Induction of VEGF and VEGF receptor gene expression by hypoxia: Divergent regulation in vivo and in vitro

Induction of VEGF and VEGF receptor gene expression by hypoxia: Divergent regulation in vivo and in vitro. This study examined the expression of EPO,VEGF and VEGF receptor gene under conditions of reduced oxygen supply in primary cultures of rat hepatocytes, and compared it with the expression of these genes in hypoxic rat livers in vivo. To this end we exposed male Sprague-Dawley rats to hypoxia (10% and 8% O2), carbon monoxide (0.1% CO) or injected cobalt chloride (60 mg/kg CoCl2) subcutaneously. For the in vitro experiments we used primary cultures of rat hepatocytes which were kept at high (20% O2) and low (1% O2) oxygen tensions for three hours. The EPO mRNA was up-regulated by hypoxia in vitro and in vivo about 10-fold. The VEGF mRNA was up-regulated fivefold in the hepatocytes only, whereas the in vivo mRNA levels remained unchanged. The mRNA levels of flt-1 were up-regulated threefold by 8% O2 in livers, dependent on the strength of hypoxia (10% caused no changes in flt-1 gene expression) and on the kind of hypoxic stimulus (8% O2 was as effective as 0.1% CO and more effective than cobalt). The mRNA levels of flk-1/KDR and flt-4 remained unchanged in the liver. In vitro there were no changes in the mRNA levels of flt-1, flt-4 and flk-1/KDR. Consequently, the in vivo regulation of VEGF, which might be modulated by induction of flt-1 receptor gene expression, differs from the in vitro cell culture situation and might be different from the EPO regulationin viv

Specific I/O-devices for several handicapped and elderly

To fulfil the requirements of several user groups with the need of assistance in tourist activities and regions an assistance system was developed. The user frontend is realised by a handheld device combined with additional features matched to the user specifics. The system assures a optimal presentation of the needed information by a easy to learn and easy to use new gesture-based GUI. This and the additional specific I/O-devices and components provide the IT-Biocompatibility. These add-ons are adaptors for wireless transfer to hearing aids, vibro-tactile belts or accumulators and sensors for measuring of vital parameters

Development of assistance systems for user groups with specific handicaps – a challenge for the ergonomic design process

The goal to develop an assistance system for handicapped users with several impairments was successfully achieved. The design process as a whole lifecycle with iterative processes was shortened by several reasons. But this newly applied design process with underlying design rules given from mechatronic and biomedical products results into a usable system for the targeted groups as well as for other potential users. The main components of the design process were an intensive task analysis and determining of user profiles and user requirements

Down-scaling of a tourist assistance system to fulfil the needs of economical poor regions and providers of tourist offers

Derived from a complex tourist assistance system for users with special needs (e.g. disabled users with physical impairments) a down-scaled system was successful tested. It consists of a handheld device like the whole system but disclaims to a permanent online server access. The reducing of components was determined by a user-centred design process with an intense requirement analysis

The design of a tourist assistance system for several handicapped and elderly

By use of knowledge from biomedical engineering, ergonomics, information and communication technologies as well as from robotics and mechatronics an assistance system for several handicapped and elderly is in development. The aim of the project called TAS (Tourist Assistance System) was the development and exemplary assembly of an assistance system for people with impairments as an access support to previously bad or not reachable tourism offers. It was implemented into a chosen model region in Thuringia / Germany. One of the main principles in this project was to use, combine and adapt market available components of the abovementioned technical areas. In this paper the design process of the assistance system and its main components and functions are described

Formation of engineering thinking at school during the lesson-game "solar system"

This paper describes the structure, conduct, and the main stages of the interdisciplinary lesson-game. Some data on the principles of educational technology are given. Methodical recommendations for conducting the lesson, as well as examples of didactic tasks are given. The proposed lesson carries the task - to build a model of the solar system. But this is not a simple design and construction but a deep didactic analysis. The results will be the construction of a model of the solar system, as a result of the application of engineering thinking skills in life, as well as the transfer of the project modeling algorithm from theory to practice

Novel Plasmids and Resistance Phenotypes in Yersinia pestis: Unique Plasmid Inventory of Strain Java 9 Mediates High Levels of Arsenic Resistance

Growing evidence suggests that the plasmid repertoire of Yersinia pestis is not restricted to the three classical virulence plasmids. The Java 9 strain of Y. pestis is a biovar Orientalis isolate obtained from a rat in Indonesia. Although it lacks the Y. pestis-specific plasmid pMT, which encodes the F1 capsule, it retains virulence in mouse and non-human primate animal models. While comparing diverse Y. pestis strains using subtractive hybridization, we identified sequences in Java 9 that were homologous to a Y. enterocolitica strain carrying the transposon Tn2502, which is known to encode arsenic resistance. Here we demonstrate that Java 9 exhibits high levels of arsenic and arsenite resistance mediated by a novel promiscuous class II transposon, named Tn2503. Arsenic resistance was self-transmissible from Java 9 to other Y. pestis strains via conjugation. Genomic analysis of the atypical plasmid inventory of Java 9 identified pCD and pPCP plasmids of atypical size and two previously uncharacterized cryptic plasmids. Unlike the Tn2502-mediated arsenic resistance encoded on the Y. enterocolitica virulence plasmid; the resistance loci in Java 9 are found on all four indigenous plasmids, including the two novel cryptic plasmids. This unique mobilome introduces more than 105 genes into the species gene pool. The majority of these are encoded by the two entirely novel self-transmissible plasmids, which show partial homology and synteny to other enterics. In contrast to the reductive evolution in Y. pestis, this study underlines the major impact of a dynamic mobilome and lateral acquisition in the genome evolution of the plague bacterium

Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer

Background Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P Conclusion Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.Peer reviewe