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1
Pinault, Lucile. "Targeting Lsr2/DNA Complexation for Dysregulation of Gene Expression in Mycobacterium tuberculosis." University of Toledo / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1365087235.
2
Gerges, Elias. "Caractérisation du rôle de la protéine Lsr2 dans la virulence des morphotypes lisse (S) et rugueux (R) de Mycobacterium abscessus." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASL131.
Abstract:
Mycobacterium abscessus (Mabs) est une mycobactérie non tuberculeuse à croissance rapide, qui provoque des infections pulmonaires chez les patients atteints de mucoviscidose. Au cours de l'infection, Mabs évolue entre un morphotype lisse (Mabs-S) et un morphotype rugueux (Mabs-R), ce dernier étant hyper-virulent. Notre équipe a précédemment identifié le gène lsr2 comme étant différentiellement exprimé pendant la transition de Mabs-S à Mabs-R. lsr2 code pour un facteur de transcription pléiotropique qui appartient à la superfamille des protéines associées aux nucléoïdes (NAPs), lesquelles jouent un rôle clé dans la structure du chromosome bactérien. L'objectif de cette thèse est d'élucider le rôle moléculaire de Lsr2 dans la pathobiologie de Mabs en utilisant trois approches de génomique fonctionnelle : RNA-seq, ChIP-seq et Hi-C. L'analyse transcriptomique révèle que Lsr2 régule différemment l'expression des gènes dans les deux morphotypes, dont la plupart sont impliqués dans divers processus cellulaires clés de Mabs, notamment l'adaptation à l'hôte et la résistance aux antibiotiques. Ces résultats ont été confirmés par RT-qPCR, ainsi que par des tests de concentration minimale inhibitrice (CMI) et des tests d'infection sur des macrophages en présence d'antibiotiques. L'analyse ChIP-seq montre que Lsr2 se lie largement au génome de Mabs (10%) au niveau de séquences riches en AT et semble former de longs domaines par oligomérisation qui participent à la répression de ses gènes cibles. Cependant, la similitude de fixation de Lsr2 entre Mabs-S et Mabs-R et la présence d'un grand nombre de gènes liés mais non régulés suggèrent que des mécanismes plus complexes, tels que le pontage d'ADN, pourraient être impliqués pour assurer la sélectivité des gènes cibles. Dans le cadre de cette thèse, nous avons développé un protocole Hi-C pour étudier la structure tridimensionnelle du chromosome de Mabs. Ce travail a également impliqué la mise en place de la technique 3C-qPCR pour analyser les interactions physiques dépendantes de la protéine Lsr2 entre les fragments d'ADN. Ces avancées méthodologiques ouvrent de nouvelles perspectives pour la compréhension de la régulation génomique chez MabsMycobacterium abscessus (Mabs) is a non-tuberculous mycobacterium, causing lung infections in cystic fibrosis patients. During infection, Mabs switches from smooth (Mabs-S) to rough (Mabs-R) morphotypes, the latter being hyper-virulent. Our team previously identified the gene lsr2 as being differentially expressed during the transition from Mabs-S to Mabs-R. lsr2 codes for a pleiotropic transcription factor that belongs to the superfamily of nucleoid-associated proteins (NAPs), which play a key role in the structure of bacterial chromosome. The objective of this thesis is to elucidate the molecular role of Lsr2 in the pathobiology of Mabs using three functional genomics approaches: RNA-seq, ChIP-seq, and Hi-C. Transcriptomic analysis reveals that Lsr2 differentially regulates gene expression in both morphotypes, with most genes being involved in various key cellular processes of Mabs, including adaptation to the host and antibiotic resistance. These results were confirmed through RT-qPCR, as well as by minimum inhibitory concentration (MIC) tests and infection tests on macrophages in the presence of antibiotics. ChIP-seq analysis revealed that Lsr2 extensively binds the Mabs genome at AT-rich sequences and appears to form long domains through oligomerization that participate in the repression of its target genes. However, the similarity in Lsr2 binding between Mabs-S and Mabs-R, and the presence of a large number of bound genes but unregulated suggest that more complex mechanisms, such as DNA bridging, may be involved in ensuring gene target selectivity. As part of this thesis, we developed a Hi-C protocol to study the three-dimensional structure of the Mabs chromosome. This work also involved the implementation of the 3C-qPCR technique to analyze Lsr2-dependent physical interactions between DNA fragments. These methodological advances open up new perspectives for understanding genomic regulation in Mabs
3
Wiechert, Johanna [Verfasser], Julia [Akademischer Betreuer] Frunzke, and Matias [Gutachter] Zurbriggen. "Silencing and counter-silencing of the Lsr2-like protein CgpS in Corynebacterium glutamicum / Johanna Wiechert ; Gutachter: Matias Zurbriggen ; Betreuer: Julia Frunzke." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2021. http://d-nb.info/1229191712/34.
4
STOTANI, SILVIA. "Design and synthesis of LsrK kinase inhibitors as Quorum Sensing modulators." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1251369.
5
STOTANI, SILVIA. "Design and synthesis of LsrK kinase inhibitors as Quorum Sensing modulators." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1251389.
6
STOTANI, SILVIA. "Design and synthesis of LsrK kinase inhibitors as Quorum Sensing modulators." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1251409.
7
STOTANI, SILVIA. "Design and synthesis of LsrK kinase inhibitors as Quorum Sensing modulators." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1277366.
8
STOTANI, SILVIA. "Design and synthesis of LsrK kinase inhibitors as Quorum Sensing modulators." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1277807.
9
STOTANI, SILVIA. "Design and synthesis of LsrK kinase inhibitors as Quorum Sensing modulators." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1281046.
10
STOTANI, SILVIA. "Design and synthesis of LsrK kinase inhibitors as Quorum Sensing modulators." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1280626.
11
STOTANI, SILVIA. "Design and synthesis of LsrK kinase inhibitors as Quorum Sensing modulators." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1281546.
12
Wang, Yinuo J. "Functions of the conserved ribosome-bound protein Lso2 in translation and physiology." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/119979.
Abstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2017.Cataloged from PDF version of thesis.
Includes bibliographical references.
The ribosome is a highly conserved macromolecular machine that carries out translation, the synthesis of proteins from mRNAs, in all domains of life. The core ribosome interacts with dozens of general translation factors that ensure accurate and efficient progression through the translation cycle. Their detailed characterization has significantly advanced our understanding of protein synthesis. However, a growing number of ribosome-associated proteins have also been discovered whose functions are less well understood. In Chapter 1, I will overview the translation cycle and describe how it is affected by nutrient availability, with a focus on functions of starvation-induced proteins that directly bind the ribosome. I will also discuss discovery approaches for expanding the study of ribosome-associated proteins. In Chapter 2, I will present the discovery and characterization of Lso2 as a conserved ribosome-bound protein required for translational recovery in budding yeast. Using quantitative mass spectrometry, we found this protein to be ribosome-associated during glucose-starved and replete growth, with moderate enrichment on translating ribosomes during starvation. Saccharomyces cerevisiae lacking Lso2 accumulate monoribosomes that are not translating normally following a shift from stationary phase to rich medium. To understand the basis of this phenotype, we used genome-wide RNA crosslinking and sequencing to determine that Lso2 binds near the A site of the ribosome tRNA channel, in a region that overlaps with the GTPase activating center, and that Lso2 also interacts with a broad spectrum of tRNAs. Consistently, Lso2 binding in the tRNA channel stabilizes ribosomal subunit association in vitro. These data, together with evidence that the accumulated ribosomes in Iso2 nulls are devoid of obvious barriers to initiation, lead to a model in which Lso2 promotes productive elongation. Finally, I show that the ribosome binding activity of Lso2 is conserved in its human ortholog, suggesting a broad importance of its molecular function. In Chapter 3, I will elaborate on the model of a function for Lso2 in elongation, propose alternative models to rationalize its effects on translation, and describe experiments for testing them. I will also describe the implications of this protein for our understanding of translation in different physiological states.
by Yinuo J. Wang.
Ph. D.
13
Lúðvíksdóttir, Hildur. "Production and characterization of LSD1 and LSD2 for fragment based drug discovery." Thesis, Uppsala universitet, Biokemi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-392958.
14
Mesli, Samir. "Rôle du Lipolysis Stimulated Receptor (LSR) : expression chez la souris adulte et au cours de l'embryogénèse : conséquences de l'invalidation du gène LSR." Bordeaux 2, 2005. http://www.theses.fr/2005BOR21308.
Abstract:
Le Lipolysis Stimulated Receptor (LSR) fixe les lipoprotéines contenant l'apolipoprotéine (apo) B et l'apoE en présence des acides gras, et son affinité est optimale pour les fractions lipoprotéiniques les plus riches en triglycérides. Dans notre étude, nous avons utilisé les techniques du Northern blot, de la PCR quantitative en temps réel et de l'immunofluorescence pour examiner l'expression du LSR chez la souris adulte et au cours du développement embryonnaire. Chez l'adulte l'ARNm LSR est retrouvé dans tous les tissus étudiés sauf dans le muscle et le coeur. Les ARNm sont abondants dans le foie, le poumon, l'intestin, le rein et dans certains tissus stéroidogéniques (ovaires et testicules). Ils sont également présents à tous les stades embryonnaires étudiés. Les résultats de l'expression protéique sont corrélés à ceux de l'expression transcriptionnelle. Ainsi, le "patron" d'expression du LSR chez la souris adulte apporte des arguments supplémentaires sur son rôle possible de ce récepteur dans le transport lipidique au niveau de ces organes. Afin d'étudier le rôle physiologique du LSR in vivo, nous avons tenté d'obtenir des souris LSR-/- par recombinaison homologue. Sur un total de 379 souris génotypées, trois homozygotes seulement ont été identifiées. Cette répartition montre une grande létalité des homozygotes. Celle-ci se produit entre 12,5 et 15,5 jours de gestation. Les embryons LSR-/- se distinguent par un foie de taille réduite. Ces résultats indiquent que le LSR est indispensable pour le développement embryonnaire. Par ailleurs, étant donné que les souris hétérozygotes ne présentent aucun phénotype particulier, nous avons voulu analyser l'impact de l'invalidation de l'un des deux allèles du LSR chez des souris totalement déficientes en un autre récepteur de lipoprotéines à apoB/E, le LDLR. Comparés aux souris LDL-/-, les doubles mutants [LSR+/- ; LDR-/-] appelés LDLSR ont des taux plasmatiques de cholestérol total significativement plus faibles par diminution du cholestérol contenu dans les lipoprotéines non LDL et HDL. Ce résultat pourrait être expliqué par l'intervention de mécanismes compensateurs comme l'augmentation de l'activité d'autres récepteurs de lipoprotéines. Grâce au modèle LDLSR, nous avons pu mettre en évidence pour la première fois un rôle in vivo du LSR dans la régulation du métabolisme du cholestérol et des lipoprotéinesThe lipolysis stimulated receptor (LSR) recognizes apolipoprotein B/E-containing lipoproteins in the presence of free fatty acids, and is thought to be involved in the clearance of triglyceride-rich lipoproteins (TRL). The distribution of LSR in mice was studied by Northern blots, quantitative PCR and immunofluorescence. In the adult, LSR mRNA was detectable in all tissues except muscle and heart, and was abundant in liver, lung, intestine, kidney, ovaries and testes. During embryogenesis, LSR mRNA was detectable at 7. 5 days post-coitum (E7) and increased up to E17 in parallel to prothrombin, a liver marker. In adult liver, immunofluorescence experiments showed a staining at the periphery of hepatocytes as well as in fetal liver at E12 and E15. These results are in agreement with the assumption that LSR is a plasma membrane receptor involved in the clearance of lipoproteins by liver, and suggest a possible role in steroidogenic organs, lung, intestine and kidney. To explore the role of LSR in vivo, the LSR gene was inactivated in 129/Ola ES cells by removing a gene segment containing exons 2-5, and 129/Ola-C57BL/6 mice bearing the deletion were produced. Although heterozygotes appeared normal, LSR homozygotes were not viable, with the exception of three males, while the total progeny of genotyped wild-type and heterozygote pups was 376. Mortzality of the homozygote embryos was observed between days 12. 5 and 15. 5 of gestation, a time at which their liver was much smaller than that of their littermates, indicating that the expression of LSR is critical for liver and embryonic devellopment. To evaluate the effect of inactivation of one allele LSR in LDL receptor-deficient mice, we produce double knockout animals [LSR+/-] called LDLSR Total plasma cholesterol concentration were approximately 40 % less as compared with LDLR-/- mice These finding supported the hypothesis of upregulation of other receptors in LDLSR mice
15
Côté, Jean-Philippe. "L'héritage religieux du discours de la League for Social Reconstruction, LSR." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ60708.pdf.
