Autophagy in photodynamic therapy

Macroautophagy (autophagy) is crucial for cell survival during starvation and plays important roles in human diseases. It is a highly conserved intracellular degradation system in eukaryotes for removal and recycling of cytoplasmic components including damaged proteins and organelles to obtain energy. The relationship between cancer and autophagy has been extensively studied in recent years. In cancer and cancer therapy, autophagy acts as a double-edged sword. Photodynamic therapy (PDT) is a kind of tumor therapy applied with a tumor-localizing photosensitizing agent which is followed by activation with the light of a specific wavelength. How much is autophagy involved in photodynamic therapy? The work in this area is still limited.Keywords: Autophagy, Photodynamic therapy, Apoptosis, Cance

Automotive Supply Chain Auswertung mit herkömmlichem Modell und integriertem Modell

ABSTRACT: Increasing competition due to market globalization, product diversity and technological breakthroughs stimulates independent automotive companies to collaborate in a supply chain that allows them to gain mutual benefits. Especially the events of the past years have shell-shocked even the most ardent industry participants – a crisis and the following hard recovery. Not only the critical challenges in implementing process lean with low cost and high quality, also critical to success is the ability to efficiently meet stricter emissions and fuel economy standards escalating in most jurisdictions. With all the factors working beneath the waves, supply chain management becomes the core source of a company’s competitive advantages and even the trump of the entire automotive industry’s success. A proper supply chain strategy provides financial returns and other key factors superior to the old concepts which brought profits before but no longer up to date now. Correctly design and effectively evaluate the supply chains, and improve the supply chain structure dynamically over time, are the key methods for an automotive company to survive and succeed in the volatile and critical automobile industrial environment. In this research work, based on the real case study in the automotive door system supply, different supply chain scenarios are designed and corresponding performance evaluations are made by applying different methods, namely the conventional model and the integrated model with their corresponding algorithms. With conventional model, the evaluation is done from different aspects, where the chosen perspectives such as costs, flexibility, stability, and reliability are assessed respectively for the multi-stage international supply chains. The data applied in this model comes from real-case door module supply, and the evaluation results helps in the decision making in localization process of that certain project. To be able to evaluate more complicated supply chain scenarios in a more accurate and efficient way, an integrated model is designed for the comprehensive performance evaluation. Based on the fuzzy theory, a MDFIE (Multilevel Dynamic Fuzzy Integrated Evaluation) algorithm is developed to assess the automotive supply chain performance. With the real case of vehicle door system supply, a detailed index system is designed based on a profound understanding of the automotive door supply chain. And with this new method, supply chain scenarios with different outsource degree and integration degree are evaluated and analyzed, a positive solution of deeper integration and downstream task shifting in the automotive supply structure is concluded in the end. In addition to the use in this research work, the integrated model, especially the index system can be flexibly adjusted for other automotive supply chains under their special interest and requirements. And with the MDFIE algorithm or other possible methods, the model can also be further developed into user-friendly software or system for the normal application. This software development is suggested for the further research. Based on the researches done in this work, a new tier structure is proposed as well. A mega system supplier which is defined as the new Tier 0,5 and other outsourced service companies which are playing as the half tiers (tier 1,5/ 2,5…) are discussed in this work. With all the theoretical researches and practical investigations, this new structure which occupies the niche positions of supply chain is supposed to be benefiting the entire automotive supply chain in many critical aspects, like the long lasting over capacity problem and the coming E-mobility trend. Some other suggestions like the application of RFID technology are also proposed for increasing the productivity and strengthen the