cssi/SciSciGPT-SciSciNet huggingface dataset:
Persistent Expression of Hepatitis C Virus Non-Structural Proteins Leads to Increased Autophagy and Mitochondrial Injury in Human Hepatoma Cells

HCV infection is a major cause of chronic liver disease and liver cancer in the United States. To address the pathogenesis caused by HCV infection, recent studies have focused on the direct cytopathic effects of individual HCV proteins, with the objective of identifying their specific roles in the overall pathogenesis. However, this approach precludes examination of the possible interactions between different HCV proteins and organelles. To obtain a better understanding of the various cytopathic effects of and cellular responses to HCV proteins, we used human hepatoma cells constitutively replicating HCV RNA encoding either the full-length polyprotein or the non-structural proteins, or cells constitutively expressing the structural protein core, to model the state of persistent HCV infection and examined the combination of various HCV proteins in cellular pathogenesis. Increased reactive oxygen species (ROS) generation in the mitochondria, mitochondrial injury and degeneration, and increased lipid accumulation were common among all HCV protein-expressing cells regardless of whether they expressed the structural or non-structural proteins. Expression of the non-structural proteins also led to increased oxidative stress in the cytosol, membrane blebbing in the endoplasmic reticulum, and accumulation of autophagocytic vacuoles. Alterations of cellular redox state, on the other hand, significantly changed the level of autophagy, suggesting a direct link between oxidative stress and HCV-mediated activation of autophagy. With the wide-spread cytopathic effects, cells with the full-length HCV polyprotein showed a modest antioxidant response and exhibited a significant increase in population doubling time and a concomitant decrease in cyclin D1. In contrast, cells expressing the non-structural proteins were able to launch a vigorous antioxidant response with up-regulation of antioxidant enzymes. The population doubling time and cyclin D1 level were also comparable to that of control cells. Finally, the cytopathic effects of core protein appeared to focus on the mitochondria without remarkable disturbances in the cytosol.
Migration of Landlocked Atlantic Salmon Smolts and Effectiveness of a Fish Bypass Structure at a Small-Scale Hydroelectric Facility

Abstract Downstream movements by smolts of Atlantic salmon Salmo salar were monitored with radiotelemetry to assess the effectiveness of an angled trash rack and fish bypass structure at a small hydroelectric dam on the Boquet River, New York. Telemetry of 170 Atlantic salmon smolts and visual observations of stocked smolts were used to determine aspects of migration behavior. Smolts began mass migrations after river temperatures reached or exceeded 10°C. Many radio-tagged smolts interrupted movements upon reaching ponded waters or the dam. River flow did not affect the frequency of migratory movements, dam passages, or rate of movement (P > 0.05). Migrations lasted approximately 30 d. Passages at the dam occurred primarily at night (61%); diurnal passages (17%) and crepuscular passages (17%) were of secondary importance, and timing of 5% of the passages was undetermined. All passages were through the bypass or over the spillway when angled trash racks were in place. Six passages occurred when trash racks...
Logistic Surplus‐Production Model with Explicit Terms for Growth, Mortality, and Recruitment

Abstract Conventional interpretations of the logistic equation and the logistic surplus-production model appear to indicate that regulation of population size occurs as a result of competition for resources among the recruited members of a population. Compensation for fishing mortality may involve increased growth of adults and an increase in fecundity, but the major compensatory factor is increased survival of early life stages. In this study, the logistic surplus-production model is formulated in explicit terms for growth, reproduction, and mortality, and in this new formulation the capacity of a population to increase and sustain a fishery is based on a stock-recruitment relation that is a more realistic interpretation of fishery dynamics. All parameters can be estimated with catch and effort data. The models were applied to the American lobster Homarus americanus fishery in Maine and the spiny dogfish Squalus acanthias fishery. There is a considerable difference in the stock-production curves between ...
“Are You My Friend?”: How Two Young Children Learned To Get Along with Others

Abstract This study recorded and analyzed the process of emotional socialization that occurred during a primary prevention program conducted in an urban day care center with 4-year-old children considered at risk for academic failure. A case study approach monitored the progress of two children through the yearlong course of the primary prevention project, using qualitative observation and interview methods. The purpose of the project was to isolate and describe the key factors in the primary prevention program that appeared particularly influential in the emotional socialization process. The study described the changes in social skills and emotional expression in the two children over the course of the intervention. The study also described and examined how the different components of the program interacted to effect change.
The chemistry of vicinal tricarbonyls. Formation of carbazole derivatives

Abstract The indole tricarbonyl derivative 1 reacts with Schiff bases 2a-c to form substituted carbazoles 3a-c.
48 GHz static frequency dividers in transferred-substrate HBT technology

In addition to an ultrahigh heterojunction bipolar transistor bandwidth, the transferred-substrate process offers the significant advantages of a low parasitic microstrip wiring environment and a low thermal impedance environment. The first digital integrated circuits using this technology, D-flipflops connected as 2:1 static frequency dividers, are reported.
Potentially avoidable hospitalizations of dually eligible Medicare and Medicaid beneficiaries from nursing facility and Home- and Community-Based Services waiver programs.

