cssi/SciSciGPT-SciSciNet huggingface dataset:
Design of high-yield defect-tolerant self-assembled nanoscale memories

Self-assembled nanoscale memories experience a high degree of hard defects compared to microscale memories. These defects degrade the yield and, along with operational faults, degrade the mean time to failure (MTTF). The common way to tolerate these defects is to reconfigure the defective elements with spares. Hence, the amount of spares is very important and a systematic yield-driven design approach to decide the amount and the allocation of these spares is essential. In this paper, we develop such a design method. We formulate a probabilistic model for the reliability of a memory considering an unclustered defect distribution with error correcting code and reconfiguration using spares local to the lowest hierarchical sub-unit. Using this model, we estimate the yield and MTTF of the memory and develop a method to design the memory for high yield.
Calculation of the Transient Plane-Wave Reflection From an $N$ -Layer Medium by the Method of Subregions

The transient reflected-field response of an arbitrarily incident plane wave from planarly-layered, dispersive materials is investigated. The reflection coefficient for the layered media is first determined in the frequency domain as a ratio of functions and a series solution is derived. Each partial sum of this series represents the reflection coefficient for a layered material consisting of a subregion of the problem of interest. It is shown that the transient reflected field may be written as a sequence of events, each of which is the late-time response of a subregion. This result can be used in time-domain methods to determine the properties of layered materials.
Functional Characterization of the Octenol Receptor Neuron on the Maxillary Palps of the Yellow Fever Mosquito, Aedes aegypti

Background: 1-Octen-3-ol (octenol) is a common attractant released by vertebrates which in combination with carbon dioxide (CO2) attracts hematophagous arthropods including mosquitoes. A receptor neuron contained within basiconic sensilla on the maxillary palps of adult mosquitoes responds selectively to 1-octen-3-ol. Recently, an odorant receptor (AaegOR8) known to occur on the maxillary palps was expressed in a heterologous system and demonstrated to be selectively sensitive to (R)-(2)-1-octen-3-ol, one of two enantiomeric forms. Lesser responses were elicited by stimulation with the (S)-enantiomer and various structural analogs. Methodology/Principal Findings: Here we characterize the specificity of the octenol receptor neuron in the yellow fever mosquito, Aedes aegypti (L.), in vivo using single cell recordings. The octenol neuron is exquisitely sensitive to (R)-(2)-1octen-3-ol; comparable responses to (S)-(+)-1-octen-3-ol were elicited only at stimulus doses over 1006that required for the (R)-enantiomer. An intermediate response closer to that elicited by the (R)-(2)-enantiomer was elicited by racemic 1-octen3-ol. Small structural changes in (R)-(2)-1-octen-3-ol resulted in large decreases in responses. Increases in spike activity were also elicited in the octenol neuron by 2-undecanone, a known repellent; other repellents (DEET, IR3535 and picaridin) were inactive. Conclusions/Significance: The results of our electrophysiological studies of the octenol receptor neuron in vivo approximates results of a previous study of the octenol receptor (AaegOR8 with its obligate partner Aaeg\ORco) expressed heterologously in Xenopus oocytes. By comparison of our current results with those of the heterologous expression study, we conclude that specificity of the octenol receptor neuron can be explained largely by characteristics of the OR alone without other associated proteins present in vivo. Our findings show that repellents may have specific stimulatory effects on receptor neurons and support the notion of repellents as modulators of mosquito odorant receptor activity.
South Asia as a Geographic Crossroad: Patterns and Predictions of Hominin Morphology in Pleistocene India

Current models of Asian Pleistocene hominin evolution are based on finds that represent a small portion of the geographic expanse of that continent. This is due to the sparse nature of the fossil record as well as varying traditions of paleoanthropological inquiry in these countries. As a result, models of hominin evolution that have emerged for Asia as a whole are not necessarily appropriate characterizations for individual regional populations. The Indian subcontinent in particular is expected to be distinct from China and Indonesia, based in part on genetic studies that suggest this was one of the first regions to be occupied by dispersing African populations. This study evaluates patterns of hominin morphology through a morphometric comparative analysis of the Hathnora specimen found along the Narmada River, and the only fairly complete Pleistocene fossil from South Asia. This fossil is compared to a sample of Old World Pleistocene specimens as well as Early Holocene South Asians and Andaman Islanders to elucidate patterns of variation both across space and through time. The results indicate that the Narmada hominin from Hathnora exhibits a mix of Southeast Asian and sub-Saharan African features. These results are consistent with India’s location between these two regions. A unique evolutionary model for Pleistocene Homo in India is proposed, incorporating the fact that this region was at a geographic crossroads, and predicting that the morphology found there will not conform to patterns found in other parts of Asia. Rather, morphological evolutionary trajectories for Pleistocene South Asian hominins are expected to reflect a blend of African and Asian traits.
Normal Ordered Products and Parafields in Conformal QFT2

