cssi/SciSciGPT-SciSciNet huggingface dataset:
Adverse effects of oral naltrexone: analysis of data from two clinical trials.

Rationale: Naltrexone treatment of alcohol dependence is associated with adverse events that may limit its effectiveness. Consequently, understanding the impact of adverse events on medication compliance and treatment retention may enhance naltrexone therapy of alcoholism. Objectives: To examine the relations among adverse events, drinking behavior, medication compliance and study retention in alcoholics receiving naltrexone for relapse prevention. Methods: The current report is based on analysis of data from 92 subjects who participated in two previously published studies. Moderate or severe adverse effects were monitored weekly and categorized as either neuropsychiatric (NP) or gastrointestinal (GI). Medication compliance was determined by weekly urinary riboflavin testing. Study retention was determined by the proportion of study weeks completed by the subject. The causal relations among adverse events, medication compliance and study retention were analyzed separately for NP and GI adverse events using regression-based recursive path models. Results: Both the NP and GI models fit the data well [NP model: χ2(4)=0.59, P=0.96; GI model: χ2(4)=2.81, P=0.59]. NP adverse events exerted little influence on medication compliance (β=–0.17, P=0.071), but directly decreased the length of study retention (β=–0.35, P<0.001). In contrast, there was a significant impact of GI adverse events on medication compliance (β=–0.29, P=0.002), but not directly on study retention (β=–0.14, P=0.081). Conclusion: Future studies aimed at enhancing the effectiveness of naltrexone should examine ways of reducing both NP and GI adverse events, in order to enhance both medication compliance and treatment retention.
Cloning and expression of a cDNA encoding uridine kinase from mouse brain.

Abstract Uridine kinase is the rate-limiting enzyme in the pyrimidine salvage pathway of all mammalian cells. A cDNA for uridine kinase from mouse brain has been isolated, sequenced, and characterized. This is the first report of a complete nucleotide sequence for mammalian uridine kinase. The isolated cDNA is only 95% complete, missing the first 17 codons. The correct 5′-terminus sequence was obtained from high-stringency screening of a mouse liver genomic DNA library. The translated cDNA sequence encodes a protein of 277 amino acids (Mr31,068). A truncated form of the cDNA was expressed inEscherichia coli.The expressed protein displayed uridine kinase activity and readily formed a tetramer, the most active form of the wild-type enzyme. Analysis of the amino acid sequence identified the three ATP-binding site consensus motifs. The predicted secondary structure for uridine kinase and the sequence comparison with three kinases having known crystal structures are consistent with uridine kinase having an α/β core structure of the nucleotide-binding fold found in many kinases. We have also isolated and cloned a nonfunctional, processed pseudogene from mouse genomic DNA. This pseudogene sequence is 94% identical with the coding DNA.
The Power of Gametes versus the Tyranny of Master Narratives: Commentary

Rosanna Hertz’ s fascinating article describes the efforts of mothers and children to turn either anonymous or known sperm donors into “ dads” of one kind or another. These families offer what Hertz describes as a window on the “ social ways in which blood kinship creates families.” In her comparative case study of twenty-e ve sperm donor‐ assisted families, Hertz uses powerful metaphors and images to guide the reader through an interactionist analysis of the genetic, psychological, and social boundaries of “ family” and “ kinship.” Hertz’ s comparison of anonymous and known donor families offers many insights into the “ uncoupling of genetic from social parenthood.” For example, with anonymous donor families, we learn how “ absence forms a presence,” how the “ gift of gametes . . . becomes a token of the child’ s identity and self,” and how mothers create “ ghostlike” fathers to help their children develop looking-glass selves by imagining how their absent fathers might think of them. Known donors provide more information for the crafting of looking-glass selves but remain in the shadows while the mothers vigilantly guard the boundaries between genetic and social parenthood. After summarizing Hertz’ s e ndings, I attempt to pull still more theory from the author’ s rich data.
tradition against itself

The Inner Conflict of Tradition: Essays in Indian Ritual, Kingship and Society. J. C. HEESTERMAN.
Behavioral and endocrine responses of sows to prostaglandin F2 alpha and cloprostenol.

