Miracle-dz/UniFAR-FTUs huggingface dataset:
Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer

Purpose: BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of BRCA2 gene affects the clinical outcome of ovarian cancer patients. Experimental Design: A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for BRCA1 and BRCA2 genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer (n = 316) was used as a validation cohort. Results: In the study cohort, 78 patients were carriers of germline mutations of BRCA2. After adjustment for FIGO stage and macroscopic residual disease, BRCA2 carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS [58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20–0.64; P = 0.001] and prolonged PFI (29.7 vs. 15.5 months, P = 0.011), compared with noncarriers. BRCA2 carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42–1.07; P = 0.094) or PFI (19 vs. 15.5 months, P = 0.146). In the TCGA cohort, only BRCA2 carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13–0.68; P = 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02–0.38; P = 0.001). Conclusions: Among ovarian cancer patients, BRCA2 carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS. Clin Cancer Res; 24(2); 326–33. ©2017 AACR.
Parent and child asthma illness representations: a systematic review

Abstract Objective: The purpose of this article is to synthesize the current literature on parent and child asthma illness representations and their consequent impact on parent–child asthma shared management. Data sources: This systematic review was conducted in concordance with the PRISMA statement. An electronic search of five computerized databases (PubMed, PsycINFO, CINAHL, Cochrane, and EMBASE) was conducted using the following key words: asthma, illness representation, and child. Due to the limited number of articles identified, the search was broadened to include illness perceptions as well. Study Selections: Studies were included if they were specific to asthma and included parent and/or child asthma illness representations or perception, were published after 2000, and available in English. Fifteen articles were selected for inclusion. All of the articles are descriptive studies that used cross-sectional designs. Seven of the studies used parent and child participants, eight used parents only, and none used only child participants. Results: None of the selected studies describe child asthma illness representations, and only three describe parental asthma illness representations. Domains of illness representations, including symptoms, timeline, consequences, cause, and controllability were described in the remaining articles. Symptoms and controllability appear to have the most influence on parental asthma management practices. Parents prefer symptomatic or intermittent asthma management and frequently cite concerns regarding daily controller medication use. Parents also primarily rely on their own objective symptom observations rather than the child’s report of symptoms. Conclusion: Asthma illness representations are an important area of future study to better understand parent–child shared asthma management.
Hydrogen bonding of redox-active tyrosine Z of photosystem II probed by FTIR difference spectroscopy.

The TyrZ. /TyrZ FTIR difference spectrum is reported for the first time in Mn-depleted photosystem II (PS II)-enriched membranes of spinach, in PS II core complexes of Synechocystis sp. PCC 6803 WT, and in the mutant lacking TyrD (D2-Tyr160Phe). In Synechocystis, the v7'a(CO) and delta(COH) infrared modes of TyrZ are proposed to account at 1279 and 1255 cm-1. The frequency of these modes indicate that TyrZ is protonated at pH 6 and involved in a strong hydrogen bond to the side chain of a histidine, probably D1-His190. A positive signal at 1512 cm-1 is assigned to the v(CO) mode of TyrZ. on the basis of the 27 cm-1 downshift observed upon 13C-Tyr labeling at the Tyr ring C4 carbon. A second IR signal, at 1532 cm-1, is tentatively assigned to the v8a(CC) mode of TyrZ. The frequency of the v(CO) mode of TyrZ. at 1512 cm-1 is comparable to that observed at 1513 cm-1 for the Tyr. obtained by UV photochemistry of tyrosinate in solution, while it is higher than that of TyrD. in WT PS II at 1503 cm-1 and that of non-hydrogen-bonded TyrD. in the D2-His189Gln mutant at 1497 cm-1 [Hienerwadel, R. , Boussac, A. , Breton, J., Diner, B. A. , and Berthomieu, C. (1997) Biochemistry 36, 14712-14723]. This latter work and the present FTIR study suggest that hydrogen bonding induces an upshift of the v(CO) IR mode of tyrosyl radicals and that TyrZ. forms (a) stronger hydrogen bond(s) than TyrD. in WT PS II. Alternatively, the frequency difference between TyrZ. and TyrD. v(CO) modes could be explained by a more localized positive charge near the tyrosyl radical oxygen of TyrD. than TyrZ. The TyrZ. /TyrZ spectrum obtained in Mn-depleted PS II membranes of spinach shows large similarities with the S3'/S2' spectrum characteristic of radical formation in Mn-containing but Ca(2+)-depleted PS II, in support of the assignment using ESEEM of TyrZ. as being responsible for the split EPR signal observed upon illumination in these conditions [Tang, X. -S. , Randall, D. W. , Force, D. A. , Diner, B. A. , and Britt, R. D. (1996) J. Am. Chem. Soc. 118, 7638-7639]. The peak at 1514 cm-1 is assigned to the v(CO) mode of TyrZ. in these preparations, which indicates that Mn depletion only very slightly perturbs the immediate environment of TyrZ. phenoxyl.
FUTURE EURO AREA MEMBERSHIP OF BULGARIA IN TERMS OF THE BUSINESS CYCLE

