767 research outputs found

    Introducing a rainfall compound distribution model based on weather patterns sub-sampling

    Get PDF
    This paper presents a probabilistic model for daily rainfall, using sub-sampling based on meteorological circulation. We classified eight typical but contrasted synoptic situations (weather patterns) for France and surrounding areas, using a "bottom-up" approach, i.e. from the shape of the rain field to the synoptic situations described by geopotential fields. These weather patterns (WP) provide a discriminating variable that is consistent with French climatology, and allows seasonal rainfall records to be split into more homogeneous sub-samples, in term of meteorological genesis. <br><br> First results show how the combination of seasonal and WP sub-sampling strongly influences the identification of the asymptotic behaviour of rainfall probabilistic models. Furthermore, with this level of stratification, an asymptotic exponential behaviour of each sub-sample appears as a reasonable hypothesis. This first part is illustrated with two daily rainfall records from SE of France. <br><br> The distribution of the multi-exponential weather patterns (MEWP) is then defined as the composition, for a given season, of all WP sub-sample marginal distributions, weighted by the relative frequency of occurrence of each WP. This model is finally compared to Exponential and Generalized Pareto distributions, showing good features in terms of robustness and accuracy. These final statistical results are computed from a wide dataset of 478 rainfall chronicles spread on the southern half of France. All these data cover the 1953–2005 period

    Applying asymptotic methods to synthetic biology: modelling the reaction kinetics of the mevalonate pathway

    Get PDF
    The mevalonate pathway is normally found in eukaryotes, and allows for the production of isoprenoids, a useful class of organic compounds. This pathway has been successfully introduced to Escherichia coli, enabling a biosynthetic production route for many isoprenoids. In this paper, we develop and solve a mathematical model for the concentration of metabolites in the mevalonate pathway over time, accounting for the loss of acetyl-CoA to other metabolic pathways. Additionally, we successfully test our theoretical predictions experimentally by introducing part of the pathway into Cupriavidus necator. In our model, we exploit the natural separation of time scales as well as of metabolite concentrations to make significant asymptotic progress in understanding the system. We confirm that our asymptotic results agree well with numerical simulations, the former enabling us to predict the most important reactions to increase isopentenyl diphosphate production whilst minimizing the levels of HMG-CoA, which inhibits cell growth. Thus, our mathematical model allows us to recommend the upregulation of certain combinations of enzymes to improve production through the mevalonate pathway

    Applying asymptotic methods to synthetic biology: modelling the reaction kinetics of the mevalonate pathway

    Get PDF
    The mevalonate pathway is normally found in eukaryotes, and allows for the production of isoprenoids, a useful class of organic compounds. This pathway has been successfully introduced to Escherichia coli, enabling a biosynthetic production route for many isoprenoids. In this paper, we develop and solve a mathematical model for the concentration of metabolites in the mevalonate pathway over time, accounting for the loss of acetyl-CoA to other metabolic pathways. Additionally, we successfully test our theoretical predictions experimentally by introducing part of the pathway into Cupriavidus necator. In our model, we exploit the natural separation of time scales as well as of metabolite concentrations to make significant asymptotic progress in understanding the system. We confirm that our asymptotic results agree well with numerical simulations, the former enabling us to predict the most important reactions to increase isopentenyl diphosphate production whilst minimizing the levels of HMG-CoA, which inhibits cell growth. Thus, our mathematical model allows us to recommend the upregulation of certain combinations of enzymes to improve production through the mevalonate pathway

    Collection Development Policies and Other Basic Tools for Building A Foreign and International Law Collection

    Get PDF
    The impact of globalization on the practice of law, legal education and legal research has been examined, discussed and debated for more than a decade among legal educators and law librarians. It is now accepted among information professionals that providing at least some access to relevant foreign and international law materials is important, if not critical, in academic, firm and other libraries. Numerous articles, research guides and foreign and international law portals and websites have been created and maintained by law librarians with expertise in researching the laws of foreign jurisdictions and/or international law. These tools have helped to make foreign and international legal materials and research methods available to researchers, librarians, lawyers and law students who are unfamiliar with foreign and international law resources and research techniques

