957 resultados para frequency response functions
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Background: There is growing evidence that individual EEG differences may aid in classifying patients with major depressive disorder (MDD) and also help predict clinical response to antidepressant treatment. This study aims to compare the effectiveness of EEG frequency band power, alpha asymmetry and prefrontal theta cordance towards escitalopram response prediction and MDD diagnosis, in a multi-site initiative. Methods: Resting EEG (eyes open and closed) was recorded from 64 electrodes in 44 depressed patients and 20 healthy controls at baseline, 2 weeks post-treatment and 8 weeks post-treatment. Clinical response was measured as change from baseline MADRS of 50% or more. EEG measures were analyzed (1) at baseline (2) at 2 weeks post-treatment and (3) as an ‘‘early change” variable defined as change in EEG from baseline to 2 weeks post-treatment. Results: At baseline, responders exhibited greater absolute alpha power in the left hemisphere versus the right while non-responders showed the opposite. Responders further exhibited a cortical asymmetry of greater right relative to left activity in parietal areas. Groups also differed in baseline relative delta power with responders showing greater power in the right hemisphere versus the left while non-responders showed the opposite. At 2 weeks post-treatment, responders exhibited greater absolute beta power in the left hemisphere relative to right and the opposite was noted for non-responders. The opposite pattern was noted for absolute and relative delta power at 2 weeks post-treatment. Responders exhibited early reduction in relative alpha power and early increments in relative theta power. Non-responders showed a significant early increase in prefrontal theta cordance. Absolute delta power helped distinguish MDD patients from healthy controls. Conclusions: Hemispheric asymmetries in the alpha and delta bands at pre-treatment baseline and at 2 weeks post-treatment have moderate to moderately strong predictive utility towards antidepressant treatment response. These findings have significant potential for improving clinical practice in psychiatry by eventually guiding clinical choice of treatments. This would greatly benefit patients awaiting relief from depressive symptoms as treatment optimization would help overcome problems associated with delayed recovery. Our results also indicate that resting EEG activity may have clinical utility in predicting MDD diagnosis.
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ABSTRACT: The ability of Antarctic krill Euphausia superba Dana to withstand the overwintering period is critical to their success. Laboratory evidence suggests that krill may shrink in body length during this time in response to the low availability of food. Nevertheless, verification that krill can shrink in the natural environment is lacking because winter data are difficult to obtain. One of the few sources of winter krill population data is from commercial vessels. We examined length-frequency data of adult krill (>35 mm total body length) obtained from commercial vessels in the Scotia-Weddell region and compared our results with those obtained from a combination of science and commercial sampling operations carried out in this region at other times of the year. Our analyses revealed body-length shrinkage in adult females but not males during overwinter, based on both the tracking of modal size classes over seasons and sex-ratio patterns. Other explanatory factors, such as differential mortality, immigration and emigration, could not explain the observed differences. The same pattern was also observed at South Georgia and in the Western Antarctic Peninsula. Fitted seasonally modulated von Bertalanffy growth functions predicted a pattern of overwintering shrinkage in all body-length classes of females, but only stagnation in growth in males. This shrinkage most likely reflects morphometric changes resulting from the contraction of the ovaries and is not necessarily an outcome of winter hardship. The sex-dependent changes that we observed need to be incorporated into life cycle and population dynamic models of this species, particularly those used in managing the fishery. KEY WORDS: Southern Ocean · Population dynamics · Production · Life cycle · Fishery
