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Metabolite production by filamentous fungi hampered because of high viscosity generated during growth. Low viscosity fermentation by mold is one of the preferred ways of large scale enzymes production. Cellulolytic enzymes play a key role during the process of lignocellulosic biomass conversion. In this study, a mutant RC-23-1 was isolated through mutagenesis (diethyl sulfate followed by UV) of Trichoderma reesei RUT-C30. RCRC-23-1 not only gave higher cellulase production but also generated lower viscosity during enzyme production. Viscosity of mutant growth was more than three times lower than parent strain. RC-23-1 shows unique, yeast-like colony morphology on solid media and small pellet-like growth in liquid media. This mutant did not spread like mold on solid media. This mutant produces cellulases constitutively when grown in sugars. Using only glucose, the cellulase production was 4.1 FPU/ml. Among polysaccharides (avicel, xylan, and pectin), avicel gave maximum of 6.2 FPU/ml and pretreated biomass (rice straw, wheat straw and sugarcane bagasse) produced 5.1-5.8 FPU/ml. At 7 L scale reactor, fed-batch process was designed for cellulase production using different carbon and nitrogen sources. Maximum yield of cellulases was 182 FPU/g of lactose consumed was observed in fed-batch process. The produced enzyme used for hydrolysis of acid pretreated rice straw (20% solid loading) and maximum of 60% glucan conversion was observed. RC-23-1 mutant is good candidate for large scale cellulase production and could be a model strain to study mold to yeast-like transformation.

We present a study based on the high-resolution spectroscopy and K2 space photometry of five chemically peculiar stars in the region of the open cluster M44. The analysis of the high-precision photometric K2 data reveals that the light variations in HD 73045 and HD 76310 are rotational in nature and caused by spots or cloud-like co-rotating structures, which are non-stationary and short-lived. The time-resolved radial velocity measurements, in combination with the K2 photometry, confirm that HD 73045 does not show any periodic variability on timescales shorter than 1.3 d, contrary to previous reports in the literature. In addition to these new rotational variables, we discovered a new heartbeat system, HD 73619, where no pulsational signatures are seen. The spectroscopic and spectropolarimetric analyses indicate that HD 73619 belongs to the peculiar Am class, with either a weak or no magnetic field considering the 200 G detection limit of our study. The Least-Squares Deconvolution (LSD) profiles for HD 76310 indicate a complex structure in its spectra suggesting that this star is either part of a binary system or surrounded by a cloud shell. When placed in the Hertzsprung-Russell diagram, all studied stars are evolved from main-sequence and situated in the $\delta$ Scuti instability strip. The present work is relevant for further detailed studies of CP stars, such as inhomogeneities (including spots) in the absence of magnetic fields and the origin of the pulsational variability in heartbeat systems., Comment: Accepted for publication in MNRAS

Global warming is one of the most alarming phenomena facing our planet today. There is a consensus among scientists that human-induced greenhouse gases (GHGs) should be regulated to slow down the heating of the Earth’s oceans and atmosphere. Energy consumption and CO2 emissions are continuously increasing in different countries, especially developing ones such as India, whose emerging economy and rapid economic development has caught the attention of the world. CO2 emission trading is executed by the various developed countries to alleviate the affect of GHG emissions. In this work, an optimal bidding strategy for a supplier has been developed, considering rival’s bidding behavior, in an hourly day-ahead pool market. Bidding problem has been formulated as a bi-level multi objective optimization problem (BLMOOP), where in the first level generator submit bid strategically to the ISO and in the next level a particle swarm optimization (PSO) approach has been employed for the maximization of social welfare with risk management. It is assumed that each generator should submit bid in sealed auction based on pay-as-bid MCP (market clearing price) mechanism with knowing the rival’s bidding behavior. The practicability of proposed optimization method is examined by an IEEE-30 bus system which consists of six suppliers.

The strength of respiratory muscles can be evaluated from static measurement (PImax and PEmax) or inferred from dynamic measurement such as maximal voluntary ventilation. Maximal inspiratory pressure and Maximal expiratory pressure are simple, convenient and non-invasive measurement of respiratory muscle strength. Respiratory muscle strength decreases in COPD patients due to multiple factors. The primary aim of this study is to obtain mean PImax and PEmax values in Indian COPD patients and its co-rrelation with anthropomatric, physiological, spirometric parameters and arterial blood gas tension.

We present a new X-ray spectroscopic study of $22$ luminous ($2\times10^{45}\lesssim L_{\rm bol}\rm /erg\,s^{-1} \lesssim 2\times10^{46}$) active galactic nuclei (AGNs) at intermediate-redshift ($0.1 \lesssim z \lesssim 0.4$), as part of the SUpermassive Black hole Winds in the x-rAYS (SUBWAYS) sample, mostly composed of quasars (QSOs) and type\,1 AGN. Here, 17 targets were observed with \textit{XMM-Newton} between 2019--2020 and the remaining 5 are from previous observations. The aim of this large campaign ($1.45\,\rm Ms$ duration) is to characterise the various manifestations of winds in the X-rays driven from supermassive black holes in AGN. In this paper we focus on the search and characterization of ultra-fast outflows (UFOs), which are typically detected through blueshifted absorption troughs in the Fe\,K band ($E>7\,\rm keV$). By following Monte Carlo procedures, we confirm the detection of absorption lines corresponding to highly ionised iron (e.g., Fe\,\textsc{xxv}\,H$\alpha$, Fe\,\textsc{xxvi}\,Ly$\alpha$) in 7/22 sources at the $\gtrsim95\%$ confidence level (for each individual line). The global combined probability of such absorption features in the sample is $>99.9\%$. The SUBWAYS campaign extends at higher luminosity and redshifts than previous local studies on Seyferts, obtained using \xmm and \suzaku observations. We find a UFO detection fraction of $\sim30\%$ on the total sample that is in agreement with the previous findings. This work independently provides further support for the existence of highly-ionised matter propagating at mildly relativistic speed ($\gtrsim0.1c$) in a considerable fraction of AGN over a broad range of luminosities, which is expected to play a key role in the self-regulated AGN feeding-feedback cycle, as also supported by hydrodynamical multiphase simulations., Comment: 30 pages, 10 figures, accepted for publication in A&A

