bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Foamy Virus Reverse Transcriptase by Human Immunodeficiency Virus Type 1 RNase H Inhibitors
Authors: Corona Angela , Schneider Anna , Schweimer Kristian , Rösch Paul , Wöhrl Birgitta M. , Tramontano Enzo
Published: May 2014

RNase H plays an essential role in the replication of human immunodeficiency virus type 1 (HIV-1). Therefore, it is a promising target for drug development. However, the identification of HIV-1 RNase H inhibitors (RHIs) has been hampered by the open morphology of its active site, the limited number of available RNase H crystal structures in complex with inhibitors, and the fact that, due to the high concentrations of Mg2+needed for protein stability, HIV-1 RNase H is not suitable for nuclear magnetic resonance (NMR) inhibitor studies. We recently showed that the RNase H domains of HIV-1 and prototype foamy virus (PFV) reverse transcriptases (RTs) exhibit a high degree of structural similarity. Thus, we examined whether PFV RNase H can serve as an HIV-1 RNase H model for inhibitor interaction studies. Five HIV-1 RHIs inhibited PFV RNase H activity at low-micromolar concentrations similar to those of HIV-1 RNase H, suggesting pocket similarity of the RNase H domains. NMR titration experiments with the PFV RNase H domain and the RHI RDS1643 (6-[1-(4-fluorophenyl)methyl-1H-pyrrol-2-yl)]-2,4-dioxo-5-hexenoic acid ethyl ester) were performed to determine its binding site. Based on these results and previous data,in silicodocking analysis showed a putative RDS1643 binding region that reaches into the PFV RNase H active site. Structural overlays were performed with HIV-1 and PFV RNase H to propose the RDS1643 binding site in HIV-1 RNase H. Our results suggest that this approach can be used to establish PFV RNase H as a model system for HIV-1 RNase H in order to identify putative inhibitor binding sites in HIV-1 RNase H.
In Vivo
Assessment of Drug Efficacy against Mycobacterium abscessus Using the Embryonic Zebrafish Test System
Authors: Bernut Audrey , Le Moigne Vincent , Lesne Tiffany , Lutfalla Georges , Herrmann Jean-Louis , Kremer Laurent
Published: May 2014

Mycobacterium abscessus
is responsible for a wide spectrum of clinical syndromes and is one of the most intrinsically drug-resistant mycobacterial species. Recent evaluation of the
in vivo
therapeutic efficacy of the few potentially active antibiotics against
M. abscessus
was essentially performed using immunocompromised mice. Herein, we assessed the feasibility and sensitivity of fluorescence imaging for monitoring the
in vivo
activity of drugs against acute
M. abscessus
infection using zebrafish embryos. A protocol was developed where clarithromycin and imipenem were directly added to water containing fluorescent
M. abscessus
-infected embryos in a 96-well plate format. The status of the infection with increasing drug concentrations was visualized on a spatiotemporal level. Drug efficacy was assessed quantitatively by measuring the index of protection, the bacterial burden (CFU), and the number of abscesses through fluorescence measurements. Both drugs were active in infected embryos and were capable of significantly increasing embryo survival in a dose-dependent manner. Protection from bacterial killing correlated with restricted mycobacterial growth in the drug-treated larvae and with reduced pathophysiological symptoms, such as the number of abscesses within the brain. In conclusion, we present here a new and efficient method for testing and compare the
in vivo
activity of two clinically relevant drugs based on a fluorescent reporter strain in zebrafish embryos. This approach could be used for rapid determination of the
in vivo
drug susceptibility profile of clinical isolates and to assess the preclinical efficacy of new compounds against
M. abscessus
.
Penetration of Daptomycin into Bone and Synovial Fluid in Joint Replacement
Authors: Montange D. , Berthier F. , Leclerc G. , Serre A. , Jeunet L. , Berard M. , Muret P. , Vettoretti L. , Leroy J. , Hoen B. , Chirouze C.
Published: May 2014

Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant
Staphylococcus aureus
. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array–high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for
Staphylococcus aureus
in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of
Staphylococcus aureus
bone and joint infections.
Posaconazole Tablet Pharmacokinetics: Lack of Effect of Concomitant Medications Altering Gastric pH and Gastric Motility in Healthy Subjects
Authors: Kraft Walter K. , Chang Peter S. , van Iersel Marlou L. P. S. , Waskin Hetty , Krishna Gopal , Kersemaekers Wendy M.
Published: May 2014

