cssi/SciSciGPT-SciSciNet huggingface dataset:
Horses for courses: reaching outside drug-like chemical space for inhibitors of challenging drug targets

Periodically, advances in understanding factors that influence success in drug discovery become formulated as rules or guidelines; these become broadly accepted for a time, until new knowledge or a sufficient number of exceptions are identified to highlight the missed opportunities that result from overly rigid adherence. We are coming out of one such cycle now, as it becomes recognized that the concept of ‘druglikeness’, which has been highly effective in focusing discovery efforts on compounds with potential for achieving good ‘pharmaceutical properties’ of absorption, distribution, metabolism and excretion (ADME), has at the same time impeded exploration of new pharmacologically useful chemotypes that do not resemble typical known drugs. At the same time, attention is turning increasingly to new classes of drug targets that are less amenable to inhibition by conventional drug-like molecules, such as protein–protein interaction (PPI) interfaces, intrinsically disordered proteins, DNA-binding, carbohydratebinding and some phosphopeptide-binding proteins. This trend has led to growing interest in identifying new chemotypes and drug modalities that possess both an ability to bind to poorly druggable sites and a high potential for good ADME properties. The features that make a target undruggable by conventional drug-like compounds generally include some combination of the following: a binding site, such as many PPI interface sites, that due to its topology (cavities are too small are too large) cannot generate a large area of intimate contact with a drug-like small ligand; a binding site that is exclusively hydrophobic, and thus lacks the ability to engage in charged or polar interactions with the ligand, as are typically required for high affinity and selectivity; a binding site that has evolved to interact with a highly polar or charged ligand, such as a sugar, a nucleic acid polymer, or a phosphopeptide, and thus is too polar for high complementarity with an amphiphilic drug-like ligand; a site that is intrinsically disordered, such that there is potentially a large entropic cost associated with organizing the binding site around a ligand. Several promising approaches have been developed to address highly challenging drug targets such as those described above. These approaches exploit compound chemotypes that differ from typical drugs, and thus require us to move beyond conventional views of druglikeness when evaluating prospects for good ADME properties.
Introducing Medical Students into the Emergency Department: The Impact upon Patient Satisfaction

Introduction: Performance on patient satisfaction surveys is becoming increasingly important for practicing emergency physicians and the introduction of learners into a new clinical environment may impact such scores. This study aimed to quantify the impact of introducing fourth-year medical students on patient satisfaction in two university-affiliated community emergency departments (EDs). Methods: Two community-based EDs in the Indiana University Health (IUH) system began hosting medical students in March 2011 and October 2013, respectively. We analyzed responses from patient satisfaction surveys at each site for seven months before and after the introduction of students. Two components of the survey, “Would you recommend this ED to your friends and family?” and “How would you rate this facility overall?” were selected for analysis, as they represent the primary questions reviewed by the Center for Medicare Services (CMS) as part of valuebased purchasing. We evaluated the percentage of positive responses for adult, pediatric, and all patients combined. Results: Analysis did not reveal a statistically significant difference in the percentage of positive response for the “would you recommend” question at both clinical sites with regards to the adult and pediatric subgroups, as well as the all-patient group. At one of the sites, there was significant improvement in the percentage of positive response to the “overall rating” question following the
Distributed Cooperative Optimization

This chapter studies a class of generic distributed convex optimization problems. In particular, each agent is associated with a private objective function and a private convex constraint set. Meanwhile, all the agents are subject to a pair of global inequality and equality constraints. The key feature of the problem is that all the component functions depend upon a global decision variable. The agents aim to agree upon two global quantities: (1) a global minimizer of the sum of all private objective functions, simultaneously enforcing all the given constraints; (2) the induced optimal value.
Advanced memory management and disk scheduling techniques for general-purpose operating systems

Operating systems have evolved into sophisticated, high-performance virtualizing platforms, to support and be fair towards concurrently running applications. However, since applications usually run oblivious of each other and prefer narrow system interfaces, they inadvertently contend for resources, resulting in inappropriate allocations and significant performance degradations. This dissertation identifies and eliminates two such problems: one we call rigidity in physical memory management which we solve using adaptive memory management, and a second we call deceptive idleness in disk schedulers that we solve through anticipatory disk scheduling . Many applications, their libraries, and runtimes can trade memory consumption for performance by maintaining caches, triggering garbage collection, etc. However, due to ignorance of memory pressure in the system, they are forced to be conservative about memory usage. Adaptive memory management is a technique that informs applications of the severity of memory pressure via a metric that quantifies the cost of using memory. This enables applications to allocate memory liberally when available (with performance benefits of 20% to 300%); and to release it under contention. The system thus reaches an equilibrium that balances the impact of memory pressure on each application; adapts to avoid paging during load bursts and improves stability and responsiveness; and reduces the need for manual configuration of memory footprints. It also provides finer control on memory usage by adapting proportional to application priorities. Disk schedulers generally schedule a request as soon as the previous request has finished. Unfortunately, many applications perform synchronous I/O by issuing a request after the previous request has been served. This causes the scheduler to suffer from deceptive idleness, a condition where it incorrectly assumes that the process has no further requests, and seeks to a request from another process. Anticipatory dish scheduling transparently solves this problem by sometimes injecting a small, controlled delay into the disk scheduler before it makes a scheduling decision, whenever it expects the current request to be quickly followed by another nearby request. This improves performance by up to 70% and enables proportional schedulers to achieve their contracts. Anticipatory scheduling has been ported to Linux, where it is now the default disk scheduler.
Frequent and extensive deletion during the 9,22 translocation in CML

