Miracle-dz/UniFAR-FTUs huggingface dataset:
Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 × 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 106 and 12 × 106 DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1–specific CD8+ cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8+ T cell infiltration, whereas nonregressing lesions lacked CD8+ T cells as well as Mage-3 mRNA expression. This study proves the principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8+ CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression.
Associations of domain‐specific physical activities with insomnia symptoms among 0.5 million Chinese adults

Previous studies have demonstrated the association between physical activity and sleep quality. However, there is little evidence regarding different domains of physical activity. This study aimed to examine the associations between domain‐specific physical activities and insomnia symptoms among Chinese men and women. Data of 452 024 Chinese adults aged 30–79 years from the China Kadoorie Biobank Study were analysed. Insomnia symptoms were assessed with self‐reported difficulties in initiating or maintaining sleep, early morning awakening, daytime dysfunction and any insomnia symptoms. Physical activity assessed by questionnaire consisted of four domains, including occupational, commuting‐related, household and leisure‐time activities. Gender‐specific multiple logistic regression models were employed to estimate independent associations of overall and domain‐specific physical activities with insomnia symptoms. Overall, 12.9% of men and 17.8% of women participants reported having insomnia symptoms. After adjustment for potential confounders, a moderate to high level of overall activity was associated with reduced risks of difficulties in initiating or maintaining sleep and daytime dysfunction in both sexes (odds ratios range: 0.87–0.94, P < 0.05). As to each domain of physical activity, similar associations were identified for occupational, household and leisure‐time activities in women but not men (odds ratios range: 0.84–0.94, P < 0.05). Commuting‐related activity, however, was associated with increased risks of difficulties in initiating or maintaining sleep and any insomnia symptoms in both sexes (odds ratios range: 1.07–1.17, P < 0.05). In conclusion, a moderate to high level of physical activity was associated with lower risks of insomnia symptoms among Chinese adults. However, such associations varied hugely in different domains of physical activity and with gender differences, which could help with better policy‐making and clinical practice.
Holistic Approach to the Usage of Idioms and Translation of their Cultural Meanings

Considering the importance and relevance of research of the translation of cultural meanings, the article analyses cultural meanings in contemporary Lithuanian literary texts, their importance in an individual literary style, and strategies of translation into the French language. The present research covers culture-specific idioms. They are considered to be differential stylistic features of literary texts that transmit cultural connotations. Besides, idioms belong to the object of contemporary translation studies, which is the whole of all extratextual, intertextual, and intratextual relations that transmit meaning. The aim of the present article is to analyse the contextual realization and the frequency of usage of idioms in Lithuanian literary texts, to determine translation strategies applied by francophone translators for the translation of cultural meaning into the French language, and to define contemporary tendencies in cultural transposition as expressed in French translations.DOI: http://dx.doi. org/10.5755/j01.sal. 0.28. 15128
Trigger loop of RNA polymerase is a positional, not acid–base, catalyst for both transcription and proofreading

Significance Synthesis of new RNA and removal of incorrect nucleotides during proofreading by RNA polymerase involve the transfer of two protons. Here, we show that a polymerase component, the trigger loop, does not directly mediate proton transfer during these reactions, as previously proposed. Instead, the trigger loop plays a central role in transcription as a positional catalyst, by orienting the reactants and promoting the polymerase backtracking necessary for proofreading. This positional-catalyst model of trigger-loop function explains its diverse effects on polymerase catalysis and reconciles contradictory reports in the literature. By establishing that the trigger loop is not an acid–base catalyst, our results also guide the search for alternative proton donors and acceptors for reactions in the active site of polymerase. The active site of multisubunit RNA polymerases (RNAPs) is highly conserved from humans to bacteria. This single site catalyzes both nucleotide addition required for RNA transcript synthesis and excision of incorrect nucleotides after misincorporation as a proofreading mechanism. Phosphoryl transfer and proofreading hydrolysis are controlled in part by a dynamic RNAP component called the trigger loop (TL), which cycles between an unfolded loop and an α-helical hairpin [trigger helices (TH)] required for rapid nucleotide addition. The precise roles of the TL/TH in RNA synthesis and hydrolysis remain unclear. An invariant histidine residue has been proposed to function in the TH form as a general acid in RNA synthesis and as a general base in RNA hydrolysis. The effects of conservative, nonionizable substitutions of the TL histidine (or a neighboring TL arginine conserved in bacteria) have not yet been rigorously tested. Here, we report that glutamine substitutions of these residues, which preserve polar interactions but are incapable of acid–base chemistry, had little effect on either phosphoryl transfer or proofreading hydrolysis by Escherichia coli RNAP. The TL substitutions did, however, affect the backtracking of RNAP necessary for proofreading and potentially the reactivity of the backtracked nucleotide. We describe a unifying model for the function of the RNAP TL, which reconciles available data and our results for representative RNAPs. This model explains diverse effects of the TL basic residues on catalysis through their effects on positioning reactants for phosphoryl transfer and easing barriers to transcript backtracking, rather than as acid–base catalysts.
Autoimmune disease preceding amyotrophic lateral sclerosis