We present a UV spectroscopic study of ionized outflows in 21 active galactic nuclei (AGN), observed with the HST. The targets of the SUBWAYS sample were selected with the aim to probe the parameter space of the underexplored AGN between the local Seyfert galaxies and the luminous quasars at high redshifts. Our targets, spanning redshifts of 0.1-0.4 and bolometric luminosities (L_bol) of 10^45-10^46 erg/s, have been observed with a large multi-wavelength campaign. Here, we model the UV spectra and look for different types of AGN outflows. We find that 60% of our targets show a presence of outflowing H I absorption, while 40% exhibit ionized outflows seen as absorption by either C IV, N V, or O VI. This is comparable to the occurrence of ionized outflows seen in the local Seyfert galaxies. All UV absorption lines in the sample are relatively narrow, with outflow velocities reaching up to -3300 km/s. We did not detect any UV counterparts to the X-ray ultra-fast outflows (UFOs), most likely due to their being too highly ionized. However, all SUBWAYS targets with an X-ray UFO demonstrate the presence of UV outflows at lower velocities. We find significant correlations between the column density (N) of the UV ions and L_bol of the AGN, with N of H I decreasing with L_bol, while N of O VI is increasing with L_bol. This is likely to be a photoionization effect, where toward higher AGN luminosities, the wind becomes more ionized, resulting in less absorption by neutral or low-ionization ions and more absorption by high-ionization ions. In addition, we find that N of the UV ions decreases as their outflow velocity increases. This may be explained by a mechanical power that is evacuating the UV-absorbing medium. Our observed relations are consistent with multiphase AGN feeding and feedback simulations indicating that a combination of both radiative and mechanical processes are in play., Comment: Accepted for publication in Astronomy & Astrophysics (A&A), 22 pages, 12 figures

Muscle diseases share common pathological features suggesting common underlying mechanisms. We hypothesized there is a common set of genes dysregulated across muscle diseases compared to healthy muscle and that these genes correlate with severity of muscle disease. We performed meta-analysis of transcriptional profiles of muscle biopsies from human muscle diseases and healthy controls. Studies obtained from public microarray repositories fulfilling quality criteria were divided into six categories: (i) immobility, (ii) inflammatory myopathies, (iii) intensive care unit (ICU) acquired weakness (ICUAW), (iv) congenital muscle diseases, (v) chronic systemic diseases, (vi) motor neuron disease. Patient cohorts were separated in discovery and validation cohorts retaining roughly equal proportions of samples for the disease categories. To remove bias towards a specific muscle disease category we repeated the meta-analysis five times by removing data sets corresponding to one muscle disease class at a time in a “leave-one-disease-out” analysis. We used 636 muscle tissue samples from 30 independent cohorts to identify a 52 gene signature (36 up-regulated and 16 down-regulated genes). We validated the discriminatory power of this signature in 657 muscle biopsies from 12 additional patient cohorts encompassing five categories of muscle diseases with an area under the receiver operating characteristic curve of 0.91, 83% sensitivity, and 85.3% specificity. The expression score of the gene signature inversely correlated with quadriceps muscle mass (r = −0.50, p-value = 0.011) in ICUAW and shoulder abduction strength (r = −0.77, p-value = 0.014) in amyotrophic lateral sclerosis (ALS). The signature also positively correlated with histologic assessment of muscle atrophy in ALS (r = 0.88, p-value = 1.62 × 10–3) and fibrosis in muscular dystrophy (Jonckheere trend test p-value = 4.45 × 10–9). Our results identify a conserved transcriptional signature associated with clinical and histologic muscle disease severity. Several genes in this conserved signature have not been previously associated with muscle disease severity.

Oscillating red-giant stars in binary systems are an ideal testbed for investigating the structure and evolution of stars in the advanced phases of evolution. With 83 known red giants in binary systems, of which only ~40 have determined global seismic parameters and orbital parameters, the sample is small compared to the numerous known oscillating stars. The detection of red-giant binary systems is typically obtained from the signature of stellar binarity in space photometry. The time base of such data biases the detection towards systems with shorter periods and orbits of insufficient size to allow a red giant to fully extend as it evolves up the red-giant branch. Consequently, the sample shows an excess of H-shell burning giants while containing very few stars in the He-core burning phase. From the ninth catalogue of spectroscopic binary orbits (SB9), we identified candidate systems hosting a red-giant primary component. Searching space photometry from the NASA missions Kepler, K2, and TESS (Transiting Exoplanet Survey Satellite) as well as the BRITE (BRIght Target Explorer) constellation mission, we find 99 systems, which were previously unknown to host an oscillating giant component. The revised search strategy allowed us to extend the range of orbital periods of systems hosting oscillating giants up to 26000days. Such wide orbits allow a rich population of He-core burning primaries, which are required for a complete view of stellar evolution from binary studies. Tripling the size of the sample of known oscillating red-giant stars in binary systems is an important step towards an ensemble approach for seismology and tidal studies. While for non-eclipsing binaries the inclination is unknown, such a seismically well-characterized sample will be a treasure trove in combination with Gaia astrometric orbits for binary~systems., A&A (accepted for publication)

