Teses / dissertações sobre o tema "Relais cellule"
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Timus, Bogdan. "Studies on the Viability of Cellular Multihop Networks with Fixed Relays". Doctoral thesis, KTH, Kommunikationssystem, CoS, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-10526.
Texto completo da fonteQC 20100812
Khan, Aroba. "Network Modeling in Heterogeneous and Cooperative Cellular Communications". Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/15436.
Texto completo da fonteSavard, Anne. "Codage pour les communications coopératives : Codage de source distribué et canaux à relais". Thesis, Cergy-Pontoise, 2015. http://www.theses.fr/2015CERG0774/document.
Texto completo da fonteThe current wireless data traffic growth cannot be handled by classical multi-hop network protocols as in interference-free wired networks, thus it has been recognized that network nodes need to cooperate in order to take advantage of source and/or channel signal correlations, which is needed to achieve fundamental capacity limits.This thesis first considers a cooperative source coding problem, namely binary source coding with coded side information (CoSI): the helper node has access to a signal that is correlated with the source and may send a compressed version on a separate link to the destination, thus rate can be saved on the main source-destination link. Using a characterization of the Hamming-space Voronoi regions of the quantizer at the helper node, an improved practical scheme based on LDPC codes is proposed.The second part of the thesis considers cooperative channel coding, where helper nodes are relays. The simplest example of such a communication is the relay channel, in which a relay node helps the source to send its message to the destination. Whereas in the source coding problem, the correlation between source and side information is given, in channel coding, the main question is to find the best relaying operation. First, a somewhat dual problem to source coding with CoSI is studied, by considering correlated noises at the relay and destination. Then, various extensions of the relay channel are characterized using upper bounds on capacity and achievable rates: the two-way relay channel with correlated noises at the relay and destinations, where two sources wish to exchange their data with the help of a relay, and the multiway relay channel with direct links, where users, grouped into fully connected clusters (users in a cluster can overhear each others' messages), wish to exchange their messages locally within a cluster with the help of one relay
Negi, Ansuya. "Analysis of Relay-based Cellular Systems". PDXScholar, 2006. https://pdxscholar.library.pdx.edu/open_access_etds/2668.
Texto completo da fonteFraser, Patrick. "Réorganisation des cellules relais et des interneurones gabaergiques du système visuel thalamofuge suite à une lésion rétinienne précoce chez le pigeon /". Thèse, Trois-Rivières, Université du Québec à Trois-Rivières, 1999. http://www.uqtr.ca/biblio/notice/resume/03-2205947R.html.
Texto completo da fonteFraser, Patrick. "Réorganisation des cellules relais et des interneurones gabaergiques du système visuel thalamofuge suite à une lésion rétinienne précoce chez le pigeon". Thèse, Université du Québec à Trois-Rivières, 1999. http://depot-e.uqtr.ca/3374/1/000663224.pdf.
Texto completo da fonteLu, Wei. "New Results on Stochastic Geometry Modeling of Cellular Networks : Modeling, Analysis and Experimental Validation". Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS253/document.
Texto completo da fonteThe increasing heterogeneity and irregular deployment of the emerging wireless networks give enormous challenges to the conventional hexagonal model for abstracting the geographical locations of wireless transmission nodes. Against this backdrop, a new network paradigm by modeling the wireless nodes as a Poisson Point Process (PPP), leveraging on the mathematical tools of stochastic geometry for tractable mathematical analysis, has been proposed with the capability of fairly accurately estimating the performance of practical cellular networks. This dissertation investigated the mathematical tractability of the PPP-based approach by proposing new mathematical methodologies, fair approximations incorporating practical channel propagation models. First, a new mathematical framework, which is referred to as an Equivalent-in-Distribution (EiD)-based approach, has been proposed for computing exact error probability of cellular networks based on random spatial networks. The proposed approach is easy to compute and is shown to be applicable to a bunch of MIMO setups where the modulation techniques and signal recovery techniques are explicitly considered. Second, the performance of relay-aided cooperative cellular networks, where the relay nodes, the base stations, and the mobile terminals are modeled according to three independent PPPs, has been analyzed by assuming flexible cell association criteria. It is shown from the mathematical framework that the performance highly depends on the path-loss exponents of one-hop and two-hop links, and the relays provide negligible gains on the performance if the system is not adequately designed. Third, the PPP modeling of cellular networks with unified signal attenuation model is generalized by taking into account the effect of line-of-sight (LOS) and non-line-of-sight (NLOS) channel propagation. A tractable yet accurate link state model has been proposed to estimate other models available in the literature. It is shown that an optimal density for the BSs deployment exists when the LOS/NLOS links are classified in saturate load cellular networks. In addition, the Monte Carlo simulation results of the real BSs deployments with empirical building blockages are compared with those with PPP distributed BSs with the proposed link state approximation at the end of this dissertation as supplementary material. In general, a good matching is observed
HABY, MATTHIAS. "Mecanismes cellulaires impliques dans la modalite de transfert et la modalite oscillatoire des cellules relais du corps genouille lateral dorsal. Etude in vitro". Paris 6, 1990. http://www.theses.fr/1990PA066158.
Texto completo da fonteMantovani, G. "Ruolo delle diverse subunità regolatorie della PKA nella regolazione della proliferazione di cellule endocrine ed endocrino-relate". Doctoral thesis, Università degli Studi di Milano, 2006. http://hdl.handle.net/2434/30895.
Texto completo da fontePandey, Sony. "Does altered expression of growth control genes relate to WT1 in leukemia?" Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1461592576.
