title: The brain near the edge

abstract:
  When viewed at a certain coarse grain, the brain seems a relatively small
dynamical system composed by a few dozen interacting areas, performing a number
of stereotypical behaviors. It is known that, even relatively small dynamical
systems can reliably generate robust and flexible behavior if they are possed
near a second order phase transition, because of the abundance of metastable
states at the critical point. The approach pursued here assumes that some of
the most fundamental properties of the functioning brain are possible because
it is spontaneously possed at the border of such instability. In this notes we
review the motivation, the arguments and recent results as well as the
implications of this view of the functioning brain.


title:
An effective model for flocculating bacteria with density-dependent
  growth dynamics

abstract:
  We present a model for a biological reactor in which bacteria tend to
aggregate in flocs, as encountered in wastewater treatment plants. The
influence of this flocculation on the growth dynamics of the bacteria is
studied. We argue that a description in terms of a specific growth rate is
possible when the flocculation dynamics is much faster than the other processes
in the system. An analytical computation shows that in this case, the growth
rate is density-dependent, i.e., depends both on the substrate and the biomass
density. When the flocculation time scale overlaps with the other time scales
present in the system, the notion of specific growth rate becomes problematic.
However, we show numerically that a density-dependent growth rate can still
accurately describe the system response to certain perturbations.


title: Integrated Cell Manipulation Systems

abstract:
  A new type of microfluidic system for biological cell manipulation, a
CMOS/microfluidic hybrid, is demonstrated. The hybrid system starts with a
custom-designed CMOS (complementary metal-oxide semiconductor) chip fabricated
in a semiconductor foundry using standard integration circuit technology. A
microfluidic channel is post-fabricated on top of the CMOS chip to provide
biocompatible environment. The motion of individual biological cells that are
tagged with magnetic beads is directly controlled by the CMOS chip that
generates localized magnetic filed patterns using an on-chip array of
micro-electromagnets. The speed and the programmability of the CMOS chip
further allow for the dynamic reconfiguration of the magnetic fields,
substantially increasing the manipulation capability of the hybrid system. The
concept of a hybrid system is verified by simultaneously manipulating
individual biological cells with microscopic resolution. A new operation
protocol that exploits the fast speed of electronics to trap and move a large
number of cells with less power consumption is also demonstrated. Combining the
advantages of microelectronics, the CMOS/microfluidic hybrid approach presents
a new model for a multifunctional lab-on-a chip for biological and medical
applications.


title: Genetic Code as a Harmonic System

abstract:
  In a certain way, this paper presents the continuation of the previous one
which discussed the harmonic structure of the genetic code (Rakocevic, 2004).
Several new harmonic structures presented in this paper, through specific unity
and coherence, together with the previously presented (Rakocevic, 2004), show
that it makes sense to understand genetic code as a set of several different
harmonic structures. Thereby, the harmonicity itself represents a specific
unity and coherence of physico-chemical properties of amino acid molecules and
the number of atoms and/or nucleons in the molecules themselves (in the form of
typical balances). A specific Gauss' arithmetical algorithm has the central
position among all these structures and it corresponds to the patterns of the
number of atoms within the side chains of amino acid molecules in the following
sense: G+V = 11; P+I = 21; S+T+L+A+G = 31; D+E+M+C+P = 41; K+R+Q+N+V = 61;
F+Y+W+H+I = 71; (L+M+Q+W) + (A+C+N+H) = 81; (S+D+K+F) + (T+E+R+Y) = 91;
(F+L+M+S+P) = (T+A+Y+H+I) = (Q+N+K+D+V) = (E+C+W+R+G) = 51. Bearing in mind all
these regularities it make sense to talk about genetic code as a harmonic
system. On the other hand, such an order provides new evidence supporting the
hypothesis established in the previous paper (Rakocevic, 2004) that genetic
code has been complete from the very beginning and as such was the condition
for the origin and evolution of life.


title: Kinesin as an electrostatic machine

abstract:
  Kinesin and related motor proteins utilize ATP fuel to propel themselves
along the external surface of microtubules in a processive and directional
fashion. We show that the observed step-like motion is possible through time
varying charge distributions furnished by the ATP hydrolysis circle while the
static charge configuration on the microtuble provides the guide for motion.
Thus, while the chemical hydrolysis energy induces appropriate local
conformational changes, the motor translational energy is fundamentally
electrostatic. Numerical simulations of the mechanical equations of motion show
that processivity and directionality are direct consequences of the
ATP-dependent electrostatic interaction between the different charge
distributions of kinesin and microtubule.


title: Stretching of proteins in a uniform flow

abstract:
  Stretching of a protein by a fluid flow is compared to that in a force-clamp
apparatus. The comparison is made within a simple topology-based dynamical
model of a protein in which the effects of the flow are implemented using
Langevin dynamics. We demonstrate that unfolding induced by a uniform flow
shows a richer behavior than that in the force clamp. The dynamics of unfolding
is found to depend strongly on the selection of the amino acid, usually one of
the termini, which is anchored. These features offer potentially wider
diagnostic tools to investigate structure of proteins compared to experiments
based on the atomic force microscopy.


title:
Correlated fragile site expression allows the identification of
  candidate fragile genes involved in immunity and associated with
  carcinogenesis

abstract:
  Common fragile sites (cfs) are specific regions in the human genome that are
particularly prone to genomic instability under conditions of replicative
stress. Several investigations support the view that common fragile sites play
a role in carcinogenesis. We discuss a genome-wide approach based on graph
theory and Gene Ontology vocabulary for the functional characterization of
common fragile sites and for the identification of genes that contribute to
tumour cell biology. CFS were assembled in a network based on a simple measure
of correlation among common fragile site patterns of expression. By applying
robust measurements to capture in quantitative terms the non triviality of the
network, we identified several topological features clearly indicating
departure from the Erdos-Renyi random graph model. The most important outcome
was the presence of an unexpected large connected component far below the
percolation threshold. Most of the best characterized common fragile sites
belonged to this connected component. By filtering this connected component
with Gene Ontology, statistically significant shared functional features were
detected. Common fragile sites were found to be enriched for genes associated
to the immune response and to mechanisms involved in tumour progression such as
extracellular space remodeling and angiogenesis. Our results support the
hypothesis that fragile sites serve a function; we propose that fragility is
linked to a coordinated regulation of fragile genes expression.


title: Cucker-Smale Flocking under Hierarchical Leadership

abstract:
  A mathematical theory on flocking serves the foundation for several
ubiquitous multi-agent phenomena in biology, ecology, sensor networks, economy,
as well as social behavior like language emergence and evolution. Directly
inspired by the recent fundamental works of Cucker and Smale on the
construction and analysis of a generic flocking model, we study the emergent
behavior of Cucker-Smale flocking under hierarchical leadership. The rates of
convergence towards asymptotically coherent group patterns in different
scenarios are established.
  The consistent convergence towards coherent patterns may well reveal the
advantages and necessities of having leaders and leadership in a complex
(biological, technological, economic, or social) system with sufficient
intelligence.


title:
Contr\^{o}le paracrine du d\'{e}veloppement du tissu adipeux par
  l'autotaxine et l'acide lysophosphatidique

abstract:
  Secretion and role of autotaxin and lysophosphatidic acid in adipose tissue
In obesity, adipocyte hypertrophy is often associated with recrutement of new
fat cells (adipogenesis) under the control of circulating and local regulatory
factors. Among the different lipids released in the extracellular compartment
of adipocytes, our group found the presence of lysophosphatidic acid (LPA). LPA
is a bioactive phospholipid able to regulate several cell responses via the
activation of specific G-protein coupled membrane receptors. Our group found
that LPA increases preadipocyte proliferation and inhibits adipogenesis via the
activation of LPA1 receptor subtype. Extracellular LPA-synthesis is catalyzed
by a lysophospholipase D secreted by adipocytes : autotaxin (ATX). Adipocyte
ATX expression strongly increases with adipogenesis as well as in individuals
exhibiting type 2 diabetes associated with massive obesity. A possible
contribution of ATX and LPA as paracrine regulators of adipogenesis and obesity
associated diabetes is proposed.


title: Perfect Sampling of the Master Equation for Gene Regulatory Networks

abstract:
  We present a Perfect Sampling algorithm that can be applied to the Master
Equation of Gene Regulatory Networks (GRNs). The method recasts Gillespie's
Stochastic Simulation Algorithm (SSA) in the light of Markov Chain Monte Carlo
methods and combines it with the Dominated Coupling From The Past (DCFTP)
algorithm to provide guaranteed sampling from the stationary distribution. We
show how the DCFTP-SSA can be generically applied to genetic networks with
feedback formed by the interconnection of linear enzymatic reactions and
nonlinear Monod- and Hill-type elements. We establish rigorous bounds on the
error and convergence of the DCFTP-SSA, as compared to the standard SSA,
through a set of increasingly complex examples. Once the building blocks for
GRNs have been introduced, the algorithm is applied to study properly averaged
dynamic properties of two experimentally relevant genetic networks: the toggle
switch, a two-dimensional bistable system, and the repressilator, a
six-dimensional genetic oscillator.


title: Homochirality in an early peptide world

abstract:
  A recently proposed model of non-autocatalytic reactions in dipeptide
reactions leading to spontaneous symmetry breaking and homochirality is
examined. The model is governed by activation, polymerization, epimerization
and depolymerization of amino acids. Symmetry breaking is primarily a
consequence of the fact that the rates of reactions involving homodimers and
heterodimers are different, i.e., stereoselective, and on the fact that
epimerization can only occur on the N-terminal residue and not on the Cterminal
residue. This corresponds to an auto-inductive cyclic process that works only
in one sense. It is argued that epimerization mimics both autocatalytic
behavior as well as mutual antagonism - both of which were known to be crucial
for producing full homochirality.


