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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.

In order to search for bioactive compounds, we have studied the chemical constituents from the organic extracts of soft coral Klyxum molle. In this study, fifteen eunicellin-type diterpenoids, including eleven new compounds, klymollins K¡VU (1¡V11), along with four known compounds 12¡V15 were isolated. Compounds 16 and 17 were prepared by chemical synthesis. The structures of all compounds were established by spectroscopic methods and comparing the spectral data with known compounds. Compound 5 represents the first eunicellin-type compound with phenylacetyl group. The cytotoxicity of compounds 1¡V17 against K562 (human erythro myeloblastoid leukemia), Molt-4 (human acute lymphoblastic leukemia), and T47D (human breast earcinoma) were determined. Compounds 1, 2, and 3 exhibited weak cytotoxicity against Molt-4 (with ED50 11.52 ¡Ó 2.75, 20.41 ¡Ó 2.92, and 13.11 ¡Ó 3.87 £gg/mL). Compound 5 was found to exhibt significant cytotoxicity toward K562, Molt-4, and T47D (with ED50 4.32 ¡Ó 1.38, 2.36 ¡Ó 0.34, and 4.65 ¡Ó 0.93 £gg/mL). Compound 5 also displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils at 10 £gg/mL (with Inh % 81.56 ¡Ó 3.23, and 89.16 ¡Ó 5.77).

Syftet med undersökningen var att undersöka behandlares uppfattningar om och erfarenheter av relationsskapande som en grund för förändring med klienter som blivit dömda för sexualbrott. Vi använde oss av en hermeneutisk utgångspunkt med kvalitativ ansats med intervju som metod eftersom respondenternas egna uppfattningar och erfarenheter var av relevans för frågeställningen. Vid analyseringen av resultatet användes meningskoncentrering som metod. Resultatet har tolkats utifrån von Wrights teori om det punktuella och relationella perspektivet. Resultatet visar att respondenterna anser att relationen mellan behandlare och klient är den viktigaste delen i behandlingsarbetet med klienter som blivit dömda för sexualbrott, och att den relationen påverkar klientens förändringsprocess. Resultatet visar även att det finns aspekter som kan främja respektive hämma allianses mellan behandlare och klient såväl som klientens förändringsprocess. Aspekter som ansågs främjande var en professionell hållning hos behandlaren, empati, flexibilitet och förmågan att vara närvarande i mötet med klienter. Aspekter som ansågs hämmande var om behandlaren var generaliserande i mötet med klienter och om behandlaren var dömande mot klienter.

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.

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.

Cholesterol is one of the most abundant lipids in the body, and like all unsaturated lipids, it can be oxidized by a variety of reactive oxygen species (ROS). Lipid peroxidation is one of the main pathways by which ROS induce oxidative damage, and has been linked to neurodegenerative and cardiovascular diseases. In 2003, Wentworth et al. detected both 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A) and its intramolecular aldolization product 3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxaldehyde (secosterol-B) in human atherosclerotic plaques – compounds which, at the time, were only known to be formed by cholesterol ozonolysis. However, our group has shown that cholesterol 5α-hydroperoxide, which is the product of the reaction of cholesterol with singlet oxygen, can undergo acid-catalyzed Hock fragmentation to generate secosterol-A and -B as well. Nevertheless, cholesterol 5α-hydroperoxide readily rearranges to a more thermodynamically stable cholesterol 7-hydroperoxide. Herein we show that cholesterol 7-hydroperoxide, the main product of cholesterol autoxidation, can also undergo acid-catalyzed Hock fragmentation that gives rise to electrophilic species with similar chromatographic characteristics to those that were allegedly identified as secosterol-A and -B. We also proposed to prepare authentic products of the Hock fragmentation of cholesterol 7-hydroperoxide by subjecting Δ⁶’⁷-cholesterol to ozonolysis. Herein, we explore the limitations and complications of Δ⁶’⁷-cholesterol ozonolysis as well as cholesterol 7-OOH Hock fragmentation which both resulted in unexpected (unprecedented) products.

