Abstract The purpose of this study was to assess leg muscle quality and give a detailed description of leg muscle involvement in a series of Duchenne muscular dystrophy patients using quantitative ...MRI and strength measurements. Fatty infiltration, as well as total and contractile (not fatty infiltrated) cross sectional areas of various leg muscles were determined in 16 Duchenne patients and 11 controls (aged 8–15). To determine specific muscle strength, four leg muscle groups (quadriceps femoris, hamstrings, anterior tibialis and triceps surae) were measured and related to the amount of contractile tissue. In patients, the quadriceps femoris showed decreased total and contractile cross sectional area, attributable to muscle atrophy. The total, but not the contractile, cross sectional area of the triceps surae was increased in patients, corresponding to hypertrophy. Specific strength decreased in all four muscle groups of Duchenne patients, indicating reduced muscle quality. This suggests that muscle hypertrophy and fatty infiltration are two distinct pathological processes, differing between muscle groups. Additionally, the quality of remaining muscle fibers is severely reduced in the legs of Duchenne patients. The combination of quantitative MRI and quantitative muscle testing could be a valuable outcome parameter in longitudinal studies and in the follow-up of therapeutic effects.
Abstract
The feeding behaviour of growing-finishing pigs is an important indicator of performance, health and welfare, but this use is limited by its large, poorly-understood variation. We explored ...the variation in basal feed intake of individual pigs by detecting circadian rhythms, extracting features of diurnal patterns and assessing consistency over time, from day-to-day and across age. Hourly feed intake data of individual pigs (n = 110) was obtained during one growing-finishing phase, using electronic feeding stations. We applied wavelet analysis to assess rhythms and a hurdle generalised additive model to extract features of diurnal patterns. We found that circadian rhythms could be detected during 58 ± 3% (mean ± standard error) of days in the growing-finishing phase (range 0–100%), predominantly at older ages. Although the group diurnal intake pattern was alternans (small morning peak, larger afternoon peak), individual pigs showed a range of diurnal patterns that changed with age, differing mostly in the extent of night fasting and day-to-day consistency. Our results suggest that the type, day-to-day consistency and age development of diurnal patterns in feed intake show general group patterns but also differ between pigs. Using this knowledge, promising features may be selected to compare against production, health and welfare parameters.
A methodology is described for probabilistic predictions of future climate. This is based on a set of ensemble simulations of equilibrium and time-dependent changes, carried out by perturbing poorly ...constrained parameters controlling key physical and biogeochemical processes in the HadCM3 coupled ocean-atmosphere global climate model. These (ongoing) experiments allow quantification of the effects of earth system modelling uncertainties and internal climate variability on feedbacks likely to exert a significant influence on twenty-first century climate at large regional scales. A further ensemble of regional climate simulations at 25 km resolution is being produced for Europe, allowing the specification of probabilistic predictions at spatial scales required for studies of climate impacts. The ensemble simulations are processed using a set of statistical procedures, the centrepiece of which is a Bayesian statistical framework designed for use with complex but imperfect models. This supports the generation of probabilities constrained by a wide range of observational metrics, and also by expert-specified prior distributions defining the model parameter space. The Bayesian framework also accounts for additional uncertainty introduced by structural modelling errors, which are estimated using our ensembles to predict the results of alternative climate models containing different structural assumptions. This facilitates the generation of probabilistic predictions combining information from perturbed physics and multi-model ensemble simulations. The methodology makes extensive use of emulation and scaling techniques trained on climate model results. These are used to sample the equilibrium response to doubled carbon dioxide at any required point in the parameter space of surface and atmospheric processes, to sample time-dependent changes by combining this information with ensembles sampling uncertainties in the transient response of a wider set of earth system processes, and to sample changes at local scales. The methodology is necessarily dependent on a number of expert choices, which are highlighted throughout the paper.
