Synthesis and Aggregation Behavior of Pluronic F87/Poly(acrylic acid) Block Copolymer with Doxorubicin

Poly(acrylic acid) (PAA) was grafted onto both termini of Pluronic F87 (PEO₆₇-PPO₃₉-PEO₆₇) via atom transfer radical polymerization to produce a novel muco-adhesive block copolymer PAA₈₀-b-F₈₇-b-PAA₈₀. It was observed that PAA₈₀-F₈₇-PAA₈₀ forms stable complexes with weakly basic anti-cancer drug, Doxorubicin. Thermodynamic changes due to the drug binding to the copolymer were assessed at different pH by isothermal titration calorimetry (ITC). The formation of the polymer/drug complexes was studied by turbidimetric titration and dynamic light scattering. Doxorubicin and PAA-b-F87-b-PAA block copolymer are found to interact strongly in aqueous solution via non-covalent interactions over a wide pH range. At pH>4.35, drug binding is due to electrostatic interactions. Hydrogen-bond also plays a role in the stabilization of the PAA₈₀-F₈₇-PAA₈₀/DOX complex. At pH 7.4 (α=0.8), the size and stability of polymer/drug complex depend strongly on the doxorubicin concentration. When CDOX <0.13mM, the PAA₈₀-F₈₇-PAA₈₀ copolymer forms stable inter-chain complexes with DOX (110 ~ 150 nm). When CDOX >0.13mM, as suggested by the light scattering result, the reorganization of the polymer/drug complex is believed to occur. With further addition of DOX (CDOX >0.34mM), sharp increase in the turbidity indicates the formation of large aggregates, followed by phase separation. The onset of a sharp enthalpy increase corresponds to the formation of a stoichiometric complex.

Shaping Inputs to Reduce Vibration: A Vector Diagram Approach

This paper describes a method for limiting vibration in flexible systems by shaping the system inputs. Unlike most previous attempts at input shaping, this method does not require an extensive system model or lengthy numerical computation; only knowledge of the system natural frequency and damping ratio are required. The effectiveness of this method when there are errors in the system model is explored and quantified. An algorithm is presented which, given an upper bound on acceptable residual vibration amplitude, determines a shaping strategy that is insensitive to errors in the estimated natural frequency. A procedure for shaping inputs to systems with input constraints is outlined. The shaping method is evaluated by dynamic simulations and hardware experiments.

Fault-Tolerant Design for Multistage Routing Networks

As the size of digital systems increases, the mean time between single component failures diminishes. To avoid component related failures, large computers must be fault-tolerant. In this paper, we focus on methods for achieving a high degree of fault-tolerance in multistage routing networks. We describe a multipath scheme for providing end-to-end fault-tolerance on large networks. The scheme improves routing performance while keeping network latency low. We also describe the novel routing component, RN1, which implements this scheme, showing how it can be the basic building block for fault-tolerant multistage routing networks.

Shaping Inputs to Reduce Vibration in Flexible Space Structures

Future NASA plans to launch large space strucutres solicit the need for effective vibration control schemes which can solve the unique problems associated with unwanted residual vibration in flexible spacecraft. In this work, a unique method of input command shaping called impulse shaping is examined. A theoretical background is presented along with some insight into the methdos of calculating multiple mode sequences. The Middeck Active Control Experiment (MACE) is then described as the testbed for hardware experiments. These results are shown and some of the difficulties of dealing with nonlinearities are discussed. The paper is concluded with some conclusions about calculating and implementing impulse shaping in complex nonlinear systems.

A Parallel Crossbar Routing Chip for a Shared Memory Multiprocessor

This thesis describes the design and implementation of an integrated circuit and associated packaging to be used as the building block for the data routing network of a large scale shared memory multiprocessor system. A general purpose multiprocessor depends on high-bandwidth, low-latency communications between computing elements. This thesis describes the design and construction of RN1, a novel self-routing, enhanced crossbar switch as a CMOS VLSI chip. This chip provides the basic building block for a scalable pipelined routing network with byte-wide data channels. A series of RN1 chips can be cascaded with no additional internal network components to form a multistage fault-tolerant routing switch. The chip is designed to operate at clock frequencies up to 100Mhz using Hewlett-Packard's HP34 $1.2\\mu$ process. This aggressive performance goal demands that special attention be paid to optimization of the logic architecture and circuit design.