Novel therapeutic targets in epilepsy: oxidative stress and iron metabolism

Malformations of Cortical Development (MCD) are one of the most frequent causes of multidrug‐resistant focal epilepsy, of which focal cortical dysplasia type IIb (FCDIIb) and Tuberous Sclerosis

Learning relative features through adaptive pooling for image classification

© 2014 IEEE. Bag-of-Feature (BoF) representations and spatial constraints have been popular in image classification research. One of the most successful methods uses sparse coding and spatial pooling to build discriminative features. However, minimizing the reconstruction error by sparse coding only considers the similarity between the input and codebooks. In contrast, this paper describes a novel feature learning approach for image classification by considering the dissimilarity between inputs and prototype images, or what we called reference basis (RB). First, we learn the feature representation by max-margin criterion between the input and the RB. The learned hyperplane is stored as the relative feature. Second, we propose an adaptive pooling technique to assemble multiple relative features generated by different RBs under the SVM framework, where the classifier and the pooling weights are jointly learned. Experiments based on three challenging datasets: Caltech-101, Scene 15 and Willow-Actions, demonstrate the effectiveness and generality of our framework

Diabetic Impairment of C-Kit+ Bone Marrow Stem Cells Involves the Disorders of Inflammatory Factors, Cell Adhesion and Extracellular Matrix Molecules

Bone marrow stem cells from diabetes mellitus patients exhibit functional impairment, but the relative molecular mechanisms responsible for this impairment are poorly understood. We investigated the mechanisms responsible for diabetes-related functional impairment of bone marrow stem cells by extensively screening the expression levels of inflammatory factors, cell cycle regulating molecules, extracellular matrix molecules and adhesion molecules. Bone marrow cells were collected from type 2 diabetic (db/db) and healthy control (db/m+) mice, and c-kit+ stem cells were purified (purity>85%) for experiments. Compared with the healthy control mice, diabetic mice had significantly fewer c-kit+ stem cells, and these cells had a lower potency of endothelial differentiation; however, the production of the angiogenic growth factor VEGF did not differ between groups. A pathway-focused array showed that the c-kit+ stem cells from diabetic mice had up-regulated expression levels of many inflammatory factors, including Tlr4, Cxcl9, Il9, Tgfb1, Il4, and Tnfsf5, but no obvious change in the expression levels of cell cycle molecules. Interestingly, diabetes-related alterations of the extracellular matrix and adhesion molecules were varied; Pecam, Mmp10, Lamc1, Itgb7, Mmp9, and Timp4 were up-regulated, but Col11a1, Fn1, Admts2, and Itgav were down-regulated. Some of these changes were also confirmed at the protein level by flow cytometry analysis. In conclusion, c-kit+ bone marrow stem cells from diabetic mice exhibited an extensive enhancement of inflammatory factors and disorders of the extracellular matrix and adhesion molecules. Further intervention studies are required to determine the precise role of each molecule in the diabetes-related functional impairment of c-kit+ bone marrow stem cells

Calculating WCET Estimates from Timed Traces

© The Author(s) 2015. This article is published with open access at Springerlink.comReal-time systems engineers face a daunting duty: They must ensure that each task in their system can always meet its deadline. To analyse schedulability they must know the worst-case execution time (WCET) of each task. However, determining exact WCETs is practically infeasible in cost-constrained industrial settings involving real-life code and COTS hardware. Static analysis tools that could yield sufficiently tight WCET bounds are often unavailable. As a result, interest in portable analysis approaches like measurement-based timing analysis (MBTA) is growing. We present an approach based on integer linear programming (ILP) for calculating a WCET estimate from a given database of timed execution traces. Unlike previous work, our method specifically aims at reducing overestimation, by means of an automatic classification of code executions into scenarios with differing worst-case behaviour. To ease the integration into existing analysis tool chains, our method is based on the implicit path enumeration technique (IPET). It can thus reuse flow facts from other analysis tools and produces ILP problems that can be solved by off-the-shelf solvers.Peer reviewe

