Interactions of cholesterol reducing agent simvastatin with charged model membranes were investigated. Effects of cholestrol reducing agent simvastatin on the phase transition behaviour and physical properties of the anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar liposome were studied as a function of temperature and simvastatin concentration. Moreover the effect of acyl chain length on the simvastatin model membrane interactions was monitored using dipalmitoyl phosphatidylglycerol (DPPG) and dimyristoyl phosphatidylglycerol (DMPG) lipids. All experiments were carried out by two non-invasive techniques namely Fourier Transform Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC). The observations made in the this study clearly showed that simvastatin interacts with the lipids of multilamellar liposomes and induces some variations in the structure of membranes. These effects are seen in the thermotropic phase transition profile of the membranes, on membrane order, acyl chain flexibility, lipid head group structures and membrane fluidity. The analysis of the C-H stretching region of FTIR spectra showed that, as simvastatin concentration increased, the phase transition curve broadened, pretransition temperature diminished, membrane order and membrane fluidity increased for anionic DPPG membrane. Moreover analysis of the C=O stretching and PO2 - stretching bands showed that simvastatin caused dehydration effect by decreasing of hydrogen bonding capacity in the glycerol backbone and also around the lipid head groups. DSC studies showed that as the simvastatin concentration increased, DSC curves broadened. In addition, simvastatin-induced lateral phase separation was observed in the DSC thermograms. In the second part of the study, the effect of acyl chain length on the simvastatin - membrane interactions was investigated for DPPG and DMPG lipid membranes. All parameters used in the FTIR studies are compared for DMPG and DPPG membranes. Similar results were observed for both membranes, except for the CH2 antisymmetric stretching band frequency at gel phase. Results showed that there are no significant effect of acyl chain length on simvastin - membrane interactions.

Amifostine is the only approved radioprotective agent by the Food and Drug Administration for reducing the damaging effects of radiation on healthy tissues. In this study, the effects of ionizing radiation on rat liver microsomal membrane and brain tissue and the protecting effects of amifostine on these systems were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated and liver microsomal membranes and different regions of the brain of these rats were analyzed using FTIR spectroscopy, FTIR microspectroscopy and synchrotron FTIR microspectroscopy. The first part of this study revealed that ionizing radiation caused a decrease in the total lipid content and CH2 groups of lipids, an increase in the carbonyl esters, olefinic=CH and CH3 groups of lipids in the white matter and grey matter regions of the brain, which could be interpreted as a result of lipid peroxidation. In addition, radiation altered the protein structure of the brain. Amifostine caused significant protective effect against all the radiation induced damages in the brain. In the second part of the study, FTIR results showed that radiation induced a decrease in the lipid/protein ratio and a degradation of lipids into smaller fragments that contain less CH2 and more carbonyl esters, olefinic=CH and CH3 groups in microsomal membranes. In addition, radiation caused an alteration in the secondary structure of proteins, an increase in lipid order and a decrease in the membrane dynamics. Amifostine prevented all the radiation induced compositional, structural and functional damages in the liver microsomal membranes.

Rheum species are medicinally important plants due to the presence of anthracene derivatives and in this study antioxidative, cytotoxic, apoptotic and chemopreventive characteristics of R. ribes extracts were evaluated. R. ribes shoot and root dry powder samples were prepared and extracted with ethyl acetate, ethanol and water. The extracts were revealed to be a potential scavenger of DPPH radicals and the chemical composition of the extracts was quantified by colorimetric determination of total phenol (GAE) and flavonoid (CAE) contents. HL&ndash / 60 cells were cultured in the presence of various concentrations of extracts up to 72 hr. R. ribes inhibited the surviv al of HL-60 cells in a concentration- and time-dependent manner, shown by trypan blue and XTT. R. ribes caused HL-60 cells apoptosis via formation of phosphatidylserine externalization, as evidenced by flow cytometry. Exposure of HL-60 cells to higher concentrations of extracts for 72 h resulted in a shift of 87% of the cell population from normal to the early/late apoptotic stage. The R. ribes induced apoptosis may be partially attributed to the activation of caspase-3 and up-regulation of caspase-3 expression was detected in western blot. The significant release of cytochrome c from the mitochondria into the cytosol was observed. The mRNA expression ratio of Bax/Bcl-2 was increased. The apoptosis was also demonstrated by DNA ladder and TUNEL. Chemopreventive effects of R.ribes were investigated at the gene level of CYP1B1 and CYP1A1, and GST enzyme activity against cDNB and concluded that R.ribes modulated activities of these enzymes generally at a time dependent level. T h ese findings suggest that Rheum ribes exhibits potential antioxidant and anticancer properties by inducing caspase-dependent cell death in HL-60 cells.

