A New Approach to Harness Probiotics Against Common Bacterial Skin Pathogens: Towards Living Antimicrobials

In this study, the potential of certain lactic acid bacteria—classified as probiotics and known to be antimicrobially active against pathogens or food-poisoning microorganisms—was evaluated with respect to their activity against bacterial skin pathogens. The aim of the study was to develop a plaster/bandage for the application of inhibitory substances produced by these probiotics when applied to diseased skin. For this purpose, two Streptococcus salivarius strains and one Lactobacillus plantarum were tested for production of antimicrobials (bacteriocin-like substances) active against Gram-positive and Gram-negative pathogens using established methods. A newly designed membrane test ensured that the probiotics produce antimicrobials diffusible through membranes. Target organisms used were Cutibacterium acnes, Staphylococcus aureus, and Pseudomonas aeruginosa. Moreover, the L. plantarum 8P-A3 strain was tested against additional bacteria involved in skin disorders. The Lactobacillales used were active against all potential skin pathogens tested. These probiotics could be enclosed between polymer membranes—one tight, the other permeable for their products, preserved by vacuum drying, and reactivated after at least three months storage. Importantly, the reactivated pads containing the probiotics demonstrated antibacterial activity on agar plates against all pathogens tested. This suggests that the probiotic containing pads may be topically applied for the treatment of skin disorders without the need for a regular antibiotic treatment or as an adjunctive therapy

Bestimmungsgründe für die Wahl von ingenieur- und naturwissenschaftlichen Studiengängen: Ausgewählte Ergebnisse einer Schwerpunktstudie im Rahmen der Berichterstattung zur technologischen Leistungsfähigkeit Deutschlands

Diese ZEW-Dokumentation enthält einen Überblick über zentrale Ergebnisse der Studie „Bestimmungsgründe für die Wahl von ingenieur- und naturwissenschaftlichen Studiengängen“, die als Schwerpunktstudie im Rahmen der Berichterstattung zur technologischen Leistungsfähigkeit Deutschlands von HIS und ZEW erarbeitet wurde

Анализ эффективности процессов планирования электроснабжения в Харьковском регионе

Ефективність процесів електропостачання запропоновано оцінювати не тільки величиною помилки прогнозування, а й кількістю негативних і позитивних помилок, що вимірюються за методикою Тейла. Виконано аналіз планованих і фактичних добових обсягів електроспоживання в Харківському регіоні в 2008 і 2009 роках. Оцінено помилки переоцінки і недооцінки фактичних обсягів, обчислені складові загальної помилки і показано, що переважає помилка неповної коваріації прогнозованих і фактичних значень добових обсягів ринку споживачів АК "Харківобленерго".The effectiveness of the processes of electricity supply was offered to assess not only with the magnitude of forecasting error, but with the number of negative and positive errors, measured by the method of Theil. The analysis of planned and actual daily volume of electricity in Kharkov region in 2008 and 2009 is realized. Errors of revaluation and underestimation of actual volumes are estimated, components of the general error are calculated and shown that the error of incomplete covariance for predicted and actual values of daily volumes of the market of consumers АК of "Kharkovo-blenergo" prevails

Pflanzliche Proteine als Fleischersatz: eine Betrachtung für die Schweiz

Soll die Eigenversorgung an pflanzlichem Protein für die menschliche Ernährung ausgebaut werden, bedarf es einer möglichst gesamthaften Betrachtung. In dieser Studie wird die Situation in der Schweiz systemisch analysiert. Es wird aufgezeigt, welche proteinreichen Pflanzen sich besonders für einen nachhaltigen und ökologischen Anbau eignen, welches ernährungsphysiologische Potenzial sie mitbringen und welche Prozessschritte notwendig sind, um sie zu Proteinkonzentraten und -isolaten aufzuarbeiten, die sich wiederum zur Herstellung von Fleischersatzprodukten eignen

Cyclin D1-CDK4 activity drives sensitivity to bortezomib in mantle cell lymphoma by blocking autophagy-mediated proteolysis of NOXA