Texto completo da fonteRajabi, Fatemeh. "Role of the xenoreceptor PXR (NR1I2) in colon cancer stem cells drug resistance and tumor relapse". Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTT027.
Texto completo da fonteTumor recurrence is one of the major obstacles to overcome in the future to improve overall survival of patients with colon cancer. High rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). Here, we demonstrate that the nuclear receptor PXR (NR1I2) acts as a key regulator of colon CSC chemoresistance and of their ability to generate post-treatment tumor relapse. We first determined that the enrichment of PXR paralleled that of CSC markers upon treatment of colon cancer cells with standard of care chemotherapy. We found that PXR was highly expressed in colorectal cancer cells displaying CSC markers and function and that it was instrumental for the emergence of CSCs following chemotherapy in vitro and in vivo. mRNA profiling experiments in colon CSCs indicated that PXR transcriptionally controls a large network of genes including markers of stemness, genes involved in resistance to drug/apoptosis or migration/invasion. Finally, PXR down-regulation altered the survival and self-renewal of colon CSCs in vitro and hampered their capacity to resist chemotherapy in vivo, leading to significant delays of post-chemotherapy tumor relapse. This study strongly suggests that targeting PXR may represent a novel treatment strategy to prevent drug resistance and recurrence through the sensitization of CSCs to standard chemotherapy. Taken together, our data strongly suggest that PXR plays an instrumental role in the so-called "intrinsic" pan-resistance of CSCs against therapy
Lunden, Jason Wesley. "The serotonergic dorsal raphe nucleus in opiate dependence and stress-induced relapse". Diss., Temple University Libraries, 2013. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/228054.
Texto completo da fontePh.D.
Opioids are used for the clinical treatment of pain, but can lead to tolerance and addiction. In this project we examined the role of the serotonin (5-HT) system originating from the dorsal raphe nucleus (DRN) during morphine exposure, withdrawal, abstinence and following an acute stressor capable of initiating behavioral relapse. Following four days of morphine exposure rats showed a preference for the morphine paired side of the conditioned place preference (CPP) chamber. After four days of morphine abstinence, rats showed no net preference for the morphine paired side. The next day rats were exposed to forced swim stress and returned to the CPP chamber where they demonstrated stress-induced reinstatement. Utilizing whole-cell patch-clamp we demonstrated an increase in the amplitude of inhibitory post-synaptic currents (IPSCs) in 5-HT DRN neurons, but not non 5-HT DRN neurons of morphine-conditioned subjects. Next the stress neurohormone corticotrophin releasing factor (CRF) was administered in vitro instead of forced swim. We found an increase in CRF-R2-mediated inward current of 5-HT DRN neurons in animals with a morphine history. From this experiment we concluded that morphine history sensitizes 5-HT DRN neurons to the GABAergic inhibitory effects of stress and to some of the effects of CRF. In the next series of experiments we surgically implanted either morphine or placebo pellets in rats for 72 hours to create physical dependence. The pellets were subsequently removed, and animals experienced up to seven days of abstinence with and without forced swim stress exposure. Real time quantitative PCR was used to measure the mRNA levels of genes at multiple points across this timeline. We examined genes involved in trophic support, stress responses and 5-HT regulation. We determined that mRNA levels for brain-derived neurotrophic factor (BDNF) and the BDNF receptor TrkB were downregulated after opiate exposure, and again following seven days of abstinence. Following seven days of abstinence there was a decrease in mRNA levels of the CRF-R1 receptor and an increase in mRNA levels of the CRF-R2 receptor. During acute opiate exposure there was a decrease in mRNA levels for the autoregulatory 5-HT1A receptor. Finally following forced swim, there was an increase in mRNA levels of the 5-HT synthesis enzyme TPH2. Collectively these results indicate that a morphine history in abstinent subjects may produce hypofunctioning of the 5-HT DRN system induced by multiple neurochemical mechanisms and this dysregulation may enhance vulnerability to stress-induced relapse.
Temple University--Theses
Miles, Olivia. "Intra-cellular mechanisms by which PAC1 receptor activation mediates stress-induced reinstatement to drug-seeking". ScholarWorks @ UVM, 2018. https://scholarworks.uvm.edu/graddis/897.
Texto completo da fonteHummel, Guillaume. "Entre silence, naissance et dégradation : vers la caractérisation de nouveaux mécanismes relatifs à la biologie des ARN de transfert et assurant l'homéostasie de la cellule végétale". Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ101.
Texto completo da fonteMy thesis project aimed at figuring out new physiological aspects related to transfer RNA (tRNAs) biology in plants. It was divided in two parts. The first one consisted in describing from an evolutionarily point of view the genomic layout of plant tRNA genes (tDNAs) onto nuclear chromosomes. Contrasting with non-plant organisms, plant nuclear tDNAs exhibit a higher order in their chromosomal scattering. This is due to centromeric regions exclusion combined to highly conserved inter-tDNA distances and tDNA repeat clusters occurrences. Moreover, that part consisted in deciphering elements of nuclear tDNA transcriptional regulation. We brought evidences of epigenetic silencing mechanisms at clustered tDNA loci. As a perspective, we propose tDNAs might play a role in three-dimensional genomes orchestration. The second aspect referred to characterizing the biogenesis and functions of small non-coding RNAs deriving from tRNAs: tRFs. The results obtained demonstrate that RNases T2 as the predominant molecular actors for their biogenesis
Villacreces, Arnaud. "L'hypoxie contribue à la quiescence et la chimiorésistance des cellules initiatrices de leucémie aigüe lymphoblastique". Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0126/document.
