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Simple Summary Gliomas are heterogenous types of cancer, therefore the therapy should be personalized and targeted toward specific pathways. We developed a methodology that corrected strong batch effects from The Cancer Genome Atlas datasets and estimated glioma grade-specific co-enrichment mechanisms using machine learning. Our findings created hypotheses for annotations, e.g., pathways, that should be considered as therapeutic targets. Gliomas develop and grow in the brain and central nervous system. Examining glioma grading processes is valuable for improving therapeutic challenges. One of the most extensive repositories storing transcriptomics data for gliomas is The Cancer Genome Atlas (TCGA). However, such big cohorts should be processed with caution and evaluated thoroughly as they can contain batch and other effects. Furthermore, biological mechanisms of cancer contain interactions among biomarkers. Thus, we applied an interpretable machine learning approach to discover such relationships. This type of transparent learning provides not only good predictability, but also reveals co-predictive mechanisms among features. In this study, we corrected the strong and confounded batch effect in the TCGA glioma data. We further used the corrected datasets to perform comprehensive machine learning analysis applied on single-sample gene set enrichment scores using collections from the Molecular Signature Database. Furthermore, using rule-based classifiers, we displayed networks of co-enrichment related to glioma grades. Moreover, we validated our results using the external glioma cohorts. We believe that utilizing corrected glioma cohorts from TCGA may improve the application and validation of any future studies. Finally, the co-enrichment and survival analysis provided detailed explanations for glioma progression and consequently, it should support the targeted treatment.
We present the discovery of a new double-detonation progenitor system consisting of a hot subdwarf B (sdB) binary with a white dwarf companion with a P (orb) = 76.34179(2) minutes orbital period. Spectroscopic observations are consistent with an sdB star during helium core burning residing on the extreme horizontal branch. Chimera light curves are dominated by ellipsoidal deformation of the sdB star and a weak eclipse of the companion white dwarf. Combining spectroscopic and light curve fits, we find a low-mass sdB star, M (sdB) = 0.383 +/- 0.028 M (circle dot) with a massive white dwarf companion, M (WD) = 0.725 +/- 0.026 M (circle dot). From the eclipses we find a blackbody temperature for the white dwarf of 26,800 K resulting in a cooling age of approximate to 25 Myr whereas our MESA model predicts an sdB age of approximate to 170 Myr. We conclude that the sdB formed first through stable mass transfer followed by a common envelope which led to the formation of the white dwarf companion approximate to 25 Myr ago. Using the MESA stellar evolutionary code we find that the sdB star will start mass transfer in approximate to 6 Myr and in approximate to 60 Myr the white dwarf will reach a total mass of 0.92 M (circle dot) with a thick helium layer of 0.17 M (circle dot). This will lead to a detonation that will likely destroy the white dwarf in a peculiar thermonuclear supernova. PTF1 J2238+7430 is only the second confirmed candidate for a double-detonation thermonuclear supernova. Using both systems we estimate that at least approximate to 1% of white dwarf thermonuclear supernovae originate from sdB+WD binaries with thick helium layers, consistent with the small number of observed peculiar thermonuclear explosions.
The West Burma Terrane (WBT) is a small terrane bounded to the east by the Asian Sibumasu Block and to the west by the Indo-Burman Ranges (IBR), the latter being an exhumed accretionary prism that formed during subduction of Indian oceanic lithosphere beneath Asia. Understanding the geological history of the WBT is important for reconstruction of the closure history of the Tethys Ocean and India-Asia collision. Currently there are major discrepancies in the proposed timings of collision between the WBT with both India and Asia; whether the WBT collided with India or Asia first is debated, and proposed timings of collisions stretch from the Mesozoic to the Cenozoic. We undertook a multi-technique provenance study involving petrography, detrital zircon U-Pb and Hf analyses, rutile U-Pb analyses and Sr-Nd bulk rock analyses on sediments of the Central Myanmar Basins of the WBT. We determined that the first arrival of Asian material into the basin occurred after the earliest late Eocene and by the early Oligocene, thus placing a minimum constraint on the timing of WBT-Asia collision. Our low temperature thermochronological study of the IBR records two periods of exhumation, in the early-middle Eocene, and at the Oligo-Miocene boundary. The Eocene event may be associated with the collision of the WBT with India. The later event at the Oligo-Miocene boundary may be associated with changes in wedge dynamics resulting from increased sediment supply to the system; however a number of other possible causes provide equally plausible explanations for both events.
