cssi/SciSciGPT-SciSciNet huggingface dataset:
Intestinal alkaline phosphatase decreases intraperitoneal adhesion formation

Abstract Background Damage to the peritoneum initiates an inflammatory response leading to the formation of adhesions, which subsequently cause significant morbidity in some patients. Intestinal alkaline phosphatase (IAP) is a gut enzyme capable of detoxifying various inflammatory mediators such as lipopolysaccharide, lipoteichoic acid, CpG DNA, and adenosine triphosphate. In this study, we aimed to examine the anti-inflammatory effects of IAP on postoperative adhesions in mice. Methods C57BL/6 mice were subjected to a midline laparotomy and then six musculoperitoneal buttons (MPBs) were created by pinching and ligating the peritoneum and underlying muscle. The buttons were half-excised and E-cauterized, and then cecal abrasion was performed. Five hundred microliters of vehicle with IAP 5000 U or vehicle alone were applied over the peritoneal cavity. In some experiments, the mice were euthanized on the first and second postoperative day (POD), and cytokines analysis was done on the MPB, peritoneal tissue, and peritoneal fluid. In separate experiments, the mice were sacrificed on the 21st POD, and adhesion to each button was scored based on type and tenacity. Results IAP group mice had significantly lower adhesion scores compared with controls (21.5 ± 1.7 versus 13.2 ± 1.3; P = 0.0014, n = 15). MPB from IAP group mice had significantly lower interleukin-1β and tumor necrosis factor-α protein level compared to control mice (105.66 ± 4.5 versus 69.8 ± 4.8 versus pg/mg, P = 0.0001; 45.25 ± 2.8 pg/mg versus 24.88 ± 4.1 pg/mg; P = 0.0007, n = 10). IAP treatment significantly decreased interleukin-1β and tumor necrosis factor-α mRNA expression in MPB in the first POD (1.14 ± 0.25 versus 0.33 ± 0.07; P = 0.0068; 1.33 ± 0.31 versus 0.33 ± 0.08; P = 0.0064, n = 10). Conclusions Application of IAP during laparotomy could represent a novel approach to prevent postoperative adhesions.
When friends exchange negative feedback

In four studies, we document an increase in the amount of negative feedback friends and colleagues exchange as their relationship deepens. We find that both actual and perceived relationship depth increase the amount of negative feedback people seek from and provide to each other, as well as their tendency to invest in a focal (relationship or performance) goal in response to negative feedback. The amount of positive feedback on goal pursuit, by contrast, remains stable as the relationship deepens. We attribute the increase in negative feedback to the different meaning of such feedback for people in deep versus shallow relationships: only in the context of deep relationships does negative feedback signal insufficient resource investment in the focal goal, and hence close friends and colleagues seek, provide, and respond to negative feedback.
Keeping Score: Academic Gamesmanship by Alexander W. Astin; The Ranking Game, by W. Patrick Dolan

(1976). Keeping Score: Academic Gamesmanship by Alexander W. Astin; The Ranking Game, by W. Patrick Dolan. Change: The Magazine of Higher Learning: Vol. 8, No. 10, pp. 57-58.
New Techniques for Modelling and Control of Flexible Automated Manufacturing Systems

Abstract We consider the problem of optimizing the performance of Flexible Manufacturing Systems (FMS). These advanced automated systems are becoming popular throughout the world for parts-manufacturing. However, the ability to analyze and optimize the performance of FMS has remained relatively primitive. This paper describes our recent efforts in modelling and control of FMS. First we motivate the need for analytical models of FMS. The main body of the paper then states our new results on analytical models of FMS. Next we show our models can be used for optimal feedback control of FMS. Based on an analytical approach, our techniques have given much better results than previously proposed heuristics. Our methods and results show the scope for achieving still better results, and it is hoped that this paper will stimulate further research in this area.
Acupuncture Analgesia: A Review of Peripheral and Central Mechanisms

Acupuncture is an ancient needling modality within Traditional Chinese Medicine used for chronic pain management. Western biophysical and Chinese meridian theory views of pain differ, and so do their respective management practices. The reversible effect of naloxone on the acupuncture induced analgesia is well known. Research has also shown correlations between acupuncture and its effect on the peripheral nerve endings, connective tissue, neurotransmitters, and inflammatory mediators. Centrally, studies with functional imaging and dynamic quantitative sensory testing substantiate the modulatory role of acupuncture in the “wind-up” phenomenon of spinal wide dynamic range neurons and different brain areas related to pain perception and modulation. Despite this increased understanding in the mechanisms and the analgesic efficacy of acupuncture, controversy continues to evolve around the issues of placebo effect and its potential therapeutic role in the main stream medicine.
Designing an In-Vehicle Air Gesture Set Using Elicitation Methods

