An Empirical Analysis of NMT-Derived Interlingual Embeddings and their Use in Parallel Sentence Identification

End-to-end neural machine translation has overtaken statistical machine translation in terms of translation quality for some language pairs, specially those with large amounts of parallel data. Besides this palpable improvement, neural networks provide several new properties. A single system can be trained to translate between many languages at almost no additional cost other than training time. Furthermore, internal representations learned by the network serve as a new semantic representation of words -or sentences- which, unlike standard word embeddings, are learned in an essentially bilingual or even multilingual context. In view of these properties, the contribution of the present work is two-fold. First, we systematically study the NMT context vectors, i.e. output of the encoder, and their power as an interlingua representation of a sentence. We assess their quality and effectiveness by measuring similarities across translations, as well as semantically related and semantically unrelated sentence pairs. Second, as extrinsic evaluation of the first point, we identify parallel sentences in comparable corpora, obtaining an F1=98.2% on data from a shared task when using only NMT context vectors. Using context vectors jointly with similarity measures F1 reaches 98.9%.Comment: 11 pages, 4 figure

Bullying and Aggression Among Adolescents

katedra: KSS; rozsah: 63 s. (71 829 znaků)This thesis deals with aggression and bullying in adolescents and is based on the literature addressing this issue. Its aim was to analyze the aggression and bullying of clients in facilities with the institutional and stored protected upbringing. It is a facility in Šluknovský process - Children's Home in Lipová Šluknov and Children's Home and School in Jiříkov. Very important was to compare the extent of bullying in both homes and awareness of the respondents in this area. The work consists of two key areas. This is the theoretical part, that the compilation of expert sources describe the problems of aggression, bullying, maturation, and explains the differences between children's homes and orphanages in school. The practical part determined by a questionnaire and empirical research on attitudes, knowledge and experience with clients of fifty ordered institutional education and stored on the issue of bullying and compares the results of the responses of respondents in the device. The purpose of my thesis was to compare the extent of bullying in both devices. The results led to the proposed concrete measures to prevent bullying and socially pathological phenomena as a whole. The greatest benefit in relation to solving problems can be considered to measure the incidence of bullying, the degree of awareness of children's homes in the area of bullying and other work as recorded in the work of educators at the Children's Home in Lipová.Bakalářská práce se zabývá problematikou agresivity a šikany u dospívajících a vychází z odborné literatury řešící tuto problematiku. Jejím cílem bylo zmapování problematiky agresivity a šikany u klientů v zařízeních s nařízenou ústavní a ochranou výchovou. Jednalo se o zařízení ve Šluknovském výběžku ? Dětský domov Lipová u Šluknova a Dětský domov se školou v Jiříkově. Velmi důležité bylo porovnání míry výskytu šikany v obou domovech a informovanosti jednotlivých respondentů v této oblasti. Práci tvoří dvě stěžejní oblasti. Jedná se o část teoretickou, která pomocí zpracování odborných zdrojů popisuje problematiku agresivity, šikany, dospívání a vysvětluje rozdíly mezi dětskými domovy a dětskými domovy se školou. Praktická část zjišťuje pomocí dotazníku a empirického výzkumu postoje, zkušenosti a znalosti padesáti klientů zařízení s nařízenou a uloženou ústavní výchovou v oblasti problematiky šikany a srovnává výsledky odpovědí respondentů jednotlivých zařízení. Smyslem práce dále bylo porovnání míry výskytu šikany v obou zařízeních. Výsledky vyústily v konkrétní navrhovaná opatření v oblasti prevence šikany a sociálně patologických jevů jako celku. Za největší přínos vzhledem k řešené problematice je možné považovat zjištění míry výskytu šikany, stupně informovanosti dětí z dětských domovů v oblasti šikany a další práce se zjištěnými výsledky při práci vychovatele v Dětském domově v Lipové

The Role of Space in the Creation of Knowledge in Austria. An Exploratory Spatial Data Analysis

