A Scalable Framework for Monte Carlo Simulation Using FPGA-based Hardware Accelerators with Application to SPECT Imaging A SCALABLE FRAMEWORK FOR MONTE CARLO SIMULATION USING FPGA-BASED HARDWARE ACCELERATORS WITH APPLICATION TO SPECT IMAGING TITLE: A Scal

Abstract As the number of transistors that are integrated onto a silicon die continues to increase, the compute power is becoming a commodity. This has enabled a whole host of new applications that rely on high-throughput computations. Recently, the need for faster and cost-effective applications in form-factor constrained environments has driven an interest in on-chip acceleration of algorithms based on Monte Carlo simula- Processor. Futhermore, we have created a framework for further increasing parallelism by scaling our architecture across multiple compute devices and by extending our original design to a multi-FPGA system nearly linear increase in acceleration with logic resources was achieved. iv Acknowledgements One could hardly put into words the contributions made to this work by the many wonderful people who surround me on a daily basis. I count myself blessed to have family, friends and colleagues that support and encourage me and to recognize each individually would be impossible. Nonetheless, there are some people without whose explicit mention this thesis would be incomplete

Internet Use among Ugandan Adolescents: Implications for HIV Intervention

BACKGROUND: The Internet is fast gaining recognition as a powerful, low-cost method to deliver health intervention and prevention programs to large numbers of young people across diverse geographic regions. The feasibility and accessibility of Internet-based health interventions in resource-limited settings, where cost-effective interventions are most needed, is unknown. To determine the utility of developing technology-based interventions in resource-limited settings, availability and patterns of usage of the Internet first need to be assessed. METHODS AND FINDINGS: The Uganda Media and You Survey was a cross-sectional survey of Internet use among adolescents (ages 12–18 years) in Mbarara, Uganda, a municipality mainly serving a rural population in sub-Saharan Africa. Participants were randomly selected among eligible students attending one of five participating secondary day and boarding schools in Mbarara, Uganda. Of a total of 538 students selected, 93% (500) participated. Of the total respondents, 45% (223) reported ever having used the Internet, 78% (175) of whom reported going online in the previous week. As maternal education increased, so too did the odds of adolescent Internet use. Almost two in five respondents (38% [189]) reported already having used a computer or the Internet to search for health information. Over one-third (35% [173]) had used the computer or Internet to find information about HIV/AIDS, and 20% (102) had looked for sexual health information. Among Internet users, searching for HIV/AIDS information on a computer or online was significantly related to using the Internet weekly, emailing, visiting chat rooms, and playing online games. In contrast, going online at school was inversely related to looking for HIV/AIDS information via technology. If Internet access were free, 66% (330) reported that they would search for information about HIV/AIDS prevention online. CONCLUSIONS: Both the desire to use, and the actual use of, the Internet to seek sexual health and HIV/AIDS information is high among secondary school students in Mbarara. The Internet may be a promising strategy to deliver low-cost HIV/AIDS risk reduction interventions in resource-limited settings with expanding Internet access

A Three-Hybrid Approach to Scanning the Proteome for Targets of Small Molecule Kinase Inhibitors

AbstractIn this study, we explored the application of a yeast three-hybrid (Y3H)-based compound/protein display system to scanning the proteome for targets of kinase inhibitors. Various known cyclin-dependent kinase (CDK) inhibitors, including purine and indenopyrazole analogs, were displayed in the form of methotrexate-based hybrid ligands and deployed in cDNA library or yeast cell array-based screening formats. For all inhibitors, known cell cycle CDKs as well as novel candidate CDK-like and/or CDK-unrelated kinase targets could be identified, many of which were independently confirmed using secondary enzyme assays and affinity chromatography. The Y3H system described here may prove generally useful in the discovery of candidate drug targets

Coral Colonisation of an Artificial Reef in a Turbid Nearshore Environment, Dampier Harbour, Western Australia

A 0.6 hectare artificial reef of local rock and recycled concrete sleepers was constructed in December 2006 at Parker Point in the industrial port of Dampier, western Australia, with the aim of providing an environmental offset for a nearshore coral community lost to land reclamation. Corals successfully colonised the artificial reef, despite the relatively harsh environmental conditions at the site (annual water temperature range 18-32°C, intermittent high turbidity, frequent cyclones, frequent nearby ship movements). Coral settlement to the artificial reef was examined by terracotta tile deployments, and later stages of coral community development were examined by in-situ visual surveys within fixed 25 x 25 cm quadrats on the rock and concrete substrates. Mean coral density on the tiles varied from 113 ± 17 SE to 909 ± 85 SE per m2 over five deployments, whereas mean coral density in the quadrats was only 6.0 ± 1.0 SE per m2 at eight months post construction, increasing to 24.0 ± 2.1 SE per m2 at 62 months post construction. Coral taxa colonising the artificial reef were a subset of those on the surrounding natural reef, but occurred in different proportions-Pseudosiderastrea tayami, Mycedium elephantotus and Leptastrea purpurea being disproportionately abundant on the artificial reef. Coral cover increased rapidly in the later stages of the study, reaching 2.3 ± 0.7 SE % at 62 months post construction. This study indicates that simple materials of opportunity can provide a suitable substrate for coral recruitment in Dampier Harbour, and that natural colonisation at the study site remains sufficient to initiate a coral community on artificial substrate despite ongoing natural and anthropogenic perturbations. © 2013 Blakeway et al

The TYK2-P1104A Autoimmune Protective Variant Limits Coordinate Signals Required to Generate Specialized T Cell Subsets

TYK2 is a JAK family member that functions downstream of multiple cytokine receptors. Genome wide association studies have linked a SNP (rs34536443) within TYK2 encoding a Proline to Alanine substitution at amino acid 1104, to protection from multiple autoimmune diseases including systemic lupus erythematosus (SLE) and multiple sclerosis (MS). The protective role of this SNP in autoimmune pathogenesis, however, remains incompletely understood. Here we found that T follicular helper (Tfh) cells, switched memory B cells, and IFNAR signaling were decreased in healthy individuals that expressed the protective variant TYK2A1104 (TYK2P). To study this variant in vivo, we developed a knock-in murine model of this allele. Murine Tyk2P expressing T cells homozygous for the protective allele, but not cells heterozygous for this change, manifest decreased IL-12 receptor signaling, important for Tfh lineage commitment. Further, homozygous Tyk2P T cells exhibited diminished in vitro Th1 skewing. Surprisingly, despite these signaling changes, in vivo formation of Tfh and GC B cells was unaffected in two models of T cell dependent immune responses and in two alternative SLE models. TYK2 is also activated downstream of IL-23 receptor engagement. Here, we found that Tyk2P expressing T cells had reduced IL-23 dependent signaling as well as a diminished ability to skew toward Th17 in vitro. Consistent with these findings, homozygous, but not heterozygous, Tyk2P mice were fully protected in a murine model of MS. Homozygous Tyk2P mice had fewer infiltrating CD4+ T cells within the CNS. Most strikingly, homozygous mice had a decreased proportion of IL-17+/IFNγ+, double positive, pathogenic CD4+ T cells in both the draining lymph nodes (LN) and CNS. Thus, in an autoimmune model, such as EAE, impacted by both altered Th1 and Th17 signaling, the Tyk2P allele can effectively shield animals from disease. Taken together, our findings suggest that TYK2P diminishes IL-12, IL-23, and IFN I signaling and that its protective effect is most likely manifest in the setting of autoimmune triggers that concurrently dysregulate at least two of these important signaling cascades

Holoprosencephaly

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life

Recent carbonate sedimentation near Abu Dhabi, Trucial Coast, Persian Gulf

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