Jensen-Feynman approach to the statistics of interacting electrons

Faussurier et al. [Phys. Rev. E 65, 016403 (2001)] proposed to use a variational principle relying on Jensen-Feynman (or Gibbs-Bogoliubov) inequality in order to optimize the accounting for two-particle interactions in the calculation of canonical partition functions. It consists in a decomposition into a reference electron system and a first-order correction. The procedure appears to be very efficient in order to evaluate the free energy and the orbital populations. In this work, we present numerical applications of the method and propose to extend it using a reference energy which includes the interaction between two electrons inside a given orbital. This is possible thanks to our efficient recursion relation for the calculation of partition functions. We also show that a linear reference energy, however, is usually sufficient to achieve a good precision and that the most promising way to improve the approach of Faussurier et al. is to apply Jensen's inequality to a more convenient convex function.Comment: submitted to Physical Review

Identification and structural characterisation of a partially arabinosylated lipoarabinomannan variant isolated from a Corynebacterium glutamicum ubiAmutant

Arabinan polysaccharide side-chains are present in both Mycobacterium tuberculosis and Corynebacterium glutamicum in the heteropolysaccharide arabinogalactan (AG), and in M. tuberculosis in the lipoglycan, lipoarabinomannan (LAM). Herein, we show by quantitative sugar and glycosyl linkage analysis that C. glutamicum possesses a much smaller LAM version, Cg-LAM, characterised by single t-Araf residues linked to th

Characterization of anomalous Zeeman patterns in complex atomic spectra

The modeling of complex atomic spectra is a difficult task, due to the huge number of levels and lines involved. In the presence of a magnetic field, the computation becomes even more difficult. The anomalous Zeeman pattern is a superposition of many absorption or emission profiles with different Zeeman relative strengths, shifts, widths, asymmetries and sharpnesses. We propose a statistical approach to study the effect of a magnetic field on the broadening of spectral lines and transition arrays in atomic spectra. In this model, the sigma and pi profiles are described using the moments of the Zeeman components, which depend on quantum numbers and Land\'{e} factors. A graphical calculation of these moments, together with a statistical modeling of Zeeman profiles as expansions in terms of Hermite polynomials are presented. It is shown that the procedure is more efficient, in terms of convergence and validity range, than the Taylor-series expansion in powers of the magnetic field which was suggested in the past. Finally, a simple approximate method to estimate the contribution of a magnetic field to the width of transition arrays is proposed. It relies on our recently published recursive technique for the numbering of LS-terms of an arbitrary configuration.Comment: submitted to Physical Review

Measurement of XUV-absorption spectra of ZnS radiatively heated foils

Time-resolved absorption of zinc sulfide (ZnS) and aluminum in the XUV-range has been measured. Thin foils in conditions close to local thermodynamic equilibrium were heated by radiation from laser-irradiated gold spherical cavities. Analysis of the aluminum foil radiative hydrodynamic expansion, based on the detailed atomic calculations of its absorption spectra, showed that the cavity emitted flux that heated the absorption foils corresponds to a radiation temperature in the range 55 60 eV. Comparison of the ZnS absorption spectra with calculations based on a superconfiguration approach identified the presence of species Zn6+ - Zn8+ and S5+ - S6+. Based on the validation of the radiative source simulations, experimental spectra were then compared to calculations performed by post-processing the radiative hydrodynamic simulations of ZnS. Satisfying agreement is found when temperature gradients are accounted for

How to Tackle Integer Weighted Automata Positivity

International audienceThis paper is dedicated to candidate abstractions to capture relevant aspects of the integer weighted automata. The expected effect of applying these abstractions is studied to build the deterministic reachability graphs allowing us to semi-decide the positivity problem on these automata. Moreover, the papers reports on the implementations and experimental results, and discusses other encodings

Pathways of cellular internalisation of liposomes delivered siRNA and effects on siRNA engagement with target mRNA and silencing in cancer cells

Design of an efficient delivery system is a generally recognised bottleneck in translation of siRNA technology into clinic. Despite research efforts, cellular processes that determine efficiency of siRNA silencing achieved by different delivery formulations remain unclear. Here, we investigated the mechanism(s) of cellular internalisation of a model siRNA-loaded liposome system in a correlation to the engagement of delivered siRNA with its target and consequent silencing by adopting siRNA molecular beacon technology. Probing of cellular internalisation pathways by a panel of pharmacological inhibitors indicated that clathrin-mediated (dynamin-dependent) endocytosis, macropinocytosis (dynamine independent), and cell membrane cholesterol dependent process(es) (clathrin and caveolea-independent) all play a role in the siRNA-liposomes internalization. The inhibition of either of these entry routes was, in general, mirrored by a reduction in the level of siRNA engagement with its target mRNA, as well as in a reduction of the target gene silencing. A dramatic increase in siRNA engagement with its target RNA was observed on disruption of endosomal membrane (by chloroquine), accompanied with an increased silencing. The work thus illustrates that employing molecular beacon siRNA technology one can start to assess the target RNA engagement – a stage between initial cellular internalization and final gene silencing of siRNA delivery systems

Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment

A single nanoparticle platform has been developed through the modular and controlled layer-by-layer process to codeliver siRNA that knocks down a drug-resistance pathway in tumor cells and a chemotherapy drug to challenge a highly aggressive form of triple-negative breast cancer. Layer-by-layer films were formed on nanoparticles by alternately depositing siRNA and poly-l-arginine; a single bilayer on the nanoparticle surface could effectively load up to 3500 siRNA molecules, and the resulting LbL nanoparticles exhibit an extended serum half-life of 28 h. In animal models, one dose via intravenous administration significantly reduced the target gene expression in the tumors by almost 80%. By generating the siRNA-loaded film atop a doxorubicin-loaded liposome, we identified an effective combination therapy with siRNA targeting multidrug resistance protein 1, which significantly enhanced doxorubicin efficacy by 4 fold in vitro and led to up to an 8-fold decrease in tumor volume compared to the control treatments with no observed toxicity. The results indicate that the use of layer-by-layer films to modify a simple liposomal doxorubicin delivery construct with a synergistic siRNA can lead to significant tumor reduction in the cancers that are otherwise nonresponsive to treatment with Doxil or other common chemotherapy drugs. This approach provides a potential strategy to treat aggressive and resistant cancers, and a modular platform for a broad range of controlled multidrug therapies customizable to the cancer type in a singular nanoparticle delivery system.Janssen Pharmaceutical Ltd. (TRANSCEND Grant)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)National Health and Medical Research Council (Australia) (CJ Martin Fellowship)National Science Foundation (U.S.). Graduate Research FellowshipNatural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship

Mind the gap: connexins and cell–cell communication in the diabetic kidney

Connexins, assembled as a hexameric connexon, form a transmembrane hemichannel that provides a conduit for paracrine signalling of small molecules and ions to regulate the activity and function of adjacent cells. When hemichannels align and associate with similar channels on opposing cells, they form a continuous aqueous pore or gap junction, allowing the direct transmission of metabolic and electrical signals between coupled cells. Regulation of gap junction synthesis and channel activity is critical for cell function, and a number of diseases can be attributed to changes in the expression/function of these important proteins. Diabetic nephropathy is associated with several complex metabolic and inflammatory responses characterised by defects at the molecular, cellular and tissue level. In both type 1 and type 2 diabetes, glycaemic injury of the kidney is the leading cause of end-stage renal failure, a consequence of multiple aetiologies, including increased deposition of extracellular matrix, glomerular hyperfiltration, albuminuria and tubulointerstitial fibrosis. In diabetic nephropathy, loss of connexin mediated cell–cell communication within the nephron may represent an early sign of disease; however, our current knowledge of the role of connexins in the diabetic kidney is sparse. This review highlights recent evidence demonstrating that maintenance of connexin-mediated cell–cell communication could benefit region-specific renal function in diabetic nephropathy and suggests that these proteins should be viewed as a tantalising novel target for therapeutic intervention

PIM2 Induced COX-2 and MMP-9 Expression in Macrophages Requires PI3K and Notch1 Signaling

Activation of inflammatory immune responses during granuloma formation by the host upon infection of mycobacteria is one of the crucial steps that is often associated with tissue remodeling and breakdown of the extracellular matrix. In these complex processes, cyclooxygenase-2 (COX-2) plays a major role in chronic inflammation and matrix metalloproteinase-9 (MMP-9) significantly in tissue remodeling. In this study, we investigated the molecular mechanisms underlying Phosphatidyl-myo-inositol dimannosides (PIM2), an integral component of the mycobacterial envelope, triggered COX-2 and MMP-9 expression in macrophages. PIM2 triggers the activation of Phosphoinositide-3 Kinase (PI3K) and Notch1 signaling leading to COX-2 and MMP-9 expression in a Toll-like receptor 2 (TLR2)-MyD88 dependent manner. Notch1 signaling perturbations data demonstrate the involvement of the cross-talk with members of PI3K and Mitogen activated protein kinase pathway. Enforced expression of the cleaved Notch1 in macrophages induces the expression of COX-2 and MMP-9. PIM2 triggered significant p65 nuclear factor -κB (NF-κB) nuclear translocation that was dependent on activation of PI3K or Notch1 signaling. Furthermore, COX-2 and MMP-9 expression requires Notch1 mediated recruitment of Suppressor of Hairless (CSL) and NF-κB to respective promoters. Inhibition of PIM2 induced COX-2 resulted in marked reduction in MMP-9 expression clearly implicating the role of COX-2 dependent signaling events in driving the MMP-9 expression. Taken together, these data implicate PI3K and Notch1 signaling as obligatory early proximal signaling events during PIM2 induced COX-2 and MMP-9 expression in macrophages