A Numerical Study of Transport and Shot Noise at 2D Hopping

We have used modern supercomputer facilities to carry out extensive Monte Carlo simulations of 2D hopping (at negligible Coulomb interaction) in conductors with the completely random distribution of localized sites in both space and energy, within a broad range of the applied electric field $E$ and temperature $T$, both within and beyond the variable-range hopping region. The calculated properties include not only dc current and statistics of localized site occupation and hop lengths, but also the current fluctuation spectrum. Within the calculation accuracy, the model does not exhibit $1/f$ noise, so that the low-frequency noise at low temperatures may be characterized by the Fano factor $F$. For sufficiently large samples, $F$ scales with conductor length $L$ as $(L_c/L)^{\alpha}$, where $\alpha=0.76\pm 0.08 < 1$, and parameter $L_c$ is interpreted as the average percolation cluster length. At relatively low $E$, the electric field dependence of parameter $L_c$ is compatible with the law $L_c\propto E^{-0.911}$ which follows from directed percolation theory arguments.Comment: 17 pages, 8 figures; Fixed minor typos and updated reference

A Numerical Study of Coulomb Interaction Effects on 2D Hopping Transport

We have extended our supercomputer-enabled Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the case of substantial electron-electron Coulomb interaction. Such interaction may not only suppress the average value of hopping current, but also affect its fluctuations rather substantially. In particular, the spectral density $S_I (f)$ of current fluctuations exhibits, at sufficiently low frequencies, a $1/f$-like increase which approximately follows the Hooge scaling, even at vanishing temperature. At higher $f$, there is a crossover to a broad range of frequencies in which $S_I (f)$ is nearly constant, hence allowing characterization of the current noise by the effective Fano factor F\equiv S_I(f)/2e \left. For sufficiently large conductor samples and low temperatures, the Fano factor is suppressed below the Schottky value (F=1), scaling with the length $L$ of the conductor as $F = (L_c / L)^{\alpha}$. The exponent $\alpha$ is significantly affected by the Coulomb interaction effects, changing from $\alpha = 0.76 \pm 0.08$ when such effects are negligible to virtually unity when they are substantial. The scaling parameter $L_c$, interpreted as the average percolation cluster length along the electric field direction, scales as $L_c \propto E^{-(0.98 \pm 0.08)}$ when Coulomb interaction effects are negligible and $L_c \propto E^{-(1.26 \pm 0.15)}$ when such effects are substantial, in good agreement with estimates based on the theory of directed percolation.Comment: 19 pages, 7 figures. Fixed minor typos and updated reference

CoWBP capping barrier layer for sub 90 nm Cu interconnects

Abstract Electroless cobalt films have been obtained by deposition using a plating bath containing two reducing agents: dimethylamineborane (DMAB) and sodium hypophosphite. This formulation allows spontaneous activation on copper followed by auto catalytic electroless plating. CoWBP and CoBP films are proposed as diffusion barriers and encapsulation layers, for copper lines and via contacts for ULSI interconnect applications. The crystalline structure, chemical composition and oxidation states of the elements were studied, as well as the electrical resistivity, topography and morphology of the films. The film composition was characterized as a function of the solution composition; the barrier properties of the films were tested and an oxidation resistance study was conducted. The films were characterized and the results show that they can be applied as capping layers for ULSI copper metallization

Failure of Fibrotic Liver Regeneration in Mice Is Linked to a Severe Fibrogenic Response Driven by Hepatic Progenitor Cell Activation

Failure of fibrotic liver to regenerate after resection limits therapeutic options and increases demand for liver transplantation, representing a significant clinical problem. The mechanism underlying regenerative failure in fibrosis is poorly understood. Seventy percent partial hepatectomy (PHx) was performed in C57Bl/6 mice with or without carbon tetrachloride (CCl4)-induced liver fibrosis. Liver function and regeneration was monitored at 1 to 14 days thereafter by assessing liver mass, alanine aminotransferase (ALT), mRNA expression, and histology. Progenitor (oval) cell mitogen tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and TWEAK-neutralizing antibody were used to manipulate progenitor cell proliferation in vivo. In fibrotic liver, hepatocytes failed to replicate efficiently after PHx. Fibrotic livers showed late (day 5) peak of serum ALT (3542 ± 355 IU/L compared to 93 ± 65 IU/L in nonfibrotic livers), which coincided with progenitor cell expansion, increase in profibrogenic gene expression and de novo collagen deposition. In fibrotic mice, inhibition of progenitor activation using TWEAK-neutralizing antibody after PHx resulted in strongly down-regulated profibrogenic mRNA, reduced serum ALT levels and improved regeneration. Failure of hepatocyte-mediated regeneration in fibrotic liver triggers activation of the progenitor (oval) cell compartment and a severe fibrogenic response. Inhibition of progenitor cell proliferation using anti-TWEAK antibody prevents fibrogenic response and augments fibrotic liver regeneration. Targeting the fibrogenic progenitor response represents a promising strategy to improve hepatectomy outcomes in patients with liver fibrosis

Causal Sets: Quantum gravity from a fundamentally discrete spacetime

In order to construct a quantum theory of gravity, we may have to abandon certain assumptions we were making. In particular, the concept of spacetime as a continuum substratum is questioned. Causal Sets is an attempt to construct a quantum theory of gravity starting with a fundamentally discrete spacetime. In this contribution we review the whole approach, focusing on some recent developments in the kinematics and dynamics of the approach.Comment: 10 pages, review of causal sets based on talk given at the 1st MCCQG conferenc

