Dissertationen: „LRHS“

1

Borba, Maira de Souza. „Descartes e o ceticismo: o estatuto da dúvida na filosofia cartesiana“. Universidade Federal de Minas Gerais, 2011. http://hdl.handle.net/1843/LRMS-8SNH8N.

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The object of this dissertation is to analyse the concept of doubt in Descartes, in order to elucidate the roots of its constitution and determine the role played by scepticism in this process. By comparing Descartes with the sceptics, one can conclude that he was influencedmostly by the modern philosophers, his contemporaries (Montaigne, Charron, La Mothe Le Vayer) and that, as to the ancient scepticism, the most important is the distinction between academic and Pyrronian scepticism, which is vital to comprehend the philosopher. Theanalysis of Popkins theory, which is central when trying to determine the role played by skepticism in Descartes philosophy, reveals that there is not enough evidence to validate the idea that Descartes primary aim was to refute scepticism. Nevertheless, one should not underestimate the place occupied by scepticism in Descartes philosophy, for his doubt must be seen as an important step in the search for the truth. It is necessary to point out the fact that scepticism influenced Descartes both in a positive and a negative way. It is by leaving aside one of these aspects that most of the philosophers commentators present radical orinsufficient theories concerning the connection between Descartes and scepticism. To avoid this, one should be attentive to the distinction between academic and Pryrrhonian scepticism, since, while Pyrrhonian scepticism is refused by Descartes, many elements of academicscepticism are assimilated by him.
O objetivo dessa dissertação é analisar o estatuto da dúvida em Descartes, tendo em vista elucidar as raízes de sua constituição e determinar o papel do ceticismo nesse processo. Por meio da comparação com os céticos chega-se a conclusão de que Descartes foi influenciado principalmente pelos modernos contemporâneos a ele (Montaigne, Charron e La Mothe Le Vayer) e que, em relação ao ceticismo antigo, o mais importante é a distinção entre acadêmicos e pirrônicos, que será fundamental para a compreensão do filósofo. A análise da tese de Popkin, que se coloca como central, tendo em vista o objetivo de determinar o papel do ceticismo na filosofia cartesiana, revela que não há provas suficientes para validar a ideia de que a refutação do ceticismo seria o principal objetivo de Descartes. Todavia, o lugar do ceticismo na filosofia cartesiana não pode ser menosprezado, pois a dúvida deve ser vista como um passo necessário na busca da verdade. Há que se destacar o fato de que o ceticismo deve ser visto como exercendo uma influência tanto negativa, quanto positiva em Descartes. É por deixar de lado um, ou outro, desses aspectos que a maioria dos comentadores do filósofo apresenta teorias radicais ou insuficientes a respeito da relação entre Descartes e o ceticismo. Para se escapar a isso se deve atentar para a distinção entre ceticismo acadêmico e pirrônico, pois enquanto o ceticismo pirrônico é recusado por Descartes, muitos dos elementos do ceticismo acadêmico são assimilados por ele.

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2

Kurth, Naëmi Langenegger Corinne. „LRS-Prävention in Literatur und Praxis /“. Zürich : Hochschule für Heilpädagogik, 2009. http://www.bscw-hfh.ch/pub/bscw.cgi/d4332387/Masterarbeit.pdf.

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3

Al-Mufaraji, Moosa N. „Libraries and the development of information-handling in the educational system of Oman“. Thesis, Loughborough University, 2000. https://dspace.lboro.ac.uk/2134/36044.

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This research investigates the existing situation regarding libraries and Learning Resource Centres (LRCs) and their infrastructure in Oman, with particular reference to those institutions in the educational system. A range of issues regarding management and organisation, resources and users are explored, as well as the adoption of modem technology in these libraries and LRCs. Two models were developed for the study. The first model was prepared to show the organisational information system, while the second model examined the impact of different types of information-seeking behaviour on the use of information sources. Data have been collected both via questionnaires and interviews. The questionnaires involved the investigation of school library users (teachers and students) in preparatory and secondary schools; and academic libraries and LRC users (faculty and students) at Sultan Qaboos University, Colleges of Education and Technical Industrial Colleges. The interview questions were put to the directors and heads of libraries and LRCs. The survey focused on eleven areas: staff; budget, acquisitions, policies, co-operation, library and LRC use, resources, services, information technology, education and future development.

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4

Cojanu, Alexandru Ioan. „Intrinsic Features of the Multisensory Cortical Area LRSS in the Ferret“. VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/159.

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Environmental events simultaneously transduced by more than one sensory modality underlie multisensory processing in the CNS. While most studies of multisensory processing examine functional effects, none have evaluated the influence of local or columnar circuitry. The goal of the present study is to examine of local features of the ferret lateral rostral suprasylvian sulcus (LRSS), a multisensory cortex. Immunostaining revealed the cytoarchitectonic features of the LRSS: thick supragranular layers, a narrow layer IV, and moderately stained but differentiated infragranular layers. Golgi-Cox techniques were used with light microscopy and digital reconstruction to document neuronal morphology. Among the 90 reconstructed neurons, 4 distinct forms or pyramidal and 2 types of non-pyramidal neurons were found. Measurement of maximal dendritic spread indicates that a cortical column in the LRSS was 250.9 um in diameter. These results describe local features of the LRSS upon which future experiments of intrinsic circuitry will be based.

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5

Hagood, Elizabeth. „Multisensory Input to the Lateral Rostral Suprasylvian Sulcus (LRSS) in Ferret“. VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1743.

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For the brain to construct a comprehensive percept of the sensory world, information from the different senses must converge onto individual neurons within the central nervous system. As a consequence, how these neurons convert convergent sensory input into multisensory information is an important question facing neuroscience today. Recent physiological studies have demonstrated the presence of a robust population of multisensory neurons in the lateral bank of the rostral suprasylvian sulcus (LRSS) in adult ferret (Keniston et al, 2008). The LRSS is a region situated between somatosensory and auditory cortices, where bimodal (somatosensory-auditory) neurons occupy the greatest percentage of the sensory-responsive cell population. The present study was designed to evaluate the anatomical connections that underlie these multisensory features. Injections of neuroanatomical tracer were first made into the LRSS. After transport and histological processing, microscopy revealed retrogradely-labeled cell bodies in identified regions of cortex and thalamus. The resultant analysis showed that the greatest number of projections to LRSS originated in auditory and somatosensory cortex. Of these, auditory cortex contributed a greater proportion of inputs. These anatomical data support the idea that LRSS is a multisensory cortex that receives primarily bimodal input from auditory and somatosensory sources.

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6

Schröter, Carolin. „AVWS »meets« LRS : Erfahrungen aus der therapeutischen Praxis“. Universität Potsdam, 2013. http://opus.kobv.de/ubp/volltexte/2013/6852/.

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1 Einleitung 2 Zusammenhänge zwischen zentral-auditiven Wahrnehmungs- und Verarbeitungsstörungen (AVWS) und Beeinträchtigungen im Lesen und Schreiben 3 Therapeutische Möglichkeiten zur Behandlung von komorbiden Störungen im Lesen und Schreiben bei Kindern mit AVWS 4 Fallbeschreibung 5 Schlussfolgerung 6 Literatur

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7

Rüdell, Edith. „Lesen: 5 - Rechtschreiben: 6 schulische Fördermöglichkeiten bei LRS“. Saarbrücken VDM Verlag Dr. Müller, 2006. http://d-nb.info/989178870/04.

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8

Baltzer, Charlotte. „LR:s inställning till kommunaliseringsreformen : En idé- och ideologianalys av "Skolvärlden" 1980-2010“. Thesis, Uppsala universitet, Institutionen för pedagogik, didaktik och utbildningsstudier, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-156762.

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9

Bytautas, Kęstutis. „LRS Seimo narių grupavimas pagal balsavimą ir balsavimo kitimo aptikimas“. Master's thesis, Lithuanian Academic Libraries Network (LABT), 2012. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2012~D_20120620_112756-41462.

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Politikai įvairiai deklaruoja savo elgesį, todėl vienintelis būdas juos kontroliuoti – stebėjimas. Šiame darbe yra analizuojamas LRS darbas, susijęs su balsavimais. Stengiamasi atsakyti į klausimą: ar informacinių technologijų įrankiai gali leisti nustatyti ar Seimo narių priklausomybė partijai (frakcijai) ar pozicijai (opozicijai) lemia jų balsavimą? Pagrindiniai darbo tikslai – Seimo narių grupavimas ir balsavimo kitimo aptikimas. Apžvelgiama 2008-2012 metų Seimo kadencijos veikla, atlikta balsavimų statistinė analizė, taip pat apžvelgti kiti tyrimai, susiję su parlamentinėmis veiklomis. Seimo narių grupavimui taikome klasterizavimo metodus. Klasterizavimas gali būti apibrėžiamas kaip objektų suskirstymas į grupes (klasterius), kuriose objektų skirtumai yra kuo mažesni, o tarp grupių skirtumai - kuo didesni. Darbe apžvelgiami įvairūs klasterizavimo metodai, jų veikimo principai, aprašomi atstumų tarp objektų skaičiavimo metodai, kokybės įvertinimo kriterijai. Balsavimų duomenys saugomi MySQL duomenų bazėje, todėl sukurtas įrankis duomenų apdorojimui. Aprašomi visi darbo etapai: naudoti įrankiai, balsavimo kodavimas, balsavimų skaidymas į periodus. Tyrimams atlikti pasirinkti k-Means, hierarchiniai tolimiausio kaimyno, vidutinių atstumų, artimiausio kaimyno klasterizavimo metodai. Objektų panašumams įvertinti naudojami Euklido (ang. Euclidean) ir Manheteno (angl. Manhattan) atstumų skaičiavimo metodai. Klasterizavimo kokybės įvertinimui naudojame PURITY, RAND, NMI metodus... [toliau žr. visą tekstą]
Politicians declare their behavior in different ways, so the only way to control it - monitoring. In this thesis tools for Lithuanian Parliament Members voting behavior are analyzed. The question is following: can Information technologies tool help to determine how membership in a faction or the position (opposition) is related with voting behavior? The main objectives of this work are Lithuanian Parliament members grouping by their voting behavior and its' change detection. In the thesis the 2008-2012 of the Parliament activities are analysed using statistical voting analysis. We use clustering for grouping members of the Parliament. A loose definition of clustering could be the process of organizing objects into groups whose members are similar in some way. A cluster (group) is a collection of objects which are similar between them and are dissimilar to the objects belonging to other clusters. We overviewed different clustering methods and their principles of operation, described the distance between the objects of calculation methods, quality evaluation criteria in this work. Voting data is stored in MySQL database, hence a tool was created for data processing. We describe all the stages of the work: the use of tools, coding of the votes, division of the votes into the periods. The following techniques were chosen: K-Means, Hierarchical Clustering with Complete (furthest neighbor), Average, Single (nearest neighbor) linkage. We use Euclidean and Manhattan methods for... [to full text]

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10

Lehnen, Daniela. „LrhA als Regulator der Flagellen, Motilität, Chemotaxis und Typ-1-Fimbrien in Escherichia coli“. [S.l.] : [s.n.], 2002. http://ArchiMeD.uni-mainz.de/pub/2002/0162/diss.pdf.

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11

Brookes, Paul Andrew. „Synthetic studies towards novel inhibitors of Ape1/Ref1 and LRH-1“. Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/39141.