The aim of this study was to investigate the effects of listening to preferred music during a warm up or exercise, on performance during a 6-min all-out exercise test (6-MT) in young adult males. Twenty-five healthy males volunteered to participate in this study. Following a within subject design, participants performed three test conditions (MDT: music during the test; MDW: music during the warm-up; WM: without music) in random order. Outcomes included mean running speed over the 6-min test (MRS6), total distance covered (TDC), heart rate responses (HRpeak, HRmean), blood lactate (3-min after the test), and the rating of perceived exertion (RPE); additionally, feeling scale scores were recorded. Listening to preferred music during running resulted in significant TDC (Delta up arrow 10%, p=0.006, ES=0.80) and MRS6 (Delta up arrow 14%, p=0.012, ES=1.02) improvement during the 6-MT, improvement was also noted for the warm-up with music condition (TDC:Delta up arrow 8%, p=0.028, ES=0.63; MRS6:Delta up arrow 8%, p=0.032, ES=0.61). A similar reverse "J-shaped" pacing profile was detected during the three conditions. Blood lactate was lower in the MDT condition by 8% (p=0.01, ES=1.10), but not the MDW condition, compared to MW. In addition, no statistically significant differences were found between the test sessions for the HR, RPE, and feeling scale scores. In conclusion, listening to music during exercise testing would be more beneficial for optimal TDC and MRS6 performances compared to MDW and WM.
This study focuses on three key aspects: (a) crude throat swab samples in a viral transport medium (VTM) as templates for RT-LAMP reactions; (b) a biotinylated DNA probe with enhanced specificity for LFA readouts; and (c) a digital semi-quantification of LFA readouts. Throat swab samples from SARS-CoV-2 positive and negative patients were used in their crude (no cleaning or pre-treatment) forms for the RT-LAMP reaction. The samples were heat-inactivated but not treated for any kind of nucleic acid extraction or purification. The RT-LAMP (20 min processing time) product was read out by an LFA approach using two labels: FITC and biotin. FITC was enzymatically incorporated into the RT-LAMP amplicon with the LF-LAMP primer, and biotin was introduced using biotinylated DNA probes, specifically for the amplicon region after RT-LAMP amplification. This assay setup with biotinylated DNA probe-based LFA readouts of the RT-LAMP amplicon was 98.11% sensitive and 96.15% specific. The LFA result was further analysed by a smartphone-based IVD device, wherein the T-line intensity was recorded. The LFA T-line intensity was then correlated with the qRT-PCR Ct value of the positive swab samples. A digital semi-quantification of RT-LAMP-LFA was reported with a correlation coefficient of R2 = 0.702. The overall RT-LAMP-LFA assay time was recorded to be 35 min with a LoD of three RNA copies/µL (Ct-33). With these three advancements, the nucleic acid testing-point of care technique (NAT-POCT) is exemplified as a versatile biosensor platform with great potential and applicability for the detection of pathogens without the need for sample storage, transportation, or pre-processing.
Urbanization promotes specific bacteria in freshwater microbiomes including potential pathogens
(2022)
Freshwater ecosystems are characterized by complex and highly dynamic microbial communities that are strongly structured by their local environment and biota. Accelerating urbanization and growing city populations detrimentally alter freshwater environments. To determine differences in freshwater microbial communities associated with urban-ization, full-length 16S rRNA gene PacBio sequencing was performed in a case study from surface waters and sedi-ments from a wastewater treatment plant, urban and rural lakes in the Berlin-Brandenburg region, Northeast Germany. Water samples exhibited highly habitat specific bacterial communities with multiple genera showing clear urban signatures. We identified potentially harmful bacterial groups associated with environmental parameters specific to urban habitats such as Alistipes, Escherichia/Shigella, Rickettsia and Streptococcus. We demonstrate that urban-ization alters natural microbial communities in lakes and, via simultaneous warming and eutrophication and creates favourable conditions that promote specific bacterial genera including potential pathogens. Our findings are evidence to suggest an increased potential for long-term health risk in urbanized waterbodies, at a time of rapidly expanding global urbanization. The results highlight the urgency for undertaking mitigation measures such as targeted lake restoration projects and sustainable water management efforts.
