Mathematical models of thrombosis are currently used to study clinical scenarios of pathological thrombus formation. As these models become more complex to predict thrombus formation dynamics high computational cost must be alleviated and inherent uncertainties must be assessed. Evaluating model uncertainties allows to increase the confidence in model predictions and identify avenues of improvement for both thrombosis modeling and anti-platelet therapies. In this work, an uncertainty quantification analysis of a multi-constituent thrombosis model is performed considering a common assay for platelet function (PFA-100®). The analysis is facilitated thanks to time-evolving polynomial chaos expansions used as a parametric surrogate for the full thrombosis model considering two quantities of interest; namely, thrombus volume and occlusion percentage. The surrogate is thoroughly validated and provides a straightforward access to a global sensitivity analysis via computation of Sobol‘ coefficients. Six out of 15 parameters linked to thrombus consitution, vWF activity, and platelet adhesion dynamics were found to be most influential in the simulation variability considering only individual effects; while parameter interactions are highlighted when considering the total Sobol‘ indices. The influential parameters are related to thrombus constitution, vWF activity, and platelet to platelet adhesion dynamics. The surrogate model allowed to predict realistic PFA-100® closure times of 300,000 virtual cases that followed the trends observed in clinical data. The current methodology could be used including common anti-platelet therapies to identify scenarios that preserve the hematological balance.Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene encoding alpha-galactosidase A (AGAL). The impact of X-chromosome inactivation (XCI) on the phenotype of female FD patients remains unclear. In this study we aimed to determine pitfalls of XCI testing in a cohort of 35 female FD patients. XCI was assessed by two methylation-based and two allele-specific expression assays. The results correlated, although some variance among the four assays was observed. GLA transcript analyses identified crossing-over in three patients and detected mRNA instability in three out of four analyzed null alleles. AGAL activity correlated with XCI pattern and was not influenced by the mutation type or by reduced mRNA stability. Therefore, AGAL activity may help to detect crossing-over in patients with unstable GLA alleles. Tissue-specific XCI patterns in six patients, and age-related changes in two patients were observed. To avoid misinterpretation of XCI results in female FD patients we show that (i) a combination of several XCI assays generates more reliable results and minimizes possible biases; (ii) correlating XCI to GLA expression and AGAL activity facilitates identification of cross-over events; (iii) age- and tissue-related XCI specificities of XCI patterning should be considered.Developing an economical, durable, and efficient electrode that performs well at high current densities and is capable of satisfying large-scale electrochemical hydrogen production is highly demanded. A self-supported electrocatalytic „Pt-like“ WC porous electrode with open finger-like holes is produced through industrial processes, and a tightly bonded nitrogen-doped WC/W (WC-N/W) heterostructure is formed in situ on the WC grains. The obtained WC-N/W electrode manifests excellent durability and stability under multi-step current density in the range of 30-1000 mA cm-2 for more than 220 h in both acidic and alkaline media. Although WC is three orders of magnitude cheaper than Pt, the produced electrode demonstrates comparable hydrogen evolution reaction performance to the Pt electrode at high current density. Density functional theory calculations attribute its superior performance to the electrode structure and the modulated electronic structure at the WC-N/W interface.

Clinical assessments are vital for gaining an understanding of a patients‘ presenting problem. A priority for Early Intervention in Psychosis Service staff is understanding and supporting their patients‘ experiences of hallucinations and/or delusions. click here We aimed to identify what cognitive-phenomenology dimensions of hallucinations and delusions EIPS staff were assessing with their patients.

We developed a brief checklist of cognitive-phenomenological dimensions of hallucinations and delusions called the Lived Experience Symptom Survey (LESS) based on relevant literature. As part of a Quality Improvement Project, we reviewed the health records of a sub-sample of EIPS patients using the LESS identifying whether each dimension was present or absent.

We found that all patients had been asked about the content of their hallucinations and/or delusions, and the majority had been asked about the valence of this content. Despite patients having experienced psychosis for almost 2 years on average, less than half of patients were asked about the potential or actual harm associated with these symptoms. All other cognitive-phenomenological dimensions were assessed inconsistently.

The assessment of hallucination and delusions in our EIPS was inconsistent and incomprehensive. These findings require replication in other EIPS‘ but may point to a need for guidelines and training around how to conduct a thorough assessment of hallucinations and delusions for current and future EIPS staff. Improved assessment of these symptoms will aid the development of risk assessments and treatment plans.