In-air gestures have become more prevalent in the vehicle cockpit in recent years. However, air gesture interfaces are still quite young and users have very little experience with such interactions. In the vehicle, ease of use relates directly to driver safety. Previous work has suggested that gesture sets created through participatory methods tend to be easier for people to grasp and use than designer-designed sets. In the present study, two novel participatory design activities -- an elicitation activity in which participants produced gestures, and an online survey in which they assessed the workload associated with those gestures -- were conducted to assess possible air gestures for control of in-vehicle menus. A recommended gesture set is presented alongside broader recommendations for vehicle gesture design.
Learning the fundamentals in a stationary environment

Abstract A Bayesian agent relies on past observations to learn the structure of a stationary process. We show that the agent's predictions about near-horizon events become arbitrarily close to those he would have made if he knew the long-run empirical frequencies of the process.
Personalized behavior change program for glaucoma patients with poor adherence: a pilot interventional cohort study with a pre-post design.

About half of people with glaucoma do not adhere to their recommended medications. Interventions for other chronic conditions have successfully utilized reminder systems and motivational interviewing (MI)-based counseling. This study was designed to pilot a personalized intervention that leverages these strategies to assess their impact on medication adherence in glaucoma patients. Glaucoma patients taking ≥ 1 medication will be pre-screened by telephone survey for adherence to their medication(s). Those who self-report poor adherence will be enrolled in a 3-month monitoring period to measure medication adherence using electronic medication monitors. Participants who are non-adherent (take </=80% of their medication doses) over the 3-month run in phase will be eligible for the study. We plan to enroll 57 participants who are non-adherent to their medications. Participants’ adherence will then be continuously measured with electronic medication monitors, by self-report, and via pharmacy refill data over 2 years, during which two successively more resource-intensive components of an intervention aimed to improve medication adherence will be administered. The first component is a 3-month period of reminders (audio and/or visual) and text message or automated phone call if a dose of medication is not taken within a pre-specified time frame. The second component is a 6-month MI-based counseling program with a trained glaucoma counselor. This component uses the eyeGuide, a computer-based personalized behavior change program that enables para-professional staff to provide personalized education and counseling for glaucoma. The primary outcome is change in medication adherence. The secondary outcomes include changes in clinical outcomes (intraocular pressure, IOP, and IOP fluctuation) and psychosocial mediators of adherence (e.g., competence, energy for change and satisfaction). Participants will undergo semi-structured interviews at 12 months to give feedback about the counseling program in order to improve it. This pilot study will provide insight into ways to deliver more personalized health care to non-adherent glaucoma patients in order to better support them in managing their chronic disease. Retrospectively registered with ClinicalTrials.gov ( NCT03159247 ).
Phonemic and Semantic Verbal Fluency in Sex Chromosome Aneuploidy: Contrasting the Effects of Supernumerary X versus Y Chromosomes on Performance

Objectives Past research suggests that youth with sex chromosome aneuploidies (SCAs) present with verbal fluency deficits. However, most studies have focused on sex chromosome trisomies. Far less is known about sex chromosome tetrasomies and pentasomies. Thus, the current research sought to characterize verbal fluency performance among youth with sex chromosome trisomies, tetrasomies, and pentasomies by contrasting how performance varies as a function of extra X number and X versus Y status. Methods Participants included 79 youth with SCAs and 42 typically developing controls matched on age, maternal education, and racial/ethnic background. Participants completed the phonemic and semantic conditions of a verbal fluency task and an abbreviated intelligence test. Results Both supernumerary X and Y chromosomes were associated with verbal fluency deficits relative to controls. These impairments increased as a function of the number of extra X chromosomes, and the pattern of impairments on phonemic and semantic fluency differed for those with a supernumerary X versus Y chromosome. Whereas one supernumerary Y chromosome was associated with similar performance across fluency conditions, one supernumerary X chromosome was associated with relatively stronger semantic than phonemic fluency skills. Conclusions Verbal fluency skills in youth with supernumerary X and Y chromosomes are impaired relative to controls. However, the degree of impairment varies across groups and task condition. Further research into the cognitive underpinnings of verbal fluency in youth with SCAs may provide insights into their verbal fluency deficits and help guide future treatments. (JINS, 2018, 24, 917-927).
Tumor cyclooxygenase 2 controls PGE2 dependent promotion of FOXP3 expression and CD4+CD25+ T regulatory cell activities in non-small cell lung cancer

