Directed motion emerging from two coupled random processes: Translocation of a chain through a membrane nanopore driven by binding proteins

We investigate the translocation of a stiff polymer consisting of M monomers through a nanopore in a membrane, in the presence of binding particles (chaperones) that bind onto the polymer, and partially prevent backsliding of the polymer through the pore. The process is characterized by the rates: k for the polymer to make a diffusive jump through the pore, q for unbinding of a chaperone, and the rate q kappa for binding (with a binding strength kappa); except for the case of no binding kappa=0 the presence of the chaperones give rise to an effective force that drives the translocation process. Based on a (2+1) variate master equation, we study in detail the coupled dynamics of diffusive translocation and (partial) rectification by the binding proteins. In particular, we calculate the mean translocation time as a function of the various physical parameters.Comment: 22 pages, 5 figures, IOP styl

Exact steady-state velocity of ratchets driven by random sequential adsorption

We solve the problem of discrete translocation of a polymer through a pore, driven by the irreversible, random sequential adsorption of particles on one side of the pore. Although the kinetics of the wall motion and the deposition are coupled, we find the exact steady-state distribution for the gap between the wall and the nearest deposited particle. This result enables us to construct the mean translocation velocity demonstrating that translocation is faster when the adsorbing particles are smaller. Monte-Carlo simulations also show that smaller particles gives less dispersion in the ratcheted motion. We also define and compare the relative efficiencies of ratcheting by deposition of particles with different sizes and we describe an associated "zone-refinement" process.Comment: 11 pages, 4 figures New asymptotic result for low chaperone density added. Exact translocation velocity is proportional to (chaperone density)^(1/3

In Silico Generation of Alternative Hypotheses Using Causal Mapping (CMAP)

Previously, we introduced causal mapping (CMAP) as an easy to use systems biology tool for studying the behavior of biological processes that occur at the cellular and molecular level. CMAP is a coarse-grained graphical modeling approach in which the system of interest is modeled as an interaction map between functional elements of the system, in a manner similar to portrayals of signaling pathways commonly used by molecular cell biologists. CMAP describes details of the interactions while maintaining the simplicity of other qualitative methods (e.g., Boolean networks)

Detection of Extended Polarized Ultraviolet Radiation from the z = 1.82 Radio Galaxy 3C 256

We have detected spatially extended linear polarized UV emission from the high-redshift radio galaxy 3C~256 ($z=1.82$). A spatially integrated ($7.8''$ diameter aperture) measurement of the degree of polarization of the $V-$band (rest frame 0.19 $\mu$m) emission yields a value of 16.4\% ($\pm 2.2$\%) with a position angle of $42{}\rlap{\rm .}^\circ 4$ ($\pm 3{}\rlap{\rm .}^\circ 9$), orthogonal to the position angle on the sky of the major axis of the extended emission. The peak emission measured with a $3.6''$ diameter circular aperture is 11.7\% ($\pm 1.5$\%) polarized with a position angle of $42{}\rlap{\rm .}^\circ 4$ ($\pm 3{}\rlap{\rm .}^\circ 6$). An image of the polarized flux is presented, clearly displaying that the polarized flux is extended and present over the entire extent of the object. While it has been suggested that the UV continuum of 3C~256 might be due to star formation (Elston 1988) or a protogalaxy (Eisenhardt \& Dickinson 1993) based on its extremely blue spectral energy distribution and similar morphology at UV and visible wavelengths, we are unable to reconcile the observed high degree of polarization with such a model. While the detection of polarized emission from HZRGs has been shown to be a common phenomena, 3C~256 is only the third object for which a measurement of the extended polarized UV emission has been presented. These data lend additional support to the suggestion first made by di Serego Alighieri and collaborators that the ``alignment effect'', the tendency for the extended UV continuum radiation and line emission from HZRGs to be aligned with the major axis of the extended radio emission, is in large part due to scattering of anisotropic nuclear emission.Comment: 11 pages, LaTeX (aaspp style) file. Figure available by request to [email protected]

A Whole-Body Model for Glycogen Regulation Reveals a Critical Role for Substrate Cycling in Maintaining Blood Glucose Homeostasis

Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active) and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile) cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into “whole-body” contextual models that mimic in vivo conditions

Mapping susceptibility loci for alcohol consumption using number of grams of alcohol consumed per day as a phenotype measure

BACKGROUND: There is substantial evidence for a significant genetic component to the risk for alcoholism. However, susceptibility loci or genes for alcohol dependence remain largely unknown. To identify susceptibility loci for alcohol dependence, we selected 329 extended families from the Framingham Heart Study population in which at least one family member reported alcohol consumption during the interview in 1970–1971, and performed genome-wide linkage analyses using various analytical methods. RESULTS: Multi-point sib-pair regression analysis using the SIBPAL program of S.A.G.E. provided strong evidence for linkage of alcohol dependence to chromosomes 9 (p-value < 0.0001) and weak evidence to chromosomes 15 and 16 (p-value < 0.005). To confirm these findings, we re-analyzed the same data set by various methods implemented in GENEHUNTER and found that only one region was significant with a LOD score > 2.0 by the variance-component method. This region is located on chromosome 9 between markers GATA21F05 and GATA81C04. CONCLUSION: Analyses of the Framingham Heart Study population provided evidence of genetic susceptibility loci for alcohol dependence on chromosomes 9, 15, and 16. The genomic region identified on chromosome 9 was particularly interesting because the region has also been previously reported to be linked to alcohol dependence in the American Indian population by another group

