Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetics of Kaposi’s Sarcoma-Associated Herpesvirus Gene Expression

ABSTRACT Herpesvirus gene expression can be classified into four distinct kinetic stages: latent, immediate early, early, and late. Here we characterize the kinetic class of a group of 16 Kaposi’s sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 genes in a cultured primary effusion cell line and examine the expression of a subset of these genes in KS biopsies. Expression of two latent genes, LANA and vFLIP, was constitutive and was not induced by chemicals that induce the lytic cycle in primary effusion lymphoma (PEL) cell lines. An immediate-early gene, Rta (open reading frame 50 [ORF50]), was induced within 4 h of the addition of n-butyrate, and its 3.6-kb mRNA was resistant to inhibition by cycloheximide. Early genes, including K3 and K5 that are homologues of the “immediate-early” gene of bovine herpesvirus 4, K8 that is a positional homologue of Epstein-Barr virus BZLF1, vMIP II, vIL-6, and polyadenylated nuclear (PAN) RNA, appeared 8 to 13 h after chemical induction. A second group of early genes that were slightly delayed in their appearance included viral DHFR, thymidylate synthase, vMIP I, G protein-coupled receptor, K12, vBcl2, and a lytic transcript that overlapped LANA. The transcript of sVCA (ORF65), a late gene whose expression was abolished by Phosphonoacetic acid, an inhibitor of KSHV DNA replication, did not appear until 30 h after induction. Single-cell assays indicated that the induction of lytic cycle transcripts resulted from the recruitment of additional cells into the lytic cycle. In situ hybridization of KS biopsies showed that about 3% of spindle-shaped tumor cells expressed Rta, ORF K8, vIL-6, vMIP I, vBcl-2, PAN RNA, and sVCA. Our study shows that several KSHV-encoded homologues of cellular cytokines, chemokines, and antiapoptotic factors are expressed during the viral lytic cycle in PEL cell lines and in KS biopsies. The lytic cycle of KSHV, probably under the initial control of the KSHV/Rta gene, may directly contribute to tumor pathogenesis.
The Heterogeneity of Prostate Cancer: A Practical Approach

Prostate cancer is a paradigm tumor model for heterogeneity in almost every sense. Its clinical, spatial, and morphological heterogeneity divided by the high-level molecular genetic diversity outline the complexity of this disease in the clinical and research settings. In this review, we summarize the main aspects of prostate cancer heterogeneity at different levels, with special attention given to the spatial heterogeneity within the prostate, and to the standard morphological heterogeneity, with respect to tumor grading and modern classifications. We also cover the complex issue of molecular genetic heterogeneity, discussing it in the context of the current evidence of the genetic characterization of prostate carcinoma; the interpatient, intertumoral (multifocal disease), and intratumoral heterogeneity; tumor clonality; and metastatic disease. Clinical and research implications are summarized and serve to address the most pertinent problems stemming from the extreme heterogeneity of prostate cancer.
Recombinant GRA4 or ROP2 Protein Combined with Alum or the gra4 Gene Provides Partial Protection in Chronic Murine Models of Toxoplasmosis

ABSTRACT The efficacy of vaccination with Toxoplasma gondii recombinant GRA4 (rGRA4) and ROP2 (rRPO2) proteins and a mix of both combined with alum were evaluated in C57BL/6 and C3H mice. In C57BL/6 mice, rGRA4 and rGRA4-rROP2 immunizations generated similar levels of immunoglobulin G1 (IgG1) and IgG2a isotypes against GRA4, whereas immunizations with rROP2 and the mix induced a predominant IgG1 production against ROP2. All groups of C3H vaccinated mice exhibited higher levels of IgG1 than IgG2a. rGRA4-stimulated splenocytes from vaccinated mice produced primarily gamma interferon while those stimulated with rROP2 produced interleukin-4. Challenge of rGRA4- or rGRA4-rROP2-vaccinated mice from both strains with ME49 cysts resulted in fewer brain cysts than the controls, whereas vaccination with rROP2 alone only conferred protection to C3H mice. Immunization with a plasmid carrying the entire open reading frame of GRA4 showed a protective level similar to that of rGRA4 combined with alum. These results suggest that GRA4 can be a good candidate for a multiantigen anti-T. gondii vaccine based on the use of alum as an adjuvant.
A co-operative beamforming solution for eliminating multi-hop communications in wireless sensor networks

