Cancer cells simultaneously harbor global losses and gains in DNA methylation. We demonstrate that inducing cellular oxidative stress by hydrogen peroxide treatment recruits DNA methyltransferase 1 ...(DNMT1) to damaged chromatin. DNMT1 becomes part of a complex(es) containing DNMT3B and members of the polycomb repressive complex 4. Hydrogen peroxide treatment causes relocalization of these proteins from non-GC-rich to GC-rich areas. Key components are similarly enriched at gene promoters in an in vivo colitis model. Although high-expression genes enriched for members of the complex have histone mark and nascent transcription changes, CpG island-containing low-expression genes gain promoter DNA methylation. Thus, oxidative damage induces formation and relocalization of a silencing complex that may explain cancer-specific aberrant DNA methylation and transcriptional silencing.
► DNMT1 becomes more tightly bound to chromatin after oxidative damage ► Oxidative damage induces formation of a complex containing DNMT1, DNMT3B and PRC4 ► DNMT-PRC4 enrichment at CpG islands may explain aberrant gene silencing in cancer ► Promoters enriched for these proteins have histone mark and DNA methylation changes
The unique characteristic of head and neck squamous cell carcinoma (HNSCC) is that local invasion rather than distant metastasis is the major route for dissemination. Therefore, targeting the locally ...invasive cancer cells is more important than preventing systemic metastasis in HNSCC and other invasive-predominant cancers. We previously demonstrate a specific mechanism for HNSCC local invasion: the epithelial-mesenchymal transition (EMT) regulator Twist1 represses microRNA let-7i expression, leading to the activation of the small GTPase Rac1 and engendering the mesenchymal-mode movement in three-dimensional (3D) culture. However, targeting the EMT regulator is relatively difficult because of its transcription factor nature and the strategy for confining HNSCC invasion to facilitate local treatment is limited. Imipramine blue (IB) is a newly identified anti-invasive compound that effectively inhibits glioma invasion. Here we demonstrate that in HNSCC cells, a noncytotoxic dose of IB represses mesenchymal-mode migration in two-and-a-half-dimensional/3D culture system. IB suppresses EMT and stemness of HNSCC cells through inhibition of Twist1-mediated let-7i downregulation and Rac1 activation and the EMT signalling. Mechanistically, IB inhibits reactive oxygen species-induced nuclear factor-κB pathway activation. Importantly, IB promotes degradation of the EMT inducer Twist1 by enhancing F-box and leucine-rich repeat protein 14 (FBXL14)-mediated polyubiquitination of Twist1. Together, this study demonstrates the potent anti-invasion and EMT-inhibition effect of IB, suggesting the potential of IB in treating local invasion-predominant cancers.
Air conditioning is essential for maintaining thermal comfort in indoor environments, particularly for hot and humid climates. Today, air conditioning, comprising cooling and dehumidification, has ...become a necessity in commercial and residential buildings and industrial processes. It accounts for a major share of the energy consumption of a building or facility. In tropical climates, the energy consumed by heating, ventilation and air-conditioning (HVAC) can exceed 50% of the total energy consumption of a building. This significant figure is primarily due to the heavy duty placed on cooling technologies to remove both sensible and latent heat loads. Therefore, there is tremendous potential to improve the overall efficiency of the air-conditioning systems in buildings.
Based on today’s practical technology for cooling, the major components of a chiller plant are (1) compressors, (2) cooling towers, (3) pumps (chilled and cooling water) and (4) fans in air handling units. They all consume mainly electricity to operate. When specifying the kW/Rton of a plant, there are two levels of monitoring cooling efficiency: (1) at the efficiency of the chiller machines or the compressors which consume a major amount of electricity; and (2) at the overall efficiency of cooling plants which include the cooling towers, pumps for moving coolant (chilled and cooling water) to all air-handling units. Pragmatically, a holistic approach is necessary towards achieving a low energy input per cooling achieved such as 0.6kW/Rton cooling or lower by considering all aspects of the cooling plant.
In this paper, we present a review of recent innovative cooling technology and strategies that could potentially lower the kW/Rton of cooling systems – from the existing mean of 0.9kW/Rton towards 0.6kW/Rton or lower. The paper, broadly divided into three key sections (see Fig. 2), begins with a review of the recent novel devices that enhances the energy efficiency of cooling systems at the component level. This is followed by a review of innovative cooling systems designs that reduces energy use for air conditioning. Lastly, the paper presents recent developments in intelligent air-control strategies and smart chiller sequencing methodologies that reduce the primary energy utilization for cooling.
The energy efficient cooling technology, innovative systems designs, and intelligent control strategies described in the paper have been recently researched or are on-going studies. Several have been implemented on a larger scale and, therefore, are examples of practical solutions that can be readily applied to suit specific needs.
A new alpha-emitting isotope U-214, produced by the fusion-evaporation reaction W-182(Ar-36,4n) U-214, was identified by employing the gas-filled recoil separator SHANS and the recoil-a correlation ...technique. More precise a-decay properties of even-even nuclei U-216,U-218 were also measured in the reactions of Ar-40, Ca-40 beams with W-180,W-182,W- 184 targets. By combining the experimental data, improved alpha-decay reduced widths delta(2) for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N = 126 are deduced. Their systematic trends are discussed in terms of the N-p N-n scheme in order to study the influence of protonneutron interaction on a decay in this region of nuclei. It is strikingly found that the reduced widths of( 214,216)U are significantly enhanced by a factor of two as compared with the NpNn systematics for the 84 <= Z <= 90 and N < 126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the pi 1f (7/2) and nu 1f(5/2) spin-orbit partner orbits, which is supported by the large-scale shell model calculation.