In the present paper, vector autoregression (VAR) is used to assess the extent to which Bulgaria’s economic cycle is synchronized with the one of the euro area (EA). The main fiscal and monetary factors affecting the coordination of the business cycles of Bulgaria and the EA are identified. Recommendations for macroeconomic policies are formulated to support the synchronization of Bulgaria’s economic cycle with the one of the EA and to prepare our country for the adoption of the euro.
MODIFYING EFFECTS OF HEALTH STATUS, PHYSIOLOGICAL, AND DOSIMETRIC FACTORS ON EXTRAPULMONARY ORGAN DISTRIBUTION AND EXCRETION OF INHALED PLUTONIUM IN WORKERS AT THE MAYAK PRODUCTION ASSOCIATION

This paper summarizes the systemic organ distribution of plutonium in workers exposed by chronic inhalation at the Mayak Production Association (MPA). Using results of radiochemical measurements in soft tissue and bone samples collected at autopsy of 853 autopsy cases, this paper provides data on the effects of various chronic diseases and malignant tumors as well as exposure time, age, sex, and body burden on systemic retention of plutonium in 22 extrapulmonary organs and on the urinary excretion rate of the nuclide. Some aspects of this work have been reported already. The results of present autopsy studies showed that liver pathology accompanied by strong fatty dystrophy of hepatocytes results in a significant relative decrease in the fraction of systemic plutonium in the liver and contravariant increase in the skeletal fraction. The average fractions of systemic plutonium in the liver and the skeleton of those MPA workers were 15% and 75%, respectively, in comparison with 47% and 45% in healthy individuals. Some of the plutonium also redistributed from the liver via blood to other systemic soft tissues. Plutonium not redistributed was excreted with urine. The results of multivariate regression analysis indicated some time-related and sex-related changes not connected with pathology for the liver and the skeleton retention fractions and excretion rate of plutonium. The current ICRP biokinetic models do not account for the influence of different pathological processes in the body on plutonium distribution in systemic organs and urinary excretion. This could have significant consequences for dosimetry calculations and risk estimations.
Analysis and design of a power factor correction rectifier with load current injection

A robust control technique for power factor correction rectifiers with average current mode control is proposed in this paper. By adding a load current loop to the conventional current mode scheme, the output voltage response to load steps is much faster and therefore the typical voltage over-shoots that this kind of converters presents are reduced. Although the load current injection is traditionally considered as a 'load feed-forward', this paper shows that this technique introduces also an additional feedback loop, which modifies the linear dynamic model of the converter. In order to validate the concept, a 250 W prototype working from universal input line has been designed and tested.
Oxidative Transformation of Aminodinitrotoluene Isomers by Multicomponent Dioxygenases