The assessment of hallucination and delusions in our EIPS was inconsistent and incomprehensive. These findings require replication in other EIPS‘ but may point to a need for guidelines and training around how to conduct a thorough assessment of hallucinations and delusions for current and future EIPS staff. Improved assessment of these symptoms will aid the development of risk assessments and treatment plans.Molybdenum nitrides and their related compounds have been focused as a catalyst for several reactions. Although the doping into molybdenum nitrides lead to the higher catalytic activity, the simultaneous control of the morphology, the crystallinity, and the dopant state in doped MoN cannot be easily achieved due to the limitation of the synthesis method. In this study, one of the mixed anion compounds, NaMoO3 F was used as a precursor for molybdenum oxynitrides with hexagonal MoN phase. This route led to the homogeneous distribution of cobalt in the molybdenum oxynitride compared with that obtained by the other method. The cobalt-doped molybdenum oxynitride from NaMoO3 F exhibited high oxygen reduction reaction catalytic activity due to the high distribution of cobalt in the crystal. This paper proposes that the mixed anion compounds can be a unique precursor for the other materials to expand the controllability of materials toward improvement of their activity.New chemical moieties continue to appear in synthetic cannabimimetics (SC), the largest group of new psychoactive substances in the EU. We describe the first comprehensive characterisation of the novel SC Cumyl-Tosyl-Indazole-3-Carboxamide (Cumyl-TsINACA) (N-[2-phenylpropan-2-yl]-1-tosyl-1H-indazole-3-carboxamide) from seized case samples. Structure elucidation was performed within the EU-project ADEBAR plus to facilitate confident identification by other researchers and practitioners worldwide. Characteristic MS fragmentations include the cleavage of the sulfonamide bond (S-N), the aryl sulfone bond (C-S) and the elimination rearrangement of SO2 in the side chain. Cumyl-TsINACA is a full receptor agonist at hCB1 (Emax = 228%) with very weak binding affinity (Ki = 292 nm) and low functional activity (EC50 = 31 μm). Thermal degradation of Cumyl-TsINACA was observed under GC conditions. The degree to which the tosyl side chain is cleaved due to pyrolysis primarily depends on solvent, the use of glass wool in the liner and injector temperature. The determination of the constitution by NMR spectroscopy was ambiguous due to the high number of neighbouring, non-proton-bearing atoms. Therefore, other possible structures compatible with the NMR correlations were generated using the WebCocon software. The unambiguous structural evidence was finally obtained by spectra comparison after the synthesis of Cumyl-TsINACA. The low thermal stability, as well as the low affinity and potency, renders this compound unfavourable for the use as a psychoactive substance. Thus, we do not expect widespread adoption of this SC.Hydrogen is a clean alternative to fossil fuels. It has applications for electricity generation and transportation and is used for the manufacturing of ammonia and steel. However, today, H2 is almost exclusively produced from coal and natural gas. As such, methods to produce H2 that do not use fossil fuels need to be developed and adopted. The biological manufacturing of H2 may be one promising solution as this process is clean and renewable. Hydrogen is produced biologically via enzymes called hydrogenases. There are three classes of hydrogenases namely [FeFe], [NiFe] and [Fe] hydrogenases. The [FeFe] hydrogenase HydA1 from the model unicellular algae Chlamydomonas reinhardtii has been studied extensively and belongs to the A1 subclass of [FeFe] hydrogenases that have the highest turnover frequencies amongst hydrogenases (21,000 ± 12,000 H2 s-1 for CaHydA from Clostridium acetobutyliticum). Yet to date, limitations in C. reinhardtii H2 production pathways have hampered commercial scale implementation, in part due to O2 sensitivity of hydrogenases and competing metabolic pathways, resulting in low H2 production efficiency. Here, we describe key processes in the biogenesis of HydA1 and H2 production pathways in C. reinhardtii. We also summarize recent advancements of algal H2 production using synthetic biology and describe valuable tools such as high-throughput screening (HTS) assays to accelerate the process of engineering algae for commercial biological H2 production.Here, we describe the design and synthesis of a new reduction-cleavable spacer (RCS) based on a nitrobenzene scaffold for constructing reduction-responsive oligonucleotides according to standard phosphoramidite chemistry. In addition, we demonstrate that the introduction of the RCS in the middle of an oligonucleotide (30 nt) enables the construction of a self-assembled microsphere capable of exhibiting a reduction-responsive disassembly.RNA interference (RNAi) selectively targets genes and silences their expression in vivo, causing developmental defects, mortality and altered behavior. Consequently, RNAi has emerged as a promising research area for insect pest management. However, it is not yet a viable alternative over conventional pesticides despite several theoretical advantages in safety and specificity. As a first step toward a more standardized approach, a machine learning algorithm was used to identify factors that predict trial efficacy. Current research on RNAi for pest management is highly variable and relatively unstandardized. The applied random forest model was able to reliably predict mortality ranges based on bioassay parameters with 72.6% accuracy. Response time and target gene were the most important variables in the model, followed by applied dose, double-stranded RNA (dsRNA) construct size and target species, further supported by generalized linear mixed effect modeling. Our results identified informative trends, supporting the idea that basic principles of toxicology apply to RNAi bioassays and provide initial guidelines standardizing future research similar to studies of traditional insecticides.