Miracle-dz/UniFAR-FTUs huggingface dataset:
Epstein-Barr Virus but Not Cytomegalovirus Is Associated with Reduced Vaccine Antibody Responses in Gambian Infants

Background Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines. Methodology/Principal Findings Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses. Conclusions The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV.
Hydrogen Sulfide Inhibits Cigarette Smoke-Induced Endoplasmic Reticulum Stress and Apoptosis in Bronchial Epithelial Cells

Background: Apoptosis of lung structural cells contributes to the process of lung damage and remodeling in chronic obstructive pulmonary disease (COPD). Our previous studies demonstrated that exogenous hydrogen sulfide (H2S) can reduce the lung tissue pathology score, anti-inflammation and anti-oxidation effects in COPD, but the effect of H2S in regulating cigarette smoke (CS) induced bronchial epithelial cell apoptosis and the underlying mechanisms are not clear. Objectives: To investigate the effect of H2S on CS induced endoplasmic reticulum stress (ERS) and bronchial epithelial cell apoptosis. Methods: Male Sprague–Dawley rats randomly divided into four groups for treatment: control, CS, NaHS + CS, and propargylglycine (PPG) + CS. The rats in the CS group were exposed to CS generated from 20 commercial unfiltered cigarettes for 4 h/day, 7 days/week for 4 months. Since the beginning of the third month, freshly prepared NaHS (14 μmol/kg) and PPG (37.5 mg/kg) were intraperitoneally administered 30 min before CS-exposure in the NaHS and PPG groups. 16HBE cells were pretreated with Taurine (10 mM), 5 mmol/L 4-phenylbutyric acid (4-PBA) or NaHS (100, 200, and 400 μM) for 30 min, and then cells were exposed to 40 μmol/L nicotine for 72 h. ERS markers (GRP94, GRP78) and ERS-mediated apoptosis markers 4-C/EBP homologous protein (CHOP), caspase-3 and caspase-12 were assessed in rat lung tissues and human bronchial epithelial cells. The apoptotic bronchial epithelial cells were detected by Hoechst staining in vitro and TUNEL staining in vivo. Results: In CS exposed rats, peritoneal injection of NaHS significantly inhibited CS induced overexpression ERS-mediated apoptosis markers and upregulation of apoptotic rate in rat lungs, and inhibiting the endogenous H2S production by peritoneal injection of PPG exacerbated these effects. In the nicotine-exposed bronchial epithelial cells, appropriate concentration of NaHS and ERS inhibitors taurine and 4-PBA inhibited nicotine-induced upregulation of apoptotic rate and overexpression of ERS-mediated apoptosis markers. Conclusion: H2S inhibited lung tissue damage by attenuating CS induced ERS in rat lung and exogenous H2S attenuated nicotine induced ERS-mediated apoptosis in bronchial epithelial cells.
Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A

Low-dose continuous or metronomic chemotherapy with several agents can exert significant antiangiogenic effects, as shown in preclinical studies. Therapy of this kind is generally well tolerated compared with conventional chemotherapy with high, temporally spaced out bolus doses. A critical point emerges when the effects on angiogenesis of low-toxic metronomic doses of chemotherapeutics in preclinical studies are to be transferred to clinical protocols, as there is a risk that a virtually non-toxic dose might also be ineffective; clearly, dose-effect data are important. We therefore sought to investigate whether a dose-dependent response exists in metronomic vinblastine chemotherapy. The surrogate tumor-free rat mesentery model, allowing the study of antiangiogenic effects per se, was used. Following systemically administered metronomic chemotherapy, it closely reflects the indirectly assessed antiangiogenic and growth-retarding effects in a syngenic cancer model. VEGF-A, which is a central proangiogenic factor in most tumors, was administered i.p. to induce angiogenesis in the mesenteric test tissue and, using morphometry, the angiogenesis-modulating effects of vinblastine were assessed in terms of objective quantitative variables. We report that continuous vinblastine treatment with an apparently non-toxic dose (1.0 mg/kg/week or 0.143 mg/kg/day) for 10 days, and a dose that substantially inhibited the physiologic body-weight gain (2.0 mg/kg/week or 0.286 mg/kg/day) for 6 days, demonstrates a dose-response relationship; the high dose significantly suppresses angiogenesis. To our knowledge, no previous study has reported on a dose-dependent antiangiogenic effect by continuous or metronomic vinblastine treatment in a mammalian in vivo model.
Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakhstan: sources of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposures in an agricultural region of southern Kazakhstan.

High levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; up to 208 pg/g fat) were measured in samples of breast milk collected in 1997 from 64 donors [41 first-time mothers (primiparae)] living on state farms in southern Kazakhstan. TCDD was the major contributor (70%) to the toxic equivalents, matching the congener patterns found in breast milk and serum samples collected in 1994 and 1996 from donors in nearby villages. The highest TCDD levels were found in state farms adjacent to a reservoir (zone A), which receives agricultural runoff from cotton fields. TCDD levels in zone A were significantly higher than levels in a region more distant (zone B; > 10 miles) from the reservoir (zone A: mean 53 pg/g, n = 17; zone B: mean 21 pg/g, n = 24; p = 0.0017). Levels of TCDD in breast milk and animal-derived foodstuffs were 10 times U.S. levels. Body burden and dietary data suggest that exposures to TCDD are chronic, environmental, and long term and may be related to the use of chemicals in cotton agriculture. The data suggest that the most likely source is the use of cotton defoliants contaminated with TCDD, and the most likely pathway for human exposure is via the consumption of contaminated foodstuffs. ImagesFigure 1Figure 2Figure 3
Prevalence of HPV After Introduction of the Vaccination Program in the United States

BACKGROUND: Since mid-2006, human papillomavirus (HPV) vaccination has been recommended for females aged 11 to 12 years and through 26 years if not previously vaccinated. METHODS: HPV DNA prevalence was analyzed in cervicovaginal specimens from females aged 14 to 34 years in NHANES in the prevaccine era (2003–2006) and 4 years of the vaccine era (2009–2012) according to age group. Prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV-6, -11, -16, and -18) and other HPV type categories were compared between eras. Prevalence among sexually active females aged 14 to 24 years was also analyzed according to vaccination history. RESULTS: Between the prevacccine and vaccine eras, 4vHPV type prevalence declined from 11.5% to 4.3% (adjusted prevalence ratio [aPR]: 0.36 [95% confidence interval (CI): 0.21–0.61]) among females aged 14 to 19 years and from 18.5% to 12.1% (aPR: 0.66 [95% CI: 0.47–0.93]) among females aged 20 to 24 years. There was no decrease in 4vHPV type prevalence in older age groups. Within the vaccine era, among sexually active females aged 14 to 24 years, 4vHPV type prevalence was lower in vaccinated (≥1 dose) compared with unvaccinated females: 2.1% vs 16.9% (aPR: 0.11 [95% CI: 0.05–0.24]). There were no statistically significant changes in other HPV type categories that indicate cross-protection. CONCLUSIONS: Within 6 years of vaccine introduction, there was a 64% decrease in 4vHPV type prevalence among females aged 14 to 19 years and a 34% decrease among those aged 20 to 24 years. This finding extends previous observations of population impact in the United States and demonstrates the first national evidence of impact among females in their 20s.
Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis.

OBJECTIVE To determine the long-term safety and efficacy of rilonacept, an anti-interleukin-1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA). METHODS In patients with systemic JIA, ages 4-20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open-label treatment (3 phases) after a 4-week, double-blind, placebo-controlled phase. Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept, patients were eligible to receive open-label treatment at their prior dose, with adjustments. Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity (i.e., decreased levels of D-dimer and myeloid-related proteins [MRPs]) were also evaluated. RESULTS Twenty-four patients entered the double-blind study and 23 entered the open-label period. Patients were predominantly white and female, and had a median age of 14.0 years at baseline. No significant differences in efficacy were observed between the rilonacept- and placebo-treated patients during the double-blind phase, but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur. Adapted ACR Pediatric 30, 50, and 70 response rates at 3 months from the start of the study were 78.3%, 60.9%, and 34.8%, respectively; these responses were generally maintained over the study duration. Levels of D-dimer and MRP-8/MRP-14 dramatically improved during the study, and in 22 of 23 patients, the prednisone dose was decreased or prednisone therapy was discontinued. No serious treatment-related adverse events were observed. CONCLUSION Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in >50% of rilonacept-treated patients over 2 years. Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated.
Manifolds covered by lines and the Hartshorne Conjecture for quadratic manifolds

Small codimensional embedded manifolds defined by equations of small degree are Fano and covered by lines. They are complete intersections exactly when the variety of lines through a general point is so and has the right codimension. This allows us to prove the Hartshorne Conjecture for manifolds defined by quadratic equations and to obtain the list of such Hartshorne manifolds.
Selection Experiments as a Tool in Evolutionary and Comparative Physiology: Insights into Complex Traits—an Introduction to the Symposium1