This paper proposes a new system architecture for continuous monitoring wireless sensor networks, utilizing recent developments in the areas of cooperative beam-forming, radio frequency integrated circuit technology, and spread-spectrum techniques. In the proposed system, nodes are activated only when they are triggered to send their own data to the fusion center directly, without burdening the network with MAC layer collisions and energy-consuming routing algorithms, thus guaranteeing long lifetime cycles. The nodes consist of a simple active reflector circuit which is synchronized by an incident wave transmitted by a distant base station. Since the nodes can be deployed in large numbers, the network acts as a single antenna array with high directive gain pointing towards the direction of the fusion center. At the receiver, data from each node can be de-multiplexed with the use of a frequency shift keying direct sequence spread spectrum modulation scheme that enables multiple access without destroying the beamforming characteristics of the network.
Resting state of the human proton channel dimer in a lipid bilayer

Significance The human proton channel hHv1 is responsible for the extrusion protons during a series of important physiological events with clinical relevance. Yet, the mechanistic details underlying voltage-dependent gating, ion selectivity, and cooperativity between homodimers remain to be determined. We carried out a structural characterization of hHv1 in a lipid bilayer using spectroscopic methods and revealed a strongly focused electric field across its putative selectivity filter. In combination with computational methods, we showed that the recently determined crystal structure of CiVSD-WT is the best structural template for dimeric hHv1, and constructed a full-length model of dimeric hHv1 with spectroscopic constraints. We proposed an explicit mechanism for hHv1 gating with functional predictions according to the one-click model recently established in CiVSD. The voltage-gated proton channel Hv1 plays a critical role in the fast proton translocation that underlies a wide range of physiological functions, including the phagocytic respiratory burst, sperm motility, apoptosis, and metastatic cancer. Both voltage activation and proton conduction are carried out by a voltage-sensing domain (VSD) with strong similarity to canonical VSDs in voltage-dependent cation channels and enzymes. We set out to determine the structural properties of membrane-reconstituted human proton channel (hHv1) in its resting conformation using electron paramagnetic resonance spectroscopy together with biochemical and computational methods. We evaluated existing structural templates and generated a spectroscopically constrained model of the hHv1 dimer based on the Ci-VSD structure at resting state. Mapped accessibility data revealed deep water penetration through hHv1, suggesting a highly focused electric field, comprising two turns of helix along the fourth transmembrane segment. This region likely contains the H+ selectivity filter and the conduction pore. Our 3D model offers plausible explanations for existing electrophysiological and biochemical data, offering an explicit mechanism for voltage activation based on a one-click sliding helix conformational rearrangement.
Early Onset of Reproductive Function in Normal Female Mice Treated with Leptin

Numerous studies have revealed an association between nutritional status, adiposity, and reproductive maturity. The role of leptin, a hormone secreted from adipose tissue, in the onset of reproductive function was investigated. Normal prepubertal female mice injected with leptin grew at a slower rate than controls as a result of the hormone's thinning effects, but they reproduced up to 9 days earlier than controls and showed earlier maturation of the reproductive tract. These results suggest that leptin acts as a signal triggering puberty, thus supporting the hypothesis that fat accumulation enhances maturation of the reproductive tract.
Monte Carlo time domain noise simulation in nuclear electronics

