97 research outputs found

    Montana Prairie Pothole Joint Venture Breeding Shorebird Project

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    Populations of several shorebird species in the Prairie Pothole Region (PPR) appear to be declining, largely because of loss of grasslands and wetlands. Marbled godwit (Limosa fedoa), long-billed curlew (Numenius americanus), willet (Tringa semipalmata), Wilson’s phalarope (Phalaropus tricolor), upland sandpiper (Bartramia longicauda), American avocet (Recurvirostra americana) and Wilson’s snipe (Gallinago delicata) are listed as priority species by Partners in Flight or the U.S. Shorebird Plan. In 2012, the USDI Fish and Wildlife Service‘s Habitat and Population Evaluation Team began conducting breeding shorebird surveys in the western portion of the Montana PPR to complement existing surveys for partners of the Prairie Pothole Joint Venture in North Dakota, South Dakota, and northeast Montana. The purpose of these surveys is to provide data for development of habitat models identifying priority conservation areas where habitat needs overlap for breeding shorebirds and breeding waterfowl.  Results will allow land managers to integrate breeding shorebird conservation with ongoing waterfowl conservation actions in the Montana PPR. This is a long-term adaptive process that includes updating models with annually collected survey data to inform and improve model performance.  We summarize the objectives and field design of the project and report results of preliminary modeling from our 2012/2013 efforts

    Montana Prairie Pothole Joint Venture Breeding Shorebird Monitoring Project

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    Populations of several shorebird species in the Prairie Pothole Region (PPR) appear to be declining, largely because of loss of grasslands and wetlands. Marbled godwit (Limosa fedoa), long-billed curlew (Numenius americanus), willet (Tringa semipalmata), Wilson’s phalarope (Phalaropus tricolor), upland sandpiper (Bartramia longicauda), American avocet (Recurvirostra americana) and Wilson’s snipe (Gallinago delicata) are listed as priority species by Partners in Flight or the U.S. Shorebird Plan. In 2004, the USDI Fish and Wildlife Service, Habitat and Population Evaluation Team (HAPET) began conducting breeding shorebird surveys to complement existing waterfowl population and habitat evaluations for the partners of the Prairie Pothole Joint Venture in North Dakota, South Dakota and northeast Montana. Survey methodology was modeled after the Breeding Bird Survey (BBS) but modified to fit the breeding ecology of these shorebirds. In 2012, surveys were expanded to include the western portion of the Montana PPR. Data from these surveys will be used to estimate shorebird population densities and distribution; however, current survey methods do not take into account areas where shorebirds may have been present but undetected, possibly resulting in an underestimation of shorebird densities. Surveys will be modified in 2013 in an effort to allow for estimation of shorebird detection probabilities, while maintaining compatibility with previous data collection methods. Results from this research will allow land managers to integrate breeding shorebird conservation with ongoing waterfowl conservation actions in the Montana PPR. We summarize the objectives and field design of the project and report results of preliminary modeling from our 2012 efforts

    The clinicomolecular landscape of de novo versus relapsed stage IV metastatic breast cancer