Objectives: Beneficiaries dually eligible for Medicare and Medicaid are of increasing interest because of their clinical complexity and high costs. The objective of this study was to examine the incidence, costs, and factors associated with potentially avoidable hospitalizations (PAH) in this population. Design: Retrospective study of hospitalizations. Setting: Hospitalizations from nursing facilities (NF) including Medicare and Medicaid-covered stays, and Medicaid Home and Community-Based Services (HCBS) waiver programs. Participants: Dually eligible individuals who received Medicare skilled nursing facility (SNF) or Medicaid NF services or HCBS waiver services in 2005. Interventions: None. Measurements: Potentiall avoidable hospitalizations were defined by an expert panel that identified conditions and associated Diagnostic Related Groups (DRGs) which can often be prevented or safely and effectively managed without hospitalization. Results: More than one-third of the population was hospitalized at least once, totaling almost 1 million hospitalizations. The admitting DRG for 382,846 (39%) admissions were identified as PAH. PAH rates varied considerably among states, and blacks had a higher rate and costs for PAH than whites. Five conditions (pneumonia, congestive heart failure, urinary tract infections, dehydration, and chronic obstructive pulmonary disease/asthma) were responsible for 78% of the PAH. The total Medicare costs for these hospitalizations were $3 billion, but only $463 million for Medicaid. A sensitivity analysis, assuming that 20%�60% of these hospitalizations could be prevented, revealed that between 77,000 and 260,000 hospitalizations and between $625 million and $1.9 billion in expenditures could be avoided annually in this population. Conclusion: Potentially avoidable hospitalizations are common and costly in the dually eligible population. New initiatives are needed to reduce PAH in this population as they are costly and can adversely affect function and quality of life.
Gregory Palamas among the Turks and Documents of His Captivity as Historical Sources

AMONG the papers of Spyridon Lampros published in the Neos Hellenomnemon posthumously' is a transcript from an Athonite manuscript containing a pastoral epistle of the leader of the hesychasts, Gregory Palamas, archbishop of Thessalonica (1347-1360), who was proclaimed a saint of the Greek Orthodox Church shortly after his death in 1360.2 The contents of this epistle are of great interest to the student of Graeco-Turkish relations, as they describe the observations and experiences of Gregory Palamas as a captive among the Osmanli Turks during that crucial period in history when they crossed the Dardanelles and gained a secure footing in Europe. Especially noteworthy are the archbishop's accounts of the Greek communities still existing in Orhan's realm and of the impact of Islam on Christianity in the last Byzantine stronghold in Asia Minor. It is to be regretted that no historian of the foundation of the Ottoman Empire has paid attention to this important document. Until 1922 it was accessible only in manuscripts, in St Panteleemon's Monastery at Mt Athos, in the National Library at Athens, in the Bibliotheque Nationale in Paris, and elsewhere. The Parisian manuscript must have been known to Du Cange, for in his Glossarium ad scriptores mediae et infimae graecitatis (p. 1535) he includes the unique word TraaLjuavns and cites the epistle of Gregory Palamas to the Thessalonians as its source. In our own times, Prof. G. Papamichael of the University of Athens, in his book on Gregory Palamas (p. 141), makes brief mention of the prelate's captivity, but does not seem to be aware of the fact that the 'Achaimenidae' whom he calls pirates (7raparaiL K TriS IVXj rS TrV 'AXagIEuevSwv), are no other than the Osmanli Turks,3 whom fourteenth-century writers called by an archaic name Achaimenidae or Persians, after the classicist fashion of the times. Papamichael evidently did not read the epistle itself, for, had he done so, the identity of the Achaimenidae would have been obvious (the text reads ros
Measurement of the flow of molten polymers through short capillaries

A method of treating experimental flow measurements on high polymers to obtain the basic shear diagram is described. Shear stress data are corrected to eliminate capillary end effects, and shear rate data are modified for the non-Newtonian behavior of the materials. Differences in flow behavior of commercial low-density polyethylenes are illustrated, and the effects of the two corrections are demonstrated. The method is applicable to other polymer melts. Although the data could be expressed by the power law, the fact that logarithmic plots of shear stress versus shear rate are not linear suggests that such relationships would be approximate. The data are expressed better by the threeconstant Powell-Eyring equation, although the significance of the three parameters is uncertain. The need to obtain the rheological constants from the basic shear diagram rather than from an uncorrected or partially corrected capillary flow diagram is emphasized. In support of previous investigators, irregularities in the extrudate were observed at high shear stresses. However, it was not possible to determine at what pressure the roughness was initiated. The shear diagrams calculated from the experimental data do not exhibit any point of inflection as reported in some studies.
A mathematical model for treatment-resistant mutations of hiv.