Asymptomatic members with SOD1 mutation in a large kindred with familial amyotrophic lateral sclerosis have abnormal water diffusion characterisitcs

DTI was carried out in FALS/SALS patients and familial members with SOD1 mutation (AFALS) who may be in a pre-symptomatic phase of ALS. The changes in FA and TT were investigated in CBT/CST and in whole brain. In FALS/SALS, diffusion pattern changes were found in cerebral peduncle, internal capsule, sub-cortical white matter, cerebellum and frontal lobe while in AFALS, abnormal pattern could also be detected in the cerebral peduncle, cerebellum and frontal lobe but with a smaller extent. Our study indicates that DTI can show early diffusion changes in members with SOD1 mutation in FALS prior to symptom-onset.published_or_final_versio

Identification of disease-causing genes using microarray data mining and gene ontology

Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes. Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results. Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth. Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers

Elevated expression of c-kit in small venous malformations of blue rubber bleb nevus syndrome

The blue rubber bleb nevus syndrome (BRBNS, syn. bean syndrome) is a rare disease characterized by multiple cutaneous and gastrointestinal venous malformations associated with severe bleeding. However, the underlying molecular mechanisms are unknown and no targeted therapeutic approach exists to date. Here we report the case of a 19-year-old male patient with severe BRBNS in whom we analyzed the expression of tyrosine kinases frequently involved in tumor development by immunohistochemistry (vascular endothelial growth factor receptor-2, stem cell growth factor receptor (c-kit), platelet-derived growth factor receptor-β, and stem cell tyrosine kinase-1). A prominent expression of c-kit was detectable in smaller blood vessels, which also showed a moderate expression of the proliferation marker MIB1. Surprisingly, other growth factor receptors stained negatively. We therefore conclude that pharmacological inhibition of the c-kit signaling pathway in cavernous hemangiomas by selective kinase inhibitors may offer options in the treatment of BRBNS patients

OUTLINE OF GRANITOIDS OF THE CENTRAL ASIA OROGENIC BELT: FOCUSED ON THE SOUTHERN PART

the Siberian craton to the north and the TarimNorth China cratons to the south, is a complex collage of microcontinental blocks, island arcs, oceanic crustal remnants and continental marginal facies rocks. It is one of the largest and most complex accretionary orogenic belts and the most important site of Phanerozoic continental growth on the Earth [Jahn et al., 2000, 2004; Kovalenko et al., 2004] The widespread occurrence of large volumes of granitoids, mostly with juvenile sources, is a typical characteristic of the CAOB. These granitoids have been intensely studied (e.g. [Jahn et al., 2000, 2004; Kovalenko et al., 2004; Sorokin et al., 2004; Vladimirov et al., 2001; Han et al., 2010; Wang et al., 2006, 2015; Wu et al., 2011; Li et al., 2013; Yarmolyuk et al., 2002]). However, these studies mainly focused on some certain countries or regions.The Central Asian Orogenic Belt (CAOB), bounded by the Siberian craton to the north and the TarimNorth China cratons to the south, is a complex collage of microcontinental blocks, island arcs, oceanic crustal remnants and continental marginal facies rocks. It is one of the largest and most complex accretionary orogenic belts and the most important site of Phanerozoic continental growth on the Earth [Jahn et al., 2000, 2004; Kovalenko et al., 2004] The widespread occurrence of large volumes of granitoids, mostly with juvenile sources, is a typical characteristic of the CAOB. These granitoids have been intensely studied (e.g. [Jahn et al., 2000, 2004; Kovalenko et al., 2004; Sorokin et al., 2004; Vladimirov et al., 2001; Han et al., 2010; Wang et al., 2006, 2015; Wu et al., 2011; Li et al., 2013; Yarmolyuk et al., 2002]). However, these studies mainly focused on some certain countries or regions