The current field of cancer treatment is undergoing a revolution. The influx of novel therapies derived from basic research on the immune system has shifted the landscape of modern medicine. Immunotherapy seeks to use the body’s own immune system as a medium to terminate neoplastic cells. This is performed by manipulating the immune system into either targeting cancer antigens or breaking down barriers towards T cell infiltration. The former mechanism uses CAR-T cells as an instrument to target specific cancer neo-antigens. CAR-T cells begin as T cells derived from a patient’s immune system. These cells are removed from the body and engineered to express a chimeric antigen receptor (CAR) through a process of viral transduction. This CAR allows the T cell to recognize and bind to a specific antigen of interest. In most cases, the antigen is present on cancer cells. The T cells, now expressing the CAR receptor, are transplanted back into the body of the patient and proceed to target cancer cells. This therapy has been used in hematological malignancies to great effect. Applying CAR-T cells to solid tumors is an ongoing process, but has been difficult to establish due to the immunosuppressive aspects of the tumor microenvironment. As such, combining CAR-T cells with traditional anti-cancer therapies has been proven to be efficacious in treating patients with solid tumors. In general, immunosuppression is a large problem in the treatment of cancer. Cancer cells and the tumor microenvironment express receptors that downregulate tumor-targeting actions of the immune system. The discovery of the programmed cell death protein 1 (PD1) allowed researchers to create novel antibodies that inhibit immunosuppression. PD1 located on T cells, binds to PDL1 on cancer and stromal cells. This interaction induces exhaustion and anergy in infiltrating T cells, thereby prevent T cells from targeting cancer cells. As such, the newly approved checkpoint blockade antibodies, Nivolumab and Pembrolizumab, block this interaction and allow T cells to carry out their targeting function. CAR-T cells and checkpoint blockade have both seen immense success in clinical trials and are currently being used the clinic. Nonetheless, development of these therapies for different types of cancers is an ongoing process and one that will require immense effort on behalf of the medical and pharmaceutical establishment

This graduation theses evaluates the current state of road safety. The work contains the current legislation in the Czech Republic, i.e., regulations and laws. It presents basic concepts in automotive safety. Another part is the analysis and synthesis and the starting point lies in measures to prevent accidents as well as in risk measures in case of accidents. It is therefore to mitigate the damage and injuries due to accidents. In addition, it monitors driver training in driving schools. The final section deals with the proposal for resolving the current situation, in particular proposed measure is applicable in real practice when training drivers.

The main objective of my thesis was to carry out a automotive market segmentation.I have chosen the company ´Autocentrum Šmucler´, Ltd., as the object of my thesis. This firm deals with sale of new cars and also second-hand vehicles.I have devided my writing into a theoretical and practical part. In the theoretical part the meaning of the word ´marketing´, ´market´ and ´car market´ is explained, then everything concerning market segmentation in the concrete {--} its process, its procedure, its reason, its type, its effective criterions, market targeting and searching of a position in the market.In the practical part the automotive market segmentation is carry out. I have made a marketing research, in this case by the questionary survey. I have got all informations needed for each segment characteristics by the research.

abstract: Contrary to many previous travel demand forecasts there is increasing evidence that vehicle travel in developed countries may be peaking. The underlying causes of this peaking are still under much debate and there has been a mobilization of research, largely focused at the national scale, to study the explanatory drivers but research focused at the metropolitan scale, where transportation policy and planning are frequently decided, is relatively thin. Additionally, a majority of this research has focused on changes within the activity system without considering the impact transportation infrastructure has on overall travel demand. Using Los Angeles County California, we investigate Peak Car and whether the saturation of automobile infrastructure, in addition to societal and economic factors, may be a suppressing factor. After peaking in 2002, vehicle travel in Los Angeles County in 2010 was estimated at 78 billion and was 20.3 billion shy of projections made in 2002. The extent to which infrastructure saturation may contribute to Peak Car is evaluated by analyzing social and economic factors that may have impacted personal automobile usage over the last decade. This includes changing fuel prices, fuel economy, population growth, increased utilization of alternate transportation modes, changes in driver demographics , travel time and income levels. Summation of all assessed factors reveals there is at least some portion of the 20 billion VMT that is unexplained in all but the worst case scenario. We hypothesize that the unexplained remaining VMT may be explained by infrastructure supply constraints that result in suppression of travel. This finding has impacts on how we see the role of hard infrastructure systems in urban growth and we explore these impacts in the research. / Dissertation/Thesis / M.S. Civil Engineering 2014

