1,284 research outputs found

    Use of soil moisture information in yield models

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    There are no author-identified significant results in this report

    Algorithmic Interpretations of Fractal Dimension

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    We study algorithmic problems on subsets of Euclidean space of low fractal dimension. These spaces are the subject of intensive study in various branches of mathematics, including geometry, topology, and measure theory. There are several well-studied notions of fractal dimension for sets and measures in Euclidean space. We consider a definition of fractal dimension for finite metric spaces which agrees with standard notions used to empirically estimate the fractal dimension of various sets. We define the fractal dimension of some metric space to be the infimum delta>0, such that for any eps>0, for any ball B of radius r >= 2eps, and for any eps-net N, we have |B cap N|=O((r/eps)^delta). Using this definition we obtain faster algorithms for a plethora of classical problems on sets of low fractal dimension in Euclidean space. Our results apply to exact and fixed-parameter algorithms, approximation schemes, and spanner constructions. Interestingly, the dependence of the performance of these algorithms on the fractal dimension nearly matches the currently best-known dependence on the standard Euclidean dimension. Thus, when the fractal dimension is strictly smaller than the ambient dimension, our results yield improved solutions in all of these settings. We remark that our definition of fractal definition is equivalent up to constant factors to the well-studied notion of doubling dimension. However, in the problems that we consider, the dimension appears in the exponent of the running time, and doubling dimension is not precise enough for capturing the best possible such exponent for subsets of Euclidean space. Thus our work is orthogonal to previous results on spaces of low doubling dimension; while algorithms on spaces of low doubling dimension seek to extend results from the case of low dimensional Euclidean spaces to more general metric spaces, our goal is to obtain faster algorithms for special pointsets in Euclidean space

    Measurement of the electric dipole moments for transitions to rubidium Rydberg states via Autler-Townes splitting

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    We present the direct measurements of electric-dipole moments for 5P3/2→nD5/25P_{3/2}\to nD_{5/2} transitions with 20<n<4820<n<48 for Rubidium atoms. The measurements were performed in an ultracold sample via observation of the Autler-Townes splitting in a three-level ladder scheme, commonly used for 2-photon excitation of Rydberg states. To the best of our knowledge, this is the first systematic measurement of the electric dipole moments for transitions from low excited states of rubidium to Rydberg states. Due to its simplicity and versatility, this method can be easily extended to other transitions and other atomic species with little constraints. Good agreement of the experimental results with theory proves the reliability of the measurement method.Comment: 12 pages, 6 figures; figure 6 replaced with correct versio

    The Substrate-Bound Crystal Structure of a Baeyer–Villiger Monooxygenase Exhibits a Criegee-like Conformation

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    The Baeyer\u2013Villiger monooxygenases (BVMOs) are a family of bacterial flavoproteins that catalyze the synthetically useful Baeyer\u2013Villiger oxidation reaction. This involves the conversion of ketones into esters or cyclic ketones into lactones by introducing an oxygen atom adjacent to the carbonyl group. The BVMOs offer exquisite regio- and enantiospecificity while acting on a wide range of substrates. They use only NADPH and oxygen as cosubstrates, and produce only NADP+ and water as byproducts, making them environmentally attractive for industrial purposes. Here, we report the first crystal structure of a BVMO, cyclohexanone monooxygenase (CHMO) from Rhodococcus sp. HI-31 in complex with its substrate, cyclohexanone, as well as NADP+ and FAD, to 2.4 \uc5 resolution. This structure shows a drastic rotation of the NADP+ cofactor in comparison to previously reported NADP+-bound structures, as the nicotinamide moiety is no longer positioned above the flavin ring. Instead, the substrate, cyclohexanone, is found at this location, in an appropriate position for the formation of the Criegee intermediate. The rotation of NADP+ permits the substrate to gain access to the reactive flavin peroxyanion intermediate while preventing it from diffusing out of the active site. The structure thus reveals the conformation of the enzyme during the key catalytic step. CHMO is proposed to undergo a series of conformational changes to gradually move the substrate from the solvent, via binding in a solvent excluded pocket that dictates the enzyme\u2019s chemospecificity, to a location above the flavin\u2013peroxide adduct where catalysis occurs.Peer reviewed: YesNRC publication: Ye

    Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study

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    BACKGROUND: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. METHODS: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509. FINDINGS: Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be required to detect a 50% reduction in SARA progression at 80% power: 118 (59 per group) if only individuals who are ambulatory are included. With ADL as the primary outcome, 190 (95 per group) patients with Friedreich's ataxia would be needed, and fewer patients would be required if only individuals with early-onset are included. INTERPRETATION: Our findings for stage-dependent progression rates have important implications for clinicians and researchers, as they provide reliable outcome measures to monitor disease progression, and enable tailored sample size calculation to guide upcoming clinical trial designs in Friedreich's ataxia. FUNDING: European Commission, Voyager Therapeutics, and EuroAtaxia

    Prediction of the disease course in Friedreich ataxia

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    We explored whether disease severity of Friedreich ataxia can be predicted using data from clinical examinations. From the database of the European Friedreich Ataxia Consortium for Translational Studies (EFACTS) data from up to five examinations of 602 patients with genetically confirmed FRDA was included. Clinical instruments and important symptoms of FRDA were identified as targets for prediction, while variables such as genetics, age of disease onset and first symptom of the disease were used as predictors. We used modelling techniques including generalised linear models, support-vector-machines and decision trees. The scale for rating and assessment of ataxia (SARA) and the activities of daily living (ADL) could be predicted with predictive errors quantified by root-mean-squared-errors (RMSE) of 6.49 and 5.83, respectively. Also, we were able to achieve reasonable performance for loss of ambulation (ROC-AUC score of 0.83). However, predictions for the SCA functional assessment (SCAFI) and presence of cardiological symptoms were difficult. In conclusion, we demonstrate that some clinical features of FRDA can be predicted with reasonable error; being a first step towards future clinical applications of predictive modelling. In contrast, targets where predictions were difficult raise the question whether there are yet unknown variables driving the clinical phenotype of FRDA

    CAG Repeats Determine Brain Atrophy in Spinocerebellar Ataxia 17: A VBM Study

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    Abnormal repeat length has been associated with an earlier age of onset and more severe disease progression in the rare neurodegenerative disorder spinocerebellar ataxia 17 (SCA17).To determine whether specific structural brain degeneration and rate of disease progression in SCA17 might be associated with the CAG repeat size, observer-independent voxel-based morphometry was applied to high-resolution magnetic resonance images of 16 patients with SCA17 and 16 age-matched healthy controls. The main finding contrasting SCA17 patients with healthy controls demonstrated atrophy in the cerebellum bilaterally. Multiple regression analyses with available genetic data and also post-hoc correlations revealed an inverse relationship again with cerebellar atrophy. Moreover, we found an inverse relationship between the CAG repeat length and rate of disease progression.Our results highlight the fundamental role of the cerebellum in this neurodegenerative disease and support the genotype-phenotype relationship in SCA17 patients. Genetic factors may determine individual susceptibility to neurodegeneration and rate of disease progression

    Proving the Equivalence of Microstep and Macrostep Semantics

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    Abstract. Recently, an embedding of the synchronous programming language Quartz (an Esterel variant) in the theorem prover HOL has been presented. This embedding is based on control flow predicates that refer to macrosteps of the pro-grams. The original semantics of synchronous languages like Esterel is however normally given at the more detailed microstep level. This paper describes how a variant of the Esterel microstep semantics has been defined in HOL and how its equivalence to the control flow predicate semantics has been proved. Beneath proving the equivalence of the micro- and macrostep semantics, the work pre-sented here is also an important extension of the existing embedding: While rea-soning at the microstep level is not necessary for code generation, it is sometimes advantageous for understanding programs, as some effects like schizophrenia or causality problems become only visible at the microstep level.
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