Low-dose primaquine for falciparum malaria

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Evolution in controls methods for the SPS power converters

In common with much accelerator specific material, there is a constant need to improve both hardware and software for power converter control. Maintenance and performance improvements of older systems have become extremely tedious and in some areas impossible. By using modern real-time software and the latest high-performance processors, such problems should be substantially reduced. This paper describes the software concepts and the hardware chosen for the upgrade of the existing facilities. Using the UNIX compatible LynxOS real time kernel, running on a PowerPC 603 in a VME environment, this new approach provides excellent performance while retaining the desired flexibility for future enhancements. The 64 channel system is implemented as a set of cooperating processes, several of which are multi-threaded. Processes include analogue function generation, analogue measurement and digital I/O, all of which are accurately scheduled by the accelerator timing system. This generalised structure, which performs complex sequences of operations is described in detail, as well as how it can be adapted to a wide variety of accelerator tasks

The All-digital Approach to LHC Power Converter Current Control

The design of the LHC machine imposes severe demands upon the control of current in the 1700 magnet circuits. This has required the use of novel methods for the control of individual power converters and of the magnet current control system as a whole. This paper will review the chosen hardware and software methods and architectures. The digital regulation techniques used to achieve the overall targets for short-term stability (<3ppm) and reproducibility (<10ppm) of the 24 principal LHC circuits will be discussed. While the proposed system architecture will follow the canonical three-layer design, so successfully exploited in LEP, the software will be far from traditional. This software must be more reliable and maintainable than ever before, and will need to integrate with advanced object-oriented applications via commercial middleware. These challenges will be faced by applying object-oriented techniques throughout the system and by harnessing the power of XML for system definition

A Strategy for Controlling the LHC Magnet Currents

The LHC will require an unprecedented precision of a few ppm in the control of the current in the major magnetic circuits. As a result of the optimisation of the machine design, the machine will be powered in eight sectors with separate power converters. This scheme, along with other operational constraints, has led to a re-evaluation of the methods needed to ensure adequate performance. An overview of the strategy envisaged to meet this new challenge is presented, along with details of digital control and correction methods, new techniques for analogue to digital conversion and improvements in DC current transducers above 10 kA

High-current performance evaluation of DCCTs

The evaluation of high performance DCCT's to the ppm level has never been an easy task. With the LHC demanding currents up to 13 kA, a whole series of problems has arisen in the accurate measurement of these devices. In order to tackle these problems, new facilities have been designed for laboratory measurements under full power operating conditions. These include a high performance low voltage 20 kA power converter, quasi-coaxial bus-bar structures, Kusters Bridge range extenders and a novel bipolar 0 - 10 A current calibrator with resolution and linearity better than ± 0.5 ppm. This paper will present an overview of the complete facility and give more detail on the new current calibrator. Initial results will be presented, along with application areas which advance the state of the art in this field of measurements

Evaluation of subcutaneous proleukin (Interleukin-2) in a randomized international trial (ESPRIT): Geographical and gender differences in the baseline characteristics of participants

Background: ESPRIT, is a phase III, open-label, randomized, international clinical trial evaluating the effects of subcutaneous recombinant interleukin-2 (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease progression and death in HIV-1-infected individuals with CD4+ T-cells ≥300 cells/μL. Objectives: To describe the baseline characteristics of participants randomized to ESPRIT overall and by geographic location. Method: Baseline characteristics of randomized participants were summarized by region. Results: 4,150 patients were enrolled in ESPRIT from 254 sites in 25 countries. 41%, 27%, 16%, 11%, and 5% were enrolled in Europe, North America, South America, Asia, and Australia, respectively. The median age was 40 years, 81% were men, and 76%, 11%, and 9% were Caucasian, Asian, and African American or African, respectively. 44% of women enrolled (n = 769) were enrolled in Thailand and Argentina. Overall, 55% and 38% of the cohort acquired HIV through male homosexual and heterosexual contact, respectively. 25% had a prior history of AIDS-defining illness; Pneumocystis jirovecii pneumonia, M. tuberculosis, and esophageal candida were most commonly reported. Median nadir and baseline CD4+ T-cell counts were 199 and 458 cells/μL, respectively. 6% and 13% were hepatitis B or C virus coinfected, respectively. Median duration of antiretroviral therapy (ART) was 4.2 years; the longest median duration was in Australia (5.2 years) and the shortest was in Asia (2.3 years). 17%, 13%, and 69% of participants began ART before 1995, between 1996 and 1997, and from 1998 onward, respectively. 86% used ART from two or more ART classes, with 49% using a protease inhibitor-based regimen and 46% using a nonnucleoside reverse transcriptase inhibitor-based regimen. 78% had plasma HIV RNA below detection (<500 cp/mL). Conclusion: ESPRIT has enrolled a diverse population of HIV-infected individuals including large populations of women and patients of African-American/African and Asian ethnicity often underrepresented in HIV research. As a consequence, the results of the study may have wide global applicability

Crowd- and Community-fuelled Archaeological Research. Early Results from the MicroPasts Project

