3,986 research outputs found
Stochastic model of transcription factor-regulated gene expression
We consider a stochastic model of transcription factor (TF)-regulated gene
expression. The model describes two genes: Gene A and Gene B which synthesize
the TFs and the target gene proteins respectively. We show through analytic
calculations that the TF fluctuations have a significant effect on the
distribution of the target gene protein levels when the mean TF level falls in
the highest sensitive region of the dose-response curve. We further study the
effect of reducing the copy number of Gene A from two to one. The enhanced TF
fluctuations yield results different from those in the deterministic case. The
probability that the target gene protein level exceeds a threshold value is
calculated with a knowledge of the probability density functions associated
with the TF and target gene protein levels. Numerical simulation results for a
more detailed stochastic model are shown to be in agreement with those obtained
through analytic calculations. The relevance of these results in the context of
the genetic disorder haploinsufficiency is pointed out. Some experimental
observations on the haploinsufficiency of the tumour suppressor gene, Nkx3.1,
are explained with the help of the stochastic model of TF-regulated gene
expression.Comment: 17 pages, 11 figures. Accepted for publication in Physical Biolog
Do Athermal Amorphous Solids Exist?
We study the elastic theory of amorphous solids made of particles with finite
range interactions in the thermodynamic limit. For the elastic theory to exist
one requires all the elastic coefficients, linear and nonlinear, to attain a
finite thermodynamic limit. We show that for such systems the existence of
non-affine mechanical responses results in anomalous fluctuations of all the
nonlinear coefficients of the elastic theory. While the shear modulus exists,
the first nonlinear coefficient B_2 has anomalous fluctuations and the second
nonlinear coefficient B_3 and all the higher order coefficients (which are
non-zero by symmetry) diverge in the thermodynamic limit. These results put a
question mark on the existence of elasticity (or solidity) of amorphous solids
at finite strains, even at zero temperature. We discuss the physical meaning of
these results and propose that in these systems elasticity can never be
decoupled from plasticity: the nonlinear response must be very substantially
plastic.Comment: 11 pages, 11 figure
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