We study the optical properties of excitons in one-dimensional (1D) nanostructures at low temperatures. In single CdSe/ZnS core-shell nanorods we observe a fine structure splitting and explain it by ...exchange interaction. Two peaks are observed with different degrees of linear polarization of DLP<0.85 and DLP>0.95. For small nanorod radii R< or =a(B)/2, an increase in the photoluminescence decay time is found when the temperature increases from 10 to 80 K. The observations are explained by a radius-dependent change in the symmetry of the 1D-exciton ground state which transforms from a dark state into bright states below a critical radius of R(crit) approximately 3.7 nm.
Abstract
Background and Aims
Given limited evidence and lack of consensus on donor acceptance for heart transplant (HT), selection practices vary widely across HT centres in the USA. Similar ...variation likely exists on a broader scale—across countries and HT systems—but remains largely unexplored. This study characterized differences in heart donor populations and selection practices between the USA and Eurotransplant—a consortium of eight European countries—and their implications for system-wide outcomes.
Methods
Characteristics of adult reported heart donors and their utilization (the percentage of reported donors accepted for HT) were compared between Eurotransplant (n = 8714) and the USA (n = 60 882) from 2010 to 2020. Predictors of donor acceptance were identified using multivariable logistic regression. Additional analyses estimated the impact of achieving Eurotransplant-level utilization in the USA amongst donors of matched quality, using probability of acceptance as a marker of quality.
Results
Eurotransplant reported donors were older with more cardiovascular risk factors but with higher utilization than in the USA (70% vs. 44%). Donor age, smoking history, and diabetes mellitus predicted non-acceptance in the USA and, by a lesser magnitude, in Eurotransplant; donor obesity and hypertension predicted non-acceptance in the USA only. Achieving Eurotransplant-level utilization amongst the top 30%–50% of donors (by quality) would produce an additional 506–930 US HTs annually.
Conclusions
Eurotransplant countries exhibit more liberal donor heart acceptance practices than the USA. Adopting similar acceptance practices could help alleviate the scarcity of donor hearts and reduce waitlist morbidity in the USA.
Reelin is a glycoprotein that is critical for proper layering of neocortex during development as well as dynamic regulation of glutamatergic postsynaptic signaling in mature synapses. Here, we show ...that Reelin also acts presynaptically, resulting in robust rapid enhancement of spontaneous neurotransmitter release without affecting properties of evoked neurotransmission. This effect of Reelin requires a modest but significant increase in presynaptic Ca2+ initiated via ApoER2 signaling. The specificity of Reelin action on spontaneous neurotransmitter release is encoded at the level of vesicular SNARE machinery as it requires VAMP7 and SNAP-25 but not synaptobrevin2, VAMP4, or vti1a. These results uncover a presynaptic regulatory pathway that utilizes the heterogeneity of synaptic vesicle-associated SNAREs and selectively augments action potential-independent neurotransmission.
•Reelin selectively augments spontaneous synaptic transmission•The effect of Reelin requires ApoER2 and VLDLR activation, PI3K activity, and Ca2+•Reelin selectively acts on VAMP7 expressing synaptic vesicles within a synapse•VAMP7 knockdown abolishes the effect of Reelin
Bal et al. find that the secreted glycoprotein Reelin selectively augments spontaneous neurotransmitter release by mobilizing vesicles enriched with the SNARE protein VAMP7, uncovering a presynaptic pathway that utilizes the heterogeneity of synaptic vesicle SNAREs to potentiate spontaneous neurotransmission.
Introduction The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East ( n = 14) and the ...European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) ( n = 13). Methods These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Results Overall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence. Discussion Differences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.
Animals that rely on acoustic communication to find mates, such as grasshoppers, are astonishingly accurate in recognizing song patterns that are specific to their own species. This raises the ...question of whether they can also solve a far more complicated task that might provide a basis for mate preference and sexual selection: to distinguish individual songs by detecting slight variations around the common species-specific theme. Using spike-train discriminability to quantify the precision of neural responses from the auditory periphery of a model grasshopper species, we show that information sufficient to distinguish songs is readily available at the single-cell level when the spike trains are analyzed on a millisecond time scale.
