The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21^Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.     

‘Nickel Allergy’ arising from decorative nickel plated and alloyed articles: prevention at source

This work builds on papers published in Transactions during 2015 and 2018 reporting research into low-cost commercial methods for the prevention of nickel release from decorative nickel plated articles, rendering them suitable for placement on the European market in accordance with the requirements of REACH. ‘Nickel Allergy’ sometimes occurs when nickel-containing articles are in direct and prolonged contact with the skin, leading to corrosion of elemental nickel by sweat, liberating sufficient nickel ions to be absorbed through the skin and initiate an allergenic effect. The EU ‘Nickel Restrictions’ impose limits on the amount of nickel released from articles intended for use in this application, but permits a non-nickel surface coating that can ensure the rate of nickel release does not exceed 0.5?µg?cm^?2 week^?1 after 2 years of normal use. The official tests for coated items are simulated wear and corrosion under EN 12472 followed by determination of nickel release under EN 1811. Earlier work concluded that suitable barrier coatings over bright electrodeposited nickel are regular chromium deposited from a hexavalent electrolyte, microporous trivalent chromium from a chloride electrolyte and UV cured PU electrophoretic coatings. Further tests reported here focused on nickel release from examples of wearable articles such as costume jewellery and watch cases. A typical flash coating of gold over bright nickel is thin and porous and being more noble, causes the rate of nickel release to be accelerated; but this can be prevented by an intermediate barrier coating of electrodeposited palladium. To round out the relevance of this study on wearable articles, nickel release tests were also conducted on nickel-containing Grades 304 (UNS S30400) and 316 (UNS S31600) austenitic stainless steels, plus a typical gold alloy containing nickel. All passed the nickel release tests satisfactorily.     

Electricity rates for the zero marginal cost grid

The electricity industry is rapidly changing: costs are increasingly dominated by capital and technology is turning loads into resources. This is similar to the early days of the Internet. Building on rate-structures used in the communications industry, utilities of the future should offer customers a portfolio of service contract options that provide a signal to the utility regarding the type and amount of infrastructure that should be deployed.     

Tensile-Strained Germanium CMOS Integration on Silicon

Monolithic integration of tensile-strained Si/ Germanium (Ge)-channel n-MOS and tensile-strained Ge p-MOS with ultrathin (equivalent oxide thickness ~14 Aring) HfO₂ gate dielectric and TaN gate stack on Si substrate is demonstrated. Defect-free Ge layer (279 nm) grown by ultrahigh vacuum chemical-vapor deposition is achieved using a two-step Ge-growth technique coupled with compliant Si/SiGe buffer layers. The epi-Ge layer experiences tensile strain of up to ~0.67% and exhibits a peak hole mobility of 250 cm²/V ldr s which is 100% higher than the universal Si hole mobility. The gate leakage current is two orders of magnitude lower compared to the reported results on Ge bulk.     

CMOS compatible dual metal gate integration with successful Vth adjustment on high-k HfTaON by high-temperature metal intermixing

In this paper, we report for the first time a novel dual metal gate (MG) integration process for gate-first CMOS platform by utilizing the intermixing (InM) of laminated ultra-thin metal layers during high-temperature annealing at 1000 °C. In this process, an ultra-thin (2 nm) TaN film is first deposited on gate dielectric as a buffer layer. Preferable laminated metal stacks for NMOS and PMOS are then formed on a same wafer through a selective wet-etching process in which the gate dielectric is protected by the TaN buffer layer. Dual work function for CMOS can finally be achieved by the intermixing of the laminated metal films during the S/D activation annealing. To demonstrate this process, prototype metal stacks of TaN/Tb/TaN (NMOS) and TaN/Ti/HfN (PMOS) has been integrated on a single wafer, with WF of 4.15 and 4.72 eV achieved, respectively. Threshold voltage (V_th) adjustment and transistor characteristics on high-k HfTaON dielectric are also studied.     

Multicast-based inference of network-internal delay distributions

Packet delay greatly influences the overall performance of network applications. It is therefore important to identify causes and locations of delay performance degradation within a network. Existing techniques, largely based on end-to-end delay measurements of unicast traffic, are well suited to monitor and characterize the behavior of particular end-to-end paths. Within these approaches, however, it is not clear how to apportion the variable component of end-to-end delay as queueing delay at each link along a path. Moreover, there are issues of scalability for large networks. In this paper, we show how end-to-end measurements of multicast traffic can be used to infer the packet delay distribution and utilization on each link of a logical multicast tree. The idea, recently introduced in Caceres et al. (1999), is to exploit the inherent correlation between multicast observations to infer performance of paths between branch points in a tree spanning a multicast source and its receivers. The method does not depend on cooperation from intervening network elements; because of the bandwidth efficiency of multicast traffic, it is suitable for large-scale measurements of both end-to-end and internal network dynamics. We establish desirable statistical properties of the estimator, namely consistency and asymptotic normality. We evaluate the estimator through simulation and observe that it is robust with respect to moderate violations of the underlying model.     

Inhibitory effects of black tea theaflavin derivatives on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and arachidonic acid metabolism in mouse ears

Tea has been shown to possess several health beneficial properties primarily due to its polyphenolic content. The major polyphenolic compounds in black tea leaves are theaflavins (TFs) formed by oxidative coupling of catechins in tea leaves during its processing. In this paper, we report the characterization of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear inflammatory model and the inhibitory effects of major black tea TFs derivatives on this inflammation. In addition, the effect on inflammatory biomarkers, such as proinflammatory cytokines and arachidonic acid metabolites, are reported as well. A single topical application of TPA to ears of CD-1 mice induced a time- and dose-dependent increase in edema as well as formation of proinflammatory cytokine proteins interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in mouse ears. A single topical application of equimolar of black tea constituents (TF, theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate) strongly inhibited TPA-induced edema of mouse ears. Application of TFs mixture to mouse ears 20 min prior to each TPA application once a day for 4 days inhibited TPA-induced persistent inflammation, as well as TPA-induced increase in IL-1beta and IL-6 protein levels. TFs also inhibited arachidonic acid (AA) metabolism via both cyclooxygenase (COX) and lipoxygenase pathways. This observation was substantiated by decreased amounts of AA metabolites prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. Combined application of TF and sulindac, a nonsteroidal anti-inflammatory drug resulted a significant synergetic anti-inflammatory effect. Oral administration of TFs or the hot water extract of black tea leaves also significantly inhibited TPA-induced edema in mouse ears. In conclusion, proinflammatory cytokines, IL-1beta and IL-6, as well as the intermediated metabolites of AA, PGE2, and LTB4 are good biomarkers for inflammation. Black tea constituents, TF and its derivatives, had strongly anti-inflammatory activity in vivo which may be due to their ability to inhibit AA metabolism via lipoxygenase and COX pathways.