In this paper, we propose and analyze a mathematical model, in the form of a system of ordinary differential equations, governing mutated strains of human immunodeficiency virus (HIV) and their interactions with the immune system and treatments. Our model incorporates two types of resistant mutations: strains that are not responsive to protease inhibitors, and strains that are not responsive to reverse transcriptase inhibitors. It also includes strains that do not have either of these two types of resistance (wild-type virus) and strains that have both types. We perform our analysis by changing the system of ordinary differential equations (ODEs) to a simple single-variable ODE, then identifying equilibria and determining stability. We carry out numerical calculations that illustrate the behavior of the system. We also examine the effects of various treatment regimens on the development of treatment-resistant mutations of HIV in this model.
Synergistic effects of food insecurity and drug use on medication adherence among people living with HIV infection

Food insecurity and drug use are closely connected in the context of poverty, and both have been suggested to interfere with HIV medication adherence among people living with HIV/AIDS (PLWH). Yet the potential interaction between the two factors on adherence has not been examined. For this study we collected longitudinal data on HIV medication adherence among PLWH in Atlanta, GA, to assess a possible synergistic effect between the two factors on HIV medication adherence. People informed about the study came to the research site and completed an audio computer-assisted self-interview and instructions for pill counting. Over the next 5 weeks participants received three unscheduled follow-up phone assessments conducted 2 weeks apart to collect pill counts of their HIV medication. The prevalence of food insecurity was 60 % (488) and that of drug use was 33 % (274) in the sample of 809 participants. Among 770 participants who completed follow-up phone assessments, both food insecurity and drug use were associated with HIV medication adherence after adjusting for socio-demographic characteristics. The negative association between drug use and adherence persisted after further adjusting for health-related characteristics. Moreover, drug use appeared to moderate the effect of food insufficiency on adherence, with drug users who were food insufficient being the least likely to achieve 85 % adherence. Results from the current study demonstrate a synergism between food insecurity and drug use that may impede adherence among PLWH. The findings imply that the disruptive effects of food insecurity and drug use on adherence are likely to be intensified with the presence of each other, and encourage interventions to address the problem of HIV medication adherence from a multi-faceted perspective that takes into account detrimental combination of problem factors.
Free-radical transport from latex particles

A rate constant for the diffusion of monomer radicals from latex particles is derived using the transport equations describing the generation, diffusion, and reaction of monomer radicals within the particles. Calculations for styrene emulsion polymerization show that this “desorption constant” accounts for nonuniform distribution of monomer radicals within the particle while some previously published theories do not. The difference in the desorption constant calculated with the model derived in this work and the “uniform concentration” models could be an order of magnitude when diffusivity of monomer radicals in the particles is small. The monomer radical transport theory is extended to emulsion copolymerization. Desorption rate constants accounting for nonuniform distribution of monomer radicals are derived for emulsion copolymerization.
Quantitative Analyse von Metallen, insbesondere von Metallspuren, mit Hilfe der Atom-Absorptions-Spektrophotometrie

Methode und Apparatur zur quantitativen Bestimmung sowohl von geringen als auch von hoheren Konzentrationen von Metallen in verschiedenen Medien mit Hilfe der Atom-Absorptions-Spektrophotometrie werden anhand von Beispielen beschrieben. Anwendungsbereich, Genauigkeit, Nachweisgrenzen und mogliche Weiterentwicklung der Methode werden diskutiert.
Portable 7-channel binary recorder with punched paper-tape interface.

An integrated circuit, static, random access memory is employed for the recording of binary (yes/no) events at periodic instants of time. Sampling rate is variable with no lower limit. Recording capacity is expandable. Recorder output is interfaced for a standard 8-bit paper-tape punch wherein the seven channels are assigned to seven of the rows and the eighth is punched continuously at each clock cycle.
Design of optimal stimulation patterns for neuronal ensembles based on Volterra-type hierarchical modeling.

This paper presents a general methodology for the optimal design of stimulation patterns applied to neuronal ensembles in order to elicit a desired effect. The methodology follows a variant of the hierarchical Volterra modeling approach that utilizes input–output data to construct predictive models that describe the effects of interactions among multiple input events in an ascending order of interaction complexity. The illustrative example presented in this paper concerns the multi-unit activity of CA1 neurons in the hippocampus of a rodent performing a learned delayed-nonmatch-to-sample (DNMS) task. The multi-unit activity of the hippocampal CA1 neurons is recorded via chronically implanted multi-electrode arrays during this task. The obtained model quantifies the likelihood of having correct performance of the specific task for a given multi-unit (spatiotemporal) activity pattern of a CA1 neuronal ensemble during the ‘sample presentation’ phase of the DNMS task. The model can be used to determine computationally (off-line) the ‘optimal’ multi-unit stimulation pattern that maximizes the likelihood of inducing the correct performance of the DNMS task. Our working hypothesis is that application of this optimal stimulation pattern will enhance performance of the DNMS task due to enhancement of memory formation and storage during the ‘sample presentation’ phase of the task.
Abstract A35: Mothers and daughters: A key to acceptability of genetic testing for breast cancer among Latina women