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ABSTRACT: The ability of Antarctic krill Euphausia superba Dana to withstand the overwintering period is critical to their success. Laboratory evidence suggests that krill may shrink in body length during this time in response to the low availability of food. Nevertheless, verification that krill can shrink in the natural environment is lacking because winter data are difficult to obtain. One of the few sources of winter krill population data is from commercial vessels. We examined length-frequency data of adult krill (>35 mm total body length) obtained from commercial vessels in the Scotia-Weddell region and compared our results with those obtained from a combination of science and commercial sampling operations carried out in this region at other times of the year. Our analyses revealed body-length shrinkage in adult females but not males during overwinter, based on both the tracking of modal size classes over seasons and sex-ratio patterns. Other explanatory factors, such as differential mortality, immigration and emigration, could not explain the observed differences. The same pattern was also observed at South Georgia and in the Western Antarctic Peninsula. Fitted seasonally modulated von Bertalanffy growth functions predicted a pattern of overwintering shrinkage in all body-length classes of females, but only stagnation in growth in males. This shrinkage most likely reflects morphometric changes resulting from the contraction of the ovaries and is not necessarily an outcome of winter hardship. The sex-dependent changes that we observed need to be incorporated into life cycle and population dynamic models of this species, particularly those used in managing the fishery. KEY WORDS: Southern Ocean · Population dynamics · Production · Life cycle · Fishery
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Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study, we conducted an extensive analysis of mutations and single-nucleotide polymorphisms (SNPs) in borderline ovarian tumors. Using the Sequenom MassArray platform, we investigated 160 mutations/polymorphisms in 33 genes involved in cell signaling, apoptosis, angiogenesis, cell cycle regulation and cellular senescence. Of 52 tumors analyzed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in eight tumors (six serous and two mucinous), BRAF V600E mutations in two serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT, respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in vascular endothelial growth factor (VEGF), ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at four loci. PHLPP2 polymorphisms were more frequent in mucinous as compared with serous tumors (P=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional SNPs in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbor somatic mutations associated with potential response to targeted therapeutics.
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PurposeTP53 mutations have been described in chronic lymphocytic leukemia (CLL) and have been associated with poor prognosis in retrospective studies. We aimed to address the frequency and prognostic value of TP53 abnormalities in patients with CLL in the context of a prospective randomized trial.Patients and MethodsWe analyzed 529 CLL samples from the LRF CLL4 (Leukaemia Research Foundation Chronic Lymphocytic Leukemia 4) trial (chlorambucil v fludarabine with or without cyclophosphamide) at the time of random assignment for mutations in the TP53 gene. TP53 mutation status was correlated with response and survival data.ResultsMutations of TP53 were found in 40 patients (7.6%), including 25 (76%) of 33 with 17p deletion and 13 (3%) of 487 without that deletion. There was no significant correlation between TP53 mutations and age, stage, IGHV gene mutations, CD38 and ZAP-70 expression, or any other chromosomal abnormality other than 17p deletion, in which concordance was high (96%). TP53 mutations were significantly associated with poorer overall response rates (27% v 83%; P <.001) and shorter progression-free survival (PFS) and overall survival (OS; 5-year PFS: 5% v 17%; 5-year OS: 20% v 59%; P <.001 for both). Multivariate analysis that included baseline clinical variables, treatment, and known adverse genetic factors confirmed that TP53 mutations have added prognostic value.ConclusionTP53 mutations are associated with impaired response and shorter survival in patients with CLL. Analysis of TP53 mutations should be performed in patients with CLL who have progressive disease before starting first-line treatment, and those with mutations should be selected for novel experimental therapies. J Clin Oncol 29: 2223-2229. (C) 2011 by American Society of Clinical Oncology
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A rede social dos sujeitos tem sido considerada fundamental para lidar com a adversidade. O objetivo central deste estudo foi caracterizar as redes sociais pessoais de jovens em regime de acolhimento institucional prolongado, na perspetiva dos próprios e dos técnicos das instituições e perceber se estas relacionam com o projeto de vida. Participaram 84 jovens, com idades compreendidas entre os 12 e os 20 anos de idade, acolhidos em 6 lares de infância e juventude do distrito de Santarém. Os participantes são na sua maioria do sexo feminino, com uma idade média de 15 anos. Para avaliação das variáveis em estudo utilizou-se a versão revista sumária do Instrumento de Avaliação de Redes Sociais Pessoais (IARSP-RS) e um questionário de autorresposta de caracterização da instituição de acolhimento. Os resultados desta investigação permitiram verificar que as redes dos jovens em situação de acolhimento institucional são fragmentadas, constituídas, em média, por 12 elementos e predominantemente compostas por familiares, amigos e profissionais das instituições, destacando-se as relações familiares. O