74 resultados para Sterol-sensing Domain
em Consorci de Serveis Universitaris de Catalunya (CSUC), Spain
Resumo:
The division problem consists of allocating an amount M of a perfectly divisible good among a group of n agents. Sprumont (1991) showed that if agents have single-peaked preferences over their shares, the uniform rule is the unique strategy-proof, efficient, and anonymous rule. Ching and Serizawa (1998) extended this result by showing that the set of single-plateaued preferences is the largest domain, for all possible values of M, admitting a rule (the extended uniform rule) satisfying strategy-proofness, efficiency and symmetry. We identify, for each M and n, a maximal domain of preferences under which the extended uniform rule also satisfies the properties of strategy-proofness, efficiency, continuity, and "tops-onlyness". These domains (called weakly single-plateaued) are strictly larger than the set of single-plateaued preferences. However, their intersection, when M varies from zero to infinity, coincides with the set of single-plateaued preferences.
Resumo:
Nanomotors are nanoscale devices capable of converting energy into movement and forces. Among them, self-propelled nanomotors offer considerable promise for developing new and novel bioanalytical and biosensing strategies based on the direct isolation of target biomolecules or changes in their movement in the presence of target analytes. The mainachievements of this project consists on the development of receptor-functionalized nanomotors that offer direct and rapid target detection, isolation and transport from raw biological samples without preparatory and washing steps. For example, microtube engines functionalized with aptamer, antibody, lectin and enzymes receptors were used for the direct isolation of analytes of biomedical interest, including proteins and whole cells, among others. A target protein was also isolated from a complex sample by using an antigen-functionalized microengine navigating into the reservoirs of a lab-on-a-chip device. The new nanomotorbased target biomarkers detection strategy not only offers highly sensitive, rapid, simple and low cost alternative for the isolation and transport of target molecules, but also represents a new dimension of analytical information based on motion. The recognition events can be easily visualized by optical microscope (without any sophisticated analytical instrument) to reveal the target presence and concentration. The use of artificial nanomachines has shown not only to be useful for (bio)recognition and (bio)transport but also for detection of environmental contamination and remediation. In this context, micromotors modified with superhydrophobic layer demonstrated that effectively interacted, captured, transported and removed oil droplets from oil contaminated samples. Finally, a unique micromotor-based strategy for water-quality testing, that mimics live-fish water-quality testing, based on changes in the propulsion behavior of artificial biocatalytic microswimmers in the presence of aquatic pollutants was also developed. The attractive features of the new micromachine-based target isolation and signal transduction protocols developed in this project offer numerous potential applications in biomedical diagnostics, environmental monitoring, and forensic analysis.
Resumo:
Report for the scientific sojourn carried out at the l’ Institute for Computational Molecular Science of the Temple University, United States, from 2010 to 2012. Two-component systems (TCS) are used by pathogenic bacteria to sense the environment within a host and activate mechanisms related to virulence and antimicrobial resistance. A prototypical example is the PhoQ/PhoP system, which is the major regulator of virulence in Salmonella. Hence, PhoQ is an attractive target for the design of new antibiotics against foodborne diseases. Inhibition of the PhoQ-mediated bacterial virulence does not result in growth inhibition, presenting less selective pressure for the generation of antibiotic resistance. Moreover, PhoQ is a histidine kinase (HK) and it is absent in animals. Nevertheless, the design of satisfactory HK inhibitors has been proven to be a challenge. To compete with the intracellular ATP concentrations, the affinity of a HK inhibidor must be in the micromolar-nanomolar range, whereas the current lead compounds have at best millimolar affinities. Moreover, the drug selectivity depends on the conformation of a highly variable loop, referred to as the “ATP-lid, which is difficult to study by X-Ray crystallography due to its flexibility. I have investigated the binding of different HK inhibitors to PhoQ. In particular, all-atom molecular dynamics simulations have been combined with enhanced sampling techniques in order to provide structural and dynamic information of the conformation of the ATP-lid. Transient interactions between these drugs and the ATP-lid have been identified and the free energy of the different binding modes has been estimated. The results obtained pinpoint the importance of protein flexibility in the HK-inhibitor binding, and constitute a first step in developing more potent and selective drugs. The computational resources of the hosting institution as well as the experience of the members of the group in drug binding and free energy methods have been crucial to carry out this work.
