cssi/SciSciGPT-SciSciNet huggingface dataset:
Introduction to High-Energy-Density Physics

This chapter begins by introducing and defining the field of high-energy-density physics. It goes on to compare its domain with those of other areas of science and to survey the historical developments that led to the emergence of this field as a discipline. The chapter then identifies and discusses the regions within which various physical effects, such as Fermi degeneracy, become important. Brief introductions to inertial confinement fusion and to laboratory astrophysics at high energy density follow. The chapter concludes with a discussion of the connections between the present book and various other books, and some discussion of variables and notation.
A computer assisted intelligent storm outage evaluator for power distribution systems

A knowledge-based approach for evaluating storm-related outages in distribution systems is proposed. At the outset, binary voltage sensors capable of transmitting the real-time voltage on/off symptoms are recommended to be installed at strategic locations in the distribution system. A semantic network model has been developed to represent the knowledge of the distribution system faults and their associated symptoms. The real-time voltage symptoms, transmitted by the sensors, serve as the basic input to the semantic network model in generating fault hypotheses. A rule base, incorporating temporal and topological knowledge of symptoms and system operators' heuristics, is used by the inference mechanism to determine the actual faults from the hypotheses set. The results suggest that the fault types and their exact sections can be diagnosed accurately. >
Ubiquitin and intracellular signaling by G protein-coupled receptors (354.2)

GPCR signaling is precisely regulated and critical for appropriate cellular responses. Our goal is to understand the mechanisms by which ubiquitin regulates GPCR signaling. Ubiquitin is best known to function in GPCR lysosomal sorting. However, we recently discovered that ubiquitin is not required for lysosomal sorting of a subset of GPCRs including protease-activated receptor-1 (PAR1) and the P2Y1 receptor. The adaptor protein ALIX directly links GPCRs to ESCRT-III to facilitate lysosomal degradation independent of receptor ubiquitination and ubiquitin-binding ESCRTs. Remarkably, however, PAR1 and P2Y1 receptor are ubiquitinated following agonist stimulation. These findings raise the question: What is the function of GPCR ubiquitination? We found that ubiquitin regulates a non-canonical GPCR-stimulated p38 MAPK signaling pathway. We showed that ubiquitination of PAR1 functions as a signal for the recruitment of TAB2 (transforming growth factor-β-activated kinase binding protein 2), an adaptor that binds ...
TREATMENT OF SUCCESSIVE GENERATIONS OF RATS WITH THYMUS EXTRACT (HANSON) AND RELATED SUBSTANCES1

IN 1930 HANSON (I) prepared a thymus extract which he hoped would prove a cure for certain types of cancer. Large quantities of this extract were turned over to Rowntree for biological study at The Philadelphia Institute for Medical Research. In 1934 Rowntree, Clark, Steinberg and Hanson (2) reported that the injection of this extract into successive generations of Wistar rats induced a remarkable precocity of growth and development which was noticeable in the 3rd generation and which became more marked in each of the five generations studied. In a more recent paper (3) they report 12 generations under study in which each generation showed a still greater precocity than the preceding generation. In searching for the active principle it was found (3) that all biologically potent extracts contained at least 15 mg.% of iodine reducing substances (calculated as gluthathione after the method of Woodward and Fry, 4).
Traumatic Dislocation of the Hip in a High School Football Player

Background: Although traumatic dislocation of the hip often occurs as a result of automobile accidents, dislocations have been reported to occur during sports activities. Objective: Using the experience in treating a 17-year-old high school football player with a posterior dislocation, complicated by involvement of the sciatic nerve, this case report provides background information on hip dislocations and provides a description of the immediate treatment by the physician, followed by 6 weeks of immobilization, and a detailed account of the 5-month intervention. Case Description: The patient was injured while making a tackle during a high school football game when another player fell on him from behind. The case report describes his plan of care after immediate hip reduction surgery and 6 weeks on crutches. Generally, the program utilized a progression of non–weight-bearing resistance training and stretching in the initial stages of intervention and progressed to weight-bearing activities (on land and in the pool) as the patient was able to tolerate more stress. In addition, the treatment of the sciatic nerve using electrical stimulation during treadmill walking is described. Outcomes: The patient was seen in an outpatient physical therapy clinic an average of 2 times per week for 5 months. At the end of 5 months, results of the Lower Extremity Functional Scale (LEFS) indicated that recreational and sporting activities were within normal limits, and the patient was able to return to playing on his high school football team the next year.
Modelling optimal grain-marketing decisions when prices are generated autoregressively

A model is developed to find decision rules that maximise expected utility of income from selling stored wheat when future price expectations are updated weekly using newly observed prices. Expected utility is approximated in terms of six moments of the income distribution, and efficient procedures are developed to calculate moments. Marketing losses that arise when the autoregressive structure of wheat prices is ignored are estimated. Losses were found to be equivalent to reductions of 1.9-14.5% in expected income, depending on initial prices and risk aversion. Copyright 1995 by Oxford University Press.
Analysis of a synchronous reluctance machine with an auxiliary single-phase winding

