bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling the Impacts of Solar Distributed Generation on U. S. Water Resources
Authors: Smith Amanda D. , Omitaomu Olufemi A. , Peck Jaron J.
Published: October 2015

Distributed electric power generation technologies typically use little or no water per unit of electrical energy produced; in particular, renewable energy sources such as solar PV systems do not require cooling systems and present an opportunity to reduce water usage for power generation. Within the US, the fuel mix used for power generation varies regionally, and certain areas use more water for power generation than others. The need to reduce water usage for power generation is even more urgent in view of climate change uncertainties. In this paper, we present an example case within the state of Tennessee, one of the top four states in water consumption for power generation and one of the states with little or no potential for developing centralized renewable energy generations. The potential for developing PV generation within Knox County, Tennessee, is studied, along with the potential for reducing water withdrawal and consumption within the Tennessee Valley stream region. Electric power generation plants in the region are quantified for their electricity production and expected water withdrawal and consumption over one year, where electrical generation data is provided over one year and water usage is modeled based on the cooling system(s) in use. Potential solar PV electrical production is modeled based on LiDAR data and weather data for the same year. Our proposed methodology can be summarized as follows: First, the potential solar generation is compared against the local grid demand. Next, electrical generation reductions are specified that would result in a given reduction in water withdrawal and a given reduction in water consumption, and compared with the current water withdrawal and consumption rates for the existing fuel mix. The increase in solar PV development that would produce an equivalent amount of power, is determined. In this way, we consider how targeted local actions may affect the larger stream region through thoughtful energy development. This model can be applied to other regions, other types of distributed generation, and used as a framework for modeling alternative growth scenarios in power production capacity in addition to modeling adjustments to existing capacity.
Successful Implementation of Methanol Firing at 50 MW Gas Turbine for Long Term Operation
Authors: Chudnovsky B. , Reshef M. , Keren M. , Baitel S.
Published: October 2015

Recently methanol’s use as a fuel is becoming more attractive. Firstly, because of the prices of NG (the main feedstock for methanol production) are now at record low. This has prompted consideration of other alternative energy sources that are not oil dependent. A second key issue has been growing global concern for environment and emphasis being placed on the use of fuels with lower SO2, NOx and particulates emissions. Methanol offers these advantages, being a derivative of natural gas which partly de-linked from oil, and is a clean burning fuel.

In this manner full scale test of methanol firing at FT4C TWIN PAC 50 MWe GT designed by Pratt & Whitney was performed. The obtained results clearly show that with minor low cost fuel system retrofit methanol firing leads to significant NOx, SO2 and particulates emission reduction. NOx emissions were reduced by more than 75% and are equal 75 mg/dNm3 at 15%O2. It is less then required standard even with water injection operation mode (the standard is 86 mg/dNm3 at 15%O2 of NOx emission). SO2 emissions were reduced to zero with methanol firing. Particulate emissions vary from 1.3 to 1.6 mg/dNm3 at 15% O2 with methanol firing, while with LFO this parameter was 13–37 mg/dNm3 at 15% O2.

However, it should be noted that methanol has a significantly lower calorific value, which is, for example, half of diesel oil and requires therefore some specific modification in gas turbine equipment. First, the existing fuel nozzles are too small for the higher volumetric methanol flow and should be replaced by high flow fuel nozzles. The existing fuel supplying pump should also be upgraded to the higher methanol flow. Modulating valve was also replaced due to the same reason.

The paper first gives an overview of some of the key technical considerations of the gas turbine conversion from diesel oil to methanol firing, and results of long term operation of gas turbine fired by methanol.

Based on the obtained results one may conclude that methanol is an attractive alternative fuel for meeting the energy needs of niche markets in an economic and environmentally sustainable manner, utilizing existing and/or new power generation units.
Breadth First Search Based COSINE Software Code Framework Automation Algorithm
Authors: Ren Hao , Mo Wentao , Zhao Guang , Ren Dangpei , Liu Shuo
Published: October 2015

Using software automation technology can significantly improve the quality and productivity of software development. Based on the tree data structure, this paper proposed the Breadth First Search (BFS) based software framework automatic generation algorithm called CFAA (Code Framework Automation Algorithm). The algorithm uses tree data structure to represent scientific computing software architecture, then uses the BFS to traverse all nodes of the tree to generate code framework of software. CFAA enable programmers to focus more on computing software architecture design and optimization, and then automatically generate the skeleton code. CFAA has been applied to COSINE (Core and System Integrated Engine for design and analysis) software development process. Practice proved that CFAA can improve the efficiency of building software framework, while reducing the defect rate of software development.
Comparing the information conveyed by envelope modulation for speech intelligibility, speech quality, and music quality
Authors: Kates James M. , Arehart Kathryn H.
Published: October 2015

