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This work presents the wire-EDM of WC-Co composite and optimization of process parameters using an integrated technique of response surface methodology (RSM), Vise Kriterijumska Optimizacija Kompromisno Resenje (VIKOR) and artificial bee colony (ABC) algorithm to obtain the best set of machinability indicators. Wire feed (WF), servo voltage (SV), pulse off-time (Pon) and pulse on-time (Poff) are the variable process parameters, whereas root mean square roughness (Rq), average surface roughness (Ra) and material removal rate (MRR) are the machinability indicators considered in the present work. A total of twenty nine experiments have been conducted based on Box Behnken design (BBD) technique of response surface methodology. VIKOR has been used for normalization of responses and followed by solving empirical models using ABC algorithm to obtain optimized process parameters setting. WF-12 m/min, SV-65V, Pon-116 µs, Poff-20 µs are the optimum wire-EDM parameters obtained by intelligent RSM-VIKOR-ABC technique that produced best values of Ra-4.51 µm, Rq-5.64 µm, MRR-0.061 mm3 /min simultaneously. The validation test confirmed an improvement up to 15% in the response characteristics which proved the effectiveness of this novel hybrid technique for optimization. The optimum parameter setting is for ready industrial reference to attain best surface quality and process productivity for WC-Co composite machining by wire-EDM.

The selection of essential variables in logistic regression is vital because of its extensive use in medical studies, finance, economics and related fields. In this paper, we explore four main typologies (test-based, penalty-based, screening-based, and tree-based) of frequentist variable selection methods in logistic regression setup. Primary objective of this work is to give a comprehensive overview of the existing literature for practitioners. Underlying assumptions and theory, along with the specifics of their implementations, are detailed as well. Next, we conduct a thorough simulation study to explore the performances of fifteen different methods in terms of variable selection, estimation of coefficients, prediction accuracy as well as time complexity under various settings. We take low, moderate and high dimensional setups and consider different correlation structures for the covariates. A real-life application, using a high-dimensional gene expression data, is also included in this study to further understand the efficacy and consistency of the methods. Finally, based on our findings in the simulated data and in the real data, we provide recommendations for practitioners on the choice of variable selection methods under various contexts.

Additional file 10: Supplementary File 9: Procedure used for metabolite analysis of peanut shell.

Following our recent identification of a fatty acid binding site in the SARS-CoV-2 spike protein (Toelzer et al., Science eabd3255 (2020)), we investigate the binding of linoleate and other potential ligands at this site using molecular dynamics simulations. The results support the hypothesis that linoleate stabilises the locked form of the spike, in which its interaction interface for the ACE2 receptor is occluded. The simulations indicate weaker binding of linoleate to the partially open conformation. Simulations of dexamethasone bound at this site indicate that it binds similarly to linoleate, and thus may also stabilize a locked spike conformation. In contrast, simulations suggest that cholesterol bound at this site may destabilize the locked conformation, and in the open conformation, may preferentially bind at an alternative site in the hinge region between the receptor binding domain and the domain below, which could have functional relevance. We also use molecular docking to identify potential ligands that may bind at the fatty acid binding site, using the Bristol University Docking Engine (BUDE). BUDE docking successfully reproduces the linoleate complex and also supports binding of dexamethasone at the spike fatty acid site. Virtual screening of a library of approved drugs identifies vitamins D, K and A, as well as retinoid ligands with experimentally demonstrated activity against SARS-CoV-2 replication in vitro, as also potentially able to bind at this site. Our data suggest that the fatty acid binding site of the SARS-CoV-2 spike protein may bind a diverse array of candidate ligands. Targeting this site with small molecules, including dietary components such as vitamins, which may stabilise its locked conformation and represents a potential avenue for novel therapeutics or prophylaxis for COVID-19.