Unmanned ground vehicles (UGVs) have been widely used in many areas such as agriculture, mining, construction and military applications. This results from the fact that UGVs can not only be easily built and controlled, but also be featured with high mobility and handling hazardous situations in complex environments. Among the competences of UGVs, autonomous navigation is one of the most challenging problems. This is because that the success in achieving autonomous navigation depends on four factors: Perception, localization, cognition, and proper motion controller. In this thesis, we introduce the realization of autonomous navigation for a two-wheeled differential ground robot under the robot operating system (ROS) environment from both the simulation and experimental perspectives. In Chapter 2, the simulation work is discussed. Firstly, the robot model is described in the unified robot description format (URDF)-based form and the working environment for the robot is simulated. Then we use the \textit{gmapping} package which is one of the packages integrating simultaneous localization and mapping (SLAM) algorithm to build the map of the working environment. In addition, ROS packages including \textit{tf}, \textit{move\_base}, \textit{amcl}, etc., are used to realize the autonomous navigation. Finally, simulation results show the feasibility and effectiveness of the autonomous navigation system for the two-wheeled UGV with the ability to avoid collisions with obstacles. In Chapter 3, we introduce the experimental studies of implementing autonomous navigation for a two-wheeled UGV. The necessary hardware peripherals on the UGV to achieve autonomous navigation are given. The process of implementation in the experiment is similar to that in simulation, however, calibration of several devices is necessary to adapt the scenario in a practical environment. Additionally, a proportional-integral-derivative (PID) controller for the robot base is used to handle the external noise during the experiment. The experimental results demonstrate the success in the implementation of autonomous navigation for the UGV in practice. / Graduate

The use of multi-robot teams in the Robot Operating System (ROS) has encountered difficulty in advancement because of a lack of effective ways for the robots to communicate. Several attempts towards solving this problem have been made, but these approaches have had trouble with either low fault tolerance or high network load. The Gray Transceiver is an interface and communication protocol for inter-robot communication using ROS. The Gray Transceiver leverages multicasting for reduced network load and increased fault tolerance. Results from simulations, high throughput testing, and live multi-robot evaluations are included. The live mult-robot and simulation evaluations show that it functions properly operating across multiple robots while tolerating faults. The high throughput test shows how the Gray Transceiver operates under high load across a several types of conditions.

Natural Language processing is a growing field and widely used in both industrial and and commercial cases. Though it is difficult to create a natural language system that can robustly react to and handle every situation it is quite possible to design the system to react to specific instruction or scenario. The problem with current natural language systems used in machines, though, is that they are focused on single instructions, working to complete the instruction given then waiting for the next instruction. In this way they are not set to respond to possible conditions that are explained to them. In the system designed and explained in this thesis, the goal is to fix this problem by introducing a method of adjusting to these conditions. The contributions made in this thesis are to design a set of instruction types that can be used in order to allow for conditional statements within natural language instructions. To create a modular system using ROS in order to allow for more robust communication and integration. Finally, the goal is to also allow for an interconnection between the written text and derived instructions that will make the sentence construction more seamless and natural for the user. The work in this thesis will be limited in its focus to pertaining to the objective of obstacle traversal. The ideas and methodology, though, can be seen to extend into future work in the area. / Master of Science / With the growth of natural language processing and the development of artificial intelligence, it is important to take a look how to best allow these to work together. The main goal of this project is to find a way of integrating natural language so that it can be used in order to program a robot and in so doing, develop a method of translating that is not only efficient but also easy to understand. We have found we can accomplish this by creating a system that not only creates a direct correlation between the sentence and the instruction generated for the robot to understand, but also one that is able to break down complex sentences and paragraphs into multiple different instructions. This allows for a larger amount of robustness in the system.