This paper uses mutual information to quantify the relationship between envelope modulation fidelity and perceptual responses. Data from several previous experiments that measured speech intelligibility, speech quality, and music quality are evaluated for normal-hearing and hearing-impaired listeners. A model of the auditory periphery is used to generate envelope signals, and envelope modulation fidelity is calculated using the normalized cross-covariance of the degraded signal envelope with that of a reference signal. Two procedures are used to describe the envelope modulation: (1) modulation within each auditory frequency band and (2) spectro-temporal processing that analyzes the modulation of spectral ripple components fit to successive short-time spectra. The results indicate that low modulation rates provide the highest information for intelligibility, while high modulation rates provide the highest information for speech and music quality. The low-to-mid auditory frequencies are most important for intelligibility, while mid frequencies are most important for speech quality and high frequencies are most important for music quality. Differences between the spectral ripple components used for the spectro-temporal analysis were not significant in five of the six experimental conditions evaluated. The results indicate that different modulation-rate and auditory-frequency weights may be appropriate for indices designed to predict different types of perceptual relationships.
The effect of different open plan and enclosed classroom acoustic conditions on speech perception in Kindergarten children
Authors: Mealings Kiri T. , Demuth Katherine , Buchholz Jörg M. , Dillon Harvey
Published: October 2015

Open plan classrooms, where several classes are in the same room, have recently re-emerged in Australian primary schools. This paper explores how the acoustics of four Kindergarten classrooms [an enclosed classroom (25 children), double classroom (44 children), fully open plan triple classroom (91 children), and a semi-open plan K–6 “21st century learning space” (205 children)] affect speech perception. Twenty-two to 23 5–6-year-old children in each classroom participated in an online four-picture choice speech perception test while adjacent classes engaged in quiet versus noisy activities. The noise levels recorded during the test were higher the larger the classroom, except in the noisy condition for the K–6 classroom, possibly due to acoustic treatments. Linear mixed effects models revealed children's performance accuracy and speed decreased as noise level increased. Additionally, children's speech perception abilities decreased the further away they were seated from the loudspeaker in noise levels above 50 dBA. These results suggest that fully open plan classrooms are not appropriate learning environments for critical listening activities with young children due to their high intrusive noise levels which negatively affect speech perception. If open plan classrooms are desired, they need to be acoustically designed to be appropriate for critical listening activities.
Listening efficiency during lessons under various types of noise
Authors: Prodi Nicola , Visentin Chiara
Published: October 2015

Pupils inside primary school classrooms can be exposed to extraneous noise, impairing their performance in the speech reception process. The different noises show a peculiar impact, depending on their level, spectral content and temporal fine structure. In order to understand how the disturbance is built up over time, in this work a large data set was analyzed, detailing the changes of pupils' performance as the lesson progresses from the start to the end. Several types of noise are considered (traffic, tapping and activity noise) and the analysis concerns III to V graders of the Italian primary school (8 to 10 year old pupils). By using as indicators the intelligibility scores, the response time and their ratio, the so-called “listening efficiency,” several findings are achieved. Pupils respond differently to each noise during the course of the lesson. In the better listening conditions, the performance in the speech reception worsens under traffic and babble noise whereas an opposite trend is found under tapping noise. On the contrary adaptation is observed in the worse listening conditions for the traffic noise alone. Moreover, indications are achieved that the age proficiency may affect differently babble noise compared to traffic and tapping noise.
Hemispherical breathing mode speaker using a dielectric elastomer actuator
Authors: Hosoya Naoki , Baba Shun , Maeda Shingo
Published: October 2015

Although indoor acoustic characteristics should ideally be assessed by measuring the reverberation time using a point sound source, a regular polyhedron loudspeaker, which has multiple loudspeakers on a chassis, is typically used. However, such a configuration is not a point sound source if the size of the loudspeaker is large relative to the target sound field. This study investigates a small lightweight loudspeaker using a dielectric elastomer actuator vibrating in the breathing mode (the pulsating mode such as the expansion and contraction of a balloon). Acoustic testing with regard to repeatability, sound pressure, vibration mode profiles, and acoustic radiation patterns indicate that dielectric elastomer loudspeakers may be feasible.
Gallium Potentiates the Antibacterial Effect of Gentamicin against Francisella tularensis
Authors: Lindgren Helena , Sjöstedt Anders
Published: October 2015

The reasons why aminoglycosides are bactericidal have not been not fully elucidated, and evidence indicates that the cidal effects are at least partly dependent on iron. We demonstrate that availability of iron markedly affects the susceptibility of the facultative intracellular bacteriumFrancisella tularensisstrain SCHU S4 to the aminoglycoside gentamicin. Specifically, the intracellular depots of iron were inversely correlated to gentamicin susceptibility, whereas the extracellular iron concentrations were directly correlated to the susceptibility. Further proof of the intimate link between iron availability and antibiotic susceptibility were the findings that a ΔfslAmutant, which is defective for siderophore-dependent uptake of ferric iron, showed enhanced gentamicin susceptibility and that a ΔfeoBmutant, which is defective for uptake of ferrous iron, displayed complete growth arrest in the presence of gentamicin. Based on the aforementioned findings, it was hypothesized that gallium could potentiate the effect of gentamicin, since gallium is sequestered by iron uptake systems. The ferrozine assay demonstrated that the presence of gallium inhibited >70% of the iron uptake. Addition of gentamicin and/or gallium to infected bone marrow-derived macrophages showed that both 100 μM gallium and 10 μg/ml of gentamicin inhibited intracellular growth of SCHU S4 and that the combined treatment acted synergistically. Moreover, treatment ofF. tularensis-infected mice with gentamicin and gallium showed an additive effect. Collectively, the data demonstrate that SCHU S4 is dependent on iron to minimize the effects of gentamicin and that gallium, by inhibiting the iron uptake, potentiates the bactericidal effect of gentamicinin vitroandin vivo.
Cardiac Effects of Echinocandins in Endotoxemic Rats
Authors: Koch Christian , Wolff Matthias , Henrich Michael , Weigand Markus A. , Lichtenstern Christoph , Uhle Florian
Published: October 2015