information flow along supply chain. In general, improving the entire automotive supply chain performance, is the ultimate goal of supply chain management, which means balancing all participators’ maximum profits and offering the highest market service level. The realization of the proposals and concepts, is also supposed to be studied in the further research.ZUSAMENFASSUNG: Die strengeren Emissions- und Kraftstoffverbrauchstandards effizient zu erfüllen, spielt neben der kritischen Herausforderungen bei der Umsetzung „Lean Prozess“ mit niedrigen Kosten und hoher Qualität für den Erfolg auch eine entscheidende Rolle. Der zunehmende Wettbewerb infolge der Globalisierung der Märkte, der Produktvielfalt und technologischer Durchbrüche stimuliert die Zusammenarbeit von unabhängiger Automobileunternehmen. Insbesondre in den letzten Jahren wurden die Teilnehmer aus dem Industriebranche von der Krise und dessen nachstehender Erholung schockiert. Mit allen Faktoren unter den Wellen bleibt das Supply-Chain-Management die Hauptquelle für die Wettbewerbsvorteile eines Unternehmens und überhaupt der Trumpf des Erfolgs in der gesamten Automobilindustrie. Eine richtige Supply Chain-Strategie bietet finanzielle Erträge und andere wichtige Faktoren, die besser als die alten Konzepte sind. Richtiges Design und gewissenhaftes Abschätzen des Supply Chains, und im Laufe der Zeit die Supply-Chain-Struktur dynamisch zu Verbessern sind die Schlüssel-Methoden für ein Automobilunternehmen, um in dem unberechenbaren und kritischen Automobilindustrieumfeld zu überleben und erfolgreich zu bleiben. Diese Arbeit basiert auf der realen Fallstudien der Türsystemlieferung in der Automobilindustrie. Verschiedene Supply Chain Szenarien werden entworfen und die entsprechenden Leistungen werden durch Anwendung unterschiedlicher Methoden bewertet, und zwar das herkömmlichen Modell und das integrierte Modell mit den entsprechenden Algorithmen. Beim herkömmlichen Modell wird unter verschiedenen Aspekten bewertet, wobei die gewählten Perspektiven wie Kosten, Flexibilität, Stabilität und Zuverlässigkeit jeweils für die mehrstufigen internationalen Lieferketten bewertet werden. Die genommenen Daten in diesem Modell stammen aus den Fällen von Türmodul - Auslieferung. Die Bewertungsergebnisse sind beim Entscheidungstreffen im Lokalisierungsprozess des gewissen Projektes hilfreich. Um die komplizierter Supply Chain Szenarien in einer genaueren und effizienteren Methode bewerten zu können, wird ein integriertes Modell für die umfassenden Leistungsbewertung gebaut. Auf der Basis von Fuzzy-Theorie, wird ein MDFIE (Multilevel Dynamische Fuzzy Integrierte Evaluation) Algorithmus entwickelt. Anhand der realen Auslieferungsfälle im Fahrzeugtürensystem wird ein detailliertes Index-System ausgelegt, welches auf einem tiefen Verständnis der Automotive Supply Chain basiert. Mit dieser neuen Methode werden Supply-Chain-Szenarien durch unterschiedliche Outsourcengrade und Integrationsgrade ausgewertet und analysiert. Eine positive Lösung von der vertiefen Integration und von der nachgeordneten Aufgabenumlagerung in der Automobilzuliefer-Struktur wird am Ende kristallisiert. Zusätzlich zu dem Einsatz in dieser Arbeit kann das integrierte Modell, vor allem das Index-System flexibel für andere Wertschöpfungsketten ihrer besonderen Interessen und Bedürfnissen entsprechend angepasst werden. Und mit dem MDFIE Algorithmus oder andere mögliche Methoden kann das Modell auch in einer benutzerfreundlichen Software oder System für die normale Anwendung integriert und entwickelt werden. Diese Software-Entwicklung wird für die weitere Forschung vorgeschlagen. Basierend auf den Untersuchungen in dieser Arbeit wird eine neue Stufenstruktur auch vorgeschlagen. Ein Mega-Systemzulieferer, die sogenannt neues Tier 0,5 ist, und ausgelagerter Service-Unternehmen, die als Hälfte Tiers (Tier 1,5 / 2,5 ...) definiert werden, sind in dieser Arbeit diskutiert. Mit theoretischen und praktischen Forschungen soll diese neue Struktur, deren Nische Positionen der Supply Chain beschäftigt sind, zu Gunsten der gesamten automobilen Wertschöpfungskette in vielen kritischen Aspekten bringen, z.B. das Überkapazitätsproblem und der kommende E-Mobilität Trend. Einige andere Vorschläge wie die Anwendung der RFID-Technologie zur Steigerung der Produktivität und zur Stärkung der Informationsfluss entlang der Lieferkette wird auch gemacht. Das ultimative Ziel des Supply-Chain- Managemenes ist die allgemeine Verbesserung der gesamten automobilen Wertschöpfungskettenleistung, die die maximale Gewinne von allen Teilnehmern zur Balancierung und den höchsten Market-Service-Level bedeutet. Die Realisierung der Vorschläge und Konzepte soll auch in der weiteren Forschung untersucht werden