The paper makes a modest attempt to shed some light on the role of space in the creation of technological knowledge in Austria. The study is exploratory rather than explanatory in nature and based on descriptive techniques such as Moran¿s I test for spatial autocorrelation and the Moran scatterplot. Clusters of the knowledge ¿output¿ [measured in terms of patent counts] are compared with spatial concentration patterns of two input measures of knowledge production: private R&D and academic research. In addition, employment in manufacturing is utilised to capture agglomeration economies. The analysis is based on data aggregated for two digit SIC industries and at the level of Austrian political districts. It explores the extent to which knowledge spillovers are mediated by spatial proximity in Austria. A time-space comparison makes it possible to study whether divergence or convergence processes in knowledge creation have occurred in the past two decades. As in the case of any exploratory data analysis, the findings need to be treated with caution and should be viewed only as an initial pre-modelling stage in the enterprise. Future research activities will be devoted to further exploring the issue of local university knowledge spillovers within a refined production framework (see Griliches 1979). (authors' abstract)Series: Discussion Papers of the Institute for Economic Geography and GIScienc

Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage

Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) catalyzes the hydrolysis of dUTP to dUMP and PPi. Although dUTP is a normal intermediate in DNA synthesis, its accumulation and misincorporation into DNA is lethal. Importantly, uracil misincorporation is a mechanism of cytotoxicity induced by fluoropyrimidine chemotherapeutic agents including 5-fluorouracil (5-FU) and elevated expression of dUTPase is negatively correlated with clinical response to 5-FU-therapy. In this study we performed the first functional characterization of the dUTPase promoter and demonstrate a role for E2F-1 and Sp1 in driving dUTPase expression. We establish a direct role for both mutant and wild-type forms of p53 in modulating dUTPase promoter activity. Treatment of HCT116 p53+/+ cells with the DNA-damaging agent oxaliplatin induced a p53-dependent transcriptional downregulation of dUTPase not observed in the isogenic null cell line. Oxaliplatin treatment induced enrichment of p53 at the dUTPase promoter with a concomitant reduction in Sp1. The suppression of dUTPase by oxaliplatin promoted increased levels of dUTP that was enhanced by subsequent addition of fluoropyrimidines. The novel observation that oxaliplatin downregulates dUTPase expression may provide a mechanistic basis contributing to the synergy observed between 5-FU and oxaliplatin in the clinic. Furthermore, these studies provide the first evidence of a direct transcriptional link between the essential enzyme dUTPase and the tumor suppressor p53

The Amsterdam Declaration on Fungal Nomenclature

The Amsterdam Declaration on Fungal Nomenclature was agreed at an international symposium convened in Amsterdam on 19–20 April 2011 under the auspices of the International Commission on the Taxonomy of Fungi (ICTF). The purpose of the symposium was to address the issue of whether or how the current system of naming pleomorphic fungi should be maintained or changed now that molecular data are routinely available. The issue is urgent as mycologists currently follow different practices, and no consensus was achieved by a Special Committee appointed in 2005 by the International Botanical Congress to advise on the problem. The Declaration recognizes the need for an orderly transitition to a single-name nomenclatural system for all fungi, and to provide mechanisms to protect names that otherwise then become endangered. That is, meaning that priority should be given to the first described name, except where that is a younger name in general use when the first author to select a name of a pleomorphic monophyletic genus is to be followed, and suggests controversial cases are referred to a body, such as the ICTF, which will report to the Committee for Fungi. If appropriate, the ICTF could be mandated to promote the implementation of the Declaration. In addition, but not forming part of the Declaration, are reports of discussions held during the symposium on the governance of the nomenclature of fungi, and the naming of fungi known only from an environmental nucleic acid sequence in particular. Possible amendments to the Draft BioCode (2011) to allow for the needs of mycologists are suggested for further consideration, and a possible example of how a fungus only known from the environment might be described is presented

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension