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time was found, suggesting that it is not a potential mechanism underlying the association between cumulative life course adversity and executive function.Ancient charcoal fragments, produced by the use of wood as fuel in archaeological contexts or during natural or anthropic forest fires, persist in soil and sediments over centuries to millennia. They thus offer a unique window to reconstruct past climate, especially palaeo-precipitation regimes thanks to their stable carbon isotope composition. However, the initial δ13C of wood is slightly modified as a function of the carbonisation temperature. Carbonisation-induced 13C fractionation is classically investigated through a transfer function between experimental carbonisation temperatures and the carbon content. This approach assumes that the carbon content is conservative through time in ancient charcoals and neglects the potential impact of post-depositional oxidation occurring in soils and sediments. In the present study, we first show that post-depositional oxidation can lead to a large underestimation of past carbonisation temperatures, thereby minimising the estimation of carbonisation-induced 13C fractionations and possibly biasing δ13C-based climate reconstructions. Secondly, by combining carbon content, Fourier-transform infrared and Raman spectroscopy, we propose a new framework to assess the carbonisation temperatures registered in ancient charcoals. This new framework paves the way to reassessing δ13C-based climate reconstruction.Some machine learning applications do not allow for data augmentation or are applied to modalities where the augmentation is difficult to define. Our study aimed to develop a new method in semi-supervised learning (SSL) applicable to various modalities of data (images, sound, text), especially when augmentation is hard or impossible to define, i.e., medical images. Assuming that all samples, labeled and unlabeled, come from the same data distribution, we can say that labeled and unlabeled data sets used in the semi-supervised learning tasks are similar. Based on this observation, the data embeddings created by the classifier should also be similar for both sets. In our method, finding these embeddings is achieved based on two models-classifier and an auxiliary discriminator model, inspired by the Generative Adversarial Network (GAN) learning process. The classifier is trained to build embeddings for labeled and unlabeled datasets to cheat discriminator, which recognizes whether the embedding comes from a labeled or unlabeled dataset. The method was named the DGSSC from Discriminator Guided Semi-Supervised Classifier. The experimental research aimed evaluation of the proposed method on the classification task in combination with the teacher-student approach and comparison with other SSL methods. In most experiments, training the networks with the DGSSC method improves accuracy with the teacher-student approach. It does not deteriorate the accuracy of any experiment.The oxidative dehydrogenation of propane using CO2 (CO2-ODP) is a promising technique for high-yield propylene production and CO2 utilization. The development of a highly efficient catalyst for CO2-ODP is of great interest and benefit to the chemical industry as well as net zero emissions. Here, we report a unique catalyst material and design concept based on high-entropy intermetallics for this challenging chemistry. A senary (PtCoNi)(SnInGa) catalyst supported on CeO2 with a PtSn intermetallic structure exhibits a considerably higher catalytic activity, C3H6 selectivity, long-term stability, and CO2 utilization efficiency at 600 °C than previously reported. Multi-metallization of the Pt and Sn sites by Co/Ni and In/Ga, respectively, greatly enhances propylene selectivity, CO2 activation ability, thermal stability, and regenerable ability. The results obtained in this study can promote carbon-neutralization of industrial processes for light alkane conversion.Energy piles have been popular globally with functions of both pile foundation and ground source heat pumps. Although several researches have been devoted to the probabilistic design and assessment of energy piles, the corresponding procedures are too complicated for engineers. As a simple variant of the reliability-based design method, the load and resistance factor design (LRFD) approach for the geotechnical design of energy piles is presented in this study. Firstly, the load-transfer model for energy piles is developed to investigate the effect of cyclic thermal loading on the pile settlement. Then, the LRFD procedures based on first-order reliability method and target reliability method are implemented into two different constrained nonlinear optimization problems, respectively. The proposed LRFD model for energy piles is demonstrated through an example pile and a series of parametric analyses.Shikonin induces glioma cell death via necroptosis, a caspase-independent programmed cell death pathway that is chiefly regulated by receptor-interacting serine/threonine protein kinase1 (RIP1) and 3 (RIP3). Chromatinolysis is considered as one of the key events leading to cell death during necroptosis. It is usually accompanied with nuclear translocation of AIF and formation of γ-H2AX. VE-821 in vitro Cyclophilin A (CypA) is reported to participate in the nuclear translocation of AIF during apoptosis. However, it remains unclear whether CypA contributes to necroptosis and regulation of chromatinolysis. In this study, our results revealed for the first time that shikonin promoted time-dependent CypA activation, which contributed to nuclear translocation of AIF and γ-H2AX formation. In vitro studies showed that knockdown of CypA by siRNA or inhibition of CypA by its specific inhibitor, cyclosporine A (CsA), not only significantly mitigated shikonin-induced glioma cell death, but also prevented chromatinolysis. Mechanistically, activated CypA targeted mitochondria and triggered mitochondrial superoxide overproduction, which then promoted AIF