Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive Analysis of the Secreted Proteins of the Parasite Haemonchus contortus Reveals Extensive Sequence Variation and Differential Immune Recognition*

Haemonchus contortus is a nematode that infects small ruminants. It releases a variety of molecules, designated excretory/secretory products (ESP), into the host. Although the composition of ESP is largely unknown, it is a source of potential vaccine components because ESP are able to induce up to 90% protection in sheep. We used proteomic tools to analyze ESP proteins and determined the recognition of these individual proteins by hyperimmune sera. Following two-dimensional electrophoresis of ESP, matrix-assisted laser desorption ionization time-of-flight and liquid chromatography-tandem mass spectrometry were used for protein identification. Few sequences of H. contortus have been determined. Therefore, the data base of expressed sequence tags (dbEST) and a data base consisting of contigs fromHaemonchus ESTs were also consulted for identification. Approximately 200 individual spots were observed in the two-dimensional gel. Comprehensive proteomics analysis, combined with bioinformatic search tools, identified 107 proteins in 102 spots. The data include known as well as novel proteins such as serine, metallo- and aspartyl proteases, in addition to H. contortus ESP components like Hc24, Hc40, Hc15, and apical gut GA1 proteins. Novel proteins were identified from matches with H. contortus ESTs displaying high similarity with proteins like cyclophilins, nucleoside diphosphate kinase, OV39 antigen, and undescribed homologues ofCaenorhabditis elegans. Of special note is the finding of microsomal peptidase H11, a vaccine candidate previously regarded as a “hidden antigen” because it was not found in ESP. Extensive sequence variation is present in the abundant Hc15 proteins. The Hc15 isoforms are differentially recognized by hyperimmune sera, pointing to a possible specific role of Hc15 in the infectious process and/or in immune evasion. This concept and the identification of multiple novel immune-recognized components in ESP should assist future vaccine development strategies.
Gli3 null mice display glandular overgrowth of the developing stomach

The role of the Hedgehog signaling pathway in various aspects of gut development is still poorly understood. In the developing stomach, Sonic (Shh) and Indian (Ihh) hedgehog are expressed in both distinct and overlapping regions. Loss of Sonic hedgehog function in the stomach results in a glandular phenotype of intestinal transformation and overgrowth. These changes are reminiscent of the pre‐malignant lesion, intestinal metaplasia. To determine the role of Hedgehog‐related transcription factors, Gli2 and Gli3, in Shh signaling during stomach development, we conducted a mutant analysis of glandular stomach from Shh, Gli2, and Gli3 mutant mice. Although Gli2 principally mediates the activator function of Shh, surprisingly we observed minimal changes in glandular development in the Gli2 mutant stomach. Furthermore, Gli3, which typically functions as a repressor of Hedgehog signal, showed a striking phenocopy of the glandular expansion and intestinal transformation found in Shh mutant stomach. A reduction in apoptotic events was seen in all mutant stomachs with no appreciable changes in proliferation. Both Shh and Gli3 mutant stomachs displayed early changes of intestinal transformation but these did not impact on the overall differentiation of the gastric epithelium. Interestingly, the observation that Gli3 shares a similar glandular phenotype to Shh mutant stomach reveals a possible novel role of Gli3 activator in the developing stomach. The embryonic stomach is a unique model of the Hedgehog pathway function and one that may help to uncover some of the mechanisms underlying the development of intestinal metaplasia. Developmental Dynamics 234:984–991, 2005. © 2005 Wiley‐Liss, Inc.
Phase I/II Trial of Outpatient PEG-interferon With Interleukin-2 in Advanced Renal Cell Carcinoma: A Cytokine Working Group Study