Echinocandins are known as effective and safe agents for the prophylaxis and treatment of different cohorts of patients with fungal infections. Recent studies revealed that certain pharmacokinetics of echinocandin antifungals might impact clinical efficacy and safety in special patient populations. The aim of our study was to evaluate echinocandin-induced aggravation of cardiac impairment in septic shock. Using an
in vivo
endotoxemic shock model in rats, we assessed hemodynamic parameters and time to hemodynamic failure (THF) after additional central-venous application of anidulafungin (2.5 mg/kg of body weight [BW]), caspofungin (0.875 mg/kg BW), micafungin (3 mg/kg BW), and control (0.9% sodium chloride). In addition, echinocandin-induced cytotoxicity was evaluated in isolated rat cardiac myocytes. THF of the animals in the caspofungin group (
n
= 7) was significantly reduced compared to that in the control (
n
= 6) (136 min versus 180 min;
P
= 0.0209). The anidulafungin group (
n
= 7) also showed a trend of reduced THF (136 min versus 180 min; log-rank test
P
= 0.0578). Animals in the micafungin group (
n
= 7) did not show significant differences in THF compared to those in the control. Control group animals and also micafungin group animals did not show altered cardiac output (CO) during our experiments. In contrast, administration of anidulafungin or caspofungin induced a decrease in CO. We also revealed a dose-dependent increase of cytotoxicity in anidulafungin- and caspofungin-treated cardiac myocytes. Treatment with micafungin did not cause significantly increased cytotoxicity. Further studies are needed to explore the underlying mechanism.
A Two-Year Surveillance in Five Colombian Tertiary Care Hospitals Reveals High Frequency of Non-CG258 Clones of Carbapenem-Resistant Klebsiella pneumoniae with Distinct Clinical Characteristics
Authors: Ocampo Ana M. , Chen Liang , Cienfuegos Astrid V. , Roncancio Gustavo , Chavda Kalyan D. , Kreiswirth Barry N. , Jiménez J. Natalia
Published: October 2015

The global spread of carbapenem-resistantKlebsiella pneumoniae(CR-Kp) has been largely associated with sequence type 258 (ST258) and its related variants (clonal group 258 [CG258]). Here we describe the molecular epidemiology of CR-Kp from five tertiary care hospitals in Medellín, the second largest city in Colombia. All CR-Kp-infected patients admitted from June 2012 to June 2014 were included (n= 193). Patients' clinical information was obtained from medical records. Carbapenemase KPC, VIM, IMP, NDM, and OXA-48 genes were detected by PCR. A CG258-tonB79cluster-specific real-time PCR (targeting the multilocus sequence type [MLST]tonB79allele), pulsed-field gel electrophoresis (PFGE), and MLST analysis were performed for typing. Remarkably, 62.2% (n= 120) of isolates were from STs unrelated to CG258 (non-CG258). KPC-3 predominated in CG258 isolates (86.3%), while KPC-2 prevailed in non-CG258 isolates (75.5%) (P< 0.001). Multidrug resistance (MDR) frequency was significantly higher in CG258 strains (91.4% versus 56.1%;P< 0.001). ST512 (a single-locus variant of ST258) is the main ST in CG258 (96.3%), and isolates in this group showed closely related pulsotype and similar resistance gene profiles, suggesting the clonal spread of this strain. In contrast, high heterogeneity of STs (34/54), including eight novel STs, was found in non-CG258 isolates. Among non-CG258 isolates, ST14 (13.3%;n= 16) and ST307 (14.2%;n= 17) were the most frequent, and they showed distinct molecular and clinical characteristics in comparison to CG258 isolates. Our results suggest that the dissemination of carbapenem resistance in Medellín is due to heterogeneousK. pneumoniaeclones, likely the result of horizontal transmission of KPC in different unrelated lineages, further highlighting the challenge in CR-Kp infection control and the need for a multifocal intervention.
Novobiocin Inhibits the Antimicrobial Resistance Acquired through DNA Damage-Induced Mutagenesis in Acinetobacter baumannii
Authors: Jara Luis M. , Pérez-Varela María , Corral Jordi , Arch Marta , Cortés Pilar , Bou Germán , Aranda Jesús , Barbé Jordi
Published: October 2015

Acinetobacter baumannii
, a worldwide emerging nosocomial pathogen, acquires antimicrobial resistances in response to DNA-damaging agents, which increase the expression of multiple error-prone DNA polymerase components. Here we show that the aminocoumarin novobiocin, which inhibits the DNA damage response in Gram-positive bacteria, also inhibits the expression of error-prone DNA polymerases in this Gram-negative multidrug-resistant pathogen and, consequently, its potential acquisition of antimicrobial resistance through DNA damage-induced mutagenesis.
Intracellular Activation of Tenofovir Alafenamide and the Effect of Viral and Host Protease Inhibitors
Authors: Birkus Gabriel , Bam Rujuta A. , Willkom Madeleine , Frey Christian R. , Tsai Luong , Stray Kirsten M. , Yant Stephen R. , Cihlar Tomas
Published: October 2015