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy Candidate: Ivana Šachová Supervisors: PharmDr. Jan Martin, PhD., Dipl. Ing. Mgr. Ferdinand Molnár, PhD. Title of diploma thesis: Preparation of strategy for studying interaction of human constitutive androstane receptor with steroid receptor coactivator-1 The aim of this study was to express wild type and mutated synthetic human SRC1 central domains in E. coli BL21 DE3 cells. Expressed recombinant proteins were purified afterwards and used for investigation of SRC1-CAR protein interaction using pull down experiments. The constitutive androstane receptor (CAR), a nuclear receptor (NR), is a transcriptional regulator, which influences the expression of various proteins, such as enzymes of biotransformation and transporters important for metabolism of both endogenous and exogenous compounds. CAR can be fully active only in presence of coactivators, such as steroid receptor coactivator-1 (SRC1). The most important fragment of SRC1 for binding to NRs is the central domain, made of three α-helical Leu-X-X-Leu-Leu (LXXLL) L1, L2, L3 motifs, in where L is a leucine and X represents any amino acid. hSRC1, as well as hCAR, can be successfully produced by expression of cDNA of interest in E. coli strains. In case of SRC1,...

The thesis describes how family life is organised in the car, with a particular focus on exploring the role and use of mobile technology in this setting. The objective of this research is to use the insights from video ethnographic data collected with families to discuss how social interaction between family members may be situated to technology use. Drawing from the notion of ‘ordinary work’ discussed in ethnomethodology and applying this to naturalistic video data of families in cars, the thesis demonstrates how family activities are locally produced, drawing on background knowledge and common-sense understandings of family members’ work. Using methods from conversation analysis, the research demonstrates how transcribed instances of talk can reveal how parents and children produce their actions and talk to jointly produce activities in relation to media use. The analysis presented in this thesis demonstrates how the family car provides an opportunity for parents and children to come together, and engage in mundane family activities of talk and play while using a range of mobile devices. The thesis draws on richly documented and closely analysed episodes of interaction to demonstrate how family life unfolds in the accomplishment of activities in which interactions are situated, orderly and observable. The production of family life within the car involves talk and embodied action that is artfully placed within interactions between parents, children and technology. The analysis elucidates how the features of negotiation, collaboration and coordination around device-use are placed alongside driving activities. The contributions of this thesis lie in providing a descriptive analysis of the social organisation of family life through technology, developing an understanding of family technology use in a mobile context and highlighting elements of interaction that will inform the development of insights for the design of technology that is sensitive to the nuances of family life, mobility and technology practices.

The thesis is focused on carsharing. Firstly, the concept of carsharing is defined , followed by specifications of different types of this business, as well as its developments and both customer and social advantages . The thesis also evaluates the developments of Czech carsharing market with main focus on the leading company on the Czech carsharing market. Regarding the history of carsharing in the developed market economies, the thesis has been evaluating strengths and weaknesses of the respective company. The thesis also tries to make the comparison of the price competitiveness of the leading Czech company compared to its direct and indirect competitors. Recommendations of the steps how to develop this particular company and how to strengthen its market position are subject to the final part of the thesis.

Thesis is about segmentation research cars market.

The purpose of my thesis is use of various methods of multicriterial evaluation of alternatives in a reality, and particularly the estimation of positions of Volkswagen brand at the market of new cars in Czech Republic and which positions do they take in comparison with other carmakers. The following purpose was to help customers who are going to get to itself the car. The aim was to order cars in each of 10 classes on the basis of results of each method. For my analysis I use methods WSA, TOPSIS and ELECTRE III. For calculations I used MS Excel and program SANNA.

The aim of this diploma thesis is to determine the strengths and weaknesses of the Škoda brand and current company marketing strategy in the Chinese market. Leading to description and analysis of what is behind the recent success on the Chinese market and what factors could cause its future further triumph or possible breakdown in China.