    Clinical, molecular and glycophenotype insights in SLC39A8-CDG

    Get PDF
    Background: SLC39A8, a gene located on chromosome 4q24, encodes for the manganese (Mn) transporter ZIP8 and its detrimental variants cause a type 2 congenital disorder of glycosylation (CDG). The common SLC39A8 missense variant A391T is associated with increased risk for multiple neurological and systemic disorders and with decreased serum Mn. Patients with SLC39A8-CDG present with different clinical and neuroradiological features linked to variable transferrin glycosylation profile. Galactose and Mn supplementation therapy results in the biochemical and clinical amelioration of treated patients. Results: Here, we report clinical manifestations, neuroradiological features and glycophenotypes associated with novel SLC39A8 variants (c.1048G > A; p.Gly350Arg and c.131C > G; p.Ser44Trp) in two siblings of the same Italian family. Furthermore, we describe a third patient with overlapping clinical features harbouring the homozygous missense variant A391T. The clinical phenotype of the three patients was characterized by severe developmental disability, dystonic postural pattern and dyskinesia with a more severe progression of the disease in the two affected siblings. Neuroimaging showed a Leigh syndrome-like pattern involving the basal ganglia, thalami and white matter. In the two siblings, atrophic cerebral and cerebellum changes consistent with SLC39A8-CDG were detected as well. Serum transferrin isoelectric focusing (IEF) yielded variable results with slight increase of trisialotransferrin isoforms or even normal pattern. MALDI-MS showed the presence of hypogalactosylated transferrin N-glycans, spontaneously decreasing during the disease course, only in one affected sibling. Total serum N-glycome depicted a distinct pattern for the three patients, with increased levels of undergalactosylated and undersialylated precursors of fully sialylated biantennary glycans, including the monosialo-monogalacto-biantennary species A2G1S1. Conclusions: Clinical, MRI and glycosylation features of patients are consistent with SLC39A8-CDG. We document two novel variants associated with Leigh syndrome-like disease presentation of SLC39A8-CDG. We show, for the first time, a severe neurological phenotype overlapping with that described for SLC39A8-CDG in association with the homozygous A391T missense variant. We observed a spontaneous amelioration of transferrin N-glycome, highlighting the efficacy of MS-based serum glycomics as auxiliary tool for the diagnosis and clinical management of therapy response in patients with SLC39A8-CDG. Further studies are needed to analyse more in depth the influence of SLC39A8 variants, including the common missense variant, on the expression and function of ZIP8 protein, and their impact on clinical, biochemical and neuroradiological features

    The Planck-LFI flight model composite waveguides

    Get PDF
    The Low Frequency Instrument on board the PLANCK satellite is designed to give the most accurate map ever of the CMB anisotropy of the whole sky over a broad frequency band spanning 27 to 77 GHz. It is made of an array of 22 pseudo-correlation radiometers, composed of 11 actively cooled (20 K) Front End Modules (FEMs), and 11 Back End Modules (BEMs) at 300K. The connection between the two parts is made with rectangular Wave Guides. Considerations of different nature (thermal, electromagnetic and mechanical), imposed stringent requirements on the WGs characteristics and drove their design. From the thermal point of view, the WG should guarantee good insulation between the FEM and the BEM sections to avoid overloading the cryocooler. On the other hand it is essential that the signals do not undergo excessive attenuation through the WG. Finally, given the different positions of the FEM modules behind the focal surface and the mechanical constraints given by the surrounding structures, different mechanical designs were necessary. A composite configuration of Stainless Steel and Copper was selected to satisfy all the requirements. Given the complex shape and the considerable length (about 1.5-2 m), manufacturing and testing the WGs was a challenge. This work deals with the development of the LFI WGs, including the choice of the final configuration and of the fabrication process. It also describes the testing procedure adopted to fully characterize these components from the electromagnetic point of view and the space qualification process they underwent. Results obtained during the test campaign are reported and compared with the stringent requirements. The performance of the LFI WGs is in line with requirements, and the WGs were successfully space qualified.Comment: this paper is part of the Prelaunch status LFI papers published on JINST: http://www.iop.org/EJ/journal/-page=extra.proc5/jins

    Emergence of antitumor cytolytic T cells is associated with maintenance of hematologic remission in children with acute myeloid leukemia.

    Get PDF
    Although the graft-versus-leukemia effect of allogeneic bone marrow transplantation (BMT) is of paramount importance in the maintenance of disease remission, the role played by the autologous T-cell response in antitumor immune surveillance is less defined. We evaluated the emergence of antileukemia cytotoxic T-lymphocyte precursors (CTLp's) and the correlation of this phenomenon with maintenance of hematologic remission in 16 children with acute myeloid leukemia (AML), treated with either chemotherapy alone (5 patients) or with autologous BMT (A-BMT, 11 patients). Antileukemia CTLp's were detectable in 8 patients in remission after induction chemotherapy; none of them subsequently had a relapse. Of the 8 patients who did not show detectable CTLp frequency while in remission after induction chemotherapy, 7 subsequently experienced leukemia relapse. In patients undergoing A-BMT, molecular fingerprinting of the TCR-Vbeta repertoire, performed on antileukemia lines, demonstrated that selected antileukemia T-cell clonotypes, detectable in bone marrow before transplantation, survived ex vivo pharmacologic purging and were found in the recipient after A-BMT. These data provide evidence for an active role of autologous T cells in the maintenance of hematologic remission and also suggest that quantification of antileukemia CTLp frequency may be a useful tool to identify patients at high risk for relapse, thus potentially benefiting from an allogeneic antitumor effect

    Design and Validation of Patient-Centered Communication Tools (PaCT) to Measure Students\u27 Communication Skills

    Get PDF
    Objective. To develop a comprehensive instrument specific to student pharmacist-patient communication skills, and to determine face, content, construct, concurrent, and predictive validity and reliability of the instrument. Methods. A multi-step approach was used to create and validate an instrument, including the use of external experts for face and content validity, students for construct validity, comparisons to other rubrics for concurrent validity, comparisons to other coursework for predictive validity, and extensive reliability and inter-rater reliability testing with trained faculty assessors. Results. Patient-centered Communication Tools (PaCT) achieved face and content validity and performed well with multiple correlation tests with significant findings for reliability testing and when compared to an alternate rubric. Conclusion. PaCT is a useful instrument for assessing student pharmacist communication skills with patients
    • …
    corecore