Behavioral and endocrine changes in the sow following injection with prostaglandin Fse (PGFse) or its analogue, cloprostenol (CLO), were monitored to identify endocrine correlatesof prepartum activity (nest-building). On Day 112 postcoitum, within 15 mm after Injection with 10 mg PGF,,,, sows offered straw in pens engaged in intense prepartum activity, but few behavioral changes occurred during the first 2 h following administration of 175 �ag CLO. The temporal pattern of prepartum activity, however, was affected by both prostaglandins. In control sows, most prepartum activity came during Hours 16-0 before delivery of first piglet (delivery). After CLO, sows engaged in nest-building more during Hours 32-17 and less during Hours 16-0. In another experiment, sows in farrowing crates were injected with saline, 175 �tg CLO, or 10 mg PGF,,, on Day 112 and blood was collected 0, 15, 30, 60, and 90 miss later. Another sample was collected when spontaneous prepartum activity was first observed. For approximately 90 miii after PGF2,, treatment, sows rooted, pawed, and bit and rubbed laces on crate bars; alter saline and CW, this behavior was rarely observed. After prostaglandin treatment, plasma progesterone tended to decline, a 10. fold rise in relaxin came within 15 mm, but estrone did not change. Plasma prolactin rose 10.fold within 30 miss after PGFse treatment, and rose more gradually after CLO treatment. When sows exhibited spontaneous prepartum activity (approximately 7 h before delivery), endocrine status was characterized by low progesterone, high estrone:progesterone ratio, and high prolactin. Similar profiles of progesterone and relaxin after either PGF2,, or CLO treatment indicated that changes in luteal hormones were not directly responsible for behavioral differences. Only prolactin was associated with both PGF,,,-induced and spontaneous prepartum activity.
Long-Term Pulmonary Function in Survivors of Childhood Cancer

Purpose This study was undertaken to determine the magnitude of pulmonary dysfunction in childhood cancer survivors when compared with healthy controls and the extent (and predictors) of decline over time. Patients and Methods Survivors underwent baseline (t1) pulmonary function tests, followed by a second comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3 years). Survivors were also compared with age- and sex-matched healthy controls at t2. Results Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9 years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years). Compared with odds for healthy controls, the odds of restrictive defects were increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to 15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0; 95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radia...
Exact solutions for chemical bond orientations from residual dipolar couplings

New methods for determining chemical structures from residual dipolar couplings are presented. The fundamental dipolar coupling equation is converted to an elliptical equation in the principal alignment frame. This elliptical equation is then combined with other angular or dipolar coupling constraints to form simple polynomial equations that define discrete solutions for the unit vector(s). The methods are illustrated with residual dipolar coupling data on ubiquitin taken in a single anisotropic medium. The protein backbone is divided into its rigid groups (namely, its peptide planes and C α frames), which may be solved for independently. A simple procedure for recombining these independent solutions results in backbone dihedral angles φ and ψ that resemble those of the known native structure. Subsequent refinement of these φ-ψ angles by the ROSETTA program produces a structure of ubiquitin that agrees with the known native structure to 1.1 A C α rmsd.
Two-dimensional equalization in coherent and incoherent page-oriented optical memory

The low-pass nature of the optical systems (both coherent and incoherent) used for volume optical storage results in the presence of intersymbol interference (ISI) at the output of these systems. Since ISI can seriously degrade retrieved data fidelity, we consider the design of linear, minimum-mean-square-error equalizers for two-dimensional finite-contrast optical ISI channels. Signal models are developed and filter design is conducted for various operating environments associated with particular implementations of page-oriented optical memories (POM’s). Specifically, we consider optically incoherent systems dominated by either postdetection thermal or photon-shot noise, and coherent systems are treated subject to either postdetection thermal or coherent speckle noise. Simple locally connected postdetection filters (equalizers) are designed to reduce the impact of ISI and finite contrast on retrieved data. It is demonstrated how these simple ISI mitigation algorithms may be used to improve the fidelity (i.e., bit error rate) of retrieved data and also to enhance the space–bandwidth-product (SBP), the storage density, and the memory capacity of POM systems. The notion of a fidelity-based SBP is quantified and shown to depend strongly on the receiver processing. The fidelity-based SBP of thermal-noise-dominated incoherent imaging systems operating at the Rayleigh resolution is shown to improve by 28% through the use of equalization, and a 48% SBP increase is found in the shot-noise-dominated case. More dramatic gains are found for thermal-noise-dominated coherent systems operating at the Rayleigh resolution, with 116% SBP gains typical in the infinite-contrast case and 30% gains possible for low-contrast (C=4) cases. Equalization is also shown to facilitate a capacity increase for holographic POM systems, providing a 47% increase in the number of stored pages and the storage density for a system operating at the Rayleigh resolution. The maximum storage density in holographic POM is increased by 20% through the use of equalization.
New Approach to Field Theory

A field theory is quantized covariantly on Lorentz-invariant surfaces. Dilatations replace time translations as dynamical equations of motion. This leads to an operator formulation for Euclidean quantum field theory. A covariant thermodynamics is developed, with which the Hagedorn spectrum can be obtained, given further hypotheses. The Virasoro algebra of the dual resonance model is derived in a wide class of 2-dimensional Euclidean field theories.
Toward a Model of Work Redesign for Better Work and Better Life

