A reference human induced pluripotent stem cell line for large-scale collaborative studies

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field

The “Projection-by-projection” (PbP) criterion for multiaxial random fatigue loadings: Guidelines to practical implementation

This work is motivated by the increasing interest towards the application of the “Projection-by-Projection” (PbP) spectral method in finite element (FE) analysis of components under multiaxial random loadings. To help users and engineers in developing their software routines, this paper presents a set of numerical case studies to be used as a guideline to implement the PbP method. The sequence of analysis steps in the method are first summarized and explained. A first numerical example is then illustrated, in which various types of biaxial random stress are applied to three materials with different tension/torsion fatigue properties. Results of each analysis step are displayed explicitly to allow a plain understanding of how the PbP method works. The examples are chosen with the purpose to show the capability of the method to take into account the effect of correlation degree among stress components, and the relationship between material and multiaxial stress in relation to the tension/torsion fatigue properties. A case study is finally discussed, in which the method is applied to a FE structural durability analysis of a simple structure subjected to random excitations. The example describes the flowchart and the program by which to implement the method through Ansys APDL software. This final example illustrates how the PbP method is an efficient tool to analyze multiaxial random stresses in complex structures

Computer-aided durability analysis of complex structures under multiaxial random loadings through the Projection-by-Projection spectral method

This letter deals with a set of numerical case studies that were devised as mean to help users in implementing the Projection‐by‐Projection (PbP) multiaxial spectral criterion. A first case study scrutinised the PbP method applied to different types of biaxial random stress and material fatigue properties. A second case study investigated a structure under random excitations and provided practical guidelines on how to implement the PbP method for a computeraided durability analysis

Clinical response to gluten withdrawal is not an indicator of coeliac disease.

OBJECTIVE: Although the diagnosis of coeliac disease requires specific histological and serological findings, patients considered to be affected by coeliac disese only on the basis of clinical improvement after gluten withdrawal are commonly referred to our outpatient clinic. The objective of this study was to investigate whether the clinical response of gastrointestinal symptoms to gluten withdrawal and subsequent dietray re-introduction could be an indicator of the presence of coeliac disease. MATERIAL AND METHODS: Form December 1998 to January 2007, 180 patients on a gluten-free diet because of a diagnosis of coeliac disease not based on proper diagnostic criteria came to our out-patient clinic. In 112 of these patients, gluten was re-introduced into their diet. Subsequent duodenal biopsies and endomysial antibodies confirmed the diagnosis of coelliac disease in 51 of them. The relationship between improvement/worsening of symptoms and withdrawal/re-introduction of dietary gluten was analysed. RESULTS: Gastrointestinal symptoms improved in 64.7% of coeliac patients and 75.0% of non-coeliac patients after gluten withdrawal (chi(2) test, p=NS). Gluten re-introduction was followed by clinical exacerbation in 71.4% of coeliac patients and 54.2% of non-coeliac patients (chi(2) test, p =NS): The positive predictive value for clinical improvement after gluten withdrawal was 36%; the positive predictive value for clinical exacerbation after gluten re-introduction was 28%. CONCLUSIONS: Clinical response to either withdrawal or re-introduction of dietary gluten has no role in the diagnosis of coeliac disease

Clinical response to gluten withdrawal is not an indicator of coeliac disease.

OBJECTIVE: Although the diagnosis of coeliac disease requires specific histological and serological findings, patients considered to be affected by coeliac disese only on the basis of clinical improvement after gluten withdrawal are commonly referred to our outpatient clinic. The objective of this study was to investigate whether the clinical response of gastrointestinal symptoms to gluten withdrawal and subsequent dietray re-introduction could be an indicator of the presence of coeliac disease. MATERIAL AND METHODS: Form December 1998 to January 2007, 180 patients on a gluten-free diet because of a diagnosis of coeliac disease not based on proper diagnostic criteria came to our out-patient clinic. In 112 of these patients, gluten was re-introduced into their diet. Subsequent duodenal biopsies and endomysial antibodies confirmed the diagnosis of coelliac disease in 51 of them. The relationship between improvement/worsening of symptoms and withdrawal/re-introduction of dietary gluten was analysed. RESULTS: Gastrointestinal symptoms improved in 64.7% of coeliac patients and 75.0% of non-coeliac patients after gluten withdrawal (chi(2) test, p=NS). Gluten re-introduction was followed by clinical exacerbation in 71.4% of coeliac patients and 54.2% of non-coeliac patients (chi(2) test, p =NS): The positive predictive value for clinical improvement after gluten withdrawal was 36%; the positive predictive value for clinical exacerbation after gluten re-introduction was 28%. CONCLUSIONS: Clinical response to either withdrawal or re-introduction of dietary gluten has no role in the diagnosis of coeliac disease