A computational fluid dynamic investigation of inhomogeneous hydrogen flame acceleration and transition to detonation

Gas explosions in homogeneous reactive mixtures have been widely studied both experimentally and numerically. However, in practice and industrial applications, combustible mixtures are usually inhomogeneous and subject to vertical concentration gradients. Limited studies have been conducted in such context which resulted in limited understanding of the explosion characteristics in such situations. The present numerical investigation aims to study the dynamics of Deflagration to Detonation Transition (DDT) in inhomogeneous hydrogen/air mixtures and examine the effects of obstacle blockage ratio in DDT. VCEFoam, a reactive density-based solver recently assembled by the authors within the frame of OpenFOAM CFD toolbox has been used. VCEFoam uses the Harten–Lax–van Leer–Contact (HLLC) scheme fr the convective fluxes contribution and shock capturing. The solver has been verified by comparing its predictions with the analytical solutions of two classical test cases. For validation, the experimental data of Boeck et al. (1) is used. The experiments were conducted in a rectangular channel the three different blockage ratios and hydrogen concentrations. Comparison is presented between the predicted and measured flame tip velocities. The shaded contours of the predicted temperature and numerical Schlieren (magnitude of density gradient) will be analysed to examine the effects of the blockage ratio on flame acceleration and DDT

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma.

Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease

Informavores: Active information foraging and human cognition

Just as the body survives by ingesting negative entropy, so the mind survives by ingesting information. In a very general sense, all higher organisms are informavores. The study of active information search is in the midst of a renaissance. Psychological research from diverse areas ranging from developmental psychology This symposium aims to bring together leading experts in this area to discuss how active information foraging can be understood from a diverse set of perspectives within cognitive science. Key themes include how prior knowledge influences search (Markant & Gureckis), how information and reward interact to determine choice (Meder & Nelson), developmental patterns in information seeking behavior (Nelson et al.), information foraging in complex sensemaking tasks (Pirolli), and the allocation of attention during statistical word learning (Yu). While each represents a distinct area of research, all discussants in the symposium share a core approach of applying computational models to understand information search in humans. The symposium should appeal to a broad set of attendees including educators, developmental psychologists, cognitive modelers, and computer scientists. The influence of priors on sequential search decisions - Doug Markant and Todd Gureckis Normative models of information acquisition predict that people's search decisions should be strongly influenced by their prior beliefs, which capture the set of alternative hypotheses they are considering. In the present experiments we tested whether people adjusted their information search behavior in response to sequential changes in the prior. Participants played a search game in which they had to identify the shape and location of multiple hidden targets in a display (similar to the board game Battleship). During the task they were told that the set of possible shapes had changed, and the key question was whether they would adjust their search decisions according to the predictions of a normative model. Manipulations of the prior included changes in the frequency of certain classes of targets as well as the introduction of higherorder constraints (e.g., that all targets would have the same shape). The results showed that an individual's prior could be recovered from their sequences of search decisions, but that there were notable differences in their ability to adjust to certain changes in the hypothesis space, an effect that is not predicted by the normative model. We discuss the implications of these findings for how people generate and represent hypotheses during the course of information foraging. Is people's information search behavior sensitive to different reward structures? -Björn Meder and Jonathan Nelson In situations where humans actively acquire information for classification, information search preferentially maximizes accurac

Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum

A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions

Distinct roles for fibroblast growth factor signaling in cerebellar development and medulloblastoma

Cerebellar granule neurons are the most abundant neurons in the brain, and a critical element of the circuitry that controls motor coordination and learning. In addition, granule neuron precursors (GNPs) are thought to represent cells of origin for medulloblastoma, the most common malignant brain tumor in children. Thus, understanding the signals that control the growth and differentiation of these cells has important implications for neurobiology and neuro-oncology. Our previous studies have shown that proliferation of GNPs is regulated by Sonic hedgehog (Shh), and that aberrant activation of the Shh pathway can lead to medulloblastoma. Moreover, we have demonstrated that Shh-dependent proliferation of GNPs and medulloblastoma cells can be blocked by basic fibroblast growth factor (bFGF). But while the mitogenic effects of Shh signaling have been confirmed in vivo, the inhibitory effects of bFGF have primarily been studied in culture. Here we demonstrate that mice lacking FGF signaling in GNPs exhibit no discernable changes in GNP proliferation or differentiation. In contrast, activation of FGF signaling has a potent effect on tumor growth: treatment of medulloblastoma cells with bFGF prevents them from forming tumors following transplantation, and inoculation of tumor-bearing mice with bFGF markedly inhibits tumor growth in vivo. These results suggest that activators of FGF signaling may be useful for targeting medulloblastoma and other Shh-dependent tumors

Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition

SummarySmoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant