P91 is a 9Cr-1Mo ferritic–martensitic steel which is used as steam generator (SG) material for fast reactor applications. Construction of SGs involves several weld joints (WJs) that are weak links ...also in the structure. Application of various types of cyclic loading and creep combinations can lead to different responses of the P91 steel WJ and thereby the resultant fatigue life. The scope of the present work is to identify the deformation and damage under the effects of various combinations of creep–fatigue interaction (CFI) waveforms. Towards this, location-specific damage has been assessed through various particles present in the steel and their cavitation propensity and severity to cause final failure under the effects of various fatigue-creep combinations. First time, it is demonstrated through 2D hardness mapping that in an unsymmetrical CFI loading waveform, short creep hold has more damaging effects in the form of strength loss as against the longer strain or creep holds. Interestingly, whereas under unsymmetrical loading, the initial strength of the weld metal was either uniformly retained (30 min CH or 30 min TH) or uniformly lost (10 min CH, 10 min TH), under symmetrical loading (CC and 5 min TCH), only a part of the weld metal lost the initial strength and the rest of it retained.
Graphical Abstract
To determine the accuracy of point-of-care ultrasonography for the diagnosis of pneumonia in children and young adults by a group of clinicians.
Prospective observational cohort study.
Two urban ...emergency departments.
Patients from birth to age 21 years undergoing chest radiography for suspected community-acquired pneumonia.
After documenting clinical examination findings, clinicians with 1 hour of focused training used ultrasonography to diagnose pneumonia in children and young adults.
Test performance characteristics for the ability of ultrasonography to diagnose pneumonia were determined using chest radiography as a reference standard. Subgroup analysis was performed in patients having lung consolidation exceeding 1 cm with sonographic air bronchograms detected on ultrasonography; specificity and positive likelihood ratio (LR) were calculated to account for lung consolidation of 1 cm or less with sonographic air bronchograms undetectable by chest radiography.
Two hundred patients were studied (median age, 3 years; interquartile range, 1-8 years); 56.0% were male, and the prevalence of pneumonia by chest radiography was 18.0%. Ultrasonography had an overall sensitivity of 86% (95% CI, 71%-94%), specificity of 89% (95% CI, 83%-93%), positive LR of 7.8 (95% CI, 5.0-12.4), and negative LR of 0.2 (95% CI, 0.1-0.4) for diagnosing pneumonia by visualizing lung consolidation with sonographic air bronchograms. In subgroup analysis of 187 patients having lung consolidation exceeding 1 cm, ultrasonography had a sensitivity of 86% (95% CI, 71%-94%), specificity of 97% (95% CI, 93%-99%), positive LR of 28.2 (95% CI, 11.8-67.6) and negative LR of 0.1 (95% CI, 0.1-0.3) for diagnosing pneumonia.
Clinicians are able to diagnose pneumonia in children and young adults using point-of-care ultrasonography, with high specificity.
Abstract
CATH (https://www.cathdb.info) identifies domains in protein structures from wwPDB and classifies these into evolutionary superfamilies, thereby providing structural and functional ...annotations. There are two levels: CATH-B, a daily snapshot of the latest domain structures and superfamily assignments, and CATH+, with additional derived data, such as predicted sequence domains, and functionally coherent sequence subsets (Functional Families or FunFams). The latest CATH+ release, version 4.3, significantly increases coverage of structural and sequence data, with an addition of 65,351 fully-classified domains structures (+15%), providing 500 238 structural domains, and 151 million predicted sequence domains (+59%) assigned to 5481 superfamilies. The FunFam generation pipeline has been re-engineered to cope with the increased influx of data. Three times more sequences are captured in FunFams, with a concomitant increase in functional purity, information content and structural coverage. FunFam expansion increases the structural annotations provided for experimental GO terms (+59%). We also present CATH-FunVar web-pages displaying variations in protein sequences and their proximity to known or predicted functional sites. We present two case studies (1) putative cancer drivers and (2) SARS-CoV-2 proteins. Finally, we have improved links to and from CATH including SCOP, InterPro, Aquaria and 2DProt.
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•Spent media wastewater recycling achieved with Aurantiochytrium sp. in batch culture.•Reuse of spent media wastewater compromises with product formation.•Self-inhibitory compounds ...accumulation reduces lipid production.•Salinity stress gives the compositional shift of fatty acids.
