bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Correlates of High-Level Antifolate Resistance in Rwandan Children with
Plasmodium falciparum
Malaria
Authors: Karema Corine , Imwong Mallika , Fanello Caterina I. , Stepniewska Kasia , Uwimana Aline , Nakeesathit Supatchara , Dondorp Arjen , Day Nicholas P. , White Nicholas J. 
Published: October 2009

ABSTRACT

Antifolate drugs have an important role in the treatment of malaria. Polymorphisms in the genes encoding the dihydrofolate reductase and dihydropteroate synthetase enzymes cause resistance to the antifol and sulfa drugs, respectively. Rwanda has the highest levels of antimalarial drug resistance in Africa. We correlated the efficacy of chlorproguanil-dapsone plus artesunate (CPG-DDS+A) and amodiaquine plus sulfadoxine-pyrimethamine (AQ+SP) in children with uncomplicated malaria caused by
Plasmodium falciparum
parasites with
p
fdhfr
and
p
fdhps
mutations, which are known to confer reduced drug susceptibility, in two areas of Rwanda. In the eastern province, where the cure rates were low, over 75% of isolates had three or more
p
fdhfr
mutations and two or three
p
fdhps
mutations and 11% had the
p
fdhfr
164-Leu polymorphism. In the western province, where the cure rates were significantly higher (
P
< 0.001), the prevalence of multiple resistance mutations was lower and the
p
fdhfr
I164L polymorphism was not found. The risk of treatment failure following the administration of AQ+SP more than doubled for each additional
p
fdhfr
resistance mutation (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.01 to 5.55;
P
= 0.048) and each
p
fdhps
mutation (OR = 2.1; 95% CI = 1.21 to 3.54;
P
= 0.008). The risk of failure following CPG-DDS+A treatment was 2.2 times higher (95% CI = 1.34 to 3.7) for each additional
p
fdhfr
mutation, whereas there was no association with mutations in the
p
fdhps
gene (
P
= 0.13). The
p
fdhfr
164-Leu polymorphism is prevalent in eastern Rwanda. Antimalarial treatments with currently available antifol-sulfa combinations are no longer effective in Rwanda because of high-level resistance.
In VitroActivity of Thimerosal against Ocular Pathogenic Fungi
Authors: Xu Yan , Pang Guangren , Zhao Dongqing , Gao Chuanwen , Zhou Lutan , Sun Shengtao , Wang Bingliang 
Published: October 2009

ABSTRACTThein vitroactivity of thimerosal versus those of amphotericin B and natamycin was assessed against 244 ocular fungal isolates. The activity of thimerosal againstFusariumspp.,Aspergillusspp., andAlternaria alternatawas 256 times, 512 times, and 128 times, respectively, greater than that of natamycin and 64 times, 32 times, and 32 times, respectively, greater than that of amphotericin B. Thimerosal's antifungal activity was significantly superior to those of amphotericin B and natamycin against ocular pathogenic fungiin vitro.
Attributable Hospital Cost and Length of Stay Associated with Health Care-Associated Infections Caused by Antibiotic-Resistant Gram-Negative Bacteria
Authors: Mauldin Patrick D. , Salgado Cassandra D. , Hansen Ida Solhøj , Durup Darshana T. , Bosso John A. 
Published: October 2009

