Dynamic disorder in receptor-ligand forced dissociation experiments

Recently experiments showed that some biological noncovalent bonds increase their lifetimes when they are stretched by an external force, and their lifetimes will decrease when the force increases further. Several specific quantitative models have been proposed to explain the intriguing transitions from the "catch-bond" to the "slip-bond". Different from the previous efforts, in this work we propose that the dynamic disorder of the force-dependent dissociation rate can account for the counterintuitive behaviors of the bonds. A Gaussian stochastic rate model is used to quantitatively describe the transitions observed recently in the single bond P-selctin glycoprotein ligand 1(PSGL-1)$-$P-selectin force rupture experiment [Marshall, {\it et al.}, (2003) Nature {\bf 423}, 190-193]. Our model agrees well to the experimental data. We conclude that the catch bonds could arise from the stronger positive correlation between the height of the intrinsic energy barrier and the distance from the bound state to the barrier; classical pathway scenario or {\it a priori} catch bond assumption is not essential.Comment: 4 pages, 2 figure

Numerical observation of non-axisymmetric vesicles in fluid membranes

By means of Surface Evolver (Exp. Math,1,141 1992), a software package of brute-force energy minimization over a triangulated surface developed by the geometry center of University of Minnesota, we have numerically searched the non-axisymmetric shapes under the Helfrich spontaneous curvature (SC) energy model. We show for the first time there are abundant mechanically stable non-axisymmetric vesicles in SC model, including regular ones with intrinsic geometric symmetry and complex irregular ones. We report in this paper several interesting shapes including a corniculate shape with six corns, a quadri-concave shape, a shape resembling sickle cells, and a shape resembling acanthocytes. As far as we know, these shapes have not been theoretically obtained by any curvature model before. In addition, the role of the spontaneous curvature in the formation of irregular crenated vesicles has been studied. The results shows a positive spontaneous curvature may be a necessary condition to keep an irregular crenated shape being mechanically stable.Comment: RevTex, 14 pages. A hard copy of 8 figures is available on reques

Flat Spacetime Vacuum in Loop Quantum Gravity

We construct a state in the loop quantum gravity theory with zero cosmological constant, which should correspond to the flat spacetime vacuum solution. This is done by defining the loop transform coefficients of a flat connection wavefunction in the holomorphic representation which satisfies all the constraints of quantum General Relativity and it is peaked around the flat space triads. The loop transform coefficients are defined as spin foam state sum invariants of the spin networks embedded in the spatial manifold for the SU(2) quantum group. We also obtain an expression for the vacuum wavefunction in the triad represntation, by defining the corresponding spin networks functional integrals as SU(2) quantum group state sums.Comment: 20 pages, 6 figure

Interpretation of AIRS Data in Thin Cirrus Atmospheres Based on a Fast Radiative Transfer Model

A thin cirrus cloud thermal infrared radiative transfer model has been developed for application to cloudy satellite data assimilation. This radiation model was constructed by combining the Optical Path Transmittance (OPTRAN) model, developed for the speedy calculation of transmittances in clear atmospheres, and a thin cirrus cloud parameterization using a number of observed ice crystal size and shape distributions. Numerical simulations show that cirrus cloudy radiances in the 800–1130-cm^(-1) thermal infrared window are sufficiently sensitive to variations in cirrus optical depth and ice crystal size as well as in ice crystal shape if appropriate habit distribution models are selected a priori for analysis. The parameterization model has been applied to the Atmospheric Infrared Sounder (AIRS) on board the Aqua satellite to interpret clear and thin cirrus spectra observed in the thermal infrared window. Five clear and 29 thin cirrus cases at nighttime over and near the Atmospheric Radiation Measurement program (ARM) tropical western Pacific (TWP) Manus Island and Nauru Island sites have been chosen for this study. A X^2-minimization program was employed to infer the cirrus optical depth and ice crystal size and shape from the observed AIRS spectra. Independent validation shows that the AIRS-inferred cloud parameters are consistent with those determined from collocated ground-based millimeter-wave cloud radar measurements. The coupled thin cirrus radiative transfer parameterization and OPTRAN, if combined with a reliable thin cirrus detection scheme, can be effectively used to enhance the AIRS data volume for data assimilation in numerical weather prediction models

High-energy scale revival and giant kink in the dispersion of a cuprate superconductor

In the present photoemission study of a cuprate superconductor Bi1.74Pb0.38Sr1.88CuO6+delta, we discovered a large scale dispersion of the lowest band, which unexpectedly follows the band structure calculation very well. The incoherent nature of the spectra suggests that the hopping-dominated dispersion occurs possibly with the assistance of local spin correlations. A giant kink in the dispersion is observed, and the complete self-energy containing all interaction information is extracted for a doped cuprate in the low energy region. These results recovered significant missing pieces in our current understanding of the electronic structure of cuprates.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Lett. on May 21, 200

Distributed functions of prefrontal and parietal cortices during sequential categorical decisions

Comparing sequential stimuli is crucial for guiding complex behaviors. To understand mechanisms underlying sequential decisions, we compared neuronal responses in the prefrontal cortex (PFC), the lateral intraparietal (LIP), and medial intraparietal (MIP) areas in monkeys trained to decide whether sequentially presented stimuli were from matching (M) or nonmatching (NM) categories. We found that PFC leads M/NM decisions, whereas LIP and MIP appear more involved in stimulus evaluation and motor planning, respectively. Compared to LIP, PFC showed greater nonlinear integration of currently visible and remembered stimuli, which correlated with the monkeys’ M/NM decisions. Furthermore, multi-module recurrent networks trained on the same task exhibited key features of PFC and LIP encoding, including nonlinear integration in the PFC-like module, which was causally involved in the networks’ decisions. Network analysis found that nonlinear units have stronger and more widespread connections with input, output, and within-area units, indicating putative circuit-level mechanisms for sequential decisions

Role of GAC63 in transcriptional activation mediated by β-catenin

β-Catenin is a key mediator in the canonical Wnt signaling pathway, which plays important roles in multiple developmental processes. Inappropriate activation of this pathway leads to developmental defects and development of certain cancers. Upon Wnt signaling, β-catenin binds TCF/LEF transcription factors. The TCF/LEF-β-catenin complex then recruits a variety of transcriptional coactivators to the promoter/enhancer region of Wnt-responsive genes and activates target gene transcription. In this article, we demonstrate that GRIP1-associated coactivator 63 (GAC63), a recently identified nuclear receptor (NR) coactivator, interacts with β-catenin. The N-terminus of GAC63 is the binding site for β-catenin, whereas a C-terminal fragment of β-catenin including armadillo repeats 10–12 binds to GAC63. Over-expression of GAC63 enhanced the transcriptional activity of β-catenin, and also greatly enhanced TCF/LEF-regulated reporter gene activity in a β-catenin-dependent manner. Endogenous GAC63 was recruited to TCF/LEF-responsive enhancer elements when β-catenin levels were induced by LiCl. In addition, reduction of endogenous GAC63 level by small interfering RNA (siRNA) inhibited TCF/LEF-mediated gene transcription. Our findings reveal a new function of GAC63 in transcriptional activation of Wnt-responsive genes

Primary role of the barely occupied states in the charge density wave formation of NbSe2

NbSe2 is a prototypical charge-density-wave (CDW) material, whose mechanism remains mysterious so far. With angle resolved photoemission spectroscopy, we mapped out the CDW gap and recovered the long-lost nesting condition over a large broken-honeycomb region in the Brillouin zone, which consists of six saddle band point regions with high density of states (DOS), and large regions away from Fermi surface with negligible DOS at the Fermi energy. We show that the major contributions to the CDW come from these barely occupied states rather than the saddle band points. Our findings not only resolve a long standing puzzle, but also overthrow the conventional wisdom that CDW is dominated by regions with high DOS.Comment: 5 pages, 4 figure

Palmitate and insulin synergistically induce IL-6 expression in human monocytes

<p>Abstract</p> <p>Background</p> <p>Insulin resistance is associated with a proinflammatory state that promotes the development of complications such as type 2 diabetes mellitus (T2DM) and atherosclerosis. The metabolic stimuli that initiate and propagate proinflammatory cytokine production and the cellular origin of proinflammatory cytokines in insulin resistance have not been fully elucidated. Circulating proinflammatory monocytes show signs of enhanced inflammation in obese, insulin resistant subjects and are thus a potential source of proinflammatory cytokine production. The specific, circulating metabolic factors that might stimulate monocyte inflammation in insulin resistant subjects are poorly characterized. We have examined whether saturated nonesterified fatty acids (NEFA) and insulin, which increase in concentration with developing insulin resistance, can trigger the production of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in human monocytes.</p> <p>Methods</p> <p>Messenger RNA and protein levels of the proinflammatory cytokines IL-6 and TNF-α were measured by quantitative real-time PCR (qRT-PCR) and Luminex bioassays. Student's <it>t</it>-test was used with a significance level of <it>p </it>< 0.05 to determine significance between treatment groups.</p> <p>Results</p> <p>Esterification of palmitate with coenzyme A (CoA) was necessary, while β-oxidation and ceramide biosynthesis were not required, for the induction of IL-6 and TNF-α in THP-1 monocytes. Monocytes incubated with insulin and palmitate together produced more IL-6 mRNA and protein, and more TNF-α protein, compared to monocytes incubated with palmitate alone. Incubation of monocytes with insulin alone did not affect the production of IL-6 or TNF-α. Both PI3K-Akt and MEK/ERK signalling pathways are important for cytokine induction by palmitate. MEK/ERK signalling is necessary for synergistic induction of IL-6 by palmitate and insulin.</p> <p>Conclusions</p> <p>High levels of saturated NEFA, such as palmitate, when combined with hyperinsulinemia, may activate human monocytes to produce proinflammatory cytokines and support the development and propagation of the subacute, chronic inflammatory state that is characteristic of insulin resistance. Results with inhibitors of β-oxidation and ceramide biosynthesis pathways suggest that increased fatty acid flux through the glycerolipid biosynthesis pathway may be involved in promoting proinflammatory cytokine production in monocytes.</p