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    Background: de novo metastatic breast cancer (dnMBC) is responsible for 6–10% of breast cancer presentations with increasing incidence and has remained resistant to detection by mammography screening. Recent publications hypothesized that in addition to poor screening uptake, the presentation of dnMBC may be due to its unfavourable biology which remains unknown at the molecular level. Here we investigated the tumour biology of dnMBC in the form of clinicopathology, genomic alterations and differential gene expression to create a comparative landscape of de novo versus relapsed metastatic breast cancer (rMBC). Additionally, to address the current screening limitations, we conducted a preliminary biomarker investigation for early dnMBC detection. Methods: In this retrospective case-control study, gene expression and clinical data were accessed from the Cancer Genome Atlas (TCGA) for primary tumours of treatment-naïve patients with dnMBC (n = 17), rMBC (n = 49), and normal tissue (n = 113). The clinical and histological data were assessed categorically using Fisher's Exact-Test for significance (p < .05), or continuously using the Mann-Whitney Test (p < .05) where appropriate. The differential gene expression analysis was performed using EdgeR's negative binomial distribution model with a false discovery rate (FDR) <0.05. The resulting gene list was analysed manually for roles in metastasis as well as ontologically using STRING-DB with FDR <0.05. Results: dnMBCs showed improved median survival vs rMBC (36 vs. 12 months). dnMBCs were more likely to be hormone receptor positive, less likely to be triple negative with lower histological lymphocytic infiltrate. In terms of genome alterations, dnMBCs had 4-fold increased PTEN mutations and poor survival with ABL2 and GATA3 alterations. Expression-wise, dnMBCs down-regulated TNFa, IL-17 signalling, and chemotaxis, while up-regulating steroid biosynthesis, cell migration, and cell adhesion. Biomarker analysis detected pre-existing and novel breast cancer biomarkers. Conclusion: The comparative tumour landscape revealed significant clinical, pathological and molecular differences between dnMBC and rMBC, indicating that dnMBC may be a separate biological entity to rMBC at the primary level with differing paths to metastasis. Additionally, we provided a list of potential serum biomarkers that may be useful in detecting dnMBC in its pre-metastatic window if such a window exists

    A Framework for Collaborative Curation of Neuroscientific Literature

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    Large models of complex neuronal circuits require specifying numerous parameters, with values that often need to be extracted from the literature, a tedious and error-prone process. To help establishing shareable curated corpora of annotations, we have developed a literature curation framework comprising an annotation format, a Python API (NeuroAnnotation Toolbox; NAT), and a user-friendly graphical interface (NeuroCurator). This framework allows the systematic annotation of relevant statements and model parameters. The context of the annotated content is made explicit in a standard way by associating it with ontological terms (e.g., species, cell types, brain regions). The exact position of the annotated content within a document is specified by the starting character of the annotated text, or the number of the figure, the equation, or the table, depending on the context. Alternatively, the provenance of parameters can also be specified by bounding boxes. Parameter types are linked to curated experimental values so that they can be systematically integrated into models. We demonstrate the use of this approach by releasing a corpus describing different modeling parameters associated with thalamo-cortical circuitry. The proposed framework supports a rigorous management of large sets of parameters, solving common difficulties in their traceability. Further, it allows easier classification of literature information and more efficient and systematic integration of such information into models and analyses

    Evolving boolean functions with conjunctions and disjunctions via genetic programming

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    Recently it has been proved that simple GP systems can efficiently evolve the conjunction of n variables if they are equipped with the minimal required components. In this paper, we make a considerable step forward by analysing the behaviour and performance of a GP system for evolving a Boolean function with unknown components, i.e. the target function may consist of both conjunctions and disjunctions. We rigorously prove that if the target function is the conjunction of n variables, then a GP system using the complete truth table to evaluate program quality evolves the exact target function in O(ℓ n log2 n) iterations in expectation, where ℓ ≥ n is a limit on the size of any accepted tree. Additionally, we show that when a polynomial sample of possible inputs is used to evaluate solution quality, conjunctions with any polynomially small generalisation error can be evolved with probability 1 - O(log2(n)/n). To produce our results we introduce a super-multiplicative drift theorem that gives significantly stronger runtime bounds when the expected progress is only slightly super-linear in the distance from the optimum

    Biomarkers reveal the effects of hydrography on the sources and fate of marine and terrestrial organic matter in the western Irish Sea