A three-phase synchronous reluctance machine having an axially laminated rotor structure and an auxiliary DC source fed single-phase control winding has utility as either as a high-speed generator or a high-torque, low-speed motor. This paper provides an understanding of its operation using electric circuit and electromagnetic field concepts in the process of which some insights are provided into the design of the windings, conditions for torque production and generation of electric power when operating in the motoring or generating modes. Some confirmatory experimental results of analytical developments are provided showing performance characteristics of an experimental machine.
THE MAMMALIAN CELL-VIRUS RELATIONSHIP VI. SUSTAINED INFECTION OF HELA CELLS BY COXSACKIE B3 VIRUS AND EFFECT ON SUPERINFECTION

Sustained infection of HeLa cells by Coxsackie B3 virus, dependent on presence of viral inhibitor in culture medium, was achieved. Persistent treatment of carrier cultures with anti-Coxsackie B3 hyperimmune monkey serum eventually eliminated virus from carrier cultures indicating that a lysogenic virus-cell relationship was not operative. Free virus was produced continuously by carrier cultures despite washing and neutralization with antiserum to eliminate free virus temporarily. In carrier cultures, about 1.5 to 1.9 plaque-forming units of virus per cell were cell-associated; approximately 6 per cent of this cell-associated virus was not neutralizable by antiserum. In growth medium containing anti-B3 antibody, cells from carrier cultures formed colonies as efficiently as cells from B3-cured cultures. Assays of carrier cultures for infectious centers indicated that less than 1 per cent of cells produced free infectious virus. The Coxsackie B3 virus-carrier state appeared to represent surface residence of B3 virus on the majority of carrier cells with restriction of productive infection to a small proportion of the population. Coxsackie B3 carrier HeLa cultures, unlike control cultures, were not destroyed by challenge with Coxsackie B1, B3, or B5 viruses. The B3 carrier state did not interfere with superinfection by herpes, vaccinia, and types 1 to 3 polioviruses. In contrast to parental or B3-cured lines, B3-carrier HeLa cultures superinfected with Coxsackie B1 virus produced no significant virus, and cultures superinfected with B5 viruses produced new virus to a limited extent only. Specific interference with Coxsackie virus superinfection by the B3-carrier state of HeLa cells was shown to be attributable to failure of attachment in the instance of Coxsackie B1 virus, and failure of penetration and/or eclipse in the instance of B5 virus. The interfering effect was circumvented successfully by superinfection of carrier cells with ribonucleic acid extracted from Coxsackie B1 and B5 viruses.
American Oresteia: Herbert Wechsler, the Model Penal Code, and the Uses of Revenge

The American Law Institute recently revised the Model Penal Code's sentencing provisions, calling for a renewed commitment to proportionality based on the gravity of offenses, the "blameworthiness" of offenders, and the "harms done to crime victims." Already, detractors have criticized this move, arguing that it replaces the Code's original commitment to rehabilitation with a more punitive attention to retribution. Yet, missing from such calumny is an awareness of retribution's subtle yet significant role in both the drafting and enactment of the first Model Penal Code (MPC). This article recovers that role by focusing on the retributive views of its first Reporter, Columbia Law Professor Herbert Wechsler. Though a dedicated utilitarian, Wechsler became increasingly aware of retribution's value to sentencing over the course of his career, using that awareness to guide both the development and adoption of the MPC. Recovering his view helps us to contextualize and perhaps even better appreciate the current revision's emphasis on proportionality.
Management of Limited Disease Small-Cell Lung Cancer

The use of combination chemotherapy for SCLC has contributed to significant improvements in local control and survival in limited-stage disease. The initial enthusiasm generated by these significant therapeutic advances has waned with the realization that a plateau has been reached and no additional survival increments have been gained in the last decade. While a number of chemotherapy regimens may be equivalent to EP or EC, alternating regimens or dose-intense regimens have not gained widespread acceptance. The role for thoracic irradiation and prophylactic cranial irradiation in LDSCLC has been firmly established. What remains to be determined is whether chemotherapy combinations incorporating some of the newer “targeted” agents will move us away from this therapeutic plateau.
Modulation of extracellular redox remodeling by regulatory T cells (33.11)