title:
Stochastic kinetics of viral capsid assembly based on detailed protein
  structures

abstract:
  We present a generic computational framework for the simulation of viral
capsid assembly which is quantitative and specific. Starting from PDB files
containing atomic coordinates, the algorithm builds a coarse grained
description of protein oligomers based on graph rigidity. These reduced protein
descriptions are used in an extended Gillespie algorithm to investigate the
stochastic kinetics of the assembly process. The association rates are obtained
from a diffusive Smoluchowski equation for rapid coagulation, modified to
account for water shielding and protein structure. The dissociation rates are
derived by interpreting the splitting of oligomers as a process of graph
partitioning akin to the escape from a multidimensional well. This modular
framework is quantitative yet computationally tractable, with a small number of
physically motivated parameters. The methodology is illustrated using two
different viruses which are shown to follow quantitatively different assembly
pathways. We also show how in this model the quasi-stationary kinetics of
assembly can be described as a Markovian cascading process in which only a few
intermediates and a small proportion of pathways are present. The observed
pathways and intermediates can be related a posteriori to structural and
energetic properties of the capsid oligomers.


title: A Dynamical Model of Lipoprotein Metabolism

abstract:
  We present a dynamical model of lipoprotein metabolism derived by combining a
cascading process in the blood stream and cellular level regulatory dynamics.
We analyse the existence and stability of equilibria and show that this
low-dimensional, nonlinear model exhibits bistability between a low and a high
cholesterol state. A sensitivity analysis indicates that the intracellular
concentration of cholesterol is robust to parametric variations while the
plasma cholesterol can vary widely. We show how the dynamical response to
time-dependent inputs can be used to diagnose the state of the system. We also
establish the connection between parameters in the system and medical and
genetic conditions.


title: Modeling Dual Pathways for the Metazoan Spindle Assembly Checkpoint

abstract:
  Using computational modelling, we investigate mechanisms of signal
transduction focusing on the spindle assembly checkpoint where a single
unattached kinetochore is able to signal to prevent cell cycle progression.
This inhibitory signal switches off rapidly once spindle microtubules have
attached to all kinetochores. This requirement tightly constrains the possible
mechanisms. Here we investigate two possible mechanisms for spindle checkpoint
operation in metazoan cells, both supported by recent experiments. The first
involves the free diffusion and sequestration of cell-cycle regulators. This
mechanism is severely constrained both by experimental fluorescence recovery
data and also by the large volumes involved in open mitosis in metazoan cells.
Using a simple mathematical analysis and computer simulation, we find that this
mechanism can generate the inhibition found in experiment but likely requires a
two stage signal amplification cascade. The second mechanism involves spatial
gradients of a short-lived inhibitory signal that propagates first by diffusion
but then primarily via active transport along spindle microtubules. We propose
that both mechanisms may be operative in the metazoan spindle assembly
checkpoint, with either able to trigger anaphase onset even without support
from the other pathway.


title:
Topological basis of signal integration in the
  transcriptional-regulatory network of the yeast, Saccharomyces cerevisiae

abstract:
  BACKGROUND. Signal recognition and information processing is a fundamental
cellular function, which in part involves comprehensive transcriptional
regulatory (TR) mechanisms carried out in response to complex environmental
signals in the context of the cell's own internal state. However, the network
topological basis of developing such integrated responses remains poorly
understood.
  RESULTS. By studying the TR network of the yeast Saccharomyces cerevisiae we
show that an intermediate layer of transcription factors naturally segregates
into distinct subnetworks. In these topological units transcription factors are
densely interlinked in a largely hierarchical manner and respond to external
signals by utilizing a fraction of these subnets.
  CONCLUSIONS. As transcriptional regulation represents the "slow" component of
overall information processing, the identified topology suggests a model in
which successive waves of transcriptional regulation originating from distinct
fractions of the TR network control robust integrated responses to complex
stimuli.


title:
Loss of AP-3 function affects spontaneous and evoked release at
  hippocampal mossy fiber synapses

abstract:
  Synaptic vesicle (SV) exocytosis mediating neurotransmitter release occurs
spontaneously at low intraterminal calcium concentrations and is stimulated by
a rise in intracellular calcium. Exocytosis is compensated for by the
reformation of vesicles at plasma membrane and endosomes. Although the adaptor
complex AP-3 was proposed to be involved in the formation of SVs from
endosomes, whether its function has an indirect effect on exocytosis remains
unknown. Using mocha mice, which are deficient in functional AP-3, we identify
an AP-3-dependent tetanus neurotoxin-resistant asynchronous release that can be
evoked at hippocampal mossy fiber (MF) synapses. Presynaptic targeting of the
tetanus neurotoxin-resistant vesicle soluble N-ethylmaleimide-sensitive factor
attachment protein receptor (SNARE) tetanus neurotoxin-insensitive
vesicle-associated membrane protein (TI-VAMP) is lost in mocha hippocampal MF
terminals, whereas the localization of synaptobrevin 2 is unaffected. In
addition, quantal release in mocha cultures is more frequent and more sensitive
to sucrose. We conclude that lack of AP-3 results in more constitutive
secretion and loss of an asynchronous evoked release component, suggesting an
important function of AP-3 in regulating SV exocytosis at MF terminals.


title: Second look at the spread of epidemics on networks

abstract:
  In an important paper, M.E.J. Newman claimed that a general network-based
stochastic Susceptible-Infectious-Removed (SIR) epidemic model is isomorphic to
a bond percolation model, where the bonds are the edges of the contact network
and the bond occupation probability is equal to the marginal probability of
transmission from an infected node to a susceptible neighbor. In this paper, we
show that this isomorphism is incorrect and define a semi-directed random
network we call the epidemic percolation network that is exactly isomorphic to
the SIR epidemic model in any finite population. In the limit of a large
population, (i) the distribution of (self-limited) outbreak sizes is identical
to the size distribution of (small) out-components, (ii) the epidemic threshold
corresponds to the phase transition where a giant strongly-connected component
appears, (iii) the probability of a large epidemic is equal to the probability
that an initial infection occurs in the giant in-component, and (iv) the
relative final size of an epidemic is equal to the proportion of the network
contained in the giant out-component. For the SIR model considered by Newman,
we show that the epidemic percolation network predicts the same mean outbreak
size below the epidemic threshold, the same epidemic threshold, and the same
final size of an epidemic as the bond percolation model. However, the bond
percolation model fails to predict the correct outbreak size distribution and
probability of an epidemic when there is a nondegenerate infectious period
distribution. We confirm our findings by comparing predictions from percolation
networks and bond percolation models to the results of simulations. In an
appendix, we show that an isomorphism to an epidemic percolation network can be
defined for any time-homogeneous stochastic SIR model.


title: Estimating degrees of freedom in motor systems

abstract:
  Studies of the degrees of freedom or "synergies" in musculoskeletal systems
rely critically on algorithms to estimate the "dimension" of kinematic or
neural data. Linear algorithms such as principal component analysis (PCA) are
used almost exclusively for this purpose. However, biological systems tend to
possess nonlinearities and operate at multiple spatial and temporal scales so
that the set of reachable system states typically does not lie close to a
single linear subspace. We compare the performance of PCA to two alternative
nonlinear algorithms (Isomap and our novel pointwise dimension estimation
(PD-E)) using synthetic and motion capture data from a robotic arm with known
kinematic dimensions, as well as motion capture data from human hands. We find
that consideration of the spectral properties of the singular value
decomposition in PCA can lead to more accurate dimension estimates than the
dominant practice of using a fixed variance capture threshold. We investigate
methods for identifying a single integer dimension using PCA and Isomap. In
contrast, PD-E provides a range of estimates of fractal dimension. This helps
to identify heterogeneous geometric structure of data sets such as unions of
manifolds of differing dimensions, to which Isomap is less sensitive. Contrary
to common opinion regarding fractal dimension methods, PD-E yielded reasonable
results with reasonable amounts of data. We conclude that it is necessary and
feasible to complement PCA with other methods that take into consideration the
nonlinear properties of biological systems for a more robust estimation of
their degrees of freedom.


title:
Heterogeneous Cell Population Dynamics: Equation-Free Uncertainty
  Quantification Computations

abstract:
  We propose a computational approach to modeling the collective dynamics of
populations of coupled heterogeneous biological oscillators. In contrast to
Monte Carlo simulation, this approach utilizes generalized Polynomial Chaos
(gPC) to represent random properties of the population, thus reducing the
dynamics of ensembles of oscillators to dynamics of their (typically
significantly fewer) representative gPC coefficients. Equation-Free (EF)
methods are employed to efficiently evolve these gPC coefficients in time and
compute their coarse-grained stationary state and/or limit cycle solutions,
circumventing the derivation of explicit, closed-form evolution equations.
Ensemble realizations of the oscillators and their statistics can be readily
reconstructed from these gPC coefficients. We apply this methodology to the
synchronization of yeast glycolytic oscillators coupled by the membrane
exchange of an intracellular metabolite. The heterogeneity consists of a single
random parameter, which accounts for glucose influx into a cell, with a
Gaussian distribution over the population. Coarse projective integration is
used to accelerate the evolution of the population statistics in time. Coarse
fixed-point algorithms in conjunction with a Poincar\'e return map are used to
compute oscillatory solutions for the cell population and to quantify their
stability.


title:
Coding static natural images using spiking event times: do neurons
  cooperate?

abstract:
  To understand possible strategies of temporal spike coding in the central
nervous system, we study functional neuromimetic models of visual processing
for static images. We will first present the retinal model which was introduced
by Van Rullen and Thorpe and which represents the multiscale contrast values of
the image using an orthonormal wavelet transform. These analog values activate
a set of spiking neurons which each fire once to produce an asynchronous wave
of spikes. According to this model, the image may be progressively
reconstructed from this spike wave thanks to regularities in the statistics of
the coefficients determined with natural images. Here, we study mathematically
how the quality of information transmission carried by this temporal
representation varies over time. In particular, we study how these regularities
can be used to optimize information transmission by using a form of temporal
cooperation of neurons to code analog values. The original model used wavelet
transforms that are close to orthogonal. However, the selectivity of realistic
neurons overlap, and we propose an extension of the previous model by adding a
spatial cooperation between filters. This model extends the previous scheme for
arbitrary--and possibly nonorthogonal--representations of features in the
images. In particular, we compared the performance of increasingly
over-complete representations in the retina. Results show that this algorithm
provides an efficient spike coding strategy for low-level visual processing
which may adapt to the complexity of the visual input.