The present single‐centre, randomized, double‐blind, placebo‐controlled phase II study investigated the effect of the balanced dual peroxisome proliferator‐activated receptor‐α/γ agonist aleglitazar ...on whole‐body and liver insulin sensitivity, β‐cell function and other components of cardiometabolic syndrome after 16 weeks of treatment in patients with type 2 diabetes inadequately controlled with metformin monotherapy who received once‐daily 150 µg aleglitazar or matching placebo as add‐on therapy to metformin. Baseline and 16‐week assessments included a two‐step hyperinsulinaemic–euglycaemic clamp, followed by a hyperglycaemic clamp, as well as evaluation of glycated haemoglobin (HbA1c), lipids and safety variables. The primary endpoint was change in whole‐body insulin sensitivity (M‐value) from baseline compared with placebo, derived from the second clamp step. M‐value improved significantly from baseline with aleglitazar (n = 16) compared with placebo (n = 24; p = 0.05 for difference between arms). We found statistically significant treatment differences with aleglitazar versus placebo in fasting hepatic insulin resistance index (p = 0.01), and in total glucose disposal (p = 0.03) at the second insulin infusion step. Aleglitazar treatment resulted in significant improvements in HbA1c and lipids and was well tolerated.
Impairment of cellular cholesterol trafficking is at the heart of atherosclerotic lesions formation. This involves egress of cholesterol from the lysosomes and 2 lysosomal proteins, the NPC1 ...(Niemann-Pick C1) and NPC2 that promotes cholesterol trafficking. However, movement of cholesterol out the lysosome and how disrupted cholesterol trafficking leads to atherosclerosis is unclear. As the Wnt ligand, Wnt5a inhibits the intracellular accumulation of cholesterol in multiple cell types, we tested whether Wnt5a interacts with the lysosomal cholesterol export machinery and studied its role in atherosclerotic lesions formation.
We generated mice deleted for the
gene in vascular smooth muscle cells. To establish whether Wnt5a also protects against cholesterol accumulation in human vascular smooth muscle cells, we used a CRISPR/Cas9 guided nuclease approach to generate human vascular smooth muscle cells knockout for Wnt5a.
We show that Wnt5a is a crucial component of the lysosomal cholesterol export machinery. By increasing lysosomal acid lipase expression, decreasing metabolic signaling by the mTORC1 (mechanistic target of rapamycin complex 1) kinase, and through binding to NPC1 and NPC2, Wnt5a senses changes in dietary cholesterol supply and promotes lysosomal cholesterol egress to the endoplasmic reticulum. Consequently, loss of Wnt5a decoupled mTORC1 from variations in lysosomal sterol levels, disrupted lysosomal function, decreased cholesterol content in the endoplasmic reticulum, and promoted atherosclerosis.
These results reveal an unexpected function of the Wnt5a pathway as essential for maintaining cholesterol homeostasis in vivo.
The autofrettage of intersecting holes leads to extremely high compressive residual stress fields. These stresses in combination with the plastic deformations decelerate fatigue cracks initiated at ...the hole intersection notch. Simulations of plasticity induced crack closure of such cracks are presented based on the strip yield and a finite element model. The strip yield model has been extended to allow for an input of residual stresses coming from elsewhere, e.g. from a finite element calculation or measurements. The calculations are applied for constant as well as variable amplitude loading. The numerical expense of the finite element based modelling for variable amplitude loading is still too high if millions of cycles have to be considered. Therefore, a new approximation method is proposed introducing compensatory load sequences. Simulation results are compared to experimentally determined results showing good agreement. However, the accuracy of crack initiation life estimates has turned out to provide a high potential for further improvement.
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