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This review systematically examines comparative international entrepreneurship (CIE) research, analyzing 259 articles published in 21 leading journals from 1989 to 2010. We outline the importance of multi-country studies of entrepreneurial activity in enabling the comparison and replication of research and generating meaningful contributions to scholarship, practice, and policy. Our systematic review classifies research findings into four levels—individual, firm, industry, and country—each with respect to characteristics, antecedents, and outcomes of entrepreneurial activities as well as theory and methodology. Taken together, our review highlights the heterogeneous nature of entrepreneurship across countries and its role in explaining outcomes at firm (e.g., financial and export performance) and country (e.g., economic growth) levels as well as antecedents at the country level (e.g., culture). We find the CIE literature is highly fragmented with substantial knowledge gaps related to content, theory, and methodology, for which we outline a detailed future research agenda. Given the atheoretical nature of most published CIE research, we provide specific suggestions to extend the current dominant theoretical perspectives (institutions, culture, resource-based view, transaction cost economics, economic growth, and human capital); consider new lenses from management, international business, and entrepreneurship; and integrate and test multiple theories. From a content perspective, we outline the need to define and cross-reference prior studies of entrepreneurship and prioritize emerging phenomena that are critical to practice, and policy, and offer specific directives for integrated and multi-level studies of characteristics, antecedents, and outcomes. Methodological suggestions include theory-based rationale for the selection of countries, greater attention to data collection and sample selection equivalence, and the solutions to the ecological fallacy problem. We urge scholars to work together and across countries, cooperating with interested agencies and associations to develop new longitudinal, multi-level data sets and introduce dual qualitative/quantitative approaches and new diverse, sophisticated analytical tools.

cation of apoptotic mediators in stellate cells and exploration of their role in clearance of activated stellate cells during the resolution of liver injury.A more comprehensive picture of liver fibrogenesis is thus emerging. This review will emphasize areas of recent progress in understanding liver fibrosis and how these exciting insights will contribute to the generation of effective therapies in the future. EXTRACELLULAR MATRIX: THE MICROENVIRONMENT OF HEPATIC FIBROSIS Extracellular matrix in normal and fibrotic liverThe extracellular matrix refers to the array of macromolecules that comprise the scaffolding of normal and INTRODUCTIONHepatic fibrosis is a wound healing or scarring process which arises in response to liver damage. This response is an attempt to encapsulate injury, but in doing so, liver function is ultimately impaired.The hepatic response to injury represents a paradigm for wound healing in other tissues including skin, lung and kidney, as it involves many of the same cell types and mediators. 1 There has been exciting progress in understanding hepatic fibrosis. Advances have occurred in the following areas: (i) characterization of components of the extracellular matrix (ECM) in normal and fibrotic liver; Department of Medicine and Liver Diseases, Mount Sinai School of Medicine, New York, USAAbstract Hepatic fibrosis is a wound-healing response to chronic liver injury, which if persistent leads to cirrhosis and liver failure. Exciting progress has been made in understanding the mechanisms of hepatic fibrosis. Major advances include: (i) characterization of the components of extracellular matrix (ECM) in normal and fibrotic liver; (ii) identification of hepatic stellate cells as the primary source of ECM in liver fibrosis; (iii) elucidation of key cytokines, their cellular sources, modes of regulation, and signalling pathways involved in liver fibrogenesis; (iv) characterization of key matrix proteases and their inhibitors; (v) identification of apoptotic mediators in stellate cells and exploration of their roles during the resolution of liver injury. These advances have helped delineate a more comprehensive picture of liver fibrosis in which the central event is the activation of stellate cells, a transformation from quiescent vitamin A-rich cells to proliferative, fibrogenic and contractile myofibroblasts. The progress in understanding fibrogenic mechanisms brings the development of effective therapies closer to reality. In the future, targeting of stellate cells and fibrogenic mediators will be a mainstay of antifibrotic therapy. Points of therapeutic intervention may include: (i) removing the injurious stimuli; (ii) suppressing hepatic inflammation; (iii) down-regulating stellate cell activation; and (iv) promoting matrix degradation. The future prospects for effective antifibrotic treatment are more promising than ever for the millions of patients with chronic liver disease worldwide.

These findings demonstrate that anthocyanin supplementation exerts beneficial metabolic effects in subjects with type 2 diabetes by improving dyslipidemia, enhancing antioxidant capacity, and preventing insulin resistance. This trial was registered at www.clinicaltrials.gov as NCT02317211.

