The behaviour of typical armour steel material under large strains, high strain rates and elevated temperatures needs to be investigated to analyse and reliably predict its response to various types ...of dynamic loading like impact. An empirical constitutive relation developed by Johnson and Cook (J–C) is widely used to capture strain rate sensitivity of the metals. A failure model proposed by Johnson and Cook is used to model the damage evolution and predict failure in many engineering materials. In this work, model constants of J–C constitutive relation and damage parameters of J–C failure model for a typical armour steel material have been determined experimentally from four types of uniaxial tensile test. Some modifications in the J–C damage model have been suggested and Finite Element simulation of three different tensile tests on armour steel specimens under dynamic strain rate (10−1s−1), high triaxiality and elevated temperature respectively has been done in ABAQUS platform using the modified J–C failure model as user material sub-routine. The simulation results are validated by the experimental data. Thereafter, a moderately high strain rate event viz. Charpy impact test on armour steel specimen has been simulated using J–C material and failure models with the same material parameters. Reasonable agreement between the simulation and experimental results has been achieved.
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A mild, efficient, and metal-free oxidative cleavage of C–C double bond to aldehydes utilizing eosin Y as an organophotoredox catalyst has been developed. The green aspects of our ...work capitalize on the utilization of visible light and air (O2) as inexpensive, readily-available, non-toxic, and eco-sustainable reagents with the removal of specialized glassware and a powerful UV light source. Moreover, a synthetic application of the photo-oxidative cleavage of C–C double bond is also demonstrated by the convenient synthesis of benzothiazoline.
Summary
Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus ...colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey‐coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD – cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy – overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site‐ and skin‐type‐specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is to present the latest evidence from animal and human studies, including recent microbiome research, to define the clinical features of bacterial infections in AD, and to summarize our current understanding of the host and bacterial factors that influence microbial colonization and virulence.
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•One-pot synthesis of tricyclic compounds incorporating tetrahydroquinoline core.•Activation of C(sp3)–H carbon followed by aromatization step at room temperature.•Utilization of ...inexpensive, readily available and easy to handle oxidant K2S2O8.•Metal-free cyclization of N-methylanilines with maleimides to tetrahydroquinolines.
A metal-free, novel and convenient way for the direct cyclization of N-methylanilines with maleimides to tetrahydroquinolines via C(sp3)–H activation is reported. The protocol utilizes inexpensive and easy to handle K2S2O8 as a radical surrogate and involves sequential formation of C(sp3)–C(sp2) and C(sp2)–C(sp2) bonds in a one-pot procedure at room temperature. The method affords excellent yield of tricyclic compounds incorporating biologically important tetrahydroquinoline core.
Histone acetylation, including acetylated H3K14 (H3K14ac), is generally linked to gene activation. Monomethylated histone H3 lysine 4 (H3K4me1), together with other gene-activating marks, denotes ...active genes. In contrast to usual gene-activating functions of H3K14ac and H3K4me1, we here show that the dual histone modification mark H3K4me1-H3K14ac is recognized by ZMYND8 (also called RACK7) and can function to counteract gene expression. We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D. ZMYND8 antagonized the expression of metastasis-linked genes, and its knockdown increased the cellular invasiveness in vitro and in vivo. The plant homeodomain (PHD) and Bromodomain cassette in ZMYND8 mediated the combinatorial recognition of H3K4me1-H3K14ac and H3K4me0-H3K14ac by ZMYND8. These findings uncover an unexpected role for the signature H3K4me1-H3K14ac in attenuating gene expression and reveal a metastasis-suppressive epigenetic mechanism in which ZMYND8’s PHD-Bromo cassette couples H3K4me1-H3K14ac with downregulation of metastasis-linked genes.
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•ZMYND8 acts as a JARID1D corepressor for JARID1D-mediated gene repression•PHD-Bromo in ZMYND8 reads H3K4me1-H3K14ac and H3K4me0-H3K14ac•ZMYND8 has an anti-metastasis function•H3K4me1-H3K14ac is associated with repression of metastasis-linked genes
Li et al. reveal that ZMYND8 recognizes the dual histone mark H3K4me1-H3K14ac and acts as a transcriptional corepressor of the H3K4 demethylase JARID1D. ZMYND8-mediated recognition of H3K4me1-H3K14ac and JARID1D-catalyzed H3K4 demethylation cooperate to antagonize the expression of metastasis-linked genes.
The network coverage and energy efficiency issues in heterogeneous cognitive-femtocell networks over the macrocell network is studied. Cognitive functions in wireless network nodes are serviceable ...with the macrocell infrastructure to achieve a balance between two desirable but incompatible features: coverage and energy efficiency. There are two basic but related aspects of cognitive radios (CRs) in the context of wireless communications: optimum CRs for energy efficiency and the act of the functioning of CRs with energy efficiency. To fully utilise the cognitive capability, a dual-tier network architecture is assumed where both the macrocell and the femtocell have a bearing on the cognitive capability. Owing to the salient features of femtocells, they can improve the coverage and enhance the spectrum efficiency by reutilising the frequency spectrum allocated to the macrocell, although, the resulting intercell interference accompanied by the same frequency coverage cannot be underestimated. The effectiveness of the scheme is verified by extensive Matlab simulation.
