338 research outputs found

    On model selection criteria for climate change impact studies

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    Climate change impact studies inform policymakers on the estimated damages of future climate change on economic, health and other outcomes. In most studies, an annual outcome variable is observed, e.g. annual mortality rate, along with higher-frequency regressors, e.g. daily temperature and precipitation. Practitioners use summaries of the higher-frequency regressors in fixed effects panel models. The choice over summary statistics amounts to model selection. Some practitioners use Monte Carlo cross-validation (MCCV) to justify a particular specification. However, conventional implementation of MCCV with fixed testing-to-full sample ratios tends to select over-fit models. This paper presents conditions under which MCCV, and also information criteria, can deliver consistent model selection. Previous work has established that the Bayesian information criterion (BIC) can be inconsistent for non-nested selection. We illustrate that the BIC can also be inconsistent in our framework, when all candidate models are misspecified. Our results have practical implications for empirical conventions in climate change impact studies. Specifically, they highlight the importance of a priori information provided by the scientific literature to guide the models considered for selection. We emphasize caution in interpreting model selection results in settings where the scientific literature does not specify the relationship between the outcome and the weather variables.Comment: Additional simulation results available from authors by reques

    Human COL2A1-directed SV40 T antigen expression in transgenic and chimeric mice results in abnormal skeletal development

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    The ability of SV40 T antigen to cause abnormalities in cartilage development in transgenic mice and chimeras has been tested. The cis- regulatory elements of the COL2A1 gene were used to target expression of SV40 T antigen to differentiating chondrocytes in transgenic mice and chimeras derived from embryonal stem (ES) cells bearing the same transgene. The major phenotypic consequences of transgenic (pAL21) expression are malformed skeleton, disproportionate dwarfism, and perinatal/neonatal death. Expression of T antigen was tissue specific and in the main characteristic of the mouse α1(II) collagen gene. Chondrocyte densities and levels of α1(II) collagen mRNAs were reduced in the transgenic mice. Islands of cells which express cartilage characteristic genes such as type IIB procollagen, long form α1(IX) collagen, α2(XI) collagen, and aggrecan were found in the articular and growth cartilages of pAL21 chimeric fetuses and neonates. But these cells, which were expressing T antigen, were not properly organized into columns of proliferating chondrocytes. Levels of α1(II) collagen mRNA were reduced in these chondrocytes. In addition, these cells did not express type X collagen, a marker for hypertrophic chondrocytes. The skeletal abnormality in pAL21 mice may therefore be due to a retardation of chondrocyte maturation or an impaired ability of chondrocytes to complete terminal differentiation and an associated paucity of some cartilage matrix components.published_or_final_versio

    Refining Humane Endpoints in Mouse Models of Disease by Systematic Review and Machine Learning-Based Endpoint Definition

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    Ideally, humane endpoints allow for early termination of experiments by minimizing an animal’s discomfort, distress and pain, while ensuring that scientific objectives are reached. Yet, lack of commonly agreed methodology and heterogeneity of cut-off values published in the literature remain a challenge to the accurate determination and application of humane endpoints. With the aim to synthesize and appraise existing humane endpoint definitions for commonly used physiological parameters, we conducted a systematic review of mouse studies of acute and chronic disease models, which used body weight, temperature and/or sickness scores for endpoint definition. In the second part of the study, we used previously published and unpublished data on weight, temperature and sickness scores from mouse models of sepsis and stroke and applied machine learning algorithms to assess the usefulness of this method for parameter selection and endpoint definition across models. Studies were searched for in two electronic databases (MEDLINE/Pubmed and Embase). Out of 110 retrieved full-text manuscripts, 34 studies were included. We found large intra- and inter-model variance in humane endpoint determination and application due to varying animal models, lack of standardized experimental protocols and heterogeneity of performance metrics (part 1). Machine learning models trained with physiological data and sickness severity score or modified DeSimoni neuroscore identified animals with a high risk of death at an early time point in both mouse models of stroke (male: 93.2% at 72h post-treatment; female: 93.0% at 48h post-treatment) and sepsis (96.2% at 24h post-treatment), thus demonstrating generalizability in endpoint determination across models (part 2)

    Consistency of a hybrid block bootstrap for distribution and variance estimation for sample quantiles of weakly dependent sequences

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    Consistency and optimality of block bootstrap schemes for distribution and variance estimation of smooth functionals of dependent data have been thoroughly investigated by Hall, Horowitz & Jing (1995), among others. However, for nonsmooth functionals, such as quantiles, much less is known. Existing results, due to Sun & Lahiri (2006), regarding strong consistency for distribution and variance estimation via the moving block bootstrap (MBB) require that b→∞, where b=⌊n/ℓ⌋ is the number of resampled blocks to be pasted together to form the bootstrap data series, n is the available sample size, and ℓ is the block length. Here we show that, in fact, weak consistency holds for any b such that 1≤b=O(n/ℓ). In other words we show that a hybrid between the subsampling bootstrap (b=1) and MBB is consistent. Empirical results illustrate the performance of hybrid block bootstrap estimators for varying numbers of blocks

