Oral Protein Therapy for the Future - Transport of Glycolipid-Modified Proteins: Vision or Fiction?

The reliable and early diagnosis of common complex multifactorial diseases depends on the individual determination of all (or as many as possible) polymorphisms of each susceptibility gene together with amount and type of the corresponding gene products and their downstream effects, including the synthesis and flux of metabolites and regulation of signalling processes. In addition, this system's biology-driven personalized diagnosis must be accompanied by options for personalized reliable and early therapy. In the midterm, the direct substitution or inhibition of the proteins encoded by the corresponding defective gene products of the susceptibility genes exerting lower or higher activity by administration of the `normal' proteins or inhibitory antibodies, respectively, seems to be most promising. The critical hurdle of oral bioavailability as well as transport into the cytoplasm of the target cells, if required, could be overcome by therapeutic proteins with carboxy-terminal modification by glycosylphosphatidylinositol (GPI). This may be deduced from recent experiments with rat adipocytes. Here this membrane-anchoring glycolipid structure induces the sequential transport of proteins from special regions of the plasma membrane via the surface of intracellular lipid droplets to special membrane vesicles, which are finally released from the adipocytes together with the associated GPI proteins. It remains to be studied whether similar molecular mechanisms operate in intestinal epithelial cells and may enable the transport of GPI proteins from the intestinal lumen into the blood stream. If so, modification of proteins encoded by (combinations of) susceptibility genes with GPI could significantly facilitate the personalized therapy of common diseases on the basis of `inborn' safety, efficacy, rapid realization and oral application. Copyright (C) 2010 S. Karger AG, Base

Personalized Prognosis and Diagnosis of Type 2 Diabetes - Vision or Fiction?

Typical civilization diseases, such as type 2 diabetes, share several features: their worldwide frequency, the complexity of the underlying pathogenic mechanisms, heterogeneity in the phenotypes and their multifactorial nature due to a wide variety of possible combinations of disease susceptibility or protective genes in different tissues and negative or positive environmental factors. This is in sharp contrast to classical inherited diseases, such as Huntington's chorea, which are often caused by complete loss- or gain-of-function mutations in a single gene. The causative polymorphisms of susceptibility genes, however, are characterized by relatively subtle alterations in the function of the corresponding gene products, i.e. low penetrance and effect size, which do not support the pathogenesis per se, and by their high frequency; these two characteristics result in high expenditures for their identification and a rather low predictive value. In the future, the reliable and early diagnosis of common diseases will thus depend on the determination of all (or as many as possible) polymorphisms of each susceptibility gene together with the corresponding gene products and the metabolites emerging thereof for each individual. Great hopes are currently associated with systems biology to cover these demands in time (i.e. along the pathogenesis) and space (i.e. in all relevant tissues). Copyright (C) 2010 S. Karger AG, Base

The “Transparent Citizen” in Web 2.0

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On Dinosaurs, Measurement Ideologists, Separatists, and Happy Souls - Proposing and Justifying a Way to Make the Global IS/BISE Community Happy

This article constitutes an "editorialized", partly shortened, and partly extended version of the paper "Business and information systems engineering: a complementary approach to information systems - what we can learn from the past and may conclude from present reflection on the future" by Hans Ulrich Buhl, Günter Müller, Gilbert Fridgen, and Maximilian Röglinger that appeared in the Journal of the Association for Information Systems 13(4):236-253, April 2012. The editorial has been presented as a keynote on the BIS conference in Vilnius, Lithuania, in May 2012 and the BISE workshop in Hannover, Germany, in October 2012. An earlier version has been published in the BIS proceedings

COSTEP: A comprehensive suprathermal and energetic particle analyzer for SOHO

The group of instruments involved in the COSTEP (comprehensive suprathermal and energetic particle analyzer) project are described. Three sensors, the LION (low energy ion and electron) instrument, the MEICA (medium energy ion composition analyzer) and the EPHIN (electron proton helium instrument) are described. They are designed to analyze particle emissions from the sun over a wide range of species (electrons through iron) and energies (60 KeV/particle to 500 MeV/nucleon). The data collected is used in studying solar and space plasma physics

Facility based cross-sectional study of self stigma among people with mental illness: towards patient empowerment approach

Background: Self stigma among people with mental illness results from multiple cognitive and environmental factors and processes. It can negatively affect adherence to psychiatric services, self esteem, hope, social integration and quality of life of people with mental illness. The purpose of this study was to measure the level of self stigma and its correlates among people with mental illness at Jimma University Specialized Hospital, Psychiatry clinic in southwest Ethiopia. Methods: Facility based cross-sectional study was conducted on 422 consecutive samples of people with mental illness using interviewer administered and pretested internalized stigma of mental illness (ISMI) scale. Data was entered using EPI-DATA and analysis was done using STATA software. Bivariate and multivariate linear regressions were done to identify correlates of self stigma. Results: On a scale ranging from 1 to 4, the mean self stigma score was 2.32 (SD = 0.30). Females had higher self stigma (std. beta = 0.11, P < 0.05) than males. Patients with a history of traditional treatment had higher self stigma (std. beta = 0.11, P < 0.05). There was an inverse relationship between level of education and self-stigma (std. beta = -0.17, P < 0.01). Perceived signs (std. beta = 0.13, P < 0.05) and supernatural causes of mental illness ( std. beta = 0.16, P < 0.01) were positively correlated with self stigma. Higher number of drug side effects were positively correlated (std. beta = 0.15, P < 0.05) while higher self esteem was negatively correlated (std. beta = -0.14, P < 0.01) with self stigma. Conclusions: High feeling of inferiority (alienation) but less agreement with common stereotypes (stereotype endorsement) was found. Female showed higher self stigma than male. History of traditional treatment and higher perceived supernatural explanation of mental illness were associated with higher self stigma. Drug side effects and perceived signs of mental illness were correlated with increased self stigma while education and self esteem decreased self stigma among people with mental illness. Patient empowerment psychosocial interventions and strategies to reduce drug side effects can be helpful in reducing self stigma among people with mental illnesses

ICIS 2008 Panel Report: Design Science in Information Systems: Hegemony, Bandwagon, or New Wave?

In the past few years, design science has become a topic of increasing importance, especially in the North American academic IS community. Some observers see a new hegemony forming. Others dispute that but suggest that design science is merely the latest bandwagon rolling through the IS domain. A panel at the 2008 International Conference on Information Systems debated views of design science prevalent in the IS community. This paper reports on the panel discussion and attempts to position design science from various perspectives, including North American and European views, the latter with a long tradition of design-based IS scholarship

ICIS 2008 Panel Report: Design Science in Information Systems: Hegemony, Bandwagon, or New Wave?

In the past few years, design science has become a topic of increasing importance, especially in the North American academic IS community. Some observers see a new hegemony forming. Others dispute that but suggest that design science is merely the latest bandwagon rolling through the IS domain. A panel at the 2008 International Conference on Information Systems debated views of design science prevalent in the IS community. This paper reports on the panel discussion and attempts to position design science from various perspectives, including North American and European views, the latter with a long tradition of design-based IS scholarship