We have determined the concentrations of carbonyl sulfide (OCS), dimethylsulfide, and carbon disulf ide (CS2) in the breath of a group of cystic fibrosis (CF) patients and one of healthy controls. At ...the detection sensitivity in these experiments, room air always contained measurable quantities of these three gases. For each subject the inhaled room concentrations were subtracted from the time-coincident concentrations in exhaled breath air. The most significant differences between the CF and control cohorts in these breath-minus-room values were found for OCS. The control group demonstrated a net uptake of$250 \pm 20$parts-per-trillion-by-volume (pptv), whereas the CF cohort had a net uptake of$110 \pm 60 pptv$(P = 0.00003). Three CF patients exhaled more OCS than they inhaled from the room. The OCS concentrations in the CF cohort were strongly correlated with pulmonary function. The dimethylsulfide concentrations in breath were greatly enhanced over ambient but no significant difference was observed between the CF and healthy control groups. The net (breath minus room) CS2concentrations for individuals ranged between +180 and -100 pptv. They were slightly greater in the CF cohort ($+26 \pm 38 pptv$) vs. the control group ($-17 \pm 15 pptv$; P = 0.04). Lung disease in CF is accompanied by the subsistence of chronic bacterial infections. Sulfides are known to be produced by bacteria in various systems and were therefore the special target for this investigation. Our results suggest that breath sulfide content deserves attention as a noninvasive marker of respiratory colonization.
Fenofibrate, a well-known normolipidemic drug, has been shown to exert strong anticancer effects against tumors of neuroectodermal origin including glioblastoma. Although some pharmacokinetic studies ...were performed in the past, data are still needed about the detailed subcellular and tissue distribution of fenofibrate (FF) and its active metabolite, fenofibric acid (FA), especially in respect to the treatment of intracranial tumors. We used high performance liquid chromatography (HPLC) to elucidate the intracellular, tissue and body fluid distribution of FF and FA after oral administration of the drug to mice bearing intracranial glioblastoma. Following the treatment, FF was quickly cleaved to FA by blood esterases and FA was detected in the blood, urine, liver, kidney, spleen and lungs. We have also detected small amounts of FA in the brains of two out of six mice, but not in the brain tumor tissue. The lack of FF and FA in the intracranial tumors prompted us to develop a new method for intracranial delivery of FF. We have prepared and tested in vitro biodegradable poly-lactic-co-glycolic acid (PLGA) polymer wafers containing FF, which could ultimately be inserted into the brain cavity following resection of the brain tumor. HPLC-based analysis demonstrated a slow and constant diffusion of FF from the wafer, and the released FF abolished clonogenic growth of glioblastoma cells. On the intracellular level, FF and FA were both present in the cytosolic fraction. Surprisingly, we also detected FF, but not FA in the cell membrane fraction. Electron paramagnetic resonance spectroscopy applied to spin-labeled phospholipid model-membranes revealed broadening of lipid phase transitions and decrease of membrane polarity induced by fenofibrate. Our results indicate that the membrane-bound FF could contribute to its exceptional anticancer potential in comparison to other lipid-lowering drugs, and advocate for intracranial delivery of FF in the combined pharmacotherapy against glioblastoma.
Ground‐based measurements of aerosols and trace gases were conducted at an urban site in Tokyo (Komaba) and a site 50 km to the north (Kisai) during July–August 2004. An Aerodyne aerosol mass ...spectrometer (AMS) was deployed at each measurement site to investigate the chemical evolution of submicron organic aerosol (OA) in polluted air. The mass concentrations of OA at the Kisai site were systematically higher than those at the Komaba site and were correlated with ozone under southerly conditions. The rate of increase of OA at the Kisai site is investigated using the photochemical age derived from the ratio of alkyl nitrates to their parent hydrocarbons. The OA concentrations in processed air (age of 8–16 h) were 4–5 times larger than those in fresh emissions (age ∼ 0), suggesting that the OA concentrations can be significantly enhanced within ∼0.5 days under conditions of high photochemical activity.