The expansion of aquaculture and the recent development of more intensive land-based marine farms require efficient and cost-effective systems for treatment of highly nutrient-rich saline wastewater. ...Constructed wetlands with halophytic plants offer the potential for waste-stream treatment combined with production of valuable secondary plant crops. Pilot wetland filter beds, constructed in triplicate and planted with the saltmarsh plant Salicornia europaea, were evaluated over 88 days under commercial operating conditions on a marine fish and shrimp farm. Nitrogen waste was primarily in the form of dissolved inorganic nitrogen (TDIN) and was removed by 98.2 ± 2.2% under ambient loadings of 109–383 μmol l−1. There was a linear relationship between TDIN uptake and loading over the range of inputs tested. At peak loadings of up to 8185 ± 590 μmol l−1 (equivalent to 600 mmol N m−2 d−1), the filter beds removed between 30 and 58% (250 mmol N m−2 d−1) of influent TDIN. Influent dissolved inorganic phosphorus levels ranged from 34 to 90 μmol l−1, with 36–89% reduction under routine operations. Dissolved organic nitrogen (DON) loadings were lower (11–144 μmol l−1), and between 23 and 69% of influent DON was removed during routine operation, with no significant removal of DON under high TDIN loading. Over the 88-day study, cumulative nitrogen removal was 1.28 mol m−2, of which 1.09 mol m−2 was retained in plant tissue, with plant uptake ranging from 2.4 to 27.0 mmol N g−1 dry weight d−1. The results demonstrate the effectiveness of N and P removal from wastewater from land-based intensive marine aquaculture farms by constructed wetlands planted with S. europaea.
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► Aquaculture wastewater was treated in filter beds planted with Salicornia europaea. ► 36–89% of influent dissolved inorganic phosphorus was removed in routine operation. ► 98.2% of influent dissolved inorganic nitrogen was removed in routine operation. ► At peak loading (8185 ± 590 μmol l−1) 30–58% of influent TDIN was removed. ► Cumulative nitrogen removal was 1.3 mol m−2, with 1.1 mol m−2 retained by plants.
Differences in the radiative feedback from clouds account for much of the variation in climate sensitivity amongst General Circulation Models (GCMs). Therefore metrics of model performance which are ...demonstrated to be relevant to the cloud response to climate change form an important contribution to the overall evaluation of GCMs. In this paper we demonstrate an alternative method for assigning model data to observed cloud regimes obtained from clustering histograms of cloud amount in joint cloud optical depth--cloud top pressure classes. The method removes some of the subjectivity that exists in previous GCM cloud clustering studies. We apply the method to ten GCMs submitted to the Cloud Feedback Model Intercomparison Project (CFMIP), evaluate the simulated cloud regimes and analyse the climate change response in the context of these regimes. We also propose two cloud regime metrics, one of which is specifically targeted at assessing GCMs for the purpose of obtaining the global cloud radiative response to climate change. Most of the global variance in the cloud radiative response between GCMs is due to low clouds, with 47% arising from the stratocumulus regime and 18% due to the regime characterised by clouds undergoing transition from stratocumulus to cumulus. This result is found to be dominated by two structurally similar GCMs. The shallow cumulus regime, though widespread, has a smaller contribution and reduces the variance. For the stratocumulus and transition regimes, part of the variance results from a large model spread in the radiative properties of the regime in the control simulation. Comparison with observations reveals a systematic bias for both the stratocumulus and transition regimes to be overly reflective. If this bias was corrected with all other aspects of the response unchanged, the variance in the low cloud response would reduce. The response of some regimes with high cloud tops differ between the GCMs. These regimes are simulated too infrequently in a few of the models. If the frequency in the control simulation were more realistic and changes within the regimes were unaltered, the variance in the cloud radiative response from high-top clouds would increase. As a result, use of observations of the mean present-day cloud regimes suggests that whilst improvements in the simulation of the cloud regimes would impact the climate sensitivity, the inter-model variance may not reduce. When the cloud regime metric is calculated for the GCMs analysed here, only one model is on average consistent with observations within their uncertainty (and even this model is not consistent with the observations for all regimes), indicating scope for improvement in the simulation of cloud regimes.
The XMM-Newton serendipitous survey Traulsen, I.; Schwope, A. D.; Lamer, G. ...
Astronomy and astrophysics (Berlin),
09/2020, Letnik:
641
Journal Article
Recenzirano
Odprti dostop
Context.
The
XMM-Newton
Survey Science Centre Consortium (SSC) develops software in close collaboration with the Science Operations Centre to perform a pipeline analysis of all
XMM-Newton
...observations. In celebration of the twentieth anniversary of the
XMM-Newton
launch, the SSC has compiled the fourth generation of serendipitous source catalogues, 4XMM.
