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New Mechanism (new + mechanism)
Selected AbstractsA New Mechanism for Ethanol Oxidation Mediated by Cytochrome P450 2E1: Bulk Polarity of the Active Site Makes a DifferenceCHEMBIOCHEM, Issue 3 2007Yong Wang Breaking the habit. A new mechanism, called reversed dual hydrogen abstraction (R-DHA), is presented for ethanol oxidation by cytochrome P450 2E1 (CYP2E1). It is shown that the competition of R-DHA with the consensus mechanism (gem -diol) is modulated by the ethanol population in the enzyme pocket. Thus, as a response to growing blood ethanol level, CYP2E1 adapts its ethanol metabolism by a mechanistic switch from gem -diol to R-DHA. [source] Pharmacodynamics of Mycophenolate Mofetil after Heart Transplantation: New Mechanisms of Action and Correlations with Histologic Severity of Graft RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2002Markus J. Barten The primary mechanism of action in vivo of mycophenolate mofetil (MMF) is believed to be inhibition of lymphocyte proliferation. We used novel assays of lymphocyte functions (pharmacodynamics, PD) in whole blood collected from rat heart allograft recipients treated with MMF to investigate the mechanisms of action of the active metabolite of MMF, mycophenolate acid (MPA) in vivo. Allograft recipients were treated orally once daily with 3 different doses of MMF. Seven days after transplantation, blood was collected 24 h after the penultimate dose and several timepoints after the last dose, after which grafts were removed for microscopic grading of rejection. Lymphocytes in whole blood samples were mitogen stimulated through calcium-dependent and -independent signaling pathways. Inhibition of PD was measured by lymphocyte proliferation and expression of several surface antigens on T cells, and was calculated as area under the time-inhibition of immune function effect curve (AUE0,24 h). We found that inhibition of lymphocyte proliferation and antigen expression by MPA correlated highly with MMF-dose, MPA level and with the histologic severities of graft rejection (p <,0.05). In summary, MPA suppressed lymphocyte proliferation and expression of T-cell surface antigens in whole blood collected from MMF-treated allograft recipients, thus demonstrating the multiple mechanisms of suppression of rejection on peripheral blood T cells after MMF treatment. [source] New mechanism of transforming growth factor-, signaling in hepatoma: Dramatic up-regulation of tumor initiating cells and epidermal growth factor receptor expressionHEPATOLOGY RESEARCH, Issue 5 2009Takeshi Nishimura Aim:, Transforming growth factor-, (TGF-,) has dual activity in tumor cells. We studied the effect of TGF-, on tumor-initiating cells (TICs), which are similar in self-renewal and differentiation features to normal adult stem cells. Methods:, We used side population (SP) cells that exclude DNA binding dye Hoechst 33342 to obtain TICs, studied the differences in the kinetics of the SP cell response to TGF-, treatment between hepatic tumor cell lines, and performed gene analysis. Results:, SP cells from all cell lines have higher proliferative ability compared to non-SP cells and they are drug resistant. TGF-, treatment increased the percentage of SP cells (%SP) and the survival rate; chemotherapeutic drug resistance developed only in K-251 SP cells. Gene analysis showed that TGF-, up-regulated epidermal growth factor receptor (EGFR) only in K-251 cells. There were no EGFR mutations in K-251, which had been reported in lung cancer. Knockdown of Smad4 using the small-interfering RNA technique in K-251 cells inhibited EGFR overexpression and significantly decreased the %SP. In contrast, the JNK inhibitor had little effect on EGFR expression or the %SP. Conclusion:, TGF-, treatment of K-251 cells causes tumor progression and the anti-cancer drug resistant phenotype by increasing SP. [source] GeV-acceleration of electron by a superintense ultrashort laser pulseLASER PHYSICS LETTERS, Issue 8 2004A. Bahari Abstract New mechanism of laser acceleration of a charged particle is discovered and explained. Particle acceleration with focused beam of superintense ultrashort laser pulse is determined by a combination of ponderomotive forces at rising and falling edges of laser pulse and a longitudinal component of laser electric field. We found that acceleration of electron, which moves along the laser wavevector, is crucially depends on whether or not the electron reaches the region z , zR behind the laser focus (here zR is the Rayleigh length). Interpretation of this effect consists in that the laser longitudinal electric field at the electron trajectory in this region is a unidirectional one (oscillatory in the case of laser linear polarization and slowly varying in the case of laser circular polarization). Due to this effect it is possible to overcome the negative influence of a phase slippage in the particle- wave interaction, which substantially suppresses electron acceleration. We revealed also that the physical reason of a unidirectional influence of laser longitudinal electric field on accelerating electron in the region z , zR consists in the difference in phase velocities of transverse and longitudinal components of a focused laser field. Owing to this mechanism, lasers of ultimate present-day parameters enable electron acceleration up to the energy , , 1 GeV. Moreover, electron acceleration along the laser wavevector (in contrast to techniques currently considered) is not sensitive to field initial phase (there is no bunch effect), it is possible to accelerate slow electrons (electrons need not to be preaccelerated to relativistic velocities), and there are no problems with a removal of accelerated electron from the laser field. (© 2004 by ASTRO, Ltd. Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA) [source] New mechanisms, old problems?INTERNATIONAL AFFAIRS, Issue 5 2004Recent books on universal jurisdiction, mixed tribunals This review article examines three recent books on two topics: universal jurisdiction and the mixed or hybrid tribunal. It reviews two volumes on universal jurisdiction that discuss the history of the concept and the rise in the exercise of universal jurisdiction, as well as some of the arguments for holding rights abusers responsible in venues far from the locus of the original crime and then turns to some of the possible pitfalls of such approaches. The article also examines some of the virtues, but also the shortcomings, of the hybrid tribunal and concludes that while these innovative tools have their uses, they cannot be viewed as a panacea, but rather as part of a continuing effort to prevent and respond to atrocities. [source] Numerical simulation of viscous fingering of shear-thinning fluidsTHE CANADIAN JOURNAL OF CHEMICAL ENGINEERING, Issue 6 2001Brajeesh K. Singh Abstract The viscous fingering instability of miscible shear-thinning fluids has been examined using a pseudo-spectral numerical technique based on the Hartley transform. The instability was studied for a flow in a rectilinear Hele-Shaw cell, and the shear-thinning character of the fluids has been modelied using the Carreau equation. New mechanisms of viscous fingering not previously observed in the case of similar Newtonian flow displacements have been identified. These mechanisms, which are reminiscent of the fractal patterns observed in experimental studies, were interpreted in terms of the velocity-dependent mobility of the flow. On a étudié l'instabilité de la digitation visqueuse pour des fluides rhéofluidifiants miscibles en utilisant une technique numérique pseudo-spectrale basée sur la transformation de Harley. L'instabilité a été étudiée pour un écoulement dans une cellule rectiligne de Hele-Shaw, et le caractère rhéofluidifiant des fluides a été modélisé par le modèle de Carreau. De nouveaux mécanismes de digitation visqueuse non observés antérieurement dans le cas de déplacements d'écoulements newtoniens similaires ont été identifiés. Ces mécanismes, qui rappellent les schémas fractals observés dans des études expérimentales, ont été interprétés en termes d'une mobilité dépendant de la vitesse de l'écoulement. [source] Accurate garbage collection in uncooperative environments revisited,CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 12 2009J. Baker Abstract Implementing a concurrent programming language such as Java by means of a translator to an existing language is attractive as it provides portability over all platforms supported by the host language and reduces development time,as many low-level tasks can be delegated to the host compiler. The C and C++ programming languages are popular choices for many language implementations due to the availability of efficient compilers on a wide range of platforms. For garbage-collected languages, however, they are not a perfect match as no support is provided for accurately discovering pointers to heap-allocated data on thread stacks. We evaluate several previously published techniques and propose a new mechanism, lazy pointer stacks, for performing accurate garbage collection in such uncooperative environments. We implemented the new technique in the Ovm Java virtual machine with our own Java-to-C/C++ compiler using GCC as a back-end compiler. Our extensive experimental results confirm that lazy pointer stacks outperform existing approaches: we provide a speedup of 4.5% over Henderson's accurate collector with a 17% increase in code size. Accurate collection is essential in the context of real-time systems, we thus validate our approach with the implementation of a real-time concurrent garbage collection algorithm. Copyright © 2009 John Wiley & Sons, Ltd. [source] Contextual constraint modeling in Grid application workflowsCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 10 2006Greg Graham Abstract This paper introduces a new mechanism for specifying constraints in distributed workflows. By introducing constraints in a contextual form, it is shown how different people and groups within collaborative communities can cooperatively constrain workflows. A comparison with existing state-of-the-art workflow systems is made. These ideas are explored in practice with an illustrative example from High-Energy Physics. Copyright © 2005 John Wiley & Sons, Ltd. [source] Vibration signals from the FT joint can induce phase transitions in both directions in motoneuron pools of the stick insect