Since radiation detectors and associated electronics operate on pulses, time domain or transient simulations are used but neglect electronic noise. Traditional noise analysis yields the rms magnitude of noise fluctuations but does not show how noise affects time-variant or nonlinear circuits. These effects are not well described by either noise-free time domain analyses or noise analyses, which yield only the rms magnitude of the noise. We have developed software that produces a time domain simulation, which represents electronic noise as a randomly varying waveform. The waveform is simulated as a superposition of random noise impulses into the preamplifier, with the appropriate noise weighting functions and with amplitude and frequency derived from the electrical parameters of the circuitry. The result has an accurate rms amplitude and frequency spectrum, including white series noise, white parallel noise, and series 1/f noise terms. The software combines this random electronic noise, time variant processes such as variations in detector risetime or pulse pile-up, and models both time-invariant and time-variant circuitry. It provides a physically intuitive and quantitative connection between noise sources, noise weighting functions, and a noisy waveform. This software was been used in designing the latest generation of Amptek’s digital processor but is generally applicable for many different systems.
Phagocytosed Bordetella pertussis Fails To Survive in Human Neutrophils

ABSTRACT Previous studies have reported that phagocytosed Bordetella pertussis survives in human neutrophils. This issue has been reexamined. Opsonized or unopsonized bacteria expressing green fluorescent protein (GFP) were incubated with adherent human neutrophils. Phagocytosis was quantified by fluorescence microscopy, and the viability of phagocytosed bacteria was determined by colony counts following treatment with polymyxin B to kill extracellular bacteria. Only 1 to 2% of the phagocytosed bacteria remained viable. Opsonization with heat-inactivated immune serum reduced the amount of attachment and phagocytosis of the bacteria but did not alter survival rates. In contrast to previous reports, these data suggest that phagocytosed B. pertussis bacteria are killed by human neutrophils.
Recruitment and retention in a 10-month social network-based intervention promoting diabetes self-management in socioeconomically deprived patients: a qualitative process evaluation

Objectives Socioeconomically deprived patients with type 2 diabetes often face challenges with self-management, resulting in more diabetes-related complications. However, these groups are often under-represented in self-management interventions. Evidence on effective recruitment and retention strategies is growing, but lacking for intensive self-management interventions. This study aims to explore recruitment, retention and effective intervention strategies in a 10-month group-based intervention among Dutch, Moroccan, Turkish and Surinamese patients from socioeconomically deprived neighbourhoods. Methods Participants were recruited through general practitioners (GPs) and participated in a 10-month social network-based intervention (10 groups, n=69): Powerful Together with Diabetes. This intervention also targeted the significant others of participants and aimed to increase social support for self-management and to decrease social influences hindering self-management. A qualitative process evaluation was conducted. Retention was measured using log books kept by group leaders. Further, we conducted 17 in-depth interviews with participants (multiethnic sample) and 18 with group leaders. Interviews were transcribed, coded and analysed using framework analyses. Results The GP's letter and reminder calls, an informational meeting and the intervention's informal nature facilitated recruitment. During the first months, positive group atmosphere, the intervention's perceived usefulness, opportunities to socialise and a reduction in practical barriers facilitated retention. After the first months, conflicting responsibilities and changes in the intervention's nature and planning hindered retention. Calls from group leaders and the prospect of a diploma helped participants overcome these barriers. Conclusion To promote retention in lengthy self-management interventions, it seems important that patients feel they are going on an outing to a social gathering that is enjoyable, recreational, useful and easy to attend. However, rewards and intensive personal recruitment and retention strategies remained necessary throughout the entire intervention period. Trial registration number Dutch Trial Register NTR1886; Results.
Discriminação como uma das Fontes de Desigualdade de Rendimentos no Mercado de Trabalho das Regiões Nordeste e Sudeste

