Confidence in prediction: an approach for dynamic weighted ensemble.

Combining classifiers in an ensemble is beneficial in achieving better prediction than using a single classifier. Furthermore, each classifier can be associated with a weight in the aggregation to boost the performance of the ensemble system. In this work, we propose a novel dynamic weighted ensemble method. Based on the observation that each classifier provides a different level of confidence in its prediction, we propose to encode the level of confidence of a classifier by associating with each classifier a credibility threshold, computed from the entire training set by minimizing the entropy loss function with the mini-batch gradient descent method. On each test sample, we measure the confidence of each classifier’s output and then compare it to the credibility threshold to determine whether a classifier should be attended in the aggregation. If the condition is satisfied, the confidence level and credibility threshold are used to compute the weight of contribution of the classifier in the aggregation. By this way, we are not only considering the presence but also the contribution of each classifier based on the confidence in its prediction on each test sample. The experiments conducted on a number of datasets show that the proposed method is better than some benchmark algorithms including a non-weighted ensemble method, two dynamic ensemble selection methods, and two Boosting methods

Trends for nanotechnology development in China, Russia, and India

China, Russia, and India are playing an increasingly important role in global nanotechnology research and development (R&D). This paper comparatively inspects the paper and patent publications by these three countries in the Thomson Science Citation Index Expanded (SCI) database and United States Patent and Trademark Office (USPTO) database (1976–2007). Bibliographic, content map, and citation network analyses are used to evaluate country productivity, dominant research topics, and knowledge diffusion patterns. Significant and consistent growth in nanotechnology papers are noted in the three countries. Between 2000 and 2007, the average annual growth rate was 31.43% in China, 11.88% in Russia, and 33.51% in India. During the same time, the growth patterns were less consistent in patent publications: the corresponding average rates are 31.13, 10.41, and 5.96%. The three countries’ paper impact measured by the average number of citations has been lower than the world average. However, from 2000 to 2007, it experienced rapid increases of about 12.8 times in China, 8 times in India, and 1.6 times in Russia. The Chinese Academy of Sciences (CAS), the Russian Academy of Sciences (RAS), and the Indian Institutes of Technology (IIT) were the most productive institutions in paper publication, with 12,334, 6,773, and 1,831 papers, respectively. The three countries emphasized some common research topics such as “Quantum dots,” “Carbon nanotubes,” “Atomic force microscopy,” and “Scanning electron microscopy,” while Russia and India reported more research on nano-devices as compared with China. CAS, RAS, and IIT played key roles in the respective domestic knowledge diffusion

The Mych Gene Is Required for Neural Crest Survival during Zebrafish Development

Background: Amomg Myc family genes, c-Myc is known to have a role in neural crest specification in Xenopus and in craniofacial development in the mouse. There is no information on the function of other Myc genes in neural crest development, or about any developmental role: of zebrafish Myc genes. Principal Findings: We isolated the zebrafish mych (myc homologue) gene. Knockdown of mych leads to sever defects in craniofacial development and in certain other tissues including the eye. These phenotypes appear to be caused by cell death in the neural crest and in the eye field in the anterior brain. Significance: Mych is a novel factor required for neural crest cell survival in zebrafish

Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

<p>Abstract</p> <p>Background</p> <p><it>NDRG</it>2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory. Previous results have shown that <it>NDRG</it>2 expressed differentially in normal and cancer tissues. Specifically, <it>NDRG</it>2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of <it>NDRG</it>2 inhibited the proliferation of cancer cells. <it>NDRG</it>2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether <it>NDRG</it>2 participates in carcinogenesis of the thyroid.</p> <p>Methods</p> <p>In this study, we investigated the expression profile of human <it>NDRG</it>2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40) and carcinomas (n = 35), along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc.</p> <p>Results</p> <p>The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of <it>NDRG</it>2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of <it>NDRG</it>2 expression with gender, age, different histotypes of thyroid cancers or distant metastases.</p> <p>Conclusion</p> <p>Our data indicates that <it>NDRG</it>2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of <it>NDRG2 </it>in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of <it>NDRG</it>2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.</p

Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

<p>Abstract</p> <p>Background</p> <p>While standard reductionist approaches have provided some insights into specific gene polymorphisms and molecular pathways involved in disease pathogenesis, our understanding of complex traits such as atherosclerosis or type 2 diabetes remains incomplete. Gene expression profiling provides an unprecedented opportunity to understand complex human diseases by providing a global view of the multiple interactions across the genome that are likely to contribute to disease pathogenesis. Thus, the goal of gene expression profiling is not to generate lists of differentially expressed genes, but to identify the physiologic or pathogenic processes and structures represented in the expression profile.</p> <p>Methods</p> <p>RNA was separately extracted from peripheral blood neutrophils and mononuclear leukocytes, labeled, and hybridized to genome level microarrays to generate expression profiles of children with polyarticular juvenile idiopathic arthritis, juvenile dermatomyositis relative to childhood controls. Statistically significantly differentially expressed genes were identified from samples of each disease relative to controls. Functional network analysis identified interactions between products of these differentially expressed genes.</p> <p>Results</p> <p><it>In silico </it>models of both diseases demonstrated similar features with properties of scale-free networks previously described in physiologic systems. These networks were observable in both cells of the innate immune system (neutrophils) and cells of the adaptive immune system (peripheral blood mononuclear cells).</p> <p>Conclusion</p> <p>Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant to perturbation.</p

Morphine activation of mu opioid receptors causes disinhibition of neurons in the ventral tegmental area mediated by β-arrestin2 and c-Src

Abstract The tyrosine kinase, c-Src, participates in mu opioid receptor (MOP) mediated inhibition in sensory neurons in which β-arrestin2 (β-arr2) is implicated in its recruitment. Mice lacking β-arr2 exhibit increased sensitivity to morphine reinforcement; however, whether β-arr2 and/or c-Src participate in the actions of opioids in neurons within the reward pathway is unknown. It is also unclear whether morphine acts exclusively through MOPs, or involves delta opioid receptors (DOPs). We examined the involvement of MOPs, DOPs, β-arr2 and c-Src in the inhibition by morphine of GABAergic inhibitory postsynaptic currents (IPSCs) recorded from neurons in the mouse ventral tegmental area. Morphine inhibited spontaneous IPSC frequency, mainly through MOPs, with only a negligible effect remaining in MOP−/− neurons. However, a reduction in the inhibition by morphine for DOP−/− c.f. WT neurons and a DPDPE-induced decrease of IPSC frequency revealed a role for DOPs. The application of the c-Src inhibitor, PP2, to WT neurons also reduced inhibition by morphine, while the inactive PP3, and the MEK inhibitor, SL327, had no effect. Inhibition of IPSC frequency by morphine was also reduced in β-arr2−/− neurons in which PP2 caused no further reduction. These data suggest that inhibition of IPSCs by morphine involves a β-arr2/c-Src mediated mechanism

Epidermal Stem Cells Are Defined by Global Histone Modifications that Are Altered by Myc-Induced Differentiation

Activation of Myc induces epidermal stem cells to exit their niche and differentiate into sebocytes and interfollicular epidermis, a process that is associated with widespread changes in gene transcription. We have identified chromatin modifications that are characteristic of epidermal stem cells and investigated the effects of Myc activation. Quiescent stem cells in the interfollicular epidermis and the hair follicle bulge had high levels of tri-methylated histone H3 at lysine 9 and H4 at lysine 20. Chromatin in both stem cell populations was hypoacteylated at histone H4 and lacked mono-methylation of histone H4 at lysine 20. Myc-induced exit from the stem cell niche correlated with increased acetylation at histone H4 and transiently increased mono-methylation at lysine 20. The latter was replaced by epigenetic modifications that are largely associated with chromatin silencing: di-methylation at histone H3 lysine 9 and histone H4 lysine 20. These modifications correlated with changes in the specific histone methyltransferases Set8 and Ash-1. The Myc-induced switch from mono- to di-methylated H4K20 required HDAC activity and was blocked by the HDAC inhibitor trichostatin A (TSA). TSA treatment induced a similar epidermal phenotype to activation of Myc, and activation of Myc in the presence of TSA resulted in massive stimulation of terminal differentiation. We conclude that Myc-induced chromatin modifications play a major role in Myc-induced exit from the stem cell compartment