Texto completo da fonteOur group showed that severe hypoxia (0.1% O2) induces G0 cell-cycle-arrest of human CD34+ cells and of murine FDCP-mix Cells. Few studies explored the existence of quiescent Leukemia Initiating Cells (LIC) in ALL and their role in primary chemoresistance and relapses. Our project is focused on the effect of very low O2 concentrations in the maintenance of quiescent LIC in ALL, that could be responsible of a percentage of relapses. Indeed in bone marrow niches, where hematopoietic stem cells and probably LIC are located, the O2 concentrations are below 0.1%.In the present study we used the NALM-6 ALL cell line to explore the effects of culture at 0.1% O2 on their survival, cell cycle and chemoresistance. Our results evidence that a 7 days culture of NALM-6 cells at 0.1% O2: - inhibits their proliferation without major cell death; - reveals a restricted LIC population of quiescent and chemoresistant LIC; - maintains quiescent chemoresistant LIC that induce leukemia when injected in immunodeficient mice. We investigated the relationships between severe hypoxia and some characteristics of ALL primary cells obtained from patients: existence and role of quiescent chemoresistant LICs in ALL relapses; location of these residual cells inside the bone marrow of engrafted mice. Our results suggest that some ALL relapses could be due to the long term persistence of “quiescent / dormant” LIC in hypoxic bone marrow niches. This model is of interest for exploring the in vitro and in vivo (xenograft) mechanisms of chemoresistance in ALL and the role of the bone marrow environment in this phenomenon
Broséus, Julien. "Approche génomique des syndromes myéloprolifératifs et des lymphomes B-diffus à grandes cellules en rechute". Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0140.
Texto completo da fonteGenomics provided new insights in our knowledge of pathophysiology, diagnostic approach, prognosis and therapeutic perspectives in hematological malignancies. In the first part of this work, we studied a large cohort of Refractory Anemia with Ring sideroblasts and marked Thrombocytosis (RARS-T). We demonstrated that RARS-T can be considered as an independent entity, with a specific molecular pattern, associating : (i) SF3B1 mutations in more than 85% of cases, accounting for its myelodysplastic aspect and (ii) JAK2 mutations, accounting for its myeloproliferative aspect in more than 50% of cases. Future prospects of the first part of this work is to identify (the) mutation(s) responsible for the myeloproliferative part of JAK2WT RARS-T. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. In the second part of this work, we performed SNP-array analysis of a homogeneous series of samples from the CORAL cohort, an international prognostic study on relapsed DLBCLs. Our purpose was to identify Copy Number Variations (CNV) associated ER or LR. ER DLBCLs are associated with high rates of CNVs affecting regulators of cell cycle, apoptosis and transcription. In LR DLBCLs, CNVs are related to immune response and cell proliferation. This study provides new insights into the genetic aberrations in relapsed DLBCLs and open up new therapeutic perspectives
Ayman, Sinem. "An investigation of the cellular mechanisms by which nitric oxide relaxes the mouse anococcygeus smooth muscle, with particular references to interactions with calcium sensitization pathways". Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404800.
Texto completo da fonteNgom, Assane. "Conception de petits réseaux d'antennes reconfigurables ou "Small Cells" pour le standard 5G". Thesis, Université Côte d'Azur (ComUE), 2019. http://www.theses.fr/2019AZUR4027.
Texto completo da fonteConsumer mobile communications, video downloads and the use of mobile applications represent most of today's use of radio resources in 4G networks; but in order to broaden the spectrum of uses and the diversity of users, many research efforts and numerous proposals are beginning to emerge for the implementation of a new standard called 5G, which targets a wide range of sectors and is important pillars of a society: energy, health, media, industry or transportation. To fulfil these challenges, this new standard will have to combine several technologies, including the creation of an Ultra-Dense Network (UDN) to obtain a dense coverage, more robust to obstacles and increase the capacity of the network. This promising solution is obtained by the deployment of dense small cells in hotspots where huge traffic is generated, and by using millimeter waves to extend the transmission bandwidth.These smalls cells must optimize the received signal according to the location of the user, by using a high gain beam reconfigurable antennas array. This method avoids using all the available power to issue "blind" hoping to fall on the terminal.The Objectives of this thesis is therefore to design a small antennas array or "Small Cells" working in mmWave bands with an ability to change the direction of the beam according to the needs of users. A dual polarized beam reconfigurable technique applied on a planar antenna array has been developed.This manuscript is divided as follows: after a reminder of the objectives of the 5G and its requirements in chapter 1, we have introduced in chapter 2, the architectures and theory of the different antenna arrays, as well as the different techniques of beam steer. The third chapter is dedicated to the design of a cross patch antenna with a dual polarization and reconfigurable beam by using switchable parasitic elements. This radiating element was then used in Chapter 4 to design a high-gain reconfigurable, multiport sub-arrays and antenna arrays
Corvaisier, Matthieu. "Implication des co-activateurs transcriptionnels YAP/TAZ dans la régulation entre la croissance et la dormance tumorale des cellules du cancer colorectal : mécanismes moléculaires et perspectives thérapeutiques". Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S028/document.
