1,968 research outputs found
A "partitioned leaping" approach for multiscale modeling of chemical reaction dynamics
We present a novel multiscale simulation approach for modeling stochasticity
in chemical reaction networks. The approach seamlessly integrates
exact-stochastic and "leaping" methodologies into a single "partitioned
leaping" algorithmic framework. The technique correctly accounts for stochastic
noise at significantly reduced computational cost, requires the definition of
only three model-independent parameters and is particularly well-suited for
simulating systems containing widely disparate species populations. We present
the theoretical foundations of partitioned leaping, discuss various options for
its practical implementation and demonstrate the utility of the method via
illustrative examples.Comment: v4: 12 pages, 5 figures, final accepted version. Error found and
fixed in Appendi
Enhancement of the stability of genetic switches by overlapping upstream regulatory domains
We study genetic switches formed from pairs of mutually repressing operons.
The switch stability is characterised by a well defined lifetime which grows
sub-exponentially with the number of copies of the most-expressed transcription
factor, in the regime accessible by our numerical simulations. The stability
can be markedly enhanced by a suitable choice of overlap between the upstream
regulatory domains. Our results suggest that robustness against biochemical
noise can provide a selection pressure that drives operons, that regulate each
other, together in the course of evolution.Comment: 4 pages, 5 figures, RevTeX
Simple Wriggling is Hard unless You Are a Fat Hippo
We prove that it is NP-hard to decide whether two points in a polygonal
domain with holes can be connected by a wire. This implies that finding any
approximation to the shortest path for a long snake amidst polygonal obstacles
is NP-hard. On the positive side, we show that snake's problem is
"length-tractable": if the snake is "fat", i.e., its length/width ratio is
small, the shortest path can be computed in polynomial time.Comment: A shorter version is to be presented at FUN 201
Analytical study of an exclusive genetic switch
The nonequilibrium stationary state of an exclusive genetic switch is
considered. The model comprises two competing species and a single binding site
which, when bound to by a protein of one species, causes the other species to
be repressed. The model may be thought of as a minimal model of the power
struggle between two competing parties. Exact solutions are given for the
limits of vanishing binding/unbinding rates and infinite binding/unbinding
rates. A mean field theory is introduced which is exact in the limit of
vanishing binding/unbinding rates. The mean field theory and numerical
simulations reveal that generically bistability occurs and the system is in a
symmetry broken state. An exact perturbative solution which in principle allows
the nonequilibrium stationary state to be computed is also developed and
computed to first and second order.Comment: 28 pages, 6 figure
Novel cruzain inhibitors for the treatment of Chagas' disease.
The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas' disease, affects millions of individuals and continues to be an important global health concern. The poor efficacy and unfavorable side effects of current treatments necessitate novel therapeutics. Cruzain, the major cysteine protease of T. cruzi, is one potential novel target. Recent advances in a class of vinyl sulfone inhibitors are encouraging; however, as most potential therapeutics fail in clinical trials and both disease progression and resistance call for combination therapy with several drugs, the identification of additional classes of inhibitory molecules is essential. Using an exhaustive virtual-screening and experimental validation approach, we identify several additional small-molecule cruzain inhibitors. Further optimization of these chemical scaffolds could lead to the development of novel drugs useful in the treatment of Chagas' disease
Maximizing Maximal Angles for Plane Straight-Line Graphs
Let be a plane straight-line graph on a finite point set
in general position. The incident angles of a vertex
of are the angles between any two edges of that appear consecutively in
the circular order of the edges incident to .
A plane straight-line graph is called -open if each vertex has an
incident angle of size at least . In this paper we study the following
type of question: What is the maximum angle such that for any finite set
of points in general position we can find a graph from a certain
class of graphs on that is -open? In particular, we consider the
classes of triangulations, spanning trees, and paths on and give tight
bounds in most cases.Comment: 15 pages, 14 figures. Apart of minor corrections, some proofs that
were omitted in the previous version are now include
Draft Genome Sequence for Desulfovibrio africanus Strain PCS.
Desulfovibrio africanus strain PCS is an anaerobic sulfate-reducing bacterium (SRB) isolated from sediment from Paleta Creek, San Diego, CA. Strain PCS is capable of reducing metals such as Fe(III) and Cr(VI), has a cell cycle, and is predicted to produce methylmercury. We present the D. africanus PCS genome sequence
Complete Genome Sequence of Pelosinus fermentans JBW45, a Member of a Remarkably Competitive Group of Negativicutes in the Firmicutes Phylum.
The genome of Pelosinus fermentans JBW45, isolated from a chromium-contaminated site in Hanford, Washington, USA, has been completed with PacBio sequencing. Nine copies of the rRNA gene operon and multiple transposase genes with identical sequences resulted in breaks in the original draft genome and may suggest genomic instability of JBW45
When Can You Fold a Map?
We explore the following problem: given a collection of creases on a piece of
paper, each assigned a folding direction of mountain or valley, is there a flat
folding by a sequence of simple folds? There are several models of simple
folds; the simplest one-layer simple fold rotates a portion of paper about a
crease in the paper by +-180 degrees. We first consider the analogous questions
in one dimension lower -- bending a segment into a flat object -- which lead to
interesting problems on strings. We develop efficient algorithms for the
recognition of simply foldable 1D crease patterns, and reconstruction of a
sequence of simple folds. Indeed, we prove that a 1D crease pattern is
flat-foldable by any means precisely if it is by a sequence of one-layer simple
folds.
Next we explore simple foldability in two dimensions, and find a surprising
contrast: ``map'' folding and variants are polynomial, but slight
generalizations are NP-complete. Specifically, we develop a linear-time
algorithm for deciding foldability of an orthogonal crease pattern on a
rectangular piece of paper, and prove that it is (weakly) NP-complete to decide
foldability of (1) an orthogonal crease pattern on a orthogonal piece of paper,
(2) a crease pattern of axis-parallel and diagonal (45-degree) creases on a
square piece of paper, and (3) crease patterns without a mountain/valley
assignment.Comment: 24 pages, 19 figures. Version 3 includes several improvements thanks
to referees, including formal definitions of simple folds, more figures,
table summarizing results, new open problems, and additional reference
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