Firstly, an improved normal ordered product is defined, which allows to write down concisely the derivative terms in operator product expansions. Secondly, it is shown that representations of chiral algebras always allow the construction of relatively local interpolating fields (parafields). If the grading of the representation is integral or half-integral, these fields become local.
Prediction variance properties of bridge designs

Bridge designs are compromise designs between D-optimal designs and Latin hypercube designs. Bridge designs are a good choice of experiments for computer simulation models with only small variance in the output response. This can occur in a wide range of computer experiments because variance reduction techniques are widely used in these studies. We expect that people will use results from bridge designs to fitting low order polynomial regression models. Bridge designs do not contain replicates, either in the original design or in projection, so they are also potentially good choices for other modelling strategies such as Gaussian process models. We compare bridge designs to D-optimal, I-optimal and Latin hypercube designs in terms of their theoretical prediction variance for experiments with 2-5 factors and polynomial models of order 2-5. The empirical results are also provided using test functions for Gaussian process models. We find that bridge designs are good choices for computer experiments when the underlying model is hypothesised to be a second or third-order polynomial, or a fourth-order polynomial of up to four factors. They also perform well in fitting Gaussian process models.
Metrics for evaluating patient navigation during cancer diagnosis and treatment: crafting a policy-relevant research agenda for patient navigation in cancer care.

BACKGROUND: Racial and ethnic minorities as well as other vulnerable populations experience disparate cancer-related health outcomes. Patient navigation is an emerging health care delivery innovation that offers promise in improving quality of cancer care delivery to these patients who experience unique health-access barriers. Metrics are needed to evaluate whether patient navigation can improve quality of care delivery, health outcomes, and overall value in health care during diagnosis and treatment of cancer. METHODS: Information regarding the current state of the science examining patient navigation interventions was gathered via search of the published scientific literature. A focus group of providers, patient navigators, and health-policy experts was convened as part of the Patient Navigation Leadership Summit sponsored by the American Cancer Society. Key metrics were identified for assessing the efficacy of patient navigation in cancer diagnosis and treatment. RESULTS: Patient navigation data exist for all stages of cancer care; however, the literature is more robust for its implementation during prevention, screening, and early diagnostic workup of cancer. Relatively fewer data are reported for outcomes and efficacy of patient navigation during cancer treatment. Metrics are proposed for a policy-relevant research agenda to evaluate the efficacy of patient navigation in cancer diagnosis and treatment. CONCLUSIONS: Patient navigation is understudied with respect to its use in cancer diagnosis and treatment. Core metrics are defined to evaluate its efficacy in improving outcomes and mitigating health-access barriers. Cancer 2011;117(15 suppl):3563–572. © 2011 American Cancer Society.
Jonas Silicone-silver Penile Prosthesis: Initial Experience in America

A new noninflatable silicone penile prosthesis incorporating a central core of braided silver (Jonas) has been implanted in 29 patients to date. Organic impotence was diagnosed in 24 patients (82 per cent). The complication rate in this initial experience has been approximately 10 per cent. Based on a questionnaire returned by 19 patients (66 per cent) the patient/partner satisfaction was uniformly high. Self-image was reported as improved in 67 per cent. Our initial experience indicates that this prosthesis provides surgical simplicity, superior cosmetic results and an acceptable complication rate compared to other available penile prostheses.
TU-FG-204-05: Diagnostic Imaging: Surveyor Education, Survey Experience, and Trends

The role of a medical physicist involved with clinical CT activities is changing rapidly. No longer is the physicist responsible for simply ensuring scanner QA. This shift is evident by looking at the trend to regulate more and more aspects of what activities must be performed to keep a CT practice within compliance. In this symposium, new guidelines from the ACR, Joint Commission, and several states will be addressed. An overview of these regulations will be provided. Then, three speakers will provide an in-depth account of how their CT protocol Optimization team functions. Lastly, a representative from the Joint Commission will provide recent surveyor education, experience, and trend information. Learning Objectives: 1.Understand the ACR, Joint Commission, and aspects of several state regulations/guidelines related to the clinical practice of CT. 2.Learn how a CT protocol optimization is organized and what tasks physicists perform from the perspective of four different institutions. T. Szczykutowicz, TPS provides CT protocols to GE Healthcare under a license agreement. TPS receives grant support from GE Healthcare.
Universality in Magnetic Field Dependencies of Critical Current for Ag-Sheathed Bi-2223 Superconducting tapes

Certain characteristics in magnetic field dependencies of critical current densities (J c) for the Ag-sheathed Bi-2223 superconducting tape have been found. One property regards the direction of the magnetic field applied to the tape. Both J c values in the field, applied parallel and perpendicular to the tape surface, are on an identical curve when the magnitude of field (B), applied parallel to the tape surface, is multiplied by a characteristic coefficient, which relates to the grain alignment of each tape. Another concerns the relationship between the J c and the magnitude of field. The J c is expressed by a simple logarithmic function of B (Log(B)) from a very low field to a high field. This relation is applicable within a wide temperature range.
Identification of Differentially Expressed and Spliced Genes with RNA Sequencing Analysis of CLL Specimens