Quantum dots (QDs) are increasingly attracting attention in recent years due to their potential in biological imaging and drug delivery applications. Despite their significant advantages over organic dyes and fluorescent proteins, cytotoxicity is still a major problem in live-cell QD labeling. In this work, in-vitro characterization of a novel CdTe/2MPA quantum dot capped with CdS-DMSA was conducted on human cervical cancer (HeLa) and mouse fibroblast (NIH/3T3) cell lines. Biocompatibility of this novel particle was evaluated in comparison to a commercial quantum dot (Qdot 565) and various QDs with CdTe core. Cytotoxicity of quantum dots was investigated using XTT and proliferation assays. Cellular internalization and localization of particles were studied using confocal laser scanning microscopy. For quantitative determination of internalization and intracellular QD stability, we also performed uptake and cadmium release assays. Optimal cell imaging concentration with CdTe-CdS/2MPA-DMSA was determined as 10-50 ug/mL in HeLa cells. Localization of the internalized QD particles was observed in the perinuclear region of the cells. XTT and proliferation assays provided identical viability results for the tested QDs. CdS-DMSA capping increased cytocompatibility of CdTe/2MPA by 15% in NIH/3T3 cells. Biocompatibility of this capped particle was further increased by 3-folds with pegylation. For pegylated CdTe-CdS/2MPA-DMSA and commercial Qdot 565, we have not observed QD-related cytotoxicity on NIH/3T3 cells following 24-hr QD exposure at 50 ug/mL. Our in-vitro characterization studies indicate that CdTe-CdS/2MPA-DMSA is a promising live-cell imaging probe which can be effectively excited in the visible range of the electromagnetic spectrum.

Drug delivery systems are designed to achieve low, local doses at the target site. Delivery systems can provide the drug in a continuous manner or in response to environmental stimuli such as temperature, pH or UV. This study aimed to develop photosensitive liposomes that achieve UV-responsive release of their content. The main mechanism was to incorporate a light sensitive molecule into the liposomal bilayer then achieve destabilization of the membrane by exposure to UV. This would result in an on demand release of the bioactive content. Suprofen, a nonstereoidal anti-inflammatory drug, also a light sensitive molecule, was selected to achieve the destabilization in this study. Lipid vesicles were prepared with different ratios of phosphatidyl choline, cholesterol and Suprofen (PC:CHOL:SPF) and characterized in terms of encapsulation efficiency, release rate and responsiveness to UV. Preliminary studies were carried out with calcein (CAL), a fluorescent dye, due to the ease of detection and the in vitro studies were carried out with the cancer drug Cisplatin.

Colorectal carcinoma (CRC) is one of the most common cancers and is the leading cause of cancer deaths in much of the developed world. Owing to the high incidence of drug resistance and potential toxic effects of chemotherapy drugs, much research is currently underway to design better strategies for smart drug delivery systems. Cyclooxygenase-2 (COX-2) pathway is associated with poor prognosis in colon carcinomas. The selective COX-2 inhibitor drug Celecoxib (CLX) has been shown to posses COX-2 independent anti-carcinogenic effects in addition to inhibition of prostaglandins synthesis. The aim of the presented thesis was to develop a liposomal delivery system for CLX and to evaluate functional effects in CRC cell lines. Starting with multilamellar vesicles capable of CLX encapsulation and retention, nano sized liposomes were prepared and characterized in vitro. The optimum composition was determined as 10:1 DSPC: Cholesterol molar ratio and Polyethylene glycol (PEG) grafting at 2% of phospholipids. The extent of cellular association of PEGylated liposome formulation was analyzed quantitatively and cellular localization was analyzed qualitatively. We detected that CLX loaded PEGylated liposomes inhibited proliferation and cellular motility of cancer cells in a 2D model system. Our results showed that, Epidermal Growth Factor Receptor (EGFR) targeted CLX loaded immunoliposomes were extremely cytotoxic in cancer cells with high EGFR expression but not in cells devoid of EGFR expression. This delivery system may pioneer studies that may potentially circumvent the harmful systemic side effects of cancer preventive and chemotherapy drugs as well as allow the use of targeted combinatorial therapies.

