Suppression of level hybridization due to Coulomb interactions

We investigate an ensemble of systems formed by a ring enclosing a magnetic flux. The ring is coupled to a side stub via a tunneling junction and via Coulomb interaction. We generalize the notion of level hybridization due to the hopping, which is naturally defined only for one-particle problems, to the many-particle case, and we discuss the competition between the level hybridization and the Coulomb interaction. It is shown that strong enough Coulomb interactions can isolate the ring from the stub, thereby increasing the persistent current. Our model describes a strictly canonical system (the number of carriers is the same for all ensemble members). Nevertheless for small Coulomb interactions and a long side stub the model exhibits a persistent current typically associated with a grand canonical ensemble of rings and only if the Coulomb interactions are sufficiently strong does the model exhibit a persistent current which one expects from a canonical ensemble.Comment: 19 pages, 6 figures, uses iop style files, version as publishe

Higher-Order Results for the Relation between Channel Conductance and the Coulomb Blockade for Two Tunnel-Coupled Quantum Dots

We extend earlier results on the relation between the dimensionless tunneling channel conductance $g$ and the fractional Coulomb blockade peak splitting $f$ for two electrostatically equivalent dots connected by an arbitrary number $N_{\text{ch}}$ of tunneling channels with bandwidths $W$ much larger than the two-dot differential charging energy $U_{2}$. By calculating $f$ through second order in $g$ in the limit of weak coupling ($g \rightarrow 0$), we illuminate the difference in behavior of the large-$N_{\text{ch}}$ and small-$N_{\text{ch}}$ regimes and make more plausible extrapolation to the strong-coupling ($g \rightarrow 1$) limit. For the special case of $N_{\text{ch}}=2$ and strong coupling, we eliminate an apparent ultraviolet divergence and obtain the next leading term of an expansion in $(1-g)$. We show that the results we calculate are independent of such band structure details as the fraction of occupied fermionic single-particle states in the weak-coupling theory and the nature of the cut-off in the bosonized strong-coupling theory. The results agree with calculations for metallic junctions in the $N_{\text{ch}} \rightarrow \infty$ limit and improve the previous good agreement with recent two-channel experiments.Comment: 27 pages, 1 RevTeX file with 4 embedded Postscript figures. Uses eps

Semiclassical theory for many-body Fermionic systems

We present a treatment of many-body Fermionic systems that facilitates an expression of the well-known quantities in a series expansion of the Planck's constant. The ensuing semiclassical result contains to a leading order of the response function the classical time correlation function of the observable followed by the Weyl-Wigner series, on top of these terms are the periodic-orbit correction terms. The treatment given here starts from linear response assumption of the many-body theory and in its connection with semiclassical theory, it makes no assumption of the integrability of classical dynamics underlying the one-body quantal system. Applications of the framework are also discussed.Comment: 18 pages, Te

Bistability in the Tunnelling Current through a Ring of NN Coupled Quantum Dots

We study bistability in the electron transport through a ring of N coupled quantum dots with two orbitals in each dot. One orbital is localized (called b orbital) and coupling of the b orbitals in any two dots is negligible; the other is delocalized in the plane of the ring (called d orbital), due to coupling of the d orbitals in the neighboring dots, as described by a tight-binding model. The d orbitals thereby form a band with finite width. The b and d orbitals are connected to the source and drain electrodes with a voltage bias V, allowing the electron tunnelling. Tunnelling current is calculated by using a nonequilibrium Green function method recently developed to treat nanostructures with multiple energy levels. We find a bistable effect in the tunnelling current as a function of bias V, when the size N>50; this effect scales with the size N and becomes sizable at N~100. The temperature effect on bistability is also discussed. In comparison, mean-field treatment tends to overestimate the bistable effect.Comment: Published in JPSJ; minor typos correcte

Fine structure in the off-resonance conductance of small Coulomb blockade systems

We show how a fine, multiple-peak structure can arise in the off-resonance, zero-bias conductance of Coulomb blockade systems. In order to understand how this effect comes about one must abandon the orthodox, mean-field understanding of the Coulomb blockade phenomenon and consider quantum fluctuations in the occupation of the single-particle electronic levels. We illustrate such an effect with a spinless Anderson-like model for multi-level systems and an equation-of-motion method for calculating Green's functions that combines two simple decoupling schemes.Comment: 5 pages, 3 figures, postscript file also available at http://www.pa.uky.edu/~palacios/papers/eom.ps One figure added. Discussion of results extende

Effect of tuberculosis screening and retention interventions on early antiretroviral therapy mortality in Botswana: a stepped-wedge cluster randomized trial.

BACKGROUND: Undiagnosed tuberculosis (TB) remains the most common cause of HIV-related mortality. Xpert MTB/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality. METHODS: At 22 clinics, ART enrollees >?12?years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation. RESULTS: We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184/?L in SOC, 246/?L in EC, and 241/?L in EC+X). By 6?months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61-0.97, p?=?0.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees. CONCLUSIONS: Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed. TRIAL REGISTRATION: Retrospectively registered: ClinicalTrials.gov (NCT02538952)

Risk scores for predicting early antiretroviral therapy mortality in sub-Saharan Africa to inform who needs intensification of care: a derivation and external validation cohort study.

BACKGROUND: Clinical scores to determine early (6-month) antiretroviral therapy (ART) mortality risk have not been developed for sub-Saharan Africa (SSA), home to 70% of people living with HIV. In the absence of validated scores, WHO eligibility criteria (EC) for ART care intensification are CD4  37.5 °C (2 points). The same variables plus CD4 < 200/μL (1 point) were included in the CD4-dependent score. Among XPRES enrollees, a CD4-independent score of ≥ 4 would provide 86% sensitivity and 66% specificity, whereas WHO EC would provide 83% sensitivity and 58% specificity. If WHO stage alone was used, sensitivity was 48% and specificity 89%. Among TBFT enrollees, the CD4-independent score of ≥ 4 would provide 95% sensitivity and 27% specificity, whereas WHO EC would provide 100% sensitivity but 0% specificity. Accuracy was similar between CD4-independent and CD4-dependent scores. Categorizing CD4-independent scores into low (< 4), moderate (4-6), and high risk (≥ 7) gave 6-month mortality of 1%, 4%, and 17% for XPRES and 1%, 5%, and 30% for TBFT enrollees. CONCLUSIONS: Sensitivity of the CD4-independent score was nearly twice that of WHO stage in predicting 6-month mortality and could be used in settings lacking CD4 testing to inform ART care intensification. The CD4-dependent score improved specificity versus WHO EC. Both scores should be considered for scale-up in SSA

Canonical Wnt signaling negatively modulates regulatory T cell function

Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that Tcell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3 transcriptional activity. A global chromatin immunoprecipitation sequencing comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt target genes. The activation of Wnt signaling reduced Treg-mediated suppression both invitro and invivo, whereas disruption of Wnt signaling in Treg cells enhanced their suppressive capacity. The activation of effector Tcells increased Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced under inflammatory conditions represses Treg cell function, allowing a productive immune response, but, if uncontrolled, could lead to the development of autoimmunity

Dissipative non-equilibrium Green function methodology to treat short range Coulomb interaction: current through a 1D nanostructure

A methodology describing Coulomb blockade in the non-equilibrium Green function formalism is presented. We carried out ballistic and dissipative simulations through a 1D quantum dot using an Einstein phonon model. Inelastic phonons with different energies have been considered. The methodology incorporates the short-range Coulomb interaction between two electrons through the use of a two-particle Green function. Unlike previous work, the quantum dot has spatial resolution i.e. it is not just parameterized by the energy level and coupling constants of the dot. Our method intends to describe the effect of electron localization while maintaining an open boundary or extended wave function. The formalism conserves the current through the nanostructure. A simple 1D model is used to explain the increase of mobility in semi-crystalline polymers as a function of the electron concentration. The mechanism suggested is based on the lifting of energy levels into the transmission window as a result of the local electron–electron repulsion inside a crystalline domain. The results are aligned with recent experimental findings. Finally, as a proof of concept, we present a simulation of a low temperature resonant structure showing the stability diagram in the Coulomb blockade regime

RACK1 Associates with Muscarinic Receptors and Regulates M2 Receptor Trafficking

Receptor internalization from the cell surface occurs through several mechanisms. Some of these mechanisms, such as clathrin coated pits, are well understood. The M2 muscarinic acetylcholine receptor undergoes internalization via a poorly-defined clathrin-independent mechanism. We used isotope coded affinity tagging and mass spectrometry to identify the scaffolding protein, receptor for activated C kinase (RACK1) as a protein enriched in M2-immunoprecipitates from M2-expressing cells over those of non-M2 expressing cells. Treatment of cells with the agonist carbachol disrupted the interaction of RACK1 with M2. We further found that RACK1 overexpression inhibits the internalization and subsequent down regulation of the M2 receptor in a receptor subtype-specific manner. Decreased RACK1 expression increases the rate of agonist internalization of the M2 receptor, but decreases the extent of subsequent down-regulation. These results suggest that RACK1 may both interfere with agonist-induced sequestration and be required for subsequent targeting of internalized M2 receptors to the degradative pathway