816 research outputs found
CPD damage recognition by transcribing RNA polymerase II.
Cells use transcription-coupled repair (TCR) to efficiently eliminate DNA lesions such as ultraviolet light–induced cyclobutane pyrimidine dimers (CPDs). Here we present the structure-based mechanism for the first step in eukaryotic TCR, CPD-induced stalling of RNA polymerase (Pol) II. A CPD in the transcribed strand slowly passes a translocation barrier and enters the polymerase active site. The CPD 5′-thymine then directs uridine misincorporation into messenger RNA, which blocks translocation. Artificial replacement of the uridine by adenosine enables CPD bypass; thus, Pol II stalling requires CPD-directed misincorporation. In the stalled complex, the lesion is inaccessible, and the polymerase conformation is unchanged. This is consistent with nonallosteric recruitment of repair factors and excision of a lesion-containing DNA fragment in the presence of Pol II
Design and validation of a partial-genome microarray for transcriptional profiling of the Bradyrhizobium japonicum symbiotic gene region
The design and use of a pilot microarray for transcriptome analysis of the symbiotic, nitrogen-fixing Bradyrhizobium japonicum is reported here. The custom-synthesized chip (Affymetrix GeneChip®) features 738 genes, more than half of which belong to a 400-kb chromosomal segment strongly associated with symbiosis-related functions. RNA was isolated following an optimized protocol from wild-type cells grown aerobically and microaerobically, and from cells of aerobically grown regR mutant and microaerobically grown nifA mutant. Comparative microarray analyses thus revealed genes that are transcribed in either a RegR- or a NifA-dependent manner plus genes whose expression depends on the cellular oxygen status. Several genes were newly identified as members of the RegR and NifA regulons, beyond genes, which had been known from previous work. A comprehensive transcription analysis was performed with one of the new RegR-controlled genes (id880). Expression levels determined by microarray analysis of selected NifA- and RegR-controlled genes corresponded well with quantitative real-time PCR data, demonstrating the high complementarity of microarray analysis to classical methods of gene expression analysis in B. japonicum. Nevertheless, several previously established members of the NifA regulon were not detected as transcribed genes by microarray analysis, confirming the potential pitfalls of this approach also observed by other authors. By and large, this pilot study has paved the way towards the genome-wide transcriptome analysis of the 9.1-Mb B. japonicum genom
Drawing Graphs within Restricted Area
We study the problem of selecting a maximum-weight subgraph of a given graph
such that the subgraph can be drawn within a prescribed drawing area subject to
given non-uniform vertex sizes. We develop and analyze heuristics both for the
general (undirected) case and for the use case of (directed) calculation graphs
which are used to analyze the typical mistakes that high school students make
when transforming mathematical expressions in the process of calculating, for
example, sums of fractions
Steric masking of a dilysine endoplasmic reticulum retention motif during assembly of the human high affinity receptor for immunoglobulin E.
International audienceSignals that can cause retention in the ER have been found in the cytoplasmic domain of individual subunits of multimeric receptors destined to the cell surface. To study how ER retention motifs are masked during assembly of oligomeric receptors, we analyzed the assembly and intracellular transport of the human high-affinity receptor for immunoglobulin E expressed in COS cells. The cytoplasmic domain of the alpha chain contains a dilysine ER retention signal, which becomes nonfunctional after assembly with the gamma chain, allowing transport out of the ER of the fully assembled receptor. Juxtaposition of the cytoplasmic domains of the alpha and gamma subunits during assembly is responsible for this loss of ER retention. Substitution of the gamma chain cytoplasmic domain with cytoplasmic domains of irrelevant proteins resulted in efficient transport out of the ER of the alpha chain, demonstrating that nonspecific steric hindrance by the cytoplasmic domain of the gamma chain accounts for the masking of the ER retention signal present in the cytoplasmic domain of the alpha chain. Such a mechanism allows the ER retention machinery to discriminate between assembled and nonassembled receptors, and thus participates in quality control at the level of the ER.Signals that can cause retention in the ER have been found in the cytoplasmic domain of individual subunits of multimeric receptors destined to the cell surface. To study how ER retention motifs are masked during assembly of oligomeric receptors, we analyzed the assembly and intracellular transport of the human high-affinity receptor for immunoglobulin E expressed in COS cells. The cytoplasmic domain of the alpha chain contains a dilysine ER retention signal, which becomes nonfunctional after assembly with the gamma chain, allowing transport out of the ER of the fully assembled receptor. Juxtaposition of the cytoplasmic domains of the alpha and gamma subunits during assembly is responsible for this loss of ER retention. Substitution of the gamma chain cytoplasmic domain with cytoplasmic domains of irrelevant proteins resulted in efficient transport out of the ER of the alpha chain, demonstrating that nonspecific steric hindrance by the cytoplasmic domain of the gamma chain accounts for the masking of the ER retention signal present in the cytoplasmic domain of the alpha chain. Such a mechanism allows the ER retention machinery to discriminate between assembled and nonassembled receptors, and thus participates in quality control at the level of the ER
Self-Averaging, Distribution of Pseudo-Critical Temperatures and Finite Size Scaling in Critical Disordered Systems
The distributions of singular thermodynamic quantities in an ensemble
of quenched random samples of linear size at the critical point are
studied by Monte Carlo in two models. Our results confirm predictions of
Aharony and Harris based on Renormalization group considerations. For an
Ashkin-Teller model with strong but irrelevant bond randomness we find that the
relative squared width, , of is weakly self averaging. , where is the specific heat exponent and is the
correlation length exponent of the pure model fixed point governing the
transition. For the site dilute Ising model on a cubic lattice, known to be
governed by a random fixed point, we find that tends to a universal
constant independent of the amount of dilution (no self averaging). However
this constant is different for canonical and grand canonical disorder. We study
the distribution of the pseudo-critical temperatures of the ensemble
defined as the temperatures of the maximum susceptibility of each sample. We
find that its variance scales as and NOT as
R_\chi\sim 70R_\chi (T_c)\chiT_c(i,l)m_i(T_c,l)T_c(i,l)(T-T_c(i,l))/T_c$. This function is found to be universal and to behave
similarly to pure systems.Comment: 31 pages, 17 figures, submitted to Phys. Rev.
