Patients with pulmonary arterial hypertension were randomly assigned to receive sotatercept at a dose of 0.3 mg per kilogram or 0.7 mg per kilogram or placebo, in addition to standard therapy. At 24 ...weeks, both sotatercept groups had a greater reduction in pulmonary vascular resistance than the placebo group.
A combination of bisulfite treatment of DNA and high-throughput sequencing (BS-Seq) can capture a snapshot of a cell's epigenomic state by revealing its genome-wide cytosine methylation at single ...base resolution. Bismark is a flexible tool for the time-efficient analysis of BS-Seq data which performs both read mapping and methylation calling in a single convenient step. Its output discriminates between cytosines in CpG, CHG and CHH context and enables bench scientists to visualize and interpret their methylation data soon after the sequencing run is completed.
Bismark is released under the GNU GPLv3+ licence. The source code is freely available from www.bioinformatics.bbsrc.ac.uk/projects/bismark/.
A new and updated version of the AVHRR (Advanced Very High Resolution Radiometer) based GIMMS (Global Inventory Modelling and Mapping Studies) NDVI (Normalized Difference Vegetation Index) dataset is ...now available covering 1981 to 2010 (GIMMS3g). Earlier versions of this global coverage 15-day composite dataset have been used for numerous local to global scale vegetation time series studies during recent years. However, several aspects of the AVHRR sensor design and data processing potentially introduce substantial noise into the NDVI dataset if not corrected for. The more recent NDVI dataset from Terra MODIS (Moderate Resolution Imaging Spectroradiometer) is considered an improvement over AVHRR data and with the release of GIMMS3g an overlapping period of 11years now provides a possibility to perform a robust evaluation of the accuracy of GIMMS3g data and derived trends. In this study the accuracy is evaluated by comparison with the global Terra MODIS NDVI (MOD13C2 Collection 5) data using linear regression trend analysis. The trends of GIMMS NDVI were found to be in overall acceptable agreement with MODIS NDVI data. A significant trend in NDVI (α=0.05) was found for 11.8% of the MODIS NDVI pixels on a global scale (5.4% characterised by positive trends and 6.3 with negative trends) whereas GIMMS NDVI analysis produced a total of 10.5% significant pixels (4.9% positive, 5.6% negative). However, larger differences were found for the Southern Hemisphere land masses (South America and Australia) and the high northern latitude Arctic regions. From a linear regression analysis the correlation coefficient between the two datasets was found to be highly significant for areas with a distinct phenological cycle. Discrepancies between the GIMMS and MODIS datasets were found in equatorial areas (broadleaved, evergreen forest), Arctic areas (sparse herbaceous or sparse shrub cover) and arid areas (herbaceous cover, closed–open). Linear regression of QA filtered Terra and Aqua MODIS NDVI (2003–2010) revealed similar inconsistencies for Arctic and equatorial areas suggesting that robust long-term NDVI trend estimates in these areas are difficult to obtain from both GIMMS and MODIS data. Additionally, GIMMS based NDVI trend analysis in arid areas of limited photosynthetic activity should be interpreted with caution. The regression coefficient (slope value) (p<0.01) was found to be close to 1 for most land cover types on a global scale (global land cover class average slope=1.00) suggesting overall compatibility between MODIS and GIMMS NDVI, but with land cover class specific variations (within class and between classes).
► Accuracy of GIMMS NDVI was assessed using Terra MODIS monthly NDVI 2000–2010. ► Overall trends of GIMMS NDVI were in acceptable agreement with Terra MODIS NDVI. ► Humid/arctic area discrepancies due to lack of high quality data from both sensors. ► Arid area discrepancies due to lower GIMMS sensitivity for low chlorophyll areas. ► GIMMS NDVI is found to include residual influence from land cover class data.
The human gastrointestinal (gut) microbiota comprises diverse and dynamic populations of bacteria, archaea, viruses, fungi, and protozoa, coexisting in a mutualistic relationship with the host. When ...intestinal homeostasis is perturbed, the function of the gastrointestinal tract and other organ systems, including the brain, can be compromised. The gut microbiota is proposed to contribute to blood-brain barrier disruption and the pathogenesis of neurodegenerative diseases. While progress is being made, a better understanding of interactions between gut microbes and host cells, and the impact these have on signaling from gut to brain is now required. In this review, we summarise current evidence of the impact gut microbes and their metabolites have on blood-brain barrier integrity and brain function, and the communication networks between the gastrointestinal tract and brain, which they may modulate. We also discuss the potential of microbiota modulation strategies as therapeutic tools for promoting and restoring brain health.
Classifying surface cover types and analyzing changes are among the most common applications of remote sensing. One of the most basic classification tasks is to distinguish water bodies from dry land ...surfaces. Landsat imagery is among the most widely used sources of data in remote sensing of water resources; and although several techniques of surface water extraction using Landsat data are described in the literature, their application is constrained by low accuracy in various situations. Besides, with the use of techniques such as single band thresholding and two-band indices, identifying an appropriate threshold yielding the highest possible accuracy is a challenging and time consuming task, as threshold values vary with location and time of image acquisition. The purpose of this study was therefore to devise an index that consistently improves water extraction accuracy in the presence of various sorts of environmental noise and at the same time offers a stable threshold value. Thus we introduced a new Automated Water Extraction Index (AWEI) improving classification accuracy in areas that include shadow and dark surfaces that other classification methods often fail to classify correctly. We tested the accuracy and robustness of the new method using Landsat 5 TM images of several water bodies in Denmark, Switzerland, Ethiopia, South Africa and New Zealand. Kappa coefficient, omission and commission errors were calculated to evaluate accuracies. The performance of the classifier was compared with that of the Modified Normalized Difference Water Index (MNDWI) and Maximum Likelihood (ML) classifiers. In four out of five test sites, classification accuracy of AWEI was significantly higher than that of MNDWI and ML (P-value<0.01). AWEI improved accuracy by lessening commission and omission errors by 50% compared to those resulting from MNDWI and about 25% compared to ML classifiers. Besides, the new method was shown to have a fairly stable optimal threshold value. Therefore, AWEI can be used for extracting water with high accuracy, especially in mountainous areas where deep shadow caused by the terrain is an important source of classification error.
