1,824 research outputs found
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
Modelling sand wave fields on the Taiwan banks, Northern South China sea:The formation of two-scale sand waves in different periods
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 crystal with a layered structure was found to have a large
thermoelectric power factor.The in-plane power factor at 300 K is
37.1~W/Kcm with resistivity () of 1.7 mcm and
thermopower () of -251~V/K, and this value is comparable to that of the
best thermoelectric material, BiTe alloy. The electrical
resistivity shows both metallic and highly anisotropic behaviors, suggesting
that the electronic structure of this TiS 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, of
TiS 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, 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
-duality in Vafa-Witten theory for non-simply laced gauge groups
Vafa-Witten theory is a twisted N=4 supersymmetric gauge theory whose
partition functions are the generating functions of the Euler number of
instanton moduli spaces. In this paper, we recall quantum gauge theory with
discrete electric and magnetic fluxes and review the main results of
Vafa-Witten theory when the gauge group is simply laced. Based on the
transformations of theta functions and their appearance in the blow-up
formulae, we propose explicit transformations of the partition functions under
the Hecke group when the gauge group is non-simply laced. We provide various
evidences and consistency checks.Comment: 14 page
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