Abstract Abstract 4582 High throughput sequencing of cellular mRNA provides a comprehensive analysis of the transcriptome. Besides identifying differentially expressed genes in different cell types, it also provides information of mRNA isoforms and splicing alterations. We have analyzed two CLL specimens and a normal peripheral blood B cells mRNA by this approach and performed data analysis to identify differentially expressed and spliced genes. The result showed CLLs specimens express approximately 40% more transcripts compared to normal B cells. The FPKM data (fragment per kilobase of exon per million) revealed a higher transcript expression on chromosome 12 in CLL#1 indicating the presence of trisomy 12, which was confirmed by fluorescent in-situ hybridization assay. With a two-fold change in FPKM as a cutoff and a p value cutoff of 0.05 as compared to the normal B cell control, 415 genes and 174 genes in CLL#1 and 676 and 235 genes in CLL#2 were up and downregulated or differentially expressed. In these two CLL specimens, 45% to 75% of differentially expressed genes are common to both the CLL specimens indicating that genetically disparate CLL specimens have a high percentage of a core set of genes that are potentially important for CLL biology. Selected differentially expressed genes with increased expression (selectin P ligand, SELPLG, and adhesion molecule interacts with CXADR antigen 1, AMICA) and decreased (Fos, Jun, CD69 and Rhob) expression based on the FPKM from RNA-sequencing data were also analyzed in additional CLL specimens by real time PCR analysis. The expression data from RNA-seq closely matches the fold-change in expression as measured by RT-PCR analysis and confirms the validity of the RNA-seq analysis. Interestingly, Fos was identified as one of the most downregulated gene in CLL. Using the Cufflinks and Cuffdiff software, the splicing patterns of genes in CLL specimens and normal B cells were analyzed. Approximately, 1100 to 1250 genes in the two CLL specimens were significantly differentially spliced as compared to normal B cells. In this analysis as well, there is a core set of 800 common genes which are differentially spliced in the two CLL specimens. The RNA-sequencing analysis accurately identifies differentially expressed novel genes and splicing variations that will help us understand the biology of CLL. Disclosures: No relevant conflicts of interest to declare.
Interactive Computation for Undergraduates: The Next Generation

A generation ago (29 years ago), Leo Kadanoff and Michael Vinson created the Computers, Chaos, and Physics course. A major pedagogical thrust of this course was to help students form and test hypotheses via computer simulation of small problems in physics. Recently, this aspect of the 1987 course has been revived for use with first year physics undergraduate students at St. Olaf College.
A Sixteenth-Century Arabic Critique of Ptolemaic Astronomy: The Work of Shams Al-Din Al-Khafri:

Apercu de la contribution de Shams Al-Din Al-Khafri a l'elaboration de modeles geometriques du mouvement des planetes et de son analyse critique de l'oeuvre astronomique de Ptolemee
Effects of Sulfuric Acid on Durability Characteristics of CFRP Composite Sheets

AbstractThis paper presents the chemical, physical, and mechanical characteristics of carbon fiber–reinforced polymer (CFRP) composite sheets subjected to sulfuric acid (H2SO4). Test coupons are su...
Voltage impact analyses of solar photovoltaics on distribution load tap changer operations

Recently, the penetration of solar photovoltaic (PV) systems in Low Voltage (LV) distribution feeders has significantly increased and is expected to increase further in the coming years. Variability in solar PV output and high R/X ratio of LV distribution feeder results in voltage fluctuations. Local distribution companies (LDCs) rely on load tap changing transformers or feeder voltage regulators to mitigate voltage fluctuations. The objective of this paper is to examine the operational impact of increase in solar PV penetration on LV distribution networks through quasi-static time series analysis. IEEE 13-node test feeder is used in this paper as a test system. Simulations are carried out for a one-year period with 1-minute time step using OpenDSS. Results show significant increase in the total number of tap operations as solar PV penetration increases. Impact on nodal voltages and feeder net power is also discussed in detail. Finally, this paper suggests various mitigation strategies that can be used by LDCs to overcome this issue.
Neighbor risk reporting in vehicular networks

