cssi/SciSciGPT-SciSciNet huggingface dataset:
Dimension reduction of biological neuron models by artificial neural networks

An artificial neural network approach to dimension reduction of dynamical systems is proposed and applied to conductance-based neuron models. Networks with bottleneck layers of continuous-time dynamical units could make a two-dimensional model from the trajectories of the Hodgkin-Huxley model and a three-dimensional model from the trajectories of a six-dimensional bursting neuron model. Nullcline analysis of these reduced models revealed the bifurcations of the dynamical system underlying firing and bursting behaviors.
Epidemiology of wilderness-acquired diarrhea: implications for prevention and treatment

The popularity of backcountry travel has brought to public attention concerns over the safety of wilderness water consumption. Epidemiologic studies are limited, but place the incidence of wilderness-acquired diarrhea (WAD) in the range of 3–5%. Although the United States Forest Service and National Park Service focus efforts on disinfecting water to prevent giardiasis, the pathogen may only account for a small proportion of diarrheal cases in backcountry travelers. Stool specimen analysis from symptomatic recreationalists suggests bacteria and viruses to be more frequent isolates. A reasonable estimate of etiology can be made based upon the expedition length. On short trips (less than 7–10 days), symptomatic diarrhea will be due to viral or bacterial pathogens and can be treated empirically with agents proven of benefit for management of traveler's diarrhea. For longer trips, illness attributable to Giardia lamblia complicates empiric therapy. Backcountry travelers should filter water to remove protozoan cysts. This should be followed by halogenation to disinfect against bacterial and viral pathogens.
Catalytic role of proton transfers in the formation of a tetrahedral adduct in a serine carboxyl peptidase.

Quantum mechanical/molecular mechanical molecular dynamics and 2D free energy simulations are performed to study the formation of a tetrahedral adduct by an inhibitor N-acetyl-isoleucyl-prolyl-phenylalaninal (AcIPF) in a serine-carboxyl peptidase (kumamolisin-As) and elucidate the role of proton transfers during the nucleophilic attack by the Ser278 catalytic residue. It is shown that although the serine-carboxyl peptidases have a fold resembling that of subtilisin, the proton transfer processes during the nucleophilic attack by the Ser residue are likely to be more complex for these enzymes compared to the case in classical serine proteases. The computer simulations demonstrate that both general base and acid catalysts are required for the formation and stabilization of the tetrahedral adduct. The 2D free energy maps further demonstrate that the proton transfer from Ser278 to Glu78 (the general base catalyst) is synchronous with the nucleophilic attack, whereas the proton transfer from Asp164 (the genera...
Effect of the SP01 DNA-binding protein, TF1, on promoter competition☆

Abstract The experiments described below represent a simple model of how DNA-binding proteins can selectively affect promoter competition . The basic protein, TF1, is known to bind preferentially to hydroxymethyl uracil-containing SP01 DNA and to inhibit the initiation of SP01 DNA transcription in vitro . We show here that TF1 inhibits SP01 transcription much more severely if competing, TF1-insensitive, DNA is available for Bacillus subtilis or Escherichia coli RNA polymerase binding and transcription.
Missed opportunities for depression screening in patients with arthritis in the United States

BACKGROUND Arthritis affects 20 % of the adult US population and is associated with comorbid depression. Depression screening guidelines have been endorsed for high-risk groups, including persons with arthritis, in the hopes that screening will increase recognition and use of appropriate interventions.
An event-driven model-view-controller framework for Smalltalk

The Smalltalk Model-View-Controller (MVC) user interface paradigm uses polling for its input control. The polling loops consume CPU cycles even when the user is not interacting with the interface. Applications using Smalltalk as their front-end often suffer unnecessary performance loss. This paper presents a prototype event-driven MVC framework to solve these problems. A solution to the compatibility problem is also provided to allow interface objects built under both polling and event-driven mechanisms to be used by each other with no modification and no performance penalty.
A Phase 2 Trial of Concurrent Chemotherapy and Proton Therapy for Stage III Non-Small Cell Lung Cancer: Results and Reflections Following Early Closure of a Single-Institution Study.

Purpose Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). Methods and Materials From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. Results Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. Conclusions Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.
Rheumatoid factor (antigammaglobulin) in women. Effects of oral contraceptive use on its prevalence

A total of 14,856 women, including 921 pregnant subjects, were tested for rheumatoid factor; 4,562 were using oral contraceptives at the time of testing. The prevalence of rheumatoid factor increased directly with age. The age-adjusted prevalence of rheumatoid factor was lower in oral contraceptive users than in nonusers but this difference was not statistically significant. Rheumatoid factor remained positive in 39% of subjects undergoing retesting after an average interval of 16 months. Those women with higher titers of rheumatoid factor were more likely to remain positive (81%). Of the women having positive tests, 5.4% were identified as having rheumatoid disease.
Assessing the Impact of Price Promotions on Consumer Response to Online Stockouts

