152 research outputs found

    Vascular health in patients in remission of Cushing's syndrome is comparable to that in BMI-matched controls.

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    CONTEXT: In active Cushing's syndrome (CS), patients suffer from endothelial dysfunction and premature atherosclerosis. However, it is uncertain to what extent vascular health recovers after long-term remission. This is highly relevant as this topic relates to future development of cardiovascular disease. OBJECTIVE: To investigate whether micro- and macrovascular health is impaired after long-term remission of CS, in patients with no or adequately treated co-morbidities. DESIGN AND SETTING: Cross-sectional case-control study in two tertiary referral centers. PATIENTS AND MAIN OUTCOME MEASURES: 63 patients (remission of CS for ≥ 4 years) and 63 healthy, well-matched controls were compared. In group A (58 patients and 58 controls) serum biomarkers associated with endothelial dysfunction, intima media thickness, pulse wave velocity and pulse wave analysis were studied. In group B (14 patients and 14 controls) endothelium-dependent and-independent vasodilatation was studied in conduit arteries (flow mediated dilation of the brachial artery) and forearm skeletal muscle resistance arteries (vasodilator response to intra-arterial acetylcholine, sodium-nitroprusside and N(G)-monomethyl-L-arginine using venous occlusion plethysmography). RESULTS: There were no significant differences between the outcome measures of vascular health of patients and controls in group A and B. CONCLUSION: Vascular health of patients in long-term remission of Cushing's syndrome seems to be comparable to that of healthy gender-, age and BMI matched controls, provided that the patients have no, or adequately controlled co-morbidities. Therefore, the effects of hypercortisolism per se on the vasculature may be reversible. This accentuates the need for stringent treatment of metabolic co-morbidities in these patients

    Schatten van grasopbrengst op basis van spectrale reflectie, grashoogte en modellering : Onderzoeksresultaten van een maaiproef op zand- klei en veengrond 2016-2017

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    For dairy farmers a good estimate of the current grass yield is essential for grassland planning. To see to what extent grass yield and nitrogen content can be measured with remote sensing, spectral reflection measurements were compared in a field trial with dry matter yields and nitrogen content of mown grass (‘ground truth’ data). These yields and contents were also used to validate a model-based estimate of the grass yield and the nitrogen content or crude protein content. A practical comparison has also been made with grass height measurements. Reflection measurements gave a rough estimate of the dry matter yield. By making a distinction between location and by including basic growth data, the estimate improved considerably. A model-based growth prediction gave a better estimate of the dry matter yield and improved even further in combination with reflection measurements or grass height. With the current techniques, nitrogen content of grass appears to be difficult to measure and predict

    GrasMaïs-Signaal; adviessysteem precisielandbouw melkveehouderij : haalbaarheidsstudie naar het genereren van opbrengst- en voederwaardekengetallen met sensoren en modellen voor gras en snijmaïs

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    A feasibility study has been worked out for an integrated advisory system for precision agriculture on the production of forage (grass and maize) for dairy farming in the Netherlands. Technology is not restrictive anymore to apply precision agriculture on important cultivation measures. It is now about achieving an effective integration of sensor data, models, metrics and equipment in a comprehensive advice system. It has been advised how a practical advice system for operational decisions can be realized on the dairy farm in the foreseeable future

    A lightweight hyperspectral mapping system and photogrammetric processing chain for unmanned aerial vehicles

