bluuebunny/crossref_metadata_2025 huggingface dataset:
Subduction and exhumation mechanisms of ultra‐high and high‐pressure oceanic and continental crust at Makbal (Tianshan, Kazakhstan and Kyrgyzstan)
Authors: Meyer M. , Klemd R. , Hegner E. , Konopelko D.
Published: June 2014

The Makbal Complex in the northern Tianshan of Kazakhstan and Kyrgyzstan consists of metasedimentary rocks, which host high‐P (HP) mafic blocks and ultra‐HP Grt‐Cld‐Tlc schists (UHP as indicated by coesite relicts in garnet). Whole rock major and trace element signatures of the Grt‐Cld‐Tlc schist suggest a metasomatized protolith from either hydrothermally altered oceanic crust in a back‐arc basin or arc‐related volcaniclastics. Peak metamorphic conditions of the Grt‐Cld‐Tlc schist reached ~580 °C and 2.85 GPa corresponding to a maximum burial depth of ~95 km. A Sm‐Nd garnet age of 475 ± 4 Ma is interpreted as an average growth age of garnet during prograde‐to‐peak metamorphism; the low initial εΝd value of −11 indicates a protolith with an ancient crustal component. The petrological evidence for deep subduction of oceanic crust poses questions with respect to an effective exhumation mechanism. Field relationships and the metamorphic evolution of other HP mafic oceanic rocks embedded in continentally derived metasedimentary rocks at the central Makbal Complex suggest that fragments of oceanic crust and clastic sedimentary rocks were exhumed from different depths in a subduction channel during ongoing subduction and are now exposed as a tectonic mélange. Furthermore, channel flow cannot only explain a tectonic mélange consisting of various rock types with different subduction histories as present at the central Makbal Complex, but also the presence of a structural ‘dome’ with UHP rocks in the core (central Makbal) surrounded by lower pressure nappes (including mafic dykes in continental crust) and voluminous metasedimentary rocks, mainly derived from the accretionary wedge.
Synthesis and characterization of Ag–Co–Ni nanowires
Authors: RAI R.K. , SINGH M. PRATAP , SRIVASTAVA C.
Published: June 2014

This work provides an electrodeposition‐based methodology for synthesizing multicomponent nanowires containing Ag, Co and Ni atoms. Nanowire morphology was obtained by using an anodic alumina membrane with cylindrical pores of ∼200‐nm diameter. Structural, compositional and magnetic characterization revealed that the as‐synthesized nanowires adopted a core–shell microstructure. The core (axial region) contained pure Ag phase volumes with a plate‐like morphology oriented perpendicular to the nanowire axis. The shell (peripheral region) contained pure Ag nanoparticles along with superparamagnetic Co and Ni rich clusters.
In Vitro Wear Behavior of Zirconia Opposing Enamel: A Systematic Review
Authors: Passos Sheila Pestana , Torrealba Ysidora , Major Paul , Linke Bernie , Flores‐Mir Carlos , Nychka John A.
Published: June 2014

Purpose

The aim of this systematic review was to assess enamel wear on teeth opposing zirconia restorations and to evaluate factors related to the wear of natural teeth opposing zirconia restorations.

Materials and Methods

Five electronic databases were searched through May 2013 without limitations. The terms “antagonist*,” “enamel,” “wear,” and “zirconi*” were used. Titles and abstracts were initially screened, and those that fulfilled the inclusion criteria were selected for a full‐text assessment. Studies that evaluated only the material wear were not included.

Results

The database search strategy retrieved 142 potentially eligible studies. After the duplicate studies were removed, 62 studies were obtained. Titles and abstracts that fulfilled the inclusion criteria were selected for a full‐text assessment (25). Seven laboratory studies met the inclusion criteria. In addition, reference lists from the finally selected studies were also screened.

Conclusions

There was a large variation in relation to wear test method quantification, applied force, lateral movement, number and frequency of cycles, number of specimens, and enamel specimen preparation. In all studies, enamel wear rates were lower against polished zirconia. Differences in the test methods did not allow for comparisons of wear rates among the studies. Clinical Significance: Polishing the surface is recommended for a full‐contour zirconia restoration because polished zirconia presents favorable wear behavior opposing natural teeth.
Detection, Identification and Phylogenetic Analysis of Indian Ralstonia solanacearum Isolates by Comparison of Partial hrpB Gene Sequences
Authors: Chandrasekhar Bhadvelu , Umesha Sharanaiah
Published: June 2014

A species‐specific Polymerase Chain Reaction (sPCR) method was developed to identify and detect isolates of Ralstonia solanacearum, the cause of bacterial wilt disease in chilli. PCR primers for R. solanacearum were identified by alignment of hrpB gene sequences and selection of sequences specific for R. solanacearum at their 3′ ends. The primers were shown to be specific for R. solanacearum, as no PCR product was obtained when genomic DNA from other bacterial species including closely related Ralstonia species, were used as test species. Lone pair of primers (RshrpBF and RshrpBR) was designed using hrpB gene sequence, unique to R. solanacearum which amplified a predicted PCR product of 810 bp from 20 different isolates. Phylogenetic analysis was also attempted to understand the evolutionary divergence of Indian R. solanacearum isolates. Based on phylogenetic analysis, Indian isolates showed homology with the standard reference isolates from other countries but, interestingly, one new isolate showed complete evolutionary divergence by forming an out‐group.
The cysteine2/histidine2‐type transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 6‐activated C‐REPEAT‐BINDING FACTOR pathway is essential for melatonin‐mediated freezing stress resistance in Arabidopsis
Authors: Shi Haitao , Chan Zhulong
Published: June 2014