walking systemDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2003Ulrich Bässler Abstract The influence of vibratory signals from the femoral chordotonal organ fCO on the activities of muscles and motoneurons in the three main leg joints of the stick insect leg, i.e., the thoraco,coxal (TC) joint, the coxa,trochanteral (CT) joint, and the femur,tibia (FT) joint, was investigated when the animal was in the active behavioral state. Vibration stimuli induced a switch in motor activity (phase transition), for example, in the FT joint motor activity switched from flexor tibiae to extensor tibiae or vice versa. Similarly, fCO vibration induced phase transitions in both directions between the motoneuron pools of the TC joint and the CT joint. There was no correlation between the directions of phase transition in different joints. Vibration stimuli presented during simultaneous fCO elongation terminated the reflex reversal motor pattern in the FT joint prematurely by activating extensor and inactivating flexor tibiae motoneurons. In legs with freely moving tibia, fCO vibration promoted phase transitions in tibial movement. Furthermore, ground vibration promoted stance,swing transitions as long as the leg was not close to its anterior extreme position during stepping. Our results provide evidence that, in the active behavioral state of the stick insect, vibration signals can access the rhythm generating or bistable networks of the three main leg joints and can promote phase transitions in motor activity in both directions. The results substantiate earlier findings on the modular structure of the single-leg walking pattern generator and indicate a new mechanism of how sensory influence can contribute to the synchronization of phase transitions in adjacent leg joints independent of the walking direction. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 125,138, 2003 [source] Enhanced immunogenicity of CTL antigens through mutation of the CD8 binding MHC class,I invariant regionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2007Linda Wooldridge Abstract CD8+ cytotoxic T,lymphocytes (CTL) are key determinants of immunity to intracellular pathogens and neoplastic cells. Recognition of specific antigens in the form of peptide-MHC class,I complexes (pMHCI) presented on the target cell surface is mediated by T cell receptor (TCR) engagement. The CD8 coreceptor binds to invariant domains of pMHCI and facilitates antigen recognition. Here, we investigate the biological effects of a Q115E substitution in the ,2,domain of human leukocyte antigen (HLA)-A*0201 that enhances CD8 binding by,,50% without altering TCR/pMHCI interactions. Soluble and cell surface-expressed forms of Q115E HLA-A*0201 exhibit enhanced recognition by CTL without loss of specificity. These CD8-enhanced antigens induce greater CD3 ,,chain phosphorylation in cognate CTL leading to substantial increases in cytokine production, proliferation and priming of naive T cells. This effect provides a fundamental new mechanism with which to enhance cellular immunity to specific T cell antigens. [source] Proximal changes in signal transduction that modify CD8+ T cell responsiveness in vivoEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2003Séverine Guillaume Abstract The antigen dose conditions the functional properties of CD8+ T cells generated after priming. At relatively low antigen doses, efficient memory T cells may be generated, while high antigen doses lead to tolerance. To determine the mechanisms leading to such different functional outcomes, we compared the proximal TCR signal transduction of naive cells, to that of memory or high-dose tolerant cells generated in vivo. In vivo activation led to the constitutive phosphorylation of CD3,, recruiting Zap70, in both memory and tolerant cells. In tolerant cells, these phenomena were much more marked, the CD3, and , chains no longer associated, and the Src kinases p56Lck and p59Fyn were inactive. Therefore, when the antigen load overcomes the capacities of immune control, a new mechanism intervenes to block signal transduction: the recruitment of Zap70 to CD3, becomes excessive, leading to TCR complex destabilization, Src kinase dysfunction, and signal arrest. [source] Dendritic nicotinic receptors modulate backpropagating action potentials and long-term plasticity of interneuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2008Balázs Rózsa Abstract Stratum radiatum interneurons, unlike pyramidal cells, are rich in nicotinic acetylcholine receptors (nAChRs); however, the role of these receptors in plasticity has remained elusive. As opposed to previous physiological studies, we found that functional ,7-subunit-containing nAChRs (,7-nAChRs) are abundant on interneuron dendrites of rats. Moreover, dendritic Ca2+ transients induced by activation of ,7-nAChRs increase as a function of distance from soma. The activation of these extrasynaptic ,7-nAChRs by cholinergic agonists either facilitated or depressed backpropagating action potentials, depending on the timing of ,7-nAChR activation. We have previously shown that dendritic ,7-nAChRs are involved in the regulation of synaptic transmission, suggesting that ,7-nAChRs may play an important role in