Using perturbation theory to understand the two body problem in general relativity

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 171-178).Binary systems composed of compact objects (neutron stars and black holes) radiate gravitational waves (GWs). The prospect of detecting these GWs using ground and space based experiments has made it imperative to understand the dynamics of such compact binaries. This work describes several advances in our ability to model compact binaries and extract the rich science they encode. A major part of this dissertation focuses on the subset of binaries composed of a massive, central black hole (105 - 10SM®) and a much smaller compact object (1 - 100M®). The emission of gravitational energy from such extreme mass ratio inspirals (EMRIs) forces the separation between the two components to shrink, leading to their merger. We treat the smaller object as a point-like particle on the stationary space-time of the larger black hole. The EMRI problem can be broken down into two related parts: (i) A determination of the inspiral trajectory followed by the smaller object, and (ii) A characterization of the gravitational waveforms that result from such an inspiral. The initial part of this work discusses the development of a numerical algorithm that solves for the GWs that result from the perturbations generated by the smaller object. It accepts any reasonable inspiral trajectory as an input and produces the resulting waveforms with an accuracy greater than 99%. Next, we present a technique to model the part of the inspiral trajectory that immediately precedes the final plunge of smaller object into the massive black hole. Along with earlier research, this enables us to compute the smaller object's complete inspiral trajectory.(cont.) We now have a versatile toolkit that can model GWs from EMRIs. Finally, we present another application of this work. GWs carry linear momentum away from a binary. Integrating the lost momentum leaves an asymmetric binary with a non-zero recoil velocity after merger. We compute the recoils from EMRIs and extrapolate them to comparable mass binaries. We find that extrapolating perturbation theory gives results that agree well with those from numerical relativity, but require far less computation time.by Pranesh Adhyam Sundararajan.Ph.D

Pseudogene Associated Recurrent Gene Fusion in Prostate Cancer.

We present the functional characterization of a pseudogene associated recurrent gene fusion in prostate cancer. The fusion gene KLK4-KLKP1 is formed by the fusion of the protein coding gene KLK4 with the noncoding pseudogene KLKP1. Screening of a cohort of 659 patients (380 Caucasian American; 250 African American, and 29 patients from other races) revealed that the KLK4-KLKP1 is expressed in about 32% of prostate cancer patients. Correlative analysis with other ETS gene fusions and SPINK1 revealed a concomitant expression pattern of KLK4-KLKP1 with ERG and a mutually exclusive expression pattern with SPINK1, ETV1, ETV4, and ETV5. Development of an antibody specific to KLK4-KLKP1 fusion protein confirmed the expression of the full-length KLK4-KLKP1 protein in prostate tissues. The in vitro and in vivo functional assays to study the oncogenic properties of KLK4-KLKP1 confirmed its role in cell proliferation, cell invasion, intravasation, and tumor formation. Presence of strong ERG and AR binding sites located at the fusion junction in KLK4-KLKP1 suggests that the fusion gene is regulated by ERG and AR. Correlative analysis of clinical data showed an association of KLK4-KLKP1 with lower preoperative PSA values and in young men (\u3c50 \u3eyears) with prostate cancer. Screening of patient urine samples showed that KLK4-KLKP1 can be detected noninvasively in urine. Taken together, we present KLK4-KLKP1 as a class of pseudogene associated fusion transcript in cancer with potential applications as a biomarker for routine screening of prostate cancer