Genome-wide association studies (GWAS) have identified up to 30 loci that associate with increased risk of coronary artery disease or myocardial infarction. Here, I tested the function of one locus that changed the amino acid sequence of a mitochondrial matrix protease called paraplegin (SPG7) that performs critical quality assurance functions. Loss-of-function mutations in this protease are associated with hereditary spastic paraplegia. Here, I show that this variant that changes an arginine to a glutamine at position 688 within the protease domain is a gain-of-function. Cells bearing this variant have increased mitochondrial fusion and number, produce higher levels of reactive oxygen species and have increased cellular proliferation. Importantly, when expressed in yeast, the Q688 variant of SPG7 rescues the growth arrest caused by a protease-deficient mutation in AFG3L2. My study identifies a novel functional variant of SPG7 and highlights the need to go beyond the GWAS paradigm.

No description available.

This report is about the issue with decreasing production rate mainly caused by failuresrelated to the multiswitch. The multiswitch is a machine at Gefleortens Mejeriföreningwhich has the function of distributing milk cartons from one incoming track into fiveoutgoing tracks. Milk cartons who gets stuck and there by causes the production to stop,is the mainly problem with this construction The purpose with this report is to understand the causing factors and make suggestions which can help solving these factors. By analyzing the machine during production, having contact with different suppliers, searching internet for information, 3d-cad drawings and the complementary with personal experiences, this machine has  been evaluated and as a result of this new problem has come to be known. The discovered problems was analyzed and resulted in new suggestions for alternative options. Later the most functional results was chosen and put as a suggestion for the new model. A new machine built with the suggestions from this report assures to be well adapted to the environment at Gefleortens Mejeriföreing and the problems it causes.

This report summarize a simple and efficient way to convert 2D into 3D designs. It explains the benefits of a 3D design compared with 2D, and how those benefits may be used. It will also give the reader a presentation of the company Clean Air Technologies, which for the most part constructs cleaning facilities for power plants. How to create 3D-libraries for some of those facilities will be introduced in this composition. The collaboration with Clean Air Technologies has resulted in several 3D animated movies and rendered images. This has increased the quality of the companies offer presentations, which has made it easier for the prospective customer to get an improved overall image of the power plant design.

This thesis describes the development ofa linear guidance system suited for NORCAN's aluminium profiles. The work took place at LP Innovation, a small technical consulting company, located in Uppsala. The work started with gathering and searching for information. A lot of the information was found in product catalogs, but my supervisor was also a great source of knowledge, as well as the other engineers at the company. I also had the opportunity to work with the rea lprofiles, to get a feeling and greater understanding how they were supposed to be used. With the use of sketching and CAD, a number of concepts were generated. One of those concepts, that me and my supervisor thought, looked good were later on made into a prototype. The prototype was tested and the results were compared to one of the current solutions. An experimental design was applied to the prototype to look for improvements. When a working solution was made, some examples of applications were given, for example two different height adjustable tables.

Impellers are important components in the field of precision machine, energy technology, and aerospace industries. Due to their complex geometries and higher degrees of interference, to produce a impeller with high precision dimension is a challenging technology. In this study, flank milling is used to machine blade surfaces of impeller instead of point cutting. Flank milling can provide a surface better than point cutting without addition processes. When blades of an impeller are designed by ruled surfaces, the impeller can be machined by flank cutting technology. Based on the type of a five-axis CNC machine, the objective of this project is aimed to develop the technology of five-axis machining for impellers. The involved techniques are : the identification of undercutting in flank cutting for ruled surfaces, five-axis tool paths generation, coordinate transformations for five-axis machining, and determination of cutting parameters. In addition, a practical application example is provided to show the feasibility and effectiveness of the developed procedure.

Thesis (Ph. D.)--Lehigh University, 2004. / Includes vita. Includes bibliographical references (leaves 294-307).

This thesis describes the development of a tank insert for diesel cars, from idea to a prototype. The idea is to design an insert which makes it impossible to refuel petrol in a diesel car. The insert shall be installed in the existing tank opening on diesel cars. The tank insert is designed for the Swedish company SverigeGrepen AB located in Vänge, just outside Uppsala. Their main product is a pitchfork that is ergonomically designed and durable. A pre-study were performed in which information relating to fuel caps, tank openings, petrol- and diesel nozzles were collected. The information comprised mainly dimensions and standards. The pre- study also included information retrieval about suitable materials that might be used in the design. Some research and surveys on existing solutions for this problem were made. After the pre-study, a user requirement specification was written to define measurable requirements and to facilitate the concept design process. After the pilot study followed a concept design process that began by sketching ideas for different concepts for the two main functions of the product, identified through a product function analysis. Simple CAD models were also created from the sketches. The best of the concepts of the respective main function were selected and combined into a new concept. The new concept was further developed. The construction and the individual parts were adapted for manufacturing and it resulted in a 3D-prototype model. Based on the 3D-prototype model a 3D-printed prototype were created and evaluated. The prototype solves the problem with misfuelling and makes it impossible to refuel petrol in a diesel car. However the prototype is not optimized but small adjustments can make it more reliable and make it operate much better.

ConneXion

This thesis presents a continuation study about the diffusion of innovation in the manufacturing companies. The focus of this study is the diffusion of innovation in technology and CAD is the selected technology that is widely used in the manufacturing companies. The foundation of this study is the previous work that has been conducted by Jan Löwstedt and Christer Norr in 1991 that explained about the diffusion of technology during that time. Thereafter, technology has experienced a rapid change. There is not a continuation study afterwards. The purpose of this study is to see how the technology has changed and how people use it over time, and what driving forces are behind it, so an extension information for the PLC perspective can be formed. Theoretical framework was built by analyzing the previous studies as the foundation to see what has changed over time. The concept of the diffusion of innovation, PLC, and the development of CAD in terms of technical and organizational perspective wise from several researchers are also disclosed to support the empirical findings. The approach of this study is based on a qualitative study where empirical data are collected through interviewing Swedish manufacturing companies that use CAD in their companies. The result of this study reveals that the usage of CAD technically is not dramatically changed: it is still mainly in providing a visceral visualization. But, the paradigm shifting in utilizing CAD in the organization is worth exploring. Where it is triggered by the need to get more advanced technology-wise. The diffusion of technology could contribute the paradigm shifting in the way of working. This study shows that the companies tend to maximize the result of the technology by integrating the result not exclusively only for the design department, but also for other parties such as: the engineering calculation department and customers. However, this study could present a sharper pattern if there were more companies that were in the early stage of CAD as the source of information.