Chromosomal translocation is one mechanism by which cellular oncogenes may be activated during tumorigenesis. The translocation of the abl oncogene to the Philadelphia chromosome in chronic myelogenous leukemia (CML) results in a new RNA transcript that fuses sequence from chromosome 22 to sequence from the abl oncogene. This RNA presumably codes for a new abl-related protein product found in CML, the activity of which is different from the normal abl protein. The molecular structure of the translocation varies from patient to patient, and the individual variation in RNA transcript and protein product remains to be defined. This report describes the frequent occurrence of chromosomal deletion within the 9q+ chromosome during these translocations. The location of the deletions suggests that some mechanism maintains the chromosomal breakpoint on the Philadelphia chromosome within a limited region. These deletions complicate the interpretation of Southern blots as a means of detecting the translocation.
Enhancing the Visibility of Small Unmanned Aerial Vehicles

Abstract The small Unmanned Aerial Vehicle (UAV) 1 has been proposed as an ideal platform for an increasing number of civilian mission roles. However, the small size of this class of UAV, while beneficial for acquisition and operational costs, presents a problem when it comes to their ability to be seen by other aircraft. Unless some means of enhancing visibility is used, the small size creates an essentially invisible entity at normal aviation visual sighting ranges and therefore an increased collision risk. In this paper, a human factors experiment is presented where the visibility of a proposed aircraft lighting system was assessed in realistic night time conditions. These results have been compared against theoretical detection range estimates based on basic photonics and the capabilities of the human vision system, and the minimum sighting distances according to current aviation regulations. Other technologies proposed to improve the detectability of the small UAV are also introduced. The outcome of this research is a proposed minimum set of safety equipment which should make the small UAV at least as safe as equivalent manned aircraft operating in the same airspace.
Juvenile Attitudes Toward the Police: An Examination of Rural Youth

The past three decades have seen an increase in research on the attitudes of juveniles toward the police. This research suggests that juveniles are generally less positive in their attitudes toward the police than are adults. However, most research on juvenile attitudes has focused on youth residing in metropolitan areas, ignoring the role of geographical location in explaining perceptions. Using survey data, the present study examined the attitudes of rural youth toward the police. The findings suggest that although the level of support among rural teenagers did not mirror the levels found within the adult literature, rural teenagers may be more supportive of the police than their metropolitan counterparts. Furthermore, whereas White teenagers were generally more positive in their perception of the police than were Black teenagers, race was not a significant predictor of attitudes toward the police. Still, many of the variables identified as theoretically relevant in the existing literature were signific...
Epigenetics: An elusive DNA base in mammals

The discovery of a modified version of the base adenine, known as N6-methyladenine, in mouse DNA puts paid to the theory that cytosine derivatives are the only modified bases in mammals. See Article p.329 DNA methylation is thought to occur exclusively on the fifth position of cytosine in mammalian cells. These authors identify an additional form of DNA modification — producing N6-methyladenine — in mouse embryonic stem cells. They show that the Alkbh1 gene encodes a demethylase for N6-methyladenine. Deposition of N6-methyladenine is found at subfamilies of young LINE-1 transposons, where it may be involved in epigenetic silencing. N6-methyladenine has previously been found in prokaryotes, algae, nematodes and insects.
Organizational Context as a Moderator of Theories on Firm Boundaries for Technology Sourcing

Three research theories used to explain firm boundaries are transaction cost economics, an options perspective, and a resource-based view of the firm. The authors' integrated model addresses the degree to which each of these three perspectives explains firm boundaries for technology sourcing is contingent on managerial risk taking, which is partly determined by organizational context. The authors' results suggest that, in general, management stockholdings, firm risk orientation, and slack resource availability moderate the extent to which the perceived threat of opportunism, the threat of commercial failure, and opportunity for sustainable advantage all influence firm boundaries.
Genetic Control of Interaction Between Class I and Class II Antigens in Murine Islet Rejection

Successfully implanted islets of Langerhans between two H-2 disparate strains are rejected following injection of cells bearing class I antigens syngeneic to the graft, together with either syngeneic or allogeneic class II antigens. Such rejection does not occur if class II syngeneic to the graft, but class I antigens are not.
155 A PHARMACY-ORIENTED INITIATIVE INCREASES DEEP VENOUS THROMBOSIS PROPHYLAXIS RATES.

Purpose Venous thromboembolism (VTE) is a disease that includes both deep venous thrombosis (DVT) and pulmonary embolism (PE). VTE accounts for more than 250,000 hospitalizations annually in the United States and may be the most common preventable cause of death in hospitalized patients (Kim, 2001). PE is a complication of DVT, and approximately 25 to 30% of untreated patients with proximal DVT will develop symptomatic PE (Geerts, 2004). In hospitalized medical patients, up to 1 in 20 patients will suffer a fatal PE (Baglin, 1997). Based on the infrequent use of thromboprophylaxis, some authors have speculated that physician awareness and recognition of patient risk factors for VTE could be improved. Experimental Design and Methods All patients admitted to the general internal medicine inpatient service over a 12-week period from Sunday 7 am to Friday 7 am were included in the study. Four inpatient medicine teams rotate every 24 hours for admissions. Two teams were designated as “interventional” and two teams as “control.” For the patients admitted to the two teams assigned to the intervention group, electronic medical records were queried by the pharmacy staff the morning after admission and the history and physical examination note identified. The admission history and physical examination note was then used and to determine the patient9s risk for DVT. The medium- to high-risk patients were then pointed out to the physician. The physician was then left to decide whether or not to institute DVT prophylaxis. IfIf pharmacologic prophylaxis was an option, they were left to decide which evidence-based therapy would be administered. TThe primary goal of the study was the appropriate administration of DVT prophylaxis within 30 hours of the patient9s hospital admission. Summary of Results The study is currently in its last stage and has 149 patients in the interventional group and 161 in the control group. Interim analysis of randomly selected subject records showed that appropriate DVT prophylaxis rates in the control group were 8 of 15 or 53% and 13 of 15 or 86% in the interventional group. Conclusions Preliminary data suggest that the pharmacy-driven DVT prophylaxis initiative, as outlined in the study, is an effective and feasible tool for increasing DVT prophylaxis rates among general internal medicine inpatients. This may be an effective tool that can increase compliance with JCAHO standards for an effective DVT prophylaxis inpatient program.
Squamous Cell Carcinoma of the Prostate: Report of 2 Cases and Review of the Literature

AbstractTwo cases of squamous cell carcinoma of the prostate are reported and criteria for diagnosis are suggested. Squamous cancer, which accounts for 0.5 to 1 per cent of prostatic malignancies, differs from the common adenocarcinoma of the prostate in certain clinical features. It also appears to have a worse prognosis and to be unresponsive to the usual therapies for prostatic cancer, perhaps because of a different cell of origin.
Fast Dissolution Dynamic Nuclear Polarization NMR of 13C-Enriched 89Y-DOTA Complex: Experimental and Theoretical Considerations

The yttrium complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(1′-13C-acetic acid) [13C]DOTA was synthesized. Fast dissolution dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) studies revealed that the 89Y, 13C, and 15N nuclei present in the complex could be co-polarized at the same optimum microwave irradiation frequency. The liquid-state spin–lattice relaxation time T1 of these nuclei were found to be reasonably long to preserve some or most of the DNP-enhanced polarization after dissolution. The hyperpolarized 13C and 89Y NMR signals were optimized in different glassing mixtures. The overall results are discussed in light of the thermal mixing model of DNP.
Bounded Awareness: Implications for Ethical Decision Making

In many of the business scandals of the new millennium, the perpetrators were surrounded by people who could have recognized the misbehavior, yet failed to notice it. To explain such inaction, management scholars have been developing the area of behavioral ethics and the more specific topic of bounded ethicality—the systematic and predictable ways in which even good people engage in unethical conduct without their own awareness. In this paper, we review research on both bounded ethicality and bounded awareness, and connect the two areas to highlight the challenges of encouraging managers and leaders to notice and act to stop unethical conduct. We close with directions for future research and suggest that noticing unethical behavior should be considered a critical leadership skill.
Performance-based task assessment of higher-order proficiencies in redesigned STEM high schools

This study explored student abilities in applying conceptual knowledge when presented with structured performance tasks. Specifically, the study gauged proficiency in higher-order applications of students enrolled in earth and environmental science or biology. The student sample was drawn from a Redesigned STEM high school model where a tested performance assessment protocol was employed for the purposes of the investigation. It was determined that performance-based proficiency was not uniform within tasks and applications, but could be recognized through student artifacts of learning on a situational basis. Based on the findings of the study, several implications are highlighted.
Survey of Business Owners: Audio of Presentation

The 2002 Survey of Business Owners is part of the Economic Census, conducted every five years for years ending in "2" and "7." Statistics describe the characteristics of U.S. businesses by ownership category (i.e., by gender, Hispanic or Latino origin, and race of principal owners for both employer and non-employer businesses). Data are presented for detailed industries and geographies, and by size of firm (receipts and employment information).
Extending Parikh’s Theorem to Weighted and Probabilistic Context-Free Grammars

We prove an analog of Parikh’s theorem for weighted context-free grammars over commutative, idempotent semirings, and exhibit a stochastic context-free grammar with behavior that cannot be realized by any stochastic right-linear context-free grammar. Finally, we show that every unary stochastic context-free grammar with polynomially-bounded ambiguity has an equivalent stochastic right-linear context-free grammar.
Tree seedling responses to multiple environmental stresses: Interactive effects of soil warming, nitrogen fertilization, and plant invasion

Abstract Temperate deciduous forest ecosystems in northeastern North America are under increasing biotic and abiotic stresses that can have interactive effects on understory vegetation, and thus impact the next generation of forest canopy trees. We examined seedling responses of the common and increasingly dominant species Acer rubrum (red maple) to the combined effects of soil warming (+5 °C), chronic nitrogen fertilization (+50 kg N ha−1 yr−1), and invasion by the phytotoxic plant Alliaria petiolata (garlic mustard), and their interactions. We planted 296 first-year A. rubrum seedlings in a multifactorial field experiment to examine the effects of all combinations of the experimental treatments. Second-year Acer rubrum seedlings demonstrated higher aboveground growth under soil warming conditions. Further, soil warming positively influenced plant-soil feedbacks through higher arbuscular mycorrhizal colonization in fine roots. However, the positive growth responses and mycorrhizal colonization observed under soil warming were moderated by both N fertilization and A. petiolata invasion. Our results highlight the importance of developing management plans that consider how multiple environmental change factors affect tree seedling performance, particularly via the plant-soil interface.
"Human Resource Slack, Financial Slack and Firm Performance Under Differing Contextual Factors."

The study presented here offers a reconceptualization of how we theoretically view and empirically measure organizational resource slack. Human resource slack is introduced and suggested to serve as a type of slack that offers effects on performance that differ from the more traditional measure of financial resource slack. This study also examines how these two types of resource slack may influence firm performance differently under two contextual factors- strategic change and the economic environment. Using a longitudinal dataset of U.S. commercial and consumer banks over a twelve-year period, the results suggest that while human resource slack is positively associated with firm performance, the effects become more positive for banks seeking to change their strategy as well as during periods of economic growth. Conversely, financial resource slack is found to have a negative relationship with overall firm performance, but less negative for firms seeking to change their strategy, and positive for firms op...
A high-order log barrier-based mesh generation and warping method

Abstract The ability to generate high-order meshes that conform to the boundary of curved geometries is a hurdle in the adoption of high-order computational methods for the numerical solution of partial differential equations. In this paper, we propose a method for generating and warping second-order Lagrange triangular and tetrahedral meshes based on a log barrier method. In the case of generation, the approach consists of modifying an initial linear mesh by first, adding nodes at the midpoint of each edge; second, displacing the newly added boundary midpoints to the curved boundary, and third, solving for the final positions of the interior nodes based on the boundary deformation. By allowing all of the boundary nodes to move, the approach can also be used to warp second-order triangular and tetrahedral meshes. We present several numerical examples in both two and three dimensions which demonstrate the capabilities of our method in generating and warping second-order curvilinear meshes.
If Many Seek, Ye Shall Find: Search Externalities and New Goods

Consumer search serves productive roles in an economy with multiple goods. In equilibrium, search promotes the sorting of consumers among producers, thereby enabling the market for new goods, and potentially increasing welfare and profits above the benchmark case (an economy with a single good, hence, no search). When competitors are few, additional direct competitors may benefit a firm, as more sellers may encourage more consumers to search. In return, consumer search entices producers of new goods to enter. Neither of these externalities, nor the coordination problems faced by consumers and producers, is appropriately recognized in the literature.
Reconciling divergent trends and millennial variations in Holocene temperatures

