Development of a high performance parallel computing platform and its use in the study of nanostructures : clusters, sheets and tubes .

Small clusters of gallium oxide, technologically important high temperature ceramic, together with interaction of nucleic acid bases with graphene and small-diameter carbon nanotube are focus of first principles calculations in this work. A high performance parallel computing platform is also developed to perform these calculations at Michigan Tech. First principles calculations are based on density functional theory employing either local density or gradient-corrected approximation together with plane wave and gaussian basis sets. The bulk Ga2O3 is known to be a very good candidate for fabricating electronic devices that operate at high temperatures. To explore the properties of Ga2O3 at nonoscale, we have performed a systematic theoretical study on the small polyatomic gallium oxide clusters. The calculated results find that all lowest energy isomers of GamOn clusters are dominated by the Ga-O bonds over the metal-metal or the oxygen-oxygen bonds. Analysis of atomic charges suggest the clusters to be highly ionic similar to the case of bulk Ga2O3. In the study of sequential oxidation of these slusters starting from Ga2O, it is found that the most stable isomers display up to four different backbones of constituent atoms. Furthermore, the predicted configuration of the ground state of Ga2O is recently confirmed by the experimental result of Neumark's group. Guided by the results of calculations the study of gallium oxide clusters, performance related challenge of computational simulations, of producing high performance computers/platforms, has been addressed. Several engineering aspects were thoroughly studied during the design, development and implementation of the high performance parallel computing platform, rama, at Michigan Tech. In an attempt to stay true to the principles of Beowulf revolutioni, the rama cluster was extensively customized to make it easy to understand, and use - for administrators as well as end-users. Following the results of benchmark calculations and to keep up with the complexity of systems under study, rama has been expanded to a total of sixty four processors. Interest in the non-covalent intereaction of DNA with carbon nanotubes has steadily increased during past several years. This hybrid system, at the junction of the biological regime and the nanomaterials world, possesses features which make it very attractive for a wide range of applicatioins. Using the in-house computational power available, we have studied details of the interaction between nucleic acid bases with graphene sheet as well as high-curvature small-diameter carbon nanotube. The calculated trend in the binding energies strongly suggests that the polarizability of the base molecules determines the interaction strength of the nucleic acid bases with graphene. When comparing the results obtained here for physisorption on the small diameter nanotube considered with those from the study on graphene, it is observed that the interaction strength of nucleic acid bases is smaller for the tube. Thus, these results show that the effect of introducing curvature is to reduce the binding energy. The binding energies for the two extreme cases of negligible curvature (i.e. flat graphene sheet) and of very high curvature (i.e. small diameter nanotube) may be considered as upper and lower bounds. This finding represents an important step towards a better understanding of experimentally observed sequence-dependent interaction of DNA with Carbon nanotubes.

Diffusion tensor imaging of two unrelated Chinese men with hereditary spastic paraplegia associated with thin corpus callosum

Hereditary spastic paraplegia (HSP) associated with thin corpus callosum is a rare autosomal recessive neurodegenerative disorder characterized by an abnormally thin corpus callosum, normal motor development, slowly progressive spastic paraparesis and cognitive deterioration. To investigate and localize abnormalities in the brains of two Chinese patients with HSP-TCC, with mutations in the spatacsin gene. Diffusion tensor imaging (DTI) was used to determine the mean diffusion (MD) and fractional anisotropy (FA) in the brains of the patients in comparison to 20 healthy subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values were performed using statistical parametric mapping (SPM). Significant changes with MD increase and FA reduction were found in the already known lesions including the corpus callosum, cerebellum and thalamus. In addition, changes were also found in regions that appear to be normal in conventional MRI, such as the brain stem, internal capsule, cingulum and subcortical white matter including superior longitudinal fascicle and inferior longitudinal fascicle. Neither increase in FA nor reduction in MD was detected in the brain. Our study provides clear in vivo MR imaging evidence of a more widespread brain involvement of HSP-TCC. MD is more sensitive than FA in detecting lesions in thalamus and subcortical white matter, suggesting that MD may be a better marker of the disease progression.

PARTITIONING THE BLOCKS OF A STEINER TRIPLE SYSTEM INTO PARTIAL PARALLEL CLASSES

Does there exist a Steiner Triple System on v points, whose blocks can be partitioned into partial parallel classes of size m, where m ≤ [v⁄3], m | b and b is the number of blocks of the STS(v)? We give the answer for 9 ≤ v ≤ 43. We also show that whenever 2|b, v ≡ 3 (mod 6) we can find an STS(v) whose blocks can be partitioned into partial parallel classes of size 2, and whenever 4|b , v ≡ 3 (mod 6), there exists an STS(v) whose blocks can be partitioned into partial parallel classes of size 4.

Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan Africa: comparison with HIV-unrelated mortality

BACKGROUND: Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa. METHODS AND FINDINGS: Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94) per 100 person-years and the SMR was 1.14 (0.47-2.77). CONCLUSIONS: Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.

Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)

BACKGROUND: Unlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist. METHODS: Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1.8 mg once a day (n=233) or exenatide 10 microg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA(1c)). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882. FINDINGS: Mean baseline HbA(1c) for the study population was 8.2%. Liraglutide reduced mean HbA(1c) significantly more than did exenatide (-1.12% [SE 0.08] vs -0.79% [0.08]; estimated treatment difference -0.33; 95% CI -0.47 to -0.18; p<0.0001) and more patients achieved a HbA(1c) value of less than 7% (54%vs 43%, respectively; odds ratio 2.02; 95% CI 1.31 to 3.11; p=0.0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (-1.61 mmol/L [SE 0.20] vs -0.60 mmol/L [0.20]; estimated treatment difference -1.01 mmol/L; 95% CI -1.37 to -0.65; p<0.0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide -3.24 kg vs exenatide -2.87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0.448, p<0.0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patient per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5%vs 33.6% had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode. INTERPRETATION: Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Baylis-Hillman reaction assisted parallel synthesis of 3, 5-disubstituted isoxazoles and their in vivo bioevaluation as antithrombotic agents

The solution phase parallel synthesis involving reactions of Baylis-Hillman products of 3-substituted-5-isoxazolecarbaldehydes with nucleophiles and their in vivo antithrombotic evaluations are described along with the results of in vitro platelet aggregation inhibition assay of a few compounds. Results of the detailed evaluation of one of the compounds as an inhibitor of platelet aggregation are also presented.

KrigInv: An efficient and user-friendly implementation of batch-sequential inversion strategies based on kriging

Several strategies relying on kriging have recently been proposed for adaptively estimating contour lines and excursion sets of functions under severely limited evaluation budget. The recently released R package KrigInv 3 is presented and offers a sound implementation of various sampling criteria for those kinds of inverse problems. KrigInv is based on the DiceKriging package, and thus benefits from a number of options concerning the underlying kriging models. Six implemented sampling criteria are detailed in a tutorial and illustrated with graphical examples. Different functionalities of KrigInv are gradually explained. Additionally, two recently proposed criteria for batch-sequential inversion are presented, enabling advanced users to distribute function evaluations in parallel on clusters or clouds of machines. Finally, auxiliary problems are discussed. These include the fine tuning of numerical integration and optimization procedures used within the computation and the optimization of the considered criteria.