The TATA-binding protein (TBP) and a transcription factor (TF) IIB-like factor are important constituents of all eukaryotic initiation complexes. The reason for the emergence and strict requirement of the additional initiation factor Bdp1 in the RNA polymerase (RNAP) III system, however, remained elusive. A poorly studied aspect in this context is the effect of DNA strain arising from DNA compaction and transcriptional activity on initiation complex formation. We made use of a DNA origami-based force clamp to follow the assembly of human initiation complexes in the RNAP II and RNAP III systems at the single-molecule level under piconewton forces. We demonstrate that TBP-DNA complexes are force-sensitive and TFIIB is sufficient to stabilise TBP on a strained promoter. In contrast, Bdp1 is the pivotal component that ensures stable anchoring of initiation factors, and thus the polymerase itself, in the RNAP III system. Thereby, we offer an explanation for the crucial role of Bdp1 for the high transcriptional output of RNAP III., TATA-binding protein (TBP) and a transcription factor (TF) IIB-like factor are important constituents of all eukaryotic initiation complexes. Here, the authors use a DNA origami-based force clamp to investigate the assembly dynamics of human initiation complexes in the RNAP II and RNAP III systems at the single-molecule level under pico newton forces.

International audience; General transcription factor TFIID is a key component of RNA polymerase II transcription initiation. Human TFIID is a megadalton-sized complex comprising TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). TBP binds to core promoter DNA, recognizing the TATA-box. We identified a ternary complex formed by TBP and the histone fold (HF) domain-containing TFIID subunits TAF11 and TAF13. We demonstrate that TAF11/TAF13 competes for TBP binding with TATA-box DNA, and also with the N-terminal domain of TAF1 previously implicated in TATA-box mimicry. In an integrative approach combining crystal coordinates, biochemical analyses and data from cross-linking mass-spectrometry (CLMS), we determine the architecture of the TAF11/TAF13/TBP complex, revealing TAF11/TAF13 interaction with the DNA binding surface of TBP. We identify a highly conserved C-terminal TBP-interaction domain (CTID) in TAF13, which is essential for supporting cell growth. Our results thus have implications for cellular TFIID assembly and suggest a novel regulatory state for TFIID function.

Mumbai city having an area of 437sq km with a population of 12 million came to a complete halt due to the unprecedented rainfall of 944 mm during the 24 hours starting on 26 th July 2005; with 380 mm falling in just 3 hours between 14:30 to 17:30 and hourly rainfall exceeding 190 mm/hr. The severity of flood was such that it took 447 lives in Mumbai alone. The financial cost of flood was unprecedented and affected the entire commercial, trading, and industrial activity for 3 days. The present study uses the HEC-HMS 3.4 (Hydrologic Engineering Centre's-Hydrologic Modeling System) and HEC-RAS 4.0 (Hydrologic Engineering Centre's-River Analysis System). The flow and water surface depth have been simulated for various flood scenarios using the model HEC-HMS 3.4 and HEC-RAS 4.0 respectively for rainfall intensities varying from 25 mm/hr. to 200 mm/hr in increment of 25 mm/hr. Runoff and water surface depth at a upstream and downstream of detention pond have been obtained for various rainfall scenarious.. The simulation result shows maximum peak reduction of 21% by JVLR (Jogeshwari- Vikhroli link road) flood detention pond. It has been seen that efficiency of JVLR detention pond decreases as the rainfall intensity increases above 50 mm/hr. Accordingly this study can be used in flood forecasting for various rainfall scenarios, sustainable development and flood management plans of Mithi River catchment. Keywords: Urbanization, Flood, Mithi River, Flood detention pond, HEC-HMS 3.4, HEC-RAS 4.0.