Tenofovir alafenamide fumarate (TAF) is an oral phosphonoamidate prodrug of the HIV reverse transcriptase nucleotide inhibitor tenofovir (TFV). Previous studies suggested a principal role for the lysosomal serine protease cathepsin A (CatA) in the intracellular activation of TAF. Here we further investigated the role of CatA and other human hydrolases in the metabolism of TAF. Overexpression of CatA or liver carboxylesterase 1 (Ces1) in HEK293T cells increased intracellular TAF hydrolysis 2- and 5-fold, respectively. Knockdown of CatA expression with RNA interference (RNAi) in HeLa cells reduced intracellular TAF metabolism 5-fold. Additionally, the anti-HIV activity and the rate of CatA hydrolysis showed good correlation within a large set of TFV phosphonoamidate prodrugs. The covalent hepatitis C virus (HCV) protease inhibitors (PIs) telaprevir and boceprevir potently inhibited CatA-mediated TAF activation (50% inhibitory concentration [IC
50
] = 0.27 and 0.16 μM, respectively)
in vitro
and also reduced its anti-HIV activity in primary human CD4
+
T lymphocytes (21- and 3-fold, respectively) at pharmacologically relevant concentrations. In contrast, there was no inhibition of CatA or any significant effect on anti-HIV activity of TAF observed with cobicistat, noncovalent HIV and HCV PIs, or various prescribed inhibitors of host serine proteases. Collectively, these studies confirm that CatA plays a pivotal role in the intracellular metabolism of TAF, whereas the liver esterase Ces1 likely contributes to the hepatic activation of TAF. Moreover, this work demonstrates that a wide range of viral and host PIs, with the exception of telaprevir and boceprevir, do not interfere with the antiretroviral activity of TAF.
Development of an Intracellular Screen for New Compounds Able To Inhibit Mycobacterium tuberculosis Growth in Human Macrophages
Authors: Sorrentino Flavia , Gonzalez del Rio Ruben , Zheng Xingji , Presa Matilla Jesus , Torres Gomez Pedro , Martinez Hoyos Maria , Perez Herran Maria Esther , Mendoza Losana Alfonso , Av-Gay Yossef
Published: October 2015

Here we describe the development and validation of an intracellular high-throughput screening assay for finding new antituberculosis compounds active in human macrophages. The assay consists of a luciferase-based primary identification assay, followed by a green fluorescent protein-based secondary profiling assay. Standard tuberculosis drugs and 158 previously recognized active antimycobacterial compounds were used to evaluate assay robustness. Data show that the assay developed is a short and valuable tool for the discovery of new antimycobacterial compounds.
Staphylococcus aureus Strain USA300 Perturbs Acquisition of Lysosomal Enzymes and Requires Phagosomal Acidification for Survival inside Macrophages
Authors: Tranchemontagne Zachary R. , Camire Ryan B. , O'Donnell Vanessa J. , Baugh Jessfor , Burkholder Kristin M.
Published: October 2015

Methicillin-resistantStaphylococcus aureus(MRSA) causes invasive, drug-resistant skin and soft tissue infections. Reports thatS. aureusbacteria survive inside macrophages suggest that the intramacrophage environment may be a niche for persistent infection; however, mechanisms by which the bacteria might evade macrophage phagosomal defenses are unclear. We examined the fate of theS. aureus-containing phagosome in THP-1 macrophages by evaluating bacterial intracellular survival and phagosomal acidification and maturation and by testing the impact of phagosomal conditions on bacterial viability. Multiple strains ofS. aureussurvived inside macrophages, and in studies using the MRSA USA300 clone, the USA300-containing phagosome acidified rapidly and acquired the late endosome and lysosome protein LAMP1. However, fewer phagosomes containing live USA300 bacteria than those containing dead bacteria associated with the lysosomal hydrolases cathepsin D and β-glucuronidase. Inhibiting lysosomal hydrolase activity had no impact on intracellular survival of USA300 or otherS. aureusstrains, suggesting thatS. aureusperturbs acquisition of lysosomal enzymes. We examined the impact of acidification onS. aureusintramacrophage viability and found that inhibitors of phagosomal acidification significantly impaired USA300 intracellular survival. Inhibition of macrophage phagosomal acidification resulted in a 30-fold reduction in USA300 expression of the staphylococcal virulence regulatoragrbut had little effect on expression ofsarA,saeR, orsigB. Bacterial exposure to acidic pHin vitroincreasedagrexpression. Together, these results suggest thatS. aureussurvives inside macrophages by perturbing normal phagolysosome formation and that USA300 may sense phagosomal conditions and upregulate expression of a key virulence regulator that enables its intracellular survival.
The LasB Elastase of Pseudomonas aeruginosa Acts in Concert with Alkaline Protease AprA To Prevent Flagellin-Mediated Immune Recognition
Authors: Casilag Fiordiligie , Lorenz Anne , Krueger Jonas , Klawonn Frank , Weiss Siegfried , Häussler Susanne
Published: October 2015

The opportunistic pathogen
Pseudomonas aeruginosa
is capable of establishing severe and persistent infections in various eukaryotic hosts. It encodes a wide array of virulence factors and employs several strategies to evade immune detection. In the present study, we screened the Harvard Medical School transposon mutant library of
P. aeruginosa
PA14 for bacterial factors that modulate interleukin-8 responses in A549 human airway epithelial cells. We found that in addition to the previously identified alkaline protease AprA, the elastase LasB is capable of degrading exogenous flagellin under calcium-replete conditions and prevents flagellin-mediated immune recognition. Our results indicate that the production of two proteases with anti-flagellin activity provides a failsafe mechanism for
P. aeruginosa
to ensure the maintenance of protease-dependent immune-modulating functions.
Fimbria-Encoding Gene
yadC
Has a Pleiotropic Effect on Several Biological Characteristics and Plays a Role in Avian Pathogenic Escherichia coli Pathogenicity
Authors: Verma Renu , Rojas Thaís Cabrera Galvão , Maluta Renato Pariz , Leite Janaína Luisa , da Silva Livia Pilatti Mendes , Nakazato Gerson , Dias da Silveira Wanderley
Published: October 2015