The main aim of this work was the optimization of recycled spent media wastewater (SMW) concentration for high biomass production of Aurantiochytrium sp. ICTFD5. Further, optimization for growth patterns and lipid accumulation capacity with three subsequent recycling runs was also performed. The biomass production after 96 h fermentation for recycling with 50% SMW was; 21.3 ± 1.5, 19.1 ± 1.3, 19 ± 1.2, and 23 ± 1.2 g/L for the first, second, third recycle runs, and control respectively. All the recycle runs were carried out with the same media and cultivation conditions. Subsequent recycling affected lipid accumulation, and it was decreased by ~4 to 9% compared to the control. The compositional shift of fatty acids was observed with sequential recycle runs, changing more towards saturated fatty acids content, suggesting it to be a new potential source for biodiesel feedstock.
Traumatic stress triggers or exacerbates multiple psychiatric illnesses, including post-traumatic stress disorder (PTSD). Nevertheless, the neurophysiological mechanisms underlying stress-induced ...pathology remain unclear, in part due to the limited understanding of neuronal signaling molecules, such as neuropeptides, in this process. Here, we developed mass spectrometry (MS)-based qualitative and quantitative analytical strategies to profile neuropeptides in rats exposed to predator odor (an ethologically relevant analogue of trauma-like stress) versus control subjects (no odor) to determine peptidomic alterations induced by trauma. In total, 628 unique neuropeptides were identified across 5 fear-circuitry-related brain regions. Brain-region-specific changes of several neuropeptide families, including granin, ProSAAS, opioids, cholecystokinin, and tachykinin, were also observed in the stressed group. Neuropeptides from the same protein precursor were found to vary across different brain regions, indicating the site-specific effects of predator stress. This study reveals for the first time the interaction between neuropeptides and traumatic stress, providing insights into the molecular mechanisms of stress-induced psychopathology and suggesting putative novel therapeutic strategies for disorders such as PTSD.
Understanding the mechanisms of protein function is indispensable for many biological applications, such as protein engineering and drug design. However, experimental annotations are sparse, and ...therefore, theoretical strategies are needed to fill the gap. Here, we present the latest developments in building functional subclassifications of protein superfamilies and using evolutionary conservation to detect functional determinants, for example, catalytic-, binding- and specificity-determining residues important for delineating the functional families. We also briefly review other features exploited for functional site detection and new machine learning strategies for combining multiple features.
Background The frequencies, cellular phenotypes, epitope specificity, and clonal diversity of allergen-specific B cells in patients with food allergy are not fully understood but are of major ...pathogenic and therapeutic significance. Objective We sought to characterize peanut allergen–specific B-cell populations and the sequences and binding activities of their antibodies before and during immunotherapy. Methods B cells binding fluorescently labeled Ara h 1 or Ara h 2 were phenotyped and isolated by means of flow cytometric sorting from 18 patients at baseline and 13 patients during therapy. Fifty-seven mAbs derived from allergen-binding single B cells were evaluated by using ELISA, Western blotting, and peptide epitope mapping. Deep sequencing of the B-cell repertoires identified additional members of the allergen-specific B-cell clones. Results Median allergen-binding B-cell frequencies were 0.0097% (Ara h 1) or 0.029% (Ara h 2) of B cells in baseline blood from allergic patients and approximately 3-fold higher during immunotherapy. Five of 57 allergen-specific cells belonged to clones containing IgE-expressing members. Almost all allergen-specific antibodies were mutated, and binding to both conformational and linear allergen epitopes was detected. Increasing somatic mutation of IgG4 members of a clone was seen in immunotherapy, whereas IgE mutation levels in the clone did not increase. Conclusion Most peanut allergen–binding B cells isolated by means of antigen-specific flow sorting express mutated and isotype-switched antibodies. Immunotherapy increases their frequency in the blood, and even narrowly defined allergen epitopes are recognized by numerous distinct B-cell clones in a patient. The results also suggest that oral immunotherapy can stimulate somatic mutation of allergen-specific IgG4.