nível de apoio social percebido é elevado na função emocional e informativa. Verificou-se uma maior reciprocidade do apoio por parte das jovens do sexo feminino, a institucionalização pode potenciar a expansão da rede social de suporte e a frequência de contactos associa-se à distância geográfica. A satisfação dos jovens com o suporte social é elevada. Metade dos jovens perspetivam a saída da instituição pela via da autonomização. A perceção dos profissionais das redes de suporte social é mais limitada, no tamanho, reciprocidade, satisfação com o suporte social e nas relações estabelecidas com a família, amigos da comunidade envolvente e relações de trabalho/estudo. Por outro lado, os técnicos identificam um nível mais elevado de densidade e de vínculos com os técnicos e educadores da instituição. Não se verificaram diferenças significativas nas características da rede social em função do projeto de vida, porém perceberam-se diferenças no projeto de vida em função da idade e da duração do acolhimento. A rede social apresenta um potencial protetor que vale a pena conhecer, fomentar e valorizar, destacando-se que é importante conhecer a perspetiva do próprio sujeito, já que esta tem um carácter muito pessoal. / The social network has been considered fundamental to deal with the adversities. The main objective of this study was to characterize the social network of the youngesters in prolonged institutional care, from the perspective of themselves and professionals of the institutions and to observe if their social network fits with their life project. 84 youngsters with ages between 12 and 20 years old living in 6 institutions of childhood and juvenile care from de district of Santarém participated in this study. The participants are mainly female, with an average age of 15 years old. To evaluate the variables in study, it was applied a version of the summary review of the Instrument of Evaluation of Personal Social Networks (IARSP-RS) and a survey of self-response to characterize the institutional care. The results of this investigation allowed to conclude that the social network of youngsters in a situation of institutional care are fragmented, composed by an average of 12 elements and primarily composed by family members, friends and professionals, but the most significant were the family relationships. It was observed that social support is high in terms of emotional and informative functions. It was observed an higher mutual support from the young ladies, institutionalization may foster the expansion of the social support network and that the frequency of connections is related with geographic distance. The satisfaction of the youngsters with social support is high. Half of the youngsters previews getting out of the institution by becoming autonomous. The understanding of the professionals of the social support network is more limited, about size, mutuality, satisfaction with the social support, family, friends of involving community and relationship of work/study. On the other side, the professionals identify an higher level of density and bonds with the technicals and educators of the institutions. Significative differences in the characteristics social network in terms of the life project weren’t found, however there were diferences in the life project in terms of the age and the duration of institutionalization. The social network has a protector potential that is worth of studying, promote and valorize, highlighting that it is important to know the perspective of the individual, because of its personal nature.
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Thesis (Ph.D.)--University of Washington, 2016-08
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Thesis (Ph.D.)--University of Washington, 2016-08
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This dissertation contains four essays that all share a common purpose: developing new methodologies to exploit the potential of high-frequency data for the measurement, modeling and forecasting of financial assets volatility and correlations. The first two chapters provide useful tools for univariate applications while the last two chapters develop multivariate methodologies. In chapter 1, we introduce a new class of univariate volatility models named FloGARCH models. FloGARCH models provide a parsimonious joint model for low frequency returns and realized measures, and are sufficiently flexible to capture long memory as well as asymmetries related to leverage effects. We analyze the performances of the models in a realistic numerical study and on the basis of a data set composed of 65 equities. Using more than 10 years of high-frequency transactions, we document significant statistical gains related to the FloGARCH models in terms of in-sample fit, out-of-sample fit and forecasting accuracy compared to classical and Realized GARCH models. In chapter 2, using 12 years of high-frequency transactions for 55 U.S. stocks, we argue that combining low-frequency exogenous economic indicators with high-frequency financial data improves the ability of conditionally heteroskedastic models to forecast the volatility of