describe the functions of sphingolipid-mediated autophagy in cancer. While our understanding of the signaling and biophysical properties of sphingolipids in autophagy remains in its infancy, the unique cross talk between the two pathways is an exciting area for further development, particularly in the context of cancer therapy.
Deinstitutionalization: A Public Policy Perspective

1. Deinstitutionalization was initiated in an era of social reform to protect the rights of the mentally ill; however, a strong research base was absent and led to major flaws in the policy's implementation. 2. The chronically mentally ill are frequently poor advocates for themselves and, without even the most simple needs fulfilled, end up homeless. 3. The homeless mentally ill require comprehensive support systems with assured continuity of care. An emerging concept to deal with this issue is that of case management. 4. The mental health professional can strive to influence future public policy as patient advocate and nonpartisan educator.
VISCOSITY OF CONCENTRATED SUSPENSIONS OF SPHERES

Abstract This paper presents a statistical mechanical description of the random motion of particles in suspension and some results derived therefrom for the viscosity of concentrated suspensions of solid spherical particles. For steady and not too large overall shear rate in the suspension and neutrally buoyant solid spheres, the net forces and torques on the particles are zero and the local fluid motion is governed by the Stokes equations. It is shown that under these conditions: (1) the particle distribution function is independent of the linear and angular velocities of the particles and so is uniquely determined by the particle positions, (2) the viscosity of the suspension must be independent of the shear rate for all concentrations, and (3) the viscosity can be written in a power series in the concentration of particles in which the term of the nth power is the incremental contribution to the viscosity from interactions involving n particles. In order to calculate the coefficients of these terms the fluid velocity near the surface of a sphere moving with its neighbors in a shear field is required. Since an exact determination of the flow field is impractical to obtain for groups of more than two particles, an approximate solution of the Stokes equations obtained by the method of weighted residuals is used in the calculations of the suspension viscosity reported here. The particle configuration is assumed to be simple cubic, and the distribution of interparticle distances is obtained from an approximate statistical model. The viscosity-concentration relationship calculated under these assumptions is found to agree well with the compilations of experimental data reported by Rutgers [21] and by Thomas [22].
An internet protocol address clustering algorithm

We pose partitioning a b-bit Internet Protocol (IP) address space as a supervised learning task. Given (IP, property) labeled training data, we develop an IPspecific clustering algorithm that provides accurate predictions for unknown addresses in O(b) run time. Our method offers a natural means to penalize model complexity, limit memory consumption, and is amenable to a non-stationary environment. Against a live Internet latency data set, the algorithm outperforms IP-naive learning methods and is fast in practice. Finally, we show the model's ability to detect structural and temporal changes, a crucial step in learning amid Internet dynamics.
EEG Source Imaging and Multimodal Neuroimaging

During most common applications, the signals produced by cortical dipoles are detected at the scalp level. While these measurements can be highly informative and feature optimal temporal resolution, their spatial detection is hindered by the conduction through the tissues of the head. A deeper understanding of cortical sources can be provided by source imaging techniques. These methods first create mathematical models of the head, assigning appropriate properties to each layer. Brain activity is then calculated based on these assigned models and the observed EEG measurements, greatly improving the spatial resolution of EEG measurement and providing insights regarding otherwise hidden cortical dynamics. Source Imaging approaches can be further enhanced by integrating a second imaging modality. This is particularly useful with imaging methods that feature high spatial resolution or whose signals are not blurred by transduction. In the following chapter, we provide a detailed introduction to the general principles and basic algorithms of source imaging techniques. The discussion then expands to explore how other modalities can interact with these techniques to improve our results. At its conclusion, readers should have a good idea on how EEG data can be expanded to provide cortical insight.
Pre-hepatic and pre-pancreatic transplant donor evaluation.

Innovations in surgical techniques coupled with advances in medical and pharmacological management in the past few decades have enabled organ transplantation to become integral to the management of end stage organ failure. In this review article, we will review the role of the radiologist in the work up of liver and pancreas donors during evaluation of their donor candidacy. The critical role of imaging in assessing the parenchymal, biliary and vascular anatomy in liver donor candidates will be reviewed, as well as highlighting the anatomical findings that may pose a contraindication to transplantation. The limited role of imaging in pancreas donor evaluation is also covered, as well as a brief overview of the surgical techniques available and how the radiologist’s findings influence operative technique selection.
Estridentistas de Estado: la colaboración de la vanguardia postrevolucionaria con el gobierno de Veracruz, 1925-1927

El presente articulo analiza la colaboracion que el Estridentismo establecio con el gobierno de Veracruz entre 1925 y 1927: concretamente, su revista Horizonte. El articulo argumenta que, lejos de representar una contradiccion con respecto a una estetica vanguardista, irreverente y antiburguesa como la que caracterizo al primer Estridentismo, dicha colaboracion expandio la concepcion de vanguardia del movimiento. Ademas de la experimentacion formal en las artes, los estridentistas incluyeron ahora la creacion de instituciones democraticas e igualitarias, ya sea escuelas rurales o bibliotecas populares, como parte de su quehacer vanguardista, y se refirieron a este nuevo proyecto como la creacion de la “obra” postrevolucionaria.
Fundamental Obstetric Procedures

A variety of healthcare disciplines intersect during the care of a pregnant woman, especially during delivery. Simulation has been effectively utilized to train a wide range of health professionals on fundamental obstetric skills including cervical exams, assessment of fetal position, spontaneous vaginal delivery, and perineal laceration repair. Educators have used simulation equipment ranging from part-task trainers and full-body mannequins to organic materials such as different fruits or beef tongue, to train individuals or teams on core pregnancy-related procedures.
A 7600 yr vegetation and fire history from Anthony Lake, northeastern Oregon, USA, with linkages to modern synoptic climate patterns

We used pollen and high-resolution charcoal analysis of lake sediment to reconstruct a 7600 yr vegetation and fire history from Anthony Lake, located in the Blue Mountains of northeastern Oregon. From 7300 to 6300 cal yr BP, the forest was composed primarily of Populus, and fire was common, indicating warm, dry conditions. From 6300 to 3000 cal yr BP, Populus declined as Pinus and Picea increased in abundance and fire became less frequent, suggesting a shift to cooler, wetter conditions. From 3000 cal yr BP to present, modern-day forests composed of Pinus and Abies developed, and from 1650 cal yr BP to present, fires increased. We utilized the modern climate-analogue approach to explain the potential synoptic climatological processes associated with regional fire. The results indicate that years with high fire occurrence experience positive 500 mb height anomalies centered over the Great Basin, with anomalous southerly component of flow delivering dry air into the region and with associated sinking motions to further suppress precipitation. It is possible that such conditions became more common over the last 1650 cal yr BP, supporting an increase in fire despite the shift to more mesic conditions.
‘Crafting a way forward’: online participation, craftivism and civic engagement in Ravelry’s Pussyhat Project group

A powerful visual symbol of social protest and a success story of online organizing, the Pussyhat is a prominent illustration of the revival of craftivism in the current political climate. Analyzin...
Membrane-Binding Cooperativity and Coinsertion by C2AB Tandem Domains of Synaptotagmins 1 and 7

Abstract Synaptotagmin-1 (Syt-1) and synaptotagmin-7 (Syt-7) contain analogous tandem C2 domains, C2A and C2B, which together sense Ca2+ to bind membranes and promote the stabilization of exocytotic fusion pores. Syt-1 triggers fast release of neurotransmitters, whereas Syt-7 functions in processes that involve lower Ca2+ concentrations such as hormone secretion. Syt-1 C2 domains are reported to bind membranes cooperatively, based on the observation that they penetrate farther into membranes as the C2AB tandem than as individual C2 domains. In contrast, we previously suggested that the two C2 domains of Syt-7 bind membranes independently, based in part on measurements of their liposome dissociation kinetics. Here, we investigated C2A-C2B interdomain cooperativity with Syt-1 and Syt-7 using directly comparable measurements. Equilibrium Ca2+ titrations demonstrate that the Syt-7 C2AB tandem binds liposomes lacking phosphatidylinositol-4,5-bisphosphate (PIP2) with greater Ca2+ sensitivity than either of its individual domains and binds to membranes containing PIP2 even in the absence of Ca2+. Stopped-flow kinetic measurements show differences in cooperativity between Syt-1 and Syt-7: Syt-1 C2AB dissociates from PIP2-free liposomes much more slowly than either of its individual C2 domains, indicating cooperativity, whereas the major population of Syt-7 C2AB has a dissociation rate comparable to its C2A domain, suggesting a lack of cooperativity. A minor subpopulation of Syt-7 C2AB dissociates at a slower rate, which could be due to a small cooperative component and/or liposome clustering. Measurements using an environment-sensitive fluorescent probe indicate that the Syt-7 C2B domain inserts deeply into membranes as part of the C2AB tandem, similar to the coinsertion previously reported for Syt-1. Overall, coinsertion of C2A and C2B domains is coupled to cooperative energetic effects in Syt-1 to a much greater extent than in Syt-7. The difference can be understood in terms of the relative contributions of C2A and C2B domains toward membrane binding in the two proteins.
Vitamin D Analogs for the Treatment of Secondary Hyperparathyroidism in Chronic Renal Failure