To understand the effect of DUX4 in vivo, and to generate a model in which to test anti-DUX4 therapeutics, we have introduced a doxycycline (dox)-inducible transgene encoding DUX4 and 3′ genomic DNA into a euchromatic region of the mouse X chromosome. Although this mouse was intended to provide doxycycline-inducible phenotypes, through expression of DUX4, we found that the transgene alone, without dox, was lethal in males. Females were runted and presented a skin pathology in the absence of dox. This is due to low level leaky expression of the DUX4 gene, as transcript can be detected by PCR in most tissues with the most consistent detection in neural tissues including retina, and in testis. We could not detect the protein in the absence of dox. Although males are not usually born live, occasional males survive to term. These animals are much more severely affected than their female counterparts, and remarkably, display a retinal vascular pathology similar to that seen in FSHD. In addition, they show a defect in spermatogenesis. Muscles from these animals were composed of smaller fibers and were weaker, but proportionally so, and no dystrophy was present prior to death, invariably before 6 weeks of age. We performed ex vivo culture experiments with myoblasts and muscle fibroadipogenic progenitors (FAPs) isolated from the iDUX4 males, and found that high levels of dox caused cell death of myoblasts and was growth inhibitory to fibroblasts. Low non-toxic levels of dox impaired differentiation of myoblasts in vitro, but had no effect on adipogenic differentiation of muscle FAPs. To evaluate the effect of DUX4 expression during regenerative repair in vivo, we crossed the Pax7-ZsGreen satellite cell marker into this strain and performed transplants of satellite cells from live-born males into female NSG-mdx4Cv mice,and treated recipients with varying doses of dox. By using dystrophin staining to quantify engraftment, we observed a consistent and easily quantifiable dose-dependent reduction in regeneration by transplanted satellite cells. These data show that DUX4 expression, even at low levels, is inhibitory to regenerative myogenesis. We further propose that the quantification of donor-derived myofibers generated by transplanted iDUX4 satellite cells can serve as a useful in vivo test system for therapeutics directed against the DUX4 protein or transcript.

The electronic structure of epitaxial films on LaCoO3(LCO) has been studied within first principle electronic structure calculations. A spin state transition is found to take place as a function of lattice strain which freezes in the intermediate spin state for non zero strain. In contrast to earlier speculations this is found to arise from substrate strain alone and angle variations are small. The intermediate spin state also stabilizes ferromagnetism in the ground state. The anomalous temperature dependence of the X-ray absorption spectra for films of LCO on LCO and its absence in films of LCO on (LaAlO_{3})_{0.3}(SrAlTaO_{6})_{0.7}$(LSAT) is also explained., Comment: To appear in Phys. Rev B (Rapid Comm.)

Research involved in developing alternative energy sources has become a necessity to face global warming. In this context, superconductivity is an appealing solution to enhance clean electrical energy provided that lower production costs can be attained. By implementation of chemical solution deposition techniques and high-throughput growth methods, low-cost nanostructured epitaxial cuprate superconductors are timely candidates. Here, we present a versatile and tunable solution method suitable for the preparation of high-performance epitaxial cuprate superconducting films. Disregarding the renowned trifluoroacetate route, we center our focus on the transient liquid-assisted growth (TLAG) that meets the requirement of being a greener chemical process together with ultrafast growth rates beyond 100 nm/s. We developed a facile, fast, and cost-effective method, starting from the synthesis of metal-propionate powders of Y, Ba, and Cu of high purity and high yields, being the precursors of the fluorine-free solutions, which enable the chemical and microstructural nanoscale homogeneity of YBa2Cu3O7-x (YBCO) precursor films. These solutions present endured stability and enable precise tunability of the composition, concentration, porosity, and film thickness. Homogeneous precursor films up to thicknesses of 2.7 μm through eight layer multidepositions are demonstrated, thus establishing the correct basis for epitaxial growth using the fast kinetics of the TLAG process. YBCO films of 500 nm thickness with a critical current density of 2.6 MA/cm2 at 77 K were obtained, showing the correlation of precursor film homogeneity to the final YBCO physical properties., The authors acknowledge the European Research Council for the ULTRASUPERTAPE project (ERC-2014-ADG-669504), IMPACT project (ERC-2019-PoC-874964), and EU COST action for CA16218 (NANOCOHYBRI). The authors also acknowledge financial support from the Spanish Ministry of Science, Innovation and Universities through the “Severo Ochoa” Programme for Centres of Excellence in FUNFUTURE (CEX2019-000917-S), SUMATE projects (RTI2018-095853-B-C21, RTI2018-095853-B-C22 co-financed by the European Regional Development Fund, MCIU/AEI/FEDER, UE), and SUPERENERTECH projects (PID2021-127297OB-C21 and PID2021-127297OB-C22). The authors also thank support from the Catalan Government with 2017-SGR-1519 and Catalan energy network XRE4S (2018 XARDI 00002). L.S., D.G., and A.K. acknowledge financial support from the Spanish Ministry of Science, Innovation and Universities through the FPI grants PRE2019-090621, PRE2018-084537, and PRE2020-091817, respectively. L.S. and D.G. would like to thank the UAB PhD program in Materials Science, and A.K. would like to thank the UAB PhD program in Physics. A.Q. would like to thank the Spanish Ministry of Science, Innovation and Universities [“Juan de la Cierva” postdoctoral fellowship (grant no. IJC2018-035034-I)]. The authors thank the Scientific Services at ICMAB and ICN2 Electron Microscopy Division. The authors acknowledge the use of instrumentation as well as the technical advice provided by the National Facility ELECMI ICTS, node “Laboratorio de Microscopías Avanzadas” at the University of Zaragoza. The content of this paper is the object of a European patent application no. EP22382741.1 filed on 29/07/2022., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

