Miracle-dz/UniFAR-FTUs huggingface dataset:
The Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) Is Associated With High GAD Antibody Titer in Latent Autoimmune Diabetes in Adults

OBJECTIVE—We previously demonstrated the presence of two different populations among individuals with adult-onset autoimmune diabetes: those having either a high titer or a low titer of antibodies to GAD (GADAs). Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) has been identified as a new susceptibility gene for type 1 diabetes and other autoimmune diseases. The aim of the present study was to evaluate whether the phenotypic heterogeneity of adult-onset autoimmune diabetes based on the GADA titer is associated with the PTPN22 C1858T polymorphism. RESEARCH DESIGN AND METHODS—Analysis for the C1858T polymorphism using the TaqMan assay was performed in 250 subjects with adult-onset autoimmune diabetes, divided into two subgroups with low (≤32 arbitrary units) or high (>32 arbitrary units) GADA titers and 450 subjects with classic type 2 diabetes (from the Non Insulin Requiring Autoimmune Diabetes [NIRAD] Study cohort of 5,330 subjects with adult-onset diabetes) and in 558 subjects with juvenile-onset type 1 diabetes and 545 normoglycemic subjects. RESULTS—Genotype, allele, and phenotype distributions of the PTPN22 C1858T variant revealed similar frequencies in autoimmune diabetes with high GADA titer and juvenile-onset type 1 diabetes. An increase in TT and CT genotypes was observed in individuals with a high GADA titer compared with a low GADA titer, those with type 2 diabetes, and control subjects (P < 0.002 for all comparisons). The PTPN22 1858T allele and phenotype frequencies were increased in high GADA titer compared with a low GADA titer, type 2 diabetic, and control subjects (P < 0.001 for all comparisons, odds ratio 2.6). CONCLUSIONS—In adult-onset autoimmune diabetes, the PTPN22 1858T variant is associated only with a high GADA titer, providing evidence of a genetic background to clinical heterogeneity identified by GADA titer.
A CENSUS OF X-RAY GAS IN NGC 1068: RESULTS FROM 450 ks of CHANDRA HIGH ENERGY TRANSMISSION GRATING OBSERVATIONS

We present models for the X-ray spectrum of the Seyfert 2 galaxy NGC 1068. These are fitted to data obtained using the High Energy Transmission Grating on Chandra. The data show line and radiative recombination continuum emission from a broad range of ions and elements. The models explore the importance of excitation processes for these lines including photoionization followed by recombination, radiative excitation by absorption of continuum radiation, and inner shell fluorescence. The models show that the relative importance of these processes depends on the conditions in the emitting gas and that no single emitting component can fit the entire spectrum. In particular, the relative importance of radiative excitation and photoionization/recombination differs according to the element and ion stage emitting the line. This in turn implies a diversity of values for the ionization parameter of the various components of gas responsible for the emission, ranging from log(ξ) = 1 to 3. Using this, we obtain an estimate for the total amount of gas responsible for the observed emission. The mass flux through the region included in the HETG extraction region is approximately 0.3 M☉ yr−1, assuming ordered flow at the speed characterizing the line widths. This can be compared with what is known about this object from other techniques.
Fast On-Line Task Placement and Scheduling on Reconfigurable Devices

This paper focus on on-line placement and scheduling of tasks with known executing time on reconfigurable devices. The notion of recognition-earliest for scheduling algorithms is introduced, that is the algorithm can arrange the start time of a newly arrived task as early as possible. A new scheduling algorithm is proposed. By exploit the knowledge about temporal properties of each task, the algorithm attains recognition-earliest. A fast placement algorithm is also presented. The evaluation results show that the proposed placement algorithm is one of the fastest algorithm, and the proposed scheduling algorithm achieves the best performance compared with previous algorithms, while has a quite low runtime cost.
An Empirical Evaluation of the First and Second Order Mutation Testing Strategies

