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SALL4 has recently been identified to promote chemo-resistance in multiple types of cancer, but the underlying mechanism remains to be fully established. Open chromatin structure is important for DNA damage response (DDR) and DNA repair. Here, we demonstrate that SALL4 promotes open chromatin by destabilizing heterochromatin protein 1α (HP1α) by recruiting ubiquitin E3 ligase CUL4B to HP1α. The silencing of SALL4 in cancer cells decreased the expression levels of Glut1 and inhibited glycolysis in cancer cells. The upregulation of HP1α in human cancer cells suppressed open chromatin, glycolysis and Glut1 expression levels. Therefore, SALL4 promotes the expression of Glut1 and open chromatin through a HP1α-dependent mechanism. Impaired DDR in SALL4-deficient human cancer cells can be rescued by the restored expression of Glut1, indicating the importance of HP1α-Glut1 axis in SALL4-mediated DDR. These findings demonstrate that SALL4 could induce drug resistance by enhancing DDR and DNA repair through promoting glycolysis and subsequent chromatin remodeling.

The pluripotency gene Nanog is not expressed in normal adult tissues but is overexpressed in some human cancers. However, the tumorigenic roles of Nanog remain unclear. The ectopic expression of Nanog is not sufficient to induce spontaneous tumors in mice but can promote metastasis of established tumors by activating the expression of metastatic genes. The expression of Nanog in mouse skin activates tumor suppressor p53, leading to the differentiation of epidermal stem cells. In the absence of p53, Nanog induces spontaneous squamous cell carcinoma, identifying a novel role of Nanog in tumorigenesis. Therefore, the induction of p53 and differentiation in Nanog-expressing skin suppresses the tumorigenic activities of Nanog, which include the induction of DNA double-stranded break damage. Notably, Nanog interacts with the KRAB-associated protein 1 (KAP1) and inhibits its sumoylation activity, impairing KAP1-mediated chromatin remodeling, which is important for efficiently activating DNA damage response. In summary, Nanog is an oncogene with multiple roles in promoting tumorigenesis and metastasis.

Distributed, small-scale energy storage has been identified as a means of improving load factors for intermittent renewable generation and displacing the need for fossil-based backup. Domestic electric storage heaters operating within a smart grid offer high density, controllable energy storage at low cost, allowing the network operator to shift demand by charging heaters to dispose of excess supply. This paper reports monitoring outcomes and simulation studies on the first field trials of such a system, in which heaters are capable of responding to instructions from the grid to vary charging level at 15-min intervals, as well as to occupant-set controls on power output. Monitoring found significant unexpected out-of-schedule power draw and under-utilisation of storage capacity. Alternative approaches to scheduling were tested using simulations, and evaluated using metrics to quantify schedule following as well as other aspects of performance to give a balanced view of system performance to the network operator. Modern insulated storage heaters are capable of supporting load shifting for up to 48 h with minimal impact on room temperatures or demand, and with high confidence that charging schedules will be followed. However, where device controllers compete with centrally generated charge scheduling, the network will experience significant out-of-schedule power draw while occupants will experience either lower temperatures or increased cost

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The area of policy formulation for the energy and carbon performance of buildings is coming under increasing focus. A major challenge is to account for the large variation within building stocks relative to factors such as location, climate, age, construction, previous upgrades, appliance usage, and type of heating/cooling/lighting system. Existing policy-related tools that rely on simple calculation methods have limited ability to represent the dynamic interconnectedness of technology options and the impact of possible future changes in climate and occupant behaviour. The use of detailed simulation tools to address these limitations in the context of policy development has hitherto been focussed on the modelling of a number of representative designs rather than dealing with the spread inherent in large building stocks. Further, these tools have been research-oriented and largely unsuitable for direct use by policy-makers, practitioners and, ultimately, building owners/occupiers. This paper summarises recent initiatives that have applied advanced modelling and simulation in the context of policy formulation for large building stocks. To exemplify the stages of the process, aspects of the ESRU Domestic Energy Model (EDEM) are described. EDEM is a policy support tool built on detailed simulation models aligned with the outcomes of national surveys and future projections for the housing stock. On the basis of pragmatic inputs, the tool is able to determine energy use, carbon emissions and upgrade/running cost for any national building stock or subset. The tool has been used at the behest of the Scottish Building Standards Agency and South Ayrshire Council to determine the impact of housing upgrades, including the deployment of new and renewable energy systems, and to rate the energy/carbon performance of individual dwellings as required by the European Commission's Directive on the Energy Performance of Buildings (EC 2002).

Focusing effect of laser-driven positron jets by self-generated target sheath fields has been observed for the first time experimentally and the results are supported by the computational studies. In the experiment, OMEGA EP short-pulse (0.7 ps, 500 J) irradiates mm-size gold targets with a concave back surface and reference flat-surface targets. Both targets exhibited positrons with quasi-monoenergetic energy peaks while targets with concave curvature also showed increased number of positrons at the detector. The data is consistent with hybrid-PIC simulations confirming that the time-varying electric fields driven by electrons escaping from the target significantly change the trajectories of positrons. These simulations show a small radius of curvature on the rear side increases the relative focusing effect and the positrons to electrons ratio in the escaping plasma. For the smallest radius of curvature, positron jets that are up to 10 times denser can be achieved.