ABSTRACTDetermination of the attributable hospital cost and length of stay (LOS) are of critical importance for patients, providers, and payers who must make rational and informed decisions about patient care and the allocation of resources. The objective of the present study was to determine the additional total hospital cost and LOS attributable to health care-associated infections (HAIs) caused by antibiotic-resistant, gram-negative (GN) pathogens. A single-center, retrospective, observational comparative cohort study was performed. The study involved 662 patients admitted from 2000 to 2008 who developed HAIs caused by one of following pathogens:Acinetobacterspp.,Enterobacterspp.,Escherichia coli,Klebsiellaspp., orPseudomonasspp. The attributable total hospital cost and LOS for HAIs caused by antibiotic-resistant GN pathogens were determined by comparison with the hospital costs and LOS for a control group with HAIs due to antibiotic-susceptible GN pathogens. Statistical analyses were conducted by using univariate and multivariate analyses. Twenty-nine percent of the HAIs were caused by resistant GN pathogens, and almost 16% involved a multidrug-resistant GN pathogen. The additional total hospital cost and LOS attributable to antibiotic-resistant HAIs caused by GN pathogens were 29.3% (P< 0.0001; 95% confidence interval, 16.23 to 42.35) and 23.8% (P= 0.0003; 95% confidence interval, 11.01 to 36.56) higher than those attributable to HAIs caused by antibiotic-susceptible GN pathogens, respectively. Significant covariates in the multivariate analysis were age ≥12 years, pneumonia, intensive care unit stay, and neutropenia. HAIs caused by antibiotic-resistant GN pathogens were associated with significantly higher total hospital costs and increased LOSs compared to those caused by their susceptible counterparts. This information should be used to assess the potential cost-efficacy of interventions aimed at the prevention of such infections.
Absence of Inflammation and Pneumonia during Infection with Nonpigmented
Yersinia pestis
Reveals a New Role for the
pgm
Locus in Pathogenesis
Authors: Lee-Lewis Hanni , Anderson Deborah M. 
Published: October 2009

ABSTRACT

Yersinia pestis
causes primary pneumonic plague in many mammalian species, including humans, mice, and rats. Virulent
Y. pestis
strains undergo frequent spontaneous deletion of a 102-kb chromosomal DNA fragment, known as the pigmentation (
pgm
) locus, when grown in laboratory media, yet this locus is present in every virulent isolate. The
pgm
locus encodes, within a high-pathogenicity island, siderophore biosynthesis genes that are required for growth in the mammalian host when inoculated by peripheral routes. Recently, higher challenge doses of nonpigmented
Y. pestis
were reported to cause fatal pneumonic plague in mice, suggesting a useful model for studies of virulence and immunity. In this work, we show that intranasal infection of BALB/c mice with nonpigmented
Yersinia pestis
does not result in pneumonic plague. Despite persistent bacterial colonization of the lungs and the eventual death of infected mice, pulmonary inflammation was generally absent, and there was no disease pathology characteristic of pneumonic plague. Iron given to mice at the time of challenge, previously shown to enhance the virulence of
pgm
-deficient strains, resulted in an accelerated disease course, with less time to bacteremia and lethality, but lung inflammation and pneumonia were still absent. We examined other rodent models and found differences in lung inflammatory responses, some of which led to clearance and survival even when high challenge doses were used. Together, the results suggest that the
Y. pestis pgm
locus encodes previously unappreciated virulence factors required for the induction of pneumonic plague that are independent of iron scavenging from the mammalian host.
CcpA and LacD.1 Affect Temporal Regulation ofStreptococcus pyogenesVirulence Genes
Authors: Kietzman Colin C. , Caparon Michael G. 
Published: October 2009

ABSTRACTProduction of H2O2follows a growth phase-dependent pattern that mimics that of many virulence factors ofStreptococcus pyogenes. To gain greater insight into mechanisms coupling virulence factor expression to growth phase, we investigated the molecular basis for H2O2generation and its regulation. Deletion of the gene encoding lactate oxidase (lctO) or culture in the presence of glucose eliminated H2O2production, implicating carbohydrate regulation oflctOas a key element of growth phase control. In examining known carbohydrate-responsive regulators, deletion of the gene encoding CcpA but not that encoding LacD.1 resulted in both derepression and an uncoupling oflctOtranscription from its growth phase pattern. Expanding this analysis to additional virulence factors demonstrated both negative (cfa, encoding CAMP factor) and positive (speB, encoding a cysteine protease) regulation by CcpA and that CcpA mutants were highly cytotoxic for cultured macrophages. This latter property resulted from enhanced transcription of the streptolysin S biogenesis operon. Examination of CcpA-promoter interactions using a DNA pull-down assay mimicking physiological conditions showed direct binding to the promoters oflctOandspeBbut not those ofsagA. CcpA but not LacD.1 mutants were attenuated in a murine model of soft-tissue infection, and analysis of gene expression in infected tissue indicated that CcpA mutants had altered expression oflctO,cfa, andspeBbut not the indirectly regulatedsagAgene. Taken together, these data show that CcpA regulates virulence genes via at least three distinct mechanisms and that disruption of growth phase regulation alters transcriptional patterns in infected tissues.
Localization and Developmental Regulation of a Dispersed Gene Family 1 Protein in
Trypanosoma cruzi
Authors: Lander Noelia , Bernal Carolina , Diez Nardy , Añez Néstor , Docampo Roberto , Ramírez José Luis 
Published: October 2009