The physiological dependence of animals on dietary intake of vitamins, amino acids, and fatty acids is ubiquitous. Sharp differences in the availability of these vital dietary biomolecules among different resources mean that consumers must adopt a range of strategies to meet their physiological needs. We review the emerging work on omega-3 long-chain polyunsaturated fatty acids, focusing predominantly on predator-prey interactions, to illustrate that trade-off between capacities to consume resources rich in vital biomolecules and internal synthesis capacity drives differences in phenotype and fitness of consumers. This can then feedback to impact ecosystem functioning. We outline how focus on vital dietary biomolecules in eco-eco-devo dynamics can improve our understanding of anthropogenic changes across multiple levels of biological organization.
The study addresses the question, if observed changes in terms of Arctic-midlatitude linkages during winter are driven by Arctic Sea ice decline alone or if the increase of global sea surface temperatures plays an additional role. We compare atmosphere-only model experiments with ECHAM6 to ERA-Interim Reanalysis data. The model sensitivity experiment is implemented as a set of four combinations of sea ice and sea surface temperature boundary conditions. Atmospheric circulation regimes are determined and evaluated in terms of their cyclone and blocking characteristics and changes in frequency during winter. As a prerequisite, ECHAM6 reproduces general features of circulation regimes very well. Tropospheric changes induced by the change of boundary conditions are revealed and further impacts on the large-scale circulation up into the stratosphere are investigated. In early winter, the observed increase of atmospheric blocking in the region between Scandinavia and the Urals are primarily related to the changes in sea surface temperatures. During late winter, we f nd a weakened polar stratospheric vortex in the reanalysis that further impacts the troposphere. In the model sensitivity study a climatologically weakened polar vortex occurs only if sea ice is reduced and sea surface temperatures are increased together. This response is delayed compared to the reanalysis. The tropospheric response during late winter is inconclusive in the model, which is potentially related to the weak and delayed response in the stratosphere. The model experiments do not reproduce the connection between early and late winter as interpreted from the reanalysis. Potentially explaining this mismatch, we identify a discrepancy of ECHAM6 to reproduce the weakening of the stratospheric polar vortex through blocking induced upward propagation of planetary waves.
This paper deals with the long-term behavior of positive operator semigroups on spaces of bounded functions and of signed measures, which have applications to parabolic equations with unbounded coefficients and to stochas-tic analysis. The main results are a Tauberian type theorem characterizing the convergence to equilibrium of strongly Feller semigroups and a generalization of a classical convergence theorem of Doob. None of these results requires any kind of time regularity of the semigroup.
In real-world scene perception, human observers generate sequences of fixations to move image patches into the high-acuity center of the visual field. Models of visual attention developed over the last 25 years aim to predict two-dimensional probabilities of gaze positions for a given image via saliency maps. Recently, progress has been made on models for the generation of scan paths under the constraints of saliency as well as attentional and oculomotor restrictions. Experimental research demonstrated that task constraints can have a strong impact on viewing behavior. Here, we propose a scan-path model for both fixation positions and fixation durations, which include influences of task instructions and interindividual differences. Based on an eye-movement experiment with four different task conditions, we estimated model parameters for each individual observer and task condition using a fully Bayesian dynamical modeling framework using a joint spatial-temporal likelihood approach with sequential estimation. Resulting parameter values demonstrate that model properties such as the attentional span are adjusted to task requirements. Posterior predictive checks indicate that our dynamical model can reproduce task differences in scan-path statistics across individual observers.