Melatonin (N‐acetyl‐5‐methoxytryptamine) is not only a widely known animal hormone, but also an important regulator in plant development and multiple abiotic stress responses. Recently, it has been revealed that melatonin alleviated cold stress through mediating several cold‐related genes, including C‐REPEAT‐BINDING FACTORs (CBFs)/Drought Response Element Binding factors (DREBs), COR15a, and three transcription factors (CAMTA1, ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10), and ZAT12). In this study, we quantified the endogenous melatonin level in Arabidopsis plant leaves and found the endogenous melatonin levels were significantly induced by cold stress (4°C) treatment. In addition, we found one cysteine2/histidine2‐type zinc finger transcription factor, ZAT6, was involved in melatonin‐mediated freezing stress response in Arabidopsis. Interestingly, exogenous melatonin enhanced freezing stress resistance was largely alleviated in AtZAT6 knockdown plants, but was enhanced in AtZAT6 overexpressing plants. Moreover, the expression levels of AtZAT6 and AtCBFs were commonly upregulated by cold stress (4°C) and exogenous melatonin treatments, and modulation of AtZAT6 expression significantly affected the induction AtCBFs transcripts by cold stress (4°C) and exogenous melatonin treatments. Taken together, AtZAT6‐activated CBF pathway might be essential for melatonin‐mediated freezing stress response in Arabidopsis.
Effects of probiotic Enterococcus faecium and Saccharomyces cerevisiae on the faecal microflora of pet rabbits
Authors: Benato L. , Hastie P. , O'Shaughnessy P. , Murray J.‐A. , Meredith A.
Published: June 2014

OBJECTIVES

Probiotics are frequently used in the treatment of gastrointestinal diseases in pet rabbits based largely on anecdotal evidence of a beneficial effect. However, there has been little work performed to assess any such benefit in health or disease. The aim of this study was to determine the effect of probiotics on faecal levels of four important candidate gastrointestinal bacteria (Bacteroides species, Enterococcus faecium, Fibrobacter succinogenes and Clostridium spiroforme) in pet rabbits. Additional aims were to evaluate the effect of probiotics on bodyweight and faecal weight and diameter.

MATERIALS AND METHODS

Double‐blind triple cross‐over study in six healthy rabbits orally administered two probiotic strains, Saccharomyces cerevisiae NCYC Sc47 and E. faecium NCIMB 30183. Levels of bacteria in faecal pellets were subsequently determined by real‐time quantitative polymerase chain reaction.

RESULTS

Oral administration of probiotic E. faecium NCIMB 30183 was associated with a significant (P = 0 · 042) increase in faecal levels of E. faecium. However, probiotic treatment did not affect faecal levels of Bacteroides species, F. succinogenes or C. spiroforme, bodyweight, or faecal weight and diameter.

CLINICAL SIGNIFICANCE

The inclusion of dietary probiotic supplementation using E. faecium NCIMB 30183 can increase faecal levels of certain bacterial flora of healthy adult rabbits. Further work is required to investigate the effects of probiotics in animals affected with gastrointestinal disease.
Use of Contrast‐Enhanced Fluid‐Attenuated Inversion Recovery Sequence to Detect Brain Lesions in Dogs and Cats
Authors: Merhof K. , Lang J. , Dürr S. , Stahl C. , Gorgas D.
Published: June 2014

Background

The diagnostic value of a contrast‐enhanced T2‐weighted FLAIR sequence (ceFLAIR) in brain imaging is unclear.

Hypothesis/Objectives

That the number of brain lesions detected with ceFLAIR would be no greater than the sum of lesions detected with nFLAIR and ceT1W sequence.

Animals

One hundred and twenty‐nine animals (108 dogs and 21 cats) undergoing magnetic resonance imaging (MRI) of the head between July 2010 and October 2011 were included in the study.

Methods

A transverse ceFLAIR was added to a standard brain MRI protocol. Presence and number of lesions were determined based on all available MRI sequences by 3 examiners in consensus and lesion visibility was evaluated for nFLAIR, ceFLAIR, and ceT1W sequences.

Results

Eighty‐three lesions (58 intra‐axial and 25 extra‐axial) were identified in 51 patients. Five lesions were detected with nFLAIR alone, 2 with ceT1W alone, and 1 with ceFLAIR alone. Significantly higher numbers of lesions were detected using ceFLAIR than nFLAIR (76 versus 67 lesions; P = 0.04), in particular for lesions also detected with ceT1W images (53 versus 40; P =.01). There was no significant difference between the number of lesions detected with combined nFLAIR and ceT1W sequences compared to those detected with ceFLAIR (82 versus 76; P =.25).

