bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of bleeding disorders in the elderly
Authors: KRUSE‐JARRES R. , QUON D. , SCHRAMM W. , DOLAN G.
Published: April 2012

Summary.  We are entering a new phase in the management of patients with bleeding disorders such as haemophilia. This is the result of the positive effects that disease management strategies have had on patient longevity over the last 10–15 years. A greater number of individuals are entering middle‐ to old‐age and, as a result, we face a new era of having to manage haemophiliac patients at risk of, or suffering from, age‐related diseases. We can clearly learn from the experiences of geriatricians who have made many advances in the management of chronic disorders such as cardiovascular diseases and osteoporosis. However, the hypocoagulable state brings challenges of its own and it is important that we communicate our experiences so that the shared information can help drive improved levels of care and better clinical outcomes. In this article we look at factors that have impacted the life expectancy of patients with haemophilia over the last few decades, and we also review some of the early literature relating to cardiovascular risk management and the treatment of osteoporosis.
Immune activation and increased IL‐21R expression are associated with the loss of memory B cells during HIV‐1 infection
Authors: Ruffin N. , Lantto R. , Pensieroso S. , Sammicheli S. , Hejdeman B. , Rethi B. , Chiodi F.
Published: April 2012

Abstract.  Ruffin N, Lantto R, Pensieroso S, Sammicheli S, Hejdeman B, Rethi B, Chiodi F (Karolinska Institutet, Stockholm; and South Hospital, Stockholm, Sweden). Immune activation and increased IL‐21R expression are associated with the loss of memory B cells during HIV‐1 infection. J Intern Med 2012; 272: 492–503.

Objectives.  Microbial translocation and chronic immune activation were previously shown to be associated with impairment of T cell functions and disease progression during infection with human immunodeficiency virus type‐1 (HIV‐1); however, their impact on B cell function and number remains unknown. By measuring markers of immune activation and molecules involved in apoptosis regulation, we have evaluated the association between microbial translocation and loss of memory B cells in HIV‐1‐infected patients.

Methods.  Markers of activation [the interleukin‐21 receptor (IL‐21R) and CD38] and apoptosis (Bim, Bcl‐2 and annexin V) were measured in B cell subpopulations by multicolour flow cytometry. Levels of soluble CD14 (sCD14) and lipopolysaccharide (LPS), measures of microbial translocation, were determined in plasma. Purified B cells were also exposed in vitro to Toll‐like receptor (TLR) ligands.

Results.  IL‐21R expression was higher in cells from HIV‐1‐infected patients, compared with control subjects, with the highest levels in nontreated patients. An inverse correlation was observed between IL‐21R expression and percentages of circulating resting memory (RM) B cells. IL‐21R‐positive memory B cells were also more susceptible to spontaneous apoptosis and displayed lower levels of Bcl‐2. It is interesting that the levels of sCD14, which are increased during HIV‐1 infection, were correlated with decreased percentages of RM B cells and high IL‐21R expression. In the plasma of HIV‐1‐infected individuals, a correlation was found between sCD14 and LPS levels. TLR activation of B cells in vitro resulted in IL‐21R up‐regulation.

Conclusions.  Microbial translocation and the associated immune activation during HIV‐1 infection may lead to high expression levels of the IL‐21R activation marker in RM B cells, a feature associated with increased apoptosis and a reduced number of these cells in the circulation.
Schizophyllum commune as an emerging fungal pathogen: a review and report of two cases
Authors: Chowdhary A. , Randhawa H. S. , Gaur S. N. , Agarwal K. , Kathuria S. , Roy P. , Klaassen C. H. , Meis J. F.
Published: April 2012

We report Schizophyllum commune as the aetiological agent of one case each of allergic broncho‐pulmonary mycosis (ABPM) and pulmonary fungal ball, and present a literature review. The fungus was characterised by clamp connections, hyphal spicules, and formation of basidiocarps with basidiospores. The phenotypic identification was confirmed by sequencing of the ITS region. To‐date, ABPM and pulmonary fungal ball to S. commune have been reported exclusively from Japan and North America respectively. Of the 71 globally reported cases due to S. commune, 45 (63%) were bronchopulmonary, 22 (31%) sinusitis and 4 extrapulmonary. Taken together, cases of bronchopulmonary disease and sinusitis numbered 67 (94%), indicating the respiratory tract as the primary target of disease. Concerning the country‐wise distribution, Japan topped the list with 33 cases (46%), followed by Iran – 7 cases (10%), U.S.A. – 6 cases (9%), and a lower prevalence of 1.4–6% for the remaining 12 countries. The preponderance of the disease in Japan may be attributed to its greater awareness vis‐à‐vis that in other countries rather than to any geographical/climatic factors. We believe that the burden of S. commune‐incited disease is currently underestimated, warranting comprehensive prospective studies to determine its prevalence.
Molecular mechanisms of cell shape changes that contribute to vertebrate neural tube closure
Authors: Suzuki Makoto , Morita Hitoshi , Ueno Naoto
Published: April 2012

During early development of the central nervous system, the neuroepithelial cells undergo dynamic changes in shape, cumulative action of which cause the neural plate to bend mediolaterally to form the neural tube. The apicobasal elongation changes the cuboidal cells into columnar ones, whereas apical constriction minimizes the cell apices, causing them to adopt wedge‐like shapes. To achieve the morphological changes required for the formation of a hollow structure, these cellular changes must be controlled in time and space. To date, it is widely accepted that spatial and temporal changes of the cytoskeletal organization are fundamental to epithelial cell shape changes, and that noncetrosomal microtubules assembled along apicobasal axis and actin filaments and non‐muscle myosin II at the apical side are central machineries of cell elongation and apical constriction, respectively. Hence, especially in the last decade, intracellular mechanisms regulating these cytoskeletons have been extensively investigated at the molecular level. As a result, several actin‐binding proteins, Rho/ROCK pathway, and cell–cell adhesion molecules have been proven to be the central regulators of apical constriction, while the regulatory mechanisms of cell elongation remain obscure. In this review, we first describe the distribution and role of cytoskeleton in cell shape changes during neural tube closure, and then summarize the current knowledge about the intracellular proteins that directly modulate the cytoskeletal organization and thus the neural tube closure.
New experimental set‐up to approach pipeline fracture behaviour by three‐point bending specimens
Authors: MINOTTI M. , SALVINI P.
Published: April 2012

A new experimental set‐up for drop weight tear tests is proposed. Its principal characteristic is the adoption of inclined supports driving the hinges connected to the specimen. This choice accomplishes the need that the specimen was subjected to a persistent stress field in the ligament, thus approaching the stress field experienced by a crack propagating in a pipeline. This set‐up requires a proper processing of the data that is accurately explained in the paper. The tests are conducted under a quasi‐static loading but the method has been designed to apply in dynamic tests.
Acinetobacter, Aeromonas and Trichococcus populations dominate the microbial community within urban sewer infrastructure
Authors: VandeWalle J. L. , Goetz G. W. , Huse S. M. , Morrison H. G. , Sogin M. L. , Hoffmann R. G. , Yan K. , McLellan S. L.
Published: April 2012

We evaluated the population structure and temporal dynamics of the dominant community members within sewage influent from two wastewater treatment plants (WWTPs) in Milwaukee, WI. We generated > 1.1 M bacterial pyrotag sequences from the V6 hypervariable region of 16S rRNA genes from 38 influent samples and two samples taken upstream in the sanitary sewer system. Only a small fraction of pyrotags from influent samples (∼ 15%) matched sequences from human faecal samples. The faecal components of the sewage samples included enriched pyrotag populations from Lactococcus and Enterobacteriaceae relative to their fractional representation in human faecal samples. In contrast to the large number of distinct pyrotags that represent faecal bacteria such as Lachnospiraceae and Bacteroides, only one or two unique V6 sequences represented Acinetobacter, Aeromonas and Trichococcus, which collectively account for nearly 35% of the total sewage community. Two dominant Acinetobacter V6 pyrotags (designated Acineto tag 1 and Acineto tag 2) fluctuated inversely with a seasonal pattern over a 3‐year period, suggesting two distinct Acinetobacter populations respond differently to ecological forcings in the system. A single nucleotide change in the V6 pyrotags accounted for the difference in these populations and corresponded to two phylogenetically distinct clades based on full‐length sequences. Analysis of wavelet functions, derived from a mathematical model of temporal fluctuations, demonstrated that other abundant sewer associated populations including Trichococcus and Aeromonas had temporal patterns similar to either Acineto tag 1 or Acineto tag 2. Populations with related temporal fluctuations were found to significantly correlate with the same WWTP variables (5‐day BOD, flow, ammonia, total phosphorous and suspended solids). These findings illustrate that small differences in V6 sequences can represent phylogenetically and ecologically distinct taxa. This work provides insight into microbial community composition and dynamics within the defined environment of urban sewer infrastructure.
Weight gain after childhood traumatic brain injury: a matter of concern
Authors: JOURDAN CLAIRE , BRUGEL DOMINIQUE , HUBEAUX KATELYNE , TOURE HANNA , LAURENT‐VANNIER ANNE , CHEVIGNARD MATHILDE
Published: April 2012

Aim  The aim of the study was to assess weight changes after traumatic brain injury (TBI) in children and the factors influencing them.

Method  We conducted a longitudinal observational study of children with TBI of mixed severity who were consecutively admitted to one rehabilitation department (39 children; 23 males, 16 females; median age 8y 7mo; 25th to 75th centiles 3y 7mo–11y 6mo). Weight and height before TBI were obtained from the children’s records and were measured monthly for 1 year after TBI. Body mass index (BMI) and BMI z‐scores were calculated, and pre‐TBI values were compared with the final values using paired tests. Linear mixed‐effect interaction models were used to assess the effect of various factors on z‐score evolution.

Results  Z‐score curves revealed early weight loss followed by a rapid increase in weight. The mean BMI gain over the period under study was 0.9kg/m² (p < 0.001) and the mean z‐score gain was 0.4 (p = 0.006). Six children had become overweight by the time of final assessment. Factors associated with a greater rate of increase in the post‐TBI z‐score were mobility restriction, male sex, and older age. Global pre‐ to post‐TBI weight gain was significantly higher in males (z‐score 0.7). Pituitary hormonal testing was available for 17 children at 3 months and for 27 at 1 year. Growth hormone deficiency was detected in one child.

Interpretation  Weight gain of children during the first year after TBI was rapid and excessive. Male sex was a risk factor for excessive weight gain.
Metabolism of deoxypyrimidines and deoxypyrimidine antiviral analogs in isolated brain mitochondria
Authors: McCann Kathleen A. , Williams David W. , McKee Edward E.
Published: April 2012

J. Neurochem. (2012) 122, 126–137.

The goal of this project was to characterize deoxypyrimidine salvage pathways used to maintain deoxynucleoside triphosphate pools in isolated brain mitochondria and to determine the extent that antiviral pyrimidine analogs utilize or affect these pathways. Mitochondria from rat brains were incubated in media with labeled and unlabeled deoxynucleosides and deoxynucleoside analogs. Products were analyzed by HPLC coupled to an inline UV monitor and liquid scintillation counter. Isolated mitochondria transported thymidine and deoxycytidine into the matrix, and readily phosphorylated both of these to mono‐, di‐, and tri‐phosphate nucleotides. Rates of phosphorylation were much higher than rates observed in mitochondria from heart and liver. Deoxyuridine was phosphorylated much more slowly than thymidine and only to dUMP. 3′‐azido‐3′‐deoxythymidine, zidovudine (AZT), an antiviral thymidine analog, was phosphorylated to AZT‐MP as readily as thymidine was phosphorylated to TMP, but little if any AZT‐DP or AZT‐TP was observed. AZT at 5.5 ± 1.7 μM was shown to inhibit thymidine phosphorylation by 50%, but was not observed to inhibit deoxycytidine phosphorylation except at levels > 100 μM. Stavudine and lamivudine were inert when incubated with isolated brain mitochondria. The kinetics of phosphorylation of thymidine, dC, and AZT were significantly different in brain mitochondria compared to mitochondria from liver and heart.
El Niño‐Southern Oscillation cyclical modulation of macrobenthic community structure in the Humboldt Current ecosystem
Authors: Pacheco Aldo S. , Riascos Jose M. , Orellana Fernanda , Oliva Marcelo E.
Published: April 2012

Understanding how natural communities confront different types of natural and anthropogenic stressors has gained much more attention as global climate change imposes nearly unpredictable ecosystem states or regimes. In the Humboldt Current ecosystem this seems to be a priority task due to the complex dynamics caused by the El Niño Southern Oscillation (ENSO). Herein a 17‐year (1991–2007) time‐series data‐set of macrobenthic community structure and environmental parameters from seasonal sampling from four fixed stations off Punta Coloso (23°45’S, 70°28’W northern of Chile) is analyzed. The aim of this study was to assess benthic responses to ENSO‐associated anomalies. nMDS analysis revealed changes in community structure associated to El Niño (1997–1998) and La Niña (1999–2000). From 1991, communities gradually increased in dissimilarity up to 1998 but after 2000 dissimilarity decreased, thus approaching the early community structure in a counterclockwise like direction. This suggested a cyclical pattern throughout time, which was tested with a cyclicity analysis. The test showed a significant correlation between the dissimilarity biotic matrix and a perfect cyclicity model matrix. The finding of a 17‐year cycle in the variation of community structure adds new insights and contrast to previous observations of increments in diversity and alternation of dominant taxa associated to environmental forcing. It needs to be revealed if this cycle forms part of a major decadal oscillation in the benthic subsystem. Nevertheless, this result is in line with the decadal pattern of variability observed for pelagic communities associated to warm and cold phases of ENSO.
Little strokes fell great oaks: minor but chronic herbivory substantially reduces birch growth
Authors: Zvereva Elena L. , Zverev Vitali , Kozlov Mikhail V.
Published: April 2012

Modern concepts of plant tolerance to herbivory are primarily based on studies of short‐term severe damage, whereas the effects of minor chronic damage to long‐lived woody plants, corresponding to background herbivory (2–15% annual loss of foliar biomass in boreal and temperate forests), remain poorly understood. In our experiment, the annual removal of 2, 4, 8 and 16% of the leaf area from naturally growing mountain birch Betula pubescens subsp. czerepanovii saplings during a seven‐year period resulted in a pronounced reduction of plant vertical growth (–30, –34, –45 and –78%, respectively). Leaf size decreased first (already after one year of the 16% treatment), resulting in the reduction of the total leaf area. This effect was followed by a considerable decrease in the length of long shoots in all treatments. Leaf number on the plant was maintained for a longer time, being reduced by the end of the experiment in 16% treatment only; no changes in specific leaf area or chlorophyll fluorescence were observed in either of the treatments. This pattern may indicate that the plant reallocates resources from the growth of the woody parts to the maintenance of the photosynthetic area, and can be seen as a strategy of tolerance to minor herbivory, whereas compensatory responses typical of severe herbivory (increased photosynthesis rates and shoot regrowth) have not been detected. The predicted 2–5% increase in background herbivory due to climate warming can potentially produce previously unrecognised negative impacts on tree growth. We conclude that in the long term, background herbivory is likely to impose stronger effects on the growth of woody plants than short‐term devastating outbreaks of defoliators, thus contributing more to the development of plant evolutionary adaptations to herbivory than severe but episodic bouts of damage.
Fear extinction and BDNF: translating animal models of PTSD to the clinic
Authors: Andero R. , Ressler K.J.
Published: April 2012