ABSTRACT The electron-withdrawing nitro substituents of 2,4,6-trinitrotoluene (TNT) make the aromatic ring highly resistant to oxidative transformation. The typical biological transformation of TNT involves reduction of one or more of the nitro groups of the ring to produce the corresponding amine. Reduction of a single nitro substituent of TNT to an amino substituent increases the electron density of the aromatic nucleus considerably. The comparatively electron-dense nuclei of the aminodinitrotoluene (ADNT) isomers would be expected to be more susceptible to oxygenase attack than TNT. The hypothesis was tested by evaluating three nitroarene dioxygenases for the ability to hydroxylate the ADNT isomers. The predominant reaction was dioxygenation of the ring to yield nitrite and the corresponding aminomethylnitrocatechol. A secondary reaction was benzylic monooxygenation to form aminodinitrobenzyl alcohol. The substrate preferences and catalytic specificities of the three enzymes differed considerably. The discovery that the ADNT isomers are substrates for the nitroarene dioxygenases reveals the potential for extensive bacterial transformation of TNT under aerobic conditions.
Requirements for Calibration in Noninvasive Glucose Monitoring by Raman Spectroscopy

Background: In the development of noninvasive glucose monitoring technology, it is highly desirable to derive a calibration that relies on neither person-dependent calibration information nor supplementary calibration points furnished by an existing invasive measurement technique (universal calibration). Method: By appropriate experimental design and associated analytical methods, we establish the sufficiency of multiple factors required to permit such a calibration. Factors considered are the discrimination of the measurement technique, stabilization of the experimental apparatus, physics-physiology-based measurement techniques for normalization, the sufficiency of the size of the data set, and appropriate exit criteria to establish the predictive value of the algorithm. Results: For noninvasive glucose measurements, using Raman spectroscopy, the sufficiency of the scale of data was demonstrated by adding new data into an existing calibration algorithm and requiring that (a) the prediction error should be preserved or improved without significant re-optimization, (b) the complexity of the model for optimum estimation not rise with the addition of subjects, and (c) the estimation for persons whose data were removed entirely from the training set should be no worse than the estimates on the remainder of the population. Using these criteria, we established guidelines empirically for the number of subjects (30) and skin sites (387) for a preliminary universal calibration. We obtained a median absolute relative difference for our entire data set of 30 mg/dl, with 92% of the data in the Clarke A and B ranges. Conclusions: Because Raman spectroscopy has high discrimination for glucose, a data set of practical dimensions appears to be sufficient for universal calibration. Improvements based on reducing the variance of blood perfusion are expected to reduce the prediction errors substantially, and the inclusion of supplementary calibration points for the wearable device under development will be permissible and beneficial.
RNA Polymerase II Blockage by Cisplatin-damaged DNA

The consequences of human RNA polymerase II (pol II) arrest at the site of DNA damaged by cisplatin were studied in whole cells and cell extracts, with a particular focus on the stability of stalled pol II and its subsequent ubiquitylation. Site-specifically platinated DNA templates immobilized on a solid support were used to perform in vitro transcription in HeLa nuclear extracts. RNA elongation was completely blocked by a cisplatin intrastrand cross-link. The stalled polymerase was quite stable, remaining on the DNA template in nuclear extracts. The stability of pol II stalled at the site of cisplatin damage was also observed in live cells. A cell fractionation experiment using cisplatin-treated HeLa cells revealed an increased level of chromatin-associated pol II proteins following DNA damage. The stalled polymerase was transcriptionally active and capable of elongating the transcript following chemical removal of platinum from the template. Transcription inhibition by α-amanitin in vitro enhanced pol II ubiquitylation at ubiquitin residues Lys-6, Lys-48, and Lys-63. In live cells expressing epitope-tagged ubiquitin mutants, several ubiquitin lysines also participated in pol II ubiquitylation following DNA damage. Cisplatin treatment triggered ubiquitylation-mediated pol II degradation in HeLa cells, which could be prevented by the proteasomal inhibitor MG132. Fractionation of pol II from cells co-treated with MG132 and cisplatin indicated that the undegraded ubiquitylated polymerase was mostly unbound or only loosely associated with chromatin. These data are consistent with a model in which only a fraction of pol II, ubiquitylated in response to cisplatin damage of DNA, dissociates from the sites of platination. This altered polymerase is rapidly destroyed by proteasomes.
Piketty's second fundamental law of capitalism as an emergent property in a kinetic wealth-exchange model of economic growth