‘‘The whole organism is so tied together that when slight variations in one part occur, and are accumulated through natural selection, other parts become modified. This is a very important subject, most imperfectly understood. ’’ (Darwin, 1859, The Origin of Species). ‘‘Hence if man goes on selecting, and thus augmenting, any peculiarity, he will almost certainly modify unintentionally other parts of the structure, owing to the mysterious laws of correlation. ’’ (Darwin, 1859, The Origin of Species). ‘‘Biological reality is so complex that we are very far from any reasonably mechanistic understanding of evolutionary processes. ’’ (Felsenstein, 1988, p. 468) ‘‘Apparent complexity usually means a lack of understanding. ’’ (McCarthy and Roberts, 1989, p. 134)
A comparison of architectural support for messaging in the TMC CM-5 and the Cray T3D

Programming models based on messaging continue to be an important programming model for parallel machines. Messaging costs are strongly influenced by a machine's network interface architecture. We examine the impact of architectural support for messaging in two machines-the TMC CM-5 and the Cray T3D-by exploring the design and performance of several messaging implementations. The additional features in the T3D support remote operations: memory access, fetch-and-increment, atomic swaps, and prefetch. Experiments on the CM-5 show that requiring processor involvement for message reception can increase the communication overheads from 60% to 300% for moderate variations in computation grain size at the destination. In contrast, the T3D hardware for remote operations decouples message reception from processor activity, producing high-performance messaging independent of computation grain size or variability. In addition, hardware support for a shared address space in the T3D can be used to solve the output contention problem (output hot spots), producing messaging implementations that are robust over a wide variety of traffic patterns. Atomic swap hardware can be used to build a distributed message queue, enabling a "pull" messaging scheme where the destination requests data transfer upon receive. This scheme uses prefetches to mask receive latency. While this yields performance robust over output contention, its base cost is competitive only for small messages (up to 64 bytes) because of the high cost of issuing and resolving prefetches in the T3D. Emulation shows that if the interaction costs can be reduced by a factor of eight (250 ns to 3 1ns), perhaps by moving the prefetch queue on chip, and there is a corresponding increase in the prefetch queue size, the pull scheme can give superior performance in all cases.
Enabling hope

This article explores the psychological concept of hope as it applies to patients with cancer and their families. Hope is an essential element in the lives of those with cancer, because it enables the living to continue on and the dying to die better. Nurses are in a unique position for enabling hope within the patient and family unit, due to the extensive contact they have with patients during the cumulative hospitalizations and outpatient care involved in cancer treatment. The role of oncology nurses in enabling realistic hope is discussed, and a number of nursing approaches toward this end are described. Examples of immediate, short-term, and long-term goals are presented. The article further explains how nurses become catalysts as they help the patient and family unit plan goals together.
MONITORING LAND USE CHANGE BY MULTI-TEMPORAL LANDSAT REMOTE SENSING IMAGERY

This paper presents a methodology through utilizing remote sensing imagery, GIS-based neuro-fuzzy approach and variety of social and environmental factors for simulating land use change. Two historical Landsat imageries of Tehran Metropolitan Area with twenty year time interval and user-selected socio-economic and environmental variables have been employed in order to simulate land use change. All images were rectified and registered to Universal Transverse Mercator (UTM) WGS 1984 zone 39N. Supervised classification was used to classify the images to different land use categories. Four classes were identified: road, residential area, service centre, administrative area. This work introduces a simulation experiment on urban land use change in which a supervised back propagation neural network has been employed in the parameterization of the simulation model, while GIS is used to model and monitor land use change and perform spatial analysis on the results. This paper adapts land use change model which parameterized for Tehran Metropolitan Area and explores how factors such as road, slope, administrative space, service centre and residential area parameters can influence it. For each cell in the study area, the real change between the two time steps is determined and analyzed compared with the provided variables in order to produce a probability of land use change layer. Parts of two datasets were used to train the neural network while full datasets were utilized to predict land use change modelling. In addition, the impact of training and prediction period on land use is examined. The creation of the GIS based neuro-fuzzy land use change modelling is the major contribution of this paper.
Is metabolic rate a universal ‘pacemaker’ for biological processes?