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    A suite of lipid biomarkers were investigated from surface sediments and particulatematter across hydrographically distinct zones associated with the western Irish Sea gyre and the seasonal bloom. The aim was to assess the variation of organic matter (OM) composition, production, distribution and fate associated with coastal and southern mixed regions and also the summer stratified region. Based on the distribution of a suite of diagnostic biomarkers, including phospholipid fatty acids, source-specific sterols, wax esters and C25 highly branched isoprenoids, diatoms, dinoflagellates and green algae were identified as major contributors of marine organic matter (MOM) in this setting. The distribution of cholesterol, wax esters and C20 and C22 polyunsaturated fatty acids indicate that copepod grazing represents an important process for mineralising this primary production. Net tow data from 2010 revealed much greater phytoplankton and zooplankton biomass in well-mixed waters compared to stratified waters. This appears to be largely reflected in MOM input to surface sediments. Terrestrial organic matter (TOM), derived from higher plants, was identified as a major source of OM regionally, but was concentrated in proximity to major riverine input at the Boyne Estuary and Dundalk Bay. Near-bottom residual circulation and the seasonal gyre also likely play a role in the fate of TOM in the western Irish Sea

    Long-term prognosis for 1-year relapse-free survivors of CD34 cell-selected allogeneic hematopoietic stem cell transplantation : a landmark analysis

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    Altres ajuts: This research was supported in part by National Institutes of Health award number P01 CA23766 and NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.CD34 selection significantly improves GVHD-free survival in allogeneic hematopoietic cell transplantation (allo-HSCT). Specific information regarding long-term prognosis and risk factors for late mortality after CD34-selected allo-HSCT is lacking, however. We conducted a single-center landmark analysis in 276 patients alive without relapse 1 year after CD34-selected allo-HSCT for AML (n=164), ALL (n=33), or MDS (n=79). At 5 years' follow-up after the 1-year landmark (range 0.03-13 years), estimated RFS was 73% and OS 76%. The 5-year cumulative incidence of relapse and NRM were 11% and 16%, respectively. In multivariate analysis, HCT-CI score ≥ 3 correlated with marginally worse RFS (HR 1.78, 95% CI 0.97-3.28, p=0.06) and significantly worse OS (HR 2.53, 95% CI 1.26-5.08, p=0.004). Despite only 24% of patients with acute GVHD within 1 year, this also significantly correlated with worse RFS and OS, with increasing grades of acute GVHD associating with increasingly poorer survival on multivariate analysis (p<0.0001). Of 63 deaths after the landmark, GVHD accounted for 27% of deaths and was the most common cause of late mortality, followed by relapse and infection. While prognosis is excellent for patients alive without relapse 1 year after CD34-selected allo-HSCT, risks of late relapse and NRM persist, particularly due to GVHD

    Experimentally-constrained biophysical models of tonic and burst firing modes in thalamocortical neurons

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    Somatosensory thalamocortical (TC) neurons from the ventrobasal (VB) thalamus are central components in the flow of sensory information between the periphery and the cerebral cortex, and participate in the dynamic regulation of thalamocortical states including wakefulness and sleep. This property is reflected at the cellular level by the ability to generate action potentials in two distinct firing modes, called tonic firing and low-threshold bursting. Although the general properties of TC neurons are known, we still lack a detailed characterization of their morphological and electrical properties in the VB thalamus. The aim of this study was to build biophysically-detailed models of VB TC neurons explicitly constrained with experimental data from rats. We recorded the electrical activity of VB neurons (N = 49) and reconstructed morphologies in 3D (N = 50) by applying standardized protocols. After identifying distinct electrical types, we used a multi-objective optimization to fit single neuron electrical models (e-models), which yielded multiple solutions consistent with the experimental data. The models were tested for generalization using electrical stimuli and neuron morphologies not used during fitting. A local sensitivity analysis revealed that the e-models are robust to small parameter changes and that all the parameters were constrained by one or more features. The e-models, when tested in combination with different morphologies, showed that the electrical behavior is substantially preserved when changing dendritic structure and that the e-models were not overfit to a specific morphology. The models and their analysis show that automatic parameter search can be applied to capture complex firing behavior, such as co-existence of tonic firing and low-threshold bursting over a wide range of parameter sets and in combination with different neuron morphologies
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