967 resultados para Combined virtual screening
Resumo:
El objetivo de este proyecto es la simulación de la Flota P del fabricante CAF comprado recientemente por la compañía Metro Sao Paulo. Esta flota forma parte de un proyecto con cuatro trenes más que LANDER había desarrollado anteriormente y deja la posibilidad de añadir más trenes en el futuro, si la compañía quisiera incorporarlos al simulador. La simulación es una herramienta segura y rentable que permite entrenar situaciones catastróficas en un entorno virtual que no se pueden reproducir en la realidad y, además, evita gastos de electricidad y de desgaste de materiales, tanto del material rodante como de la infraestructura porque la que se mueve el tren. Por otra parte, para el entrenamiento de maquinistas en trenes reales se emplean las horas nocturnas ya que durante el día las vías están ocupadas por trenes que deben cumplir horarios de las líneas; por tanto, un simulador ofrece una amplia disponibilidad para el entrenamiento. Sin embargo, los simuladores no sólo se emplean con futuros maquinistas sino con maquinistas veteranos para evitar que aquellos que nunca han tenido ningún contratiempo, actúen de forma relajada, despreocupada o, incluso inconsciente. Además, el simulador les permite ejercitar situaciones que exijan reacciones rápidas, como objetos en la vía o averías, de este modo entrenan protocolos de actuación para normalizar en lo posible el servicio de la línea.
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[EN] This paper is based in the following project:
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[ES] Ribera es un pueblo abandonado dentro del parque natural de Valderejo, el único edificio que queda en pie es la antigua iglesia. La razón por la que este edificio no fue derribado es la presencia de un conjunto de pinturas murales de época medieval. Por lo demás, el edificio (de unos 25 x 12 metros en planta) se encontraba en un mal estado de conservación (de hecho, un par de años más tarde de la realización de este trabajo se derrumbó la sacristía).
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This thesis presents the development of chip-based technology for informative in vitro cancer diagnostics. In the first part of this thesis, I will present my contribution in the development of a technology called “Nucleic Acid Cell Sorting (NACS)”, based on microarrays composed of nucleic acid encoded peptide major histocompatibility complexes (p/MHC), and the experimental and theoretical methods to detect and analyze secreted proteins from single or few cells.
Secondly, a novel portable platform for imaging of cellular metabolism with radio probes is presented. A microfluidic chip, so called “Radiopharmaceutical Imaging Chip” (RIMChip), combined with a beta-particle imaging camera, is developed to visualize the uptake of radio probes in a small number of cells. Due to its sophisticated design, RIMChip allows robust and user-friendly execution of sensitive and quantitative radio assays. The performance of this platform is validated with adherent and suspension cancer cell lines. This platform is then applied to study the metabolic response of cancer cells under the treatment of drugs. Both cases of mouse lymphoma and human glioblastoma cell lines, the metabolic responses to the drug exposures are observed within a short time (~ 1 hour), and are correlated with the arrest of cell-cycle, or with changes in receptor tyrosine kinase signaling.
The last parts of this thesis present summaries of ongoing projects: development of a new agent as an in vivo imaging probe for c-MET, and quantitative monitoring of glycolytic metabolism of primary glioblastoma cells. To develop a new agent for c-MET imaging, the one-bead-one-compound combinatorial library method is used, coupled with iterative screening. The performance of the agent is quantitatively validated with cell-based fluorescent assays. In the case of monitoring the metabolism of primary glioblastoma cell, by RIMChip, cells were sorting according to their expression levels of oncoprotein, or were treated with different kinds of drugs to study the metabolic heterogeneity of cancer cells or metabolic response of glioblastoma cells to drug treatments, respectively.
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High-order harmonics and single attosecond pulse generation by using an infrared laser pulse combined with attosecond pulse trains (APT) interacting with He+ have been investigated. We show that the ionization for different instant time intervals can be controlled by altering the time delay between the APT and the infrared pulse. Consequently, APT can be used as a tool to control the efficiency of high-order harmonics emitted at different times. By choosing appropriate APT and time delay, the driving pulse width for single attosecond pulse generation can be extended up to six optical cycles. (c) 2007 Optical Society of America.
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Melting temperature calculation has important applications in the theoretical study of phase diagrams and computational materials screenings. In this thesis, we present two new methods, i.e., the improved Widom's particle insertion method and the small-cell coexistence method, which we developed in order to capture melting temperatures both accurately and quickly.
We propose a scheme that drastically improves the efficiency of Widom's particle insertion method by efficiently sampling cavities while calculating the integrals providing the chemical potentials of a physical system. This idea enables us to calculate chemical potentials of liquids directly from first-principles without the help of any reference system, which is necessary in the commonly used thermodynamic integration method. As an example, we apply our scheme, combined with the density functional formalism, to the calculation of the chemical potential of liquid copper. The calculated chemical potential is further used to locate the melting temperature. The calculated results closely agree with experiments.
We propose the small-cell coexistence method based on the statistical analysis of small-size coexistence MD simulations. It eliminates the risk of a metastable superheated solid in the fast-heating method, while also significantly reducing the computer cost relative to the traditional large-scale coexistence method. Using empirical potentials, we validate the method and systematically study the finite-size effect on the calculated melting points. The method converges to the exact result in the limit of a large system size. An accuracy within 100 K in melting temperature is usually achieved when the simulation contains more than 100 atoms. DFT examples of Tantalum, high-pressure Sodium, and ionic material NaCl are shown to demonstrate the accuracy and flexibility of the method in its practical applications. The method serves as a promising approach for large-scale automated material screening in which the melting temperature is a design criterion.
We present in detail two examples of refractory materials. First, we demonstrate how key material properties that provide guidance in the design of refractory materials can be accurately determined via ab initio thermodynamic calculations in conjunction with experimental techniques based on synchrotron X-ray diffraction and thermal analysis under laser-heated aerodynamic levitation. The properties considered include melting point, heat of fusion, heat capacity, thermal expansion coefficients, thermal stability, and sublattice disordering, as illustrated in a motivating example of lanthanum zirconate (La2Zr2O7). The close agreement with experiment in the known but structurally complex compound La2Zr2O7 provides good indication that the computation methods described can be used within a computational screening framework to identify novel refractory materials. Second, we report an extensive investigation into the melting temperatures of the Hf-C and Hf-Ta-C systems using ab initio calculations. With melting points above 4000 K, hafnium carbide (HfC) and tantalum carbide (TaC) are among the most refractory binary compounds known to date. Their mixture, with a general formula TaxHf1-xCy, is known to have a melting point of 4215 K at the composition Ta4HfC5, which has long been considered as the highest melting temperature for any solid. Very few measurements of melting point in tantalum and hafnium carbides have been documented, because of the obvious experimental difficulties at extreme temperatures. The investigation lets us identify three major chemical factors that contribute to the high melting temperatures. Based on these three factors, we propose and explore a new class of materials, which, according to our ab initio calculations, may possess even higher melting temperatures than Ta-Hf-C. This example also demonstrates the feasibility of materials screening and discovery via ab initio calculations for the optimization of "higher-level" properties whose determination requires extensive sampling of atomic configuration space.
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Wide field-of-view (FOV) microscopy is of high importance to biological research and clinical diagnosis where a high-throughput screening of samples is needed. This thesis presents the development of several novel wide FOV imaging technologies and demonstrates their capabilities in longitudinal imaging of living organisms, on the scale of viral plaques to live cells and tissues.
The ePetri Dish is a wide FOV on-chip bright-field microscope. Here we applied an ePetri platform for plaque analysis of murine norovirus 1 (MNV-1). The ePetri offers the ability to dynamically track plaques at the individual cell death event level over a wide FOV of 6 mm × 4 mm at 30 min intervals. A density-based clustering algorithm is used to analyze the spatial-temporal distribution of cell death events to identify plaques at their earliest stages. We also demonstrate the capabilities of the ePetri in viral titer count and dynamically monitoring plaque formation, growth, and the influence of antiviral drugs.
We developed another wide FOV imaging technique, the Talbot microscope, for the fluorescence imaging of live cells. The Talbot microscope takes advantage of the Talbot effect and can generate a focal spot array to scan the fluorescence samples directly on-chip. It has a resolution of 1.2 μm and a FOV of ~13 mm2. We further upgraded the Talbot microscope for the long-term time-lapse fluorescence imaging of live cell cultures, and analyzed the cells’ dynamic response to an anticancer drug.
We present two wide FOV endoscopes for tissue imaging, named the AnCam and the PanCam. The AnCam is based on the contact image sensor (CIS) technology, and can scan the whole anal canal within 10 seconds with a resolution of 89 μm, a maximum FOV of 100 mm × 120 mm, and a depth-of-field (DOF) of 0.65 mm. We also demonstrate the performance of the AnCam in whole anal canal imaging in both animal models and real patients. In addition to this, the PanCam is based on a smartphone platform integrated with a panoramic annular lens (PAL), and can capture a FOV of 18 mm × 120 mm in a single shot with a resolution of 100─140 μm. In this work we demonstrate the PanCam’s performance in imaging a stained tissue sample.
