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More broadly, these results suggest that the application of data-driven methods to neuroimaging data can be a promising approach to investigate how brains shape and are shaped by individuals' positions in their real-world social networks.The strength of the different materials specimens containing a central hole subjected to varying loading areas constitutes lots of underground engineering such as entry arrangement and mining process. In this study, the failure resulted from micro-fracturing in the specimen, which can be characterized by the crack propagation path if the damage events are monitored by using Digital Image Correlation (DIC), infrared thermal imager and high-speed camera. The experimental results demonstrate that there are three different types of typical failure modes for specimens with central holes according to the loading areas. The evolution of the temperature field is shown for various loading areas, the smaller loading area, the greater the stress concentration, and the more pronounced the thermodynamic features. The temperature field can also be associated with material properties in addition to loading area. Additionally, failure around the hole with redistributed stress has been observed, and strain energy density (SED) can help explain the failure mechanisms. The progressive damage process, which takes into account the heterogeneity in elastic modulus and rock strength characteristic, is demonstrated by developing a constitutive model that uses the uniaxial compression and Brazilian disc tests to parameterize it. By comparison with plastic zone, the proposed constitutive model is used to quantitatively evaluate the accumulation of damage. Failure mechanisms are established based on this work and are anticipated to be extensively utilized in engineering applications.Projected potential of 2.5-4.0 Å cryo-EM structures for structure-based drug design is not well realized yet. Here we show that a 3.1 Å structure of PRMT5 is suitable for selecting computed poses of a chemical inhibitor and its analogs for enhanced potency. PRMT5, an oncogenic target for various cancer types, has many inhibitors manifesting little cooperativity with MTA, a co-factor analog accumulated in MTAP-/- cells. To achieve MTA-synergic inhibition, a pharmacophore from virtual screen leads to a specific inhibitor (11-2 F). Cryo-EM structures of 11-2 F / MTA-bound human PRMT5/MEP50 complex and its apo form resolved at 3.1 and 3.2 Å respectively show that 11-2 F in the catalytic pocket shifts the cofactor-binding pocket away by ~2.0 Å, contributing to positive cooperativity. Computational analysis predicts subtype specificity of 11-2 F among PRMTs. Structural analysis of ligands in the binding pockets is performed to compare poses of 11-2 F and its redesigned analogs and identifies three new analogs predicted to have significantly better potency. One of them, after synthesis, is ~4 fold more efficient in inhibiting PRMT5 catalysis than 11-2 F, with strong MTA-synergy. These data suggest the feasibility of employing near-atomic resolution cryo-EM structures and computational analysis of ligand poses for small molecule therapeutics.The aim of this study was to investigate the sociodemographic characteristics of patients based on the poison chosen and different types of organophosphorus compounds. The data were collected to explore the sociodemographic characteristics of organophosphate (OP)-poisoned patients based on the source, site, and route of poisoning, education level, occupational status, and the purpose of poisoning. Furthermore, we estimated the serotonin and dopamine levels in the plasma samples of patients, and survival plots were also described. During the study of OP pesticide poisoning in 116 human subjects and 5 healthy volunteers, we observed, based on the survival plot, that75.9% of the patients were discharged, and the remaining patients died (24.1% of the patients) due to respiratory failure followed by cardiac arrest. Our findings suggest that the serotonin levels significantly (p less then 0.01 and p less then 0.001) decreased from 12 to 36 h, whereas the dopamine levels slightly increased from 12 to 36 h in the group with OP poisoning compared to the control group. Based on these findings, this study may aid in deciphering the precise mechanism by which pesticides cause behavioural changes that influence serotonin and dopamine levels in OP-poisoned patients. The purpose of this work was to serve as a small reminder of the risk to public health associated with organophosphate pesticides.Aim of this study was to examine the accuracy of widely used conventional radiography-based (2D) neck-shaft angle measurements compared to 3D reconstruction. In our retrospective study, EOS 2D/3D images of 156 patients (312 limbs) were selected from our database (4-16 years old 6 girls and 6 boys/year), where no pathology was revealed. Using the 2D modality of the EOS method neck-shaft angle was measured using the "biggest diameter" and "circle fitting" techniques to define the femoral neck axis and 1/3, 1/2 and full femur to determine the femoral shaft axis. EOS 3D reconstructions of same images were also performed and a comparison of 2D and 3D results was made. We did not find any significant difference between accuracy of the four examined 2D methods, although the deviation between 2 and 3D results was considerable (average difference 5.11-5.58°, p less then 0,001). In 31% of the cases, difference was more than 10°. Only femoral torsion showed significant influence on the difference (correlation coefficient 0.380, p less then 0.001). We did not find a clinically significant difference between the examined 2D methods, although their accuracy