Miracle-dz/UniFAR-FTUs huggingface dataset:
Cholesterol Is Required for Surface Transport of Influenza Virus Hemagglutinin

Transport from the TGN to the basolateral surface involves a rab/N-ethylmaleimide–sensitive fusion protein (NSF)/soluble NSF attachment protein (SNAP)/SNAP receptor (SNARE) mechanism. Apical transport instead is thought to be mediated by detergent-insoluble sphingolipid–cholesterol rafts. By reducing the cholesterol level of living cells by 60–70% with lovastatin and methyl-β-cyclodextrin, we show that the TGN-to-surface transport of the apical marker protein influenza virus hemagglutinin was slowed down, whereas the transport of the basolateral marker vesicular stomatitis virus glycoprotein as well as the ER-to-Golgi transport of both membrane proteins was not affected. Reduction of transport of hemagglutinin was accompanied by increased solubility in the detergent Triton X-100 and by significant missorting of hemagglutinin to the basolateral membrane. In addition, depletion of cellular cholesterol by lovastatin and methyl-β-cyclodextrin led to missorting of the apical secretory glycoprotein gp-80, suggesting that gp-80 uses a raft-dependent mechanism for apical sorting. Our data provide for the first time direct evidence for the functional significance of cholesterol in the sorting of apical membrane proteins as well as of apically secreted glycoproteins.
Health actions and social class among older Australians

This paper aims to identify aspects of social class that are related to health actions important for older Australians. Data are from the 1994 Health Status of Older People Project baseline survey of 1,000 participants aged 65 and over in Melbourne. Analyses employed logistic regression controlling for age and gender. Physical activity was related to both former occupation and current income; social activity to former occupation; and not smoking to home ownership. Health promotion strategies require a better understanding of the ways in which aspects of social class affect the life course experiences of different birth cohorts. Promotion of physical and social activity in old age needs to take account of the continuing influence of advantages associated with social class.
A Diversity-Promoting Objective Function for Neural Conversation Models

Sequence-to-sequence neural network models for generation of conversational responses tend to generate safe, commonplace responses (e.g., "I don't know") regardless of the input. We suggest that the traditional objective function, i.e., the likelihood of output (response) given input (message) is unsuited to response generation tasks. Instead we propose using Maximum Mutual Information (MMI) as the objective function in neural models. Experimental results demonstrate that the proposed MMI models produce more diverse, interesting, and appropriate responses, yielding substantive gains in BLEU scores on two conversational datasets and in human evaluations.
Teaching Writing to Adults: Examining Assumptions and Revising Expectations for Adult Learners in the Writing Class.

Traditionally, teachers of writing have considered it their challenge to prepare students for the workplace. But in growing numbers, students are entering classrooms from the workplace. New trends in the way Americans define themselyes as workers and life-long learners call for a redefinition of the role of writing in the academic world. Some creative solutions can help teachers address the sensitive issues of writing anxiety in returning adult students, who are confident on the job but uneasy with academic writing after being away from the classroom setting for a number of years. Being overwhelmed with first writing assignments is common to all students, but because they feel isolated, returning students may not realize this. A solution is to create a Saturday afternoon student forum where they may talk with other students as well as with administration and faculty. Another example is the creation of a writing center as a permanent place offering ongoing help on an individualized basis for adult students. Paths for dialogue among faculty of all disciplines should be explored to face the challenge of the shared issue of teaching the returning student. (CR) *********************************************************************** Reproductions supplied by EDRS are the best that can be made from the original document. ***********************************************************************
The Lyn Kinase Activator MLR-1023 Is a Novel Insulin Receptor Potentiator that Elicits a Rapid-Onset and Durable Improvement in Glucose Homeostasis in Animal Models of Type 2 Diabetes

MLR-1023 [Tolimidone; CP-26154; 2(1H)-pyrimidinone, 5-(3-methylphenoxy)] is an allosteric Lyn kinase activator that reduces blood glucose levels in mice subjected to an oral glucose tolerance test (J Pharmacol Exp Ther 342:15–22, 2012). The current studies were designed to define the role of insulin in MLR-1023-mediated blood glucose lowering, to evaluate it in animal models of type 2 diabetes, and to compare it to the activities of selected existing diabetes therapeutics. Results from these studies show that in an acute oral glucose tolerance test MLR-1023 evoked a dose-dependent blood glucose-lowering response that was equivalent in magnitude to that of metformin without eliciting a hypoglycemic response. In streptozotocin-treated, insulin-depleted mice, MLR-1023 administration did not affect blood glucose levels. However, MLR-1023 potentiated the glucose-lowering activity of exogenously administered insulin, showing that MLR-1023-mediated blood glucose lowering was insulin-dependent. In a hyperinsulinemic/euglycemic clamp study, orally administered MLR-1023 increased the glucose infusion rate required to sustain blood glucose levels, demonstrating that MLR-1023 increased insulin receptor sensitivity. In chronically treated db/db mice, MLR-1023 elicited a dose-dependent and durable glucose-lowering effect, reduction in HbA1c levels and preservation of pancreatic β-cells. The magnitude of effect was equivalent to that seen with rosiglitazone but with a faster onset of action and without causing weight gain. These studies show that MLR-1023 is an insulin receptor-potentiating agent that produces a rapid-onset and durable blood glucose-lowering activity in diabetic animals.
Is There Room for Second-Generation Antipsychotics in the Pharmacotherapy of Panic Disorder? A Systematic Review Based on PRISMA Guidelines

A role for second-generation antipsychotics (SGAs) in the treatment of panic disorders (PD) has been proposed, but the actual usefulness of SGAs in this disorder is unclear. According to the PRISMA guidelines, we undertook an updated systematic review of all of the studies that have examined, in randomized controlled trials, the efficacy and tolerability of SGAs (as either monotherapy or augmentation) in the treatment of PD, with or without other comorbid psychiatric disorders. Studies until 31 December 2015 were identified through PubMed, PsycINFO, Embase, Cochrane Library and Clinical trials.gov. Among 210 studies, five were included (two involving patients with a principal diagnosis of PD and three involving patients with bipolar disorder with comorbid PD or generalized anxiety disorder). All were eight-week trials and involved treatments with quetiapine extended release, risperidone and ziprasidone. Overall, a general lack of efficacy of SGAs on panic symptoms was observed. Some preliminary indications of the antipanic effectiveness of risperidone are insufficient to support its use in PD, primarily due to major limitations of the study. However, several methodological limitations may have negatively affected all of these studies, decreasing the validity of the results and making it difficult to draw reliable conclusions. Except for ziprasidone, SGAs were well tolerated in these short-term trials.
A physical model of multiple-image radiography

We recently proposed a phase-sensitive x-ray imaging method called multiple-image radiography (MIR), which is an improvement on the diffraction-enhanced imaging technique. MIR simultaneously produces three images, depicting separately the effects of absorption, refraction and ultra-small-angle scattering of x-rays, and all three MIR images are virtually immune to degradation caused by scattering at higher angles. Although good results have been obtained using MIR, no quantitative model of the imaging process has yet been developed. In this paper, we present a theoretical prediction of the MIR image values in terms of fundamental physical properties of the object being imaged. We use radiative transport theory to model the beam propagation, and we model the object as a stratified medium containing discrete scattering particles. An important finding of our analysis is that the image values in all three MIR images are line integrals of various object parameters, which is an essential property for computed tomography to be achieved with conventional reconstruction methods. Our analysis also shows that MIR truly separates the effects of absorption, refraction and ultra-small-angle scattering for the case considered. We validate our analytical model using real and simulated imaging data.
Ultrastructural alterations induced by two ergosterol biosynthesis inhibitors, ketoconazole and terbinafine, on epimastigotes and amastigotes of Trypanosoma (Schizotrypanum) cruzi