Computer simulation of the critical behavior of 3D disordered Ising model
The critical behavior of the disordered ferromagnetic Ising model is studied
numerically by the Monte Carlo method in a wide range of variation of
concentration of nonmagnetic impurity atoms. The temperature dependences of
correlation length and magnetic susceptibility are determined for samples with
various spin concentrations and various linear sizes. The finite-size scaling
technique is used for obtaining scaling functions for these quantities, which
exhibit a universal behavior in the critical region; the critical temperatures
and static critical exponents are also determined using scaling corrections. On
the basis of variation of the scaling functions and values of critical
exponents upon a change in the concentration, the conclusion is drawn
concerning the existence of two universal classes of the critical behavior of
the diluted Ising model with different characteristics for weakly and strongly
disordered systems.Comment: 14 RevTeX pages, 6 figure
Congested Traffic States in Empirical Observations and Microscopic Simulations
We present data from several German freeways showing different kinds of
congested traffic forming near road inhomogeneities, specifically lane
closings, intersections, or uphill gradients. The states are localized or
extended, homogeneous or oscillating. Combined states are observed as well,
like the coexistence of moving localized clusters and clusters pinned at road
inhomogeneities, or regions of oscillating congested traffic upstream of nearly
homogeneous congested traffic. The experimental findings are consistent with a
recently proposed theoretical phase diagram for traffic near on-ramps [D.
Helbing, A. Hennecke, and M. Treiber, Phys. Rev. Lett. {\bf 82}, 4360 (1999)].
We simulate these situations with a novel continuous microscopic single-lane
model, the ``intelligent driver model'' (IDM), using the empirical boundary
conditions. All observations, including the coexistence of states, are
qualitatively reproduced by describing inhomogeneities with local variations of
one model parameter.
We show that the results of the microscopic model can be understood by
formulating the theoretical phase diagram for bottlenecks in a more general
way. In particular, a local drop of the road capacity induced by parameter
variations has practically the same effect as an on-ramp.Comment: Now published in Phys. Rev. E. Minor changes suggested by a referee
are incorporated; full bibliographic info added. For related work see
http://www.mtreiber.de/ and http://www.helbing.org
Derivation, Properties, and Simulation of a Gas-Kinetic-Based, Non-Local Traffic Model
We derive macroscopic traffic equations from specific gas-kinetic equations,
dropping some of the assumptions and approximations made in previous papers.
The resulting partial differential equations for the vehicle density and
average velocity contain a non-local interaction term which is very favorable
for a fast and robust numerical integration, so that several thousand freeway
kilometers can be simulated in real-time. The model parameters can be easily
calibrated by means of empirical data. They are directly related to the
quantities characterizing individual driver-vehicle behavior, and their optimal
values have the expected order of magnitude. Therefore, they allow to
investigate the influences of varying street and weather conditions or freeway
control measures. Simulation results for realistic model parameters are in good
agreement with the diverse non-linear dynamical phenomena observed in freeway
traffic.Comment: For related work see
http://www.theo2.physik.uni-stuttgart.de/helbing.html and
http://www.theo2.physik.uni-stuttgart.de/treiber.htm
Wang-Landau study of the 3D Ising model with bond disorder
We implement a two-stage approach of the Wang-Landau algorithm to investigate
the critical properties of the 3D Ising model with quenched bond randomness. In
particular, we consider the case where disorder couples to the nearest-neighbor
ferromagnetic interaction, in terms of a bimodal distribution of strong versus
weak bonds. Our simulations are carried out for large ensembles of disorder
realizations and lattices with linear sizes in the range . We apply
well-established finite-size scaling techniques and concepts from the scaling
theory of disordered systems to describe the nature of the phase transition of
the disordered model, departing gradually from the fixed point of the pure
system. Our analysis (based on the determination of the critical exponents)
shows that the 3D random-bond Ising model belongs to the same universality
class with the site- and bond-dilution models, providing a single universality
class for the 3D Ising model with these three types of quenched uncorrelated
disorder.Comment: 7 pages, 7 figures, to be published in Eur. Phys. J.
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