ABSTRACT

The dispersed gene family 1 (
DGF-1
) is the fifth largest gene family in the
T
rypanosoma cruzi
genome, with over 500 members (11). Many of the predicted
DGF-1
protein products have several transmembrane domains and N
-
glycosylation and phosphorylation sites and were thought to localize in the plasma membrane. Here, we report that affinity-purified antibodies against a region of one of these proteins (DGF-1.2) localized it intracellularly in different stages of the parasite. DGF-1.2 is more abundant in the amastigote stage than in trypomastigotes and epimastigotes, as detected by immunofluorescence and Western blot analyses. The protein changed localization during intracellular or extracellular differentiation from the trypomastigote to the amastigote stage, where it finally localized to small bodies in close contact with the inner side of the amastigote plasma membrane. DGF-1.2 did not colocalize with markers of other subcellular organelles, such as acidocalcisomes, glycosomes, reservosomes, lipid droplets, or endocytic vesicles. During extracellular differentiation, the protein was detected in the culture medium from 0 to 22 h, peaking at 14 h. The presence of DGF-1.2 in the differentiation culture medium was confirmed by mass spectrometry analysis. Finally, when epimastigotes were subjected to starvation, there was a decrease in the labeling of the cells and, in Western blots, the appearance of bands of lower molecular mass, suggesting its cleavage. These results represent the first report of direct immunodetection and developmental expression and secretion of a DGF-1 protein.
Growth and variation in the non-marine lamellibranch fauna above the Sand Rock Mine of the Lancashire Millstone Grit
Authors: Eagar Richard Michael Cardwell 
Published: October 2009

SummaryShells from a recently discovered band of non-marine lamellibranchs above the Sand Rock Mine (near the top of the Millstone Grit Series) west of Wigan have been statistically investigated at four localities. The dominant fauna,Carbonicola exporre tagar and variants, is systematically described and the variation analysed. The affinity of this fauna appear to lie with Carbonicolidae characterizing lower horizons in the Namurian, whereas a second group of shells, much less commonly represented in the band, shows similarity with the succeeding faunas ofAnthraconaia bellula(Bolton) andCarbonicola fallaxWright.The shells range in length between 3 and 49 mm. Studies in the growth of both groups include the measurement of early growth-lines in the larger individuals and reveal considerable changes in the proportions of the shell. For the mean relative growth of communities evidence points to a linear relationship between the logarithms of shell height and length. This cannot yet be fully defined.Petrological differences in the shell-bearing stratum have been investigated by Professor K. C. Dunham. It is shown, with the further support of chemical analysis, that a progressive decrease in the percentage of carbonaceous matter in the fossiliferous shale is accompanied by increase in the thickness of the band, decrease in the number of shells it contains per unit thickness, decrease in the mean size of the shells and a slight change in their relative growth-rates with respect to height and length. The latter two points indicate stunting of the fauna. The first three changes are considered to be the result of increased sedimentation.Evidence is submitted for considering theC. exporrectafaunas to have been invaded by those of the second shell group. Detailed collecting at Upholland Station cutting reveals similarities in the succession of the latter faunas to that characterizing the base of sedimentary cycles in the Soft Bed—Bassy Mine succession of the lowerlenisulcataZone. Differences in the two horizons are discussed. No internal features of the shell are revealed in the second group, but numerous cases of perfect gradation betweenCarbonicola-like andAnthraconaia-like forms confirm previous observation in the lowerlenisulcataZone. The evolution of certain species ofCarbonicolafrom a group in which the generaCarbonicolaandAnthraconaiawere apparently not yet distinct is briefly discussed.
Organizing functional code for parallel execution or, foldl and foldr considered slightly harmful
Authors: Steele Guy L. 
Published: October 2009