was highly questionable compared to 3D results. We suggest using any 3D imaging method for surgical planning and in uncertain cases.A special in vitro model maintained with ultrathin cardiac slices with a preserved architecture, multi-cellularity, and physiology of the heart tissue was used. In our experiments, we performed label-free quantitative SWATH-MS proteomic analysis of the adult myocardial slices in vitro after biomimetic electromechanical stimulation. Rat myocardial slices were stretched to sarcomere lengths (SL) within the physiological range of 1.8-2.2 μm. Electromechanically stimulated slices were compared with slices cultured without electromechanical stimulation (unloaded and nonstimulated-TW) on a liquid-air interface and with fresh myocardial slices (0 h-C). Quantitative (relative) proteomic analyses were performed using a label-free SWATH-MS technique on a high-resolution microLC-MS/MS TripleTOF 5600+ system (SCIEX). The acquired MS/MS spectra from the DDA LC-MS/MS analyses of the rat heart samples were searched against the UniProt Rattus norvegicus database (version of 15.05.2018) using the Paragon algorithm incorporated into ProteinPilot 4.5 (SCIEX) software. The highest number of differential proteins was observed in the TW group-121 when compared to the C group. In the 1.8 and 2.2 groups, 79 and 52 proteins present at a significantly different concentration from the control samples were found, respectively. A substantial fraction of these proteins were common for two or more comparisons, resulting in a list of 169 significant proteins for at least one of the comparisons. This study found the most prominent changes in the proteomic pattern related to mitochondrial respiration, energy metabolism, and muscle contraction in the slices that were stretched and fresh myocardial slices cultured without electromechanical stimulation.Whether, and under what conditions, groups exhibit "crowd wisdom" has been a major focus of research across the social and computational sciences. Much of this work has focused on the role of social influence in promoting the wisdom of the crowd versus leading the crowd astray and has resulted in conflicting conclusions about how social network structure determines the impact of social influence. Here, we demonstrate that it is not enough to consider the network structure in isolation. Using theoretical analysis, numerical simulation, and reanalysis of four experimental datasets (totaling 2885 human subjects), we find that the wisdom of crowds critically depends on the interaction between (i) the centralization of the social influence network and (ii) the distribution of the initial individual estimates. By adopting a framework that integrates both the structure of the social influence and the distribution of the initial estimates, we bring previously conflicting results under one theoretical framework and clarify the effects of social influence on the wisdom of crowds.Plant chloroplasts conduct photosynthesis to convert solar energy into sugars for the carbon source essential for cell living and growth during the day. Pilaralisib ic50 One fraction of photosynthetic products is stored in chloroplasts by forming starch granules to continue the provision of carbon energy during the night. Currently, profiling the starch temporal pattern requires either (i) sacrificing the leaves, or (ii) generating transgenic plants at the risk of changing the metabolisms by incorporating a genetically modified granule-bound starch synthase (GBSS). In this paper, we demonstrated a nondestructive method using two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging to quantify starch granules within chloroplasts of fresh intact leaves across a day-night cycle. We did so using two Arabidopsis lines having normal and excess starch contents wild-type (Columbia-0) and starch excess 1 (sex1). The starch granules were visualized by SHG imaging, while the chloroplasts in mesophyll cells were visualized by TPF imaging. Our results provided micron scale spatial resolution of starch distribution within leaves and showed starch circadian patterns consistent with those profiled by enzymatic assays in previous studies. We demonstrated that TPF-SHG imaging is a potential tool for revealing the real-time heterogeneity of starch circadian rhythm in leaf cells, without the need for destructive sample preparation.Cannabis is the main illicit psychoactive substance used by pregnant women in France. The aim of the present national survey was to describe adverse events (AEs) of recreational cannabis use during pregnancy reported to the French Addictovigilance Network (FAN). Spontaneous reports (SRs) of AEs related to recreational cannabis use during pregnancy were collected by the FAN between 01/01/2011 and 31/01/2021 (excluding cannabidiol and synthetic cannabinoids). Over the study period, 160 SRs involved cannabis use alone or in association with tobacco (59% of all SRs) which increased. Among the 175 maternal AEs, the most commons were psychiatric AEs experienced by 96 (64.9%) women, in particular cannabis use disorders (n = 89, 60.1%), dependence (n = 54, 36.5%) and abuse (n = 21, 14.2%). Among the 57 fetal AEs, the most common were heart rhythm disorders that affected 25 (16.9%) fetuses and intrauterine growth restriction (IUGR) (n = 20, 13.5%). Among the 140 neonatal AEs, the most common were IUGR experienced by 39 (26.3%) newborns and prematurity (n = 32, 21.6%). Twelve cases of congenital malformations were observed and 4 intrauterine/neonatal deaths. Furthermore, some of these AEs (n = 13) were unexpected. Cannabis use during pregnancy has problematic consequences for both mothers and infants who need close monitoring.
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