Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Convolutional coding techniques for data protection

Results of research on the use of convolutional codes in data communications are presented. Convolutional coding fundamentals are discussed along with modulation and coding interaction. Concatenated coding systems and data compression with convolutional codes are described

From Instantly Decodable to Random Linear Network Coding

Our primary goal in this paper is to traverse the performance gap between two linear network coding schemes: random linear network coding (RLNC) and instantly decodable network coding (IDNC) in terms of throughput and decoding delay. We first redefine the concept of packet generation and use it to partition a block of partially-received data packets in a novel way, based on the coding sets in an IDNC solution. By varying the generation size, we obtain a general coding framework which consists of a series of coding schemes, with RLNC and IDNC identified as two extreme cases. We then prove that the throughput and decoding delay performance of all coding schemes in this coding framework are bounded between the performance of RLNC and IDNC and hence throughput-delay tradeoff becomes possible. We also propose implementations of this coding framework to further improve its throughput and decoding delay performance, to manage feedback frequency and coding complexity, or to achieve in-block performance adaption. Extensive simulations are then provided to verify the performance of the proposed coding schemes and their implementations.Comment: 30 pages with double space, 14 color figure