Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome complex causes the processing and release of mature IL-1β, with mitochondria playing key roles in its assembly. An orally active NLRP3 inflammasome inhibitor would be a significant advance in therapy for IL-1β-driven diseases. To overcome both, the variability among primary immune cells and the limitations of genetic manipulation of differentiated human or murine macrophages, we developed a simplified, reliable and relevant cell-based model for studying the NLRP3 inflammasome using the undifferentiated human myelomonocytic cell line THP1. We established that undifferentiated THP1 cells are fully competent for activation of the NLRP3 inflammasome and production of IL-1β, without differentiation into macrophages. CP-456,773 is a potent and selective inhibitor of the NLRP3 inflammasome, and it is an analogue of glyburide, a sulfonylurea receptor (SUR) inhibitor. Despite the extensive experimental use of CP-456,773, its molecular target remains unknown. Here we tested the hypothesis that mitochondrial ABCb7 or ABCb10 could be the pharmacologic targets of CP-456,773. We optimized a viral shRNA transduction method for genetic manipulations in THP1 cells and generated ABCb7 and ABCb10 knockdown (KD) THP1 cells. We demonstrate that NLRP3 inflammasome activation and CP-456,773 pharmacology are not altered in ABCb7- or ABCb10-deficient THP1 cells. For ABCb10, we confirmed these results using CRISPR/CAS9-mediated ABCb10 knockout (KO) THP1 sub-lines. In studies of mitochondrial fitness, we found that a previously observed reduction in oxygen consumption rate (OCR) following nigericin treatment was completely blocked in NLRP3 KO cells. Our data demonstrating that CP-456,773 rescues the NLRP3-dependent nigericin-induced decline in OCR and protects undifferentiated THP1 cells from nigericin-induced pyroptosis are consistent with the possibility that the NLRP3 protein itself may be the molecular target of CP-456,773. Moreover, we showed that ABCb10 KO THP1 cells exhibit increased rates of basal ATP production and glycolysis, suggesting an important role for ABCb10 in mitochondrial metabolism. Finally, RNA-Seq analysis of ABCb7 and ABCb10 KD in undifferentiated THP1 cells indicate new functions for these proteins, including cell communication and migration, apoptosis and cell adhesion. Overall, our findings demonstrate that undifferentiated THP1 cells are an ideal system in which to study the NLRP3 inflammasome.

Engagement is the active involvement in experiences which allows for development. For children with severe mobility impairments however, challenges arise in accessing experience which can lead to learned helplessness. Due to these challenges powered mobility has been suggested as a mechanism for the provision of self-initiated access to experiences. However, powered mobility is out of reach of the majority of children with disabilities in South Africa hence a non-powered alternative has been sought. This study sought to determine the effect of non-powered, self-initiated mobility on the engagement of young children, with severe mobility impairment, in play. A multiple probe design across participants was used. Four participants, aged 2 years 10 months to 6 years 9 months with severe mobility impairment (Gross Motor Function Classification Scale (GMFCS) level V) underwent a minimum of 5 baseline sessions, followed by 8 intervention sessions. Engagement was measured during each session using the Individual Child Engagement Record –Revised (ICER-R). The data was analysed using visual graphic and statistical analysis. All participants demonstrated an improvement in engagement in play with the introduction of non-powered, self-initiated mobility. A reciprocal deterioration in non-engagement was also recorded. A decrease in engagement in play at the start of intervention was attributed to the focus of engagement being on mobility skills as the device was introduced but this reverted as the participants spent more time on the mobility device. Functional abilities were identified as having a greater role in engagement than age. The introduction of non-powered, self-initiated mobility correlated with the improvement of engagement of young children with severe motor impairment. Non-powered, self-initiated mobility is a viable, cost effective mechanism for mobility at a young age. / Thesis (PhD)--University of Pretoria, 2015. / Centre for Augmentative and Alternative Communication (CAAC) / PhD / Unrestricted