2657 Cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) underlies an immunosuppressive network that is important in the pathogenesis of non-small cell lung cancer (NSCLC). CD4+CD25+ T regulatory (Treg) cell activities increase in lung cancer, suppressing antitumor immune responses. The identification of molecules controlling Treg differentiation and function is important in understanding host immune responses in malignancy. Here we show that PGE2 enhances the in vitro inhibitory function of human purified CD4+CD25+ Treg cells and induces a regulatory phenotype in CD4+CD25- T cells. PGE2-treated T cells mediated inhibition of responder anti-CD3 stimulated lymphocytes in both a cell-contact dependent and independent manner. Phenotypic analysis revealed that PGE2 diminished CD25 expression in both CD4+CD25- T cells and CD4+CD25+ Treg cells. PGE2 exposure induced the Treg cell specific transcription factor FOXP3 in CD4+CD25- T cells and significantly upregulated its expression in CD4+CD25+ Treg cells. Supernatants from COX-2 overexpressing lung cancer cells that secrete high level PGE2 significantly induced FOXP3 in CD4+CD25- T cells. PGE2 upregulated FOXP3 at both mRNA and protein levels and enhanced FOXP3 promoter activity in Jurkat T cells. Based on these results in human Treg cells, we determined the role of tumor COX-2 expression on the frequency and activity of CD4+CD25+ Treg cells in murine lung cancer models in vivo. Tumor-derived COX-2/PGE2 induced expression of Foxp3 and increased Treg cell suppressive activities in vivo. Utilization of lymphocytes from EP2 and EP4 receptor knockout mice showed that the PGE2 mediated increase in Foxp3 gene expression in Treg cells was EP2 receptor dependent. In vivo, COX-2 inhibition reduced Treg cell frequency and activity, attenuated Foxp3 expression in tumor infiltrating lymphocytes and decreased tumor burden. Transfer of Treg cells or administration of PGE2 to mice receiving COX-2 inhibitors reversed these effects. We conclude that inhibition of COX-2/PGE2 suppresses Treg cell activity and enhances antitumor responses. This is the first report indicating that tumor-derived PGE2 can modulate FOXP3 expression and Treg function. These findings strengthen the rationale for the evaluation of COX-2 inhibition in lung cancer prevention and therapy.
Weaving geodesic foliations

We study discrete geodesic foliations of surfaces---foliations whose leaves are all approximately geodesic curves---and develop several new variational algorithms for computing such foliations. Our key insight is a relaxation of vector field integrability in the discrete setting, which allows us to optimize for curl-free unit vector fields that remain well-defined near singularities and robustly recover a scalar function whose gradient is well aligned to these fields. We then connect the physics governing surfaces woven out of thin ribbons to the geometry of geodesic foliations, and present a design and fabrication pipeline for approximating surfaces of arbitrary geometry and topology by triaxially-woven structures, where the ribbon layout is determined by a geodesic foliation on a sixfold branched cover of the input surface. We validate the effectiveness of our pipeline on a variety of simulated and fabricated woven designs, including an example for readers to try at home.
Developing visitor thresholds of sound from shale natural gas compressors for motorized and non-motorized recreation users in Pennsylvania State Forests

Abstract Understanding visitor evaluations of human-caused sounds is an essential component to managing recreation experiences in parks and protected areas. In this study, the impact of sounds from natural gas compressors in Pennsylvania State Forests is explored. Using data collected from over 400 onsite visitors, researchers developed a threshold model that shows how visitor experiences change with sounds from natural gas compressors. The threshold model shows that increased sound levels (dBA) from natural gas compressors have a negative impact on visitor experiences. Further segmentation by activity type shows that there is a negligible impact on motorized users and a negative impact on non-motorized visitors. The threshold model shows that sounds from natural gas compressors become unacceptable to non-motorized users at about 55 dBA. The results from this study can be used to help managers of forests plan for high-quality recreational experiences in an era of expanding natural gas extraction.
Slowdown of group velocity in periodic waveguides

We consider the propagation of acoustic, electromagnetic and elastic waves in a one-dimensional periodic two-component material. Accurate asymptotic formulas are provided for the group velocity as a function of the material parameters when the concentration of scatterers is small or the characteristic impedances of the two media differ substantially. In the latter case, it is shown that the minimum group velocity occurs when the volume fractions of the components of the material are equal. In both asymptotic cases we show that the leading terms of the group velocity do not depend on frequency. Thus slowdown is frequency-independent and is not related to the resonance phenomena.
Multi-Discriminator Distributed Generative Model for Multi-Layer RF Metasurface Discovery

Metasurface-based antenna beam control is defining a new engineering paradigm in radio-frequency applications such as communications, radar, and analog spatial signal processing. Metasurfaces are composite electromagnetic material surfaces that are made of subwavelength scattering particles, or meta-atoms, with negligible thickness and optimized to control electromagnetic waves in unprecedented fashions through modified boundary conditions. Conventional metasurface design is a tedious process that requires iteratively solving Maxwell's equations. This becomes increasingly challenging as state-of-the-art metasurfaces require complex bi-anisotropic responses over multiple layers of meta- atoms and several frequency bands. In this paper, to reduce design time and optimization overhead, we employ a multi-discriminator distributed generative adversarial network for inverse design of multi- layer metasurfaces. Unlike conventional design approaches, our proposed approach is able to jointly design multiple layers, discover new meta- atom patterns, and avoid solving Maxwell’s equations numerically or analytically. Results show that generated triple-layer meta-atoms can achieve frequency resonances within 7% of the input values.
Self-healing magnetic nanocomposites with robust mechanical properties and high magnetic actuation potential prepared from commodity monomers via graft-from approach