returns, their full multi-step ahead conditional distribution and the multi-period Value-at-Risk. Using a refined version of the Realized LGARCH model allowing for time-varying intercept and implemented with realized kernels, we document that nominal corporate profits and term spreads have strong long-run predictive ability and generate accurate risk measures forecasts over long-horizon. The results are based on several loss functions and tests, including the Model Confidence Set. Chapter 3 is a joint work with David Veredas. We study the class of disentangled realized estimators for the integrated covariance matrix of Brownian semimartingales with finite activity jumps. These estimators separate correlations and volatilities. We analyze different combinations of quantile- and median-based realized volatilities, and four estimators of realized correlations with three synchronization schemes. Their finite sample properties are studied under four data generating processes, in presence, or not, of microstructure noise, and under synchronous and asynchronous trading. The main finding is that the pre-averaged version of disentangled estimators based on Gaussian ranks (for the correlations) and median deviations (for the volatilities) provide a precise, computationally efficient, and easy alternative to measure integrated covariances on the basis of noisy and asynchronous prices. Along these lines, a minimum variance portfolio application shows the superiority of this disentangled realized estimator in terms of numerous performance metrics. Chapter 4 is co-authored with Niels S. Hansen, Asger Lunde and Kasper V. Olesen, all affiliated with CREATES at Aarhus University. We propose to use the Realized Beta GARCH model to exploit the potential of high-frequency data in commodity markets. The model produces high quality forecasts of pairwise correlations between commodities which can be used to construct a composite covariance matrix. We evaluate the quality of this matrix in a portfolio context and compare it to models used in the industry. We demonstrate significant economic gains in a realistic setting including short selling constraints and transaction costs.
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The present study was undertaken to identify proteins interacting with PrPC that could provide new insights into its physiological functions and pathological role. We performed a target search for lysosomal network protein, Rab7a and Rab9, in frontal cortex and cerebellum of human brain from patients with sCJD-MM1 and sCJD-VV2. The intracellular level of Rab7a was increased significantly, when compared with healthy age-matched control. Interactions of PrPC and Rab7a/Rab9 were further investigated by using confocal laser scanning microscopy. Immunofluorescence results suggested potential interactions of Rab7a and PrPC. siRNA against the Rab7a gene was used to knockdown the expression of Rab7a protein in primary cell culture of cortical neurons from wild type mice. This depleted Rab7a resulted an impairment of PrPC trafficking leading to an accumulation of PrPC in the endocytosis pathway. Furthermore, interactions of Tau and Rab7a were investigated by using western blot analysis and confocal laser scanning microscopy. Cell cultures of cortex of wildtype mice were treated with siRNA-Tau, siRNA-Rab7 and control siRNA followed by immunofluorescence. The results of immunofluorescence suggested potential interaction of Tau and Rab7a. Cells lines treated with siRNA-Tau, the intracellular levels of Rab7a and Rab9 significantly increases and their localization is also modified. When we transfected this cells lines with siRNA-rab7a the accumulation of Tau decreases in cytosolic region and their localization was also modified when compared with control cells. In conclusion, this study may help to understand and characterize the subtype specific disease progression in CJD cases. Furthermore, it could be a step ahead to development of new treatment strategies for diseases subtype specific manner.
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In this Letter we introduce a continuum model of neural tissue that include the effects of so-called spike frequency adaptation (SFA). The basic model is an integral equation for synaptic activity that depends upon the non-local network connectivity, synaptic response, and firing rate of a single neuron. A phenomenological model of SFA is examined whereby the firing rate is taken to be a simple state-dependent threshold function. As in the case without SFA classical Mexican-Hat connectivity is shown to allow for the existence of spatially localized states (bumps). Importantly an analysis of bump stability using recent Evans function techniques shows that bumps may undergo instabilities leading to the emergence of both breathers and traveling waves. Moreover, a similar analysis for traveling pulses leads to the conditions necessary to observe a stable traveling breather. Direct numerical simulations both confirm our theoretical predictions and illustrate the rich dynamic behavior of this model, including the appearance of self-replicating bumps.