The recent growth of e-commerce technologies has disrupted the traditional retail environment, leading to more consumers shopping online. While the manner in which consumers shop is changing rapidly, our understanding of how changing consumer behaviors affect retail supply chain management is lacking. In particular, our understanding of how consumers react to stockouts in an online shopping environment remains unclear. Making the challenge even more difficult is the fact that price promotions are heavily used to attract consumers in an online retail environment where consumer switching costs are low. This research develops a theoretical framework, based on expectation-disconfirmation theory, to explain the effect of price promotions on consumer expectations of product availability and their reactions to stockouts in an online retail environment. Surprisingly, our findings suggest that consumers are actually less dissatisfied with a stockout of a price promoted item than a nonprice promoted product and are less likely to switch to another retailer's website. These findings may suggest that price promotions actually create a type of switching cost in the online retail environment, leading to interesting implications for researchers and supply chain managers.
The family history score tool identifies high risk families for colorectal cancer

Background Assessing family history risk of colorectal cancer (CRC) is often difficult due to complex permutations and combinations. A family history score has been developed and validated to simplify familial risk assessment. This study examines the usefulness of this scoring system to identify families at risk through public outreach programs.
Intervention in gene regulatory networks with maximal phenotype alteration.

Motivation: A basic issue for translational genomics is to model gene interaction via gene regulatory networks (GRNs) and thereby provide an informatics environment to study the effects of intervention (say, via drugs) and to derive effective intervention strategies. Taking the view that the phenotype is characterized by the long-run behavior (steadystate distribution) of the network, we desire interventions to optimally move the probability mass from undesirable to desirable states Heretofore, two external control approaches have been taken to shift the steady-state mass of a GRN: (i) use a user-defined cost function for which desirable shift of the steady-state mass is a by-product and (ii) use heuristics to design a greedy algorithm. Neither approach provides an optimal control policy relative to long-run behavior. Results: We use a linear programming approach to optimally shift the steady-state mass from undesirable to desirable states, i.e. optimization is directly based on the amount of shift and therefore must outperform previously proposed methods. Moreover, the same basic linear programming structure is used for both unconstrained and constrained optimization, where in the latter case, constraints on the optimization limit the amount of mass that may be shifted to ‘ambiguous’ states, these being states that are not directly undesirable relative to the pathology of interest but which bear some perceived risk. We apply the method to probabilistic Boolean networks, but the theory applies to any Markovian GRN.
Dystonia and the Role of Deep Brain Stimulation

Dystonia is a painful, disabling disease whose cause in many cases remains unknown. It has historically been treated with a variety methodologies including baclofen pumps, Botox injection, peripheral denervation, and stereotactic surgery. Deep brain stimulation (DBS) is emerging as a viable treatment option for selected patients with dystonia. Results of DBS for dystonia appear to be more consistently superior in patients with primary versus secondary forms of the disorder. Patients with secondary dystonia, due to a variety of causes, may still be candidates for DBS surgery, although the results may not be as consistently good. The procedure is relatively safe with a small likelihood of morbidity and mortality. A randomized trial is needed to determine who are the best patients and when it is best to proceed with surgery.
LIM App: Reflecting on Audience Feedback for Improving Presentation Skills

In order to successfully give a lecture or do a presentation in a conference, presenters need certain skills as well as previous preparation. In such scenarios, reflective learning offers a great potential to improve professional skills and presenter's performance by relying on data captured during the presentation. For this purpose, we developed the Live Interest Meter LIM App which allows capturing, aggregating and visualizing live feedback from the audience. After developing the first prototype, testing it and conducting a user study, we developed the second prototype presented in this paper. This further development made emphasis on the recalling and revisiting of past experiences by exploring the collected data. We conducted the evaluation of the LIM App with three university lectures. Our evaluation showed positive results regarding the capturing and sharing of feedback to improve presentation skills. Whilst the LIM App guided the lecturers to reflect and to remember their presentations better, some time and advice to get accustomed to using it is still needed so that it is optimally integrated in their presentations.
A silent epidemic: childhood falls from height