We report the ultrastructural alterations induced during the proliferative stages of Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease, by two ergosterol biosynthesis inhibitors, ketoconazole and terbinafine, which had previously been shown to be potent growth inhibitors whose effects are potentiated when used in combination (J. A. Urbina, K. Lazardi, T. Aguirre, M. M. Piras, and R. Piras, Antimicrob. Agents Chemother. 32:1237-1242, 1988). Epimastigotes treated with a low concentration of ketoconazole (1 microM), which blocks ergosterol biosynthesis at the level of C-14 demethylation of lanosterol and induces cell lysis coincident with total ergosterol depletion, showed gross alterations of the kinetoplast-mitochondrion complex, which swelled and lost the organization of its inner membrane and the electron-dense bodies of its matrix. Thus, coincident with the beginning of cell lysis, the kinetoplast-mitochondrion complex occupied greater than 80% of the cell volume, while other subcellular structures such as the nucleus and subpellicular microtubules were not affected. Terbinafine, which blocks ergosterol synthesis in these cells at the level of squalene synthetase and thus leads to almost immediate arrest of growth at concentrations greater than 1 microM, produced proliferation of glycosomelike bodies, binucleated cells (arrest at cytokinesis), and eventually massive vacuolization. When the drugs were combined, the predominant effect was mitochondrial swelling, which was more drastic and took place earlier than that observed in cells treated with ketoconazole alone. In amastigotes proliferating in Vero cells, ketoconazole at the concentration required to eradicate the parasites (10 nM) produced mitochondrial swelling, the appearance of autophagic vacuoles containing partially degraded subcellular material, and finally a general breakdown of the subcellular structures. Terbinafine at 3 microM induced more limited ultrastructural damage to the amastigotes consistent with increased vacuolization of the cells and the appearance of occasional autophagic vacuoles. When the drugs were used in combination, just 1 nM was required for the total eradication of parasites, the ultrastructural effects were more extensive, and cell disintegration occurred earlier than when any of the drugs was used alone at a much higher concentration. No effect of the drugs on the ultrastructure of the host cells were observed at any of the concentrations tested.
A comparison of the use of cone-beam computed tomography and panoramic radiography in the assessment of pre-eruptive intracoronal resorption

Abstract Objective: This study aimed to investigate the prevalence of pre-eruptive intracoronal resorption (PIR) using cone beam computed tomography (CBCT) and panoramic radiography and to compare the findings of these imaging techniques. Methods: This retrospective study consisted of 733 patients who had at least one unerupted tooth and had undergoneimaging with both three-dimensional (3D) CBCT and two-dimensional (2D) panoramic radiography. In all the images, the number of teeth with intracoronal resorption, affected tooth type and number, and size and location of the PIR defects were recorded. The McNemar test was used to compare the prevalence of PIR in the CBCT and panoramic images. Results: Fewer PIR defects were detected in the panoramic images (3.1% of the patients) than in the CBCT images (9.5% of the patients) (p< .001). According to the CBCT images, the distribution of PIR defects was as follows: third molars (59.5%), canine teeth (11.4%), second molars and premolars (7.6% for both), supernumerary teeth (5.1%), second molars (3.8%), central incisors (2.5%), and first premolar and primary second molar teeth (1.5% for both). According to the scoring classification system for PIR defects, PIR 1 defects were the most common (65.8%), followed by PIR 3 (24.1%) and PIR 2 (10.1%). Of these defects, 69.6% were located in the central aspect of the crown. Ectopically positioned teeth showing intracoronal resorption accounted for 51.9% of the cases of PIR. Conclusions: CBCT detected more cases of PIR than panoramic radiography. The mandibular third permanent molar was the most commonly affected tooth.
A 1.75 GHz highly-integrated narrow-band CMOS transmitter with harmonic-rejection mixers

A 1.75 GHz transmitter with harmonic and double image reject mixer integrates the full signal path from the DAC to the RF output with two frequency synthesizers in a 0.35 /spl mu/m double-poly five-metal CMOS process. The IC consumes 151 mA from a 3 V supply and achieves 1.3/spl deg/ rms phase error. Active area is 3/spl times/9.9 mm/sup 2/.
THE EFFECTS OF THE EFFECTIVE BLACK PARENTING PROGRAM ON THE PARENTING PRACTICES OF PARENTS OF PRESCHOOLERS