SabR enhances nikkomycin production via regulating the transcriptional level of sanG, a pathway-specific regulatory gene in Streptomyces ansochromogenes

<p>Abstract</p> <p>Background</p> <p><it>sabR </it>is a pleiotropic regulatory gene which has been shown to positively regulate the nikkomycin biosynthesis and negatively affect the sporulation of <it>Streptomyces ansochromogenes</it>. In this study, we investigate the mechanism of SabR on modulating nikkomycin production in <it>Streptomyces ansochromogenes</it>.</p> <p>Results</p> <p>The transcription start point of <it>sabR </it>was determined by high-resolution S1 nuclease mapping and localized at the nucleotide T at position 37 bp upstream of the potential <it>sabR </it>translation start codon (GTG). Disruption of <it>sabR </it>enhanced its own transcription, but retarded the nikkomycin production. Over-expression of <it>sabR </it>enhanced nikkomycin biosynthesis in <it>Streptomyces ansochromogenes</it>. EMSA analysis showed that SabR bound to the upstream region of <it>sanG</it>, but it did not bind to the upstream region of its encoding gene (<it>sabR</it>), <it>sanF </it>and the intergenic region between <it>sanN </it>and <it>sanO</it>. DNase 1 footprinting assays showed that the SabR-binding site upstream of <it>sanG </it>was 5'-CTTTAAGTCACCTGGCTCATTCGCGTTCGCCCAGCT-3' which was designated as SARE. Deletion of SARE resulted in the delay of nikkomycin production that was similar to that of <it>sabR </it>disruption mutant.</p> <p>Conclusions</p> <p>These results indicated that SabR modulated nikkomycin biosynthesis as an enhancer via interaction with the promoter region of <it>sanG</it>, and expanded our understanding about regulatory cascade in nikkomycin biosynthesis.</p

Querying Graph Databases.

Real life data can often be modeled as graphs, in which nodes represent objects and edges indicate their relationships. Large graph datasets are common in many emerging applications. To fully exploit the wealth of information encoded in graphs, systems for managing and analyzing graph data are critical. To address the need of complex analysis on graph data, this thesis presents a graph querying toolkit, called Periscope/GQ. This toolkit is built on top of a commodity RDBMS. It provides a uniform schema for storing graphs and supports various graph query operations. Users can easily combine several operations to perform complex analysis on graphs. The key feature of Periscope/GQ is the support of various sophisticated graph query operations besides the simple ones like node/edge selection and path search. In particular, this thesis focuses on two classes of sophisticated queries: graph matching and graph summarization. The database community has largely focus on exact graph matching problems. However, due to the noisy and incomplete nature of real graph datasets, approximate, rather than exact graph matching is required. This thesis presents a novel approximate graph matching technique, called SAGA. SAGA employs a flexible graph similarity model and utilizes an index-based matching algorithm to efficiently evaluate matching queries. SAGA is effective and efficient for small query graphs (with tens of nodes and edges), but is expensive when applied to large query graphs (with hundreds to thousands of nodes and edges). To handle large query graphs, TALE is proposed. TALE employs a novel indexing technique, which achieves high pruning power and scales linearly with the database sizes. The matching algorithm utilizes the index to first match the important nodes in the query, and then extends them to produce large graph matches. Graph summarization techniques are useful for understanding underlying characteristics of graphs. To summarize large graphs, this thesis introduces an aggregation method. This method produces summary graphs by grouping nodes based on user-selected node attributes and relationships. It further allows users to control the resolutions of summaries, and provides the "drill-down" and "roll-up" abilities to navigate through summaries with different resolutions.Ph.D.Computer Science & EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/61640/1/ytian_1.pd