Herein, we report the design, synthesis and characterization of self-healing magnetic nanocomposites prepared from readily available commodity monomers. These multi-functional materials demonstrate robust mechanical properties, with a Young's modulus of 70 MPa and over 500% extensibility. The magnetic nanocomposites also show self-healing ability, achieving 46% recovery of extensibility in 5 hours in ambient conditions while retaining high magnetic actuation with a commodity magnet.
Further improvement of wet process treatments in GEOS-Chem v12.6.0: Impact on globaldistributions of aerosol precursors and aerosols

Abstract. Wet processes, including aqueous phase chemistry, wet scavenging, and wet surface uptakes during dry deposition, are important for global modeling of aerosol precursors and aerosols. In this study, we improved the treatments of these wet processes in the GEOS-Chem v12.6.0, including pH calculation for cloud, rain, and wet surface, fraction of cloud available for aqueous phase chemistry, rainout efficiencies for various types of cloud, empirical washout by rain and snow, and wet surface uptakes during dry deposition. We compared simulated surface mass concentrations of aerosol precursors and aerosols with surface monitoring networks over the United States, Europe, Asia, and Arctic regions, and showed that the model results with the updated wet processes agree better with measurements for most species. With the implementation of these updates, normalized mean biases (NMB) of surface nitric acid, nitrate, and ammonium are reduced from 78 %, 126 %, and 45 % to 13 %, 24 %, and 6.2 % over US sites, from 56 %, 105 %, and 91 % to −20 %, −5.1 %, and 22 % over Europe sites, and from 121 %, 269 %, and 167 % to −18 %, 40 %, and 86 % over Asia sites. Comparison with surface measured SO2, sulfate and black carbon at four Arctic sites indicated that these species simulated with the updated wet processes match well with observations except large underestimation of black carbon at one of the sites. Furthermore, we compared model simulation with aircraft measurement of nitric acid and aerosols during ATom-1 and ATom-2 periods and found seasonal variation and vertical profile of these species have been successfully improved by considering the updated wet processes. The investigation of impacts of updated wet process treatments on surface mass concentrations indicated that the updated wet processes have strong impacts on the global means of nitric acid, sulfate, nitrate, and ammonium and relative small impacts on the global means of sulfur dioxide, dust, sea salt, black carbon, and organic carbon.
Early Implementation of Comprehensive Medication Management within an Academic Medical Center Primary Care Pharmacy Team.

Introduction University of Utah Health is an academic health care system that serves residents in Utah and beyond. Clinical pharmacists with the health care system's pharmacy primary care services (PPCS) team provide medication education, population-based care, and medication management through collaborative practice agreements. With the expansion of clinical pharmacist and technician positions and services, the need to measure and assess the impact of pharmacy services and create a value proposition for internal and external stakeholders became an important goal, and the decision was made to better align practices across all PPCS sites. This paper highlights University of Utah Health's approach to implement comprehensive medication management (CMM) across all primary care clinics with embedded clinical pharmacy staff and subsequent evaluation of implementation fidelity. Methods Implementation of CMM was assisted by participation in the National A3 Collaborative and by using selected principles from the Active Implementation Framework. Stages of implementation included exploration, instillation, and initiating improvement cycles. An implementation team consisting of PPCS employees was created to help with standardization, developing implementation plans, and creating a dissemination strategy for all PPCS team members. The CMM care process was subsequently presented and implemented by clinical pharmacists in primary care clinics. Following implementation, fidelity measures were collected including identification and resolution of medication therapy problems (MTPs) and responses from a questionnaire distributed to the clinical pharmacists to self-report understanding and implementation of CMM key elements. The number and type of MTPs identified were tracked over 18 months. Results Within the measurement window, clinical pharmacists identified 17,953 MTPs. Of the total number of MTPs identified, 21% were related to indication, 53% to efficacy, 15% to safety and 11% to adherence. The questionnaire was distributed to clinical pharmacists 9 months after CMM implementation, with a 71% response rate. Pharmacists reported "always" or "often" performing each step in the patient care process as follows: indication (93%), effectiveness (93%), safety (87%), and adherence (93%). Reported barriers to implementation of the CMM include lack of time to complete all aspects of the process efficiently, lack of a standardized format for documentation, and changing practice habits. Conclusion Implementation of a CMM process within University of Utah Health's PPCS services with the help of a national collaborative and implementation framework yielded identification of 17,953 MTPs over 18 months and foundational fidelity to core principles.
qDKT: Question-centric Deep Knowledge Tracing

