bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Contribution of Candidate Genes to Artemisinin Resistance in
Plasmodium falciparum
Authors: Imwong Mallika , Dondorp Arjen M. , Nosten Francois , Yi Poravuth , Mungthin Mathirut , Hanchana Sarun , Das Debashish , Phyo Aung Phae , Lwin Khin Maung , Pukrittayakamee Sasithon , Lee Sue J. , Saisung Suwannee , Koecharoen Kitti , Nguon Chea , Day Nicholas P. J. , Socheat Duong , White Nicholas J. 
Published: April 2010

ABSTRACT

The reduced
in vivo
sensitivity of
Plasmodium falciparum
has recently been confirmed in western Cambodia. Identifying molecular markers for artemisinin resistance is essential for monitoring the spread of the resistant phenotype and identifying the mechanisms of resistance. Four candidate genes, including the
P. falciparum mdr1
(
pfmdr1
) gene, the
P. falciparum
ATPase6
(
pfATPase6
) gene, the 6-kb mitochondrial genome, and
ubp-1
, encoding a deubiquitinating enzyme, of artemisinin-resistant
P. falciparum
strains from western Cambodia were examined and compared to those of sensitive strains from northwestern Thailand, where the artemisinins are still very effective. The artemisinin-resistant phenotype did not correlate with
pfmdr1
amplification or mutations (full-length sequencing), mutations in
pfATPase6
(full-length sequencing) or the 6-kb mitochondrial genome (full-length sequencing), or
ubp-1
mutations at positions 739 and 770. The
P. falciparum
CRT K76T mutation was present in all isolates from both study sites. The
pfmdr1
copy numbers in western Cambodia were significantly lower in parasite samples obtained in 2007 than in those obtained in 2005, coinciding with a local change in drug policy replacing artesunate-mefloquine with dihydroartemisinin-piperaquine. Artemisinin resistance in western Cambodia is not linked to candidate genes, as was suggested by earlier studies.
Antifungal Susceptibility Profile of Human-Pathogenic Species of
Lichtheimia
Authors: Alastruey-Izquierdo Ana , Cuesta Isabel , Walther Grit , Cuenca-Estrella Manuel , Rodriguez-Tudela Juan Luis 
Published: April 2010

ABSTRACT

Forty-four isolates belonging to human pathogenic species of
Lichtheimia
were tested against nine antifungal agents by using the EUCAST methodology. No remarkable differences were found between the clinical species, although
L. ramosa
showed slightly higher MICs for all drugs. Amphotericin B was the most active drug. Among azole drugs, posaconazole had the best activity
in vitro
and voriconazole was inactive. Echinocandins showed activity for some isolates, suggesting a potential role in combination therapy.
Use of Plasma Procalcitonin Levels as an Adjunct to Clinical Microbiology
Authors: Gilbert David N. 
Published: April 2010

ABSTRACT
Procalcitonin (PCT) is synthesized by a large number of tissues and organs in response to invasion by pathogenic bacteria, fungi, and some parasites. Current PCT assays are rapid, specific, and of sufficient sensitivity to detect increases in PCT serum levels within 4 to 6 h of initiation of infection. Clinically, PCT levels may help in decisions regarding the need for empirical antibiotic therapy, “source control” of infection, and duration of antibiotic therapy. The addition of PCT levels to bacterial culture and viral detection results can assist with the separation of colonization and invasion by pathogenic bacteria.
Cloud-TM
Authors: Romano Paolo , Rodrigues Luis , Carvalho Nuno , Cachopo Joäo 
Published: April 2010

One of the main challenges to harness the potential of Cloud computing is the design of programming models that simplify the development of large-scale parallel applications and that allow ordinary programmers to take full advantage of the computing power and the storage provided by the Cloud, both of which made available, on demand, in a pay-only-forwhat-you-use pricing model.
In this paper, we discuss the use of the Transactional Memory programming model in the context of the cloud computing paradigm, which we refer to as Cloud-TM. We identify where existing Distributed Transactional Memory platforms still fail to meet the requirements of the cloud and of its users, and we point several open research problems whose solution we deem as essential to materialize the Cloud-TM vision.
Stratospheric Gravity Waves Generated by Typhoon Saomai (2006): Numerical Modeling in a Moving Frame Following the Typhoon
Authors: Kim So-Young , Chun Hye-Yeong 
Published: April 2010

Abstract
Stratospheric gravity waves generated by Typhoon Saomai (2006) were simulated using a mesoscale model in a moving frame of reference following the typhoon. Waves with large amplitudes appear near the domain center because of strong convection in the eyewall of the typhoon. Convection bands propagating outward from the storm center also generate waves propagating to the stratosphere. Convective forcing is significant in various propagation directions, with maximum power in slowly moving eastward components due to convection in the eyewall. The forcing exhibits large amplitude at a speed of 8–16 m s−1 in the eastward direction in which spiral bands are mainly developed. Induced gravity waves in the stratosphere are dominant in the eastward, northeastward, and southeastward propagation directions, since westward waves are mostly filtered by the background wind below z = 25 km. While the typhoon moves northwestward for 78 h, the wave characteristics vary through time depending on the evolution of the eyewall and spiral bands. Horizontal wavelengths of waves are longer in the mature and decaying stages than in the developing stage of the typhoon, likely because of a more dominant concentric eyewall in the mature and decaying stages. The spectral peak of the waves is at ∼20 km (∼50 km) horizontal wavelength in the developing (mature) stage, and the wave amplitudes are larger in the developing stages. The dominant contribution to the momentum flux is from waves with horizontal wavelengths longer than 80 km. Positive momentum flux decreases with overall height and the resultant positive drag can cause deceleration of northeasterly background wind. Sensitivity of the model results to horizontal resolution reveals that small-scale waves resolved in the present simulations with 3-km resolution cannot be fully represented with 9- or 27-km resolutions.
Multidisciplinary Analysis of an Unusual Tornado: Meteorology, Climatology, and the Communication and Interpretation of Warnings*
Authors: Schumacher Russ S. , Lindsey Daniel T. , Schumacher Andrea B. , Braun Jeff , Miller Steven D. , Demuth Julie L. 
Published: April 2010

Abstract
On 22 May 2008, a strong tornado—rated EF3 on the enhanced Fujita scale, with winds estimated between 136 and 165 mi h−1 (61 and 74 m s−1)—caused extensive damage along a 55-km track through northern Colorado. The worst devastation occurred in and around the town of Windsor, and in total there was one fatality, numerous injuries, and hundreds of homes significantly damaged or destroyed. Several characteristics of this tornado were unusual for the region from a climatological perspective, including its intensity, its long track, its direction of motion, and the time of day when it formed. These unusual aspects and the high impact of this tornado also raised a number of questions about the communication and interpretation of information from National Weather Service watches and warnings by decision makers and the public. First, the study examines the meteorological circumstances responsible for producing such an outlier to the regional severe weather climatology. An analysis of the synoptic and mesoscale environmental conditions that were favorable for significant tornadoes on 22 May 2008 is presented. Then, a climatology of significant tornadoes (defined as those rated F2 or higher on the Fujita scale, or EF2 or higher on the Enhanced Fujita scale) near the Front Range is shown to put the 22 May 2008 event into climatological context. This study also examines the communication and interpretation of severe weather information in an area that experiences tornadoes regularly but is relatively unaccustomed to significant tornadoes. By conducting interviews with local decision makers, the authors have compiled and chronicled the flow of information as the event unfolded. The results of these interviews demonstrate that the initial sources of warning information varied widely. Decision makers’ interpretations of the warnings also varied, which led to different perceptions on the timeliness and clarity of the warning information. The decision makers’ previous knowledge of the typical local characteristics of tornadoes also affected their interpretations of the tornado threat. The interview results highlight the complex series of processes by which severe weather information is communicated after a warning is issued by the National Weather Service. The results of this study support the growing recognition that societal factors are just as important to the effectiveness of weather warnings as the timeliness of and information provided in those warnings, and that these factors should be considered in future research in addition to the investments and attention given to improving detection and warning capabilities.
Participant expectancies in double-blind randomized placebo-controlled trials: potential limitations to trial validity
Authors: Colagiuri Ben 
Published: April 2010

Background Randomized controlled trials (RCTs) that use placebo controls to achieve double-blinding intend to establish the efficacy of a treatment over and above expectancy and other forms of bias. Despite this, a growing body of research suggests that participant expectancies can influence the outcomes of these trials. Purpose and Methods This nonsystematic review examines research assessing the role of participant expectancies in double-blind placebo-controlled RCTs in order to determine if and how they can limit these types of trials. Results There appear to be at least three ways in which participant expectancies can limit the validity of double-blind placebo-controlled RCTs. First, when blinding fails researches cannot determine whether any observed improvement in the group receiving active treatment resulted because of the treatment’s effect or because of participants’ expectancies. Second, participant expectancies could create ceiling effects if there are strong placebo effects in each treatment arm and this may falsely suggest that the active treatment is ineffective without expectancy. Third, the knowledge that a participant will be allocated active treatment or placebo in double-blind placebo-controlled RCTs is likely to lead to weaker treatment responses than would be expected in standard clinical practice, in which patients are unlikely to doubt that they have been given an active treatment. Conclusions Participants’ expectancies can undermine the validity of double-blind placebo-controlled RCTs. Researchers conducting these trials should assess participants’ beliefs about their treatment allocation and actively investigate if and how these beliefs may have influenced the trial’s outcome. Clinical Trials 2010; 7: 246—255. http://ctj.sagepub.com
Monazite structure from dehydrated CaSeO4·2H2O
Authors: Crichton W. A. , Müller H. , Merlini M. , Roth T. , Detlefs C. 
Published: April 2010

AbstractThe structure of the high-temperature form of CaSeO4, formed by dehydration of the gyspum-type structure dihydrate is presented. The material is equivalent to that described previously as aP212121form, but is however, a monazite with unit cella= 6.85661(16) Å,b= 7.04962(15) Å,c= 6.68817(15) Å and β = 104.2675(21)° in space groupP121/n1. Also presented is evidence for two intermediate trigonal and pseudo-trigonal phases related to the structurally similar minerals rhabdophane, bassanite, and γ-CaSO4. This result permits closer comparisons between intermediate-temperature structures of the selenate with related sulphates, and orthophosphates with a view to extending structural stabilityviasynthesis of solid-solutions.
Structural evolution of aqueous mercury sulphide precipitates: energy-dispersive X-ray diffraction studies
Authors: Bell A. M. T. , Pattrick R. A. D. , Vaughan D. J. 
Published: April 2010

AbstractIn situ, high-temperature energy-dispersive X-ray powder diffraction (EDXRD) data have been collected on synthetic and a natural sample of mercury sulphide (HgS). These measurements were made between temperatures of 295 and 798 K. Synthetic samples of HgS were prepared by reaction between sulphide and mercury in aqueous solution. In a subsequently dried and aged synthetic HgS sample, heated in vacuo, there is a change from a poorly crystalline pseudocubic material into a well crystalline cubic material in the temperature region 583–623 K. At higher temperature (748 K), there is evidence for a partial phase transition to the high temperature hypercinnabar HgS structure. In a neoformed synthetic sample, heated in a sealed Ti container, the initial ‘pseudocubic’ metacinnabar phase partially transforms to a previously unknown phase (XHgS) in the temperature range 467–522 K. This phase disappears at 527 K, and the metacinnabar phase changes to a well crystalline cubic phase; cinnabar develops at 542 K. The proportion of cinnabar continues to increase up to 647 K. Both metacinnabar and cinnabar phases are retained on cooling. No phase transitions were observed for the natural cinnabar sample.
XBP1s levels are implicated in the biology and outcome of myeloma mediating different clinical outcomes to thalidomide-based treatments
Authors: Bagratuni Tina , Wu Ping , Gonzalez de Castro David , Davenport Emma L. , Dickens Nicholas J. , Walker Brian A. , Boyd Kevin , Johnson David C. , Gregory Walter , Morgan Gareth J. , Davies Faith E. 
Published: April 2010

Abstract
Immunoglobulin production by myeloma plasma cells depends on the unfolded protein response for protein production and folding. Recent studies have highlighted the importance of IRE1α and X box binding protein 1 (XBP1), key members of this pathway, in normal B-plasma cell development. We have determined the gene expression levels of IRE1α, XBP1, XBP1UNSPLICED (XBP1u), and XBP1SPLICED (XBP1s) in a series of patients with myeloma and correlated findings with clinical outcome. We show that IRE1α and XBP1 are highly expressed and that patients with low XBP1s/u ratios have a significantly better overall survival. XBP1s is an independent prognostic marker and can be used with β2 microglobulin and t(4;14) to identify a group of patients with a poor outcome. Furthermore, we show the beneficial therapeutic effects of thalidomide in patients with low XBP1s/u ratios. This study highlights the importance of XBP1 in myeloma and its significance as an independent prognostic marker and as a predictor of thalidomide response. This trial was registered at www.controlled-trials.com/ISRCTN68454111/68454111 as #ISRCTN684541111.
Structural fragment clustering reveals novel structural and functional motifs in α-helical transmembrane proteins
Authors: Marsico Annalisa , Henschel Andreas , Winter Christof , Tuukkanen Anne , Vassilev Boris , Scheubert Kerstin , Schroeder Michael 
Published: April 2010

Abstract

Background
A large proportion of an organism's genome encodes for membrane proteins. Membrane proteins are important for many cellular processes, and several diseases can be linked to mutations in them. With the tremendous growth of sequence data, there is an increasing need to reliably identify membrane proteins from sequence, to functionally annotate them, and to correctly predict their topology.

Results
We introduce a technique called structural fragment clustering, which learns sequential motifs from 3D structural fragments. From over 500,000 fragments, we obtain 213 statistically significant, non-redundant, and novel motifs that are highly specific to α-helical transmembrane proteins. From these 213 motifs, 58 of them were assigned to function and checked in the scientific literature for a biological assessment. Seventy percent of the motifs are found in co-factor, ligand, and ion binding sites, 30% at protein interaction interfaces, and 12% bind specific lipids such as glycerol or cardiolipins. The vast majority of motifs (94%) appear across evolutionarily unrelated families, highlighting the modularity of functional design in membrane proteins. We describe three novel motifs in detail: (1) a dimer interface motif found in voltage-gated chloride channels, (2) a proton transfer motif found in heme-copper oxidases, and (3) a convergently evolved interface helix motif found in an aspartate symporter, a serine protease, and cytochrome b.

Conclusions
Our findings suggest that functional modules exist in membrane proteins, and that they occur in completely different evolutionary contexts and cover different binding sites. Structural fragment clustering allows us to link sequence motifs to function through clusters of structural fragments. The sequence motifs can be applied to identify and characterize membrane proteins in novel genomes.
Phylogeography of the Italian vairone (Telestes muticellus, Bonaparte 1837) inferred by microsatellite markers: evolutionary history of a freshwater fish species with a restricted and fragmented distribution
Authors: Marchetto Flavio , Zaccara Serena , Muenzel Frauke M , Salzburger Walter 
Published: April 2010

Abstract

Background
Owing to its independence from the main Central European drainage systems, the Italian freshwater fauna is characterized by a high degree of endemicity. Three main ichthyogeographic districts have been proposed in Italy. Yet, the validity of these regions has not been confirmed by phylogenetic and population genetic analyses and a phylogeographic scenario for Italy's primary freshwater fish fauna is still lacking. Here, we investigate the phylogeography of the Italian vairone (Telestes muticellus).

Results
We sampled 38 populations representing the species' entire distribution range and covering all relevant drainage systems, and genotyped 509 individuals at eight variable microsatellite loci. Applying various population genetic analyses, we identify five distinct groups of populations that are only partly in agreement with the proposed ichthyogeographic districts. Our group I, which is formed by specimens from Veneto and the Po River system draining into the Adriatic Sea, corresponds to the Padano-Venetian ichthyogeographic district (PV), except for two Middle Adriatic drainages, which we identify as a separate group (III). The Tuscano-Latium district (TL) is equivalent to our group V. A more complex picture emerges for the Ligurian drainages: populations from Central Liguria belong to group I, while populations from West (group II) and East Liguria (group IV) form their own groups, albeit with affinities to PV and TL, respectively.

