# <span class=strong>Reception and Poster Session</span>

Monday, April 21, 2008 - 5:00pm - 6:30pm

Lind 400

**Evolution of song culture in the zebra finch**

Haibin Wang (Cold Spring Harbor Laboratory)

A number of Oscine songbirds are vocal learners. In these species, song shares a remarkable characteristic with human language: both are acquired through imitative learning. When reared in social and acoustic isolation, the Zebra Finch (the species of songbird under study here) can still sing, revealing the genetically encoded aspect of song. However, the isolate songs usually have longer syllables, and appear to be more variable than the wild type (WT) songs found in the wild or in laboratory colonies.

In order to understand how the isolate song might evolve over multiple generations, we successively trained naïve juveniles starting with an isolate founding father. The first generation learners are in turn used as tutors to train the next generation, and so on. Thus, tutoring lineages are established through a recursive training processes. We found that small, yet systematic variations accumulate over generations of training. Remarkably, the descendants’ song structures are gradually transformed towards WT songs.**The advantage of two step transport problem**

Ezio Marchi (Instituto de Matemática Aplicada)

Here, we present a transport model which indroduce a variant in

the transport theory. Here the mass or merchandize in order to

go from a port to a destination must pass through a deposit,

without accumulation. It is possible to consider deposit

constraint. We obtain the corresponding linear program

associated to it, as well as the dual. The application of this

model to biological sciences, specially in human body, lungs, blood and biological systems seems promising.

We obtain the dual, which appear in a natural way from the

incidence matrix, which has many interesting properties.

The rank is the number of the ports, deposits plus the

destination minus on.

We study and characterize all the extremals extending the ideas

of Jurkar-Ryser, and von Neumann in the case of the classical

transpot model. A relation with the material in the papers by

E. Marchi:Z.Wahrscheinlichtheorie verww. geb,12,220-230

(1969) and 23,7-17, (1972), is underway.

We were succesful to extend this theory to mixed model

considering that in a deposit, there exists the possibility to

stay or passing. This rich study permits more potentiality to

the tools. An extension to several steps has been performed and

its potentiality for applications is vast.**Trajectory measures describing the locomotor behavior of Drosophila melanogaster in a circular arena**

Dan Valente (Cold Spring Harbor Laboratory)

Measuring locomotor behavior of Drosophila in enclosed arenas is a powerful way to obtain a quantitative behavioral phenotype. The measures previously used for this purpose are relatively coarse, thus ignoring fine scale movements of the fly. More importantly, they do not explicitly take into account how the arena shapes the dynamics of the locomotion. We acquired data using a video-tracking system to measure the trajectory of a fly over extended periods as it explores a circular arena. Based on this data, we present some metrics that take into consideration the dynamics of the trajectory, as well as the interactions of the trajectory with the geometry of the arena. The basic idea is to treat the locomotor trajectory of the fly as a stochastic process, and then estimate a set of marginal distributions of the probability measure describing this process. The measures include joint or individual distributions of position, speed, path curvature, inter-event times and re-orientation angles after stopping. These probability measures can be worked into other behavioral setups, are relatively easy to calculate using robust statistical estimation procedures, and can account for environmental effects on the behavior. They also serve as foundation for a quantitative stochastic process model of the walking behavior.**Biological project: The construction of the cycle in Lotka-Volterra of n-species**

Ezio Marchi (Instituto de Matemática Aplicada)

Lotka-Volterra equations are very famous by two biological

spices. Generally the most common presentations are in ecology

science. We study this models without considering the

antisymmetric condition among the parameters.(see Marchi and

Velasco Revista Mexicana de Fisica,36,No4(1990)665-679).We

obtain a movement constant for the systems which satisfies the

Hamilton equation. For more than two interacting species the

result the Volterra result are biologically improper. This is

due to the antisymetric conditions. Following Volterra original

methods combined with the variation of Montroll et. all, who

applied such equation to maser and laser, we obtain some

powerful personal procedure that we applied to the three and

four species obtaining and general condition and build the

cycle. Moreover this can be extended for an arbitrary number of

biological species obtaining constructively the cycle. The

background idea is to delete one variable at that time using

partial differentials equations of second power of the first

order. Furthermore we consider the conservation of the density

of point in the fase space (LIoville theorem) an we postulate

that the same distributions following the Gibbs Canonical Law.