Flexible work accommodations provided by employers purport to help individuals struggling to manage work and family demands. The underlying model for change is accommodation—helping individuals accommodate their work demands with no changes in the structure of work or cultural expectations of ideal workers. The purpose of this article is to derive a Work Redesign Model and compare it with the Accommodation Model. This article centers around two change initiatives—Predictability, Teaming and Open Communication and Results Only Work Environment—that alter the structure and culture of work in ways that enable better work and better lives.
How Next-Generation Sequencing and Multiscale Data Analysis Will Transform Infectious Disease Management

Recent reviews have examined the extent to which routine next-generation sequencing (NGS) on clinical specimens will improve the capabilities of clinical microbiology laboratories in the short term, but do not explore integrating NGS with clinical data from electronic medical records (EMRs), immune profiling data, and other rich datasets to create multiscale predictive models. This review introduces a range of “omics” and patient data sources relevant to managing infections and proposes 3 potentially disruptive applications for these data in the clinical workflow. The combined threats of healthcare-associated infections and multidrug-resistant organisms may be addressed by multiscale analysis of NGS and EMR data that is ideally updated and refined over time within each healthcare organization. Such data and analysis should form the cornerstone of future learning health systems for infectious disease.
The One-Box Challenge: Providing a Federated Search That Benefits the Research Process

The one-box federated search of databases brings as many challenges as promises to database searching, especially in terms of adapting these systems to user needs and the effects this new mode of searching will have on users' research behaviors. This issue of “The Balance Point” presents several librarians with strong interests in reference and instruction, who tell the story of adapting a federated search system for their libraries and reflect upon how federated searching can change the way students do research and on the implications federated searching has on information literacy skills and the quality of results found.
Old and new pathways of protein export in chloroplasts and bacteria

Targeting of chloroplast proteins to the thylakoid membrane is analogous to bacterial secretion, and much of what we know has been learned from secretory mechanisms in Escherichia coli. However, chloroplasts also use a delta pH-dependent pathway to target thylakoid proteins, at least some of which are folded before transport. Previously, this pathway seemed to have no cognate in bacteria, but recent results have shown that the HCF106 gene in maize encodes a component of this pathway and has bacterial homologues. This delta pH-dependent pathway might be an ancient conserved mechanism for protein translocation that evolved before the endosymbiotic origin of plastids and mitochondria.
Prevalence of health-related behaviors among physicians and medical trainees.

The authors studied the prevalence of health-promoting and health-risking behaviors among physicians and physicians-in-training. Given the significant potential for negative outcomes to physicians’ own health as well as the health and safety of their patients, examination of the natural history of this acculturation process about physician self-care and wellness is critical to the improvement of the western health care delivery system. 963 matriculating medical students, residents, or attending physicians completed the Empathy, Spirituality, and Wellness in Medicine (ESWIM) survey between the years 2000 and 2004. Items specific to physician wellness were analyzed. These included healthy behaviors as well as risk behaviors. Both medical students and attending physicians scored higher in overall wellness than did residents. Residents were the lowest scoring group for getting enough sleep, using seatbelts, and exercising. Medical students were more likely to smoke tobacco and drink alcohol. Medical students reported less depression and anxiety and more social contacts. Medical school training may prevent students from maintaining healthy behaviors, so that by the time they are residents they exercise less sleep less and spend less time in organizational activities outside of medical school. If physicians do not engage in these healthy behaviors, they are less likely to encourage such behaviors in their patients and patients are less likely to listen to them even if they do talk about it.
The Life of the Saint and the Animal: Asian Religious Influence in the Medieval Christian West

This paper seeks to challenge the notion that European Christianity was untouched by Asian religious influence during much of the Common Era. Rather, I propose that certain Indian ethical tenets were incorporated into Christian ascetic practices as a consequence of interaction with heretical intermediaries. In medieval Europe, the spiritual kinship of animals and humans was widely taken for granted by common folk and heretical clerics. Indic religious doctrines on this subject may have diffused gradually into Western popular religion even while the Church worked systematically through official channels to prevent their transmission. Inspired by the work of Graeme MacQueen, I examine evidence of saint–animal interactions in several medieval hagiographies. These saints’ lives model ethical responsibility toward nonhuman life. I argue that Buddhist Jataka stories provide the prototype for these characters. Ultimately, similar ethical tenets were integrated into orthodox Christian asceticism by Saint Francis of Assisi. Some of Francis’s inspiration may have originated in Asia, later carried to Europe along the Silk Road as doctrines of the Manichees: secretive, syncretistic heretics continuously persecuted by the Church over the better part of a millennium.
A general framework for formalizing UML with formal languages

