36 research outputs found

    Systems Level Modeling of the Cell Cycle Using Budding Yeast

    Get PDF
    Proteins involved in the regulation of the cell cycle are highly conserved across all eukaryotes, and so a relatively simple eukaryote such as yeast can provide insight into a variety of cell cycle perturbations including those that occur in human cancer. To date, the budding yeast Saccharomyces cerevisiae has provided the largest amount of experimental and modeling data on the progression of the cell cycle, making it a logical choice for in-depth studies of this process. Moreover, the advent of methods for collection of high-throughput genome, transcriptome, and proteome data has provided a means to collect and precisely quantify simultaneous cell cycle gene transcript and protein levels, permitting modeling of the cell cycle on the systems level. With the appropriate mathematical framework and sufficient and accurate data on cell cycle components, it should be possible to create a model of the cell cycle that not only effectively describes its operation, but can also predict responses to perturbations such as variation in protein levels and responses to external stimuli including targeted inhibition by drugs. In this review, we summarize existing data on the yeast cell cycle, proteomics technologies for quantifying cell cycle proteins, and the mathematical frameworks that can integrate this data into representative and effective models. Systems level modeling of the cell cycle will require the integration of high-quality data with the appropriate mathematical framework, which can currently be attained through the combination of dynamic modeling based on proteomics data and using yeast as a model organism

    Knowledge-based energy functions for computational studies of proteins

    Full text link
    This chapter discusses theoretical framework and methods for developing knowledge-based potential functions essential for protein structure prediction, protein-protein interaction, and protein sequence design. We discuss in some details about the Miyazawa-Jernigan contact statistical potential, distance-dependent statistical potentials, as well as geometric statistical potentials. We also describe a geometric model for developing both linear and non-linear potential functions by optimization. Applications of knowledge-based potential functions in protein-decoy discrimination, in protein-protein interactions, and in protein design are then described. Several issues of knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe

    Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

    Get PDF
    The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

    Highly-parallelized simulation of a pixelated LArTPC on a GPU

    Get PDF
    The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

    Sexualidade e deficiência intelectual: narrativas de pais de adolescentes Sexuality and intellectual handicap: parents' narratives

    No full text
    Pelo senso comum, adolescentes com deficiência intelectual têm a sexualidade exacerbada ou são assexuados. Para conhecer como vivenciam as manifestações sexuais de seus filhos, entrevistamos 14 pais de adolescentes com essa deficiência. A análise das narrativas obtidas foi baseada em autores da antropologia. Nelas, observaram-se os preconceitos e o desconhecimento sobre o tema, bem como a reprodução da ideologia de gênero da nossa sociedade. Nas narrativas dos pais de adolescentes do sexo masculino, a masturbação, a relação sexual e o medo de abuso sexual foram destaques, enquanto nas dos pais das adolescentes privilegiaram-se como tema as mudanças corporais e também o receio de que fossem abusadas sexualmente. A inadequação entre desenvolvimento físico e um comportamento sexual considerado socialmente impróprio também foi alvo de narrativas. Aponta-se a necessidade de ampliação do debate com os adolescentes, seus pais e diversos setores da sociedade para minimizar os preconceitos em relação à sexualidade das pessoas com deficiência intelectual, propiciando a garantia de seus direitos sexuais.<br>By common sense, adolescents with intellectual disabilities have a heightened sexuality or are asexual. To learn how they experience the sexual manifestations of their children, we interviewed 14 parents of adolescents with this deficiency. The analysis of the narratives obtained was based on authors of anthropology. In them, there were prejudices and ignorance on the subject, as well as playing the gender ideology of our society. In the narratives of parents of adolescent males, masturbation, sex and fear of sexual abuse were highlighted, while parents privileged themes such as bodily changes and also the fear that they were sexually abused. The mismatch between physical development and sexual behavior considered socially improper was also the target of narratives. The paper points up the need to expand the discussion with teens, their parents and various sectors of society to minimize biases regarding sexuality of people with intellectual disabilities, providing a guarantee of their sexual rights

    Molecular Targets for Malarial Chemotherapy: A Review

    No full text
    corecore