Ion Transport in a Polymer-Plastic Solid Soft Matter Electrolyte in the Light of Solvent Dynamics and Ion Association

Ion transport in a recently demonstrated promising soft matter solid plastic-polymer electrolyte is discussed here in the context of solvent dynamics and ion association. The plastic-polymer composite electrolytes display liquid-like ionic conductivity in the solid state,compliable mechanical strength (similar to 1 MPa), and wide electrochemical voltage stability (>= 5 V). Polyacrylonitrile (PAN) dispersed in lithium perchlorate (LiClO4)-succinonitrile (SN) was chosen as the model system for the study (abbreviated LiClO4-SN:PAN). Systematic observation of various mid-infrared isomer and ion association bands as a function of temperature and polyme concentration shows an effective increase in trans conformer concentration along with free Li+ ion concentration. This strongly supports the view that enhancement in LiClO4-SN:PAN ionic conductivity over the neat plastic electrolyte (LiClO4-SN) is due to both increase in charge mobility and concentration. The ionic conductivity and infrared spectroscopy studies are supported by Brillouin light scattering. For the LiClO4-SN:PAN composites, a peak at 17 GHz was observed in addition to the normal trans-gauche isomerism (as in neat SN) at 12 GHz. The fast process is attributed to increased dynamics of those SN molecules whose energy barrier of transition from gauche to trans has reduced under influences induced by the changes in temperature and polymer concentration. The observations from ionic conductivity, spectroscopy, and light scattering studies were further supplemented by temperature dependent nuclear magnetic resonance H-1 and Li-7 line width measurements.

Mode coupling theory analysis of electrolyte solutions: Time dependent diffusion, intermediate scattering function, and ion solvation dynamics

A self-consistent mode coupling theory (MCT) with microscopic inputs of equilibrium pair correlation functions is developed to analyze electrolyte dynamics. We apply the theory to calculate concentration dependence of (i) time dependent ion diffusion, (ii) intermediate scattering function of the constituent ions, and (iii) ion solvation dynamics in electrolyte solution. Brownian dynamics with implicit water molecules and molecular dynamics method with explicit water are used to check the theoretical predictions. The time dependence of ionic self-diffusion coefficient and the corresponding intermediate scattering function evaluated from our MCT approach show quantitative agreement with early experimental and present Brownian dynamic simulation results. With increasing concentration, the dispersion of electrolyte friction is found to occur at increasingly higher frequency, due to the faster relaxation of the ion atmosphere. The wave number dependence of intermediate scattering function, F(k, t), exhibits markedly different relaxation dynamics at different length scales. At small wave numbers, we find the emergence of a step-like relaxation, indicating the presence of both fast and slow time scales in the system. Such behavior allows an intriguing analogy with temperature dependent relaxation dynamics of supercooled liquids. We find that solvation dynamics of a tagged ion exhibits a power law decay at long times-the decay can also be fitted to a stretched exponential form. The emergence of the power law in solvation dynamics has been tested by carrying out long Brownian dynamics simulations with varying ionic concentrations. The solvation time correlation and ion-ion intermediate scattering function indeed exhibit highly interesting, non-trivial dynamical behavior at intermediate to longer times that require further experimental and theoretical studies. (c) 2015 AIP Publishing LLC.

Electron-Nuclear Correlation in Laser-Driven Diatomic Molecules

The interaction of short intense laser pulses with atoms/molecules produces a multitude of highly nonlinear processes requiring a non-perturbative treatment. Detailed study of these highly nonlinear processes by numerically solving the time-dependent Schrodinger equation becomes a daunting task when the number of degrees of freedom is large. Also the coupling between the electronic and nuclear degrees of freedom further aggravates the computational problems. In the present work we show that the time-dependent Hartree (TDH) approximation, which neglects the correlation effects, gives unreliable description of the system dynamics both in the absence and presence of an external field. A theoretical framework is required that treats the electrons and nuclei on equal footing and fully quantum mechanically. To address this issue we discuss two approaches, namely the multicomponent density functional theory (MCDFT) and the multiconfiguration time-dependent Hartree (MCTDH) method, that go beyond the TDH approximation and describe the correlated electron-nuclear dynamics accurately. In the MCDFT framework, where the time-dependent electronic and nuclear densities are the basic variables, we discuss an algorithm to calculate the exact Kohn-Sham (KS) potentials for small model systems. By simulating the photodissociation process in a model hydrogen molecular ion, we show that the exact KS potentials contain all the many-body effects and give an insight into the system dynamics. In the MCTDH approach, the wave function is expanded as a sum of products of single-particle functions (SPFs). The MCTDH method is able to describe the electron-nuclear correlation effects as the SPFs and the expansion coefficients evolve in time and give an accurate description of the system dynamics. We show that the MCTDH method is suitable to study a variety of processes such as the fragmentation of molecules, high-order harmonic generation, the two-center interference effect, and the lochfrass effect. We discuss these phenomena in a model hydrogen molecular ion and a model hydrogen molecule. Inclusion of absorbing boundaries in the mean-field approximation and its consequences are discussed using the model hydrogen molecular ion. To this end, two types of calculations are considered: (i) a variational approach with a complex absorbing potential included in the full many-particle Hamiltonian and (ii) an approach in the spirit of time-dependent density functional theory (TDDFT), including complex absorbing potentials in the single-particle equations. It is elucidated that for small grids the TDDFT approach is superior to the variational approach.

Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18

Background: Implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanisms. A hepatic melanoma metastasis model where a majority of metastases are generated via interleukin-18-dependent mechanisms was used to test whether anti-inflammatory properties of resveratrol can interfere with mechanisms of metastasis. Methods: Two experimental treatment schedules were used: 1) Mice received one daily oral dose of 1 mg/kg resveratrol after cancer cell injection and the metastasis number and volume were determined on day 12. 2) Mice received one daily oral dose of 1 mg/kg resveratrol along the 5 days prior to the injection of cancer cells and both interleukin-18 (IL-18) concentration in the hepatic blood and microvascular retention of luciferase-transfected B16M cells were determined on the 18(th) hour. In vitro, primary cultured hepatic sinusoidal endothelial cells were treated with B16M-conditioned medium to mimic their in vivo activation by tumor-derived factors and the effect of resveratrol on IL-18 secretion, on vascular cell adhesion molecule-1 (VCAM-1) expression and on tumor cell adhesion were studied. The effect of resveratrol on melanoma cell activation by IL-18 was also studied. Results: Resveratrol remarkably inhibited hepatic retention and metastatic growth of melanoma cells by 50% and 75%, respectively. The mechanism involved IL-18 blockade at three levels: First, resveratrol prevented IL-18 augmentation in the blood of melanoma cell-infiltrated livers. Second, resveratrol inhibited IL-18-dependent expression of VCAM-1 by tumor-activated hepatic sinusoidal endothelium, preventing melanoma cell adhesion to the microvasculature. Third, resveratrol inhibited adhesion-and proliferation-stimulating effects of IL-18 on metastatic melanoma cells through hydrogen peroxide-dependent nuclear factor-kappaB translocation blockade on these cells. Conclusions: These results demonstrate multiple sites for therapeutic intervention using resveratrol within the prometastatic microenvironment generated by tumor-induced hepatic IL-18, and suggest a remarkable effect of resveratrol in the prevention of inflammation-dependent melanoma metastasis in the liver.

Energetic protons emitted from coulomb explosion dynamics of large-sized hydrogen clusters driven by an ultrashort intense laser pulse

Protons with very high kinetic energy of about 10keV and the saturation effect of proton energy for laser intensity have been observed in the interaction of an ultrashort intense laser pulse with large-sized hydrogen clusters. Including the cluster-size distribution as well as the laser-intensity distribution on the focus spot, the theoretical calculations based on a simplified Coulomb explosion model have been compared with our experimental measurements, which are in good agreement with each other.

Klebsiella pneumoniae targets an EGF receptor-dependent pathway to subvert inflammation

The NF-kB transcriptional factor plays a key role governing the activation of immune responses. Klebsiella pneumoniae is an important cause of community-acquired and nosocomial pneumonia. Evidence indicates that K. pneumoniae infections are characterized by lacking an early in?ammatory response. Recently, we have demonstrated that Klebsiella antagonizes the activation of NF-kB via the deubiquitinase CYLD. In this work, by applying a high-throughput siRNA gain-of-function screen interrogating the human kinome, we identi?ed 17 kinases that when targeted by siRNA restored IL-1b-dependent NF-kB translocation in infected cells. Further characterization revealed that K. pneumoniae activates an EGF receptor (EGFR)- phosphatidylinositol 3-OH kinase (PI3K)–AKT–PAK4–ERK–GSK3b signalling pathway to attenuate the cytokine-dependent nuclear translocation of NF-kB. Our data also revealed that CYLD is a downstream effector of K. pneumoniae-induced EGFR–
PI3K–AKT–PAK4–ERK–GSK3b signalling pathway. Our efforts to identify the bacterial factor(s) responsible for EGFR activation demonstrate that a capsule (CPS) mutant did not activate EGFR hence
suggesting that CPS could mediate the activation of EGFR. Supporting this notion, puri?ed CPS did activate EGFR as well as the EGFR-dependent PI3K–AKT–PAK4–ERK–GSK3b signalling pathway. CPS-mediated EGFR activation was dependent on a TLR4–MyD88–c-SRC-dependent pathway. Several promising drugs have been developed to antagonize this cascade. We propose that agents targeting this signalling pathway might provide selective alternatives for the management of K. pneumoniae pneumonias.

Structural basis for the nuclear import of the human androgen receptor

Ligand-dependent nuclear import is crucial for the function of the androgen receptor (AR) in both health and disease. The unliganded AR is retained in the cytoplasm but, on binding 5alpha-dihydrotestosterone, it translocates into the nucleus and alters transcription of its target genes. Nuclear import of AR is mediated by the nuclear import factor importin-alpha, which functions as a receptor that recognises and binds to specific nuclear localisation signal (NLS) motifs on cargo proteins. We show here that the AR binds to importin-alpha directly, albeit more weakly than the NLS of SV40 or nucleoplasmin. We describe the 2.6-angstroms-resolution crystal structure of the importin-alpha-AR-NLS complex, and show that the AR binds to the major NLS-binding site on importin-alpha in a manner different from most other NLSs. Finally, we have shown that pathological mutations within the NLS of AR that are associated with prostate cancer and androgen-insensitivity syndrome reduce the binding affinity to importin-alpha and, subsequently, retard nuclear import; surprisingly, however, the transcriptional activity of these mutants varies widely. Thus, in addition to its function in the nuclear import of AR, the NLS in the hinge region of AR has a separate, quite distinct role on transactivation, which becomes apparent once nuclear import has been achieved.

Études spectroscopiques expérimentales et théoriques de complexes de métaux de transition

Cette thèse présente une série d'études qui visent la compréhension de la structure électronique de complexes de métaux de transition en employant diverses méthodes de spectroscopie. L'information sur la structure électronique aide à comprendre et développer des nouveaux matériaux, des nouvelles voies de synthèses, ainsi que des nouveaux modèles théoriques. Habituellement, afin d'explorer la structure électronique d'un système qui comporte en son centre un métal de transition, l'information fournie par les spectres d'un seul composé n'est pas suffisante. On étudie une série de composés similaires, qui ont le même métal de transition à un degré d'oxydation donné, ainsi que des ligands qui forment des liaisons de différentes forces et caractéristiques avec le métal. Cependant, ces changements, bien qu'on les désire de faible impact, créent une grande perturbation de la structure électronique visée par les études. Afin d'étudier en profondeur une seule structure électronique, nous employons une stratégie d'analyse moins perturbante. Nous appliquons une pression hydrostatique sur les complexes de métaux de transition. Cette pression perturbe le système suffisamment pour nous livrer davantage d'informations sur la structure électronique, sans la « dénaturer ». Afin d'étudier précisément ces systèmes perturbés, la technique d'application de pression est conjuguée, dans la littérature, aux diverses techniques de spectroscopie d'absorption UV-visible, de luminescence, ainsi que de diffusion Raman. Pour extraire un maximum d'informations de ces expériences, on emploie des techniques de calculs de structure électronique ainsi que de dynamique des noyaux. Dans cette thèse, on tente de mettre en lumière la structure électronique de composés de molybdène(IV), de platine(II) et palladium(II) à l'aide de la technique de pression couplée aux spectroscopies de luminescence et de diffusion Raman. Dans le chapitre 3, on observe un déplacement de la bande de luminescence de +12 cm-1/kbar entre la pression ambiante et 25 kbar pour le complexe trans-[MoOCl(CN-t-Bu)4]BPh4, dont le centre métallique molybdène(IV)est de configuration électronique 4d2. Il s'agit de la première variation positive observée pour un complexe de type métal-oxo. À des pressions plus élevées, la tendance s'inverse. Le maximum d'énergie de la bande de luminescence se déplace de -8 cm-1/kbar. Ce changement de variation présage d'une compétition interne entre les ligands situés sur les différents axes de l'octaèdre. À l'aide de calculs basés sur la théorie de la fonctionnelle de la densité, on propose un mécanisme pour expliquer ce phénomène. Au cours du chapitre 4, on étudie des complexes de palladium(II) et de platine(II) qui ont les mêmes ligands. Un de ces ligands est le 1,4,7-trithiacyclononane (ttcn). On constate qu'à basse pression le ligand est bidentate. Par contre, lorsque la pression augmente, on constate, par exemple à l'aide du complexe [Pt(ttcn)Cl2], qu'une interaction anti-liante supplémentaire se produit entre le ligand ttcn et le métal, ce qui change la nature de l'orbitale HOMO. On observe un déplacement de la bande de luminescence de -19 cm-1/kbar. Tel que pour le complexe de molybdène(IV), le déplacement de la bande de luminescence dépend de la compétition entre les ligands situés sur les différents axes de l'octaèdre. L'interaction liante entre l'ion platine(II) et l'atome de soufre axial est l'effet le plus plausible qui peut induire un déplacement de la bande de luminescence vers les basses énergies. Ceci nous indique que cette interaction domine. Par contre, pour ce qui est du complexe palladium(II), la compétition est remportée par d'autres effets, car le déplacement de la bande de luminescence est de +6 cm-1/kbar. Encore une fois, des calculs, basés sur la théorie de la fonctionnelle de la densité, aident à explorer les causes de ces observations en suggérant des explications corroborées simultanément par les diverses expériences de spectroscopie. Lors du chapitre 5, une étude plus exacte de la structure électronique ainsi que de la dynamique des noyaux de complexes de métaux de transition est présentée. En effet, les complexes de palladium(II) et de platine(II), de type [M(X)4]2-, ont une structure simple, très symétrique. Le premier état excité de ces molécules subit la distorsion Jahn-Teller. On veut établir un protocole de travail pour les expérimentateurs afin d'analyser des spectres de molécules pour lesquelles l'approximation de Born-Oppenheimer n'est pas valide. On utilise la théorie de la fonctionnelle de la densité dépendante du temps ainsi que le modèle de Heidelberg afin de décrire des effets non adiabatique. On tente d'établir l'influence des effets non adiabatiques sur les spectres de ce type de complexe.

"Análisis de la aplicación del tratado de no proliferación nuclear, en el pilar de la “no proliferación” para el mantenimiento del equilibro del poder en materia de seguridad en oriente medio desde 2000

Los niveles de armamento nuclear existentes en el mundo, aun siguen siendo una grave amenaza para la paz y la seguridad mundial. Después de más de dos décadas de terminada la Guerra Fría los procesos de desarme nucleares no han sido satisfactorios, lo cual representa una peligro latente. Es así como la proliferación nuclear es una de las más grandes preocupaciones de los Estados en tanto que compromete la seguridad y la estabilidad internacional. Actualmente, las dinámicas nucleares han puesto en tela de juicio el mantenimiento de la paz y la seguridad. En particular, la compleja situación de Oriente Medio con el fortalecimiento del programa nuclear iraní que aparentemente busca el desarrollo de un programa de energía nuclear bélico, ha encendido las alarmas de todos los Estados. Analizar la situación de Oriente Medio enfocándose en la “no proliferación”, permite visibilizar la importancia de concentrar esfuerzos para evitar el renacimiento de los programas nucleares con fines militares en el mundo.