Heat pump systems offer economical alternatives of recovering heat from different sources for use in various industrial, commercial and residential applications. As the cost of energy continues to ...rise, it becomes imperative to save energy and improve overall energy efficiency. In this light, the heat pump becomes a key component in an energy recovery system with great potential for energy saving. Improving heat pump performance, reliability, and its environmental impact has been an ongoing concern. Recent progresses in heat pump systems have centred upon advanced cycle designs for both heat- and work-actuated systems, improved cycle components (including choice of working fluid), and exploiting utilisation in a wider range of applications. For the heat pump to be an economical proposition, continuous efforts need to be devoted to improving its performance and reliability while discovering novel applications. Some recent research efforts have markedly improved the energy efficiency of heat pump. For example, the incorporation of a heat-driven ejector to the heat pump has improved system efficiency by more than 20%. Additionally, the development of better compressor technology has the potential to reduce energy consumption of heat pump systems by as much as 80%. The evolution of new hybrid systems has also enabled the heat pump to perform efficiently with wider applications. For example, incorporating a desiccant to a heat pump cycle allowed better humidity and temperature controls with achievable COP as high as 6. This review paper provides an update on recent developments in heat pump systems, and is intended to be a “one-stop” archive of known practical heat pump solutions. The paper, broadly divided into three main sections, begins with a review of the various methods of enhancing the performance of heat pumps. This is followed by a review of the major hybrid heat pump systems suitable for application with various heat sources. Lastly, the paper presents novel applications of heat pump systems used in select industries.
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
Long noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific gene expression. Here, an enhancer-like lncRNA termed NeST (nettoie Salmonella pas Theiler’s cleanup ...Salmonella not Theiler’s) is shown to be causal for all phenotypes conferred by murine viral susceptibility locus Tmevp3. This locus was defined by crosses between SJL/J and B10.S mice and contains several candidate genes, including NeST. The SJL/J-derived locus confers higher lncRNA expression, increased interferon-γ (IFN-γ) abundance in activated CD8+ T cells, increased Theiler’s virus persistence, and decreased Salmonella enterica pathogenesis. Transgenic expression of NeST lncRNA alone was sufficient to confer all phenotypes of the SJL/J locus. NeST RNA was found to bind WDR5, a component of the histone H3 lysine 4 methyltransferase complex, and to alter histone 3 methylation at the IFN-γ locus. Thus, this lncRNA regulates epigenetic marking of IFN-γ-encoding chromatin, expression of IFN-γ, and susceptibility to a viral and a bacterial pathogen.
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► Dissection of viral susceptibility locus reveals the role of a long noncoding RNA, NeST ► NeST RNA expression is required for inducible IFN-γ synthesis in CD8+ T cells ► NeST RNA increases Theiler’s virus persistence and reduces Salmonella lethality ► NeST binds to histone modification complex, changing epigenetic marks at the Ifng locus
NeST, a long noncoding RNA whose expression and sequence are polymorphic in murine and human populations, epigenetically controls the expression of interferon-γ and confers differential pathogen susceptibility in the mouse.
A new type of biofuel, pine oil, is introduced in this work for the purpose of fueling diesel engine. The viscosity, boiling point and flash point of the reported oil are lower, when compared to that ...of diesel. Also, the calorific value of pine oil biofuel is comparable to diesel. As a result, it can be directly used in diesel engine without trans-esterifying it. Pine oil biofuel and their blends of 25%, 50%, and 75% with diesel were tested in a single cylinder, four-stroke, direct injection diesel engine and the combustion, emissions and performance results were compared with diesel. The results show that at full load condition, 100% pine oil reduces CO (carbon monoxide), HC (hydrocarbon) and smoke emissions by 65%, 30% and 70%, respectively. The brake thermal efficiency and maximum heat release rate increase by 5% and 27%, respectively. However, the NOx (oxides of nitrogen) emission is higher than that of diesel fuel at full load condition. The experimental work reveals that 100% pine oil can be directly used in diesel engine and potential benefits of pine oil biofuel have been reaped.
•The paper brings in to light a new type of biofuel, pine oil, for diesel engine.•The Pine oil possesses low viscosity and the calorific value of it is comparable to diesel.•The reported biofuel is used directly in diesel engine without trans-esterification.•The brake thermal efficiency and maximum heat release rate increase by up to 5% and 27%.•The HC, CO and smoke emissions are considerably reduced for pine oil at most of the loads.
Ferroptosis is a form of regulated non-apoptotic cell death that has been implicated in several disease contexts. A better understanding of the ferroptotic death mechanism could lead to the ...development of new therapeutics for degenerative diseases, and a better understanding of how to induce ferroptosis in specific tumor contexts. We performed an unbiased genome-wide siRNA screen to find genetic suppressors of ferroptosis. We determined that loss of CARS, the cysteinyl-tRNA synthetase, suppresses ferroptosis induced by erastin, which inhibits the cystine-glutamate antiporter known as system xc(-). Knockdown of CARS inhibited erastin-induced death by preventing the induction of lipid reactive oxygen species, without altering iron homeostasis. Knockdown of CARS led to the accumulation of cystathionine, a metabolite on the transsulfuration pathway, and upregulated genes associated with serine biosynthesis and transsulfuration. In addition, inhibition of the transsulfuration pathway resensitized cells to erastin, even after CARS knockdown. These studies demonstrate a new mechanism of resistance to ferroptosis and may lead to strategies for inducing and suppressing ferroptosis in diverse contexts.
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