Posaconazole oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new posaconazole tablet formulation has demonstrated improved bioavailability over the oral suspension in healthy adults in a fasting state. This study evaluated the effects of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and gastric motility (metoclopramide) on the pharmacokinetics of posaconazole tablets. This was a prospective open-label 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg dose (4 100-mg tablets) of posaconazole was administered alone or with 20 ml antacid (2 g of aluminum hydroxide and 2 g of magnesium hydroxide), ranitidine (150 mg), esomeprazole (40 mg), or metoclopramide (15 mg). There was a ≥10-day washout between treatment periods. Posaconazole exposure, time to maximum concentration of drug in serum (
T
max
), and apparent terminal half-life (
t
1/2
) were similar when posaconazole was administered alone or with medications affecting gastric pH and gastric motility. Geometric mean ratios (90% confidence intervals [CIs]) of the area under the concentration-time curve from time zero to infinity (AUC
0–inf
) (posaconazole with medications affecting gastric pH and gastric motility versus posaconazole alone) were 1.03 (0.88–1.20) with antacid, 0.97 (0.84–1.12) with ranitidine, 1.01 (0.87–1.17) with esomeprazole, and 0.93 (0.79–1.09) with metoclopramide. Geometric mean ratios (90% CIs) of the maximum concentration of drug in serum (
C
max
) were 1.06 (0.90–1.26) with antacid, 1.04 (0.88–1.23) with ranitidine, 1.05 (0.89–1.24) with esomeprazole, and 0.86 (0.73–1.02) with metoclopramide. In summary, in healthy volunteers, the pharmacokinetics of a single 400-mg dose of posaconazole tablets was not altered to a clinically meaningful extent when posaconazole was administered alone or with medications affecting gastric pH or gastric motility.
Pediatric Infection and Intestinal Carriage Due to Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae
Authors: Zerr Danielle M. , Qin Xuan , Oron Assaf P. , Adler Amanda L. , Wolter Daniel J. , Berry Jessica E. , Hoffman Lucas , Weissman Scott J.
Published: May 2014

The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistantEnterobacteriaceaein children with index infections with these organisms. Patients with resistantEscherichia coliorKlebsiellabacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistantE. coli(n= 92) orKlebsiella(n= 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistantEnterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistantEnterobacteriaceaeinfections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistantEnterobacteriaceae, but carriage and reinfection with different resistantEnterobacteriaceaestrains also occurred.
Limited Activity of Clofazimine as a Single Drug in a Mouse Model of Tuberculosis Exhibiting Caseous Necrotic Granulomas
Authors: Irwin Scott M. , Gruppo Veronica , Brooks Elizabeth , Gilliland Janet , Scherman Michael , Reichlen Matthew J. , Leistikow Rachel , Kramnik Igor , Nuermberger Eric L. , Voskuil Martin I. , Lenaerts Anne J.
Published: May 2014

New drugs and drugs with a novel mechanism of action are desperately needed to shorten the duration of tuberculosis treatment, to prevent the emergence of drug resistance, and to treat multiple-drug-resistant strains of
Mycobacterium tuberculosis
. Recently, there has been renewed interest in clofazimine (CFZ). In this study, we utilized the C3HeB/FeJ mouse model, possessing highly organized, hypoxic pulmonary granulomas with caseous necrosis, to evaluate CFZ monotherapy in comparison to results with BALB/c mice, which form only multifocal, coalescing cellular aggregates devoid of caseous necrosis. While CFZ treatment was highly effective in BALB/c mice, its activity was attenuated in the lungs of C3HeB/FeJ mice. This lack of efficacy was directly related to the pathological progression of disease in these mice, since administration of CFZ prior to the formation of hypoxic, necrotic granulomas reconstituted bactericidal activity in this mouse strain. These results support the continued use of mouse models of tuberculosis infection which exhibit a granulomatous response in the lungs that more closely resembles the pathology found in human disease.
Anti-Candida Activity of Fluoxetine Alone and Combined with Fluconazole: a Synergistic Action against Fluconazole-Resistant Strains
Authors: Oliveira Ana S. , Gaspar Carlos A. , Palmeira-de-Oliveira Rita , Martinez-de-Oliveira José , Palmeira-de-Oliveira Ana
Published: May 2014

The purpose of this work was to determine the antimicrobial activity of fluoxetine, alone and combined with fluconazole, against 29
Candida
strains isolated from patients with vulvovaginal candidiasis. MIC and minimum lethal concentration values ranged from 9.8 to 625 μg/ml for all strains tested. The combination of fluconazole with fluoxetine resulted in synergistic activity against six
Candida
strains, with fractional inhibitory index (FIX) values between 0.15 and 0.31. An indifferent effect was found for the remaining strains, with FIX values between 0.63 and 1.
Impact of Different Antimicrobial Therapies on Clinical and Fiscal Outcomes of Patients with Bacteremia Due to Vancomycin-Resistant Enterococci
Authors: Hayakawa Kayoko , Martin Emily T. , Gudur Uma Mahesh , Marchaim Dror , Dalle Dalia , Alshabani Khaled , Muppavarapu Kalyan Srinivas , Jaydev Fnu , Bathina Pradeep , Sundaragiri Pranathi Rao , Rajuri Shashi Dhar , Khatri Jaikumar , Pogue Jason M. , Lephart Paul R. , Rybak Michael J. , Kaye Keith S.
Published: May 2014

