779 research outputs found

    Surface Roughness and Porosity of Hydrated Cement Pastes

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    . Seventy-eight graphs were plotted to describe and analyze the dependences of the height and roughness irregularities on the water-to-cement ratio and on the porosity of the cement hydrates. The results showed unambiguously that the water-to-cement ratio or equivalently the porosity of the specimens has a decisive influence on the irregularities of the fracture surfaces of this material. The experimental results indicated the possibility that the porosity or the value of the water-to-cement ratio might be inferred from the height irregularities of the fracture surfaces. It was hypothesized that there may be a similarly strong correlation between porosity and surface irregularity, on the one hand, and some other highly porous solids, on the other, and thus the same possibility to infer porosity from the surfaces of their fracture remnants

    Stocking strategies for a pre-alpine whitefish population under temperature stress

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    Cold-water fish stocks are increasingly affected by steadily increasing water temperatures. The question arises whether stock management can be adapted to mitigate the consequences of this climatic change. Here, we estimate the effects of increasing water temperatures on fisheries yield and population dynamics of whitefish, a typical cold-water fish species. Using a process-based population model calibrated on an empirical long-term data set for the whitefish population (Coregons lavaretus (L.) species complex) of the pre-alpine Lake Irrsee, Austria, we project density-dependent and temperature-dependent population growth and compare established stock enhancement strategies to alternative stocking strategies under the aspect of increasing water temperatures and cost neutrality. Additionally, we contrast the results obtained from the process-based model to the results from simple regression models and argue that the latter show qualitative inadequacies in projecting catch with rising temperatures. Our results indicate that increasing water temperatures reduce population biomass between 2.6% and 7.9% and catch by the fishery between 24% and 48%, depending on temperature scenario and natural mortality calculation. These reductions are caused by accelerated growth, smaller asymptotic size and lower annual survival of whitefish. Regarding stocking strategies under constant temperatures, we find that stocking mostly whitefish larvae, produces higher population biomass than stocking mostly one-summer-old whitefish, while catch remains almost constant. With increasing temperatures, stocking one-summer-old fish is more beneficial for the angling fishery. Adaption to climate change by changing stocking strategies cannot, however, prevent an overall reduction in catch and population size of this cold-water fish species

    Freshwater Ecosystems: From Models to Applications

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    Freshwater ecosystems—lakes and streams—are being endangered by agricultural, urban, and industrial pollution; hydraulic engineering; and overexploitation, which threaten their capacity to provide important services (recreation and supply of food and clean water, among others). Ecological modeling may be employed to estimate impacts and analyze mitigation strategies. Toy models are easy to construct, but applying them to real-world problems is often challenging. Here, we show in two case studies how the connection from model to application can be made. The first study analyzes whether and how the impact of climatic change on a mostly recreational fishery in an Alpine lake can be mitigated, while the second looks at restoring biodiversity after cleaning up pollution in a Korean river system, using aquatic insects, which play an essential functional role in aquatic food-webs and are very sensitive to water quality, as indicators of ecosystem health. These studies highlight the ability of process-based eco-evolutionary models to generate testable hypotheses and contribute solutions to real-world problems

    Effect of a patient engagement tool on positive airway pressure adherence: analysis of a German healthcare provider database

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    Objective/background: This study investigated the addition of a real-time feedback patient engagement tool on positive airway pressure (PAP) adherence when added to a proactive telemedicine strategy. Patients/methods: Data from a German healthcare provider (ResMed Healthcare Germany) were retrospectively analyzed. Patients who first started PAP therapy between 1 September 2009 and 30 April 2014, and were managed using telemedicine (AirViewℱ; proactive care) or telemedicine + patient engagement tool (AirViewℱ + myAirℱ; patient engagement) were eligible. Patient demographics, therapy start date, sleep- disordered breathing indices, device usage hours, and therapy termination rate were obtained and compared between the two groups. Results: The first 500 patients managed by telemedicine-guided care and a patient engagement tool were matched with 500 patients managed by telemedicine-guided care only. The proportion of nights with device usage ≄4 h was 77 ± 25% in the patient engagement group versus 63 ± 32% in the proactive care group (p < 0.001). Therapy termination occurred less often in the patient engagement group (p < 0.001). The apnea-hypopnea index was similar in the two groups, but leak was significantly lower in the patient engagement versus proactive care group (2.7 ± 4.0 vs 4.1 ± 5.3 L/min; p < 0.001). Conclusions: Addition of a patient engagement tool to telemonitoring-guided proactive care was associated with higher device usage and lower leak. This suggests that addition of an engagement tool may help improve PAP therapy adherence and reduce mask leak

    Endobronchial Valve (Zephyr) Treatment in Homogeneous Emphysema:One-Year Results from the IMPACT Randomized Clinical Trial