By the way Prigogyne at all applied Lotka-Volterra system in

non-equilibrium thermodynamics. Moreover, there are several

applications of Lotka-Volterra to the theory of membrane. We

can show you some of them. Finally, we point out that

there are about four hundred papers in the subject in the last

ten years, and non of them apply our methods. The potentiality

for real application is very important even if the system of

Lotka-Volterra is asymptotically unstable.**A design principle in biochemical reaction networks**

based on realization theory

Bassam Bamieh (University of California)

We attempt to address the question of why there are so many intermediate species in biochemical

reaction networks using an idea from realization theory. We describe how prescribed biological

function can be designed with very low dimensional models, which are however not implementable

with the physically allowable biochemical reaction mechanisms. It then becomes apparent that

the introduction of a large number of intermediate species can be interpreted as a realization technique

to enable the implementation of prescribed function with the available dynamical building blocks.

By reversing this realization scheme, we propose a model reduction paradigm for biochemical reaction networks.**Architecture and inherent robustness of a bacterial cell cycle control system**

David Dill (Stanford University)

Joint work with Xiling Shen, Justine Collier, Lucy Shapiro, Mark Horowitz, and Harley H. McAdams.

We developed a mechanistic model of the cell cycle control of Caulobacter Crescentus. Symbolic model checking reveals that the cell cycle is extremely robust to parameter variations, and that the cell cycle starts and stops reliably to accommodate arbitrary starvation periods.**A transcriptional regulatory switch underlying B-cell terminal**

differentiation and its disruption by dioxin

Sudin Bhattacharya (The Hamner Institutes for Health Sciences)

Joint work with Qiang Zhang^{(1)}, Melvin E. Andersen^{(1)}

and Rory B.

Conolly^{(2)}.

The terminal differentiation of B cells in lymphoid organs into

antibody-secreting plasma cells upon antigen stimulation is a

crucial

step in the humoral immune response. The architecture of the

B-cell

transcriptional regulatory network consists of coupled

mutually-repressive feedback loops involving the three

transcription

factors Bcl6, Blimp1 and Pax5. This structure forms the basis

of an

irreversible bistable switch directing the B-cell to plasma

cell

differentiation process - i.e., the switch remains on even

after the

activating stimulus (antigen) is removed. The environmental

contaminant

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to suppress

the

humoral immune response by interfering with this

differentiation

program. We have developed a computational model of the

biochemical

pathways that regulate B-cell differentiation, and the

molecular

mechanism by which TCDD impairs this process through the action

of the

aryl hydrocarbon receptor (AhR). Using a kinetic model and

bifurcation

analysis, we propose that TCDD regulates the proportion of

B-cells that

differentiate into plasma cells by raising the threshold dose

of antigen

lipopolysaccharide (LPS) required to trigger the

differentiation switch.

We also show that stochastic modeling of gene expression, which

allows

cell-to-cell differences in content of signaling proteins,

introduces

distributional characteristics to the timing and probability of

differentiation among a population of B-cells. This

cell-to-cell

variability is likely to be a key determinant of dose-response

and

sensitivity of individual cells to differentiation.^{(1)}Division of Computational Biology, The Hamner Institutes

for Health

Sciences, Research Triangle Park, NC 27709, USA^{(2)}

National Center for Computational Toxicology, U.S.

Environmental

Protection Agency, Research Triangle Park, NC 27711, USA**Computational hemodynamics analysis in large blood**

vessels: Effects of hematocrit variation on flow stability

Oluwole Makinde (University of Limpopo)

Understanding the effects of blood viscosity

variation plays

a very crucial role in hemodynamics, thrombosis and

inflammation and

could provide useful information for diagnostics and therapy of

(cardio)

vascular disease. Blood viscosity, which arises from frictional

interactions between all major blood constituents, i.e. plasma,

plasma

proteins and red blood cells, constitutes blood inherent

resistance to

flow in the blood vessel. Because red blood cells (RBCs) are

the main

constituent of the cellular phase of blood, white blood cells

and

platelets normally do not have a great influence on whole blood

viscosity. When blood flows through a vessel, it tends to

separate in

two different phases. In direct contact with the wall a low

viscosity

phase exists, which is deficient in cells and rich in plasma

and acts as

a lubricant for the blood transport. In the central core region

of the

vessel a high viscosity phase exists, which depends on the

hematocrit.