T cell activation and proliferation requires a reducing microenvironment that is provided by dendritic cells (DC). Naturally occurring CD4 + CD25 + regulatory T cells (Treg) can suppress autoimmunity by inhibiting CD4 + CD25 - effector T cells (Teff). The mechanism is not fully understood. In this study, we have tested the hypothesis that inhibition by Treg cells of DC-induced extracellular redox remodeling is a component of the Treg immunosuppressive mechanism. We demonstrate that the increase in extracellular Cys concentration upon co-culture of DCs with Teff cells results from the system x c - -dependent import of cystine, its conversion to glutathione, which is subsequently exported and degraded by γ-glutamyltranspeptidase and a dipeptidase, to furnish Cys. Suppression of DC-dependent Teff cell proliferation by Treg cells is correlated with a significant diminution in extracellular Cys concentration and is abrogated by addition of exogenous Cys. The decrease in the extracellular redox potential during T cell activation is associated with an increase in the levels of exofacial surface thiols in both DCs and T cells, which is diminished in the presence of Treg cells. This study elucidates the pathway of thiol release by DCs in response to T cell stimulation, demonstrates that Treg cells interfere with the process of extracellular redox remodeling and identifies a novel mechanism for immunomodulation.
The Effect of Temperature and Menthol on Carbonation Bite

Temperature and chemesthesis interact, but this interaction has not been fully examined for most irritants. The current experiments focus on oral pungency from carbonation. Previous work showed that cooling carbon dioxide (CO2) solutions to below tongue temperature enhanced rated bite. However, to the best of our knowledge, the effects of warming to above tongue temperature have not been examined. In Experiment 1, subjects sampled CO2 solutions at 4 nominal concentrations (0.0, 2.0, 2.8, and 4.0 v/v) × 5 temperatures (18.3, 24.5, 29.9, 34.5, and 39.6 (o)C). Subjects dipped their tongue tips into samples and rated bite. As in previous work, subjects rated cool solutions (25.0 (o)C and lower) as more intense. Warming solutions above tongue temperature (39.6 (o)C) did not affect ratings. Experiment 2 examined warmer temperatures (18.3, 33.9, 39.0, 44.9, and 48.2 oC). Bite was enhanced only at 48.2 oC, and a follow-up experiment suggested that enhancement was probably due to confusion between carbonation bite and mild heat pain. Experiment 3 examined the effect of menthol cooling by pretreating the tongue with menthol. Unlike physical cooling, menthol cooling had little or no effect on rated bite. The results are discussed in the context of candidate transduction mechanisms for carbonation sensation.
Characterization of the Internal Flow Dynamics of Combustion Powered Actuators

The internal flow properties of small-scale combustion-powered fluidic actuator for flow control applications are characterized over a range of combustion chamber geometries and gas mixture flow conditions. Momentary (pulsed) actuation jets are produced by the ignition of a mixture of gaseous fuel and oxidizer within a cubic-centimeter-scale chamber. The combustion process yields a high pressure burst and the ejection of a high-speed exhaust jet. Modular chambers were constructed specifically to allow optical access to the chamber for phase-locked Particle Image Velocimetry (PIV) measurements over both the baseline and combusting flows as well as dynamic pressure measurements. It was observed that for low flow inlet velocities (in both remixed and non-premixed actuator configurations) an essentially laminar flame propagation process is observed. At increased mean inlet flow velocities for the non-premixed geometry, a transition quickly occurs to produce significant wrinkling of the flame front and an apparently irregular flame propagation process through the chamber. Information obtained during this and future similar studies will be used to create actuator designs with improved refill and combustion processes.
Evaluating Responses of Honey Bees to Sugar Solutions Using an Artificial-Flower Feeder

An artificial-flower feeder was designed to compare the acceptibility of sugar solutions to foraging honey bees, Apis mellifera L. Discrimination against the least preferred solutions was apparently reduced and then eliminated as the number of bees imbibing was increased. Honey bees collected sucrose in preference to fructose and fructose in preference to glucose; 30-50% sucrose in preference to higher or lower concentrations; showed no preference between solutions ranging in p H from 3.2 to 8.8 but rejected those with a p H lower or higher; and showed an aversion to sucrose solutions containing potassium salts.
Energy Intake and Energy Expenditure for Determining Excess Weight Gain in Pregnant Women.

OBJECTIVE To conduct a secondary analysis designed to test whether gestational weight gain is the result of increased energy intake or adaptive changes in energy expenditures. METHODS In this secondary analysis, energy intake and energy expenditure of 45 pregnant women (body mass index [BMI] 18.5-24.9 [n=33] and BMI 25 or greater [n=12]) were measured preconceptionally and at 22 and 36 weeks of gestation. Energy intake was calculated as the sum of total energy expenditure measured by doubly-labeled water and energy deposition determined by the four-compartment body composition model. Measurements of weight, body composition, and basal metabolic rate were completed preconceptionally and 9, 22, and 36 weeks of gestation. Basal metabolic rate was measured by indirect calorimetry in a room calorimeter and activity energy expenditure by doubly-labeled water. RESULTS Energy intake from 22 to 36 weeks of gestation was significantly higher in high gainers (n=19) (3,437±99 kcal per day) compared with low+ideal gainers (n=26) (2,687±110, P<.001) within both BMI categories. Basal metabolic rate increased in proportion to gestational weight gain; however, basal metabolic rate adjusted for body composition changes with gestational weight gain was not significantly different between high gainers and low+ideal gainers (151±33 compared with 129±36 kcal per day; P=.66). Activity energy expenditure decreased throughout pregnancy in both groups (low+ideal gainers: -150±70 kcal per day; P=.04 and high gainers: -230±92 kcal per day; P=.01), but there was no difference between high gainers and low+ideal gainers (P=.49). CONCLUSION Interventions designed to increase adherence to the Institute of Medicine guidelines for weight gain in pregnancy may have increased efficacy if focused on limiting energy intake while increasing nutrient density and maintaining levels of physical activity.
On the Officer Training in the Public Security Forces