Knowledge tracing (KT) models, e.g., the deep knowledge tracing (DKT) model, track an individual learner's acquisition of skills over time by examining the learner's performance on questions related to those skills. A practical limitation in most existing KT models is that all questions nested under a particular skill are treated as equivalent observations of a learner's ability, which is an inaccurate assumption in real-world educational scenarios. To overcome this limitation we introduce qDKT, a variant of DKT that models every learner's success probability on individual questions over time. First, qDKT incorporates graph Laplacian regularization to smooth predictions under each skill, which is particularly useful when the number of questions in the dataset is big. Second, qDKT uses an initialization scheme inspired by the fastText algorithm, which has found success in a variety of language modeling tasks. Our experiments on several real-world datasets show that qDKT achieves state-of-art performance on predicting learner outcomes. Because of this, qDKT can serve as a simple, yet tough-to-beat, baseline for new question-centric KT models.
A Pre-Test–Post-Test Trial of a Breast Cancer Risk Report for Women in Their 40s

Introduction Guidelines recommend individualized breast cancer screening and prevention interventions for women in their 40s. Yet, few primary care clinicians assess breast cancer risk. Study design Pretest-Posttest trial. Setting/participants Women aged 40–49 years were recruited from one large Boston-based academic primary care practice between July 2017 and April 2019. Intervention Participants completed a pretest, received a personalized breast cancer risk report, saw their primary care clinician, and completed a posttest. Main outcome measures Using mixed effects models, changes in screening intentions (0–100 scale [0=will not screen to 100=will screen]), mammography knowledge, decisional conflict, and receipt of screening were examined. Analyses were conducted from June 2019 to February 2020. Results Patient (n=337) mean age was 44.1 (SD=2.9) years, 61.4% were non-Hispanic white, and 76.6% were college graduates; 306 (90.5%) completed follow-up (203 with 5–year breast cancer risk Conclusions Receipt of a personalized breast cancer report was associated with women in their 40s making more-informed and less-conflicted mammography screening decisions and with high-risk women discussing breast cancer prevention interventions with clinicians. Trial registration This study is registered at www.clinicaltrials.gov NCT03180086 .
Statistical Analysis of County-Level Contributing Factors to Opioid-Related Overdose Deaths in the United States

This paper examines county-level characteristic factors contributing to opioid-related overdose deaths in the United States. We categorized factors into three groups: demographic, socio-economic, and health care environmental group. These features were used as predictors to model the overdose deaths from all types of opioids including prescription (e.g., oxycodone and hydrocodone) and illicit opioids (e.g., heroin and fentanyl) to investigate general trend, as well as separate models for heroin and fentanyl. Multilevel mixed-effect regression was adopted to adequately model grouping effect across counties.
The role of cognitive reserve in the relationship between metabolic syndrome and cognitive functioning.

Metabolic syndrome (MetS) is a cluster of vascular risk factors that can impact cognition. Cognitive reserve (CR), specifically early operators of reserve (e.g., education), have not been explored ...
How to Lower the Volatility in the Stock Market? More Reading Less Trading

This paper presents steps to lower the overall volatility in the stock market; as a large portion is unrewarded and unjustified and driven by overreaction accompanies with herd behavior. We first map the key factors that cause volatility, such as: earnings surprise, CEO turnovers, merge and acquisitions, etc. and then present our suggestions; where the key elements are: (i) fewer day/hours of trading, which in turn increases time to processing information; and (ii) semi-annual earnings reports instead of quarterly; smoothing the surprises. Following these suggestions, the volatility decreases by at least 15.5% per day. Collectively, we suggest to trade less and read more.
Introduction of Varroa destructor has not altered honey bee queen mating success in the Hawaiian archipelago.

Beekeepers struggle to minimize the mortality of their colonies as a consequence of the parasitic mite Varroa destructor in order to maintain a sustainable managed pollinator population. However, little is known about how varroa mites might diminish local populations of honey bee males (drones) that might affect the mating success of queens. As one of the world’s last localities invaded by varroa mites, the Hawaiian Islands offer a unique opportunity to examine this question by comparing queens mated on mite-infested and mite-free islands. We raised queen bees on four Hawaiian Islands (Kaua‘i, O‘ahu, Maui, and Hawai‘i) and subsequently collected their offspring to determine queen mating frequency and insemination success. No significant difference for mating success was found between the islands with and without varroa mites, and relatively high levels of polyandry was detected overall. We also found a significant association between the number of sperm stored in the queens’ spermathecae and the number of managed colonies within the localities of the queens mated. Our findings suggest that varroa mites, as they currently occur in Hawai‘i, may not significantly reduce mating success of honey bee queens, which provides insight for both the reproductive biology of honey bees as well as the apiculture industry in Hawai‘i.
Students Experience on the Efficacy of Virtual Labs in Online Biology