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The work described within this thesis relates to the development and identification of novel inhibitors of two recently identified chemotherapeutic targets: (i) Apurinic/Apyrimidinic Endonuclease 1-(Ape1/Ref1). The base excision repair (BER) pathway is a vital eukaryotic process that acts to recognise, process and remove damaged DNA from the genome. A critical step in BER involves the processing of an apurinic/apyrimidinic (AP) site intermediate by Ape1/Ref1. Such AP site intermediates are generated when DNA bases undergo spontaneous damage, and as such are continuously and ubiquitously being generated. Therefore, through its innate function Ape1/Ref1 offers direct protection to cells from the effects of DNA damaging agents, including commonly employed chemotherapeutics. Interestingly, Ape1/Ref1 is over-expressed in many cancers and this particularity has been shown to correlate with resistances to both radio and chemotherapy regimens. Considering this, Ape1/Ref1 has emerged as a potential chemotherapeutic target. The availability of robust X-ray crystal data allowed for the implementation of a grass roots computer-aided drug design (CADD) approach. Multiple inhibitor scaffolds were identified, designed, synthesised and biologically evaluated in vitro. Furthermore, during this project several publications emerged detailing novel inhibitors of Ape1/Ref1, investigations into these reports are detailed within. (ii) Liver Receptor Homolog-1 (LRH-1). Nuclear receptors (NRs) are ligand regulated transcription factors and have been described as nearly ideal drug targets due to their three-dimensional structure. NRs contain vast hydrophobic internal pockets that bind to hydrophobic, drug-like molecules. In the presence of a natural endogenous substrate, ligand-induced conformational changes modulate the recruitment of transcriptional regulators to gene promoters. Liver receptor homolog-1 is a NR that has recently been shown to modulate the estrogen response in breast cancers through the regulation of estrogen receptor-α (ERα) expression. Resorcylic acid lactones (RALs) were recently shown by Barrett et. al. to be capable of antagonising this receptor in the low micromolar range. Such action could possibly translate to the potential blocking of co-activator recruitment and ERα expression in vivo and therefore these compounds served as a start point for a ligand based drug discovery campaign. Additional synthetic investigations and biological developments upon these RALs are discussed and detailed within.

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12

Schwaderer, Juliane [Verfasser]. „LRH-1/NR5a2 in regulation of the immune system / Juliane Schwaderer“. Konstanz : Bibliothek der Universität Konstanz, 2017. http://d-nb.info/1140736418/34.

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13

Kramer, Holly. „The role of liver receptor homologue-1 (LRH-1) in colorectal cancer“. Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/50192.

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The development of colorectal cancer (CRC) occurs sequentially through the accumulation of genetic changes, or mutations, resulting in unrestrained cellular proliferation and survival. The genetic changes leading to CRC are well defined, with aberrant activation of the Wnt signalling pathway and loss of the tumour suppressor p53 playing key roles. This project aimed to investigate the role of the orphan nuclear receptor liver receptor homologue-1 (LRH-1) in the development of CRC. Previous work in this laboratory identified LRH-1 as an important mediator of the estrogen response in breast cancer cells. LRH-1 has also been implicated in the development of CRC, where it promotes cell cycle progression and synergises with β-catenin. Here I provide evidence for novel mutations in the DNA binding domain of LRH-1 in CRC. I found that CRC-associated LRH-1 mutations affect its ability to bind LRH-1 response elements. To better define the mechanisms of LRH-1 action in CRC, gene expression microarray analyses were performed in two CRC cell lines following siRNA-mediated LRH-1 knockdown. Several previously undescribed candidate LRH-1-regulated genes were identified and validated. While I found no evidence for crosstalk between LRH-1 and the Wnt pathway in the CRC cell lines examined, pathway analyses coupled to gene expression profiling suggested a role for LRH-1 in p53 signalling. LRH-1 silencing was shown to be associated with growth inhibition and up-regulation of the cell cycle inhibitor p21 in CRC cells. This occurs in a p53-dependent manner and was not observed in cell lines where p53 is mutated or deleted. I further demonstrated LRH-1-mediated modulation of p53 activity at the p21 promoter. Collectively, this work demonstrates a novel role for LRH-1 in the suppression of p53 signalling in CRC tumours that retain wild-type p53, and identifies LRH-1 as an important prospective target for treatment of these tumours.

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14

Lai, Chun Fui. „The role of liver receptor homologue-1 (LRH-1) in breast cancer“. Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/30730.

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Estrogens play a critical role in the development and progression of breast cancer. The biological functions of estrogen are mainly mediated by estrogen receptors (ER), which act by regulating gene expression in breast cancer cells. Previously our laboratory identified liver receptor homologue-1 (LRH-1), a member of the nuclear receptor superfamily of transcription factors to which ER also belongs, as an estrogen-responsive gene. Subsequent work showed that LRH-1 is important in mediating the growth of breast cancer cells. Herein, I show that LRH-1 in turn regulates the expression of ERα, providing a positive feedback loop, which may act to promote stable co-expression of ERα and LRH-1 in breast cancer cells. To better define the mechanisms of LRH-1 action in breast cancer cells, gene expression microarray analysis was performed following RNA interference mediated LRH-1 knockdown. Microarray analysis demonstrated that LRH-1 regulates the expression of many estrogen-responsive genes. ChIP-seq analysis, carried out to identify global LRH-1 binding sites, showed that LRH-1 is recruited to a substantial proportion of estrogen-regulated genes, frequently binding to ERα binding sites, suggesting LRH-1 directly regulates a subset of ERα-target genes in breast cancer cells. Analysis of select binding sites confirmed the direct LRH-1 regulation of ERα target genes through LRH-1 binding to estrogen response elements (ERE), as exemplified by the TFF1/pS2 gene. Moreover, LRH-1 was shown to stimulate the recruitment of ERα to the ERE in the shared/common target genes, suggesting a co-operative function between LRH-1 and ERα. Collectively, these findings show that LRH-1 is a key mediator of the estrogen response in breast cancer cells and raises the possibility of targeting LRH-1 for the treatment of breast cancer. Towards this end, I also describe the identification of novel LRH-1 antagonists that inhibit breast cancer cell growth. Development of these compounds will offer investigational tools for validating the importance of LRH-1 in breast cancer, towards a therapeutic strategy in breast cancer treatment.

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15

Kyle, Fiona. „LRH-1 as a target for the development of new breast cancer therapies“. Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/55285.

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Estrogen drives the growth and development of estrogen receptor alpha (ERα) positive breast cancer and ERα is the target for hormonal therapies that inhibit its activity. A substantial proportion of patients become resistant to these therapies, demonstrating a need for new therapies. Gene expression microarray studies have been performed with a view to identifying potential novel therapeutic targets, biomarkers or forming the basis of identifying a molecular signature for endocrine resistance. These studies have identified candidate genes whose expression is altered in models of endocrine resistance. Investigation of the molecular pathways particularly highlights cell survival and regulation of apoptosis and indicates that these pathways play a key role in the development of resistance. Microarray analysis also identified the liver receptor homolog 1 (LRH-1, NR5A2), a member of the nuclear receptor superfamily of transcription factors, as an estrogen regulated gene in MCF7 cells. Functional analysis showed that LRH-1 regulates breast cancer cell growth, acting in part by regulating ERα expression. Gene expression profiling of MCF-7 cells following RNAi for LRH-1 identified LRH-1 regulated genes. LRH-1 is known to regulate expression of CYP19A1 (aromatase), responsible for estrogen biosynthesis through the aromatisation of aromatase. Together, our findings identify LRH-1 as a potential therapeutic target for breast cancer treatment. Results of screening for small molecule inhibitors of LRH-1 will be presented, together with analysis of gene expression profiling for LRH-1 regulated genes.

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16

Thiruchelvam, Paul. „LRH-1 as a key regulator of estrogen responses in breast cancer cells“. Thesis, Imperial College London, 2010. http://hdl.handle.net/10044/1/10685.

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Liver receptor homolog-1 (LRH-1; NR5A2) is an orphan member of the Ftz-F1 family of nuclear receptors, which comprises four members (NR5A1-NR5A4). LRH- 1 has been linked to a number of key developmental, metabolic and proliferative processes and is known to play an important role in the regulation of cholesterol biosynthesis, lipid homeostasis and the control of steroid aromatisation. In this respect, LRH-1 is recognised to play an important role in breast cancer, where it acts to regulate aromatase activity, leading to the paracrine production of estrogen. Recent findings have also suggested a direct role for LRH-1 in cancer, where LRH-1 is found to be involved in the induction of intestinal tumours and LRH-1 has been found by immunohistochemistry in tumour cells of human mammary ductal carcinomas. Recently, a gene expression microarray analysis of estrogen responses in an engineered breast cancer cell line, where Estrogen Receptor-α (ERα) activity can be conditionally repressed, provisionally identified LRH-1 as an estrogen responsive gene that may be important in the estrogen-regulated growth of breast cancer cells. Based on this initial observation, I have gone on to study the role of LRH-1 in the estrogen response in breast cancer cells. Using ERα-positive breast cancer cell lines, I have confirmed that LRH-1 levels increase in response to estrogen and are inhibited by anti-estrogens (tamoxifen and ICI 182,780). Using 5`RNA Ligase Mediated Rapid Amplification of cDNA Ends (5`RLM-RACE) to characterise the 5’ end of the LRH-1 mRNA, I have found that the estrogen regulation of LRH-1 is mediated through a previously undescribed gene promoter, which results in the production of a variant LRH-1 mRNA species that initiates transcription just upstream of exon 2 of the LRH-1 gene. Further, reverse transcriptase polymerase chain reaction (RT-PCR) showed that the newly identified variant LRH-1 transcript is expressed in tissues in which LRH-1 expression has previously been described. Moreover, this variant was seen to be the major form of LRH-1 expressed in breast cancer cell lines. Having established the estrogen regulation of LRH-1, studies were carried out to investigate the role of LRH-1 in growth and gene expression in breast cancer cells. siRNA-mediated inhibition of LRH-1 expression inhibited proliferation of MCF-7, ZR-75-1 and T47-D breast cancer cell lines but did not inhibit BT474 and MDAMB- 231 breast cancer cells, in which LRH-1 is not expressed. Further, a group of recently described synthetic agonists for LRH-1 stimulated the growth of breast cancer cell lines expressing LRH-1 in a dose dependent manner, but did not stimulate growth in those breast cancer cell lines which do not express LRH-1. Finally, RNA interference experiments directed against LRH-1 identified ERα as an important LRH-1 regulated gene. These results show that LRH-1 potentially plays a key role in regulating estrogen responses in ERα–positive breast cancer cells, primarily through the direct regulation of ERα gene expression. These new findings, taken together with the previously described role for LRH-1 in regulating aromatase gene expression identify LRH-1 as a potentially important target for the development of new therapies for the treatment of breast cancer.

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17

Zhao, Jing. „Protein Kinases can differentially regulate transactivation activities of hLRH-1 through the modulation of cofactors interactions“. Kent State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=kent1271686070.

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18

Mueller, Melanie. „Towards the development of modulators of LRH-1 as potential anti-cancer therapeutic leads“. Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/29112.

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Breast cancer is the most common cancer in women worldwide and afflicts about 30 % of all women between 35 and 50 years. The majority of breast cancers are estrogen dependent. This means that they need estrogen for their development and growth. Estrogen dependent breast cancers can be treated with hormone therapy to block estrogen action and prevent cancer growth. Unfortunately, there are many side effects associated with this treatment and therefore, there is a great need for the development of new therapies for breast cancer. Liver receptor homologe-1 (LRH-1) is a nuclear receptor that recently came into focus for its implications in breast cancer development and growth. Targeting LRH-1 could present an alternative approach for the treatment of breast cancer. There are two potential sites to target nuclear receptors: the ligand binding pocket or the co-activator binding site. Both sites are known to be crucial for the transcriptional activity of nuclear receptors. This thesis gives an overview about breast cancer and the role of nuclear receptors in this disease. In particular, approaches to the regulation of nuclear receptors using small molecule antagonists are discussed both in terms of traditional 'ligand binding pocket' inhibitors and the more recently explored 'co-activator binding inhibitors'. Both approaches are explained generally and in the context of LRH-1. The work described here is divided into two parts: The first part describes the synthesis and evaluation of a library of benzimidazole-based potential antagonists of LRH-1. These molecules are expected to bind into the ligand binding pocket and act as traditional antagonists. The second part of this thesis explains the synthesis of an α-helix mimetic. A previous PhD student in the group developed a route for the synthesis of an α-helix mimetic. The mimetic targeted here was anticipated to bind competitively to the co-activator binding site of LRH-1 and prevents co-activators from binding and consequently blocks transcriptional activity.

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Semrén, Philip. „On the Interaction Between Electromagnetic, Gravitational, and Plasma Related Perturbations on LRS Class II Spacetimes“. Thesis, Umeå universitet, Institutionen för fysik, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-184078.

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In this thesis, we investigate the interaction between electromagnetic, gravitational, and plasma related perturbations on homogeneous and hypersurface orthogonal Locally Rotationally Symmetric (LRS) class II spacetimes. By using these spacetimes, which allow for the inclusion of a non-zero magnetic field, as backgrounds in a perturbative approach, we are able to see interactions between the electromagnetic and gravitational variables already to first order in the perturbations. This is in contrast to earlier works using isotropic Friedmann-Lemaı̂tre-Robertson-Walker (FLRW) backgrounds, where one is usually faced with going to second order in the perturbations. To get the equations governing our perturbations, we use a 1+1+2 covariant approach and gather relations from the Ricci and Bianchi identities, Maxwell’s equations, particle conservation, and energy-momentum conservation for the individual plasma components. After linearising these equations around a LRS background, performing a harmonic decomposition, and using the Magnetohydrodynamic (MHD) approximation for a cold plasma, we then arrive at a closed system for the first order perturbations. This system, consisting of ordinary differential equations in time and a set of constraints, is then reduced to two separate subsectors, containing seven and nine variables respectively. These variables include quantities related to the Weyl tensor, the vorticity, and the electromagnetic fields, as well as perturbations in the plasma velocity and energy density. Through numerical calculations, we use the equations for these variables to show that perturbations in the magnetic field can be sourced by perturbations in both the plasma velocity and the gravitational variables. We also observe beat-like interference patterns for large values of the Alfvén velocity. These results can be of interest when considering the large scale cosmic magnetic fields, as their origin still seems to elude us. However, since we neglect thermal pressures and dissipative fluxes, it should be noted that our results are mainly applicable in the limit of low temperature and in cases where the thermal pressure is smaller than the pressure due to the electromagnetic fields.

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20

Seitz, Carina [Verfasser]. „Role of the nuclear receptor LRH-1 in T cell development and function / Carina Seitz“. Konstanz : KOPS Universität Konstanz, 2018. http://d-nb.info/1209055694/34.

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21

França, Mônica Malheiros. „O papel do fator de transcrição POD-1 na regulação de SF-1 e LRH-1 em células tumorais da suprarrenal humana“. Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-03062014-162141/.

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SF-1 e LRH-1 são fatores de transcrição que exercem um papel fundamental na produção de esteroides nas gônadas e na suprarrenal, além de estarem envolvidos no processo tumorigênico desses órgãos. Por outro lado, POD-1 apresenta menor expressão em carcinomas adrenocorticais, e parece regular Sf-1. Nesse trabalho foi analisado o papel de POD-1 na regulação de SF-1 e de LRH-1 em células de tumores adrenocorticais. A hiperexpressão de POD-1 resultou em redução da expressão SF-1/SF-1. Em contraste, houve um aumento da expressão gênica de LRH-1, devido à diminuição da expressão de SHP, um regulador negativo de LRH-1. Nas células transfectadas com siRNA-POD-1, os níveis de POD-1 foram reduzidos e de SF-1 aumentado, reforçando o mecanismo regulatório entre os fatores. No ChIP assay, POD-1 se ligou a sequência E-box do promotor de SF-1. Por outro lado, não foi caracterizado a ligação de POD-1 no promotor LRH-1, embora POD-1 tenha se ligado ao E-box do promotor SHP. A redução de SF-1 diminuiu a expressão de StAR, mas não modulou a proliferação das células tumorais. Em resumo, POD-1 pode ter um papel mais amplo como regulador da transcrição de fatores que controlam o processo tumorigênico, e é um candidato a gene supressor de tumor nas células adrenocorticais.
SF-1 and LRH-1 have played a critical role in steroid production, adrenal and gonads. Moreover, there are evidences that they have acted in tumorigenesis process in these organs. POD-1 is downregulated in adrenocortical carcinoma (ACC) it seems to regulate Sf-1. In this work, it has been to analyse the role of POD-1 in SF-1 and LRH-1 regulation in adrenocortical tumor cells. The POD-1 overexpression has reduced SF-1/SF-1 expression. However, there was an increase of LRH-1 gene expression due to SHP expression decrease which is negative regulate of LRH-1. The POD-1 and SF-1 gene expression in transfected cells with siRNA-POD-1 has shown POD-1 decrease and SF-1 increase emphasizing a regulatory mechanism between POD-1 and SF-1. By ChIP assay it was shown that POD-1 binded in SF-1 promoter E-box sequence. It was not characterized that POD-1 binded in LRH-1 promoter, although POD-1 can bind in SHP promoter E-box sequence. The reduction of SF-1 expression by POD-1 has decreased the StAR expression, however, it was not enough to change tumor cell proliferation. In summary, POD-1 must have a wider role as regulator of fator transcription which controls tumorigenese process being a possible candidate as tumor supressor gene in adrenocortical cells.

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Costa, Mariana Amalia Figueiredo. „Proteção induzida pela imunização de camundongos BALB/c com proteínas ribossomais de Leishmania (LRPs) contra a infecção com L. chagasi“. Universidade Federal de Minas Gerais, 2010. http://hdl.handle.net/1843/UCSD-8H7K4N.

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Visceral leishmaniasis is a disease caused by obligate intracellular protozoa of the Leishmania (Ross, 1903) genus, which are found in countries of the Old World and in the Americas. It is a severe disease and can lead to death if not treated. The acquisition of immunity after cure of infection caused by L. major culminates in protection against re-infection by the parasite, indicating the possibility of developing a vaccine against the disease. In this study, immunization with Leishmania ribosomal proteins (LRPS), isolated from the species L. infantum, associated with the saponin adjuvant was able to induce a Th1 cellular immune response observed by the high production of IFN-, IL-12p70, GM-CSF and antibody isotype IgG2a, specific for the LRPs. It was observed that the immune response was able to induce protection in animals against L. chagasi infection, verified by the parasite burden reduction in spleen and liver of the immunized animals compared to control groups (saline and saponin). Protection was related to high production of IFN-, IL-12p70 and GM-CSF and low production of IL-4 and IL-10, and IFN- production was IL-12-dependent and mainly from lymphocytes CD4+ , CD8+ and natural killer cells. Therefore, the LRPs, as proteins highly conserved among different species of Leishmania sp., can constitute a candidate to form a pan-Leishmania vaccine.
A leishmaniose visceral é uma doença causada por protozoários intracelulares obrigatórios do gênero Leishmania (Ross, 1903), que são encontrados em países do Velho Mundo e nas Américas. É uma doença grave e que pode levar à morte, se não tratada. A aquisição de imunidade após a cura da infecção causada por L. major culmina na proteção contra a re-infecção pelo parasito, indicando a possibilidade do desenvolvimento de uma vacina contra a doença. Neste trabalho, a imunização com proteínas ribossomais de Leishmania (LRPs), isoladas da espécie L. infantum, associadas ao adjuvante saponina, foi capaz de induzir uma resposta imune celular do tipo Th1, observada pela produção elevada de IFN-, IL-12p70, GM-CSF e de anticorpos do isotipo IgG2a, específicos às LRPs. Observou-se que essa resposta imune foi capaz de induzir proteção nos animais contra a infecção com L. chagasi, verificada pela redução significativa da carga parasitária no baço e fígado dos animais imunizados, quando comparados aos grupos controle (salina e saponina). A proteção foi relacionada com a produção elevada de IFN-, IL-12p70 e GM-CSF e à baixa produção de IL-4 e IL-10, sendo a produção de IFN- dependente de IL-12 e proveniente principalmente de linfócitos T CD4+ , CD8+ e células natural killer. Portanto, as LRPs, como proteínas altamente conservadas entre as diferentes espécies de Leishmania sp., podem se constituir em candidatas para compor uma vacina pan-Leishmania.

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Semrén, Philip. „Dissipative Perturbations on LRS Class II Cosmologies Using the 1+1+2 Covariant Split of Spacetime“. Thesis, Umeå universitet, Institutionen för fysik, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-176037.

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By including dissipative fluxes in the description, this thesis extends previous results regarding first order perturbations on homogeneous and hypersurface orthogonal locally rotationally symmetric (LRS) class II cosmologies using the 1 + 1 + 2 covariant split of spacetime. Whereas previous works consider perturbations of perfect fluid type, perturbations pertaining to heat flux and fluid viscosity are here studied with the aim to ascertain their effect on the evolution of the fluid vorticity. The studied perturbations include scalar, vector, and tensor modes, and are harmonically decomposed to yield a system of ordinary differential equations. These equations, originating from the Bianchi identities, the Ricci identities for certain preferred vector fields, and the thermodynamic Eckart theory, then decouple into two independent systems. These separately closed systems, with four and eight remaining variables respectively, describe the evolution of perturbations pertaining to the Weyl tensor and the fluid shear, vorticity, heat flow, energy density, and number density. From the final system of equations it is seen that the inclusion of heat flux and fluid viscosity has the possibility to yield mechanisms for generating vorticity, even if this vorticity vanishes initially. This is in contrast to the case of barotropic perfect fluids, for which it can be shown that vorticity perturbations cannot be generated. The validity of the results presented here can be questioned, as the Eckart theory, which violates causality, is employed to describe the detailed thermodynamic properties of the fluid. However, on time scales much larger than the relaxation times of the fluid, it should still provide a decent description of the dissipative phenomena, provided that certain couplings between the dissipative fluxes can be neglected.

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Barnouin, Romain. „Étude des fonctions du récepteur nucléaire Liver Receptor Homolog-1 (Lrh-1) dans le système nerveux central“. Université Louis Pasteur (Strasbourg) (1971-2008), 2007. https://publication-theses.unistra.fr/restreint/theses_doctorat/2007/BARNOUIN_Romain_2007.pdf.

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Le liver receptor homolog-1 (Lrh-1, Nr5a2) appartient à la famille des récepteurs nucléaires. L’objectif de ce doctorat a été de comprendre les fonctions de Lrh-1 dans les différentes régions du système nerveux murin. Lrh-1 est détecté dans la moelle épinière ventrale et les ganglions sensitifs des nerfs spinaux (DRG) pendant le développement. Chez la souris adulte, Lrh-1 est exprimé dans plusieurs régions du cerveau, en particulier dans le noyau arqué de l’hypothalamus. Implication de Lrh-1 dans le développement du réseau neuronal de la moelle épinière ventrale et des DRG. Lrh-1 est exprimé dans une sous-population d’interneurones de la moelle épinière ventrale et des DRG. Ces neurones appartiennent au réseau locomoteur et proprioceptif. L’absence de Lrh-1 conduit à des défauts proprioceptifs par la réduction des fibres afférentes des DRG vers la moelle épinière ventrale. De plus, l’expression de plusieurs protéines de guidance axonale est modifiée chez les souris mutantes, pouvant contribuer au phénotype. Les fonctions de Lrh-1 dans le noyau arqué de l’hypothalamus : Lrh-1 est exprimé dans une sous-population de neurones exprimant les neuropeptides Pomc et Agrp. L’invalidation de Lrh-1 dans ces neurones conduit à la modification du profil transcriptionnel de l’hypothalamus, en particulier les gènes de l’homéostasie énergétique. De plus le niveau de leptine circulante et de l’expression du gène de la leptine au niveau du tissu adipeux. Nous avons également montré que l’expression de gènes de la signalisation associée au stress est également modifiée. De plus, en situation de stress, les souris mutantes pour Lrh-1 ne parviennent pas à réguler leur taux de corticostérone
Liver receptor homolog-1 (Lrh-1, Nr5a2) belongs to the family of the nuclear receptors. The objective of this PhD was to understand the functions of Lrh-1 in the various areas of the murine nervous system where it is expressed. Lrh-1 is detected in the ventral spinal cord and the dorsal root ganglia (DRG) during the development. In the adult mouse, Lrh-1 is expressed in several areas of the brain, in particular in the arcuate nucleus of the hypothalamus. Fonctions of Lrh-1 in the development of the neural network of the ventral spinal cord and the DRG. Lrh-1 is expressed in a sub-population of interneurons of the ventral spinal cord and DRG. These neurons belong to the locomotor and proprioceptive network. The absence of Lrh-1 leads to defects of proprioception by the reduction of related fibers of the DRG towards the ventral spinal cord. Moreover, the expression of several proteins of axonal guidance is modified in the mutant mice and could contribute to the phenotype. Functions of Lrh-1 in the arcuate nucleus of the hypothalamus: Lrh-1 is expressed in a sub-population of neurons expressing the neuropeptides Pomc and Agrp. The deletion of Lrh-1 in the neurons leads to the modification of the transcriptional profile of the hypothalamus, in particular the genes involved in energy and stress homeostasis. These alterations in genes expression are associated with impaired leptin production and glucocorticoids homeostasis, indicating that, in mice that lack Lrh-1 specifically in the CNS, several adaptive mechanisms to maintain homeostasis are severely disrupted

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Barnouin, Romain Auwerx Johan. „Étude des fonctions du récepteur nucléaire Liver Receptor Homolog-1 (Lrh-1) dans le système nerveux central“. Strasbourg : Université de Strasbourg, 2009. http://eprints-scd-ulp.u-strasbg.fr:8080/00001140.

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Magnier, Benjamin. „Rôle du récepteur nucléaire Liver Receptor Homolog-1 (LRH-1) dans l’homéostasie du cholestérol et des acides biliaires“. Université Louis Pasteur (Strasbourg) (1971-2008), 2007. https://publication-theses.unistra.fr/restreint/theses_doctorat/2007/MAGNIER_Benjamin_2007.pdf.

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Le but de notre étude a tout d’abord été d’évaluer le rôle in vivo du récepteur nucléaire Liver Receptor Homolog 1 (LRH-1) dans la régulation du transport inverse du cholestérol et du métabolisme des acides biliaires. Pour cela, nous avons généré des souris dont le gène LRH-1 est invalidé de manière spatio-temporelle. Ces souris présentent une réduction drastique de la synthèse de l’acide cholique engendrant une profonde modification qualitative du pool d’acides biliaires, ce qui modifie les caractéristiques physico-chimique de la bile et résulte en une malabsorption des lipides. Ainsi, cette étude démontre le rôle essentiel de LRH-1 dans le maintien de l’absorption intestinale des lipides. La seconde étape de ce travail a consister à étudier les conséquences de l’absence de LRH-1 sur le transcriptôme hépatique. Nos résultats suggèrent un rôle potentiel de LRH-1 dans la régulation du métabolisme des acides gras ainsi que dans la régulation de la cascade du complément
The goal of this work was to evaluate the in vivo role of the nuclear receptor Liver receptor homolog 1 (LRH-1) in the control of cholesterol and bile acid homeostasis. To this end, a mouse model in which the LRH-1 gene is specifically deleted in the hepatocytes was generated. These mice show a massive reduction of CYP8B1 and fail to produce cholic acid. In addition, we also show that the profound remodeling of the BA composition reduces significantly the efficacy of intestinal absorption of lipids and re-uptake of BAs and facilitates the removal of lipids from the body. Our studies hence unequivocally demonstrate a pivotal role for LRH-1 in determining the composition of BAs, which, in turn, has major consequences on the whole body lipid homeostasis. The second step of this work was to study the impact of the absence of LRH-1 on the hepatic transcriptome. The preliminary outcome of this study is suggestive for a predominant role of LRH-1 in both lipid metabolism and immune defense

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Magnier, Benjamin Auwerx Johan. „Rôle du récepteur nucléaire Liver Receptor Homolog-1 (LRH-1) dans l'homéostasie du cholestérol et des acides biliaires“. Strasbourg : Université de Strasbourg, 2009. http://eprints-scd-ulp.u-strasbg.fr:8080/00001130.

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Thèse de doctorat : Sciences du Vivant. Aspects moléculaires et cellulaires de la Biologie : Strasbourg 1 : 2007.
Thèse soutenue sur un ensemble de travaux. Titre provenant de l'écran-titre. Bibliogr. 21 p.

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Williams, Jolin Shan. „Dynamics of Discrete Irregular Cosmological Models“. Thesis, Stockholms universitet, Fysikum, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-110841.

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This thesis investigates the dynamics of a set of 8-600 Schwarzschild masses, randomly distributed inside cells which tessellate a 3-sphere. Furthermore the contents of each cell are mirror images of its neighbor. This symmetry give rise to a locally rotationally symmetric (LRS) curve, along which the Einstein field equations governing dynamics can be exactly integrated. The result is an irregular model consisting of discrete matter content, but where the dynamics is easy to calculate. We see that these local inhomogeneities will cause behavior deviating from the spherical dust-filled FLRW model. For instance, there are cases where configurations exhibit acceleration along the LRS curve, even though the content consists solely of ordinary matter with a vacuum filled exterior and no cosmological constant.
Denna avhandling undersöker konfigurationer av 8-600 Schwarzschild-massor, som är slumpmässigt utplacerade inom celler som tessellerar en 3-sfär. Utöver det är även innehållet i varje cell en spegelbild av granncellen. Denna symmetri ger upphov till en lokalt rotationssymmetrisk (LRS) kurva där Einsteins fältekvationer som beskriver dynamiken längs med är exakt integrerbara. Resultatet är en oregelbunden modell som består av diskreta massor, men vars dynamik är enkel att beräkna. Vi ser att dessa lokala inhomogeniteter ger upphov till beteenden som avviker från den sfäriska partikel-fyllda FLRW-modellen. Till exempel uppstår konfigurationer som uppvisar acceleration längs med LRS-kurvan, trots att innehållet består endast av ordinära massor med vakuum utanför och ingen kosmologisk konstant.

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Annicotte, Jean-Sébastien. „Etude de fonctions pancréatiques du récepteur nucléaire orphelin Liver Receptor Homolog-1 (LRH-1) et du facteur de transcription E2F1“. Université Louis Pasteur (Strasbourg) (1971-2008), 2004. https://publication-theses.unistra.fr/public/theses_doctorat/2004/ANNICOTTE_Jean-Sebastien_2004.pdf.

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Le pancréas est un organe essentiel à la digestion et à l'homéostasie du glucose. Un dysfonctionnement du pancréas résulte en de nombreuses pathologies comme le diabète, la pancréatite et le cancer. De nombreuses avancées ont été effectuées dans l'étude du développement du pancréas, identifiant de nombreux facteurs de transcription et des voies de signalisation primordiales pour la différenciation des différents types cellulaires pancréatiques. Le pancréas possède une fonction exocrine, impliquée dans la libération d'enzymes au niveau du tube digestif, et une fonction endocrine, permettant la synthèse d'hormones libérées dans le sang et régulant l'utilisation du glucose par les tissus. Le pancréas exocrine est constitué par les cellules acineuses qui produisent des enzymes de digestion (amylase, elastase, protease, nuclease, etc) et les cellules ductales qui transportent ces enzymes vers l'intestin. L'unité fonctionnelle du pancréas endocrine est représentée par les îlots de Langerhans, disséminés dans le pancréas exocrine, et constituée de 4 types cellulaires, les cellules a, b, d et PP. Les cellules b productrices d'insuline représentent la majorité de la population des cellules endocrine, et constituent le noyau de l'îlot, alors que les cellules a, d et PP sécrètent le glucagon, la somatostatine et le polypeptide pancréatique, respectivement, et sont localisées à la périphérie de l'îlot. L'organogénèse du pancréas implique l'induction d'une cascade de signaux extra-cellulaire ainsi que l'activation de facteurs de transcription spécifiques du pancréas. Au cours du développement, le pancréas prend naissance au niveau de l'endoderme après invagination de cellules épithéliales, formant d'abord un bourgeon dorsal, puis un bourgeon ventral. Ces bourgeons vont ensuite proliférer et fusionner pour former un organe pleinement fonctionnel. Au cours de ce processus, il semble que les cellules endocrines et exocrines proviennent de cellules progénitrices pluripotentes dérivant de l'endoderme. Ainsi, la détermination des mécanismes impliqués dans la différenciation pancréatique pourrait constituer une voie thérapeutique dans le traitement de maladies liées au dysfonctionnement pancréatique. Le LRH-1 (Liver Receptor Homolog-1) est un récepteur nucléaire orphelin de la sous-famille Ftz-F1. Chez l'adulte, cette protéine est fortement exprimée dans le pancréas exocrine et plus faiblement dans le foie et l'intestin, et joue un rôle crucial dans le métabolisme du cholestérol. De plus, LRH-1 semble posséder des fonctions importantes dans le contrôle de l'expression de gènes impliqués dans le développement hépatique et pancréatique. Cependant, la contribution et la fonction de LRH-1 dans le pancréas reste inconnue. Le but de ce travail était donc d'étudier la régulation transcriptionnelle de LRH-1 au cours du développement pancréatique. [. . . ]
The liver receptor homolog 1 (LRH-1) and the pancreatic-duodenal homeobox-1 (PDX-1) are coexpressed in the pancreas during mouse embryonic development. Analysis of the regulatory region of the human LRH-1 gene demonstrates the presence of three functional binding sites for PDX-1. Electromobility shift assays and chromatin immunoprecipitation analysis show that PDX-1 binds to the LRH-1 promoter, both in cultured cells in vitro and during pancreatic development in vivo. Retroviral expression of PDX-1 in pancreatic cells induces the transcription of LRH-1, whereas reduced PDX-1 levels by RNA interference attenuate its expression. Consistent with a direct regulation of LRH-1 expression by PDX-1, PDX-1-/- mice expressed lower amounts of LRH-1 mRNA in the embryonic pancreas. Taken together, our data indicate that PDX-1 controls LRH-1 expression and identify LRH-1 as a novel downstream target in the PDX-1 regulatory cascade governing pancreatic development, differentiation and function. We evaluated the effects of E2F1 on glucose homeostasis using E2F1-/- mice. E2F1-/- mice show an overall reduction in pancreatic size, as the result of impaired postnatal pancreatic growth. These animals furthermore have dysfunctional b-cells, linked to impaired PDX-1 activity. Because of the disproportionate small pancreas and dysfunctional islets, E2F1-/- mice secrete insufficient amounts of insulin in response to a glucose load, resulting in glucose intolerance. Despite this glucose intolerance, E2F1-/- mice do not develop overt diabetes mellitus because they are insulin hypersensitive, secondary to a diminished adipose tissue mass and altered adipocytokine levels, which compensates for the defect in insulin secretion. These data demonstrate that factors controlling cell proliferation, such as E2F1, determine pancreatic growth and function, subsequently affecting metabolic homeostasis

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Weißmann, Katja [Verfasser], Bernhard [Akademischer Betreuer] Blanz, Marcus [Akademischer Betreuer] Wilke und Christian [Akademischer Betreuer] Gaser. „Hirnmorphologische Unterschiede zwischen Kindern, Jugendlichen, Erwachsenen mit Lese-Rechtschreibstörung (LRS) und Kontrollprobanden / Katja Weißmann. Gutachter: Bernhard Blanz ; Marcus Wilke ; Christian Gaser“. Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2013. http://d-nb.info/1036873137/34.

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Van, Ghelder Cyril. „Le locus de résistance Ma des Prunus vis-à-vis des nématodes à galles : Originalité structurale et évolution dans la famille des NBS-LRRs chez les plantes“. Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2019. http://www.theses.fr/2019AZUR6006.