Objective: To study whether the risk of amyotrophic lateral sclerosis (ALS) is increased in people with prior autoimmune disease. Methods: An all-England hospital record-linkage dataset spanning 1999–2011 was used. Cohorts were constructed of people with each of a range of autoimmune diseases; the incidence of ALS in each disease cohort was compared with the incidence of ALS in a cohort of individuals without prior admission for the autoimmune disease. Results: There were significantly more cases than expected of ALS associated with a prior diagnosis of asthma, celiac disease, younger-onset diabetes (younger than 30 years), multiple sclerosis, myasthenia gravis, myxedema, polymyositis, Sjögren syndrome, systemic lupus erythematosus, and ulcerative colitis. Conclusions: Autoimmune disease associations with ALS raise the possibility of shared genetic or environmental risk factors.
Inheritance of Resistance to the Cry1Ab Bacillus thuringiensis Toxin in Ostrinia nubilalis (Lepidoptera: Crambidae)

Abstract Laboratory selection with Cry1Ab, the predominant Bacillus thuringiensis (Bt) toxin in transgenic corn, Zea mays L. , produced >1000-fold resistance in two laboratory strains of European corn borer, Ostrinia nubilalis (Hübner). We tested the offspring of various crosses to determine the mode of inheritance of resistance to Cry1Ab. Patterns of inheritance of resistance were similar in the two resistant strains. The progeny of reciprocal F1 crosses (resistant male × susceptible female and vice versa) responded alike in bioassays, indicating autosomal inheritance. The median lethal concentrations (LC50 values) of F1 were intermediate between the resistant and susceptible parents, indicating approximately additive inheritance. However, the dominance of resistance increased as the concentration of Cry1Ab decreased. Analysis of progeny from backcrosses (F1 × susceptible strain) suggests that resistance was controlled by more than one locus. In particular, the fit of observed to expected mortality improved as the number of putative loci increased from 1 to 10. The polygenic nature of resistance in these two laboratory strains suggests that major genes for resistance to Cry1Ab were not common in the founding populations of O. nubilalis. A low initial frequency of major genes for Cry1Ab resistance might be an important factor in delaying evolution of resistance to Bt corn in this pest.
Sustained Domestic Vector Exposure Is Associated With Increased Chagas Cardiomyopathy Risk but Decreased Parasitemia and Congenital Transmission Risk Among Young Women in Bolivia.

BACKGROUND We studied women and their infants to evaluate risk factors for congenital transmission and cardiomyopathy in Trypanosoma cruzi-infected women. METHODS Women provided data and blood for serology and quantitative polymerase chain reaction (PCR). Infants of infected women had blood tested at 0 and 1 month by microscopy, PCR and immunoblot, and serology at 6 and 9 months. Women underwent electrocardiography (ECG). RESULTS Of 1696 women, 456 (26.9%) were infected; 31 (6.8%) transmitted T. cruzi to their infants. Women who transmitted had higher parasite loads than those who did not (median, 62.0 [interquartile range {IQR}, 25.8-204.8] vs 0.05 [IQR, 0-29.6]; P < .0001). Transmission was higher in twin than in singleton births (27.3% vs 6.4%; P = .04). Women who had not lived in infested houses transmitted more frequently (9.7% vs 4.6%; P = .04), were more likely to have positive results by PCR (65.5% vs 33.9%; P < .001), and had higher parasite loads than those who had lived in infested houses (median, 25.8 [IQR, 0-64.1] vs 0 [IQR, 0-12.3]; P < .001). Of 302 infected women, 28 (9.3%) had ECG abnormalities consistent with Chagas cardiomyopathy; risk was higher for older women (odds ratio [OR], 1.06 [95% confidence interval {CI}, 1.01-1.12] per year) and those with vector exposure (OR, 3.7 [95% CI, 1.4-10.2]). We observed a strong dose-response relationship between ECG abnormalities and reported years of living in an infested house. CONCLUSIONS We hypothesize that repeated vector-borne infection sustains antigen exposure and the consequent inflammatory response at a higher chronic level, increasing cardiac morbidity, but possibly enabling exposed women to control parasitemia in the face of pregnancy-induced Th2 polarization.
Investigating the Macro Perspective Affecting the Passing Rate in Board Examinations: A Take-off Point in Designing a Causal Model