Vancomycin-resistant enterococci (VRE) are a growing health problem, and uncertainties exist regarding the optimal therapy for bloodstream infection due to VRE. We conducted systematic comparative evaluations of the impact of different antimicrobial therapies on the outcomes of patients with bloodstream infections due to VRE. A retrospective study from January 2008 to October 2010 was conducted at Detroit Medical Center. Unique patients with blood cultures due to VRE were included and reviewed. Three major therapeutic classes were analyzed: daptomycin, linezolid, and β-lactams. Three multivariate models were conducted for each outcome, matching for a propensity score predicting the likelihood of receipt of one of the therapeutic classes. A total of 225 cases of bacteremia due to VRE were included, including 86 (38.2%) cases of VR
Enterococcus faecalis
and 139 (61.8%) of VR
Enterococcus faecium
. Bacteremia due to VR
E. faecalis
was more frequent among subjects treated with β-lactams than among those treated with daptomycin or linezolid. The median dose of daptomycin was 6 mg/kg of body weight (range, 6 to 12 mg/kg). After controlling for propensity score and bacteremia due to VR
E. faecalis
, differences in mortality were nonsignificant among the treatment groups. Therapy with daptomycin was associated with higher median variable direct cost per day than that for linezolid. This large study revealed the three therapeutic classes (daptomycin, linezolid, and β-lactams) are similarly efficacious in the treatment of bacteremia due to susceptible strains of VRE.
Reduced Emergence of Isoniazid Resistance with Concurrent Use of Thioridazine against Acute Murine Tuberculosis
Authors: Dutta Noton K. , Pinn Michael L. , Karakousis Petros C.
Published: May 2014

The repurposing of existing drugs is being pursued as a means by which to accelerate the development of novel regimens for the treatment of drug-susceptible and drug-resistant tuberculosis (TB). In the current study, we assessed the activity of the antipsychotic drug thioridazine (TRZ) in combination with the standard regimen in a well-validated murine TB model. Single-dose and steady-state pharmacokinetic studies were performed in BALB/c mice to establish human-equivalent doses of TRZ. To determine the bactericidal activity of TRZ against TB in BALB/c mice, three separate studies were performed, including a dose-ranging study of TRZ monotherapy and efficacy studies of human-equivalent doses of TRZ with and without isoniazid (INH) or rifampin (RIF). Therapeutic efficacy was assessed by the change in mycobacterial load in the lung. The human-equivalent dose of thioridazine was determined to be 25 mg/kg of body weight, which was well tolerated in mice. TRZ was found to accumulate at high concentrations in lung tissue relative to serum levels. We observed modest synergy during coadministration of TRZ with INH, and the addition of TRZ reduced the emergence of INH-resistant mutants in mouse lungs. In conclusion, this study further illustrates the opportunity to reevaluate the contribution of TRZ to the sterilizing activity of combination regimens to prevent the emergence of drug-resistant
M. tuberculosis
.
Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses
Authors: Cheng Shaoji , Clancy Cornelius J. , Hartman Douglas J. , Hao Binghua , Nguyen M. Hong
Published: May 2014

The pathogenesis of
Candida glabrata
infections is poorly understood. We studied the pathogenesis of intra-abdominal candidiasis (IAC) in mice that were infected intraperitoneally with
C. glabrata
and sterile feces.
C. glabrata
BG2 (5 × 10
8
CFU) caused a 100% mortality rate. Sublethal inocula of BG2 (1 × 10
8
or 1 × 10
7
CFU) caused peritonitis that progressed to abscesses. Three clinical
C. glabrata
strains (5 × 10
8
CFU) caused 80 to 100% mortality rates, while a fourth (strain 346) caused a 29% mortality rate. Following sublethal inocula (1 × 10
7
CFU), the intra-abscess burdens of virulent strain 356 were ∼1 log greater than those of strain 346. A
C. glabrata
Δ
plb1-2
mutant (phospholipase B genes disrupted) killed mice as well as BG2 did. When sublethal inocula were used, however, the Δ
plb1-2
mutant was associated with more rapid abscess resolution and lower intra-abscess burdens; these findings were reversed by
PLB1
and
PLB2
reinsertion. The Δ
plb1-2
mutant was also more susceptible than BG2 to killing by human neutrophils
in vitro
. BG2 and the Δ
plb1-2
mutant were indistinguishable during hematogenously disseminated candidiasis.
C. albicans
SC5314 was more virulent than
C. glabrata
BG2 during IAC, causing a 100% mortality rate following a challenge with 5 × 10
7
CFU. In contrast, a sublethal inoculum (1 × 10
7
CFU) of BG2 caused less neutrophil infiltration and greater burdens in peritoneal fluid than SC5314 did and abscesses that persisted longer and contained greater burdens. In conclusion, a mouse model of
C. glabrata
IAC mimics disease in humans and distinguishes the relative virulence of clinical and gene disruption strains.
C. glabrata
differed from
C. albicans
during IAC by being less lethal and eliciting dampened neutrophil responses but resulting in more persistent peritonitis and abscesses.
Bile Acids and Bicarbonate Inversely Regulate Intracellular Cyclic di-GMP in Vibrio cholerae
Authors: Koestler Benjamin J. , Waters Christopher M.
Published: May 2014

