145 research outputs found

    The Cdc48 Shp1 complex mediates cell cycle progression by positive regulation of Glc7

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    Competing in the Clouds: A Strategic Challenge for ITSP Ltd.

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    By 2010, cloud computing had become established as a new model of IT provisioning for service providers. New market players and businesses emerged, threatening the business models of established market players. This teaching case explores the challenges arising through the impact of the new cloud computing technology on an established, multinational IT service provider called ITSP. Should the incumbent vendors adopt cloud computing offerings? And, if so, what form should those offerings take? The teaching case focuses on the strategic dimensions of technological developments, their threats and opportunities. It requires strategic decision making and forecasting under high uncertainty. The critical question is whether cloud computing is a disruptive technology or simply an alternative channel to supply computing resources over the Internet. The case challenges students to assess this new technology and plan ITSP’s responses

    Auswirkungen der Statin- und Aspirin-Therapie auf thrombozytäre oxLDL-Spiegel bei Patienten mit symptomatischer koronarer Herzerkrankung

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    Hintergrund: Zirkulatorisches oxidiertes Low-Density-Lipoprotein (oxLDL) ist wesentlich an der Entwicklung koronarer Herzkrankheit (KHK) und Atherosklerose beteiligt. Malondialdehyd-modifiziertes-LDL (MDA-LDL) ist eine der Formen von oxLDL. Bei KHK-Patienten sind die intrazellulären thrombozytären oxLDL-Spiegel erhöht. Insbesondere Patienten mit akutem Koronarsyndrom (ACS) zeigen signifikant höhere intrazelluläre sowie thrombozytär-gebundene oxLDL-Spiegel als jene mit stabiler KHK. Intrazelluläre thrombozytäre oxLDL-Spiegel sind zudem bei ACS-Patienten mit angiographischem Nachweis von intrakoronaren Thromben signifikant erhöht. Thrombozyten sind selbstständig in der Lage, Lipide enzymatisch und oxidativ zu modifizieren. Somit tragen sie aktiv zur Krankheitsprogression bei. Das thrombozytäre Lipidom unterliegt insbesondere bei ACS-Patienten dynamischen Veränderungen. Es enthält unter anderem vermehrt oxidierte Lipidmetabolite. In der vorliegenden Studie wird der Einfluss der Statin- und Acetylsalicylsäure- (ASS) Therapie auf intrazelluläre thrombozytäre oxLDL-Spiegel sowie auf zirkulatorische Serum MDA-LDL-Spiegel untersucht. Zudem wird der Zusammenhang zwischen intrazellulären thrombozytären oxLDL-Spiegeln und Serum MDA-LDL untersucht. Methoden: Für diese Studie wurde während einer perkutanen Koronarintervention (PCI) 151 Patienten mit symptomatischer KHK (stabile KHK n = 94, ACS n = 57) Vollblut abgenommen. Unmittelbar im Anschluss wurde die Höhe der intrazellulären thrombozytären oxLDL-Spiegel, ausgedrückt durch die mittlere Fluoreszenzintensität (MFI), über Durchflusszytometrie bestimmt. Mittels Enzyme-linked immunosorbent assay (ELISA) wurde die Höhe von MDA-LDL (U/l) im Serum ermittelt. Ergebnisse: Die intrazellulären thrombozytären oxLDL-Spiegel unterschieden sich signifikant bei Patienten, die eine Kombination aus Statin- und ASS-Therapie erhielten, verglichen mit Patienten mit alleiniger ASS-Therapie. Eine alleinige Statin-Therapie ohne Kombination mit ASS hatte keinen signifikanten Einfluss auf die oxLDL-Spiegel der Thrombozyten. Die Studie liefert Hinweise, dass die intrazellulären thrombozytären oxLDL-Spiegel unabhängig von MDA-LDL sind. Es konnten keine statistisch signifikanten Unterschiede der MDA-LDL-Spiegel zwischen Patienten ohne Medikation und denen, die ein Statin erhielten, festgestellt werden. Zudem zeigten sich keine signifikanten Unterschiede der MDA-LDL-Spiegel zwischen Patienten, die ASS, und solchen, die ASS und ein Statin nahmen. Schlussfolgerung: Die Studie liefert Hinweise darauf, dass sich intrazelluläre thrombozytäre oxLDL-Spiegel möglicherweise durch eine medikamentöse Therapie aus Statin und ASS beeinflussen lassen. Thrombozytäres oxLDL könnte somit als neuer therapeutischer Angriffspunkt in der KHK-Therapie dienen