Tagoloan Community College is now challenged with producing graduates who are globally competitive, most especially graduates who are going to take board examinations. The study aimed to investigate the factors affecting the board examination performance of TCC in the board examinations. This study used the descriptive method of research, using a researcher-made questionnaire, focused group discussion and guided interviews to gather data. With three sets of respondents, adding up to a total of 147, it was found out that among the three courses (Criminology, BEED and BSED), and in the four years that TCC took part in the board examinations, the passing rate achieved was never below the National Passing Rate. The performance of TCC can be said to have started unsatisfactorily, but has been improving to render a good to a very good performance level. When the data gathered from all the sets of respondents were summarized, it was found out that it was the internal and stable factors over which the examinees can exercise an amount of control that affect their performance. It is the “Moving Automobile Causal Model” that best fits and represents the factors that have direct effect on the performance of TCC. Another model was also created, the “Airplane Taking-Off Model”, to show all the attributions that are perceived by the respondents and are proven by other researches to have bearing on the results of the board examinations. Two review programs are proposed to be implemented by TCC.
Pathway Linking Internet Health Information Seeking to Better Health: A Moderated Mediation Study

ABSTRACT The Internet increasingly has been recognized as an important medium with respect to population health. However, little is known about the mechanisms that underlie the potential impact of health-related Internet use on health outcomes. Based on the three-stage model of health promotion using interactive media, this study empirically tested a moderated mediation pathway model. Results showed that the effect of Internet health information seeking on three health outcomes (general, emotional, and physical) was completely mediated by respondents’ access to social support resources. In addition, users’ online health information seeking experience positively moderated this mediation path. The findings have significant theoretical and practical implications for the design of Internet-based health promotion resources to improve health outcomes.
Analysis of scientists social representations in action based on words associated by scientific articles

Les representations des chercheurs se caracterisent par le fait qu'elles associent des elements heterogenes, des savoirs et des savoirs faire. Elles sont composees de concepts, de dispositifs experimentaux, d'instruments de mesure etc. Nous proposons de les appeler representations en action. Celles-ci conduisent a l'hypothese de representations multiples simultanement mises en oeuvre a l'interieur d'un domaine de recherche donne. Ces representations dependent des sous-cultures des scientifiques et sont articulees a travers un processus dit de traduction. C'est la raison pour laquelle nous avons construit une nouvelle methodologie pour decrire, a travers l'articulation de representations partielles, la dynamique des representations sociales dans le contexte de la science en construction, l'analyse des mots associes (programmes Leximappe et Sampler). Il en resulte un outil capable de decrire la dynamique reelle d'un domaine de recherche a partir d'une analyse des representations des chercheurs.
Multicentre individual randomised controlled trial of screening and brief alcohol intervention to prevent risky drinking in young people aged 14–15 in a high school setting (SIPS JR-HIGH): study protocol

Introduction Drinking has adverse impacts on health, well-being, education and social outcomes for adolescents. Adolescents in England are among the heaviest drinkers in Europe. Recently, the proportion of adolescents who drink alcohol has fallen, although consumption among those who do drink has actually increased. This trial seeks to investigate how effective and efficient an alcohol brief intervention is with 11–15 years olds to encourage lower alcohol consumption. Methods and analysis This is an individually randomised two-armed trial incorporating a control arm of usual school-based practice and a leaflet on a healthy lifestyle (excl. alcohol), and an intervention arm that combines usual practice with a 30 min brief intervention delivered by school learning mentors and a leaflet on alcohol. At least 30 schools will be recruited from four regions in England (North East, North West, London, Kent and Medway) to follow-up 235 per arm. The primary outcome is total alcohol consumed in the last 28 days, using the 28 day Timeline Follow Back questionnaire measured at the 12-month follow-up. The analysis of the intervention will consider effectiveness and cost-effectiveness. A qualitative study will explore, via 1:1 in-depth interviews with (n=80) parents, young people and school staff, intervention experience, intervention fidelity and acceptability issues, using thematic narrative synthesis to report qualitative data. Ethics and dissemination Ethical approval was granted by Teesside University. Dissemination plans include academic publications, conference presentations, disseminating to local and national education departments and the wider public health community, including via Fuse, and engaging with school staff and young people to comment on whether and how the project can be improved. Trial registration trial ISRCTN45691494; Pre-results.
Selecting anti-HIV therapies based on a variety of genomic and clinical factors