Resulting from the long-term influence of the general education,the mode of officer training tends to fit in with the mode of the general education.In order to improve the efficiency of this training,it is urgent to make a research to adapt to the training characteristics.Meanwhile,it also should creatively employ various teaching ways and means in the training practice.
Synthesis and Validation of Cyanine-Based Dyes for DIGE

The application of difference gel electrophoresis (DIGE), in particular its most common "minimal labeling" variety, utilizes N-hydroxysuccinimide esters of Cy2, Cy3, and Cy5 dyes, which are commercially available. We describe methods for the efficient synthesis of all three dyes from relatively inexpensive and commercially available precursors in only a few steps and with relatively high yields. In model DIGE experiments, the newly synthesized dyes proved to be indistinguishable from commercially available ones and have been shown to be stable for years while stored under argon as dry solids or after being dissolved in N,N-dimethylformamide.
Pharmacokinetic considerations in exchange transfusion in neonates.

Neonates undergoing blood exchange often receive concomitant therapy. Questions may be raised whether dosage regimen alterations are necessary to replace drug lost as a result of the exchange procedure. Our study reports the changes in plasma concentration of kanamycin during an exchange transfusion and a pharmacokinetic analysis of the effect of the exchange on drug elimination. The relationships of the volumes of distribution, elimination rate constant, and time after dosing on the fraction of the dose eliminated in the blood exchange are developed on the basis of a one-compartment body model. Computer simulations using the equations developed were used to estimate the fraction of a dose that might be removed as a result of an exchange transfusion. As the disposition rate constant or the apparent volume of distribution increase, i.e., the clearance of the drug increases, the fraction of the dose removed by the exchange process decreases. Thus, significant amounts of drug removal may occur in an exchange transfusion for drugs with low clearance when the exchange is initiated early in the drug dosing interval. In our study, only 3% of the kanamycin dose was removed as a result of the exchange process, and dosing adjustment would not be required. This was in part due to initiation of the exchange late in the dosing interval, although the maximum calculated percentage of the dose which could have been removed under the exchange conditions employed was only 10%.
Assessing subtle structural changes in Alzheimer's disease patients

Magnetic resonance imaging (MRI) allows the assessment of structural changes in subjects with Alzheimer's disease (AD). Early studies used visual assessments of MRI or manual measurements of structures of interest, although these methods were limited by inter-rater variability. Techniques have now been developed which allow automated analysis of both cross-sectional and longitudinal MRI data and have provided valuable information concerning the patterns and progression of atrophy in subjects with AD. It is also now possible using machine learning-based techniques to provide individual-level diagnostic information from MRI scans. Various analysis techniques have been applied to validate the use of MRI to capture subtle structural changes due to atrophy in AD and its usefulness in providing diagnostic and prognostic information, as well as tracking the disease progression in AD.
Hypoglycemia Prevention Using Low Glucose Suspend Systems

The fear of nocturnal hypoglycemia was one of the main motivations behind the development of continuous glucose monitors (CGM) and hypoglycemic alarms. Since many individuals do not awake to these alarms, the next step is to implement a low glucose suspend (LGS) algorithm that shuts off the insulin infusion pump to avoid hypoglycemia. A threshold-based LGS simply shuts off the pump when the CGM signal has violated a lower limit on glucose. A predictive LGS shuts off the pump when a glucose threshold is predicted to occur within a specified time limit, or horizon. A review of algorithms hypoglycemic predictors/alarms is followed by a presentation of threshold and predictive LGS algorithms. Finally, an overview of the implementation challenges that remain is provided.
Openatom: Scalable AB-initio molecular dynamics with diverse capabilities

The complex interplay of tightly coupled, but disparate, computation and communication operations poses several challenges for simulating atomic scale dynamics on multi-petaflops architectures. OpenAtom addresses these challenges by exploiting overdecomposition and asynchrony in Charm++, and scales to thousands of cores for realistic scientific systems with only a few hundred atoms. At the same time, it supports several interesting ab-initio molecular dynamics simulation methods including the Car-Parrinello method, Born-Oppenheimer method, k-points, parallel tempering, and path integrals. This paper showcases the diverse functionalities as well as scalability of OpenAtom via performance case studies, with focus on the recent additions and improvements to OpenAtom. In particular, we study a metal organic framework (MOF) that consists of 424 atoms and is being explored as a candidate for a hydrogen storage material. Simulations of this system are scaled to large core counts on Cray XE6 and IBM Blue Gene/Q systems, and time per step as low as \(1.7\,s\) is demonstrated for simulating path integrals with 32-beads of MOF on 262,144 cores of Blue Gene/Q.
Generalized Structural Mean Models for Evaluating Depression as a Post-treatment Effect Modifier of a Jobs Training Intervention