Vibrio cholerae
is a Gram-negative bacterium that persists in aquatic reservoirs and causes the diarrheal disease cholera upon entry into a human host.
V. cholerae
employs the second messenger molecule 3′,5′-cyclic diguanylic acid (c-di-GMP) to transition between these two distinct lifestyles. c-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and hydrolyzed by phosphodiesterase (PDE) enzymes. Bacteria typically encode many different DGCs and PDEs within their genomes. Presumably, each enzyme senses and responds to cognate environmental cues by alteration of enzymatic activity. c-di-GMP represses the expression of virulence factors in
V. cholerae
, and it is predicted that the intracellular concentration of c-di-GMP is low during infection. Contrary to this model, we found that bile acids, a prevalent constituent of the human proximal small intestine, increase intracellular c-di-GMP in
V. cholerae
. We identified four c-di-GMP turnover enzymes that contribute to increased intracellular c-di-GMP in the presence of bile acids, and deletion of these enzymes eliminates the bile induction of c-di-GMP and biofilm formation. Furthermore, this bile-mediated increase in c-di-GMP is quenched by bicarbonate, the intestinal pH buffer secreted by intestinal epithelial cells. Our results lead us to propose that
V. cholerae
senses distinct microenvironments within the small intestine using bile and bicarbonate as chemical cues and responds by modulating the intracellular concentration of c-di-GMP.
Identification and Characterization of a Peculiar
vtx2
-Converting Phage Frequently Present in Verocytotoxin-Producing Escherichia coli O157 Isolated from Human Infections
Authors: Tozzoli Rosangela , Grande Laura , Michelacci Valeria , Fioravanti Rosa , Gally David , Xu Xuefang , La Ragione Roberto , Anjum Muna , Wu Guanghui , Caprioli Alfredo , Morabito Stefano
Published: May 2014

Certain verocytotoxin-producing
Escherichia coli
(VTEC) O157 phage types (PTs), such as PT8 and PT2, are associated with severe human infections, while others, such as PT21, seem to be restricted to cattle. In an attempt to delve into the mechanisms underlying such a differential distribution of PTs, we performed microarray comparison of human PT8 and animal PT21 VTEC O157 isolates. The main differences observed were in the
vtx2
-converting phages, with the PT21 strains bearing a phage identical to that present in the reference strain EDL933, BP933W, and all the PT8 isolates displaying lack of hybridization in some regions of the phage genome. We focused on the region spanning the
gam
and
cII
genes and developed a PCR tool to investigate the presence of PT8-like phages in a panel of VTEC O157 strains belonging to different PTs and determined that a
vtx2
phage reacting with the primers deployed, which we named Φ8, was more frequent in VTEC O157 strains from human disease than in bovine strains. No differences were observed in the production of the VT2 mRNA when Φ8-positive strains were compared with VTEC O157 possessing BP933W. Nevertheless, we show that the
gam-cII
region of phage Φ8 might carry genetic determinants downregulating the transcription of the genes encoding the components of the type III secretion system borne on the locus of enterocyte effacement pathogenicity island.
Comparative cervical profiles of adult and under-18 front-row rugby players: implications for playing policy
Authors: Hamilton D F , Gatherer D , Robson J , Graham N , Rennie N , MacLean J G B , Simpson A H R W
Published: May 2014

Objective

To compare the cervical isometric strength, fatigue endurance and range of motion of adult and under-18 age-grade front-row rugby players to inform the development of a safe age group policy with particular reference to scrummaging.

Design

Cross-sectional cohort study.

Setting

‘Field testing’ at Murrayfield stadium.

Participants

30 high-performance under-18 players and 22 adult front-row rugby players.

Outcome measures

Isometric neck strength, height, weight and grip strength.

Results

Youth players demonstrated the same height and grip strength as the adult players; however, the adults were significantly heavier and demonstrated substantially greater isometric strength (p<0.001). Only two of the ‘elite’ younger players could match the adult mean cervical isometric strength value. In contrast to school age players in general, grip strength was poorly associated with neck strength (r=0.2) in front-row players; instead, player weight (r=0.4) and the number of years’ experience of playing in the front row (r=0.5) were the only relevant factors in multivariate modelling of cervical strength (R2=0.3).

Conclusions

Extreme forces are generated between opposing front rows in the scrum and avoidance of mismatch is important if the risk of injury is to be minimised. Although elite youth front-row rugby players demonstrate the same peripheral strength as their adult counterparts on grip testing, the adults demonstrate significantly greater cervical strength. If older youths and adults are to play together, such findings have to be noted in the development of age group policies with particular reference to the scrum.
‘Only connect’: the case for public health humanities
Authors: Saffran Lise
Published: May 2014

Humanities in health has until now been primarily understood to mean humanities in medicine and has generally failed to include public health. I will argue in this paper that the common justifications for the former—including increased empathy among practitioners—are at least as applicable, if not more, to the latter. Growing emphasis on the social determinants of health and cultural competency in public health require public health students and professionals to develop a nuanced understanding of the influence of social context on health behaviour and to empathise with people in difficult circumstances. Literary fiction has been demonstrated to have an impact on skills related to empathy and social intelligence. Further, translating epidemiological evidence into public policy is a core task of public health and there is a growing body of research to indicate that statistical evidence is more persuasive when combined with narrative evidence. In this article I explore similarities and differences between proposed humanities in public health and programmes in humanities in medicine and highlight research gaps and possible implications of a more expansive view of humanities in health.
N-methylpyrazinium ion derivatives of an iron (II) dimethylglyoximatoborate complex
Authors: Stynes Dennis V. , Doan Tran Ngoc
Published: May 2014

New iron (II) bis(dimethylglyoximatoborate) complexes [Fe(dmgBR2)2(MePz)L]+, R = 4-methoxyphenyl and L = N-methylpyrazinium ion (MePz), tetracyanoethylene (tcne), carbon monoxide, or pyridine are described. The dicationic bis MePz derivative is the first example of a complex containing two small cationic ligands. All adopt the C2vconformation in solution, which serves to sandwich one axial ligand between 4-methoxyphenyl groups. Charge transfer spectra, conformational dynamics, and electrospray mass spectrometry studies are reported. Equilibrium and rate constants for ligand substitution reactions give a binding order trans to MePz: MePz ∼ CO < pyridine, CH3CN.
New information on the rare horned dinosaurArrhinoceratops brachyops(Ornithischia: Ceratopsidae) from the Upper Cretaceous of Alberta, Canada
Authors: Mallon Jordan C. , Holmes Robert , Anderson Jason S. , Farke Andrew A. , Evans David C.
Published: May 2014

Arrhinoceratops brachyops is a poorly understood chasmosaurine ceratopsid from the Upper Cretaceous Horseshoe Canyon Formation of Alberta, previously described on the basis of only a single skull. Here, we report on a second specimen attributable to this species, including a relatively complete skull, syncervical, and partial left forelimb. This second specimen clarifies aspects of morphology not visible in the holotype, and also elucidates variation in A. brachyops. The species is distinguished by a square-shaped triangular process of the premaxilla, a steeply inclined triturating surface of the predentary, and a triangular nasal horncore in horizontal section. The dentary is also distinctive in bearing a bony lateral ridge similar to that of Anchiceratops ornatus, but more strongly developed. Phylogenetic analysis cannot resolve the relationships of Arrhinoceratops beyond the level of Chasmosaurinae, owing to both missing data and conflicting characters. However, we do find some support for a deep split within Chasmosaurinae, contrary to conventional topologies. We also report on other fragmentary specimens plausibly attributable to A. brachyops that suggest a minimum age range of approximately 750 ka for this species.
The economics of timber and bioenergy production and carbon storage in Scots pine stands
Authors: Pihlainen Sampo , Tahvonen Olli , Niinimäki Sami
Published: May 2014

We optimize timber and bioenergy production combined with carbon storage in Scots pine (Pinus sylvestris L.) stands, using an ecological-economic model. Forest growth is specified with a highly detailed process-based growth specification, and optimization is based on an efficient generalized pattern search algorithm. The optimized variables are rotation length, initial stand density, and the number, intensity, timing, and type of thinnings. The carbon pool includes all aboveground biomass (including dead trees) and timber products. The analysis includes the comparison of different carbon subsidy systems. The results are presented for the most relevant site types and thermal zones in Finland. Carbon storage increases the optimal rotation length, number of thinnings, and initial density at all forest sites. Carbon storage effects on stand density and harvests are strongest at poor sites. Timber output increases with carbon price. High natural mortality in our results implies notable carbon storage in dead trees and a positive contribution to biodiversity. The stand-level analysis is extended to a cost-efficient national-level carbon storage plan.
Specific inhibitors for identifying pathways for methane production from carbon monoxide by a nonadapted anaerobic mixed culture
Authors: Navarro Silvia Sancho , Cimpoia Ruxandra , Bruant Guillaume , Guiot Serge R.
Published: May 2014

Specific inhibitors such as 2-bromoethanesulfonate (BES) and vancomycin were employed in activity batch tests to decipher metabolic pathways that are preferentially used by a mixed anaerobic consortium (sludge from an anaerobic digester) to transform carbon monoxide (CO) into methane (CH4). We first evaluated the inhibitory effect of both BES and vancomycin on the microbial community, as well as the efficiency and stability of vancomycin at 35 °C, over time. The activity tests with CO2–H2, CO, glucose, acetate, formate, propionate, butyrate, methanol, and ethanol showed that vancomycin does not inhibit some Gram-negative bacteria, and 50 mmol/L BES effectively blocks CH4production in the sludge. However, when sludge was incubated with propionate, butyrate, methanol, or ethanol as the sole energy and carbon source, methanogenesis was only partially inhibited by BES. Separate tests showed that 0.07 mmol/L vancomycin is enough to maintain its inhibitory efficiency and stability in the population for at least 32 days at 35 °C. Using the inhibitors above, it was demonstrated that CO conversion to CH4is an indirect, 2-step process, in which the CO is converted first to acetate and subsequently to CH4.
Effect of thermal annealing in a-InxGa1–xN films prepared by reactive RF-sputtering
Authors: Suzuki Toshimasa , Katayama Ruichi , Hibino Shun , Kato Yoshinori , Ohashi Fumitaka , Itoh Takashi , Nonomura Shuichi
Published: May 2014

We deposited amorphous indium gallium nitride (a-InxGa1–xN) films at room temperature by reactive radio frequency sputtering with GaN and InN targets and investigated the change of their properties from thermal annealing at annealing temperatures, Ta, below 200 °C. A large change in the indium and nitrogen composition ratios was not observed by thermal annealing at a Ta below 200 °C. In the X-ray diffraction patterns of the films annealed at a Ta below 200 °C, no perceivable peaks assigned to crystalline InxGa1–xN were found. The photoconductivty, σp, increased with an increase in Ta. On the other hand, the increase of the dark conductivity, σd, was very small with an increase in Ta below 200 °C. As a result, the photosensitivity, σp/σd, increased from 252 to 2500 by thermal annealing at a Ta of 200 °C.
SCREEN IMAGE SEGMENTATION AND CORRECTION FOR A COMPUTER DISPLAY
Authors: CHEN YUNG-SHENG , LIN KUN-LI
Published: May 2014