    Epidemiology of common infectious diseases before and during the COVID-19 pandemic in Bavaria, Germany, 2016 to 2021: an analysis of routine surveillance data

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    Background Unprecedented non-pharmaceutical interventions to control the COVID-19 pandemic also had an effect on other infectious diseases. Aim We aimed to determine their impact on transmission and diagnosis of notifiable diseases other than COVID-19 in Bavaria, Germany, in 2020 and 2021. Methods We compared weekly cases of 15 notifiable infectious diseases recorded in Bavaria between 1 January 2016 and 31 December 2021 in time series analyses, median age and time-to-diagnosis using Wilcoxon rank sum test and hospitalisation rates using univariable logistic regression during three time periods: pre-pandemic (weeks 1 2016–9 2020), pandemic years 1 (weeks 10–52 2020) and 2 (2021). Results Weekly case numbers decreased in pandemic year 1 for all diseases assessed except influenza, Lyme disease and tick-borne encephalitis; markedly for norovirus gastroenteritis (IRR = 0.15; 95% CI: 0.12–0.20) and pertussis (IRR = 0.22; 95% CI: 0.18–0.26). In pandemic year 2, influenza (IRR = 0.04; 95% CI: 0.02–0.09) and pertussis (IRR = 0.11; 95% CI: 0.09–0.14) decreased markedly, but also chickenpox, dengue fever, Haemophilus influenzae invasive infection, hepatitis C, legionellosis, noro- and rotavirus gastroenteritis and salmonellosis. For enterohaemorrhagic Escherichia coli infections, median age decreased in pandemic years 1 and 2 (4 years, interquartile range (IQR): 1–32 and 3 years, IQR: 1–18 vs 11 years, IQR: 2–42); hospitalisation proportions increased in pandemic year 1 (OR = 1.60; 95% CI: 1.08–2.34). Conclusion Reductions for various infectious diseases and changes in case characteristics in 2020 and 2021 indicate reduced transmission of notifiable diseases other than COVID-19 due to interventions and under-detection.Peer Reviewe

    Mechanical modeling of the maturation process for tissue-engineered implants: application to biohybrid heart valves

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    The development of tissue-engineered cardiovascular implants can improve the lives of large segments of our society who suffer from cardiovascular diseases. Regenerative tissues are fabricated using a process called tissue maturation. Furthermore, it is highly challenging to produce cardiovascular regenerative implants with sufficient mechanical strength to withstand the loading conditions within the human body. Therefore, biohybrid implants for which the regenerative tissue is reinforced by standard reinforcement material (e.g. textile or 3d printed scaffold) can be an interesting solution. In silico models can significantly contribute to characterizing, designing, and optimizing biohybrid implants. The first step towards this goal is to develop a computational model for the maturation process of tissue-engineered implants. This paper focuses on the mechanical modeling of textile-reinforced tissue-engineered cardiovascular implants. First, we propose an energy-based approach to compute the collagen evolution during the maturation process. Then, we apply the concept of structural tensors to model the anisotropic behavior of the extracellular matrix and the textile scaffold. Next, the newly developed material model is embedded into a special solid-shell finite element formulation with reduced integration. Finally, we use our framework to compute two structural problems: a pressurized shell construct and a tubular-shaped heart valve. The results show the ability of the model to predict collagen growth in response to the boundary conditions applied during the maturation process. Consequently, we can predict the implant's mechanical response, such as the deformation and stresses of the implant.Comment: Preprint submitted to Elsevie