16
Fujimoto, Shinji. "Beam commissioning and suppression of transverse coherent instability at S-LSR." 京都大学 (Kyoto University), 2007. http://hdl.handle.net/2433/136765.
17
Lee, Byeong-Seok. "Linear Switched Reluctance Machine Drives with Electromagnetic Levitation and Guidance Systems." Diss., Virginia Tech, 2000. http://hdl.handle.net/10919/29751.
Abstract:
Many electrically propelled, and magnetically levitated and guided actuation systems (maglev) use either linear induction or synchronous machine topologies. From the cost, reliability, fault tolerance, and phase independence points of view, linear switched reluctance topologies are attractive for transportation application. This thesis investigates a novel topology in which a linear switched reluctance machine (LSRM) propulsion drive is incorporated in the magnetically levitated and guided vehicle. Designs of the LSRM and dc electromagnet, analytical aspects of modeling and dynamics of the vehicle, and closed loop control of propulsion, levitation, and guidance systems are discussed with comprehensive simulations and experimental results.
Due to the lack of standard design procedure for LSRM, a novel design procedure is proposed using the current knowledge and design procedure of rotating switched reluctance machines. Analysis procedures for the phase winding inductance, propulsion and normal forces with translator position are developed with a lumped-parameter magnetic circuit model and the results from it are verified with two-dimensional finite element analysis. Extensive experimental correlation of inductance, propulsion and normal forces to validate the analysis and design procedure is presented.
For the stable operation of the electromagnetic levitation and guidance systems, which have inherent unstable characteristics, the air gap position and force/current control loops are designed using PID (or PD) and PI controllers, respectively, and implemented and tested. The step-by-step design procedures for each controller are systematically derived. A feedforward compensation strategy for the levitation air gap control is proposed to reject the external force disturbance mainly caused by the normal force component generated in the LSRM propulsion drive system. The reduction of mechanical vibration and hence the enhancement of ride quality is achieved. Extensive dynamic simulations and experimental results for the integrated maglev system are presented with a 6 m long prototype system. Experimental correlation proves the validity of the controller design procedure based on the single-input and single-output model, and shows the feasibility of the LSRM-propelled electromagnetic levitation and guidance systems.
A novel maglev topology in which only two sets of LSRMs are utilized to control individually propulsion, levitation, and guidance forces is proposed. One set of the linear switched reluctance actuator produces the levitation and propulsion forces and the other set generates the propulsion and guidance forces. The proposed architecture, thereby, obviates the need for design, development, and implementation of separate actuation systems for individual control of propulsion, levitation, and guidance forces and in contrast to most of the present practice. Further, the proposed system utilizes each of the linear switched reluctance actuation system for producing the propulsion force, thereby giving an overall high force density package for the entire system. The feasibility of the proposed system by finite element analysis is demonstrated.Ph. D.
18
Denis-Lagache, Nicolas. "Commutation ou extinction de l'expression du BCR et impact sur la cellule B." Thesis, Limoges, 2015. http://www.theses.fr/2015LIMO0071/document.
Abstract:
Lors de la reconnaissance de leur antigène spécifique, les lymphocytes B vont s’activer et interagir avec les autres cellules des organes lymphoïdes secondaires (cellules folliculaires dendritiques, lymphocytes T, …) pour former un centre germinatif où le locus IgH va être remanié afin d’accroitre l’affinité des immunoglobulines pour l’antigène (grâce à l’hypermutation somatique des régions variables (SHM) et de décliner l’activité effectrice des anticorps selon plusieurs types de fonction grâce à la commutation de classe des régions constantes ou « switch u CSR», afin d’éliminer selon diverses stratégies l’antigène . Ces deux mécanismes sont initiés par l’Activation Induced Deaminase (AID) qui cible l’ADN au niveau des cytosines pour les changer en uracile, aboutissant à des cassures simple brin ou double brin lorsque que les mésappariements sont proches les uns des autres.Il a été montré qu’AID est capable de cibler la région régulatrice en 3’ du locus IgH au niveau de régions LS, action qui aboutit à la délétion complète des gènes C du locus, à la perte de l’expression du BCR et à la mort cellulaire lors de la recombinaison suicide du locus (LSR). Dans notre étude, nous avons réalisé un modèle knock-in du gène Cμ humain en aval de la dernière région LS dans le but de sauver les cellules B réalisant la LSR sur les dernières régions LS par l’expression d’un BCR humanisé (modèle LSR-μKI). Notre modèle indique que l’insertion du gène Cμ humain en aval de l’élément hs4 de la 3’RRpermet en effet de remplacer certaines recombinaisons LSR par un switch vers l’expression d’IgM humanisée », et module en outre qualitativement certains aspects de la réponse immunitaire humorale. Notre modèle « rapporteur » de la LSR suggère aussi que l’évènement de LSR est un phénomène régulé qui augmente avec l’activation B. L’étude ex vivo de cellules B issues du modèle suggère que la LSR est possible lors d’une réponse T indépendante comme T dépendante. Elle se montre aussi inductible par les ligands TLR4 mais non TLR9. L’étude du répertoire des IgM humaines indique une utilisation biaisée des familles de VH, avec notamment sur utilisation de la famille VH5murine, suggérant donc que l’incidence de la LSR varie avec la structure des régions variables du BCR et pourrait donc être dépendante de l’affinité contre des antigènes/ligands qui restent à caractériserAfter antigen recognition, B cells are activated and interact with other cells within secondarylymphoid organs (dendritic cells, T lymphocytes …) to form a germinal center. In the GC, the IgH locusis reorganized in order to increase the affinity of immunoglobulins for antigen through somatichypermutation (SHM) of V(D)J regions and to configure them into several forms harboring diversifiedmodes of action after “class switc recombination” (CSR). Both mechanisms are initiated by ActivationInduced Deaminase (AID) which targets DNA cytosines to convert them into uracil, then causing singleor double strand breaks in DNA when the mismatchs are located close to each other. It has been shownthat AID can target the IgH locus 3’ regulatory region on specific regions called LS, then leading to thetotal deletion of IgH locus C genes, loss of BCR expression and cell death by locus suicide recombination(LSR). In our study, we created a human Cμ knock-in model distal to the hs4 element of the 3’RR, in anattempt to rescue cells after the LSR event. Our model showed that this insertion indeed succeededinto replacing LSR by “class switching to humanized IgM” and also qualitatively modulated someaspects of the humoral response. This new LSR reporter model additionally supports the hypothesisthat LSR is regulated and increases with B cell activation. Studies of ex vivo B cells from the modelsuggest that LSR can occur in T dependent and independent manners, but is induced by triggering TLR4but not TLR9. Studies of the human IgM repertoire showed a biased use of VH families, and notably themouse VH5 family was used more frequently than in the control group. The BCR repertoire bias stronglysuggests that LSR is at least in part a matter of affinity of the BCR variable regions for antigens andligands that remain to be characterized
19
Shirai, Toshiyuki. "One-dimensional beam ordering of protons at ion storage ring, S-LSR." 京都大学 (Kyoto University), 2007. http://hdl.handle.net/2433/59310.
20
Lebourgeois, Sophie. "Cibler les transporteurs xc- et les récepteurs métabotropiques du glutamate dans l'addiction à l'alcool : études précliniques." Thesis, Amiens, 2017. http://www.theses.fr/2017AMIE0002/document.
Abstract:
Le trouble de l'usage d'alcool (TUA) est une pathologie chronique et hautement récidivante caractérisée par un usage compulsif d'alcool. Ces dernières années, un nombre grandissant d'études suggère un rôle clé du glutamate dans les aspects renforçant et motivationnel de l'alcool. Durant cette thèse, nous avons donc cherché à déterminer si l'utilisation de modulateurs pharmacologiques des transmissions glutamatergiques pouvait permettre de réduire les propriétés addictives de l'alcool 1) dans un modèle préclinique de binge drinking, caractérisé par une consommation excessive d'alcool sur une courte période de temps et 2) dans un modèle d'alcoolodépendance marqué par un fort état émotionnel négatif au cours du sevrage. Dans un premier temps, nous avons démontré que la N-acétylcystéine, un précurseur de la cystéine, nécessaire au fonctionnement des échangeurs cystine/glutamate (xc-), permet de réduire la consommation d'alcool et la rechute dans ces 2 modèles de TUA. De façon intéressante, nous avons pu constater que la N-acétylcystéine est plus efficace chez les animaux alcoolodépendants (possédant moins de transporteurs xc-). Pour finir, nous avons révélé que le LSP2-9166, un nouvel agoniste orthostérique des récepteurs métabotropiques au glutamate du groupe III, permet également de réduire la consommation d'alcool, la motivation et la rechute dans le modèle de binge drinking. Ces résultats s'ajoutent à un nombre croissant d'études montrant que les récepteurs métabotropiques au glutamate jouent un rôle clé dans la dépendance à l'alcool, faisant d'eux un nouvel espoir thérapeutique pour le traitement du TUAAlcohol Use disorder (AUD) is a chronic and highly relapsing disorder characterized by a loss of control over alcohol consumption. Since many years, a growing body of evidences suggests a key role of glutamate in rewarding and motivational aspects of alcohol. During my PhD, I tried to determine if pharmacological modulation of glutamatergic transmission could limit addictive’s properties of alcohol 1) in a preclinical model of binge drinking, characterized by an excessive ethanol intake on a short period of time and 2) in a model of alcohol dependence characterized by a strong negative emotional state during withdrawal. In a first series of experiments, we have shown that N-acetylcysteine (NAC), a precursor of cysteine, required for cystine/glutamate exchanger (xc-), reduces alcohol consumption and relapse in these 2 models of AUD. Interestingly, we have observed that N-acetylcysteine is more efficient in alcohol dependent rats (having less xc- exchanger). We further showed that LSP2-9166, a new orthosteric agonist of group III metabotropic glutamate receptors, is also able to limit alcohol intake, motivation to consume alcohol and relapse in model of binge drinking in rats. Our results add to the growing body of evidence showing that metabotropic glutamate receptors play a key role in alcohol dependence, making them a new therapeutic approach for the treatment of TUA
21
Hagström, Adrian, and Rustam Stanikzai. "Writer identification using semi-supervised GAN and LSR method on offline block characters." Thesis, Högskolan i Halmstad, Akademin för informationsteknologi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-43316.