A common, long‐held belief is that metabolic rate drives the rates of various biological, ecological and evolutionary processes. Although this metabolic pacemaker view (as assumed by the recent, influential ‘metabolic theory of ecology’) may be true in at least some situations (e.g. those involving moderate temperature effects or physiological processes closely linked to metabolism, such as heartbeat and breathing rate), it suffers from several major limitations, including: (i) it is supported chiefly by indirect, correlational evidence (e.g. similarities between the body‐size and temperature scaling of metabolic rate and that of other biological processes, which are not always observed) – direct, mechanistic or experimental support is scarce and much needed; (ii) it is contradicted by abundant evidence showing that various intrinsic and extrinsic factors (e.g. hormonal action and temperature changes) can dissociate the rates of metabolism, growth, development and other biological processes; (iii) there are many examples where metabolic rate appears to respond to, rather than drive the rates of various other biological processes (e.g. ontogenetic growth, food intake and locomotor activity); (iv) there are additional examples where metabolic rate appears to be unrelated to the rate of a biological process (e.g. ageing, circadian rhythms, and molecular evolution); and (v) the theoretical foundation for the metabolic pacemaker view focuses only on the energetic control of biological processes, while ignoring the importance of informational control, as mediated by various genetic, cellular, and neuroendocrine regulatory systems. I argue that a comprehensive understanding of the pace of life must include how biological activities depend on both energy and information and their environmentally sensitive interaction. This conclusion is supported by extensive evidence showing that hormones and other regulatory factors and signalling systems coordinate the processes of growth, metabolism and food intake in adaptive ways that are responsive to an organism's internal and external conditions. Metabolic rate does not merely dictate growth rate, but is coadjusted with it. Energy and information use are intimately intertwined in living systems: biological signalling pathways both control and respond to the energetic state of an organism. This review also reveals that we have much to learn about the temporal structure of the pace of life. Are its component processes highly integrated and synchronized, or are they loosely connected and often discordant? And what causes the level of coordination that we see? These questions are of great theoretical and practical importance.
Flow Graph Representation

Methodologies based on simple components, such as gate arrays and standard cells, are not adequate when designing complex VLSI systems. Silicon compilation, an evolutionary step from standard cell methodology, offers an increase in design complexity with an increase in design productivity. Silicon compilers can be broadly divided into structural, functional, and intelligent silicon compilers ([GajsSS]). In structural silicon compilation, the designer explicitly defines the microarchitecture; i.e. a structure consisting of registers, busses, RAMS and ALUs. Functional silicon compilers transform a behavioral description into a microarchitecture automatically.
The Adolescent and Child Health Initiative to Encourage Vision Empowerment (ACHIEVE) Study Design and Baseline Data

Purpose. The purpose of this study was to describe the baseline characteristics of subjects and methods for a multicenter, randomized clinical trial to compare the effects of contact lens wear and spectacle wear on children's self-perception. Methods. Eligible subjects are randomly assigned to wear glasses or contact lenses throughout the 3-year study. Self-perceptions are measured 1 month after randomization and every 6 months using the Self-Perception Profile for Children (SPPC). Children's satisfaction with spectacles and refractive error-related visual quality of life are also measured using surveys developed for the study. Visual acuity, cycloplegic autorefraction, corneal curvature, and axial dimensions are measured annually. Results. Five clinical sites enrolled 484 subjects with a mean (± standard deviation [SD]) age of 10.4 ± 1.1 years. Approximately three-fifths of the subjects are girls, 47.1% of the subjects are white, 21.5% are black, and 21.5% are Hispanic. The mean (± SD) cycloplegic spherical equivalent autorefraction of the right eye is –2.38 ± 1.04 D, and the average (± SD) axial length of the right eye is 24.32 ± 0.77 mm. The average (± SD) Global Self-Worth score on the SPPC is 3.20 ± 0.62 on a scale from one (low perceived competence) to 4 (high perceived competence). The average (± SD) spectacle satisfaction is 59.1 ± 26.6 on a scale from zero (no satisfaction) to 100 (perfect satisfaction). The average refractive error-related quality of life score is 63.5 ± 12.8 on a scale from zero (poor quality of life) to 100 (excellent quality of life). Conclusions. Subjects enrolling in the ACHIEVE Study are an ethnically diverse group of young myopic children. Ocular characteristics of the sample are consistent with data presented in other randomized clinical trials evaluating treatments for myopic children. The data reported here represent the baseline data for a 3-year randomized clinical trial to investigate the effects of contact lens vs. spectacle wear on children's self-perceptions.
A Cutoff Technique for the Verification of Parameterised Interpreted Systems with Parameterised Environments

We put forward a cutoff technique for determining the number of agents that is sufficient to consider when checking temporal-epistemic specifications on a system of any size. We identify a special class of interleaved interpreted systems for which we give a parameterised semantics and an abstraction methodology. This enables us to overcome the significant limitations in expressivity present in the state-of-the-art. We present an implementation and discuss experimental results.