Informal and graphical modeling techniques enable developers to construct abstract representations of systems. Object-oriented modeling techniques further facilitate the development process. The Unified Modeling Language (UML), an object-oriented modeling approach, could be broad enough in scope to represent a variety of domains and gain widespread use. Currently, UML comprises several different notations with no formal semantics attached to the individual diagrams. Therefore, it is not possible to apply rigorous automated analysis or to execute a UML model in order to test its behavior, short of writing code and performing exhaustive testing. We introduce a general framework for formalizing a subset of UML diagrams in terms of different formal languages based on a homomorphic mapping between metamodels describing UML and the formal language. This framework enables the construction of a consistent set of rules for transforming UML models into specifications in the formal language. The resulting specifications derived from UML diagrams enable either execution through simulation or analysis through model checking, using existing tools. This paper describes the use of this framework for formalizing UML to model and analyze embedded systems. A prototype system for generating the formal specifications and results from an industrial case study are also described.
On Moral Enhancement

John Shook (2012) defines moral enhancement as something that results in detectable modifications of one's moral conduct. This account fails to distinguish moral enhancement from moral compulsion. ...
Contralateral acoustic reflex thresholds for tonal activators using wideband energy reflectance and admittance

The purpose of this study was to evaluate a new method for estimating the acoustic reflex threshold incorporating wideband (250–8000 Hz) measures of energy reflectance and admittance (M. P. Feeney ...
Issues in local government reform in India.

This paper reviews the status of rural and urban local governments in India. The focus is on the recent constitutional reforms that strengthen local government, (including subsequent supporting legislation), and the implications for changing local government to achieve more effective delivery of services to constituent populations. Particular attention is paid to finances and revenues, since enhancing local government fiscal resources is crucial for the success of reform in this dimension . An overview of the financial situation and resources of this level of government is provided, plus an economic analysis of the political, managerial and other institutional constraints on effective local government service provision.
Sailing into the wind: Exploring the relationships among ambidexterity, vacillation, and organizational performance

While sustainable high performance requires the capacity to simultaneously explore and exploit, the management literature is divided on the most feasible and efficient route toward this end. We review two proposed approaches for achieving simultaneously high levels of exploration and exploitation: organizational ambidexterity and organizational vacillation. To facilitate comparison, we map these approaches onto a common performance landscape, making precise the empirical question of which delivers superior long run performance. We then analyze canonical cases from both literatures, examining patterns of decision making and corresponding performance over time. These cases suggest that vacillation may offer higher long run performance than ambidexterity, while ambidexterity enhances performance on the margin when utilized within larger epochs of vacillation. We conclude that ambidexterity and vacillation are complements with respect to performance, albeit through different mechanisms. Copyright © 2012 John Wiley & Sons, Ltd.
Learning and memory deficits in mice lacking protease activated receptor-1

The roles of serine proteases and protease activated receptors have been extensively studied in coagulation, wound healing, inflammation, and neurodegeneration. More recently, serine proteases have been suggested to influence synaptic plasticity. In this context, we examined the role of protease activated receptor 1 (PAR1), which is activated following proteolytic cleavage by thrombin and plasmin, in emotionally motivated learning. We were particularly interested in PAR1 because its activation enhances the function of NMDA receptors, which are required for some forms of synaptic plasticity. We examined several baseline behavioral measures, including locomotor activity, expression of anxiety-like behavior, motor task acquisition, nociceptive responses, and startle responses in C57Bl/6 mice in which the PAR1 receptor has been genetically deleted. In addition, we evaluated learning and memory in these mice using two memory tasks, passive avoidance and cued fear-conditioning. Whereas locomotion, pain response, startle, and measures of baseline anxiety were largely unaffected by PAR1 removal, PAR1-/- animals showed significant deficits in a passive avoidance task and in cued fear conditioning. These data suggest that PAR1 may play an important role in emotionally motivated learning.
Designing Multithreaded Algorithms for Breadth-First Search and st-connectivity on the Cray MTA-2

Graph abstractions are extensively used to understand and solve challenging computational problems in various scientific and engineering domains. They have particularly gained prominence in recent years for applications involving large-scale networks. In this paper, we present fast parallel implementations of three fundamental graph theory problems, Breadth-First Search, st-connectivity and shortest paths for unweighted graphs, on multithreaded architectures such as the Cray MTA-2. The architectural features of the MTA-2 aid the design of simple, scalable and high-performance graph algorithms. We test our implementations on large scale-free and sparse random graph instances, and report impressive results, both for algorithm execution time and parallel performance. For instance, Breadth-First Search on a scale-free graph of 400 million vertices and 2 billion edges takes less than 5 seconds on a 40-processor MTA-2 system with an absolute speedup of close to 30. This is a significant result in parallel computing, as prior implementations of parallel graph algorithms report very limited or no speedup on irregular and sparse graphs, when compared to the best sequential implementation.
Development and testing of the Asthma Self-Management Questionnaire.

