Search

Pure Niobium is a material of interest for high-energy-physics applications including superconducting accelerators. Cold-rolled sheets of Nb exhibit significant plastic anisotropy. Here we report on the mechanical and forming properties of 99.95% pure, 1.02 mm thin, cold-rolled sheet. Uniaxial tension, biaxial tension and disc compression experiments are performed, the first two at multiple angles to the rolling direction of the sheet. The material is very ductile (uniform elongation ~30%), and exhibits significant plastic anisotropy (e.g., the R-values range from 1.2 in 45o to 2.5 in 90o). The results are used to calibrate the Yld2000-2D anisotropic yield function, with an exponent of 6 as Nb is BCC. They are also used to extract the hardening curve beyond the limit load in uniaxial tension. Deep-drawing experiments are performed using a die of 27.6 mm dia. and a punch of 25.4 mm dia. Blanks of various diameters are used. The successfully drawn cups exhibit significant earing. The experiments are simulated using Abaqus/Standard and shell elements. It is shown that a properly calibrated material model enables the numerical simulations to match the experiments.

Supplemental Digital Content is available in the text.

Multicentric carpotarsal osteolysis syndrome (MCTO; MIM #166300) is a rare skeletal disorder characterized by osteolysis affecting particularly the carpal, metacarpal, and tarsal bones, although other bones might be involved. MCTO is an autosomal dominant disease caused by heterozygous variants in the MAFBgene, frequently misdiagnosed as juvenile rheumatoid arthritis due to similar clinical manifestations. This study reports the first Brazilian family diagnosed with MCTO with progressive osteolysis of the carpal and tarsal bones, presenting a c.161C>T (p.Ser54Leu) heterozygous variant in the MAFBgene, describing the clinical, radiological, and molecular findings, compared with literature data, and discussing the different clinical and molecular diagnosis, as well as the natural history of the disease. Since MCTO is a disorder with progressive symptoms, an early diagnosis is important to avoid unnecessary investigations and treatments and to provide the proper follow-up.

Background: A considerable proportion of acute noncardiogenic ischemic stroke patients continue to experience recurrent ischemic events after standard therapy. Aim: We aimed to identify risk factors for recurrent ischemic event prediction at an early stage. Methods: 286 non-cardioembolic ischemic stroke patients with the onset of symptoms within 24 hours were enrolled. Vascular risk factors, routine laboratory data on admission, thromboelastography test seven days after clopidogrel therapy and any recurrent events within one year were assessed. Patients were divided into case group (patients with clinical adverse events, including ischemic stokes, transient ischemic attack, myocardial infarction and vascular related mortality) and control group (events-free patients). The risk of the recurrent ischemic events was determined by the receiver operating characteristic curve and multivariable logistic regression analysis. Results: Clinical adverse events were observed in 43 patients (case group). The mean levels of Mean Platelet Volume (MPV), Platelet/Lymphocyte Ratio (PLR), Lymphocyte Count (LY) and Fibrinogen (Fib) on admission were significantly higher in the case group as compared to the control group (P<0.001). Seven days after clopidogrel therapy, the ADP-induced platelet inhibition rate (ADP%) level was lower in the case group, while the Maximum Amplitude (MA) level was higher in the case group as compared to the control group (P<0.01). The Area Under the Curve (AUC) of receiver operating characteristic(ROC) curve of LY, PLR, , Fib, MA, ADP% and MPV were 0.602, 0.614, 0.629, 0.770, 0.800 and 0.808, respectively. The logistic regression analysis showed that MPV, ADP% and MA were indeed predictive factors. Conclusion: MPV, ADP% and MA were risk factors of recurrent ischemic events after acute noncardiogenic ischemic stroke. Urgent assessment and individual drug therapy should be offered to these patients as soon as possible.

Keutel syndrome is caused by mutations in the matrix gamma-carboxyglutamic acid (MGP) gene (OMIM 154870) and is inherited in an autosomal recessive fashion. It is characterized by brachydactyly, pulmonary artery stenosis, a distinctive facial phenotype, and cartilage calcification. To date, only 36 cases have been reported worldwide. We describe clinical and molecular findings of the first Brazilian patient with Keutel syndrome. Keutel syndrome was suspected based on clinical and morphological evaluation, so we sequenced the MGPgene using the TruSight One Sequencing Panel (Illumina). The obtained MGPgene sequence was then validated by Sanger sequencing. We identified a novel pathogenic homozygous variant of the MGPgene (c.2T>C; p.Met1Thr) confirming Keutel syndrome. Proper diagnosis of this syndrome is important for clinical management and is an indication for genetic counseling. Keutel syndrome should be suspected in patients with cartilage calcifications and brachydactyly when associated with a distinctive facial phenotype and pulmonary artery stenosis.

Background: Next-generation sequencing has had a significant impact on genetic disease diagnosis, but the interpretation of the vast amount of genomic data it generates can be challenging. To address this, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology have established guidelines for standardized variant interpretation. In this manuscript, we present the updated Hospital Israelita Albert Einstein Standards for Constitutional Sequence Variants Classification, incorporating modifications from leading genetics societies and the ClinGen initiative. Results: First, we standardized the scientific publications, documents, and other reliable sources for this document to ensure an evidence-based approach. Next, we defined the databases that would provide variant information for the classification process, established the terminology for molecular findings, set standards for disease-gene associations, and determined the nomenclature for classification criteria. Subsequently, we defined the general rules for variant classification and the Bayesian statistical reasoning principles to enhance this process. We also defined bioinformatics standards for automated classification. Our workgroup adhered to gene-specific rules and workflows curated by the ClinGen Variant Curation Expert Panels whenever available. Additionally, a distinct set of specifications for criteria modulation was created for cancer genes, recognizing their unique characteristics. Conclusions: The development of an internal consensus and standards for constitutional sequence variant classification, specifically adapted to the Brazilian population, further contributes to the continuous refinement of variant classification practices. The aim of these efforts from the workgroup is to enhance the reliability and uniformity of variant classification.

