Abstracts Keynote & Plenary

mainly stabilized by the H-bonds from water molecules, especially in the case of three water molecules
where the carboxyl O atoms are largely coordination-saturated by three H-bonds of medium strengths
and thus make the zwitterion stability even superior to the canonical isomer. With the presence of two
and three water molecules, the energy barriers for the conversion processes from the canonical isomers
to the zwitterions
are equal to 4.96 and 3.13 kcal mol-1, respectively. It indicated that the zwitterion formation is facile to
take place with the addition of two molecules and further facilitated by more water molecules. Besides,
the zwitterion formation of BL is finished in a single step, unlike other NA inhibitors. Owing to the
above advantages, BL is a good candidate of NA inhibitors and more attention should be paid in the
explorations of BL-based drugs.
OR-007
A strategy for parameter estimation for mRNA and protein dynamics
Fortunato Bianconi , Mauro Boccadoro , Gabriele Lillacci , Paolo Valigi
This paper proposes a methodology of parameter identification for nonlinear
systems, in particular
biochemical networks, based on a least squares procedure that treats the signals provided by a high gain
observer. Prior to the estimation phase, identifiability and sensitivity analysis determine which
parameters can and/or should be estimated. The procedure is tested on the data obtained by in silico
experiments for a simple instance of a proposed general dynamic model of protein synthesis.
Keywords: Biochemical Networks, Parameter, Identification, Identifiability , State
OR-008
Mathematical
Platform to Explore Comprehensive Effects of Different Drug Treatments in
Patients with Multiple Myeloma
Yan Wang1, David W. Smith2, Peter Pivonka2
1. Department of Civil & Environmental Engineering,
University of Melbourne, Melbourne, VIC,
Australia
2. Faculty of
Engineering, Computing and Mathematics, University of Western Australia, Perth, WA,
Australia
Multiple Myeloma
(MM) is an incurable but tractable blood cancer, in which over 70% of patients with
MM are involved in bone disease such as bone pain, bone lesions and fracture. Besides widespread
used Bisphosphonates (i.e. Pamidronate), published experimental data indicate that Denosumab, a fully
human monoclonal antibody of RANKL, is very promising in terms of improving bone loss. Recently,
Marathe et al. [1] coupled Denosumab pharmacokinetics in MM patients with bone homoestasishas to
break through ‘black box’ limitations brought by using traditional approach of pharmacodynamics.
However, impacts of MM on bone environment are ignored in the model. Hence, we aim to develop a
MM disease model to be a mathematical platform, based on which comprehensive effects of different
drug treatments in MM patients can be explored pre-clinically and a couple of regimes might be
suggested for clinical trials.
In this study, MM disease model
focuses on examining the impacts of over-expressed RANKL and
DKK1 by MM cells, which exerts their roles through increasing of ratio of RANKL to OPG and
inhibiting activation of Wnt signaling respectively. On the other hand, counteractions of bone
environment on MM cells are also examined in the model, which might be through bone resorption
released TGF-β and over production of IL-6. Being a case study, we integrate the MM disease model
with Denosumab and Pamidronate pharmacokinetics and then optimize the integrated model based on