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    During the last years commercial hyperspectral imaging sensors have been miniaturized and their performance has been demonstrated on Unmanned Aerial Vehicles (UAV). However currently the commercial hyperspectral systems still require minimum payload capacity of approximately 3 kg, forcing usage of rather large UAVs. In this article we present a lightweight hyperspectral mapping system (HYMSY) for rotor-based UAVs, the novel processing chain for the system, and its potential for agricultural mapping and monitoring applications. The HYMSY consists of a custom-made pushbroom spectrometer (400–950 nm, 9 nm FWHM, 25 lines/s, 328 px/line), a photogrammetric camera, and a miniature GPS-Inertial Navigation System. The weight of HYMSY in ready-to-fly configuration is only 2.0 kg and it has been constructed mostly from off-the-shelf components. The processing chain uses a photogrammetric algorithm to produce a Digital Surface Model (DSM) and provides high accuracy orientation of the system over the DSM. The pushbroom data is georectified by projecting it onto the DSM with the support of photogrammetric orientations and the GPS-INS data. Since an up-to-date DSM is produced internally, no external data are required and the processing chain is capable to georectify pushbroom data fully automatically. The system has been adopted for several experimental flights related to agricultural and habitat monitoring applications. For a typical flight, an area of 2–10 ha was mapped, producing a RGB orthomosaic at 1–5 cm resolution, a DSM at 5–10 cm resolution, and a hyperspectral datacube at 10–50 cm resolution

    Deriving Hourly Evapotranspiration Rates with SEBS: A Lysimetric Evaluation

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    Numerous energy balance (EB) algorithms have been developed to use remote sensing data for mapping evapotranspiration (ET) on a regional basis. Adopting any single or combination of these models for an operational ET remote sensing program requires a thorough evaluation. The Surface Energy Balance System (SEBS) was evaluated for its ability to estimate hourly ET rates of summer tall and short crops grown in the Texas High Plains by using 15 Landsat 5 Thematic Mapper scenes acquired during 2006 to 2009. Performance of SEBS was evaluated by comparing estimated hourly ET values with measured ET data from four large weighing lysimeters, each located at the center of a 4.3 ha field in the USDA-ARS Conservation and Production Research Laboratory in Bushland, TX. The performance of SEBS in estimating hourly ET was good for crops under both irrigated and dryland conditions. A locally derived, surface albedo-based soil heat flux (G) model further improved the G estimates. Root mean square error and mean bias error were 0.11 and −0.005 mm h−1, respectively, and the Nash–Sutcliff model efficiency was 0.85 between the measured and calculated hourly ET. Considering the equal or better performance with a minimal amount of ancillary data as compared to with other EB algorithms, SEBS is a promising tool for use in an operational ET remote sensing program in the semiarid Texas High Plains. However, thorough sensitivity and error propagation analyses of input variables to quantify their impact on ET estimations for the major crops in the Texas High Plains under different agroclimatological conditions are needed before adopting the SEBS into operational ET remote sensing programs for irrigation scheduling or other purposes

    Decreased Aerobic Exercise Capacity After Long-Term Remission From Cushing Syndrome: Exploration of Mechanisms.

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    BACKGROUND: Although major improvements are achieved after cure of Cushing syndrome (CS), fatigue and decreased quality of life persist. This is the first study to measure aerobic exercise capacity in patients in remission of CS for more than 4 years in comparison with matched controls, and to investigate whether the reduction in exercise capacity is related to alterations in muscle tissue. METHODS: Seventeen patients were included. A control individual, matched for sex, estrogen status, age, body mass index, smoking, ethnicity, and physical activity level was recruited for each patient. Maximal aerobic capacity (VO2peak) was assessed during incremental bicycle exercise to exhaustion. In 8 individually matched patients and controls, a percutaneous muscle biopsy was obtained and measures were made of cross-sectional areas, capillarization, and oxphos complex IV (COXIV) protein content as an indicator of mitochondrial content. Furthermore, protein content of endothelial nitric oxide synthase (eNOS) and eNOS phosphorylated on serine1177 and of the NAD(P)H-oxidase subunits NOX2, p47phox, and p67phox were measured in the microvascular endothelial layer. FINDINGS: Patients showed a lower mean VO2peak (SD) (28.0 [7.0] vs 34.8 [7.9] ml O2/kg bw/min, P < .01), maximal workload (SD) (176 [49] vs 212 [67] watt, P = .01), and oxygen pulse (SD) (12.0 [3.7] vs 14.8 [4.2] ml/beat, P < .01) at VO2peak. No differences were seen in muscle fiber type-specific cross-sectional area, capillarization measures, mitochondrial content, and protein content of eNOS, eNOS-P-ser1177, NOX2, p47phox, and p67phox. INTERPRETATION: Because differences in muscle fiber and microvascular outcome measures are not statistically significant, we hypothesize that cardiac dysfunction, seen in active CS, persists during remission and limits blood supply to muscles

