236 research outputs found
Cell fate reprogramming by control of intracellular network dynamics
Identifying control strategies for biological networks is paramount for
practical applications that involve reprogramming a cell's fate, such as
disease therapeutics and stem cell reprogramming. Here we develop a novel
network control framework that integrates the structural and functional
information available for intracellular networks to predict control targets.
Formulated in a logical dynamic scheme, our approach drives any initial state
to the target state with 100% effectiveness and needs to be applied only
transiently for the network to reach and stay in the desired state. We
illustrate our method's potential to find intervention targets for cancer
treatment and cell differentiation by applying it to a leukemia signaling
network and to the network controlling the differentiation of helper T cells.
We find that the predicted control targets are effective in a broad dynamic
framework. Moreover, several of the predicted interventions are supported by
experiments.Comment: 61 pages (main text, 15 pages; supporting information, 46 pages) and
12 figures (main text, 6 figures; supporting information, 6 figures). In
revie
Emergence of scaling in random networks
Systems as diverse as genetic networks or the world wide web are best
described as networks with complex topology. A common property of many large
networks is that the vertex connectivities follow a scale-free power-law
distribution. This feature is found to be a consequence of the two generic
mechanisms that networks expand continuously by the addition of new vertices,
and new vertices attach preferentially to already well connected sites. A model
based on these two ingredients reproduces the observed stationary scale-free
distributions, indicating that the development of large networks is governed by
robust self-organizing phenomena that go beyond the particulars of the
individual systems.Comment: 11 pages, 2 figure
Mathematics Is Physics
In this essay, I argue that mathematics is a natural science---just like
physics, chemistry, or biology---and that this can explain the alleged
"unreasonable" effectiveness of mathematics in the physical sciences. The main
challenge for this view is to explain how mathematical theories can become
increasingly abstract and develop their own internal structure, whilst still
maintaining an appropriate empirical tether that can explain their later use in
physics. In order to address this, I offer a theory of mathematical
theory-building based on the idea that human knowledge has the structure of a
scale-free network and that abstract mathematical theories arise from a
repeated process of replacing strong analogies with new hubs in this network.
This allows mathematics to be seen as the study of regularities, within
regularities, within ..., within regularities of the natural world. Since
mathematical theories are derived from the natural world, albeit at a much
higher level of abstraction than most other scientific theories, it should come
as no surprise that they so often show up in physics.
This version of the essay contains an addendum responding to Slyvia
Wenmackers' essay and comments that were made on the FQXi website.Comment: 15 pages, LaTeX. Second prize winner in 2015 FQXi Essay Contest (see
http://fqxi.org/community/forum/topic/2364
Preformed defense responses in a powdery mildew-resistant Hungarian cherry pepper cultivar
A Hungarian cherry pepper (Capsicum annuum var. cerasiformé) cultivar ('Szentesi') displays resistance to pepper powdery mildew caused by Leveillula taurica. Resistance also develops in susceptible sweet pepper (C. annuum) when grafted on resistant cherry pepper cv. Szentesi rootstocks. Powdery mildew (PM) resistance is correlated with high levels of the defense regulator reactive oxygen species superoxide (O2 ') even in healthy plants. In order to further elucidate the mechanisms of preformed defense responses in cherry pepper cv. Szentesi we have monitored levels of salicylic acid (SA), a key molecule of plant defense signaling and expression of so-called pathogenesis/defense related (PR) genes in healthy pepper plants. Assays of free and bound (glycosylated) SA by high performance liquid chromatography (HPLC) revealed that in leaves of PM-resistant pepper levels of free SA are ca. twice as high compared to that of PM-sensitive plants. No difference occurred in levels of bound (glycosylated) SA. Expression of the CaPR-1 gene was several times higher in leaves of PM-resistant pepper than in sensitive plants as assayed by real time reverse transcription quantitative polymerase chain reaction (real time RT-qPCR). On the other hand, high expression levels of the CaPR-2 (glucanase) gene did not entirely correlate with PM-resistance, being detectable only in PM-resistant cv. Szentesi plants but neither in PM-resistant sweet pepper cv. Totál grafted on cv. Szentesi rootstocks nor in susceptible controls (cv. Totál). It seems that graft-transmissible PMresistance of the cherry pepper cv. Szentesi is correlated not only with high levels of superoxide but also with elevated levels of free salicylic acid and enhanced expression of the defense-related CaPR-1 gene
The urban economy as a scale-free network
We present empirical evidence that land values are scale-free and introduce a
network model that reproduces the observations. The network approach to urban
modelling is based on the assumption that the market dynamics that generates
land values can be represented as a growing scale-free network. Our results
suggest that the network properties of trade between specialized activities
causes land values, and likely also other observables such as population, to be
power law distributed. In addition to being an attractive avenue for further
analytical inquiry, the network representation is also applicable to empirical
data and is thereby attractive for predictive modelling.Comment: Submitted to Phys. Rev. E. 7 pages, 3 figures. (Minor typos and
details fixed
Predicting essential components of signal transduction networks: a dynamic model of guard cell abscisic acid signaling
Plants both lose water and take in carbon dioxide through microscopic
stomatal pores, each of which is regulated by a surrounding pair of guard
cells. During drought, the plant hormone abscisic acid (ABA) inhibits stomatal
opening and promotes stomatal closure, thereby promoting water conservation.
Here we synthesize experimental results into a consistent guard cell signal
transduction network for ABA-induced stomatal closure, and develop a dynamic
model of this process. Our model captures the regulation of more than forty
identified network components, and accords well with previous experimental
results at both the pathway and whole cell physiological level. Our analysis
reveals the novel predictions that the disruption of membrane depolarizability,
anion efflux, actin cytoskeleton reorganization, cytosolic pH increase, the
phosphatidic acid pathway or of K+ efflux through slowly activating K+ channels
at the plasma membrane lead to the strongest reduction in ABA responsiveness.
Initial experimental analysis assessing ABA-induced stomatal closure in the
presence of cytosolic pH clamp imposed by the weak acid butyrate is consistent
with model prediction. Our method can be readily applied to other biological
signaling networks to identify key regulatory components in systems where
quantitative information is limited.Comment: 17 pages, 8 figure
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