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18076号 / 理博第3954号 / 新制||理||1570(附属図書館) / 30934 / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)准教授 野村 正, 教授 中家 剛, 教授 鶴 剛 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(経済学) / 甲第18763号 / 経博第514号 / 新制||経||273(附属図書館) / 31714 / 京都大学大学院経済学研究科経済学専攻 / (主査)教授 西山 慶彦, 准教授 奥井 亮, 講師 末石 直也 / 学位規則第4条第1項該当 / Doctor of Economics / Kyoto University / DGAM

The frightful statistics regarding road accidents draws a dreadful picture for individuals, communities, and nations across the globe. The number of fatalities exceeds a million every year. To address this issue, an initiative called Vision Zero was introduced first in Sweden 1997. The goal is to reach zero road fatalities and severe injuries by 2045. However, to achieve this goal, Vision Zero is being divided in 4 categories, called Days. Day 4 represents fully automated, cooperative, and connected mobility (CCAM). Now, one of the typical cases that causes road accidents is overtaking. CCAM is a way to enhance safety in such cases. Therefore, this thesis proposes a system that is based on Vehicle-to-Vehicle (V2V) communication where vehicles exchange their intentions and cooperatively perform overtaking manoeuvres. The prevalent approach nowadays is depending on the vehicles’ onboard sensors only, blocking it from having knowledge about the intentions of other actors. Thus, it prevents vehicles from cooperation and coordination. We evaluate the performance of our approach and compare it against the sensors only approach. We show that the proposed approach outperforms the prevalent one in performance. Therefore, vehicle communication must be considered in the upcoming mobility for higher accuracy and safety. / Den skrämmande statistiken angående trafikolyckor tecknar en fruktansvärd bild för individer, samhällen och nationer över världen. Antalet dödsfall överstiger en miljon varje år. Ett initiativ som kallas Vision Zero introducerades i Sverige 1997, vars syfte är att ta itu med detta problem. Målet är att nå noll trafik dödsfall, och allvarliga skador år 2045. För att verkställa det målet, Vision Zero delades in i 4 kategorier, som kallas för Dagar. Dag 4 representerar fullt automatiserad, kooperativ och kommunikativ mobilitet (CCAM). Ett av det vanligaste fallen som orsaker trafikolyckor är omkörningar. CCAM är ett sätt att förbättra säkerheten i sådana fall. Därför presenterar denna avhandling ett system som bygger på fordon-till-fordon (Vehicle-to-Vehicle V2V) kommunikation. Detta system tillåter fordon att utbyta avsikter för att samarbeta och utföra säkra omkörningar. Den ledande teknologin nuförtiden beror enbart av fordonens sensorer, vilket hindrar dem från att ha kunskap om andra aktörers avsikter. Därmed hindrar det dem från att samarbeta. Vi utvärderar prestandan av vårt system och jämför det med den ledande teknologin. Vi visar att vårt system är överlägsen det ledande sättet (dvs. enbart sensorer) i prestanda. Därför måste fordon kommunikation tas hänsyn till i kommande mobilitet för högre noggrannhet och säkerhet.

A fundamental assumption of our universe has been that equal amounts of matter and antimatter were created during the Big Bang. Since the world we live in is made entirely of matter, one either needs to question this assumption, or explain how matter was enriched with respect to antimatter. This is a puzzle that scientists all over the world are trying to solve. Particle accelerator experiments like Belle II in Tsukuba, Japan, enable precision studies of the heavier siblings of protons, for example charmed baryons. Since these baryons are unstable, they offer a unique tool to understand the matter-antimatter-asymmetry of the universe: by comparing the decay-patterns of the baryons and antibaryons, we look for tiny differences in the interactions that, if they exist, can have led to the matter-antimatter imbalance. The project aims to examine the capacity of the Belle II generator, which is a crucial part of analysis in experimental particle physics. The aim of this project is also to develop a toolkit for estimating decay-parameters from baryon decay distributions: one single-step process and one multi-step process, and compare statistical properties of the estimators in order to see which one yields a more precise estimation.