Texto completo da fonteColorectal cancer is the most frequent and lethal cancerous pathology from the digestive system. Each year in France, 41 000 new cases are diagnosed and 17 000 patients die due to this pathology. This high mortality is mainly due to the rate of patients with liver metastatic lesions and the early relapse of those metastases after treatment. The use of chemotherapy prior to surgery induces a decrease of early relapse, however 2 years after resection this advantage is lost. Thus, understanding the mechanisms underlying escape to treatment is required to try to delay or prevent tumor recurrence.The aim of this doctoral work was to analyze clonal chemoresistant subpopulations derived from the colorectal cancer cell line HT29 after chronic exposure to 5-Fluorouracil (5FU) and molecular mechanisms associated with chemoresistance. The most chemoresistant clonal subpopulation, 5F31, stops its proliferation after treatment with high dose of 5FU, this behavior being associated with the modulation of the c-Yes/YAP axis. After treatment, 5F31 cells enter quiescence, interaction between c-Yes and YAP is lost and total and nuclear YAP protein expression reduces significantly (Igoudjil, Touil, Corvaisier et al. 2014, Clinical Cancer Research). The next step was to study functions of YAP protein in this chemotherapy- induced quiescence.Pharmacological or transient inhibition of YAP and its homolog TAZ, induces quiescence and reduces cellular growth in several colorectal cancer cell lines. On the other hand, overexpression of a constitutively active form of YAP in 5F31 cells forces cells to remain proliferative under 5FU treatment, enhancing 5F31 cell chemosensitivity to 5FU.Regarding proteic effectors, quiescence (either induced by 5FU or YAP/TAZ inhibition) is associated with loss of expression of the transcription factor c-Myc and Cyclin E1. In 5F31 cells expressing the active mutant form of YAP, Cyclin E1 expression is sustained after 5FU treatment through the activation of the transcription factor CREB. Cyclin E1 inhibition is sufficient to induce quiescence, therefore introducing this protein as one of the final effectors of YAP/TAZ co-activators in the regulation of the proliferation/quiescence switch in colorectal cancer cells (Corvaisier et al. 2016, Oncotarget).To conclude, our work reveals the importance of YAP/TAZ proteins for the maintenance of colorectal cancer cells proliferation through Cyclin E1 expression. Our work on liver metastases from patients with colorectal cancer shows that high expression of YAP/TAZ is connected to a higher proliferative index in metastatic lesions. Moreover, high YAP/TAZ expression is associated with shorter patient progression-free survival and shorter overall survival. Studying the expression and level of YAP/TAZ activation could be an interesting prognosis marker to anticipate metastatic relapse and potent druggable target to delay tumoral recurrence
Altieri, Andres Oscar. "On Large Cooperative Wireless Network Modeling through a Stochastic Geometry Approach". Thesis, Supélec, 2014. http://www.theses.fr/2014SUPL0019/document.
Texto completo da fonteThe main goal of this work is to study cooperative aspects of large wireless networks from the perspective of stochastic geometry. This allows the consideration of important effects such as the random spatial distribution of nodes, as well as the effects of interference and interference correlation at receivers, which are not possible when a single link is considered in isolation.First, some aspects of the performance of the relay channel in the context of a large wireless network are considered. Mainly, the performance, in terms of outage probability (OP), of a single full-duplex relay channel utilizing decode-and-forward (DF) or compress-and-forward, when the interference is generated by uniform spatial deployment of nodes, modeled as a Poisson point process. The OP performance of these two protocols is compared with a point-to-point transmission and with a half-duplex DF protocol. Afterwards, the case in which more than one transmitter in the network may use a relay is considered. The effects of cooperation versus interference are studied, when the users use either full-duplex DF, or point-to-point transmissions. In a second phase, this work explores the advantages that could be obtained through out-of-band device-to-device (D2D) video file exchanges in cellular networks. These advantages are measured in terms of the fraction of requests that can be served in a time-block through D2D, thus avoiding a downlink file transfer from the base station. For this, a stochastic geometry framework is introduced, in which the user file-caching policy, user pairing strategy, and link quality and scheduling issues are considered
Boudet-Devaud, François. "La protéine prion cellulaire : un relai de neurotoxicité commun aux protéines amyloïdes et aux nanoparticules Protective role of cellular prion protein against TNFα-mediated inlammation through TACE α-secretase PrPSc-induced PDK1 overactivation promotes the production of seedable Amyloid-β peptides in prion diseases Corruption of cellular prion protein signaling by titanium dioxide or carbon black nanoparticles promotes the accumulation of amyloid-β peptides". Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB127.
