京都大学 / 新制・課程博士 / 博士(医学) / 甲第24189号 / 医博第4883号 / 新制||医||1060(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小林 恭, 教授 羽賀 博典, 教授 伊藤 貴浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The main idea of this thesis is to formulate the smooth variable structure filter (SVSF) for target tracking applications in the presence of measurement origin uncertainty. Tracking, by definition is the recursive estimation of the states of an unknown target from indirect, inaccurate and uncertain measurements. The measurement origin uncertainty introduces the data association problem to the tracking system. The SVSF estimation strategy was first presented in 2007. This filter is based on sliding mode concepts formulated in a predictor-corrector form. Essentially, the SVSF uses an existence subspace and smoothing boundary layer to bind the estimated state trajectory to within a subspace around the true trajectory. The SVSF is demonstrated to be robust to modeling uncertainties and provide extra measures of performance such as magnitude of the chattering signal. Therefore, with respect to specific nature of car tracking problems that involves modeling uncertainty, it was hypothesized that a robust estimation strategy such as the SVSF, would improve the performance of the tracking system and give more robust tracking results. Also, having the extra information provided by the SVSF strategy, i.e. the chattering magnitude signal, would lead to algorithms that could better account for measurement origin uncertainty in the context of the data association process. Further to these hypotheses, this research has focused on investigating the performance of the SVSF in the target tracking problems, advancing the development of the SVSF, and employing its characteristics to deal with data association problems. The performance of the SVSF, in its current form, can be improved when there is fewer measurements than states by using its error covariance in target tracking. As the first contribution in this research, the SVSF is formulated in the context of target tracking in clutter and combined with data association algorithms, resulting in the SVSF-based probabilistic data association (PDA) and joint probabilistic data association (JPDA) for non-maneuvering and maneuvering targets. The results are promising in the tracking scenarios with modeling uncertainties. Therefore, the thesis is then expanded by generalizing the covariance of the SVSF for the cases where the number of measurements is less than the number of states. The generalized covariance formulation is then used to derive a generalized variable boundary layer (GVBL) SVSF. This new derivation gives an estimation method that is optimal in the MMSE sense and in the meantime preserves the robustness of the SVSF. The proposed algorithm improves the performance measures and makes a more reliable tracking algorithm. This thesis explores the hypothesis that multiple target tracking performance can be substantially improved by including chattering information from SVSF-based filtering in the data association method. A Bayesian framework is used to formulate a new set of augmented association probabilities which include the chattering information. The simulation and experimental results demonstrate that the proposed augmented probabilistic data association improves the performance of the tracking system including maneuvering cars, in particular for highly cluttered environments. The derived methods are applied on simulations and also on real data from an experimental setup. This thesis is made up of a compilation of papers that include three conference papers and three journal papers. / Thesis / Doctor of Philosophy (PhD)

<p> The Killarney Igneous Complex, composed of an intrusive granite and a hypabyssal or extrusive porphyry was implaced near and at the surface in the general locality of Killarney, Ontario. The crystallization age of the intrusive portion of the complex is approximately 1740 million years. These rocks have experienced deformation by forces which in some instances produced complicated shearing motions. Mesoscopic samples show a foliation and a lineation supporting a history of deformation. The foliation is clearly the more visible fabric and is interpreted as a plane of flattening.</p> <p> Kinematic indicators, specifically asymmetric pressure shadow wings, are present within the rocks; however the patterns are too complicated to interpret by a simple sense of shear. The geometry of these kinematic indicators does suggest an active plane of foliation.</p> / Thesis / Bachelor of Science (BSc)

<p> Study of the ecology of concretion and host sediment fossils from a shell bed in middle Bajocian clays of northwestern Germany indicates a predominantly epifaunal suspension-feeding community living on a firm mud bottom. The shell bed, firm bottom and low turbidity required by suspension feeders suggests a hiatus or reduced sedimentation at the time. Depth estimates of 50 to 150 m are indicated by ammonite and belemnite siphuncle and septal strength indices.</p> <p> Preservation of calcitic fossils is excellent in both concretions and host sediments. Aragonitic fossils show good preservation in the concretions. Aragonite has been replaced by at least two generations of calcite. Preservation in the host sediments is poor. Pyrite is common in void spaces of concretion fossils but less so in those from the host sediments.</p> <p> Eight concretions were studied, containing numerous Stephanoceras mutabile (macroconch) and Stephanoceras quenstedti (microconch). These are of opposite sexes but are not a dimorphic pair.</p> <p> Distribution of shell debris and other fossils within the concretions suggests that the ammonites were swept by currents into shallow depressions in the sea floor lined with shell debris. Such depressions have been observed in modern sediments as the result of the feeding activity of rays. The presence of currents is indicated by the southwest orientation of belemnite rostra in the host sediments. Carbonate content of concretion matrix is high indicating concretion growth in very fluid muds. This contrast with the firm bottom indicated by fossil ecology suggests rapid burial of the benthic community by either a mudflow or a sudden, large increase in sedimentation. Concretion growth was initiated by decomposition of organic matter within the mud.</p> / Thesis / Master of Science (MSc)

Tumors are composed of proliferating cells that invade healthy tissue and grow over time. Even though it is still unclear, it is a common opinion that the cells of origin should possess a proliferative capacity (Blanpain, 2013; Visvader, 2011). Particularly for brain cancers, the transition of neural progenitors to differentiated postmitotic neurons is considered irreversible in physiological and pathological conditions. Therefore, postmitotic neurons have not been considered as suitable cell of origin for brain cancer. Here, we show that neurons reprograming may occur upon Shh activation leading to medulloblastoma (MB) formation in vivo. Human SHH medulloblastoma (MB) is a brain tumor affecting adults and infants that is thought to originate from cerebellar granule neuron progenitors. Notably, several groups have shown that Shh pathway activation (SmoM2 overexpression) in mouse granule neuron progenitors is able to induce Shh MB (Schuller et al., 2008; Z.-J. Yang et al., 2008). These progenitors are present in infants and newborn mice, but they seem to be absent in adult humans and mice (Biran, Verney, &amp; Ferriero, 2012; Marzban et al., 2014; Z.-J. Yang et al., 2008). Furthermore, it was recently discovered that the two different forms of SHH MB are distinguished by different transcriptome/methylome levels suggesting that the adult SHH MB may originate from a different cell of origin (Cavalli et al., 2017; Kool et al., 2014). Relying on these data, we take advantage of a conditional Cre-Lox recombination system to recapitulate the human adult medulloblastoma pathogenesis in mice, demonstrating that cerebellar post-migratory mature granule neurons upon SmoM2 overexpression can dedifferentiate and give rise to SHH MB in vivo. Moreover, human adult patients present inactivating mutations of the chromatin reader BRPF1 that are associated with SMO mutations and absent in pediatric and adolescent patients. Here we found that truncated BRPF1 protein, as found in human adult patients, is able to induce medulloblastoma in adult mice upon SmoM2 activation. Notably, gene expression profiling on our samples allowed to associate “cerebellar granule progenitors-derived MB” with the human infant form while “truncated BRPF1-induced tumors” clustered with human adult SHH MB. Furthermore, as previously described by Kool et al., 2014, human adult SHH MB is characterised by the copresence of p-AKT and p-S6, compared to the human infant SHH MB that are positive for either p- AKT or p-S6 and always in a mutually exclusive way. Truncated BRPF1-induced tumors are double positive for p-AKT and p-S6, similarly to adult patients, while cerebellar granule progenitors derived MB present only p-S6. Furthermore, to define the contribution of chromatin changes in granule neurons dedifferentiation in response to Shh activation, we profiled changes in chromatin accessibility by ATAC-seq analysis on mice cerebella. SmoM2 overexpression changed the epigenetic landscape of granule neurons, enriching the number of open chromatin regions 12 associated with stem/progenitor-like genes. Moreover, the cooperation between truncated BRPF1 and SmoM2 in reshaping the chromatin arrangement of granule neurons was explored applying ATAC-seq on differentiated human cerebellar neurons derived from neuroepithelial cells. ATAC-seq analysis pointed out a synergistic mechanism between SmoM2 and truncated BRPF1 in modifying the epigenetic landscape of postmitotic neurons, increasing the chromatin accessibility of super-enhancers, associated with stemness and chromatin organization/modification genes. Our novel model of cancer development could explain the human SHH medulloblastoma onset in adult individuals where granule neuron progenitors are no more present. For these reasons, we strongly believe that our model configures as an important starting point for a new field in cancer and stem cell biology focusing on the study of mechanisms driving tumorigenesis in postmitotic cells.

Purpose: The purpose of this paper is to study how the country of origin affects Swedish consumers when buying food products. Both from a product and brand perspective for the use of business leaders and marketers. Method: Qualitative study using focus groups Results: This study shows that country of origin of food products has a significant effect on Swedish consumers' purchasing decisions. The results show that countries' perceptions and stereotypes transcend into the product and brand. It also shows that Swedish consumers favorably buy domestic products over foreign in many cases.

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No description available.

<p> Popular theories about the origin of life can be classified to two classes: metabolism first or genes first. As a metabolism first theory, the lipid world theory, in which non-covalent assemblies of lipids, such as micelles and vesicles store information in the form of a non-random molecular composition, has been proposed to investigate the possibility of inheritance without genes. Our models assume that interaction occurs between nearest neighbour molecules only, and account for spatial segregation of molecules of different types within the assembly. We also draw a distinction between a self-assembly model, in which the composition is determined by mutually favourable interaction energies between the molecules, and a catalytic model, in which the composition is determined by mutually favourable catalysis. We show that compositional inheritance occurs in both models, although the self-assembly case seems more relevant if the molecules are simple lipids. In the case where the assemblies are composed of just two types of molecules, there is a strong analogy with the classic two-allele Moran model from population genetics. This highlights the parallel between compositional inheritance and genetic inheritance. We also investigated the polymerization reactions which may bridge the gap between simple organic molecules and the beginning of the RNA world, which belongs to the class of genes first theories. We found that different from normal chemical systems, catalysts for the polymerization system can shift the equilibrium toward longer polymers. Together with RNA's potential as catalyst, the RNA polymerization system may form a feedback loop which makes the formation of functional RNA molecules easier, and come more close to the beginning of RNA world.</p> / Thesis / Master of Science (MSc)

In hypothesized RNA-World scenarios, replication of RNA strands is catalyzed by error-prone polymerase ribozymes. Incorrect replication leads to the creation of non-functional, parasitic strands which can invade systems of replicators and lead to their death. Studies have shown two solutions to this problem: spatial clustering of polymerases in models featuring elements to limit diffusion, and group selection in models featuring protocells. Making a quantitative comparison of the methods using results from the literature has proven difficult due to differences in model design. Here we develop computational models of replication of a system of polymerases, polymerase complements and parasites in both spatial models and protocell models with near identical dynamics to make meaningful comparison viable. We compare the models in terms of the maximum mutation rate survivable by the system (the error threshold) as well as the minimum replication rate constant required. We find that protocell models are capable of sustaining much higher maximum mutation rates, and survive under much lower minimum replication rates than equivalent surface models. We then consider cases where parasites are favoured in replication, and show that the advantage of protocell models is increased. Given that a system of RNA strands undergoing catalytic replication by a polymerase is fairly survivable in protocell models, we attempt to determine whether isolated strands can develop into genomes. We extend our protocell model to include additional functional strands varying in length (and thus replication rate) and allow for the linkage of strands to form proto-chromosomes. We determine that linkage is possible over a broad range of lengths, and is stable when considering the joining of short functional strands to the polymerase (and the same for the complementary sequences). Moreover, linkage of short functional strands to the polymerase assures more cells remain viable post division by ensuing a good quantity of polymerase equivalents are present in the parent cell prior to splitting. / Thesis / Master of Science (MSc) / Collections of RNA polymers are good candidates for the origin of life. RNA is able to store genetic information and act as polymerase ribozymes allowing RNA to replicate RNA. Polymerases have been experimentally developed in labs, however none are sufficiently general to work well in an origins of life setting. These polymerases are vulnerable to mistakes during copying, making survival of RNA systems difficult. Such systems have been studied by computer simulations, showing that the strands need to be kept together for survival, either on surfaces or in primitive cells. Differences in the details of the models has made comparing the surfaces to cells difficult. This work creates a unified model base allowing for comparison of these two environments. We find that the existence of primitive cells is very beneficial to systems of RNA polymers and thus it is likely such cells existed at the origin of life.