    Block bootstrap optimality and empirical block selection for sample quantiles with dependent data

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    We establish a general theory of optimality for block bootstrap distribution estimation for sample quantiles under mild strong mixing conditions. In contrast to existing results, we study the block bootstrap for varying numbers of blocks. This corresponds to a hybrid between the sub- sampling bootstrap and the moving block bootstrap, in which the number of blocks is between 1 and the ratio of sample size to block length. The hybrid block bootstrap is shown to give theoretical benefits, and startling improvements in accuracy in distribution estimation in important practical settings. The conclusion that bootstrap samples should be of smaller size than the original sample has significant implications for computational efficiency and scalability of bootstrap methodologies with dependent data. Our main theorem determines the optimal number of blocks and block length to achieve the best possible convergence rate for the block bootstrap distribution estimator for sample quantiles. We propose an intuitive method for empirical selection of the optimal number and length of blocks, and demonstrate its value in a nontrivial example

    Commissioning of the vacuum system of the KATRIN Main Spectrometer

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    The KATRIN experiment will probe the neutrino mass by measuring the beta-electron energy spectrum near the endpoint of tritium beta-decay. An integral energy analysis will be performed by an electro-static spectrometer (Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a volume of 1240 m^3, and a complex inner electrode system with about 120000 individual parts. The strong magnetic field that guides the beta-electrons is provided by super-conducting solenoids at both ends of the spectrometer. Its influence on turbo-molecular pumps and vacuum gauges had to be considered. A system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter strips has been deployed and was tested during the commissioning of the spectrometer. In this paper the configuration, the commissioning with bake-out at 300{\deg}C, and the performance of this system are presented in detail. The vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is demonstrated that the performance of the system is already close to these stringent functional requirements for the KATRIN experiment, which will start at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure

    Acclimatization of the crustose coralline alga Porolithon onkodes to variable pCO2

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    Ocean acidification (OA) has important implications for the persistence of coral reef ecosystems, due to potentially negative effects on biomineralization. Many coral reefs are dynamic with respect to carbonate chemistry, and experience fluctuations in pCO2 that exceed OA projections for the near future. To understand the influence of dynamic pCO2 on an important reef calcifier, we tested the response of the crustose coralline alga Porolithon onkodes to oscillating pCO2. Individuals were exposed to ambient (400 ??atm), high (660 ??atm), or variable pCO2 (oscillating between 400/660 ??atm) treatments for 14 days. To explore the potential for coralline acclimatization, we collected individuals from low and high pCO2 variability sites (upstream and downstream respectively) on a back reef characterized by unidirectional water flow in Moorea, French Polynesia. We quantified the effects of treatment on algal calcification by measuring the change in buoyant weight, and on algal metabolism by conducting sealed incubations to measure rates of photosynthesis and respiration. Net photosynthesis was higher in the ambient treatment than the variable treatment, regardless of habitat origin, and there was no effect on respiration or gross photosynthesis. Exposure to high pCO2 decreased P. onkodes calcification by >70%, regardless of the original habitat. In the variable treatment, corallines from the high variability habitat calcified 42% more than corallines from the low variability habitat. The significance of the original habitat for the coralline calcification response to variable, high pCO2 indicates that individuals existing in dynamic pCO2 habitats may be acclimatized to OA within the scope of in situ variability. These results highlight the importance of accounting for natural pCO2 variability in OA manipulations, and provide insight into the potential for plasticity in habitat and species-specific responses to changing ocean chemistry.Funding was provided by grants from the National Science Foundation (OCE-0417412, OCE-10-26852, OCE-1041270) and gifts from the Gordon and Betty Moore Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

    A novel μCT analysis reveals different responses of bioerosion and secondary accretion to environmental variability

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    Corals build reefs through accretion of calcium carbonate (CaCO3) skeletons, but net reef growth also depends on bioerosion by grazers and borers and on secondary calcification by crustose coralline algae and other calcifying invertebrates. However, traditional field methods for quantifying secondary accretion and bioerosion confound both processes, do not measure them on the same time-scale, or are restricted to 2D methods. In a prior study, we compared multiple environmental drivers of net erosion using pre- and post-deployment micro-computed tomography scans (μCT; calculated as the % change in volume of experimental CaCO3 blocks) and found a shift from net accretion to net erosion with increasing ocean acidity. Here, we present a novel μCT method and detail a procedure that aligns and digitally subtracts pre- and post-deployment μCT scans and measures the simultaneous response of secondary accretion and bioerosion on blocks exposed to the same environmental variation over the same time-scale. We tested our method on a dataset from a prior study and show that it can be used to uncover information previously unattainable using traditional methods. We demonstrated that secondary accretion and bioerosion are driven by different environmental parameters, bioerosion is more sensitive to ocean acidity than secondary accretion, and net erosion is driven more by changes in bioerosion than secondary accretion
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