Yes / Background and Objective Visible light has beneficial effects on cutaneous wound healing, but the role of potential photoreceptors in human skin is unknown. In addition, inconsistency in the parameters of blue and red light‐based therapies for skin conditions makes interpretation difficult. Red light can activate cytochrome c oxidase and has been proposed as a wound healing therapy. UV‐blue light can activate Opsin 1‐SW, Opsin 2, Opsin 3, Opsin 4, and Opsin 5 receptors, triggering biological responses, but their role in human skin physiology is unclear. Materials and Methods Localization of Opsins was analyzed in situ in human skin derived from face and abdomen by immunohistochemistry. An ex vivo human skin wound healing model was established and expression of Opsins confirmed by immunohistochemistry. The rate of wound closure was quantitated after irradiation with blue and red light and mRNA was extracted from the regenerating epithelial tongue by laser micro‐dissection to detect changes in Opsin 3 (OPN3) expression. Retention of the expression of Opsins in primary cultures of human epidermal keratinocytes and dermal fibroblasts was confirmed by qRT‐PCR and immunocytochemistry. Modulation of metabolic activity by visible light was studied. Furthermore, migration in a scratch‐wound assay, DNA synthesis and differentiation of epidermal keratinocytes was established following irradiation with blue light. A role for OPN3 in keratinocytes was investigated by gene silencing. Results Opsin receptors (OPN1‐SW, 3 and 5) were similarly localized in the epidermis of human facial and abdominal skin in situ. Corresponding expression was confirmed in the regenerating epithelial tongue of ex vivo wounds after 2 days in culture, and irradiation with blue light stimulated wound closure, with a corresponding increase in OPN3 expression. Expression of Opsins was retained in primary cultures of epidermal keratinocytes and dermal fibroblasts. Both blue and red light stimulated the metabolic activity of cultured keratinocytes. Low levels of blue light reduced DNA synthesis and stimulated differentiation of keratinocytes. While low levels of blue light did not alter keratinocyte migration in a scratch wound assay, higher levels inhibited migration. Gene silencing of OPN3 in keratinocytes was effective (87% reduction). The rate of DNA synthesis in OPN3 knockdown keratinocytes did not change following irradiation with blue light, however, the level of differentiation was decreased. Conclusions Opsins are expressed in the epidermis and dermis of human skin and in the newly regenerating epidermis following wounding. An increase in OPN3 expression in the epithelial tongue may be a potential mechanism for the stimulation of wound closure by blue light. Since keratinocytes and fibroblasts retain their expression of Opsins in culture, they provide a good model to investigate the mechanism of blue light in wound healing responses. Knockdown of OPN3 led to a reduction in early differentiation of keratinocytes following irradiation with blue light, suggesting OPN3 is required for restoration of the barrier function. Understanding the function and relationship of different photoreceptors and their response to specific light parameters will lead to the development of reliable light‐based therapies for cutaneous wound healing. / European Commission 7th Framework Programme for Research and Technical Development - Marie Curie Innovative Training Networks (ITN), Grant agreement no.: 607886

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Drivers' mistakes in making immediate decision facing yellow signal interval to stop or go through the intersection is one of main factors contributing to intersection's safety. Incorrect decision might lead to a red light running and a right-angle Collison when passing through the intersection or a rear-end collision when failing to stop safely.Improperly timed traffic signal intervals result in the inability of the drivers to make the right decision and can place them in the dilemma zone. Advance warning systems (AWS) have been used to provide information about the downstream traffic signal change prior to approaching the intersection. On the other hand, advance warning systems increase drivers approach speed according to the literature. However, effect of AWS on dilemma zone has not been studied before. The goal of this thesis is to minimize the number of vehicles caught in dilemma zone by determining more precise boundaries for dilemma zone and to reduce the number of red light violations by predicting the red light runners before arriving to the intersection. Here, dilemma zone boundaries at the presence of AWS has been reexamined with the aid of a large dataset (more than 1870 hours of data for two different intersections). Upper dilemma zone boundaries found to be higher for the intersections with AWS. This is due to vehicles' increasing the speed at the flashing yellow sings to escape the dilemma zone.Moreover, an algorithm for predicting red light runners and distinguishing them from right turners is presented. / Master of Science