The extraintestinal pathogen termed avian pathogenic
Escherichia coli
(APEC) is known to cause colibacillosis in chickens. The molecular basis of APEC pathogenesis is not fully elucidated yet. In this work, we deleted a component of the Yad gene cluster (
yadC
) in order to understand the role of Yad in the pathogenicity of the APEC strain SCI-07.
In vitro
, the transcription level of
yadC
was upregulated at 41°C and downregulated at 22°C. The
yadC
expression
in vivo
was more pronounced in lungs than in spleen, suggesting a role in the early steps of the infection. Chicks infected with the wild-type and mutant strains presented, respectively, 80% and 50% mortality rates. The Δ
yadC
strain presented a slightly decreased ability to adhere to HeLa cells with or without the
d
-mannose analog compared with the wild type. Real-time PCR (RT-PCR) assays showed that
fimH
was downregulated (
P
< 0.05) and
csgA
and
ecpA
were slightly upregulated in the mutant strain, showing that
yadC
modulates expression of other fimbriae. Bacterial internalization studies showed that the Δ
yadC
strain had a lower number of intracellular bacteria recovered from Hep-2 cells and HD11 cells than the wild-type strain (
P
< 0.05). Motility assays in soft agar demonstrated that the Δ
yadC
strain was less motile than the wild type (
P
< 0.01). Curiously, flagellum-associated genes were not dramatically downregulated in the Δ
yadC
strain. Taken together, the results show that the fimbrial adhesin Yad contributes to the pathogenicity and modulates different biological characteristics of the APEC strain SCI-07.
Real-Time Imaging of Interactions of Neutrophils with Cryptococcus neoformans Demonstrates a Crucial Role of Complement C5a-C5aR Signaling
Authors: Sun Donglei , Zhang Mingshun , Liu Gongguan , Wu Hui , Zhu Xiaoping , Zhou Hong , Shi Meiqing
Published: October 2015

Neutrophils have been shown to efficiently killCryptococcus neoformans, a causative agent of meningoencephalitis. Here, using live-cell imaging, we characterize the dynamic interactions of neutrophils withC. neoformansand the underlying mechanisms in real time. Neutrophils were directly seen to chaseC. neoformanscells and then rapidly internalize them. Complement C5a-C5aR signaling guided neutrophils to migrate to the yeast cells, resulting in optimal phagocytosis and subsequent killing of the organisms. The addition of recombinant complement C5a enhanced neutrophil movement but did not induce chemotaxis, suggesting that the C5a gradient is crucial. Incubation withC. neoformansresulted in enhanced activation of Erk and p38 mitogen-activated protein (MAP) kinases (MAPKs) in neutrophils. Inhibition of the p38 MAPK pathway, but not the Erk pathway, significantly impaired neutrophil migration and its subsequent killing ofC. neoformans. Deficiency of CD11b or blocking of CD11b did not affect the migration of neutrophils towardC. neoformansbut almost completely abolished phagocytosis and killing of the organisms by neutrophils. C5a-C5aR signaling induced enhanced surface expression of CD11b. Interestingly, the original surface expression of CD11b was essential and sufficient for neutrophils to attach toC. neoformansbut was unable to mediate phagocytosis. In contrast, the enhanced surface expression of CD11b induced by C5a-C5aR signaling was essential for neutrophil phagocytosis and subsequent killing of yeast cells. Collectively, this is the first report of the dynamic interactions of neutrophils withC. neoformans, demonstrating a crucial role of C5a-C5aR signaling in neutrophil killing ofC. neoformansin real time.
Involvement of an Skp-Like Protein, PGN_0300, in the Type IX Secretion System of Porphyromonas gingivalis
Authors: Taguchi Yuko , Sato Keiko , Yukitake Hideharu , Inoue Tetsuyoshi , Nakayama Masaaki , Naito Mariko , Kondo Yoshio , Kano Konami , Hoshino Tomonori , Nakayama Koji , Takashiba Shogo , Ohara Naoya
Published: October 2015

The oral Gram-negative anaerobic bacterium
Porphyromonas gingivalis
is an important pathogen involved in chronic periodontitis. Among its virulence factors, the major extracellular proteinases, Arg-gingipain and Lys-gingipain, are of interest given their abilities to degrade host proteins and process other virulence factors. Gingipains possess C-terminal domains (CTDs) and are translocated to the cell surface or into the extracellular milieu by the type IX secretion system (T9SS). Gingipains contribute to the colonial pigmentation of the bacterium on blood agar. In this study, Omp17, the PGN_0300 gene product, was found in the outer membrane fraction. A mutant lacking Omp17 did not show pigmentation on blood agar and showed reduced proteolytic activity of the gingipains. CTD-containing proteins were released from bacterial cells without cleavage of the CTDs in the
omp17
mutant. Although synthesis of the anionic polysaccharide (A-LPS) was not affected in the
omp17
mutant, the processing of and A-LPS modification of CTD-containing proteins was defective. PorU, a C-terminal signal peptidase that cleaves the CTDs of other CTD-containing proteins, was not detected in any membrane fraction of the
omp17
mutant, suggesting that the defective maturation of CTD-containing proteins by impairment of Omp17 is partly due to loss of function of PorU. In the mouse subcutaneous infection experiment, the
omp17
mutant was less virulent than the wild type. These results suggested that Omp17 is involved in
P. gingivalis
virulence.
Sarcosine Catabolism in Pseudomonas aeruginosa Is Transcriptionally Regulated by SouR
Authors: Willsey Graham G. , Wargo Matthew J.
Published: October 2015