Various mutation approximation techniques have been proposed in the literature in order to reduce the expenses of mutation. This paper presents results from an empirical study conducted for first and second order mutation testing strategies. Its scope is to evaluate the relative application cost and effectiveness of the different mutation strategies. The application cost was based: on the number of mutants, the equivalent ones and on the number of test cases needed to expose them by each strategy. Each strategy's effectiveness was evaluated by its ability to expose a set of seeded faults. The results indicate that on the one hand the first order mutation testing strategies can be in general more effective than the second order ones. On the other hand, the second order strategies can drastically decrease the number of the introduced equivalent mutants, generally forming a valid cost effective alternative to mutation testing.
The Phosphoproteome of Bloodstream Form Trypanosoma brucei, Causative Agent of African Sleeping Sickness

The protozoan parasite Trypanosoma brucei is the causative agent of human African sleeping sickness and related animal diseases, and it has over 170 predicted protein kinases. Protein phosphorylation is a key regulatory mechanism for cellular function that, thus far, has been studied in T.brucei principally through putative kinase mRNA knockdown and observation of the resulting phenotype. However, despite the relatively large kinome of this organism and the demonstrated essentiality of several T. brucei kinases, very few specific phosphorylation sites have been determined in this organism. Using a gel-free, phosphopeptide enrichment-based proteomics approach we performed the first large scale phosphorylation site analyses for T.brucei. Serine, threonine, and tyrosine phosphorylation sites were determined for a cytosolic protein fraction of the bloodstream form of the parasite, resulting in the identification of 491 phosphoproteins based on the identification of 852 unique phosphopeptides and 1204 phosphorylation sites. The phosphoproteins detected in this study are predicted from their genome annotations to participate in a wide variety of biological processes, including signal transduction, processing of DNA and RNA, protein synthesis, and degradation and to a minor extent in metabolic pathways. The analysis of phosphopeptides and phosphorylation sites was facilitated by in-house developed software, and this automated approach was validated by manual annotation of spectra of the kinase subset of proteins. Analysis of the cytosolic bloodstream form T. brucei kinome revealed the presence of 44 phosphorylated protein kinases in our data set that could be classified into the major eukaryotic protein kinase groups by applying a multilevel hidden Markov model library of the kinase catalytic domain. Identification of the kinase phosphorylation sites showed conserved phosphorylation sequence motifs in several kinase activation segments, supporting the view that phosphorylation-based signaling is a general and fundamental regulatory process that extends to this highly divergent lower eukaryote.
Fusion of Ubiquitin to HIV Gag Impairs Human Monocyte-Derived Dendritic Cell Maturation and Reduces Ability to Induce Gag T Cell Responses

The efficient induction of CD8 T cell immunity is dependent on the processing and presentation of antigen on MHC class I molecules by professional antigen presenting cells (APC). To develop an improved T cell vaccine for HIV we investigated whether fusing the ubiquitin gene to the N terminus of the HIV gag gene enhanced targeting to the proteasome resulting in better CD8 T cell responses. Human monocyte derived dendritic cells (moDC), transduced with adenovirus vectors carrying either ubiquitinated or non-ubiquitinated gag transgene constructs, were co-cultured with autologous naïve T cells and T cell responses were measured after several weekly cycles of stimulation. Despite targeting of the ubiquitin gag transgene protein to the proteasome, ubiquitination did not increase CD8 T cell immune responses and in some cases diminished responses to gag peptides. There were no marked differences in cytokines produced from ubiquitinated and non-ubiquitinated gag stimulated cultures or in the expression of inhibitory molecules on expanded T cells. However, the ability of moDC transduced with ubiquitinated gag gene to upregulate co-stimulatory molecules was reduced, whilst no difference in moDC maturation was observed with a control ubiquitinated and non-ubiquitinated MART gene. Furthermore moDC transduced with ubiquitinated gag produced more IL-10 than transduction with unmodified gag. Thus failure of gag ubiquitination to enhance CD8 responses may be caused by suppression of moDC maturation. These results indicate that when designing a successful vaccine strategy to target a particular cell population, attention must also be given to the effect of the vaccine on APCs.
The Node-weighted Steiner Problem in Graphs of Restricted Node Weights