Introduction Falls from height are a leading cause of morbidity and mortality in children over 1 year of age. The authors suspected a high incidence of childhood falls from buildings and windows in the region served by our hospital. Significant falls lead to acute injury including loss of life and long-term disability. The burden to the hospital and NHS is large. Aim Determine the incidence of children and babies (less than 16 years of age) attending hospital following falls from buildings. Evaluate the burden of injury and cost. Explore causes and prevention strategies. Method Retrospective case notes review of all children ( Results Average of one child per month who has fallen from a building (n=20) Age of patients: range 8 months–14 years Cost per patient £6000 or £71 000/year Each patient occupies 1 psychiatric intensive care unit, 1.3 high dependency unit and 4.4 standard bed-days on average. Injuries sustained limb fracture 8 Skull fracture 3 Intracranial bleed 3 Spinal fracture 2 Pelvic/thoracic/abdominal injury 3 Surgery Orthopaedic 3 Neurosurgery 3 Discussion Many falls were from relatively low heights of two storeys or less. People may be more casual about safety on the upper floors of low buildings. Precipitating factors included a lack of appropriate supervision and a potentially dangerous home environment. Injuries sustained include the expected spectrum of limb, head and organ injuries. Documentation was limited but revealed a lack of window security. The locks supplied to our hospital cost £4.35 per lock (bulk). Pressley and Barlow1 found that window guards are associated with reduced falls from windows and recommended that they should be mandatory through legislation in multifamily dwellings where small children reside. Keogh et al 2 found that frequency of falling was related to urban deprivation, poor building maintenance and lack of safety information for residents. A health education programme in New York City began in 1972 to address their high incidence of children falling from windows. Entitled “Children Can9t Fly”, the programme was a clear success with a 50% reduction in falls over a two-year period.
In Vivo Neutron Activation Analysis for Body Fat: Comparisons by Seven Methods

All current well-accepted traditional methods for measuring body fat are indirect, in that they measure fat-free mass (FFM) based on the assumed constancy of water, potassium, or density in the FFM7–3. Newer methods such as bio electrical impedance analysis (BIA) are calibrated by traditional indirect methods. Dual-photon absorptiometry (DPA) is the most promising and relatively available new method4,5 which bypasses the traditional assumptions of chemical constancy, in that it avoids the errors due to the assumptions underlying each of the traditional methods. However, recent studies indicate that the currently used DPA system is not yet well calibrated for measuring fat content in soft tissue areas with thickness less than 10 cm or greater than 30 cm. In vivo neutron activation analysis (IVNA) measures the FFM by the direct measurement of each of the chemical elements in the FFM6, and thus sets a better standard for measuring body composition in vivo. The purposes of this report were 1) to make comparisons between IVNA and seven currently widely used methods for estimating body fat, and 2) to develop models for predicting IVNA-measured body fat by these seven indirect methods in whites and blacks.
International Human Rights Class Actions: New Frontiers for Group Litigation

This article is a contribution to a symposium on Multi-Jurisdictional and Cross-Border Class Actions, organized by Professor Debra Lyn Bassett. It focuses on international human rights class actions. Over the last few decades, the United States courts have seen the emergence of a novel form of social justice litigation in the form of international human rights class actions. Much-publicized lawsuits of this type include actions based on the horrible genocide and ethnic cleansing in the former Yugoslavia and suits on behalf of victims of the Holocaust in Nazi Germany. The emergence of international human rights class actions should not be surprising. Commentators have lavishly discussed and analyzed globalization for years. New human rights problems are accompanying globalization. Globalizing litigation, through the class action device reflects the increasing - or at least heightened awareness of the - economic, political, and social connections between nations. As has been observed, class actions challenge the basic notion that litigation is between private parties. By further expanding litigation, international human rights class actions challenge the concept of national borders and sovereignty as well. Despite the emergence of international human rights class actions, mass tort class actions grab the bulk of academic attention. Mass tort class actions, of course, raise significant social justice, as well as judicial economy and efficiency, concerns. Courts have spent considerable time grappling with these difficult issues. In two relatively recent decisions, for example, the Supreme Court addressed complex issues in asbestos class actions. By comparison, little sustained attention has been paid to the emerging international human rights class actions from a procedural standpoint. A small, but growing, body of articles has considered these new class actions. Because they raise profound social justice issues not found in the average mass tort case, class actions that cross national borders deserve greater scrutiny. International human rights class actions fit uncomfortably within the Federal Rule of Civil Procedure 23, which governs class actions, and may push the limits of the class action device in new directions. This article hopes to broaden the discussion of international human rights class actions. Part I of this article analyzes the emergence of the new class actions, including the important functions that they serve. Part II considers a case study of a modern international human rights class action, which has both domestic and international dimensions and can be expected to arise with greater frequency in the future.
Selective Ablation of Human T-Cell Lymphotropic Virus Type 1 p12I Reduces Viral Infectivity In Vivo

Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia and HTLV-1-associated myelopathy. Novel, yet conserved RNA transcripts encoded from open reading frames (ORFs) I and II of the viral pX region are expressed both in vitro and in infected individuals. The ORF I mRNA encodes the protein p12I, which has been shown to localize to cellular endomembranes, cooperate with bovine papillomavirus E5 in transformation, as well as bind to the IL-2 receptor β and γ chains and the H+ vacuolar ATPase. It is unknown what role p12I plays in the viral life cycle. Using an infectious molecular clone of HTLV-1 (ACH) and a derivative clone, ACH.p12I, which fails to produce the p12Imessage, we investigated the importance of p12I in infected primary cells and in a rabbit model of the infection. ACH.p12I was infectious in vitro as shown by viral passage in culture and no qualitative or quantitative differences were noted between ACH and ACH.p12I in posttransfection viral antigen production. However, in contrast to ACH, ACH.p12I failed to establish persistent infection in vivo as indicated by reduced anti-HTLV-1 antibody responses, failure to demonstrate viral p19 antigen production in peripheral blood mononuclear cell (PBMC) cultures, and only transient detection of provirus by polymerase chain reaction in PBMC from ACH.p12I-inoculated rabbits. These results are the first to show the essential role of HTLV-1 p12I in the establishment of persistent viral infection in vivo and suggest potential new targets in antiviral strategies to prevent HTLV-1 infection.
The Contraception Mandate Accomodated: Why the RFRA Claim in Zubik v. Burwell Fails

The Affordable Care Act requires that health care plans include all FDA-approved contraception without any cost sharing. In Hobby Lobby v. Burwell, for-profit businesses with religious objections successfully challenged this “contraception mandate.” In this term’s Zubik v. Burwell, it is religiously affiliated nonprofits like Baptist universities and Catholic Charities challenging the contraception benefit. But there is a major difference: these religiously affiliated nonprofits are exempt from the contraception mandate. Once they certify that they are religiously opposed to contraception and notify either their insurance carriers or the Department of Health and Human Services, the responsibility for contraception coverage shifts to private insurance companies. The nonprofits do not have to provide, pay for, or even inform their employees or students of the separate coverage. Despite the ability to opt out of contraception coverage, many nonprofits complain that the religious accommodation itself imposes a substantial religious burden in violation of the Religious Freedom Restoration Act (RFRA). According to these nonprofits, providing notice of their objections triggers the provision of contraception to their employees and students, thus making them complicit in sin. Their RFRA claim cannot succeed. RFRA requires that the contraception regulations impose a substantial religious burden and fail strict scrutiny, and neither requirement is met. First, filing paperwork to receive an exemption is not a substantial burden on the nonprofits’ religious exercise. The nonprofits’ claims to the contrary are based on a mistake of law, and while court must defer to the nonprofits’ interpretation of religious theology, courts should not defer to their interpretation of federal law. Second, the contraception mandate passes strict scrutiny: it advances compelling government interests in women’s health and equality, and the accommodation provided to objecting nonprofits is the least restrictive means of accomplishing those interests.
Inhibition of eosinophilotaxis by chloroquine and corticosteroids.

SummaryIn an in vitro chemotactic assay using a modified Boyden chamber, the action of anti-inflammatory agents on eosinophilotaxis was studied. Hydrocortisone sodium succinate, methylprednisolone sodium succinate, and chloroquine hydrochloride induced a dose-related inhibition of migration of eosinophils to ECF-A and C5a, The inhibitory action appeared to be directly on the cells and it was not caused by lysis Of cells.
28 case reports of surfactant therapy (Curosurt) in neonates with meconium aspiration syndrome

Objective: To study the efficacy of pulmonary surfactant (PS) in the newborn infants with severe meconium aspiration syndrome(MAS). Methods: 28 infants with severe MAS were randomly divided into two groups. The treatment group (13 cases) were treated with PS, control group (15 cases) were treated in usually way. Results: The mean oxygenation index (OI) of the PS group decreased from 21.5±4.6 to 12.8±1.6,which was significantly lower compared with control group (P 0.05); arterial/alveolar oxygen tension ratio (a/APO2) of the PS group increased form 0.10±0.04 to 0.31±0.05, which was significantly higher compared with control group (P 0.05). The durations of mechanical, oxygen therapy, and admission were significantly short in the PS group than in control group. Conclusion: PS therapy may result in a rapid improvement in oxygenation, and reduce the duration of mechanical ventilation and hospitalization time of newborn infants with severe MAS.
Impact of PM_(2.5) in teaching environment during spring on pupils' respiratory health in Guangzhou City

Objective To investigate the influence of mass concentration of PM2. 5in springtime on pupils' respiratory system in primary schools in Guangzhou City. Methods The mass concentration of PM2. 5in teaching environment of primary schools in spring was detected. The pupils' lung function indexes( FVC,FEV1and MMEF) and symptom indexes( cough,sore throat,and rhinitis) were obtained by the student symptom- monitoring network and physical examinations during the same period. The relationships between the health indexes and the mass concentration of PM2. 5were analyzed. Results The average mass concentration of PM2. 5in teaching environment of primary schools in spring was the highest in Yuexiu District,but it was the lowest in Nansha District. The pupils' lung function indexes( FVC,FEV1,MMEF) were the lowest in Yuexiu District,but they were the highest in Nansha District,and the differences were statistically significant( P 0. 05). There were significant negative correlations between the mass concentration of PM2. 5and the pupils' lung function indexes( FVC,FEV1and MMEF),with the correlation coefficients of- 0. 839( P 0. 05),- 0. 828( P 0. 05),and- 0. 847( P 0. 05),respectively. The incidence of cough and sore throat was the highest in Yuexiu District,but it was the lowest in Nansha District. There were significant positive correlations between the mass concentration of PM2. 5and the incidences of cough and sore throat,with the correlation coefficients of 0. 975( P 0. 05) and 0. 999( P 0. 05),respectively. No statistically significant difference was found in the incidence of rhinitis among the pupils in Yuexiu District,Nansha District and Huangpu District. Conclusions The mass concentration of PM2. 5in the teaching environment affects the pupils' respiratory system function. It is negatively correlated with FVC,FEV1,and MMEF,but positively correlated with the incidences of cough and sore throat.
Nonsurgical management of burns to the lips and commissures.