A phase I/II trial was undertaken to determine the maximum tolerated dose of polyethylene glycol interferon-α-2b (PEG-IFN) with interleukin-2 (IL-2), and to evaluate the efficacy and toxicity in patients with metastatic renal cell carcinoma. Patients initially received subcutaneous PEG-IFN, 3.0 mcg/kg/wk, combined with IL-2, but owing to unexpected toxicity a revised phase I schedule ensued. Patients received 1.0, 1.5, 2.0, or 3.0 mcg/kg/wk of PEG-IFN on days 1, 8, 15, and 22; subcutaneous IL-2 was given at a dose of 5×106 IU/m2 every 8 hours×3 on day 1, followed daily at 5×106 IU/m2 days 2, 3, 4, and 5 of week 1, then 5 times per week for 3 weeks, followed by 2 weeks off. The maximum tolerated dose of PEG-IFN was 2.0 mcg/kg/wk. Fifty-four patients were enrolled. Frequent grade III/IV cardiac and neurologic toxicities led to an expanded phase I trial. Eleven serious events in 33 patients in the phase II portion led to early termination. No patient died from treatment. The overall response rate in 53 evaluable patients was 30.2% (95% confidence interval 20.5-39.9), with 2 complete responses and 14 partial responses and at least 1 response at each dose level. The median duration of response was 11 months (range, 2 to 65+ mo); median survival was 20 months (range, 2 to 71+ mo); median time to progression was 4 months. Despite clinical efficacy, the study was closed prematurely owing to excess toxicity. Although all serious adverse events resolved, this degree of toxicity is unacceptable for an outpatient treatment regimen.
Nutrient-dense, Plant-rich Dietary Intervention Effective at Reducing Cardiovascular Disease Risk Factors for Worksites: A Pilot Study.

UNLABELLED conduct interventions for health promotion and disease prevention to ameliorate chronic risk factors for disease, such as for cardiovascular disease (CVD). Likewise, nutrient-dense, plant-rich (NDPR) dietary patterns have been shown to be effective at preventing and improving chronic-disease conditions, including CVD. Objective • The study's aim was to determine the feasibility and effectiveness of an NDPR dietary intervention for worksites to lower CVD risk factors. Design • The study was a 6-wk pilot intervention using a pretest and posttest design. SETTING The intervention was conducted at the Northern Arizona University (Flagstaff, AZ, USA) and sponsored by its Employee Assistance and Wellness Department. Participants • Participants were 35 employees with body mass indexes (BMIs) >25 kg/m2 who were ready and willing to make a lifestyle change, who were not currently participating in a weight loss program, and who were not taking any medications that could increase medical risk or had weight loss as a primary side effect. The average age of participants was 42.57 y; 91.4% were female, and 80% were Caucasian. Intervention • The intervention used a dietary protocol consisting of the daily consumption of greens, beans, legumes, and a variety of other vegetables, as well as fresh or frozen whole fruits, nuts, seeds, and whole grains. Participants were encouraged to minimize the consumption of refined grains, vegetable oils, processed foods, and animal products. Outcome Measures • The study measured serum lipids, height, weight, waist and hip circumference, waist-to-hip ratio, and blood pressure. Results • Based on paired-sample t tests and Wilcoxon signed-ranks test with a maximum level of P = . 05, the intervention resulted in significant changes in weight, BMI, waist and hip measurements, high-density lipoproteins, low-density lipoproteins, and estimated average glucose. Conclusions • The findings favorably revealed that an NDPR dietary intervention that was developed for worksites was an effective approach for reducing CVD risk factors.
Social work perceptions and identity: How social workers perceive public and professional attitudes towards their vocation and discipline

INTRODUCTION: A century after Abraham Flexner’s (1915/2001) infamous speech conveyed his “dismissive attitude toward social work’s professionalism,” Gelman and Gonzalez (2016) reflected that social work is again at a critical juncture. The fight for recognition of social work’s professional status has been influenced by multiple factors including negative public perceptions of the occupation. In Aotearoa New Zealand, professionalisation campaigns have been far from unifying, with diverse ideas about practice standards and accountability polarising opinions. At a time that the country is grappling with mandatory registration of social workers, this research considers the ways in which social workers perceive themselves, and the profession that they identify with. METHODS: Semi-structured interviews with 83 social workers in Aotearoa New Zealand were conducted. Participants were required to be eligible for social work registration. Interview transcripts were thematically analysed. FINDINGS: Several identity themes emerged during the analysis of the 83 interviews. The first theme relates to the ways in which statutory child protection social work has impacted on identity. The second, and perhaps predictable theme, is that many social workers in this study experienced significant professional marginalisation from their colleagues. The third theme emerged from participants’ views about the likelihood of mandatory registration of social workers impacting on their identity and the professional standing of social work. CONCLUSION: Most participants in the current study believed that mandatory social worker registration may positively influence the public’s view of social workers, other professionals, and also social workers themselves. However, many participants seemed to experience levels of self-stigma – and potentially believe they are viewed more negatively by the public than they actually are. Social workers’ perceptions of their role and profession is an area that warrants further investigation.
Increased Swelling Complications Associated With Off-Label Usage of rhBMP-2 in the Anterior Cervical Spine

Study Design/Setting. Independent, retrospective clinical record review with a concurrent control. Objective. To identify whether rhBMP-2 is associated with an increased incidence of clinically relevant postoperative prevertebral swelling problems in patients undergoing anterior cervical fusions. Summary of Background Data. Bone Morphogenetic Protein-2 (rhBMP-2) is FDA approved as a bone graft substitute in anterior lumbar interbody fusions. rhBMP-2 has also been used “off-label” in anterior cervical fusions. We suspected that rhBMP-2 might increase the incidence of adverse swelling events. Methods. A total of 234 consecutive patients (ages 12–82 years) undergoing anterior cervical fusion with and without rhBMP-2 over a 2-year period at one institution comprised the study population. The incidence of clinically relevant prevertebral swelling was calculated. The populations were compared and statistical significance was determined. Results. A total of 234 patients met the study criteria, 69 of whom underwent anterior cervical spine fusions using rhBMP-2; 27.5% of those patients in the rhBMP-2 group had a clinically significant swelling event versus only 3.6% of patients in the non-rhBMP-2 group. This difference was statistically significant (P < 0.0001) and remained so after controlling for other significant predictors of swelling. Conclusions. Off-label use of rhBMP-2 in the anterior cervical spine is associated with an increased rate of clinically relevant swelling events.
How do employee training and knowledge stocks affect product innovation?

ABSTRACT The main purpose of this paper is to explore how interactions of knowledge flows and knowledge stocks could shape firms’ innovative performance. Knowledge flows are measured on the grounds of human resource training practices while different levels and forms of knowledge stocks (i.e. educational attainment, exporting activity, and firm age) are considered. We make use of two-period panel probit regressions and a rich data survey of the 524 largest Greek manufacturing firms conducted in two waves (2011 and 2013). Our findings suggest that the beneficial effects of knowledge flows strengthen when knowledge stocks accumulated by employees’ education and firm age are low. When knowledge stocks are limited, knowledge flows can act as a bridge for product innovation. On the contrary, when knowledge stocks are high, higher investments in knowledge flows may lead to diminishing returns and, thus, to decreased innovation performance beyond a certain point.
Systematic Variation and Differences in Insulin-Autoantibody Measurements

Insulin autoantibodies (IAAs) are currently the subject of intensive investigation as potential markers for autoimmune insulitis. However, the results of different reports vary widely. In an attempt to elucidate the reasons for the discrepant reports and to initiate standardization procedures, the International Diabetes Workshop (IDW) undertook two studies in which 22 centers worldwidemeasured IAA in coded samples. The variance in binding signal from the 49 sera in study 1 was considerable, even when results were standardized, but was largely systematic and attributable to basic differences in assay type (liquid phase versus solid phase) and to differences in the ligand used (human vs. nonhuman insulin). In study 2, 5 sera were prepared and presented blindly to compare dilution curves, insulin-species specificity, interference from irrelevant serum proteins, precision, and dose-dependent displaceability. Many assays, both liquid and solid phase, were influenced by marked and unpredictable nonspecific binding, revealed by loss of parallelism between dilution curves in pooled normal serum and buffer, by variable binding signals with different normal sera, and by difficulty in distinguishing human insulin-specific from crossreactive IAA sera. It was concluded from the experience of both studies that variance could probably be reduced by using a standard curve with derived common units, a single species of ligand, and methodology to minimize the effect of nonspecific binding. Variation related to assay type was probably due to liquid-versus solid-phase systems being differentially more sensitive to certain aspects of antigen-antibody binding; this issue will be addressed in future serum exchanges and workshops.
Composition of the HLA‐DR‐associated human thymus peptidome