the regulation of the spike timing-dependent plasticity. Here we provide evidence that long-term potentiation is indeed boosted by stimulation of dendritic ,7-nAChRs. Our results suggest a new mechanism for a cholinergic switch in memory encoding and retrieval. [source] Erythropoietin protects the in vitro blood,brain barrier against VEGF-induced permeabilityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2003Ofelia María Martínez-Estrada Abstract The blood,brain barrier (BBB) ensures the homeostasis of the brain microenvironment, mostly through complex tight junctions between brain endothelial cells that prevent the passage of hydrophilic molecules from blood to brain and vice versa. A recent study has shown in vivo that systemic administration of erythropoietin (Epo) protects against brain injury. Using an in vitro model of the bovine BBB, we observed that the expression of the Epo receptor is modulated by its ligand and hypoxic stimuli such as vascular endothelial growth factor (VEGF) treatment. In addition, Epo protects against the VEGF-induced permeability of the BBB, decreases the levels of endothelial nitric oxide synthase and restores junction proteins. The kinetic transport experiments revealed the capacity of Epo to cross the in vitro BBB in a saturable and specific way. Our results suggest a new mechanism for Epo-induced neuroprotection, in which circulating Epo controls and maintains the BBB through an Epo receptor signalling pathway and the re-establishment of cell junctions. [source] Importance of tyrosine residues of Bacillus stearothermophilus serine hydroxymethyltransferase in cofactor binding and l - allo -Thr cleavageFEBS JOURNAL, Issue 18 2008Crystal structure, biochemical studies Serine hydroxymethyltransferase (SHMT) from Bacillus stearothermophilus (bsSHMT) is a pyridoxal 5,-phosphate-dependent enzyme that catalyses the conversion of l -serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. In addition, the enzyme catalyses the tetrahydrofolate-independent cleavage of 3-hydroxy amino acids and transamination. In this article, we have examined the mechanism of the tetrahydrofolate-independent cleavage of 3-hydroxy amino acids by SHMT. The three-dimensional structure and biochemical properties of Y51F and Y61A bsSHMTs and their complexes with substrates, especially l - allo -Thr, show that the cleavage of 3-hydroxy amino acids could proceed via C, proton abstraction rather than hydroxyl proton removal. Both mutations result in a complete loss of tetrahydrofolate-dependent and tetrahydrofolate-independent activities. The mutation of Y51 to F strongly affects the binding of pyridoxal 5,-phosphate, possibly as a consequence of a change in the orientation of the phenyl ring in Y51F bsSHMT. The mutant enzyme could be completely reconstituted with pyridoxal 5,-phosphate. However, there was an alteration in the ,max value of the internal aldimine (396 nm), a decrease in the rate of reduction with NaCNBH3 and a loss of the intermediate in the interaction with methoxyamine (MA). The mutation of Y61 to A results in the loss of interaction with C, and C, of the substrates. X-Ray structure and visible CD studies show that the mutant is capable of forming an external aldimine. However, the formation of the quinonoid intermediate is hindered. It is suggested that Y61 is involved in the abstraction of the C, proton from 3-hydroxy amino acids. A new mechanism for the cleavage of 3-hydroxy amino acids via C, proton abstraction by SHMT is proposed. [source] Comparative metal binding and genomic analysis of the avian (chicken) and mammalian metallothioneinFEBS JOURNAL, Issue 3 2006Laura Villarreal Chicken metallothionein (ckMT) is the paradigm for the study of metallothioneins (MTs) in the Aves class of vertebrates. Available literature data depict ckMT as a one-copy gene, encoding an MT protein highly similar to mammalian MT1. In contrast, the MT system in mammals consists of a four-member family exhibiting functional differentiation. This scenario prompted us to analyse the apparently distinct evolutionary patterns followed by MTs in birds and mammals, at both the functional and structural levels. Thus, in this work, the ckMT metal binding abilities towards Zn(II), Cd(II) and Cu(I) have been thoroughly revisited and then compared with those of the mammalian MT1 and MT4 isoforms, identified as zinc- and copper-thioneins, respectively. Interestingly, a new mechanism of MT dimerization is reported, on the basis of the coordinating capacity of the ckMT C-terminal histidine. Furthermore, an evolutionary study has been performed by means of in silico analyses of avian MT genes and proteins. The joint consideration of the functional and genomic data obtained questions the two features until now defining the avian MT system. Overall, in vivo and in vitro metal-binding results reveal that the Zn(II), Cd(II) and Cu(I) binding abilities of ckMT lay between those of mammalian MT1 and MT4, being closer to those of MT1 for the divalent metal ions but more similar to those of MT4 for Cu(I). This is consistent with a strong functional constraint operating on low-copy number genes that must cope with differentiating functional limitation. Finally, a second MT gene