In this paper, the microstructure and grain orientation uniformity of Ti-17 titanium alloy under high temperature compression and axial upsetting and drawing processing (AUDP) conditions were ...investigated by light microscopy (LM) and electron backscatter diffraction (EBSD) technique. The relationship between the microstructure and grain orientation evolution in different hot working modes and hot deformation parameters was systematically investigated. The results indicate that grain size of β phase affects the precipitation behavior of α phase, the smaller β grains resulting in a higher grain misorientation angle, thereby improving grain orientation uniformity of the material. AUDP can obtain finer uniformity microstructure, but the homogeneity of β phase grain orientation has not been obviously improved and the anisotropy of the β matrix still exists. Subsequently, when annealing in the (α+β) region, the grain growth and the interface become more clearly, but the annealing process cannot eliminate the macro-zones induced by the β phase with a grain orientation concentrated area.
To investigate the influence of common and low-frequency genetic variants on the risk of ischemic stroke (all IS) and etiologic stroke subtypes.
We meta-analyzed 12 individual genome-wide association ...studies comprising 10,307 cases and 19,326 controls imputed to the 1000 Genomes (1 KG) phase I reference panel. We selected variants showing the highest degree of association (p < 1E-5) in the discovery phase for replication in Caucasian (13,435 cases and 29,269 controls) and South Asian (2,385 cases and 5,193 controls) samples followed by a transethnic meta-analysis. We further investigated the p value distribution for different bins of allele frequencies for all IS and stroke subtypes.
We showed genome-wide significance for 4 loci: ABO for all IS, HDAC9 for large vessel disease (LVD), and both PITX2 and ZFHX3 for cardioembolic stroke (CE). We further refined the association peaks for ABO and PITX2. Analyzing different allele frequency bins, we showed significant enrichment in low-frequency variants (allele frequency <5%) for both LVD and small vessel disease, and an enrichment of higher frequency variants (allele frequency 10% and 30%) for CE (all p < 1E-5).
Our findings suggest that the missing heritability in IS subtypes can in part be attributed to low-frequency and rare variants. Larger sample sizes are needed to identify the variants associated with all IS and stroke subtypes.
Pediatric supratentorial tumors such as embryonal tumors, high-grade gliomas, and ependymomas are difficult to distinguish by histopathology and imaging because of overlapping features. We applied ...machine learning to uncover MR imaging-based radiomics phenotypes that can differentiate these tumor types.
Our retrospective cohort of 231 patients from 7 participating institutions had 50 embryonal tumors, 127 high-grade gliomas, and 54 ependymomas. For each tumor volume, we extracted 900 Image Biomarker Standardization Initiative-based PyRadiomics features from T2-weighted and gadolinium-enhanced T1-weighted images. A reduced feature set was obtained by sparse regression analysis and was used as input for 6 candidate classifier models. Training and test sets were randomly allocated from the total cohort in a 75:25 ratio.
The final classifier model for embryonal tumor-versus-high-grade gliomas identified 23 features with an area under the curve of 0.98; the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.85, 0.91, 0.79, 0.94, and 0.89, respectively. The classifier for embryonal tumor-versus-ependymomas identified 4 features with an area under the curve of 0.82; the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.93, 0.69, 0.76, 0.90, and 0.81, respectively. The classifier for high-grade gliomas-versus-ependymomas identified 35 features with an area under the curve of 0.96; the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.82, 0.94, 0.82, 0.94, and 0.91, respectively.
In this multi-institutional study, we identified distinct radiomic phenotypes that distinguish pediatric supratentorial tumors, high-grade gliomas, and ependymomas with high accuracy. Incorporation of this technique in diagnostic algorithms can improve diagnosis, risk stratification, and treatment planning.
Background: Calreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor ...behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB. Patients and methods: Sixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings. Results: Among 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (≤1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan–Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions. Conclusions: CRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.
Coral reefs in the Central Indo-Pacific region comprise some of the most diverse and yet threatened marine habitats. While reef monitoring has grown throughout the region in recent years, studies of ...coral reef benthic cover remain limited in spatial and temporal scales. Here, we analysed 24,365 reef surveys performed over 37 years at 1972 sites throughout East Asia by the Global Coral Reef Monitoring Network using Bayesian approaches. Our results show that overall coral cover at surveyed reefs has not declined as suggested in previous studies and compared to reef regions like the Caribbean. Concurrently, macroalgal cover has not increased, with no indications of phase shifts from coral to macroalgal dominance on reefs. Yet, models incorporating socio-economic and environmental variables reveal negative associations of coral cover with coastal urbanisation and sea surface temperature. The diversity of reef assemblages may have mitigated cover declines thus far, but climate change could threaten reef resilience. We recommend prioritisation of regionally coordinated, locally collaborative long-term studies for better contextualisation of monitoring data and analyses, which are essential for achieving reef conservation goals.
This paper focused on the light source optimization for visual inspection of piston surface defects. A novel structured lighting system was developed to overcome the difficulties in the ...well-qualified imaging of tiny and random defects on the cylindrical smooth surface of components such as pistons. A polarized light-filtering based method was proposed to enhance the defect image contrast, enlarge the detection range, and suppress the noise of flawless area. It was both experimentally proven and theoretically proven effective by mathematical modeling of light intensity loss during light propagation. To analyze the influence of the pose and position of light sources on defect imaging quality, the system model for camera, light source, and workpiece was established, and the structure parameters of the lighting system were optimized to improve the brightness uniformity over the entire inspection region and lighting efficiency. Moreover, a soft lighting method was introduced as a subsidiary means of removing the surface noise at two ends of a piston. This method was found to be more effective compared with conventional software filtering algorithm. Finally, a case was examined. The defects on the automotive brake master piston surface were captured using the optimized light source system. A random sampling experiment with 600 specimens revealed that the false-positive rate was about 2.3%, and with no leak detection. The findings have been applied in the production, and it is expected to be referred in inspecting defects on other smooth cylindrical surfaces.