translocation from mitochondria into the nucleus by depolarizing the mitochondria and intensified the formation of γ-H2AX by promoting intracellular accumulation of ROS. Additionally, the CypA in the nucleus can form DNA degradation complexes with AIF and γ-H2AX, which also promote the execution of chromatinolysis. Thus, we demonstrate that CypA contributes to shikonin-induced glioma cell necroptosis and promotion of chromatinolysis.Sacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate with an SN-38 payload. In the ASCENT study, patients with metastatic triple-negative breast cancer (mTNBC) relapsed/refractory to ≥2 prior chemotherapy regimens (≥1 in the metastatic setting), received SG or single-agent treatment of physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine). This ASCENT safety analysis includes the impact of age and UGT1A1 polymorphisms, which hinder SN-38 detoxification. SG demonstrated a manageable safety profile in patients with mTNBC, including those ≥65 years; neutropenia/diarrhea are key adverse events (AE). Patients with UGT1A1 *28/*28 genotype versus those with 1/*28 and *1/*1 genotypes had higher rates of grade ≥3 SG-related neutropenia (59% vs 47% and 53%), febrile neutropenia (18% vs 5% and 3%), anemia (15% vs 6% and 4%), and diarrhea (15% vs 9% and 10%), respectively. Individuals with UGT1A1 *28/*28 genotype should be monitored closely; active monitoring and routine AE management allow optimal therapeutic exposure of SG.The sustainability of wave energy linked to the intra- and inter-annual variability in wave climate is crucial in wave resource assessment. In this study, we quantify the dependency of stability of wave energy flux (power) on long-term variability of wind and wave climate to detect a relationship between them. We used six decades of re-analysis wind and simulated wave climate in the entire globe and using two 30-yearly periods, we showed that not only the previously suggested minimum period of 10 years for wave energy assessment appears to be insufficient for detecting the influence of climate variability, but also the selection period for wave energy assessment can lead to an over/underestimation of about 25% for wave power. In addition, we quantified the dependency of rates of change of wave power, wind speed and wave parameters and showed that the change in wave power is mainly a function of change in swell wave climate globally. Finally, we redefined the suitability of global hotspots for wave energy extraction using intra-annual fluctuation, long-term change, and the available wave power for the period of six decades. The results highlight the importance of climate variability in resource assessment, sustainability, and prioritizing the hotspots for future development.Fertility treatments like in vitro fertilization (IVF) or oocyte cryopreservation (OC) require the daily use of injectable gonadotropins and has been associated with treatment burden and attrition from fertility treatment. We conducted a randomized clinical trial to determine (1) whether educational videos about fertility medications improved infertility self-efficacy scale (ISES), fertility quality of life treatment (FertiQoL-T), and Perceived stress scale (PSS) scores and (2) if such videos improved confidence and reduced medication errors during a first ovarian stimulation cycle. Participants were given access to an online portal with randomized access to either placebo control videos focused on an orientation to IVF or experimental videos that reviewed the preparation and administration of medications used during ovarian stimulation in addition to the placebo videos. Participants completed pre and post-treatment questionnaires. 368 patients enrolled and 257 participants completed the study. There were no differences in ISES, FertiQoL-T or PSS scores between the two groups in an intention-to-treat (p = 0.18, 0.72, and 0.92, respectively) or per-protocol analysis (p = 0.11, 0.38, and 0.37, respectively). In the per protocol analysis, participants who watched experimental videos were four-fold more likely to report confidence administering medications OR 4.70 (95% CI 2.10, 11.1; p  less then  0.01) and were 63% less likely to make medication errors OR 0.37 (95% CI 0.14, 0.90; p = 0.03). Participants had similar likelihoods of rating videos as helpful and recommending videos to others (p = 0.06 and 0.3, respectively). Educational videos about fertility medications may not influence psychological well-being but might improve confidence in medication administration and reduce medication errors. Trial registration number NCT02979990.Recent epigenetic age studies suggested accelerated aging in schizophrenia. Although antipsychotics may modulate epigenetic age, direct estimation of their roles was impeded when tissues derived from patients were used for analysis. By using a cellular model, we found that antipsychotics generally worked as epigenetic age regulators in vitro.Pancreatic ductal adenocarcinoma (PDAC) is a multifactorial disease, the molecular profile of which remains unclear. This study aimed at unveiling the disease-related protein networks associated with different outcomes of resectable, node-positive PDAC cases. We assessed laser-microdissected cancerous cells from PDAC tissues of a poor outcome group (POG; n = 4) and a better outcome group (BOG; n = 4). Noncancerous pancreatic duct tissues (n = 5) were used as the reference. We identified four representative network modules by applying a weighted network correlation analysis to the obtained quantitative PDAC proteome datasets. Two network modules that were significant for POG were associated with the heat shock response to hypoxia-related stress; in the latter, a large involvement of the non-canonical Hedgehog pathway (regulated by GLI1), the internal ribosome entry site-mediated cap-independent translation, the inositol requiring enzyme 1-alpha (IRE1α)/X-box binding protein 1 pathway of the unfolding protein response (UPR), and the aerobic glycolysis was observed.

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