Nuclear magnetic relaxation for the spin-degenerate Anderson model

A renormalization-group calculation of the temperature-dependent nuclear spin relaxation rate for a magnetic impurity in a metallic host is reported. The calculation follows a simplified procedure, which produces accurate rates in the low-temperature Fermi-liquid regime, although yielding only qualitatively reliable results at higher temperatures. In all cases considered, as the temperature T diminishes, the rates peak before decaying linearly to zero in the Fermi-liquid range. For T → 0, the results agree very well with Shiba's expression relating the low-temperature coefficient of the relaxation rate to the squared zero-temperature susceptibility. In the Kondo limit, the enhanced susceptibility associated with the Kondo resonance produces a very sharp peak in the relaxation rate near the Kondo temperature. © 1991.

Protein kinase C alpha-dependent phosphorylation of the mRNA-stabilizing factor HuR: implications for posttranscriptional regulation of cyclooxygenase-2

In this study, we investigated the molecular mechanisms underlying the ATP analogue adenosine-5'-O-(3-thio)triphosphate-induced nucleocytoplasmic shuttling of the mRNA stabilizing factor HuR in human (h) mesangial cells (MC). Using synthetic protein kinase C (PKC) inhibitors and small interfering RNA approaches, we demonstrated that knockdown of PKC alpha efficiently blocked the ATP-dependent nuclear HuR export to the cytoplasm. The functional importance of PKC alpha in HuR shuttling is highlighted by the high cytosolic HuR content detected in hMC stably overexpressing PKC alpha compared with mock-transfected cells. The ATP-induced recruitment of HuR to the cytoplasm is preceded by a direct interaction of PKC alpha with nuclear HuR and accompanied by increased Ser phosphorylation as demonstrated by coimmunoprecipitation experiments. Mapping of putative PKC target sites identified serines 158 and 221 as being indispensable for HuR phosphorylation by PKC alpha. RNA pull-down assay and RNA electrophoretic mobility shift assay demonstrated that the HuR shuttling by ATP is accompanied by an increased HuR binding to cyclooxygenase (COX)-2 mRNA. Physiologically, the ATP-dependent increase in RNA binding is linked with an augmentation in COX-2 mRNA stability and subsequent increase in prostaglandin E(2) synthesis. Regulation of HuR via PKC alpha-dependent phosphorylation emphasizes the importance of posttranslational modification for stimulus-dependent HuR shuttling.

NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway

Trypanosomes mostly regulate gene expression through post-transcriptional mechanisms, particularly mRNA stability. However, much mRNA degradation is cytoplasmic such that mRNA nuclear export must represent an important level of regulation. Ribosomal RNAs must also be exported from the nucleus and the trypanosome orthologue of NMD3 has been confirmed to be involved in rRNA processing and export, matching its function in other organisms. Surprisingly, we found that TbNMD3 depletion also generates mRNA accumulation of procyclin-associated genes (PAGs), these being co-transcribed by RNA polymerase I with the procyclin surface antigen genes expressed on trypanosome insect forms. By whole transcriptome RNA-seq analysis of TbNMD3-depleted cells we confirm the regulation of the PAG transcripts by TbNMD3 and using reporter constructs reveal that PAG1 regulation is mediated by its 5'UTR. Dissection of the mechanism of regulation demonstrates that it is not dependent upon translational inhibition mediated by TbNMD3 depletion nor enhanced transcription. However, depletion of the nuclear export factors XPO1 or MEX67 recapitulates the effects of TbNMD3 depletion on PAG mRNAs and mRNAs accumulated in the nucleus of TbNMD3-depleted cells. These results invoke a novel RNA regulatory mechanism involving the NMD3-dependent nuclear export of mRNA cargos, suggesting a shared platform for mRNA and rRNA export.