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    RATIONALE: The long-term safety and effectiveness of bronchoscopic lung volume reduction with Zephyr endobronchial valves in subjects with severe homogeneous emphysema with little to no collateral ventilation beyond 3 months have yet to be established. METHODS: Ninety-three subjects were randomized to either bronchoscopic lung volume reduction with Zephyr valves or standard of care (SoC) (1:1). Zephyr valve subjects were assessed at 3, 6, and 12 months. SoC subjects were assessed at 3 and 6 months; they were then offered crossover to Zephyr valve treatment. RESULTS: The mean group difference (Zephyr valve − SoC) for change in FEV1 from baseline to 6 months was 16.3 ± 22.1% (mean ± SD; p < 0.001). Secondary outcomes showed the mean between-group difference for the six-minute walk distance of +28.3 ± 55.3 m (p = 0.016); St. George's Respiratory Questionnaire, −7.51 ± 9.56 points (p < 0.001); modified Medical Research Council, −0.42 ± 0.81 points (p = 0.019); BODE index, −0.85 ± 1.39 points (p = 0.006); and residual volume of −430 ± 830 mL (p = 0.011) in favor of the Zephyr valve group. At 6 months, there were significantly more responders based on the minimal clinically important difference for these same measures in the Zephyr valve versus the SoC group. The clinical benefits were persistent at 12 months. The percentage of subjects with respiratory serious adverse events was higher in the Zephyr valve group compared to SoC during the first 30 days post-procedure but not statistically different for the Zephyr valve and SoC groups from 31 days to 6 months, and stable in the Zephyr valve group out to 12 months. There were 2 deaths in the SoC group in the 31-day to 6-month period and none in the Zephyr valve group out to 12 months. CONCLUSIONS: Bronchoscopic lung volume reduction with Zephyr valves in subjects with severe homogeneous emphysema and little to no collateral ventilation provides clinically meaningful change from baseline in lung function, quality of life, exercise capacity, dyspnea, and the BODE index at 6 months, with benefits maintained out to 12 months

    The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking

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    Heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of cancer. Several Hsp90 inhibitors have entered clinical trials. However, some toxicological detriments have arisen, such as cardiotoxicity resulting from hERG inhibition following the administration of Hsp90 inhibitors. We sought to investigate this toxicity as hERG has been previously reported as a client protein that depends upon Hsp90 for its maturation and functional trafficking. In this study we show that hERG depends upon a single Hsp90 isoform. hERG preferentially co-immunoprecipitated with Hsp90α and genetic knockdown of Hsp90α, but not Hsp90ÎČ, resulted in a trafficking-defective hERG channel. This study demonstrates the importance of delineating the isoform dependence of Hsp90 client proteins and provides rationale for the design of isoform-selective Hsp90 inhibitors that avoid detrimental effect

    Relationship of hyperlipidemia to comorbidities and lung function in COPD: Results of the COSYCONET cohort

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    Although hyperlipidemia is common in COPD, its relationship to comorbidities, risk factors and lung function in COPD has not been studied in detail. Using the baseline data of the COSYCONET cohort we addressed this question. Data from 1746 COPD patients (GOLD stage 1–4; mean age 64.6 y, mean FEV1%pred 57%) were evaluated, focusing on the comorbidities hyperlipidemia, diabetes and cardiovascular complex (CVC; including arterial hypertension, cardiac failure, ischemic heart disease). Risk factors comprised age, gender, BMI, and packyears of smoking. The results of linear and logistic regression analyses were implemented into a path analysis model describing the multiple relationships between parameters. Hyperlipidemia (prevalence 42.9%) was associated with lower intrathoracic gas volume (ITGV) and higher forced expiratory volume in 1 second (FEV1) when adjusting for its multiple relationships to risk factors and other comorbidities. These findings were robust in various statistical analyses. The associations between comorbidities and risk factors were in accordance with previous findings, thereby underlining the validity of our data. In conclusion, hyperlipidemia was associated with less hyperinflation and airway obstruction in patients with COPD. This surprising result might be due to different COPD phenotypes in these patients or related to effects of medication

    Trafficking-Deficient G572R-hERG and E637K-hERG Activate Stress and Clearance Pathways in Endoplasmic Reticulum

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    Background: Long QT syndrome type 2 (LQT2) is the second most common type of all long QT syndromes. It is well-known that trafficking deficient mutant human ether-a-go-go-related gene (hERG) proteins are often involved in LQT2. Cells respond to misfolded and trafficking-deficient proteins by eliciting the unfolded protein response (UPR) and Activating Transcription Factor (ATF6) has been identified as a key regulator of the mammalian UPR. In this study, we investigated the role of ER chaperone proteins (Calnexin and Calreticulin) in the processing of G572R-hERG and E637K-hERG mutant proteins. Methods: pcDNA3-WT-hERG, pcDNA3-G572R-hERG and pcDNA3-E637K-hERG plasmids were transfected into U2OS and HEK293 cells. Confocal microscopy and western blotting were used to analyze subcellular localization and protein expression. Interaction between WT or mutant hERGs and Calnexin/Calreticulin was tested by coimmunoprecipitation. To assess the role of the ubiquitin proteasome pathway in the degradation of mutant hERG proteins, transfected HEK293 cells were treated with proteasome inhibitors and their effects on the steady state protein levels of WT and mutant hERGs were examined. Conclusion: Our results showed that levels of core-glycosylated immature forms of G572R-hERG and E637K-hERG in association with Calnexin and Calreticulin were higher than that in WT-hERG. Both mutant hERG proteins could activate the UPR by upregulating levels of active ATF6. Furthermore, proteasome inhibition increased the levels of core-glycosylated immature forms of WT and mutant hERGs. In addition, interaction between mutant hERGs and Calnexin/Calreticulin wa
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