Brain‐derived neurotrophic factor (BDNF) is the most studied neurotrophin involved in synaptic plasticity processes that are required for long‐term learning and memory. Specifically, BDNF gene expression and activation of its high‐affinity tropomyosin‐related kinase B (TrkB) receptor are necessary in the amygdala, hippocampus and prefrontal cortex for the formation of emotional memories, including fear memories. Among the psychiatric disorders with altered fear processing, there is post‐traumatic stress disorder (PTSD) which is characterized by an inability to extinguish fear memories. Since BDNF appears to enhance extinction of fear, targeting impaired extinction in anxiety disorders such as PTSD via BDNF signalling may be an important and novel way to enhance treatment efficacy. The aim of this review is to provide a translational point of view that stems from findings in the BDNF regulation of synaptic plasticity and fear extinction. In addition, there are different systems that seem to alter fear extinction through BDNF modulation like the endocannabinoid system and the hypothalamic–pituitary adrenal axis. Recent work also finds that the pituitary adenylate cyclase‐activating polypeptide and PAC1 receptor, which are upstream of BDNF activation, may be implicated in PTSD. Especially interesting are data that exogenous fear extinction enhancers such as antidepressants, histone deacetylases inhibitors and d‐cycloserine, a partial N‐methyl d‐aspartate agonist, may act through or in concert with the BDNF–TrkB system. Finally, we review studies where recombinant BDNF and a putative TrkB agonist, 7,8‐dihydroxyflavone, may enhance extinction of fear. These approaches may lead to novel agents that improve extinction in animal models and eventually humans.
Posterior reversible encephalopathy syndrome following chemotherapy with oxaliplatin and a fluoropyrimidine: A case report and literature review
Authors: FEMIA Giuseppe , HARDY Todd A , SPIES Judith M , HORVATH Lisa G
Published: April 2012

Posterior reversible encephalopathy syndrome (PRES) is a neuro‐radiological syndrome characterized by seizures, altered level of consciousness and visual disturbance. PRES is associated with hyperintense lesions on magnetic resonance imaging (MRI) most commonly seen in the posterior regions. In most cases symptoms and radiological lesions are reversible. The aims of this article are: (i) to review the literature for all cases involving oxaliplatin, fluoropyrimidine and bevacizumab and (ii) highlight the increasing number of cases attributed to anti‐neoplastic agents. An in‐depth literature review was conducted by utilizing Pubmed's MEDLINE and Google Scholar databases. We found that there have been nine cases of PRES associated with oxaliplatin or fluoropyrimidine therapy; five cases also involved therapy with bevacizumab. Eight of the nine patients made a full recovery with a complete resolution of MRI changes. This is the first Australian case of PRES following treatment with oxaliplatin and a fluoropyrimidine and only the second case reported in which the patient did not recover despite appropriate medical management. It appears that PRES maybe more commonly associated with multi‐agent therapies and although reversible in most cases, PRES may result in adverse outcomes despite rapid intervention.
The N‐terminal Region of CXCL11 as Structural Template for CXCR3 Molecular Recognition: Synthesis, Conformational Analysis, and Binding Studies
Authors: Palladino Pasquale , Portella Luigi , Colonna Giovanni , Raucci Raffaele , Saviano Gabriella , Rossi Filomena , Napolitano Maria , Scala Stefania , Castello Giuseppe , Costantini Susan
Published: April 2012

The chemokines and their receptors play a key role in immune and inflammatory responses by promoting recruitment and activation of different subpopulations of leukocytes. The membrane receptor CXCR3 binds three chemokines, CXCL9, CXCL10, and CXCL11, and its involvement is recognized in many inflammatory diseases and cancers. Therefore, the inhibition of CXCR3 pathway through interactions with three ligands was indicated as putative therapeutic target for the treatment of these diseases, and some inhibitory compounds have already been described in the literature. Recently, we studied the interaction between CXCR3 and its three natural ligands and showed that three CXCR3 ligands bound the receptor mainly by their N‐terminal regions using aromatic and electrostatic interactions, and, in particular, CXCL11 had the highest affinity for CXCR3. In light of these results, we focused our attention on what structural region(s) of CXCL11 interacted with CXCR3 and what were the structural features. Therefore, we have synthesized three peptides, corresponding to the N‐terminal region of CXCL11, but with different aromatic amino acids, analyzed their conformations by circular dichroism, NMR, and molecular dynamics simulations, simulated their complexes with CXCR3 by docking methods, and validated these data by in vitro studies. The results showed that two peptides were able to bind CXCR3 and to mimic the molecular recognition of CXCL11 and demonstrated that N‐terminal region of CXCL11 can be used as template and starting point to obtain new molecules by de novo design approaches.
Two Truths and a Lie: In re John Z. and Other Stories at the Juncture of Teen Sex and the Law
Authors: Oberman Michelle
Published: April 2012

Laws governing adolescent sexuality are incoherent and chaotically enforced, and legal scholarship on the subject neither addresses nor remedies adolescents’ vulnerability in sexual encounters. To posit a meaningful relationship between the criminal law and adolescent sexual encounters, one must examine what we know about adolescent sexuality from both the academic literature and the adults who control the criminal justice response to such interactions. This article presents an in-depth study of
In re John Z., a 2003 rape prosecution involving two seventeen-year-olds. Using this case, I explore the implications of the prosecution by interviewing a variety of experts and analyzing the contemporary literature on sexual norms among youth. I also relate a series of interviews conducted with the major players in the prosecution. Examining this case from a variety of perspectives permits a deeper understanding of how the law regulates adolescent sexual encounters and why it fails.
Linking Global Climate Models to an Integrated Hydrologic Model: Using an Individual Station Downscaling Approach
Authors: Mejia John F. , Huntington Justin , Hatchett Benjamin , Koracin Darko , Niswonger Richard G.
Published: April 2012

This paper implements an individual station‐based downscaled approach based on a quantil–quantile bias correction mapping to further downscale regional gridded simulated output into individual station locations. We describe and propose a framework to optimize the usefulness of this downscaling approach over small watersheds in mountain regions, where downscale gridded data (∼10km) is still too coarse for use in sub‐regional hydrologic simulation studies. Two regional downscaled data sets were downscaled to individual station locations: the Desert Research Institute‐Regional Climate Model based on the Weather Research and Forecasting model (DRI‐RCM; 12 km resolution); and the US Bureau of Reclamation Bias‐Corrected Spatial Disaggregation (BCSD; 12 km resolution). We applied the station‐based downscaled data in the integrated hydrologic model, GSFLOW, as adapted to the Incline Creek watersheds in the northeastern Lake Tahoe basin. Hydrologic model results showed that the proposed downscaled approach provides reasonable downscaled climate data that can be used to evaluate sub‐regional scale hydrologic processes.
Intranational Cooperation and Conflict over Freshwater: Examples from the Western United States
Authors: Eidem Nathan T. , Fesler Kristel J. , Wolf Aaron T.
Published: April 2012

From the Klamath basin in the Pacific Northwest to the Jordan basin in the Middle East, water conflicts can be disruptive, and affect a wide range of stakeholders, often with varying interests. As competition between water users and water use sectors increases, the potential for conflict increases, especially when governing institutions differ (Jarvis et al. 2005). However, research has shown that cooperation is more prevalent than conflict in international river basins (Wolf 1998; Wolf et al. 2003). As the demand for water approaches or meets available supply, intranational conflicts may increase (Postel and Wolf 2001). This paper explores cooperative and conflictive behavior over freshwater at two intranational scales in the western United States. Incidents of cooperation and conflict were collected and coded using a standardized classification system and compiled into event databases. As was found in international river basins, cooperation is more common than conflict in intranational settings.
Parametric Identification of Nonlinear Systems by Haar Wavelets: Theory and Experimental Validation
Authors: Chen Shy-Leh , Liang Jin-Wei , Ho Keng-Chu
Published: April 2012

This study addresses the identification of nonlinear systems. It is assumed that the function form in the nonlinear system is known, leaving some unknown parameters to be estimated. Since Haar wavelets can form a complete orthogonal basis for the appropriate function space, they are used to expand all signals. In doing so, the state equation can be transformed into a set of algebraic equations in unknown parameters. The technique of Kronecker product is utilized to simplify the expressions of the associated algebraic equations. Together with the least square method, the unknown system parameters are estimated. The proposed method is applied to the identification of an experimental two-well chaotic system known as the Moon beam. The identified model is validated by comparing the chaotic characteristics, such as the largest Lyapunov exponent and the correlation dimension, of the experimental data with that of the numerical results. The simple least square approach is also performed for comparison. The results indicate that the proposed method can reliably identify the characteristics of the nonlinear chaotic system.
Solvent-assisted growth of metal phthalocyanine thin films on Au(111)
Authors: Tskipuri Levan , Shao Qian , Reutt-Robey Janice
Published: April 2012

Thin films of metal phthalocyanine (MPc) are grown on an Au(111) support with a newly developed aerosol molecular beam deposition source and characterized in situ via ultrahigh vacuum scanning tunneling microscopy. MPcs are delivered to Au(111) in a series of N2-entrained microsized solvent droplets of variable surface residence time. Phthalocyanine film registration to the herringbone reconstruction of the Au(111) surface, indicative of thermodynamically favored structure, is observed at submonolayer coverages for aromatic solvents with long residence times. Aerosol-deposited monolayer film structures are noncrystalline with tilted MPc orientations and vacancy nanocavities. Upon annealing, MPc molecules adopt flat-lying orientations with respect to the substrate and vacancies are eliminated. Film morphologies indicate solvation-mediated film nucleation and growth, with less long-range ordering that in vapor-generated films.
In Vitro
Activities of the New Antitubercular Agents PA-824 and BTZ043 against Nocardia brasiliensis
Authors: Vera-Cabrera Lucio , Campos-Rivera Mayra Paola , Gonzalez-Martinez Norma Alejandra , Ocampo-Candiani Jorge , Cole Stewart T.
Published: April 2012

The
in vitro
activity of PA-824 and BTZ043 against 30
Nocardia brasiliensis
isolates was tested. The MIC
50
and MIC
90
values for PA-824 were both >64 μg/ml. The same values for BTZ043 were 0.125 and 0.250 μg/ml. Given the MIC values for benzothiazinone (BTZ) compounds, we consider them good candidates to be tested
in vivo
against
N. brasiliensis
.
Isolation and Characterization of Signermycin B, an Antibiotic That Targets the Dimerization Domain of Histidine Kinase WalK
Authors: Watanabe Takafumi , Igarashi Masayuki , Okajima Toshihide , Ishii Eiji , Kino Hirokazu , Hatano Masaki , Sawa Ryuichi , Umekita Maya , Kimura Tomoyuki , Okamoto Sho , Eguchi Yoko , Akamatsu Yuzuru , Utsumi Ryutaro
Published: April 2012

The WalK (histidine kinase)/WalR (response regulator) two-component signal transduction system is a master regulatory system for cell wall metabolism and growth. This system is conserved in low G+C Gram-positive bacteria, including
Bacillus subtilis
,
Staphylococcus aureus
,
Enterococcus faecalis
, and
Streptococcus mutans
. In this study, we found the first antibiotic that functions as a WalK inhibitor (signermycin B) by screening 10,000
Streptomyces
extracts. The chemical structure (C
23
H
35
NO
4
; molecular weight, 389.5) comprises a tetramic acid moiety and a decalin ring. Signermycin B exhibited antimicrobial activity, with MIC values ranging from 3.13 μg/ml (8 μM) to 6.25 μg/ml (16 μM) against Gram-positive bacteria that possess the WalK/WalR two-component signal transduction system, including the drug-resistant bacteria methicillin-resistant
Staphylococcus aureus
and vancomycin-resistant
Enterococcus faecalis
. The half-maximal inhibitory concentrations of signermycin B against WalK in these organisms ranged from 37 to 61 μM. To determine the mechanism of action of signermycin B, surface plasmon resonance response analysis with the two WalK domains of
Bacillus subtilis
and competition assay with ATP were performed. The results showed that signermycin B binds to the dimerization domain but not the ATP-binding domain of WalK. In the presence of the cross-linker glutaraldehyde, signermycin B did not cause protein aggregation but interfered with the cross-linking of WalK dimers. These results suggest that signermycin B targets the conserved dimerization domain of WalK to inhibit autophosphorylation. In
Bacillus subtilis
and
Staphylococcus aureus
, signermycin B preferentially controlled the WalR regulon, thereby inhibiting cell division. These phenotypes are consistent with those of cells starved for the WalK/WalR system.
Etravirine Concentrations in the Cervicovaginal Compartment in HIV-1-Infected Women Receiving Etravirine-Containing Antiretroviral Therapy: DIVA 02 Study
Authors: Clavel C. , Peytavin G. , Tubiana R. , Soulié C. , Courbon E. , Crenn-Hebert C. , Ichou H. , Blanc C. , Schneider L. , Katlama C. , Marcelin A.-G. , Mandelbrot L.
Published: April 2012

We studied the penetration of etravirine and HIV shedding in the genital tract among 12 HIV-1-infected women receiving an etravirine-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median etravirine concentrations were 663 ng/ml in BP and 857 ng/ml in CVF, with a CVF/BP etravirine ratio of approximately 1.2. This good penetration of etravirine may contribute to the control of viral replication in the female genital tract.
Complete Genome Sequence of Canine Papillomavirus Type 9
Authors: Yuan Hang , Luff Jennifer , Zhou Dan , Wang Jingang , Affolter Verena , Moore Peter , Schlegel Richard
Published: April 2012

Papillomaviruses are nonenveloped, double-stranded DNA viruses that are associated with both benign and malignant tumors in animals and humans. We report the complete genome sequence of canine papillomavirus type 9 isolated from a solitary pigmented plaque on a mixed-breed bloodhound.
A PARAMETRICALLY FORCED NONLINEAR SYSTEM WITH REVERSIBLE EQUILIBRIA
Authors: WIEBE R. , VIRGIN L. N. , WITELSKI T. P.
Published: April 2012

A nonlinear Duffing-type dynamical system, in which the stability of equilibria is modulated in a time-dependent manner, is investigated both experimentally and numerically. This is a low-order dynamical system with some interesting available choices in the coordinate system. The system is found to exhibit a variety of interesting nonlinear behavior including ultrasubharmonic resonance. Frequency content is used to characterize periodic and chaotic behavior and their relation to the parameter space.
BIFURCATION OF QUASI-PERIODIC OSCILLATIONS IN MUTUALLY COUPLED HARD-TYPE OSCILLATORS: DEMONSTRATION OF UNSTABLE QUASI-PERIODIC ORBITS
Authors: KAMIYAMA KYOHEI , KOMURO MOTOMASA , ENDO TETSURO
Published: April 2012

In this paper, we obtain bifurcations of quasi-periodic orbits occuring in mutually coupled hard-type oscillators by using our recently developed computer algorithm to directly determine the unstable quasi-periodic orbits. So far, there is no computer algorithm to draw unstable invariant closed curves on a Poincare map representing quasi-periodic orbits. Recently, we developed a new algorithm to draw unstable invariant closed curves by using the bisection method. The results of this new algorithm are compared with the previously obtained averaging method results. Several new results are found, which could not be clarified by the averaging method.
DYNAMICS OF A DRIVEN OSCILLATOR CARRYING A FREELY SLIDING MASS
Authors: TÖBBENS ALEXANDER , METTIN ROBERT , PARLITZ ULRICH
Published: April 2012

A mathematical model for a nonlinear oscillator, which is composed of an oscillating mass interacting with a freely sliding friction damper, is introduced and investigated. This oscillator is a strongly simplified model for a damping principle applied to turbine blades to suppress oscillations induced by inhomogeneous flow fields. It exhibits periodic, quasi-periodic, as well as chaotic dynamics occuring suddenly due to adding sliding bifurcations. Mathematically, the oscillator is given as a piecewise smooth (Filippov) system with a switching manifold corresponding to the sticking phase of the damper mass. The rich dynamics of this system is analyzed and illustrated by means of resonance curves, Lyapunov diagrams, Poincaré sections and reductions to iterated one-dimensional maps.
APPLICATIONS OF SYMBOLIC DYNAMICS ON AN INFINITE ALPHABET
Authors: JOHNSON CHRISTOPHER
Published: April 2012

Symbolic dynamics are often used to study the behavior of other dynamical systems. This paper describes the dynamics of some interesting examples of one-dimensional dynamical systems using symbolic dynamics on an infinite alphabet.
DIRECT HAMILTONIZATION — GENERALIZATION OF AN ALTERNATIVE HAMILTONIZATION
Authors: ESPINDOLA MARIA LEWTCHUK
Published: April 2012

A new procedure named direct Hamiltonization presents an alternative foundation to Analytical Mechanics, since in this formalism the Hamiltonian function can be obtained for all mechanical systems. The principal change proposed in this procedure is that the conjugate momenta cannot be defined a priori, but are established as a consequence of a canonical description of the mechanical system. The direct Hamiltonization is a generalization of the alternative one, where the usual Hamiltonization and momenta are recovered whenever they exist. Also this procedure assures the existence of a Hamiltonian function without any constraints for any mechanical system, therefore the usual quantization is always allowed. This procedure can be applied to non-Lagrangian, Nambu, nonholonomic and dynamical systems since there are no restrictions in this formalism as, for example, the number of equations of motion.
CONTROLLABLE V-SHAPE MULTISCROLL BUTTERFLY ATTRACTOR: SYSTEM AND CIRCUIT IMPLEMENTATION
Authors: ZIDAN M. AFFAN , RADWAN A. G. , SALAMA K. N.
Published: April 2012

In this paper, a new controllable V-shape multiscroll attractor is presented, where a variety of symmetrical and unsymmetrical attractors with a variable number of scrolls can be controlled using new staircase nonlinear function and the parameters of the system. This attractor can be used to generate random signals with a variety of symbol distribution. Digital implementation of the proposed generator is also presented using a Xilinx Virtex® 4 Field Programmable Gate Array and experimental results are provided. The digital realization easily fits into a small area (<1.5% of the total area) and expresses a high throughput (4.3 Gbit/sec per state variable).
ENERGY β-CONFORMAL CHANGE IN FINSLER GEOMETRY
Authors: SOLEIMAN A.
Published: April 2012

The present paper deals with an intrinsic generalization of the conformal change and energy β-change on a Finsler manifold (M.L.), namely the energy β-conformal change ([Formula: see text] with [Formula: see text]; [Formula: see text] being a concurrent π-vector field and σ(x) is a function on M). The relation between the two Barthel connections Γ and [Formula: see text], corresponding to this change, is found. This relation, together with the fact that the Cartan and the Barthel connections have the same horizontal and vertical projectors, enable us to study the energy β-conformal change of the fundamental linear connection in Finsler geometry: the Cartan connection, the Berwald connection, the Chern connection and the Hashiguchi connection. Moreover, the change of their curvature tensors is obtained.

It should be pointed out that the present work is formulated in a prospective modern coordinate-free form.
A GEOMETRIC STUDY OF SOME EQUATIONS OF MATHEMATICAL PHYSICS
Authors: PITEA ARIANA
Published: April 2012

We introduce geometric structures (connections, pseudo-Riemannian metrics) adapted to some fundamental problems of Differential Geometry, and find geometrical characteristics associated to equations of Mathematical Physics. Also, we introduce a geometric study of some boundary problems. Throughout this work, as main tool we employed an adequate Riemannian Hessian structure, suggested in [Int. J. Geom. Meth. Mod. Phys.7(7) (2010) 1104–1113].
COHOMOLOGY OF 𝔬𝔰𝔭(1|2) ACTING ON THE SPACE OF BILINEAR DIFFERENTIAL OPERATORS ON THE SUPERSPACE ℝ1|1
Authors: BEN AMMAR MABROUK , JABEUR AMINA , SAFI IMEN
Published: April 2012

We compute the first cohomology of the ortosymplectic Lie superalgebra 𝔬𝔰𝔭(1|2) on the (1, 1)-dimensional real superspace with coefficients in the superspace 𝔇λ, μ of bilinear differential operators acting on weighted densities (λ ∈ ℝ2 and μ ∈ ℝ). This work is the simplest superization of a result by Bouarroudj [Cohomology of the vector fields Lie algebras on ℝℙ1 acting on bilinear differential operators, Int. J. Geom. Meth. Mod. Phys.2(1) (2005) 23–40].
AN APPROXIMATE SOLUTION OF THE JAYNES–CUMMINGS MODEL WITH DISSIPATION II: ANOTHER APPROACH
Authors: FUJII KAZUYUKI , SUZUKI TATSUO
Published: April 2012

In the preceding paper (arXiv: 1103.0329 [quant-ph]) we treated the Jaynes–Cummings model with dissipation and gave an approximate solution to the master equation for the density operator under the general setting by making use of the Zassenhaus expansion.

However, to obtain a compact form of the approximate solution (which is in general complicated infinite series) is very hard when an initial condition is given. To overcome this difficulty we develop another approach and obtain a compact approximate solution when some initial condition is given.
HIERARCHY OF CERTAIN TYPES OF DNA SPLICING SYSTEMS
Authors: YUSOF YUHANI , SARMIN NOR HANIZA , GOODE T. ELIZABETH , MAHMUD MAZRI , HENG FONG WAN
Published: April 2012

A Head splicing system (H-system)consists of a finite set of strings (words) written over a finite alphabet, along with a finite set of rules that acts on the strings by iterated cutting and pasting to create a splicing language. Any interpretation that is aligned with Tom Head's original idea is one in which the strings represent double-stranded deoxyribonucleic acid (dsDNA) and the rules represent the cutting and pasting action of restriction enzymes and ligase, respectively. A new way of writing the rule sets is adopted so as to make the biological interpretation transparent. This approach is used in a formal language- theoretic analysis of the hierarchy of certain classes of splicing systems, namely simple, semi-simple and semi-null splicing systems. The relations between such systems and their associated languages are given as theorems, corollaries and counterexamples.
On approximating multicriteria TSP
Authors: Manthey Bodo
Published: April 2012

We present approximation algorithms for almost all variants of the multicriteria traveling salesman problem (TSP).

First, we devise randomized approximation algorithms for multicriteria maximum traveling salesman problems (Max-TSP). For multicriteria Max-STSP where the edge weights have to be symmetric, we devise an algorithm with an approximation ratio of 2/3 - ε. For multicriteria Max-ATSP where the edge weights may be asymmetric, we present an algorithm with a ratio of 1/2 - ε. Our algorithms work for any fixed number
k
of objectives. Furthermore, we present a deterministic algorithm for bicriteria Max-STSP that achieves an approximation ratio of 7/27.

Finally, we present a randomized approximation algorithm for the asymmetric multicriteria minimum TSP with triangle inequality (Min-ATSP). This algorithm achieves a ratio of log
n
+ ε.
Complexity of Data Dependence Problems for Program Schemas with Concurrency
Authors: Danicic Sebastian , Hierons Robert M. , Laurence Michael R.
Published: April 2012

The problem of deciding whether one point in a program is data dependent upon another is fundamental to program analysis and has been widely studied. In this article we consider this problem at the abstraction level of
program schemas
in which computations occur in the Herbrand domain of terms and predicate symbols, which represent arbitrary predicate functions, are allowed. Given a vertex
l
in the flowchart of a schema
S
having only equality (variable copying) assignments, and variables
v
,
w
, we show that it is PSPACE-hard to decide whether there exists an execution of a program defined by
S
in which
v
holds the initial value of
w
at at least one occurrence of
l
on the path of execution, with membership in PSPACE holding provided there is a constant upper bound on the arity of any predicate in
S
. We also consider the ‘dual’ problem in which
v
is required to hold the initial value of
w
at every occurrence of
l
, for which the analogous results hold. Additionally, the former problem for programs with nondeterministic branching (in effect, free schemas) in which assignments with functions are allowed is proved to be polynomial-time decidable provided a constant upper bound is placed upon the number of occurrences of the concurrency operator in the schemas being considered. This result is promising since many concurrent systems have a relatively small number of threads (concurrent processes), especially when compared with the number of statements they have.
An Implicit Characterization of PSPACE
Authors: Gaboardi Marco , Marion Jean-Yves , Ronchi Della Rocca Simona
Published: April 2012

We present a type system for an extension of lambda calculus with a conditional construction, named STA
B
, that characterizes the PSPACE class. This system is obtained by extending STA, a type assignment for lambda-calculus inspired by Lafont’s Soft Linear Logic and characterizing the PTIME class. We extend STA by means of a ground type and terms for Booleans and conditional. The key issue in the design of the type system is to manage the contexts in the rule for conditional in an additive way. Thanks to this rule, we are able to program polynomial time Alternating Turing Machines. From the well-known result APTIME = PSPACE, it follows that STA
B
is complete for PSPACE.

Conversely, inspired by the simulation of Alternating Turing machines by means of Deterministic Turing machine, we introduce a call-by-name evaluation machine with two memory devices in order to evaluate programs in polynomial space. As far as we know, this is the first characterization of PSPACE that is based on lambda calculus and light logics.
A Yield and Reliability Improvement Methodology Based on Logic Redundant Repair with a Repairable Scan Flip-Flop Designed by Push Rule
Authors: Kurimoto Masanori , Matsushima Jun , Ohbayashi Shigeki , Fukui Yoshiaki , Komoda Michio , Tsuda Nobuhiro
Published: April 2012

We propose a yield improvement methodology which repairs a faulty chip due to logic defect by using a repairable scan flip-flop (R-SFF). Our methodology improves area penalty, which is a large issue for logic repair technology in actual products, by using repair grouping and a redundant cell insertion algorithm and by pushing the design rule for the repairable area of R-SFF. Additionally, compared with the conventional method, we reduce the number of wire connections around redundant cells by improving the replacement method of the faulty cell by the redundant cell. The proposed methodology reduces the total area penalty caused by the logic redundant repair to 3.6% and improves the yield, that is the number of good chips on a wafer, by 4.7% when the defect density is 1.0[1/cm^2]. Furthermore, we propose the strategy to repair the in-field failures due to latent defect for the chip whose repair function had not been used in the shipment test.
Digitally possessed
Authors: Greengard Samuel
Published: April 2012

Virtual possessions play an increasingly important role in our daily lives. How we think about them and deal with them is changing the way we think and interact with others.
The future of the past
Authors: Anderson David
Published: April 2012

Reflections on the changing face of the history of computing.
Managing technical debt
Authors: Allman Eric
Published: April 2012

Shortcuts that save money and time today can cost you down the road.
A massively parallel adaptive fast multipole method on heterogeneous architectures
Authors: Lashuk Ilya , Chandramowlishwaran Aparna , Langston Harper , Nguyen Tuan-Anh , Sampath Rahul , Shringarpure Aashay , Vuduc Richard , Ying Lexing , Zorin Denis , Biros George
Published: April 2012

We describe a parallel fast multipole method (FMM) for highly nonuniform distributions of particles. We employ both distributed memory parallelism (via MPI) and shared memory parallelism (via OpenMP and GPU acceleration) to rapidly evaluate two-body nonoscillatory potentials in three dimensions on heterogeneous high performance computing architectures. We have performed scalability tests with up to 30 billion particles on 196,608 cores on the AMD/CRAY-based Jaguar system at ORNL. On a GPU-enabled system (NSF's Keeneland at Georgia Tech/ORNL), we observed 30× speedup over a single core CPU and 7× speedup over a multicore CPU implementation. By combining GPUs with MPI, we achieve less than 10 ns/particle and six digits of accuracy for a run with 48 million nonuniformly distributed particles on 192 GPUs.