Texto completo da fonteThe cellular prion protein (PrPC) is a protein mostly expressed at the plasma membrane of neurons. Its transconformation into the pathogenic prion PrPSc is at the root of prion diseases. It is clearly established that the PrPSc-induced neurodegeneration depends on the expression of PrPC in neurons and results from the corruption of PrPC function(s) by PrPSc. Unravelling the role of PrPC is thus a prerequisite to grasp neurodegeneration mechanisms in prion diseases. Part of my work shows that PrPC exerts a cytoprotective function against TNFalpha inflammatory cytokine. PrPC silencing in neurons (PrPnull-neurons) renders these cells highly sensitive to TNFalpha due to surface accumulation of TNFalpha receptor (TNFR). My work demonstrates that the loss of PrPC regulatory function on the clustering and signaling downstream of bêta 1 integrins in PrPnull neurons provokes the overactivation of the kinase PDK1, subsequent internalization of TACE alpha-secretase, and uncoupling of TACE from TNFR substrate. Because of the phenotypic proximity between PrPnull neurons (Ezpeleta et al. 2017) and PrPSc-infected neurons (Pietri et al. 2013; Alleaume-Butaux et al. 2015), my work supports the view of a loss of PrPC protective function in prion diseases. As concerns prion infection, my work shows that after PDK1 overactivation, internalized TACE is uncoupled from another substrate, the amyloid peptides precursor protein (APP), leading to the accumulation of neurotoxic peptides Abêta 40 and Abêta 42, hallmarks of Alzheimer's disease. Within a prion infectious context, Abêta 40/42 peptides are predominantly present as monomers, and to a lesser extent, as trimers and tetramers. By combining in vitro and in vivo approaches, we show that Abêta peptides produced by infected neurons do not alter replication nor the infectivity of prions. Nevertheless, we demonstrate that oligomerized Abêta is able to form amyloid plaques in the brain of transgenic APP23 mice infected by prions. In these mice, Abêta deposits accelerate prion pathogenesis. The last axis of my work deals with nanoparticles, that is, nanometric materials commonly found in manufactured products and industrial processes. My work shows that, as PrPSc and Abêta, titanium dioxide or carbon black assemblies interact with PrPC at the surface of neurons and deviate its signaling function, which leads, inter alia, to PDK1 overactivation, TACE internalization, TNFR accumulation at the plasma membrane, and neuronal cells hypersensitivity to TNFalpha inflammatory stress. We also found that nanoparticle-induced TACE uncoupling from APP increases Abêta peptide production by neurons. Even if no epidemiological study has demonstrated to date a link between nanoparticle exposure and Alzheimer's disease, my work suggests an causal implication of nanoparticles in the initiation or amplification of this disease
Campeggio, Mimma. "Prognostic Role of Minimal Residual Disease before and after Haematopoietic Stem Cell Transplantation in pediatric ALL patients and evaluation of droplet digital PCR applicability in pre-HSCT MRD monitoring". Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3425313.
Texto completo da fonteLa Leucemia Linfoblastica Acuta (LLA) rappresenta la patologia tumorale più frequente in età pediatrica. Oltre l’80% dei bambini affetti da LLA viene trattato con successo grazie agli attuali protocolli di chemioterapia intensiva e basata sul rischio di ricaduta, ma sfortunatamente, il restante 20% ricade. Il trapianto di cellule staminali ematopoietiche (TCSE) ha un ruolo fondamentale nella guarigione di circa il 10% dei pazienti definiti ad alto rischio di ricaduta LLA in prima linea e per gran parte dei pazienti recidivati. Sfortunatamente, anche dopo il TCSE, la ricaduta si conferma come principale causa di fallimento terapeutico nelle LLA pediatriche. Il principale indicatore prognostico nelle LLA infantili è rappresentato dalla Malattia Residua Minima (MRM). La MRM è definita come la persistenza, all’interno del midollo osseo, di cellule leucemiche a livelli non identificabili attraverso esame citomorfologico. La valutazione della MRM è ormai parte integrante dei principali schemi terapeutici di prima linea, in cui viene usata per stratificare i pazienti in diverse classi di rischio di ricaduta (standard, intermedio o alto), con l'obiettivo di adattare la terapia al rischio individuale di ciascun paziente, ottimizzando le cure e riducendo al minimo la tossicità. Il monitoraggio della MRM è stato identificato come uno dei maggiori fattori predittivi di prognosi, anche per i pazienti ricaduti e per quelli trapiantati, in cui risulta ulteriormente vantaggioso per valutare la risposta alla terapia dei pazienti LLA. Ciononostante, il significato clinico della MRM nei pazienti sottoposti al TCSE non è ancora stato pienamente validato. L’approccio standard utilizzato per monitorare la MRM è attualmente rappresentato dalla real-time quantitative PCR (RQ-PCR), un saggio molecolare altamente sensibile e specifico, basato sulle regioni giunzionali dei riarrangiamenti dei geni delle immunoglobuline e del recettore dei linfociti T, identificati sugli aspirati midollari della diagnosi (o ricaduta) del paziente LLA. Nel primo progetto (descritto nel capitolo 1) del mio percorso di dottorato, abbiamo quantificato la MRM mediante PCR quantitativa immediatamente prima del TCSE, per valutare il suo significato clinico e l’impatto sull’outcome in una vasta coorte di pazienti pediatrici affetti da LLA (119), in prima remissione completa (1RC), seconda (2RC) o altre. Abbiamo poi analizzato MRM mediante RQ-PCR in 98/119 e 59/119 pazienti, rispettivamente durante il primo (post-TCSE1) e il terzo (post-TCSE3) trimestre dopo il trapianto. L’obiettivo di queste analisi è stato quello di capire se la valutazione MRM potesse fornire ulteriori informazioni, utili a identificare preventivamente i pazienti con maggior rischio di ricaduta leucemica dopo il trapianto. Dalle analisi di sopravvivenza in relazione ai livelli di MRM pre-TCSE nei pazienti LLA, qualsiasi livello di positività correla con un outcome sfavorevole (pEFS = 39% per MRM positiva < 1x10-3 e pEFS = 18% per MRM positiva ≥ 1x10-3), rispetto ai pazienti con MRM negativa (pEFS = 73%, P<0.0001). Inoltre, analizzando i pazienti in base al tipo di remissione al TCSE, livelli diversi di positività MRM correlano con un diverso impatto sulla pEFS: bassi livelli di positività MRM indicano infatti, una prognosi