“What is certain is that the question of […] re-making a landscape of prostitution in the city […] needs to be viewed as part of a changing, global discourse on the nature of contemporary cities” (Aalbers & Sabat 2012, p. 114).Prostitution – associated with well-known Red-Light Districts – has for a long time been seen as “a significant urban activity that relates to other economic and social functions of the city [and contributes] […] to the cognitive image of a city held by both residents and non-residents, even those who have never frequented them” (Ashworth, White & Winchester 1988, p. 201). It is therefore no surprise that within the neoliberal framework of inter-city competition, these once notorious districts, commonly associated with crime and violence, ascended into spaces of entertainment and consumption, neatly aligning with entrepreneurial city branding strategies. The Reeperbahn, Hamburg’s famous mile of sin, located within the district of St. Pauli is no exception to this rule. As a place traditionally located outside Hamburg’s social and physical city limits, it is nowadays frequented by thousands of tourists and party seekers, drawn in by the area’s myths and shady reputation (Khan 2012). Actively fostering the (economic) attractiveness of the so-called Kiez has long been part of Hamburg’s city politics and was reinforced with the creation of the Hamburg Brand Marketing Strategy in 2002, where the Entertainment Mile Reeperbahn alongside Hamburg’s Pulsating Scenes became two of the key success modules in branding the city. The repercussion this has had not only for the district and its inhabitants but specifically for the red-light industry has largely been understudied.This Master’s Thesis therefore, aims at studying the general effects of city branding, such as displacement and conflict over spatial uses in the face of Over-Tourism and re-development strategies. Looking at the specific case of the Reeperbahn, it closes the gap of the somewhat understudied effects of gentrification on St. Pauli’s unique culture. By interviewing different local stakeholders, conducting a broad literature review as well as undertaking field work, the Hamburg-St.-Pauli-Brand-Dialectic will be analyzed subsequently, showing, how the Hamburg Brand and the city as a whole have profited from St. Pauli’s reputation and what consequences this has had in turn for the district.

Advance warning signals installed upstream of a high-speed signalized intersection (HSSI) warn motorists of impending signal changes in an effort to reduce the frequency of red-light running (RLR) and crashes. A new advance warning signal design was tested on an approach to an HSSI in Utah to study the effects of the modified design on motorist behavior. The new design utilized an overhead dynamic blank-out sign and flashers. A state-of-the-art digital wave radar evaluation system was installed at the study site to collect continuous data of vehicle speeds and RLR events by a non-intrusive method. Crash data were collected from the jurisdiction responsible for the study site and for an additional control intersection. Data were collected prior to, immediately after, and eight months after installation The blank-out overhead dynamic advance warning signal (BODAWS) system reduced RLR at the site during the time period immediately after installation. Eight months later, the number of RLR violations was slightly higher on one approach than before BODAWS system installation. Crash results showed that six months after BODAWS installation, the number of crashes declined at the study site. The number of crashes proportionately declined at the control intersection as well indicating a need to continue to evaluate and monitor changes. Mean vehicle speeds recorded before the onset of the yellow signal increased on the approaches to the study site immediately after BODAWS installation, and remained higher eight months later. Mean vehicle speeds recorded during the yellow signal, increased eight months after BODAWS installation to speeds higher than before the system was installed. Higher speeds during the yellow signal, combined with an increase in the number of RLR violations eight months after BODAWS installation, suggest that motorists may have begun to use the advance warning to speed up in an attempt to enter the intersection before the signal turned red. It is recommended that the lead flash time between activation of the BODAWS signs and flashers and the onset of the yellow signal should be adjusted so that motorists are not provided with more time than is necessary to safely clear the intersection.