    A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes

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    Yeast cells can be killed upon expression of pro-apoptotic mammalian proteins. We have established a functional yeast survival screen that was used to isolate novel human anti-apoptotic genes overexpressed in treatment-resistant tumors. The screening of three different cDNA libraries prepared from metastatic melanoma, glioblastomas and leukemic blasts allowed for the identification of many yeast cell death-repressing cDNAs, including 28% of genes that are already known to inhibit apoptosis, 35% of genes upregulated in at least one tumor entity and 16% of genes described as both anti-apoptotic in function and upregulated in tumors. These results confirm the great potential of this screening tool to identify novel anti-apoptotic and tumor-relevant molecules. Three of the isolated candidate genes were further analyzed regarding their anti-apoptotic function in cell culture and their potential as a therapeutic target for molecular therapy. PAICS, an enzyme required for de novo purine biosynthesis, the long non-coding RNA MALAT1 and the MAST2 kinase are overexpressed in certain tumor entities and capable of suppressing apoptosis in human cells. Using a subcutaneous xenograft mouse model, we also demonstrated that glioblastoma tumor growth requires MAST2 expression. An additional advantage of the yeast survival screen is its universal applicability. By using various inducible pro-apoptotic killer proteins and screening the appropriate cDNA library prepared from normal or pathologic tissue of interest, the survival screen can be used to identify apoptosis inhibitors in many different systems

    Evaluation of hypochlorous acid as an ear flush in dogs with chronic otitis externa

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    BackgroundChronic otitis externa (OE) in dogs frequently requires anaesthetised ear flushing. ObjectivesTo evaluate hypochlorous acid as an ear flushing and antimicrobial agent in dogs with chronic OE. AnimalsTwenty dogs with chronic OE caused by the same organisms bilaterally. Materials and MethodsOne ear was flushed under anaesthesia with hypochlorous acid, the other with saline solution. Subsequently, the ear flushed with hypochlorous acid was cleaned with the same solution twice daily for 2 weeks, the other ear with a commercial ear cleaner. An ear medication containing miconazole, polymyxin B and prednisolone was used once daily in both ears. Clinical scores were determined before the flush. Ear cytological results were obtained, a hearing test was conducted before and after the ear flush, and a culture was taken directly after flushing. Ears were evaluated after 2 weeks of therapy. ResultsYeast was present in the ears of 11, cocci in one and a mixed infection in eight dogs. Five ears were negative on culture after flushing with hypochlorous acid, one after the saline flush. Clinical and cytological scores decreased significantly with both solutions after 2 weeks of treatment. There was no difference between treatments in any of the scores at any time point between treatments and in the results of the hearing test before and after the flushing procedure. Adverse effects were not seen. Conclusions and Clinical RelevanceHypochlorous acid is a suitable cleaning solution for canine OE

    Berufliche Anforderungen und ihre Auswirkungen auf das Privatleben von doppelerwerbstätigen Paaren

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    Steigende zeitliche, physische und psychische Arbeitsbelastungen können die Qualität und die Stabilität von Partnerschaften und Familien bedrohen. In unserem Beitrag vergleichen wir, wie dadurch Work-Family-Konflikte, belastender Streit innerhalb der Partnerschaft und das Trennungsrisiko beeinflusst werden. Wir erklären diese Beeinträchtigungen zum einen über individuelle Belastungen im Erwerbsleben, zum anderen über partnerschaftliche Muster der Beteiligung an der Erwerbsarbeit und Hausarbeit. Empirische Basis sind die Studie "Beschäftigungsverhältnisse als sozialer Tausch" sowie das Sozio-oekonomische Panel. Die Ergebnisse zeigen, dass sowohl die Qualität als auch die Stabilität von Partnerschaften durch hohe Erwerbsarbeitsbelastungen negativ beeinfl usst werden, aber in je unterschiedlicher Weise.It has almost become a commonplace that increasing temporal, physical and psychological work demands and pressures have challenged capabilities for maintaining strong intimate relationships and families. In our article we compare how work-to-family conflicts, serious conflicts within partnerships, and the risk of separation are influenced by antecedents located in two dominant research traditions: on the one hand individual work strains, and on the other research on balancing work and family, taking account of different patterns of employment and housework within partnerships. For our analyses we draw on two different data sets: the German Socio-Economic Panel Study (SOEP) and the study entitled 'Employment relationships a social exchange'. The results reveal the different negative infl uences of high work strains on both the quality and the stability of partnerships
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