Major histocompatibility complex class II (MHC‐II) molecules bind to and display antigenic peptides on the surface of antigen‐presenting cells (APCs). In the absence of infection, MHC‐II molecules on APCs present self‐peptides and interact with CD4+ T cells to maintain tolerance and homeostasis. In the thymus, self‐peptides bind to MHC‐II molecules expressed by defined populations of APCs specialised for the different steps of T‐cell selection. Cortical epithelial cells present peptides for positive selection, whereas medullary epithelial cells and dendritic cells are responsible for peptide presentation for negative selection. However, few data are available on the peptides presented by MHC molecules in the thymus. Here, we apply mass spectrometry to analyse and identify MHC‐II‐associated peptides from five fresh human thymus samples. The data show a diverse self‐peptide repertoire, mostly consisting of predicted MHC‐II high binders. Despite technical limitations preventing single cell population analyses of peptides, these data constitute the first direct assessment of the HLA‐II‐bound peptidome and provide insight into how this peptidome is generated and how it drives T‐cell repertoire formation.
The role of education in promoting positive attitudes towards migration at times of stress

The paper examines the role of education in shaping individuals’ attitudes towards migration in European countries using data from the 2012, 2014 and 2016 editions of the European Social Survey (rounds 6, 7 and 8). Results indicate that, despite the large influx of migrants experienced by many European countries in 2015, attitudes towards migration reported by 25-65 year olds did not vary significantly over the period considered. Education was strongly associated with individuals’ attitudes towards migration although the strength of the association and how the association changed over time varied greatly across countries. On average a difference of one standard deviation in educational participation is associated with a difference of 20% of a standard deviation in reported opposition to migration. Around three quarters of the association between education and opposition to migration can be explained by the lower economic threat, cultural threat and prejudice that individuals with higher educational participation experience.
Selective harmonic mitigation technique for multilevel cascaded H-bridge converters

The increasing demand of energy and proliferation of non-linear loads have leaded to the appearance of new grid codes which limit the maximum acceptable harmonic levels. In this context, multilevel topologies are very attractive because can generate output waveforms with a low harmonic content using a low switching frequency. In this paper, the recently presented selective harmonic mitigation technique (SHMPWM) is adapted to a nine-level converter. Its flexibility is exploited to meet the EN 50160 and CIGRE WG 36−05 grid codes without any additional filtering system using 10 switching angles per quarter of period in a wide range of amplitudes of the fundamental harmonic from 0.70 to 1.22. Some results validating this technique applied to this topology are presented. A comparison with the well known selective harmonic elimination method is included showing the advantages of the SHMPWM technique.
Phasor measurement units placement for power system state estimation: A greedy approach

This paper considers the placement of synchronized Phasor Measurement Units (PMUs) in power systems to improve state estimation results. Since currently the number of PMUs deployed in the power system is far away from being sufficient achieve full system observability, one has to install the PMUs on a carefully selected subset of buses, such that the state estimation error is minimized. In this paper, we formulate the optimal PMU placement problem as an optimal experiment design problem, with a class of well-known optimality criteria, which are studied in the statistics literature. Since it has been shown that the optimal experiment design is NP-hard, we consider efficient suboptimal PMU placement algorithms. In particular, we show that the design criteria are usually related to a key property, submodularity, which often allows a greedy algorithm to achieve good approximation ratio. Specifically, we show that for typical power systems, a greedy PMU placement algorithm achieves at least 63% of the optimal reduction in total variance. The performance of the greedy PMU placement algorithms are further verified by simulation results.
Precocious expression of the Wilms' tumor gene xWT1 inhibits embryonic kidney development in Xenopus laevis.