In the treatment of burns involving the lips and commissures, early splinting often precludes the need for surgical reconstruction. Early scarring of the commissure can be modified using an expansile appliance. Splinting in conjunction with surgery of the commissure often enhances the final result.
Composable Bounds on Information Flow from Distribution Differences

We define information leakage in terms of a "difference" between the a priori distribution over some remote behavior and the a posteriori distribution of the remote behavior conditioned on a local observation from a protocol run. Either a maximum or an average may be used. We identify a set of notions of "difference;" we show that they reduce our general leakage notion to various definitions in the literature. We also prove general composability theorems analogous to the data-processing inequality for mutual information, or cascading channels for channel capacities.
Photopolymerized and Photografted Porous Polymer Monoliths for Fabrication of Microfluidic Analytical Systems

Two building blocks required for the construction of complex microfluidic systems, namely an enzymatic reactor and a separation unit, have been designed, prepared, and evaluated. These elements consisting of porous polymer monoliths were prepared in situ via a UV initiated polymerization of a monolithic material followed by photoinitiated grafting of polymer chains involving desired functionalities. The function of the monolithic reactor was demonstrated with digestion of a variety of proteins using immobilized trypsin. Extremely efficient electrochromatographic separation of proteins has been achieved at elevated temperature in isocratic mode.
Functional Implications of Biochemical and Molecular Characteristics of Donation After Circulatory Death Livers.

Liver transplantation provides outstanding outcomes and quality of life to patients with end-stage liver disease. Unfortunately, the shortage of organs results in more than 3000 deaths per year in the United States alone (http://optn.transplant.hrsa.gov/latestData/rptData.asp). One way to reduce wait list deaths is to increase the number of grafts used for transplant. Current methods to predict organ performance are imperfect and rely on donor history, laboratory values, graft appearance, histology, duration of profound hypotension in the donor after withdrawal of support, and duration of cold storage time.1,2 A test to more accurately identify livers likely to provide good function, or conversely, those likely to fail would be an important advance. Such a test would be particularly useful for livers from donors after circulatory death (DCD). Recent data demonstrate that DCD is an independent risk factor for poor outcomes after liver transplantation.3 The DCD organs have increased rates of primary nonfunction and ischemic cholangiopathy (IC) compared to donation after brain death (DBD) transplantation.4 These patients generally require retransplant. With increasing regulatory oversight and anecdotal poor experience with DCD livers, the total number of DCD livers discarded in the United States rose from 22% to 32%, and since 2002, the total number of DCD livers transplanted decreased.5,6 On the other hand, a number of centers continue to use DCD livers with excellent results, in many cases with outcomes equal to DBD.7,8 This disparity suggests that criteria to predict subsequent function are not optimal. With current decision-making tools, it is likely that incorrect decisions are being made with useable livers being discarded and unusable ones being implanted. A diagnostic test to predict the degree of injury of DCD livers would allow better prediction of outcomes. We therefore performed a biochemical and molecular analysis of DCD compared to DBD livers to define parameters that might predict a successful transplant. We found that adenosine triphosphate (ATP) levels immediately postperfusion distinguished between DCD and DBD organs and were highly correlated with peak aspartate aminotransferase (AST) levels in the recipient. Transcriptional profiling revealed a DCD signature that may provide insight into processes occurring during the ischemic period.
The Contributions of the P4-P2 Positions in PAR1 and 4 for Thrombin Recognition and Cleavage.