    The Transcriptional Response to DNA-Double-Strand Breaks in Physcomitrella patens

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    The model bryophyte Physcomitrella patens is unique among plants in supporting the generation of mutant alleles by facile homologous recombination-mediated gene targeting (GT). Reasoning that targeted transgene integration occurs through the capture of transforming DNA by the homology-dependent pathway for DNA double-strand break (DNA-DSB) repair, we analysed the genome-wide transcriptomic response to bleomycin-induced DNA damage and generated mutants in candidate DNA repair genes. Massively parallel (Illumina) cDNA sequencing identified potential participants in gene targeting. Transcripts encoding DNA repair proteins active in multiple repair pathways were significantly up-regulated. These included Rad51, CtIP, DNA ligase 1, Replication protein A and ATR in homology-dependent repair, Xrcc4, DNA ligase 4, Ku70 and Ku80 in non-homologous end-joining and Rad1, Tebichi/polymerase theta, PARP in microhomology-mediated end-joining. Differentially regulated cell-cycle components included up-regulated Rad9 and Hus1 DNA-damage-related checkpoint proteins and down-regulated D-type cyclins and B-type CDKs, commensurate with the imposition of a checkpoint at G2 of the cell cycle characteristic of homology-dependent DNA-DSB repair. Candidate genes, including ATP-dependent chromatin remodelling helicases associated with repair and recombination, were knocked out and analysed for growth defects, hypersensitivity to DNA damage and reduced GT efficiency. Targeted knockout of PpCtIP, a cell-cycle activated mediator of homology-dependent DSB resection, resulted in bleomycin-hypersensitivity and greatly reduced GT efficiency

    Modeling double strand break susceptibility to interrogate structural variation in cancer

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    Abstract Background Structural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. Many SVs are thought to emerge from errors in the repair processes following DNA double strand breaks (DSBs). Results We used experimentally quantified DSB frequencies in cell lines with matched chromatin and sequence features to derive the first quantitative genome-wide models of DSB susceptibility. These models are accurate and provide novel insights into the mutational mechanisms generating DSBs. Models trained in one cell type can be successfully applied to others, but a substantial proportion of DSBs appear to reflect cell type-specific processes. Using model predictions as a proxy for susceptibility to DSBs in tumors, many SV-enriched regions appear to be poorly explained by selectively neutral mutational bias alone. A substantial number of these regions show unexpectedly high SV breakpoint frequencies given their predicted susceptibility to mutation and are therefore credible targets of positive selection in tumors. These putatively positively selected SV hotspots are enriched for genes previously shown to be oncogenic. In contrast, several hundred regions across the genome show unexpectedly low levels of SVs, given their relatively high susceptibility to mutation. These novel coldspot regions appear to be subject to purifying selection in tumors and are enriched for active promoters and enhancers. Conclusions We conclude that models of DSB susceptibility offer a rigorous approach to the inference of SVs putatively subject to selection in tumors

    Drosophila DNA polymerase theta utilizes both helicase-like and polymerase domains during microhomology-mediated end joining and interstrand crosslink repair

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    Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase theta (Pol theta), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol theta contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear. Here, we utilize genetic and biochemical analyses to examine the roles of the helicase-like and polymerase domains of Drosophila Pol theta. We demonstrate an absolute requirement for both polymerase and ATPase activities during ICL repair in vivo. However, similar to mammalian systems, polymerase activity, but not ATPase activity, is required for ionizing radiation-induced DSB repair. Using a site-specific break repair assay, we show that overall end-joining efficiency is not affected in ATPase-dead mutants, but there is a significant decrease in templated insertion events. In vitro, Pol theta can efficiently bypass a model unhooked nitrogen mustard crosslink and promote DNA synthesis following microhomology annealing, although ATPase activity is not required for these functions. Together, our data illustrate the functional importance of the helicase-like domain of Pol theta and suggest that its tethering to the polymerase domain is important for its multiple functions in DNA repair and damage tolerance
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