This dissertation examines the development of the corporate sustainability evaluation system as a tool to implement the concept of sustainability management into business operations in China. The research focuses upon the theory construction and evolution, the application as a management tool, and the response to problems in corporate sustainability. The thesis presents a series of case studies that outline differing approaches to implement it during the business operation. It also presents the evaluation system enable corporation and related stakeholders group to improve corporate management towards sustainable development. Corporations are part of our increasingly complex and global system, drawing on and impacting on that system. Sustainable development poses a challenge to the traditional mindset of business operation. Increasingly the corporate performance is judged not just by the services, products and profits they make but also by the impacts they have on human and social well-being and on the natural environment on which we all depend for life. This thesis develops a special system to evaluate corporate sustainability and its impact to social and environment. In a quest for improved corporate sustainability performance, many organizations have developed numerous methods to monitor and measure its process. Unfortunately, many of these methods appear to be neither applicable nor able to promote effective decision-making. As a potential remedy, a theoretical framework was developed in this thesis using principles of integrated system to create a performance measurement system for corporations in China. On the basis of literature reviews and theoretical analysis, this thesis constructs a framework to identify key factors in sustainability, redefined procedure towards sustainable business. The discussion also argues that sustainability evaluation will change the way that companies perform, their day-to-day operations and improve corporate productivity through combining the agenda of sustainable development with corporate interests. The thesis also developed a practice oriented business management tool, through experiment by internal and external approaches in various corporations in China with considering all factors affected business operations and managing all factors in holistic way.

Wissenschaft und Praxis stimmen darin überein, dass Status eine hohe organisatorische Relevanz besitzt. Angesichts dieser Bedeutung und gleichzeitig existierender Defizite in der organisationswissenschaftlichen Erforschung des Phänomens ist es das Ziel der Dissertation, Auswirkungen von Status auf das Verhalten von Organisationsmitgliedern zu erklären und zu bewerten. Es wird untersucht, wann Organisationsmitglieder nach höherem Status streben und wann Organisationsmitglieder mit unterschiedlichem Status ihre Zusammenarbeit aufgrund von Statusdifferenzen einschränken. Die theoretisch-konzeptionellen Analysen indizieren dabei einen Trade-off zwischen dem Nutzen einer Statusdifferenzierung, in Form zusätzlicher Möglichkeiten zur Motivation und Steuerung von Organisationsmitgliedern, und den Kosten der Statusdifferenzierung, die vor allem durch Einschränkungen der Zusammenarbeit aufgrund von Statusdifferenzen entstehen. Eine Untersuchung des Einflusses ausgewählter organisatorischer Prozesse und Strukturen bestätigt diesen Trade-off.

Referenzmodelle können als Speicher für explizites Domänenwissen interpretiert werden. Obgleich in der Literatur inzwischen zahlreiche Referenzmodelle dokumentiert sind, ist der Zugang zu diesen Wissensspeichern uneinheitlich und nicht systematisch möglich. Referenzmodellkataloge ermöglichen Referenzmodelle nach einheitlichen Gesichtspunkten zu ordnen und nach spezifischen Gesichtspunkten zugreifbar zu machen. Damit bilden sie ein zentrales Instrument zur Erschließung der Wissensquelle Referenzmodell und bilden die Schnittstelle zwischen den Prozessen der Entwicklung von Referenzmodellen einerseits und der Anwendung von Referenzmodellen andererseits.

Die Herausforderungen des globalisierten Marktes und der verkürzten Produktlebenszyklen bei zunehmender Teilevielfalt erfordern von kleinen und mittleren Unternehmen, alle Verbesserungspotenziale in den Wertschöpfungsprozessen auszuschöpfen, um so die Erfüllung der Kundenanforderungen an Produkte und Leistungen unter Beachtung von Zeit und Kosten sicherzustellen. Eine entscheidende Bedeutung kommt dabei dem Einsatz effizienter Kontroll- und Steuerungswerkzeuge und der planmäßigen Anwendung des Erfahrungswissens qualifizierter Mitarbeiter als ''viertem Produktionsfaktor'' zu. In der Arbeit wird hierzu ein entscheidungsunterstützendes Softwaresystem konzipiert, dessen rechentechnische Umsetzung mitgestaltet sowie die Einführung und der praktische Einsatz in KMUs vorbereitet. Das System verbindet das logistische Kennzahlencontrolling mit der Wis-sensverarbeitung zur Diagnose- und Therapieunterstützung sowie mit der Simulation zur Prognose künftiger Prozessabläufe und Bewertung von Steuerungsentscheidungen. Für die Systemeinführung werden unterstützende Methoden und Werkzeugen ausgewählt. An einem Praxisbeispiel wird die Anwendbarkeit des Konzepts verifiziert. Teillösungen der Arbeit sind Konzepte zur organisatorischen und rechentechnischen Integration der Lösungskomponenten sowie ein Konzept zur mehrkriteriellen Bewertung der Prozessqualität, die Erstellung einzelner Software-Prototypen und der Entwurf der Datenbankstrukturen der Datenbasen sowie der Syntax einer Wissensbeschreibungssprache.