In this paper we study a variant of the Node-Weighted Steiner Tree problem in which the weights (costs) of vertices are restricted, in the sense that the ratio of the maximum node weight to the minimum node weight is bounded by a quantity α. This problem has applications in multicast routing where the cost of participating routers must be taken into consideration and the network is relatively homogenous in terms of the cost of the routers. We consider both online and offline versions of the problem. For the offline version we show an upper bound of O(min{log α, log k}) on the approximation ratio of deterministic algorithms (where k is the number of terminals). We also prove that the bound is tight unless P = NP . For the online version we show a tight bound of Θ(max{min{α, k}, log k}), which applies to both deterministic and randomized algorithms. We also show how to apply (and extend to node-weighted graphs) recent work of Alon et al. so as to obtain a randomized online algorithm with competitive ratio O(log m log k), where m is the number of the edges in the graph, independently of the value of α. All our bounds also hold for the Generalized Node-Weighted Steiner Problem, in which only connectivity between pairs of vertices must be guaranteed.
SimilarTech: Automatically recommend analogical libraries across different programming languages

Third-party libraries are an integral part of many software projects. It often happens that developers need to find analogical libraries that can provide comparable features to the libraries they are already familiar with. Existing methods to find analogical libraries are limited by the community-curated list of libraries, blogs, or Q&A posts, which often contain overwhelming or out-of-date information. This paper presents our tool SimilarTech (https://graphofknowledge. appspot.com/similartech) that makes it possible to automatically recommend analogical libraries by incorporating tag embeddings and domain-specific relational and categorical knowledge mined from Stack Overflow. SimilarTech currently supports recommendation of 6,715 libraries across 6 different programming languages. We release our SimilarTech website for public use. The SimilarTech website attracts more than 2,400 users in the past 6 months. We observe two typical usage patterns of our website in the website visit logs which can satisfy different information needs of developers. The demo video can be seen at https://youtu.be/ubx8h4D4ieE.
BRCA1 and BRCA2 genetic testing in Italian breast and/or ovarian cancer families: mutation spectrum and prevalence and analysis of mutation prediction models.

BACKGROUND Breast cancer is an extremely complex disease, characterized by a progressive multistep process caused by interactions of both genetic and non-genetic factors. A combination of BRCA1 and BRCA2 gene mutations appears responsible for about 20%-30% of the cases with breast cancer familial history. The prevalence of BRCA1/2 pathogenic mutations largely varies within different populations; in particular, the rate of mutations in Italian breast and/or ovarian cancer families is rather controversial and ranges from 8% to 37%. PATIENTS AND METHODS Of the 152 breast/ovarian cancer families counseled in our centre, 99 were selected for BRCA1/2 mutation screening according to our minimal criteria. The entire coding sequences and each intron/exon boundary of BRCA1/2 genes were screened by direct sequencing (PTT limited to BRCA1 exon 11). For each proband, the a priori probability of carrying a pathogenic BRCA1/2 germline mutation was calculated by means of different mutation prediction models (BRCApro, IC and Myriad Table) in order to evaluate their performances. RESULTS Our analysis resulted in the identification of 25 and 52 variants in the BRCA1 and BRCA2 genes, respectively. Seventeen of them represent novel variants, including four deleterious truncating mutations in the BRCA2 gene (472insA, E33X, C1630X and IVS6+1G>C). Twenty-seven of the 99 probands harbored BRCA1 (n = 15) and BRCA2 (n = 12) pathogenic germline mutations, indicating an overall detection rate of 27.3% and increasing by more than 15% the spectrum of mutations in the Italian population. Furthermore, we found the lowest detection rate (19.4%) in pure hereditary breast cancer family subset. All of the prediction models showed praises and faults, with the IC software being extremely sensitive but poorly specific, compared to BRCApro. In particular all models accumulated most false-negative prediction in the HBC subset. Interestingly preliminary results of a study addressing the presence of genomic rearrangements in HBC probands with BRCApro or IC prediction scores >/=95%, provided evidence for additional mutations undetectable with our conventional screening for point mutations. CONCLUSIONS Altogether our results suggest that HBC families, the largest pool in our series, represent an heterogeneous group where the apparently faulty performances of the prediction models might be at least partially explained by the presence of additional kinds of BRCA1/2 alteration (such as genomic rearrangements) or by mutations on different breast cancer related genes.
KIF6 719Arg Carrier Status Association with Homocysteine and C-Reactive Protein in Amnestic Mild Cognitive Impairment and Alzheimer's Disease Patients