Epigenetic modifiers frequently harbor loss-of-function mutations in lung cancer, but their tumor-suppressive roles are poorly characterized. Histone methyltransferase KMT2D (a COMPASS-like enzyme, ...also called MLL4) is among the most highly inactivated epigenetic modifiers in lung cancer. Here, we show that lung-specific loss of Kmt2d promotes lung tumorigenesis in mice and upregulates pro-tumorigenic programs, including glycolysis. Pharmacological inhibition of glycolysis preferentially impedes tumorigenicity of human lung cancer cells bearing KMT2D-inactivating mutations. Mechanistically, Kmt2d loss widely impairs epigenomic signals for super-enhancers/enhancers, including the super-enhancer for the circadian rhythm repressor Per2. Loss of Kmt2d decreases expression of PER2, which regulates multiple glycolytic genes. These findings indicate that KMT2D is a lung tumor suppressor and that KMT2D deficiency confers a therapeutic vulnerability to glycolytic inhibitors.
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•Lung-specific Kmt2d loss in mice promotes lung tumorigenesis•Kmt2d loss impairs enhancers, including a super-enhancer for the tumor suppressor Per2•KMT2D activates Per2 expression and thereby represses glycolytic genes•Glycolysis inhibition impedes the growth of KMT2D-mutant lung cancer
Histone methyltransferase KMT2D is frequently mutated in lung tumors, and Alam et al. identify KMT2D as a lung tumor suppressor. KMT2D deficiency induces aberrant metabolic reprogramming via super-enhancer impairment, conferring sensitivity to glycolytic inhibitors in lung cancer with KMT2D-inactivating mutations.
•GaAsSb layers were grown using Ga-As-Sb and Ga-As-Sb-Bi melts by LPE.•Bi is found to control the Sb/As ratio in GaAsSb epilayers.•Layers grown using Bi melt show improved crystalline quality.
Bi is ...used for the first time to control the Sb content in GaAsSb epitaxial layers, grown by liquid phase epitaxy (LPE) with high Sb in the layers (>10 at%). This is evidenced by a steady decrease of the Sb incorporation in the layers, obtained from high resolution X-ray diffraction (HRXRD) measurements, with increased Bi addition to the growth melt. X-ray photoelectron spectroscopy (XPS) is used to study the different surface bonding states of the constituting elements of the epilayer, and the results suggest that Bi is not incorporated in the layer but reside over the surface of the material, in metallic or in oxide states. A band gap reduction of 220 meV is measured in GaAsSb layer containing 11 at% Sb, by low temperature photoluminescence (PL) spectroscopy. Addition of Bi to the growth melt resulted in a blue shift of the band gap upto 40 meV. From low temperature PL and temperature dependent PL, it is observed that the luminescence intensity increases and the full width at half maximum (FWHM) decreases for the layers, grown from Ga-As-Sb-Bi melts compared to layers grown from the a melt without Bi, suggesting improved surface and crystalline quality of the epitaxial layers.
Histone methyltransferases and demethylases reversibly modulate histone lysine methylation, which is considered a key epigenetic mark associated with gene regulation. Recently, aberrant regulation of ...gene expression by histone methylation modifiers has emerged as an important mechanism for tumorigenesis. However, it remains largely unknown how histone methyltransferases and demethylases coregulate transcriptional profiles for cancer cell characteristics. Here, we show that in breast cancer cells, the histone H3 lysine 27 (H3K27) demethylase UTX (also known as KDM6A) positively regulates gene expression programs associated with cell proliferation and invasion. The majority of UTX-controlled genes, including a cohort of oncogenes and prometastatic genes, are coregulated by the H3K4 methyltransferase mixed lineage leukemia 4 (MLL4, also called ALR, KMT2D, and MLL2). UTX interacted with a C-terminal region of MLL4. UTX knockdown resulted in significant decreases in the proliferation and invasiveness of breast cancer cells in vitro and in a mouse xenograft model. Such defective cellular characteristics of UTX-depleted cells were phenocopied by MLL4 knockdown cells. UTX-catalyzed demethylation of trimethylated H3K27 and MLL4-mediated trimethylation at H3K4 occurred interdependently at cotarget genes of UTX and MLL4. Clinically, high levels of UTX or MLL4 were associated with poor prognosis in patients with breast cancer. Taken together, these findings uncover that coordinated regulation of gene expression programs by a histone methyltransferase and a histone demethylase is coupled to the proliferation and invasion of breast cancer cells.
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