In randomized controlled trials, the evaluation of an overall treatment effect is often followed by effect modification or subgroup analyses, where the possibility of a different magnitude or direction of effect for varying values of a covariate is explored. While studies of effect modification are typically restricted to pretreatment covariates, longitudinal experimental designs permit the examination of treatment effect modification by intermediate outcomes, where intermediates are measured after treatment but before the final outcome. We present a novel application of generalized structural mean models (GSMMs) for simultaneously assessing effect modification by post-treatment covariates and accounting for noncompliance to assigned treatment status. The proposed approach may also be used to identify post-treatment effect modifiers in the absence of noncompliance. The methods are evaluated using a simulation study that demonstrates that our approach retains consistent estimation of effect modification by intermediate variables that are affected by treatment and also predict outcomes. We illustrate the method using a randomized trial designed to promote re-employment through teaching skills to enhance self-esteem and inoculate job seekers against setbacks in the job search process. Our analysis provides some evidence that the intervention was much less successful among subjects that displayed higher levels of depression at intermediate post-treatment waves of the study. We also compare the assumptions of our approach and principal stratification as alternatives to account for differences in effects by intermediate variables.
Neoliberalism and Applied Linguistics, by Block, D., Gray, J., & Holborow, M.

Rampton (1997) in his landmark paper Returning in Applied Linguistics described applied linguistics as “an open field of interest in language” (p. 14). He argued that it was not just about language...
Li‐Ion Synaptic Transistor for Low Power Analog Computing

Nonvolatile redox transistors (NVRTs) based upon Li-ion battery materials are demonstrated as memory elements for neuromorphic computer architectures with multi-level analog states, "write" linearity, low-voltage switching, and low power dissipation. Simulations of backpropagation using the device properties reach ideal classification accuracy. Physics-based simulations predict energy costs per "write" operation of <10 aJ when scaled to 200 nm × 200 nm.
Acquired Factor XIII inhibitor associated with mantle cell lymphoma.

BACKGROUND Acquired Factor (F)XIII deficiency is a very rare bleeding diathesis with a potentially fatal outcome, previously described in the context of autoimmune disorders and leukemias. There is minimal information on autoantibody characterization and the role of antifibrinolytic therapy in patient management. CASE REPORT A 79-year-old woman with a 3-month history of bruising and heavy menorrhagia presented with ongoing vaginal bleeding, symptomatic anemia, and a right thigh hematoma. Initial management included an axillary lymph node biopsy and coagulation evaluation. Pathologic examination of the biopsy specimen revealed mantle cell lymphoma. Clot solubility assay was consistent with a FXIII activity of less than 3%. An anti-FXIII inhibitor was suspected, the epitope specificity of which was mapped by micropeptide array analysis to regions in the β-sandwich and catalytic core domain of the FXIII-A subunit. Management with cryoprecipitate, steroids, rituximab, and antifibrinolytic therapy resolved the bleeding diathesis and suppressed the inhibitor. CONCLUSION This is the first reported case of an acquired FXIII inhibitor associated with mantle cell lymphoma in which the epitope specificity of the pathologic autoantibody was accurately defined. Antifibrinolytic therapy played a prominent role in the prevention of bleeding complications in the window period between initiation of immunosuppression and disappearance of the pathologic anti-FXIII autoantibody.
Abstract 2650: PI 3-Kinase inhibitors enhance the synthetic lethality of Parp inhibitors

