A quasi-2D integrated experimental–numerical approach to high-fidelity mechanical analysis of metallic microstructures

Integrated experimental–numerical testing on bulk metal alloys with fine, complex microstructures is known to be highly challenging, since measurements are restricted to the sample surface, thereby failing to capture the effects of the 3D subsurface microstructure. Consequently, a quantitative comparison of deformation fields between experiments and simulations is hardly possible. To overcome this, we propose a novel ‘quasi-2D’ integrated experimental–numerical testing methodology that hinges on the fabrication of μm-thin specimens with practically through-thickness microstructures over large regions of &gt;100 μm. The specimens are fully characterized from both surfaces and tested in-situ to retrieve microstructure-resolved deformation fields. Simultaneously, the full microstructure is discretized in 3D and simulated. This allows for a detailed, one-to-one quantitative comparison of deformation fields between experiments and simulations, with negligible uncertainty in the subsurface microstructure. Consequently, a degree of agreement between experiments and simulations is attained which we believe to be unprecedented at this scale. We demonstrate the capabilities of the framework on polycrystalline ferritic steel and dual-phase ferritic–martensitic steel specimens. At the mesoscale, the methodology enables quantitative comparisons of the interaction between multiple grains, while, at the microscale, it enables advancement of numerical models by direct confrontation with detailed experimental observations. Specifically, it is revealed that the individual slip system activity maps, identified with SSLIP, near a grain boundary can only be reasonably predicted by enhancing the adopted crystal plasticity simulations with a discrete slip plane model. Additionally, the experimentally observed strong anisotropic plasticity of martensite can only be captured with a substructure-enriched crystal plasticity model.</p

Students’ and Teachers’ Experiences With the Implementation of Problem-Based Learning at a University Law School

A few years ago, the Erasmus School of Law implemented problem-based learning (PBL) as an instructional method in the bachelor’s program. Transition to a PBL program often brings some difficulties for the teaching staff. To find out whether the implementation at the Erasmus School of Law has been successful, students and teachers were asked about their experiences with and perceptions of the PBL program. Both students and teachers reported positive study behaviors, such as regular studying and active involvement of students as a result of PBL. However, some issues also arose after implementing PBL: staff members reported dissatisfaction regarding the PBL program and students reported feelings of insufficient preparation for the legal profession. Recommendations on how to address these issues are discussed

Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach

Hereditary non-polyposis colorectal cancer is an autosomal dominant condition due to germline mutations in DNA-mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Here we describe the application of a novel technique for the detection of genomic deletions in MLH1 and MSH2. This method, called multiplex ligation-dependent probe amplification, is a quantitative multiplex PCR approach to determine the relative copy number of each MLH1 and MSH2 exon. Mutation screening of genes was performed in 126 colorectal cancer families selected on the basis of clinical criteria and in addition, for a subset of families, the presence of microsatellite instability (MSI-high) in tumours. Thirty-eight germline mutations were detected in 37 (29.4%) of these kindreds, 31 of which have a predicted pathogenic effect. Among families with MSI-high tumours 65.7% harboured germline gene defects. Genomic deletions accounted for 54.8% of the pathogenic mutations. A complete deletion of the MLH1 gene was detected in two families. The multiplex ligation-dependent probe amplification approach is a rapid method for the detection of genomic deletions in MLH1 and MSH2. In addition, it reveals alterations that might escape detection using conventional diagnostic techniques. Multiplex ligation-dependent probe amplification might be considered as an early step in the molecular diagnosis of hereditary non-polyposis colorectal cancer

О параллельной обработке потока данных, адаптированной к области бит произвольной конфигурации

Предлагается модель операции свёртки арифметических многорядных двоичных кодов (МРК), которая учитывает неравномерность распределения бит данных по разрядам. На основе этой модели разрабатываются процедуры и методы свёртки МРК, которые позволяют снизить задержку на обработку.Пропонується модель операції згортки арифметичних багаторядних двійкових кодів (БРК), яка зважає на нерівномірність розподілу біт даних за разрядами. На основі цієї моделі розроблюються процедури і методи згортки БРК, які дозволяють зменшити затримку на обробку.Model of the compressing operation of arithmetic multi-row binary codes (MRC) is offered. In this model irregularity allocation of data bit per digits is considered. Procedures and methods of compressing MRC based on this model allow diminish delay of processing are designed (developed)

Perinatal stabilisation of infants born with congenital diaphragmatic hernia: A review of current concepts

Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, th

Loss of histone methyltransferase Ezh2 stimulates an osteogenic transcriptional program in chondrocytes but does not affectcartilage development

Ezh2 is a histone methyltransferase that suppresses osteoblast maturation and skeletal development. We evaluated the roleof Ezh2 in chondrocyte lineage differentiation and endochondral ossification. Ezh2 was genetically inactivated in the mesenchymal, osteoblastic, and chondrocytic lineages in mice using the Prrx1-Cre,Osx1-Cre, and Col2a1-Cre drivers, respectively. Wild-type and conditional knockout mice were phenotypically assessed by grossmorphology, histology, and micro-CT imaging. Ezh2-deficient chondrocytes in micromass culture models were evaluated usingRNA-sequencing, histologic evaluation, and western blotting. Aged mice with Ezh2 deficiency were also evaluated for prematuredevelopment of osteoarthritis using radiographic analysis. Ezh2 deficiency in murine chondrocytes reduced bone density at 4 weeks of age, although caused no other gross developmentaleffects. Knockdown of Ezh2 in chondrocyte micromass cultures resulted in a global reduction in trimethylation of histone 3lysine 27 (H3K27me3) and altered differentiation in vitro. RNA-seq analysis revealed enrichment of an osteogenic gene expressionprofile in Ezh2 deficient chondrocytes. Joint development proceeded normally in the absence of Ezh2 in chondrocytes withoutinducing excessive hypertrophy or premature osteoarthritis in vivo. In summary, loss of Ezh2 reduced H3K27me3 levels, increased expression of osteogenic genes in chondrocytes, and resulted ina transient post-natal bone phenotype. Remarkably, Ezh2 activity is dispensable for normal chondrocyte maturation and endochondralossification in vivo, even though it appears to have a critical role during early stages of mesenchymal lineage-commitment