The invasiveness evaluation of nonfunctional pituitary adenoma (NFPAs) is crucial for the prediction of the malignant potential and for making surgical plans of NFPAs. Current invasiveness evaluation of NFPAs is based on neuroimaging, which can hardly predict the invasive potential and dynamically monitor disease progress. Here we used microbead-assisted flow cytometry to detect and analyze the serum extracellular vesicles (EVs) from 30 NFPAs patients (15 invasive and 15 noninvasive). Lower expressions of folate receptor 1 (FOLR1) and epithelial cell adhesion molecule (EpCAM) were found in serum EVs from the invasive NFPAs patients compared to the noninvasive ones [area under the curve (AUC) of 0.94 for FOLR1 and 0.88 for EpCAM]. Meanwhile, increased mRNA expression of vimentin and N-cadherin, two mesenchymal markers, was found in serum EVs from the invasive NFPAs patients compared to the noninvasive ones. Consistent results were observed in the tumor tissue that invasive NFPAs have lower expression of the epithelial markers while higher expression of the mesenchymal markers. These results suggested the possible role of epithelial–mesenchymal transition (EMT) in the invasiveness of NFPAs. Pituitary tumor transforming gene 1 (PTTG1) mRNA in serum EVs was also found to be an indicator for invasive NFPAs and is related with EMT. These results provide a method for the blood-based diagnosis and invasiveness evaluation of NFPAs and would be beneficial to the diagnosis, prognosis prediction, and surgical risk evaluation of NFPAs.

The range of blank-holding force (BHF) for which deep drawing of AA1100-H24 is successful is investigated using a combination of experiments and simulations. The experiments involve circular blanks of three different diameters: 35 mm, 37 mm and 40 mm. The thickness of the blanks is 0.51 mm. These are drawn with a punch of 20 mm diameter, i.e., at drawing ratios of 1.75, 1.85 and 2.0, respectively, using a custom, modular forming apparatus where the BHF can be controlled at will, between 0 and 2,400 N. The experiments are performed in an Instron 8872 servo-hydraulic frame that allows precise measurements of the punch force and displacement. The working envelopes are determined experimentally in the space of BHF and draw depth, which can be categorized into three regimes: wrinkling, safe and tearing. It is found that grey zones exist between the three regimes. These experiments are then simulated in Abaqus/Standard, using two types of elements: axisymmetric and shell. In the latter case, plastic anisotropy is introduced, using the Yld2000-2D anisotropic yield function. Wrinkling and tearing failure are triggered by inducing suitable geometric imperfections. It is shown that the models are able to reproduce the experiments well. This serves as a verification of the modelling framework, which can then be used for the simulations of more complex forming processes.

The hydraulic bulge test provides a useful tool to characterize the mechanical behavior of sheet metal under nearly equibiaxial loading, such as the material hardening response. However, the kinematic relationships during bulge tests of anisotropic sheets are still less understood and need further clarification. To this end, extensive numerical simulations of bulge tests are first performed, covering different die geometries and materials that exhibit distinct hardening features and Hill48 anisotropy. Based on the general scaling laws of the kinematic relationships, the numerical results are then used to establish an analytical model that explicitly relates the dome height, apex strain, and radii of curvatures in terms of the die ratio, material hardening parameter, and anisotropy. In addition, the general extraction procedure, which incorporates the analytical model to obtain the hardening responses of anisotropic sheets, is also provided. Finally, the effectiveness of the analytical model is confirmed based on representative results of AA6061 and DP600 sheet experiments and supplementary numerical simulations. The proposed model is expected to help facilitate the application of bulge tests in characterizing the plasticity and forming behavior of anisotropic sheet materials.

• Scaling laws between apex strain, radius of curvature and dome height are developed. • The power-law relationships hold for both circular and elliptical bulge tests. • The power-law relationships can be applied to any materials. • The general kinematic theory is validated numerically and experimentally. The hydraulic circular and elliptical bulge tests have been widely used in extracting mechanical properties of sheet materials. Theoretical analysis of bulge tests usually requires the kinematic relationships between the apex strains, radii of curvatures and dome heights to be established. Most of the available analytical solutions are derived on a case-by-case basis and are often limited to circular bulge tests of isotropic materials, and thus cannot be applied to materials with more complicated constitutive behaviors or non-circular bulge tests. Based on the variable-separable assumption and proportional kinematic conditions at the apex, this study develops a set of power-law relationships between the apex strains, radii of curvatures and dome heights that hold for both circular and elliptical bulge tests, irrespective of material properties. Numerical simulations of a set of circular and elliptical bulge tests with different material models are performed and the scaling laws between the apex strains, radii of curvatures and dome heights are verified. An extensive set of experimental results of circular and elliptical bulge tests from the literature are compared with the theoretical predictions and the power-law kinematic relationships are again validated. This general and unified theory contributes to the fundamental understanding of the intrinsic kinematic constraints in circular and elliptical bulge tests and is expected to facilitate the application of bulge tests to a broader class of sheet materials. [ABSTRACT FROM AUTHOR]