Perception of content displayed on the screen of a computer display using computer vision is a challenging topic if the treated target is changed from physical world to digital world. Screen area from the given computer display image should be segmented and corrected primarily before perceiving the content displayed on the screen. An automatic approach is proposed to the segmentation and deformation correction of screen area for a computer display image. Due to some inherent characteristics existing on ordinary computer displays, the segmentation can be performed by contour tracing. After contouring the screen area, its four corner locations can be readily identified. By approximating the obtained corners to the closest normal screen region, the deformed screen image can be further restored with affine transformation. As a computer vision application on the "look at" screen image, the effectively segmented screen region can be fixed after a little time. The experiments demonstrate that about 70% cases can be fixed under 33 processed frames, others under 51 processed frames, and thus confirm the feasibility of the proposed approach.
BERGE–ZHUKOVSKII EQUILIBRIA: EXISTENCE AND CHARACTERIZATION
Authors: NESSAH RABIA , LARBANI MOUSSA
Published: May 2014

In this paper, we investigate the existence of Berge–Zhukovskii equilibrium in general normal form games. We characterize its existence via the existence of a symmetric Nash equilibrium of some n-person subgame derived of the initial game. The significance of the obtained results is illustrated by two applications. One in economy with environmental externalities and the other in oligopoly markets.
Spatio–temporal entanglement of twin photons: An intuitive picture
Authors: Gatti Alessandra , Caspani Lucia , Corti Tommaso , Brambilla Enrico , Jedrkiewicz Ottavia
Published: May 2014

We draw an intuitive picture of the spatio–temporal properties of the entangled state of twin photons, where they are described as classical wave-packets. This picture predicts a precise relation between their temporal and transverse spatial separations at the crystal output. The space-time coupling described by classical arguments turns out to determine in a precise way the spatio–temporal structure of the quantum entanglement, analyzed by means of the biphotonic correlation and of the Schmidt dimensionality of the entanglement.
Bracket states for communication protocols with coherent states
Authors: Allevi Alessia , Olivares Stefano , Bondani Maria
Published: May 2014

We present the generation and characterization of the class of bracket states, namely phase-sensitive mixtures of coherent states exhibiting symmetry properties in the phase-space description. A bracket state can be seen as the statistical ensemble arriving at a receiver in a typical coherent-state-based communication channel. We show that when a bracket state is mixed at a beam splitter with a local oscillator, both the emerging beams exhibit a Fano factor larger than 1 and dependent on the relative phase between the input state and the local oscillator. We discuss the possibility to exploit this dependence to monitor the phase difference for the enhancement of the performances of a simple communication scheme based on direct detection. Our experimental setup involves linear optical elements and a pair of photon-number-resolving detectors operated in the mesoscopic photon-number domain.
Computational study on zinc porphyrin analogs for use in dye-sensitized solar cells
Authors: Xia Hong-Qiang , Chen Jie , Bai Fu-Quan , Zhang Hong-Xing
Published: May 2014

The density functional theory (DFT) and time-dependent DFT (TD-DFT) approaches have been applied to obtain the optimized geometries, electronic structures, molecular orbitals and absorption spectra of a series of meso-substituted zinc porphyrin analogs with phenyl and thiophene groups as the π bridging unit and cyanoacrylic acid as the acceptor unit. The results showed that the introduction of thiophene group increases the orbital splitting and changes the absorption spectra properties significantly. It is indicated that when there is only one thiophene group included in the π bridge, the oscillator strength of B absorption band is much stronger. The increasing length of thiophene chain just changes the scope of specific absorption enhancement. The effect of attaching an additional electron-donating group diphenylamine instead of phenyl to the porphyrin core also has been shown. It is found that the diphenylamine group reduces the band gap, and leads to facile intramolecular charge transfer from diphenylamine and porphyrin ring unit to acceptor unit. These kinds of zinc porphyrin analogs have the LUMO energy close to the conduction band of TiO 2 and more red-shifted absorption spectrum compared with phenyl substituted analogs.
DIFFERENCES IN THE EXPRESSION OF INNATE IMMUNE RESPONSE-MODULATING GENES IN BLOOD MONOCYTES BETWEEN SUBCLINICALLY PORCINE CIRCOVIRUS TYPE 2 (PCV2)-INFECTED AND PCV2-FREE PIGS PRIOR TO AND AFTER LIPOPOLYSACCHARIDE STIMULATIONIN VITRO
Authors: Tsai Yi-Chieh , Jeng Chian-Ren , Chang Chih-Cheng , Hsiao Shih-Hsuan , Chang Hui-Wen , Lin Chun-Ming , Chia Mi-Yuan , Wan Cho-Hua , Pang Victor Fei
Published: May 2014

