Sensitivity analysis of initial value problems with mixed odes and algebraic equations

An efficient method is described for sensitivity analysis of nonlinear initial value problems, which may include algebraic equations as well as ordinary differential equations.The linearity of the sensitivity equations is utilized to solve them directly via the local Jacobian of the state equations. The method is implemented with the implicit integrator DASSL and is demonstrated on a stiff industrial reaction model.     

Periodic dynamics of coupled cell networks I: rigid patterns of synchrony and phase relations

It has recently been proved by Golubitsky and coworkers that in any network of coupled dynamical systems, the possible 'rigid' patterns of synchrony of hyperbolic equilibria are determined by purely combinatorial properties of the network, known as 'balanced equivalence relations'. A pattern is 'rigid' if it persists under small 'admissible' perturbations of the differential equation — ones that respect the network structure. We discuss a natural generalisation of these ideas to time-periodic states, and motivate two basic conjectures, the Rigid Synchrony Conjecture and the Rigid Phase Conjecture. These conjectures state that for rigid hyperbolic time-periodic patterns, cells with synchronous dynamics must have synchronous input cells, and cells with phase-related dynamics must have input cells that have the same phase relations. We provide evidence supporting the two conjectures, by proving them for a special class of periodic orbits, which we call 'tame', under strong assumptions on the network architecture and the symmetries of the periodic state. The discussion takes place in the formal setting of coupled cell networks. We prove that rigid patterns of synchrony are balanced, together with the analogous result for rigid patterns of phase relations. The assumption on the network architecture simplifies the geometry of admissible vector fields, while tameness rules out patterns with non-trivial local or multilocal symmetry. The main idea is to perturb an admissible vector field in a way that retains sufficient control over the associated perturbed periodic orbit. We present two techniques for constructing these perturbations, both using a general theorem on groupoid-symmetrisation of vector fields, which has independent interest. In particular we introduce a method of 'patching' that makes local changes to an admissible vector field. Having established these results for all-to-all coupled networks and tame periodic orbits we prove more general versions that require these assumptions only on a suitable quotient network. These conditions are weaker and encompass a larger class of networks and periodic orbits. We give an example to show that rigidity cannot be relaxed to hyperbolicity. We also prove, without any technical assumptions, that rigidly synchronous or phase-related cells must be input-isomorphic, a necessary precondition for the two conjectures to hold.     

High Throughput Primer Walking of cDNA Clones

Primer walking of cloned DNA is a standard research tool. It has been used in the past to determine the sequence of individual clones of interest. With the expansion of DNA sequencing capacity the need to be able to walk larger numbers of clones has become necessary. Our laboratory is a mid-sized genomics facility. In conjunction with the Advanced Biomedical Computing Center (ABCC) we have developed methods for automating the primer selection, DNA sequencing, contig assembly and sequence analysis for clones arrayed in microtiter format. This approach has allowed us to walk 475 clones (five microtiter plates) selected from a cDNA library.     

Working memory and work with memory: visual-spatial and further components of processing

Empirical and theoretical evidence for the concept of working memory is considered. We argue that the major weakness of this concept is its loose connection with the knowledge about background perceptive and cognitive processes. Results of two relevant experiments are provided. The first study demonstrated the classical chunking effect in a speeded visual search and comparison task, the proper domain of a large-capacity very short term sensory store. Our second study was a kind of extended levels-of-processing experiment. We attempted to manipulate visual, phonological, and (different) executive components of long-term memory in the hope of finding some systematic relationships between these forms of processing. Indeed, the results demonstrated a high degree of systematicity without any apparent need for a concept such as working memory for the explanation. Accordingly, the place for working memory is at all the interfaces where our metacognitive strategies interfere with mostly domain-specific cognitive mechanisms. Working memory is simply our work with memory.     

Retroviral display of antibody fragments; interdomain spacing strongly influences vector infectivity

Five different single-chain antibody fragments (scFv) against human cell-surface antigens were displayed on murine ecotropic retroviral vectors by fusing them to the Moloney SU envelope glycoprotein. The spacing between the scFv and the SU glycoprotein was varied by fusing the scFv to residue +7 or to residue +1 of Moloney SU and by inserting linker sequences of different lengths between the domains. All of the chimeric envelopes were efficiently incorporated into vector particles and could bind to human cells through their displayed antibody fragments, but did not infect them. The spacing between the scFvs and the SU glycoproteins had no significant effect on the efficiency of envelope expression or viral incorporation and did not affect the binding properties of the chimeric envelopes, nor did it influence the efficiency of targeted gene delivery to human cells by scFv-displaying vectors. However, on murine fibroblasts the infectivity of vectors incorporating the chimeric envelopes was strongly influenced by the length of the interdomain spacer. The titers were very low when the single-chain antibodies were fused through a tripeptide linker to SU residue +7 and were greatly enhanced (up to 10(5)-fold) when they were fused to SU residue +1 through a heptapeptide linker. These results point to the importance of steric interactions between the domains of chimeric envelope glycoproteins and may have implications for retroviral vector design for human gene therapy.