Engineering microorganisms into biological factories that convert renewable feedstocks into valuable materials is a major goal of synthetic biology; however, for many nonmodel organisms, we do not ...yet have the genetic tools, such as suites of strong promoters, necessary to effectively engineer them. In this work, we developed a computational framework that can leverage standard RNA-seq data sets to identify sets of constitutive, strongly expressed genes and predict strong promoter signals within their upstream regions. The framework was applied to a diverse collection of RNA-seq data measured for the methanotroph Methylotuvimicrobium buryatense 5GB1 and identified 25 genes that were constitutively, strongly expressed across 12 experimental conditions. For each gene, the framework predicted short (27–30 nucleotide) sequences as candidate promoters and derived −35 and −10 consensus promoter motifs (TTGACA and TATAAT, respectively) for strong expression in M. buryatense. This consensus closely matches the canonical E. coli sigma-70 motif and was found to be enriched in promoter regions of the genome. A subset of promoter predictions was experimentally validated in a XylE reporter assay, including the consensus promoter, which showed high expression. The pmoC, pqqA, and ssrA promoter predictions were additionally screened in an experiment that scrambled the −35 and −10 signal sequences, confirming that transcription initiation was disrupted when these specific regions of the predicted sequence were altered. These results indicate that the computational framework can make biologically meaningful promoter predictions and identify key pieces of regulatory systems that can serve as foundational tools for engineering diverse microorganisms for biomolecule production.
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IJS, KILJ, NUK, PNG, UL, UM
This study investigates the use of total column CH4 (XCH4) retrievals from the SCIAMACHY satellite instrument for quantifying large-scale emissions of methane. A unique data set from SCIAMACHY is ...available spanning almost a decade of measurements, covering a period when the global CH4 growth rate showed a marked transition from stable to increasing mixing ratios. The TM5 4DVAR inverse modelling system has been used to infer CH4 emissions from a combination of satellite and surface measurements for the period 2003–2010. In contrast to earlier inverse modelling studies, the SCIAMACHY retrievals have been corrected for systematic errors using the TCCON network of ground-based Fourier transform spectrometers. The aim is to further investigate the role of bias correction of satellite data in inversions. Methods for bias correction are discussed, and the sensitivity of the optimized emissions to alternative bias correction functions is quantified. It is found that the use of SCIAMACHY retrievals in TM5 4DVAR increases the estimated inter-annual variability of large-scale fluxes by 22% compared with the use of only surface observations. The difference in global methane emissions between 2-year periods before and after July 2006 is estimated at 27–35 Tg yr−1. The use of SCIAMACHY retrievals causes a shift in the emissions from the extra-tropics to the tropics of 50 ± 25 Tg yr−1. The large uncertainty in this value arises from the uncertainty in the bias correction functions. Using measurements from the HIPPO and BARCA aircraft campaigns, we show that systematic errors in the SCIAMACHY measurements are a main factor limiting the performance of the inversions. To further constrain tropical emissions of methane using current and future satellite missions, extended validation capabilities in the tropics are of critical importance.
The first measurement of transverse-spin-dependent azimuthal asymmetries in the pion-induced Drell-Yan (DY) process is reported. We use the CERN SPS 190 GeV/c π^{-} beam and a transversely polarized ...ammonia target. Three azimuthal asymmetries giving access to different transverse-momentum-dependent (TMD) parton distribution functions (PDFs) are extracted using dimuon events with invariant mass between 4.3 GeV/c^{2} and 8.5 GeV/c^{2}. Within the experimental uncertainties, the observed sign of the Sivers asymmetry is found to be consistent with the fundamental prediction of quantum chromodynamics (QCD) that the Sivers TMD PDFs extracted from DY have a sign opposite to the one extracted from semi-inclusive deep-inelastic scattering (SIDIS) data. We present two other asymmetries originating from the pion Boer-Mulders TMD PDFs convoluted with either the nucleon transversity or pretzelosity TMD PDFs. A recent COMPASS SIDIS measurement was obtained at a hard scale comparable to that of these DY results. This opens the way for possible tests of fundamental QCD universality predictions.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline–taxane–based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically ...in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses.
Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, β = 0.8) 379 events had to be observed in the bevacizumab arms.
With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1–3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups.
Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline–taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients.
NCT 00567554, www.clinicaltrials.gov.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report an improved measurement of the cosmic microwave background B-mode polarization power spectrum with the Polarbear experiment at 150 GHz. By adding new data collected during the second season ...of observations (2013-2014) to re-analyzed data from the first season (2012-2013), we have reduced twofold the band-power uncertainties. The band powers are reported over angular multipoles , where the dominant B-mode signal is expected to be due to the gravitational lensing of E-modes. We reject the null hypothesis of no B-mode polarization at a confidence of 3.1 including both statistical and systematic uncertainties. We test the consistency of the measured B-modes with the Λ Cold Dark Matter (ΛCDM) framework by fitting for a single lensing amplitude parameter AL relative to the Planck 2015 best-fit model prediction. We obtain 0.14(foreground) 0.04(multi), where is the fiducial ΛCDM value.
Context . The HD 15337 (TIC 120896927, TOI-402) system was observed by the Transiting Exoplanet Survey Satellite (TESS), revealing the presence of two short-period planets situated on opposite sides ...of the radius gap. This offers an excellent opportunity to study theories of formation and evolution, as well as to investigate internal composition and atmospheric evaporation. Aims . We aim to constrain the internal structure and composition of two short-period planets situated on opposite sides of the radius valley: HD 15337 b and c. We use new transit photometry and radial velocity data. Methods . We acquired 6 new transit visits with the CHaracterising ExOPlanet Satellite (CHEOPS) and 32 new radial velocity measurements from the High Accuracy Radial Velocity Planet Searcher (HARPS) to improve the accuracy of the mass and radius estimates for both planets. We re-analysed the light curves from TESS sectors 3 and 4 and analysed new data from sector 30, correcting for long-term stellar activity. Subsequently, we performed a joint fit of the TESS and CHEOPS light curves, along with all available RV data from HARPS and the Planet Finder Spectrograph (PFS). Our model fit the planetary signals, stellar activity signal, and instrumental decorrelation model for the CHEOPS data simultaneously. The stellar activity was modelled using a Gaussian-process regression on both the RV and activity indicators. Finally, we employed a Bayesian retrieval code to determine the internal composition and structure of the planets. Results . We derived updated and highly precise parameters for the HD 15337 system. Our improved precision on the planetary parameters makes HD 15337 b one of the most precisely characterised rocky exoplanets, with radius and mass measurements achieving a precision better than 2% and 7%, respectively. We were able to improve the precision of the radius measurement of HD 15337 c to 3%. Our results imply that the composition of HD 15337 b is predominantly rocky, while HD 15337 c exhibits a gas envelope with a mass of at least 0.01 M ⊕ . Conclusions . Our results lay the groundwork for future studies, which can further unravel the atmospheric evolution of these exoplanets and offer new insights into their composition and formation history as well as the causes behind the radius gap.
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FMFMET, NUK, UL, UM, UPUK
Permafrost and methane hydrates are large, climate-sensitive old carbon reservoirs that have the potential to emit large quantities of methane, a potent greenhouse gas, as the Earth continues to ...warm. We present ice core isotopic measurements of methane (Δ
C, δ
C, and δD) from the last deglaciation, which is a partial analog for modern warming. Our results show that methane emissions from old carbon reservoirs in response to deglacial warming were small (<19 teragrams of methane per year, 95% confidence interval) and argue against similar methane emissions in response to future warming. Our results also indicate that methane emissions from biomass burning in the pre-Industrial Holocene were 22 to 56 teragrams of methane per year (95% confidence interval), which is comparable to today.
An inverse error variance weighting of the anomalies of three terrestrial evaporation (ET) products from the WACMOS-ET project based on FLUXNET sites is presented. The three ET models were run daily ...and at a resolution of 25 km for 2002–2007, and based on common input data when possible. The local weights, derived based on the variance of the difference between the tower ET anomalies and the modelled ET anomalies, were made dynamic by estimating them using a 61-day running window centred on each day. These were then extrapolated from the tower locations to the global landscape by regressing them on the main model inputs and derived ET using a neural network. Over the stations, the weighted scheme usefully decreased the random error component, and the weighted ET correlated better with the tower data than a simple average. The global extrapolation produced weights displaying strong seasonal and geographical patterns, which translated into spatiotemporal differences between the ET weighted and simple average ET products. However, the uncertainty of the weights after the extrapolation remained large. Out-sample prediction tests showed that the tower data set, mostly located at temperate regions, had limitations with respect to the representation of different biome and climate conditions. Therefore, even if the local weighting was successful, the extrapolation to a global scale remains problematic, showing a limited added value over the simple average. Overall, this study suggests that merging tower observations and ET products at the timescales and spatial scales of this study is complicated by the tower spatial representativeness, the products' coarse spatial resolution, the nature of the error in both towers and gridded data sets, and how all these factors impact the weights extrapolation from the tower locations to the global landscape.
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