The objective of the present study was to characterize and compare the differences in gene expression associated with innate immune response of blood monocytes (Mos) between healthy subclinically PCV2-infected and PCV2-free pigs prior to and after lipopolysaccharide (LPS) stimulation in vitro by relative quantitative real-time PCR (q-rt-PCR). Genes coding for 24 innate molecules, including toll-like receptors (TLRs), interferon-regulatory factors (IRFs), nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) and pro-inflammatory cytokines were evaluated. When compared with PCV2-free pigs, Mos from subclinically PCV2-infected pigs showed significantly lower mRNA expression levels in TLR-9, IRF-3, IRF-6, IRF-7, IL-6, IL-12p35, IL-12p40 and IFN-α under no further stimulation. Following LPS stimulation in vitro, a broad and/or obvious reduction in TLRs, IRFs, IL-12 and IFN-α along with increase in IL-1α, IL-6, IL-8, IL-10 and/or TNF-α were seen in both PCV2-free and subclinically PCV2-infected pigs; when compared with PCV2-free pigs, the subclinically PCV2-infected pigs had significantly higher expression levels in TLR-10 and IRF-1 but lower expression levels in IRF-6, IL-1α and IL-12p40. On the contrary, the expression level of NF-κB was consistently higher in subclinically PCV2-infected pigs than in PCV2-free pigs with or without LPS stimulation. The changes seen in the present study suggest that the subclinically PCV2-infected pigs may look healthy clinically, but their innate immunity has become dis-regulated or is in an improper status. The adverse condition may become even worse when exposed to certain bacterial products such as endotoxin. Such alterations in the innate immune system may make the subclinically PCV2-infected pigs more vulnerable to the secondary infection and subsequent PCV2-associated disease development.
The Role of the Actin Cytoskeleton and Lipid Rafts in the Localization and Function of the ABCC1 Transporter
Authors: Kok Jan Willem , Klappe Karin , Hummel Ina
Published: May 2014

ATP-binding cassette (ABC) transporters are known to be important factors in multidrug resistance of tumor cells. Lipid rafts have been implicated in their localization in the plasma membrane, where they function as drug efflux pumps. This specific localization in rafts may support the activity of ABC/Abc transporters. This raises questions regarding the nature and composition of the lipid rafts that harbor ABC/Abc transporters and the dependence of ABC/Abc transporters—concerning their localization and activity—on lipid raft constituents. Here we review our work of the past 10 years aimed at evaluating whether ABC/Abc transporters are dependent on a particular membrane environment for their function. What is the nature of this membrane environment and which of the lipid raft constituents are important for this dependency? It turns out that cortical actin is of major importance for stabilizing the localization and function of the ABC/Abc transporter, provided it is localized in an actin-dependent subtype of lipid rafts, as is the case for human ABCC1/multidrug resistance-related protein 1 (MRP1) and rodent Abcc1/Mrp1 but not human ABCB1/P-glycoprotein (PGP). On the other hand, sphingolipids do not appear to be modulators of ABCC1/MRP1 (or Abcc1/Mrp1), even though they are coregulated during drug resistance development.
Using Eye Tracking to Assess Reading Performance in Patients with Glaucoma: A Within-Person Study
Authors: Smith Nicholas D. , Glen Fiona C. , Mönter Vera M. , Crabb David P.
Published: May 2014

Reading is often cited as a demanding task for patients with glaucomatous visual field (VF) loss, yet reading speed varies widely between patients and does not appear to be predicted by standard visual function measures. Thiswithin-personstudy aimed to investigate reading duration and eye movements when reading short passages of text in a patient’s worse eye (most VF damage) when compared to their better eye (least VF damage). Reading duration and saccade rate were significantly different on average in the worse eye when compared to the better eye (P<0.001) in 14 patients with glaucoma that had median (interquartile range) between-eye difference in mean deviation (MD; a standard clinical measure for VF loss) of 9.8 (8.3 to 14.8) dB; differences were not related to the size of the difference in MD between eyes. Patients with a more pronounced effect of longer reading duration on their worse eye made a larger proportion of “regressions” (backward saccades) and “unknown” EMs (not adhering to expected reading patterns) when reading with the worse eye when compared to the better eye. A between-eye study in patients with asymmetric disease, coupled with eye tracking, provides a useful experimental design for exploring reading performance in glaucoma.
Release of the Diclofenac Sodium by Nanofibers of Poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) Obtained from Electrospinning and Solution Blow Spinning
Authors: Souza Michelle Andrade , Sakamoto Karine Yamamura , Mattoso Luiz Henrique Capparelli
Published: May 2014

Electrospun fibers are explored as a new system for controlled drug delivery. Novel techniques capable of obtaining polymer nanofibers have been reported in the literature. They include solution blow spinning (SBS), which is a technique to produce polymer nanofibers in the same range as electrospinning, using pressurized gas instead of high voltage. The present study investigates release characteristics of diclofenac sodium encapsulated at three concentrations (5, 10, and 20% w/v) in poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) nanofibers made by electrospinning and SBS and determines the drug’s effect on fiber morphology and structural properties. PHBV nanofibers were characterized using scanning electronic microscopy, differential scanning calorimetry, and X‐ray diffraction, and the release profile was examined via UV‐Vis spectrophotometry. Both electrospinning and SBS encapsulated diclofenac sodium in PHBV membranes efficiently and effectively. The profile of the in vitro release of diclofenac sodium was dependent on drug concentration and temperature. The drug reduced crystallinity and increased flexibility.
Traffic Pattern Prediction and Spectrum Allocation with Multiple Channel Width in Cognitive Cellular Networks
Authors: Wang Lu , Zhou Zhong , Wu Wei
Published: May 2014