Abstract:
Block characters are often used when filling out forms, for example when writing ones personal number. The question of whether or not there is recoverable, biometric (identity related) information within individual digits of hand written personal numbers is then relevant. This thesis investigates the question by using both handcrafted features and extracting features via Deep learning (DL) models, and successively limiting the amount of available training samples. Some recent works using DL have presented semi-supervised methods using Generative adveserial network (GAN) generated data together with a modified Label smoothing regularization (LSR) function. Using this training method might improve performance on a baseline fully supervised model when doing authentication. This work additionally proposes a novel modified LSR function named Bootstrap label smooting regularizer (BLSR) designed to mitigate some of the problems of previous methods, and is compared to the others. The DL feature extraction is done by training a ResNet50 model to recognize writers of a personal numbers and then extracting the feature vector from the second to last layer of the network.Results show a clear indication of recoverable identity related information within the hand written (personal number) digits in boxes. Our results indicate an authentication performance, expressed in Equal error rate (EER), of around 25% with handcrafted features. The same performance measured in EER was between 20-30% when using the features extracted from the DL model. The DL methods, while showing potential for greater performance than the handcrafted, seem to suffer from fluctuation (noisiness) of results, making conclusions on their use in practice hard to draw. Additionally when using 1-2 training samples the handcrafted features easily beat the DL methods.When using the LSR variant semi-supervised methods there is no noticeable performance boost and BLSR gets the second best results among the alternatives.
22
Masuda, Sayuri. "Angulin/LSR defines cell corners for tricellular tight junction formation in epithelial cells." Kyoto University, 2011. http://hdl.handle.net/2433/142056.
23
Reilly, Liam. "LSRP : defence styles, alexithymia, illness perceptions, and HRQOL in IBD ; Systematic lit : neurodegenerative diseases and third wave therapies." Thesis, Queen's University Belfast, 2018. https://pure.qub.ac.uk/portal/en/theses/lsrp-defence-styles-alexithymia-illness-perceptions-and-hrqol-in-ibd-systematic-lit-neurodegenerative-diseases-and-third-wave-therapies(15fb8a2d-8e69-4740-a18e-095c495b9cae).html.
Abstract:
The effectiveness of third wave therapies on neurodegenerative diseases. Objectives: Previous research has identified the effectiveness of third wave therapies in reducing the symptoms of a variety of physical and psychological presentations. This systematic review will assess the efficacy of third wave therapies for adults with neurodegenerative diseases. Methods: The selected electronic databases, Medline, PsychInfo, Embase and Cinahl, were used to search for studies that were published from the inception of each database to January 2018. Third wave therapies (e.g. Acceptance and Commitment Therapy, Dialectical Behaviour Therapy, Mindfulness-Based Cognitive Therapy) and neurodegenerative diseases (e.g. Alzheimer disease, Parkinson’s disease, Prion disease) were included as search terms. Results: The systematic literature search revealed 570 potentially relevant papers. From this number, seven studies were found to be eligible for inclusion in the narrative synthesis. These studies reported on four neurodegenerative diseases and five adapted third wave therapy interventions. There were found to be mixed results on the effectiveness of third wave therapies for improving both physical and psychological symptoms in a variety of neurodegenerative diseases. Conclusions: At this stage, it is not possible to deem whether third wave therapies are feasible in offering psychological or physical benefits to the neurodegenerative disease population. However, despite not being able to draw any firm conclusions, the use of third wave therapies has shown some potential benefits. Further randomised controlled trials to assess the effectiveness of adapted third wave therapies are required. Practitioner Points: + Three studies identified improvements in cognitive functioning in the intervention group in comparison with the control group. + Some studies also found improvements in anxiety, depression, quality of life, and mindfulness following third wave therapy interventions. - However, an increase in depression, stress and a reduction in quality of life found following third wave therapies. - As this is the first review of this population and third wave therapies, it has not been possible to focus more closely on just one specific third wave therapy or neurodegenerative disease. Further research on the effectiveness of third wave therapies in this population is required. LSRP: Defence styles, alexithymia, illness perceptions, and HRQOL in IBD. Background/aims: The role of psychological factors in the development and progression of Inflammatory Bowel Disease (IBD) is not completely understood. Several studies have suggested that defence styles, alexithymia and illness perceptions each individually influence the way a person experiences their disease, thereby impacting on health related quality of life (HRQoL). The study aimed to expand the knowledge base and assist in offering a better understanding of these variables. Methods: The study employed a survey design and used opportunity sampling to recruit participants with IBD from a Regional Crohn’s and Colitis support group and outpatient Gastroenterology clinics. Participants were given questionnaire packs containing measures and were asked to post them back to the researcher. One hundred and thirty-nine participants were included in the study, of these 73.5% were female and 26.5% were males. 53.6% of participants reported being diagnosed with Crohn’s disease, where as 41.3% were diagnosed with Ulcerative Colitis, 1.4% were diagnosed with both, and 3.6% had a diagnosis of IBD but did not have a clear diagnosis of either Crohn’s or Colitis. The majority of participants identified that they were diagnosed with IBD between the ages of 20 and 29. Most participants (60.4%) felt that stress and worry was the cause of their IBD. Results: The study found that defence styles, alexithymia and illness perceptions were all correlated with HRQoL. However, multiple regression analysis revealed that the alexithymia subtest, “difficulty identifying feelings” and the neurotic defence style were the only variables that had a significant relationship with HRQoL. It was also found that females and people that were recently diagnosed also had a worse HRQoL. Conclusion: These findings suggest that females who are recently diagnosed with IBD and have difficulty identifying feelings as well as a reliance on neurotic defence styles have a worse HRQoL. Therefore, screening of this population and the introduction of psychotherapy to assist with emotional care might be beneficial in improving HRQoL. Practitioner Points: + Gender, time since diagnosis, neurotic defence styles and difficulties identifying own emotional experiences found to potentially contribute to poorer HRQoL. + Therefore, therapy using emotional identification, especially when a person is just diagnosed, might be beneficial to people with IBD. - The study used a cross sectional design, therefore it is not possible to infer causation. Future research should use a prospective design.
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Pinçon, Anthony. "Implication du récepteur LSR (lipolysis stimulated lipoprotein receptor) dans le contrôle de l’homéostasie du cholestérol cérébral et les capacités cognitives au cours du vieillissement." Thesis, Université de Lorraine, 2014. http://www.theses.fr/2014LORR0141/document.
Abstract:
La maladie d'Alzheimer (MA) est une maladie neurodégénérative touchant plusieurs millions de personnes. La MA a une origine multifactorielle. Diverses études suggèrent qu'une perturbation du métabolisme du cholestérol contribue au développement de la MA. Cependant, la littérature présente beaucoup de confusion. Il est donc crucial de mieux caractériser le métabolisme et l'implication du cholestérol dans la MA. Ce travail s'est intéressé au récepteur Lipolysis Stimulated Lipoprotein Receptor (LSR) qui est un récepteur hépatique aux lipoprotéines participant à la clairance des lipides en phase post prandiale. Les objectifs de cette thèse ont été de caractériser la présence du récepteur LSR dans le cerveau de souris, de déterminer son rôle dans le contrôle de l'homéostasie du cholestérol cérébral et dans la physiopathologie de la MA. Ainsi, nous avons caractérisé la présence de LSR dans des structures cérébrales importantes pour les capacités cognitives et le métabolisme énergétique. Grâce à un modèle de souris hétérozygote pour le récepteur LSR, nous avons mis en évidence que la délétion d'un allèle LSR entraine une altération du métabolisme du cholestérol cérébral au cours du vieillissement, qui est corrélée avec une augmentation de la sensibilité au stress amyloïde. Ces résultats suggèrent un rôle du récepteur LSR dans le contrôle de l'homéostasie du cholestérol cérébral et renforcent l'idée qu'une altération de cette dernière peut impacter la physiopathologie de la MA. Enfin, nous avons observé que la déficience d'un allèle LSR chez des souris placées sous un régime hyperlipidique pouvait impacter le métabolisme lipidique périphérique ainsi que l'anxiété de ces sourisAlzheimer's disease (AD) is a neurodegenerative disease affecting millions of people. The origin of AD is multifactorial. Studies suggest that disturbance of cholesterol metabolism contributes to AD development. However, data in the literature is conflicting. It is therefore crucial to better characterize the metabolism and involvement of cholesterol in AD. This work focused on the Lipolysis Stimulated Lipoprotein Receptor (LSR), a hepatic lipoprotein receptor involved in the clearance of lipoproteins during the postprandial phase. The objectives of this thesis were to characterize LSR receptor expression profile in the mouse brain, and to determine its role in both brain cholesterol homeostasis and in the pathophysiology of AD. We identified and characterized LSR expression in brain structures that are involved in cognitive abilities and the regulation of energy metabolism. Next, using a mouse model heterozygous for the LSR receptor, we were able to demonstrate that the deletion of one allele LSR causes impaired brain cholesterol metabolism in aging, which was correlated with increased susceptibility to amyloid stress. These results suggest a role of LSR receptor in brain cholesterol homeostasis and show that alterations of the brain cholesterol metabolism can impact AD pathophysiology. Finally, we observed that the deficiency of an LSR allele in mice on a high fat diets affected peripheral lipid metabolism and the anxiety in these mice
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Dalloul, Iman. "Switch Canonique en Cis ou Trans et Recombinaisons Suicides du Locus IgH." Thesis, Limoges, 2018. http://www.theses.fr/2018LIMO0049.
Abstract:
L'activation des cellules B est connue pour s’accompagner de remodelages des gènes d’immunoglobulines qui permettent la maturation d'affinité des régions variables d'Ig par hypermutation somatique SHM et la commutation de classe CSR. Ces deux processus sont sous le contrôle de la région régulatrice 3’ (3’RR) du locus IgH. Pendant la CSR, le locus IgH subit des changements tridimensionnels mettant les régions switch ciblés par AID à proximité de la région 3’RR afin de faciliter la recombinaison. La sous-unité MED1 du complexe Médiateur favorise cette interaction à longue distance avec la 3’RR mais elle intervient aussi dans la transcription germinale qui précède la CSR afin de faciliter l’activité d’AID. Comme récemment démontré chez la souris, la région 3’RR peut aussi être ciblée par des recombinaison médiée par AID, mais contrairement à la CSR, ce type de recombinaison qui joint la région Sμ et la 3’RR et qui s’appelle recombinaison suicide du locus IgH ou LSR entraîne une délétion complète de l’ensemble des gènes constants conduisant à la mort des cellules B par la perte de l’expression du BCR. Nous montrons maintenant que la LSR médiée par AID se produit aussi dans les cellules B humaines activées avec les deux régions 3’RR (3’RR1 en aval de Cα1 et 3’RR2 en aval de Cα2) et qui peut toucher l’allèle fonctionnel mais elle peut aussi être biallélique marqué par une quasi-absence de ce type de recombinaison dans les plasmocytes de la moelle mais aussi dans les cellules B mémoires quiescents du sang et qui peut par contre être réinduite à haut niveau lorsque les cellules B mémoires sont réactivées. Toutes nos conditions de stimulation utilisées in-vitro induit la LSR, sans permettre de discerner comment se fait « le choix » entre la CSR et la LSR. Nos résultats montrent par contre que la sous-unité MED1 semble influencer la transcription de la 3’RR et la recombinaison LSR chez la souris. L’inactivation conditionnelle de MED1 influence l’accessibilité transcriptionnelle et donc les recombinaisons sans affecter les marques épigénétiques du locus IgH. Cette étude de MED1 a aussi révélé que l’ensemble des processus stimulés par l’IgH 3’RR sont « Médiateur-dépendants » (SHM, CSR sans distinction de la cis et la trans-CSR, expression augmentée du locus dans les plasmocytes…), comme semble l’être également le processus de choix des segments variables au cours des réarrangements VHDJHB-cell activation is accompanied by remodeling of immunoglobulin genes resulting in affinity maturation of Ig variable regions by somatic hypermutation (SHM) and class switch recombination (CSR). These two processes are under the control of the 3' regulatory region (3’RR) of the IgH locus. During CSR, the IgH locus undergoes three dimensional changes bringing the AID-targeted switch regions near the 3'RR region to facilitate recombination. The MED1 subunit of the Mediator complex promotes this long-distance interaction with the 3'RR, but it is also implicated in germinal transcription preceding CSR in order to facilitate AID activity. As recently demonstrated in mice, the 3'RR region can also be targeted by AID-mediated recombination, but unlike CSR, this type of recombination joining the Sμ region and 3'RR (called Locus Suicide Recombination or LSR) results in a complete deletion of all the constant genes leading to B-cell death by loss of B Cell Receptor expression. We now show that AID-mediated LSR also occurs in activated human B cells with the two 3'RR (3'RR1downstream of Cα1 and 3'RR2 downstream of Cα2) and affects the functional allele. It can also be bi-allelic marked by the absence of this type of recombination in plasma cells of the bone marrow but also in quiescent blood memory B cells. LSR occurs at high level when the memory B cells are reactivated. All in-vitro stimulations induce LSR, without identifying conditions favoring either CSR and the LSR. Our results also show that the MED1 subunit appears to influence 3’ RR transcription and LSR in mice. Conditional inactivation of MED1 influences transcriptional accessibility and therefore recombination without affecting epigenetic markers of the IgH locus. This study also revealed that all the processes controlled by the 3'RR are "mediator -dependent" (SHM, CSR without distinction between Cis and Trans -CSR, increased expression of the IgH locus in the plasma cells ...), as well as the choice of varia ble segments during VDJH rearrangements
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Xie, Ting. "Interactions épistatiques et modifications épigénétiques pour la stratification moléculaire des maladies chroniques." Thesis, Université de Lorraine, 2017. http://www.theses.fr/2017LORR0339/document.