title: Feature detection using spikes: the greedy approach

abstract:
  A goal of low-level neural processes is to build an efficient code extracting
the relevant information from the sensory input. It is believed that this is
implemented in cortical areas by elementary inferential computations
dynamically extracting the most likely parameters corresponding to the sensory
signal. We explore here a neuro-mimetic feed-forward model of the primary
visual area (VI) solving this problem in the case where the signal may be
described by a robust linear generative model. This model uses an over-complete
dictionary of primitives which provides a distributed probabilistic
representation of input features. Relying on an efficiency criterion, we derive
an algorithm as an approximate solution which uses incremental greedy inference
processes. This algorithm is similar to 'Matching Pursuit' and mimics the
parallel architecture of neural computations. We propose here a simple
implementation using a network of spiking integrate-and-fire neurons which
communicate using lateral interactions. Numerical simulations show that this
Sparse Spike Coding strategy provides an efficient model for representing
visual data from a set of natural images. Even though it is simplistic, this
transformation of spatial data into a spatio-temporal pattern of binary events
provides an accurate description of some complex neural patterns observed in
the spiking activity of biological neural networks.


title: The Factors of the Classification of Protein Amino Acids

abstract:
  In this work it is shown that three pairs of the factors appear to be the
key, i.e. main factors of a natural classification of protein (canonical) amino
acids within the amino acid (genetic) code. First pair: the factors of the
habit of an amino acid molecule (size and polarity). Second pair: the factors
of the association (type of the amino acid/enzyme reactivity and degree of the
hydrophobicity/hydrophilicity of an amino acid molecule). Third pair: the
factors of the dissociation (degree of the acidity-basicity, over acidic group,
COOH and degree of the basicity/acidity over the basic group, NH2). As a result
of the influence and interdependence of all six factors (measured through
correspondent valid parameters) it appears still one natural classification
into polar and non-polar amino acids, where polar amino acids possess negative
and non-polar, the positive values of hydropathy index.


title:
Biological Consequences of Tightly Bent DNA: The Other Life of a
  Macromolecular Celebrity

abstract:
  The mechanical properties of DNA play a critical role in many biological
functions. For example, DNA packing in viruses involves confining the viral
genome in a volume (the viral capsid) with dimensions that are comparable to
the DNA persistence length. Similarly, eukaryotic DNA is packed in DNA-protein
complexes (nucleosomes) in which DNA is tightly bent around protein spools. DNA
is also tightly bent by many proteins that regulate transcription, resulting in
a variation in gene expression that is amenable to quantitative analysis. In
these cases, DNA loops are formed with lengths that are comparable to or
smaller than the DNA persistence length. The aim of this review is to describe
the physical forces associated with tightly bent DNA in all of these settings
and to explore the biological consequences of such bending, as increasingly
accessible by single-molecule techniques.


title:
Benthic inputs as predictors of seagrass (Posidonia oceanica) fish
  farm-induced decline

abstract:
  Fish farms represent a growing source of disturbance to shallow benthic
ecosystems like seagrass meadows. Despite some existing insights on the
mechanisms underlying decline, efficient tools to quantitatively predict the
response of benthic communities to fish farm effluents have not yet been
developed. We explored relationships of fish farm organic and nutrient input
rates to the sediments with population dynamics of the key seagrass species
(Posidonia oceanica) in deep meadows growing around four Mediterranean Sea
bream and Sea bass fish farms. We performed 2 annual shoot censuses on
permanent plots at increasing distance from cages. Before each census we
measured sedimentation rates adjacent to the plots using benthic sediment
traps. High shoot mortality rates were recorded near the cages, up to 20 times
greater than at control sites. Recruitment rates remained similar to
undisturbed meadows and could not compensate mortality, leading to rapid
seagrass decline within the first 100 meters from cages. Seagrass mortality
increased with total (R2= 0.47, p< 0.0002), organic matter (R2= 0.36, p=
0.001), nitrogen (R2= 0.34, p= 0.002) and phosphorus (R2= 0.58, p< 3 x 10-5)
sedimentation rates. P. oceanica decline accelerated above a phosphorus loading
threshold of 50 mg m-2 day-1. Benthic sedimentation rates seem a powerful
predictor of seagrass mortality from fish farming, integrating local
hydrodynamics, waste effluents variability and several environmental
mechanisms, fuelled by organic inputs and leading to seagrass loss. Coupling
direct measurements of benthic sedimentation rates with dynamics of key species
is proposed as an efficient way to predict and minimize fish farm impacts to
benthic communities.


title: The Bayesian `star paradox' persists for long finite sequences

abstract:
  The `star paradox' in phylogenetics is the tendency for a particular resolved
tree to be sometimes strongly supported even when the data is generated by an
unresolved (`star') tree. There have been contrary claims as to whether this
phenomenon persists when very long sequences are considered. This note settles
one aspect of this debate by proving mathematically that there is always a
chance that a resolved tree could be strongly supported, even as the length of
the sequences becomes very large.


title: Effect of supercoiling on formation of protein mediated DNA loops

abstract:
  DNA loop formation is one of several mechanisms used by organisms to regulate
genes. The free energy of forming a loop is an important factor in determining
whether the associated gene is switched on or off. In this paper we use an
elastic rod model of DNA to determine the free energy of forming short (50--100
basepair), protein mediated DNA loops. Superhelical stress in the DNA of living
cells is a critical factor determining the energetics of loop formation, and we
explicitly account for it in our calculations. The repressor protein itself is
regarded as a rigid coupler; its geometry enters the problem through the
boundary conditions it applies on the DNA. We show that a theory with these
ingredients is sufficient to explain certain features observed in modulation of
in vivo gene activity as a function of the distance between operator sites for
the lac repressor. We also use our theory to make quantitative predictions for
the dependence of looping on superhelical stress, which may be testable both in
vivo and in single-molecule experiments such as the tethered particle assay and
the magnetic bead assay.


title:
Quantum Effects and Genetics Code: Dynamics and Information Transfer in
  DNA Replication

abstract:
  The possible role of quantum effects in transfer of genetic information is
studied. It's argued that the nucleotides selection during DNA replication is
performed by means of proton tunneling between nucleotide and DNA-polimerase
bound by hydrogen bonds. Such mechanism is sensitive to the structure of
nucleotide hydrogen bonds, consequently only one nucleotide sort is captured by
DNA-polimerase in each event.The algorithm of this multistep selection
mechanism is also analysed from the point of its optimality. It's shown that
it's equivalent to Grover algorithm of data base search.


title:
Immunolocalization of Na+,K+-ATPase in the branchial cavity during the
  early development of the crayfish Astacus leptodactylus (Crustacea, Decapoda)

abstract:
  The ontogeny of osmoregulation was examined in the branchial cavity of
embryonic and early post-embryonic stages of the crayfish Astacus leptodactylus
maintained in freshwater, at the sub-cellular level through the detection of
the sodium-potassium adenosine triphosphatase (Na(+),K(+)-ATPase). The
embryonic rate of development was calculated according to the eye index (EI)
which was 430-450 microm at hatching. The distribution of the enzyme was
identified by immunofluorescence microscopy using a monoclonal antibody
IgGalpha5 raised against the avian alpha-subunit of the Na(+),K(+)-ATPase.
Immunoreactivity staining, indicating the presence of Na(+), K(+)-ATPase
appeared in the gills of late embryos (EI>/=400 microm), i.e. a few days before
hatching time, and steadily increased throughout the late embryonic and early
post-embryonic development. The appearance of the enzyme correlates with the
ability to osmoregulate which also occurs late in the embryonic development at
EI 410-420 microm and with tissue differentiation within the gill filaments.
These observations indicate that the physiological shift from osmoconforming
embryos to hyper-regulating late embryos and post-hatching stages in freshwater
must originate partly from the differentiation in the gill epithelia of
ionocytes which are the site of ion pumping, as suggested by the location of
Na(+),K(+)-ATPase. Only the gills were immunostained and a lack of specific
staining was noted in the lamina and the branchiostegites. Therefore,
osmoregulation through Na(+)active uptake is likely achieved in embryos at the
gill level; all the newly formed gills in embryos function in ion regulation;
other parts of the branchial chamber such as the branchiostegites and lamina do
not appear to be involved in osmoregulation.


title: Manipulating single enzymes by an external harmonic force

abstract:
  We study a Michaelis-Menten reaction for a single two-state enzyme molecule,
whose transition rates between the two conformations are modulated by an
harmonically oscillating external force. In particular, we obtain a range of
optimal driving frequencies for changing the conformation of the enzyme thereby
controlling the enzymatic activity (i.e. product formation). This analysis
demonstrates that it is, in principle, possible to obtain information about
particular rates within the kinetic scheme.


title: Mind model seems necessary for the emergence of communication

abstract:
  We consider communication when there is no agreement about symbols and
meanings. We treat it within the framework of reinforcement learning. We apply
different reinforcement learning models in our studies and simplify the problem
as much as possible. We show that the modelling of the other agent is
insufficient in the simplest possible case, unless the intentions can also be
modelled. The model of the agent and its intentions enable quick agreements
about symbol-meaning association. We show that when both agents assume an
`intention model' about the other agent then the symbol-meaning association
process can be spoiled and symbol meaning association may become hard.