Conclusions
We propose a phylogeographic scenario for T. muticellus in which an initial T. muticellus stock became isolated from the 'Alpine' clade and survived the various glaciation cycles in several refugia. These were situated in the Upper Adriatic (groups I and II), the Middle Adriatic (group III), (East) Liguria (group IV) and Tuscano-Latium (group V). The population structure in the vairone is, in principal, in agreement with the two main ichthyogeographic districts (PV and TL), except for the two populations in the Middle Adriatic, which we identify as additional major "district".
Aryl hydrocarbon receptor (AHR)-regulated transcriptomic changes in rats sensitive or resistant to major dioxin toxicities
Authors: Moffat Ivy D , Boutros Paul C , Chen Hanbo , Okey Allan B , Pohjanvirta Raimo 
Published: April 2010

AbstractBackgroundThe major toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) appear to result from dysregulation of mRNA levels mediated by the aryl hydrocarbon receptor (AHR). Dioxin-like chemicals alter expression of numerous genes in liver, but it remains unknown which lie in pathways leading to major toxicities such as hepatotoxicity, wasting and lethality. To identify genes involved in these responses we exploited a rat genetic model. Rats expressing an AHR splice-variant lacking a portion of the transactivation domain are highly resistant to dioxin-induced toxicities. We examined changes in hepatic mRNA abundances 19 hours after TCDD treatment in two dioxin-resistant rat strains/lines and two dioxin-sensitive rat strains/lines.ResultsResistant rat strains/lines exhibited fewer transcriptional changes in response to TCDD than did rats with wildtype AHR. However, well-known AHR-regulated and dioxin-inducible genes such asCYP1A1,CYP1A2, andCYP1B1remained fully responsive to TCDD in all strains/lines. Pathway analysis indicated that the genes which respond differently to TCDD between sensitive and resistant rats are mainly involved in lipid metabolism, cellular membrane function and energy metabolism. These pathways previously have been shown to respond differently to dioxin treatment in dioxin-sensitive versus dioxin-resistant rats at a biochemical level and in the differential phenotype of toxicologic responses.ConclusionThe transactivation-domain deletion in dioxin-resistant rats does not abolish global AHR transactivational activity but selectively interferes with expression of subsets of genes that are candidates to mediate or protect from major dioxin toxicities such as hepatotoxicity, wasting and death.
Differences in transcription between free-living and CO2-activated third-stage larvae of Haemonchus contortus
Authors: Cantacessi Cinzia , Campbell Bronwyn E , Young Neil D , Jex Aaron R , Hall Ross S , Presidente Paul JA , Zawadzki Jodi L , Zhong Weiwei , Aleman-Meza Boanerges , Loukas Alex , Sternberg Paul W , Gasser Robin B 
Published: April 2010

Abstract

Background
The disease caused by Haemonchus contortus, a blood-feeding nematode of small ruminants, is of major economic importance worldwide. The infective third-stage larva (L3) of this gastric nematode is enclosed in a cuticle (sheath) and, once ingested with herbage by the host, undergoes an exsheathment process that marks the transition from the free-living (L3) to the parasitic (xL3) stage. This study explored changes in gene transcription associated with this transition and predicted, based on comparative analysis, functional roles for key transcripts in the metabolic pathways linked to larval development.

Results
Totals of 101,305 (L3) and 105,553 (xL3) expressed sequence tags (ESTs) were determined using 454 sequencing technology, and then assembled and annotated; the most abundant transcripts encoded transthyretin-like, calcium-binding EF-hand, NAD(P)-binding and nucleotide-binding proteins as well as homologues of Ancylostoma-secreted proteins (ASPs). Using an in silico-subtractive analysis, 560 and 685 sequences were shown to be uniquely represented in the L3 and xL3 stages, respectively; the transcripts encoded ribosomal proteins, collagens and elongation factors (in L3), and mainly peptidases and other enzymes of amino acid catabolism (in xL3). Caenorhabditis elegans orthologues of transcripts that were uniquely transcribed in each L3 and xL3 were predicted to interact with a total of 535 other genes, all of which were involved in embryonic development.

Conclusion
The present study indicated that some key transcriptional alterations taking place during the transition from the L3 to the xL3 stage of H. contortus involve genes predicted to be linked to the development of neuronal tissue (L3 and xL3), formation of the cuticle (L3) and digestion of host haemoglobin (xL3). Future efforts using next-generation sequencing and bioinformatic technologies should provide the efficiency and depth of coverage required for the determination of the complete transcriptomes of different developmental stages and/or tissues of H. contortus as well as the genome of this important parasitic nematode. Such advances should lead to a significantly improved understanding of the molecular biology of H. contortus and, from an applied perspective, to novel methods of intervention.