Accelerated cellular senescence in solid tumor therapy

Accelerated cellular senescence (ACS) is an emerging concept that implicates sustained, telomere-independent cell cycle arrest of neoplastic cells in response to chemotherapeutic agents, ionizing radiation, oxidative stress, or the presence of selective oncogenic stimuli. Recent evidence suggests that a subset of tumor cells induced in a state of reversible ACS can escape cell cycle arrest and resume proliferation accounting for cancer progression. The purpose of this review is to describe our current understanding of ACS including signaling pathways of senescence escape, role of senescence biomarkers, and rationale for senescence-based therapy. This article is part of a Special Issue entitled “Apoptosis: Four Decades Later”

Robust optimization in simulation: Taguchi and response surface methodology

Optimization of simulated systems is tackled by many methods, but most methods assume known environments. This article, however, develops a `robust' methodology for uncertain environments. This methodology uses Taguchi's view of the uncertain world, but replaces his statistical techniques by Response Surface Methodology (RSM). George Box originated RSM, and Douglas Montgomery recently extended RSM to robust optimization of real (non-simulated) systems. We combine Taguchi's view with RSM for simulated systems. We illustrate the resulting methodology through classic Economic Order Quantity (EOQ) inventory models, which demonstrate that robust optimization may require order quantities that differ from the classic EOQ

Proteome response of Phaeodactylum tricornutum, during lipid accumulation induced by nitrogen depletion

Nitrogen stress is a common strategy employed to stimulate lipid accumulation in microalgae, a biofuel feedstock of topical interest. Although widely investigated, the underlying mechanism of this strategy is still poorly understood. We examined the proteome response of lipid accumulation in the model diatom, Phaeodactylum tricornutum (CCAP 1055/1), at an earlier stage of exposure to selective nitrogen exclusion than previously investigated, and at a time point when changes would reflect lipid accumulation more than carbohydrate accumulation. In total 1043 proteins were confidently identified (≥ 2 unique peptides) with 645 significant (p < 0.05) changes observed, in the LC-MS/MS based iTRAQ investigation. Analysis of significant changes in KEGG pathways and individual proteins showed that under nitrogen starvation P. tricornutum reorganizes its proteome in favour of nitrogen scavenging and reduced lipid degradation whilst rearranging the central energy metabolism that deprioritizes photosynthetic pathways. By doing this, this species appears to increase nitrogen availability inside the cell and limit its use to the pathways where it is needed most. Compared to previously published proteomic analysis of nitrogen starvation in Chlamydomonas reinhardtii, central energy metabolism and photosynthesis appear to be affected more in the diatom, whilst the green algae appears to invest its energy in reorganizing respiration and the cellular organization pathways

Superconductivity in MgB_2 doped with Ti and C

Measurements of the superconducting upper critical field, H_{c2}, and critical current density, J_c, have been carried out for MgB_2 doped with Ti and/or C in order to explore the problems encountered if these dopants are used to enhance the superconducting performance. Carbon replaces boron in the MgB_2 lattice and apparently shortens the electronic mean free path thereby raising H_c2. Titanium forms precipitates of either TiB or TiB_2 that enhance the flux pinning and raise J_c. Most of these precipitates are intra-granular in the MgB_2 phase. If approximately 0.5% Ti and approximately 2% C are co-deposited with B to form doped boron fibers and these fibers are in turn reacted in Mg vapor to form MgB_2, the resulting superconductor has H_{c2}(T=0) ~ 25 T and J_c ~ 10,000 A/cm**2 at 5 K and 2.2 T.Comment: 11 pages, 10 figure

Nuclear interactions of topoisomerase II α and β with phospholipid scramblase 1

DNA topoisomerase (topo) II modulates DNA topology and is essential for cell division. There are two isoforms of topo II (α and β) that have limited functional redundancy, although their catalytic mechanisms appear the same. Using their COOH-terminal domains (CTDs) in yeast two-hybrid analysis, we have identified phospholipid scramblase 1 (PLSCR1) as a binding partner of both topo II α and β. Although predominantly a plasma membrane protein involved in phosphatidylserine externalization, PLSCR1 can also be imported into the nucleus where it may have a tumour suppressor function. The interactions of PLSCR1 and topo II were confirmed by pull-down assays with topo II α and β CTD fusion proteins and endogenous PLSCR1, and by co-immunoprecipitation of endogenous PLSCR1 and topo II α and β from HeLa cell nuclear extracts. PLSCR1 also increased the decatenation activity of human topo IIα. A conserved basic sequence in the CTD of topo IIα was identified as being essential for binding to PLSCR1 and binding of the two proteins could be inhibited by a synthetic peptide corresponding to topo IIα amino acids 1430-1441. These studies reveal for the first time a physical and functional interaction between topo II and PLSCR1

Large Thermoelectric Power Factor in TiS2 Crystal with Nearly Stoichiometric Composition

A TiS$_{2}$ crystal with a layered structure was found to have a large thermoelectric power factor.The in-plane power factor $S^{2}/ \rho$ at 300 K is 37.1~$\mu$W/K$^{2}$cm with resistivity ($\rho$) of 1.7 m$\Omega$cm and thermopower ($S$) of -251~$\mu$V/K, and this value is comparable to that of the best thermoelectric material, Bi$_{2}$Te$_{3}$ alloy. The electrical resistivity shows both metallic and highly anisotropic behaviors, suggesting that the electronic structure of this TiS$_{2}$ crystal has a quasi-two-dimensional nature. The large thermoelectric response can be ascribed to the large density of state just above the Fermi energy and inter-valley scattering. In spite of the large power factor, the figure of merit, $ZT$ of TiS$_{2}$ is 0.16 at 300 K, because of relatively large thermal conductivity, 68~mW/Kcm. However, most of this value comes from reducible lattice contribution. Thus, $ZT$ can be improved by reducing lattice thermal conductivity, e.g., by introducing a rattling unit into the inter-layer sites.Comment: 11 pages, 4 figures, to be published in Physical Review