Secondary hyperparathyroidism (2°HPT) is a common complication in patients with chronic renal failure. The pathogenesis of 2°HPT is attributed primarily to phosphate retention and low serum 1,25(OH)2D3. Replacement therapy with calcitriol [1,25-dihydroxyvitamin D3 or 1,25(OH)2D3] or its precursor alfacalcidol [1α(OH)D3] often produces hypercalcemia, especially when combined with calcium-based phosphate binders. In addition, these natural vitamin D compounds can aggravate the hyperphosphatemia in these patients. Furthermore a high Ca x P product has been correlated with the severity of vascular calcification leading to coronary artery disease, the most common cause of mortality in renal patients. Several vitamin D analogs have now been developed that retain the direct suppressive action of 1,25(OH)2D3 on the parathyroid glands but have less calcemic activity, thereby offering a safer and more effective means of controlling 2°HPT. 22-Oxa-1,25(OH)2D3 (22-oxacalcitriol or OCT), 19-nor-l,25(OH)2D2(19-norD2) and 1α(OH)D2 are currendy available in Japan (OCT) and the United States (19-norD2 and 1α(OH)D2). The mechanisms by which these analogs exert their selective actions on the parathyroid glands are under investigation. The low calcemic activity of OCT has been attributed to its rapid clearance which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression. The selectivity of 19-norD2 and 1α(OH)D2 is achieved by other mechanisms. A clear understanding of how these compounds exert their selective actions on the parathyroid glands may allow the design of more effective analogs in the future.
The Agony of Flint: Poisoned Water, Racism and the Specter of Neoliberal Fascism

“Flint still doesn't have clean water.”1Michelle Wolf, White House Correspondents Dinner, April 28, 2018 “Neoliberal fascism, as a form of extreme capitalism, views democracy as the enemy.”2Henry G...
Analysis of the transmutation of long lived fission products using a charged particle beam

Abstract The aim of this study is to analyze the transmutation of Long Lived Fission Products (LLFPs) using an accelerator based system. The seven LLFP’s are investigated based upon their decay mechanics, yields from fission, and neutron absorption cross sections to select potential target nuclides. MCNPX is the primary modeling tool used. Initially, infinite targets are modeled to determine dependence on the energy of the incident beam. Finite targets containing only nuclides to be transmuted are modeled to compare different LLFPs. 135 Cs and 129 I are rejected as targets due to small cross sections and 99 Tc is selected as the primary transmutation target. Custom cross sections produced in MCNPX are used to model a target containing non target materials and multiple regions. A cylindrical target design is decided upon where the 99 Tc content and the dimensions of the target are varied to improve transmutation characteristics. The final target design contains 131 kg of 99 Tc mixed with lead in a cylindrical target with a radius of 40 cm and a length of 120 cm, with a cylindrical hole with a 10 cm radius extending 30 cm into the technetium-lead region and a cylindrical graphite reflector region extending 40 cm radially from the target, 50 cm from the front of the target and 80 cm from the back of the target. The incident particle energy requirement per transmutation is 56.9 MeV. Using a 1200 MeV proton beam with a power of 2.4 MW (the rate at which the kinetic energy of protons enters the target), the transmutation rate obtained under continuous operation is 1.36 kg/year, corresponding to an initial effective halflife of 66.7 years.
Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.

Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (saline) intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL) at 24 h was reduced (P<0.05) in VPA (2.7±1.8) and Dex (2.3±1.2) compared to Vehicle (3.8±0.5) group. At 3 h, urine albumin (mg/mL) was higher in Vehicle (1.47±0.10), VPA (0.84±0.62) and Dex (1.04±0.73) compared to naive (uninjured/untreated control) (0.14±0.26) group. At 24 h post-IR urine lipocalin-2 (μg/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (9.61–11.36) compared to naive group (0.67±0.29); also, kidney injury molecule-1 (KIM-1; ng/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (13.7–18.7) compared to naive group (1.7±1.9). Histopathology demonstrated reduced (P<0.05) ischemic injury in the renal cortex in VPA (Grade 1.6±1.5) compared to Vehicle (Grade 2.9±1.1). Inflammatory cytokines IL1β and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI.
Outcomes of Concussion Injuries to Running Backs and Wide Receivers in the National Football League

Objectives:Concussion injuries are common in professional football players, however the impact on player careers remains unclear. The purpose of this study was to quantify the effect of concussions...
Effects of focal impulse and rotor modulation-guided ablation on atrial arrhythmia termination and inducibility: Impact on outcomes after treatment of persistent atrial fibrillation.