Background: Breast cancer is a devastating disease. Identification of the BRCA1 and BRCA2 genetic mutations associated with it offer a potentially efficacious “early warning system.” However, investigators have expressed doubt that whether women are interested in knowing if they possess gene mutations, particularly minorities traditionally averse to dealing with a complex medical system. Additionally, effective means of addressing different levels of motivation among ethnic groups are unidentified. Here we determine the extent of interest in genetic testing among Latinas compared to non-Hispanic white (NHW) women. We also identify factors associated with interest in genetic testing. Finally, we show why differences in interest in genetic testing for breast cancer exist among groups of women. Material and Methods: We surveyed 290 women (153 Hispanic, 137 NHW) aged 26+ drawn from the catchment area of the San Antonio Cancer Therapy and Research Center. Targeted surveys included demographic information, measures assessing breast cancer knowledge, attitudes, behaviors, and medical and family history data. Based on verbal report, participants were assigned “high” or “moderate/low” cancer risk status according to American College of Medical Genetics Foundation guidelines. Pearson chi-square and student9s t-tests assessed bivariate relationships. Cochran Mantel-Haenszel chi-square identified analytic strata. Multivariate logistic regression revealed factors associated with interest in genetic testing. Results: 20% of women were not “very interested” in genetic testing for the BRCA1/BRCA2 mutation. Bivariate results showed ethnicity, use of nontraditional health care sources and negative perceptions of genetic testing were associated with low interest in genetic testing among all women. A multivariate model of genetic testing interest revealed several measures significantly associated with it, including Hispanic ethnicity (OR 5.74, p Conclusion: Genetic testing is generally acceptable to NHW and Hispanic women. However, Latinas are less likely to accept it than NHW. Whereas NHW women are influenced in their decision chiefly by use of nontraditional sources of medical care, Latinas are strongly influenced by perceptions of personal risk and having biological daughters. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A35.
THE MORPHOLOGY AND VITALITY OF BUSINESS DISTRICTS IN UPSTATE NEW YORK VILLAGES1

Field examination of 40 upstate New York villages reveals their commercial structure consists of six common elements: CBDs, railroad-oriented districts, early automobile expansion zones, mixed use areas, outlying commercial strips, and highway commercial intersections. The economic health of CBDs is quantified by a “downtown vitality index.”Variation in the observed vitality of downtowns may be attributed to site and situation factors, including downtown centrality with respect to the surrounding population, route layout, and regional location of the community. Downtowns are not being abandoned so much as changing their function.
The Development of the Coparenting Relationship Over the Transition to Parenthood.

Cette etude a porte sur le developpement de relations de coparentage, de son debut, des la transition a la condition de parent. Les experiences de coparentage et les interactions de 101 couples maries ont ete evaluees afin de determiner la validite du concept de coparentage et afin d'identifier des differences individuelles dans les trajectoires d'experiences de coparentage. Cinq conclusions principales ont emerge. Tout d'abord, le coparentage et le mariage sont des dimensions liees mais differenciees de la relation du couple, meme dans la toute petite enfance. Deuxiement, en moyenne, les experiences de coparentage sont positives et stables durant les six premiers mois de parentage, mais les peres sont bien plus satisfaits du coparentage que ne le sont les meres. Troisiemement, la relation maritale d'avant la naissance, et surtout les interactions maritales positives des peres, sont un indicateur important de si les deux parents se sentiront soutenus et valides dans le coparentage. Quatriemement, les changements dans les experiences maritales apres la naissance sont inversement lies au changement dans les experiences de coparentage, ce qui suggere qu'un aspect de la relation du couple peut etre maintenu au depens de l'autre aspect. Cinquiemement, d'autres facteurs qui changent avec le temps, particulierement les changements dans la division du mode de soin de l'enfant, predisent les manieres dont les experiences de coparentage se developpent. De plus, les peres ont fait etat de meilleures experiences de coparentage lorsque les bebes etaient percus comme ayant des temperaments plus faciles. En general, le developpement du coparentage semble prendre des chemins differents pour les meres et les peres.
Lahars initiated by the 13 November 1985 eruption of Nevado del Ruiz, Colombia

The eruption of Nevado del Ruiz in Colombia on 13 November 1985 was accompanied by the formation of four lahars (mud flows) triggered by the melting of glacial ice near the summit of the volcano. The lahars began as flows of water, sand and gravel, but they incorporated clay by eroding the soil along the steep valleys through which they passed. The largest flow was a cohesive debris flow, more than 45 m deep and moving at ∼12 ms−1 when it debouched from the canyon of the Rio Lagunilla 2.5 km from Armero, where it killed 25,000 people. The continuing volcanic activity and abundant remaining glacial ice create an extremely high risk of future destructive flows.
Uncovering generalized-network structure in matrices