has been identified in silico in the chicken genome, ckMT2, exhibiting all the features to be considered an active coding region. The results presented here allow a new insight into the metal binding abilities of warm blooded vertebrate MTs and their evolutionary relationships. [source] Allosteric activation of pyruvate kinase via NAD+ in rat liver cellsFEBS JOURNAL, Issue 14 2001Anne Devin In isolated rat hepatocytes, it has previously been reported that a rise in the ATP content induces a proportional increase in cytosolic NAD+ concentration [Devin, A., Guérin, B. & Rigoulet, M. (1997) FEBS Lett.410, 329,332]. This occurs under physiological conditions such as various substrates or different energetic states. To investigate the effect of a physiological rise in cytosolic [NAD+] per se on glycolysis and gluconeogenesis, an increase in [NAD+] induced by exogenous nicotinamide addition was obtained without a change in redox potential, ATP/ADP ratio and ATP concentration. Using dihydroxyacetone as substrate, we found that an increase in cytosolic [NAD+] decreases gluconeogenesis and enhances glycolysis without significant alteration of dihydroxyacetone consumption rate. These modifications are the consequence of an allosteric activation of pyruvate kinase via cytosolic NAD+ content. Thus, in addition to the well-known thermodynamic control of glycolysis by pyridine-nucleotide redox status, our study points to a new mechanism of glycolytic flux regulation by NAD+ concentration at the level of pyruvate kinase activity. [source] Rearrangement of upstream sequences of the hTERT gene during cellular immortalizationGENES, CHROMOSOMES AND CANCER, Issue 11 2009Yuanjun Zhao Telomerase expression, resulting from transcriptional activation of the hTERT gene, allows cells to acquire indefinite proliferative potential during cellular immortalization and tumorigenesis. However, mechanisms of hTERT gene activation in many immortal cell lines and cancer cells are poorly understood. Here, we report our studies on hTERT activation using genetically related pairs of telomerase-negative (Tel,) and -positive (Tel+) fibroblast lines. First, whereas transiently transfected plasmid reporters did not recapitulate the endogenous hTERT promoter, the promoter in chromosomally integrated bacterial artificial chromosome (BAC) reporters was activated in a subset of Tel+ cells, indicating that activation of the hTERT promoter required native chromatin context and/or distal regulatory elements. Second, the hTERT gene, located near the telomere of chromosome 5p, was translocated in all three Tel+ cell lines but not in their parental precrisis cells and Tel, immortal siblings. The breakage points were mapped to regions upstream of the hTERT promoter, indicating that the hTERT gene was the target of these chromosomal rearrangements. In two Tel+ cell lines, translocation of the endogenous hTERT gene appeared to be the major mechanism of its activation as the activity of hTERT promoter in many chromosomally integrated BAC reporters, with intact upstream and downstream neighboring loci, remained relatively low. Therefore, our results suggest that rearrangement of upstream sequences is an important new mechanism of hTERT promoter activation during cellular immortalization. The chromosomal rearrangements likely occurred during cellular crisis and facilitated by telomere dysfunction. Such translocations allowed the hTERT promoter to escape from the native condensed chromatin environment. © 2009 Wiley-Liss, Inc. [source] Nanodot Formation: Spontaneous Outcropping of Self-Assembled Insulating Nanodots in Solution-Derived Metallic Ferromagnetic La0.7Sr0.3MnO3 Films (Adv. Funct.ADVANCED FUNCTIONAL MATERIALS, Issue 13 2009Mater. Epitaxial self-assembled Sr-La oxide insulating nanodots are formed through a new mechanism at the surface of an epitaxial metallic ferromagnetic La0.7Sr0.3MnO3 film grown on SrTiO3 from chemical solutions, as reported by C. Moreno et al. on page 2139. TEM analysis reveals that, underneath the La-Sr oxide nanodots, the film switches from the compressive out-of-plane stress component to a tensile component. [source] Spontaneous Outcropping of Self-Assembled Insulating Nanodots in Solution-Derived Metallic Ferromagnetic La0.7Sr0.3MnO3 FilmsADVANCED FUNCTIONAL MATERIALS, Issue 13 2009César Moreno Abstract A new mechanism is proposed for the generation of self-assembled nanodots at the surface of a film based on spontaneous outcropping of the secondary phase of a nanocomposite epitaxial film. Epitaxial self-assembled Sr,La oxide insulating nanodots are formed through this mechanism at the surface of an epitaxial metallic ferromagnetic La0.7Sr0.3MnO3 (LSMO) film grown on SrTiO3 from chemical solutions. TEM analysis reveals that, underneath the La,Sr oxide (LSO) nanodots, the film switches from the compressive out-of-plane stress component to a tensile one. It is shown that the size and concentration of the nanodots can be tuned by means of growth kinetics and through modification of the La excess in the precursor chemical solution. The driving force for the nanodot formation can be attributed to a cooperative effect involving the minimization of the elastic strain energy and a thermodynamic