Spermatozoa undergo a poorly understood activation process induced by bicarbonate and mediated by cyclic adenosine 3′,5′-monophosphate (cAMP). It has been assumed that bicarbonate mediates its ...effects through changes in intracellular pH or membrane potential; however, we demonstrate here that bicarbonate directly stimulates mammalian soluble adenylyl cyclase (sAC) activity in vivo and in vitro in a pH-independent manner. sAC is most similar to adenylyl cyclases from cyanobacteria, and bicarbonate regulation of cyclase activity is conserved in these early forms of life. sAC is also expressed in other bicarbonate-responsive tissues, which suggests that bicarbonate regulation of cAMP signaling plays a fundamental role in many biological systems.
Background: Tardive dyskinesia (TD) is a severe and potentially irreversible adverse effect of long‐term antipsychotic treatment. Typical antipsychotics are commonly binding to the dopamine receptor ...D2 (DRD2), but the occurrence of antipsychotic‐induced TD is rather delayed; therefore, the development of TD may be associated with mediators or signalling complexes behind DRD2, such as β‐arrestin 2 (ARRB2), an important mediator between DRD2 and serine–threonine protein kinase (AKT) signal cascade.
Methods: A case–control study to evaluate the association between rs1045280 (Ser280Ser) and antipsychotic‐induced TD was performed amongst 381 patients (TD/non‐TD = 228/153).
Results: There was a significant difference in the genotype distribution between TD and non‐TD groups (P = 0.025); furthermore, the allelic analysis indicated that patients with T allele had increased risk of TD occurrence (ORT = 1.58, 95% CI = 1.14–2.19, P = 0.007).
Conclusions: To the best of our knowledge, this is the first study reporting a positive association between the SNP rs1045280 and TD in schizophrenic patients.
Low bone mineral density (BMD) is a risk factor for fracture. Although the current “gold standard” test is DXA of the hip and spine, this method is not universally available. No large studies have ...evaluated the ability of new, less expensive peripheral technologies to predict fracture. We studied the association between BMD measurements at peripheral sites and subsequent fracture risk at the hip, wrist/forearm, spine, and rib in 149,524 postmenopausal white women, without prior diagnosis of osteoporosis. At enrollment, each participant completed a risk assessment questionnaire and had BMD testing at the heel, forearm, or finger. Main outcomes were new fractures of the hip, wrist/forearm, spine, or rib within the first 12 months after testing. After 1 year, 2259 women reported 2340 new fractures. Based on manufacturers' normative data and multivariable adjusted analyses, women who had T scores ≤ −2.5 SD were 2.15 (finger) to 3.94 (heel ultrasound US) times more likely to fracture than women with normal BMD. All measurement sites/devices predicted fracture equally well, and risk prediction was similar whether calculated from the manufacturers' young normal values (T scores) or using SDs from the mean age of the National Osteoporosis Risk Assessment (NORA) population. The areas under receiver operating characteristic (ROC) curves for hip fracture were comparable with those published using measurements at hip sites. We conclude that low BMD found by peripheral technologies, regardless of the site measured, is associated with at least a twofold increased risk of fracture within 1 year, even at skeletal sites other than the one measured.
Psychotic disorders are complex disorders with multiple etiologies. While increased dopamine synthesis capacity has been proposed to underlie psychotic episodes, dopamine-independent processes are ...also involved (less responsive to dopamine receptor-blocking medications). The underlying mechanism(s) of the reduction in antipsychotic responsiveness over time, especially after repeated relapses, remain unclear. Despite the consistent evidence of dopamine overactivity and hippocampal volume loss in schizophrenia, few accounts have been provided based on the interactive effect of dopamine on hippocampal synapse plasticity mediating autobiographical memory processes. The present hypothesis builds upon previous works showing the potential effects of dopamine overactivity on hippocampal-mediated neuroplasticity underlying autobiographical memory, alongside known patterns of autobiographical memory dysfunction in psychosis. We propose that spurious autobiographical memory of psychosis (SAMP) produced during active psychosis may be a key mechanism mediating relapses and treatment non-responsiveness. In a hyperdopaminergic state, SAMP is expected to be generated at an increased rate during active psychosis. Similar to other memories, it will undergo assimilation, accommodation, and extinction processes. However, if SAMP fails to integrate with existing memory, a discontinuity in autobiographical memory may result. Inadequate exposure to normalizing experiences and hyposalience due to overmedication or negative symptoms may also impede the resolution of SAMP. Residual SAMP is hypothesized to increase the propensity for relapse and treatment non-responsiveness. Based on recent findings on the role of dopamine in facilitating hippocampal synapse plasticity and autobiographical memory formation, the SAMP hypothesis is consistent with clinical observations of DUP effects, including the repetition of contents in psychotic relapses as well as the emergence of treatment non-responsiveness after repeated relapses. Clinical implications of the hypothesis highlight the importance of minimizing active psychosis, integrating psychosis memory, avoiding over-medication, and fostering normalizing experiences.
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