Anti-solar differential rotation profiles have been found for decades in numerical simulations of convective envelopes of solar-type stars. These profiles are characterized by a slow equator and fast poles (i.e., reversed with respect to the Sun) and have been found in simulations for high Rossby numbers (slow rotators). Rotation profiles like this have been reported observationally in evolved stars, but have never been unambiguously observed for cool solar-type stars on the main sequence. In this context, detecting this regime in main-sequence solar-type stars would improve our understanding of their magnetorotational evolution. The goal of this study is to identify the most promising cool main-sequence stellar candidates for anti-solar differential rotation in the \textit{Kepler} sample. First, we introduce a new theoretical formula to estimate fluid Rossby numbers, $Ro_{\rm f}$, of main-sequence solar-type stars, from observational quantities, and taking the influences of the internal structure and metallicity into account. We obtain a list of the most promising stars that are likely to show anti-solar differential rotation. We identify two samples: one at solar metallicity, including 14 targets, and another for other metallicities, including 8 targets. We find that the targets with the highest $Ro_{\rm f}$ are likely to be early-G or late-F stars at about log$_{10}g=4.37$~dex. We conclude that cool main-sequence stellar candidates for anti-solar differential rotation exist in the \textit{Kepler} sample. The most promising candidate is KIC~10907436, and two other particularly interesting candidates are the solar analog KIC~7189915 and the seismic target KIC~12117868. Future characterization of these 22 stars is expected to help us understand how dynamics can impact magnetic and rotational evolution of old solar-type stars at high Rossby number., 12 pages + Appendix ; 9 Figures ; 3 Tables ; Accepted for publication in A&A

The Kepler and, to a lesser extent, the CoRoT missions opened the era of large-scale photometric stellar surveys with space instruments. Corotating dark spots and bright faculae on the stellar surface lead to brightness variations and therefore those long-term photometric surveys provide ideal datasets to measure stellar surface rotation periods and build stellar rotation catalogs. Such catalogs can then be used to constrain gyrochronology models or to study the interplay between rotation and magnetic activity. Taking the best possible advantage of those large-scale surveys, the main challenge that we face today is finding efficient methods to analyse the large amount of data. It has been shown that a combination of methods (auto-correlation function, time-frequency analysis) applied on light curves with different high-pass filtering provide reliable rotation estimates. However, the results yielded by those methods require a significant amount of visual inspection. In the work presented here, random forest learning abilities are exploited to automate the extraction of rotation periods and magnetic activity index in Kepler light curves and to reduce the number of required visual inspections in the dataset. We train three different classifiers: one to detect if rotation modulations are present in the light curve, one to flag classical pulsators or close binary candidates that can bias our rotation-period determination, and finally one classifier to provide the final rotation period. We test our machine learning pipeline, ROOSTER (Breton et al. 2021), on the Kepler K and M dwarf sample using the reference catalog of Santos et al (2019). We show that we are able to detect rotation modulations with an accuracy of 94.2% and to retrieve final rotation periods with an accuracy of 95.3%. This value is raised to 99.5% after visually inspecting 25.2% of the stars. Over the two main analysis steps, the pipeline yields a global accuracy of 92.1% before visual checks, 96.9% after. The method is then applied to analyse the F and G Kepler sample (Santos et al. 2021). This allowed us to derive the largest catalog of surface rotation periods for the Kepler targets with more than 55,000 entries. The work we performed used only time series from the Kepler mission, but the methodology presented here could be adapted to extract surface rotation periods for stars observed by other missions, like K2, TESS, or PLATO.

During the survey phase of the Kepler mission, several thousands of stars were observed in short cadence, allowing the detection of solar-like oscillations in more than 500 main-sequence and sub-giant stars. Later, the Kepler Science Office discovered an issue in the calibration that affected half of the short-cadence data, leading to a new data release (DR25) with improved corrections. We re-analyze the one-month time series of the Kepler survey phase to search for new solar-like oscillations. We study the seismic parameters of 99 stars (46 targets with new reported solar-like oscillations) increasing by around 8% the known sample of solar-like stars with asteroseismic analysis of the short-cadence data from Kepler. We compute the masses and radii using seismic scaling relations and find that this new sample populates the massive stars (above 1.2Ms and up to 2Ms) and subgiant phase. We determine the granulation parameters and amplitude of the modes, which agree with previously derived scaling relations. The stars studied here are slightly fainter than the previously known sample of main-sequence and subgiants with asteroseismic detections. We also study the surface rotation and magnetic activity levels of those stars. Our sample of has similar levels of activity compared to the previously known sample and in the same range as the Sun between the minimum and maximum of its activity cycle. We find that for 7 stars, a possible blend could be the reason for the previous non detection. We compare the radii obtained from the scaling relations with the Gaia ones and find that the Gaia radii are overestimated by 4.4% on average compared to the seismic radii and a decreasing trend with evolutionary stage. We re-analyze the DR25 of the main-sequence and sub-giant stars with solar-like oscillations previously detected and provide their global seismic parameters for a total of 526 stars., 18 pages, 21 figures. Accepted for publication in A&A

Background Globally, the prevalence of chronic kidney disease (CKD) is higher in women than in men; however, women have been historically under-represented in nephrology clinical trials. Metabolic acidosis increases risk of progressive loss of kidney function, causes bone demineralization and muscle protein catabolism, and may be more consequential in women given their lower bone and muscle mass. Veverimer, an investigational, non-absorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as treatment for metabolic acidosis. Methods This was a Phase 3, multicenter, randomised, blinded, placebo-controlled trial in 196 patients with CKD (eGFR: 20–40 mL/min/1.73 m2) and metabolic acidosis who were treated for up to 1 year with veverimer or placebo. We present the findings from a pre-specified subgroup analysis evaluating the effects of veverimer on metabolic acidosis and physical function among women (N = 77) enrolled in this trial. Results At week 52, women treated with veverimer had a greater increase in mean (± standard error) serum bicarbonate than the placebo group (5.4 [0.5] vs. 2.2 [0.6] mmol/L; P P P = 0.0002). Conclusions Veverimer was effective in treating metabolic acidosis in women with CKD, and significantly improved how they felt and functioned. Trial registration ClinicalTrials.gov Identifier: NCT03390842. Registered on January 4, 2018.

Background Efforts to develop efficient lignocellulose-degrading enzymatic preparations have led to the relatively recent discovery of a new class of novel cellulase boosters, termed lytic polysaccharide monoxygenases (LPMOs). These enzymes are copper-dependent metalloenzymes that initiate the biomass deconstruction process and subsequently work together with cellulases, hemicellulases, and other accessory enzymes to enhance their hydrolytic action. Given their wide distribution and diversity, screening and isolation of potent LPMOs from natural fungal diversity may provide an important avenue for increasing the efficiency of cellulases and thereby decreasing cellulosic ethanol production costs. However, methods for quick screening and detection are still not widely available. In this article, a simple and sensitive method is described by combining nonhydrolytic activity enhancement followed by LC–MS-based quantitation of LPMOs. Results In this study, a screening approach has been developed for the detection of nonhydrolytic cellulase-enhancing enzymes in crude fungal supernatants. With the application of a saturating benchmark cocktail of Celluclast 1.5L, fungal isolates were selected which had the capability of hydrolyzing pretreated rice straw by their synergistic enzyme fractions. Subsequently, these fungal extracts along with an LPMO-enriched commercial enzyme were investigated for their ability to produce Type I LPMO activity. An LC–MS-based methodology was applied to quantitate gluconic acid in enzymatic hydrolysates as an indirect measurement of Type I LPMO activity. Conclusion The present study describes an LC–MS-based separation method to detect and quantitate LPMO activity in a commercial enzyme. This method was also applied to screen fungal extracts. The developed screening strategy has enabled detection of LPMO activity in two industrially important Penicillium strains. Electronic supplementary material The online version of this article (10.1186/s13068-019-1526-4) contains supplementary material, which is available to authorized users.

Study Objective To describe the diagnostic and surgical challenges in the management of second trimester placenta percreta. Design Case Review, review of surgical technique and video documentation. Setting Laparoscopic hysterectomy at a tertiary care centre. Patients or Participants The patient was a 39-year-old female, G7P3 at 17+2 weeks gestation who presented with acute abdominal pain to a community hospital. Imaging such as CT and ultrasound were inconclusive during initial work up for appendicitis. She experienced a drop in her hemoglobin, received a unit of pRBC and was taken to the operating room for exploratory laparoscopy. In the OR, acute hemoperitoneum was visualized with placenta like tissue invading through the anterior lower uterine segment. She was then transferred to our centre for urgent work up which confirmed the diagnosis of second trimester placenta percreta with active bleeding. Interventions Laparoscopy. Measurements and Main Results Once the patient was transferred to our centre an urgent MRI was done and this confirmed placenta percreta with invasion at the level of bladder and lateral parametrial involvement. An extensive discussion was had with our multidisciplinary team and given that were was ongoing bleeding from the invading placental tissue, pregnancy continuation was not possible. Second trimester placenta percreta is a rare entity with very few case reports in the literature. Our video demonstrates the challenges of a minimally invasive approach, which has not been previously described. We describe five main challenges and a step wise approach to mitigating these challenges. In addition, we combine the use of a dilatation and evacuation technique to allow for a complete minimally invasive approach. Conclusion Placenta accrete spectrum disorders pose significant challenges in diagnosis and management. A minimally invasive approach has not been described in the literature. We demonstrate that a minimally invasive approach to hysterectomy in management of midtrimester placenta percreta is a feasible option.

Micro-algae have significant potential for the production of biofuel. It has been previously shown that existing processes of producing micro-algal biofuels are not yet economically viable at commercial scale. Fundamentally, this process will require the implementation of inexpensive harvesting methods and productive algal strains that are tolerant to harsh conditions. The use of freshwater in the large-scale cultivation of microalgae is currently unsustainable; hence, the studies which target the use of seawater medium can reduce the demand of freshwater. Chlorella pyrenoidosa has been extensively studied in freshwater. However, information on the cultivation of C. pyrenoidosa for growth productivity in recycled seawater medium, generated after harvesting through autoflocculation is scarce. In this context, the present study investigates the effect of nutrients sufficient seawater medium following reuse of nutrients exhausted seawater medium on the biochemical composition, biomass and lipid productivities of an in-house developed, thermotolerant strain of C. pyrenoidosa under high temperature (45 °C), outdoor culture conditions. The strain C. pyrenoidosa M18 was found to thrive in seawater medium resulting in increased biomass and lipid productivity. Lipid productivity in seawater medium exceeded 51 mg/Ld−1 which was nearly 2-fold greater than freshwater. Furthermore, the strain was able to grow well and autoflocculate at recycled seawater medium giving biomass and lipid productivities, respectively of 338 mgL−1d−1 and 66 mgL−1d−1. The dry cell weight comprised of 28–32% carbohydrate content when cultivated in recycled seawater medium. Additionally, exposure to high salinity led to an enhanced chlorophyll content as well as increased Fv/Fm ratio. The auto-flocculating property of thermotolerant C. pyrenoidosa M18 strain, in addition to the high biomass and lipid productivities in nutrient exhausted recycled seawater medium, make this microalga an excellent candidate for large-scale outdoor cultivation for biodiesel production.