``Superfast'' Reaction in Turbulent Flow with Potential Disorder

We explore the regime of ``superfast'' reactivity that has been predicted to occur in turbulent flow in the presence of potential disorder. Computer simulation studies confirm qualitative features of the previous renormalization group predictions, which were based on a static model of turbulence. New renormalization group calculations for a more realistic, dynamic model of turbulence show that the superfast regime persists. This regime, with concentration decay exponents greater than that for a well-mixed reaction, appears to be a general result of the interplay among non-linear reaction kinetics, turbulent transport, and local trapping by potential disorder.Comment: 14 pages. 4 figures. Uses IOP styles. To appear in J. Phys. A: Math. Ge

An X-ray Selected Galaxy Cluster at z=1.26

We report the discovery of an X-ray luminous galaxy cluster at z=1.26. RXJ0848.9+4452 was selected as an X-ray cluster candidate in the ROSAT Deep Cluster Survey, on the basis of its spatial extent. Deep optical and near-IR imaging have revealed a galaxy overdensity around the peak of the X-ray emission, with a significant excess of red objects with J-K colors typical of elliptical galaxies at z>1. Spectroscopic observations at the Keck II telescope have secured 6 galaxy redshifts in the range 1.257=1.261), within a 35 arcsec radius around the peak X-ray emission. This system lies only 4.2 arcmin away (5.0 h^{-1}_{50} comoving Mpc, q_0=0.5) from the galaxy cluster ClG J0848+4453, which was identified by Stanford et al. (1997) at z=1.273 in a near-IR field galaxy survey, and is also known to be X-ray luminous. Assuming that the X-ray emission is entirely due to hot intra-cluster gas, both these systems have similar rest frame luminosities L_x ~=1x10^{44} ergs/s (0.5-2.0 keV band). In combination with our spectrophotometric data for the entire 30 arcmin^2 field, this suggests the presence of a superstructure, consisting of two collapsed, possibly virialized clusters, the first detected to date at z>1.Comment: To appear in The Astronomical Journal, 24 pages, 8 figures, 1 color jpg plate (fig.7), see http://www.eso.org/~prosati/lynx/plate_fig7.jp

Three and four current reversals versus temperature in correlation ratchets with a simple sawtooh potential

Transport of Brownian particles on a simple sawtooth potential subjected to both unbiased thermal and nonequilibrium symmetric three-level Markovian noise is considered. The new effects of three and four current reversals as a function of temperature are established in such correlation ratchets. The parameter space coordinates of the fixed points associated with these current reversals and the necessary and sufficient conditions for the existence of the novel current reversals are found.Comment: 4 pages, 5 figures; some changes introduced; accepted for publication in Physical Review

Pathological Features of Breast Cancer seen in Northwestern Tanzania: A Nine Years Retrospective Study.

Breast cancer is more common in Western Countries compared to African populations. However in African population, it appears that the disease tends to be more aggressive and occurring at a relatively young age at the time of presentation. The aim of this study was to describe the trend of Breast Cancer in Northwestern Tanzania. This was a retrospective study which involved all cases of breast cancer diagnosed histologically at Bugando Medical Center from 2002 to 2010. Histological results and slides were retrieved from the records in the Pathology department, clinical information and demographic data for patients were retrieved from surgical wards and department of medical records. Histology slides were re-evaluated for the histological type, grade (By modified Bloom-Richardson score), and presence of necrosis and skin involvement. Data was entered and analyzed by SPSS computer software version 15. There were 328 patients histologically confirmed to have breast cancer, the mean age at diagnosis was 48.7 years (+/- 13.1). About half of the patients (52.4%) were below 46 years of age, and this group of patients had significantly higher tendency for lymph node metastasis (p = 0.012). The tumor size ranged from 1 cm to 18 cm in diameter with average (mean) of 5.5 cm (+/- 2.5), and median size of 6 cm. Size of the tumor (above 6 cm in diameter) and presence of necrosis within the tumor was significantly associated with high rate of lymph node metastasis (p = 0.000). Of all patients, 64% were at clinical stage III (specifically IIIB) and 70.4% had lymph node metastasis at the time of diagnosis. Only 4.3% of the patients were in clinical stage I at the time of diagnosis. Majority of the patients had invasive ductal carcinoma (91.5%) followed by mucinous carcinoma (5.2%), Invasive lobular carcinoma (3%) and in situ ductal carcinoma (0.3%). In all patients, 185 (56.4%) had tumor with histological grade 3. Breast cancer in this region show a trend towards relative young age at diagnosis with advanced stage at diagnosis and high rate of lymph node metastasis. Poor Referral system, lack of screening programs and natural aggressive biological behavior of tumor may contribute to advanced disease at the time of diagnosis