Motivation: Optimizing HIV therapies is crucial since the virus rapidly develops mutations to evade drug pressure. Recent studies have shown that genotypic information might not be sufficient for the design of therapies and that other clinical and demographical factors may play a role in therapy failure. This study is designed to assess the improvement in prediction achieved when such information is taken into account. We use these factors to generate a prediction engine using a variety of machine learning methods and to determine which clinical conditions are most misleading in terms of predicting the outcome of a therapy. Results: Three different machine learning techniques were used: generative–discriminative method, regression with derived evolutionary features, and regression with a mixture of effects. All three methods had similar performances with an area under the receiver operating characteristic curve (AUC) of 0.77. A set of three similar engines limited to genotypic information only achieved an AUC of 0.75. A straightforward combination of the three engines consistently improves the prediction, with significantly better prediction when the full set of features is employed. The combined engine improves on predictions obtained from an online state-of-the-art resistance interpretation system. Moreover, engines tend to disagree more on the outcome of failure therapies than regarding successful ones. Careful analysis of the differences between the engines revealed those mutations and drugs most closely associated with uncertainty of the therapy outcome. Availability: The combined prediction engine will be available from July 2008, see http://engine.euresist. org Contact: rosen@il.ibm. com
Feasibility and acceptability of an iPad application to explore symptom clusters in adolescents and young adults with cancer

The aim of this study was to evaluate the feasibility and acceptability of a computer‐based symptom cluster heuristics tool designed to explore symptom clusters experienced by adolescents and young adults (AYAs) with cancer. The Computerized Symptom Capture Tool (C‐SCAT) is a newly developed iPad application, which combines graphical images and free text responses in an innovative heuristics approach to explore symptoms and symptom clusters.
Evaluación de la Práctica Docente. Una Revisión desde España

Se analizan los modos y condiciones para que la evaluación de la práctica docente pueda promover la mejora y, sobre todo, su papel para asegurar la equidad de todos los alumnos en su derecho a la educación. La evaluación del desempeño docente debe dirigirse a capacitar a escuelas y profesores para conseguir los estándares deseados e incrementar dicha calidad. La evaluación docente ha de posibilitar la construcción de la capacidad de cambio de los centros y contar con un contexto de apoyo externo, al tiempo que presión para cambiar. El artículo revisa la situación de la evaluación del profesorado en España, así como las nuevas vías que abre la nueva Ley de Educación. Si la política educativa quiere incrementar la cualidad y los resultados, tiene que invertir en el conocimiento y competencias necesarias para conseguirlos. Esto requiere un nuevo modelo de responsabilización por los resultados, como señala Elmore. Al respecto, la autoevaluación institutucional precede a la responsabilidad externa de los resultados y debe combinarse actualmente con una responsabilidad por los resultados inteligente, que contribuya a presionar e incentivar la mejora.Palabras clave: Evaluación del profesorado, responsabilidad por los resultados, capacidad de mejora, España. The ways and conditions are analyzed so that the evaluation of the educational practice can promote the improvement and, above all, its role to assure the equity of all the students in its right to the education. The teacher evaluation and performance they should be directed to qualify to schools and professors to obtain the standards desired and to increase quality. Teacher evaluation should make possible change capacity building of the schools and count on an external supporting context, and also the pressure to change. The paper review the situation of the teacher evaluation in Spain, as well as the new routes that the new Education Act opens. If the policymakers want to increase quality and performance, they have to invest in the knowledge and skill necessary to produce it. This requires a new model of accountability, as says Elmore. As regards this, internal accountability precedes external accountability and should be presently combined with an authentic and intelligent accountability, contributing to push (top-up strategy) and stimulate improvement.Keywords: Teacher evaluation, accountability, improvement capacity, Spain.