Supporting Technical Customer Services with Mobile Devices: Towards an Integrated Information System Architecture

Due to increasing complexity of machines and plants, information tailored to the needs of Technical Customer Services(TCS) is a prerequisite for the execution of efficient service processes. This paper describes the conception of a supportingarchitecture incorporating an integration platform to meet the TCS’ demand for information. On the one hand, the developedarchitecture directs the integration of data from different specialized systems to cover the aforementioned information needs.On the other hand, it enables the feedback of the TCS to other corporate departments which is often neglected. The systemclasses to be integrated are presented besides options and technologies for realizing the integration platform. The articlecreates a framework for future discussions on information technology integration to support the TCS

Mobile Anwendungssysteme im Gesundheitswesen: eine empirische Anforderungsanalyse am Beispiel der präklinischen Notfallmedizin

Viele Geschäftsprozesse in der Unternehmenspraxis werden bereits wirkungsvoll durch mobile Anwendungssysteme unterstützt. Von überall sind Informationen aller Art zugänglich und können während der Prozessausführung abgerufen und weiterverarbeitet werden. Dieser Trend wird auch vermehrt in der präklinischen Notfallmedizin Einzug halten, wo bereits spezialisierte Systeme für einige wenige Krankheitsbilder und Teilprozesse eingebracht werden. Im Rahmen dieses Beitrags wird auf Basis einer Anforderungserhebung per Online-Umfrage ein erster theoretischer Ansatz abgeleitet, welcher die Grundlage bietet die Einsatzkräfte direkt im Notfalleinsatz bei der Behandlung des Patienten durch prozessorientierte Informationsweitergabe, sowie in relevanten vor- und nachgelagerten Prozessen zu unterstützen

Human Intestinal Transporter Database: QSAR Modeling and Virtual Profiling of Drug Uptake, Efflux and Interactions

Membrane transporters mediate many biological effects of chemicals and play a major role in pharmacokinetics and drug resistance. The selection of viable drug candidates among biologically active compounds requires the assessment of their transporter interaction profiles

Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum

The post-translational farnesylation of proteins serves to anchor a subset of intracellular proteins to membranes in eukaryotic organisms and also promotes protein-protein interactions. Inhibition of protein farnesyltransferase (PFT) is lethal to the pathogenic protozoa Plasmodium falciparum. Parasites were isolated that were resistant to BMS-388891, a tetrahydroquinoline (THQ) PFT inhibitor. Resistance was associated with a 12-fold decrease in drug susceptibility. Genotypic analysis revealed a single point mutation in the beta subunit in resistant parasites. The resultant tyrosine 837 to cysteine alteration in the beta subunit corresponded to the binding site for the THQ and peptide substrate. Biochemical analysis of Y837C-PFT demonstrated a 13-fold increase in BMS-388891 concentration necessary for inhibiting 50% of the enzyme activity. These data are consistent with PFT as the target of BMS-388891 in P. falciparum and suggest that PFT inhibitors should be combined with other antimalarial agents for effective therapy

NASH limits anti-tumour surveillance in immunotherapy-treated HCC.

Hepatocellular carcinoma (HCC) can have viral or non-viral causes1-5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment

Structurally Simple Farnesyltransferase Inhibitors Arrest The Growth Of Malaria Parasites

(Chemical Equation Presented) Antimalarial compounds: Structurally simple acyclic inhibitors of protein farnesyltransferase (active-site model shown) from the malaria parasite Plasmodium falciparum may allow third world countries access to an effective and inexpensive antimalarial therapy to counter the estimated half billion infections that occur annually. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA

Informationssystemarchitekturen zur Unterstützung technischer Kundendienstleistungen

Vor dem Hintergrund immer komplexer werdender Maschinenund Anlagen ist die passgenaue Bereitstellung von Informationenfür den Technischen Kundendienst (TKD) zunehmend eine Voraussetzungfür effiziente Dienstleistungsprozesse. Der Beitragbeschreibt die Konzeption einer Architektur zur Unterstützungdes TKD in Form einer Integrationsplattform. Diese deckt einerseitsden Informationsbedarf des TKD durch die Bereitstellungintegrierter Daten aus den spezialisierten Teilsystemen ab. Andererseitsermöglicht sie eine in der Praxis oft vernachlässigte Rückkopplungdes TKD mit den anderen Unternehmensbereichen.Neben der Identifikation zu integrierender Systemklassen werdenOptionen und Technologien zur Umsetzung der Integrationsplattformaufgezeigt. Der Beitrag schafft einen Rahmen für zukünftigeDiskussionen zur informationstechnischen Unterstützung technischerKundendienstleistungen

Phosphatidylinositol 4-kinase III beta is essential for the replication of human rhinovirus and its inhibition causes a lethal phenotype in vivo

Human rhinovirus (HRV) is the predominant cause of the common cold, but more importantly infection may have serious repercussions in asthmatics and COPD patients. A cell-based antiviral screen against HRV was performed with a subset of our proprietary compound collection, and an aminothiazole series with pan-HRV species and enteroviral activity was identified. The series was found to act at the level of replication in the HRV infectious cycle. In vitro selection and sequencing of aminothiazole series-resistant HRV variants revealed a single nucleotide mutation leading to the amino acid change I42V in the essential HRV 3A protein. This same mutation has been previously implicated in resistance to enviroxime, a former clinical-stage anti-picornaviral agent. Enviroxime-like compounds have recently been shown to target the lipid kinase phophatidylinositol 4-kinase III beta (PI4KIIIβ). A good correlation between PI4KIIIβ activity and HRV antiviral potency was found when analyzing the data over 80 compounds of the aminothiazole series, covering a 750-fold potency range. The mechanism of action through PI4KIIIβ inhibition was further demonstrated by siRNA knockdown of PI4KB, which reduced HRV replication and also increased the potency of the PI4KIIIβ inhibitors. Inhibitors from two different structural classes with promising pharmacokinetic profiles and with very good selectivity for PI4KIIIβ were used to dissociate compound-related toxicity from target-related toxicity. Mortality was seen in all dosing groups of mice treated with either compound, therefore suggesting that short term inhibition of PI4KIIIβ is deleterious.status: publishe