Recent research has demonstrated associations between statin use, KIF6 719Arg carrier status, and cholesterol levels and amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) patients. The association between 719Arg carrier status with homocysteine (tHcy) and c-reactive protein (CRP) levels in aMCI and AD has not been previously investigated. Data from 175 aMCI and AD patients were used for the analysis. 719Arg carriers had significantly lower levels of tHcy than noncarriers (P = 0.02). No significant difference in CRP levels between 719Arg carriers and noncarriers was present (P = 0.37). Logistic regression yielded no significant effect for 719Arg status on CRP [OR = 1.79 (0.85, 3.83), P = 0.13] but did demonstrate a significant effect for tHcy [OR = 0.44 (0.23, 0.83), P = 0.01] after adjusting for ApoE ε4 carrier status, age, gender, and statin use. This study is the first to explore the relationship between KIF6 719Arg carrier status with tHcy and CRP levels. 719Arg carriers were more likely to have normal tHcy levels after adjusting for ApoE ε4 status, age, gender, and statin use. These results suggest that the KIF6 gene might influence cardiovascular pathways associated with AD.
Brazilian Journal of Otorhinolaryngology the Effects of Concurrent Cognitive Tasks on Postural Sway in Healthy Subjects Palavras-chave

The effects of concurrent cognitive tasks on postural sway in healthy subjects Abstract Introduction: Keeping balance of the upright stance is a highly practiced daily task for healthy adults and is effectively performed without overt attentional control in most. Objective: The purpose of this study was to examine the influence of concurrent cognitive tasks on postural sway in healthy participants. Methods: This was a prospective study. 20 healthy volunteer subjects were included. The cog-nitive and balance tasks were performed separately and then, concurrently. Postural control task consisted of 6 conditions (C) of the Sensory Organization Test. The cognitive task consisted of digit rehearsal task of varying presentation and varying levels of difficulty. Results: A statistically significant difference was noted between dual task and no task for C1, C2, C3 and C4 Sensory Organization Test scores (p < 0.05). There was no statistically significant difference between dual task versus non-task for C5, C6 and combined Sensory Organization Test scores (p > 0.05). Conclusion: During dual task, increase has been determined in postural sway for C1, C2, C3 and C4 for all presentation modes and difficulty levels of the cognitive tasks. Equilíbrio postural; Realização e análise de tarefas; Memória de curto prazo; Atenção Efeitos de tarefas cognitivas simultâneas no equilíbrio postural em indivíduos saudáveis Resumo Introdução: Manter o equilíbrio na postura vertical é uma tarefa cotidiana constantemente praticada por adultos saudáveis, e é efetivamente realizada pela maioria sem a necessidade de um controle atencional. Objetivo: A finalidade deste estudo foi examinar a influência de tarefas cognitivas concomi-tantes no equilíbrio postural de indivíduos saudáveis. Método: Trata-se de um estudo prospectivo em que participaram 20 voluntários saudáveis. As tarefas cognitivas e de equilíbrio foram realizadas separadamente; e em seguida, real-izadas simultaneamente. A tarefa de controle postural consistiu em seis condições (C) do Teste de Organização Sensorial (TOS). A tarefa cognitiva consistiu na repetição de dígitos com apresentações variadas e vários níveis de dificuldade. Resultados: Houve diferença estatisticamente significante entre os escores do TOS para as condições C1, C2, C3 e C4 para ''dupla tarefa'' vs. ''não tarefa'' (p < 0,05). Não houve diferença estatisticamente significante entre os escores do TOS para as condições C5 e C6 e para a combinação dos escores do TOS para ''dupla tarefa'' vs. ''não tarefa'' (p > 0,05). Conclusão: Durante a realização de dupla tarefa, foram determinados aumentos na oscilação postural para as condições C1, C2, C3 e C4 …
Classification of radiation effects for dose limitation purposes: history, current situation and future prospects