Cooling during most of the past two millennia has been widely recognized and has been inferred to be the dominant global temperature trend of the past 11,700 years (the Holocene epoch). However, long-term cooling has been difficult to reconcile with global forcing, and climate models consistently simulate long-term warming. The divergence between simulations and reconstructions emerges primarily for northern mid-latitudes, for which pronounced cooling has been inferred from marine and coastal records using multiple approaches. Here we show that temperatures reconstructed from sub-fossil pollen from 642 sites across North America and Europe closely match simulations, and that long-term warming, not cooling, defined the Holocene until around 2,000 years ago. The reconstructions indicate that evidence of long-term cooling was limited to North Atlantic records. Early Holocene temperatures on the continents were more than two degrees Celsius below those of the past two millennia, consistent with the simulated effects of remnant ice sheets in the climate model Community Climate System Model 3 (CCSM3). CCSM3 simulates increases in 'growing degree days'-a measure of the accumulated warmth above five degrees Celsius per year-of more than 300 kelvin days over the Holocene, consistent with inferences from the pollen data. It also simulates a decrease in mean summer temperatures of more than two degrees Celsius, which correlates with reconstructed marine trends and highlights the potential importance of the different subseasonal sensitivities of the records. Despite the differing trends, pollen- and marine-based reconstructions are correlated at millennial-to-centennial scales, probably in response to ice-sheet and meltwater dynamics, and to stochastic dynamics similar to the temperature variations produced by CCSM3. Although our results depend on a single source of palaeoclimatic data (pollen) and a single climate-model simulation, they reinforce the notion that climate models can adequately simulate climates for periods other than the present-day. They also demonstrate that amplified warming in recent decades increased temperatures above the mean of any century during the past 11,000 years.
Preparation of Electrochromic Nickel Oxide Film by Wet Method

Nickel oxide films were prepared onto transparent conducting film on glass substrate by dip-coating technique using a solution of nickel nitrate hexahydrate in an aquo-organic solvent. The formed films showed electrochromic behavior in 1M KOH aqueous solution as electrolytic solution. The difference of solar transmittance between coloring and bleaching state of the films increased with an increasing of the cyclic numbers of coloring and bleaching reactions, whereas it decreased with an increasing of the calcination temperature. The calcination gave also great influence on the other electrochromic behaviors of nickel oxide films.
The Treatment of Risk in Analysis: A Framework for Discussion

A large portion of the cost of a weapon system is incurred after the hardware is delivered. Ownership costs due to operations, maintenance, support equipment, repairs, and spare parts usually exceed the procurement costs of design, development, and production. These ownership costs together with procurement costs comprise the life-cycle cost (LCC) of a system. Clearly, total life-cycle cost of a weapon system must be carefully considered if investments are to be made wisely.
Social factors related to antiretroviral therapy use in injection drug users

This study applied a behavioral model of health services use that included health-related attitudes and indicators of social contact and support to use of antiretroviral therapy (ART) in a cross-sectional survey of 241 disadvantaged, inner-city injection drug users (IDUs). Only 44% of this sample reported taking ART despite relatively high levels of health care utilization; ART nonuse was associated with distrust of physicians (OR = 4.76, 95% CI 1.75–13.5). In a logistic regression model that controlled for severity of HIV disease and access to health care, the belief that HIV medications make the respondent feel healthier (OR = 3.24, 95% CI 1.70–6.15) and increased social isolation since becoming HIV-positive (OR = 2.60, 95% CI 1.38–4.89) were correlated with ART use. These findings underscore the importance of including social and behavioral characteristics in models that attempt to explain ART use by marginalized populations.
Theta lifts and periods with respect to a quadratic extension

In this chapter we summarize a part of the first author’s recent work on the period conjectures of Shimura. Compared with the other chapters, the writing here is more terse. This chapter should more properly be viewed as a guide to the relevant literature, where elaborations on technical aspects can be found.
Bee-pollination in Hibbertia fasciculata (Dilleniaceae)

In direct contrast to mostHibbertia spp., the flowers ofH. fasciculataR. Br. ex D. C. bear only a single whorl of stamens and these stamens are arranged separately (not in typical “bundles”). The short filaments are appressed to the three carpels so that the inflated, porose and introrsive anthers form a centralized cluster obscuring the three ovaries. The three slender styles emerge at right angles from between the filaments. These styles curve upward and the stigmas form the three points of a triangle; each stigma is approximately one millimeter outside the centralized cluster of anthers. The flowers are nectarless and bear a bright yellow corolla. A pungent and unpleasant fragrance appears to be concentrated within the pollenkitt. When native bees attempt to forage for the pollen, within the cluster of anthers, the ventrally deposited loads of pollen, on the bees' abdomens, contact the outer triangle of stigmas. The major pollinators ofH. fasciculata are female bees in the polylectic genera,Lasioglossum (subgenusChilalictus, Halictidae) andLeioproctus (Colletidae). These bees carry an average of more than two pollen taxa when they are caught foraging onH. fasciculata. 78% of the 47 bees, captured onH. fasciculata carried the pollen from at least one sympatric taxon bearing nectariferous flowers (e.g., genera in theMyrtaceae, Compositae, andEpacridaceae). The pollination biology ofH. fasciculata is assessed in relation to the known radiation of bee-pollinated flowers in the genusHibbertia, and within theDilleniaceae s. l.
Herpes Simplex Virus 1 Infection Promotes the Growth of a Subpopulation of Tumor Cells in Three-Dimensional Uveal Melanoma Cultures

