Prototyping parallel functional intermediate languages

Non-strict higher-order functional programming languages are elegant, concise, mathematically sound and contain few environment-specific features, making them obvious candidates for harnessing high-performance architectures. The validity of this approach has been established by a number of experimental compilers. However, while there have been a number of important theoretical developments in the field of parallel functional programming, implementations have been slow to materialise. The myriad design choices and demands of specific architectures lead to protracted development times. Furthermore, the resulting systems tend to be monolithic entities, and are difficult to extend and test, ultimatly discouraging experimentation. The traditional solution to this problem is the use of a rapid prototyping framework. However, as each existing systems tends to prefer one specific platform and a particular way of expressing parallelism (including implicit specification) it is difficult to envisage a general purpose framework. Fortunately, most of these systems have at least one point of commonality: the use of an intermediate form. Typically, these abstract representations explicitly identify all parallel components but without the background noise of syntactic and (potentially arbitrary) implementation details. To this end, this thesis outlines a framework for rapidly prototyping such intermediate languages. Based on the traditional three-phase compiler model, the design process is driven by the development of various semantic descriptions of the language. Executable versions of the specifications help to both debug and informally validate these models. A number of case studies, covering the spectrum of modern implementations, demonstrate the utility of the framework

Propagation and Structure of Planar Streamer Fronts

Streamers often constitute the first stage of dielectric breakdown in strong electric fields: a nonlinear ionization wave transforms a non-ionized medium into a weakly ionized nonequilibrium plasma. New understanding of this old phenomenon can be gained through modern concepts of (interfacial) pattern formation. As a first step towards an effective interface description, we determine the front width, solve the selection problem for planar fronts and calculate their properties. Our results are in good agreement with many features of recent three-dimensional numerical simulations. In the present long paper, you find the physics of the model and the interfacial approach further explained. As a first ingredient of this approach, we here analyze planar fronts, their profile and velocity. We encounter a selection problem, recall some knowledge about such problems and apply it to planar streamer fronts. We make analytical predictions on the selected front profile and velocity and confirm them numerically. (abbreviated abstract)Comment: 23 pages, revtex, 14 ps file

Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

<p>Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.</p> <p>Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.</p> <p>Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.</p&gt

Student performance assessment using clustering techniques

The application of informatics in the university system management allows managers to count with a great amount of data which, rationally treated, can offer significant help for the student programming monitoring. This research proposes the use of clustering techniques as a useful tool of management strategy to evaluate the progression of the students’ behavior by dividing the population into homogeneous groups according to their characteristics and skills. These applications can help both the teacher and the student to improve the quality of education. The selected method is the data grouping analysis by means of fuzzy logic using the Fuzzy C-means algorithm to achieve a standard indicator called Grade, through an expert system to enable segmentation.Universidad de la Costa, 2 Universidad Nacional Experimental Politécnica “Antonio José de Sucre”, Universidad Simón Bolívar, Corporación Universitaria Latinoamericana, Corporación Universitaria Minuto de Dios

Acute gabapentin administration in healthy adults. A double-blind placebo-controlled study using transcranial magnetic stimulation and 7T 1H-MRS

Gamma-aminobutyric acid (GABA) and glutamate are the primary neurotransmitters responsible for modulating excitatory and inhibitory signalling within the human brain. Dysfunctional GABAergic and glutamatergic signalling has been identified as a key factor in a range of neuropsychiatric conditions; hence measurement and modulation of these neurometabolites is important for improving our understanding of neuropsychiatric conditions and treatment options. Gabapentin (GBP) is one of several drugs developed to increase GABA levels and is routinely prescribed for conditions such as epilepsy and neuralgia. While animal and human studies indicate that GBP can elevate GABA levels, its exact mechanisms of action are not fully understood, although animal studies indicate that GBP does not have a direct effect upon GABAergic receptors.To investigate the impact of acute GBP administration in the human motor system we used two complimentary approaches – transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). MRS and TMS measures of GABA have repeatedly been found to be uncorrelated and are likely to reflect different pools of synaptic and extra synaptic GABA, hence, measuring both within the same participants allows for an in-depth assessment of GBP effects.Despite significantly increased ratings of fatigue and tiredness within the GBP group, we failed to find any statistically significant changes in our MRS or TMS measures of GABA. Measures of MRS Glutamate (glu) and glutamine (gln) were also not affected by the administration of GBP. These findings are important as they run counter to previous work, and suggest that the effect of an acute dose of GBP is likely to be subject to substantial individual variation, with timing of measures particularly likely to impact observed effects. These findings have implications for the use of acute GBP dosing as a means to explore GABAergic function in health and disease