Abstract The angiotensin converting enzyme breakdown product of bradykinin, bradykinin 1–5 (RPPGF), inhibits thrombin induced human or mouse platelet aggregation by preventing proteolysis of PAR1 and PAR4 by binding adjacent to the thrombin cleavage site and thus preventing activation of these receptors (Am. J. Physiol. 285:H183–H193, 2003; J. Pharmacol. Exp. Ther. 311:492–501, 2004; FEBS Lett. 579:25–29, 2005). Alanine scanning mutagenesis determined that RPPGF binds to Pro46 at the P2 position of PAR4 to block thrombin cleavage. New studies determined the amino acids required for thrombin to bind and cleave PAR4. Wild type PAR4 exodomain is cleaved by thrombin with a Km of 17 μM, kcat of 3.5 s−1 and kcat/Km of 2x105 M−1 s−1. In contrast, PAR4 exodomain in which the P2 (PAR4-P46A) is changed to alanine, is not efficiently cleaved with 10 nM alpha thrombin. Alteration of PAR4's P4 position (e.g., PAR4-P44A) does not influence the PAR4's rate of cleavage. The ability of the PAR4 exodomain to inhibit thrombin proteolysis of H-D-Phe-Pip-pNA was also determined as an independent measure of the thrombin/PAR4 interaction. Wild type PAR4 exodomain and PAR4-P44A are competitive inhibitors of thrombin hydrolysis of the chromogenic substrate with a Ki of 23 ± 6 micromolar and 19.6 ± 4 μM respectively. In contrast, PAR4-P46A and PAR4-P44A/P46A have a Ki > 300 μM nd the nature of the inhibition changes from competitive to noncompetitive. Taken together, these data demonstrate that Pro46 of PAR4 is important for alpha thrombin to bind and orient PAR4 in its active site for efficient cleavage. Further studies examined the role of the combined amino acids in the P4 to P3 positions of PAR4 and PAR1 to contribute to the rate of thrombin cleavage. Chimeric molecules were prepared in which the P4 and P3 positions of PAR4 (ProAla) are replaced with those from PAR1 (LeuAsp) to generate PAR4-LD. The reciprocal chimera was also made (PAR1-PA). PAR4-LD is proteolyzed by 10 nM alpha thrombin more efficiently than PAR4-wt. Alternatively, the rate of PAR1-PA proteolysis by alpha thrombin is less efficient than PAR1-wt but better than PAR4-wt due to the presence of the exosite I binding region in the PAR1 exodomain. However, if the exosite I binding domain is removed from PAR1-PA the rate of cleavage is like that seen with PAR4-wt exodomain. These data indicate PAR1 is cleaved by alpha thrombin at a faster rate than PAR4 due to the amino acids in the P4 and P3 positions as well as the exosite I binding region. In sum, these data demonstrate that the P2 position of PAR4 is the most important amino acid in thrombin binding to the region adjacent to the thrombin cleavage site. However the combined P4 and P3 positions are also important determinants of the rate of receptor cleavage. These data indicate that the amino acids around the thrombin cleavage site of both PAR4 and 1 influence its rate of cleavage. Designing thrombin receptor activation antagonists directed to the thrombin cleavage site on PAR1 and 4 should be effective anti-platelet agents.
Analyzing the impact of social attributes on commit integration success

As the software development community makes it easier to contribute to open source projects, the number of commits and pull requests keep increasing. However, this exciting growth renders it more difficult to only accept quality contributions. Recent research has found that both technical and social factors predict the success of project contributions on GitHub. We take this question a step further, focusing on predicting continuous integration build success based on technical and social factors involved in a commit. Specifically, we investigated if social factors (such as being a core member of the development team, having a large number of followers, or contributing a large number of commits) improve predictions of build success. We found that social factors cause a noticeable increase in predictive power (12%), core team members are more likely to pass the build tests (10%), and users with 1000 or more followers are more likely to pass the build tests (10%).
Posttraumatic stress disorder in opioid agonist therapy: A review.

Objective Posttraumatic stress disorder (PTSD) and opioid use disorder (OUD) co-occur at high rates, and this co-occurrence is associated with a range of problems related to mental and physical health. OUD is commonly treated with opioid agonist therapies (OAT), which have been shown to be effective for reducing opiate use and related negative health consequences. Given the high comorbidity of PTSD and OUD, many individuals in OAT have PTSD and continue to experience symptoms of both disorders despite OAT treatment. In this review, the extant literature on PTSD among individuals in OAT is presented. Method Relevant studies (N = 26) were identified systematically through a search of PubMed and PsychInfo databases. Results Literature regarding prevalence and clinical characteristics of patients with PTSD in OAT and treatment outcomes related to both OUD and PTSD is reviewed. Conclusion Clinical implications of the body of work and recommendations for future research are provided. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Issues Associated with the Development of Nuclear Power Plant “Programm Effectiveness” Indicators for Regulatory Use

This paper outlines several data issues related to the development of programmatic indicators for monitoring nuclear power plants (NPP) safety.
Deoxygenation of palmitic and lauric acids over Pt/ZIF-67 membrane/zeolite 5A bead catalysts

The deoxygenation of palmitic and lauric acids over 0.5 wt % Pt/ZIF-67 membrane/zeolite 5A bead catalysts is demonstrated. Almost complete conversion (% deoxygenation of ≥95%) of these two fatty acids was observed over both fresh and recycled catalyst after a 2 h reaction time. The catalysts displayed high selectivity to pentadecane and undecane via decarboxylation reaction pathway even at low 0.5 wt % Pt loading. Selectivity to pentadecane and undecane as high as ∼92% and ∼94% was observed under CO2 atmosphere when palmitic and lauric acids were used respectively as reactants. Depending on the reaction gas atmosphere, two distinctive reaction pathways were observed: decarboxylation and hydrodeoxygenation. Specifically, it was found that decarboxylation reaction pathway was more favorable in the presence of helium and CO2, while hydrodeoxygenation pathway strongly competed against the decarboxylation pathway when hydrogen was employed during the deoxygenation reactions. Esters were identified as the key r...
The Oxygen Reduction Reaction on Graphene from Quantum Mechanics: Comparing Armchair and Zigzag Carbon Edges

Using density functional theory (PBE-D2 flavor), we report the mechanism for the oxygen reduction reaction (ORR) on graphene sheets. We find that ORR starts with OO chemisorbing onto the carbon edges, rather than the basal plane face, which is not energetically favorable. The carbon edges were described as one-dimensional periodic graphene ribbons with both armchair and zigzag edges. We calculated the binding energies of the ORR products (OO, OOH, O, OH, HOH, HOOH) for the zigzag and armchair edges, examining both the Langmuir–Hinshelwood (LH) and Eley–Rideal (ER), to understand how OO is reduced. For the armchair edge, we calculate an onset potential of 0.55 V vs reversible hydrogen electrode (RHE), which corresponds to −0.22 V at pH 13 in agreement with experiments. We find that the rate-determining step (RDS) to form peroxide (a 2e– process) is hydrogenation of adsorbed OO with a barrier of 0.92 eV. The process to make water (a 4e– process) was found to be unfavorable at the onset potential but becomes...
Toward Network Coding for Cyber‐Physical Systems: Security Challenges and Applications

This survey summarizes the research on the applications and security challenges of network coding in wireless networks and cyber‐physical systems. Network coding technique generalizes the store‐and‐forward routing by mixing the received packets at the intermediate nodes to a single packet before forwarding them. Network coding has received a lot of attention from the community, and researchers have widely studied its application in increasing the throughput and transmissions reliability of networks and cyber‐physical systems. Applying network coding can be a challenge to the security of the networks. However, network coding can also provide a natural way to conceal the transmitted data from eavesdroppers. As a result of mixing the received packets at the intermediate nodes, the transmission protocols in network coding are more vulnerable against some attacks, such as pollution and Byzantine attacks. A single polluted packet can easily pollute many packets. Also, because of encoding at the intermediate nodes, the security mechanisms that are proposed for the traditional transmission protocols might not be appropriate for the protocols with network coding. On the other hand, since the transmitted packets are encoded, an eavesdropper cannot get meaningful data by overhearing a single encoded packet, which makes the transmissions more robust against eavesdropping attack. In this survey, in addition to discussing the security challenges in network coding protocols, we explain the applications of network coding in providing security. Our main focus in this paper is on the applications of network coding in providing security.
The Chaos and Cosmos of Kurosawa Tokiko: One Woman’s Transit from Tokugawa to Meiji Japan

Laura Nenzi has written a masterful account of the life of Kurosawa Tokiko (1806–90), a Japanese commoner woman who participated in the political events that ended the rule of the Tokugawa shoguns....
Generalized direct phase-coordinates control of inverter-interfaced distributed energy resources on fault ride through strategies

This paper presents two improvements concerning a newly-developed fault ride through (FRT) strategy based on the direct phase-coordinates approach for the distributed energy resources (DER). Taking into account the unsymmetrical three-phase voltage phasors at the point of common coupling, one improvement is on eliminating the double-frequency output power ripples through a generalized reference current calculation. Furthermore, the FRT strategy application scenario has been generalized from the single DER connection to the multiple DERs (multi-DER) integration. The other improvement is a cooperative fault current management scheme to minimize the total fault current contribution from the multi-DER. Simulation results are presented to evaluate the effectiveness of the generalized approach under the unbalanced fault condition.
Realization of spin wave switch for data processing

In this work, experimental data on a spin wave switch based on spin wave interference is reported. The switch is a three terminal device where spin wave propagation between the source and the drain is modulated by the control spin wave signal. The prototype is a micrometer scale device based on Y3Fe2(FeO4)3 film. The output characteristics show the oscillation of the output spin wave signal as a function of the phase difference between the source and the drain spin wave signals. The On/Off ratio of the prototype exceeds 20 dB at room temperature. The utilization of phase in addition to amplitude for information encoding offers an innovative route towards multi-state logic circuits. The advantages and shortcomings of spin wave switches are also discussed.In this work, experimental data on a spin wave switch based on spin wave interference is reported. The switch is a three terminal device where spin wave propagation between the source and the drain is modulated by the control spin wave signal. The prototype is a micrometer scale device based on Y3Fe2(FeO4)3 film. The output characteristics show the oscillation of the output spin wave signal as a function of the phase difference between the source and the drain spin wave signals. The On/Off ratio of the prototype exceeds 20 dB at room temperature. The utilization of phase in addition to amplitude for information encoding offers an innovative route towards multi-state logic circuits. The advantages and shortcomings of spin wave switches are also discussed.
Drinking Patterns of College- and Non-College-Attending Young Adults: Is High-Intensity Drinking Only a College Phenomenon?