Introduction: Clinical trials have shown promising responses of BRCA-linked breast and ovarian cancers to PARP inhibitor therapy, but remissions are often short-lived and incomplete. Frequent loss of INPP4B and PTEN leads to activation in the PI3K pathway in TNBC, making the PI3K pathway an attractive treatment target. Here we present mechanistic data that explain how PI3K- and PARP-inhibition enhance each other. Methods: We examined the effects of PI3K-inhibitors BKM120 or BYL719 and PARP-inhibitor Olaparib on the metabolism of HCC1937 cells (BRCA1 5382C mutation and homozygous deletion of PTEN and p53) measuring lactic acid production, via seahorse analysis, carbon metabolism using targeted Mass Spectrometry (LC-MS/MS) and DNA synthesis. PI3K- but not Akt- or SGK-inhibition induced a DNA damage response in this BRCA1 mutant cell line as well as in a mouse model of BRCA1-related breast cancer (K14-Cre BRCA1f/f p53f/f) mouse model. Summary: Metabolic profiling showed that PI3K-inhibition decreased flux through glycolysis and specifically through the non-oxidative pentose-phosphate pathway, the main source of ribose-5-phosphate required for the de novo synthesis of nucleotides in BRCA1-mutant breast cancer cells. Nucleotide shortage led to replication stress with the appearance of γH2AX, increased poly-ADP-ribosylation and an acute drop in DNA synthesis in cell cultures as well as in vivo. PI3K inhibition led to a reduced and error-prone S-phase due to a decrease in nucleotide biosynthesis which could be rescued upon exogenous supply of nucleosides. In a mouse model (K14-Cre BRCA1f/fp53f/f induced breast cancers) we could confirm that both BKM120 and BYL719 enhanced the efficacy of Parp-inhibitor Olaparib (median PFS for Olaparib 50 days, for BKM120 4 days, for BYL719 6 days and for both combinations, BKM120+Olaparib and BYL719+Olaparib > 120 days). Conclusion: Preceding cell cycle arrest, PI3K-inhibition leads to a decrease in DNA synthesis due to decreased Ribose-5-phosphate production required for nucleotide synthesis. PI3K-inhibitors lower nucleotide pools, lead to impaired DNA damage repair and S-phase progression and further augment the synthetic lethality of Parp-inhibitors in BRCA1-related breast cancer. Citation Format: Ashish P. Juvekar, Sina Yadegarynia, Hai Hu, Costas A. Lyssiotis, Hui Liu, John M. Asara, Ralph Scully, Lewis C. Cantley, Gerburg M. Wulf. PI 3-Kinase inhibitors enhance the synthetic lethality of Parp inhibitors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2650. doi:10.1158/1538-7445.AM2015-2650
Critical Review of Methods for Deriving Stable Reduced-Order Models

Abstract Various methods for generating stable reduced order models are investigated. It is shown that the reduced models may approximate the nondominant poles of the system and hence lead to erroneous approximations. Further, when applied to multivariable systems the methods may lead to reduced models that are higher in order than the original systems. Several examples are given to illustrate these failures.
Radioimmunotherapy in Oncology

Radioimmunotherapy (RIT) is the targeting of radiosensitive tumors through the use of monoclonal antibodies. The purpose of this review is to discuss the benefit and challenges of RIT. We appraise factors that determine optimal targeting of tumor such as choice of target, targeting antibody, and the associated radionuclide, as well as the current methods to potentiate RIT effect. Radioimmunotherapy has a well-established role in the treatment of hematological malignancies. Recent completed and current studies in the treatment of solid malignancies are however demonstrating good clinical response with acceptable toxicity profiles. Since its inception, improved molecular engineering and targeting of new molecules, the discovery of new potential tumor targets, and the incorporation of methods to potentiate effect and reduce toxicity, will probably see radioimmunotherapy becoming a more commonplace treatment in the management of both hematological and solid malignancies.
Quantum chemistry benchmarking of binding and selectivity for lanthanide extractants

Computer-aided screening methods facilitate the discovery of new extractants for heavy and rare-earth metal separations. In this work, we have benchmarked the accuracy of different quantum chemistry methods for calculating extractant binding energies and selectivities. Specifically, we compare calculated data from different exchange correlation functionals (B3LYP-D3, ωB97X-D3, and M06-L) and different basis sets (including large-core effective core potentials and all-electron basis sets). We report aqueous-phase binding energy and selectivity trends for 1:1 and 3:1 extractant/lanthanide models for the complexes. We find that binding selectivities are not particularly sensitive to model chemistry, but binding energies are sensitive. Furthermore, calculated trends in selectivity using 3:1 extractant/lanthanide models are in better agreement with available experimental trends than trends using 1:1 extractant/lanthanide models. Lastly, we find that the B3LYP-D3/6-31 + G* model chemistry with the Stuttgart large-core relativistic effective core potentials on the lanthanide sufficiently reproduces results from larger basis set calculations and is confirmed as suitable for relatively fast and efficient screening of lanthanide binding energies and selectivities.
Chapter 10 – Culture and resilience: How music has fostered resilience in post-Katrina New Orleans

Abstract Music and musicians are integral to the culture of New Orleans. This research examines the resilience of a group of musicians after Hurricane Katrina. Resilience and vulnerability to the impacts of Hurricane Katrina were assessed using qualitative research methods employing ethnographic interview techniques. Data were analyzed using the Variable-Generating Activity (VGA) protocol. Research questions addressed themes of Risk Factors, Stress, and Mental Health; Protective Factors and Assets; Social Support; Connections to Community and Mentoring; and the Impact of Music Performance on Performers and Audience Members. The results, based upon interviews with 10 New Orleans musicians, reflect the important relationships between culture and resilience and provide an evidence base for disaster-relief work, community-based healing and practice, and interventions with at-risk populations.
Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.
Fiber type-specific analysis of AMPK isoforms in human skeletal muscle: advancement in methods via capillary nanoimmunoassay