Title of thesis: THE EFFECTS OF THE EFFECTIVE BLACK PARENTING PROGRAM ON THE PARENTING PRACTICES OF PARENTS OF PRESCHOOLERS Diane Elizabeth Wessel, Masters of Science, 2005 Thesis directed by: Associate Professor Suzanne M. Randolph Department of Family Studies The purpose of this study was to examine the impact of the Effective Black Parenting intervention on the parenting practices of African American parents with children in preschool. Although studies have previously examined the relationship between parent education programs and parenting, few studies have been conducted with at-risk African Americans. This study proposes a secondary analysis of data from the larger study entitled, “Fostering Resiliency in At-Risk African American Children. ” These data were used to evaluate the Effective Black Parenting (EBP) program, which was adapted and implemented with 33 parents in the urban Washington, DC area, who had a child in Head Start. In addition, 31 parents served as the comparison group in a quasiexperimental design. Analyses revealed that following the program, the intervention group demonstrated more use of positive control and less use of spanking than the comparison group. Programmatic implications and future directions for research are presented. THE EFFECTS OF THE EFFECTIVE BLACK PARENTING PROGRAM ON THE PARENTING PRACTICES OF PARENTS OF PRESCHOOLERS by Diane Elizabeth Wessel Thesis submitted to the Faculty of the Graduate School of the University of Maryland, College Park in partial fulfillment of the requirements for the degree of Masters of Science 2005 Advisory Committee: Associate Professor Suzanne M. Randolph, Chair Professor Sally A. Koblinsky Instructor Carol A. Werlinich © Copyright by Diane Elizabeth Wessel 2005
Teleoperation with kinematically redundant robot manipulators with sub-task objectives

In this paper, control of nonlinear teleoperator systems where both the master and slave systems are kinematically redundant robot manipulators is addressed. The controller is developed under the assumption that the user and environmental input forces are unmeasurable. Lyapunov-based stability analysis is used to prove that the proposed controller yields asymptotic tracking results and ensures the coordination of the master and slave systems while satisfying a sub-task objective.
Subjective Well-Being Is Desirable, but Not the Summum Bonum

Abstract Subjective well-being is a broad term that encompasses the various ways people evaluate their lives, including concepts such as life satisfaction, pleasant emotions, satisfaction with domains such as work and health, feelings of fulfillment and meaning, and low levels of unpleasant emotions. Subjective well-being (SWB) is one component of the good life because lives that are bereft of joy, affection, feelings of fulfillment and meaning, and laden with dissatisfaction, anger, and depression cannot be thought of as ideal, no matter how many other good qualities might be present. On the other hand, we argue that subjective well-being is not the sufficient and final good for which people strive, and to which all other desirable objects are merely a means. People want to be happy, but for the right reasons, and they want certain valued things even in the absence of feelings of happiness. Thus, we argue that subjective well-being is only one of several valued ends that comprise the good life. Social scientists have developed some understanding based on empirical studies of what leads people to evaluate their lives in positive terms. In very recent years, there has also been an analysis of the outcomes of subjective well-being, with the tentative finding that happiness helps people to be successful in some life tasks such as social relationships and earning money. However, there might be optimal levels of certain forms of SWB, such as pleasant emotions, that are only functional when in the long-term they are at submaximal levels – that is, SWB is likely to be dysfunctional if a person is locked into a state of intense positive emotions, and is not able to react to good and bad events. A challenge for future research is to determine whether it is possible to produce interventions to heighten happiness, which at the same time allow people to function effectively in the pursuit of valued social goals.
Testing for structural breaks in a non-stationary linear model