The purpose of this study was to investigate how maximal power output (PMAX), as measured via the inertial load cycling technique, changes throughout a collegiate soccer season in relation to ...training load completed. The current investigation took place throughout the 2010 Big XII soccer season. Nineteen Division I female collegiate soccer players (age: 19.9 ± 1.2 years, stature: 165.1 ± 6.6 cm, mass: 61.0 ± 6.8 kg) from the same team completed regular inertial load cycling tests and perceptual fatigue questionnaires throughout the season. Players were divided into STARTERS and NON-STARTERS based on percentage of matches started throughout the season. The results demonstrated that STARTERS experience much greater load throughout the season than NON-STARTERS (2247 ± 176 arbitrary units AU and 1585 ± 174 AU, p < 0.05), accounted for by increased load during matches. This increased load throughout the season was accompanied by decline in PMAX in STARTERS (to 92.3 ± 6.6%, p < 0.05), whereas PMAX was maintained in NON-STARTERS for the duration of the season (99.0 ± 4.9%). Furthermore, STARTERS experienced greater muscle soreness throughout the in-season period compared with NON-STARTERS. The main finding of this study is that PMAX declined throughout the middle and latter parts of the season in STARTERS, after experiencing significantly greater match loads than NON-STARTERS throughout the season. The current findings, combined with previous investigations, suggest that load needs to be carefully monitored throughout the in-season period to maintain optimal neuromuscular performance throughout a team's entire sporting season.
Abstract Objectives To evaluate the diagnostic accuracy of MR urography (MRU) in detecting bladder carcinoma. Methods A retrospective review of 107 MRU exams obtained to evaluate for possible upper ...urinary tract urothelial carcinoma from 5/2005 to 5/2009 was performed by two experienced abdominal radiologists. Interpretation of the presence or absence of bladder carcinoma and lesion conspicuity in each imaging phase was made using 5-point confidence grading scales. Exams included 3D T1-weighted spoiled gradient-recalled echo images through the kidneys, ureters and bladder in the coronal plane during parenchymal phases and in both coronal and axial planes during pyelographic phases after intravenous administration of gadolinium and furosemide. Standard of reference was cystoscopy or cystectomy within 30 days of MRU. Statistical measures of performance, including receiver operating characteristics area under the curve (Az) values were calculated. Results Bladder carcinoma was present in 26/107 patients (24%). Sensitivity, specificity, accuracy, positive predictive value, negative predictive value and Az value were 73.1%, 91.4%, 86.9%, 73.1%, 91.4%, 0.89 for the first reviewer, and 84.6%, 75.3%, 77.6%, 52.4%, 93.8%, 0.86 for the second. Lesion conspicuity was superior on the parenchymal phase compared to the pyelographic phase ( p = 0.04). Conclusions MRU obtained for suspicion of upper urinary tract TCC has a moderate accuracy in detecting bladder carcinoma.
Early efforts to apply the concept of fisheries co-management in Southeast Asia focused primarily on building the effectiveness of local management institutions and advocating the merits of the ...approach so that it would be applied in new sites, while gradually learning and adapting to a range of obstacles in practice. Today, with co-management widely embraced by the research community and adopted as policy by an increasing number of governments, a second-generation perspective has emerged. This perspective is distinguished by efforts to navigate and influence change in the broader institutional and governance context: (a) a more sophisticated appreciation of politics, power relations, and the role of the state, (b) efforts to manage resource competition beyond the fisheries sector, (c) building institutions for adaptation and learning, and (d) recognizing divergent values and goals influencing fisheries management. This paper traces the evolution of this second-generation perspective, noting how it has built on learning from early practice and how it has been cross-fertilized by theoretical innovations in related fields, notably resilience thinking and political ecology. We illustrate this evolution through analysis of experience in the Philippines, with a relatively long experience of learning and adaptation in fisheries co-management practice, and Vietnam, where fisheries co-management policies have been embraced more recently. Characterizing the second-generation perspective helps identify points of convergence in the research and policy community about what needs attention, providing a basis for more systematic cross-country and cross-regional learning.
► Early fisheries co-management focused on building local capacity and advocacy. ► Second-generation perspective focuses on institutional and governance context. ► Co-management practice in Philippines and Vietnam illustrates this evolution. ► Improving cross-scale governance requires addressing power, competition, learning, and values. ► These challenges provide a basis for cross-country and cross-regional exchange of experience.