Thymocyte development requires a complex orchestration of multiple transcription factors. Ablating either TCF-1 or HEB in CD4+CD8+ thymocytes elicits similar developmental outcomes including increased proliferation, decreased survival, and fewer late Tcra rearrangements. Here, we provide a mechanistic explanation for these similarities by showing that TCF-1 and HEB share ~7,000 DNA-binding sites genome wide and promote chromatin accessibility. The binding of both TCF-1 and HEB was required at these shared sites for epigenetic and transcriptional gene regulation. Binding of TCF-1 and HEB to their conserved motifs in the enhancer regions of genes associated with T cell differentiation promoted their expression. Binding to sites lacking conserved motifs in the promoter regions of cell-cycle-associated genes limited proliferation. TCF-1 displaced nucleosomes, allowing for chromatin accessibility. Importantly, TCF-1 inhibited Notch signaling and consequently protected HEB from Notch-mediated proteasomal degradation. Thus, TCF-1 shifts nucleosomes and safeguards HEB, thereby enabling their cooperation in establishing the epigenetic and transcription profiles of CD4+CD8+ thymocytes. Thymocyte development requires a complex orchestration of multiple transcription factors. Gournari and colleagues find that Tcf-1 and HEB cooperate to establish the epigenetic and transcription profiles of CD4+CD8+ thymocytes

We report new photometric and spectroscopic observations of the K2-99 planetary system. Asteroseismic analysis of the short-cadence light curve from K2’s Campaign 17 allows us to refine the stellar properties. We find K2-99 to be significantly smaller than previously thought, with R⋆ = 2.55 ± 0.02 R⊙. The new light curve also contains four transits of K2-99 b, which we use to improve our knowledge of the planetary properties. We find the planet to be a non-inflated warm Jupiter, with Rb = 1.06 ± 0.01 RJup⁠. 60 new radial velocity measurements from HARPS, HARPS-N, and HIRES enable the determination of the orbital parameters of K2-99 c, which were previously poorly constrained. We find that this outer planet has a minimum mass Mcsin ic = 8.4 ± 0.2 MJup⁠, and an eccentric orbit (ec = 0.210 ± 0.009) with a period of 522.2 ± 1.4 d. Upcoming TESS observations in 2022 have a good chance of detecting the transit of this planet, if the mutual inclination between the two planetary orbits is small. © 2022 The Author(s)., This work is done under the framework of the KESPRINT collaboration (http://www.kesprint.science). KESPRINT is an international consortium devoted to the characterization and research of exoplanets discovered with space-based missions. Based on observations made with ESO Telescopes at the La Silla Observatory (Chile) under programmes 097.C-0948(A), 099.C-0491(B), 099.C-0491(A), 0100.C-0808(A), 0101.C-0829(A), 60.A-9700(G), and 1102.C-0923(A), and the TNG telescope at Roque de Los Muchachos Observatory (Spain) under programmes A33TAC_15, A34TAC_10, OPT17A_64, A35TAC_26, OPT17B_59, CAT17B_99, CAT18A_130, OPT18A_44, A37TAC_37, OPT18B_52, and A38TAC_26. This paper includes data collected by the Kepler mission. Funding for the Kepler mission is provided by the NASA Science Mission directorate. Some of the data presented in this paper were obtained from the Mikulski Archive for Space Telescopes (MAST). STScI is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555. Support for MAST for non-HST data is provided by the NASA Office of Space Science via grant NNX09AF08G and by other grants and contracts. This research has made use of the Exoplanet Follow-up Observation Program website, and the NASA Exoplanet Archive, which are operated by the California Institute of Technology, under contract with the National Aeronautics and Space Administration under the Exoplanet Exploration Program. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2013-2016) under grant agreement No. 312430 (OPTICON). This research has made use of NASA’s Astrophysics Data System, the SIMBAD data base, operated at CDS, Strasbourg, France, and the Exoplanets Encyclopaedia at exoplanet.eu. We also used ASTROPY, a community-developed core PYTHON package for Astronomy (Astropy Collaboration 2013; Price-Whelan et al. 2018). This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium). Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. KWFL, SC, and APH were supported by Deutsche Forschungsgemeinschaft grants HA3279/12-1 and RA714/14-1 within the DFG Schwerpunkt SPP 1992, Exploring the Diversity of Extrasolar Planets. SC is also supported by Deutsche Forschungsgemeinschaft Research Unit 2440: ‘Matter Under Planetary Interior Conditions: High Pressure Planetary and Plasma Physics’. HJD acknowledges support from the Spanish Research Agency of the Ministry of Science and Innovation (AEI-MICINN) under grant PID2019-107061GB-C66, DOI: 10.13039/501100011033. JK gratefully acknowledge the support of the Swedish National Space Agency (SNSA; DNR 2020-00104). SM acknowledges support by the Spanish Ministry of Science and Innovation with the Ramon y Cajal fellowship number RYC-2015-17697 and the grant number PID2019-107187GB-I00. SNB and RAG acknowledge the support of the PLATO CNES grant. LMS and DG gratefully acknowledge financial support from the CRT foundation under Grant No. 2018.2323 ‘Gaseous or rocky? Unveiling the nature of small worlds’. We thank Erik Petigura for his contribution to the collection and analysis of the Keck/HIRES data. Finally, we thank the referee for their careful reading of the manuscript and constructive suggestions, which resulted in improvements to this paper., With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709.