Background: Young adults report the heaviest drinking of any age group, and many are at risk for experiencing an alcohol use disorder. Most research investigating young adult drinking has focused o...
Relatedness of Virion and Intracellular Proteins of the Murine Coronaviruses JHM and A59

Coronaviruses are a group of RNA viruses with positive polarity that cause a wide variety of diseases in many species including man. The structural proteins of coronaviruses have been studied extensively (reviewed in Robb and Bond, 1979). However, little attention has been focused on the intracellular proteins (Bond et al. 1979, Anderson et al. 1979, Siddel et al. 1980).
American Doctrine: The Foundation of Grand Strategy:

There is an organic American grand strategy, expressed over three centuries in multiple presidential doctrines. Through an examination of grand strategy and doctrines, a clear pattern of success an...
Mimicking, errors, and the optimal standard of proof

Abstract Criminals often engage in costly avoidance to lower their likelihood of being detected and sanctioned. Such avoidance, in turn, affects the optimal enforcement policy. This paper studies how the optimal standard of proof is affected by a specific type of avoidance, namely investments by guilty defendants to mimic innocent individuals. We show that when mimicking is possible the optimal standard of proof is weaker than preponderance of the evidence. This stands in contrast to much of the literature, which shows that non-deterrence costs usually cause the standard of proof to be stronger than preponderance. Thus, it is important not to ignore criminals’ secondary behavior when determining the optimal standard of proof.
Automated Collaboration Coach for Video-conferencing based Group Discussions

Maintaining a positive and respectful attitude during a group discussion is the key to a healthy collaboration. Automatically capturing and effectively showcasing the attitudes expressed through one's face, voice, and quote can make the group members more aware of their emotions and behaviors. My work is on developing fully automated systems to analyze group discussions and provide feedback to improve discussion experience and team cohesion. I explore the automatic capture and analysis of audio-video data from the discussions, and the effective design principles of machine mediation for effective behavior changes. In this proposal, I describe the developed system that senses group dynamics and provides automated feedback for videoconferencing based group discussions, and discuss the ways in which it can evolve to address different challenges regarding effective collaboration.
The Diabetes Susceptibility Gene SLC30A8 that Encodes the Zinc Transporter ZnT8 is a Pseudogene in Guinea Pigs Potentially Contributing to Low Guinea Pig Islet Zinc Content

In most mammals pancreatic islet beta cells have very high zinc levels that promote the crystallization and storage of insulin. Guinea pigs are unusual amongst mammals in that their islets have very low zinc content. The selectionist theory of insulin evolution proposes that low environmental zinc led to the selection of a mutation in Guinea pig insulin that negated the requirement for zinc binding. In mice deletion of the Slc30a8 gene, that encodes the zinc transporter ZnT8, markedly reduces islet zinc content. We show here that SLC30A8 is a pseudogene in Guinea pigs. We hypothesize that inactivation of the SLC30A8 gene led to low islet zinc content that allowed for the evolution of insulin that no longer bound zinc.
Hemophagocytic Lymphohistiocytosis in Pregnancy: A Case Series and Review of the Current Literature

Background. Hemophagocytic lymphohistiocytosis (HLH) is a rare disease that can be fatal in pregnancy. We report two cases of severe HLH that highlight etoposide use in pregnancy. Case 1. 28-year-old G2P1 with lupus presented at 18 weeks with acute hypoxic respiratory failure, hepatic dysfunction, leukopenia, thrombocytopenia, and elevated ferritin. Bone marrow biopsy confirmed HLH. Etoposide and corticosteroid treatment was initiated per HLH protocol; however clinical status declined rapidly. Fetal demise occurred at 21 weeks and she subsequently suffered a massive cerebral vascular accident. She was transitioned to comfort measures and the patient deceased. Case 2. 37-year-old G4P3 presented at 25 weeks with fever, acute liver failure, thrombocytopenia, and elevated ferritin. HLH treatment was initiated, including etoposide, and diagnosis confirmed with liver biopsy. Fetal growth restriction was diagnosed at 27 weeks. Delivery occurred at 37 weeks. The neonate was found to be CMV positive despite negative maternal serology. Conclusion. The addition of etoposide to corticosteroid use is a key component in HLH treatment of nonpregnant individuals. While this is usually avoided in pregnancy, the benefit to the mother may outweigh the potential harm to the fetus in severe cases and it should be strongly considered.