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Les nématodes à galles, Meloidogyne spp., sont des ravageurs extrêmement polyphages qui, à l’échelle mondiale, occasionnent de graves dommages aux plantes. La résistance génétique spécifique des plantes aux maladies et ravageurs s’appuie principalement sur les gènes de la famille des récepteurs NBS-LRR (ou NLRs), regroupant les TNLs, CNLs et RNLs. Chez les Prunus, le gène Ma du prunier appartient à la sous-famille des TNLs et confère une résistance à toutes les espèces de Meloidogyne testées, alors que le gène RMja de l’amandier exprime un spectre de résistance (R) plus restreint vis-à-vis de ces ravageurs. De plus, la protéine Ma présente une région C-terminale particulière constituée de cinq domaines répétés, désignés domaines post-LRR (PLs). Notre travail de thèse a caractérisé l’originalité et la distribution de cette région à travers de nombreux protéomes de plantes et a identifié la relation génétique entre les gènes Ma et RMja.Nous avons tout d’abord étudié la fréquence, la distribution et les caractéristiques structurales des gènes TNL et des domaines PL dans le génome du pêcher, génome de référence des Rosaceae. Les domaines PL, retrouvés chez les deux tiers des 195 TNLs identifiés, nous ont permis d’établir des signatures améliorant la détection de ce domaine, jusqu’alors peu étudié, dans divers génomes d’Angiospermes. Nous avons pu établir que le domaine PL est spécifique aux TNLs et qu’il est retrouvé dans des proportions similaires à celle établie chez le pêcher. Par ailleurs, les TNLs disposant de domaines PL multiples sont rares chez les plantes étudiées. La structure à cinq domaines répétés est probablement unique à Ma et ses orthologues et a vraisemblablement été héritée de leur ancêtre commun dans l’ordre des Rosales. Nous avons ensuite étudié le répertoire des NBS-LRRs chez les conifères (Gymnospermes), groupe taxonomique ancien, dont les données sur cette famille de gènes étaient parcellaires. En analysant sept transcriptomes de référence, nous avons pu établir que l’arsenal des NBS-LRRs chez les conifères était large et varié mais, étonnamment, qu’aucun domaine PL précédemment défini n’y était présent. L’examen de protéomes de plantes plus anciennes a montré que seul le Ginkgo biloba portait quelques signatures PL. Ces observations suggèrent une acquisition partielle précoce du domaine chez les plantes à graines et une expansion adaptative chez les Angiospermes. En complément, nous avons montré que les conifères, tout comme les Rosaceae, possèdent de nombreux RNLs et TNLs. En étendant notre étude à diverses plantes terrestres, nous avons mis en évidence un rapport moyen de 1:10 reliant les effectifs de RNLs et de TNLs à travers les divers génomes étudiés. Nous avons finalement conduit une cartographie haute résolution du gène RMja chez l’amandier. En nous appuyant sur une banque BAC, RMja a été localisé dans le cluster de résistance Ma et l’orthologue de Ma est de très loin le meilleur candidat. La comparaison de séquence entre les régions orthologues du locus Ma, chez le prunier (spectre R complet), l’amandier (spectre R incomplet) et le pêcher (spectre R nul) a mis en évidence une structure conservée unique des trois orthologues de Ma. Nos résultats suggèrent que le polymorphisme des répétitions du domaine PL sous-tend des interactions différentielles de résistance vis-à-vis des Meloidogyne et un mécanisme d’immunité original chez les plantes pérennes. Dans ces processus immuns de reconnaissance ou de signalisation, d’autres composants tels les RNLs pourraient être impliqués. Notre travail ouvre la voie à des approches comparative et fonctionnelle d’identification des déterminants moléculaires impliqués dans la résistance aux nématodes à galles
Root-knot nematodes (RKNs), Meloidogyne spp., are extremely polyphagous pests that severely challenge plants worldwide and especially perennials. The specific genetic resistance of plants mainly relies on NBS-LRR receptor genes (or NLRs grouping TNL, CNL and RNL subfamilies) that are pivotal factors for control of pests and pathogens. In Prunus spp., the Ma plum TNL gene confers resistance to all RKNs tested, whereas the RMja almond gene displays a more restricted spectrum of resistance (R). Moreover, the Ma predicted protein shows a peculiar TNL structure due to a C-terminal region made of five repeated domains, designated post-LRR domains (PLs). In this context, this thesis work has characterised the originality and the distribution of this uncommon structure among diverse plant proteomes and has revealed the genetic relationship between the Ma and RMja genes.We first studied the frequency, distribution and structural characteristics of TNL genes and PL domains within the peach genome, the reference genome for Rosaceae. The finding of PL domains, which have been identified in two thirds of the 195 TNLs, allowed us to define specific motifs that improve the detection of this poorly known domain in Angiosperms. We found that the PL domain is specific of TNLs and is present in Angiosperm genomes in a proportion similar to the one established for peach. Besides, TNLs displaying multiple PL domains are rare in plants. The five-PL domain pattern is probably unique to Ma and its orthologues and was probably inherited from their common ancestor in the order Rosales. We then investigated the NBS-LRR repertoire of the conifers (Gymnosperms), an ancient taxonomic group, for which the data related to this gene family are unclear. By analysing seven reference transcriptomes, we highlighted a large and diverse NBS-LRR arsenal in conifers but, surprisingly, no PL signatures have been detected. The examination of ancient plant proteomes revealed that only Ginkgo biloba displayed a few PL signatures. Our results suggest that a partial acquisition of the PL domain occurred early in seed plants and was followed by an adaptive expansion in Angiosperms. Additionally, we showed that conifers and Rosaceae have numerous RNLs and TNLs. By enlarging our study to other land plant genomes, we uncovered an average ratio of 1:10 between RNLs and TNLs numbers.We finally carried out a high-resolution mapping of the RMja gene in almond. Using a BAC library, RMja was localised into the Ma resistance cluster and the Ma orthologue is by far the best candidate. The sequence comparison between three orthologous regions of the Ma locus, i.e. plum (complete R spectrum), almond (incomplete R spectrum) and peach (null R spectrum) highlighted a unique conserved structure of the Ma orthologues. Our results suggest that the polymorphism contained in the PL-domain repeats might underlie differential resistance interactions with RKNs and an original immune mechanism in woody perennials. In these immune processes for recognition or signalling, other components such as RNLs might be involved. This work paves the way for future comparative and functional approaches aiming to unravel the molecular determinants involved in the resistance to RKNs

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Ничипорчук, Артем Олексійович. „Дослідження стандартів сумісності систем e-learning з метою створення системи дистанційного навчання ВНЗ“. ЗДІА, 2016. http://dspace.zsea.edu.ua:8080/jspui/handle/12345/5.

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При виконанні кваліфікаційної роботи було розглянуто становлення дистанційного навчання в Україні та світі, досліджено стандарти систем дистанційного навчання та їх практичне використання. За результатами дослідження було створено сховище навчальних записів, яке дає можливість зберігати дані про навчання з різних систем, а також виводити ці дані у вигляді звітів. Також був розроблений плагін для системи Moodle за допомогою якого можна під’єднати цю систему до сховища.

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Repass, Lawrence M. „Optimal stationing of radar pickets and anti-ballistic missile defenders for long range surveillance and tracking (LRS & T) and ballistic missile defense (BMD) operations“. Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 2006. http://library.nps.navy.mil/uhtbin/hyperion/06Sep%5FRepass.pdf.

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Thesis (M.S. in Operations Research)--Naval Postgraduate School, September 2006.
Thesis Advisor(s): Gerald Brown. "September 2006." Includes bibliographical references (p. 51-52). Also available in print.

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Bott, Christof. „Welches Trainingsverfahren ist zur Therapie von Kindern mit LRS am effektivsten? Auswirkungen auf die Lese- und Rechtschreibleistung und die funktionale Organisation von Sprache im Gehirn /“. [S.l. : s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975678280.

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Hoffman, Bradley R. „Evaluation of the Automated Laser Rut Measurement System Used by the Ohio Department of Transportation“. Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1321627068.

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Freudenberger, Martin [Verfasser]. „Analytische Untersuchungen plutoniumhaltiger Loesungen mittels Laser-Raman-Spektroskopie (LRS) unter besonderer Beruecksichtigung der Reaktionen Pu(IV)-Ru(III)-HNO₃ und Pu(VI)-H₂O₂ / Martin Freudenberger“. Karlsruhe : KIT-Bibliothek, 2018. http://d-nb.info/1197076743/34.

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Lefèvre, Lise. „Rôle de la polarisation M2 des macrophages dans le contrôle d'infections fongiques et parasitaires : implication des récepteurs nucléaires PPARgamma et LRH-1 et des récepteurs lectine de type C“. Toulouse 3, 2013. http://www.theses.fr/2013TOU30088.

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Les macrophages, cellules clés de la réponse immune innée, possèdent une remarquable plasticité phénotypique et fonctionnelle qui leur permet de s'adapter aux différents signaux présents dans leur microenvironnement. Parmi ces éléments, l'état inflammatoire général et métabolique de l'individu, ainsi que la présence d'agents étrangers potentiellement pathogènes vont influencer l'état de polarisation des macrophages. Dans ce travail de thèse, nous nous sommes plus particulièrement intéressés à deux types de facteurs environnementaux (i) le diabète de type 2, caractérisé par une inflammation à bas bruit et une susceptibilité accrue aux infections fongiques (ii) une infection parasitaire, la leishmaniose viscérale. Nous avons montré qu'une insulino-résistance engendrée par un régime hyperlipidique induit une polarisation inflammatoire M2b des macrophages associée à une susceptibilité accrue à une infection candidosique gastro-intestinale. Nous avons ensuite démontré que des ligands du récepteur nucléaire PPAR? orientent la polarisation M2b vers un phénotype M2a, efficace pour l'élimination de Candida albicans. Cette différenciation est caractérisée par la surexpression des récepteurs membranaires Dectine-1 et Mannose (MR), deux récepteurs lectine de type C impliqués dans l'internalisation de cette levure par le macrophage et dans la production d'intermédiaires réactifs de l'oxygène. Ce travail est publié dans PLoS One 2010 Sep 20;5(9):e12828. Doi: 10. 1371/journal. Pone. 0012828. Ainsi, approfondir les voies de signalisation conduisant à l'activation de PPARgamma présente un intérêt thérapeutique majeur. Lors de ce travail de thèse, nous nous sommes intéressés au récepteur nucléaire LRH-1, connu pour réguler l'expression d'enzymes impliquées dans la synthèse de dérivés d'acides gras, ligands potentiels de PPARgamma. Nous avons démontré l'implication de LRH-1 dans la polarisation M2. LRH-1 serait impliqué dans la production de ligands endogènes de PPARgamma et ainsi dans son activation. Nous avons également montré que les souris déficientes pour LRH-1 spécifiquement dans les macrophages présentent une susceptibilité accrue aux infections candidosiques avec des fonctions microbicides associées à la polarisation M2 altérées. Ces résultats suggèrent que LRH-1 pourrait être une nouvelle cible thérapeutique dans le traitement des infections fongiques en favorisant la production de ligands de PPARgamma et une polarisation M2 bénéfique pour l'hôte. Ce travail est actuellement en cours de soumission. Dans la deuxième partie de ce travail, nous avons étudié l'influence d'une leishmaniose viscérale sur la polarisation des macrophages. De façon originale, nous avons montré l'induction d'un phénotype M2b-like des macrophages en présence de Leishmania infantum, associé à une surexpression de trois récepteurs lectine de type C (Dectine-1, MR et SIGNR3/DC-SIGN). Nous avons également démontré que ces récepteurs influençaient le devenir de l'infection à L. Infantum. Ainsi, les récepteurs Dectine-1 et MR interviennent dans l'entrée de Leishmania dans les macrophages et la production d'intermédiaires réactifs de l'oxygène et de médiateurs inflammatoires lipidiques et cytokiniques, tels que le leucotriène B4 (LTB4) et l'interleukine 1beta, qui permettent l'élimination du parasite. Inversement, SIGNR3/DC-SIGN participe à la phagocytose de Leishmania et favorise la prolifération du parasite en inhibant l'activité microbicide des macrophages. Ce travail réalisé sur des souris invalidées pour ces récepteurs lectine a été confirmé dans des macrophages humains et mettent en évidence le rôle divergent de ces lectines de type C et des voies de signalisation qui leur sont associées dans la pathogenèse de la leishmaniose viscérale. Ce travail démontre l'importance de l'axe lectines/LTB4/LXA4 dans le contrôle de la production de médiateurs inflammatoires responsables de l'élimination des parasites, axe qui constitue donc une cible de premier ordre pour le traitement et la prévention de la leishmaniose viscérale. Ainsi, la modulation de ces facteurs cellulaires et moléculaires pourrait permettre d'orienter l'interaction Leishmania-macrophage pour le bénéfice du patient. Ce travail est publié dans Immunity, 2013, May 23;38(5):1038-49. Doi: 10. 1016/j. Immuni. 2013. 04. 010
Macrophages are key cells of the innate immune response and have phenotypic and functional plasticity which allows them to adapt to their microenvironment. Among these signals, the inflammatory and metabolic states, as well as the pathogenic agents, will influence the macrophage polarization. In this work, we focused on two environmental factors (i) the type 2 diabetes, characterized by a low grade inflammation and an increased susceptibility to fungal infections (ii) a parasitic infection, the visceral leishmaniasis. We have shown that a high fat diet induced-insulin resistance promoted an inflammatory M2b polarization of macrophages associated with an increased susceptibility to gastrointestinal candidiasis. We then demonstrated that ligands of the nuclear receptor PPARgamma shift the M2b polarization toward M2a phenotype, effective to eliminate Candida albicans. This macrophage polarization is characterized by the overexpression of Dectin-1 and Mannose (MR), two membrane macrophage C-type lectin receptors involved in the yeast internalization and in the production of reactive oxygen intermediates (ROS). This work is published in PLoS One, 2010, September 20, 5 (9): e12828. Doi: 10. 1371/journal. Pone. 0012828. Thus, the study of the signaling pathways leading to PPAR? activation could be of therapeutic interest during fungal infections. Therefore, we focused on the LRH-1 nuclear receptor, known to regulate the expression of enzymes involved in the synthesis of potential PPARgamma ligands. Here, we demonstrated for the first time the involvement of LRH-1 in the M2 macrophage polarization. Indeed, LRH-1 is implicated in the production of PPARgamma endogenous ligands and hence in its activation. We also showed that mice deficient for LRH-1 specifically in macrophages exhibit increased susceptibility to Candida albicans infection, associated with altered M2 polarization related-candidacidal functions. These results suggest that LRH-1 could be a novel therapeutic target in the treatment of fungal infections, promoting M2 polarization favorable for the host. This work is currently under submission. In the second part of this work, we studied the influence of visceral leishmaniasis on the macrophage polarization. Interestingly, we report that the macrophage response in vivo against Leishmania infantum is characterized by a M2b-like phenotype displaying a C-type lectin receptors signature composed of Dectin-1, MR and the DC-SIGN homologue SIGNR3. We also demonstrated that these receptors influenced the outcome of L. Infantum infection. Indeed, Dectin-1 and MR are involved in the L. Infantum internalization by macrophages and in the production of ROS, inflammatory bioactive lipids, and cytokines such as leukotriene B4 (LTB4) and interleukin 1beta, which enable parasite elimination. By contrast, SIGNR3/DC-SIGN favors parasite resilience through inhibition of the microbicidal functions of macrophages. Confirmation of these results in primary human macrophages highlights the divergent role for these C-type lectin receptors to the pathogenesis of Leishmania infantum. This work demonstrates the importance of lectins/LTB4/LXA4 axis in the control of the inflammatory mediator's production responsible for parasite elimination. Our findings suggest that effective modulation of these cellular and molecular factors might shift the Leishmania-macrophage interaction for the benefit of the patient. This work is published in Immunity, 2013, May 23;38(5):1038-49. Doi: 10. 1016/j. Immuni. 2013. 04. 010

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Venteclef, Nicolas. „Etude du rôle << Liver Receptor Homolog-1 >> dans la régulation de la réponse inflammatoire hépatique et dans l'homéostasie du cholestérol“. Paris 6, 2007. http://www.theses.fr/2007PA066268.

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Etude du rôle de « Liver Receptor Homolog-1 » (LRH-1 ; NR5A2) dans la régulation de la réponse inflammatoire hépatique et dans l’homéostasie du cholestérol Les récepteurs nucléaires sont des facteurs de transcription impliqués dans des processus biologiques cruciaux tels que la reproduction, le développement et la différenciation. Le « liver receptor homolog-1 » (LRH-1 ; NR5A2) est un facteur de transcription, constitutivement actif, appartenant à la famille des récepteurs nucléaires. Il est essentiellement exprimé dans les tissus d’origine endodermique tels que le foie, le pancréas et l’intestin. LRH-1 joue un rôle majeur dans le développement, la stéroïdogénèse et l’homéostasie du cholestérol via la régulation du transport réverse du cholestérol et la biosynthèse des acides biliaires. Récemment, nous avons démontré le rôle de LRH-1 dans la régulation de la réponse de phase aiguë au niveau hépatique. En effet, la sur-expression de LRH-1dans des hépatocytes résulte en l’inhibition de l’induction de l’expression d’haptoglobine et SAA par les cytokine IL1 et IL6. De plus, l’induction de la réponse inflammatoire est significativement exacerbée dans des cellules hépatiques déficientes pour LRH-1. Des études de promoteur, d’ARN interférence et de chromatine immuno-précipitation révèlent que LRH-1 régule la réponse inflammatoire d’une part en antagonisant la voie de signalisation C/EBP et d’autre part en induisant l’expression de IL-1RA (« Interleukin-1 Receptor Antagonist »). L’activité anti-inflammatoire de LRH-1 est démontrée in vivo dans les souris hétérozygote pour LRH-1. LRH-1 est décrit comme régulateur du métabolisme lipidique en contrôlant l’expression des gènes impliqués dans la régulation de la synthèse des acides biliaires et dans l’homéostasie du cholestérol. Les particules HDL sont considérées comme des particules anti-anthérogène par leur capacité à promouvoir le transport réverse du cholestérol. Des études récentes rapporte que ApoM semble important dans la formation des particules prè-HDL et dans l’efflux cholestérol induit par les particules HDL. Par ailleurs, ApoM inhibe la progression de l’athérosclérose dans les souris LDLr KO. Nous avons étudié le rôle de LRH-1 dans la régulation du gène codant ApoM. En utilisant des hépatocytes déficient pour LRH-1 ou sur exprimant LRH-1, nous avons démontré que LRH-1 régule l’expression de ApoM en se liant à un LRH-1 RE localisé dans le promoteur du gène. Nous démontrons également que le répresseur transcriptionnelle SHP inhibe l’expression de ApoM en inhibant l’activité transcriptionnelle de LRH-1 in vitro et in vivo. Les propriétés anti-inflammatoires de LRH-1 et son rôle dans l’homéostasie du cholestérol sont confirmés par la caractérisation des souris LRH-1 conditionnelles KO. L’ensemble de ces résultats démontre que LRH-1 est un régulateur physiologique de la réponse de phase aiguë et joue un rôle majeur dans le métabolisme du HDL-cholestèrol.

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Guitarra, Silvana Raquel. „Modélisation multi-échelles des mémoires de type résistives (ReRAM)“. Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0537/document.

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Un modèle de commutation de mémoires résistives (ReRAM) est présenté. Celui-ci est basé sur deux hypothèses : (1) la commutation résistive est causée par des changements qui se produisent dans la zone étroite (région active) du filament conducteur sous l'influence du champ électrique et (2) la commutation résistive est un processus stochastique, donc régi par une probabilité. La région active est représentée par un réseau de connexions verticales, chacune composée de trois éléments électriques : deux d'entre eux sont de faible résistance tandis que le troisième agit comme un disjoncteur et peut être soit de résistance faible (LR) ou élevée (HR). Dans ce modèle, le changement d'état du disjoncteur est régi par une probabilité de commutation (P$_{s}$) qui est comparée à un nombre aléatoire « p ». P$_{s}$ dépend de la chute de tension le long du disjoncteur et de la tension de seuil, V$_{set}$ ou V$_{reset}$, pour définir les processus de « set » (HR à LR) et « reset » (LR à HR). Deux mécanismes de conduction ont été envisagés : ohmique pour un état LR et pour un état de résistance élevée l'effet tunnel facilité par un piège (TAT). Le modèle a été implémenté avec le langage de programmation Python et fonctionne avec une bibliothèque C externe qui optimise les calculs et le temps de traitement. Les résultats de la simulation ont été validés avec succès en les comparant avec des courbes courant-tension (IV) mesurées sur dispositifs ReRAM réels dont l'oxyde était fait de HfO$_{2}$ et pour neuf aires différentes. La flexibilité et la facilité de mise en œuvre de ce modèle de commutation résistive en font un outil puissant pour l'étude des ReRAM
A model for the switching of resistive random-access memories (ReRAM) is presented. This model is based on two hypotheses: (1) the resistive switching is caused by changes that occur in the narrow zone (active region) of the conductive filament under the influence of the electric field and (2) the resistive switching is a stochastic process governed by a switching probability. The active region is represented by a net of vertical connections, each one composed of three electrical elements: two of them are always low resistive (LR) while the third one acts as a breaker and can be low or high resistive (HR). In the model, the change of the breaker's state is governed by a switching probability (P$_{s}$) that is compared with a random number $p$. P$_{s}$ depend on the voltage drop along the breaker and the threshold voltage, V$_{set}$ or V$_{reset}$ for set (HR to LR) or reset (LR to HR) processes. Two conduction mechanism has been proposed: ohmic for the low resistive state and trap-assisted tunneling (TAT) for the high resistive state. The model has been implemented in Python and works with an external C-library that optimizes calculations and processing time. The simulation results have been successfully validated by comparing measured and modeled IV curves of HfO$_{2}$-based ReRAM devices of nine different areas. It is important to note that the flexibility and easy implementation of this resistive switching model allow it to be a powerful tool for the design and study of ReRAM memories

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Jacquemin, Godefroy. „Implication des monocytes-macrophages dans le développement de l'inflammation colique et de la carcinose péritonéale d'origine colorectale : rôle des récepteurs lectine de type-c et des récepteurs nucléaires PPARy et LRH-1“. Thesis, Toulouse 3, 2021. http://www.theses.fr/2021TOU30277.

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Implication des monocytes/macrophages dans le développement de l’inflammation colique et de la carcinose péritonéale d’origine colorectale : Rôle des récepteurs lectine de type-C et des récepteurs nucléaires PPARγ et LRH-1.Les monocytes et les macrophages, cellules clés de l’immunité innée, expriment un large panel de récepteurs membranaires et nucléaires leur permettant de moduler leurs phénotypes et leurs fonctions en réponse aux stimuli présents dans leur environnement. Du fait de cette adaptabilité cellulaire, les monocytes/macrophages contrôlent la réponse immunitaire innée et adaptative. Ainsi, ces cellules jouent un rôle central dans le développement de nombreuses pathologies, et par conséquent, représentent des cibles thérapeutiques pertinentes. Dans ce travail de thèse, nous nous sommes, dans un premier temps, intéressés au rôle des récepteurs lectine de type-C des macrophages dans le contrôle de l’inflammation colique. Nous montrons grâce à l’utilisation de deux modèles murins spécifiquement invalidés pour Dectine-1 et le récepteur mannose (RM) dans la lignée myéloïde, que Dectine-1 participe au développement de l’inflammation intestinale, tandis qu’inversement, le RM la prévient. En effet, dans un modèle de colite induite au DSS (Dextran Sodium Sulfate), le récepteur Dectine-1 des macrophages induit une augmentation du recrutement de monocytes inflammatoires dans le colon de façon CCL2-dépendante. Nous mettons également en évidence que Dectine-1 est impliqué dans la polarisation des macrophages du colon vers un phénotype pro-inflammatoire. En effet, Dectine-1 favorise la synthèse du leucotriène B4 (LTB4) qui à son tour induit la sécrétion de l’interleukine-1β (IL-1β). Ces résultats mettent en évidence l’implication délétère de l’axe Dectine-1/CCL2/LTB4/IL-1β dans le développement de l’inflammation colique et attribuent, inversement, un rôle protecteur au RM dans ce contexte. Ces données ont été corrélées avec une augmentation de l’expression de Dectine-1 et une diminution de l’expression du RM au niveau du colon de patients atteints de maladies inflammatoires chroniques de l’intestin (MICI). Ce travail est publié dans Cell Reports 2020 : Divergent Roles for Macrophage C-type Lectin Receptors, Dectin-1 and Mannose Receptors, in the Intestinal Inflammatory Response. Cell Rep. 30, 4386-4398.e5Dans un deuxième temps, nous nous sommes intéressés aux rôles des récepteurs nucléaires PPARγ (peroxisome proliferator-activated receptor) et LRH-1 (Liver receptor homolog-1) des macrophages dans le développement d’une carcinose péritonéale d’origine colorectale (CPCR). Nous avons mis en évidence pour la première fois, en utilisant deux modèles murins délétés pour LRH-1 ou PPARγ spécifiquement dans la lignée myéloïde, que ces récepteurs nucléaires jouent un rôle majeur dans la différenciation des précurseurs myéloïdes en cellules immunosuppressives dérivées de la lignée myéloïde (MDSC) au cours de la CPCR. En effet, l’absence de LRH-1 et de PPARγ dans les cellules myéloïdes inhibe la différenciation des MDSC et favorise la réactivation du système immunitaire anti-tumoral. En association à cette réactivation immunitaire, les souris présentent une forte diminution de la charge tumorale, identifiant LRH-1 et PPARγ comme des cibles thérapeutiques innovantes capables de lever l’immunosuppression. A l’aide d’un modèle in vitro de différenciation des MDSC, nous avons montré l’interdépendance de LRH-1 et PPARγ dans la différenciation des MDSC via l’activation de l’axe LRH-1/15-HETE/PPARγ. Parallèlement, nous avons mis en évidence la capacité d’un agoniste inverse de LRH-1 (ML-180) à inhiber le développement de la CPCR, la différenciation des MDSC et la prolifération des cellules tumorales de colon
Involvement of monocytes/macrophages in the development of colonic inflammation and peritoneal carcinomatosis of colorectal origin: Role of C-type lectin receptors and nuclear receptors PPARγ and LRH-1.Monocytes and macrophages, key cells of innate immunity, express a large panel of membrane and nuclear receptors allowing them to modulate their phenotypes and functions in response to environmental stimuli. Due to this cellular adaptability, monocytes/macrophages control the innate and adaptive immune responses. Thus, these cells play a central role in the development of many pathologies, and consequently, represent relevant therapeutic targets. In this work, we first focused on the role of macrophage C-type lectin receptors in the control of colonic inflammation. We show, using two mouse models specifically invalidated for Dectin-1 and mannose receptor (MR) in the myeloid lineage, that Dectin-1 participates in the development of intestinal inflammation, whereas MR prevents it. Indeed, in a DSS (Dextran Sodium Sulfate)-induced colitis model, the Dectin-1 receptor on macrophages induces an increase in the recruitment of inflammatory monocytes in the colon in a CCL2-dependent manner. We also demonstrate that Dectin-1 is involved in the polarization of colonic macrophages towards a pro-inflammatory phenotype. Indeed, Dectin-1 promotes the synthesis of leukotriene B4 (LTB4) which, in turn, induces the secretion of interleukin-1β (IL-1β). These results highlight the involvement of the Dectin-1/CCL2/LTB4/IL-1β axis in the development of colonic inflammation and conversely assign a protective role to MR in this context. These data were correlated with an increase in Dectin-1 expression and a decrease in MR expression in the colon of inflammatory bowel disease (IBD) patients. This work is published in Cell Reports 2020: Divergent Roles for Macrophage C-type Lectin Receptors, Dectin-1 and Mannose Receptors, in the Intestinal Inflammatory Response. Cell Rep. 30, 4386-4398.e5In a second step, we investigated the roles of the nuclear receptors PPARγ (peroxisome proliferator-activated receptor) and LRH-1 (Liver receptor homolog-1) of macrophages in the development of peritoneal carcinomatosis of colorectal origin (PCR). We have demonstrated for the first time, using two mouse models deleted for LRH-1 or PPARγ specifically in the myeloid lineage, that these nuclear receptors play a major role in the differentiation of myeloid precursors into myeloid-derived suppressor cells (MDSC) during PCR. Indeed, the absence of LRH-1 and PPARγ in myeloid cells inhibits MDSC differentiation and promotes the reactivation of the anti-tumor immune system. Associated with this immune reactivation, the mice show a strong decrease in tumor burden, identifying LRH-1 and PPARγ as novel therapeutic targets capable of removing immunosuppression. Using an in vitro model of MDSC differentiation, we demonstrated the interdependence of LRH-1 and PPARγ in MDSC differentiation via the activation of the LRH-1/15-HETE/PPARγ axis. In parallel, we demonstrated the ability of an LRH-1 inverse agonist (ML-180) to inhibit PCR development, MDSC differentiation and colon tumor cell proliferation. This work identifies the nuclear receptor LRH-1 as a key element in PCR progression and opens new therapeutic perspectives allowing both to remove immunosuppression by blocking MDSC differentiation and to directly inhibit colon tumor cell proliferation. This work is in progress

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Wu, Marcio Jolhben. „Análise do efeito do investimento inicial no dilema do prisioneiro contínuo iterado simultâneo e alternado na presença e ausência de ruído em diferentes cenários de incerteza: contrapondo as estratégias RTS e LRS por meio da simulação bas“. Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/47/47132/tde-02032016-153429/.

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O dilema do prisioneiro é geralmente visto como o ponto de partida para entender o problema da cooperação. Em comparação com o dilema do prisioneiro discreto e iterado, poucos estudos existem sobre o dilema do prisioneiro contínuo e iterado. A maioria dos trabalhos que investigaram o dilema do prisioneiro contínuo e iterado concentrou-se no período de 1990 a 2000, não obtendo resultados conclusivos sobre a melhor estratégia a ser adotada neste tipo de jogo. Duas estratégias diferentes se destacam neste tipo de dilema. A primeira é a estratégia RTS (Raise-the-Stakes) de Roberts e Sherrat (1998) que testa o terreno antes de aumentar os investimentos na relação. A segunda deriva do modelo LRS (Linear Reactive Strategies) de Wahl e Nowak (1999a). Esta última estratégia estando em equilíbrio de Nash cooperativo apresenta três características: (i) generosidade, i.e., investir o máximo possível no início da relação de cooperação; (ii) otimismo, i.e., contar com o melhor cenário para as próximas rodadas, e (iii) intransigência. Esta pesquisa tem como objetivo principal contrapor as estratégias RTS e LRS num dilema do prisioneiro contínuo e iterado, na presença e ausência de ruído, com jogadas simultâneas e alternadas e para diferentes valores do parâmetro w (probabilidade de interagir novamente). Restringimos a nossa análise a um conjunto de seis estratégias: ALLC, ALLD, TFT, RTS, LRS e RTSM. O método utilizado foi o da simulação baseada em agente (ABM) no formato de torneios, semelhante ao de Axelrod (2006), Roberts & Sherratt (1998), Nowak & Sigmund (1992) e Nowak & Sigmund (1993). Utilizamos o software Netlogo e documentamos todo o processo da concepção e construção do modelo por meio da ferramenta TRACE (TRAnsparent and Comprehensive model Evaludation). Os resultados mostram que as estratégias mais cooperativas são mais favorecidas quando o jogo consiste em jogadas alternadas ao invés de simultâneas. A estratégia RTS teve melhor desempenho em jogos simultâneos para valores intermediários de w, na presença ou ausência de ruído. Por sua vez, a estratégia LRS teve melhor desempenho nos jogos simultâneos, na presença ou ausência de ruído, ou alternados e na presença de ruído, em ambos os casos para valores grandes de w
The prisoner\'s dilemma is generally seen as the starting point for understanding the problem of cooperation. In comparison with the discreet and iterated prisoner\'s dilemma, few studies exist on the continuous iterated prisoner\'s dilemma. Most of the works that have investigated the continuous iterated prisoner\'s dilemma has concentrated in the period from 1990 to 2000, not getting conclusive results on the best strategy to be adopted in this type of game. Two different strategies stand out in this kind of dilemma. The first is the RTS strategy (Raise-the-Stakes) of Roberts and Sherrat (1998) that tests the ground before increasing investment in the relationship. The second is the model deriva LRS (Linear Reactive Strategies) de Wahl and Nowak (1999a). This last strategy being in Nash equilibrium cooperative presents three characteristics: (i) generosity, i.e., investing as much as possible at the beginning of the cooperation relationship; (ii) optimism, i.e., rely on the best scenario for the next rounds, and (iii) intransigence. This research has as main goal to reconcile opposing RTS strategies and LRS in a continuous iterated prisoner\'s dilemma, in the presence and absence of noise, with simultaneous moves and alternate and for different values of the parameter w (probability of interacting again). We restrict our analysis to a set of six strategies: ALLC, ALLD, TFT, RTS, LRS and RTSM (halfway between RTS and LRS). The method used was the agent-based simulation (ABM) in tournament format, similar to that of Axelrod (2006), Roberts (1998), Sherratt & Nowak & Sigmund (1992) and Nowak & Sigmund (1993). We use the NetLogo software and document the whole process of design and construction of the tool model TRACE (TRAnsparent and Comprehensive model Evaludation). The results show that most strategies are more favoured unions when the game consists of alternating plays rather than simultaneous. The RTS strategy had better performance in simultaneous games for intermediate values of w, in the presence or absence of noise. In turn, the IRS strategy had better performance when simultaneous games, in the presence or absence of noise, or switched, and in the presence of noise, in both cases, for large values of w

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Hofsten, Jonas von. „Developmental and reproductive regulation of NR5A genes in teleosts“. Doctoral thesis, Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-374.

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Santos, Pablo Vieira dos. „Utiliza??o de m?todos n?o destrutivos na avalia??o da qualidade da madeira de Cariniana legalis (Mart.) Kuntze proveniente de plantios de restaura??o florestal“. Universidade Federal Rural do Rio de Janeiro, 2016. https://tede.ufrrj.br/jspui/handle/jspui/1793.

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Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2017-06-20T15:28:09Z No. of bitstreams: 1 2016 - Pablo Vieira dos Santos.pdf: 2713237 bytes, checksum: 034b9528933152d64f409aa5701ceba6 (MD5)
Made available in DSpace on 2017-06-20T15:28:09Z (GMT). No. of bitstreams: 1 2016 - Pablo Vieira dos Santos.pdf: 2713237 bytes, checksum: 034b9528933152d64f409aa5701ceba6 (MD5) Previous issue date: 2016-02-26
Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Forest restoration is an important mechanism which can recover anthropized environments. In this context, the use of native species in order to wood production has become a very positive alternative in the economic viability of this activity, so that, know information about native species with potential for production of high quality wood, used in forest restoration, is an important task. Concerning this, the objective of this study was to evaluate the quality of the wood Cariniana legalis (Mart.) Kuntze from forest restoration plantings, through non-destructive methods. Were selected 20 individuals in the field through a silvicultural assessment and then were determined dendrometric characteristics: diameter at breast height (DBH), total height, tree standing volume and bark thickness. Four different non-destructive methods of assessing wood quality based on the DBH (1.30 m from the base of the tree): extensometry, resistograph, impulse tomograph and x-ray densitometry (pulling out wood samples by Pressler probe). The longitudinal residual strain (LRS) average of wood was 0.054 mm, a value lower than that found in the literature for many species, as for the Eucalyptus genus. The amplitudes generated by resistograph allowed the estimation the basic density values of wood Cariniana legalis, presenting a positive and significant correlation (r = 0.68) at 1% significance level. The average apparent density average, obtained by X-ray densitometry, was 0.528 g / cm3. In general, Cariniana legalis threes were homogeneous, with good sanity wood (without internal rot or hollow) and moderately dense density being easy workability and suitable for the furniture industry.
A restaura??o florestal ? um importante mecanismo, no qual se consegue recuperar ambientes antropizados. Neste contexto, o uso de esp?cies nativas visando a produ??o madeireira tem se tornado uma alternativa bastante positiva na viabiliza??o econ?mica desta atividade, de modo que, conhecer informa??es a respeito de esp?cies nativas com potencial na produ??o de madeira de alta qualidade, utilizadas na restaura??o florestal, ? uma tarefa de grande import?ncia. Nesse sentido, o objetivo deste trabalho foi avaliar a qualidade da madeira de Cariniana legalis (Mart.) Kuntze proveniente de plantios de restaura??o florestal, atrav?s de m?todos n?o destrutivos. Foram selecionados 20 indiv?duos no campo por meio de uma avalia??o silvicultural e em seguida determinou-se as caracter?sticas dendrom?tricas (di?metro ? altura do peito (DAP), altura total, volume da ?rvore em p? e a espessura da casca). Quatro diferentes m?todos n?o destrutivos de avalia??o da qualidade da madeira foram utilizados, sendo eles a extensometria, resistograf?a, tomografia de impulso e densitometria de raios X (retirando-se amostras do lenho por meio da sonda de Pressler), todos os ensaios tiveram como refer?ncia a altura do DAP (1,30m a partir da base da ?rvore). A deforma??o residual longitudinal (DRL) m?dia da madeira foi de 0,054 mm, valor este inferior ao encontrado na literatura para muitas esp?cies, como para o g?nero Eucalyptus. As amplitudes geradas pelo resist?grafo permitiram estimar os valores de densidade b?sica da madeira de Cariniana legalis, apresentando uma correla??o positiva e significativa (r = 0,68) ao n?vel de 1% de signific?ncia. A densidade aparente m?dia, obtida por meio da densitometria de raios X, foi de 0,528 g/cm3. De maneira geral os indiv?duos de Cariniana legalis se mostraram homog?neos, apresentando boa sanidade do lenho (sem ocos internos ou podrid?es) e densidade moderadamente densa, sendo de f?cil trabalhabilidade e indicada para a ind?stria moveleira

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Křížová, Martina. „Indexování dat pohybujících se objektů“. Master's thesis, Vysoké učení technické v Brně. Fakulta informačních technologií, 2010. http://www.nusl.cz/ntk/nusl-237256.

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This thesis deals with indexing of spatio-temporal data. It describes existing approaches to indexing data and support for indexing in Oracle Database 11g. The aim of this work is to design structures of databases for storing spatio-temporal data over Oracle Database 11g to propose experiments for these databases. Ways of spatio-temporal data storage are evaluated according to these experiments in terms of time demands of queries and appropriateness of using available indexing structure and spatial operators.

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Bischof, Dorothea. „Modellorientierte Therapie bei Störungen des Leseerwerbs“. Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/21345.

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Ein ausreichendes Lesetempo, eine hohe Lesegenauigkeit und ein entwickeltes Leseverständnis sind in fast allen Schulfächern Voraussetzung für eine erfolgreiche Teilnahme am Unterricht. Internationale Schulleistungsstudien belegen, dass ein hoher Anteil von Schülern bereits in der Grundschule unzureichende Lesekompetenzen aufweist und daher auf zusätzliche Förder- oder Therapiemaßnahmen angewiesen ist. Im Hinblick darauf wurden in einem Gruppen-Prä-Post-Follow-Up-Design mit zweifacher Prä-Messung zwei unterschiedliche Interventionen zur Verbesserung der Lesefähigkeiten bei Zweit- und Drittklässlern evaluiert: Ein modellgeleitetes Therapieverfahren zur Verbesserung der Lesegeschwindigkeit von Wörtern und ein von Eltern durchgeführtes Fördertraining zur Verbesserung der Lesegenauigkeit und Lesegeschwindigkeit von Pseudowörtern. Zur Teilnahme an den Interventionen wurden 58 Zweit- und Drittklässler mit einem gravierenden Leserückstand ausgewählt und entweder dem Therapieprogramm oder dem Fördertraining zugeteilt. Beide Gruppen erhielten über 5 Wochen ein tägliches 45-minütiges Training. Während das Training der Therapiegruppe von einem ausgebildeten Therapeuten durchgeführt wurde und in der Schule stattfand, wurde das Training der Fördergruppe von Eltern zu Hause durchgeführt. Es wurden Veränderungen in der Lesegeschwindigkeit, dem Leseverständnis und verschiedenen Blickbewegungsparametern ausgewertet.
In order to follow the lessons in school, children must be able to read with speed as well as with accuracy and a proven ability to comprehend texts. International school performance studies show that a high proportion of students already have inadequate reading skills in elementary school and therefore need additional support or therapy measures. Based on this observation, an evaluation of two different interventions among second- and third-graders is reported: A pre-post follow-up design with double pre-measurement, aiming at the increase of the students' reading skills. A model-guided therapy method for improving the reading speed of words and a parental training course for the improvement of reading accuracy and reading speed of pseudowords. 58 second- and third-graders with a serious reading backlog were selected to participate in the interventions and were assigned to either the therapy program or the parental training. Both groups received daily 45-minute training over a 5 week period. While the training of the therapy group was held by a therapist and took place at school, the training of the support group was carried out by parents at home. Changes in reading speed, reading comprehension and various eye movement parameters were evaluated.

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Guitarra, Silvana Raquel. „Modélisation multi-échelles des mémoires de type résistives (ReRAM)“. Electronic Thesis or Diss., Aix-Marseille, 2018. http://theses.univ-amu.fr.lama.univ-amu.fr/181210_GUITARRA_584ohbsor62rwx899lsxvt26qyx_TH.pdf.

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Un modèle de commutation de mémoires résistives (ReRAM) est présenté. Celui-ci est basé sur deux hypothèses : (1) la commutation résistive est causée par des changements qui se produisent dans la zone étroite (région active) du filament conducteur sous l'influence du champ électrique et (2) la commutation résistive est un processus stochastique, donc régi par une probabilité. La région active est représentée par un réseau de connexions verticales, chacune composée de trois éléments électriques : deux d'entre eux sont de faible résistance tandis que le troisième agit comme un disjoncteur et peut être soit de résistance faible (LR) ou élevée (HR). Dans ce modèle, le changement d'état du disjoncteur est régi par une probabilité de commutation (Ps) qui est comparée à un nombre aléatoire « p ». Ps dépend de la chute de tension le long du disjoncteur et de la tension de seuil, V_{set} ou V_{reset}, pour définir les processus de « set » (HR à LR) et « reset » (LR à HR). Deux mécanismes de conduction ont été envisagés : ohmique pour un état LR et pour un état de résistance élevée l'effet tunnel facilité par un piège (TAT). Le modèle a été implémenté avec le langage de programmation Python et fonctionne avec une bibliothèque C externe qui optimise les calculs et le temps de traitement. Les résultats de la simulation ont été validés avec succès en les comparant avec des courbes courant-tension (IV) mesurées sur dispositifs ReRAM réels dont l'oxyde était fait de HfO₂ et pour neuf aires différentes. La flexibilité et la facilité de mise en œuvre de ce modèle de commutation résistive en font un outil puissant pour l'étude des ReRAM
A model for the switching of resistive random-access memories (ReRAM) is presented. This model is based on two hypotheses: (1) the resistive switching is caused by changes that occur in the narrow zone (active region) of the conductive filament under the influence of the electric field and (2) the resistive switching is a stochastic process governed by a switching probability. The active region is represented by a net of vertical connections, each one composed of three electrical elements: two of them are always low resistive (LR) while the third one acts as a breaker and can be low or high resistive (HR). In the model, the change of the breaker's state is governed by a switching probability (Ps) that is compared with a random number p. Ps depend on the voltage drop along the breaker and the threshold voltage, V_{set} or V_{reset} for set (HR to LR) or reset (LR to HR) processes. Two conduction mechanism has been proposed: ohmic for the low resistive state and trap-assisted tunneling (TAT) for the high resistive state. The model has been implemented in Python and works with an external C-library that optimizes calculations and processing time. The simulation results have been successfully validated by comparing measured and modeled IV curves of HfO₂-based ReRAM devices of nine different areas. It is important to note that the flexibility and easy implementation of this resistive switching model allow it to be a powerful tool for the design and study of ReRAM memories

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Pan, Chien-Ting, und 潘建廷. „Preparation of LRH-1 Antibody & Regulation of CYP11A1 Gene by LRH-1“. Thesis, 2005. http://ndltd.ncl.edu.tw/handle/20779153362660582943.

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碩士
國立臺灣大學
生理學研究所
93
CYP11A1 gene encodes P450scc enzyme, which controls the first and rate-limiting step of steroidogenesis by conversion of cholesterol to pregnenolone. CYP11A1 gene is expressed in many steroidogenic tissues like adrenal and gonad. Liver receptor homolog-1 (LRH-1) is a transcription factor and belongs to a member of nuclear receptor NR5A family. LRH-1 is expressed in some steroidogenic tissues such as ovary and may play a role in the regulation of steroidogenic gene. To study the function of LRH-1, two peptides of mouse LRH-1 were produced in E. coli for the generation of antibody. This antibody was used to detect the presence of LRH-1 in rat primary luteal cells by Western blotting. Transfection of LRH-1 expression vector in 293T cell line also can be detected by Western blotting. To examine the ability of LRH-1 in the regulation of CYP11A1 gene expression, we cotransfected LRH-1 expression vector and human CYP11A1 promoter construct into 293T cell line. LRH-1 can enhance the shortest 1.5 kb CYP11A1 promoter activity. Two functional SF-1 binding sites were located at -40 and -1600 in CYP11A1 promoter. By mutating the SF-1 binding sites, we found that SF-1 binding site located at -40 is the major site of LRH-1 binding to CYP11A1 promoter. Induction of CYP11A1 promoter activity by LRH-1 was inhibited by Dax-1. LRH-1 can be conjugated with post-translation modification protein SUMO-1 and we found that lysine 289 is the major conjugation site of SUMO-1. When LRH-1 was conjugated with SUMO-1 the ability of LRH-1 inducing CYP11A1 promoter activity was inhibited and that was independent of Dax-1 function. We found that LRH-1 may not be stable in the transfected cell.The proteasome inhibitor, MG-132, can increase the amount of LRH-1 protein in transfected cell.

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Ferguson, Ronald Aubrey. „Units in integral cyclic group rings for order LRPS“. Thesis, 1997. http://hdl.handle.net/2429/6770.

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For a finite abelian group A, the group of units in the integral group ring ZA may be written as the direct product of its torsion units ±A with a free group U2A . Of finite index in U2A is the group ΩA, the elements of U2 which are mapped to cyclotomic units by each character of A. The order of U2A/ΩA depends on class numbers [formula] in real cyclotomic rings [formula]. Of finite index in ΩA is the group of constructible units YA, for which a multiplicative basis may be explicitly written. The order of ΩA/YA is the circular index c(A). In many cases, for example where A is a p-group with p a regular prime, this index is trivial. This thesis develops an inductive theory for determining c(Cn) where Cn is a cyclic group of order n = lrps, with I and p distinct primes, and also for giving some description of the group ΩCnjYCn. This is a continuation of the work of Hoechsmann for the case n = Ip. It turns out that the methods required for n = lrps are, in general, very different from the ones used for r = s = 1.

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Wu, Mei-Ling, und 吳美伶. „Regulation of LRH-1 transcriptional activity“. Thesis, 2006. http://ndltd.ncl.edu.tw/handle/57874887924244892222.

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碩士
國立臺灣大學
生理學研究所
94
Liver receptor homolog-1 (LRH-1) is a member of nuclear receptor 5A subfamily. LRH-1 is expressed in steroidogenic tissues and has been shown to possess the ability to regulate the expression of steroidogenic genes. The aim of this study is to evaluate the regulation of mouse LRH-1 (mLRH-1) transcriptional activity. Our previous studies indicated that mLRH-1 stimulated the expression of human CYP11A1 promoter and N-terminal deletion of mLRH-1 enhanced the transcriptional activity of mLRH-1. In this study, two C-terminal deletions of mLRH-1 were constructed to examine the effect of C-terminus on mLRH-1. We found that mLRH-11-240 lacking of ligand binding domain almost lose transcriptional activity and had a dominant negative effect on mLRH-1 mediated transcription. The mLRH-11-191 with further deletion of hinge region and a part of DNA binding domain still located in the nucleus but had no dominant negative effect on mLRH-1-mediated transcription. LRH-1 can be conjugated with a post-translational modifier protein, small ubiquitin-related modifier-1 (SUMO-1). By mutating the potential SUMO-1 binding sites, we found that the lysine 289 of mLRH-1 is the major SUMO-1 conjugation site. In addition, the sumoylation at lysine 289 may inhibit mLRH-1 transcriptional activity. The members of PIAS family are recently known to be E3-like ligases that control the conjugation of SUMO-1 to target protein. Our cotransfection experiment showed that PIASxα, PIASxβ and PIASy can repress mLRH-1-induced transcription and PIASy had a most significant effect. And it’s suggested that PIASxαand PIASy-mediated repression of mLRH-1 is independent of mLRH-1 sumoylation. We further proved that mLRH-1 could interact with PIASy in vitro. In this study we found that: 1、The C-terminus of mLRH-1 is necessary for its transcriptional activity. Deletion of C-terminus increases the protein amount of mLRH-1. 2、SUMO-1 is mainly conjugated to lysine 289 of mLRH-1 that represses the transcriptional activity of mLRH-1. 3、SUMO E3 ligase PIASxα, PIASxβ and PIASy can repress mLRH-1-induced transcription. The repression of mLRH-1 transcriptional activity mediated by PIASxαand PIASy is independent of mLRH-1 sumoylation. 4、PIASy can directly interact with mLRH-1.

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Richards, Gregory R. „The regulator LrhA and lipase activity in Xenorhabdus nematophila insect pathogenesis“. 2008. http://www.library.wisc.edu/databases/connect/dissertations.html.

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Dissertationen zum Thema „LRHS“

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