With the issuance of the Notice of Proposed Rule Making (NPRM) for Vehicle to Vehicle (V2V) communications by the United States National Highway Traffic Safety Administration (NHTSA), the goal of the widespread deployment of vehicular communications and networking has taken a significant step towards becoming a reality. As with most connected technologies, protection of privacy is an ongoing concern. In order for consumers to accept the technology, it is expected that reasonable mechanisms will be in place to protect their privacy. Cooperative Caching has been proposed as an approach that can be used to improve privacy by distributing and caching data items throughout the mobile network as they are requested. When a device requires a data item, it will first query other devices for the data item before querying a centralized server. The privacy improvement is achieved by alleviating the need to send all requests to a centralized location that may be vulnerable to an attack. However, with this approach, the requesting device exposes itself to one or more generally unknown devices in the network as part of the data discovery process. This presents another privacy concern in the sense that these devices may expose information related to the request. In this paper we present a novel Cooperative Caching system in support of non-safety based applications (such as the many location based services) in which devices monitor the relative risk associated with each of its neighbors. Based on this information, requesting devices select and query specific neighbors that present little risk while avoiding neighbors that might present higher risk. We have conducted a preliminary performance evaluation of our approach that demonstrates a significant reduction in the overall risk of exposure when compared with simply broadcasting the request to all neighbors.
Effects of resistance training on MRI-derived epicardial fat volume and arterial stiffness in women with obesity: a randomized pilot study.

To date, few studies have analyzed the effects of exercise on cardiac adipose tissue. Overall, exercise programs did not meet the recommendations for significant weight loss, the utilization of resistance training was minimal, and the conclusions derived from these studies have diminished exercise as a strategy for cardiac fat loss. The objective of this pilot study was to analyze the effects of 3-week high-intensity, moderate-volume muscular endurance resistance training (RT) on cardiac fat and arterial stiffness. A total of 11 young females with obesity, BMI = 34.13 (± 3.16) kg/m2 (n = 5 control, n = 6 intervention) completed the study. Absolute strength was assessed using one repetition maximum test (1RM) for bench press (BP) and leg press (LP), and relative strength was calculated using body weight (BW) as BP-to-BW and LP-to-BW ratio. Magnetic resonance was used to quantify epicardial and paracardial adipose tissue (EAT and PAT) volume, and applanation tonometry was used to assess arterial stiffness by estimating pulse wave velocity (PWV). EAT and PAT volumes (ml) showed significant interaction effects (p = 0.037 and p = 0.031), and very large changes (d > 1) of EAT (p = 0.006) and PAT (p = 0.036) in the intervention group. In addition, strength was significantly improved, including BP (p = 0.003), LP (p = 0.001), BP-to-BW ratio (p = 0.001), and LP-to-BW ratio (p = 0.002), while no changes were found in PWV. High-intensity, moderate-volume RT, designed to enhance muscular endurance following the recommendations reduces EAT and PAT volumes, improves physical fitness in females with obesity, and has no negative effects on arterial stiffness.
The Global Integrated Circuit Supply Chain Flow and the Hardware Trojan Attack

The complexity of modern designs, the significant cost of research and development, and the shrinking time-to-market window heavily enforce the horizontal integrated circuit design flow. Many entities across the globe might be involved in the flow and none are necessarily trusted. A malicious party can implement a hardware Trojan attack through manipulating a circuit to undermine its characteristics under rare circumstances at different stages of the flow before and after circuit manufacturing. Detection of hardware Trojans using existing pre-silicon and post-silicon verification techniques is a very challenging task because of the complexity of modern designs, their verity of application, and limited time for verification. This chapter provides an overview on the global supply chain for integrated circuits and the hardware Trojan attack.
Neuroendocrine Differentiation in Prostate Cancer: Emerging Biology, Models, and Therapies

Although a de novo clinical presentation of small cell neuroendocrine carcinoma of the prostate is rare, a subset of patients previously diagnosed with prostate adenocarcinoma may develop neuroendocrine features in later stages of castration-resistant prostate cancer (CRPC) progression as a result of treatment resistance. Despite sharing clinical, histologic, and some molecular features with other neuroendocrine carcinomas, including small cell lung cancer, castration-resistant neuroendocrine prostate cancer (CRPC-NE) is clonally derived from prostate adenocarcinoma. CRPC-NE therefore retains early prostate cancer genomic alterations and acquires new molecular changes making them resistant to traditional CRPC therapies. This review focuses on recent advances in our understanding of CRPC-NE biology, the transdifferentiation/plasticity process, and development and characterization of relevant CRPC-NE preclinical models.
Perceived Benefits of Using Complementary and Alternative Medicine by Race/Ethnicity Among Midlife and Older Adults in the United States:

Objective: To describe, for a national sample of midlife and older adults, the types of complementary and alternative medicine (CAM) used for health and wellness and the perceived benefits of CAM use by race/ethnicity. Method: Using data from the 2012 National Health Interview Survey, we ran multiple logistic regression models to estimate the odds of each perceived benefit among adults ages 50 and older. Results: More than 38% of midlife and older adults used CAM in the past year. For six of seven perceived benefits examined, we found significant differences by race/ethnicity, with each group having higher odds of two or more perceived benefits compared with non-Hispanic Whites. Discussion: Although racial/ethnic minority groups are less likely to use CAM compared with non-Hispanic Whites, those who use CAM perceive great benefit. Future research should examine the potential contribution of evidence-based CAM to promoting health and well-being in a diverse aging population.
An Ecological Theory of Sexual Dimorphism in Animals