We investigated the integration of transient liquid-assisted growth (TLAG) approach for epitaxial YBa2Cu3O7−x (YBCO) films by physical deposition methodologies (pulsed laser deposition (PLD)), as an additional opportunity for high-throughput growth of YBCO. As a prerequisite, highly flat and amorphous YBCO precursor films were deposited by PLD at temperatures below 400 °C on single-crystalline SrTiO3 (STO) and LaMnO3 (LMO)/STO, as well as industrial coated conductor architectures. Contrary to TLAG based on chemical solution deposition, where BaCO3 elimination is a key factor for the YBCO growth, TLAG-PLD growth is controlled by the transformation of Ba-Cu-O (s) to a transient liquid. High-quality c-axis YBCO films were successfully grown on different substrates, as demonstrated by high-resolution x-ray diffraction and transmission electron microscopy. In-situ resistance measurements revealed that the growth rates around 1000 nm s−1 can be achieved, outperforming the capabilities of standard PLD growth of REBa2Cu3O7 films by few orders of magnitude. Experimental conditions such as temperature, oxygen partial pressure, and heating ramp, were optimized to obtain critical temperature (T c) values up to 90 K. Critical current densities of 15 MA cm−2 at 5 K and 1.7 MA cm−2 at 77 K were obtained for YBCO films of 450 nm on LMO/STO., The authors acknowledge European Research Council for the ULTRASUPERTAPE project (ERC-2014-ADG-669504), IMPACT project (ERC-2019-PoC-874964) and SMS-INKS project (ERC-2022-PoC-101081998), as well as the EU COST actions CA16218 (NANOCOHYBRI), CA20116 (OPERA) and CA21144 (SUPERQUMAP). We also thank financial support from the Spanish Ministry of Economy and Competitiveness, and Spanish Ministry of Science, Innovation and Universities through the 'Severo Ochoa' Programme for Centres of Excellence in R&D (SEV-2015-0496 and CEX2019-000917-S), FUNFUTURE-FIP-2020-DATOPTICON, SUPERENERTECH project (PID2021-127297OB-C21), and SUMATE project (RTI2018-095853-B-C21, co-financed by the European Regional Development Fund). We also acknowledge support from the Catalan Government with 2017-SGR-1519 and the Catalan energy network XRE4S (2018 XARDI 00002). A Q thanks the Spanish Ministry of Science, Innovation and Universities for his 'Juan de la Cierva' postdoctoral fellowship (Grant No. IJC2018-035034-I). L S acknowledges financial support from Spanish Ministry of Science, Innovation and Universities through the FPI grants PRE2019-090621. Dr Silvia Rasi and Dr Roxana Vlad are thanked for fruitful discussions. We acknowledge the Scientific Services at ICMAB and ICN2 Electron Microscopy Division. Authors also acknowledge the use of instrumentation as well as the technical advice provided by the National Facility ELECMI ICTS, node 'Laboratorio de Microscopías Avanzadas' at University of Zaragoza. SuNAM Co. is acknowledged for providing metallic substrates., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).