title:
Bow-tie topological features of metabolic networks and the functional
  significance

abstract:
  Exploring the structural topology of genome-based large-scale metabolic
network is essential for investigating possible relations between structure and
functionality. Visualization would be helpful for obtaining immediate
information about structural organization. In this work, metabolic networks of
75 organisms were investigated from a topological point of view. A spread
bow-tie model was proposed to give a clear visualization of the bow-tie
structure for metabolic networks. The revealed topological pattern helps to
design more efficient algorithm specifically for metabolic networks. This
coarse-grained graph also visualizes the vulnerable connections in the network,
and thus could have important implication for disease studies and drug target
identifications. In addition, analysis on the reciprocal links and main cores
in the GSC part of bow-tie also reveals that the bow-tie structure of metabolic
networks has its own intrinsic and significant features which are significantly
different from those of random networks.


title:
Modeling for evolving biological networks with scale-free connectivity,
  hierarchical modularity, and disassortativity

abstract:
  We propose a growing network model that consists of two tunable mechanisms:
growth by merging modules which are represented as complete graphs and a
fitness-driven preferential attachment. Our model exhibits the three prominent
statistical properties are widely shared in real biological networks, for
example gene regulatory, protein-protein interaction, and metabolic networks.
They retain three power law relationships, such as the power laws of degree
distribution, clustering spectrum, and degree-degree correlation corresponding
to scale-free connectivity, hierarchical modularity, and disassortativity,
respectively. After making comparisons of these properties between model
networks and biological networks, we confirmed that our model has inference
potential for evolutionary processes of biological networks.


title:
Phylogenetic tree constructing algorithms fit for grid computing with
  SVD

abstract:
  Erikkson showed that singular value decomposition(SVD) of flattenings
determined a partition of a phylogenetic tree to be a split. In this paper,
based on his work, we develop new statistically consistent algorithms fit for
grid computing to construct a phylogenetic tree by computing SVD of flattenings
with the small fixed number of rows.


title:
How Xenopus laevis replicates DNA reliably even though its origins of
  replication are located and initiated stochastically

abstract:
  DNA replication in Xenopus laevis is extremely reliable, failing to complete
before cell division no more than once in 10,000 times; yet replication origins
sites are located and initiated stochastically. Using a model based on 1d
theories of nucleation and growth and using concepts from extreme-value
statistics, we derive the distribution of replication times given a particular
initiation function. We show that the experimentally observed initiation
strategy for Xenopus laevis meets the reliability constraint and is close to
the one that requires the fewest resources of a cell.


title: Physics of Psychophysics: it is critical to sense

abstract:
  It has been known for about a century that psychophysical response curves
(perception of a given physical stimulus vs. stimulus intensity) have a large
dynamic range: many decades of stimulus intensity can be appropriately
discriminated before saturation. This is in stark contrast with the response
curves of sensory neurons, whose dynamic range is small, usually covering only
about one decade. We claim that this paradox can be solved by means of a
collective phenomenon. By coupling excitable elements with small dynamic range,
the {\em collective} response function shows a much larger dynamic range, due
to the amplification mediated by excitable waves. Moreover, the dynamic range
is optimal at the phase transition where self-sustained activity becomes
stable, providing a clear example of a biologically relevant quantity being
optimized at criticality. We present a pedagogical account of these ideas,
which are illustrated with a simple mean field model.

categories: q-bio.NC cond-mat.dis-nn nlin.AO physics.bio-ph


title:
Mutation, selection, and ancestry in branching models: a variational
  approach

abstract:
  We consider the evolution of populations under the joint action of mutation
and differential reproduction, or selection. The population is modelled as a
finite-type Markov branching process in continuous time, and the associated
genealogical tree is viewed both in the forward and the backward direction of
time. The stationary type distribution of the reversed process, the so-called
ancestral distribution, turns out as a key for the study of mutation-selection
balance. This balance can be expressed in the form of a variational principle
that quantifies the respective roles of reproduction and mutation for any
possible type distribution. It shows that the mean growth rate of the
population results from a competition for a maximal long-term growth rate, as
given by the difference between the current mean reproduction rate, and an
asymptotic decay rate related to the mutation process; this tradeoff is won by
the ancestral distribution.
  Our main application is the quasispecies model of sequence evolution with
mutation coupled to reproduction but independent across sites, and a fitness
function that is invariant under permutation of sites. Here, the variational
principle is worked out in detail and yields a simple, explicit result.


title:
Postprandial morphological response of the intestinal epithelium of the
  Burmese python (Python molurus)

abstract:
  The postprandial morphological changes of the intestinal epithelium of
Burmese pythons were examined using fasting pythons and at eight time points
after feeding. In fasting pythons, tightly packed enterocytes possess very
short microvilli and are arranged in a pseudostratified fashion. Enterocyte
width increases by 23% within 24 h postfeeding, inducing significant increases
in villus length and intestinal mass. By 6 days postfeeding, enterocyte volume
had peaked, following as much as an 80% increase. Contributing to enterocyte
hypertrophy is the cellular accumulation of lipid droplets at the tips and
edges of the villi of the proximal and middle small intestine, but which were
absent in the distal small intestine. At 3 days postfeeding, conventional and
environmental scanning electron microscopy revealed cracks and lipid extrusion
along the narrow edges of the villi and at the villus tips. Transmission
electron microscopy demonstrated the rapid postprandial lengthening of
enterocyte microvilli, increasing 4.8-fold in length within 24 h, and the
maintaining of that length through digestion. Beginning at 24 h postfeeding,
spherical particles were found embedded apically within enterocytes of the
proximal and middle small intestine. These particles possessed an annular-like
construction and were stained with the calcium-stain Alizarine red S suggesting
that they were bone in origin. Following the completion of digestion, many of
the postprandial responses were reversed, as observed by the atrophy of
enterocytes, the shortening of villi, and the retraction of the microvilli.
Further exploration of the python intestine will reveal the underlying
mechanisms of these trophic responses and the origin and fate of the engulfed
particles.


title:
Exploring the assortativity-clustering space of a network's degree
  sequence

abstract:
  Nowadays there is a multitude of measures designed to capture different
aspects of network structure. To be able to say if the structure of certain
network is expected or not, one needs a reference model (null model). One
frequently used null model is the ensemble of graphs with the same set of
degrees as the original network. In this paper we argue that this ensemble can
be more than just a null model -- it also carries information about the
original network and factors that affect its evolution. By mapping out this
ensemble in the space of some low-level network structure -- in our case those
measured by the assortativity and clustering coefficients -- one can for
example study how close to the valid region of the parameter space the observed
networks are. Such analysis suggests which quantities are actively optimized
during the evolution of the network. We use four very different biological
networks to exemplify our method. Among other things, we find that high
clustering might be a force in the evolution of protein interaction networks.
We also find that all four networks are conspicuously robust to both random
errors and targeted attacks.


title: A Note on Genome Organisation in RNA Viruses with Icosahedral Symmetry

abstract:
  The structural organisation of the viral genome within its protein container,
called the viral capsid, is an important aspect of virus architecture. Many
single-stranded (ss) RNA viruses organise a significant part of their genome in
a dodecahedral cage as a RNA duplex structure that mirrors the symmetry of the
capsid. Bruinsma and Rudnick have suggested a model for the structural
organisation of the RNA in these cages. It is the purpose of this paper to
further develop their approach based on results from the areas of graph theory
and DNA network engineering. We start by suggesting a scenario for pariacoto
virus, a representative of this class of viruses, that is energetically more
favorable than those derived previously. We then show that it is a
representative of a whole family of cage structures that abide to the same
construction principle, and then derive the energetically optimal configuration
for a second family of cage structures along similar lines. Finally, we give
reasons for the conjecture that these two families are more likely to occur in
nature than other scenarios.


title:
Variable-free exploration of stochastic models: a gene regulatory
  network example

abstract:
  Finding coarse-grained, low-dimensional descriptions is an important task in
the analysis of complex, stochastic models of gene regulatory networks. This
task involves (a) identifying observables that best describe the state of these
complex systems and (b) characterizing the dynamics of the observables. In a
previous paper [13], we assumed that good observables were known a priori, and
presented an equation-free approach to approximate coarse-grained quantities
(i.e, effective drift and diffusion coefficients) that characterize the
long-time behavior of the observables. Here we use diffusion maps [9] to
extract appropriate observables ("reduction coordinates") in an automated
fashion; these involve the leading eigenvectors of a weighted Laplacian on a
graph constructed from network simulation data. We present lifting and
restriction procedures for translating between physical variables and these
data-based observables. These procedures allow us to perform equation-free
coarse-grained, computations characterizing the long-term dynamics through the
design and processing of short bursts of stochastic simulation initialized at
appropriate values of the data-based observables.


title:
An individual-based predator-prey model for biological coevolution:
  Fluctuations, stability, and community structure

abstract:
  We study an individual-based predator-prey model of biological coevolution,
using linear stability analysis and large-scale kinetic Monte Carlo
simulations. The model exhibits approximate 1/f noise in diversity and
population-size fluctuations, and it generates a sequence of quasi-steady
communities in the form of simple food webs. These communities are quite
resilient toward the loss of one or a few species, which is reflected in
different power-law exponents for the durations of communities and the
lifetimes of species. The exponent for the former is near -1, while the latter
is close to -2. Statistical characteristics of the evolving communities,
including degree (predator and prey) distributions and proportions of basal,
intermediate, and top species, compare reasonably with data for real food webs.


title: Spontaneous emergence of spatial patterns ina a predator-prey model

abstract:
  We present studies for an individual based model of three interacting
populations whose individuals are mobile in a 2D-lattice. We focus on the
pattern formation in the spatial distributions of the populations. Also
relevant is the relationship between pattern formation and features of the
populations' time series. Our model displays travelling waves solutions,
clustering and uniform distributions, all related to the parameters values. We
also observed that the regeneration rate, the parameter associated to the
primary level of trophic chain, the plants, regulated the presence of
predators, as well as the type of spatial configuration.


title: Individual-based model for coevolving competing populations

abstract:
  Classical models for competition between two species usually predict
exclusion or divergent evolution of resource exploitation. However, recent
experimental data show that coexistence is possible for very similar species
competing for the same resources \textit{without} niche partition. Motivated by
this experimental challenge to classical competition theory, we propose an
individual-based stochastic competition model, which is essentially a
modification of a deterministic Lotka-Volterra type model. The proposed model
of competition dynamics incorporates the effects of a discrete genotype, which
determines the individual's adaptation to the environment, as well as its
interaction with the other species.


