141 research outputs found
Designing for Situational Visual Impairments:Supporting Early-Career Designers of Mobile Content
Evaluation of strain and stress states in the single point incremental forming process
Single point incremental forming (SPIF) is a promising
manufacturing process suitable for small batch production.
Furthermore, the material formability is enhanced in
comparison with the conventional sheet metal forming processes,
resulting from the small plastic zone and the incremental
nature. Nevertheless, the further development of the SPIF
process requires the full understanding of the material deformation
mechanism, which is of great importance for the effective
process optimization. In this study, a comprehensive
finite element model has been developed to analyse the state
of strain and stress in the vicinity of the contact area, where the
plastic deformation increases by means of the forming tool
action. The numerical model is firstly validated with experimental
results from a simple truncated cone of AA7075-O
aluminium alloy, namely, the forming force evolution, the
final thickness and the plastic strain distributions. In order to
evaluate accurately the through-thickness gradients, the blank
is modelled with solid finite elements. The small contact area
between the forming tool and the sheet produces a negative
mean stress under the tool, postponing the ductile fracture
occurrence. On the other hand, the residual stresses in both
circumferential and meridional directions are positive in the
inner skin of the cone and negative in the outer skin. They
arise predominantly along the circumferential direction due to
the geometrical restrictions in this direction.The authors would like to gratefully acknowledge the
financial support from the Portuguese Foundation for Science and Technology
(FCT) under project PTDC/EMS-TEC/1805/2012. The first author is
also grateful to the FCT for the postdoctoral grant SFRH/BPD/101334/2014.info:eu-repo/semantics/publishedVersio
Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations
Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling.This research was funded by Jubiläumsfonds der Österreichischen Nationalbank, grant no.16678 (to A.R.J.), grant no. 18019 (to G.-F.V.) and Tiroler Wissenschaftsfonds, grant No. 0404/2386 (toG.-F.V.).info:eu-repo/semantics/publishedVersio
A novel fast mechanism for GPCR-mediated signal transduction—control of neurotransmitter release
In addition to calcium influx, charge movement in the G protein–coupled M2-muscarinic receptor is required for the control of acetylcholine release
Bialellic Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) Cause Common Variable Immunodeficiency-Like Phenotype with Enteropathy
TTC7A deficiency typically causes severe gastrointestinal manifestations such as multiple intestinal atresia or early-onset inflammatory bowel disease. In some cases, this is associated with severe combined immunodeficiency. Partial loss-of-function mutations appear to be associated with a milder phenotype resulting in common variable immunodeficiency-like condition with enteropathy
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Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations.
Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling
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