Alan Perlis, inverting OscarWilde's famous quip about cynics, once suggested, decades ago, that a Lisp programmer is one who knows the value of everything and the cost of nothing. Now that the conference on Lisp and Functional Programming has become ICFP, some may think that OCaml and Haskell programmers have inherited this (now undeserved) epigram.
I do believe that as multicore processors are becoming prominent, and soon ubiquitous, it behooves all programmers to rethink their programming style, strategies, and tactics, so that their code may have excellent performance. For the last six years I have been part of a team working on a programming language, Fortress, that has borrowed ideas not only from Fortran, not only from Java, not only from Algol and Alphard and CLU, not only from MADCAP and MODCAP and MIRFAC and the Klerer-May system-but also from Haskell, and I would like to repay the favor.
In this talk I will discuss three ideas (none original with me) that I have found to be especially powerful in organizing Fortress programs so that they may be executed equally effectively either sequentially or in parallel: user-defined associative operators (and, more generally, user-defined monoids); conjugate transforms of data; and monoid-caching trees (as described, for example, by Hinze and Paterson). I will exhibit pleasant little code examples (some original with me) that make use of these ideas.
Experience report
Authors: Balat Vincent , Vouillon Jérôme , Yakobowski Boris 
Published: October 2009

The evolution of Web sites towards very dynamic applications makes it necessary to reconsider current Web programming technologies. We believe that Web development would benefit greatly from more abstract paradigms and that a more semantical approach would result in huge gains in expressiveness. In particular, functional programming provides a really elegant solution to some important Web interaction problems, but few frameworks take advantage of it.
The Ocsigen project is an attempt to provide global solutions to these needs. We present our experience in designing this general framework for Web programming, written in Objective Caml. It provides a fully featured Web server and a framework for programming Web applications, with the aim of improving expressiveness and safety. This is done by taking advantage of functional programming and static typing as much as possible.
Complete and decidable type inference for GADTs
Authors: Schrijvers Tom , Peyton Jones Simon , Sulzmann Martin , Vytiniotis Dimitrios 
Published: October 2009

GADTs have proven to be an invaluable language extension, for ensuring data invariants and program correctness among others. Unfortunately, they pose a tough problem for type inference: we lose the principal-type property, which is necessary for modular type inference.
We present a novel and simplified type inference approach for local type assumptions from GADT pattern matches. Our approach is complete and decidable, while more liberal than previous such approaches.
Aspects of the Iranian Code of Islamic Punishment: The Principle of Legality and the Temporal, Spatial and Personal Applicability of the Law
Authors: Tellenbach Silvia 
Published: October 2009

AbstractIran declares itself an Islamic Republic in which all laws and regulations must be based on Islamic criteria as interpreted by the Shi'ite dja-farī School. As a consequence, Islamic law has to be applied to all the everyday legal problems of a modern state of about 73 million inhabitants and, in addition, the position of Iran in the international community must be in accordance with Islamic law. This contribution deals with selected topics of criminal law looking at the solutions that exist in Iranian criminal law. Furthermore, it examines to what extent Islamic law as understood in Iran accepts regulations which are internationally generally applied and what are the points on which Islamic law and Western law do not reach a common understanding.
An Objective Method of Evaluating and Devising Storm-Tracking Algorithms
Authors: Lakshmanan Valliappa , Smith Travis 
Published: October 2009

Abstract
Although storm-tracking algorithms are a key ingredient of nowcasting systems, evaluation of storm-tracking algorithms has been indirect, labor intensive, or nonspecific. A set of easily computable bulk statistics that can be used to directly evaluate the performance of tracking algorithms on specific characteristics is introduced. These statistics are used to evaluate five widely used storm-tracking algorithms on a diverse set of radar reflectivity data cases. Based on this objective evaluation, a storm-tracking algorithm is devised that performs consistently and better than any of the previously suggested techniques.
Active screening at entry for tuberculosis among new immigrants: a systematic review and meta-analysis
Authors: Arshad S. , Bavan L. , Gajari K. , Paget S. N. J. , Baussano I. 
Published: October 2009