We propose in this work a kinetic wealth-exchange model of economic growth by introducing saving as a non consumed fraction of production. In this new model, which starts also from microeconomic arguments, it is found that economic transactions between pairs of agents leads the system to a macroscopic behavior where total wealth is not conserved and it is possible to have an economic growth which is assumed as the increasing of total production in time. This last macroeconomic result, that we find both numerically through a Monte Carlo based simulation method and analytically in the framework of a mean field approximation, corresponds to the economic growth scenario described by the well known Solow model developed in the economic neoclassical theory. If additionally to the income related with production due to return on individual capital, it is also included the individual labor income in the model, then the Thomas Piketty's second fundamental law of capitalism is found as a emergent property of the system. We consider that the results obtained in this paper shows how Econophysics can help to understand the connection between macroeconomics and microeconomics.
Genetics of onset of asthma

Purpose of reviewMost asthma starts early in life. Defining phenotypes of asthma at this age is difficult as many preschool children have asthma-like respiratory symptoms. This review discusses progress in defining early wheezing phenotypes and describes genetic factors associated with the age of onset of asthma. Recent findingsLatent class analyses confirmed transient and persistent wheezing phenotypes, and identified a novel intermediate-onset wheezing phenotype that was strongly associated with atopy and asthma at age 8 years. However, no single cross-sectional or longitudinal definition of respiratory symptoms in childhood strongly predicts asthma later in life. Genome-wide association (GWA) studies have identified a locus on chromosome 17q12–21 (encoding ORMDL3 and GSDMB) as a risk factor for predominantly childhood-onset asthma, but not for atopy, and overall not for adult-onset asthma. Other loci found by GWA studies appear to increase asthma risk both in children and adults. Atopy genes do not explain early-onset asthma. SummaryAlthough most asthma starts early in life, no valid test is able to identify asthma at that age period. GWA studies have provided more insight into the unique and common genetic origins of adult-onset and childhood-onset asthma. The 17q12–21 locus is predominantly associated with childhood-onset asthma.
Blind Verification of Elevated Platelet Autoantibodies in Serum of Schizophrenic Patients – Part I: Young Subjects

Background: It has been hypothesized that the etiology of schizophrenia, in a distinct group of patients, originates from an autoimmune reaction against platelets. Previous open screenings have recorded significantly higher blood titers of platelet-associated autoantibodies (PAA) in schizophrenic patients as compared to normal healthy subjects. In addition, young schizophrenic patients at the early stages of their disorder displayed higher PAA titers than older patients with a longer duration of the disorder. A blood test based on these observations was proposed. Aim: To verify by a blind test a significant difference in PAA between young schizophrenic patients and matched healthy control subjects, for the validation of a blood test for schizophrenia. Methods: A total of 36 young schizophrenic patients in an active psychotic state, aged 13–20 years (mean ± SD: 16.2 ± 2.1 years) with an average PANSS score of 115.6 ± 14.5 and illness duration of 9.5 ± 9.4 months, were examined. The control group consisted of 49 healthy young subjects between the ages of 13 and 21 years (16.2 ± 2.2 years). The blood titers of PAA were evaluated blindly using an optimized ELISA test, expressed by a linear optical density (OD) scale. The blood samples of all participants were tested anonymously, and were scored under a code number. A test recording above 1.3 OD units was defined as positive. Results: The PAA titers of schizophrenia patients (1.6 ± 0.4 OD units, range: 0.7–2.3 OD units) were significantly higher than those of the control group (1.0 ± 0.4 OD units, range: 0.4–1.8 OD units; p < 0.0001). In 61% of the young schizophrenic patients (22 out of the 36 patients), a positive result (OD >1.3 units) was recorded. In the control group, only 12.2% (6 of the 49 subjects) displayed a positive result (p < 0.0001). Conclusions: These findings support further assessment of PAA titers as a potential biomarker for patients with clinical signs and symptoms of schizophrenia.
Role of sleep and circadian disruption on energy expenditure and in metabolic predisposition to human obesity and metabolic disease