Background Assessing self-management knowledge can guide physicians in teaching patients necessary skills. Objective To develop and test the Asthma Self-Management Questionnaire (ASMQ). Methods The ASMQ was developed from patient interviews. Validity was evaluated by comparison with the established Knowledge, Attitude, and Self-Efficacy Asthma Questionnaire, and test-retest reliability was evaluated with repeated administration (mean, 5 days apart) in 25 patients (mean age, 41 years; 96% women). The ASMQ was further described in additional patients by comparison with cross-sectional self-management practices and longitudinal change in Asthma Quality of Life Questionnaire scores. Results The 16-item, multiple-choice ASMQ measures knowledge of preventive strategies, inhaler use, and medications and generates a score of 0 to 100, with higher scores indicating more correct responses. The ASMQ was correlated with the Knowledge, Attitude, and Self-Efficacy Questionnaire ( r = 0.58) and had a Cronbach α of 0.71. The correlation between administrations was 0.78, and the intraclass correlation coefficient was 0.58. When given to another 231 patients (mean age, 41 years; 74% women), the mean (SD) ASMQ score was 60 (20). Patients with better ASMQ scores were more likely to own peak flow meters ( P = .04) and to have received flu vaccines ( P = .03). For 12 months, these patients received self-management information through workbooks and telephone reinforcement. Patients with higher ASMQ scores after 12 months were more likely to have clinically important improvements in quality of life compared with patients with lower ASMQ scores (65% vs 46%; P = .01). Conclusions The ASMQ is valid and reliable and is associated with clinical markers of effective self-management and better asthma outcomes.
Deleuze and Film

David Martin-Jones and William Brown’s volume provides a provocative tour of Gilles Deleuze’s complex and creative thinking on film-philosophy. The twelve essays are primarily a commentary on Deleu...
Thymic Endocrinology and Prospects for Treating Thymic Involution

In the early 1960s, the central role of the thymus in cellular immunity was simultaneously and independently discovered by R. A. Good and co-workers and J. F. A. R Miller and co-workers (Good, 1991; Miller, 1991). The thymus has only recently been analyzed in a manner that allows an understanding, on the one hand, of the complicated and stepwise manner by which T cells mature and acquire the many surface receptors necessary for identifying antigen and the molecular and cellular world around them and, on the other hand, of the autocrine, paracrine, and endocrine influences that regulate their differentiation, proliferation, secretion, and cytotoxicity. It is the purpose of this review to focus on the endocrine thymus and to elaborate on those factors and mechanisms that contribute to thymic development and involution. The possibilities for therapeutic intervention to reverse thymic involution and induce new T-cell development for the treatment of secondary cellular immune deficiencies associated with diseases such as cancer, infection, and autoimmunity will be discussed.
Laboratory and Clinical Evaluation of White Blood Cell Differential Counts: Comparison of the Coulter VCS, Technicon H-1, and 800 Cell Manual Method

Eight hundred-cell manual white blood cell differential count evaluations of Coulter VCSTM and Technicon H-lTM included estimates of accuracy, imprecision, random and systematic errors, clinical relevance, and detection of immature neutrophils. Accuracy was acceptable, except for H-l testing of monocytes. Instrument imprecision was similar, except for tighter monocyte values as measured by the VCS. Deming regression determined random errors were greater for H-l monocytes and proportional errors were similar. Constant errors for the VCS were less than the H-l for neutrophils and monocytes and greater than the H-1 for eosinophils and lymphocytes. H-l morphologic false-negative rates were twice those for VCS. True-positive and falsenegative rates in cases with immature neutrophils were 70.6% and 20.3% for the VCS and 35% and 55.9% for the H-l. The reference false-positive rate was 4.4%. Clinically appropriate VCS flags were generated in distributionally abnormal cases. Predictive values were higher for the VCS.
The Effect of Deformation and Reinforcement Particles on the Grain Growth Behavior of MoSi2

The grain growth behavior of polycrystalline MoSi 2 and composites containing SiC particulates has been studied in the temperature range of 1200-1800°C during static annealing as well as under concurrent deformation conditions. Monolithic MoSi 2 , with ∼ 26 μm grain size appears to be extremely resistant to grain growth up to 1500°C. However, the grain growth rate above this temperature is quite rapid. When particulate reinforcements are used to reduce the grain size of MoSi 2 to 4.4 μm, a stable microstructure is maintained up to 1500°C. Accelerated grain growth kinetics are observed at 1800°C under conditions of large plastic strain. This enhanced grain boundary mobility is associated with particle sweeping and particle agglomeration effects. At lower temperatures, where dislocation creep is the more dominant deformation mechanism these effects are absent. In the presence of a Si concentration gradient extremely high growth rates of columnar MoSi 2 grains have been observed during reaction synthesis of MoSi 2 .
In Search of a Diversity Text: A Critical Review

