Comment on "Josephson Current through a Nanoscale Magnetic Quantum Dot"

In a recent work [Phys. Rev. Lett. 93, 047002 (2004)], Siano and Egger (SE) studied Josephson current through a quantum dot in the Kondo regime using the quantum Monte Carlo (QMC) method. Several of their results were inconsistent with those from the numerical renormalization group (NRG) calculations [Phys. Rev. B 70, R020502 (2004); J. Phys. Soc. Jpn. 69, 1812 (2000)] among other previous studies. The results of SE are not reliable for the following two reasons: (i) The definition of the Kondo temperature was not correct; (ii) There were substantial fintie-temperature effects

Diffusion Theory for Cell Membrane Fluorescence Microscopy

Since the discovery of fluorescent proteins and the development of DNA recombinant techniques, various fluorescence methods have significantly improved our understanding of cell biology at a molecular level. In particular, thanks, in large part, to technological advances in these fields, fluorescence techniques such as fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), and single-particle tracking (SPT) have become standard tools in studying cell membrane structure as well as the diffusion and interaction of biomolecules in the cell membrane. In this chapter, we will review some topics of the diffusion theory from both deterministic and probabilistic approaches, which are relevant to cell membrane fluorescence microscopy. Additionally, we will derive some basic equations for FARP and FCS based on the diffusion theory

Nucleocytoplasmic Distribution and Dynamics of the Autophagosome Marker EGFP-LC3

The process of autophagy involves the formation of autophagosomes, double-membrane structures that encapsulate cytosol. Microtubule-associated protein light chain 3 (LC3) was the first protein shown to specifically label autophagosomal membranes in mammalian cells, and subsequently EGFP-LC3 has become one of the most widely utilized reporters of autophagy. Although LC3 is currently thought to function primarily in the cytosol, the site of autophagosome formation, EGFP-LC3 often appears to be enriched in the nucleoplasm relative to the cytoplasm in published fluorescence images. However, the nuclear pool of EGFP-LC3 has not been specifically studied in previous reports, and mechanisms by which LC3 shuttles between the cytoplasm and nucleoplasm are currently unknown. In this study, we therefore investigated the regulation of the nucleo-cytoplasmic distribution of EGFP-LC3 in living cells. By quantitative fluorescence microscopy analysis, we demonstrate that soluble EGFP-LC3 is indeed enriched in the nucleus relative to the cytoplasm in two commonly studied cell lines, COS-7 and HeLa. Although LC3 contains a putative nuclear export signal (NES), inhibition of active nuclear export or mutation of the NES had no effect on the nucleo-cytoplasmic distribution of EGFP-LC3. Furthermore, FRAP analysis indicates that EGFP-LC3 undergoes limited passive nucleo-cytoplasmic transport under steady state conditions, and that the diffusional mobility of EGFP-LC3 was substantially slower in the nucleus and cytoplasm than predicted for a freely diffusing monomer. Induction of autophagy led to a visible decrease in levels of soluble EGFP-LC3 relative to autophagosome-bound protein, but had only modest effects on the nucleo-cytoplasmic ratio or diffusional mobility of the remaining soluble pools of EGFP-LC3. We conclude that the enrichment of soluble EGFP-LC3 in the nucleus is maintained independently of active nuclear export or induction of autophagy. Instead, incorporation of soluble EGFP-LC3 into large macromolecular complexes within both the cytoplasm and nucleus may prevent its rapid equilibrium between the two compartments

Kondo Effect and Josephson Current through a Quantum Dot between Two Superconductors

We investigate the supercurrent through a quantum dot for the whole range of couplings using the numerical renormalization group method. We find that the Josephson current switches abruptly from a $\pi$- to a 0-phase as the coupling increases. At intermediate couplings the total spin in the ground state depends on the phase difference between the two superconductors. Our numerical results can explain the crossover in the conductance observed experimentally by Buitelaar \textit{et al.} [Phys. Rev. Lett. \textbf{89}, 256 801 (2002)].Comment: Fig.2 and corresponding text have been changed; Several other small change

Distinct effects of rosuvastatin and rosuvastatin/ezetimibe on senescence markers of CD8+ T cells in patients with type 2 diabetes mellitus: a randomized controlled trial

ObjectivesChronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to β-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers.MethodsIn this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication.ResultsThe fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (Treg) significantly decreased after intervention in the rosuvastatin/ezetimibe group (−4.5 ± 14.1% and −1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (p=0.314) or LDL-C (p=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (p=0.011), but not in the rosuvastatin group (p=0.339).ConclusionsWe observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels

G protein-coupled receptor-mediated calcium signaling in astrocytes

Astrocytes express a large variety of G~protein-coupled receptors (GPCRs) which mediate the transduction of extracellular signals into intracellular calcium responses. This transduction is provided by a complex network of biochemical reactions which mobilizes a wealth of possible calcium-mobilizing second messenger molecules. Inositol 1,4,5-trisphosphate is probably the best known of these molecules whose enzymes for its production and degradation are nonetheless calcium-dependent. We present a biophysical modeling approach based on the assumption of Michaelis-Menten enzyme kinetics, to effectively describe GPCR-mediated astrocytic calcium signals. Our model is then used to study different mechanisms at play in stimulus encoding by shape and frequency of calcium oscillations in astrocytes.Comment: 35 pages, 6 figures, 1 table, 3 appendices (book chapter

Non linear behavior of power HBT

To understand the linear characteristics of HBT more accurately, an analytical nonlinear HBT model using Volterra Series analysis is developed. The model considers four nonlinear components: rπ, Cdiff , Cdepl, and gm. It shows that nonlinearities of rπ and Cdiff are almost completely cancelled by gm nonlinearity at all frequencies. The residual gm nonlinearity are highly degenerated by the input impedances. Therefore, rπ, Cπ and gm nonlinearities generate less IM3 than Cbc. If Cbc is linearized, Cdepl and gm are the main nonlinear sources of HBT, and Cdepl becomes very important at a high frequency. It was also found that the degeneration resistor, RE, is more effective than RB for reducing gm nonlinearity. This analysis also provides the dependency of the source second harmonic impedance on the linearity of HBT. The IM3 of HBT is significantly reduced by setting the second harmonic impedance of ZS,2ω2 = 0 and ZS,ω2-ω1 = 0

Mathematical Modeling of Fluorescence Microscopy and Its Applications to Cancer Systems Biology

All living cells sense, integrate, and respond to their environment through a complex communication system known as “cell signaling,” which is mostly mediated by protein-protein interactions. Therefore, determining proteins’ binding partners and binding rate constants are crucial steps to understanding cell signaling. While high-throughput methods to screen binary protein binding pairs are well-established, still no genomic scale kinetic rate calibration tools are available. To this end, simple, accessible—yet accurate—methods to measure kinetic constants under physiological condition were sought by a combination of mathematical modeling and fluorescence microscopy techniques, such as Fluorescence Recovery After Photobleaching (FRAP) and Förster Resonance Energy Transfer (FRET). In addition to the aforementioned, Kang will also discuss further application of this research to cancer systems biology