Weight gain, obesity and diabetes have reached alarming levels in the developed world. Traditional risk factors such as over‐eating, poor nutritional choices and lack of exercise cannot fully account for the high prevalence of metabolic disease. This review paper examines the scientific evidence on two novel risk factors that contribute to dys‐regulated metabolic physiology: sleep disruption and circadian misalignment. Specifically, fundamental relationships between energy metabolism and sleep and circadian rhythms and the impact of sleep and circadian disruption on metabolic physiology are examined. Millions of individuals worldwide do not obtain sufficient sleep for healthy metabolic function, and many participate in shift work and social activities at times when the internal physiological clock is promoting sleep. These behaviours predispose an individual for poor metabolic health by promoting excess caloric intake in response to reduced sleep, food intake at internal biological times when metabolic physiology is not prepared, decreased energy expenditure when wakefulness and sleep are initiated at incorrect internal biological times, and disrupted glucose metabolism during short sleep and circadian misalignment. In addition to the traditional risk factors of poor diet and exercise, disturbed sleep and circadian rhythms represent modifiable risk factors for prevention and treatment of metabolic disease and for promotion of healthy metabolism.
Opinion Toward Living Liver Donation of Hospital Personnel From Units Related to Organ Donation and Transplantation: A Multicenter Study From Spain and Latin-America

Background: Hospital personnel of services related to donation and transplantation process play a fundamental role in the development of transplantation. Objectives: The aim of this study was to investigate the attitude toward living liver donation (LLD) among hospital personnel from services related to donation and transplantation in hospital centers in Spain and Latin America. Materials and Methods: Eight hospitals within the “International Donor Collaborative Project” were selected, three in Spain, three in Mexico and two in Cuba. The study was performed in transplant-related services, using a randomized sample, which was stratified by the type of service and job category. Results: In total, 878 workers were surveyed of which 82% (n = 720) were in favor of related LLD, 10% (n = 90) were against and 8% (n = 68) undecided. Attitudes toward related LLD were more favorable in the following groups: the Latin Americans (86% in favor vs. 77% among the Spanish; P = 0.007); younger people (37 vs. 40 years, P = 0.002); those in favor of either deceased donation (P < 0.001) or living kidney donation (P < 0.001); those who believed that they might need a transplant in the future (P < 0.001); those who would accept a liver from a living donor (P < 0.001); those who discussed the subject of donation and transplantation with their families (P = 0.040); and those whose partner was in favor of donation and transplantation (P = 0.044). Conclusions: Personnel from donation and transplantation-related units had a favorable attitude toward LLD. This attitude was not affected by psychosocial factors, although it was influenced by factors directly and indirectly related to the donation and transplantation process.
Increased Expression of Fas (APO-1, CD95) on CD4+ and CD8+ T Lymphocytes during Total Body Irradiation

Fas/APO-1 (CD95) is a cell surface molecule that can transduce apoptotic signals into cells. We examined the expression of Fas antigen on CD4+ and CD8+ T cells of patients who received total body irradiation (TBI) as a preparative regimen for allogeneic bone marrow transplantation. Numbers of peripheral blood lymphocytes were significantly reduced after TBI. Cytofluorometric analysis revealed a significantly higher expression of Fas on CD4+ and CD8+ T cells after TBI. Serum soluble Fas concentrations were significantly elevated after TBI. Changes in the Fas system were therefore accompanied by TBI-induced lymphocytopenia, suggesting that Fas plays a role in irradiation-induced apoptosis in vivo.