Both male ornamentation and male combat result in increased male mortality. Because population sizes are limited by a carrying capacity, increased age-specific adult male mortality will result in decreased age-specific adult female mortality, as well as decreased juvenile mortality. As intersexual competition is one form of intraspecific competition, through choosing to mate with ornamented and/or combative males, females in polygamous systems reduce intraspecific competition. Because average male fitness must exactly equal average female fitness, male fitness will paradoxically rise with increasing male mortality. This theory also offers new perspectives on peripheral problems to sexual theory, such as mate location, resource guarding, leks, harems, and others.
Spotlight on fevipiprant and its potential in the treatment of asthma: evidence to date

Asthma is a heterogeneous disease, which may be classified into phenotypes and endotypes based on clinical characteristics and molecular mechanisms. The best described endotype of severe asthma is type 2 (T2)-high asthma, characterized by release of inflammatory cytokines by T helper 2 (TH2) cells and type 2 innate lymphoid cells cells. Prostaglandin D2 contributes to T2 inflammation through binding of the G-protein-coupled receptor chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2). Fevipiprant is an oral competitive antagonist of CRTH2. Early-phase trials have demonstrated safety and potential efficacy in patients with asthma, specifically, improvement in FEV1 and eosinophilic airway inflammation. However, no clear biomarker identified patients who responded favorably to fevipiprant, although patients with moderate-to-severe asthma and evidence of T2 inflammation may be more likely to respond to treatment. Additional studies are needed to determine the efficacy and target population for use of this drug in patients with asthma.
Scaffolding kidney organoids on silk

End stage kidney disease affects hundreds of thousands of patients in the United States. The therapy of choice is kidney replacement, but availability of organs is limited, and alternative sources of tissue are needed. Generation of new kidney tissue in the laboratory has been made possible through pluripotent cell reprogramming and directed differentiation. In current procedures, aggregates of cells known as organoids are grown either submerged or at the air-liquid interface. These studies have demonstrated that kidney tissue can be generated from pluripotent stem cells, but they also identify limitations. The first is that perfusion of cell aggregates is limited, restricting the size to which they can be grown. The second is that aggregates lack the structural integrity required for convenient engraftment and suturing or adhesion to regions of kidney injury. In this study, we evaluated the capacity of silk to serve as a support for the growth and differentiation of kidney tissue from primary cells and from human induced pluripotent stem cells. We find that cells can differentiate to epithelia characteristic of the developing kidney on this material and that these structures are maintained following engraftment under the capsule of the adult kidney. Blood vessel investment can be promoted by the addition of vascular endothelial growth factor to the scaffold, but the proliferation of stromal cells within the graft presents a challenge, which will require some readjustment of cell growth and differentiation conditions. In summary, we find that silk can be used to support growth of stem cell derived kidney tissue.
Conditions for global stability of two linearly interconnected nonlinear systems

Abstract : Simple and easy to use conditions are developed which guarantee global stability of two linearly interconnected nonlinear systems. The conditions consist of scalar frequency response conditions of Popov type on the linear dynamical subsystems and inequalities involving the sector bounds and parameters in the problem; the inequalities have a simple graphical interpretation in terms of the product of the interconnection coefficients. Examples with particular numerical values are presented to illustrate application of the results.
Pricing Errors as Positive Alpha

We consider a simple equilibrium model of active fund managers and consumers. Our model features zero net-of-fee alpha in equilibrium. However, using a common, but misspecified, model for the stochastic discount factor (SDF) implies positive measured alpha. This note, thus, warns against interpreting pricing errors as alpha: That is only true if the SDF is correctly specified. Our model is tractable enough to provide closed form solutions for all quantities of interest.
The Controversial Role of Corticosteroids in Septic Shock.

Abstract Background Several clinical trials and literature reviews have been conducted to evaluate the impact of corticosteroids on the physiological markers and clinical outcomes of patients in septic shock. While the findings have been somewhat contradictory, there is evidence of moderate benefit from the administration of low-dose corticosteroids to patients in septic shock. In this review, we discuss recent studies evaluating the impact of corticosteroids on morbidity and mortality in septic shock and explore future directions to fully elucidate when and how the administration of corticosteroid therapies can be beneficial. Methods A literature review was performed using the Mesh database of PubMed with the term “septic shock” and subheadings “therapeutic use”, “drug therapy”, “pharmacology”, and “therapy” followed by the addition of “steroid”. Filters were added to restrict the search to 18+ age, English and human studies, and articles published within the last 10 years. One hundred sixty-five articles were examined and twenty-five were deemed relevant to this review. Results The twenty-five articles reviewed here provide conflicting evidence as to the usefulness of corticosteroid treatments during septic shock. Several showed improved physiological outcomes, including rates of organ failure, need for life supporting interventions, adverse effects, inflammatory markers, and perfusion during the course of septic shock, as well as decreased mortality for a statistically significant number of patients. Conclusions There remains a need for improved therapy for patients in septic shock. Corticosteroids have shown some potential in improving mortality rates and clinical markers. Additional studies are needed to determine the optimal role of corticosteroids in septic shock.
Abstract 1327: UM-9107: A selective wild-type and T315I Bcr-Abl inhibitor with in vivo activity against chronic myelogenous leukemia