We demonstrate the viability of applying capillary nanoimmunoassay technology to the study of fiber type-specific protein analysis in human muscle fibers. This novel technique enables a ~20-fold-lo...
Ecotourism, Religious Tourism, and Religious Naturalism

Much can be learned about both ecotourism and religious naturalism by bringing the two into conversation through the concept of religious tourism. In Part One I argue that ecotourism can be perceived as religious tourism based on the claim that the concept of nature that serves as a basis for ecotourism is also used in the process of ‘making nature sacred’. I use the example of tourism in Monte Verde, Costa Rica to show how nature can be made sacred in ecotourism and end the section by suggesting what we might gain from looking at ecotourism in this way. In Part Two I describe religious naturalism, then explore how thinking of ecotourism as religious tourism might address concerns regarding religious practice, conceptions of nature, and the apparent inability of religious naturalism’s non-anthropocentric ethic to deal with issues of environmental racism and social justice.
Corporate environmental commitment and financial performance: Moderating effects of marketing and operations capabilities

Abstract Previous studies linking corporate environmental initiatives with financial performance primarily have focused on main effects and generated inconsistent findings, offering an incomplete understanding of this relationship and potential contingency factors. This study examines whether marketing and operations capabilities enhance the financial effects of corporate environmental commitment (CEC). Analyses of a large panel data sample reveal that CEC can improve both near-term profitability and forward-looking value for firms with strong marketing capability. In contrast, operations capability only moderates the impact of CEC on firm value. In addition, this study reveals a bidirectional relationship between CEC and firm performance and finds that a firm's slack resource (short-term profitability) and marketing capability serve as antecedents of CEC. These findings suggest unique implications for marketing managers, chief executives, investors, and policy makers.
Acute Ischemic Stroke in a Young Woman With No Known Risk Factors.

We aim to highlight a potentially morbid consequence of foam-sclerotherapy for the treatment of varicose veins.We report a case of a 41-year-old woman with no significant medical history who presented to the emergency department with sudden onset of focal neurologic deficits. She had undergone varicose vein treatment with foam sclerotherapy 2 days prior. Magnetic resonance imaging of the brain showed acute cerebellar infarct. Computed tomography angiography was unremarkable. Transesophageal echocardiography showed the presence of a very small patent foramen ovale.Transient neurologic symptoms reported in patients undergoing venous foam sclerotherapy might have been transient ischemic attacks or acute ischemic strokes. The risk of these neurologic complications should be explained to all patients undergoing foam sclerotherapy so they can make an informed decision of screening echocardiography prior to the procedure.Onset of neurologic symptoms can be immediate or delayed in patients undergoing venous foam sclerotherapy. Early recognition of neurologic deficits resulting from paradoxical gas embolism and its treatment with hyperbaric oxygen can prevent permanent disability.
The importance of genotype identity, genetic heterogeneity, and bioinformatic handling for properly assessing genomic variation in transgenic plants.

The advent of –omics technologies has enabled the resolution of fine molecular differences among individuals within a species. DNA sequence variations, such as single nucleotide polymorphisms or small deletions, can be tabulated for many kinds of genotype comparisons. However, experimental designs and analytical approaches are replete with ways to overestimate the level of variation present within a given sample. Analytical pipelines that do not apply proper thresholds nor assess reproducibility among samples are susceptible to calling false-positive variants. Furthermore, issues with sample genotype identity or failing to account for heterogeneity in reference genotypes may lead to misinterpretations of standing variants as polymorphisms derived de novo. A recent publication that featured the analysis of RNA-sequencing data in three transgenic soybean event series appeared to overestimate the number of sequence variants identified in plants that were exposed to a tissue culture based transformation process. We reanalyzed these data with a stringent set of criteria and demonstrate three different factors that lead to variant overestimation, including issues related to the genetic identity of the background genotype, unaccounted genetic heterogeneity in the reference genome, and insufficient bioinformatics filtering. This study serves as a cautionary tale to users of genomic and transcriptomic data that wish to assess the molecular variation attributable to tissue culture and transformation processes. Moreover, accounting for the factors that lead to sequence variant overestimation is equally applicable to samples derived from other germplasm sources, including chemical or irradiation mutagenesis and genome engineering (e.g., CRISPR) processes.
Selenium and Reproductive Function in Boars Fed a Low Selenium Diet