Aims.
The catalogue described here, 4XMM-DR9s, explores sky areas that were observed more than once by
XMM-Newton
. These observations are bundled in groups referred to as stacks. Stacking leads to a higher sensitivity, resulting in newly discovered sources and better constrained source parameters, and unveils long-term brightness variations.
Methods.
The 4XMM-DR9s catalogue was constructed from simultaneous source detection on overlapping observations. As a novel feature, positional rectification was applied beforehand. Observations with all filters and suitable camera settings were included. Exposures with a high background were discarded. The high-background thresholds were determined through a statistical analysis of all exposures in each instrument configuration. The X-ray background maps used in source detection were modelled via an adaptive smoothing procedure with newly determined parameters. Source fluxes were derived for all contributing observations, irrespective of whether the source would be detectable in an individual observation.
Results.
The new catalogue lists the X-ray sources detected in 1329 stacks with 6604 contributing observations over repeatedly covered 300 square degrees in the sky. Most stacks are composed of two observations, the largest one comprises 352 observations. We find 288 191 sources of which 218 283 were observed several times. The number of observations of a source ranges from 1 to 40. Auxiliary products, like X-ray full-band and false-colour images, long-term X-ray light curves, and optical finding charts, are published as well.
Conclusions.
4XMM-DR9s contains new detections and is considered a prime resource to explore long-term variability of X-ray sources discovered by
XMM-Newton
. Regular incremental releases, including new public observations, are planned.
Artemisinins are extracted from sweet wormwood (Artemisia annua) and are the most potent antimalarials available, rapidly killing all asexual stages of Plasmodium falciparum. Artemisinins are ...sesquiterpene lactones widely used to treat multidrug-resistant malaria, a disease that annually claims 1 million lives. Despite extensive clinical and laboratory experience their molecular target is not yet identified. Activated artemisinins form adducts with a variety of biological macromolecules, including haem, translationally controlled tumour protein (TCTP) and other higher-molecular-weight proteins. Here we show that artemisinins, but not quinine or chloroquine, inhibit the SERCA orthologue (PfATP6) of Plasmodium falciparum in Xenopus oocytes with similar potency to thapsigargin (another sesquiterpene lactone and highly specific SERCA inhibitor). As predicted, thapsigargin also antagonizes the parasiticidal activity of artemisinin. Desoxyartemisinin lacks an endoperoxide bridge and is ineffective both as an inhibitor of PfATP6 and as an antimalarial. Chelation of iron by desferrioxamine abrogates the antiparasitic activity of artemisinins and correspondingly attenuates inhibition of PfATP6. Imaging of parasites with BODIPY-thapsigargin labels the cytosolic compartment and is competed by artemisinin. Fluorescent artemisinin labels parasites similarly and irreversibly in an Fe2+-dependent manner. These data provide compelling evidence that artemisinins act by inhibiting PfATP6 outside the food vacuole after activation by iron.
The altered iron concentration in many neurodegenerative diseases such as Alzheimer's disease (AD) has led to the development of MRI sequences that are sensitive to the accompanying changes in the ...transverse relaxation rate. Heavily T2*-weighted imaging sequences at high magnetic field strength (7T and above), in particular, show potential for detecting small changes in iron concentration. However, these sequences require a long echo time in combination with a long scanning time for high resolution and are therefore prone to image artifacts caused by physiological fluctuations, patient motion or system instabilities. Many groups have found that the high image quality that was obtained using high resolution T2*-weighted sequences at 7T in healthy volunteers, could not be obtained in AD patients. In this study the source of the image artifacts was investigated in phantom and in healthy volunteer experiments by incorporating movement parameters and resonance frequency (f0) variations which were measured in AD patients. It was found that image degradation caused by typical f0 variations was a factor-of-four times larger than artifacts caused by movement characteristic of AD patients in the scanner. In addition to respiratory induced f0 variations, large jumps in the f0 were observed in AD patients. By implementing a navigator echo technique to correct for f0 variations, the image quality of high resolution T2*-weighted images increased considerably. This technique was successfully applied in five AD patients and in five subjective memory complainers. Visual scoring showed improvements in image quality in 9 out of 10 subjects. Ghosting levels were reduced by 24±13%.
The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to ...pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and--unexpectedly--lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractants.
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