Purpose: Long-term treatment of chronic myelogenous leukemia (CML) with the Bcr-Abl inhibitor imatinib, is initially successful but gives rise to several drug-resistant mutations. The most prevalent of these is the T315I ‘gatekeeper’ mutation that is sensitive to the second-line therapy, ponatinib. However, ponatinib causes serious vascular adverse events, including fatalities, in over 25% of patients, in part due to its target promiscuity. We have designed a novel Bcr-Abl inhibitor (UM-9107) that shows significant in vitro and in vivo anti-CML activity against wild-type and drug-resistant mutants, including the gatekeeper mutant. Furthermore, UM-9107 has excellent selectivity across the kinome and in vitro surrogate toxicity assessment models demonstrate a low likelihood of vascular adverse events as compared to ponatinib. Experimental Design: We designed a series of compounds to specifically interact with a specific kinked conformation of the phosphate-binding loop of Abl. Since only a small proportion of kinases display this kinked conformation, we hypothesized that our compounds would be selective for Abl. We have analyzed the compound series biochemically and in vitro. The most potent compound, UM-9107, has been comprehensively characterized including: biochemical inhibition, cellular target engagement, kinome-wide profiling, in vitro cell proliferation, pharmacokinetic studies, and in vivo activity in xenograft models of CML. Results: We demonstrate that UM-9107 potently inhibits all clinical mutants of Bcr-Abl, including the T315I gatekeeper mutant. UM-9107 shows robust activity against CML cell lines, comparable to ponatinib, with significantly fewer off-targets, as determined by kinome-wide profiling. Phenotypic profiling of UM-9107 in human primary cells shows low risk of vascular adverse events as indicated by specific biomarker readouts. UM-9107 demonstrates good oral bioavailability and in vivo activity in xenograft models of CML, with low toxicity. Conclusions: The success of imatinib has been revolutionary and has led to an increase in the number of patients on long-term therapy. This inevitably gives rise to drug resistance through point mutations in the Bcr-Abl protein. Our results suggest that UM-9107 is a safe and efficacious preclinical candidate for the treatment of imatinib-resistant CML. Citation Format: Sameer Phadke, Lluis Lopez-Barcons, Taylor K. Johnson, Eric J. Lachacz, Sofia D. Merajver, Matthew B. Soellner. UM-9107: A selective wild-type and T315I Bcr-Abl inhibitor with in vivo activity against chronic myelogenous leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1327.
Dopamine fuels its own release.

A new study shows that the enzyme monoamine oxidase funnels a byproduct of dopamine metabolism, H2O2, directly into the mitochondrial electron transport chain, stimulating ATP production. This alternative energy pathway may protect dopaminergic neurons from the toxicity induced by dopamine metabolism while supporting phasic firing.
Catch me if you care: International development organizations and national corruption

Many international development organizations (IDOs) have officially mandated anti-corruption criteria for aid selectivity. Substantial debate remains over whether corruption deters aid and whether anti-corruption rules are effectively implemented. We argue that the extent to which both corruption and anti-corruption mandates factor into IDO allocation depends on the composition of the donors. Using existing data on corruption alongside newly collected data on anti-corruption mandates, we demonstrate that organizations composed of corrupt donors are just as likely to adopt, but less likely to enforce, anti-corruption mandates. Organizations composed of less corrupt donors, by contrast, tend to divert aid away from corrupt states, with or without formal anti-corruption rules in place. The findings have implications for the debate over whether international efforts to institutionalize “good governance” standards are sincere or cheap talk, whether multilateral strategies are in fact less politicized than bilateral aid allocation strategies, and whether international organizations should be inclusive, open to membership by many or even all states, including those with dubious track records.
Abstract WP343: Machine Learning Predicts Sex Difference in Acute Ischemic Stroke

Introduction: Stroke is a common cause of physical disability. Women generally suffer from more severe strokes, have poorer stroke outcomes, and higher mortality than that of men. Cytokines play an...
CHAPTER X – Aeroelasticity

Publisher Summary This chapter describes some effects of aeroelasticity on stability and control, and on handling qualities. The chapter focuses on the static changes in aerodynamic derivatives as a result of elasticity. Some of the aeroelastic effects have become very important since the advent of thin, swept wings and flight at high dynamic pressures. It is simply not feasible to design a rigid airplane of modern configuration and performance, and the consequences of elasticity must be considered. Elasticity changes the way forces and moments vary with angle of attack, and so it will alter the angle-of-attack derivatives that appear in both neutral and maneuver point calculations. The effects are functions of dynamic pressure, and so they depend on velocity. In any set of flight conditions, where velocity varies, there will be an additional effect.
Efficacy of vertical lid split versus lateral canthotomy and cantholysis in the management of orbital compartment syndrome.