sfavorevole solo in pazienti trapiantati in seconda o altre RC, mentre in prima RC solo una positività alta si associa ad un aumentato rischio di ricaduta. Pertanto la MRM pre-TCSE si conferma come importante fattore predittivo di outcome e il suo effetto varia col variare del tipo di remissione al trapianto. È stata valutata, inoltre, la pEFS dei pazienti in base ai livelli di MRM post-TCSE1 e post-TCSE3; MRM negativa post-TCSE correla significativamente con un outcome favorevole, sia al 1° trimestre (pEFS = 63%), che ancor più se riscontrata al 3° trimestre (pEFS = 84%). Anche la valutazione prospettica del cambiamento di MRM è risultata significativa. In particolare, valutando la variazione di MRM dal 1° al 3° trimestre post-TCSE, i pazienti con MRM crescente hanno una prognosi sfavorevole (pEFS = 8%), mentre tutti gli altri gruppi correlano con una buona prognosi (pEFS ≥ 80%). Questi risultati confermano l’importanza del monitoraggio della MRM sia nel periodo precedente che successivo al TCSE, nell’identificare preventivamente pazienti ad alto rischio di ricaduta, possibili beneficiari di interventi immunologici preventivi. Il secondo progetto trattato (descritto nel capitolo 2) è stato uno studio preliminare, focalizzato su una PCR di terza generazione, la Droplet Digital PCR (ddPCR). Essa consente una quantifica di tipo assoluto, con un’accurata concentrazione del DNA target. La RQ-PCR fornisce, invece, una quantifica di tipo relativo, basata su una curva standard di calibrazione fatta con il DNA della diagnosi del paziente, per la quantificazione dei livelli di MRM di ciascun follow-up. Per cui, la PCR quantitativa può essere limitata dalla disponibilità di materiale diagnostico. Un ampio spettro di marcatori molecolari è già stato indagato mediante ddPCR per scopi diagnostici in varie patologie tumorali. Studi recenti hanno valutato l’applicabilità della ddPCR nell’ambito delle malattie linfoproliferative dell’adulto, come i linfomi e le LLA, mostrando una buona correlazione dei risultati fra le due metodiche in entrambi gli ambiti. Tuttavia, non sono ancora disponibili lavori che valutino questa correlazione nel campo delle leucemie pediatriche. Alla luce di questo, abbiamo eseguito analisi ddPCR sugli aspirati midollari di 65 pazienti pediatrici sottoposti a TCSE, utilizzando stessi primer e stesse sonde fluorescenti usati negli esperimenti RQ-PCR, nelle medesime condizioni di reazione. Mettendo a confronto i livelli di MRM emersi coi due approcci molecolari, si è investigata l’applicabilità della metodica assoluta per il monitoraggio della MRM anche in questo contesto. Inizialmente, sono stati valutati campioni risultati, mediante RQ-PCR, positivi ma non quantificabili (PNQ), per verificare se invece si potessero quantificare mediante ddPCR. Successivamente, è stato valutato anche l’impatto prognostico dei livelli MRM pre-TCSE ottenuti tramite ddPCR. Un buon livello di concordanza è emerso dai risultati ottenuti con entrambe le metodiche (Pearson r = 0.98, P < 0.0001); la ddPCR ha permesso, inoltre, di quantificare numerosi campioni risultati non quantificabili tramite RQ-PCR. I risultati suggeriscono che il metodo assoluto possieda sensibilità, accuratezza e riproducibilità almeno paragonabili alla PCR quantitativa convenzionale. I pazienti LLA analizzati sono stati stratificati sulla base dei livelli di MRD ottenuti con le due tecniche molecolari, ma nelle analisi di sopravvivenza non sono emerse differenze significative sulla prognosi. Infatti le pEFS dei pazienti con MRM negativa e positiva quantificabile per i due metodi risultano molto simili (rispettivamente 71% e 68%). Ciononostante, dal presente studio è emerso che col metodo digital sia stato possibile misurare un valore di MRM positivo e quantificabile per almeno 12 pazienti LLA che, in seguito al trapianto, hanno presentato una recidiva; viceversa, la RQ-PCR non era stata in grado di identificare anticipatamente la ricaduta di questi pazienti. Questi dati preliminari mostrano che la ddPCR possa essere un valido strumento per il monitoraggio della MRM e applicabile anche nel contesto dei trials clinici per pazienti LLA pediatrici. Tuttavia una prosecuzione dello studio ddPCR, con estensione della casistica analizzata, potrebbe essere utile a definire con precisione la significatività delle misurazioni con questa recente metodica.
Pittari, Gianfranco. "NK Cell Tolerance of Self-Specific Apecific Activating Receptor KIR2DS1 in Individuals with Cognate HLA-C2 Ligand". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T043.
Texto completo da fonteNK cells are regulated by inhibiting and activating cell surface receptors. Most inhibitory receptors recognize MHC-class I antigens, and protect healthy cells from NK cell-mediated auto-aggression. However, certain activating receptors, including the human killer cell Ig-like receptor (KIR) 2DS1, also recognize MHC-class I. This raises the question of how NK cells expressing such activating receptors are tolerized to host tissues. We investigated whether the presence of HLA-C2, the cognate ligand for 2DS1, induces tolerance in 2DS1-expressing NK cells. Anti-HLA-C2 activity could be detected in vitro in some 2DS1 positive NK clones irrespective of presence or absence of HLA-C2 ligand in the donor. The frequency of anti-HLA-C2 reactivity was high in donors homozygous for HLA-C1. Surprisingly, there was no significant difference in frequency of anti-HLA-C2 cytotoxicity in donors heterozygous for HLA-C2 and donors without HLA-C2 ligand. However, donors homozygous for HLA-C2 had significantly reduced frequency of anti-HLA-C2 reactive clones as compared to all other donors. 2DS1 positive clones that express inhibitory KIR for self-HLA class I were commonly non-cytotoxic, and anti-HLA-C2 cytotoxicity was nearly exclusively restricted to 2DS1 single positive clones lacking inhibitory KIR. 2DS1 single positive NK clones with anti-HLA-C2 reactivity were also present post-transplantation in HLA-C2 positive recipients of hematopoietic stem cell transplants from 2DS1 positive donors. These results demonstrate that many NK cells with anti-HLA-C2 reactivity are present in HLA-C1 homozygous and heterozygous donors with 2DS1. In contrast, 2DS1 positive clones from HLA-C2 homozygous donors are frequently tolerant to HLA-C2
Ibrahim, Rita. "Utilisation des communications Device-to-Device pour améliorer l'efficacité des réseaux cellulaires". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLC002/document.