The current thesis addresses the various facets of the chemistry of photocytotoxic iron complexes including their syntheses, characterization, evaluation of the anti-proliferative activities in various cancer cell lines upon photo-exposure, mechanism of cell death, the cellular uptake, localization inside cells, the interaction with double stranded DNA and their ability to induce DNA photocleavage. Chapter I presents a general introduction to cancer and the anticancer agents. It covers various procedures available for cancer treatment and different aspects of chemotherapy are discussed in details. The mechanism of action of several chemotherapeutic agents, the DNA cleavage pathways and the anticancer activity of bleomycins are delineated. Photo-chemotherapy or photodynamic therapy which has emerged as an alternative treatment modality is described. It also contains a brief description of ideal photosensitizers and the ones that are currently approved. The potential of transition metal complexes as photo-chemotherapeutic agents is discussed based on the recent literature reports on the prospective photocytotoxic metal complexes, the photo-release of cytotoxic molecules from metal complexes, the DNA cleavage activities and their cytotoxicities. The biochemistry of iron and its medical utility which prompted the development of iron based cytotoxins has been presented. The objective of the present investigation is also defined in this chapter. Chapter II describes the syntheses, characterization, evaluation of visible light induced cytotoxicity and interaction with DNA of a series of iron(II) bis-terpyridine complexes. Some interesting redox behaviour observed for two of the complexes has been described in details and rationalized from theoretical calculations. The DNA binding affinities of the complexes and their ability to induce DNA photocleavage in green light are discussed. The importance of this work lies in the remarkable photocytotoxic behaviour of the iron(II) complexes with visible light which was not reported earlier. Chapter III addresses the syntheses of a series of iron(III) catecholate complexes which upon irradiation with red light can initiate photoreactions to generate cytotoxic species and induce death in HeLa, HaCaT, MCF-7 and A549 cells. The mechanisms of cell death, effect of the complexes on the cell cycle under various conditions, the uptake inside cells and the cellular localization of the complexes are studied. The DNA binding affinities of the five complexes and their ability to induce DNA photocleavage in red light are also presented here. These are the first iron based complexes to show red light induced photocytotoxicity. Chapter IV addresses the drawbacks associated with the aforementioned iron(III) catecholates and their modification with a mitochondria targeting triphenylphosphonium unit. The synthesis, characterization, photocytotoxicities in HeLa, HaCaT, MCF-7 and A549, cell death mechanisms and cellular uptake and localization of four iron(III) complexes are discussed. Chapter V describes the syntheses, characterization and the biological activities of carbohydrate appended iron(III) complexes and their non-glucose analogues. The selective and faster internalization of the glyco-conjugated complexes in HeLa cells has been studied using various spectroscopic and microscopic techniques. The red light induced cytotoxicities of the complexes, their effect on the progression of the cell cycle with and without irradiation and the mechanisms of cell death are explored. DNA binding abilities and photocleavage of DNA are also discussed. Chapter VI presents the syntheses, characterization of a series of iron(III) complexes of a pyridoxal derivative and their salicyldehyde analogues for exploring their differential photocytotoxicity and cellular uptake in cancer cells compared to normal cells. The visible light induced cytotoxicities of the complexes in HeLa, HaCaT, MCF-7 A549 cells and HPL1D cells, their effect on the progression of the cell cycle in dark and light, the mechanisms of cell death and the localization of the complexes inside the cells are explored. The references have been compiled at the end of each chapter and given as superscripts in the text. The complexes presented in this thesis are indicated by bold-faced numbers. Crystallography data of the complexes that are structurally characterized by single crystal X-ray crystallography are given in CIF format in the enclosed CD (Appendix-I). Due acknowledgements have been made wherever the work described is based on the findings of other investigators. Any unintentional omission that might have happened due to oversight is regretted. INDEX WORDS: Iron complexes • Crystal structure • Red light induced cytotoxicity • Cellular imaging • DNA binding • DNA photocleavage.