374 research outputs found
Data requirements for crop modelling-Applying the learning curve approach to the simulation of winter wheat flowering time under climate change
A prerequisite for application of crop models is a careful parameterization based on observational data. However, there are limited studies investigating the link between quality and quantity of observed data and its suitability for model parameterization. Here, we explore the interactions between number of measurements, noise and model predictive skills to simulate the impact of 2050′s climate change (RCP8.5) on winter wheat flowering time. The learning curve of two winter wheat phenology models is analysed under different assumptions about the size of the calibration dataset, the measurement error and the accuracy of the model structure. Our assessment confirms that prediction skills improve asymptotically with the size of the calibration dataset, as with statistical models. Results suggest that less precise but larger training datasets can improve the predictive abilities of models. However, the non-linear relationship between number of measurements, measurement error, and prediction skills limit the compensation between data quality and quantity. We find that the model performance does not improve significantly with a theoretical minimum size of 7–9 observations when the model structure is approximate. While simulation of crop phenology is critical to crop model simulation, more studies are needed to explore data needs for assessing entire crop models
CAR-T cell. the long and winding road to solid tumors
Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles
Curing of Plasmid pXO1 from Bacillus anthracis Using Plasmid Incompatibility
The large plasmid pXO1 encoding the anthrax toxin is important for the virulence of Bacillus anthracis. It is essential to cure pXO1 from B. anthracis to evaluate its role in the pathogenesis of anthrax infection. Because conventional methods for curing plasmids (e.g., curing agents or growth at elevated temperatures) can induce mutations in the host chromosomal DNA, we developed a specific and reliable method to eliminate pXO1 from B. anthracis using plasmid incompatibility. Three putative replication origins of pXO1 were inserted into a temperature-sensitive plasmid to generate three incompatible plasmids. One of the three plasmids successfully eliminated the large plasmid pXO1 from B. anthracis vaccine strain A16R and wild type strain A16. These findings provided additional information about the replication/partitioning of pXO1 and demonstrated that introducing a small incompatible plasmid can generate plasmid-cured strains of B. anthracis without inducing spontaneous mutations in the host chromosome
Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC
We present the first results of meson production in the K^+K^- decay channel
from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by
the PHENIX detector at RHIC. Precision resonance centroid and width values are
extracted as a function of collision centrality. No significant variation from
the PDG accepted values is observed. The transverse mass spectra are fitted
with a linear exponential function for which the derived inverse slope
parameter is seen to be constant as a function of centrality. These data are
also fitted by a hydrodynamic model with the result that the freeze-out
temperature and the expansion velocity values are consistent with the values
previously derived from fitting single hadron inclusive data. As a function of
transverse momentum the collisions scaled peripheral.to.central yield ratio RCP
for the is comparable to that of pions rather than that of protons. This result
lends support to theoretical models which distinguish between baryons and
mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be
submitted to Physical Review C as a regular article. Plain text data tables
for the points plotted in figures for this and previous PHENIX publications
are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm
The International Heat Stress Genotype Experiment for modeling wheat response to heat: field experiments and AgMIP-Wheat multi-model simulations
The data set contains a portion of the International Heat Stress Genotype Experiment (IHSGE) data used in the AgMIP-Wheat project to analyze the uncertainty of 30 wheat crop models and quantify the impact of heat on global wheat yield productivity. It includes two spring wheat cultivars grown during two consecutive winter cropping cycles at hot, irrigated, and low latitude sites in Mexico (Ciudad Obregon and Tlaltizapan), Egypt (Aswan), India (Dharwar), the Sudan (Wad Medani), and Bangladesh (Dinajpur). Experiments in Mexico included normal (November-December) and late (January-March) sowing dates. Data include local daily weather data, soil characteristics and initial soil conditions, crop measurements (anthesis and maturity dates, anthesis and final total above ground biomass, final grain yields and yields components), and cultivar information. Simulations include both daily in-season and end-of-season results from 30 wheat models
Impaired Nuclear Nrf2 Translocation Undermines the Oxidative Stress Response in Friedreich Ataxia
BACKGROUND: Friedreich ataxia originates from a decrease in mitochondrial frataxin, which causes the death of a subset of neurons. The biochemical hallmarks of the disease include low activity of the iron sulfur cluster-containing proteins (ISP) and impairment of antioxidant defense mechanisms that may play a major role in disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We thus investigated signaling pathways involved in antioxidant defense mechanisms. We showed that cultured fibroblasts from patients with Friedreich ataxia exhibited hypersensitivity to oxidative insults because of an impairment in the Nrf2 signaling pathway, which led to faulty induction of antioxidant enzymes. This impairment originated from previously reported actin remodeling by hydrogen peroxide. CONCLUSIONS/SIGNIFICANCE: Thus, the defective machinery for ISP synthesis by causing mitochondrial iron dysmetabolism increases hydrogen peroxide production that accounts for the increased susceptibility to oxidative stress