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Part I
Present experimental data on nucleon-antinucleon scattering allow a study of the possibility of a phase transition in a nucleon-antinucleon gas at high temperature. Estimates can be made of the general behavior of the elastic phase shifts without resorting to theoretical derivation. A phase transition which separates nucleons from antinucleons is found at about 280 MeV in the approximation of the second virial coefficient to the free energy of the gas.
Part II
The parton model is used to derive scaling laws for the hadrons observed in deep inelastic electron-nucleon scattering which lie in the fragmentation region of the virtual photon. Scaling relations are obtained in the Bjorken and Regge regions. It is proposed that the distribution functions become independent of both q2 and ν where the Bjorken and Regge regions overlap. The quark density functions are discussed in the limit x→1 for the nucleon octet and the pseudoscalar mesons. Under certain plausible assumptions it is found that only one or two quarks of the six types of quarks and antiquarks have an appreciable density function in the limit x→1. This has implications for the quark fragmentation functions near the large momentum boundary of their fragmentation region. These results are used to propose a method of measuring the proton and neutron quark density functions for all x by making measurements on inclusively produced hadrons in electroproduction only. Implications are also discussed for the hadrons produced in electron-positron annihilation.
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Esta dissertação tem como objetivo analisar a intervenção de elementos linguísticos no processo leitor em espanhol como língua estrangeira (E/LE) ,em ambiente virtual, de docente desse idioma. A partir desse objetivo macro, estabelecemos um recorte e nos focamos na análise de como/se elementos linguísticos mais característicos de uma linguagem coloquial podem afetar mais a leitura de um docente de E/LE que teve na sua formação e na sua atividade profissional um contato maior com a língua formal. Nesse contexto, escolhemos o blog como o suporte virtual dos textos a serem lidos pelo sujeito por apresentar uma linguagem mais coloquial. No que se refere ao aporte teórico, esta pesquisa tem com principais bases a Linguística Textual (KOCH, 2009, 2002, 2007; KOCH ; TRAVAGLIA, 1996, 2000) e a leitura sócio-interacional (KATO, 1986, 2007; KLEIMAN, 1993, 1996, 2008; NUNES, 2005; VERGNANO-JUNGER, 2009). Também utilizamos alguns elementos da Análise do Discurso de base enunciativa em pontos nos quais ela dialoga com a perspectiva sócio-interacional, como, por exemplo, na noção de gênero do discurso (MAINGUENEAU, 1996, 2003; BAKTHIN, 2003). A Sociolinguística (MORENO FERNANDÉZ, 1996; ALKMIN, 2001) contribuiu para estabelecer os parâmetros da língua coloquial e formal. Quanto à leitura em ambiente virtual, seguimos Ribeiro (2005), Marcuschi (2007), Santaella (2008) e Vergnano-Junger (2009). Para a elaboração deste trabalho, utilizamos uma metodologia híbrida composta de uma parte documental e de um estudo de caso. A fase documental teve como metas classificar os blogs de docentes de E/LE e selecionar dois para a elaboração de atividades de leitura guiada. O estudo de caso realizado com um docente de E/LE, por sua vez, teve como etapas uma leitura livre, duas guiadas e uma entrevista. Objetivou observar e discutir o perfil e o processo leitor do sujeito, com foco na intervenção de elementos linguísticos. Dos resultados obtidos, podemos destacar uma proposta de classificação dos blogs de professores de E/LE. Com base no estudo de caso, duas considerações merecem destaque: (a) uma maior dificuldade de leitura do texto coloquial, ao que tudo indica, gerada pela variedade lexical e (b) uma tendência do sujeito à leitura linear em ambiente virtual, com atenção voltada, frequentemente, para os aspectos de vocabulário e como esses afetavam a compreensão, demonstrando uma tendência à leitura decodificadora
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El tramo litoral entre Deba y Zumaia constituye una de las zonas más conocidas y mejor estudiadas de todo el ámbito geológico de los Pirineos y, más particularmente, de su porción más occidental: la denominada cuenca o Región Vasco Cantábrica. Tal circunstancia deriva de los atributos particulares de su registro geológico: un potente conjunto de rocas sedimentarias de persistente estratificación, formadas en un antiguo fondo marino que, a pesar de grandes semejanzas, era muy distinto a los fondos marinos actuales. A este potente conjunto de rocas sedimentarias se le conoce bajo la denominación genérica de “flysch”, término de amplia raigambre geológica, cuya concepción y uso han cambiado considerablemente con el tiempo y el avance del conocimiento.