Este artigo analisa a discriminacao salarial por genero e raca dentro das densidades das distribuicoes de salario dos setores de atividade, comparando as regioes Nordeste e Sudeste. Para este objetivo, foram usados os dados da PNAD 2002 e uma metodologia semiparametrica – estimador de nucleo ponderado e outra parametrica – regressao quantilica. O primeiro metodo mostra com base em simulacoes contrafatuais, que existe discriminacao contra mulheres e negros no mercado de trabalho em ambas as regioes e que esta e maior contra mulheres, pois, enquanto a desigualdade salarial entre racas e causada principalmente por diferencas na educacao, o diferencial de salarios entre homens e mulheres decorre de uma possivel discriminacao, visto que elas sao mais escolarizadas do que eles. Alem disso, verificou-se numa representacao visualmente clara que a discriminacao contra a raca negra e maior no Sudeste para todos os setores de atividade, enquanto que nao se conseguiu identificar em qual regiao a discriminacao contra mulheres e maior, visto que ela depende do setor considerado. Ja os resultados da regressao quantilica mostraram que a discriminacao salarial cresce com os salarios. Conclui-se a partir deste estudo que, para a reducao das desigualdades de raca e genero devem-se formular politicas publicas que incentivem a educacao da populacao negra e combatam a discriminacao no trabalho, principalmente, entre os cargos de maiores salarios.
Financial Innovations and the Distributional Effects of Interest Rate Changes in the UK

Two alternative functional forms of the demand for money that focus on how an economy as a whole adjusts its cash balances have been discussed in the literature. One functional form is obtained by regarding the money supply as exogenous and the price level as endogenous and the other by regarding the money supply as endogenous and the price level as exogenous. In this paper the author has offered a third view, a general view which regards both variables as endogenous such that the two alternative views are special cases. Subjecting these hypotheses to empirical testing, the author finds that the Canadian data for the period of 1973-86 reject the two special hypotheses in favor of his general specification.
Teaching alveolar ventilation with simple, inexpensive models.

When teaching and learning about alveolar ventilation with our class of 300 first-year medical students, we use four simple, inexpensive "models. " The models, which encourage research-oriented learning and help our students to understand complex ideas, are distributed to the students before class. The students anticipate something new every day, and the models provide elements of surprise and physical examples and are designed to help students to understand 1) cohesive forces of the intrapleural space, 2) chest wall and lung dynamics, 3) alveolar volumes, and 4) regional differences in ventilation. Students are drawn into discussion by the power of learning that is associated with manipulating and thinking about objects. Specifically, the models encourage thinking about complex interactions, and the students appreciate manipulating objects and actually understanding how they work. Using models also allows us to show students how we think as well as what we know. Finally, students enjoy taking the models home to demonstrate to friends and family "how the body works" as well as use the models as future study aids.
A mixer-first receiver with enhanced selectivity by capacitive positive feedback achieving +39dBm IIP3 and <3dB noise figure for SAW-less LTE Radio

A mixer-first receiver enhanced with capacitive positive feedback is proposed to obtain a steeper filter roll-off and enhanced linearity, while keeping low noise figure. It covers all sub-6GHz cellular bands and achieves a high IIP3 of +39dBm and blocker 1dB gain compression point of +12dBm for a blocker frequency-offset of 80MHz at fLO=2GHz. The NF ranges from 2.4dB at fLO=1GHz to 5.4dB at fLO=6GHz. The chip has been fabricated in Globalfoundries 45nm SOI technology on a high resistivity substrate.
Sex Differences in Pay in a 'New Monopsony' Model of the Labor Market

We use a simple framework, adopted from general equilibrium search models, to estimate the extent to which monopsony power (or labor market frictions) can account for gender differences in pay, using data from a chain of regional grocery stores. In this framework, the elasticity of labor supply to the firm can be inferred from estimates of the elasticity of the separation rate with respect to the wage. We identify elasticities of separation from differences in wages and separation rates across job titles and across different years. We estimate elasticities of labor supply to the firm of about 3.5 for men and about 2.7 for women, suggesting significant wage-setting power for the firm. The differences in estimated elasticities of labor supply predict wage differences that are close to the observed male/female wage differences at the firm.
Mood changes associated with blood glucose fluctuations in insulin-dependent diabetes mellitus.