The MicroPasts project is a novel experiment in the use of crowd-based methodologies to enable participatory archaeological research. Building on a long tradition of offline community archaeology in the UK, this initiative aims to integrate crowd-sourcing, crowd-funding and forum-based discussion to encourage groups of academics and volunteers to collaborate on the web. This paper will introduce MicroPasts, its aims, methods and initial results, with a particular emphasis on project evaluation. The evaluative work conducted over the first few months of the project already demonstrates the potential for crowd-sourced archaeological 3D modelling, especially amongst younger audiences, next to more traditional kinds of crowd-sourcing such as transcription. It has also allowed a comparative assessment of different methods for sustaining contributor participation through time and a discussion of their implications for the sustainability of the MicroPasts project and (potentially) other archaeological crowd-sourcing endeavours

A structural role for arginine in proteins: Multiple hydrogen bonds to backbone carbonyl oxygens

We propose that arginine side chains often play a previously unappreciated general structural role in the maintenance of tertiary structure in proteins, wherein the positively charged guanidinium group forms multiple hydrogen bonds to backbone carbonyl oxygens. Using as a criterion for a “structural” arginine one that forms 4 or more hydrogen bonds to 3 or more backbone carbonyl oxygens, we have used molecular graphics to locate arginines of interest in 4 proteins: Arg 180 in Thermus thermophilus manganese superoxide dismutase, Arg 254 in human carbonic anhydrase II, Arg 31 in Streptomyces rubiginosus xylose isomerase, and Arg 313 in Rhodospirillum rubrum ribulose‐1,5‐bisphosphate carboxylase/oxygenase. Arg 180 helps to mold the active site channel of superoxide dismutase, whereas in each of the other enzymes the structural arginine is buried in the “mantle” (i.e., inside, but near the surface) of the protein interior well removed from the active site, where it makes 5 hydrogen bonds to 4 backbone carbonyl oxygens. Using a more relaxed criterion of 3 or more hydrogen bonds to 2 or more backbone carbonyl oxygens, arginines that play a potentially important structural role were found in yeast enolase, Bacillus stearothermophilus glyceraldehyde‐3‐phosphate dehydrogenase, bacteriophage T4 and human lysozymes, Enteromorpha prolifera plastocyanin, HIV‐1 protease, Trypanosoma brucei brucei and yeast triosephosphate isomerases, and Escherichia coli trp aporepressor (but not trp repressor or the trp repressor/operator complex). In addition to helping form the active site funnel in superoxide dismutase, the structural arginines found in this study play such diverse roles as stapling together 3 strands of backbone from different regions of the primary sequence, and tying α‐helix to α‐helix, βturn to β‐turn, and subunit to subunit. Copyright © 1994 The Protein Societ

Glucose-6-phosphate dehydrogenase status and risk of hemolysis in Plasmodium falciparum-infected African children receiving single-dose primaquine.

Glucose-6-phosphate dehydrogenase (G6PD) enzyme function and genotype were determined in Ugandan children with uncomplicated falciparum malaria enrolled in a primaquine trial after exclusion of severe G6PD deficiency by fluorescent spot test. G6PD A- heterozygotes and hemizygotes/homozygotes experienced dose-dependent lower hemoglobin concentrations after treatment. No severe anemia was observed

Ecological and Genomic Attributes of Novel Bacterial Taxa That Thrive in Subsurface Soil Horizons.

While most bacterial and archaeal taxa living in surface soils remain undescribed, this problem is exacerbated in deeper soils, owing to the unique oligotrophic conditions found in the subsurface. Additionally, previous studies of soil microbiomes have focused almost exclusively on surface soils, even though the microbes living in deeper soils also play critical roles in a wide range of biogeochemical processes. We examined soils collected from 20 distinct profiles across the United States to characterize the bacterial and archaeal communities that live in subsurface soils and to determine whether there are consistent changes in soil microbial communities with depth across a wide range of soil and environmental conditions. We found that bacterial and archaeal diversity generally decreased with depth, as did the degree of similarity of microbial communities to those found in surface horizons. We observed five phyla that consistently increased in relative abundance with depth across our soil profiles: Chloroflexi, Nitrospirae, Euryarchaeota, and candidate phyla GAL15 and Dormibacteraeota (formerly AD3). Leveraging the unusually high abundance of Dormibacteraeota at depth, we assembled genomes representative of this candidate phylum and identified traits that are likely to be beneficial in low-nutrient environments, including the synthesis and storage of carbohydrates, the potential to use carbon monoxide (CO) as a supplemental energy source, and the ability to form spores. Together these attributes likely allow members of the candidate phylum Dormibacteraeota to flourish in deeper soils and provide insight into the survival and growth strategies employed by the microbes that thrive in oligotrophic soil environments.IMPORTANCE Soil profiles are rarely homogeneous. Resource availability and microbial abundances typically decrease with soil depth, but microbes found in deeper horizons are still important components of terrestrial ecosystems. By studying 20 soil profiles across the United States, we documented consistent changes in soil bacterial and archaeal communities with depth. Deeper soils harbored communities distinct from those of the more commonly studied surface horizons. Most notably, we found that the candidate phylum Dormibacteraeota (formerly AD3) was often dominant in subsurface soils, and we used genomes from uncultivated members of this group to identify why these taxa are able to thrive in such resource-limited environments. Simply digging deeper into soil can reveal a surprising number of novel microbes with unique adaptations to oligotrophic subsurface conditions