A study was conducted with 24 crossbred boars (77.5 +/- 2.8 days of age) to determine the effects of low Se status on various spermatozoal characteristics and on Se concentration in semen, serum and primary and accessory reproductive tissues. All boars were fed a low Se diet (cornstarch and Torula yeast) ad libitum. Twelve boars were injected every 14 +/- 1 days with sodium selenite (.33 mg Se/kg body weight) and 12 served as saline-treated controls (low Se status). At 210 +/- 5 days of age, six boars in each group were slaughtered, and serum and various tissues were collected and assayed for Se. Treated boars had higher concentrations of Se in the serum (P less than .001), kidney (P less than .001), liver (P less than .001), heart (P less than .001), skeletal muscle (P less than .01), testis (P less than .01), epididymis (P less than .05), seminal vesicle (P less than .01), bulbourethral gland (P less than .001) and prostate (P less than .001) tissues. Starting at 230 +/- 4 days of age, semen samples were collected from the remaining boars at 4- to 6-day intervals until a total of four ejaculates had been obtained from all but two boars. There were no significant treatment differences in semen volume, percentage normal spermatozoa, percentage viability or spermatozoa concentration/milliliter; however, for combined semen Se data, treated boars had more Se than control boars in the whole semen (.165 vs .07 ppm, respectively), spermatozoa (.418 vs .199 micrograms/10(9) spermatozoa, respectively) and seminal plasma (.03 vs .007 ppm, respectively). The boars were castrated around 250 days of age, and no differences in testis length, diameter, weight and spermatozoal concentration were found between groups. Additionally, there were no apparent differences in daily gain, daily feed consumed and the feed to gain ratio between control and treated boars. Although concentrations of Se in serum, semen and reproductive tissues were much lower in control boars than in treated boars, no apparent impairment of sperm morphology or viability resulted from low Se status.
Dividing up the question answering process

This paper describes a question answering program which divides question answering into two separate processes: answer formation and answer expression. Rather than gathering possible answers and choosing the best among them, the program accesses the database and finds all components of possible answers, e.g. a causal chain, and then passes this information to an expression program which formulates a proper answer.
Mitral paravalvular leak: description and assessment of a novel anatomical method of localization

PERCUTANEOUS CLOSURE OF MITRAL PARAVALVULAR LEAKS (PVL) has been demonstrated to be a safe and effective alternative to open surgical repair in selected patients with mitral paravalvular regurgitation [(1,2)][1]. Successful PVL closure depends on accurate localization of the site of regurgitation
The Contingent Attorney's Fee Tax Trap: Ethical, Fiduciary Duty, and Malpractice Implications

In employment and civil rights lawsuits, the alternative minimum tax may cause a plaintiff's net recovery to be taxed at rates significantly higher than the current maximum rate of 35 percent. This Essay discusses the ethical, fiduciary duty and malpractice implications for lawyers representing plaintiffs who may be affected by this tax trap.
The Deconstruction of the Administrative Judiciary

This article addresses the controversial divergence of opinions by the U.S. Court of Appeals for the Tenth Circuit and the U.S. Court of Appeals for the District of Columbia regarding the constitutionality of the appointment of administrative law judges. After a thorough analysis of both decisions, the author concludes the Tenth Circuit's holding that the Securities and Exchange Commission's administrative law judges are inferior officers under the Appointments Clause is well-reasoned and correctly applies Supreme Court precedent. The author then discusses the impact this holding will have on the administrate adjudicatory process if the Tenth Circuit's decision is upheld by the Supreme Court. The author concludes by addressing potential means for reconstructing the administrative judiciary.
American Muslim Physician Attitudes Toward Organ Donation

Religious beliefs and values impact Muslim patients' attitudes toward a variety of healthcare decisions, including organ donation. Muslim physician attitudes toward organ donation, however, are less well studied. Utilizing a national survey of physician members of the Islamic Medical Association of North America, relationships between religiosity, patterns of bioethics resource utilization, and sociodemographic characteristics with attitudes toward organ donation were assessed. Of 255 respondents, 251 answered the target question, “in your understanding, does Islamic bioethics and law permit organ donation?.” 177 respondents (70%) answered positively, 30 (12%) negatively, and 46 (18%) did not know. Despite the overwhelming majority of respondents believing organ donation to be permitted by Islamic bioethics and law, fewer than one-third (n = 72, 30%) are registered donors. Several sociodemographic features had a positive association with believing organ donation to be permitted: ethnic descent other than that of South Asian, having immigrated to the USA as an adult, and male sex. When using a logistic regression model controlling for these three variables as potential confounders, the best predictor of Muslim physicians believing organ donation to be permissible was utilization of an Imam as a bioethical resource (odds ratio 5.9, p = 0.02). Religiosity variables were not found to be associated with views on the Islamic permissibility of organ donation. While Muslim American physicians appear to believe there is religious support for organ donation, only a minority sign up to be donors. Greater study is needed to understand how physicians' attitudes regarding donation impact discussions between patients and physicians regarding the possibility of donating and of receiving a transplant.
The Future of Pacifism

In this chapter the future of pacifism is contemplated. Five alternative futurescapes are sketched, each a possible scenario for the future. In three of them wars between belligerents continue to take place as either limited conflicts or as a new world war. In the fourth a supranational world order is adopted or imposed, which enforces peace using military might where necessary. In the fifth futurescape there emerges a sense of world family that puts violence toward other members of that family beyond the pale of consideration. Pacifism would have a role to play in the first four futurescapes. In the fifth, however, the advocacy of pacifism as a repudiation of war would lose its point, for the renunciation of war would already be essentially universal.