Although there is no evidence that imported tuberculosis increases the incidence of the disease in host countries, the rise in migration worldwide raises concerns regarding the adequacy of surveillance and control of immigrant-associated tuberculosis in low incidence countries. Assessing the performance of screening of immigrants for tuberculosis is key to rationalising control policies for the detection and management of immigrant-associated tuberculosis.We performed a systematic review and meta-analysis to determine the yield of active screening for tuberculosis among new immigrants at the point of entry.The yield for pulmonary tuberculosis was 3.5 cases per 1,000 screened (95% CI 2.9–4.1; I2 = 94%); for refugees, asylum seekers and regular immigrants the estimates were 11.9 (95% CI 6.7–17.2; I2 = 92%), 2.8 (95% CI 2.0–3.7; I2 = 96%) and 2.7 (95% CI 2.0–3.4; I2 = 81%), respectively. The yield estimates for immigrants from Europe, Africa and Asia were 2.4 (95% CI 1.3–3.4; I2 = 51.5%), 6.5 (95% CI 3.2–10.0; I2 = 62%) and 11.2 (95% CI 6.2–16.1; I2 = 95%), respectively.These results provide useful data to inform the development of coherent policies and rational screening services for the detection of immigrant-associated tuberculosis.
Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants
Authors: Miyake Y. , Sasaki S. , Tanaka K. , Hirota Y. 
Published: October 2009

The present prospective study examined the association between maternal consumption of dairy products, calcium, and vitamin D during pregnancy and the risk of wheeze and eczema in the infants aged 16–24 months.Subjects were 763 Japanese mother–child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire. Symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood.Higher maternal intake of total dairy products, milk, cheese and calcium during pregnancy was significantly related to a decreased risk of infantile wheeze, but not eczema (adjusted ORs (95% CI) between extreme quartiles were 0.45 (0.25−0.79), 0.50 (0.28−0.87), 0.51 (0.31−0.85), and 0.57 (0.32−0.99), respectively). When maternal vitamin D consumption during pregnancy was categorised into two groups using a cut-off point at the 25th percentile, children whose mothers had consumed ≥4.309 μg·day−1had a significantly reduced risk of wheeze and eczema (adjusted ORs (95% CI) were 0.64 (0.43−0.97) and 0.63 (0.41−0.98), respectively).Higher consumption of calcium and dairy foods other than yoghurt during pregnancy may reduce the risk of infantile wheeze. Higher vitamin D intake during pregnancy may be protective against childhood wheeze and eczema.
Cigarette smoke modulates rhinovirus-induced airway epithelial cell chemokine production
Authors: Hudy M. H. , Traves S. L. , Wiehler S. , Proud D. 
Published: October 2009

Human rhinovirus (HRV) infections induce epithelial cell production of chemokines that may contribute to the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. Cigarette smoking is the predominant risk factor for the development of COPD and also aggravates asthma symptoms. We examined whether cigarette smoke extract (CSE) modulates viral inflammation by altering the profile of HRV-induced epithelial chemokine production.Purified HRV-16, and CSE were used to examine the effects on CXC chemokine ligand (CXCL)8 and CXCL10 production from both primary human bronchial epithelial cells and the BEAS-2B epithelial cell line.Both CSE and HRV-16 induced CXCL8 production and, when used in combination, induced at least an additive production of CXCL8 compared with either stimulus alone. In contrast, CSE did not induce CXCL10 and markedly inhibited HRV-16-induced CXCL10 production. Inhibition of HRV-16-induced CXCL10 by CSE was mediated, at least in part,viatranscriptional regulation. The increased CXCL8 production seen with the combination of CSE and HRV-16 was not due to transcriptional regulation but was associated with CXCL8 mRNA stabilisation.Thus, CSE differentially modulates HRV-16-induced chemokine production from human airway epithelial cells in a manner that might be expected to alter inflammatory cell profiles.