Diversity courses can take on different structures depending on the needs of the student body, preferences of the instructor, and goals of the university. One major challenge is selecting a text that is comprehensive enough to address the needs of students and practitioners to facilitate strategies for managerial effectiveness. Three diversity texts were selected for this review, each contributing a unique perspective based on both subjective and objective meanings of diversity:1 Carr-Ruffino's (2007) seventh edition text, Managing Diversity: People Skills for a Multicultural Workplace; Harvey and Allard's (2008) fourth edition text, Understanding and Managing Diversity; and Thomas's (2005) Diversity Dynamics in the Workplace.
A HG-IFE-PIC Simulation Model for Ion Thruster Optics Plasma Flow

A three dimensional ion optics simulation model is developed based on the recently developed hybrid-grid immersed-finite-element particle-in-cell (HG-IFE-PIC) algorithm. This algorithm uses two dierent meshes, a uniform Cartesian mesh for PIC and a stretched Cartesian-based tetrahedral mesh for the field solve. The algorithm is designed to handle the complex boundary condition accurately while maintaining the computational speed of a standard PIC code. Simulations are performed to study the plasma flow inside the ion optics.
Abstract 3537: Stem-cell based selective delivery of alpha keto reductases for therapeutic targeting of residual androgens in prostate cancer

The twice as high incidence and mortality among African Americans (AA) compared to Caucasian Americans and other ethnic minorities remains elusive. The de novo synthesis of androgens by prostate tumors provides a significant survival advantage leading to outgrowth of castration resistant tumors. The “intracrine” production of androgens in the tumor microenvironment is greatly influenced by the synthesis of androgen metabolizing enzymes (AMEs) and the level of circulating hormones. Currently, targeting de novo synthesis of androgens in tumor microenvironment is singularly the toughest challenge presented to oncologists. Our present research attempts to identify and exploit the key players among the AMEs for targeting the backdoor pathway of DHT synthesis in castration resistant prostate cancer (CRPC). Comparative analysis of gene expression of AMEs in microdissected cells versus the adjacent normal tissue revealed AKR1C4 to be the most promising candidate for targeting the backdoor pathway in DHT synthesis. Existing literature supports this view since Type 1 3a-HSD enzyme has been shown to readily oxidize testosterone to Δ4-androstene-3, 17-dione in a substrate dependent reaction. Our analysis using recombinant AKR1C4 induced cytotoxicity and apoptosis in androgen dependent PC cells in vitro. Next, using a lentivirus construct, we genetically engineered tumor-tropic adipose-derived stem cells (ASCs) to express and secreted AKR1C14 (mouse homolog of AKR1C4). The results showed that ASCs are capable of expressing the enzyme, which can catabolize DHT in vitro and induce apoptosis in androgen dependent prostate cancer cells as shown by DHT Elisa, psPSA reporter assays and cytotoxicity and survival assays. Our current research plan is to examine the efficacy of tumor-tropic AKR1C14-expressing ASCs in targeting and inhibiting prostate metastatic growth in an animal model system. Citation Format: Manish Ranjan, Zakaria Abd Elmageed, Hogyoung Kim, Amrita Datta, Nobel Bhasin, Steven E. Braun, Debasis Mondal, Asim B. Abdel-Mageed. Stem-cell based selective delivery of alpha keto reductases for therapeutic targeting of residual androgens in prostate cancer. [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 3537. doi:10.1158/1538-7445.AM2015-3537
Identification and monitoring drug resistance of fungus in respiratory tract specimen in children

Objective:To understand the denomination of fungous infection and drug resistance in respiratory tract specimen at our hospital.Methods:665 fungi from Respiratory Tract specimen were identified by YBC verification card and drug sensitive experiment by ATB-FUNGS 2 INT trial. Results:Candida albicans occupied 57.1% in 665 fungi, Candida tropicalis,slick Monilia and Candida kruse occupied 24.8%?16.2% and 1.4% respectively.Respiration department,medical department, neonatorum department and blood department were 30.1%?13.5%?13.1% and 12.1% respectively.The sensitive rate of 665 fungi to 5FC,AMB,FAC and ITR was 93.4%?88.8%?89.6% and 75.2% respectively.Conclusion:Fungous infection and drug resistance are ascending tendency. Sensitivity of fungus to 5FC, AMB,FAC is comparatively high,sensitivity of fungus to ITR is comparatively low.Must be enhanced attention in the clinic.
T cells and eosinophils in asthma.