This paper describes Wald-type tests of structural breaks in regression parameters and error variances of a linear model when regressors and errors are nonstationary and change points are unknown. Nonstationarity considered here includes time trends and shifts in distributions of errors and regressors. Andrews (1993), Andrews and Ploberger (1994) introduced Sup, Ave and Exp tests of structural breaks in model parameters under the assumption that regressors and errors are second order stationary. Bai and Perron (1998)'s tests for multiple breaks in regression parameters also rely on that assumption. If marginal distributions of errors and/or regressors are nonstationarity, then the above tests may have an underor overrejection problem leading to wrong inference. Hansen (2000) addressed that problem by deriving bootstrap tests for conditional models when a break size in model parameters asymptotically shrinks to 0 and regressors may have shifts in their marginal distributions. The errors were assumed to be second order stationary. In autoregressive models distributional breaks in dependent regressors can be caused by distributional breaks in errors. This paper introduces a testing procedure that takes into account both the nonstationarity in errors and regressors keeping break sizes in model parameters and error variances xed. Models considered in this paper need not be conditional. They also allow for correlation and heteroscedasticity in errors. If error variances admit step-like breaks then this paper shows how to sequentially estimate such breaks when regression parameters also break.
ATP Enhances Spontaneous Calcium Activity in Cultured Suburothelial Myofibroblasts of the Human Bladder

Background Suburothelial myofibroblasts (sMF) are located underneath the urothelium in close proximity to afferent nerves. They express purinergic receptors and show calcium transients in response to ATP. Therefore they are supposed to be involved in afferent signaling of the bladder fullness. Since ATP concentration is likely to be very low during the initial filling phase, we hypothesized that sMF Ca2+ activity is affected even at very low ATP concentrations. We investigated ATP induced modulation of spontaneous activity, intracellular calcium response and purinergic signaling in cultured sMF. Methodology/Principal Findings Myofibroblast cultures, established from cystectomies, were challenged by exogenous ATP in presence or absence of purinergic antagonist. Fura-2 calcium imaging was used to monitor ATP (10−16 to 10−4 mol/l) induced alterations of calcium activity. Purinergic receptors (P2X1, P2X2, P2X3) were analysed by confocal immunofluorescence. We found spontaneous calcium activity in 55.18%±1.65 of the sMF (N = 48 experiments). ATP significantly increased calcium activity even at 10−16 mol/l. The calcium transients were partially attenuated by subtype selective antagonist (TNP-ATP, 1 µM; A-317491, 1 µM), and were mimicked by the P2X1, P2X3 selective agonist α,β-methylene ATP. The expression of purinergic receptor subtypes in sMF was confirmed by immunofluorescence. Conclusions/Significance Our experiments demonstrate for the first time that ATP can modulate spontaneous activity and induce intracellular Ca2+ response in cultured sMF at very low concentrations, most likely involving P2X receptors. These findings support the notion that sMF are able to register bladder fullness very sensitively, which predestines them for the modulation of the afferent bladder signaling in normal and pathological conditions.
Reflectance model for diffraction

We present a novel method of simulating wave effects in graphics using ray-based renderers with a new function: the Wave BSDF (Bidirectional Scattering Distribution Function). Reflections from neighboring surface patches represented by local BSDFs are mutually independent. However, in many surfaces with wavelength-scale microstructures, interference and diffraction requires a joint analysis of reflected wavefronts from neighboring patches. We demonstrate a simple method to compute the BSDF for the entire microstructure, which can be used independently for each patch. This allows us to use traditional ray-based rendering pipelines to synthesize wave effects. We exploit the Wigner Distribution Function (WDF) to create transmissive, reflective, and emissive BSDFs for various diffraction phenomena in a physically accurate way. In contrast to previous methods for computing interference, we circumvent the need to explicitly keep track of the phase of the wave by using BSDFs that include positive as well as negative coefficients. We describe and compare the theory in relation to well-understood concepts in rendering and demonstrate a straightforward implementation. In conjunction with standard raytracers, such as PBRT, we demonstrate wave effects for a range of scenarios such as multibounce diffraction materials, holograms, and reflection of high-frequency surfaces.