Science education relies on laboratory activities to provide practical skills to learners in both K-12 and college level. With the rapid advancements in technology, online delivery of instruction is increasingly becoming popular among learning institutions. Accommodating the increasing number of students enrolling for online biology courses requires alternative means of instructing laboratory component. Most importantly, these alternative means of instruction must ensure that learning outcomes are attained just like in the traditional methods of teaching and learning. The most notable approach is the use of virtual lab simulations. The current study reviewed the available literature to realize whether virtual labs in online instruction of biology courses for undergraduate courses are as effective compared to traditional Face to face (F2F) learning. The study reviewed a total of 13 articles relevant to the research question. The results of the review highlighted the positive and negative effects of virtual labs and the students' perceptions of their effectiveness. Based on the results of the review, the study provides recommendations for further studies on virtual labs and how they can be improved in teaching and learning in online biology instruction.
Optimal Epidemic Control as a Contextual Combinatorial Bandit with Budget

In light of the COVID-19 pandemic, it is an open challenge and critical practical problem to find a optimal way to dynamically prescribe the best policies that balance both the governmental resources and epidemic control in different countries and regions. To solve this multi-dimensional tradeoff of exploitation and exploration, we formulate this technical challenge as a contextual combinatorial bandit problem that jointly optimizes a multi-criteria reward function. Given the historical daily cases in a region and the past intervention plans in place, the agent should generate useful intervention plans that policy makers can implement in real time to minimizing both the number of daily COVID-19 cases and the stringency of the recommended interventions. We prove this concept with simulations of multiple realistic policy making scenarios.
CoV-er all the bases: Structural perspectives of SARS-CoV-2 RNA synthesis

The ongoing Covid-19 pandemic has spurred research in the biology of the nidovirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Much focus has been on the viral RNA synthesis machinery due to its fundamental role in viral propagation. The central and essential enzyme of the RNA synthesis process, the RNA-dependent RNA polymerase (RdRp), functions in conjunction with a coterie of viral-encoded enzymes that mediate crucial nucleic acid transactions. Some of these enzymes share common features with other RNA viruses, while others play roles unique to nidoviruses or CoVs. The RdRps are proven targets for viral pathogens, and many of the other nucleic acid processing enzymes are promising targets. The purpose of this review is to summarize recent advances in our understanding of the mechanisms of RNA synthesis in CoVs. By reflecting on these studies, we hope to emphasize the remaining gaps in our knowledge. The recent onslaught of structural information related to SARS-CoV-2 RNA synthesis, in combination with previous structural, genetic and biochemical studies, have vastly improved our understanding of how CoVs replicate and process their genomic RNA. Structural biology not only provides a blueprint for understanding the function of the enzymes and cofactors in molecular detail, but also provides a basis for drug design and optimization. The concerted efforts of researchers around the world, in combination with the renewed urgency toward understanding this deadly family of viruses, may eventually yield new and improved antivirals that provide relief to the current global devastation.
Impact of Section 201 of SOX on the Relationship between Audit and Non-Audit Fees

This study aims to investigate the changes that the prohibition of the non-audit services by section 201 of SOX brought in the relationship between the audit fees and non-audit fees. Both univariate and multivatiate regression methodologies has been used to test the hypotheses. Using both OLS and two-stage least squares, this study find a weak positive relationship between audit fees and non-audit fees. This result suggests that the companies need to pay an increased rate of both audit and non-audit fees after SOX. The findings of this paper will be the use of financial reporting regulatory authorities such as Public Company Accounting Oversight Board (PCAOB). It will also guide the researchers for future investigations. This study will be the one of the first to provide evidence on the changes in the relationship between audit and non-audit fees because of the Section 201 of Sarbanes-Oxley Act.
Trisporic Acid Biosynthesis in Separate Plus and Minus Cultures of Blakeslea trispora: Identification by Mucor Assay of Two Mating-Type-Specific Components

Separate plus and minus cultures of Blakeslea trispora synthesize small amounts of trisporic acids under specific conditions. These amounts are expressed as a percentage of the trisporic acids (50 mg/liter of medium) synthesized by mixed plus-minus cultures in 5 days. Plus cultures, without additives from minus cultures, synthesize 0.1% trisporic acids. Plus cultures synthesize 0.4% trisporic acids when stimulated by M-factor, a mating-type-specific component synthesized by minus cultures. Minus cultures, without additives from plus cultures, do not synthesize even 0.0001% trisporic acids. Minus cultures synthesize 1% trisporic acids when stimulated by P-factor, a mating-type-specific component synthesized by plus cultures. Minus cultures synthesize M-factor when stimulated by π, a component synthesized by plus cultures. We speculate that (i) minus cultures synthesize a component, μ, which stimulates P-factor synthesis in plus cultures, and (ii) both M-factor and P-factor are precursors of trisporic acids.
ChatterBots, TinyMuds, and the Turing test: entering the Loebner Prize competition

The Turing Test was proposed by Alan Turing in 1950; he called it the Imitation Game. In 1991 Hugh Loebner started the Loebner Prize competition, offering a $100,000 prize to the author of the first computer program to pass an unrestricted Turing test. Annual competitions are held each year with smaller prizes for the best program on a restricted Turing test. This paper describes the development of one such Turing System, including the technical design of the program and its performance on the first three Loebner Prize competitions. We also discuss the program's four year development effort, which has depended heavily on constant interaction with people on the Internet via Tinymuds (multiuser network communication servers). Finally, we discuss the design of the Loebner competition itself, and address its usefulness in furthering the development of Artificial Intelligence.
Unstable genomes elevate transcriptome dynamics

