This paper develops and tests a model of an individual's intention to reenter entrepreneurship following business exit. Two long–standing theories, prospect theory and self–efficacy, seem to develop ...opposite predictions in this context. To reconcile these conflicting predictions, we theorize a moderating model and test the boundary conditions of both theories. Relying on two experimental studies, we find that prospect theory explains reentry intentions of entrepreneurs who have lost money when their self–efficacy is moderate or low. Thereby, we provide an explanation for the puzzling empirical finding that so many failed entrepreneurs reenter entrepreneurship even if failure has undermined their self–efficacy.
ABSTRACT
In about 20%–30% of phenylketonuria (PKU) patients (all phenotypes of PAH deficiency), Phe levels may be controlled through phenylalanine hydroxylase cofactor tetrahydrobiopterin therapy. ...These patients can be diagnosed by an oral tetrahydrobiopterin challenge and are characterized by mutations coding for proteins with substantial residual PAH activity. They can be treated with a commercially available synthetic form of tetrahydrobiopterin, either as a monotherapy or as adjunct to the diet. This review article summarizes molecular and metabolic bases of PKU and the importance of the tetrahydrobiopterin loading test used for PKU patients. On the basis of in vitro residual PAH activity, more than 1,200 genotypes from patients challenged with tetrahydrobiopterin were categorized as predictive for tetrahydrobiopterin responsiveness or non‐responsiveness and correlated with the loading test, phenotype, and residual in vitro PAH activity. The coexpression of two distinct PAH mutant alleles revealed possible dominance effects (positive or negative) by one of the mutations on residual activity as result of interallelic complementation. The treatment of the transfected cells with tetrahydrobiopterin showed an increase in residual PAH activity with several mutations coexpressed.
Tetrahydrobiopterin (BH4; Kuvan®) induces a gain‐of‐function in phenylalanine hydroxylase (PAH) in a multifactorialresponse mechanism with a notable stabilization of protein structure. In about 20%‐30% of phenylketonuria patients (all phenotypes of PAH deficiency), Phelevels may be controlled through PAHcofactor BH4 therapy. A substantial residual PAH activity is essential for the stabilization of enzyme activity and depends on specific PAH gene variations and on interallelic complementation, as shown from in vitro co‐expression experiments.
Genome-wide association studies (GWAS) with intermediate phenotypes, like changes in metabolite and protein levels, provide functional evidence to map disease associations and translate them into ...clinical applications. However, although hundreds of genetic variants have been associated with complex disorders, the underlying molecular pathways often remain elusive. Associations with intermediate traits are key in establishing functional links between GWAS-identified risk-variants and disease end points. Here we describe a GWAS using a highly multiplexed aptamer-based affinity proteomics platform. We quantify 539 associations between protein levels and gene variants (pQTLs) in a German cohort and replicate over half of them in an Arab and Asian cohort. Fifty-five of the replicated pQTLs are located in trans. Our associations overlap with 57 genetic risk loci for 42 unique disease end points. We integrate this information into a genome-proteome network and provide an interactive web-tool for interrogations. Our results provide a basis for novel approaches to pharmaceutical and diagnostic applications.
We explore the structure and content of developmental networks depicted in 62 National Baseball Hall of Fame induction speeches to identify which developers and what support mattered most to ...inductees' career achievement. Our analysis illustrates two new support subfunctions ("freedom and opportunity for skill development" and "inspiration and motivation") and shows that first-ballot inductees had larger, more diverse developmental networks featuring greater multiplexity and more single-function ties, plus greater supplementary psychosocial and complementary career support from a wider range of core and peripheral career communities, than later-ballot inductees. We conclude with a theoretical model of extraordinary career achievement.
X-linked Alport syndrome is a form of progressive renal failure caused by pathogenic variants in the
COL4A5
gene. More than 700 variants have been described and a further 400 are estimated to be ...known to individual laboratories but are unpublished. The major genetic testing laboratories for X-linked Alport syndrome worldwide have established a Web-based database for published and unpublished
COL4A5
variants (
https://grenada.lumc.nl/LOVD2/COL4A/home.php?select_db=COL4A5
). This conforms with the recommendations of the Human Variome Project: it uses the Leiden Open Variation Database (LOVD) format, describes variants according to the human reference sequence with standardized nomenclature, indicates likely pathogenicity and associated clinical features, and credits the submitting laboratory. The database includes non-pathogenic and recurrent variants, and is linked to another
COL4A5
mutation database and relevant bioinformatics sites. Access is free. Increasing the number of
COL4A5
variants in the public domain helps patients, diagnostic laboratories, clinicians, and researchers. The database improves the accuracy and efficiency of genetic testing because its variants are already categorized for pathogenicity. The description of further
COL4A5
variants and clinical associations will improve our ability to predict phenotype and our understanding of collagen IV biochemistry. The database for X-linked Alport syndrome represents a model for databases in other inherited renal diseases.
Convective cloud systems in the maritime tropics play a critical role in
global climate, but accurately representing aerosol interactions within
these clouds persists as a major challenge for weather ...and climate
modelling. We quantify the effect of ice-nucleating particles (INPs) on the
radiative properties of a complex tropical Atlantic deep convective cloud
field using a regional model with an advanced double-moment microphysics
scheme. Our results show that the domain-mean daylight outgoing radiation
varies by up to 18 W m−2 depending on the chosen INP parameterisation.
The key distinction between different INP parameterisations is the
temperature dependence of ice formation, which alters the vertical
distribution of cloud microphysical processes. The controlling effect of the
INP temperature dependence is substantial even in the presence of
Hallett–Mossop secondary ice production, and the effects of secondary ice
formation depend strongly on the chosen INP parameterisation. Our results
have implications for climate model simulations of tropical clouds and
radiation, which currently do not consider a link between INP particle type
and ice water content. The results also provide a challenge to the INP
measurement community, as we demonstrate that INP concentration
measurements are required over the full mixed-phase temperature regime,
which covers around 10 orders of magnitude.
Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues ...but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is unknown. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as human embryonic stem cells (hESC) by transcriptomics (RNA-seq) and quantitative proteomics (nanoLC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. Particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC.
In scholarly publications, multiple graphical elements such as plots or raster images are traditionally combined into a single compound figure using panels arranged in a grid. Package ...multipanelfigure is a GPL-3 licensed R package that eases assembly of such compound figures, allowing for straightforward integration of R specific plots using base graphics, lattice and ggplot2 plots, as well as grid grobs in general. Also provided are facilities to incorporate R external graphical output stored as SVG, PNG, JPEG, or TIFF formatted files.
SomaLogic's SOMAscan™ assay platform allows the analysis of the relative abundance of over 1300 proteins directly from biological matrices such as blood plasma and serum. The data resulting from the ...assay is provided in a proprietary text-based format not easily imported into R.
readat is an R package for working with the SomaLogic ADAT file format. It provides functionality for importing, transforming and annotating data from these files. The package is free, open source, and available on Bioconductor and Bitbucket.
readat integrates into both Bioconductor and traditional R workflows, rendering it easy to make use of ADAT files.
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