Abstract A generalized-network matrix is a matrix that has at most two nonzeros per column. The generalized-network recognition problem for an arbitrary matrix A is the problem of determining a nonsingular matrix T , if one exists, such that TA is a generalized-network matrix. This paper presents a polynomial-time algorithm that under an assumption on the combinatorial structure of A solves the generalized-network recognition problem. A class of matroids called bicircular matroids play an important role in the development of the algorithm.
Effects of electric field annealing on recrystallization texture and plastic strain ratio (r value) of IF steel sheet

Effects of electric field annealing on recrystallization texture and average plastic strain ratio (r value) of IF steel sheet were studied by mean of X ray diffraction ODF analysis and the tensile test. Specimens of 75% cold-rolled IF steel sheet were annealed at 850flC for 25min,with and without electric field annealing respectively. Results show that the electric field annealing does not change the type of recrystallization texture and its formation mechanism in IF deep-drawing steel sheet, but improves the formation and development of recrystallization i-fiber texture, enhances the intensity of i-fiber texture, and retards the formation and development of c-fiber texture. Comparing with the conventional annealing, electric field annealing improves the average plastic strain ratio (r value). Possible reasons for the intensification of recrystallization i-fiber texture with the electric field applied may attribute to the reduction of stored energy, thus hindering the formation of other orientated nuclei and enhancing the nucleating ratio of i-oriented nuclei. And the intensification of recrystallization i-fiber texture was considered as the main reason for the enhancement of the plastic strain ratio (r value) in IF steel sheet.
A unified mathematical framework for population dynamics modeling

Abstract We report the development of a generalized mathematical framework that both unifies most existing ecological models as special cases that can be derived from a master equation and provides a flexible procedure for generating more general models with additional variables. In this sense, we present a general unified model of ecosystems (GUME). The master equation describes populations in terms of distribution functions on a linear vector space spanned by an arbitrary number of variables, both biotic and abiotic. These distribution functions are solutions of a system of coupled nonlinear transport equations with source and interaction terms that may include a variety of effects, including nonlinearities, random variables, time lags, hysteresis, integrated history dependence, and empirical or phenomenological correlations. We show how the general mathematical framework is used by specializing the master equation to recover several simpler models in current usage.
Countertrade practices in Indonesia

Abstract This articles investigates countertrade transactions in Indonesia. An analysis of 31 reported countertrade transactions reveals that compensation, counterpurchase, and offset are the more frequently used forms of countertrade. Japan, Iran, Algeria, Pakistan, and the United States are the major trading partners. The primary categories of Indonesian exports and imports are raw material inputs and finished capital goods, respectively. A familiarity with recent trends in Indonesian countertrade will enable international marketing managers to identify and take advantage of emerging opportunities in the Indonesian marketplace.
DIETARY CARBOHYDRATE AND METABOLISM OF INGESTED PROTEIN

Abstract Six normal people were fed a lean beef meal while on a normal diet and after seven days on a very low carbohydrate (
Transfer matrix study of d ≥ 3 Ising models

Abstract A novel method to perform numerical transfer matrix studies of models in high dimensions is described. The problem to be overcome is that the size of the transfer matrix is much larger than the available memory on any supercomputer. To overcome this problem, scaling is performed on a transfer matrix which has the same form as the physical transfer matrix, but does not correspond to a physical system. Results will be presented for the Ising model on hypercubic lattices for d = 3,4,5,6 and 7.
Probability measures over fuzzy spaces

A probability measure is defined on subsets of an underlying space. In classical probability theory, both the underlying space and the subsets whose probabilities we measure are crisp subsets. Zadeh provided an extension of this to the case in which the subsets whose probabilities we are measuring can be fuzzy. Here, we provide a further generalization of the idea of a probability measure to the case in which the underlying space itself can be a fuzzy subset. In addition to providing a method for determining the probabilities of subsets in this more general environment, we provide a definition for the entropy associated with this type of distribution.
Influence of Surgical and Minimally Invasive Facial Cosmetic Procedures on Psychosocial Outcomes: A Systematic Review

Importance Millions of surgical and minimally invasive cosmetic procedures of the face are performed each year, but objective clinical measures that evaluate surgical procedures, such as complication rates, have limited utility when applied to cosmetic procedures. While there may be subjective improvements in appearance, it is important to determine if these interventions have an impact on patients in other realms such as psychosocial functioning. This is particularly important in light of the Patient Protection and Affordable Care Act and its emphasis on patient-centered outcomes and effectiveness. Objectives To review the literature investigating the impact of facial cosmetic surgery and minimally invasive procedures on relevant psychological variables to guide clinical practice and set norms for clinical performance. Evidence Review English-language randomized clinical trials and prospective cohort studies that preoperatively and postoperatively assessed psychological variables in at least 10 patients seeking surgical or minimally invasive cosmetic procedures of the face. Findings Only 1 study investigating minimally invasive procedures was identified. Most studies reported modest improvement in psychosocial functioning, which included quality of life, self-esteem, and body image. Unfortunately, the overall quality of evidence is limited owing to an absence of control groups, short follow-up periods, or loss to follow-up. Conclusions and Relevance The current literature suggests that a number of psychosocial domains may improve following facial cosmetic surgery, although the quality of this evidence is limited (grade of recommendation 2A). Despite the dramatic rise in nonsurgical cosmetic procedures, there is a paucity of information regarding the impact of chemodenervation and soft-tissue augmentation on psychosocial functioning.
Precautions Principals Can Take To Avert Censorship Protests