Consensus-Phenotype Integration of Transcriptomic and Metabolomic Data Implies a Role for Metabolism in the Chemosensitivity of Tumour Cells
Using transcriptomic and metabolomic measurements from the NCI60 cell line panel,
together with a novel approach to integration of molecular profile data, we show
that the biochemical pathways associated with tumour cell chemosensitivity to
platinum-based drugs are highly coincident, i.e. they describe a consensus
phenotype. Direct integration of metabolome and transcriptome data at the point
of pathway analysis improved the detection of consensus pathways by 76%,
and revealed associations between platinum sensitivity and several metabolic
pathways that were not visible from transcriptome analysis alone. These pathways
included the TCA cycle and pyruvate metabolism, lipoprotein uptake and
nucleotide synthesis by both salvage and de novo pathways. Extending the
approach across a wide panel of chemotherapeutics, we confirmed the specificity
of the metabolic pathway associations to platinum sensitivity. We conclude that
metabolic phenotyping could play a role in predicting response to platinum
chemotherapy and that consensus-phenotype integration of molecular profiling
data is a powerful and versatile tool for both biomarker discovery and for
exploring the complex relationships between biological pathways and drug
response
Botulinum Neurotoxin D Uses Synaptic Vesicle Protein SV2 and Gangliosides as Receptors
Botulinum neurotoxins (BoNTs) include seven bacterial toxins (BoNT/A-G) that target presynaptic terminals and act as proteases cleaving proteins required for synaptic vesicle exocytosis. Here we identified synaptic vesicle protein SV2 as the protein receptor for BoNT/D. BoNT/D enters cultured hippocampal neurons via synaptic vesicle recycling and can bind SV2 in brain detergent extracts. BoNT/D failed to bind and enter neurons lacking SV2, which can be rescued by expressing one of the three SV2 isoforms (SV2A/B/C). Localization of SV2 on plasma membranes mediated BoNT/D binding in both neurons and HEK293 cells. Furthermore, chimeric receptors containing the binding sites for BoNT/A and E, two other BoNTs that use SV2 as receptors, failed to mediate the entry of BoNT/D suggesting that BoNT/D binds SV2 via a mechanism distinct from BoNT/A and E. Finally, we demonstrated that gangliosides are essential for the binding and entry of BoNT/D into neurons and for its toxicity in vivo, supporting a double-receptor model for this toxin
Scholarly Context Not Found: One in Five Articles Suffers from Reference Rot
The emergence of the web has fundamentally affected most aspects of information communication, including scholarly communication. The immediacy that characterizes publishing information to the web, as well as accessing it, allows for a dramatic increase in the speed of dissemination of scholarly knowledge. But, the transition from a paper-based to a web-based scholarly communication system also poses challenges. In this paper, we focus on reference rot, the combination of link rot and content drift to which references to web resources included in Science, Technology, and Medicine (STM) articles are subject. We investigate the extent to which reference rot impacts the ability to revisit the web context that surrounds STM articles some time after their publication. We do so on the basis of a vast collection of articles from three corpora that span publication years 1997 to 2012. For over one million references to web resources extracted from over 3.5 million articles, we determine whether the HTTP URI is still responsive on the live web and whether web archives contain an archived snapshot representative of the state the referenced resource had at the time it was referenced. We observe that the fraction of articles containing references to web resources is growing steadily over time. We find one out of five STM articles suffering from reference rot, meaning it is impossible to revisit the web context that surrounds them some time after their publication. When only considering STM articles that contain references to web resources, this fraction increases to seven out of ten. We suggest that, in order to safeguard the long-term integrity of the web-based scholarly record, robust solutions to combat the reference rot problem are required. In conclusion, we provide a brief insight into the directions that are explored with this regard in the context of the Hiberlink project
A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America
Background: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America.
Methods: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome.
Results: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet.
Conclusion: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.Radium Hospital Foundation (Oslo, Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, Helse Sør-Øst (Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, the French Association Recherche contre le Cancer (ARC) in the analysis, and interpretation of data, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (Gefluc) in the analysis, and interpretation of data, the Association Nationale de la Recherche et de la Technologie (ANRT, CIFRE PhD fellowship to H.T.) in the analysis, and interpretation of data and by the OpenHealth Institute in the analysis, and interpretation of data. Barretos Cancer Hospital received financial support by FINEP-CT-INFRA (02/2010)info:eu-repo/semantics/publishedVersio
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