Abstract:
Les maladies chroniques, comme les maladies cardiovasculaires (MCV), la maladie d'Alzheimer (AD), la dépression et l'ostéoporose, sont les principales causes de mortalité dans le monde. L'identification de facteurs de risque communs à ces maladies pourrait contribuer à un vieillissement «sain» mieux surveillé en utilisant des stratégies personnalisées de prédiction des risques, de prévention précoce et de traitement adéquat, en tenant compte des comorbidités très souvent existantes. Dans cette thèse, 8 publications ont été développées. Dans un premier temps, j'ai résumé, dans un article de revue, les défis actuels et les opportunités de la pharmacogénomique des médicaments contre les maladies cardiovasculaires. J'ai participé à la formation d'un consortium international, le Consortium VEGF et j'ai participé à une étude qui a identifié des interactions épistasiques entre les polymorphismes qui régulent les niveaux de VEGF et la pression artérielle et les indices d'adiposité. J'ai également démontré qu’un marqueur génétique de VEGF, le rs4416670, était significativement associé à un risque accru de dépression. En outre, j'ai signalé deux interactions significatives entre les variantes liées au VEGF affectant la densité minérale osseuse du col fémoral chez les femmes ménopausées. J'ai également étudié deux marqueurs liés au métabolisme des lipides : l'apolipoprotéine E (APOE) et le «lipolysis-stimulated receptor» (LSR). J'ai trouvé que le variant LSR rs916147 peut interagir avec APOE d'une manière qui inverse l'effet protecteur de l'allèle ε2 de l'APOE sur les lipides sanguins, fournissant ainsi de nouvelles connaissances sur les mécanismes de l'hyperlipoprotéinémie de type III. Les interactions épistasiques entre ces deux gènes augmentent également le risque d’AD même en l'absence de l'allèle à risque, APOE ε4. Finalement, j'ai réalisé des études épigénetiques (EWAS) sur l'obésité centrale et les traits lipidiques chez des individus sains. Les résultats suggèrent qu'un CpG pourrait affecter le tour de taille à travers une voie de signalisation de l'insuline. En outre, deux CpGs ont été associées aux niveaux des triglycérides par des gènes liés aux maladies cardiaques génétiques (PRKAG2) et à l'inhibition de la signalisation Wnt / bêta-caténine impliquée dans le développement des MCV et d’AD (KREMEN2). En conclusion, dans cette thèse j’ai utilisé l'étude de l'épistasie et de l'épigénétique pour identifier des interrelations complexes entre VEGF, LSR, APOE et différentes maladies chroniques (MCV, AD, ostéoporose, dépression) proposant ainsi de nouveaux mécanismes et des dénominateurs communs de ces maladies qui devraient être utilisés comme biomarqueurs de médecine personnaliséeChronic diseases, like cardiovascular diseases (CVD), Alzheimer’s disease (AD), depression and osteoporosis, are major causes of mortality in the world. Identification of common to those diseases risk factors could help for a better-monitored ‘healthy’ aging, by promotion of personalised strategies for risk prediction, early prevention and adequate treatment, all taking into account the very often existing comorbidities. In this thesis, 8 publications have been developed. Initially, in a review paper, I have summarised the current challenges and opportunities of pharmacogenomics of CVD medications. I have participated in the formation of an international consortium, the VEGF Consortium, and I have participated in a study that identified significant epistatic interactions between polymorphisms that regulate the levels of VEGF and their effects on blood pressure and adiposity indexes. I have also demonstrated that one genetic marker of VEGF, rs4416670, was significantly associated with an increased risk for depression. Furthermore, I have reported two significant interactions between VEGF-related variants affecting the femoral neck bone mineral density in post-menopausal women. I have focused also on two markers linked with lipids metabolism: the apolipoprotein E (APOE) and the lipolysis-stimulated receptor (LSR). I have found that the LSR variant rs916147 can interact with APOE in a way that reverses the protective effect of the ε2 allele of APOE on blood lipids, thus providing new insights in the mechanisms underlying type III hyperlipoproteinemia. Epistatic interactions between these two genes have also been shown to increase the risk of AD, even in the absence of the known risk allele APOE ε4. Finally, I have performed epigenome-wide association studies (EWAS) on central obesity and blood lipid traits in healthy individuals. The results suggest that one methylation probe could affect waist circumference through an insulin-signaling pathway. Furthermore, two methylations probes were associated with triglycerides levels through genes linked with genetic heart diseases (PRKAG2) and with inhibition of the Wnt/beta-catenin signaling that is involved in CVD and AD development (KREMEN2). In conclusion, this thesis used the study of epistasis and epigenetics and identified complex inter-relationships between VEGF, LSR, APOE and different chronic diseases (CVD, AD, osteoporosis, depression) and novel mechanisms that link disease development with DNA methylation, thus demonstrating their role as common denominators of diseases that can be used as valuable markers in personalised medicine
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El, Hajj Aseel. "Rôle du LSR dans la régulation de l’homéostasie du cholestérol dans le système nerveux central." Electronic Thesis or Diss., Université de Lorraine, 2019. http://www.theses.fr/2019LORR0317.
Abstract:
Le cholestérol est un lipide crucial dans le système nerveux central (SNC) et sa régulation stricte assure un développement et une fonction neuronaux appropriés. Le cholestérol est synthétisé dans le SNC par les cellules gliales qui produisent et sécrètent le cholestérol pour répondre aux besoins neuronaux. Les lipoprotéines et leurs récepteurs sont des éléments clés de ce transport intercellulaire : où ces derniers reconnaissent, lient et endocytent les lipoprotéines contenant du cholestérol. Le récepteur de lipoprotéine stimulé par lipolyse (LSR) est le récepteur le plus récemment découvert dans le SNC. C'est un complexe protéique multimère qui subit des changements conformationnels lors de la liaison des acides gras libres, révélant ainsi un site de liaison qui reconnaît les apolipoprotéines B et E. L'inactivation complète du gène LSR est létale au niveau embryonnaire, probablement due à une fuite de la barrière hématoencéphalique. De plus, des études sur des souris LSR +/- ont révélé une modification de la distribution du cholestérol et des fonctions cognitives. Notre premier objectif était de réaliser le profilage LSR au niveau des tissus et des cellules. Nos résultats ont révélé une expression différentielle des sous-unités de LSR. Les études in vitro sur des cultures de cellules primaires ont démontré que le LSR était fortement exprimé dans différentes régions du SNC, à la fois dans les cellules gliales et neuronales. Notre hypothèse est qu'une forte expression du LSR dans les cellules gliales pourrait jouer un rôle dans le contrôle de la synthèse du cholestérol, en limitant le cholestérol en circulation dans le liquide extracellulaire du cerveau. Pour vérifier cette hypothèse, nous avons développé un système inductible Cre-lox ciblant spécifiquement les cellules gliales. Le phénotypage comportemental démontre un déficit de la fonction olfactive ayant un impact sur la mémoire sociale de ces animaux. Bien qu'aucun problème de vision n'ait été détecté, le test de reconnaissance d'objet a démontré que la mémoire visuelle était affectée. En outre, les tests sur le labyrinthe en Y et celui de Barns semblent affecter la mémoire à court et à long terme. Nos résultats suggèrent que l'inactivation spécifique de LSR dans les cellules gliales altère la mémoire des animaux, affectant la mémoire spatiale et sociale. Fait intéressant et similaire à AD, le signe précoce était lié au déficit en olfaction. En utilisant une stratégie combinant phénotypage comportemental, immunomarquage et analyse biochimique de marqueurs spécifiques de la plasticité synaptique, ce modèle pourrait également être utilisé pour déterminer le rôle du LSR dans la cognition cérébrale et le trafic de cholestérol dans le SNC, et pourrait fournir les moyens de valider le LSR en tant que cible thérapeutique potentielle pour le traitement des dommages causés par le stockage des lipides et le développement de maladies neurodégénératives dans le cerveau vieillissantCholesterol is a crucial lipid in the central nervous system (CNS) and its strict regulation ensures proper neuronal development and function. Cholesterol is synthesized in the CNS by glial cells which produce and secrete cholesterol to meet neuronal needs. Lipoproteins and their receptors are key elements of this intercellular transport: where the latter recognize, bind and endocytose lipoproteins containing cholesterol. The lipolysis stimulated lipoprotein receptor (LSR) is the most recently discovered receptor in the CNS. It is a multimeric protein complex that undergoes conformational changes during the binding of free fatty acids, thus revealing a binding site which recognizes apolipoproteins B and E. Complete inactivation of the LSR gene is lethal at embryonic level, probably due to a leaky blood brain barrier. In addition, studies in LSR +/- mice have revealed a change in the distribution of cholesterol and cognitive functions. Our first goal was to perform LSR profiling at the tissue and cell level. Our results revealed a differential expression of the LSR subunits. In vitro studies in primary cell cultures have shown that LSR is highly expressed in different regions of the CNS, both in glial and neuronal cells. Our hypothesis was that a strong expression of LSR in glial cells could play a role in controlling the synthesis of cholesterol, by limiting the cholesterol circulating in the extracellular fluid of the brain. To verify this hypothesis, we have developed an inducible Cre-lox system specifically targeting glial cells. Behavioral phenotyping demonstrated a deficit in olfactory function which has an impact on the social memory of these animals. Although no visual problems were detected, the object recognition test showed that the visual memory was affected. Additionally, Y and Barnes mazes tests revealed an impacted short- and long-term memory. Our results suggest that specific inactivation of LSR in glial cells impairs animal memory, affecting spatial and social memory. Interestingly and similarly to AD, the early signs monitored olfactory deficits. Using a strategy combining behavioral phenotyping, immunostaining and biochemical analysis of specific markers of synaptic plasticity, this model could also be used to determine the role of LSR in brain cognition and cholesterol trafficking in the CNS, and could provide the means to validate LSR as a potential therapeutic target for the treatment of damage caused by lipid storage and the development of neurodegenerative diseases in the aging brain
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Spiess, Matthias. "Evolution of the SH3 domain protein interaction networks in yeast : functions and interactions of the Lsb1 and Lsb2 protein family." Strasbourg, 2010. https://publication-theses.unistra.fr/public/theses_doctorat/2010/SPIESS_Matthias_2010.pdf.