title:
Propagation of fluctuations in interaction networks governed by the law
  of mass action

abstract:
  Using an example of physical interactions between proteins, we study how
perturbations propagate in interconnected networks whose equilibrium state is
governed by the law of mass action. We introduce a comprehensive matrix
formalism which predicts the response of this equilibrium to small changes in
total concentrations of individual molecules, and explain it using a heuristic
analogy to a current flow in a network of resistors. Our main conclusion is
that on average changes in free concentrations exponentially decay with the
distance from the source of perturbation. We then study how this decay is
influenced by such factors as the topology of a network, binding strength, and
correlations between concentrations of neighboring nodes. An exact analytic
expression for the decay constant is obtained for the case of uniform
interactions on the Bethe lattice. Our general findings are illustrated using a
real biological network of protein-protein interactions in baker's yeast with
experimentally determined protein concentrations.

categories: q-bio.MN cond-mat.stat-mech physics.bio-ph q-bio.GN


title: Theory of genomic dark matter and biological relativity

abstract:
  Significant fraction (about 98.5% in humans, 24% in microbe Rickettsia
prowazekii) of most animal genomes is non-coding DNA. Although recent studies
established functions of its certain portions, it remains genomic dark matter.
The paper unravels its unusual nature with time reversal approach. Any genome
emerged in evolutionary selection of the fittest survivors. Survivability of
modern species is extensively quantified. Accurate analysis establishes that
under specified conditions it is dominated by the same law in species from
human to single-cell yeast. Since all violators of the law perished in the
previous evolution, it presents the exact law of unanticipated universal
(rather than species specific natural) evolutionary selection of survivors. The
law implies their rapid hereditary, thus genetic, adaptation which is navigated
by operating system of non-coding DNA. Such adaptation to drastic environmental
changes was a must for survival, thus evolved, in otherwise lethal major mass
extinctions. Navigator genome allows for rapid, artificial included, biological
changes (e.g., Methuselah lifespan). Universal law establishes biological
relativity to age transformation in any species; quantifies applicability of
animal models to humans; implies certain universality in biological complexity
and reduces it to exact science problem. Evolutionary and experimental data
corroborate all above conclusions. Further theoretical study and test-stone
experiments are suggested.

categories: q-bio.GN cond-mat.other nlin.AO physics.bio-ph q-bio.PE


title:
Periodic solutions of piecewise affine gene network models: the case of
  a negative feedback loop

abstract:
  In this paper the existence and unicity of a stable periodic orbit is proven,
for a class of piecewise affine differential equations in dimension 3 or more,
provided their interaction structure is a negative feedback loop. It is also
shown that the same systems converge toward a unique stable equilibrium point
in dimension 2. This extends a theorem of Snoussi, which showed the existence
of these orbits only. The considered class of equations is usually studied as a
model of gene regulatory networks. It is not assumed that all decay rates are
identical, which is biologically irrelevant, but has been done in the vast
majority of previous studies. Our work relies on classical results about fixed
points of monotone, concave operators acting on positive variables. Moreover,
the used techniques are very likely to apply in more general contexts, opening
directions for future work.


title:
Approximating genealogies for partially linked neutral loci under a
  selective sweep

abstract:
  Consider a genetic locus carrying a strongly beneficial allele which has
recently fixed in a large population. As strongly beneficial alleles fix
quickly, sequence diversity at partially linked neutral loci is reduced. This
phenomenon is known as a selective sweep. The fixation of the beneficial allele
not only affects sequence diversity at single neutral loci but also the joint
allele distribution of several partially linked neutral loci. This distribution
can be studied using the ancestral recombination graph for samples of partially
linked neutral loci during the selective sweep. To approximate this graph, we
extend recent work by Schweinsberg & Durrett 2005 and Etheridge, Pfaffelhuber &
Wakolbinger 2006 using a marked Yule tree for the genealogy at a single neutral
locus linked to a strongly beneficial one. We focus on joint genealogies at two
partially linked neutral loci in the case of large selection coefficients
\alpha and recombination rates \rho = O(\alpha/\log\alpha) between loci. Our
approach leads to a full description of the genealogy with accuracy of O((\log
\alpha)^{-2}) in probability. As an application, we derive the expectation of
Lewontin's D as a measure for non-random association of alleles.


title:
Attentional modulation in layer 4 of the visual cortex could be mediated
  by interneurons with complex receptive field characteristics

abstract:
  Many neurons in the visual cortex are orientation-selective, increase their
firing rate with contrast and are modulated by attention. What is the cortical
circuit that underlies these computations? We examine how synchrony can be
modulated by the excitability of interneurons, in a model layer 4 network
displaying contrast-invariant orientation-tuning. We did not find parameter
settings for which the standard ring model (Somers et al, 1995), which contains
only cells with simple receptive fields (RF), behaved appropriately. Only when
interneurons with complex receptive fields were included, similar to those
found recently in cat primary visual cortex (Hirsch et al, 2003), did the
network behave appropriately. A critical feature in the model was that complex
interneurons projected to simple interneurons but the simple interneurons did
not project back to them. The network was switched from the non-attended state
to the attended state by increasing the depolarization of the complex
interneurons. In addition to contrast-invariant orientation tuning, the model
reproduced the following experimental results: (1) the gamma-frequency range
coherence between the estimated local field potential (eLFP) and spike trains
of excitatory cells was higher in the attended state than in the non-attended
state, but the firing rates of the excitatory cells did not vary between
states; (2) the gamma-frequency-range power in the eLFP increased with
contrast. The model predicts that there are two populations of inhibitory
cells, one with complex RF characteristics whose firing rate increases with
attention and the other with simple RF characteristics whose firing rate
decreases with attention.


title:
Evolution Equation of Phenotype Distribution: General Formulation and
  Application to Error Catastrophe

abstract:
  An equation describing the evolution of phenotypic distribution is derived
using methods developed in statistical physics. The equation is solved by using
the singular perturbation method, and assuming that the number of bases in the
genetic sequence is large. Applying the equation to the mutation-selection
model by Eigen provides the critical mutation rate for the error catastrophe.
Phenotypic fluctuation of clones (individuals sharing the same gene) is
introduced into this evolution equation. With this formalism, it is found that
the critical mutation rate is sometimes increased by the phenotypic
fluctuations, i.e., noise can enhance robustness of a fitted state to mutation.
Our formalism is systematic and general, while approximations to derive more
tractable evolution equations are also discussed.


title: Towards the Human Genotope

abstract:
  The human genotope is the convex hull of all allele frequency vectors that
can be obtained from the genotypes present in the human population. In this
paper we take a few initial steps towards a description of this object, which
may be fundamental for future population based genetics studies. Here we use
data from the HapMap Project, restricted to two ENCODE regions, to study a
subpolytope of the human genotope. We study three different approaches for
obtaining informative low-dimensional projections of this subpolytope. The
projections are specified by projection onto few tag SNPs, principal component
analysis, and archetypal analysis. We describe the application of our geometric
approach to identifying structure in populations based on single nucleotide
polymorphisms.


title: Genetic Code: A New Understanding of Codon - Amino Acid Assignment

abstract:
  In this work it is shown that 20 canonical amino acids (AAs) within genetic
code appear to be a whole system with strict AAs positions; more exactly, with
AAs ordinal number in three variants; first variant 00-19, second 00-21 and
third 00-20. The ordinal number follows from the positions of belonging codons,
i.e. their digrams (or doublets). The reading itself is a reading in quaternary
numbering system if four bases possess the values within a specific logical
square: A = 0, C = 1, G = 2, U = 3. By this, all splittings, distinctions and
classifications of AAs appear to be in accordance to atom and nucleon number
balance as well as to the other physico-chemical properties, such as
hydrophobicity and polarity.


title:
Compression stress in opposite wood of angiosperms: observations in
  chestnut, mani and poplar

abstract:
  In order to face environmental constraints, trees are able to re-orient their
axes by controlling the stress level in the newly formed wood layers.
Angiosperms and gymnosperms evolved into two distinct mechanisms: the former
produce a wood with large tension pre-stress on the upper side of the tilted
axis, while the latter produce a wood with large compression pre-stress on the
lower side. In both cases, the difference between this stress level and that of
the opposite side, in light tension, generates the bending of the axis.
However, light values of compression were sometimes measured in the opposite
side of angiosperms. By analysing old data on chestnut and mani and new data on
poplar, this study shows that these values were not measurement artefacts. This
reveals that generating light compression stress in opposite wood contributes
to improve the performance of the re-orientation mechanism.


title:
Action for perception : influence of handedness in visuo-auditory
  sensory substitution

abstract:
  In this preliminary study we address the question of the influence of
handedness on the localization of targets perceived through a visuo-auditory
substitution device. Participants hold the device in one hand in order to
explore the environment and to perceive the target. They point to the estimated
location of the target with the other hand. This preliminary results support
our hypothesis that pointing is more accurate when the device is held in the
right dominant hand. Dexterity has to be attributed to the active part of the
perceptive system. This study has obviously to be completed but it shows how
the concept of enaction is important and how it can be experimentaly addressed
in the field of sensory substitution.


title:
Analyse cin\'{e}matique de l'\'{e}paule chez des patients
  h\'{e}mipar\'{e}tiques lors de la saisie d'objets pesants

abstract:
  The aim of this study is to produce a kinematic analysis of movements of the
shoulder complex when hemiparetic patients achieve the grasping of weighted
objects. We propose to describe the influence of the weight on kinematic
characteristics of the gesture and to establish the relevance of several
quantitative indexes concerning the quality of the grasping gesture.


