Gas adsorption experiments have been carried out on a copper benzene tricarboxylate metal−organic framework material, HKUST-1. Hydrogen adsorption at 1 and 10 bar (both 77 K) gives an adsorption ...capacity of 11.16 mmol H2 per g of HKUST-1 (22.7 mg g-1, 2.27 wt %) at 1 bar and 18 mmol per g (36.28 mg g-1, 3.6 wt %) at 10 bar. Adsorption of D2 at 1 bar (77 K) is between 1.09 (at 1 bar) and 1.20(at <100 mbar) times the H2 values depending on the pressure, agreeing with the theoretical expectations. Gravimetric adsorption measurements of NO on HKUST-1 at 196 K (1 bar) gives a large adsorption capacity of ∼9 mmol g-1, which is significantly greater than any other adsorption capacity reported on a porous solid. At 298 K the adsorption capacity at 1 bar is just over 3 mmol g-1. Infra red experiments show that the NO binds to the empty copper metal sites in HKUST-1. Chemiluminescence and platelet aggregometry experiments indicate that the amount of NO recovered on exposure of the resulting complex to water is enough to be biologically active, completely inhibiting platelet aggregation in platelet rich plasma.
Peptides are commonly used as therapeutic agents. However, they suffer from easy degradation and instability. Replacing natural by non-natural amino acids can avoid these problems, and potentially ...improve the affinity towards the target protein. Here, we present a computational pipeline to optimize peptides based on adding non-natural amino acids while improving their binding affinity. The workflow is an iterative computational evolution algorithm, inspired by the PARCE protocol, that performs single-point mutations on the peptide sequence using modules from the Rosetta framework. The modifications can be guided based on the structural properties or previous knowledge of the biological system. At each mutation step, the affinity to the protein is estimated by sampling the complex conformations and applying a consensus metric using various open protein-ligand scoring functions. The mutations are accepted based on the score differences, allowing for an iterative optimization of the initial peptide. The sampling/scoring scheme was benchmarked with a set of protein-peptide complexes where experimental affinity values have been reported. In addition, a basic application using a known protein-peptide complex is also provided. The structure- and dynamic-based approach allows users to optimize bound peptides, with the option to personalize the code for further applications. The protocol, called mPARCE, is available at:
https://github.com/rochoa85/mPARCE/
.
Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. ...Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans.
Data from 15 sites with loblolly pine (Pinus taeda L.) plantations located in the southeastern United States were used to predict site index (SI) from soil physical and chemical properties from the ...top 15 cm of the mineral soil. Two modeling approaches were used to predict SI from soil properties. First, the ordinary least-squares method of multiple linear regression was used, which selected calcium, potassium, and sand percentage as the significant predictor variables. Second, partial least-squares regression was used, which selected total nitrogen, carbon, calcium, magnesium, and sand percentage as the significant predictor variables. The partial least-squares regression approach addressed multicollinearity in the data and produced a better model to predict SI. The partial least-squares regression model explained 77% of the variation in SI.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive alternative to resuscitative thoracotomy (RT) for patients with hemorrhagic shock. However, the potential ...benefits of this approach remain subject of debate. The aim of this study was to compare the outcomes of REBOA and RT for traumatic cardiac arrest.
A planned secondary analysis of the United States Department of Defense-funded Emergent Truncal Hemorrhage Control study was performed. Between 2017 and 2018, a prospective observational study of noncompressible torso hemorrhage was conducted at six Level I trauma centers. Patients were dichotomized by REBOA or RT, and baseline characteristics and outcomes were compared between groups.
A total of 454 patients were enrolled in the primary study, of which 72 patients were included in the secondary analysis (26 underwent REBOA and 46 underwent resuscitative thoracotomy). Resuscitative endovascular balloon occlusion of the aorta patients were older, had a greater body mass index, and were less likely to be the victims of penetrating trauma. Resuscitative endovascular balloon occlusion of the aorta patients also had less severe abdominal injuries and more severe extremity injuries, although the overall injury severity scores were similar. There was no difference in mortality between groups (88% vs. 93%, p = 0.767). However, time to aortic occlusion was longer in REBOA patients (7 vs. 4 minutes, p = 0.001) and they required more transfusions of red blood cells (4.5 vs. 2.5 units, p = 0.007) and plasma (3 vs. 1 unit, p = 0.032) in the emergency department. After adjusted analysis, mortality remained similar between groups (RR, 0.89; 95% confidence interval, 0.71-1.12, p = 0.304).