instability of the LSMO phase against the formation of a Ruddelsden,Popper phase Sr3Mn4O7 embedded in the film, and LSO surface nanodots. The mechanism can be described as a generalization of the classical Stranski,Krastanov growth mode involving phase separation. LSO islands induce an isotropic strain to the LSMO film underneath the island which decreases the magnetoelastic contribution to the magnetic anisotropy. [source] Octamer 4 (Oct4) mediates chemotherapeutic drug resistance in liver cancer cells through a potential Oct4,AKT,ATP-binding cassette G2 pathway,HEPATOLOGY, Issue 2 2010Xiao Qi Wang Chemoresistance presents a major obstacle to the efficacy of chemotherapeutic treatment of cancers. Using chemotherapeutic drugs to select drug-resistant cancer cells in hepatocellular carcinoma (HCC) and several other cancer cell lines, we demonstrate that chemoresistant cells displayed cancer stem cell features, such as increased self-renewal ability, cell motility, multiple drug resistance, and tumorigenicity. Octamer 4 (Oct4) messenger RNA (mRNA) levels were dramatically increased in chemoresistant cancer cells due to DNA demethylation regulation of Oct4. By functional study, Oct4 overexpression enhanced whereas Oct4 knockdown reduced liver cancer cell resistance to chemotherapeutic drugs in vitro and in xenograft tumors. It is known that the Oct4-TCL1-AKT pathway acts on embryonic stem cells and cancer stem cells in cell proliferation through inhibition of apoptosis. We further demonstrate that Oct4 overexpression induced activation of TCL1, AKT, and ABCG2 to mediate chemoresistance, which can be overcome by addition of the PI3K/AKT inhibitor; therefore, a direct pathway of Oct4-TCL1-AKT-ABCG2 or a combination of Oct4-TCL1-AKT with the AKT-ABCG2 pathway could be a potential new mechanism involved in liver cancer cell chemoresistance. Moreover, the clinical significance of the Oct4-AKT-ABCG2 pathway can be demonstrated in HCC patients, with a strong correlation of expression patterns in human HCC tumors. The role of the Oct4-AKT-ABCG2 axis in cancer cell chemoresistant machinery suggests that AKT pathway inhibition (PI3K inhibitors) not only inhibits cancer cell proliferation, but may also enhance chemosensitivity by target potential chemoresistant cells. Conclusion: Oct4, a transcriptional factor of pluripotent cells, can mediate chemoresistance through a potential Oct4-AKT-ABCG2 pathway. (HEPATOLOGY 2010;) [source] Laminin-5 stimulates hepatocellular carcinoma growth through a different function of ,6,4 and ,3,1 integrins,HEPATOLOGY, Issue 6 2007Carlo Bergamini Hepatocellular carcinoma (HCC) growth severely affects prognosis. Ki-67, a known marker of cell proliferation, is a negative prognostic factor in HCC. Growth factors such as the epidermal growth factor (EGF) induce HCC cell proliferation but do not explain the great heterogeneity of HCC growth. Laminin-5 (Ln-5) is an extracellular matrix protein (ECM) present in the tissue microenvironment of HCC. The two main receptors for Ln-5, integrins ,3,1 and ,6,4, are expressed on the cell surface of HCC cells. The aim of this study is to investigate an alternative mechanism of HCC growth whereby Ln-5 promotes HCC cell proliferation through ,3,1 and ,6,4. HCC tissues containing Ln-5 display a larger diameter and higher number of positive cells for Ki-67, a well known proliferative index, as determined by double immunofluorescence staining and real-time PCR on microdissected tissues. In vitro, Ln-5, but not collagen I, collagen IV or fibronectin, induces proliferation as much as EGF does, via Erk phosphorylation as a consequence of ,4 integrin phosphorylation. However, the two HCC cell lines do not proliferate in presence of Ln-5 despite ,4 integrin and Erk1/2 activation. After transfection with ,3 integrin, in the presence of Ln-5 one of these HCC cell lines acquires a proliferative activity whereas one of the proliferative HCC cell lines, knocked-down for ,3 integrin, loses its proliferative activity. Conclusions: Our study suggests a new mechanism of HCC growth whereby Ln-5 stimulates proliferation via a different function of ,6,4 and ,3,1. (HEPATOLOGY 2007.) [source] Understanding the Nature of Ultrafast Polarization Dynamics of Ferroelectric Memory in the Multiferroic BiFeO3ADVANCED MATERIALS, Issue 28 2009Dhanvir Singh Rana The crystallographic anisotropy in electromagnetic terahertz radiation from multiferroic BiFeO3 (100), (110), and (111) films suggests the ultrafast depolarization of ferroelectric order as a new mechanism of terahertz emission. This implies that the spontaneous polarization in ferroelectric materials can be manipulated in time scale of picoseconds, thus paving the way to ultrafast data-storage devices based on nonvolatile ferroelectric memories. [source] MYCN regulates oncogenic MicroRNAs in neuroblastomaINTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Johannes H. Schulte Abstract MYCN amplification is a common feature of aggressive tumour biology in neuroblastoma. The MYCN transcription factor has been demonstrated to induce or repress expression of numerous genes. MicroRNAs (miRNA) are a recently discovered class of short RNAs that repress translation and promote mRNA