This paper investigates the traffic pattern prediction based on seasonal deviation and spectrum reallocation with multiple channel width in cognitive cellular networks. Compared to the existing approaches based on time series or classical statistic method, the binary exponential deviation offset prediction proposed in this paper focuses on the increment or decrement on every sampling point during an exponential offset period. Then the deviations will be revised at different levels in the next prediction process. The proposed approach is validated with some real end-user data from a WiFi network and simulation experiments. Based on such a precise prediction, we allocate the channels with different bandwidth to end-users according to diverse quality-of-service (QoS), which increases both the system's profits and actual spectrum utilization. The multidimensional bounded knapsack problem is introduced to divide channels, to which the proposed balance between value density and request probability strategy gets the approximate solution. The simulation experiment results show its good performance in not only utility but also spectrum utilization of the base-stations, especially when the resources are deficient.
Hot Corrosion Behaviour of Detonation Gun Sprayed Stellite-6 and Stellite-21 Coating on Boiler Steel SAE 431 at 900°C
Authors: Mishra N. K. , Rai A. K. , Mishra S. B. , Kumar R.
Published: May 2014

Hot corrosion is the serious problem in gas turbines, superheaters, and economizers of coal-fired boilers. It occurs due to the usage of wide range of fuels such as coal, oil, and so on at the elevated temperatures. Protective coatings on boiler steels are used under such environments. In the present investigation, Stellite-6 and Stellite-21 coatings have been deposited on boiler steel SAE 431 by detonation gun method. The hot corrosion performance of Stellite-6 and Stellite-21 coated as well as uncoated SAE 431 steel has been evaluated in aggressive environment of Na2SO4-82%Fe2(SO4)3under cyclic conditions at an elevated temperature of 900°C for total duration of 50 cycles. Thermogravimetric technique was used to approximate the kinetics of hot corrosion. Stellite-6 coating imparted better hot corrosion resistance than Stellite-21 coating in the given environment. Scanning electron microscopy was used to characterize the surface of hot corrosion products.
Dynamics of Foreign Exchange Networks: A Time-Varying Copula Approach
Authors: Wang Gang-Jin , Xie Chi , Zhang Peng , Han Feng , Chen Shou
Published: May 2014

Based on a time-varying copula approach and the minimum spanning tree (MST) method, we propose a time-varying correlation network-based approach to investigate dynamics of foreign exchange (FX) networks. In piratical terms, we choose the daily FX rates of 42 major currencies in the international FX market during the period of 2005–2012 as the empirical data. The empirical results show that (i) the distributions of cross-correlation coefficients (distances) in the international FX market (network) are fat-tailed and negatively skewed; (ii) financial crises during the analyzed period have a great effect on the FX network’s topology structure and lead to the US dollar becoming more centered in the MST; (iii) the topological measures of the FX network show a large fluctuation and display long-range correlations; (iv) the FX network has a long-term memory effect and presents a scale-free behavior in the most of time; and (v) a great majority of links between currencies in the international FX market survive from one time to the next, and multistep survive rates of FX networks drop sharply as the time increases.
Power Geometric Operators of Hesitant Multiplicative Fuzzy Numbers and Their Application to Multiple Attribute Group Decision Making
Authors: Wang Lei , Ni Mingfang , Yu Zhanke , Zhu Lei
Published: May 2014

Multiplicative relations are one of most powerful techniques to express the preferences over alternatives (or criteria). In this paper, we propose a wide range of hesitant multiplicative fuzzy power aggregation geometric operators on multiattribute group decision making (MAGDM) problems for hesitant multiplicative information. In this paper, we first develop some compatibility measures for hesitant multiplicative fuzzy numbers, based on which the corresponding support measures can be obtained. Then we propose several aggregation techniques, and investigate their properties. In the end, we develop two approaches for multiple attribute group decision making with hesitant multiplicative fuzzy information and illustrate a real world example to show the behavior of the proposed operators.
Resizing Technique‐Based Hybrid Genetic Algorithm for Optimal Drift Design of Multistory Steel Frame Buildings
Authors: Park Hyo Seon , Kwon Eunmi , Kim Yousok , Choi Se Woon
Published: May 2014

Since genetic algorithm‐based optimization methods are computationally expensive for practical use in the field of structural optimization, a resizing technique‐based hybrid genetic algorithm for the drift design of multistory steel frame buildings is proposed to increase the convergence speed of genetic algorithms. To reduce the number of structural analyses required for the convergence, a genetic algorithm is combined with a resizing technique that is an efficient optimal technique to control the drift of buildings without the repetitive structural analysis. The resizing technique‐based hybrid genetic algorithm proposed in this paper is applied to the minimum weight design of three steel frame buildings. To evaluate the performance of the algorithm, optimum weights, computational times, and generation numbers from the proposed algorithm are compared with those from a genetic algorithm. Based on the comparisons, it is concluded that the hybrid genetic algorithm shows clear improvements in convergence properties.