In data, analysis clustering plays a major role. In the past decade varieties of clustering algorithms are proposed and produced better results. But many of them required prior information on the ...number of clusters and failed to produce optimum results when such information is not available. In real-life problems, it is difficult to predict the number of clusters due to the complexity of data in shape and dimensionality. Therefore predicting the number of clusters is a difficult task and this draws the attention of many researchers. In this work, we proposed DKCSMO, dynamic kernel clustering with a spider monkey optimization algorithm. In this work for better clustering results, the local leader phase of the spider monkey optimization algorithm is improved with the neighborhood search strategy. Further to improve the quality of results, we modified CS-Index with Gaussian kernel distribution. The proposed algorithm is compared with five well-known meta-heuristic algorithms and seven previously published automatic clustering algorithms. Experimental results show that the proposed algorithm produced better results in terms of the predicted clusters, DB, SIL, and ARI measures.
This study aimed to assess the nature and magnitude of perceptions of wife-beating among women and men in Nepal and experiences of domestic violence (DV) and help-seeking among DV victims. The Nepal ...Demographic Health Surveys (NDHS) (2001, 2006, 2011, 2016) included questions on whether women and men justify wife-beating and whether DV victims sought help (NDHS 2011 and 2016). Covariates in regression models were guided by the socioecological model. We estimated odds ratios for dichotomous outcomes. Compiled data from Multiple Indicator Cluster Surveys was used to understand trends. About 29.1% women justified wife-beating in 2001, 24.2% in 2006, and 29.1% in 2016. About 32.4% of women experienced any DV in 2011 and 28.0% in 2016. In 2011 about 21.8% of those abused sought help and in 2016 about 25.8% sought help. Women who justified wife-beating were more likely to experience DV in 2011 (OR 5.8, p < 0.001) and in 2016 (OR 1.5, p < 0.001) and less likely to seek help in 2011 (OR 0.3, p < 0.001) and in 2016 (OR 0.8, p < 0.001). Perceptions of wife-beating play an important role in actual experiences of DV and help-seeking behavior of DV victims. Societal and individual beliefs are intertwined, and cultural norms have a great bearing on these beliefs. Both individual and wider societal-level acceptance of violence needs to be addressed simultaneously.
Intense stress precipitates symptoms in disorders such as post-traumatic stress (PTSD) and schizophrenia. Patients with these disorders have dysfunctional sensorimotor gating as indexed by disrupted ...prepulse inhibition of the startle response (PPI), which refers to decreased startle response when a weak pre-stimulus precedes a startling stimulus. Stress promotes release of norepinephrine (NE) and corticotrophin releasing factor (CRF) within the brain, neurotransmitters that also modulate PPI. We have shown that repeated stress causes sensitization of NE receptors within the basolateral amygdala (BLA) via CRF receptors and promotes long-lasting PPI disruptions and startle abnormalities. The bed nucleus of the stria terminalis (BNST) is another crucial brain region that could be involved in stress-induced alterations in NE and CRF functions to promote PPI changes as this anatomical structure is enriched in CRF and NE receptors that have been shown to regulate each other. We hypothesized that repeated infusions of NE into the BNST would cross-sensitize CRF receptors or vice versa to alter PPI. Separate groups of male Sprague Dawley rats received, CRF (200ng/0.5 μl), NE (20μg/0.5 μl), or vehicle into the BNST, once/day for 3 days and PPI was tested after each infusion. Repeated CRF-or vehicle-treated rats were then challenged with a subthreshold dose of NE (0.3μg/0.5 μl) while repeated NE-treated rats were challenged with CRF (200ng/0.5 μl), and PPI was measured. Surprisingly, initial/repeated CRF or vehicle in the BNST had no effects on PPI. In contrast, initial and repeated NE disrupted PPI. Sub-threshold NE challenge in rats that previously received repeated CRF had no effect on PPI. Interestingly though, intra-BNST challenge dose of CRF significantly disrupted PPI in rats that previously had received repeated NE infusions. Taken together, these results indicate that repeated stress-induced NE release could alter the activity of CRF receptors in the BNST to modulate sensorimotor gating as measured through PPI.
•BNST modulates sensorimotor gating via norepinephrine and CRF interactions.•Repeated norepinephrine in BNST sensitizes the CRF system.•BNST is a crucial brain region for modulating stress-induced changes in sensorimotor gating.
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