Abstract The bronchial inflammation characterising asthma represents a specialised form of cell-mediated immune reactions, in which products of activated CD4+ T cells orchestrate the accumulation and activation of granulocytes, particularly eosinophils. Through their toxic granule proteins, membrane derived lipid mediators and proinflammatory cytokines, eosinophils are suggested to be responsible for the changes in airway submucosal tissue resulting in altered airway responsiveness. T cell activation is followed by the synthesis and release of cytokines of which IL-3, IL-5 and GM-CSF are particularly important in the site-specific accumulation, prolonged survival and activation of eosinophils. This review focuses on the interaction of these two cell types with particular interest in the cytokines which may be responsible for the development of eosinophilic airway inflammation.
Trends and variability in the global dataset of glacier mass balance

Glacier mass balance (i.e., accumulation and ablation) is the most direct connection between climate and glaciers. We perform a comprehensive evaluation of the available global network of mass-balance measurements. Each mass-balance time series is decomposed into a trend and the variability about that trend. Observed variability ranges by an order of magnitude, depending on climate setting (i.e., maritime vs continental). For the great majority of glaciers, variability is well characterized by normally distributed, random fluctuations that are uncorrelated between seasons, or in subsequent years. The magnitude of variability for both summer and winter is well correlated with mean wintertime balance, which reflects the climatic setting. Collectively, summertime variability exceeds wintertime variability, except for maritime glaciers. Trends in annual mass balance are generally negative, driven primarily by summertime changes. Approximately 25 % of annual-mean records show statistically significant negative trends when judged in isolation. In aggregate, the global trend is negative and significant. We further evaluate the magnitude of trends relative to the variability. We find that, on average, trends are approximately −0.2 standard deviations per decade, although there is a broad spread among individual glaciers. Finally, for two long records we also compare mass-balance trends and variability with nearby meteorological stations. We find significant differences among stations meaning caution is warranted in interpreting any point measurement (such as mass balance) as representative of region-wide behavior. By placing observed trends in the context of natural variability, the results are useful for interpreting past glacial history, and for placing constraints on future predictability.
Rules and Rituals

All meaningful human action rests on shared understandings of what is intended by words, gestures, and behavior. Much of what is referenced by the term “culture” merely describes the content of those shared understandings within one community or another and the boundaries of meaning that divide them. “Political culture” thus refers to the limits and content of shared understandings within a community with respect to the deployment of power, including the creation of institutions, collective decision making within those institutions, and the selection of those to whom authority is assigned. The boundaries of a political community are defined by what the members have in common in terms of shared understandings of meaningful human action. In that sense, a shallow, limited set of understandings would define a much larger political community than a deep, extensive set. At one extreme, the notion of a “global” political culture might mean very little because only a very small number of actions carry universally understood meaning. At the other extreme, very small political communities often have a very rich political culture, so much so that an action by one of its members can simultaneously communicate multiple meanings that convey future intentions in great specificity. At both extremes, either a global political culture encompassing all humanity or extremely small communities containing a very small number of people, formal political institutions either do not exist or are very weak.
The unintended consequences of The Centers for Medicare and Medicaid Services pay-for-performance structures on safety-net hospitals and the low-income, medically vulnerable population:

Safety-net hospitals are hospitals with patient mix that is substantially composed of the uninsured, underinsured, and low-income, medically vulnerable patient populations. They are the hospitals of last resort for poor patients. This article examined the impact of The Centers for Medicare and Medicaid Services pay-for-performance reimbursement policies on the financial viability of safety-net hospitals. Studies showed that these policies, which are based on the principle of reward and punishment, might have unintentionally placed safety-net hospitals on financial disadvantage compared to other hospital organizations. Several studies implied that these payment structures might have resulted in a situation where safety-net hospitals that are serving poor patient populations become more susceptible to penalties than hospitals that are serving affluent patients.
Infectious Diseases: Leishmaniasis

The focus of this chapter is cutaneous infections due to Leishmania and the available evidence supporting specific treatments, both medical and surgical, for these conditions in children and adolescents. For some infections, adjunctive therapies are recommended in addition to first-line, second-line, and third-line treatments.
Elastic-plastic axisymmetric sinusoidal surface asperity contact

Closed-form finite-element empirical solutions are available for elastic-plastic spherical and sinusoidal contact. However, some of these models do not consider the effect of interaction with adjacent asperities or require extensive numerical resources because they employ a full 3-D model. The present work has considered these factors during modeling. The current finite element model (FEM) represents an axisymmetric elastic-plastic sinusoidal surface in contact with a rigid flat for a wide range of material properties and different values of the amplitude to wavelength ratio. The numerical results are compared with the existing elastic-plastic spherical contact model. Empirical equations are derived for the critical pressure at which two surface will reach complete contact. Complete contact occurs when there is no gap remaining between two contacting surfaces. An equation for the critical value of the amplitude of the sinusoidal asperity below which it will deform completely elastically from initial to complete contact is also established. The current study finds that for the cases which have amplitudes that fall below the critical value, and are elastic in nature, that the previously published perfectly elastic model can be used. The results are applicable for almost all kinds of metallic materials.
The Impending Ubiquity of Cognitive Objects