degradation by sequence-specific interaction with mRNA. Here, we sought to analyse the role of MYCN in regulation of miRNA expression. Using a miRNA microarray containing 384 different miRNAs and a set of 160 miRNA real-time PCR assays to validate the microarray results, 7 miRNAs were identified that are induced by MYCN in vitro and are upregulated in primary neuroblastomas with MYCN amplification. Three of the seven miRNAs belong to the miR-106a and miR-17 clusters, which have previously been shown to be regulated by c-Myc. The miR-17,92 polycistron also acts as an oncogene in haematopoietic progenitor cells. We show here that miR-221 is also induced by MYCN in neuroblastoma. Previous studies have reported miR-221 to be overexpressed in several other cancer entities, but its regulation has never before been associated with Myc. We present evidence of miRNA dysregulation in neuroblastoma. Additionally, we report miRNA induction to be a new mechanism of gene expression downregulation by MYCN. © 2007 Wiley-Liss, Inc. [source] A New Scenario in Probe Local Oxidation: Transient Pressure-Wave-Assisted Ionic Spreading and Oxide Pattern Formation,ADVANCED MATERIALS, Issue 18 2007N. Xie A new mechanism based on transient shock-wave-assisted lateral ionic spreading and oxide growth is reported for atomic force microscopy probe local oxidation (see figure). Transitory high pressure waves generated in the nanoscopic tip,sample junction significantly extend the distribution of hydroxyl oxidants to facilitate micrometer-scale disk-oxide growth on a silicon substrate. The results show that shock propagation may be a general phenomenon in AFM nanolithography. [source] MLCC: A new hash-chained mechanism for multicast source authenticationINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 9 2009H. Eltaief Abstract Asymmetric cryptography has been widely used to generate a digital signature for message authentication. However, such a strategy cannot be used for packet authentication. Neither the source nor the receiver will be capable of handling the computational cost of asymmetric cryptography. For unicast communication, the solution adopted is based on symmetric cryptography. Solutions based on symmetric cryptography do not scale for multicast communication. Several solutions have been reported to authenticate multicast streams, with the possibility of packet losses. Proposed solutions are based on the concept of signature amortization, where a single signature is amortized on several packets. In this paper we present a new mechanism for multicast data source authentication based on signature amortization. Multi-layers connected chains divides the packet stream into a multi-layer structure, where each layer is a two-dimensional matrix. The hash of a packet is included into a forward chain of packets within the same layer as well as a downward chain of packets across multiple layers. The values of the key parameters that influence the mechanism efficiency as well as its performance are selected following a mathematical analysis. Comparisons of performance results with the well-known efficient multi-chained stream signature scheme as well as a recently reported scheme multiple connected chains model show that the proposed mechanism achieves a stronger resistance to packet losses with low overhead and high authentication probability. Copyright © 2008 John Wiley & Sons, Ltd. [source] WTCP: an efficient mechanism for improving wireless access to TCP servicesINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 1 2003Karunaharan Ratnam Abstract The transmission control protocol (TCP) has been mainly designed assuming a relatively reliable wireline network. It is known to perform poorly in the presence of wireless links because of its basic assumption that any loss of a data segment is due to congestion and consequently it invokes congestion control measures. However, on wireless access links, a large number of segment losses will occur more often because of wireless link errors or host mobility. For this reason, many proposals have recently appeared to improve TCP performance in such environment. They usually rely on the wireless access points (base stations) to locally retransmit the data in order to hide wireless losses from TCP. In this paper, we present Wireless-TCP (WTCP), a new mechanism for improving wireless access to TCP services. We use extensive simulations to evaluate TCP performance in the presence of congestion and wireless losses when the base station employs WTCP, and the well-known Snoop proposal (A comparison of mechanisms for improving TCP performance in wireless networks. In ACM SIGCOMM Symposium on Communication, Architectures and Protocols, August 1996). Our results show that WTCP significantly improves the throughput of TCP connections due to its unique feature of hiding the time spent by the base station to locally recover from wireless link errors so that TCPs round trip time estimation at the source is not affected. This proved to be critical since otherwise the ability of the source to effectively detect congestion in the fixed wireline network is hindered. Copyright © 2003 John Wiley & Sons, Ltd. [source] A Simple, Effective Boron-Halide Ethoxylation CatalystADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 5 2010Kenneth Abstract Boron esters B(OR)3, readily derived from boric acid and alcohols, combine with iodide or bromide to catalyze the ethoxylation of alcohols and phenols, giving good rates and narrow product distributions. The combined action of a weak electrophile [B(OR)3] and a weak nucleophile (halide) allows for the ethoxylation of base-sensitive alcohols. Experiment suggests a new mechanism for this commercially important reaction proceeding through key ,-haloalkoxy intermediates. [source] Structure of charge-transfer reaction complexes in anionic polymerization of isoprene: Quantum chemical calculationsINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 2 2005K. K. Kalninsh Abstract A new mechanism of isoprene anionic polymerization is proposed. Its central moment is thermal electronic excitation of a living polyisoprene,isoprene complex into the quasi-degenerate electronically excited state (S · T)1, which is of the charge (electron) transfer character. It is asserted that the probability of chemical bond formation is determined by the free valence index on carbon atoms and by the geometry of reacting complex in the excited state (S · T)1. Semi-empirical AM1 and ab initio 6-31G* quantum chemical calculations revealed low energies of triplet excited levels (<10 kcal/mole). Comparison of isoprene polymerization on free anions and on solvated ion pairs shows that both types of active centers produce vinyl 1,2 (4,3)-units. Free anions generate predominantly 1,2-units, whereas solvated ion pairs tend to form units with the 4,3-structure. Analysis of energies of excited isoprenyl lithium + isoprene complexes shows that the formation of 1,4 (4,1)- cis -polyisoprene in an inert media is most preferable. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [source] The role of PAS kinase in regulating energy metabolismIUBMB LIFE, Issue 4 2008Huai-Xiang Hao Abstract Metabolic disorders, such as diabetes and obesity, are fundamentally caused by cellular energy imbalance and dysregulation. Therefore, understanding the regulation of cellular fuel and energy metabolism is of great importance to develop effective therapies for metabolic disease. The cellular nutrient and energy sensors, AMPK and TOR, play a key role in maintaining cellular energy homeostasis. Like AMPK and TOR, PAS kinase (PASK) is also a nutrient responsive protein kinase. In yeast, PAS kinase phosphorylates the enzyme Ugp1 and thereby shifts glucose partitioning toward cell wall glucan synthesis at the expense of glycogen synthesis. Consistent with this function, yeast PAS kinase is activated by both cell integrity stress and growth in non-fermentative carbon sources. PASK is also important for proper regulation of glucose metabolism in mammals at both the hormonal and cellular level. In cultured pancreatic ,-cells, PASK is activated by elevated glucose concentrations and is required for glucose-stimulated transcription of the insulin gene. PASK knockdown in cultured myoblasts causes increased glucose oxidation and elevated cellular ATP levels. Mice lacking PASK exhibit increased metabolic rate and resistance to diet-induced obesity. Interestingly, PGC-1 expression and AMPK and TOR activity were not affected in PASK deficient mice, suggesting PASK may exert its metabolic effects through a new mechanism. We propose that PASK plays a significant role in nutrient sensing, metabolic regulation, and energy homeostasis, and is a potential therapeutic target for metabolic disease. © 2008 IUBMB IUBMB Life, 60(4): 204,209, 2008 [source] Toughening of recycled polystyrene used for TV backsetJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2008Xiaoting Fu Abstract The recycled polystyrene (rPS) was toughened with ethylene-octylene copolymer thermoplastic elastomer (POE) and high-density polyethylene (HDPE) with various melt flow index (MFI), compatibilized by styrene-butadiene-styrene copolymer (SBS) to enhance the toughness of rPS for use as TV backset. The rPS/POE binary blends exhibited an increased impact strength with 5,10 wt % POE content followed by a decrease with the POE content up to 20 wt %, which could be due to poor compatibility between POE and rPS. For rPS/POE/SBS ternary blends with 20 wt % of POE content, the impact strength increased dramatically and a sharp brittle-ductile transition was observed as the SBS content was around 3,5 wt %. Rheological study indicated a possible formation of network structure by adding of SBS, which could be a new mechanism for rPS toughening. In rPS/POE/HDPE/SBS (70/20/5/5) quaternary blends, a fibril-like structure was observed as the molecular weight of HDPE was higher (with lower MFI). The presence of HDPE fibers in the blends could not enhance the network structure, but could stop the crack propagation during fracture process, resulting in a further increase of the toughness. The prepared quaternary blend showed an impact strength of 9.3 kJ/m2 and a tensile strength of 25 MPa, which can be well used for TV backset to substitute HIPS because this system is economical and environmental friendly. © 2008 Wiley Periodicals, Inc. 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