Search results for "init"
showing 10 items of 6629 documents
Cytotoxicity of 4-hydroxy-N-(naphthalen-1-yl)-2-oxo-2H-chromene-3-carboxamide in multidrug-resistant cancer cells through activation of PERK/eIF2α/AT…
2021
After decades of research, multidrug resistance (MDR) remains a huge challenge in cancer treatment. In this study, the cytotoxic of 4-hydroxy-N-(naphthalen-1-yl)-2-oxo-2H-chromene-3-carboxamide (MCC1734) has been investigated towards multidrug-resistant cancer cell lines. MCC1734 exerted cytotoxicity on cell lines expressing different mechanisms of drug resistance (P-glycoprotein, BCRP, ABCB5, EGFR, p53 knockout) to a different extent. Interestingly, sensitive CCRF-CEM cells and multidrug-resistant P-gp-overexpressing CEM/ADR5000 cells represented similar sensitivity towards MCC1734, indicating MCC1734 can bypass P-gp-mediated resistance. Microarray-based mRNA expression revealed that MCC17…
Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell death in human cancer cells.
2010
Background Cancer cells present a sustained de novo fatty acid synthesis with an increase of saturated and monounsaturated fatty acid (MUFA) production. This change in fatty acid metabolism is associated with overexpression of stearoyl-CoA desaturase 1 (Scd1), which catalyses the transformation of saturated fatty acids into monounsaturated fatty acids (e.g., oleic acid). Several reports demonstrated that inhibition of Scd1 led to the blocking of proliferation and induction of apoptosis in cancer cells. Nevertheless, mechanisms of cell death activation remain to be better understood. Principal Findings In this study, we demonstrated that Scd1 extinction by siRNA triggered abolition of de nov…
(H, ρ)-induced dynamics and the quantum game of life
2017
Abstract We propose an extended version of quantum dynamics for a certain system S , whose evolution is ruled by a Hamiltonian H, its initial conditions, and a suitable set ρ of rules, acting repeatedly on S . The resulting dynamics is not necessarily periodic or quasi-periodic, as one could imagine for conservative systems with a finite number of degrees of freedom. In fact, it may have quite different behaviors depending on the explicit forms of H, ρ as well as on the initial conditions. After a general discussion on this (H, ρ)-induced dynamics, we apply our general ideas to extend the classical game of life, and we analyze several aspects of this extension.
Intrinsic Acidity of Surface Sites in Calcium Silicate Hydrates and Its Implication to Their Electrokinetic Properties
2014
Calcium Silicate Hydrates (C–S–H) are the major hydration products of portland cement paste. The accurate description of acid–base reactions at the surface of C–S–H particles is essential for both understanding the ion sorption equilibrium in cement and prediction of mechanical properties of the hardened cement paste. Ab initio molecular dynamics simulations at the density functional level of theory were applied to calculate intrinsic acidity constants (pKa’s) of the relevant ≡SiOH and ≡CaOH2 groups on the C–S–H surfaces using a thermodynamic integration technique. Ion sorption equilibrium in C–S–H was modeled applying ab initio calculated pKa’s in titrating Grand Canonical Monte Carlo simu…
Hunting for the high-affinity state of G-protein-coupled receptors with agonist tracers: Theoretical and practical considerations for positron emissi…
2019
Abstract The concept of the high‐affinity state postulates that a certain subset of G‐protein‐coupled receptors is primarily responsible for receptor signaling in the living brain. Assessing the abundance of this subset is thus potentially highly relevant for studies concerning the responses of neurotransmission to pharmacological or physiological stimuli and the dysregulation of neurotransmission in neurological or psychiatric disorders. The high‐affinity state is preferentially recognized by agonists in vitro. For this reason, agonist tracers have been developed as tools for the noninvasive imaging of the high‐affinity state with positron emission tomography (PET). This review provides an…
Variational approach to the mechanics of metal V-belt systems
2005
The mechanical behaviour of metal V-belt drives is strongly dependent on the elastic properties of both the belt and the pulley, which influence the belt penetration into the groove and the sliding on the pulley wall. The distribution of tension and penetration is quite different from the rubber belts, which may be dealt with in the assumption of perfectly rigid pulleys. The restoring effect of the centrifugal forces of the plate elements has also to be taken into account. The present analysis considers the combination of all those effects, choosing a three parameter deformation function to describe the plate bending and applying the principle of virtual work for the calculation of the unkn…
RPGR ORF15 isoform co-localizes with RPGRIP1 at centrioles and basal bodies and interacts with nucleophosmin
2005
The ORF15 isoform of RPGR (RPGR(ORF15)) and RPGR interacting protein 1 (RPGRIP1) are mutated in a variety of retinal dystrophies but their functions are poorly understood. Here, we show that in cultured mammalian cells both RPGR(ORF15) and RPGRIP1 localize to centrioles. These localizations are resistant to the microtubule destabilizing drug nocodazole and persist throughout the cell cycle. RPGR and RPGRIP1 also co-localize at basal bodies in cells with primary cilia. The C-terminal (C2) domain of RPGR(ORF15) (ORF15(C2)) is highly conserved across 13 mammalian species, suggesting that it is a functionally important domain. Using matrix-assisted laser desorption ionization time-of-flight mas…
The retinitis pigmentosa 28 protein FAM161A is a novel ciliary protein involved in intermolecular protein interaction and microtubule association
2012
Loss-of-function mutations in the gene encoding FAM161A were recently discovered as the cause for RP28, an autosomal recessive form of retinitis pigmentosa. To initiate the characterization of the cellular role of FAM161A in the retina, we focused on its subcellular localization and conducted in vitro studies to identify FAM161A-interacting proteins and associated cellular structures. Immunohistochemistry revealed the presence of mouse FAM161A in the photoreceptor inner segments, the synaptic regions of the outer and inner plexiform layers and the ganglion cells. In mouse and human retinal sections from unfixed eyes, FAM161A localized to the ciliary region linking photoreceptor outer and in…
The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the Golgi and the primary cilium.
2010
Photoreceptors are complex ciliated sensory neurons. The basal body and periciliary ridge of photoreceptors function in association with the Golgi complex to regulate the export of proteins from the inner segment to the outer segment sensory axoneme. Here, we show that the retinitis pigmentosa protein RP2, which is a GTPase activating protein (GAP) for Arl3, localizes to the ciliary apparatus, namely the basal body and the associated centriole at the base of the photoreceptor cilium. Targeting to the ciliary base was dependent on N-terminal myristoylation. RP2 also localized to the Golgi and periciliary ridge of photoreceptors, which suggested a role for RP2 in regulating vesicle traffic an…
E-2-Benzylidenebenzocycloalkanones. IV. Studies on transmission of substituent effects on 13C NMR chemical shifts of E-2-(X-benzylidene)-1-tetralones…
2005
Abstract Single substituent parameter (SSP) and dual substituent parameter (DSP) analyses were applied to study the transmission of substituent effects on selected 13C NMR chemical shifts of the cyclic chalcone analogues, E-2-(4′-X-benzylidene)-1-tetralones (2) and E-2-(4′-X-benzylidene)-1-benzosuberones (3). In order to study how the geometry of the cyclic chalcone analogues affects the transmission of substituent effects similar investigations with the respective chalcones (4) were also performed. The results obtained earlier with the five-membered analogue E-2-(4′-X-benzylidene)-1-indanones (1) were also involved in the comparisons. Geometry optimization of the unsubstituted 1a, 2a, 3a a…