Background: Mantle cell lymphoma (MCL) is an aggressive B-non-Hodgkin lymphoma with generally poor outcome. MCL is characterized by an aberrantly high cyclin D1-driven CDK4 activity. New molecular targeted therapies such as inhibitors of the ubiquitin-proteasome system (UPS) have shown promising results in preclinical studies and MCL patients. Our previous research revealed stabilization of the short-lived pro-apoptotic NOXA as a critical determinant for sensitivity to these inhibitors. It is currently unclear how cyclin D1 overexpression and aberrant CDK4 activity affect NOXA stabilization and treatment efficacy of UPS inhibitors in MCL. Methods: The effect of cyclin D1-driven CDK4 activity on response of MCL cell lines and primary cells to proteasome inhibitor treatment was investigated using survival assays (Flow cytometry, AnnexinV/PI) and Western blot analysis of NOXA protein. Half-life of NOXA protein was determined by cycloheximide treatment and subsequent Western blot analysis. The role of autophagy was analyzed by LC3-II protein expression and autophagolysosome detection. Furthermore, silencing of autophagy-related genes was performed using siRNA and MCL cells were treated with autophagy inhibitors in combination with proteasome and CDK4 inhibition. Results: In this study, we show that proteasome inhibitor-mediated cell death in MCL depends on cyclin D1-driven CDK4 activity. Inhibition of cyclin D1/CDK4 activity significantly reduced proteasome inhibitor-mediated stabilization of NOXA protein, mainly driven by an autophagy-mediated proteolysis. Bortezomib-induced cell death was significantly potentiated by compounds that interfere with autophagosomal function. Combined treatment with bortezomib and autophagy inhibitors enhanced NOXA stability leading to super-induction of NOXA protein. In addition to established autophagy modulators, we identified the fatty acid synthase inhibitor orlistat to be an efficient autophagy inhibitor when used in combination with bortezomib. Accordingly, this combination synergistically induced apoptosis both in MCL cell lines and in patient samples. Conclusion: Our data demonstrate that CDK4 activity in MCL is critical for NOXA stabilization upon treatment with UPS inhibitors allowing preferential induction of cell death in cyclin D transformed cells. Under UPS blocked conditions, autophagy appears as the critical regulator of NOXA induction. Therefore, inhibitors of autophagy are promising candidates to increase the activity of proteasome inhibitors in MCL

Assessing the Conditions for Multilateral Interventions or Non-Interventions: Intervention and Non-Intervention in the Asia Pacific Region

The focus of this thesis has been on the identification of the primary conditions that attract or deter multilateral interventions into internal conflicts in the Asia Pacific region. This thesis develops a framework which is applied to four cases of internal conflict to see what roles twenty-two structural and perceptual conditions have played in determining why multilateral intervention was initiated in two of the cases, and why multilateral intervention failed to be initiated in the other two cases. The research found that multilateral organizations will accept risks and costs associated with intervention if certain structural and perceptual conditions make intervention an attractive option. These conditions are, a favourable or significant international environment or international event(s), the consent of a sovereign state (even if it is induced), sustained and critical regional and international media coverage, a complete collapse of the state in conflict tainting it with the term 'failed state', a high probability of success, potential economic benefits, a humanitarian crisis (in respect of Unregulated Population Movements and genocide/politicide), the possibility of a clear exit strategy, and a self-interested Member State who can greatly subsidize an intervention. Multilateral non-interventions, on the contrary, are driven by a combination of a lack of sustained and critically analyzed media coverage on conflict issues and consequences, generally positive tactics and strategies adopted by disputants, conflicts of a long duration, the international environment, economic factors unfavourable to intervention, resistance levels to intervention or a failure to call for intervention, lack of any clear exit points, and an escalation phase. The importance of these conditions suggest that multilateral organizations are reluctant to take risks and costs when political will, for the collective and self, are not provoked. Consequently, particular structural and perceptual conditions trigger or influence political will. The analysis of four case studies (East Timor, Solomon Islands, Philippines (Moros), and West Papua) concludes that multilateral interventions will be the exception to the rule in the foreseeable future given the obvious selection bias evident in these policies, and the project questions the ad hoc determinants of current multilateral intervention policies