In this paper, the nature and stability of blood flow in a

large artery

is investigated numerically using a spectral collocation

technique with

expansions in Chebyshev polynomials. The study reveals that a

rise in

hematocrit concentration in the central core region of a large

artery

has a stabilizing effect on the flow.

Keywords: Arterial blood flow; Hematocrit; Variable viscosity;

Temporal

stability; Chebyshev spectral collocation technique

References:

1.) Pedley T. J.: The Fluid Mechanics of Large Blood Vessels.

Cambridge

University Press, London, 1980.

2.) Makinde O. D.: Magneto-Hydromagnetic Stability of plane-

Poiseuille

flow using Multi-Deck asymptotic technique. Mathematical &

Computer

Modelling Vol. 37, No. 3-4, 251-259, 2003.

3.) Makinde O. D. and Mhone P. Y.: Temporal stability of small

disturbances in MHD Jeffery-Hamel flows. Computers and

Mathematics with

Applications, Vol. 53, 128–136, 2007.

4.) Makinde O. D.: Entropy-generation analysis for

variable-viscosity

channel flow with non-uniform wall temperature. Applied Energy,

Vol. 85,

384-393, 2008.**Recurrent and robust patterns underlying human relative preference, and associations with brain circuitry plus genetics**

Hans Breiter MD (Massachusetts General Hospital)

Joint work with BW Kim.

The Phenotype Genotype Project on Addiction and Depression (PGP), with support from the Departments of Neurology, Psychiatry, and Radiology, and Center for Human Genetic Research; Massachusetts General Hospital and Harvard Medical School; Boston, MA, USA

Positive and negative preferences can be assessed by keypress procedures that quantify (i) decision-making regarding approach, avoidance, indifference, and ambivalence responses, and (ii) judgments that determine the magnitude of approach and avoidance. Most prior studies of relative preference have not used keypress procedures, but have used ratings of personal utility, as a composite index of approach and avoidance. Such composite ratings can be calibrated against an absolute framework such as the macroeconomic pricing of commodities, as is done with Prospect Theory. It leaves open questions of whether or not splitting composite ratings of utility into approach and avoidance measures reveals any patterns in behavior, as observed for Prospect Theory. Such patterns might include a trade-off relationship between approach and avoidance, or a value function that might not need an absolute macroeconomic framework. We assessed these questions across multiple sets of healthy control sub

jects with a keypress procedure, and found a set of patterns for approach and avoidance are (i) recurrent across many stimulus types, and (ii) robust to the injection of noise. These patterns include: (a) a preference trade-off plot that counterbalances approach and avoidance responses and represents biases in preference and consistency/uncertainty of preference, (b) a value function linking preference intensity to uncertainty about preference, and (c) a preference saturation plot that represents how avoidance actions are over-determined relative to approach actions. One can consider this set of patterns to be a form of relative preference theory (RPT), since they meet the same requirements for recurrency and robustness to noise as the Weber-Fechner-Stevens Law. As with the value function for Prospect Theory, the value function in RPT has a steeper slope for negative relative to positive preferences (i.e., loss aversion), and can be described as a power law, or a logarithmic functi

on. All of these patterns show symmetry between group and individual data in that they have similar mathematical formulations as manifolds or boundary asymptotes for group data, or as fitted functions for individual data across multiple variables. These patterns verify known biases between females and males regarding viewing beautiful and average faces. When used to evaluate cocaine dependent subjects versus healthy controls, these patterns quantify the phenotype of the restricted behavioral repertoire observed in addiction. When used as regressors in the analysis of fMRI data, RPT measures are associated with significant BOLD signal change across a set of reward/aversion brain regions. Both keypress behavior and fMRI BOLD signal can be further associated with polymorphisms is genes such as CREB1 and BDNF. Given RPT scaling between groups of subjects and individuals, further work is warranted to assess if scaling can be achieved to brain circuitry and genetics.**Quantitative systems analysis of multicellular morphodynamics**

Anand Asthagiri (California Institute of Technology)

The goal of my research program is to better understand how biological circuits program multicellular phenotypes. While a major focus of the group involves phenotypes associated with human epithelial systems, we have also drawn upon more tractable model systems, such as C. elegans and yeast, to glean deeper fundamental insights. Each of these three biological systems provides unique advantages that my lab has sought to exploit using a combination of computational and quantitative experimental approaches.