The word symbiosis (Merriam-Webster 2015) has its origins in biology where it means “the relationship between two different kinds of living things that live together and depend on each other.” When referring to symbiotic cognitive computing, we expand this definition to include both people and intelligent computational agents who work together in a partnership (Farrell et. al 2005). Cognitive objects embody these intelligent agents, providing a physical object that may sense, compute, react, and interact with the power of cognitive computing. In this paper, we describe a few preliminary design explorations that investigate the impact of being surrounded by cognitive objects during group meetings. We frame a research agenda around the construction, programming, and usage of cognitive objects in work and home environments, and for use cases across industries such as oil and gas, healthcare and agriculture.
Exotic meson decay widths using lattice QCD

A decay width calculation for a hybrid exotic meson h, with JPC=1-+, is presented for the channel h->pi+a1. This quenched lattice QCD simulation employs Luescher's finite box method. Operators coupling to the h and pi+a1 states are used at various levels of smearing and fuzzing, and at four quark masses. Eigenvalues of the corresponding correlation matrices yield energy spectra that determine scattering phase shifts for a discrete set of relative pi+a1 momenta. Although the phase shift data is sparse, fits to a Breit-Wigner model are attempted, resulting in a decay width of about 60 MeV when averaged over two lattice sizes.
The Making of Economics: Volume I: The Foundation

A classic returns. The third edition of The Making of Economics appeared in 1987. Now, in a major revision, Ray Canterbery brings the book right up to date with new chapters on the "casino economy" (a term the author invented to describe an economy driven by making money with money rather than focusing on real production, now overtaken by reality), Joseph Schumpeter, globalization, and general equilibrium. Canterbery retains the engaging flavor of the earlier editions by covering the times and ideas of the major economists, such as Smith, Ricardo, Malthus, Mill, and Marshall, while giving ample ink to the remarkable dissidents — Marx, Veblen, Galbraith, Heilbroner, and other "radicals". Canterbery again unmasks a traditional economics eschewing value judgements but itself standing on hidden ones even as he traces its origins to Isaac Newton's idea of an orderly universe. Personal references relate the great economists' ideas to the societies in which they lived, making the historical figures really come alive. Economics is displayed as a developing discipline, a discipline still evolving. This book is also available as a set with Volume II: The Modern Superstructure and Volume III: The Radical Assault.
Environmental Certification Systems and U.S. Environmental Law: Closer than You May Think

Many industrial organizations are committing to achieve improved environmental performance through non-governmentally instituted environmental certification programs. Such programs typically define the environmental standards that firms must meet as well as the organizational mechanisms required to achieve and "certify" compliance. Well known examples include the chemical industry's "Responsible Care" program, the International Organization for Standardization's "ISO 14000" environmental management program, and the Forest Stewardship Council's well-managed forests program. Because of their ostensibly private and voluntary nature, environmental certification programs are often presumed to be separate and distinct from law. In fact, however, they are deeply intertwined with law, and seem likely to have a significant influence on it over time. This paper describes the main areas of law likely to be affected, including traditional "environmental" law, as well as tort, property, tax, information, financial, and trade law. It ventures that many of the change processes will be informal and barely visible, as legal agents adjust their behavior and expectations to take account of the standards and organizational mechanisms established by certification systems. Because of the potentially high degree of legal influence wielded by certification systems, the legal system is likely to try to constrain or seek to channel certification systems, so the paper also describes the primary means through which this may happen. The effects of certification systems on environmental performance and economic efficiency have dominated discussion of their desirability to date. Preliminary scholarship indicates moderate gains on both dimensions, provided certain framework conditions (particularly functional public information systems and watchdog groups) exist. This paper argues that certification systems also pose larger questions for public governance. These include a structural expansion in the power of industrial organizations, a possible redefinition of the nature of public legitimacy, and a potential reconfiguration of the legal system itself, wherein law making processes may once again be privatized.
Three-dimensional model of electron beam generated plasma

A three-dimensional model for magnetized electron beam generated plasma is described, which includes a coupled fluid simulation of the bulk plasma and a Monte Carlo model for beam electrons. A modified form of the classical expressions for magnetized-plasma electron transport coefficients is used in the fluid plasma model. The plasma model is calibrated and validated using Langmuir probe measurements in a cylindrical electron beam generated plasma, where the beam is launched parallel to the magnetic field. The electron density (n e ) and temperature (T e ) are measured along and across the beam for several gas pressures and magnetic fields in Ar. The validated plasma model is then used to examine a three-dimensional electron beam generated plasma system. Generally, plasma densities are on the order of 1016 m−3 and, since there is no externally applied electric field in the plasma region, T e is below 1.25 eV in Ar. The chamber in the simulation is slightly asymmetric perpendicular to the axis of the electron beam and the magnetic field. This asymmetry combined with the E × B drift produce non-uniformities in the plasma even if the magnetic field is spatially uniform in the chamber. However, the cross-field plasma uniformity can be controlled by tailoring the magnetic field profile to enhance or reduce plasma production near the periphery of the chamber.