No description available.

This study compared seven syntactic measures which can be automatically generated by the Computerized Profiling (CP) software: Mean Length of Utterance in morphemes or words (MLUm or MLUw), Mean Syntactic Length (MSL), the Index of Productive Syntax (IPSyn), the Picture Elicited Scoring Procedure (PESP) for the Language Analysis Remediation and Screening Profile (LARSP), the Syntactic Complexity Score (MSC) scoring of LARSP, and Developmental Sentence Scoring (DSS). Language samples came from 192 children, 106 typically developing children, ages 5;6 to 11;2 and 86 children with language impairment, ages 5;6 to 11;1. Patterns of correlation were consistent for children with or without language impairment. All measures were computed with CP software, and all coding decisions that were made by the software were accepted. The three measures of length (MLUm, MLUw, and MSL) were highly intercorrelated. MSC correlated with the measures of length and with DSS. DSS correlated with the length measures, though not as highly as MSC. DSS also correlated with IPSyn. IPSyn correlated moderately with PESP, correlated less with MSC, and correlated the least with the measures of length. PESP correlated moderately with each measure. PESP, DSS, and IPSyn correlated more highly for the children with language impairment. These measures correlated highly sometimes and sometimes they did not correlate much. This suggests that they are measuring different aspects of syntactic ability.

This thesis studies CP violation in the decay of the Ξ− hyperon, also known as the cascade baryon, which decays in the sequence Ξ− → Λπ− → pπ−π−. A difference between the angular distribution of this decay sequence and the angular distribution of the charge conjugate decay sequence ͞Ξ+ →͞Λπ+ → ͞pπ+π+, after taking into account the inversion of the momenta due to the parity operation, is indicative of CP violation. The decay sequence is described by three asymmetry parameters: αΞ, αΛ and φΞ, while the charge conjugate decay's sequence is described by: ͞αΞ, ͞αΛ and ͞φΞ. A measure of CP violation is given by the CP violating observables: AΞ, AΛ and ΦΞ. The aim of this thesis is to study how the normalised statistical uncertainties in the asymmetry parameters and in the CP violating observables depend on the magnitude of the polarisation vector (polarisation) of the cascade and the anticascade. This was done by simulating 1.0×107 Ξ− → Λπ− → pπ−π− and  ͞Ξ+ →͞Λπ+ → ͞pπ+π+ decays for different values of polarisation of the cascades using Monte Carlo, and then utilising maximum likelihood estimation and error propagation to estimate the uncertainties in the parameters and in the observables. It was shown using the methods of this thesis that the normalised statistical uncertainties in the asymmetry parameters and the CP violating observables decreased whenever the polarisation was increased, although with diminishing returns. In the region of 10% − 50% polarisation, the decrease in the uncertainties was substantial. An increase from 10% to 50% polarisation lowered all of the uncertainties by 76% − 80%. In the region of 50% − 100% polarisation, the decrease in the uncertainties was slightly less. An increase from 50% to 100% polarisation lowered the uncertainties in αΞ,  ͞αΞ and AΞ by roughly 33%, in αΛ,  ͞αΛ and AΛ by roughly 40%, and in φΞ,  ͞φΞ and ΦΞ it went down by 53%. It was also shown that, if one were to produce 60% polarised cascades and use the method of this thesis, it would require a sample of 1.1×1011 − 1.3×1011 Ξ− → Λπ− → pπ−π− and  ͞Ξ+ →͞Λπ+ → ͞pπ+π+ decays to reach the precision in the observables of the order given by the Standard Model. However, if one wished to match the uncertainty given by the most recent and best measurement of the observables, using 60% polarised cascades, one would only need a sample of 5.7×104 − 8.6×104 for each decay sequence.

No description available.