The challenge of identifying common expression signatures in cancer is well known, however the reason behind this is largely unclear. Traditionally variation in expression signatures has been attributed to technological problems, however recent evidence suggests that chromosome instability (CIN) and resultant karyotypic heterogeneity may be a large contributing factor. Using a well-defined model of immortalization, we systematically compared the pattern of genome alteration and expression dynamics during somatic evolution. Co-measurement of global gene expression and karyotypic alteration throughout the immortalization process reveals that karyotype changes influence gene expression as major structural and numerical karyotypic alterations result in large gene expression deviation. Replicate samples from stages with stable genomes are more similar to each other than are replicate samples with karyotypic heterogeneity. Karyotypic and gene expression change during immortalization is dynamic as each stage of progression has a unique expression pattern. This was further verified by comparing global expression in two replicates grown in one flask with known karyotypes. Replicates with higher karyotypic instability were found to be less similar than replicates with stable karyotypes. This data illustrates the karyotype, transcriptome, and transcriptome determined pathways are in constant flux during somatic cellular evolution (particularly during the macroevolutionary phase) and this flux is an inextricable feature of CIN and essential for cancer formation. The findings presented here underscore the importance of understanding the evolutionary process of cancer in order to design improved treatment modalities.
Prevention of breast cancer by recapitulation of pregnancy hormone levels.

At the present time, the only approved method of breast cancer prevention is use of the selective estrogen receptor modulator (SERM) tamoxifen. Many breast cancers are driven to grow by estrogen, and tamoxifen exploits this by blocking estrogen action at the estrogen receptor. A counter-intuitive and controversial approach to breast cancer prevention is administration of estrogen and progestin at an early age to achieve pregnancy levels. This approach is supported by the fact that breast cancer incidence is halved by early (≤ 20 years of age) full-term pregnancy. Moreover, it has been demonstrated in rodent models that mimicking the hormonal milieu can effectively prevent carcinogen-induced mammary cancer. In this issue of Breast Cancer Research Rajkumar and colleagues use the rodent model to further define the timing and type of hormonal therapy that is effective in preventing mammary carcinogenesis. Clearly, application of this approach in humans may be difficult, but the potential benefit is intriguing.
Detection of Early Human T-Cell Lymphotropic Virus Type I Antibody Patterns During Seroconversion Among Transfusion Recipients

From a cohort of human T-cell lymphotropic virus type I (HTLV-I) exposed transfusion recipients (N = 71) enrolled in the Jamaican Transfusion Study, 11 were selected for detailed laboratory evaluation. All recipients were followed at monthly intervals for 6 months and then bimonthly up to 1 year for evidence of HTLV-I seroconversion. Without regard to results on screening assays, pretransfusion and posttransfusion samples were tested with two licensed HTLV-1 whole-virus screening enzyme immunoassays (EIAs), recombinant EIAs for antibody against tax (p40x) and p21e envelope, standard whole virus Western blot (WB), WB enhanced with recombinant p21e, and radioimmunoprecipitation assay (RIPA). In the early period posttransfusion, antibody to gag core protein was predominant with anti-p24 generally appearing before anti-p19. Recombinant anti-p21e envelope protein, in EIA and WB format, was frequently the earliest envelope reactivity detected, while anti-gp46 in WB and anti-gp61/68 in RIPA system appeared later. Anti-tax antibodies appeared later in the time course of seroconversion. The whole-virus EIAs were less sensitive than the confirmatory assays. The combination of WB and RIPA or WB enhanced with recombinant p21e appeared equally effective in confirming samples as positive by the Public Health Service two gene group confirmatory algorithm. However, specificity of this assay approach could not be addressed in this study.
Catalytic Antibody Bridges Innate and Adaptive Immunity

Neutrophils of the innate immune system are well equipped to kill invading pathogens by generating a variety of reactive oxygen intermediates including singlet oxygen. In his Perspective, [Nathan][1] discusses the surprising finding ([Wentworth][2] et al .) that stalwart members of the acquired immune system, the antibodies produced by B cells, can contribute to this armamentarium by catalytically reacting singlet oxygen with water to produce hydrogen peroxide and a powerful ozone-like oxidant, O3. [1]: http://www.sciencemag.org/cgi/content/full/298/5601/2143 [2]: http://www.sciencemag.org/cgi/content/short/298/5601/2195
Improving Retention through Implementation of a Nurse Externship