Individuals with insulin-dependent diabetes mellitus (IDDM) and their healthcare practitioners believe that extreme blood glucose (BG) fluctuations are characterized by changes in subjective mood states and emotional behavior, as well as physical symptoms. This study examined relationships between BG levels and self-reported mood in a group of 34 IDDM adults. The method followed a within-subject, repeated-measures design employed in previous studies of physical symptoms associated with diabetic glucose. Four times each day, participants completed a mood/symptom checklist just prior to a self-measurement of BG until 40 checklists had been completed. Half the items on the checklist described physical symptoms and half described mood states. In addition, half the mood items described negative states and half described positive states. Within-subject correlations and regressions showed that moods were related to BG for the majority of participants and that, like physical symptoms, mood-BG relationships were highly idiosyncratic. Low BG levels tended to be associated with negative mood states, primarily self-reported "nervousness. " Positive mood items were almost always associated with high BG. High BG levels also frequently correlated with negative mood states, although the negative mood items that tended to relate to high glucose (anger, sadness) differed from those that tended to relate to low BG. The implications of these findings for self-treatment and glucose perception in the IDDM individual are discussed.
Expert opinion on current therapies for nonalcoholic fatty liver disease

Introduction: Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of most common liver diseases in industrialized countries owing to the increasing prevalence of obesity and being overweight. Until now, loss of weight and physical activity have represented the cornerstone of treatment, but they are very difficult to achieve and to maintain. Therefore, new treatments based on pathogenetic mechanisms leading to NAFLD are under evaluation to establish an effective pharmacological therapy for this disorder. Areas covered: An overview of current therapeutic interventions to treat NAFLD is given. This review provides evidence of the efficacy of natural and pharmacological agents used so far in the treatment of both adult and pediatric NAFLD, on the basis of clinical trials published in the last 10 years. Expert opinion: In the last 10 years, many pharmacological agents on the basis of the pathogenetic mechanism of NAFLD have been attempted, but so far guidelines for the management of NAFLD are lacking. We believe that the advance in the understanding of pathogenesis and factors involved in the progression of the disease may disclose the way to defining new, solid, therapeutic strategies. A multidisciplinary approach considering the risk factors and comorbidities of fatty liver will represent in the future a successful therapeutic strategy for NAFLD.
Saccharomyces cerevisiae Acyl-CoA Oxidase Follows a Novel, Non-PTS1, Import Pathway into Peroxisomes That Is Dependent on Pex5p*

The peroxisomal protein acyl-CoA oxidase (Pox1p) ofSaccharomyces cerevisiae lacks either of the two well characterized peroxisomal targeting sequences known as PTS1 and PTS2. Here we demonstrate that peroxisomal import of Pox1p is nevertheless dependent on binding to Pex5p, the PTS1 import receptor. The interaction between Pex5p and Pox1p, however, involves novel contact sites in both proteins. The interaction region in Pex5p is located in a defined area of the amino-terminal part of the protein outside of the tetratricopeptide repeat domain involved in PTS1 recognition; the interaction site in Pox1p is located internally and not at the carboxyl terminus where a PTS1 is normally found. By making use ofpex5 mutants that are either specifically disturbed in binding of PTS1 proteins or in binding of Pox1p, we demonstrate the existence of two independent, Pex5p-mediated import pathways into peroxisomes in yeast as follows: a classical PTS1 pathway and a novel, non-PTS1 pathway for Pox1p.
Effects of hippocampal injections of a novel ligand selective for the alpha 5 beta 2 gamma 2 subunits of the GABA/benzodiazepine receptor on Pavlovian conditioning.

Benzodiazepine pharmacology has led to greater insight into the neural mechanisms underlying learning and anxiety. The synthesis of new compounds capable of modulating responses produced by these receptors has been made possible by the development of an isoform model of the GABA(A)/benzodiazepine receptor complex. In the current experiment, rats were pretreated with several concentrations of the novel ligand RY024 (an alpha 5 beta 2 gamma 2 -selective benzodiazepine receptor inverse agonist) in the hippocampus and were trained in a Pavlovian fear conditioning paradigm. RY024 independently produced fear-related behavior prior to training and, at the highest concentration, decreased the strength of conditioning observed 24 h after training. These data provide further evidence for the involvement of hippocampal GABA(A)/benzodiazepine receptors in learning and anxiety.