Sub-electron Charge Relaxation via 2D Hopping Conductors

We have extended Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the process of external charge relaxation. In this situation, a conductor of area $L \times W$ shunts an external capacitor $C$ with initial charge $Q_i$. At low temperatures, the charge relaxation process stops at some "residual" charge value corresponding to the effective threshold of the Coulomb blockade of hopping. We have calculated the r.m.s$.$ value $Q_R$ of the residual charge for a statistical ensemble of capacitor-shunting conductors with random distribution of localized sites in space and energy and random $Q_i$, as a function of macroscopic parameters of the system. Rather unexpectedly, $Q_{R}$ has turned out to depend only on some parameter combination: $X_0 \equiv L W \nu_0 e^2/C$ for negligible Coulomb interaction and $X_{\chi} \equiv LW \kappa^2/C^{2}$ for substantial interaction. (Here $\nu_0$ is the seed density of localized states, while $\kappa$ is the dielectric constant.) For sufficiently large conductors, both functions $Q_{R}/e =F(X)$ follow the power law $F(X)=DX^{-\beta}$, but with different exponents: $\beta = 0.41 \pm 0.01$ for negligible and $\beta = 0.28 \pm 0.01$ for significant Coulomb interaction. We have been able to derive this law analytically for the former (most practical) case, and also explain the scaling (but not the exact value of the exponent) for the latter case. In conclusion, we discuss possible applications of the sub-electron charge transfer for "grounding" random background charge in single-electron devices.Comment: 12 pages, 5 figures. In addition to fixing minor typos and updating references, the discussion has been changed and expande

Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease

Biomarkers are increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous molecules. Here we describe the development of exogenously administered `synthetic biomarkers' composed of mass-encoded peptides conjugated to nanoparticles that leverage intrinsic features of human disease and physiology for noninvasive urinary monitoring. These protease-sensitive agents perform three functions in vivo: target sites of disease, sample dysregulated protease activities and emit mass-encoded reporters into host urine for multiplexed detection by mass spectrometry. Using mouse models of liver fibrosis and cancer, we show that they can noninvasively monitor liver fibrosis and resolution without the need for invasive core biopsies and can substantially improve early detection of cancer compared with clinically used blood biomarkers. This approach of engineering synthetic biomarkers for multiplexed urinary monitoring should be broadly amenable to additional pathophysiological processes and to point-of-care diagnostics

Lipopolysaccharide stress induces cell-type specific production of murine leukemia virus type-endogenous retroviral virions in primary lymphoid cells

Some murine-endogenous retroviruses, making up ∼10 % of the mouse genome, are induced during the course of experimental sepsis in which lipopolysaccharide (LPS), a pathogenic component of Gram-negative bacteria, often plays a critical role. In this study, we investigated whether LPS stress induces the production of murine leukemia virus type-endogenous retrovirus (MuLV-ERV) virions in primary lymphoid cells. LPS treatment of cells (single-cell suspensions and sorted B- and T-cells) isolated from seven lymphoid organs of C57BL/6J mice resulted in a differential increase in the production of MuLV-ERV virions in most cells examined. Interestingly, among the 34 unique MuLV-ERV U3 sequences cloned from the viral genomic RNAs, the nuclear respiratory factor 1 (transcription factor) element was present only in the 20 U3 sequences that were derived from the LPS-induced MuLV-ERV U3 bands. Using the U3 sequences as a probe, 55 putative MuLV-ERV loci were mapped onto the C57BL/6J mouse genome and 15 of them retained full coding potential. Furthermore, one full-length recombinant MuLV-ERV originating from a locus on chromosome 13 was determined to be responsive to LPS stress. The findings from this study suggest that LPS stress differentially activates MuLV-ERV virion production in lymphoid organs in a cell type- and MuLV-ERV-specific manner. Further investigation is needed to define the role of MuLV-ERVs in the LPS signalling pathway(s) in general, as well as in the pathogenesis of sepsis

Caveolae-dependent and -independent uptake of albumin in cultured rodent pulmonary endothelial cells

Although a critical role for caveolae-mediated albumin transcytosis in pulmonary endothelium is well established, considerably less is known about caveolae-independent pathways. In this current study, we confirmed that cultured rat pulmonary microvascular (RPMEC) and pulmonary artery (RPAEC) endothelium endocytosed Alexa488-labeled albumin in a saturable, temperature-sensitive mode and internalization resulted in co-localization by fluorescence microscopy with cholera B toxin and caveolin-1. Although siRNA to caveolin-1 (cav-1) in RPAEC significantly inhibited albumin uptake, a remnant portion of albumin uptake was cav-1-independent, suggesting alternative pathways for albumin uptake. Thus, we isolated and cultured mouse lung endothelial cells (MLEC) from wild type and cav-1-/- mice and noted that ∼ 65% of albumin uptake, as determined by confocal imaging or live cell total internal reflectance fluorescence microscopy (TIRF), persisted in total absence of cav-1. Uptake of colloidal gold labeled albumin was evaluated by electron microscopy and demonstrated that albumin uptake in MLEC from cav-1-/- mice was through caveolae-independent pathway(s) including clathrin-coated pits that resulted in endosomal accumulation of albumin. Finally, we noted that albumin uptake in RPMEC was in part sensitive to pharmacological agents (amiloride [sodium transport inhibitor], Gö6976 [protein kinase C inhibitor], and cytochalasin D [inhibitor of actin polymerization]) consistent with a macropinocytosis-like process. The amiloride sensitivity accounting for macropinocytosis also exists in albumin uptake by both wild type and cav-1 -/- MLEC. We conclude from these studies that in addition to the well described caveolar-dependent pulmonary endothelial cell endocytosis of albumin, a portion of overall uptake in pulmonary endothelial cells is cav-1 insensitive and appears to involve clathrin-mediated endocytosis and macropinocytosis-like process. © 2013 Li et al