The role of the conserved N -terminal domain of STAT3 in STAT3 dephosphorylation and nuclear export

Rapid redistribution of STAT subcellular localization is an essential feature of cytokine signaling. To elucidate the molecular basis of STAT3 function, which plays a critical role in controlling innate immune responses in vivo, we initiated studies to determine the mechanisms controlling STAT3 nuclear trafficking. We found that STAT3 is transported to the nucleus in the absence of cytokine treatment, as judged by indirect immunofluorescence studies in the presence of leptomycin B, an inhibitor of CRM1-dependent nuclear export, suggesting that the non-phosphorylated STAT3 protein contains a functional nuclear import signal. An isoform lacking the STAT3 N-terminal domain (Δ133STAT3) retains the ability to undergo constitutive nuclear localization, indicating that this region is not essential for cytokine-independent nuclear import. Δ133STAT3 is also transported to the nucleus following stimulation with interleukin-6 (IL-6). Interestingly, IL-6-dependent tyrosine phosphorylation of Δ133STAT3 appears to be prolonged and the nuclear export of the protein delayed in cells expressing endogenous STAT3, consistent with defective Δ133STAT3 dephosphorylation. Endogenous STAT3 does not promote the nuclear export of Δ133STAT3, although dimerization between endogenous Stat3 and Δ133STAT3 is detected readily. Thus, the STAT3 N-terminal domain is not required for dimerization with full-length STAT3, yet appears to play a role in proper export of Stat3 from the nucleus following cytokine stimulation. STAT3-deficient cells reconstituted with Δ133STAT3 show enhanced and prolonged Stat1 signaling in response to IL-6, suggesting that induction of the STAT3-dependent negative regulator SOCS3 is impaired. In fact, Δ133STAT3 fails to induce SOCS3 mRNA efficiently. These studies collectively indicate that the STAT3 N-terminal region may be important for IL-6-dependent target gene activation and nuclear dephosphorylation, while dispensable for nuclear import. STAT3 is an oncogene. STAT3 is constitutively activated in primary tumors of many types. Thus far, research in the design of STAT3 protein inhibitors has focused on the SH2 and DNA-binding domains of STAT3. Interference with these domains eliminates all signaling through STAT3. If the N-terminal domain is involved in tetramerization on a subset of target genes, inhibition of this region may lead to a more selective inhibition of some STAT3 functions while leaving others intact. ^

Dynamics of gas bubbles encapsulated by a viscoelastic fluid shell under acoustic fields

The dynamics of a gas-filled microbubble encapsulated by a viscoelastic fluid shell immersed in a Newtonian liquid and subject to an external pressure field is theoretically studied. The problem is formulated by considering a nonlinear Oldroyd type constitutive equation to model the rheological behavior of the fluid shell. Heat and mass transfer across the surface bubble have been neglected but radiation losses due to the compressibility of the surrounding liquid have been taken into account. Bubble collapse under sudden increase of the external pressure as well as nonlinear radial oscillations under ultrasound fields are investigated. The numerical results obtained show that the elasticity of the fluid coating intensifies oscillatory collapse and produces a strong increase of the amplitudes of radial oscillations which may become chaotic even for moderate driving pressure amplitudes. The role played by the elongational viscosity has also been analyzed and its influence on both, bubble collapse and radial oscillations, has been recognized. According to the theoretical predictions provided in the present work, a microbubble coated by a viscoelastic fluid shell is an oscillating system that, under acoustic driving, may experience volume oscillations of large amplitude, being, however, more stable than a free bubble. Thus, it could be expected that such a system may have a suitable behavior as an echogenic agent.

Calmodulin activates nuclear protein import: A link between signal transduction and nuclear transport

In addition to the well-characterized GTP-dependent nuclear transport observed in permeabilized cells, we detected a mode of nuclear transport that was GTP-independent at elevated cytoplasmic calcium concentrations. Nuclear transport under these conditions was blocked by calmodulin inhibitors. Recombinant calmodulin restored ATP-dependent nuclear transport in the absence of cytosol. Calmodulin-dependent transport was inhibited by wheat germ agglutinin consistent with transport proceeding through nuclear pores. We propose that release of intracellular calcium stores upon cell activation inhibits GTP-dependent nuclear transport; the elevated cytosolic calcium then acts through calmodulin to stimulate the novel GTP-independent mode of import.