7 research outputs found
Automated derivation of the adjoint of high-level transient finite element programs
In this paper we demonstrate a new technique for deriving discrete adjoint
and tangent linear models of finite element models. The technique is
significantly more efficient and automatic than standard algorithmic
differentiation techniques. The approach relies on a high-level symbolic
representation of the forward problem. In contrast to developing a model
directly in Fortran or C++, high-level systems allow the developer to express
the variational problems to be solved in near-mathematical notation. As such,
these systems have a key advantage: since the mathematical structure of the
problem is preserved, they are more amenable to automated analysis and
manipulation. The framework introduced here is implemented in a freely
available software package named dolfin-adjoint, based on the FEniCS Project.
Our approach to automated adjoint derivation relies on run-time annotation of
the temporal structure of the model, and employs the FEniCS finite element form
compiler to automatically generate the low-level code for the derived models.
The approach requires only trivial changes to a large class of forward models,
including complicated time-dependent nonlinear models. The adjoint model
automatically employs optimal checkpointing schemes to mitigate storage
requirements for nonlinear models, without any user management or intervention.
Furthermore, both the tangent linear and adjoint models naturally work in
parallel, without any need to differentiate through calls to MPI or to parse
OpenMP directives. The generality, applicability and efficiency of the approach
are demonstrated with examples from a wide range of scientific applications
Multiple molecular forms of adaptor protein Ruk/CIN85 specifically associate with different subcellular compartments in human breast adenocarcinoma MCF-7 cells
Ruk/CIN85 is a receptor-proximal ‘signalling’ adaptor that possesses three SH3 domains, Pro- and Ser-rich regions and C-terminal coiled-coil domain. It employs distinct domains and motifs to act as a transducer platform in intracellular signalling. Based on cDNA analysis, various isoforms of Ruk/CIN85 with different combination of protein-protein interaction domains as well as additional Ruk/CIN85 forms that are the products of post-translational modifications have been demonstrated. Nevertheless, there is no precise information regarding both the subcellular distribution and the role of Ruk/CIN85 multiple molecular forms in cellular responses. Using MCF-7 human breast adenocarcinoma cells and cell fractionation technique, specific association of Ruk/CIN85 molecular forms with different subcellular compartments was demonstrated. Induction of apoptosis of MCF-7 cells by doxorubicin treatment or by serum deprivation resulted in the system changes of Ruk/CIN85 molecular forms intracellular localization as well as their ratio. The data obtained provide a new insight into potential physiological significance of Ruk/CIN85 molecular forms in the regulation of various cellular functions