The tumor suppressor WT1 has been demonstrated to have a wide variety of activities in vitro and is required for metanephric development in vivo. In the experiments presented here, the Xenopus pronephros was used as a simple model system to examine the activity of Xenopus WT1 (xWT1) during kidney development. xWT1 was ectopically expressed in Xenopus embryos by mRNA injection and found to inhibit pronephric tubule development. Confocal microscopy confirmed this observation and revealed that the inhibition was the result of a failure to form a pronephric anlage of appropriate size rather than a defect in epithelialization. Examination of Xlim-1 expression, an early molecular marker of pronephric specification, in tailbud embryos indicated that injected xWT1 mRNA inhibited pronephric specification prior to any overt sign of morphogenesis (Xenopus stage 21). These results suggest that xWT1 may act to repress tubule-specific gene expression in the portion of the pronephros fated to form its vascular structure, the glomus.
–455G/A β-fibrinogen gene polymorphism, factor V Leiden, prothrombin G20210A mutation and MTHFR C677T, and placental vascular complications

Hyperfibrinogenaemia is associated with systemic arterial and venous thromboembolism and therefore may contribute to placental vascular disease associated with obstetric complications. The fibrinogen-raising −455G/A β-fibrinogen gene polymorphism may enhance the physiological increase in fibrinogen levels during pregnancy and thereby predispose to obstetric complications. This retrospective case–control study looked at the association between the β-fibrinogen gene polymorphism −455G/A, the hereditary thrombophilic markers factor V Leiden, prothrombin G20210A mutation (PGM) and C677T methylene tetrahydrofolate reductase (MTHFR), and obstetric complications associated with placental vascular disease. The study group (n = 247) comprised 147 women (90 Caucasian) who met the clinical criteria and a control group of 100 parous women (90 Caucasian) with no history of obstetric or medical complications. No significant differences were observed in the −455A allelic frequencies of the patient and normal control groups, with (allelic frequencies, 0.156 and 0.178, respectively; P = 0.5716, χ2 test, odds ratio = 1.17, 95% confidence interval = 0.65–2.13) or without (allelic frequencies, 0.129 and 0.170, respectively; P = 0.2077, χ2 test, odds ratio = 1.38, 95% confidence interval = 0.81–2.35) the exclusion of non-Caucasian women. There was an increased prevalence of factor V Leiden among Caucasian patients compared with normal controls (allelic frequencies, 0.056 and 0.017, respectively; P = 0.048, χ2 test, odds ratio = 0.29, 95% confidence interval = 0.05–1.15) but there were no differences in the prevalences of PGM or MTHFR. These data suggest that factor V Leiden is associated with an increased risk of obstetric complications, but that the −455A allele of β-fibrinogen, PGM and MTHFR do not appear to be implicated.
Ca2+/cAMP-Sensitive Covariation of IA and IH Voltage Dependences Tunes Rebound Firing in Dopaminergic Neurons

The level of expression of ion channels has been demonstrated to vary over a threefold to fourfold range from neuron to neuron, although the expression of distinct channels may be strongly correlated in the same neurons. We demonstrate that variability and covariation also apply to the biophysical properties of ion channels. We show that, in rat substantia nigra pars compacta dopaminergic neurons, the voltage dependences of the A-type (IA) and H-type (IH) currents exhibit a high degree of cell-to-cell variability, although they are strongly correlated in these cells. Our data also demonstrate that this cell-to-cell covariability of voltage dependences is sensitive to cytosolic cAMP and calcium levels. Finally, using dynamic clamp, we demonstrate that covarying IA and IH voltage dependences increases the dynamic range of rebound firing while covarying their amplitudes has a homeostatic effect on rebound firing. We propose that the covariation of voltage dependences of ion channels represents a flexible and energy-efficient way of tuning firing in neurons.
The Role of Population in Economic Growth

The relationship between population growth and economic growth is controversial. This article draws on historical data to chart the links between population growth, growth in per capita output, and overall economic growth over the past 200 years. Low population growth in high-income countries is likely to create social and economic problems while high population growth in low-income countries may slow their development. International migration could help to adjust these imbalances but is opposed by many. Drawing on economic analyses of inequality, it appears that lower population growth and limited migration may contribute to increased national and global economic inequality.