Negative regulation of the hepatic fibrogenic response by suppressor of cytokine signaling 1 (SOCS1)
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Abstract: Suppressor of cytokine signaling 1 (SOCS1) is an indispensable regulator of IFN-γ signaling and has been implicated in the regulation of liver fibrosis. However, it is not known whether SOCS1 mediates its anti-fibrotic functions in the liver directly, or via modulating IFN-γ, which has been implicated in attenuating hepatic fibrosis. Additionally, it is possible that SOCS1 controls liver fibrosis by regulating hepatic stellate cells (HSC), a key player in fibrogenic response. While the activation pathways of HSCs have been well characterized, the regulatory mechanisms are not yet clear. The goals of this study were to dissociate IFN-γ-dependent and SOCS1-mediated regulation of hepatic fibrogenic response, and to elucidate the regulatory functions of SOCS1 in H SC activation. Liver fibrosis was induced in Socs1[superscript -/-]Ifng[superscript -/-] mice with dimethylnitrosamine or carbon tetrachloride. Ifng[superscript -/-] and C57BL/6 mice served as controls. Following fibrogenic treatments, Socs1[superscript -/-]Ifng[superscript -/-] mice showed elevated serum ALT levels and increased liver fibrosis com-pared to mice Ifng[superscript -/-]. The latter group showed higher alanine aminotransferase (ALT) levels and fibrosis than C57BL/6 controls. The livers of Socs1-deficient mice showed bridging fibrosis, which was associated with increased accumulation of myofibroblasts and abundant collagen deposition. Socs1-deficient livers showed increased expression of genes coding for smooth muscle actin, collagen, and enzymes involved in remodeling the extracellular matrix, namely matrix metalloproteinases and tissue inhibitor of metalloproteinases. Primary HSCs from Socs1-deficient mice showed increased proliferation in response to growth factors such as HGF, EGF and PDGF, and the fibrotic livers of Socs1-deficient mice showed increased expression of the Pdgfb gene. Taken together, these data indicate that SOCS1 controls liver fibrosis independently of IFN-γ and that part of this regulation may occur via regulating HSC proliferation and limiting growth factor availability.
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Wnt signalling is involved in a wide range of physiological and pathological processes. The presence of an extracellular Wnt stimulus induces cytoplasmic stabilisation and nuclear translocation of beta-catenin, a protein that also plays an essential role in cadherin-mediated adhesion. Two main hypotheses have been proposed concerning the balance between beta-catenin's adhesive and transcriptional functions: either beta-catenin's fate is determined by competition between its binding partners, or Wnt induces folding of beta-catenin into a conformation allocated preferentially to transcription. The experimental data supporting each hypotheses remain inconclusive. In this paper we present a new mathematical model of the Wnt pathway that incorporates beta-catenin's dual function. We use this model to carry out a series of in silico experiments and compare the behaviour of systems governed by each hypothesis. Our analytical results and model simulations provide further insight into the current understanding of Wnt signalling and, in particular, reveal differences in the response of the two modes of interaction between adhesion and signalling in certain in silico settings. We also exploit our model to investigate the impact of the mutations most commonly observed in human colorectal cancer. Simulations show that the amount of functional APC required to maintain a normal phenotype increases with increasing strength of the Wnt signal, a result which illustrates that the environment can substantially influence both tumour initiation and phenotype.
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Distributed generation systems must fulfill standards specifications of current harmonics injected to the grid. In order to satisfy these grid requirements, passive filters are connected between inverter and grid. This work compares the characteristic response of the traditional inductive (L) filter with the inductive-capacitive-inductive (LCL) filter. It is shown that increasing the inductance L leads to a good ripple current suppression around the inverter switching frequency. The LCL filter provides better harmonic attenuation and reduces the filter size. The main drawback is the LCL filter impedance, which is characterized by a typical resonance peak, which must be damped to avoid instability. Passive or active techniques can be used to damp the LCL resonance. To address this issue, this dissertation presents a comparison of current control for PV grid-tied inverters with L filter and LCL filter and also discuss the use of active and passive damping for different regions of resonance frequency. From the mathematical models, a design methodology of the controllers was developed and the dynamic behavior of the system operating in closed loop was investigated. To validate the studies developed during this work, experimental results are presented using a three-phase 5kW experimental platform. The main components and their functions are discussed in this work. Experimental results are given to support the theoretical analysis and to illustrate the performance of grid-connected PV inverter system. It is shown that the resonant frequency of the system, and sampling frequency can be associated in order to calculate a critical frequency, below which is essential to perform the damping of the LCL filter. Also, the experimental results show that the active buffer per virtual resistor, although with a simple development, is effective to damp the resonance of the LCL filter and allow the system to operate stable within predetermined parameters.