What is the ethical and practical stance that principals should take when censorship controversies arise in their schools? The author advises principals how to prepare for such events in order to avoid the hassles that are implied.
The Cbl Family and Other Ubiquitin Ligases: Destructive Forces in Control of Antigen Receptor Signaling

Regulation of tyrosine kinase-mediated cellular activation through antigen receptors is of great biological and practical significance. The evolutionarily conserved Cbl family ubiquitin ligases have emerged as key negative regulators of activated tyrosine kinase-coupled receptors, and their impaired function switches a normal immune response into autoimmunity. Cbl proteins facilitate the ubiquitinylation of activated tyrosine kinases and other signaling proteins and of the signaling chains of receptors themselves; monoubiquitin tag promotes sorting of activated receptors and associated proteins into internal vesicles of the multivesicular body, facilitating their lysosomal degradation, whereas polyubiquitin tag promotes proteasomal degradation. Notably, increased expression of Cbl proteins and other ubiquitin ligases is a component of anergic signaling program in T cells. Thus, controlled destruction of the signaling apparatus has emerged as a key to fine-tuning antigen receptor signaling. Further studies of this pathway are likely to elucidate the pathogenesis of autoimmune diseases and offer new therapeutic targets.
Escherichia coli K-1 Interaction with Human Brain Micro-vascular Endothelial Cells Triggers Phospholipase C-γ1 Activation Downstream of Phosphatidylinositol 3-Kinase

Escherichia coli, the most common Gram-negative bacterium that causes meningitis in neonates, invades human brain microvascular endothelial cells (HBMEC) by rearranging host cell actin via the activation of phosphatidylinositol 3-kinase (PI3K) and PKC-α. Here, further, we show that phospholipase (PLC)-γ1 is phosphorylated on tyrosine 783 and condenses at the HBMEC membrane beneath the E. coli entry site. Overexpression of a dominant negative (DN) form of PLC-γ, the PLC-z fragment, in HBMEC inhibits PLC-γ1 activation and significantly blocks E. coli invasion. PI3K activation is not affected in PLC-z/HBMEC upon infection, whereas PKC-α phosphorylation is completely abolished, indicating that PLC-γ1 is downstream of PI3K. Concomitantly, the phosphorylation of PLC-γ1 is blocked in HBMEC overexpressing a dominant negative form of the p85 subunit of PI3K but not in HBMEC overexpressing a dominant negative form of PKC-α. In addition, the recruitment of PLC-γ1 to the cell membrane in both PLC-z/HBMEC and DN-p85/HBMEC is inhibited. Activation of PI3K is associated with the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 1,4,5-trisphosphate (PIP3), which in turn recruits PLC-γ1 to the cell membrane via its interaction with pleckstrin homology domain of PLC-γ1. Utilizing the pleckstrin homology domains of PKC-δ and Btk proteins fused to green fluorescent protein (GFP), which specifically interact with PIP2 and PIP3, respectively, we show herein that E. coli invasion induces the breakdown of PIP2 at the plasma membrane near the site of E. coli interaction. PIP3, on the other hand, recruits the GFPBkt to the cell membrane beneath the sites of E. coli attachment. Our studies further show that E. coli invasion induces the release of Ca2+ from intracellular pools as well as the influx of Ca2+ from the extracellular medium. This elevation in Ca2+ levels is completely blocked both in PLC-z/HBMEC and DN-p85/HBMEC, but not in DN-PKC/HBMEC. Taken together, these results suggest that E. coli infection of HBMEC induces PLC-γ1 activation in a PI3K-dependent manner to increase Ca2+ levels in HBMEC. This is the first report demonstrating the recruitment of activated PLC-γ1 to the sites of bacterial entry.
Swallowing and speech production in Parkinson's disease

Videofluoroscopy was used to examine movement patterns during swallowing and speech production in 6 parkinsonian subjects and 6 age-matched controls. Motility patterns for liquid and semisolid swallows were documented. We performed temporospatial analyses of oropharyngeal structures, particularly the velum, which is prominently involved in both motor speech production and swallowing. Differences were found between groups and conditions. All of the parkinsonian subjects exhibited abnormal oropharyngeal movement patterns and timing during the volitional oral as well as the pharyngeal stage of swallowing; only 50% of these subjects admitted to any swallowing difficulty upon questioning. Two of the subjects with Parkinson's disease aspirated liquids. Duration of velar movement during speech production significantly differentiated the groups (p less than 0.01), reflecting reduced range of velar motion. Our findings suggest that rigidity and bradykinesia underlie the volitional speech abnormality as well as the disordered oral and pharyngeal stages of swallowing. Findings indicate that parkinsonian patients may be "silent aspirators" with decreased cough reflexes and lack of awareness of aspiration. The clinical value of videofluoroscopic monitoring of swallowing is that aspiration may be detected and managed early.
A road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors

Kinases are principal components of signal transduction pathways and the focus of intense basic and drug discovery research. Irreversible inhibitors that covalently modify non-catalytic cysteines in kinase active sites have emerged as valuable probes and approved drugs. Many protein classes, however, have functional cysteines, and therefore understanding the proteome-wide selectivity of covalent kinase inhibitors is imperative. Here, we accomplish this objective using activity-based protein profiling coupled with quantitative MS to globally map the targets, both specific and nonspecific, of covalent kinase inhibitors in human cells. Many of the specific off-targets represent nonkinase proteins that, notably, have conserved active site cysteines. We define windows of selectivity for covalent kinase inhibitors and show that, when these windows are exceeded, rampant proteome-wide reactivity and kinase target-independent cell death conjointly occur. Our findings, taken together, provide an experimental road map to illuminate opportunities and surmount challenges for the development of covalent kinase inhibitors.
The “Problem of Preferences”: Medicare and Business Support for the Welfare State*

Few political observers would readily assume that a present-day politician's or interest group's claims about their preferences accurately reflect their genuine views. However, scholars often unwittingly make this very assumption when inferring the preferences of historical political actors. In this article I explore the influence of business groups on Medicare's passage to illustrate how inattention to political actors’ strategic misrepresentations can bias qualitative and quantitative research. An ongoing debate wrestles with the pattern that businesses often grant support to welfare-state expansions just before they occur, a regularity some take as evidence that business interests dictate these expansions. I use Medicare as a case study and document that key business groups and their allies did not truly favor the program. However, I also show that these actors strategically misrepresented their preferences as Medicare's passage became likely in order to advance more limited alternatives. The strategic nature of this position is exceptionally easy to miss; yet inattention to it produces the opposite, erroneous conclusion about these actors’ historical role. Medicare's legislative history thus illustrates the methodological necessity of documenting whether political actors are misrepresenting their preferences. I discuss how scholars can do so by tracing actors’ stated preferences across strategic circumstances, including audiences and time.
SimSelect: a system for simulation software selection

SimSelect is a system developed for the purpose of providing support for users when selecting simulation software. SimSelect consists of a database which is linked to an interface developed using Visual Basic 3.0. The system queries a database and finds a simulation package suitable to the user, based on requirements which have been specified. It also provides a recommendation of alternative packages suitable to the user, and allows prioritisation of requirements in levels of importance. This paper provides an insight into the development of SimSelect, in addition to the reasoning behind the system.
Modification of fresh crater landforms: Evidence from the Moon and Mercury

The morphology of fresh lunar and Mercurian craters provides insight into processes of crater formation and modification. Measurements determined for Mercurian craters and compared to previously presented lunar data are depth/diameter, central peak and wall-related mass movement frequencies as functions of diameter, crater rim wall width/rim diameter, rim diameter/floor diameter, and central peak height/rim diameter. Two important results are as follows: (1) there is no evidence for direct gravity scaling of crater morphology, although some slight scaling relationship may be indicated, and (2) mass movements are responsible for the change in depth/diameter relationship observed near 2-km depth and 10-km diameter. The latter result is helpful in explaining gravitational and topographic data which suggest low-density regions beneath large fresh craters.
Challenges and Opportunities: Civil Society in a Globalizing World

What role can social movements and civil society play in promoting transformative development in the global South? This paper argues that inclusive and democratic forms of development depend on a delicate balance between the market, the state and civil society. Globalization has created new opportunities for economic development, but market power has often expanded at the expense of democratic and social accountability. Democratization in the global South and the emergence of new forms of transnational activism offer the hope of re-embedding markets. The paper explores these possibilities both through an analysis of existing global configurations of power and emergent forms of global civil society, as well as through an analysis of how movements and civil society have shaped three very different developmental trajectories in Brazil, India and South Africa. It argues that at both the global and domestic level, prospects for more inclusive development depend largely on the balance between civil society and political society.
Translating the Diabetes Prevention Program into the Community: The DEPLOY Pilot Study