Conclusion and Clinical Importance

Use of ceFLAIR as a complementary sequence to nFLAIR and ceT1W sequences did not improve the detection of brain lesions and cannot be recommended as part of a routine brain MRI protocol in dogs and cats with suspected brain lesions.
Application of Lactobacillus johnsonii expressing phage endolysin for control of Clostridium perfringens
Authors: Gervasi T. , Lo Curto R. , Minniti E. , Narbad A. , Mayer M.J.
Published: June 2014

Clostridium perfringens is frequently found in food and the environment and produces potent toxins that have a negative impact on both human and animal health and particularly on the poultry industry. Lactobacillus johnsonii FI9785, isolated from the chicken gastrointestinal tract, has been demonstrated to exclude Cl. perfringens in poultry. We have investigated the interaction of wild-type Lact. johnsonii FI9785 or an engineered strain expressing a cell wall-hydrolysing endolysin with Cl. perfringens in vitro, using a batch culture designed to simulate human gastrointestinal tract conditions. Co-culture experiments indicated that acid production by Lact. johnsonii is important in pathogen control. The co-culture of the endolysin-secreting Lact. johnsonii with Cl. perfringens showed that the engineered strain had the potential to control the pathogen, but the ability to reduce Cl. perfringens numbers was not consistent. Results obtained indicate that survival of high numbers of Lact. johnsonii will be essential for effective pathogen control.

Significance and Impact of the Study

The bacterium Lactobacillus johnsonii FI9785 reduces numbers of the pathogen Clostridium perfringens in vitro. Biocontrol was improved by engineering the strain to produce and export a cell wall-hydrolysing endolysin, but good survival of the producer strain is essential. The production of bacteriophage endolysins by commensal bacteria has the potential to improve competitive exclusion of pathogens in the gastrointestinal tract.
Phylogeography of Heliconius cydno and its closest relatives: disentangling their origin and diversification
Authors: Arias Carlos F. , Salazar Camilo , Rosales Claudia , Kronforst Marcus R. , Linares Mauricio , Bermingham Eldredge , McMillan W. Owen
Published: June 2014

The origins of the extraordinary diversity within the Neotropics have long fascinated biologists and naturalists. Yet, the underlying factors that have given rise to this diversity remain controversial. To test the relative importance of Quaternary climatic change and Neogene tectonic and paleogeographic reorganizations in the generation of biodiversity, we examine intraspecific variation across the Heliconius cydno radiation and compare this variation to that within the closely related Heliconius melpomene and Heliconius timareta radiations. Our data, which consist of both mtDNA and genome‐scan data from nearly 2250 amplified fragment length polymorphism (AFLP) loci, reveal a complex history of differentiation and admixture at different geographic scales. Both mtDNA and AFLP phylogenies suggest that H. timareta and H. cydno are probably geographic extremes of the same radiation that probably diverged from H. melpomene prior to the Pliocene–Pleistocene boundary, consistent with hypotheses of diversification that rely on geological events in the Pliocene. The mtDNA suggests that this radiation originated in Central America or the northwestern region of South America, with a subsequent colonization of the eastern and western slopes of the Andes. Our genome‐scan data indicate significant admixture among sympatric H. cydno/H. timareta and H. melpomene populations across the extensive geographic ranges of the two radiations. Within H. cydno, both mtDNA and AFLP data indicate significant population structure at local scales, with strong genetic differences even among adjacent H. cydno colour pattern races. These genetic patterns highlight the importance of past geoclimatic events, intraspecific gene flow, and local population differentiation in the origin and establishment of new adaptive forms.
Novel therapeutic agents in neurogastroenterology: advances in the past year
Authors: Camilleri M.
Published: June 2014

Background

There have been significant advances in understanding the pathophysiological mechanisms in patients with neurogastroenterological disorders including irritable bowel syndrome (IBS) and functional abdominal pain, functional diarrhea, chronic constipation, gastroparesis, and functional dyspepsia. These advances have led to the development of novel pharmacological therapy of neurogastroenterological disorders.

Purpose

To review peer‐reviewed articles or prominent preliminary communications presented in the past year regarding medications in development for functional gastrointestinal disorders or gastroparesis. The medications fall into two main categories: first, established classes of medications within established classes, such as 5‐HT3 receptor antagonists and 5‐HT4 receptor agonists, and second, new classes of medications such as a combined μ‐opioid agonist and δ‐antagonist, or a small molecule ghrelin agonist.
Function and regulation of primary cilia and intraflagellar transport proteins in the skeleton
Authors: Yuan Xue , Serra Rosa A. , Yang Shuying
Published: June 2014

Primary cilia are microtubule‐based organelles that project from the cell surface to enable transduction of various developmental signaling pathways. The process of intraflagellar transport (IFT) is crucial for the building and maintenance of primary cilia. Ciliary dysfunction has been found in a range of disorders called ciliopathies, some of which display severe skeletal dysplasias. In recent years, interest has grown in uncovering the function of primary cilia/IFT proteins in bone development, mechanotransduction, and cellular regulation. We summarize recent advances in understanding the function of cilia and IFT proteins in the regulation of cell differentiation in osteoblasts, osteocytes, chondrocytes, and mesenchymal stem cells (MSCs). We also discuss the mechanosensory function of cilia and IFT proteins in bone cells, cilia orientation, and other functions of cilia in chondrocytes.
Review of the cost components of introducing industrially fortified rice
Authors: Roks Eveline
Published: June 2014