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La construction des biosystèmes d’oxydation passive du méthane (BOPM) est une option économique et durable pour réduire les émissions de méthane des sites d’enfouissement de déchets et des effets subséquents du réchauffement climatique. Les BOPM sont constitués de deux couches principales: la couche d'oxydation du méthane (MOL) et la couche de distribution du gaz (GDL). L'oxydation du méthane se produit dans la MOL par les réactions biochimiques des bactéries méthanotrophes, et la GDL est construite sous la MOL pour intercepter et distribuer les émissions fugitives de biogaz à la base de la MOL. Fondamentalement, l'efficacité d'un BOPM est définie en fonction de l'efficacité d'oxydation du méthane dans la MOL. Par conséquent, il est indispensable de fournir des conditions adéquates pour les activités bactériennes des méthanotrophes. En plus des paramètres environnementaux, l'intensité et la distribution du biogaz influencent l'efficacité des BOPM, et ils peuvent rendre le matériau de la MOL - avec une grande capacité d'accueillir les activités bactériennes - inutilisables en termes d'oxydation du méthane sur place. L'effet de barrière capillaire le long de l'interface entre la GDL et la MOL peut provoquer des émissions localisées de méthane, due à la restriction ou la distribution non uniforme de l’écoulement ascendant du biogaz à la base de la MOL. L'objectif principal de cette étude est d'incorporer le comportement hydraulique non saturé des BOPM dans la conception des BOPM, afin d’assurer la facilité et la distribution adéquates de l'écoulement du biogaz à la base de la MOL. Les fonctions de perméabilité à l'air des matériaux utilisés pour construire la MOL des BOPM expérimentaux au site d’enfouissement des déchets de St Nicéphore (Québec, Canada), ainsi que celles d'autres de la littérature technique, ont été étudiés pour évaluer le comportement d'écoulement non saturé du gaz dans les matériaux et pour identifier le seuil de migration sans restriction du gaz. Ce dernier seuil a été introduit en tant que un paramètre de conception avec lequel le critère de conception recommandé ici, c’est à dire la longueur de la migration sans restriction de gaz (LMSG), a été défini. La LMSG est considérée comme la longueur le long de l'interface entre la GDL et la MOL où le biogaz peut migrer à travers la MOL sans restriction. En réalisant des simulations numériques avec SEEP/W, les effets de la pente de l'interface, des paramètres définissant la courbe de rétention d'eau, de la fonction de la conductivité hydraulique du matériau de la MOL sur la valeur de la LMSG (représentant la facilité d'écoulement du biogaz à l'interface) et de la distribution de l'humidité (et par conséquent celle du biogaz) ont été évalués. Selon les résultats des simulations, la conductivité hydraulique saturée et la distribution des tailles de pores du matériau de la MOL sont les paramètres les plus importants sur la distribution de l'humidité le long de l'interface. Ce dernier paramètre influe également sur la valeur du degré de saturation et donc la facilité du biogaz à la base de la MOL. La densité sèche du matériau de MOL est un autre paramètre qui contrôle la facilité d'écoulement ascendant du biogaz. Les limitations principales de la présente étude sont associées au nombre de matériaux de MOL testés et à l'incapacité de SEEP/W de considérer l'évapotranspiration. Toutefois, compte tenu des hypothèses raisonnables dans les simulations et en utilisant les données de la littérature, on a essayé de réduire ces limitations. En utilisant les résultats des expériences et des simulations numériques, des étapes et des considérations de conception pour la sélection du matériau de MOL et de la pente d'interface ont été proposées. En effet,le comportement hydraulique non saturé des matériaux serait intégré dans les nécessités de conception pour un BOPM efficace, de sorte que la capacité maximale possible d'oxydation du méthane du matériau de la MOL soit exploitée.