Abstract:
Chez S. Cerevisiae, les nutriments, les lipides et les protéines membranaires sont internalisés par endocytose. Ce processus requiert des filaments d’actine dynamiques. Un facteur clé pour la polymérisation de l’actine est le nucléateur Arp2/3, activé par des facteurs de promotion de la nucléation (NPF). Pendant l’endocytose, la polymérisation de l’actine est initiée, entre autre, par les NPFs Las17 et les myosines de type I. Nous avons caractérisé deux protéines, Lsb1 et Lsb2 qui lient Las17 par leurs domaines SH3 et qui inhibent in vitro la polymérisation de l’actine dépendante du complexe Arp2/3. Lsb1 et Lsb2 colocalisent avec des protéines du cytosquelette, Las17, Abp1 et Sla1 et influencent la stabilité de Las17 in vivo. Nous avons ainsi identifié deux nouveaux régulateurs négatifs de l’activité NPF de Las17 ce qui permet de mieux comprendre son rôle dans la polymérisation de l’actine et l’endocytose. Nous avons également caractérisé chez des levures S. Cerevisiae, A. Gossypii, C. Albicans et S. Pombe des réseaux d’interactions protéine-protéine à travers des spécificités de liaison des domaines SH3 par la technique SPOT. Une conservation de la spécificité des myosines de type I, connu par ailleurs, a été montrée par analyse bioinformatique et valide notre méthode. De plus, nous montrons que la fonction de la myosine I de recruter la machinerie de polymérisation dans un extrait de S. Cerevisiae est conservée de S. Cerevisiae à A. Gossypii. Nous faisons des analyses similaires pour de nombreuses autres protéines à domaine SH3 ce qui nous permettra de prédire des interactions protéines-protéines ainsi de mieux comprendre l’évolution des réseaux d’interaction protéiqueIn S. Cerevisiae, nutrients, lipids and membrane proteins are internalized by endocytosis. These processes require dynamic actin filament assembly. A key factor for actin polymerization is the nucleating complex Arp2/3 that is activated by nucleation promoting factors (NPF). During the process of endocytosis, a strong NPF activity is exhibited by Las17, the unique S. Cerevisiae homolog of WASP and the type I myosin, Myo5, among others. Here, we characterize two SH3 domain containing proteins Lsb1 and Lsb2. We could show that both proteins bind to the proline rich sequence of the NPF Las17 via their SH3 domains and efficiently inhibit Las17 induced Arp2/3-dependent actin polymerization in vitro. We could also show that Lsb1 and Lsb2 partially colocalize with Las17 and that they influence the stability of Las17 in vivo. However, we did not detect any defect in endocytosis for the single or double deletion mutants of LSB1 and LSB2. In conclusion, we identified two new negative regulators of the NPF activity of Las17 that will help us to further understand actin nucleation and endocytosis. The characterization of the SH3 domain binding specificity in four yeast species S. Cerevisiae, A. Gossypii, C. Albicans and S. Pombe showed high conservation of the type I myosin specificity during evolution, validating our method. The ability of type I myosin to recruit the actin polymerization machinery in S. Cerevisiae is conserved from S. Cerevisiae to A. Gossypii. Similar analysis of numerous other SH3 domains, including Lsb1 and Lsb2, is in progress, which will allow us to predict new protein-protein interactions and to gain insights into the evolution of protein interaction networks
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Hornuß, Daniel [Verfasser], and Klaus [Akademischer Betreuer] Aktories. "Untersuchungen zur Wechselwirkung zwischen dem C. difficile-Toxin CDT und seinem zugehörigen Zellrezeptor LSR an Plasmamembranen." Freiburg : Universität, 2014. http://d-nb.info/1123478481/34.
30
Xiaoyu, Dang, Zhang Yong, and Zhou Tingxian. "A METHOD TO ENHANCE THE BIT RATE OF LINEAR CODE GENERATOR IN SPREAD-SPECTRUM COMMUNICATION SYSTEM." International Foundation for Telemetering, 1999. http://hdl.handle.net/10150/607337.
Abstract:
International Telemetering Conference Proceedings / October 25-28, 1999 / Riviera Hotel and Convention Center, Las Vegas, NevadaBecause of the limits of feedback devices, high-speed pseudo-noise code generators cannot depend simply on the improvement of clock rate. Based on the characteristic equation of linear feedback registers and the m-sequence sampling theory as well, deduction is made to indicate a novel way to improve the speed of pseudo-noise code generators 2^l (2^l < n, n is the length of registers) times as fast as the conventional one. Also, we extend our applications to non-reducible and non-primitive polynomials. It could be a good way to generate these linear codes at higher rates.
31
Kadir, Joanne, and Petra Forsberg. "Logistik och distribution ur ett hållbarhetsperspektiv : I vilken utsträckning läkemedelsföretag har LSR som en del i sitt övergripande hållbarhetsarbete." Thesis, Uppsala universitet, Företagsekonomiska institutionen, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-417815.
Abstract:
Studien syftar till att öka kunskapsutvecklingen om hur företag arbetar med Logistik SocialResponsibility (LSR) genom att studera hållbarhets- och årsrapporter. Studien är avgränsad motläkemedelsbranschen och ämnar därför att undersöka i vilken utsträckning läkemedelsföretagenhar LSR som en del i sitt övergripande hållbarhetsarbete. Utformningen följer metodiken kvalitativriktad innehållsanalys. De utvalda studieobjekten är följande fem läkemedelsföretag: Johnson &Johnson, Roche, GlaxoSmithKline, Eli Lilly och AstraZeneca. Med en modifierad LSR-modellanalyserades utfallet med hjälp av fyra utvalda faktorer. Samtliga är kopplade till LSR:shuvudområden miljö, ekonomi och samhälle. Resultatet av den insamlade datan ska ge en plattformför kunskap- och erfarenhetsutbyte inom men även branscher emellan. Slutsatsen konkluderas tillatt samtliga läkemedelsföretag har omfattande hållbarhetsrapporter, dock på annat fokus än LSR,vilket kan tolkas till avsaknad av alternativ inom logistik och därmed även motivation då det inteleder till något värdeskapande.
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Kiška, Martin. "Technologie MultiProtocol Label Switching v sítích Ethernet." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2014. http://www.nusl.cz/ntk/nusl-220653.
Abstract:
In the introduction of this thesis the reasons for transition from older to a new technology called MultiProtocol Label Switching are mentioned – the modern technology enables simple network extension. The theoretical part contains basic principles of this techno- logy and their practical application for supplying private networks to the customers using provider’s network. In practical part packets are analyzed considering the theory. In addi- tion. All the technologies tested on a real network. Experience gained while working on this thesis are assessed during creating laboratory task for class Architecture of Networks intended for students of Bachelor’s study programme.
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Hanse, Marine. "Rôle du récepteur aux lipoprotéines, LSR, dans la régulation du transport et de la distribution des lipides alimentaires." Thesis, Vandoeuvre-les-Nancy, INPL, 2011. http://www.theses.fr/2011INPL086N/document.
Abstract:
Le récepteur hépatique aux lipoprotéines LSR est impliqué dans la clairance des lipoprotéines riches en triglycérides telles que les résidus de chylomicrons pendant la phase postprandiale. La réduction de l’expression du LSR chez la souris (LSR+/-) est associée à une dyslipidémie et une lipémie postprandiale élevée. Afin de mieux comprendre la régulation de la distribution des lipides alimentaires, nous avons cherché quels étaient les facteurs pouvant affecter le niveau protéique de LSR. La leptine, hormone sécrétée par le tissu adipeux et connue pour son action d’hormone de satiété au niveau du système nerveux central, a été démontrée dans cette thèse comme modulant l’expression de LSR par la régulation de la transcription du gène lsr. La leptine est impliquée dans la régulation de la lipogénèse à travers SREBP-1. Grâce à l’utilisation d’un extrait de Garcinia cambogia contenant un inhibiteur de l’ATP citrate lyase, nous avons démontré une interaction importante entre les enzymes lipogéniques, l’expression de LSR et d’autres récepteurs lipoprotéiques, afin de maintenir un équilibre entre la synthèse de lipides endogènes et l’apport alimentaire de lipides exogènes. Soumises à un régime hyperlipidique, les souris sauvages montrent une diminution de l’expression des enzymes lipogéniques hépatiques, aggravée chez les souris LSR+/-. Ces résultats indiquent qu’il existe un mécanisme de maintien de l’équilibre entre la lipogénèse (synthèse endogène de lipides), la lipolyse (utilisation lipidique comme substrat énergétique) et le stockage de lipides à travers une forte interaction entre les enzymes lipogéniques et LSRThe hepatic lipoprotein receptor LSR is involved in the clearance of triglyceride-rich lipoproteins including chylomicrons remnants during the post-prandial phase. Reduced LSR protein expression in mice (LSR+/-) is associated with dyslipidemia and increased postprandial lipemia; these mice exhibit increased weight gain with aging or when placed under a high-fat diet. In order to better understand the regulation of the distribution of dietary lipids, we looked for factors that could regulate LSR protein levels. Leptin is a hormone secreted by the adipose tissue that is a centrally-acting satiety factor, and was demonstrated to modulate LSR mRNA and protein expression through the modulation of transcription of the gene lsr. Leptin has been reported be involved in the control of lipogenesis through SREBP-1c. Using Garcinia cambogia extract containing an inhibitor of ATP citrate lyase, we demonstrated that there is an important link between lipogenic enzymes and LSR protein levels and with other lipoprotein receptors that provides the means to maintain a balance between endogenous lipid synthesis and dietary intake of exogenous lipids. When exogenous lipid intake is increased in the form of a high-fat diet, mice exhibited a decrease in hepatic lipogenic enzymes expression, but a deficiency of LSR led to increased lipid content in the peripheral tissues. These results suggest the presence of mechanisms for the maintenance for the balance between lipogenesis (de novo endogenous lipid synthesis), lipolysis (lipids used as energy substrate), and lipid storage through an important link between lipogenic enzymes and LSR
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Harkous, Ali. "Analyse du comportement thermo-rhéo-cinétique et de l’adhésion des silicones liquides." Nantes, 2015. http://archive.bu.univ-nantes.fr/pollux/show.action?id=de408d5c-1177-445f-bdc1-27f99ba483c1.