Background: The Diabetes Prevention Program (DPP) found that an intensive lifestyle intervention can reduce the development of diabetes by more than half in adults with prediabetes, but there is little information about the feasibility of offering such an intervention in community settings. This study evaluated the delivery of a group-based DPP lifestyle intervention in partnership with the YMCA. Methods: This pilot cluster-randomized trial was designed to compare group-based DPP lifestyle intervention delivery by the YMCA to brief counseling alone (control) in adults who attended a diabetes risk-screening event at one of two semi-urban YMCA facilities and who had a BMI 24 kg/m 2 , 2 diabetes risk factors, and a random capillary blood glucose of 110 –199 mg/dL. Multivariate regression was used to compare between-group differences in changes in body weight, blood pressures, HbA1c, total cholesterol, and HDL-cholesterol after 6 and 12 months. Results: Among 92 participants, controls were more often women (61% vs 50%) and of nonwhite race (29% vs 7%). After 6 months, body weight decreased by 6.0% (95% CI4.7, 7.3) in intervention participants and 2.0% (95% CI0.6, 3.3) in controls (p0.001; difference between groups). Intervention participants also had greater changes in total cholesterol (–22 mg/dL vs 6 mg/dL controls; p0.001). These differences were sustained after 12 months, and adjustment for differences in race and gender did not alter these findings. With only two matched YMCA sites, it was not possible to adjust for potential clustering by site. Conclusions: The YMCA may be a promising channel for wide-scale dissemination of a low-cost approach
Test Compaction by Sharing of Transparent-Scan Sequences Among Logic Blocks

An approach to test application called transparent scan provides an opportunity to share tests among different logic blocks whose primary inputs and outputs are included in scan chains even if the blocks have different numbers of state variables. A transparent-scan sequence for one block is likely to detect faults in other blocks since transparent scan does not distinguish between functional and scan clock cycles, and allows faults to be detected at all the clock cycles of the sequence. Such sharing of tests is not meaningful with conventional scan-based tests, especially when the blocks have different numbers of state variables. Transparent scan thus enhances the ability to produce a compact test set for a group of logic blocks. The static test compaction procedure described in this paper uses transparent-scan sequences that follow the application of conventional scan-based tests precisely. The procedure obtains a set of transparent-scan sequences for a group of logic blocks from compacted test sets for the logic blocks in the group. From this set, it selects a subset that detects all the target faults, which are detected by the complete set.
Risk factors associated with lower extremity stress fractures in runners: a systematic review with meta-analysis

Background Stress fractures are common overuse injuries with up to 95% occurring in the lower extremities. Among runners, stress fractures account for 15–20% of all musculoskeletal injuries. Purpose We systematically reviewed and critiqued the evidence regarding risk factors associated with increased risk of lower extremity stress fractures in runners. Study design Systematic review. Methods A systematic, computerised literature search of Medline, Embase, PubMed, SPORTDiscus, and CINAHL databases (from database inception through 9 January 2014) using keywords related to risk factors and stress fractures. This systematic review with meta-analysis utilised the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the search and reporting phases of the study. Inverse variance meta-analyses, using a random effects model were used to summarise ORs. Results 8 articles met the inclusion criteria; 7 were considered low risk. 4 articles qualified for meta-analysis. Results of the meta-analysis identified previous history of stress fracture and female sex as the primary risk factors for future stress fracture with a pooled OR of 4.99 (95% CI 2.91 to 8.56; p 2 =0%) and 2.31 (95% CI 1.24 to 4.29; p 2 =0%), respectively. Conclusions Currently, only previous history of stress fracture and female sex are risk factors for lower extremity stress fractures strongly supported by the data.
Microbes modeling ontogeny

Model organisms are central to contemporary biology and studies of embryogenesis in particular. Biologists utilize only a small number of species to experimentally elucidate the phenomena and mechanisms of development. Critics have questioned whether these experimental models are good representatives of their targets because of the inherent biases involved in their selection (e.g., rapid development and short generation time). A standard response is that the manipulative molecular techniques available for experimental analysis mitigate, if not counterbalance, this concern. But the most powerful investigative techniques and molecular methods are applicable to single-celled organisms (‘microbes’). Why not use unicellular rather than multicellular model organisms, which are the standard for developmental biology? To claim that microbes are not good representatives takes us back to the original criticism leveled against model organisms. Using empirical case studies of microbes modeling ontogeny, we break out of this circle of reasoning by showing: (a) that the criterion of representation is more complex than earlier discussions have emphasized; and, (b) that different aspects of manipulability are comparable in importance to representation when deciding if a model organism is a good model. These aspects of manipulability harbor the prospect of enhancing representation. The result is a better understanding of how developmental biologists conceptualize research using experimental models and suggestions for underappreciated avenues of inquiry using microbes. More generally, it demonstrates how the practical aspects of experimental biology must be scrutinized in order to understand the associated scientific reasoning.
Covert Pay Discrimination: How Authority Predicts Pay Differences between Women and Men

Research repeatedly highlights the gap between male and female earnings across the public and private sectors. The authors address an overlooked manifestation of pay discrimination against women in the labor market. Using a survey of 384 public sector chief procurement officers, they analyze the indirect effects of gender on women’s pay through the intervening variable of authority. Gender affects the amount of authority that is delegated to an employee, which, in turn, affects the variance in pay between men and women. Results reveal that gender plays a hidden role in influencing compensation levels by shifting the chain of authority given to executives as they build a career portfolio. The conclusion underscores why gender pay disparities should account for both the indirect and the direct effects of gender on pay.