title: Adaptive Filtering Enhances Information Transmission in Visual Cortex

abstract:
  Sensory neuroscience seeks to understand how the brain encodes natural
environments. However, neural coding has largely been studied using simplified
stimuli. In order to assess whether the brain's coding strategy depend on the
stimulus ensemble, we apply a new information-theoretic method that allows
unbiased calculation of neural filters (receptive fields) from responses to
natural scenes or other complex signals with strong multipoint correlations. In
the cat primary visual cortex we compare responses to natural inputs with those
to noise inputs matched for luminance and contrast. We find that neural filters
adaptively change with the input ensemble so as to increase the information
carried by the neural response about the filtered stimulus. Adaptation affects
the spatial frequency composition of the filter, enhancing sensitivity to
under-represented frequencies in agreement with optimal encoding arguments.
Adaptation occurs over 40 s to many minutes, longer than most previously
reported forms of adaptation.


title: Oscillation patterns in negative feedback loops

abstract:
  Organisms are equipped with regulatory systems that display a variety of
dynamical behaviours ranging from simple stable steady states, to switching and
multistability, to oscillations. Earlier work has shown that oscillations in
protein concentrations or gene expression levels are related to the presence of
at least one negative feedback loop in the regulatory network. Here we study
the dynamics of a very general class of negative feedback loops. Our main
result is that in these systems the sequence of maxima and minima of the
concentrations is uniquely determined by the topology of the loop and the
activating/repressing nature of the interaction between pairs of variables.
This allows us to devise an algorithm to reconstruct the topology of
oscillating negative feedback loops from their time series; this method applies
even when some variables are missing from the data set, or if the time series
shows transients, like damped oscillations. We illustrate the relevance and the
limits of validity of our method with three examples: p53-Mdm2 oscillations,
circadian gene expression in cyanobacteria, and cyclic binding of cofactors at
the estrogen-sensitive pS2 promoter.


title:
Protein structural variation in computational models and
  crystallographic data

abstract:
  Normal mode analysis offers an efficient way of modeling the conformational
flexibility of protein structures. Simple models defined by contact topology,
known as elastic network models, have been used to model a variety of systems,
but the validation is typically limited to individual modes for a single
protein. We use anisotropic displacement parameters from crystallography to
test the quality of prediction of both the magnitude and directionality of
conformational variance. Normal modes from four simple elastic network model
potentials and from the CHARMM forcefield are calculated for a data set of 83
diverse, ultrahigh resolution crystal structures. While all five potentials
provide good predictions of the magnitude of flexibility, the methods that
consider all atoms have a clear edge at prediction of directionality, and the
CHARMM potential produces the best agreement. The low-frequency modes from
different potentials are similar, but those computed from the CHARMM potential
show the greatest difference from the elastic network models. This was
illustrated by computing the dynamic correlation matrices from different
potentials for a PDZ domain structure. Comparison of normal mode results with
anisotropic temperature factors opens the possibility of using ultrahigh
resolution crystallographic data as a quantitative measure of molecular
flexibility. The comprehensive evaluation demonstrates the costs and benefits
of using normal mode potentials of varying complexity. Comparison of the
dynamic correlation matrices suggests that a combination of topological and
chemical potentials may help identify residues in which chemical forces make
large contributions to intramolecular coupling.


title:
Capacitance fluctuations causing channel noise reduction in stochastic
  Hodgkin-Huxley systems

abstract:
  Voltage-dependent ion channels determine the electric properties of axonal
cell membranes. They not only allow the passage of ions through the cell
membrane but also contribute to an additional charging of the cell membrane
resulting in the so-called capacitance loading. The switching of the channel
gates between an open and a closed configuration is intrinsically related to
the movement of gating charge within the cell membrane. At the beginning of an
action potential the transient gating current is opposite to the direction of
the current of sodium ions through the membrane. Therefore, the excitability is
expected to become reduced due to the influence of a gating current. Our
stochastic Hodgkin-Huxley like modeling takes into account both the channel
noise -- i.e. the fluctuations of the number of open ion channels -- and the
capacitance fluctuations that result from the dynamics of the gating charge. We
investigate the spiking dynamics of membrane patches of variable size and
analyze the statistics of the spontaneous spiking. As a main result, we find
that the gating currents yield a drastic reduction of the spontaneous spiking
rate for sufficiently large ion channel clusters. Consequently, this
demonstrates a prominent mechanism for channel noise reduction.


title: Nucleotide Frequencies in Human Genome and Fibonacci Numbers

abstract:
  This work presents a mathematical model that establishes an interesting
connection between nucleotide frequencies in human single-stranded DNA and the
famous Fibonacci's numbers. The model relies on two assumptions. First,
Chargaff's second parity rule should be valid, and, second, the nucleotide
frequencies should approach limit values when the number of bases is
sufficiently large. Under these two hypotheses, it is possible to predict the
human nucleotide frequencies with accuracy. It is noteworthy, that the
predicted values are solutions of an optimization problem, which is commonplace
in many nature's phenomena.


title: Proteomic nonlinear waves in networks of transcriptional regulators

abstract:
  A chain of connected genes with activation-repression links is analysed. It
is shown that for various promoter activity functions (parametrised by Hill
coefficient) the equations describing the concentrations of transcription
factors, are differential-difference KdV-type with perturbations. In the case
of large Hill coefficient the proteomic signal along the gene network is given
by a superposition of perturbed dark solitons of defocusing
differential-difference mKdV equation. Biological implications are discussed.


title:
Networks from gene expression time series: characterization of
  correlation patterns

abstract:
  This paper describes characteristic features of networks reconstructed from
gene expression time series data. Several null models are considered in order
to discriminate between informations embedded in the network that are related
to real data, and features that are due to the method used for network
reconstruction (time correlation).


title: DNA: From rigid base-pairs to semiflexible polymers

abstract:
  The sequence-dependent elasticity of double-helical DNA on a nm length scale
can be captured by the rigid base-pair model, whose strains are the relative
position and orientation of adjacent base-pairs. Corresponding elastic
potentials have been obtained from all-atom MD simulation and from
high-resolution structural data. On the scale of a hundred nm, DNA is
successfully described by a continuous worm-like chain model with homogeneous
elastic properties characterized by a set of four elastic constants, which have
been directly measured in single-molecule experiments. We present here a theory
that links these experiments on different scales, by systematically
coarse-graining the rigid base-pair model for random sequence DNA to an
effective worm-like chain description. The average helical geometry of the
molecule is exactly taken into account in our approach. We find that the
available microscopic parameters sets predict qualitatively similar mesoscopic
parameters. The thermal bending and twisting persistence lengths computed from
MD data are 42 and 48 nm, respectively. The static persistence lengths are
generally much higher, in agreement with cyclization experiments. All
microscopic parameter sets predict negative twist-stretch coupling. The
variability and anisotropy of bending stiffness in short random chains lead to
non-Gaussian bend angle distributions, but become unimportant after two helical
turns.


title:
Phase transition in the collective migration of tissue cells: experiment
  and model

abstract:
  We have recorded the swarming-like collective migration of a large number of
keratocytes (tissue cells obtained from the scales of goldfish) using long-term
videomicroscopy. By increasing the overall density of the migrating cells, we
have been able to demonstrate experimentally a kinetic phase transition from a
disordered into an ordered state. Near the critical density a complex picture
emerges with interacting clusters of cells moving in groups. Motivated by these
experiments we have constructed a flocking model that exhibits a continuous
transition to the ordered phase, while assuming only short-range interactions
and no explicit information about the knowledge of the directions of motion of
neighbors. Placing cells in microfabricated arenas we found spectacular
whirling behavior which we could also reproduce in simulations.

categories: q-bio.CB cond-mat.stat-mech physics.bio-ph q-bio.QM q-bio.TO


title: An analysis of B cell selection mechanisms in germinal centers

abstract:
  Affinity maturation of antibodies during immune responses is achieved by
multiple rounds of somatic hypermutation and subsequent preferential selection
of those B cells that express B cell receptors with improved binding
characteristics for the antigen. The mechanism underlying B cell selection has
not yet been defined. By employing an agent-based model, we show that for
physiologically reasonable parameter values affinity maturation can neither be
driven by competition for binding sites nor antigen -- even in the presence of
competing secreted antibodies. Within the tested mechanisms, only clonal
competition for T cell help or a refractory time for the interaction of
centrocytes with follicular dendritic cells are found to enable affinity
maturation while generating the experimentally observed germinal center
characteristics and tolerating large variations in the initial antigen density.


title: How much non-coding DNA do eukaryotes require?

abstract:
  Despite tremendous advances in the field of genomics, the amount and function
of the large non-coding part of the genome in higher organisms remains poorly
understood. Here we report an observation, made for 37 fully sequenced
eukaryotic genomes, which indicates that eukaryotes require a certain minimum
amount of non-coding DNA (ncDNA). This minimum increases quadratically with the
amount of DNA located in exons. Based on a simple model of the growth of
regulatory networks, we derive a theoretical prediction of the required
quantity of ncDNA and find it to be in excellent agreement with the data. The
amount of additional ncDNA (in basepairs) which eukaryotes require obeys Ndef =
1/2 (Nc / Np) (Nc - Np), where Nc is the amount of exonic DNA, and Np is a
constant of about 10Mb. This value Ndef corresponds to a few percent of the
genome in Homo sapiens and other mammals, and up to half the genome in simpler
eukaryotes. Thus our findings confirm that eukaryotic life depends on a
substantial fraction of ncDNA and also make a prediction of the size of this
fraction, which matches the data closely.


title:
Can all muscular load sharing patterns be regarded as optimal in some
  sense?

abstract:
  Muscles crossing a joint usually outnumber its degrees of freedom, which
renders the motor system underdetermined. Typically, optimization laws are
postulated to cope with this redundancy. A natural question then arises whether
all muscular load sharing patterns can be regarded as results of optimization.
To answer it, we propose a method of constructing an objective function whose
minimization yields a given load sharing pattern. We give necessary conditions
for this construction to be feasible and investigate its uniqueness. For linear
load sharing patterns the Crowninshield and Brand objective function is
reproduced, nonlinear ones require a more general formula.