Radiation exposure causes cancer and non-cancer health effects, each of which differs greatly in the shape of the dose–response curve, latency, persistency, recurrence, curability, fatality and impact on quality of life. In recent decades, for dose limitation purposes, the International Commission on Radiological Protection has divided such diverse effects into tissue reactions (formerly termed non-stochastic and deterministic effects) and stochastic effects. On the one hand, effective dose limits aim to reduce the risks of stochastic effects (cancer/heritable effects) and are based on the detriment-adjusted nominal risk coefficients, assuming a linear-non-threshold dose response and a dose and dose rate effectiveness factor of 2. On the other hand, equivalent dose limits aim to avoid tissue reactions (vision-impairing cataracts and cosmetically unacceptable non-cancer skin changes) and are based on a threshold dose. However, the boundary between these two categories is becoming vague. Thus, we review the changes in radiation effect classification, dose limitation concepts, and the definition of detriment and threshold. Then, the current situation is overviewed focusing on (i) stochastic effects with a threshold, (ii) tissue reactions without a threshold, (iii) target organs/tissues for circulatory disease, (iv) dose levels for limitation of cancer risks vs prevention of non-life-threatening tissue reactions vs prevention of life-threatening tissue reactions, (v) mortality or incidence of thyroid cancer, and (vi) the detriment for tissue reactions. For future discussion, one approach is suggested that classifies radiation effects according to whether effects are life threatening, and radiobiological research needs are also briefly discussed.
Prevention in a school environment of hearing loss due to leisure noise

Purpose To verify the habits and attitudes of school-age youths regarding the use of personal music players, and assess their knowledge level about the harmful effects to the hearing of exposure to amplified music before and after an educational lecture. Methods A total of 58 elementary and middle school students aged 10 to 17 years participated in the study. We presented an educational lecture using an expository dialogue format with audiovisual resources. To evaluate the students, we applied two online questionnaires before and 15 days after the lecture. Descriptive analysis was also performed. Results Most students reported using personal music players with earphones above the mean intensity of the equipment and for fewer than 3 hours a day. The most frequent complaint was tinnitus. After the educational lecture, there were differences in knowledge about the concept of hearing loss and the fact that high-intensity music in moments of leisure may cause hearing loss. There was also a difference in the intensity used to listen to music with earphones, which decreased. Conclusion Most students had prior knowledge of the harmful effect of amplified music on hearing and even then, some indicated inadequate habits. The educational lecture showed significant changes in only some of the aspects investigated, reflecting a need to structure continuous actions towards hearing loss prevention in this population. The inclusion of the school and the family in educational actions and the continuity of these actions are fundamental to effective changes in habits and attitudes among children and adolescents.
Generating optimal CUDA sparse matrix–vector product implementations for evolving GPU hardware

The CUDA model for graphics processing units (GPUs) presents the programmer with a plethora of different programming options. These includes different memory types, different memory access methods and different data types. Identifying which options to use and when is a non‐trivial exercise. This paper explores the effect of these different options on the performance of a routine that evaluates sparse matrix–vector products (SpMV) across three different generations of NVIDIA GPU hardware. A process for analysing performance and selecting the subset of implementations that perform best is proposed. The potential for mapping sparse matrix attributes to optimal CUDA SpMV implementations is discussed. Copyright © 2011 John Wiley & Sons, Ltd.