Resumo:
The pseudo-spectral time-domain (PSTD) method is an alternative time-marching method to classicalleapfrog finite difference schemes in the simulation of wave-like propagating phenomena. It is basedon the fundamentals of the Fourier transform to compute the spatial derivatives of hyperbolic differential equations. Therefore, it results in an isotropic operator that can be implemented in an efficient way for room acoustics simulations. However, one of the first issues to be solved consists on modeling wallabsorption. Unfortunately, there are no references in the technical literature concerning to that problem. In this paper, assuming real and constant locally reacting impedances, several proposals to overcome this problem are presented, validated and compared to analytical solutions in different scenarios.
Resumo:
The Pseudo-Spectral Time Domain (PSTD) method is an alternative time-marching method to classical leapfrog finite difference schemes inthe simulation of wave-like propagating phenomena. It is based on the fundamentals of the Fourier transform to compute the spatial derivativesof hyperbolic differential equations. Therefore, it results in an isotropic operator that can be implemented in an efficient way for room acousticssimulations. However, one of the first issues to be solved consists on modeling wall absorption. Unfortunately, there are no references in thetechnical literature concerning to that problem. In this paper, assuming real and constant locally reacting impedances, several proposals toovercome this problem are presented, validated and compared to analytical solutions in different scenarios.
Resumo:
The objective of the PANACEA ICT-2007.2.2 EU project is to build a platform that automates the stages involved in the acquisition,production, updating and maintenance of the large language resources required by, among others, MT systems. The development of a Corpus Acquisition Component (CAC) for extracting monolingual and bilingual data from the web is one of the most innovative building blocks of PANACEA. The CAC, which is the first stage in the PANACEA pipeline for building Language Resources, adopts an efficient and distributed methodology to crawl for web documents with rich textual content in specific languages and predefined domains. The CAC includes modules that can acquire parallel data from sites with in-domain content available in more than one language. In order to extrinsically evaluate the CAC methodology, we have conducted several experiments that used crawled parallel corpora for the identification and extraction of parallel sentences using sentence alignment. The corpora were then successfully used for domain adaptation of Machine Translation Systems.
Resumo:
El tema de este estudio es el aumento de la comprensión teórica y empírica de la estrategia de negocio de código abierto en el dominio de sistemas embebidos por investigar modelos de negocios de código abierto, retos, recursos y capacidades operativas y dinámicas.
Resumo:
Expected utility theory (EUT) has been challenged as a descriptive theoryin many contexts. The medical decision analysis context is not an exception.Several researchers have suggested that rank dependent utility theory (RDUT)may accurately describe how people evaluate alternative medical treatments.Recent research in this domain has addressed a relevant feature of RDU models-probability weighting-but to date no direct test of this theoryhas been made. This paper provides a test of the main axiomatic differencebetween EUT and RDUT when health profiles are used as outcomes of riskytreatments. Overall, EU best described the data. However, evidence on theediting and cancellation operation hypothesized in Prospect Theory andCumulative Prospect Theory was apparent in our study. we found that RDUoutperformed EU in the presentation of the risky treatment pairs in whichthe common outcome was not obvious. The influence of framing effects onthe performance of RDU and their importance as a topic for future researchis discussed.
Resumo:
In this article we propose using small area estimators to improve the estimatesof both the small and large area parameters. When the objective is to estimateparameters at both levels accurately, optimality is achieved by a mixed sampledesign of fixed and proportional allocations. In the mixed sample design, oncea sample size has been determined, one fraction of it is distributedproportionally among the different small areas while the rest is evenlydistributed among them. We use Monte Carlo simulations to assess theperformance of the direct estimator and two composite covariant-freesmall area estimators, for different sample sizes and different sampledistributions. Performance is measured in terms of Mean Squared Errors(MSE) of both small and large area parameters. It is found that the adoptionof small area composite estimators open the possibility of 1) reducingsample size when precision is given, or 2) improving precision for a givensample size.