Sarcosine (
N
-methylglycine) is present in many environments inhabited by pseudomonads and is likely most often encountered as an intermediate in the metabolism of choline, carnitine, creatine, and glyphosate. While the enzymology of sarcosine metabolism has been relatively well studied in bacteria, the regulatory mechanisms governing catabolism have remained largely unknown. We previously determined that the sarcosine-catabolic (
sox
) operon of
Pseudomonas aeruginosa
is induced by the AraC family regulator GbdR in response to glycine betaine and dimethylglycine. However, induction of these genes was still observed in response to sarcosine in a
gbdR
deletion mutant, indicating that an independent sarcosine-responsive transcription factor also acted at this locus. Our goal in this study was to identify and characterize this regulator. Using a transposon-based genetic screen, we identified PA4184, or SouR (
s
arcosine
o
xidation and
u
tilization
r
egulator), as the sarcosine-responsive regulator of the
sox
operon, with tight induction specificity for sarcosine. The
souR
gene is required for appreciable growth on sarcosine as a carbon and nitrogen source. We also characterized the transcriptome response to sarcosine governed by SouR using microarray analyses and performed electrophoretic mobility shift assays to identify promoters directly regulated by the transcription factor. Finally, we characterized PA3630, or GfnR (
g
lutathione-dependent
f
ormaldehyde
n
eutralization
r
egulator), as the regulator of the glutathione-dependent formaldehyde detoxification system in
P. aeruginosa
that is expressed in response to formaldehyde released during the catabolism of sarcosine. This study expands our understanding of sarcosine metabolic regulation in bacteria through the identification and characterization of the first known sarcosine-responsive transcriptional regulator.

IMPORTANCE
The
Pseudomonas aeruginosa
genome encodes many diverse metabolic pathways, yet the specific transcription regulators controlling their expression remain mostly unknown. Here, we used a genetic screen to identify the sarcosine-specific regulator of the sarcosine oxidase operon, which we have named SouR. SouR is the first bacterial regulator shown to respond to sarcosine, and it is required for growth on sarcosine. Sarcosine is found in its free form and is also an intermediate in the catabolic pathways of glycine betaine, carnitine, creatine, and glyphosate. The similarity of SouR to the regulators of carnitine and glycine betaine catabolism suggests evolutionary diversification within this regulatory family to allow response to structurally similar but physiologically distinct ligands.
Pilot study of a cluster randomised trial of a guided e-learning health promotion intervention for managers based on management standards for the improvement of employee well-being and reduction of sickness absence: GEM Study
Authors: Stansfeld Stephen A , Kerry Sally , Chandola Tarani , Russell Jill , Berney Lee , Hounsome Natalia , Lanz Doris , Costelloe Céire , Smuk Melanie , Bhui Kamaldeep
Published: October 2015

Objectives

To investigate the feasibility of recruitment, adherence and likely effectiveness of an e-learning intervention for managers to improve employees’ well-being and reduce sickness absence.

Methods

The GEM Study (guided e-learning for managers) was a mixed methods pilot cluster randomised trial. Employees were recruited from four mental health services prior to randomising three services to the intervention and one to no-intervention control. Intervention managers received a facilitated e-learning programme on work-related stress. Main outcomes were Warwick Edinburgh Mental Wellbeing Scale (WEMWBS), 12-item GHQ and sickness absence <21 days from human resources. 35 in-depth interviews were undertaken with key informants, managers and employees, and additional observational data collected.

Results

424 of 649 (65%) employees approached consented, of whom 350 provided WEMWBS at baseline and 284 at follow-up; 41 managers out of 49 were recruited from the three intervention clusters and 21 adhered to the intervention. WEMWBS scores fell from 50.4–49.0 in the control (n=59) and 51.0–49.9 in the intervention (n=225), giving an intervention effect of 0.5 (95% CI −3.2 to 4.2). 120/225 intervention employees had a manager who was adherent to the intervention. HR data on sickness absence (n=393) showed no evidence of effect. There were no effects on GHQ score or work characteristics. Online quiz knowledge scores increased across the study in adherent managers. Qualitative data provided a rich picture of the context within which the intervention took place and managers’ and employees’ experiences of it.

Conclusions

A small benefit from the intervention on well-being was explained by the mixed methods approach, implicating a low intervention uptake by managers and suggesting that education alone may be insufficient. A full trial of the guided e-learning intervention and economic evaluation is feasible. Future research should include more active encouragement of manager motivation, reflection and behaviour change.

Trial Registration number

ISRCTN58661009.
Prevalence of vestibular dysfunction and associated factors in South Korea
Authors: Koo Ja-Won , Chang Mun Young , Woo Sook-young , Kim Seonwoo , Cho Yang-Sun
Published: October 2015

Objective

To report the nationwide prevalence of dizziness and vestibular dysfunction in the Korean population and determine the associated factors.