title:
Extinction Rates for Fluctuation-Induced Metastabilities : A Real-Space
  WKB Approach

abstract:
  The extinction of a single species due to demographic stochasticity is
analyzed. The discrete nature of the individual agents and the Poissonian noise
related to the birth-death processes result in local extinction of a metastable
population, as the system hits the absorbing state. The Fokker-Planck
formulation of that problem fails to capture the statistics of large deviations
from the metastable state, while approximations appropriate close to the
absorbing state become, in general, invalid as the population becomes large. To
connect these two regimes, a master equation based on a real space WKB method
is presented, and is shown to yield an excellent approximation for the decay
rate and the extreme events statistics all the way down to the absorbing state.
The details of the underlying microscopic process, smeared out in a mean field
treatment, are shown to be crucial for an exact determination of the extinction
exponent. This general scheme is shown to reproduce the known results in the
field, to yield new corollaries and to fit quite precisely the numerical
solutions. Moreover it allows for systematic improvement via a series expansion
where the small parameter is the inverse of the number of individuals in the
metastable state.


title:
Pathways and kinetic barriers in mechanical unfolding and refolding of
  RNA and proteins

abstract:
  Using self-organized polymer models, we predict mechanical unfolding and
refolding pathways of ribo-zymes, and the green fluorescent protein. In
agreement with experiments, there are between six and eight unfolding
transitions in the Tetrahymena ribozyme. Depending on the loading rate, the
number of rips in the force-ramp unfolding of the Azoarcus ribozymes is between
two and four. Force-quench refolding of the P4-P6 subdomain of the Tetrahymena
ribozyme occurs through a compact intermediate. Subsequent formation of
tertiary contacts between helices P5b-P6a and P5a/P5c-P4 leads to the native
state. The force-quench refolding pathways agree with ensemble experiments. In
the dominant unfolding route, the N-terminal a helix of GFP unravels first,
followed by disruption of the N terminus b strand. There is a third
intermediate that involves disruption of three other strands. In accord with
experiments, the force-quench refolding pathway of GFP is hierarchic, with the
rate-limiting step being the closure of the barrel.


title:
Back-stepping, hidden substeps, and conditional dwell times in molecular
  motors

abstract:
  Processive molecular motors take more-or-less uniformly sized steps, along
spatially periodic tracks, mostly forwards but increasingly backwards under
loads. Experimentally, the major steps can be resolved clearly within the noise
but one knows biochemically that one or more mechanochemical substeps remain
hidden in each enzymatic cycle. In order to properly interpret experimental
data for back/forward step ratios, mean conditional step-to-step dwell times,
etc., a first-passage analysis has been developed that takes account of hidden
substeps in $N$-state sequential models. The explicit, general results differ
significantly from previous treatments that identify the observed steps with
complete mechanochemical cycles; e.g., the mean dwell times $\tau_+$ and
$\tau_-$ prior to forward and back steps, respectively, are normally {\it
unequal} although the dwell times $\tau_{++}$ and $\tau_{--}$ between {\it
successive} forward and back steps are equal. Illustrative (N=2)-state examples
display a wide range of behavior. The formulation extends to the case of two or
more detectable transitions in a multistate cycle with hidden substeps.


title: Grid Added Value to Address Malaria

abstract:
  Through this paper, we call for a distributed, internet-based collaboration
to address one of the worst plagues of our present world, malaria. The spirit
is a non-proprietary peer-production of information-embedding goods. And we
propose to use the grid technology to enable such a world wide "open source"
like collaboration. The first step towards this vision has been achieved during
the summer on the EGEE grid infrastructure where 46 million ligands were docked
for a total amount of 80 CPU years in 6 weeks in the quest for new drugs.


title:
Integration and mining of malaria molecular, functional and
  pharmacological data: how far are we from a chemogenomic knowledge space?

abstract:
  The organization and mining of malaria genomic and post-genomic data is
highly motivated by the necessity to predict and characterize new biological
targets and new drugs. Biological targets are sought in a biological space
designed from the genomic data from Plasmodium falciparum, but using also the
millions of genomic data from other species. Drug candidates are sought in a
chemical space containing the millions of small molecules stored in public and
private chemolibraries. Data management should therefore be as reliable and
versatile as possible. In this context, we examined five aspects of the
organization and mining of malaria genomic and post-genomic data: 1) the
comparison of protein sequences including compositionally atypical malaria
sequences, 2) the high throughput reconstruction of molecular phylogenies, 3)
the representation of biological processes particularly metabolic pathways, 4)
the versatile methods to integrate genomic data, biological representations and
functional profiling obtained from X-omic experiments after drug treatments and
5) the determination and prediction of protein structures and their molecular
docking with drug candidate structures. Progresses toward a grid-enabled
chemogenomic knowledge space are discussed.


title: Grid enabled virtual screening against malaria

abstract:
  WISDOM is an international initiative to enable a virtual screening pipeline
on a grid infrastructure. Its first attempt was to deploy large scale in silico
docking on a public grid infrastructure. Protein-ligand docking is about
computing the binding energy of a protein target to a library of potential
drugs using a scoring algorithm. Previous deployments were either limited to
one cluster, to grids of clusters in the tightly protected environment of a
pharmaceutical laboratory or to pervasive grids. The first large scale docking
experiment ran on the EGEE grid production service from 11 July 2005 to 19
August 2005 against targets relevant to research on malaria and saw over 41
million compounds docked for the equivalent of 80 years of CPU time. Up to
1,700 computers were simultaneously used in 15 countries around the world.
Issues related to the deployment and the monitoring of the in silico docking
experiment as well as experience with grid operation and services are reported
in the paper. The main problem encountered for such a large scale deployment
was the grid infrastructure stability. Although the overall success rate was
above 80%, a lot of monitoring and supervision was still required at the
application level to resubmit the jobs that failed. But the experiment
demonstrated how grid infrastructures have a tremendous capacity to mobilize
very large CPU resources for well targeted goals during a significant period of
time. This success leads to a second computing challenge targeting Avian Flu
neuraminidase N1.


title: Estimating body mass in the leatherback turtle Dermochelys coriacea

abstract:
  Body mass is a major life history trait and provides a scale for all living
processes of organisms. Unfortunately body mass cannot be easily measured for
many species, because of the logistical difficulties involved in actually
catching and weighing them. This is particularly true for sea turtles which are
large vertebrates that spend most of their life at sea. Here we developed a
general linear model to predict body mass from 17 morphometric measurements
obtained from 49 leatherback turtles nesting in Awala Yalimapo beach, French
Guiana, South America. A stepwise backward analysis removing independent
parameters with P > 0.001 indicated that body mass can be estimated with 93%
accuracy by Body Mass (kg) = - 709.146 + 3.391MedianBodyCirc (cm) + 2.664SCCL
(cm), where SCCL is the standard curvilinear carapace length and MedianBodyCirc
is body circumference at half of SCCL. A sensibility test showed that this
parsimonious model is robust, as estimated body mass may change by 0.7-1.3% for
1-2 cm changes in SCCL, by 0.9-1.7% for 1-2 cm changes in circumference.
Leatherback turtles from French Guiana were larger and heavier than in all
other nesting sites studied so far, suggesting either that gravid leatherbacks
feed during the nesting season in French Guiana, and/or that this species may
exhibits site-specific growth strategies. Further studies are required to test
these hypotheses, including implementation of similar simple models for other
nesting populations, in order to better understand the life history of this
endangered species.


title:
Dispersal and dive patterns in gravid leatherback turtles during the
  nesting season in French Guiana

abstract:
  We present the first combined analysis of diving behaviour and dispersal
patterns in gravid leatherback turtles during 3 consecutive nesting seasons in
French Guiana. In total 23 turtles were fitted with Argos satellite
transmitters and 16 individuals (including 6 concurrently satellite-tracked)
were equipped with an electronic time-depth recorder for single inter-nesting
intervals, i.e. between two consecutive ovi-positions. The leatherbacks
dispersed over the continental shelf, ranging from the coastal zone to the
shelf break and moved over 546.2 $\pm$ 154.1 km (mean $\pm$ SD) in waters of
French Guiana and neighbouring Surinam. They mostly performed shallow (9.4
$\pm$ 9.2 m) and short (4.4 $\pm$ 3.4 min) dives with a slight diurnal pattern.
They dived deeper as they moved away from the coast suggesting that they were
predominantly following the seabed. Inter-nesting intervals could be divided
into two phases: during the first 75% of the time turtles spent at sea, they
dived on average 47 min h-1 before showing a lower and more variable diving
effort as they came back to the shore. The extended movements of leatherbacks
and the fine analysis of dive shapes suggest that in French Guiana leatherbacks
may feed during the inter-nesting interval, probably to compensate for the
energy costs associated with reproduction. This results in this endangered
species being exposed to high risks of interactions with local fisheries
throughout the continental shelf.


title:
Modeling emergent tissue organization involving high-speed migrating
  cells in a flow equilibrium

abstract:
  There is increasing interest in the analysis of biological tissue, its
organization and its dynamics with the help of mathematical models. In the
ideal case emergent properties on the tissue scale can be derived from the
cellular scale. However, this has been achieved in rare examples only, in
particular, when involving high-speed migration of cells. One major difficulty
is the lack of a suitable multiscale simulation platform, which embeds
reaction-diffusion of soluble substances, fast cell migration and mechanics,
and, being of great importance in several tissue types, cell flow homeostasis.
In this paper a step into this direction is presented by developing an
agent-based mathematical model specifically designed to incorporate these
features with special emphasis on high speed cell migration. Cells are
represented as elastic spheres migrating on a substrate in lattice-free space.
Their movement is regulated and guided by chemoattractants that can be derived
from the substrate. The diffusion of chemoattractants is considered to be
slower than cell migration and, thus, to be far from equilibrium. Tissue
homeostasis is not achieved by the balance of growth and death but by a flow
equilibrium of cells migrating in and out of the tissue under consideration. In
this sense the number and the distribution of the cells in the tissue is a
result of the model and not part of the assumptions. For purpose of
demonstration of the model properties and functioning, the model is applied to
a prominent example of tissue in a cellular flow equilibrium, the secondary
lymphoid tissue. The experimental data on cell speed distributions in these
tissues can be reproduced using reasonable mechanical parameters for the
simulated cell migration in dense tissue.


