Designing for Situational Visual Impairments:Supporting Early-Career Designers of Mobile Content

Mobile devices are a substantial part of our lives, supporting communication, work, and play. However, situational visual impairments (SVIs) can make completing tasks a challenge (e.g., browsing online in bright sunlight) and poorly designed content can cause or exacerbate SVIs. We surveyed 43 mobile content designers and ran four follow-on interviews to understand what designers currently do regarding SVIs, what resources they know of, and what is required to best support them in designing to reduce SVIs. Our findings highlight key similarities and differences between accessibility and designing to reduce SVIs. Our participants requested improved guidelines, education, and digital design tools for SVIs. To accommodate the growing number of people affected by SVIs and improve the inclusion of accessibility in design, we introduce recommendations that leverage the overlap between accessibility and SVIs to minimise the effort required in extending current design processes.</p

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

From Diarrhea to Obesity in Prohormone Convertase 1/3 Deficiency

GoalsThe aim of this report is to delineate the clinical, pathologic, and enteroendocrine (EE) features of prohormone convertase 1/3 (PC1/3) deficiency in children.BackgroundProhormone convertases play a pivotal role in the activation of biologically inactive hormones. Congenital defects in the EE axis, such as PC1/3 deficiency, have been rarely reported and their pathophysiological mechanisms are largely unknown.StudyEE function and pathology was evaluated in 4 males (1, 2, 7, and 10 y old) from 2 families with PC1/3 deficiency at a university children's hospital. Clinical course, pathology analysis including immunohistochemistry for PC1/3, PC2, and glucagon-like peptide 1 (GLP-1) and electron microscopy, as well as EE function tests (GLP-1, GLP-2, oral glucose tolerance test) were performed.ResultsAll (n=4) suffered from congenital severe diarrhea associated with malabsorption. The diarrhea improved during the first year of life and hyperphagia with excessive weight gain (BMI&gt;97th percentile) became the predominant phenotype at an older age. Analysis of the enteroendocrine axis revealed high proinsulin levels (57 to 1116 pmol/L) in all patients, low serum GLP-2 levels, and impaired insulin and GLP-1 secretion after an oral glucose tolerance test at a young age, with improvement in 1 older child tested. Electron microscopy showed normal ultrastructure of enterocytes and EE cells. Immunohistochemistry revealed normal expression of chromogranin A, a marker of EE cells but markedly reduced immunostaining for PC1/3 and PC2 in all patients.ConclusionsPC1/3 deficiency is associated with an age dependent, variable clinical phenotype caused by severe abnormalities in intestinal and EE functions. Serum level of proinsulin can be used as an effective screening tool

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

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