Design

Cross-sectional analysis of a nationwide health survey.

Methods

We obtained data from the 2009 to 2010 Korea National Health and Nutrition Examination Surveys, which were cross-sectional surveys of the South Korean civilian, non-institutionalised population aged 40 years and older (N=3267). A field survey team performed interviews and physical examinations. Structured questionnaires were handed out and balance function tests using the modified Romberg test of standing balance on firm and compliant support surfaces were performed on participants. Failure on the modified Romberg test was regarded to indicate vestibular dysfunction.

Results

The prevalence of dizziness during the past year was 16.70% (95% CI 14.65% to 18.76%). The presence of vestibular dysfunction was noted in 1.84% (95% CI 1.18% to 2.51%). In addition, the prevalence of experiencing falls and positional dizziness were 1.46% (95% CI 0.87% to 2.06%) and 1.73% (95% CI 1.17% to 2.29%), respectively. Multivariable analysis revealed that dizziness was associated with increased age, female gender, hearing loss and stress. Vestibular dysfunction was associated with increased age, history of dizziness and hearing loss.

Conclusions

Vertigo and dizziness are the greatest contributors to the burden of disability in the aged population. Screening for dizziness and vestibular dysfunction, and management of associated factors might be important for improving compromised quality of life due to postural imbalance caused by vestibular problems.
Acupuncture for treating alopecia areata: a protocol of systematic review of randomised clinical trials
Authors: Lee Hye Won , Jun Ji Hee , Lee Ju Ah , Lim Hyun-Ja , Lim Hyun-Suk , Lee Myeong Soo
Published: October 2015

Introduction

Acupuncture is frequently used in dermatology for treating a number of skin disorders. There is no critically appraised evidence of the potential benefits and harm of acupuncture for alopecia areata (AA). This review aims to systematically evaluate the efficacy of acupuncture for the management of AA in randomised clinical trials (RCTs).

Methods and analysis

13 databases will be searched from their inception. These include PubMed, AMED, EMBASE, the Cochrane Library, 6 Korean medical databases (Koreanstudies Information Service System, DBPIA, The Town Society of Science Technology, Research Information Sharing Service, KoreaMed and the Korean National Assembly Library), 3 Chinese Databases (China National Knowledge Infrastructure Database (CNKI), the Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and the Wanfang Database). Only randomised clinical trials (RCTs) using any type of acupuncture for AA will be considered. The selection of the studies, data abstraction and validation will be performed independently by two researchers. Methodological quality will be assessed with Cochrane risk of bias.

Dissemination

The systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print. Updates of the review will be conducted to inform and guide the healthcare practice and policy.

Trial registration number

PROSPERO 2015: CRD42015020397.
The Health and Sport Engagement (HASE) Intervention and Evaluation Project: protocol for the design, outcome, process and economic evaluation of a complex community sport intervention to increase levels of physical activity
Authors: Mansfield Louise , Anokye Nana , Fox-Rushby Julia , Kay Tess
Published: October 2015

Introduction

Sport is being promoted to raise population levels of physical activity for health. National sport participation policy focuses on complex community provision tailored to diverse local users. Few quality research studies exist that examine the role of community sport interventions in raising physical activity levels and no research to date has examined the costs and cost-effectiveness of such provision. This study is a protocol for the design, outcome, process and economic evaluation of a complex community sport intervention to increase levels of physical activity, the Health and Sport Engagement (HASE) project part of the national Get Healthy Get Active programme led by Sport England.

Methods and analysis

The HASE study is a collaborative partnership between local community sport deliverers and sport and public health researchers. It involves designing, delivering and evaluating community sport interventions. The aim is to engage previously inactive people in sustained sporting activity for 1×30 min a week and to examine associated health and well-being outcomes. The study uses mixed methods. Outcomes (physical activity, health, well-being costs to individuals) will be measured by a series of self-report questionnaires and attendance data and evaluated using interrupted time series analysis controlling for a range of sociodemographic factors. Resource use will be identified and measured using diaries, interviews and records and presented alongside effectiveness data as incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. A longitudinal process evaluation (focus groups, structured observations, in-depth interview methods) will examine the efficacy of the project for achieving its aim using the principles of thematic analysis.

Ethics and dissemination

The results of this study will be disseminated through peer-reviewed publications, academic conference presentations, Sport England and national public health organisation policy conferences, and practice-based case studies. Ethical approval was obtained through Brunel University London's research ethics committee (reference number RE33—12).
Multimorbidity in elderly hospitalised patients and risk ofClostridium difficileinfection: a retrospective study with the Cumulative Illness Rating Scale (CIRS)
Authors: Ticinesi Andrea , Nouvenne Antonio , Folesani Giuseppina , Prati Beatrice , Morelli Ilaria , Guida Loredana , Turroni Francesca , Ventura Marco , Lauretani Fulvio , Maggio Marcello , Meschi Tiziana
Published: October 2015

Objectives

To identify the role of chronic comorbidities, considered together in a literature-validated index (Cumulative Illness Rating Scale, CIRS), and antibiotic or proton-pump inhibitor (PPI) treatments as risk factors for hospital-acquiredClostridium difficileinfection (CDI) in elderly multimorbid hospitalised patients.

Design

Retrospective cohort study.

