A closer look at mutation in genetic algorithms

This paper examines the influence of mutation on the behavior of genetic algorithms through a series of examples and experiments. The results provide an existence proof that mutation is a far more profound operator than has ever been recognized. Implications are discussed which point to the importance of open questions concerning genetic algorithms. The paper also reviews the implementation of the infinite population model of Vose which forms the computational basis of this investigation.     

Friction-Induced Lines of Attraction and Repulsion for Parts Sliding on an Oscillated Plate

We show that the frictional forces arising from simultaneous small amplitude periodic translation and rotation of a rigid plate cause parts on the plate to converge to or diverge from a line coinciding with the rotation axis. The relative phase between the translation and rotation determines whether the parts are attracted to or repelled from the rotation axis. Assuming that both the translational and rotational accelerations of the plate are ldquobang-bangrdquo and have identical frequencies, we derive the resultant velocity fields for point parts on the plate. For many choices of phase the speed of the part is approximately proportional to its distance from the rotation axis. The strength of the velocity field can be controlled by modulating the amplitude of the translational acceleration, or modulating the relative phase between the translational and rotational acceleration profiles. We also determine the phases that maximize part speed towards and away from the rotation axis. These optimal phases not only maximize part speed but also generate velocity fields that are nearly independent of the coefficient of friction.     

The simple genetic algorithm and the Walsh transform: Part I, Theory

This paper is the first part of a two-part series. It proves a number of direct relationships between the Fourier transform and the simple genetic algorithm. (For a binary representation, the Walsh transform is the Fourier transform). The results are of a theoretical nature and are based on the analysis of mutation and crossover. The Fourier transform of the mixing matrix is shown to be sparse. An explicit formula is given for the spectrum of the differential of the mixing transformation. By using the Fourier representation and the fast Fourier transform, one generation of the infinite population simple genetic algorithm can be computed in time O(cllog2(3)), where c is arity of the alphabet and l is the string length. This is in contrast to the time of O(c3l) for the algorithm as represented in the standard basis. There are two orthogonal decompositions of population space that are invariant under mixing. The sequel to this paper will apply the basic theoretical results obtained here to inverse problems and asymptotic behavior.     

The simple genetic algorithm and the Walsh transform: Part II, The inverse

This paper continues the development, begun in Part I, of the relationship between the simple genetic algorithm and the Walsh transform. The mixing scheme (comprised of crossover and mutation) is essentially "triangularized" when expressed in terms of the Walsh basis. This leads to a formulation of the inverse of the expected next generation operator. The fixed points of the mixing scheme are also determined, and a formula is obtained giving the fixed point corresponding to any starting population. Geiringer's theorem follows from these results in the special case corresponding to zero mutation.     

Generalizing the notion of schema in genetic algorithms

In this paper we examine some of the fundamental assumptions which are frequently used to explain the practical success which Genetic Algorithms (GAs) have enjoyed. Specifically, the concept of schema and the Schema Theorem are interpreted from a new perspective. This allows GAs to be regarded as a constrained random walk, and offers a view which is amenable to generalization. The minimal deceptive problem (a problem designed to mislead the genetic paradigm) is analyzed in the context provided by our interpretation, where a different aspect of its difficulty emerges.     

A linear algorithm for generating random numbers with a givendistribution

Let ξ be a random variable over a finite set with an arbitrary probability distribution. Improvements to a fast method of generating sample values for ξ in constant time are suggested. The proposed modification reduces the time required for initialization to O( n). For a simple genetic algorithm, this improvement changes an O(g n 1n n) algorithm into an O(g n) algorithm (where g is the number of generations, and n is the population size)     

A heuristic technique for CTIS image reconstruction

An iterative method is presented for computed tomography imaging spectrometer (CTIS) image reconstruction in the presence of both photon noise in the image and postdetection Gaussian system noise. The new algorithm, which assumes the transfer matrix of the system has a particular structure, is evaluated experimentally with the result that it is significantly better, for larger problems, than both the multiplicative algebraic reconstruction technique (MART) and the mixed-expectation image-reconstruction technique (MERT) with respect to accuracy and computation time.     

A Novel Triple-Action Inhibitor Targeting B-Cell Receptor Signaling and BRD4 Demonstrates Preclinical Activity in Chronic Lymphocytic Leukemia

B-cell chronic lymphocytic leukemia (CLL) results from intrinsic genetic defects and complex microenvironment stimuli that fuel CLL cell growth through an array of survival signaling pathways. Novel small-molecule agents targeting the B-cell receptor pathway and anti-apoptotic proteins alone or in combination have revolutionized the management of CLL, yet combination therapy carries significant toxicity and CLL remains incurable due to residual disease and relapse. Single-molecule inhibitors that can target multiple disease-driving factors are thus an attractive approach to combat both drug resistance and combination-therapy-related toxicities. We demonstrate that SRX3305, a novel small-molecule BTK/PI3K/BRD4 inhibitor that targets three distinctive facets of CLL biology, attenuates CLL cell proliferation and promotes apoptosis in a dose-dependent fashion. SRX3305 also inhibits the activation-induced proliferation of primary CLL cells in vitro and effectively blocks microenvironment-mediated survival signals, including stromal cell contact. Furthermore, SRX3305 blocks CLL cell migration toward CXCL-12 and CXCL-13, which are major chemokines involved in CLL cell homing and retention in microenvironment niches. Importantly, SRX3305 maintains its anti-tumor effects in ibrutinib-resistant CLL cells. Collectively, this study establishes the preclinical efficacy of SRX3305 in CLL, providing significant rationale for its development as a therapeutic agent for CLL and related disorders.     

Erythropoietin for mobilization of circulating progenitor cells in patients with previously treated relapsed malignancies

A trial to determine the usefulness of recombinant human erythropoietin (rhEpo) as a mobilizing cytokine for patients with previously treated relapsed malignancies was performed. An initial peripheral stem cell apheresis collection was conducted during steady-state hematopoiesis for each patient to provide baseline data. rhEpo, 200 U/kg/day, was administered subcutaneously until the last apheresis procedure was completed. Immediately after the fourth daily dose of Epo, apheresis procedures were resumed and continued beyond five collections, when necessary, to accrue a total of 6.5 x 10(8) mononuclear cells (MNCs)/kg. Eight female and four male patients (median age = 44 years) were evaluated. Five to 14 (median = 8) apheresis procedures were performed for each patient. Toxicity attributable to Epo administration was negligible. Mobilization effects, as determined by an increase in the number of colony-forming units granulocyte/macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E) in the apheresis products after Epo administration, were observed in all patients. Nine patients received high-dose chemotherapy and Epo-mobilized peripheral stem cell transplantation (PSCT). Beginning the day of the transplant, GM-CSF was administered until neutrophil recovery was satisfactory. The median time to recover 0.5 x 10(9)/L granulocytes was 16 days after PSCT. Epo appears to have mobilization properties. Further studies are needed to determine the clinical usefulness of Epo as a mobilizing cytokine. The addition of Epo to other mobilizing cytokines may provide increased effectiveness without adding toxicity.     

General cardinality genetic algorithms

A complete generalization of the Vose genetic algorithm model from the binary to higher cardinality case is provided. Boolean AND and EXCLUSIVE-OR operators are replaced by multiplication and addition over rings of integers. Walsh matrices are generalized with finite Fourier transforms for higher cardinality usage. Comparison of results to the binary case are provided.