Abstract-Insulin resistance is associated with obesity and may be accompanied by left ventricular diastolic dysfunction and myocardial remodeling. Decreased insulin metabolic signaling and increased oxidative stress may promote these maladaptive changes. In this context, the ␤-blocker nebivolol has been reported to improve insulin sensitivity, increase endothelial NO synthase activity, and reduce NADPH oxidase-induced superoxide generation. We hypothesized that nebivolol would attenuate diastolic dysfunction and myocardial remodeling by blunting myocardial oxidant stress and promoting insulin metabolic signaling in a rodent model of obesity, insulin resistance, and hypertension. Six-week-old male Zucker obese and age-matched Zucker lean rats were treated with nebivolol (10 mg ⅐ kg Ϫ ⅐ day Ϫ1 ) for 21 days, and myocardial function was assessed by cine MRI. Compared with untreated Zucker lean rats, untreated Zucker obese rats exhibited prolonged diastolic relaxation time (27.7Ϯ2.5 versus 40.9Ϯ2.0 ms; PϽ0.05) and reduced initial diastolic filling rate (6.2Ϯ0.5 versus 2.8Ϯ0.6 L/ms; PϽ0.05) in conjunction with increased homeostatic model assessment of insulin resistance (7Ϯ2 versus 95Ϯ21; PϽ0.05), interstitial and pericapillary fibrosis, abnormal cardiomyocyte histoarchitecture, 3-nitrotyrosine, and NADPH oxidase-dependent superoxide. Nebivolol improved diastolic relaxation (32.8Ϯ0.7 ms; PϽ0.05 versus untreated Zucker obese), reduced fibrosis, and remodeling in Zucker obese rats, in concert with reductions in nitrotyrosine, NADPH oxidase-dependent superoxide, and improvements in the insulin metabolic signaling, endothelial NO synthase activation, and weight gain (381Ϯ7 versus 338Ϯ14 g; PϽ0.05). Results support the hypothesis that nebivolol reduces myocardial structural maladaptive changes and improves diastolic relaxation in concert with improvements in insulin sensitivity and endothelial NO synthase activation, concomitantly with reductions in oxidative stress. (Hypertension. 2010;55:880-888.) Key Words: nebivolol Ⅲ oxidative stress Ⅲ insulin resistance Ⅲ diastolic relaxation Ⅲ MRI O besity-induced cardiomyopathy is characterized by impaired left ventricular (LV) relaxation in association with insulin resistance (IR). 1,2 This cardiomyopathy develops independent of blood pressure, ischemia, impaired systolic function, and age. 1,2 Impaired insulin metabolic signaling and increased generation of reactive oxygen species (ROS) play important roles in maladaptive myocardial remodeling 3-5 and impaired diastolic relaxation. 6,7 Excessive ROS in the heart and vasculature, derived from several enzymatic sources, including NADPH oxidase, 8 can lead to decreased bioavailable NO and reduced delivery of glucose and insulin to myocardial tissue. 4,9 ␤-Adrenergic receptor blockers have clinical use in treating heart failure, but traditional ␤-blockers have been associated with weight gain and worsening of IR. Nebivolol, a third-generation ␤ 1 -receptor blocker improves diastolic dysfunction 10 and reduces mortality in elderly he...

Most of the state-of-the-art sentiment classification methods are based on supervised learning algorithms which require large amounts of manually labeled data. However, the labeled resources are usually imbalanced in different languages. Cross-lingual sentiment classification tackles the problem by adapting the sentiment resources in a resource-rich language to resource-poor languages. In this study, we propose an attention-based bilingual representation learning model which learns the distributed semantics of the documents in both the source and the target languages. In each language, we use Long Short Term Memory (LSTM) network to model the documents, which has been proved to be very effective for word sequences. Meanwhile, we propose a hierarchical attention mechanism for the bilingual LSTM network. The sentence-level attention model learns which sentences of a document are more important for determining the overall sentiment while the word-level attention model learns which words in each sentence are decisive. The proposed model achieves good results on a benchmark dataset using English as the source language and Chinese as the target language.

Cross-lingual sentiment classification aims to adapt the sentiment resource in a resource-rich language to a resource-poor language. In this study, we propose a representation learning approach which simultaneously learns vector representations for the texts in both the source and the target languages. Different from previous research which only gets bilingual word embedding, our Bilingual Document Representation Learning model BiDRL directly learns document representations. Both semantic and sentiment correlations are utilized to map the bilingual texts into the same embedding space. The experiments are based on the multilingual multi-domain Amazon review dataset. We use English as the source language and use Japanese, German and French as the target languages. The experimental results show that BiDRL outperforms the state-of-the-art methods for all the target languages.

Purpose Enterprise social media platforms (ESMPs) are web 2.0-based computer media tools that facilitate knowledge sharing by employees. The purpose of this paper is to outline the potential of ESMPs in both enabling and hindering knowledge sharing from the perspective of affordances. Design/methodology/approach This is a conceptual paper which integrates the literature on ESMPs’ affordances and knowledge sharing. Findings This paper finds that prior research on affordances only considered artifacts without much attention on the role of individual goals and organizational context. ESMPs may both enable and hinder knowledge sharing by affording different user behaviors contingent on artifacts, individual goals and organizational context. Practical implications The results of the paper will help managers and ESMPs designers to better understand the potential of ESMPs and pay attention to the positive and negative impacts of ESMPs in the process of knowledge sharing. Originality/value The paper derives a new categorization of affordances based on individual goals and organization context and portrays a model to describe how and when these affordances enable knowledge sharing through the development of transactive memory system and social capital and hinder knowledge sharing through overload, groupthink and privacy invasion.

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Supplementary key words adenosine 5 ′ -monophosphate-activated protein kinase • cholesterol • hydroxy-methylglutaryl coenzyme A reductaseThe liver plays a vital role in regulating cholesterol homeostasis in the body. HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in cholesterol biosynthesis ( 1 ), so its activity is instrumental in controlling de novo cholesterol synthesis. To maintain cholesterol homeostasis, HMGCR could be regulated by multiple mechanisms such as transcription, translation ( 2 ), enzyme degradation rate ( 3 ), phosphorylation-dephosphorylation ( 4 ), and feedback inhibition ( 5 ). Hormones could regulate the expression of HMGCR by acting at different levels. For example, glucocorticoids act at a posttranslational level ( 1 ), whereas insulin reportedly affects both the transcriptional and posttranslational processes ( 6 ). Recently, Wu et al. ( 7 ) found that the changes of the phosphorylated HMGCR play an important role in regulation of the hepatic cholesterol biosynthesis process. The site of phosphorylation on HMGCR has been identifi ed as serine 871 in rodents ( 8 ) and serine 872 in humans ( 9 ). The HMGCR is physiologically present in the cell in unphosphorylated active form and phosphorylated inactive form. In general, phosphorylation of HMGCR leads to inactivation of the enzyme, while dephosphorylation activates it. The ratio of the phosphorylated form to total form indicates an inactivation state of HMGCR. Abstract

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