Languages that allow free word order, such as Arabic dialects, are of significant difficulty for neural machine translation (NMT) because of many scarce words and the inefficiency of NMT systems to ...translate these words. Unknown Word (UNK) tokens represent the out-of-vocabulary words for the reason that NMT systems run with vocabulary that has fixed size. Scarce words are encoded completely as sequences of subword pieces employing the Word-Piece Model. This research paper introduces the first Transformer-based neural machine translation model for Arabic vernaculars that employs subword units. The proposed solution is based on the Transformer model that has been presented lately. The use of subword units and shared vocabulary within the Arabic dialect (the source language) and modern standard Arabic (the target language) enhances the behavior of the multi-head attention sublayers for the encoder by obtaining the overall dependencies between words of input sentence for Arabic vernacular. Experiments are carried out from Levantine Arabic vernacular (LEV) to modern standard Arabic (MSA) and Maghrebi Arabic vernacular (MAG) to MSA, Gulf–MSA, Nile–MSA, Iraqi Arabic (IRQ) to MSA translation tasks. Extensive experiments confirm that the suggested model adequately addresses the unknown word issue and boosts the quality of translation from Arabic vernaculars to Modern standard Arabic (MSA).
We show analytically that training a neural network by conditioned stochastic mutation or neuroevolution of its weights is equivalent, in the limit of small mutations, to gradient descent on the loss ...function in the presence of Gaussian white noise. Averaged over independent realizations of the learning process, neuroevolution is equivalent to gradient descent on the loss function. We use numerical simulation to show that this correspondence can be observed for finite mutations, for shallow and deep neural networks. Our results provide a connection between two families of neural-network training methods that are usually considered to be fundamentally different.
Accurate and rapid identification of perturbed pathways through the analysis of genome-wide expression profiles facilitates the generation of biological hypotheses. We propose a statistical framework ...for determining whether a specified group of genes for a pathway has a coordinated association with a phenotype of interest. Several issues on proper hypothesis-testing procedures are clarified. In particular, it is shown that the differences in the correlation structure of each set of genes can lead to a biased comparison among gene sets unless a normalization procedure is applied. We propose statistical tests for two important but different aspects of association for each group of genes. This approach has more statistical power than currently available methods and can result in the discovery of statistically significant pathways that are not detected by other methods. This method is applied to data sets involving diabetes, inflammatory myopathies, and Alzheimer's disease, using gene sets we compiled from various public databases. In the case of inflammatory myopathies, we have correctly identified the known cytotoxic T lymphocyte-mediated autoimmunity in inclusion body myositis. Furthermore, we predicted the presence of dendritic cells in inclusion body myositis and of an IFN-α/β response in dermatomyositis, neither of which was previously described. These predictions have been subsequently corroborated by immunohistochemistry.
ABSTRACT
The receptor for advanced glycan end products (RAGE) has been identified as a susceptibility gene for chronic obstructive pulmonary disease (COPD) in genome‐wide association studies (GWASs). ...However, less is known about how RAGE is involved in the pathogenesis of COPD. To determine the molecular mechanism by which RAGE influences COPD in experimental COPD models, we investigated the efficacy of the RAGE‐specific antagonist FPS‐ZM1 administration in in vivo and in vitro COPD models. We injected elastase intratracheally and the RAGE antagonist FPS‐ZM1 in mice, and the infiltrated inflammatory cells and cytokines were assessed by ELISA. Cellular expression of RAGE was determined in protein, serum, and bronchoalveolar lavage fluid of mice and lungs and serum of human donors and patients with COPD. Downstream damage‐associated molecular pattern (DAMP) pathway activation in vivo and in vitro and in patients with COPD was assessed by immunofluorescence staining, Western blot analysis, and ELISA. The expression of membrane RAGE in initiating the inflammatory response and of soluble RAGE acting as a decoy were associated with up‐regulation of the DAMP‐related signaling pathway via Nrf2. FPS‐ZM1 administration significantly reversed emphysema in the lung of mice. Moreover, FPS‐ZM1 treatment significantly reduced lung inflammation in Nrf2+/+, but not in Nrf2‒/‒ mice. Thus, our data indicate for the first time that RAGE inhibition has an essential protective role in COPD. Our observation of RAGE inhibition provided novel insight into its potential as a therapeutic target in emphysema/COPD.—Lee, H., Park, J.‐R., Kim, W. J., Sundar, I. K., Rahman, I., Park, S.‐M., Yang. S.‐R. Blockade of RAGE ameliorates elastase‐induced emphysema development and progression via RAGE‐DAMP signaling. FASEB J. 31, 2076–2089 (2017). www.fasebj.org