Introduction The role of focal impulse and rotor modulation (FIRM)-guided ablation for the treatment of atrial fibrillation (AF) remains unclear. Previous studies on the FIRM-guided ablation outcomes have been limited by a focus on AF termination as an endpoint and by patient population heterogeneity. We sought to determine differences in rates of AF termination, inducibility, and recurrence in patients with persistent AF undergoing first-time ablation with a FIRM-guided approach compared with patients undergoing conventional ablation. Methods and results Eight-five consecutive patients (38 FIRM, 47 conventional) with persistent AF undergoing first-time ablation were retrospectively analyzed. There were no significant differences in the rates of AF termination in the FIRM group compared to the conventional group (26% vs 15%; P = .15). Rates of inducible AF after ablation were 37% in the FIRM group and 30% in the conventional group (P = .32). Over a median follow-up of 2.4 years, the rates of freedom from AF were similar between the FIRM and conventional groups (1-year freedom from AF 65% vs 50%, respectively; P = .18). Procedural termination of AF with either FIRM ablation or conventional ablation was not associated with any significant reduction in AF recurrence. Conclusion A FIRM-guided approach was not associated with a significant difference in freedom from AF when compared to conventional ablation. Termination of AF with ablation was not associated with increased freedom from AF. While AF termination using substrate-based ablation may have mechanistic implications for understanding AF rotor physiology, its impact on clinical outcomes remains unclear.
A quasi-Monte Carlo solver for thermal radiation in participating media

Abstract The Monte Carlo (MC) method is the most accurate method for resolving radiative heat transfer in participating media. However, it is also computationally prohibitive in large-scale simulations. To alleviate this, this study proposes a quasi-Monte Carlo (QMC) method for thermal radiation in participating media with a focus on combustion-related problems. The QMC method employs low-discrepancy sequences (LDS) in place of the traditional random numbers. Three different low-discrepancy sequences – Sobol, Halton, and Niederreiter – were examined as part of this work. The developed QMC method was first validated against analytical solutions of radiative heat transfer in several one-dimensional configurations. Then it was extended to three-dimensional practical combustion configurations. The results from QMC and traditional Monte Carlo are compared against benchmark solutions for each cases. It is shown that the error of the predicted radiation field from QMC is lower than an equivalent MC simulation. The computational cost of QMC was also found lower than MC due to the avoidance of requirement of several statistical runs for traditional Monte Carlo methods alongside achieving the reduction in error. In conclusion, significant improvements in computational costs and accuracy seen in the QMC method makes it an attractive alternative to traditional Monte Carlo methods in high-fidelity simulations.
Poly-Strengths and Peer Violence Perpetration: What Strengths Can Add to Risk Factor Analyses.

Adolescence is a high-risk time for perpetration of different forms of peer-based violence including harassment, bullying, and sexual assault. Research documents a number of important risk factors but less understood are protective factors like sense of mattering or how combinations of strengths may reduce perpetration risk. The current study examined how protective factors (i.e., positive social norms), including a diversity of strengths (termed poly-strengths), influenced the perpetration of harassment, bullying, and sexual assault for young people, while accounting for the use of alcohol both cross-sectionally and over time. Youth (N = 2232, 52.6% female) in grades 7–10 enrolled in a study using active parental consent (53% response rate) and completed online surveys in school that asked about bullying and harassment, alcohol use, positive social norms related to violence prevention, and a composite of intra-personal strengths. Follow-up surveys took place 6 months later (N = 2150). Logistic regression analyses examined how social norms and poly-strengths influenced odds of perpetration after accounting for demographic variables and the risk factor of alcohol use. Use of alcohol increased the odds of perpetrating all forms of violence. Strengths were significantly related to lower perpetration at Time 1 but not Time 2. Positive social norms reduced perpetration at both time points. The findings suggest adolescent perpetration of bullying, harassment, and sexual violence is lower in the presence of positive social norms over time and more proximally, in the presence of a diverse strengths portfolio. Prevention efforts that incorporate positive social norms and alcohol reduction strategies may reduce peer violence.
A review of contact dermatitis.

Abstract Objective To familiarize the reader with the mechanisms and causes of contact dermatitis. Data Sources Recent research articles, relevant review articles, and case series/reports in English from PubMed database, mostly from 2010 onwards. Study Selections Most data were in the form of retrospective studies. Efforts were made to include clinical trials; however, for newer allergens and data on biologics, case series and case reports were included. Older studies regarding the mechanism were included if they were of particular importance. Results An understanding of this review should enable the reader to approach the patient with unknown dermatitis with a better understanding of the cause and management. Conclusion Clinical suspicion for relevant allergens combined with the interpretation of patch tests are important in the diagnosis and treatment of patients with contact dermatitis.
An Examination of Reproductive Phenology with Implications for Understanding Climate Change Effects

Climate change has impacted ecological systems in a variety of ways, leading to advancement in spring events, shifts in species distributions, and changes in phenology (the timing of life history events) for many plants and animals. Earlier spring temperatures have been correlated with earlier emergence of a number of butterfly species in Europe. It is possible that changes in the spring could also influence the timing of events throughout the season. The Clodius Parnassian (Parnassius clodius) butterfly has one flight per year that averages 3 weeks in length. The males emerge first, followed shortly by the females. Reproductive success of these butterflies depends on the timing of emergence and mating events. A disturbance in the timing of emergence between males and females could cause an incomplete temporal overlap between the sexes, leading to reproductive asynchrony. Reproductive asynchrony occurs when males and females within a population do not overlap completely in time, and it can significantly affect population dynamics of species with narrowly defined breeding periods, such as univoltine butterflies. Our research examined how climate change may influence flight time and mating success in Parnassius clodius butterflies. A mark-recapture study to assess timing of emergence and mating success was performed in Grand Teton National Park. Six plots were surveyed daily for Parnassius clodius butterflies using mark recapture techniques during the annual flight period from late June until mid-July 2009. Each captured butterfly was marked with a permanent marker on both of its hindwings prior to release. The sex and wing condition of each butterfly was determined and recorded at time of capture. A total of 838 butterflies were marked during the 2009 flight period, with a recapture rate of 26%. Preliminary examination of the data reveals the expected pattern of male emergence prior to female emergence. The emergence times appear consistent with other survey years. We also observed a small number of unmated females at the end of the season. Further data analysis needs to be performed before any additional conclusions can be made. This study provides a baseline understanding of climatic and phenological trends in an effort to understand how gender-specific emergence times and mating status of a common species of butterfly (Parnassius clodius) may be affected by climatic changes.
Client-Centric Access Device Selection for Heterogeneous QoS Requirements in Beyond 5G IoT Networks

The expected manifolds increase in the traffic and the massive number of connected Internet of Things (IoT) devices would be a challenge to ensure a certain Quality of Service (QoS) in Beyond 5G (B5G) networks. Due to the increased availability of processing and energy resources and heterogeneous QoS requirements in modern IoT nodes, a client-centric access device selection approach for QoS provisioning in multiple Radio Access Technologies (RATs) scenario is proposed in this paper. The proposed algorithm provides the ability to specify node-specific QoS requirements at each node, a better access device selection, and improved network scalability. For experimental evaluation, a hybrid indoor network consisting of Wireless Fidelity (WiFi) and Light Fidelity (LiFi) RATs has been considered. Experimental results show that the proposed technique outperforms several conventional client-based access device selection approaches by up to 32.66% in network emulation experiments and up to 50% in hardware experimentation. The contribution of this paper includes the proposed algorithm, its complexity and game-theory based convergence analyses, evaluation of the proposed algorithm using network emulation and hardware-based setups, and LiFi channel analysis. The analyses and results imply that the proposed algorithm could be utilized in next-generation IoT networks as it performs better than conventionally used access device selection techniques for QoS provisioning.
Rethinking the Testamentary Capacity of Minors

Minors lack the legal capacity to execute wills. Subject to limited exceptions in some states, a will executed by a child is void. Because this testamentary age requirement conflicts with the primary objective of the law of wills, which is to allow decedents to freely choose how their estates will be distributed, this rule should be founded upon a coherent and compelling policy rationale. Nonetheless, it is not.Three potential rationales might explain the testamentary incapacity of minors. First, the age requirement could represent a categorical capacity threshold that is aimed at protecting children from their immaturity and indiscretion. Second, the age requirement could be seen as a proxy for the minimum mental competency that the law requires of all testators. Finally, the age requirement could implement forced parental inheritance, under which the estates of minors are funneled into intestacy and are distributed to their parents.This article explains how each of these potential rationales fails to adequately align with the mechanics of the current testamentary age requirement. The article ultimately calls for the elimination of the categorical age restriction on testamentary capacity. It also proposes additional reforms that would better serve the policy objectives of the testamentary age restriction but that would allow children to more frequently execute wills.