title: Mechanisms of organogenesis of primary lymphoid follicles

abstract:
  Primary lymphoid follicles in secondary lymphoid tissue of mammals are the
backbone for the formation of follicular dendritic cell networks. These are
important for germinal center reactions. In the context of organogenesis
molecular requirements for the formation of follicles have been identified. The
present study complements this work with a simulation of the dynamics of the
primary lymphoid follicle formation. In contrast to other problems of pattern
formation, here, the homeostasis of the cell population is not governed by a
growth-death balance but by a flow equilibrium of migrating cells. The influx
of cells into secondary lymphoid tissue was extensively studied while less
information is available about the efflux of lymphocytes from secondary
lymphoid tissues. This study formulates the minimal requirements for cell
efflux that guarantee a flow equilibrium and, thus, a stable primary lymphoid
follicle. The model predicts that in addition to already identified mechanisms
a negative regulation of the generation of follicular dendritic cells is
required. Furthermore, a comparison with data concerning the microanatomy of
secondary lymphoid tissues yields the conclusion that dynamical changes during
the formation of FDC networks of the lymphatic endothelium are necessary to
understand the genesis and maintenance of follicles.


title: Di-nucleotide Entropy as a Measure of Genomic Sequence Functionality

abstract:
  Considering vast amounts of genomic sequences of mostly unknown
functionality, in-silico prediction of functional regions is an important
enterprise. Many genomic browsers employ GC content, which was observed to be
elevated in gene-rich functional regions. This report shows that the entropy of
di- and tri-nucleotides distributions provides a superior measure of genomic
sequence functionality, and proposes an explanation on why the GC content must
be elevated (closer to 50%) in functional regions. Regions with high entropy
strongly co-localize with exons and provide genome-wide evidences of purifying
selection acting on non-coding regions, such as decreased SNPs density. The
observations suggest that functional non-coding regions are optimised for
mutation load in a way, that transition mutations have less impact on
functionality than transversions, leading to the decrease in transversions to
transitions ratio in functional regions.


title: Genetic Variability of Splicing Sites

abstract:
  Splicing sites provide unique statistics in human genome due to their large
number and reasonably complete annotation. Analyses of the cumulative SNPs
distribution in splicing sites reveal a few interesting observations. While a
degree of the nucleotide conservation reflects on the SNPs density
monotonically, no detectable changes in the SNPs frequencies spectrum were
found. Semi-conserved nucleotide sites harbor transition mutations
predominantly. We propose that such transition preference is caused by
co-evolution of a site with corresponding binding agents. Since transitions in
humans and similarly in other organisms are almost twice as frequent as
transversions, this adaptation significantly lowers the mutation load.


title:
Nucleation phenomena in protein folding: The modulating role of protein
  sequence

abstract:
  For the vast majority of naturally occurring, small, single domain proteins
folding is often described as a two-state process that lacks detectable
intermediates. This observation has often been rationalized on the basis of a
nucleation mechanism for protein folding whose basic premise is the idea that
after completion of a specific set of contacts forming the so-called folding
nucleus the native state is achieved promptly. Here we propose a methodology to
identify folding nuclei in small lattice polymers and apply it to the study of
protein molecules with chain length N=48. To investigate the extent to which
protein topology is a robust determinant of the nucleation mechanism we compare
the nucleation scenario of a native-centric model with that of a sequence
specific model sharing the same native fold. To evaluate the impact of the
sequence's finner details in the nucleation mechanism we consider the folding
of two non- homologous sequences. We conclude that in a sequence-specific model
the folding nucleus is, to some extent, formed by the most stable contacts in
the protein and that the less stable linkages in the folding nucleus are solely
determined by the fold's topology. We have also found that independently of
protein sequence the folding nucleus performs the same `topological' function.
This unifying feature of the nucleation mechanism results from the residues
forming the folding nucleus being distributed along the protein chain in a
similar and well-defined manner that is determined by the fold's topological
features.


title:
Cooperativity and the origins of rapid, single-exponential kinetics in
  protein folding

abstract:
  The folding of naturally occurring, single domain proteins is usually
well-described as a simple, single exponential process lacking significant
trapped states. Here we further explore the hypothesis that the smooth energy
landscape this implies, and the rapid kinetics it engenders, arises due to the
extraordinary thermodynamic cooperativity of protein folding. Studying
Miyazawa-Jernigan lattice polymers we find that, even under conditions where
the folding energy landscape is relatively optimized (designed sequences
folding at their temperature of maximum folding rate), the folding of
protein-like heteropolymers is accelerated when their thermodynamic
cooperativity enhanced by enhancing the non-additivity of their energy
potentials. At lower temperatures, where kinetic traps presumably play a more
significant role in defining folding rates, we observe still greater
cooperativity-induced acceleration. Consistent with these observations, we find
that the folding kinetics of our computational models more closely approximate
single-exponential behavior as their cooperativity approaches optimal levels.
These observations suggest that the rapid folding of naturally occurring
proteins is, at least in part, consequences of their remarkably cooperative
folding.


title: Asexual and sexual replication in sporulating organisms

abstract:
  This paper develops models describing asexual and sexual replication in
sporulating organisms. Replication via sporulation is the replication strategy
for all multicellular life, and may even be observed in unicellular life (such
as with budding yeast). We consider diploid populations replicating via one of
two possible sporulation mechanisms: (1) Asexual sporulation, whereby adult
organisms produce single-celled diploid spores that grow into adults
themselves. (2) Sexual sporulation, whereby adult organisms produce
single-celled diploid spores that divide into haploid gametes. The haploid
gametes enter a haploid "pool", where they may recombine with other haploids to
form a diploid spore that then grows into an adult. We consider a haploid
fusion rate given by second-order reaction kinetics. We work with a simplified
model where the diploid genome consists of only two chromosomes, each of which
may be rendered defective with a single point mutation of the wild-type. We
find that the asexual strategy is favored when the rate of spore production is
high compared to the characteristic growth rate from a spore to a reproducing
adult. Conversely, the sexual strategy is favored when the rate of spore
production is low compared to the characteristic growth rate from a spore to a
reproducing adult. As the characteristic growth time increases, or as the
population density increases, the critical ratio of spore production rate to
organism growth rate at which the asexual strategy overtakes the sexual one is
pushed to higher values. Therefore, the results of this model suggest that, for
complex multicellular organisms, sexual replication is favored at high
population densities, and low growth and sporulation rates.


title:
Frequency and phase synchronization of two coupled neurons with channel
  noise

abstract:
  We study the frequency and phase synchronization in two coupled identical and
nonidentical neurons with channel noise. The occupation number method is used
to model the neurons in the context of stochastic Hodgkin-Huxley model in which
the strength of of channel noise is represented by ion channel cluster size of
the initiation region of neuron. It is shown that frequency synchronization
only was achieved at arbitrary value of couple strength as long as two neurons'
channel cluster sizes are the same. We also show that the relative phase of
neurons can display profuse dynamic behavior under the combined action of
coupling and channel noise. Both qualitative and quantitative descriptions are
applied to describe the transitions between those behaviors. Relevance of our
findings to controlling neural synchronization experimentally is discussed.


title:
An axiomatic theory for interaction between species in ecology: Gause's
  exclusion conjecture

abstract:
  I introduce an axiomatic representation, called ecoset, to consider
interactions between species in ecological systems. For interspecific
competition, the exclusion conjecture (Gause) is put in a symbolic way and used
as a basic operational tool to consider more complex cases like two species
with two superposed resources (niche differentiation) and apparent competitors.
Competition between tortoises and invaders in Galapagos islands is considered
as a specific example. Our theory gives us an operative language to consider
elementary process in ecology and open a route to more complex systems.


title: Kinetics of viral self-assembly: the role of ss RNA antenna

abstract:
  A big class of viruses self-assemble from a large number of identical capsid
proteins with long flexible N-terminal tails and ss RNA. We study the role of
the strong Coulomb interaction of positive N-terminal tails with ss RNA in the
kinetics of the in vitro virus self-assembly. Capsid proteins stick to
unassembled chain of ss RNA (which we call "antenna") and slide on it towards
the assembly site. We show that at excess of capsid proteins such
one-dimensional diffusion accelerates self-assembly more than ten times. On the
other hand at excess of ss RNA, antenna slows self-assembly down. Several
experiments are proposed to verify the role of ss RNA antenna.


title: Periodical cicadas: a minimal automaton model

abstract:
  The Magicicada spp. life cycles with its prime periods and highly
synchronized emergence have defied reasonable scientific explanation since its
discovery. During the last decade several models and explanations for this
phenomenon appeared in the literature along with a great deal of discussion.
Despite this considerable effort, there is no final conclusion about this long
standing biological problem. Here, we construct a minimal automaton model
without predation/parasitism which reproduces some of these aspects. Our
results point towards competition between different strains with limited
dispersal threshold as the main factor leading to the emergence of prime
numbered life cycles.


title: Gene expression from polynomial dynamics in the 2-adic information space

abstract:
  We perform geometrization of genetics by representing genetic information by
points of the 4-adic {\it information space.} By well known theorem of number
theory this space can also be represented as the 2-adic space. The process of
DNA-reproduction is described by the action of a 4-adic (or equivalently
2-adic) dynamical system. As we know, the genes contain information for
production of proteins. The genetic code is a degenerate map of codons to
proteins. We model this map as functioning of a polynomial dynamical system.
The purely mathematical problem under consideration is to find a dynamical
system reproducing the degenerate structure of the genetic code. We present one
of possible solutions of this problem.