Purpose: To compare the efficacy of the vertical lid split (VLS) to the standard lateral canthotomy and cantholysis (LC/C) for orbital compartment syndrome (OCS) in the cadaveric model.Methods: Simulated OCS was achieved in seven fresh frozen cadaveric orbits. Orbital pressure (OP) was monitored in one control orbit and six interventional orbits. Initial OP was recorded before three right orbits underwent lateral canthotomy with superior and inferior cantholysis, and three left orbits underwent vertical lid split of the upper and lower eyelids. In all 7 orbits, OP was recorded for a total of 16 min. The main outcome measure was the amount of OP reduction at timed intervals.Results: Beginning OP in the control orbit was 109 mmHg, and average initial OP of the LC/C and VLS orbits were 90 and 103 mmHg, respectively. The control orbit maintained high OP without intervention. One minute after LC/C, OP decreased an average of 58.7 mmHg (65.2%; range 48-65 mmHg). One minute following VLS, OP decreased an average of 63 mmHg (61.0%; range 39-102 mmHg). At 16 min, OP reduction in the LC/C orbits averaged 65.3 mmHg (72.6%; range 56-71 mmHg), and OP reduction in the VLS orbits averaged 78 mmHg (75.5%; range 54-121 mmHg). Both interventions produced a comparable reduction in OP.Conclusions: Vertical lid split was found to be as effective as LC/C in reducing OP. The technical simplicity of the VLS lends itself well to utilization by physicians who are unfamiliar with eyelid surgery.
Holography on tessellations of hyperbolic space

We compute boundary correlation functions for scalar fields on tessellations of two- and three-dimensional hyperbolic geometries. We present evidence that the continuum relation between the scalar bulk mass and the scaling dimension associated with boundary-to-boundary correlation functions survives the truncation of approximating the continuum hyperbolic space with a lattice.
Burnout in psychosocial oncology clinicians: A systematic review.

Objective Few studies have examined burnout in psychosocial oncology clinicians. The aim of this systematic review was to summarize what is known about the prevalence and severity of burnout in psychosocial clinicians who work in oncology settings and the factors that are believed to contribute or protect against it. Method Articles on burnout (including compassion fatigue and secondary trauma) in psychosocial oncology clinicians were identified by searching PubMed/MEDLINE, EMBASE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, and the Web of Science Core Collection. Results Thirty-eight articles were reviewed at the full-text level, and of those, nine met study inclusion criteria. All were published between 2004 and 2018 and included data from 678 psychosocial clinicians. Quality assessment revealed relatively low risk of bias and high methodological quality. Study composition and sample size varied greatly, and the majority of clinicians were aged between 40 and 59 years. Across studies, 10 different measures were used to assess burnout, secondary traumatic stress, and compassion fatigue, in addition to factors that might impact burnout, including work engagement, meaning, and moral distress. When compared with other medical professionals, psychosocial oncology clinicians endorsed lower levels of burnout. Significance of results This systematic review suggests that psychosocial clinicians are not at increased risk of burnout compared with other health care professionals working in oncology or in mental health. Although the data are quite limited, several factors appear to be associated with less burnout in psychosocial clinicians, including exposure to patient recovery, discussing traumas, less moral distress, and finding meaning in their work. More research using standardized measures of burnout with larger samples of clinicians is needed to examine both prevalence rates and how the experience of burnout changes over time. By virtue of their training, psychosocial clinicians are well placed to support each other and their nursing and medical colleagues.
Effects of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients

SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2), cause of COVID-19 (Coronavirus Disease of 2019), represents a significant risk to people living with pre-existing conditions associated with exacerbated inflammatory responses and consequent dysfunctional immunity. In this paper, we have evaluated the effects of obesity, a condition associated with chronic systemic inflammation, on the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. Results have shown that SARS-CoV-2 IgG antibodies are negatively associated with Body Mass Index (BMI) in COVID-19 obese patients, as expected based on the known effects of obesity on humoral immunity. Antibodies in COVID-19 obese patients are also negatively associated with serum levels of pro-inflammatory and metabolic markers of inflammaging and pulmonary inflammation, such as SAA (serum amyloid A protein), CRP (C-reactive protein) and ferritin, but positively associated with NEFA (nonesterified fatty acids). These results altogether could help to identify an inflammatory signature with strong predictive value for immune dysfunction that could be targeted to improve humoral immunity in individuals with obesity as well as with other chronic inflammatory conditions.
Incorporating fiber recruitment in hyperelastic modeling of vascular tissues by means of kinematic average.