Type 2 diabetes mellitus is a complex disorder associated with multiple genetic, epigenetic, developmental, and environmental factors. Animal models of type 2 diabetes differ based on diet, drug ...treatment, and gene knockouts, and yet all display the clinical hallmarks of hyperglycemia and insulin resistance in peripheral tissue. The recent advances in gene-expression microarray technologies present an unprecedented opportunity to study type 2 diabetes mellitus at a genome-wide scale and across different models. To date, a key challenge has been to identify the biological processes or signaling pathways that play significant roles in the disorder. Here, using a network-based analysis methodology, we identified two sets of genes, associated with insulin signaling and a network of nuclear receptors, which are recurrent in a statistically significant number of diabetes and insulin resistance models and transcriptionally altered across diverse tissue types. We additionally identified a network of protein-protein interactions between members from the two gene sets that may facilitate signaling between them. Taken together, the results illustrate the benefits of integrating high-throughput microarray studies, together with protein-protein interaction networks, in elucidating the underlying biological processes associated with a complex disorder.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The purpose of this study was to evaluate the influence of avascular necrosis of the femoral head (AVN) following hip reconstructions on the future hip development of cerebral palsy (CP) ...patients. A retrospective study of 394 hips in 205 nonambulatory patients with spastic CP who underwent reconstructive hip surgery was performed. The mean age at surgery was 7.3 ± 2.4 years. The mean follow-up duration was 5.6 ± 2.7 years, and the mean age at the latest follow-up was 12.8 ± 3.4 years. AVN was classified in terms of its severity and location. Femoral head remodelling was assessed by the spherical index and the Mose circle. An unsatisfactory radiological outcome was defined as having a migration percentage of more than 30% at the final follow-up. AVN was observed in 169 (42.9%) hips. Older age at the time of surgery, higher preoperative migration percentage, and open reduction procedures were predictors for the development of AVN. Hips with AVN confined to the lateral epiphysis, and AVN involving the entire epiphysis with preserved height experienced successful remodelling. 27 (65.9%) of the 41 hips with unsatisfactory outcomes experienced AVN. Younger age, higher postoperative migration percentage, and occurrence of AVN were related to unsatisfactory outcomes. The highest incidence of failed remodelling and unsatisfactory outcomes were observed in hips with entire epiphyseal involvement and more than 50% loss of its height. AVN following hip reconstructions is not necessarily associated with poor hip development, however, depending on the severity and location, it is a prognostic factor for unsatisfactory radiological outcomes.
We analyze a time series of global temperature anomaly distributions to identify and estimate persistent features in climate change. We employ a formal test for the existence of functional unit roots ...in the time series of these densities, and we develop a new test to distinguish functional unit roots from functional deterministic trends or explosive behavior. Results suggest that temperature anomalies contain stochastic trends (as opposed to deterministic trends or explosive roots), two trends are present in the Northern Hemisphere while one stochastic trend is present in the Southern Hemisphere, and the probabilities of observing moderately positive anomalies have increased. We postulate that differences in the pattern and number of unit roots in each hemisphere may be due to a natural experiment which causes human emissions of greenhouse gases and sulfur to be greater in the Northern Hemisphere, decreasing the mean temperature anomaly but increasing the spatial variance relative to the Southern Hemisphere. Together, these results are consistent with the theory of anthropogenic climate change.
It is widely accepted that long-run elasticities of demand for electricity are not stable over time. We model long-run sectoral electricity demand using a time-varying cointegrating vector. ...Specifically, the coefficient on income (residential sector) or output (commercial and industrial sectors) is allowed to follow a smooth semiparametric function of time, providing a flexible specification that allows more accurate out-of-sample forecasts than either fixed or discretely changing regression coefficients. We fit the model to Korean data over 1995:01-2012:12 for the residential sector and 1985:01-2012:12 for the commercial and industrial sectors. The rapid development of Korea over this period provides a very clear case for allowing the coefficient on income/output to vary over time, but the essential modeling strategy is widely applicable.
•Introduced a long-run electricity demand model with smoothly varying income/output elasticity•Demonstrated that conventional fixed-coefficient models overestimate income/output elasticities•Estimated using a flexible semiparametric technique and applied to Korean sectoral data•Found that Korean elasticities have increased dramatically over the past few decades•Found substantial forecasting improvement using the time-varying approach over the conventional approach
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