Texto completo da fonteThis thesis considers Device-to-Device (D2D) communications as a promising technique for enhancing future cellular networks. Modeling, evaluating and optimizing D2D features are the fundamental goals of this thesis and are mainly achieved using the following mathematical tools: queuing theory, Lyapunov optimization and Partially Observed Markov Decision Process (POMDP). The findings of this study are presented in three parts. In the first part, we investigate a D2D mode selection scheme. We derive the queuing stability regions of both scenarios: pure cellular networks and D2D-enabled cellular networks. Comparing both scenarios leads us to elaborate a D2D vs cellular mode selection design that improves the capacity of the network. In the second part, we develop a D2D resource allocation algorithm. We observe that D2D users are able to estimate their local Channel State Information (CSI), however the base station needs some signaling exchange to acquire this information. Based on the D2D users' knowledge of their local CSI, we provide an energy efficient resource allocation framework that shows how distributed scheduling outperforms centralized one. In the distributed approach, collisions may occur between the different CSI reporting; thus, we propose a collision reduction algorithm. Moreover, we give a detailed description on how both centralized and distributed algorithms can be implemented in practice. In the third part, we propose a mobile relay selection policy in a D2D relay-aided network. Relays' mobility appears as a crucial challenge for defining the strategy of selecting the optimal D2D relays. The problem is formulated as a constrained POMDP which captures the dynamism of the relays and aims to find the optimal relay selection policy that maximizes the performance of the network under cost constraints
Varga, Caroline. "Dendroarchitecture des cellules de relais thalamiques chez le rat /". 2002. http://proquest.umi.com/pqdweb?did=766579291&sid=26&Fmt=2&clientId=9268&RQT=309&VName=PQD.
Texto completo da fonteJacobson, Kevin Robert. "MIMO Relays for Increased Coverage and Capacity in Broadband Cellular Systems". Phd thesis, 2010. http://hdl.handle.net/10048/1565.
Texto completo da fonteCommunications
Hsu, Shang-Hong, e 許尚宏. "Minimizing Upload Latency for Critical Tasks in Cellular-based IoT Networks using Multiple Relays". Thesis, 2017. http://ndltd.ncl.edu.tw/handle/4d7828.
Texto completo da fonteChen, Han Ting, e 陳菡廷. "Cellular Mechanism Underlying the Methamphetamine Extinction and Relapse: Role of Ventral Tegmental Area". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/97571182114662110929.
Texto completo da fonteTEDESCO, Vincenzo. "MOLECULAR AND CELLULAR MECHANISMS UNDERLYING COGNITIVE NEUROADAPTATION IN ADDICTION: AN IN VIVO-VITRO INTEGRATIVE APPROACH". Doctoral thesis, 2013. http://hdl.handle.net/11562/523350.
Texto completo da fonteTobacco use through cigarette smoking is the leading preventable cause of death in the developed world. The pharmacological effect of nicotine plays a crucial role in tobacco addiction. Nicotine is positively and negatively reinforcing and leads to the development of “operant conditioning” (motivated behaviour to nicotine consumption) in smokers during the acquisition phase of addiction. Several preclinical and clinical studies have also underlined the importance of non-pharmacological factors, such as environmental stimuli, in maintaining smoking behaviour and promoting relapse. Initially neutral stimuli that are repeatedly paired with a reinforcing drug (e.g. lighter) acquire a new conditioned value (conditioned stimuli, CS) through “Pavlovian conditioning” and become able to elicit craving even in the absence of the drug. Given the importance of the learned association between stimuli and nicotine in the phenomenon of relapse to nicotine-seeking behaviour, it has been proposed that treatment that disrupts the nicotine-associated memories could act as a pro-abstinent and anti-relapse therapy. After learning experience, memories are stored by a process called consolidation. Operant conditioning (also called instrumental learning) and Pavlovian conditioning lead to different drug-related memories formation (instrumental memories and Pavlovian memories) responsible for the relapse even after prolonged abstinence. However converging evidence from animal and human studies have revealed that memories may return to a vulnerable phase during which they can be updated, maintained and even disrupted. The retrieval of a memory indeed may destabilize the consolidated memory that requires a new process to be maintained. This hypothetical process is called reconsolidation. There is strong evidence that Pavlovian fear memories undergo reconsolidation and it was proposed that interventions to disrupt reconsolidation may help for specific and selective inhibition of fear related memories and, similarly, appetitive memories (i.e., for drug addiction). The disruption of drug-related memories reconsolidation has been proposed as a potential therapeutic target to prevent the CS-induced relapse in ex drug-addicts. Several animal studies have shown that the reconsolidation of some drug-related memories can be disrupted by the administration of an amnestic drug contingently upon retrieval of the memory acting at specific molecular levels (i.e. adrenergic and glutamatergic systems). However it is not known if all memories or only certain kind of memories could be retrieved and reconsolidated or disrupted. To date reconsolidation of instrumental memories is still under discussion and behavioural experiments targeting the pure instrumental memory reconsolidation disruption are needed to clarify this issue. The main objective of the present thesis was to study if it is possible to disrupt Pavlovian and instrumental nicotine-related memories reconsolidation by β-adrenergic receptor antagonist propranolol, or N-methyl-d-aspartate receptors (NMDARs) antagonist MK-801 respectively. We also verified the feasibility and reliability of Zif268 (a