Can Interactions between Timing of Vaccine-Altered Influenza Pandemic Waves and Seasonality in Influenza Complications Lead to More Severe Outcomes?

Vaccination can delay the peak of a pandemic influenza wave by reducing the number of individuals initially susceptible to influenza infection. Emerging evidence indicates that susceptibility to severe secondary bacterial infections following a primary influenza infection may vary seasonally, with peak susceptibility occurring in winter. Taken together, these two observations suggest that vaccinating to prevent a fall pandemic wave might delay it long enough to inadvertently increase influenza infections in winter, when primary influenza infection is more likely to cause severe outcomes. This could potentially cause a net increase in severe outcomes. Most pandemic models implicitly assume that the probability of severe outcomes does not vary seasonally and hence cannot capture this effect. Here we show that the probability of intensive care unit (ICU) admission per influenza infection in the 2009 H1N1 pandemic followed a seasonal pattern. We combine this with an influenza transmission model to investigate conditions under which a vaccination program could inadvertently shift influenza susceptibility to months where the risk of ICU admission due to influenza is higher. We find that vaccination in advance of a fall pandemic wave can actually increase the number of ICU admissions in situations where antigenic drift is sufficiently rapid or where importation of a cross-reactive strain is possible. Moreover, this effect is stronger for vaccination programs that prevent more primary influenza infections. Sensitivity analysis indicates several mechanisms that may cause this effect. We also find that the predicted number of ICU admissions changes dramatically depending on whether the probability of ICU admission varies seasonally, or whether it is held constant. These results suggest that pandemic planning should explore the potential interactions between seasonally varying susceptibility to severe influenza outcomes and the timing of vaccine-altered pandemic influenza waves

Defining the Molecular Basis of Tumor Metabolism: a Continuing Challenge Since Warburg's Discovery

Cancer cells are the product of genetic disorders that alter crucial intracellular signaling pathways associated with the regulation of cell survival, proliferation, differentiation and death mechanisms. the role of oncogene activation and tumor suppressor inhibition in the onset of cancer is well established. Traditional antitumor therapies target specific molecules, the action/expression of which is altered in cancer cells. However, since the physiology of normal cells involves the same signaling pathways that are disturbed in cancer cells, targeted therapies have to deal with side effects and multidrug resistance, the main causes of therapy failure. Since the pioneering work of Otto Warburg, over 80 years ago, the subversion of normal metabolism displayed by cancer cells has been highlighted by many studies. Recently, the study of tumor metabolism has received much attention because metabolic transformation is a crucial cancer hallmark and a direct consequence of disturbances in the activities of oncogenes and tumor suppressors. in this review we discuss tumor metabolism from the molecular perspective of oncogenes, tumor suppressors and protein signaling pathways relevant to metabolic transformation and tumorigenesis. We also identify the principal unanswered questions surrounding this issue and the attempts to relate these to their potential for future cancer treatment. As will be made clear, tumor metabolism is still only partly understood and the metabolic aspects of transformation constitute a major challenge for science. Nevertheless, cancer metabolism can be exploited to devise novel avenues for the rational treatment of this disease. Copyright (C) 2011 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed ABC UFABC, CCNH, Santo Andre, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilUniv Fed Sao Carlos UFSCar, DFQM, Sorocaba, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilFAPESP: 10/16050-9FAPESP: 10/11475-1FAPESP: 08/51116-0Web of Scienc

Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs

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