Micronutrient deficiencies affect over two billion people worldwide, particularly in developing countries. Fortification of staple foods with multiple micronutrients is a cost‐effective strategy to increase vitamin and mineral intake. The objective of this paper is to review the cost elements of industrially fortified rice by identifying the costs related to the implementation of rice fortification programs, using the experience of the United Nations World Food Programme in its pilot countries. The actual total costs of rice fortification are not easily captured. Core cost elements include the production of fortified rice kernels, transportation to the point of blending, blending of fortified with unfortified rice, costs related to sales or distribution, quality control and assurance, and additional planning. In the introduction phase, organizations or coalitions seeking to advance rice fortification will face additional costs related to the initiation of rice fortification. In the scale‐up phase, greater efficiency in the supply chain and economies of scale can be expected. Different cost elements are normally borne by different stakeholders. This makes the implementation of rice fortification programs a feasible option to reach vulnerable populations with inadequate access to affordable nutrition solutions.
Positive‐pressure ventilation during transport: a randomized crossover study of self‐inflating and flow‐inflating resuscitators in a simulation model
Authors: Lucy Malcolm J. , Gamble Jonathan J. , Daku Brian L. , Bryce Rhonda D. , Rana Masud
Published: June 2014

Background

Positive‐pressure ventilation during transport of intubated patients is generally delivered via a hand‐pressurized device. Of these devices, self‐inflating resuscitators (SIR) and flow‐inflating resuscitators (FIR) constitute the two major types used. Selection of a particular device for transport, however, remains largely an institutional practice.

Objective

To evaluate the hypothesis that transport ventilation goals of intubated pediatric patients are better achieved using an FIR compared to an SIR.

Methods

This randomized crossover simulation study compared the performance of SIR and FIR among anesthesia providers in a pediatric transport scenario. Subjects hand‐ventilated a test lung while simultaneously maneuvering a stretcher bed to simulate patient transport. Hand ventilation was carried out using a Jackson–Rees circuit (FIR) and a Laerdal pediatric silicone resuscitator (SIR). The primary outcome was the proportion of total breaths delivered within the predefined target PIP/PEEP range (30+/− 3, 10+/− 3 cm H2O). Secondary outcomes included proportion of total breaths delivered with operationally defined unacceptable breath variables (PIP > 35 cm H2O or PEEP < 5 cm H2O).

Results

Overall, participants were four times more likely to deliver target breaths and one‐third less likely to deliver unacceptable breaths using the FIR compared to the SIR. When comparing device performance, a 44% increase in the proportions of target breaths and a 40.4% decrease in unacceptable breaths using the FIR were observed (P < 0.0001 for both).

Conclusions

Hand ventilation during patient transport is superior using the FIR compared to the SIR to achieve target ventilatory goals and avoid unacceptable ventilatory cycles.
Treatment planning: A key milestone to prevent treatment dropout in adolescents with borderline personality disorder
Authors: Desrosiers Lyne , Saint‐Jean Micheline , Breton Jean‐Jacques
Published: June 2014

Objective

The aim of this study was to gain a broader appreciation of processes involved in treatment dropout in adolescents with borderline personality disorder (BPD).

Design

A constructivist grounded theory was chosen using a multiple‐case research design with three embedded levels of analysis (adolescent, parent, and care setting).

Method

Theoretical sampling and the different stages of analysis specific to grounded theory were performed according to the iterative process of constant comparative analysis. Twelve cases were examined (nine dropouts among adolescents with BPD and for the purpose of falsification, one dropout of suicidal adolescent without BPD and two completed treatments among adolescents with BPD). To document the cases, three groups of informants were recruited (adolescents, parents, and therapists involved in the treatment) and 34 interviews were conducted.

Results

Psychological characteristics, perception of mental illness and mental health care, and help‐seeking context were the specific treatment dropout vulnerabilities identified in adolescents with BPD and in their parents. However, their disengagement became an issue only when care‐setting response – including mitigation of accessibility problems, adaptation of services to needs of adolescents with BPD, preparation for treatment, and concern for clinicians' disposition to treat – was ill‐suited to these treatment dropout vulnerabilities. Treatment planning proves to be a key milestone to properly engage adolescents with BPD and their parent.

Conclusions

Systematic assessment of treatment dropout vulnerabilities before the intervention plan is laid out could foster better‐suited responses of the care setting thus decreasing the incidence of treatment discontinuation in adolescents with BPD.

Practitioner points

Treatment dropout vulnerabilities specific to adolescents with BPD and their parents can be detected before the beginning of treatment.

Premature treatment termination may be prevented if the care setting considers these vulnerabilities at treatment planning.

Fears and negative reaction to treatment can be attenuated if the reasons behind the therapeutic orientation are explained and if the adolescent understand how the treatment will affect his condition.