Poster Presentation Purpose for the Program This program was designed as a collaboration between a local university, nursing students, and a community hospital. All shared a common desire to promote 1st‐year retention for new graduates. Resumes and brief interviews with unit leadership are often the only information available for hiring decisions. Leaders express concern over the ability to choose appropriate candidates from limited interaction in the interview process. A primary program goal was to allow nurse leaders to better determine the success of potential employees through sustained interaction. For student nurse externs, participation was designed to expand clinical experiences and assist in the transition from academia to professional practice. Proposed Change To provide a mutual opportunity for informed decision making, a nurse externship was proposed. Student nurses were able to experience specialties within nursing to determine compatibility. Prospective employers were able to spend more time with potential employees to allow better determination of future employer–employee relationship success. Implementation, Outcomes, and Evaluation Care of the Neonate was a 10‐week elective course for senior nursing students that included didactic content, skills labs, case studies, and quality improvement projects. The externship was dedicated to hands‐on experiences under the direction of a clinical coach. Patient assignments, conferences, and learning activities were designed to address cognitive, affective, and psychomotor learning domains. Externs compiled a portfolio linking clinical objectives to outcomes. These were evaluated by program facilitators, clinical coaches, and extern participants to determine successful completion. A Likert‐type scale questionnaire showed an increase in confidence, time management, and critical thinking skills. Externs unanimously reported decreased anxiety and increased perception as valued health care team members. Unit leaders were able to confidently select appropriate candidates for employment and continued to experience 100% retention beyond the 1st year of employment for all externs hired. Implications for Nursing Practice Studies indicate that investment into an externship can increase nurse retention. Externships allow novice nurses to practice skills, increase confidence levels, become inside members of the health care team, and develop communication skills with patients, families, and other health care providers. Throughout the literature, nursing students, nurse educators, and employers expressed concern over the lack of hands‐on learning and practice readiness that academic clinical time provides new nurses. Provision of additional clinical time and skill repetition, as in an externship program, is reported to increase confidence, reduce anxiety, and promote critical thinking.
Computer Skills And Usage Of Students In Grades 10-12 Who Are Legally Blind: A Descriptive Analysis

This research project was a descriptive analysis of the computer usage and skills of academic students in grades 10-12 who are legally blind and attending public school in the Region 10 Education Service Center service area of Texas. In addition, this study provided a process that other regions in the state or educational agencies may duplicate to document the computer skills and usage of students with visual impairments in their area. Twenty-seven students who are legally blind were surveyed by their teachers of the visually impaired regarding their computer usage and skill abilities, and eleven of the twenty-seven students were interviewed by the researcher to gain further information pertaining to computer usage and future plans upon graduation. Using prior research as a basis for understanding how sighted students used the computer, it was found that students who are legally blind used the computer similarly to their sighted peers except that students with significant visual impairments seemed to use to the computer to listen to music more than their sighted counterparts. In addition, students who are legally blind indicated that they learned most of their computer skills at school rather than at home like their sighted teenagers. Furthermore, it was determined that students who are legally blind were not learning the computer skills necessary for success in post-secondary education and vocational endeavors. Although the students were being exposed to many different computer applications, most did not use the applications weekly, nor report that they were experienced with the majority of basic skills related to applications such as word processing, Internet searching, emailing, spreadsheets and databases.
DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING UPLC METHOD FOR THE ESTIMATION OF R-TELAPREVIR IN DRUG SUBSTANCE AND PHARMACEUTICAL DOSAGE FORM OF TELAPREVIR BY ENHANCED APPROACH

Objective: To develop a novel, simple, precise and stability indicating reverse phase ultra-performance liquid chromatographic (RP-UPLC) method and validate as per ICH guidelines for the quantification of R-Telaprevir in drug substance and pharmaceutical dosage form of Telaprevir. Methods: The chromatographic separation was achieved with Acquity UPLC-BEH C-18 column (100 mm X 2.1 mm, 1.7 μm particle size column with mobile phase containing a gradient mixture of Mobile phase-A and B, flow rate of 0.25 ml/min and a detection wavelength of 210 nm. Mobile phase-A contains a mixture of 10 mm di-Potassium hydrogen phosphate anhydrous, pH adjusted to 11.5 with potassium hydroxide and methanol in the ratio 85:15 (v/v) and the mobile phase-B contains a mixture of Acetonitrile, methanol, 2-propanol and ethanol in the ratio 80:10:7:3 (v/v/v/v) respectively. Chromatographic separation was achieved on UPLC in gradient elution mode by QbD with Design-of-Experiments approach. Results: The method exhibited consistent, high-quality recoveries [100±10%] with a high precision for R - Telaprevir. Linear regression analysis revealed an excellent correlation between peak responses and concentrations (r 2 value of 0.9996) for R - Telaprevir. The method is sensitive enough to quantifyR - Telaprevir above 0.05% and detect above 0.015% in Telaprevir. Forced degradation studies proved that the method is specific for R - Telaprevir. Conclusion: An accurate, precise, linear, robust and specific UPLC method was developed and validated for the quantification of R-Telaprevir in drug substance and pharmaceutical dosage form of Telaprevir as per ICH guidelines. The method is stability-indicating and can be used for routine analysis of production samples and to check the stability of samples.