Decomposing Noise in Biochemical Signaling Systems Highlights the Role of Protein Degradation

AbstractStochasticity is an essential aspect of biochemical processes at the cellular level. We now know that living cells take advantage of stochasticity in some cases and counteract stochastic effects in others. Here we propose a method that allows us to calculate contributions of individual reactions to the total variability of a system’s output. We demonstrate that reactions differ significantly in their relative impact on the total noise and we illustrate the importance of protein degradation on the overall variability for a range of molecular processes and signaling systems. With our flexible and generally applicable noise decomposition method, we are able to shed new, to our knowledge, light on the sources and propagation of noise in biochemical reaction networks; in particular, we are able to show how regulated protein degradation can be employed to reduce the noise in biochemical systems

Weak Localization and Integer Quantum Hall Effect in a Periodic Potential

We consider magnetotransport in a disordered two-dimensional electron gas in the presence of a periodic modulation in one direction. Existing quasiclassical and quantum approaches to this problem account for Weiss oscillations in the resistivity tensor at moderate magnetic fields, as well as a strong modulation-induced modification of the Shubnikov-de Haas oscillations at higher magnetic fields. They do not account, however, for the operation at even higher magnetic fields of the integer quantum Hall effect, for which quantum interference processes are responsible. We then introduce a field-theory approach, based on a nonlinear sigma model, which encompasses naturally both the quasiclassical and quantum-mechanical approaches, as well as providing a consistent means of extending them to include quantum interference corrections. A perturbative renormalization-group analysis of the field theory shows how weak localization corrections to the conductivity tensor may be described by a modification of the usual one-parameter scaling, such as to accommodate the anisotropy of the bare conductivity tensor. We also show how the two-parameter scaling, conjectured as a model for the quantum Hall effect in unmodulated systems, may be generalized similarly for the modulated system. Within this model we illustrate the operation of the quantum Hall effect in modulated systems for parameters that are realistic for current experiments.Comment: 15 pages, 4 figures, ReVTeX; revised version with condensed introduction; two figures taken out; reference adde

Axial anomaly in the reduced model: Higher representations

The axial anomaly arising from the fermion sector of \U(N) or \SU(N) reduced model is studied under a certain restriction of gauge field configurations (the ``\U(1) embedding'' with $N=L^d$). We use the overlap-Dirac operator and consider how the anomaly changes as a function of a gauge-group representation of the fermion. A simple argument shows that the anomaly vanishes for an irreducible representation expressed by a Young tableau whose number of boxes is a multiple of $L^2$ (such as the adjoint representation) and for a tensor-product of them. We also evaluate the anomaly for general gauge-group representations in the large $N$ limit. The large $N$ limit exhibits expected algebraic properties as the axial anomaly. Nevertheless, when the gauge group is \SU(N), it does not have a structure such as the trace of a product of traceless gauge-group generators which is expected from the corresponding gauge field theory.Comment: 21 pages, uses JHEP.cls and amsfonts.sty, the final version to appear in JHE

Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States

In industrialized populations, Hodgkin's disease (HD) has an initial peak in young adulthood, whereas in economically developing populations the initial peak occurs in childhood. This pattern resembles that of infection with poliovirus and suggests an infectious cofactor in the etiology. Serologic studies have linked Epstein-Barr virus (EBV) to young adult and adult HD, and viral nucleic acids and antigens have been detected in a subset of Hodgkin's tumor specimens. To investigate the association of childhood HD with EBV we studied tumor specimens from 11 children treated in Honduras and 25 children treated in the United States using in situ hybridization and antigen detection techniques. Among the patients from Honduras, tumor specimens from all cases were EBV positive. Among the patients from the United States, tumor specimens from six of seven patients with mixed cellularity histology, 2 of 15 with nodular sclerosis histology, and neither of two patients with lymphocyte-predominant histologies were EBV positive. These findings support the hypothesis that EBV contributes to the pathogenesis of HD in children, particularly in mixed cellularity HD, and raises the possibility that there are important geographic, racial, or ethnic factors in the EBV association with HD

Cooperative AUV Navigation using a Single Maneuvering Surface Craft

In this paper we describe the experimental implementation of an online algorithm for cooperative localization of submerged autonomous underwater vehicles (AUVs) supported by an autonomous surface craft. Maintaining accurate localization of an AUV is difficult because electronic signals, such as GPS, are highly attenuated by water. The usual solution to the problem is to utilize expensive navigation sensors to slow the rate of dead-reckoning divergence. We investigate an alternative approach that utilizes the position information of a surface vehicle to bound the error and uncertainty of the on-board position estimates of a low-cost AUV. This approach uses the Woods Hole Oceanographic Institution (WHOI) acoustic modem to exchange vehicle location estimates while simultaneously estimating inter-vehicle range. A study of the system observability is presented so as to motivate both the choice of filtering approach and surface vehicle path planning. The first contribution of this paper is to the presentation of an experiment in which an extended Kalman filter (EKF) implementation of the concept ran online on-board an OceanServer Iver2 AUV while supported by an autonomous surface vehicle moving adaptively. The second contribution of this paper is to provide a quantitative performance comparison of three estimators: particle filtering (PF), non-linear least-squares optimization (NLS), and the EKF for a mission using three autonomous surface craft (two operating in the AUV role). Our results indicate that the PF and NLS estimators outperform the EKF, with NLS providing the best performance.United States. Office of Naval Research (Grant N000140711102)United States. Office of Naval Research. Multidisciplinary University Research InitiativeSingapore. National Research FoundationSingapore-MIT Alliance for Research and Technology. Center for Environmental Sensing and Monitorin

Measurement of the Running of the Electromagnetic Coupling at Large Momentum-Transfer at LEP

The evolution of the electromagnetic coupling, alpha, in the momentum-transfer range 1800GeV^2 < -Q^2 < 21600GeV^2 is studied with about 40000 Bhabha-scattering events collected with the L3 detector at LEP at centre-of-mass energies 189-209GeV. The running of alpha is parametrised as: alpha(Q^2) = alpha_0/(1-C Delta alpha(Q^2)), where alpha_0=\alpha(Q^2=0) is the fine-structure constant and C=1 corresponds to the evolution expected in QED. A fit to the differential cross section of the e+e- ->e+e- process for scattering angles in the range |cos theta|<0.9 excludes the hypothesis of a constant value of alpha, C=0, and validates the QED prediction with the result: C = 1.05 +/- 0.07 +/- 0.14, where the first uncertainty is statistical and the second systematic

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Review Section : Nature/Nurture Revisited I

Biologically oriented approaches to the study of human conflict have thus far been limited largely to the study of aggression. A sample of the literature on this topic is reviewed, drawing upon four major approaches: comparative psychology, ethology (including some popularized accounts), evolutionary-based theories, and several areas of human physiology. More sophisticated relationships between so-called "innate" and "acquired" determinants of behavior are discussed, along with the proper relevance of animal behavior studies for human behavior. Unless contained in a comprehensive theory which includes social and psychological variables, biolog ically oriented theories (although often valid within their domain) offer at best severely limited and at worst highly misleading explanations of complex social conflicts. The review concludes with a list of several positive contributions of these biological approaches and suggests that social scientists must become more knowledgeable about them.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68270/2/10.1177_002200277401800206.pd

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie