355 research outputs found

    Hydrology of mediterranean and semiarid regions

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    Solving the Klein-Gordon equation using Fourier spectral methods: A benchmark test for computer performance

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    The cubic Klein-Gordon equation is a simple but non-trivial partial differential equation whose numerical solution has the main building blocks required for the solution of many other partial differential equations. In this study, the library 2DECOMP&FFT is used in a Fourier spectral scheme to solve the Klein-Gordon equation and strong scaling of the code is examined on thirteen different machines for a problem size of 512^3. The results are useful in assessing likely performance of other parallel fast Fourier transform based programs for solving partial differential equations. The problem is chosen to be large enough to solve on a workstation, yet also of interest to solve quickly on a supercomputer, in particular for parametric studies. Unlike other high performance computing benchmarks, for this problem size, the time to solution will not be improved by simply building a bigger supercomputer.Comment: 10 page

    Parallel Processing for a Better Understanding of Equifinality in Hydrological Models

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    The aim of conceptual modeling of watersheds is to realize a numeric scheme for determining rainfallrunoff at the outlet of a basin. This modeling consists of a number of parameters that are identified by calibration methods using a series of measured rainfall-runoff data. One of the difficulties of this method is due to equifinality problems. The definition of the parameters, and their relation with the data, extends the space of acceptable parameters (zone of equivalence), which in turn makes the combination of acceptable parameters very large. In addition, the calibration methods currently used simplify the parameter hyper-space and yield equally acceptable results which may be situated in the zone of equivalence, but which are not necessarily the optimal combination parameters of the model. Therefore, a possible approach for determining the optimal combination of parameters is to simulate an important set of possible parameters. This needs a considerable number of simulations that exceeds the capabilities of traditional computation. For example, the systematic exploration of the objective function structure of the four-parameter model MEDOR, specific to the Mediterranean climate, requires 1,476,800 simulations which needs days of computation using a personnel computer. To accelerate this computation, parallel processing based on a master-slave model was used. This model allows a dynamic task scheduling among the different processors, thus maximizing the efficiency. The surface criteria exhibits a ridgeline which indicates that the origin of equifinality resides in the existence of a relationship between parameters. The use of parallel processing , and consequent reduction of the computational time, allows for an exhaustive exploration of the parameters space and its characteristics

    Vaccine antibodies against a synthetic epidermal growth factor variant enhance the antitumor effects of inhibitors targeting the MAPK/ERK and PI3K/Akt pathways

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    We thank Isabel Crespo and Sara Ozcoz from the Cytomics Core Facility of the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) for technical assistance. The study was funded by grants from IN3BIO.Background: The EGFR pathway is involved in intrinsic and acquired resistance to a wide variety of targeted therapies in cancer. Vaccination represents an alternative to the administration of anti-EGFR monoclonal antibodies, such as cetuximab or panitumumab. Here, we tested if anti-EGF antibodies generated by vaccination (anti-EGF VacAbs) could potentiate the activity of drugs targeting the ERK/MAPK and PI3K/Akt pathways. Methods: Non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and melanoma cell lines harboring KRAS, NRAS, BRAF and PIK3CA mutations were used. Anti-EGF VacAbs were obtained by immunizing rabbits with a fusion protein containing a synthetic, highly mutated variant of human EGF. Cell viability was determined by MTT, total and phosphorylated proteins by Western blotting, cell cycle distribution and cell death by flow cytometry and emergence of resistance by microscopic examination in low density cultures. Results: Anti-EGF VacAbs potentiated the antiproliferative effects of MEK, KRAS G12C, BRAF, PI3K and Akt inhibitors in KRAS, NRAS, BRAF and PIK3CA mutant cells and delayed the appearance of resistant clones in vitro. The effects of anti-EGF VacAbs were comparable or superior to those of panitumumab and cetuximab. The combination of anti-EGF VacAbs with the targeted inhibitors effectively suppressed EGFR downstream pathways and sera from patients immunized with an anti-EGF vaccine also blocked activation of EGFR effectors. Conclusions: Anti-EGF VacAbs enhance the antiproliferative effects of drugs targeting the ERK/MAPK and PIK3CA/Akt pathways. Our data provide a rationale for clinical trials testing anti-EGF vaccination combined with inhibitors selected according to the patient's genetic profile
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