Herpes simplex virus 1 (HSV-1)-mediated oncolytic therapy is an emerging cancer treatment modality with potential effectiveness against a variety of malignancies. To better understand the interaction of HSV-1 with neoplastic cells, we inoculated three-dimensional (3D) cultures of human uveal melanoma cells with HSV-1. 3D melanoma cultures were established by placing tumor cells on the surface of a Matrigel matrix, which was followed by the growth of tumor cells on the matrix surface and invasion of the Matrigel matrix by some tumor cells to form multicellular tumor spheroids within the matrix. When established 3D melanoma cultures were inoculated with HSV-1 by placing virus on the surface of cultures, virus infection caused extensive death of melanoma cells growing on the surface of the 3D matrix and significantly decreased the number of tumor cell spheroids within the matrix. However, HSV-1 infection did not lead to a complete destruction of tumor cells in the 3D cultures during a 17-day observation period and, surprisingly, HSV-1 infection promoted the growth of some melanoma cells within the matrix as determined by the significantly increased size of residual viable multicellular tumor spheroids in virus-inoculated 3D cultures at 17 days after virus inoculation. Acyclovir treatment inhibited HSV-1-induced tumor cell killing but did not block the virus infection-induced increase in spheroid size. These findings suggest that although HSV-1 oncolytic virotherapy may cause extensive tumor cell killing, it may also be associated with the unintended promotion of the growth of some tumor cells.IMPORTANCE Cancer cells are exposed to HSV-1 during oncolytic virotherapy with the intention of killing tumor cells. Our observations reported here suggest that potential dangers of HSV-1 oncolytic therapy include promotion of growth of some tumor cells. Furthermore, our findings raise the possibility that HSV-1 infection of neoplastic cells during natural infections or vaccinations may promote the growth of tumors. Our study indicates that HSV-1 infection of 3D tumor cell cultures provides an experimental platform in which mechanisms of HSV-1-mediated promotion of tumor cell growth can be effectively studied.
A review of computational modeling techniques in study and design of shape memory ceramics

Abstract Shape memory ceramics are a unique family of shape memory materials with a wide variety of applications, such as ultra-high energy dissipation and high-temperature actuation. Along with significant progress in the experimental study of zirconia-based shape memory ceramics in recent years, computational simulations have exhibited powerful capabilities in revealing nano/microstructure-dependent deformation and failure mechanisms in these materials. In this work, we review the recent progress in understanding the phase transformation behavior in shape memory ceramics, focusing on computational modeling of zirconia-based ceramics. Electronic structure calculations have provided new data on the phase stability and surface properties of shape memory ceramics. At the nanometer length scale, molecular dynamics simulations have captured fundamental information about martensitic phase transformation and the effects of grain boundaries and defects on mechanical response of bi- and polycrystalline zirconia-based ceramics. At the micrometer length scale, advanced phase-field models have shown the ability to predict morphological evolution of microstructures and the corresponding mechanical responses in good agreement with experimental observations. Despite the recent multiscale computational advancements, further developments are required to establish processing-structure-property-performance relations that will lead to reliable and practical strategies for designing zirconia-based (or other) ceramics with improved and sustained shape memory responses. This article critically reviews current computational modeling techniques and provides an outlook for the study and design of the next generation of shape memory ceramics.
The Responsibilities of White Teacher Candidates and Teacher Educators in Developing Racial Literacy

This article aims to help teacher educators consider how to build racial literacy in their White teacher candidates, providing guidance through pedagogical strategies and approaches based on our an...
High-Throughput, DC-Parametric Evaluation of Flux-Activated-Switch-Based TDM and CDM SQUID Multiplexers

The successful realization and broad deployment of transition edge sensor (TES)-based detector systems has led to significant demand for time-division and code-division superconducting quantum interference device (SQUID) multiplexers time division multiplexing (TDM) and code division multiplexing (CDM) as essential components of the cryogenic readout chain. TDM and CDM circuits are produced by the Boulder Microfabrication Facility in large quantities and in multiple varieties to meet the needs of various bolometric and calorimetric applications. In most cases, the basic functionality of these devices must be verified before they are passed along to internal or external collaborators for integration into scientific instruments. We have developed a test bed that utilizes the NIST TDM/CDM read-out electronics to make automated multiplexed measurements on sixteen devices simultaneously in a 4 K liquid-helium dip probe. The optimization of the measurement process has resulted in vastly improved throughput and enhanced data products. We present a thorough analysis of results from the application of the test process to flux-activated-switch-style multiplexers. The utility of this approach in identifying fabrication trends, yield indicators, and common failure modes will be demonstrated.
Predicting Cardiac Recovery before Durable Left Ventricular Assist Device Implantation in Advanced Heart Failure Patients