Urban tree species mapping is an important prerequisite to understanding the value of urban vegetation in ecological services. In this study, we explored the potential of bi-temporal WorldView-2 (WV2, acquired on 14 September 2012) and WorldView-3 images (WV3, acquired on 18 October 2014) for identifying five dominant urban tree species with the object-based Support Vector Machine (SVM) and Random Forest (RF) methods. Two study areas in Beijing, China, Capital Normal University (CNU) and Beijing Normal University (BNU), representing the typical urban environment, were evaluated. Three classification schemes-classification based solely on WV2; WV3; and bi-temporal WV2 and WV3 images-were examined. Our study showed that the single-date image did not produce satisfying classification results as both producer and user accuracies of tree species were relatively low (44.7%-82.5%), whereas those derived from bi-temporal images were on average 10.7% higher. In addition, the overall accuracy increased substantially (9.7%-20.2% for the CNU area and 4.7%-12% for BNU). A thorough analysis concluded that near-infrared 2, red-edge and green bands are always more important than the other bands to classification, and spectral features always contribute more than textural features. Our results also showed that the scattered distribution of trees and a more complex surrounding environment reduced classification accuracy. Comparisons between SVM and RF classifiers suggested that SVM is more effective for urban tree species classification as it outperforms RF when working with a smaller amount and imbalanced distribution of samples.

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Sun R, Xia M. Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction. Am J Physiol Endocrinol Metab 306: E975-E988, 2014. First published March 4, 2014; doi:10.1152/ajpendo.00699.2013Adiponectin is an adipose tissue-secreted adipokine with beneficial effects on the cardiovascular system. In this study, we evaluated a potential role for adiponectin in the protective effects of anthocyanin on diabetes-related endothelial dysfunction. We treated db/db mice on a normal diet with anthocyanin cyanidin-3-O-␤-glucoside (C3G; 2 g/kg diet) for 8 wk. Endothelium-dependent and -independent relaxations of the aorta were then evaluated. Adiponectin expression and secretion were also measured. C3G treatment restores endotheliumdependent relaxation of the aorta in db/db mice, whereas diabetic mice treated with an anti-adiponectin antibody do not respond. C3G treatment induces adiponectin expression and secretion in cultured 3T3 adipocytes through transcription factor forkhead box O1 (Foxo1). Silencing Foxo1 expression prevented C3G-stimulated induction of adiponectin expression. In contrast, overexpression of Foxo1-ADA promoted adiponectin expression in adipocytes. C3G activates Foxo1 by increasing its deacetylation via silent mating type information regulation 2 homolog 1 (Sirt1). Furthermore, purified anthocyanin supplementation significantly improved flow-mediated dilation (FMD) and increased serum adiponectin concentrations in patients with type 2 diabetes. Changes in adiponectin concentrations positively correlated with FMD in the anthocyanin group. Mechanistically, adiponectin activates cAMP-PKA-eNOS signaling pathways in human aortic endothelial cells, increasing endothelial nitric oxide bioavailability. These results demonstrate that adipocyte-derived adiponectin is required for anthocyanin C3G-mediated improvement of endothelial function in diabetes.anthocyanin; adiponectin; diabetes; endothelial function OBESITY AND DIABETES are major risk factors for the initiation of vascular dysfunction and cardiovascular disease (21, 22). Adipose tissue is now recognized as an important metabolic and endocrine organ in the regulation of glucose metabolism. Dysregulation of adipose tissue contributes to the development of insulin resistance and the vascular complications of diabetes (12). Adiponectin is an adipocyte-derived plasma protein with both antiatherogenic and insulin-sensitizing properties, and lower plasma concentrations of adiponectin are closely correlated with obesity, insulin resistance, and diabetes mellitus (15,26,30,44). In addition, hypoadiponectinemia is strongly associated with impaired endothelium-dependent vasorelaxation in both diabetic and nondiabetic human subjects (25, 33). Thus, modulating adiponectin levels in diabetic conditions would be beneficial for maintaining vascular function (35,46).Anthocyanins, as a group of flavonoids, are most abundant in various colorful fruits, vegetables, red wine, and grains (13,16,38,45). Epidemiological studies have dem...

Foot-and-mouth disease is a frequently occurring disease of cloven-hoofed animals that is caused by infection with the foot-and-mouth virus (FMDV). FMDV circumvents the type-I IFN response by expressing proteins that antagonize cellular innate immunity, such as leader protease and 3C protease. We identified the FMDV structural protein VP3 as a negative regulator of the virustriggered IFN-b signaling pathway. Expression of FMDV VP3 inhibited the Sendai virus-triggered activation of IFN regulatory factor-3 and the expression of retinoic acidinducible gene-I/melanoma differentiation-associated protein-5. Transient transfection and coimmunoprecipitation confirmed that the structural protein VP3 interacts with virus-induced signaling adapter (VISA), which is dependent on the C-terminal aa 111-220 of VP3. In addition, we found that FMDV VP3 inhibits the expression of VISA by disrupting its mRNA. Taken together, our findings reveal a novel strategy used by the structural VP3 protein of FMDV to evade host innate