Concerns for autonomy of the adolescent, parental help‐seeking context as well as ensuring that the clinician has the skills, interest, and motivation to work with the family may have a positive effect on families' commitment to treatment.
A multilevel analysis of fruit growth of two tomato cultivars in response to fruit temperature
Authors: Okello Robert C. O. , de Visser Pieter H. B. , Heuvelink Ep , Lammers Michiel , de Maagd Ruud A. , Struik Paul C. , Marcelis Leo F. M.
Published: June 2014

Fruit phenotype is a resultant of inherent genetic potential in interaction with impact of environment experienced during crop and fruit growth. The aim of this study was to analyze the genetic and physiological basis for the difference in fruit size between a small (‘Brioso’) and intermediate (‘Cappricia’) sized tomato cultivar exposed to different fruit temperatures. It was hypothesized that fruit heating enhances expression of cell cycle and expansion genes, rates of carbon import, cell division and expansion, and shortens growth duration, whereas increase in cell number intensifies competition for assimilates among cells. Unlike previous studies in which whole‐plant and fruit responses cannot be separated, we investigated the temperature response by varying fruit temperature using climate‐controlled cuvettes, while keeping plant temperature the same. Fruit phenotype was assessed at different levels of aggregation (whole fruit, cell and gene) between anthesis and breaker stage. We showed that: (1) final fruit fresh weight was larger in ‘Cappricia’ owing to more and larger pericarp cells, (2) heated fruits were smaller because their mesocarp cells were smaller than those of control fruits and (3) no significant differences in pericarp carbohydrate concentration were detected between heated and control fruits nor between cultivars at breaker stage. At the gene level, expression of cell division promoters (CDKB2, CycA1 and E2Fe‐like) was higher while that of the inhibitory fw2.2 was lower in ‘Cappricia’. Fruit heating increased expression of fw2.2 and three cell division promoters (CDKB1, CDKB2 and CycA1). Expression of cell expansion genes did not corroborate cell size observations.
Stop and revive? The effectiveness of nap and active rest breaks for reducing driver sleepiness
Authors: Watling Christopher N. , Smith Simon S. , Horswill Mark S.
Published: June 2014

The purpose of this study was to compare the effects of two commonly utilized sleepiness countermeasures: a nap break and an active rest break. The effects of the countermeasures were evaluated by physiological (EEG), subjective, and driving performance measures. Participants completed 2 h of simulated driving, followed by a 15‐min nap break or a 15‐min active rest break, then completed the final hour of simulated driving. The nap break reduced EEG and subjective sleepiness. The active rest break did not reduce EEG sleepiness, with sleepiness levels eventually increasing, and resulted in an immediate reduction of subjective sleepiness. No difference was found between the two breaks for the driving performance measure. The immediate reduction of subjective sleepiness after the active rest break could leave drivers with erroneous perceptions of their sleepiness, particularly with increases of physiological sleepiness after the break.
Epidemiology, clinical manifestations, and outcomes of Scedosporium infections among solid organ transplant recipients
Authors: Johnson L.S. , Shields R.K. , Clancy C.J.
Published: June 2014

Background

Few studies of Scedosporium infections following solid organ transplantation have been performed in the era of induction immunosuppression and widespread antifungal prophylaxis.

Methods

We performed a single‐center, retrospective study of transplant recipients from 2000 through 2010 who had a positive Scedosporium culture.

Results

Among 27 patients, 67% (n = 18) and 33% (n = 9) were infected with Scedosporium apiospermum and Scedosporium prolificans, respectively. A total of 67% received induction immunosuppression and 74% received prior antifungal therapy. Isolates were broadly resistant to antifungals. Of these patients, 59% (n = 16) were colonized by Scedosporium, and 41% (n = 11) had disease (scedosporiosis). No significant clinical differences were seen between species. Colonization occurred exclusively in the lungs of lung transplant recipients (LTR). Scedosporiosis followed lung transplantation in 55%, and other organ transplants (multivisceral [18%]; and heart, liver, small intestine [9% each]) in 45%. Scedosporiosis was preceded by colonization in 36%. Diseases included pneumonia (64%), mediastinitis (18%), and fungemia/disseminated infections (18%). The 6‐month outcomes were death in 55%, progression in 18%, stability in 9%, and resolution in 18%. Patients who died had earlier onset scedosporiosis post transplant (median: 80.5 vs. 1388 days; P = 0.04), and were more likely to have mediastinitis or disseminated infections than pneumonia (100% vs. 29%; P = 0.06). The 3 patients who developed scedosporiosis >1 year post transplant survived. All patients who survived were treated with a voriconazole‐containing regimen.

Conclusions

LTR were most susceptible to Scedosporium colonization and scedosporiosis, particularly within the lungs. Death was common with scedosporiosis in the first year after all types of organ transplants, consistent with profound immunosuppression and antifungal resistance, but not encountered thereafter.
Disseminated Cunninghamella bertholletiae infection with spinal epidural abscess in a kidney transplant patient: case report and literature review
Authors: Navanukroh O. , Jitmuang A. , Chayakulkeeree M. , Ngamskulrungroj P.
Published: June 2014

Cunninghamella bertholletiae is a rare cause of invasive mucormycosis. We report the case of a 42‐year‐old Thai woman who suffered from disseminated C. bertholletiae infection. The patient developed dry cough, sharp shooting pain in the left buttock referred to the left leg, and fever 1 month after undergoing deceased‐donor kidney transplantation. Radiographic studies exhibited multiple pulmonary cavities, osteomyelitis of the sacral spine, epidural abscess along the lumbrosacral spine, and paravertebral soft tissue involvement. Surgical debridement of the epidural abscess concurrent with prolonged intravenous administration of amphotericin B resulted in a good outcome.
Large Eddy Simulation of Flow and Heat Transfer Around Two Square Cylinders in a Tandem Arrangement
Authors: Duchaine F. , Boileau M. , Sommerer Y. , Poinsot T.
Published: June 2014