Setting

Subacute hospital geriatric care ward in Italy.

Participants

505 (238 male (M), 268 female (F)) elderly (age ≥65) multimorbid patients.

Main outcome measures

The relationship between CDI and CIRS Comorbidity Score, number of comorbidities, antibiotic, antifungal and PPI treatments, and length of hospital stay was assessed through age-adjusted and sex-adjusted and multivariate logistic regression models. The CIRS Comorbidity Score was handled after categorisation in quartiles.

Results

Mean age was 80.7±11.3 years. 43 patients (22 M, 21 F) developed CDI. The prevalence of CDI increased among quartiles of CIRS Comorbidity Score (3.9% first quartile vs 11.1% fourth quartile, age-adjusted and sex-adjusted p=0.03). In the multivariate logistic regression analysis, patients in the highest quartile of CIRS Comorbidity Score (≥17) carried a significantly higher risk of CDI (OR 5.07, 95% CI 1.28 to 20.14, p=0.02) than patients in the lowest quartile (<9). The only other variable significantly associated with CDI was antibiotic therapy (OR 2.62, 95% CI 1.21 to 5.66, p=0.01). PPI treatment was not associated with CDI.

Conclusions

Multimorbidity, measured through CIRS Comorbidity Score, is independently associated with the risk of CDI in a population of elderly patients with prolonged hospital stay.
Protocol for the Care-IS Trial: a randomised controlled trial of a supportive educational intervention for carers of patients with high-grade glioma (HGG)
Authors: Halkett Georgia K B , Lobb Elizabeth A , Miller Lisa , Phillips Jane L , Shaw Thérése , Moorin Rachael , Long Anne , King Anne , Clarke Jenny , Fewster Stephanie , Hudson Peter , Agar Meera , Nowak Anna K
Published: October 2015

Introduction

High-grade glioma (HGG) is a rapidly progressive and debilitating disease. Primary carers experience significant levels of distress which impacts on their experience of caregiving, the quality of care received and the community in terms of the increased reliance on healthcare due to the potential development of complicated grief. This paper describes the protocol for testing the efficacy and feasibility of an intervention for primary carers of patients with HGG in order to improve preparedness to care and reduce carer distress.

Methods

Randomised controlled trial. The target population is carers of patients with HGG who are undergoing combined chemoradiotherapy. The intervention consists of 4 components: (1) initial telephone assessment of unmet needs of the carer, (2) tailoring of a personalised resource folder, (3) home visit, (4) ongoing monthly telephone contact and support for 12 months. The control arm will receive usual care.

Primary hypothesis

This intervention will improve preparedness for caring and reduce carer psychological distress.

Secondary hypothesis

This intervention will reduce carer unmet needs. The longer term aim of the intervention is to reduce patient healthcare resource utilisation and, by doing so, reduce costs. Assessments will be obtained at baseline, 8 weeks post intervention, then 4, 6 and 12 months. Participants will also complete a healthcare utilisation checklist and proxy performance status which will be assessed at baseline and monthly. 240 carers will be recruited. The sample size is 180. Multilevel mixed effects regression models will be applied to test the effect of the intervention.

Ethics

Ethics approval has been gained from Curtin University and the participating sites.

Dissemination

Results will be reported in international peer-reviewed journals.

Trial registration number

Australian and New Zealand Clinical Trials Registration (ACTRN)12612001147875.
miR-19a and SOCS-1 expression in the differential diagnosis of laryngeal (glottic) verrucous squamous cell carcinoma
Authors: Marioni Gino , Agostini Marco , Cappellesso Rocco , Bedin Chiara , Ottaviano Giancarlo , Marchese-Ragona Rosario , Lovato Andrea , Cacco Tommaso , Giacomelli Luciano , Nitti Donato , Blandamura Stella , Stellini Edoardo , de Filippis Cosimo
Published: October 2015

Background

Laryngeal verrucous squamous cell carcinoma (VSCC) is a highly differentiated squamous cell carcinoma (SCC), the diagnosis of which can meet with many pitfalls: benign hyperplastic lesions and conventional SCC are the most important differential diagnoses. The microRNA miR-19a is overexpressed in many solid tumours and regulates the suppressor of cytokine signalling-1 (SOCS-1) expression.

Aims

The main endpoints were to assess miR-19a and SOCS-1 expression in glottic VSCC, and the former's potential role in differentiating between glottic VSCC, conventional SCC and hyperplastic lesions.

Methods

The expression of MiR-19a (by reverse transcription and quantitative real-time PCR) and SOCS-1 (by immunohistochemistry, rabbit polyclonal anti-SOCS-1 antibody) was assessed in 11 consecutive cases of glottic VSCC, 20 of papillary hyperplasia and 42 cases of conventional SCC.

Results

Mean miR-19a expression was significantly higher (p=0.000) in malignant glottic lesions (conventional SCC/VSCC) than in benign conditions. Significant differences in mean miR-19a expression also emerged between conventional SCC and papillary hyperplasia (p=0.000), and between conventional SCC and VSCC (p=0.03). miR-19a expression was not statistically associated with SOCS-1 immunoreactivity or immunostaining intensity in VSCC, conventional SCC or papillary hyperplasia.

Conclusions

Our preliminary outcomes suggest the utility of miR-19a in the challenging differential diagnosis of laryngeal VSCC. Although miR-19a has been found to regulate SOCS-1 expression, this evidence was not confirmed by this investigation.