Resuscitative endovascular balloon occlusion of the aorta and RT were associated with similar survival after traumatic cardiac arrest, although time to successful aortic occlusion was longer in the REBOA group. Further research is needed to better define the role of REBOA in trauma.
Therapeutic/Care Management; Level III.
Living wall systems are a relatively new form of façade cladding treatment on buildings. Bringing a host of benefits such as added biodiversity, they also have the potential to aid the thermal ...efficiency of a wall construction by offering an extra layer of thermal resistance. Yet few studies have been conducted to ascertain the thermal influence of living wall systems can have on existing buildings.
This study reviews the impact of living walls upon the thermal and environmental performance of buildings and isolates a lack of research that directly measures associated retrofitted living wall thermal performance. A case study then monitors the heat flux through a pre 1970s uninsulated cavity masonry wall construction that has been retrofitted with an external living wall system face. Results are compared with an identical wall build-up on the same elevation without the living wall cladding.
Results found that the calculated thermal transmission value for the pre 1970s wall with an additional Living wall façade cladding was 31.4% lower than that of the same wall without the living wall. Furthermore, diurnal fluctuations in heat flux were lower over the study period for the wall with the living wall system cladding. These findings demonstrate that a living wall façade offers a viable solution for helping to minimise heat loss from existing buildings of this construction.
•Green and living facades can improve the thermal performance of existing buildings.•There is a lack of empirical data on effects of living wall to building insulation.•Findings demonstrate a 31% improvement to traditional masonry wall U-values.
Purpose
Create a new definition of near-occlusion with full collapse to predicting recurrent stroke.
Methods
Pooled analysis of two studies. Patients with symptomatic ≥ 50% carotid stenoses were ...included. Outcome was preoperative recurrent ipsilateral ischemic stroke or retinal artery occlusion within 28 days of presenting event. We analyzed several artery diameters on computed tomography angiography and stenosis velocity on ultrasound.
Results
A total of 430 patients with symptomatic ≥ 50% carotid stenosis were included, 27% had near-occlusion. By traditional definition, 27% with full collapse and 11% without full collapse reached the outcome (
p
= 0.047). Distal internal carotid artery (ICA) diameter, ICA ratio, and ICA-to-external carotid artery ratio were associated with the outcome. Best new definition of full collapse was distal ICA diameter ≤ 2.0 mm and/or ICA ratio ≤ 0.42. With this new definition, 36% with full collapse and 4% without full collapse reached the outcome (
p
< 0.001).
Conclusions
Defining near-occlusion with full collapse as distal ICA diameter ≤ 2.0 mm and/or ICA ratio ≤ 0.42 seems to yield better prognostic discrimination than the traditional appearance-based definition. This novel definition can be used in prognostic and treatment studies of near-occlusion with full collapse.
Rooks
Corvus frugilegus
are common and widespread in urban and agricultural habitats in Denmark. Large numbers are killed annually by derogation shooting to control population growth to reduce noise ...near populated areas and prevent agricultural damage. Responding to increasing public complaints about noise nuisance from urban rookeries, we investigated changes in extent of urban and agricultural habitats within 500 m, 1000 m and 2000 m of all known breeding rook colonies (rookeries) in eastern Jutland, Denmark in 1991 compared to 2021 based on open access land cover GIS layers in 1990 and 2019. Numbers of rookeries increased by 40% from 95 (1991) to 133 (2021) but nest abundance increased only by 6% from 10,299 to 10,887 due to more and significantly smaller rookeries, increasingly associated with urban sites. In both years, the proportion of urban area within distance classes of rookeries was significantly higher, and the area of agriculture significantly lower, than at randomly chosen points in the same region. The proportion of urban area around each rookery decreased with increasing distance, whereas the proportion of agricultural land cover increased. The proportional area of urban land use within the distance classes increased between 1991 and 2021 whereas agricultural land cover decreased. Given no simultaneous major change in overall land use, our results indicate an increasing selection by rooks for smaller urban rookeries over agricultural landscapes, where rookeries have declined. We consider these trends, especially the proliferation of smaller rookeries in urban areas, as a potential explanation for the upsurge in public complaints about rookery noise in residential areas. We urge further research to explain the causes behind these trends before we can provide science-based solutions to resolve such conflicts effectively.
Abstract
Supporting self-management is key in improving disease control, with technology increasingly utilised. We hypothesised the addition of telehealth support following assessment in an ...integrated respiratory clinic could reduce unscheduled healthcare visits in patients with asthma and COPD. Following treatment optimisation, exacerbation-prone participants or those with difficulty in self-management were offered telehealth support. This comprised automated twice-weekly telephone calls, with a specialist nurse triaging alerts. We performed a matched cohort study assessing additional benefits of the telehealth service, matching by: confirmed diagnosis, age, sex, FEV
1
percent predicted, smoking status and ≥1 exacerbation in the last year. Thirty-four telehealth participants were matched to twenty-nine control participants. The telehealth cohort generated 165 alerts, with 29 participants raising at least one alert; 88 (53.5%) alerts received a call discussing self-management, of which 35 (21%) received definitive advice that may otherwise have required an unscheduled healthcare visit. There was a greater reduction in median exacerbation rate across both telehealth groups at 6 months post-intervention (1 to 0,
p
< 0.001) but not in control groups (0.5 to 0.0,
p
= 0.121). Similarly, there was a significant reduction in unscheduled GP visits across the telehealth groups (1.5 to 0.0,
p
< 0.001), but not the control groups (0.5 to 0.0,
p
= 0.115). These reductions led to cost-savings across all groups, but greater in the telehealth cohorts. The addition of telehealth support to exacerbation-prone patients with asthma or COPD, following comprehensive assessment and treatment optimisation, proved beneficial in reducing exacerbation frequency and unscheduled healthcare visits and thus leads to significant cost-savings for the NHS.
Clinical Trial Registration: ClinicalTrials.gov: NCT03096509
Pancreatic ductal adenocarcinoma (PDAC) tumor growth is enhanced by tumor-associated macrophages (TAMs), yet the mechanisms by which tumor cells and TAMs communicate are not fully understood. Here we ...show that exosomes secreted by PDAC cell lines differed in their surface proteins, lipid composition, and efficiency of fusing with THP-1-derived macrophages in vitro. Exosomes from AsPC-1, an ascites-derived human PDAC cell line, were enriched in ICAM-1, which mediated their docking to macrophages through interactions with surface-exposed CD11c on macrophages. AsPC-1 exosomes also contained much higher levels of arachidonic acid (AA), and they fused at a higher rate with THP-1-derived macrophages than did exosomes from other PDAC cell lines or from an immortalized normal pancreatic ductal epithelial cell line (HPDE) H6c7. Phospholipase A2 enzymatic cleavage of arachidonic acid from AsPC-1 exosomes reduced fusion efficiency. PGE2 secretion was elevated in macrophages treated with AsPC-1 exosomes but not in macrophages treated with exosomes from other cell lines, suggesting a functional role for the AsPC-1 exosome-delivered arachidonic acid in macrophages. Non-polarized (M0) macrophages treated with AsPC-1 exosomes had increased levels of surface markers indicative of polarization to an immunosuppressive M2-like phenotype (CD14hi CD163hi CD206hi). Furthermore, macrophages treated with AsPC-1 exosomes had significantly increased secretion of pro-tumoral, bioactive molecules including VEGF, MCP-1, IL-6, IL-1β, MMP-9, and TNFα. Together, these results demonstrate that compared to exosomes from other primary tumor-derived PDAC cell lines, AsPC-1 exosomes alter THP-1-derived macrophage phenotype and function. AsPC-1 exosomes mediate communication between tumor cells and TAMs that contributes to tumor progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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