Ab initio molecular dynamics of liquid water using embedded-fragment second-order many-body perturbation theory towards its accurate property prediction

A direct, simultaneous calculation of properties of a liquid using an ab initio electron-correlated theory has long been unthinkable. Here we present structural, dynamical, and response properties of liquid water calculated by ab initio molecular dynamics using the embedded-fragment spin-component-scaled second-order many-body perturbation method with the aug-cc-pVDZ basis set. This level of theory is chosen as it accurately and inexpensively reproduces the water dimer potential energy surface from the coupled-cluster singles, doubles, and noniterative triples with the augcc-pVQZ basis set, which is nearly exact. The calculated radial distribution function, self-diffusion coefficient, coordinate number, and dipole moment, as well as the infrared and Raman spectra are in excellent agreement with experimental results. The shapes and widths of the OH stretching bands in the infrared and Raman spectra and their isotropic-anisotropic Raman noncoincidence, which reflect the diverse local hydrogen-bond environment, are also reproduced computationally. The simulation also reveals intriguing dynamic features of the environment, which are difficult to probe experimentally, such as a surprisingly large fluctuation in the coordination number and the detailed mechanism by which the hydrogen donating water molecules move across the first and second shells, thereby causing this fluctuationopen

Multidimensional Conservation Laws: Overview, Problems, and Perspective

Some of recent important developments are overviewed, several longstanding open problems are discussed, and a perspective is presented for the mathematical theory of multidimensional conservation laws. Some basic features and phenomena of multidimensional hyperbolic conservation laws are revealed, and some samples of multidimensional systems/models and related important problems are presented and analyzed with emphasis on the prototypes that have been solved or may be expected to be solved rigorously at least for some cases. In particular, multidimensional steady supersonic problems and transonic problems, shock reflection-diffraction problems, and related effective nonlinear approaches are analyzed. A theory of divergence-measure vector fields and related analytical frameworks for the analysis of entropy solutions are discussed.Comment: 43 pages, 3 figure

Trypanosomatid RACK1 Orthologs Show Functional Differences Associated with Translation Despite Similar Roles in Leishmania Pathogenesis

RACK1 proteins belong to the eukaryote WD40-repeat protein family and function as spatial regulators of multiple cellular events, including signaling pathways, the cell cycle and translation. For this latter role, structural and genetic studies indicate that RACK1 associates with the ribosome through two conserved positively charged amino acids in its first WD40 domain. Unlike RACK1s, including Trypanosoma brucei RACK1 (TbRACK1), only one of these two positively-charged residues is conserved in the first WD40 domain of the Leishmania major RACK1 ortholog, LACK. We compared virulence-attenuated LACK single copy (LACK/-) L. major, with L. major expressing either two LACK copies (LACK/LACK), or one copy each of LACK and TbRACK1 (LACK/TbRACK1), to evaluate the function of these structurally distinct RACK1 orthologs with respect to translation, viability at host temperatures and pathogenesis. Our results indicate that although the ribosome-binding residues are not fully conserved in LACK, both LACK and TbRACK1 co-sedimented with monosomes and polysomes in LACK/LACK and LACK/TbRACK1 L. major, respectively. LACK/LACK and LACK/TbRACK1 strains differed in their sensitivity to translation inhibitors implying that minor sequence differences between the RACK1 proteins can alter their functional properties. While biochemically distinguishable, both LACK/LACK and LACK/TbRACK1 lines were more tolerant of elevated temperatures, resistant to translation inhibitors, and displayed robust pathogenesis in vivo, contrasting to LACK/- parasites

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.info:eu-repo/semantics/publishedVersio