specific marker of memory reconsolidation) expression assessment by immunohistochemistry after retrieval of Palovian memory in rodents. The experimental approach used to address this issue was the laboratory model of nicotine self-administration in rats, based on the paradigms of operant and Pavlovian conditioning to nicotine and nicotine-associated cues. We performed two studies in which the pharmacological treatment (propranolol or MK-801) was associated to retrieval of Pavlovian or instrumental nicotine-related memories. We therefore assessed the effect of these pharmacological treatments on relapse to nicotine seeking behaviour. Retrieval of Pavlovian memories consists in presenting the CS in the absence of US. Retrieval of instrumental memories consists in allowing the animal to press the lever previously paired to nicotine reinforcement, without nicotine infusion. We also performed an immunohistochemistry assay in which the Zif268 level of expression was determined in basolateral amygdala (the most important region involved in memory reconsolidation) after nicotine CS presentation. Results showed that propranolol given after retrieval of Pavlovian memories (30 CS presentations) did not reduce the relapse to nicotine seeking behaviour compared to control groups that received vehicle injection in both retrieved or no-retrieved groups. It could be possible that instrumental memories, still present, do not undergo reconsolidation and could not be disrupted. To address this issue we tested the effect of MK-801, known to be more effective against instrumental memory than propranolol, given 30 minutes before the retrieval of instrumental memories. Results showed that pre-retrieval MK-801 injection did not prevent the relapse to nicotine-seeking behaviour when compared to control groups. This effect suggests a potential role of MK-801 in inhibition of the memory destabilization process instead of reconsolidation disruption. Further experiments in which MK-801 was given after memory destabilization was engaged (i.e. given after memory retrieval) showed that MK-801 prevented the relapse to nicotine-seeking behaviour. Finally immunohistochemistry showed an increased level of Zif268 expression in basolateral amygdala after retrieval of Pavlovian nicotine-related memories. These data confirm the validity and feasibility of immunohistochemistry to assess the expression of molecular markers correlating reconsolidation such as Zif268 after memory retrieval. In conclusion, our findings suggest that: i) propranolol did not disrupt Pavlovian memory reconsolidation in our conditions, ii) MK-801 given prior to retrieval session could prevent instrumental memory destabilization, but did not disrupt memory reconsolidation in our conditions, iii) MK-801 given after retrieval session disrupted memory reconsolidation in our conditions, iiii) immunohistochemistry is a feasible technique to investigate the expression of molecular markers correlating reconsolidation such as Zif268, thus it can be used to support our future behavioural studies. These data suggest that instrumental memory could be responsible for the lack of effect of some anti-relapse pharmacological treatments and that this kind of memory can be disrupted. New and specific pharmacological intervention, acting at specific molecular mechanisms that underlies reconsolidation of different kind of memories (i.e. Pavlovian but also instrumental memories), could be used as a potential co-adjuvant to current therapeutic interventions for smoking cessation and abstinence maintenance.
BOCCALINI, GIULIA. "CELLULAR MODELS OF HYPOXIA-REOXYGENATION FOR THE STUDY OF NEW MOLECULES WITH THERAPEUTIC POTENTIAL IN ISCHEMIC HEART DISEASE". Doctoral thesis, 2015. http://hdl.handle.net/2158/1045351.
Texto completo da fonte"High-Throughput Platforms for Tumor Dormancy-Relapse and Biomolecule Binding Using Aminoglycoside-Derived Hydrogels". Doctoral diss., 2016. http://hdl.handle.net/2286/R.I.38425.
Texto completo da fonteDissertation/Thesis
Doctoral Dissertation Bioengineering 2016
Fénelon, Karine. "Les mécanismes synaptiques et intrinsèques qui sous-tendent l’activité des cellules réticulospinales (RS) en réponse à une stimulation sensorielle de type cutané chez la lamproie". Thèse, 2008. http://hdl.handle.net/1866/2836.
Texto completo da fonteIn various animal species, sensory information can initiate locomotion. This relies on the integration of sensory inputs by the central nervous system. In lampreys, the spinal locomotor networks are activated and controlled by the reticulospinal cells (RS) which constitute the main descending system. In turn, RS cells receive information coming from various synaptic inputs such as the sensory afferents. Once activated by a brief cutaneous stimulation of sufficient strength, RS cells display sustained depolarizations of various durations that rely on calcium-dependant intrinsic properties and lead to the onset of escape swimming. During the course of this Ph.D, we aimed at determining whether synaptic inputs can modulate the duration of the sustained depolarizations and if the different populations of RS cells share the same integrative properties, possibly involving the internal calcium stores. First, our results show for the first time that excitatory glutamatergic inputs, including ascending spinal feedback, contribute to prolong the sustained depolarizations for long periods of time. Cutaneous inputs do not contribute to maintain the sustained depolarizations and inhibitory glycinergic and GABAergic inputs are not sufficient to stop them. Second, we show that in response to cutaneous stimulation, the RS located in the four reticular nuclei display a similar activation pattern and can all produce sustained depolarizations which do not depend on internal calcium release to be maintained. Finally, the results obtained during this Ph.D allowed us to better understand the cellular mechanisms by which the RS cells integrate and transform a brief sensory information into a sustained response associated with a motor command.