Resumo:
This paper proposes an exploration of the methodology of utilityfunctions that distinguishes interpretation from representation. Whilerepresentation univocally assigns numbers to the entities of the domainof utility functions, interpretation relates these entities withempirically observable objects of choice. This allows us to makeexplicit the standard interpretation of utility functions which assumesthat two objects have the same utility if and only if the individual isindifferent among them. We explore the underlying assumptions of suchan hypothesis and propose a non-standard interpretation according towhich objects of choice have a well-defined utility although individualsmay vary in the way they treat these objects in a specific context.We provide examples of such a methodological approach that may explainsome reversal of preferences and suggest possible mathematicalformulations for further research.
Resumo:
This paper proposes a new time-domain test of a process being I(d), 0 < d = 1, under the null, against the alternative of being I(0) with deterministic components subject to structural breaks at known or unknown dates, with the goal of disentangling the existing identification issue between long-memory and structural breaks. Denoting by AB(t) the different types of structural breaks in the deterministic components of a time series considered by Perron (1989), the test statistic proposed here is based on the t-ratio (or the infimum of a sequence of t-ratios) of the estimated coefficient on yt-1 in an OLS regression of ?dyt on a simple transformation of the above-mentioned deterministic components and yt-1, possibly augmented by a suitable number of lags of ?dyt to account for serial correlation in the error terms. The case where d = 1 coincides with the Perron (1989) or the Zivot and Andrews (1992) approaches if the break date is known or unknown, respectively. The statistic is labelled as the SB-FDF (Structural Break-Fractional Dickey- Fuller) test, since it is based on the same principles as the well-known Dickey-Fuller unit root test. Both its asymptotic behavior and finite sample properties are analyzed, and two empirical applications are provided.
Resumo:
Remote sensing spatial, spectral, and temporal resolutions of images, acquired over a reasonably sized image extent, result in imagery that can be processed to represent land cover over large areas with an amount of spatial detail that is very attractive for monitoring, management, and scienti c activities. With Moore's Law alive and well, more and more parallelism is introduced into all computing platforms, at all levels of integration and programming to achieve higher performance and energy e ciency. Being the geometric calibration process one of the most time consuming processes when using remote sensing images, the aim of this work is to accelerate this process by taking advantage of new computing architectures and technologies, specially focusing in exploiting computation over shared memory multi-threading hardware. A parallel implementation of the most time consuming process in the remote sensing geometric correction has been implemented using OpenMP directives. This work compares the performance of the original serial binary versus the parallelized implementation, using several multi-threaded modern CPU architectures, discussing about the approach to nd the optimum hardware for a cost-e ective execution.
Resumo:
The ability to regulate specific genes of energy metabolism in response to fasting and feeding is an important adaptation allowing survival of intermittent food supplies. However, little is known about transcription factors involved in such responses in higher organisms. We show here that gene expression in adipose tissue for adipocyte determination differentiation dependent factor (ADD) 1/sterol regulatory element binding protein (SREBP) 1, a basic-helix-loop-helix protein that has a dual DNA-binding specificity, is reduced dramatically upon fasting and elevated upon refeeding; this parallels closely the regulation of two adipose cell genes that are crucial in energy homeostasis, fatty acid synthetase (FAS) and leptin. This elevation of ADD1/SREBP1, leptin, and FAS that is induced by feeding in vivo is mimicked by exposure of cultured adipocytes to insulin, the classic hormone of the fed state. We also show that the promoters for both leptin and FAS are transactivated by ADD1/SREBP1. A mutation in the basic domain of ADD1/SREBP1 that allows E-box binding but destroys sterol regulatory element-1 binding prevents leptin gene transactivation but has no effect on the increase in FAS promoter function. Molecular dissection of the FAS promoter shows that most if not all of this action of ADD1/SREBP1 is through an E-box motif at -64 to -59, contained with a sequence identified previously as the major insulin response element of this gene. These results indicate that ADD1/SREBP1 is a key transcription factor linking changes in nutritional status and insulin levels to the expression of certain genes that regulate systemic energy metabolism.