Abstract:
Le silicone liquide (LSR) est un élastomère bi-composant réticulable à chaud, dont la formulation peut être ajustée selon le domaine d’application. La formulation auto-adhérente permet le surmoulage du LSR sur des pièces plastiques par des méthodes d’injection bi-matières. Dans la présente étude, nous analysons ce procédé de surmoulage dans des conditions de mise en oeuvre industrielles en vue de déterminer les facteurs influents sur la qualité de l’adhésion. Dans un premier temps, la caractérisation thermo-rhéo-cinétique du LSR nous permet de comprendre le comportement thermique et rhéologique de la matière, et de calculer le modèle cinétique décrivant la réticulation. Le modèle, ainsi que les paramètres mesurés, sont utilisés dans la conception d’un moule qui sert à la réalisation des essais de surmoulage du LSR sur des pièces en thermoplastique dans des conditions contrôlées. Pour cela, le moule est instrumenté et régulé thermiquement pour simuler et reproduire les conditions de mise en oeuvre industrielles. Une instrumentation permettant la détection in-situ de la réticulation du LSR, avec modulation du signal, est également intégrée dans le moule. Les facteurs influents sur le procédé de surmoulage sont ensuite étudiés et présentés dans un plan d’expérience. Les pièces surmoulées sont caractérisées en cisaillement en mesurant des critères liés à l’adhésion, dont la force de rupture et la déformation. L’analyse des résultats permettra de déterminer l’influence de chaque facteur sur la qualité de l’adhésion et de calculer des modèles décrivant le phénomèneThe Liquid Silicone Rubber (LSR) is a two-component elastomer that crosslinks at high temperature, its formulation can be adjusted depending on the application domain. The self-adhesive formulation of LSR allows its overmolding onto plastic parts through bi-material injection methods. In this study, the LSR-plastic overmolding is analyzed in industrial implementation conditions in order to identify the key factors influencing the adhesion quality. Initially, thermo-rheo-kinetic characterization of LSR allows us to understand the thermal and rheological behavior, and calculate the kinetic model that describes the material crosslinking process. The model and the measured parameters are used in the design of a mold dedicated for performing the LSR-plastic overmolding tests under controlled conditions. As such, the mold is instrumented and thermally controlled to simulate and reproduce the industrial implementation conditions. Thermocouples instrumentation is also integrated into the mold for in-situ detection of the LSR crosslinking reaction. It uses the modulation of signal method. Then, influential factors on the overmolding process are studied and presented in an experimental design. The overmolded parts are characterized by shear test to measure the adhesion criteria, including the breaking stress and the shear strain. The analysis of the results determines the influence of each factor on the quality of adhesion and computes the models that describe the phenomenon
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Wells, Jennifer [Verfasser], and Roland [Akademischer Betreuer] Beckmann. "Structural and functional analysis of translationally inactive Eukaryotic ribosomes : regulation of hibernation with Lso2/CCDC124 and stalling on the fungal arginine attenuator peptide / Jennifer Wells ; Betreuer: Roland Beckmann." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1219852031/34.
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Kawale, Ashish [Verfasser], Michael [Akademischer Betreuer] Sattler, Dierk [Gutachter] Niessing, and Michael [Gutachter] Sattler. "Structural and functional evolution of the alternative splicing factor LS2 from Drosophila melanogaster / Ashish Kawale ; Gutachter: Dierk Niessing, Michael Sattler ; Betreuer: Michael Sattler." München : Universitätsbibliothek der TU München, 2017. http://d-nb.info/115238404X/34.
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Schmolke, Alexander Sebastian [Verfasser], and Markus [Akademischer Betreuer] Hess. "Messung der Elastizität von Stimmlippen im ungeschädigten und geschädigten Zustand unter Verwendung des Linear Skin Rheometers (LSR) / Alexander Sebastian Schmolke. Betreuer: Markus Hess." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2012. http://d-nb.info/1024772233/34.
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Engwirda, Anthony, and N/A. "Self-Reliance Guidelines for Large Scale Robot Colonies." Griffith University. Griffith School of Engineering, 2007. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20070913.100750.
Abstract:
A Large Scale Robot Colony (LSRC) is a complex artifact comprising of a significant population of both mobile and static robots. LSRC research is in its literary infancy and it is therefore necessary to rely upon external fields for the appropriate framework, Multi Agent Systems (MAS) and Large Scale Systems (LSS). At the intersection of MAS, LSS and LSRC exist near identical issues, problems and solutions. If attention is paid to coherence then solution portability is possible. The issue of Self-Reliability is poorly addressed by the MAS research field. Disparity between the real world and simulation is another area of concern. Despite these deficiencies, MAS and LSS are perceived as the most appropriate frameworks. MAS research focuses on three prime areas, cognitive science, management and interaction. LSRC is focused on Self-Sustainability, Self-Management and Self-Organization. While LSS research was not primarily intended for populations of mobile robots, it does address key issues of LSRC, such as effective sustainability and management. Implementation of LSRC that is based upon the optimal solution for any one or two of the three aspects will be inferior to a coherent solution based upon all three. LSRCs are complex organizations with significant populations of both static and mobile robots. The increase in population size and the requirement to address the issue of Self-Reliance give rise to new issues. It is no longer sufficient to speak only in terms of robot intelligence, architecture, interaction or team behaviour, even though these are still valid topics. Issues such as population sustainability and management have greater significance within LSRC. As the size of a robot populations increases, minor uneconomical decisions and actions inhibit the performance of the population. Interaction must be made economical within the context of the LSRC. Sustainability of the population becomes significant as it enables stable performance and extended operational lifespan. Management becomes significant as a mechanism to direct the population so as to achieve near optimal performance. The Self-Sustainability, Self-Management and Self-Organization of LSRC are vastly more complex than in team robotics. Performance of the overall population becomes more significant than individual or team achievement. This thesis is a presentation of the Cooperative Autonomous Robot Colony (CARC) architecture. The CARC architecture is novel in that it offers a coherent baseline solution to the issue of mobile robot Self-Reliance. This research uses decomposition as a mechanism to reduce problem complexity. Self-Reliance is decomposed into Self-Sustainability, Self-Management, and Self-Organization. A solution to the issue of Self-Reliance will comprise of conflicting sub-solutions. A product of this research is a set of guidelines that manages the conflict of sub-solutions and maintains a coherent solution. In addressing the issue of Self-Reliance, it became apparent that Economies of Scale, played an important role. The effects of Economies of Scale directed the research towards LSRCs. LSRCs demonstrated improved efficiency and greater capability to achieve the requirements of Self-Reliance. LSRCs implemented with the CARC architecture would extend human capability, enabling large scale operations to be performed in an economical manner, within real world and real time environments, including those of a remote and hostile nature. The theory and architecture are supported using published literature, experiments, observations and mathematical projections. Contributions of this work are focused upon the three pillars of Self-Reliance addressed by CARC: Self-Sustainability, Self-Management and Self-Organization. The chapter on Self-Sustainability explains and justifies the relevance of this issue, what it is, why it is important and how it can be achieved. Self-Sustainability enables robots to continue to operate beyond disabling events by addressing failure and routine maintenance. Mathematical projections are used to compare populations of non-sustained and sustained robots. Computer modeling experiments are used to demonstrate the feasibility of Self-Sustainability, including extended operational life, the maintenance of optimal work flow and graceful physical degradation (GPD). A detailed explanation is presented of Sustainability Functions, Colony Sites, Static Robot Roles, Static Robot Failure Options, and Polymorphism. The chapter on Self-Management explores LSS research as a mechanism to exert influence over a LSRC. An experimental reactive management strategy is demonstrated. This strategy while limited does indicate promising potential directions for future research including the Man in the Loop (MITL) strategy highly desired by NASA JPL for off world command and control of a significant robot colony (Huntsberger, et. al., 2000). Experiments on Communication evaluate both Broadcast Conveyance (BC) and Message Passing Conveyance (MPC). These experiments demonstrate the potential of Message Passing as a low cost system for LSRC communication. Analysis of Metrics indicates that a Performance Based Feedback Method (PBFM) and a Task Achievement Method (TAM) are both necessary and sufficient to monitor a LSRC. The chapter on Self-Organization describes a number of experiments, algorithms and protocols on Reasoning Robotics, a minor variant of Reactive Robotics. Reasoning Robotics utilizes an Event Driven Architecture (EDA) rather than a Stimulus Driven Architecture (SDA) common to Reactive Robotics. Enhanced robot performance is demonstrated by a combination of EDA and environmental modification enabling stigmergy. These experiments cover Intersection Navigation with contingency for Multilane Intersections, a Radio Packet Controller (RPC) algorithm, Active and Passive Beacons including a communication protocol, mobile robot navigation using Migration Decision Functions (MDFs), including MDF positional errors. The central issue addressed by this thesis is the production of Self-Reliance guidelines for LSRCs. Self-Reliance is perceived as a critical issue in advancing the useful and productive applications for LSRCs. LSRCs are complex with many issues in related fields of MAS and LSS. Decomposition of Self-Reliance into Self-Sustainability, Self-Management and Self-Organization were used to aid in problem understanding. It was found that Self-Sustainability extends the operational life of individual robots and the LSRC. Self-Management enables the exertion of human influence over the LSRC, such that the ratio of humans to robots is reduced but not eliminated. Self-Organization achieves and enhances performance through a routine and reliable LSRC environment. The product of this research was the novel CARC architecture, which consists of a set of Self-Reliance guidelines and algorithms. The Self-Reliance guidelines manage conflict between optimal solutions and provide a framework for LSRC design. This research was supported by literature, experiments, observations and mathematical projections.
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Engwirda, Anthony. "Self-Reliance Guidelines for Large Scale Robot Colonies." Thesis, Griffith University, 2007. http://hdl.handle.net/10072/368079.
Abstract:
A Large Scale Robot Colony (LSRC) is a complex artifact comprising of a significant population of both mobile and static robots. LSRC research is in its literary infancy and it is therefore necessary to rely upon external fields for the appropriate framework, Multi Agent Systems (MAS) and Large Scale Systems (LSS). At the intersection of MAS, LSS and LSRC exist near identical issues, problems and solutions. If attention is paid to coherence then solution portability is possible. The issue of Self-Reliability is poorly addressed by the MAS research field. Disparity between the real world and simulation is another area of concern. Despite these deficiencies, MAS and LSS are perceived as the most appropriate frameworks. MAS research focuses on three prime areas, cognitive science, management and interaction. LSRC is focused on Self-Sustainability, Self-Management and Self-Organization. While LSS research was not primarily intended for populations of mobile robots, it does address key issues of LSRC, such as effective sustainability and management. Implementation of LSRC that is based upon the optimal solution for any one or two of the three aspects will be inferior to a coherent solution based upon all three. LSRC’s are complex organizations with significant populations of both static and mobile robots. The increase in population size and the requirement to address the issue of Self-Reliance give rise to new issues. It is no longer sufficient to speak only in terms of robot intelligence, architecture, interaction or team behaviour, even though these are still valid topics. Issues such as population sustainability and management have greater significance within LSRC. As the size of a robot populations increases, minor uneconomical decisions and actions inhibit the performance of the population. Interaction must be made economical within the context of the LSRC. Sustainability of the population becomes significant as it enables stable performance and extended operational lifespan. Management becomes significant as a mechanism to direct the population so as to achieve near optimal performance. The Self-Sustainability, Self-Management and Self-Organization of LSRC are vastly more complex than in team robotics. Performance of the overall population becomes more significant than individual or team achievement. This thesis is a presentation of the Cooperative Autonomous Robot Colony (CARC) architecture. The CARC architecture is novel in that it offers a coherent baseline solution to the issue of mobile robot Self-Reliance. This research uses decomposition as a mechanism to reduce problem complexity. Self-Reliance is decomposed into Self-Sustainability, Self-Management, and Self-Organization. A solution to the issue of Self-Reliance will comprise of conflicting sub-solutions. A product of this research is a set of guidelines that manages the conflict of sub-solutions and maintains a coherent solution. In addressing the issue of Self-Reliance, it became apparent that Economies of Scale, played an important role. The effects of Economies of Scale directed the research towards LSRC’s. LSRC’s demonstrated improved efficiency and greater capability to achieve the requirements of Self-Reliance. LSRC’s implemented with the CARC architecture would extend human capability, enabling large scale operations to be performed in an economical manner, within real world and real time environments, including those of a remote and hostile nature. The theory and architecture are supported using published literature, experiments, observations and mathematical projections. Contributions of this work are focused upon the three pillars of Self-Reliance addressed by CARC: Self-Sustainability, Self-Management and Self-Organization. The chapter on Self-Sustainability explains and justifies the relevance of this issue, what it is, why it is important and how it can be achieved. Self-Sustainability enables robots to continue to operate beyond disabling events by addressing failure and routine maintenance. Mathematical projections are used to compare populations of non-sustained and sustained robots. Computer modeling experiments are used to demonstrate the feasibility of Self-Sustainability, including extended operational life, the maintenance of optimal work flow and graceful physical degradation (GPD). A detailed explanation is presented of Sustainability Functions, Colony Sites, Static Robot Roles, Static Robot Failure Options, and Polymorphism. The chapter on Self-Management explores LSS research as a mechanism to exert influence over a LSRC. An experimental reactive management strategy is demonstrated. This strategy while limited does indicate promising potential directions for future research including the Man in the Loop (MITL) strategy highly desired by NASA JPL for off world command and control of a significant robot colony (Huntsberger, et. al., 2000). Experiments on Communication evaluate both Broadcast Conveyance (BC) and Message Passing Conveyance (MPC). These experiments demonstrate the potential of Message Passing as a low cost system for LSRC communication. Analysis of Metrics indicates that a Performance Based Feedback Method (PBFM) and a Task Achievement Method (TAM) are both necessary and sufficient to monitor a LSRC. The chapter on Self-Organization describes a number of experiments, algorithms and protocols on Reasoning Robotics, a minor variant of Reactive Robotics. Reasoning Robotics utilizes an Event Driven Architecture (EDA) rather than a Stimulus Driven Architecture (SDA) common to Reactive Robotics. Enhanced robot performance is demonstrated by a combination of EDA and environmental modification enabling stigmergy. These experiments cover Intersection Navigation with contingency for Multilane Intersections, a Radio Packet Controller (RPC) algorithm, Active and Passive Beacons including a communication protocol, mobile robot navigation using Migration Decision Functions (MDF’s), including MDF positional errors. The central issue addressed by this thesis is the production of Self-Reliance guidelines for LSRC’s. Self-Reliance is perceived as a critical issue in advancing the useful and productive applications for LSRC’s. LSRC’s are complex with many issues in related fields of MAS and LSS. Decomposition of Self-Reliance into Self-Sustainability, Self-Management and Self-Organization were used to aid in problem understanding. It was found that Self-Sustainability extends the operational life of individual robots and the LSRC. Self-Management enables the exertion of human influence over the LSRC, such that the ratio of humans to robots is reduced but not eliminated. Self-Organization achieves and enhances performance through a routine and reliable LSRC environment. The product of this research was the novel CARC architecture, which consists of a set of Self-Reliance guidelines and algorithms. The Self-Reliance guidelines manage conflict between optimal solutions and provide a framework for LSRC design. This research was supported by literature, experiments, observations and mathematical projections.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Griffith School of Engineering
Faculty of Engineering and Information Technology
Full Text
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Akbar, Samina. "Régulation de l'expression hépatique de récepteur LSR (lipolys stimulated lipoprotein receptor) : rôles de l'acide docosahexaénoïque et du récepteur PPARa ( peroxisome proliferator-activated receptor alpha)." Thesis, Université de Lorraine, 2013. http://www.theses.fr/2013LORR0288/document.
Abstract:
Le récepteur LSR est un acteur important du métabolisme hépatique, puisqu'il joue un rôle dans la clairance des lipoprotéines à ApoB/ApoE riches en triglycérides durant la période postprandiale. Dans cette étude, nous avons montré qu'un traitement in vitro par DHA peut augmenter les niveaux de protéine et d'activité LSR dans les cellules d'hépatome de souris Hepa 1-6. En toute cohérence, un régime supplémenté en DHA a conduit à élever les niveaux de protéine LSR hépatique chez la souris. Mais aucune de ces deux études n'a montré de changement au niveau des ARNm. Ceci suggère que l'enrichissement en DHA influe positivement sur le microenvironnement de LSR et son ancrage à la surface de la cellule. Nous avons ensuite étudié le rôle du récepteur PPAR[alpha] dans la régulation du gène lsr. Une analyse in silico nous a permis d'identifier des éléments PPRE dans la région 5' régulatrice du gène humain et de ses homologues de souris et de rat. Des traitements pharmacologiques par des agoniste et antagoniste spécifiques de PPAR[alpha] ont montré que ce récepteur est impliqué dans la régulation transcriptionnelle de l'expression du LSR dans les cellules Hepa 1 6. Enfin, une analyse transcriptomique a révélé une diminution de l'expression de PPAR[alpha] et d'autres gènes impliqués dans le métabolisme lipidique hépatique chez la souris LSR+/- sous régime standard ou riche en graisses. En conclusion, toutes ces études indiquent que l'activité LSR hépatique est sous le contrôle de facteurs nutritionnels capables d'activer divers mécanismes de régulation, faisant du LSR une cible d'intérêt potentiel pour des stratégies nutritionnelles ou thérapeutiques destinées à prévenir ou traiter les dyslipidémiesLipolysis stimulated lipoprotein receptor (LSR) plays an important role in the clearance of ApoB/ApoE containing triglyceride-rich lipoproteins during postprandial phase. In this study, we demonstrated that in vitro treatment of mouse hepatoma cells, Hepa 1-6, with docosahexaenoic acid (DHA) led to an increase in LSR protein levels as well as its activity. Furthermore, the mice placed on the diet supplemented with DHA showed an increase in hepatic LSR protein. However, the mRNA levels remained unchanged in both in vitro and in vivo studies, suggesting that DHA enrichment may result in changes in LSR microenvironment that could affect its anchorage at the surface of cell membrane. Specific peroxisome proliferator response elements were identified in the upstream region of human, mouse and rat lsr gene by in silico analysis. We therefore sought to determine the role of the transcription factor, peroxisome proliferator-activated receptor (PPAR[alpha]), in LSR regulation. In vitro pharmacological studies using PPAR[alpha]-selective agonist and antagonist agents demonstrated that PPAR[alpha] is indeed involved in the transcriptional regulation of LSR expression. Furthermore, qPCR array analysis revealed the downregulation of PPAR[alpha] and various genes involved in hepatic lipid metabolism in LSR+/- mice on standard and high-fat diets. In conclusion, these studies show that the hepatic LSR activity is controlled by dietary factors that can activate various pathways involved in regulating lipid homeostasis, therefore representing LSR as a potential target for either nutritional or therapeutic strategies towards the prevention or treatment of dyslipidemia
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Zheng, Yilei. "IFSO: A Integrated Framework For Automatic/Semi-automatic Software Refactoring and Analysis." Digital WPI, 2004. https://digitalcommons.wpi.edu/etd-theses/241.
Abstract:
To automatically/semi-automatically improve internal structures of a legacy system, there are several challenges: most available software analysis algorithms focus on only one particular granularity level (e.g., method level, class level) without considering possible side effects on other levels during the process; the quality of a software system cannot be judged by a single algorithm; software analysis is a time-consuming process which typically requires lengthy interactions. In this thesis, we present a framework, IFSO (Integrated Framework for automatic/semi-automatic Software refactoring and analysis), as a foundation for automatic/semi-automatic software refactoring and analysis. Our proposed conceptual model, LSR (Layered Software Representation Model), defines an abstract representation for software using a layered approach. Each layer corresponds to a granularity level. The IFSO framework, which is built upon the LSR model for component-based software, represents software at the system level, component level, class level, method level and logic unit level. Each level can be customized by different algorithms such as cohesion metrics, design heuristics, design problem detection and operations independently. Cooperating between levels together, a global view and an interactive environment for software refactoring and analysis are presented by IFSO. A prototype was implemented for evaluation of our technology. Three case studies were developed based on the prototype: three metrics, dead code removing, low coupled unit detection.
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MacCleery, Brian C. "Position Sensorless Implementation for a Linear Switched Reluctance Machine." Thesis, Virginia Tech, 2000. http://hdl.handle.net/10919/33856.
Abstract:
The development of an add-on sensorless position estimator for a 4.8 m Linear Switched Reluctance Machine (LSRM) with minimal modifications to the transducer-based controller is investigated for the first time in this study. LSRMs require position feedback for closed-loop control but present a low cost, high energy efficiency alternative for linear actuation due to their rugged construction and single-sided excitation. Mechanical position transducers mounted on the vehicle are expensive and can impact reliability. The use of a sensorless position estimator removes all electronics from the passive vehicle, resulting in considerable reductions in cost, maintenance, and mechanical complexity.
This study examines the use of an add-on processor and data acquisition system for sensorless position estimation. An approach exploiting the active phase windings is used to preserve the normal operation of the transducer-based DSP controller with the goal of limiting reductions in high performance features such as force ripple reduction and velocity control [3]. The estimator system is retrofit to the transducer-based DSP controller by mimicking the output of a mechanical position sensor by emulating a Quadrature encoder. The feasibility and design issues for an add-on or retrofit position estimator are investigated. Although sensorless schemes for rotary Switched Reluctance Machines (SRMs) have been studied in detail, the problem of sensorless implementations for LSRMs has not been addressed. Experimental validation of the proposed sensorless estimation scheme is attempted, but closed-loop operation is not achieved successfully due to air gap fluctuations. In depth analysis of the sources and propagation of error is presented.Master of Science
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Пухкан, Н. М. "Ліквідність банків України: оцінка та пруденційне регулювання." Thesis, Одеський національний економічний університет, 2021. http://local.lib/diploma/PUHKAN.pdf.
Abstract:
Доступ до роботи тільки на території бібліотеки ОНЕУ, для переходу натисніть на посилання нижчеКваліфікаційна робота магістра складається з трьох розділів. Об’єкт дослідження – процеси оцінки та пруденційного регулювання ліквідності банків України. У роботі розглядаються теоретичні аспекти ліквідності. Визначено сутність поняття «ліквідність» банків та банківської системи. Описано методичні підходи до кількісної оцінки ліквідності та прибутковості. Розглянуто пруденційне регулювання банківської системи. Проаналізовано функціональні зв’язки у банківських системах України і світових країнах. Побудовано регресійні моделі для перевірки теоретичного припущення ‒ більша ліквідність негативно впливає на показники рентабельності. Досліджено тенденції та взаємозв’язки показників ліквідності та прибутковості банківських систем країн Європи. Запропоновано рекомендації макропруденційного регулювання ліквідності сучасних банків України.
The master's qualification work consists of three sections. The object of research is the processes of assessment and prudential regulation of liquidity of Ukrainian banks. The theoretical aspects of liquidation are considered in the work. The essence of the concept of "liquidity" of banks and the banking system is defined. Methodical approaches to quantitative assessment of liquidity and profitability are described. Prudential regulation of the banking system is considered. Functional connections in the banking systems of Ukraine and world countries are analyzed. Regression models have been built to test the theoretical output - greater liquidity of the negative impact on profitability. Trends and interrelations of liquidity and profitability indicators of European banking systems are studied. Recommendations of macroprudential regulation of liquidity of modern banks of Ukraine are offered.
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Маслак, Михайло Олексійович. "Транспортні мережі на основі технології MPLS, принципи, перспективи розвитку." Bachelor's thesis, КПІ ім. Ігоря Сікорського, 2021. https://ela.kpi.ua/handle/123456789/41589.
Abstract:
Мета роботи – дослідження транспортних мереж на основі технології MPLS. Аналіз напрямків адаптації технології MPLS для досягнення відповідності вимогам транспортних мереж.
У даній роботі розглядається транспортна мережа як невід’ємна частина телекомунікаційної системи, аналізуються технічні принципи функціювання мереж MPLS, проводиться огляд основних технічних принципів транспортних мереж MPLS TP та їх відмінностей від принципів MPLS, аналізується питання моніторингу і керування мережами MPLS TP та питання щодо напрямку подальшого розвитку мереж MPLS TP, зокрема, переходу до технології GMPLS.The purpose of the work is to study transport networks based on MPLS technology. Analysis of directions of MPLS technology adaptation to achieve compliance with the requirements of transport networks. This paper considers transport network as an integral part of telecommunication system, analyzes technical principles of MPLS networks operation, reviews main technical principles of MPLS TP transport networks and their differences from MPLS principles, analyzes the issue of monitoring and management of MPLS TP networks and the direction of further development of MPLS TP networks, in particular, the transition to GMPLS technology.
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Dunfee, Scott E. "Evolution of ORV Trails in the Little Sahara Recreation Area, Utah, 1952 - 1997." Ohio : Ohio University, 2008. http://www.ohiolink.edu/etd/view.cgi?ohiou1225292205.
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Hundessa, Gonfa Lemma. "Enhanced Fast Rerouting Mechanisms for Protected Traffic in MPLS Networks." Doctoral thesis, Universitat Politècnica de Catalunya, 2003. http://hdl.handle.net/10803/5977.
Abstract:
Multiprotocol Label Switching (MPLS) fuses the intelligence of routing with the performance of switching and provides significant benefits to networks with a pure IP architecture as well as those with IP and ATM or a mix of ther Layer 2 technologies. MPLS technology is key to scalable virtual private networks (VPNs) and end-to-end quality of service (QoS), enabling efficient utilization of existing networks to meet future growth. The technology also helps to deliver highly scalable, differentiated end-to-end IP services with simpler configuration, management, and provisioning for both Internet providers and end-users. However, MPLS is a connection-oriented architecture. In case of failure MPLS first has to establish a new label switched path (LSP) and then forward the packets to the newly established LSP. For this reason MPLS has a slow restoration response to a link or node failure on the LSP.The thesis provides a description of MPLS-based architecture as a preferred technology for integrating ATM and IP technologies, followed by a discussion of the motivation for the fast and reliable restoration mechanism in an MPLS network. In this thesis first we address the fast rerouting mechanisms for MPLS networks and then we focus on the problem of packet loss, packet reordering and packet delay for protected LSP in MPLS-based network for a single node/link failure. In order to deliver true service assurance for guaranteed traffic on a protected LSP we use the fast rerouting mechanism with a preplanned alternative LSP. We propose enhancements to current proposals described in extant literature. Our fast rerouting mechanism avoids packet disorder and significantly reduces packet delay during the restoration period.
An extension of the Fast Rerouting proposal, called Reliable and Fast Rerouting (RFR), provides some preventive actions for the protected LSP against packet loss during a failure. RFR maintains the same advantages of Fast Rerouting while eliminating packet losses, including those packet losses due to link or node failure (circulating on the failed links), which were considered to be "inevitable" up to now.
For the purpose of validating and evaluating the behavior of these proposals a simulation tool was developed. It is based on the NS, a well-known network simulator that is being used extensively in research work. An extension featuring the basic functionality of MPLS (MNS) is also available for the NS, and this is the basis of the developed simulation tool.
Simulation results allow the comparison of Fast Rerouting and RFR with previous rerouting proposals.
In addition to this we propose a mechanism for multiple failure recovery in an LSP. This proposal combines the path protection, segment protection and local repair methods. In addition to the multiple link/node failure protection, the multiple fault tolerance proposal provides a significant reduction of delay that the rerouted traffic can experience after a link failure, because the repair action is taken close to the point of failure.
Then we proceed to address an inherent problem of the preplanned alternative LSP. As alternative LSPs are established together with the protected LSP it may happen that the alternative is not the optimal LSP at the time the failure occurs. To overcome this undesired behavior, we propose the Optimal and Guaranteed Alternative Path (OGAP). The proposal uses a hybrid of fast-rerouting and a dynamic approach to establish the optimal alternative LSP while rerouting the affected traffic using the preplanned alternative LSP. This hybrid approach provides the best of the fast rerouting and the dynamic approaches.
At the same time we observed that the protection path becomes in fact unprotected from additional failures after the traffic is rerouted onto it.
To address this we propose a guarantee mechanism for protection of the new protected LSP carrying the affected traffic, by establishing an alternative LSP for the rerouted traffic after a failure, avoiding the vulnerability problem for the protected traffic.
Finally, we present a further optimization mechanism, adaptive LSP, to enhance the existing traffic engineering for Quality of Services (QoS)provision and improve network resource utilization. The adaptive LSP proposal allows more flexibility in network resource allocation and utilization by adapting the LSP to variations in all network loads,resulting in an enhancement of existing MPLS traffic engineering.
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Ikram, Imran. "Traffic Engineering with MPLS and QOS." Thesis, Blekinge Tekniska Högskola, Avdelningen för telekommunikationssystem, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-1217.
Abstract:
In the modern era there exist applications that require very high resources and generate a tremendous amount of traffic so they require considerable amount of bandwidth and QOS to operate and perform correctly. MPLS is a new and a fast technology that offers much remuneration both in terms of providing trouble-free and efficient security together with the high speed of switching. MPLS not only guarantees quality of service of IP networks but in addition to provides scope for traffic engineering it offers many enhanced features of IP networks as it does not replace IP routing, but works along with existing and future routing technologies to provide high-speed data forwarding between label-switched routers (LSRs) together with QOS. Many network carriers are facing the problem of how to accommodate such ever-growing demands for bandwidth. And the static nature of current routing algorithms, such as OSPF or IS-IS, the situation is going even worse since the traffic is concentrated on the "least cost" paths which causes the congestion for some links while leaving other links lightly loaded. Therefore, MPLS traffic engineering is proposed and by taking advantage of MPLS, traffic engineering can route the packets through explicit paths to optimize network resource utilization and traffic performance. MPLS provides a robust quality of service control feature in the internet. MPLS class of service feature can work in accordance with other quality of service architectures for IP networks.
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Gordon, Blair. "Lsr2: An H-NS Functional Analog and Global Regulator of Mycobacterium tuberculosis." Thesis, 2013. http://hdl.handle.net/1807/35832.
Abstract:
Mycobacterium tuberculosis (M. tb), the etiological agent of tuberculosis (TB), continues to be one of the leading global health challenges causing ~2 million deaths annually. In the majority of infected individuals, the bacteria establish a latent, asymptomatic infection capable of persisting for decades with 5-10% of infected individuals developing active disease in their lifetime. Currently it is estimated that one-third of the world’s population is latently infected, representing a large reservoir for disease reactivation and subsequent spread. Latent TB infection is a paucibacillary disease in which a small heterogeneous population of bacilli is present in the body. M. tb persisters, which are characterized by reduced or altered metabolic activity and enhanced drug tolerance, are thought to be the major contributor towards latent infection and disease relapse following chemotherapy; however, the molecular mechanisms governing persisters formation remain poorly understood.
My thesis concerns the characterization of the highly conserved DNA binding protein Lsr2 of mycobacteria. Previous biochemical study of Lsr2 revealed it exhibits DNA-bridging activity analogous to H-NS, an important nucleoid associated protein found in the proteobacteria.
iii
Here I show using in vivo complementation assays that Lsr2 is functionally equivalent to H-NS, even though these proteins share no sequence similarity. I also present genetic evidence that Lsr2 is a global regulator of M. tb that acts primarily as a transcriptional repressor. Notably, I found that Lsr2 represses a large cohort of genes induced in M.tb during in vitro models of latency including genes implicated in persister formation. I also present evidence that lsr2 is selectively inactivated during long-term hypoxia, a condition thought to be important for persister formation during latency. Lastly, I tested the lsr2deletion mutant in a mouse model of infection and found it had reduced growth relative to the WT but was still able to persist. Taken together my work implicates Lsr2 as a central regulator of persister formation and opens up exciting future research avenues on latent TB infection.
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Lu, You-Jhen, and 盧宥蓁. "The effects of Lsr2 on biofilm formation, resistance to oxidative stress and tetracycline-class antibiotics in Mycobacterium abscessus." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/v9jzq8.
Abstract:
碩士國立陽明大學
微生物及免疫學研究所
103
Lsr2, a global transcription regulator highly conserved in mycobacteria, is involved in biofilm formation, oxidative stress tolerance, antibiotic resistance, and virulence of M. smegmatis and M. tuberculosis, while its role in M. abscessus has not been studied. M. abscessus is a rapid-growing and most chemotherapy-resistant bacterium, causing localized soft tissue infections, pulmonary disease and disseminated infections. To investigate whether Lsr2 plays the same role in M. abscessus as in other mycobacteria, the Δlsr2 mutant strain was generated by recombineering (recombination-mediated genetic engineering) method. It was discovered that lsr2 is required for the formation of pellicle, a kind of biofilm covered on the liquid surface. It was known that some mycolic acid-biosynthesis associated genes were associated with biofilm formation in M. smegmatis. To investigate whether Lsr2 affects the expression of these genes, qRT-PCR assay was performed to quantify the RNA level of lsr2 and these genes in wild type strain during pellicle formation. The results revealed that the expression of these tested genes was increased, which was correlated to the result that all the mycolic acid-biosynthesis associated genes were down regulated in Δlsr2 mutant. Taken together of these results, it was postulated that Lsr2 might affect the expression of mycolic acid-biosynthesis associated genes, in turn regulating the biofilm formation. Since the lsr2 positively affected the expression of the biofilm-associated genes that are involved in the biosynthesis (kasA, kasB, groEL1, inhA, and mmaA4) and the transport (mmpL11) of mycolic acid, the lipid profiles of the wild type, Δlsr2 mutant, and complement strain were analyzed by thin layer chromatography (TLC) and MALDI-TOF. No difference of lipid profile was observed among these tested bacteria by TLC analysis, but MALDI-TOF analysis revealed that the Δlsr2 mutant had different peaks at 1002 ~ 1131 (Region 1) m/z and 1200 ~1273 (Region 2) m/z. This result indicated that the lsr2 indeed affected the production of lipid composition in M. abscessus. In addition, it was found that deletion of lsr2 reduced the H2O2 tolerance and tetracycline-class antibiotic resistance of M. abscessus. Since the Δlsr2 mutant was more sensitive to all tetracycline-class antibiotics, it was postulated that these antibiotics might be accumulated in Δlsr2 mutant. The tetracycline fluorescence assay confirmed this hypothesis. To test whether this accumulation was due to the function of efflux pump inhibited in the absence of lsr2, the efflux pump inhibitor CCCP was added with tetracycline for MIC test. The result showed that CCCP indeed reduced the MIC of tetracycline for these strains in the same degree, indicating that Lsr2 did affect the efflux pump that was inhibited by CCCP. Besides, the CCCP non-related gene mab_1409c, a putative drug antiporter precursor was also investigated for its association with lsr2. The result demonstrated that the expression of mab_1409c was decreased in Δlsr2 mutant, indicating that lsr2 maintain the gene expression of this putative efflux pump. To the best of our knowledge, this is the first report indicating that lsr2 contributed to tetracycline resistance and the involved mechanism in mycobacteria. In conclusion, this study demonstrates that lrs2 is an important modulator that mediates many biological functions in M. abscessus.
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Bozikian, George. "CICS LSR buffer simulator (CLBS)." Thesis, 1990. http://spectrum.library.concordia.ca/2713/1/MM59181.pdf.