Using large-scale molecular dynamics simulations, we model a 9.2nm liquid bridge between two solid plates having a regular hexagonal lattice and analyse the forces acting at the various interfaces ...for a range of liquid-solid interactions. Our objective is to study the mechanical equilibrium of the system, especially that at the three-phase contact line. We confirm previous MD studies that have shown that the internal pressure inside the liquid is given precisely by the Laplace contribution and that the solid exerts a global force at the contact line in agreement with Young's equation, validating it down to the nanometre scale, which we quantify. In addition, we confirm that the force exerted by the liquid on the solid has the expected normal component equal to γlvsinθ0, where γlv is the surface tension of the liquid and θ0 is the equilibrium contact angle measured on the scale of the meniscus. Recent thermodynamic arguments predict that the tangential force exerted by the liquid on the solid should be equal to the work of adhesion expressed as Wa0=γlv(1+cosθ0). However, we find that this is true only when any layering of the liquid molecules close to liquid-solid interface is negligible. The force significantly exceeds this value when strong layering is present.
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•Large-scale molecular dynamic simulations of nanoscale partial wetting system.•Normal and tangential forces at contact line quantified and shown consistent with Young's equation.•Tangential force of liquid on solid at contact line: Wa0≥γ(1+cosθ0) when there is liquid layering at solid-liquid interface.•Lower size of system to which Young's equation may be applied identified.
DTNBP1 (dystrobrevin binding protein 1) remains a top candidate gene in schizophrenia. Reduced expression of this gene and of its encoded protein, dysbindin-1, have been reported in the brains of ...schizophrenia cases. It has not been established, however, if the protein reductions encompass all dysbindin-1 isoforms or if they are associated with decreased DTNBP1 gene expression. Using a matched pairs design in which each of 28 Caucasian schizophrenia cases was matched in age and sex to a normal Caucasian control, Western blotting of whole-tissue lysates of dorsolateral prefrontal cortex (DLPFC) revealed significant reductions in dysbindin-1C (but not in dysbindin-1A or -1B) in schizophrenia (P = 0.022). These reductions occurred without any significant change in levels of the encoding transcript in the same tissue samples and in the absence of the only DTNBP1 risk haplotype for schizophrenia reported in the USA. Indeed, no significant correlations were found between case–control differences in any dysbindin-1 isoform and the case–control differences in its encoding mRNA. Consequently, the mean 60% decrease in dysbindin-1C observed in 71% of our case–control pairs appears to reflect abnormalities in mRNA translation and/or processes promoting dysbindin-1C degradation (e.g. oxidative stress, phosphorylation and/or ubiquitination). Given the predominantly post-synaptic localization of dysbindin-1C and known post-synaptic effects of dysbindin-1 reductions in the rodent equivalent of the DLPFC, the present findings suggest that decreased dysbindin-1C in the DLPFC may contribute to the cognitive deficits of schizophrenia by promoting NMDA receptor hypofunction in fast-spiking interneurons.
The plains spotted skunk (Spilogale interrupta) is of conservation concern because of widespread population declines and is being considered for listing under the United States Endangered Species ...Act. Although the taxon is relatively rare and difficult to study, recent research and reports provided some information about spotted skunks in Arkansas and Missouri, USA. Using this information, we employed full and simplified multivariate species distribution models to evaluate cover type associations and identify regions of high predicted presence for plains spotted skunks. The simple model contained percent forest and percent development within 5 km, land cover category, and distance to water. Percent forest within 5 km was the most important variable based on permutation importance in both models, indicating that plains spotted skunk habitat may persist in contiguous forest at the landscape scale. Regions predicted to have high presence occurred in northern, western, and southern Arkansas and southern Missouri, totaling >300,000 ha. The resulting plains spotted skunk distribution map can be used for research and management efforts in areas of high probability of occurrence, and future statewide survey efforts may validate our results.
Information on the remaining distribution of the plains spotted skunk is imperative to inform its listing potential under the United States Endangered Species Act and to guide future research efforts on the taxon. We employed multivariate species distribution models in MaxEnt to evaluate cover type associations and identify regions of high predicted presence for plains spotted skunks and determined that percent forest within 5 km was the most important predictor of presence. The resulting distribution map highlighted areas of high probability of presence in northern, western, and southern Arkansas and southern Missouri.
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