•We introduced a new automated method that improves surface water mapping accuracy.•The new method improves mapping accuracy by enhancing spectral contrast.•The new method was tested on several water bodies in different parts of the world.•Accuracy of the new method is consistently higher than that of MNDWI and MaxLike.•The new index also has fairly stable optimal threshold for accurate classification.
The Peres-Horodecki criterion of positivity under partial transpose is studied in the context of separability of bipartite continuous variable states. The partial transpose operation admits, in the ...continuous case, a geometric interpretation as mirror reflection in phase space. This recognition leads to uncertainty principles, stronger than the traditional ones, to be obeyed by all separable states. For all bipartite Gaussian states, the Peres-Horodecki criterion turns out to be a necessary and sufficient condition for separability.
In a randomized phase 3 trial involving patients with acute intermittent porphyria, the use of givosiran, an oligonucleotide drug designed to target messenger RNA encoding aminolevulinic acid ...synthase, led to a 74% lower annualized porphyria attack rate than the use of placebo at 6 months.
Rationale
Continuous performance tests (CPTs) are widely used to assess attentional processes in a variety of disorders including Alzheimer’s disease and schizophrenia. Common human CPTs require ...discrimination of sequentially presented, visually patterned ‘target’ and ‘non-target’ stimuli at a single location.
Objectives
The aims of this study were to evaluate the performance of three popular mouse strains on a novel rodent touchscreen test (rCPT) designed to be analogous to common human CPT variants and to investigate the effects of donepezil, a cholinesterase inhibitor and putative cognitive enhancer.
Methods
C57BL/6J, DBA/2J and CD1 mice (
n
= 15–16/strain) were trained to baseline performance using four rCPT training stages. Then, probe tests assessed the effects of parameter changes on task performance: stimulus size, duration, contrast, probability, inter-trial interval or inclusion of flanker distractors. rCPT performance was also evaluated following acute administration of donepezil (0–3 mg/kg, i.p.).
Results
C57BL/6J and DBA/2J mice showed similar acquisition rates and final baseline performance following rCPT training. On probe tests, rCPT performance of both strains was sensitive to alteration of visual and/or attentional demands (stimulus size, duration, contrast, rate, flanker distraction). Relative to C57BL/6J, DBA/2J mice exhibited (1) decreasing sensitivity (
d
′) across the 45-min session, (2) reduced performance on probes where the appearance of stimuli or adjacent areas were changed (size, contrast, flanking distractors) and (3) larger dose- and stimulus duration-dependent changes in performance following donepezil administration. In contrast, CD1 mice failed to acquire rCPT (stage 3) and pairwise visual discrimination tasks.
Conclusions
rCPT is a potentially useful translational tool for assessing attention in mice and for detecting the effects of nootropic drugs.
Knowledge of genome-wide genealogies for thousands of individuals would simplify most evolutionary analyses for humans and other species, but has remained computationally infeasible. We have ...developed a method, Relate, scaling to >10,000 sequences while simultaneously estimating branch lengths, mutational ages and variable historical population sizes, as well as allowing for data errors. Application to 1,000 Genomes Project haplotypes produces joint genealogical histories for 26 human populations. Highly diverged lineages are present in all groups, but most frequent in Africa. Outside Africa, these mainly reflect ancient introgression from groups related to Neanderthals and Denisovans, while African signals instead reflect unknown events unique to that continent. Our approach allows more powerful inferences of natural selection than has previously been possible. We identify multiple regions under strong positive selection, and multi-allelic traits including hair color, body mass index and blood pressure, showing strong evidence of directional selection, varying among human groups.
Wireless Sensor Networks (WSNs) are usually formed with many tiny sensors which are randomly deployed within sensing field for target monitoring. These sensors can transmit their monitored data to ...the sink in a multi-hop communication manner. However, the ‘hot spots’ problem will be caused since nodes near sink will consume more energy during forwarding. Recently, mobile sink based technology provides an alternative solution for the long-distance communication and sensor nodes only need to use single hop communication to the mobile sink during data transmission. Even though it is difficult to consider many network metrics such as sensor position, residual energy and coverage rate etc., it is still very important to schedule a reasonable moving trajectory for the mobile sink. In this paper, a novel trajectory scheduling method based on coverage rate for multiple mobile sinks (TSCR-M) is presented especially for large-scale WSNs. An improved particle swarm optimization (PSO) combined with mutation operator is introduced to search the parking positions with optimal coverage rate. Then the genetic algorithm (GA) is adopted to schedule the moving trajectory for multiple mobile sinks. Extensive simulations are performed to validate the performance of our proposed method.
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