Purpose Predicting cardiac recovery (CR) in advanced heart failure (HF) patients before left ventricular assist device (LVAD) implantation remains challenging. This study sought to investigate whether CR after LVAD unloading can be predicted by cardiac functional and structural parameters together with clinical characteristics. Methods From 2008 to 2016, consecutive advanced chronic HF patients (N=347) supported with durable continuous-flow LVADs were prospectively evaluated. Patients with acute HF etiologies or without adequate post-LVAD follow up ( Results CR occurred in 13.7% of patients. Univariate analysis showed that responders were more likely to be young, female, non-ischemic cardiomyopathy, with shorter HF symptoms duration and no prior heart surgery. They had lower blood urea nitrogen and were less likely to be on temporary mechanical support before LVAD. The multivariable UCAR model (AUC=0.755; p Conclusion Univariate and multivariable predictors of CR include both modifiable and non-modifiable patient characteristics that are known prior to LVAD implantation. The UCAR score can serve as a practical tool for targeted patient selection to implement protocols that facilitate CR in the advanced HF patient subpopulation that is most likely to respond.
The association between high-normal blood pressure and the development of preeclampsia in twin pregnancies.

Objective: We sought to determine if women with twin pregnancies and blood pressure (BP) above the 95th percentile but within normal ranges (i.e. less than 140 systolic and 90 diastolic) are at inc...
mTOR Inhibitor in Combination with Cyclosporine as Primary Maintenance Immunosuppression in Combined Kidney/Pancreas Transplant Recipients

We report our experience employing a steroid-free, mammalian target of rapamycin (mTOR) inhibitor–based immunosuppression regimen in pancreas transplantation and review literature germane to the use of this regimen. In our experience, using mTOR inhibitor–based, steroid-free immunosuppression with low-dose cyclosporine and anti-thymocyte globulin (ATG) induction in 309 combined kidney/pancreas transplants resulted in one-year patient survival and death censored graft survivals of 95.8%, 93.5% (pancreas), and 96.1% (kidney). The biopsy-proven acute rejection incidence was 15.2% at 1 year. De novo donor-specific antibodies developed in 9.4% at last follow-up. Little data currently exists reporting steroid-free, mTOR-based immunosuppression in pancreas transplant recipients. Excellent results have been reported in a small cohort of 25 recipients in Germany. Thus, data used in kidney transplant recipients must be extrapolated to pancreas transplantation. There are some data, including our own, that indicate there are good outcomes with this immunosuppression regimen in combined kidney and pancreas recipients. Data suggest that avoidance of steroids and minimizing CNI exposure are desirable attributes to pancreas transplant immunosuppression to optimize post-transplant pancreas function.
Fast Method for First-Principles-Based Parasitic Extraction of Integrated Circuit Layout

In this paper, we develop an accurate yet fast method to perform parasitic extraction of integrated circuit layout. Starting from coupled full-wave Maxwell’s equations, we decompose the layout response rigorously into R-, C-, L- and full-wave components. We show how to obtain the RC-component based on first principles, which captures complicated 3-D and distributed effects that cannot be captured by prevailing heuristic RC-extraction. Fast algorithms are also developed to efficiently obtain the layout model. Numerical results and comparisons with measurements have validated the proposed method for layout extraction.
Single port robotic surgery: my way or highway?

Urologic surgery as a field has always been obsessed with advancement. In fact, new development is imperative in our field, without it, we would still be performing maximally invasive open surgery for several indications which now can be accomplished with minimally invasive way. Robotic assisted surgery is one of the technological developments after endourology and ESWL which has impacted our field tremendously. Robotic surgery has revolutionized the field of Urology over the past 20 years.
Obstetric Emergency Critical Care

Management of critical illness in pregnancy can be intellectually challenging, emotionally devastating, and uniquely rewarding for the practitioner of adult emergency and critical care. Serious illness in pregnancy is rare; so, reliance on well-oiled patterns of recognition and management is often not possible. Yet, many pregnant women are resilient and can recover from critical illness without sequelae. The care these women receive may make an enormous difference in outcome. In this chapter, we cover the important aspects of the initial diagnosis and management of the most common critical illnesses that affect pregnant and peripartum patients in the United States. These include disease processes unique to the obstetric population; illnesses that are not limited to pregnancy but may strike with greater severity; and non-obstetric diseases for which there may be uncertainty about management because of the pregnancy, including cardiac arrest. In addition, we have provided tips on relevant pharmacology and diagnostic imaging in the pregnant patient.
Targeting energy pathways in kidney disease: the roles of sirtuins, AMPK, and PGC1α.

The kidney has extraordinary metabolic demands to sustain the active transport of solutes that is critical to renal filtration and clearance. Mitochondrial health is vital to meet those demands and maintain renal fitness. Decades of studies have linked poor mitochondrial health to kidney disease. Key regulators of mitochondrial health—adenosine monophosphate kinase, sirtuins, and peroxisome proliferator-activated receptor γ coactivator-1α—have all been shown to play significant roles in renal resilience against disease. This review will summarize the latest research into the activities of those regulators and evaluate the roles and therapeutic potential of targeting those regulators in acute kidney injury, glomerular kidney disease, and renal fibrosis.
Array Shading to Maximize Deflection Coefficient for Broadband Signal Detection With Conventional Beamforming

This paper develops and applies a numerical optimization procedure to compute broadband noise-adaptive weights for delay and sum beamforming that are conditioned to maximize the deflection coefficient at the output of a square law detector for a given set of underwater pressure measurements. The resulting optimal weights mitigate the effects of noise and interferers and maximize signal detection. Comparison of the optimal weights with minimum variance distortionless response weights show that the presented algorithm provides higher attenuation of interferers. We also use the noise-adaptive algorithm to find the optimal sparse array geometry for a given number of sensors and aperture. Comparison of the resulting optimal array with coprime, nested, and semi-coprime arrays shows that the proposed sparse array suppresses interferers more than the other sparse arrays.
Using Biotin to Demonstrate Western and Dot Blotting in University Practical Classes: A Guide to Instructors

This chapter details a foolproof technique described by Millar et al. to quickly and economically show immunological detection of proteins to undergraduate biology students using biotinylated proteins or biotin itself as targets for detection. Such an approach avoids the requirement for a particular primary antibody and thus saves money and time. Also, one does not need special technical know-how to carry out these methods owing to the easy availability of safe reagents. Consequently, school staff can confidently assign Western blotting to the student that will also help develop scientific inquiry skills and promote student inspiration and engagement.
Foreign aid policy and its growth effect in Nepal

Donors are perplexed, as aid has been unable to reinforce growth in many underdeveloped countries. In this paper, specific attention has been diverted towards various issues pertinent to the aid-growth relationship; in particular, we discuss Nepal due to its uniqueness. A general conclusion is that donors should conduct more research to country-specific problems and attributes, such as the sociocultural factors before they disburse any kind of aid. In case of Nepal, the country would be better off if the donors assume exclusive control over the project and work directly with the local bodies, NGOs or other consulting companies, rather than the government.
Judging judges: How do children weigh the importance of capability and objectivity for being a good decision maker?

Two studies examined developmental differences in how children weigh capability and objectivity when evaluating potential judges. In Study 1, 84 6- to 12-year-olds and adults were told stories about pairs of judges that varied in capability (i.e., perceptual capacity) and objectivity (i.e., the relationship to a contestant) and were asked to predict which judge would be more accurate. Participants generally preferred capable over incapable judges. Additionally, 10- and 12-year-olds adjusted their preferences for the most capable judgebasedonobjectivityinformation.Seventy6-and8-year-oldsparticipatedinStudy2, which was similar to Study 1 except that the judges could both seem incapable unless children understood how different decisions require different kinds of perceptual capabilities. While 8-year-olds chose judges based on the relevance of the perceptual capability, 6-year-olds struggled, seeming to be distracted by the valence of the judges’ relationships to the contestants. Overall, these results support that there are important shifts in how children evaluate decision makers from early to middle childhood.
Introduction to the Economics, Markets and Policy Minitrack, Electric Energy Minitrack

Public concerns about the adverse environmental and health effects of using fossil fuels and nuclear power to generate electricity have led to a greater reliance on renewable sources of generation that are inherently variable and uncertain. This trend is accompanied by increased proliferation of distributed resources, storage and smart grid technologies that facilitate demand response and greater observability of the grid. As a result the electric power industry faces new challenges in planning and operation of the power system that require new market mechanisms and computational optimization tools to achieve productive and allocative efficiencies. A key concept in addressing the new challenges associated with renewables integration and in mobilizing a diverse resource portfolio to mitigate the uncertainty and variability of these intermittent resources is flexibility. Hence the central theme of this mini track revolves around defining metrics for flexibility, characterizing market products and public policies that incentivizes flexibility and optimizing resource use to meet flexibility needs so as to assure system reliability in face of uncertainty at least cost.
Evidence for a Widespread Brain Stem Escape Network in Larval Zebrafish

Zebrafish escape behaviors, which typically consist of a C bend, a counter-turn, and a bout of rapid swimming, are initiated by firing of the Mauthner cell and two segmental homologs. However, afte...