The molecular and functional diversity of regulatory T-cells (Tregs) in health and in disease remains unclear. We previously described in colorectal cancer (CRC) patients a subpopulation of RORγt+ Tregs with elevated expression of β-catenin and pro-inflammatory properties. Here we observed progressive expansion of RORγt+ Tregs in inflammatory bowel disease (IBD) patients during inflammation and early dysplasia. Activating Wnt/β-catenin signaling in human and murine Tregs was sufficient to recapitulate the disease-associated increase in frequencies of RORγt+ Tregs expressing IL-17, IFN-γ, and TNFa. We found that binding of the β-catenin interacting partner, TCF-1, to DNA overlapped with Foxp3 binding at enhancer sites of pro-inflammatory pathway genes. Sustained Wnt/β-catenin activation induced newly accessible chromatin sites in these genes and upregulated their expression. These findings indicate that TCF-1 and Foxp3 together limit the expression of pro-inflammatory genes in Tregs. Activation of ꞵ-catenin signaling interferes with this function and promotes the disease-associated RORγt+ Treg phenotype.

Economic production of lignocellulose degrading enzymes for biofuel industries is of considerable interest to the biotechnology community. While these enzymes are widely distributed in fungi, their industrial production from other sources, particularly by thermophilic anaerobic bacteria (growth Topt ≥ 60 °C), is an emerging field. Thermophilic anaerobic bacteria produce a large number of lignocellulolytic enzymes having unique structural features and employ different schemes for biomass degradation, which can be classified into four systems namely; ‘free enzyme system’, ‘cell anchored enzymes’, ‘complex cellulosome system’, and ‘multifunctional multimodular enzyme system’. Such enzymes exhibit high specific activity and have a natural ability to withstand harsh bioprocessing conditions. However, achieving a higher production of these thermostable enzymes at current bioprocessing targets is challenging. In this review, the research opportunities for these distinct enzyme systems in the biofuel industry and the associated technological challenges are discussed. The current status of research findings is highlighted along with a detailed description of the categorization of the different enzyme production schemes. It is anticipated that high temperature-based bioprocessing will become an integral part of sustainable bioenergy production in the near future.

To identify Janus kinase (JAK) inhibitors that selectively target gastrointestinal tissues with limited systemic exposures, a class of imidazopyrrolopyridines with a range of physical properties was prepared and evaluated. We identified compounds with low intrinsic permeability and determined a correlation between permeability and physicochemical properties, clogP and tPSA, for a subset of compounds. This low intrinsic permeability translated into compounds displaying high colonic exposure and low systemic exposure after oral dosing at 25 mg/kg in mouse. In a mouse PK/PD model, oral dosing of lead compound 2 demonstrated dose-dependent inhibition of pSTAT phosphorylation in colonic explants post-oral dose but low systemic exposure and no measurable systemic pharmacodynamic activity. We thus demonstrate the utility of JAK inhibitors with low intrinsic permeability as a feasible approach to develop gut-restricted, pharmacologically active molecules with a potential advantage over systemically available compounds that are limited by systemic on-target adverse events.

The primary aim of the research reported in this paper was to understand the effect of change of gusty simple shear inflow’s gradient on the force and moment patterns of a flapping wing in the 3D reference frame. A wing undergoing one degree of freedom asymmetric flapping and rectangular planform shape was considered. The gradient of the gusty simple shear inflow profile, Vgrad, was varied from –10 to +10 in steps of 5 and corresponding vertical and horizontal forces and moment about the flapping axis were computed. Time series of these forces and moment were used to plot the global recurrence plots and were compared. Quantitative analysis of the findings was carried out by the windowed recurrence quantification analysis of the force and moment patterns. Eight recurrence parameters, viz. recurrence rate, determinism, laminarity, trapping time, ratio, entropy, maximum line and trend were calculated and compared. Numerical investigations revealed that negative gusty shear gradient induced a considerable increase in vertical force and moment and marginally decreased the horizontal forces. Positive gusty shear gradient induced a marginal increase in horizontal forces but caused a substantial decrement in vertical force and moment.

The GOLF instrument on board SoHO has been in operation for almost 25 years but aging of the instrument has now strongly affected its performance, especially in the low-frequency p-mode region. At the end of the SoHO mission, the ground-based network BiSON will remain the only facility able to perform Sun-integrated helioseismic observations. Therefore, we want to assess the helioseismic performances of an \'echelle spectrograph like SONG. Indeed, the high precision of such an instrument and the quality of the data acquired for asteroseismic purpose calls for an evaluation of the instrument ability to perform global radial-velocity measurements of the solar disk. Data acquired during the Solar-SONG 2018 observation campaign at the Teide Observatory are used to study mid- and low-frequency p modes. A Solar-SONG time series of 30-day duration is reduced with a combination of the traditional IDL iSONG pipeline and a new Python pipeline described in this paper. A mode fitting method built around a Bayesian approach is then performed on the Solar-SONG and contemporaneous GOLF, BiSON, and HMI data. For this contemporaneous time series, Solar-SONG is able to characterise p modes at a lower frequency than BiSON and GOLF (1750{\mu}Hz against 1946 and 2157 {\mu}Hz respectively), while for HMI it is possible to characterise a mode at 1686 {\mu}Hz. The decrease of GOLF sensitivity is then evaluated through the evolution of its low-frequency p-mode characterisation abilities over the years. [abridged], Comment: 24 pages, 17 figures. Accepted in A&A

Dilute acid pretreatment of biomass generates enormous amount of hydrolysate (rich in inhibitors and pentose sugars), that remains unutilized for bioethanol production due to inadequacy of efficient C5-fermenting organisms. In this study, a predominantly pentose fermenting extremely thermophilic bacterium strain DBT-IOC-X2, pertaining to the genus Thermoanaerobacter was isolated from Himalayan hot spring. Batch experiments indicated substantial inhibitor resistance (2 g dm−3 for furfural, 5-HMF, and acetic acid), substrate tolerance (∼15 g dm−3), co-sugar fermentation ability (co-production ethanol yield of 0.29 g/g), and high ethanol yield (83.57% and 91.12% of the theoretical maximum from 5 g dm−3 glucose and xylose, respectively) by the bacterium at 70 °C and pH 8.0. Here, bioethanol production process was developed using pre-treated rice straw hydrolysate (PRSH) as low-cost agro-waste and 83.47% of the total sugar conversion was obtained. This study shows that Thermoanaerobacter sp. DBT-IOC-X2 could utilize diluted PRSH efficiently to improve the overall cost-effectiveness of biomass processing to bioethanol.