We present a framework for considering the gradual recruitment of collagen fibers in hyperelastic constitutive modeling. An effective stretch, which is a response variable representing the true stretch at the tissue-scale, is introduced. Properties of the effective stretch are discussed in detail. The effective stretch and strain invariants derived from it are used in selected hyperelastic constitutive models to describe the tissue response. This construction is investigated in conjunction with Holzapfel-Gasser-Ogden family strain energy functions. The ensuing models are validated against a large body of uniaxial and bi-axial stress–strain response data from human aortic aneurysm tissues. Both the descriptive and the predictive capabilities are examined. The former is evaluated by the quality of constitutive fitting, and the latter is assessed using finite element simulation. The models significantly improve the quality of fitting, and reproduce the experiment displacement, stress, and strain distributions with high fidelity in the finite element simulation.
Factors associated with not having a healthcare visit in the past year among US adults with hypertension: Data from NHANES 2013-2018.

BACKGROUND Not having a healthcare visit in the past year has been associated with a higher likelihood of uncontrolled blood pressure (BP) among individuals with hypertension. METHODS We examined factors associated with not having a healthcare visit in the past year among US adults with hypertension using data from the US National Health and Nutrition Examination Survey 2013-2018 (n=5,985). Hypertension was defined as systolic BP ≥140 mmHg, diastolic BP ≥90 mmHg, or antihypertensive medication use. Having a healthcare visit in the past year was self-reported. RESULTS Overall, 7.0% of US adults with hypertension reported not having a healthcare visit in the past year. Those without versus with a healthcare visit in the past year were less likely to be aware they had hypertension (45.0% versus 83.9%), to be taking antihypertensive medication (36.7% versus 91.4%, among those who were aware they had hypertension) and to have controlled BP (systolic/diastolic BP <140/90 mmHg; 9.1% versus 51.7%). After multivariable adjustment, not having a healthcare visit in the past year was more common among US adults without health insurance (prevalence ratio [PR]: 2.22; 95%CI 1.68-2.95), without a usual source of healthcare (PR: 5.65; 95%CI 4.16-7.67), who smoked cigarettes (PR: 1.34; 95%CI 1.02-1.77), and with heavy versus no alcohol consumption (PR: 1.55; 95%CI 1.16-2.08). Also, not having a healthcare visit in the past year was more common among those without diabetes or a history of atherosclerotic cardiovascular disease, and those not taking a statin. CONCLUSION Interventions should be considered to ensure all adults with hypertension have annual healthcare visits.
Restoring “The Church‐porch”: George Herbert's Architectural Style

AbstractWhile many of the devotional lyrics in George Herbert's The Temple (1633) have attracted sustained critical attention over the past several decades, “The Church‐porch” has lain in comparative neglect for at least a century. This essay draws on sources in local history and ecclesiology to argue that the poem's proverbial style and didactic content—features that modern readers have found distasteful—are deliberate reflections of its architectural setting. Marginal as “The Church‐porch” has been in recent scholarship, the church porch itself would not have been marginal in seventeenth‐century parish life: the first part of the baptismal and marriage ceremonies, for instance, were originally solemnized in the church porch; children were taught there, contracts witnessed, alms disbursed, and debts paid. Herbert's didactic and moral precepts thus represent a common verbal and moral currency whose circulation and constant reuse mirror the kind of public exchange that took place in the church porch. (A.M.M.)
Educating Student Managerial Leaders: What Critical Behaviors Should Be Developed?

If we want student leaders to be prepared for the workforce, we need to develop their managerial leadership behaviors while they are in school. Peterson and Peterson (2012) identified a set of critical managerial leadership behaviors that should be taught while students are in college. However, the empirical work was done at a single Southwest university. This manuscript replicates the Peterson and Peterson study at a Midwest university. In addition, it extends the research by having the subjects rank order the managerial leadership behaviors they initially selected. The results identify a set of managerial leadership behaviors that could be taught and practiced by student leaders while they are still in a university setting. These students could then enter the workforce prepared to lead and manage.
Polynomial Fermionic Forms for the Branching Functions of the Rational Coset Conformal Field Theories $\widehat{su}(2)_{M}\times \widehat{su}(2)_{N}/\widehat{su}(2)_{M+N}$}

General fermionic expressions for the branching functions of the rational coset conformal field theories $\widehat{su}(2)_{M}\times \widehat{su}(2)_N/\widehat{su}(2)_{M+N}$ are given. The equality of the bosonic and fermionic representations for the branching functions is proven by introducing polynomial truncations of these branching functions which are the configuration sums of the RSOS models in regime III. The path space interpretation of the RSOS models provides recursion relations for the configuration sums. The proof of the recursion relations for the fermionic expressions is given by using telescopic expansion techniques. The configuration sums of the RSOS model in regime II which correspond to the branching functions of the $Z_{M+N}$-parafermion conformal field theory are obtained by the duality transformation $q\rightarrow q^{-1}$.