This paper presents a large eddy simulation (LES) of flow and heat transfer in a tandem configuration of two square cylinders at moderate Reynolds number (Re=16,000). Compressible LES on a hybrid mesh is used to predict the flow structure and the heat transfer at the wall. The goals of this work are to analyze the flow and the heat transfer around a tandem arrangement of two inline square cylinders as well as to propose a LES approach that can be applied to convective heat transfer problems in industrial configurations. The meshing strategy allows to resolve the flow field until the viscous sublayer with y+ of the order unity. The wall adapting linear eddy model is chosen to model the subgrid turbulent viscosity. Aerodynamics results are validated versus experimental measurements performed on isolated cylinders and on tandem configurations. The main flow structures responsible for heat transfer are analyzed. Finally, heat transfer around both cylinders of the tandem is described.
A Molecular Dynamics Study on Heat Transfer Characteristics Over the Interface of Self-Assembled Monolayer and Water Solvent
Authors: Kikugawa Gota , Ohara Taku , Kawaguchi Tohru , Kinefuchi Ikuya , Matsumoto Yoichiro
Published: June 2014

We performed molecular dynamics (MD) simulations of the interface which is comprised of self-assembled monolayer (SAM) and water solvent to investigate heat transfer characteristics. In particular, local thermal boundary conductance (TBC), which is an inverse of so-called Kapitza resistance, at the SAM–solvent interface was evaluated by using the nonequilibrium MD (NEMD) technique in which the one-dimensional thermal energy flux was imposed across the interface. By using two kinds of SAM terminal with hydrophobic and hydrophilic properties, the local TBCs of these interfaces with water solvent were evaluated, and the result showed a critical difference due to an affinity between SAM and solvent. In order to elucidate the molecular-scale mechanism that makes this difference, microscopic components contributing to thermal energy flux across the interface of hydrophilic SAM and water were evaluated in detail, i.e., the total thermal energy flux is decomposed into the heat transfer modes such as the contribution of molecular transport and that of energy exchange by molecular interactions. These heat transfer modes were also compared with those in the bulk water.
Resource Letter HECR-1: High-Energy Cosmic Rays
Authors: Kotera Kumiko , Olinto Angela
Published: June 2014

This Resource Letter provides a guide to the literature on high energy cosmic rays and their associated messengers. Journal articles and books are cited for the following topics: cosmic rays from high to ultrahigh energies, gamma-rays, neutrinos, high energy astrophysical sources, particle acceleration mechanisms, cosmic ray interactions and propagation.
A daylight experiment for teaching stellar interferometry
Authors: Illarramendi M. A. , Hueso R. , Zubia J. , Aldabaldetreku G. , Durana G. , Sánchez-Lavega A.
Published: June 2014

We discuss the design of a simple experiment that reproduces the operation of the Michelson stellar interferometer. The emission of stellar sources has been simulated using light emerging from circular end-faces of step-index polymer optical fibers and from diffuse reflections of laser beams. Interference fringes have been acquired using a digital camera, coupled to a telescope obscured by a double aperture lid. The experiment is analogous to the classical determination of stellar sizes by Michelson and can be used during the day. Using this experimental set-up, we can determine the size of extended sources, located at a distance of about 75 m from our telescope, with errors less than 25%.
Population Pharmacokinetics of Bedaquiline (TMC207), a Novel Antituberculosis Drug
Authors: McLeay Sarah C. , Vis Peter , van Heeswijk Rolf P. G. , Green Bruce
Published: June 2014

Bedaquiline is a novel agent for the treatment of pulmonary multidrug-resistant
Mycobacterium tuberculosis
infections, in combination with other agents. The objective of this study was to develop a population pharmacokinetic (PK) model for bedaquiline to describe the concentration-time data from phase I and II studies in healthy subjects and patients with drug-susceptible or multidrug-resistant tuberculosis (TB). A total of 5,222 PK observations from 480 subjects were used in a nonlinear mixed-effects modeling approach. The PK was described with a 4-compartment disposition model with dual zero-order input (to capture dual peaks observed during absorption) and long terminal half-life (
t
1/2
). The model included between-subject variability on apparent clearance (CL/F), apparent central volume of distribution (
V
c
/F), the fraction of dose via the first input, and bioavailability (F). Bedaquiline was widely distributed, with apparent volume at steady state of >10,000 liters and low clearance. The long terminal
t
1/2
was likely due to redistribution from the tissue compartments. The final covariate model adequately described the data and had good simulation characteristics. The CL/F was found to be 52.0% higher for subjects of black race than that for subjects of other races, and
V
c
/F was 15.7% lower for females than that for males, although their effects on bedaquiline exposure were not considered to be clinically relevant. Small differences in F and CL/F were observed between the studies. The residual unexplained variability was 20.6% and was higher (27.7%) for long-term phase II studies.
Exposure of Staphylococcus aureus to Subinhibitory Concentrations of β-Lactam Antibiotics Induces Heterogeneous Vancomycin-Intermediate Staphylococcus aureus
Authors: Roch Mélanie , Clair Perrine , Renzoni Adriana , Reverdy Marie-Elisabeth , Dauwalder Olivier , Bes Michèle , Martra Annie , Freydière Anne-Marie , Laurent Frédéric , Reix Philippe , Dumitrescu Oana , Vandenesch François
Published: June 2014