Se revisa el registro fósil ediacárico del Grupo de Jodhpur en los alrededores de la ciudad de Jodhpur, al oeste de Rajastán. Sus mejores afloramientos son considerados como sitios potenciales de Geopatrimonio. Se prevé una protección específica contra la explotación de sus canteras.

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To overcome the challenges associated with combined bioprocessing of lignocellulosic biomass to biofuel, finding good organisms is essential. An ethanol producing bacteria DBT-IOC-DC21 was isolated from a compost site via preliminary enrichment culture on a pure hemicellulosic substrate and identified as a Clostridium strain by 16S rRNA analysis. This strain presented broad substrate spectrum with ethanol, acetate, lactate, and hydrogen as the primary metabolic end products. The optimum conditions for ethanol production were found to be an initial pH of 7.0, a temperature of 70 °C and an L-G ratio of 0.67. Strain presented preferential hemicellulose fermentation when compared to various substrates and maximum ethanol concentration of 26.61 mM and 43.63 mM was produced from xylan and xylose, respectively. During the fermentation of varying concentration of xylan, a substantial amount of ethanol ranging from 25.27 mM to 67.29 mM was produced. An increased ethanol concentration of 40.22 mM was produced from a mixture of cellulose and xylan, with a significant effect observed on metabolic flux distribution. The optimum conditions were used to produce ethanol from 28 g L−1 rice straw biomass (RSB) (equivalent to 5.7 g L−1 of the xylose equivalents) in which 19.48 mM ethanol production was achieved. Thus, Clostridium strain DBT-IOC-DC21 has the potential to perform direct microbial conversion of untreated RSB to ethanol at a yield comparative to xylan fermentation.

Bio-ethanol from lignocellulosic biomass via enzymatic route has received wide acceptance as liquid fuel for transport sector. It has been regarded as alternative sustainable source of energy, however; economic feasibility still remains a question. Cellulase is still considered to add to the major cost components in the bio-ethanol production process. Trichoderma reesei, which is considered as the most potent cellulase producer is known to be deficient in β-glucosidase, hence, Penicillium cellulases being rich in β-glucosidase have got recognition. Thus Penicillium cellulases give higher efficiencies during saccharification of biomass resulting in lower cellulase requirement; decreasing the cost of cellulases in the process. This review gives an account of cellulases produced from Penicillium and its superiority over existing cellulase champions. It also discusses the possible targets to improve cellulase secretion from Penicillium at genetic level. This article justifies that Penicillium could be the next champions for cellulase production for biofuel applications.

The reconstruction of defects in the intergluteal region following pilonidal sinus excision is challenging due to its anatomical location, close proximity to the anus, and being a high-tension area prone to wound-healing problems. Excision and primary closure is known to carry a higher risk of recurrence and subsequent complications compared with using nearby local healthy tissue, such as a flap, to reconstruct defect. Extra due diligence should be given to patient selection and flap choice when deciding the reconstruction of a defect. The senior author, who has briefly reviewed complication rates in previous published literature, prefers the transverse lumbar artery perforator (TLAP) flap for reconstruction following pilonidal sinus excision in the intergluteal region. This paper illustrates the operative approach used by the senior author when raising a TLAP flap.

b-glucosidases are very important in the improvement of cellulose degradation rates by diminishing the inhibition of end products. Although, cellulase cost has reduced significantly in last decade but still the high costs of biomass saccharification is one of the main challenges for the commercialization of ethanol from LC biomass. In this work, -glucosidase immobilization in calcium alginate was optimized using response surface methodology. 89% immobilization efficiency was achieved under optimum conditions (i.e., calcium alginate 4.19% (w/v), calcium chloride 0.14 M and -glucosidase 4.42% (v/v) or 57.46 U/mL of reaction mixture). pH and temperature optima of both free and immobilized -glucosidase was found to be 5 and 50 C, respectively. Enzyme kinetics of free and immobilized -glucosidase was done to evaluate Michaelis constant (Km) and Vmax values, using pnitrophenyl- -D-glucopyranoside (pNPG) as the substrate and glucose as inhibitor. Increase in Km value (0.995 mM) for immobilized -glucosidase as compared to the free -glucosidase (0.617 mM) was observed. A decrease in Vmax from (1191.74 mol min-1 for free -glucosidase) to (736.65 mol min-1 immobilized -glucosidase) was observed after immobilization. Glucose was found to inhibit -glucosidase by competitive mode of inhibition (Ki= 3.01 mM). Studies were carried out in a batch reactor using 2% cellobiose, 0.1 M sodium acetate buffer, 5 pH and 50 C. 84% cellobiose to glucose conversion was found in first cycle which was about 67% in fifth cycle. This study suggests that enzyme immobilization improved enzyme stability, substrate inhibition and permits enzyme reusability.

In this study, an innovative approach is proposed for the valorization of all sugars (cellulosic and hemicellulosic) contained in a lignocellulosic feedstock, as is rice straw biomass (RSB), for the production of second-generation bioethanol. For this purpose, the whole slurry obtained after dilute sulfuric acid pretreatment at a biomass loading of 5% (w/v) was subjected to consolidated bioprocessing without previous solid-liquid separation and/or detoxification and the concentrated solution of carbohydrates recovered was fermented to bioethanol by a co-culture of thermophilic anaerobic bacteria. To bypass the inhibitory effect of undetoxified whole slurry on the lower fermentability of the co-culture, the concentration of different additives was optimized for improved buffering capacity, enhanced substrate-microbe interaction, and by-product elimination. The individual supplementation of 3 selected additives at optimum concentration; 20 mM calcium carbonate, 0.4% (v/v) polyethylene glycol, and 1% (w/v) sodium acetate resulted in enhanced ethanol yield of 130.83 mM, 106.37 mM, and 99.10 mM, respectively, compared to 75.03 mM ethanol yield in control. The combined effect of optimal dosage of these additives was able to improve the ethanol concentration and yield to 142 mM and 48% of the theoretical maximum respectively, suggesting about 88.58% increase compared to control medium without additives supplementation. The combined supplementation of additives proved to be an advantageous strategy for bioethanol production using undetoxified whole slurry biomass.

We present a detailed analysis of XMM-Newton X-ray spectra of the Narrow-Line Seyfert 1 galaxy Mrk 1044. We find robust evidence for a multi-phase, ultra-fast outflow, traced by four separate components in the grating spectrum. One component has high column density and ionization state, and is outflowing at 0.15c. The other three wind components have lower temperature, lower column density, and have outflow velocities 0.08c. This wind structure is strikingly similar to that found in IRAS 17020+4544, suggesting that stratified winds may be a common feature of ultra-fast outflows. Such structure is likely produced by fluid instabilities that form when the nuclear wind shocks the ambient medium. We show that in an energy-driven wind scenario, the wind in Mrk 1044 might carry enough energy to produce significant feedback on its host galaxy. We further discuss the implications of the presence of a fast wind in yet another NLS1 galaxy with high Eddington ratio., Comment: Accepted for publication in ApJ

Lignocellulosic (LC) biomass is abundantly available as a low-cost resource on the Earth. LC conversion into energy carriers is the most accepted alternative energy production policy because it is non-competitor to food or feed. LC ethanol has brought cellulases to the forefront which was otherwise lost in oblivion during last decades. LC biomass can be converted into value added products or into sugars by various routes, e.g., thermo-chemical, chemical, or biological methods. Biological route via enzymes is one of the most eco-friendly and feasible method. Both fungi and bacteria are known to degrade biomass. Fungi have been greatly exploited for cellulase production due to their inherent properties of secreting extracellular cellulase. These microorganisms are known as cellulase producers for many decades, however, to bring the enzymatic biomass conversion to an economically feasible status, extensive research efforts have been made in last decade to enhance cellulase titers. Mutations and genetic interventions along with bioprocess development have played a very important role for enhancing cellulase production. This review will present a critical overview of the on-going research towards improving cellulase production for biofuel industry via genetic modification, which will include mutation and genetic engineering employed to exert changes at genetic level in microorganisms.

Background: Pruritus is a distressing hallmark of the uremic condition, affecting approximately 60% of hemodialysis patients. Abnormal endogenous opioid ligand activity at μ and κ-opioid receptors has been postulated as a mechanism in uremic pruritus. Nalbuphine is a μ-opioid antagonist and κ-opioid agonist. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg (NAL 120), 60 mg (NAL 60), or placebo and treated for 8 weeks. Three hundred seventy-one were analyzed for efficacy. The primary endpoint was the change from baseline to treatment weeks 7 and 8 in itching intensity on a Numerical Rating Scale (NRS, 0 [no itching]; 10 [worst possible itching]) using an intent-to-treat approach. The aim was to evaluate the safety and antipruritic efficacy of NAL. Results: The mean duration of itching was 3.2 years. From a baseline NRS of 6.9 (1.5), the mean NRS declined by 3.5 (2.4) and by 2.8 (2.2) in NAL 120 mg and the placebo groups, respectively (p = 0.017). There was no evidence of tolerance. A trend for less sleep disruption due to itching (p = 0.062, NAL 120 vs. placebo) was also observed. There were no significant differences between NAL 60 vs. placebo. Serious adverse events occurred in 6.7, 12.7, and 15.4% in the NAL 120, NAL 60, and placebo groups respectively. Conclusions: In this largest-to-date randomized controlled trial in uremic pruritus, NAL 120 durably and significantly reduced the itching intensity among hemodialysis patients.

Most of ethanol production processes are limited by lower ethanol production rate and recyclability problem of ethanologenic organism. In the present study, immobilized co-fermenting Saccharomyces cerevisiae GSE1618 was employed for ethanol fermentation using rice straw enzymatic hydrolysate in a packed bed reactor (PBR). The immobilization of S . cerevisiae was performed by entrapment in Ca-alginate for optimization of ethanol production by varying alginic acid concentration, bead size, glucose concentration, temperature and hardening time. Remarkably, extra hardened beads (EHB) immobilized with S . cerevisiae could be used up to repeated 40 fermentation batches. In continuous PBR, maximum 81.82 g L −1 ethanol was obtained with 29.95 g L −1 h −1 productivity with initial glucose concentration of 180 g L −1 in feed at dilution rate of 0.37 h −1 . However, maximum ethanol concentration of 40.33 g L −1 (99% yield) with 24.61 g L −1 h −1 productivity was attained at 0.61 h −1 dilution rate in fermentation of un-detoxified rice straw enzymatic hydrolysate (REH). At commercial scale, EHB has great potential for continuous ethanol production with high productivity using lignocellulosic hydrolysate in PBR.