Glycopeptides are known to select for heterogeneous vancomycin-intermediate
Staphylococcus aureus
(h-VISA) from susceptible strains. In certain clinical situations, h-VISA strains have been isolated from patients without previous exposure to glycopeptides, such as cystic fibrosis patients, who frequently receive repeated treatments with beta-lactam antibiotics. Our objective was to determine whether prolonged exposure to beta-lactam antibiotics can induce h-VISA. We exposed 3 clinical vancomycin-susceptible methicillin-resistant
Staphylococcus aureus
(MRSA) strains to ceftazidime, ceftriaxone, imipenem, and vancomycin (as a control) at subinhibitory concentrations for 18 days
in vitro
. Population analyses showed progressive increases in vancomycin resistance; seven of the 12 derived strains obtained after induction were classified as h-VISA according to the following criteria: area under the curve (AUC) on day 18/AUC of Mu3 of ≥90% and/or growth on brain heart infusion (BHI) agar with 4 mg/liter vancomycin. The derived isolates had thickened cell walls proportional to the level of glycopeptide resistance. Genes known to be associated with glycopeptide resistance (
vraSR
,
yvqF
, SA1703,
graRS
,
walKR
, and
rpoB
) were PCR sequenced; no
de novo
mutations were observed upon beta-lactam exposure. To determine whether
trfA
, a gene encoding a glycopeptide resistance factor, was essential in the selection of h-VISA upon beta-lactam pressure, a
trfA
-knockout strain was generated by allelic replacement. Indeed, beta-lactam exposure of this mutated strain showed no capacity to induce vancomycin resistance. In conclusion, these results showed that beta-lactam antibiotics at subinhibitory concentrations can induce intermediate vancomycin resistance
in vitro
. This induction required an intact
trfA
locus. Our results suggest that prior use of beta-lactam antibiotics can compromise vancomycin efficacy in the treatment of MRSA infections.
Fosmidomycin Decreases Membrane Hopanoids and Potentiates the Effects of Colistin on Burkholderia multivorans Clinical Isolates
Authors: Malott Rebecca J. , Wu Chia-Hung , Lee Tracy D. , Hird Trevor J. , Dalleska Nathan F. , Zlosnik James E. A. , Newman Dianne K. , Speert David P.
Published: June 2014

Burkholderia cepacia
complex (Bcc) pulmonary infections in people living with cystic fibrosis (CF) are difficult to treat because of the extreme intrinsic resistance of most isolates to a broad range of antimicrobials. Fosmidomycin is an antibacterial and antiparasitic agent that disrupts the isoprenoid biosynthesis pathway, a precursor to hopanoid biosynthesis. Hopanoids are involved in membrane stability and contribute to polymyxin resistance in Bcc bacteria. Checkerboard MIC assays determined that although isolates of the Bcc species
B. multivorans
were highly resistant to treatment with fosmidomycin or colistin (polymyxin E), antimicrobial synergy was observed in certain isolates when the antimicrobials were used in combination. Treatment with fosmidomycin decreased the MIC of colistin for isolates as much as 64-fold to as low as 8 μg/ml, a concentration achievable with colistin inhalation therapy. A liquid chromatography-tandem mass spectrometry technique was developed for the accurate quantitative determination of underivatized hopanoids in total lipid extracts, and bacteriohopanetetrol cyclitol ether (BHT-CE) was found to be the dominant hopanoid made by
B. multivorans
. The amount of BHT-CE made was significantly reduced upon fosmidomycin treatment of the bacteria. Uptake assays with 1-
N
-phenylnaphthylamine were used to determine that dual treatment with fosmidomycin and colistin increases membrane permeability, while binding assays with boron-dipyrromethene-conjugated polymyxin B illustrated that the addition of fosmidomycin had no impact on polymyxin binding. This work indicates that pharmacological suppression of membrane hopanoids with fosmidomycin treatment can increase the susceptibility of certain clinical
B. multivorans
isolates to colistin, an agent currently in use to treat pulmonary infections in CF patients.
Levofloxacin-Ceftriaxone Combination Attenuates Lung Inflammation in a Mouse Model of Bacteremic Pneumonia Caused by Multidrug-Resistant Streptococcus pneumoniae via Inhibition of Cytolytic Activities of Pneumolysin and Autolysin
Authors: Majhi Arnab , Adhikary Rana , Bhattacharyya Aritra , Mahanti Sayantika , Bishayi Biswadev
Published: June 2014

In this study, our objective was to determine whether a synergistic antimicrobial combination
in vitro
would be beneficial in the downregulation of pneumococcal virulence genes and whether the associated inflammation of the lung tissue induced by multidrug-resistant
Streptococcus pneumoniae
infection
in vivo
needs to be elucidated in order to consider this mode of therapy in case of severe pneumococcal infection. We investigated
in vivo
changes in the expression of these virulence determinants using an efficacious combination determined in previous studies. BALB/c mice were infected with 10
6
CFU of bacteria. Intravenous levofloxacin at 150 mg/kg and/or ceftriaxone at 50 mg/kg were initiated 18 h postinfection; the animals were sacrificed 0 to 24 h after the initiation of treatment. The levels of cytokines, chemokines, and C-reactive protein (CRP) in the serum and lungs, along with the levels of myeloperoxidase and nitric oxide the inflammatory cell count in bronchoalveolar lavage fluid (BALF), changes in pneumolysin and autolysin gene expression and COX-2 and inducible nitric oxide synthase (iNOS) protein expression in the lungs were estimated. Combination therapy downregulated inflammation and promoted bacterial clearance. Pneumolysin and autolysin expression was downregulated, with a concomitant decrease in the expression of COX-2 and iNOS in lung tissue. Thus, the combination of levofloxacin and ceftriaxone can be considered for therapeutic use even in cases of pneumonia caused by drug-resistant isolates.
Synergy of Streptogramin Antibiotics Occurs Independently of Their Effects on Translation
Authors: Noeske Jonas , Huang Jian , Olivier Nelson B. , Giacobbe Robert A. , Zambrowski Mark , Cate Jamie H. D.
Published: June 2014

Streptogramin antibiotics are divided into types A and B, which in combination can act synergistically. We compared the molecular interactions of the streptogramin combinations Synercid (type A, dalfopristin; type B, quinupristin) and NXL 103 (type A, flopristin; type B, linopristin) with the
Escherichia coli
70S ribosome by X-ray crystallography. We further analyzed the activity of the streptogramin components individually and in combination. The streptogramin A and B components in Synercid and NXL 103 exhibit synergistic antimicrobial activity against certain pathogenic bacteria. However, in transcription-coupled translation assays, only combinations that include dalfopristin, the streptogramin A component of Synercid, show synergy. Notably, the diethylaminoethylsulfonyl group in dalfopristin reduces its activity but is the basis for synergy in transcription-coupled translation assays before its rapid hydrolysis from the depsipeptide core. Replacement of the diethylaminoethylsulfonyl group in dalfopristin by a nonhydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that the synergistic antimicrobial activity of streptogramins can occur independently of the effects of streptogramin on translation.
Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner
Authors: Dulek Daniel E. , Newcomb Dawn C. , Goleniewska Kasia , Cephus Jaqueline , Zhou Weisong , Reiss Sara , Toki Shinji , Ye Fei , Zaynagetdinov Rinat , Sherrill Taylor P. , Blackwell Timothy S. , Moore Martin L. , Boyd Kelli L. , Kolls Jay K. , Peebles R. Stokes
Published: June 2014

The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, includingKlebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminishex vivoandin vivoIL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection withK. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acuteK. pneumoniaeinfection and thereby increases the lungK. pneumoniaeburden. As hypothesized, we found that allergic airway inflammation decreased the number ofK. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lungK. pneumoniaeburden and postinfection mortality. We showed that the decreased lungK. pneumoniaeburden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lungK. pneumoniaeburden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity againstK. pneumoniaeand suggest new mechanisms of orchestrating lung antibacterial immunity.
Intestinal Epithelium-Specific MyD88 Signaling Impacts Host Susceptibility to Infectious Colitis by Promoting Protective Goblet Cell and Antimicrobial Responses
Authors: Bhinder Ganive , Stahl Martin , Sham Ho Pan , Crowley Shauna M. , Morampudi Vijay , Dalwadi Udit , Ma Caixia , Jacobson Kevan , Vallance Bruce A.
Published: June 2014

Intestinal epithelial cells (IECs), including secretory goblet cells, form essential physiochemical barriers that separate luminal bacteria from underlying immune cells in the intestinal mucosa. IECs are common targets for enteric bacterial pathogens, with hosts responding to these microbes through innate toll-like receptors that predominantly signal through the MyD88 adaptor protein. In fact, MyD88 signaling confers protection against several enteric bacterial pathogens, including
Salmonella enterica
serovar Typhimurium and
Citrobacter rodentium
. Since IECs are considered innately hyporesponsive, it is unclear whether MyD88 signaling within IECs contributes to this protection. We infected mice lacking MyD88 solely in their IECs (
IEC-Myd88
−/−
) with
S.
Typhimurium. Compared to wild-type (WT) mice, infected
IEC-Myd88
−/−
mice suffered accelerated tissue damage, exaggerated barrier disruption, and impaired goblet cell responses (Muc2 and RELMβ). Immunostaining revealed
S.
Typhimurium penetrated the IECs of
IEC-Myd88
−/−
mice, unlike in WT mice, where they were sequestered to the lumen. When isolated crypts were assayed for their antimicrobial actions, crypts from
IEC-Myd88
−/−
mice were severely impaired in their antimicrobial activity against
S.
Typhimurium. We also examined whether MyD88 signaling in IECs impacted host defense against
C. rodentium
, with
IEC-Myd88
−/−
mice again suffering exaggerated tissue damage, impaired goblet cell responses, and reduced antimicrobial activity against
C. rodentium
. These results demonstrate that MyD88 signaling within IECs plays an important protective role at early stages of infection, influencing host susceptibility to infection by controlling the ability of the pathogen to reach and survive at the intestinal mucosal surface.