\u3ci\u3eIn Vivo\u3c/i\u3e And \u3ci\u3eIn Vitro\u3c/i\u3e Studies Of Polyamides That Are Active Antiviral Agents Against HPV16

Long-term, persistent infection with high-risk strains of human papillomavirus (HPV) is the precursor of most cervical cancers and an increasing number of the head and neck cancers. While HPV vaccines can protect patients under twenty-five years old from possible infections, no HPV antiviral drugs are available for the definitive treatment of preexisting or future viral infections. To treat current or future HPV infections, drugs that selectively block virus-specific processes, but do not damage the host cells, are needed. The compounds developed in our group are unique Imidazole-pyrrole polyamides, analogs of natural products Distamycin A and Netropsin that function by interfering with natural virus-host interactions. Within the overall program of my group, my work focuses on three specific projects. The first project (Chapter 2) includes bioavailability LC-MS/MS analysis study of one of the leading compounds in plasma and whole blood. The second project includes the biophysical study of interactions between two polyamides, called TMG Asymmetric Hairpin Polyamides (TMG-AHP), and an essential viral DNA segment. The aim of this study was to determine where and how strongly the compounds bind to the viral DNA. In this work, two methods were used: the quantitative deoxyribonuclease (DNase I) footprinting method and the affinity cleavage assay (AC). The results are presented in Chapters 3 and 4. The remarkable findings resulted in binding location maps that help us to better understand the mechanism of action of AHPs and to address the question: what is the primary reason for neutralizing a virus by our polyamides. Based on the knowledge gathered from the results of the first project, a complex study (RNA-Seq) concerned with genome expression was performed. The aim of the third project is to find the common features and differences in the polyamides’ mechanism of action by quantifying messenger RNA (mRNA), after treatment of HPV infected skin cells with 8 different polyamides. In parallel with the analysis of human and viral transcriptome, a separate study concerned with the differential expression profile of seven DDR genes that are components of the homologous recombination (HR) pathway have been studied by RT-qPCR method. The results are presented in Chapter 5 and 6. Data gathered from the third project help us further understand the mechanism of polyamide action

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

Search of S3 LIGO data for gravitational wave signals from spinning black hole and neutron star binary inspirals

We report on the methods and results of the first dedicated search for gravitational waves emitted during the inspiral of compact binaries with spinning component bodies. We analyze 788 hours of data collected during the third science run (S3) of the LIGO detectors. We searched for binary systems using a detection template family designed specially to capture the effects of the spin-induced precession of the orbital plane. We present details of the techniques developed to enable this search for spin-modulated gravitational waves, highlighting the differences between this and other recent searches for binaries with non-spinning components. The template bank we employed was found to yield high matches with our spin-modulated target waveform for binaries with masses in the asymmetric range 1.0 Msol < m1 < 3.0 Msol and 12.0 Msol < m2 < 20.0 Msol which is where we would expect the spin of the binary's components to have significant effect. We find that our search of S3 LIGO data had good sensitivity to binaries in the Milky Way and to a small fraction of binaries in M31 and M33 with masses in the range 1.0 Msol < m1, m2 < 20.0 Msol. No gravitational wave signals were identified during this search. Assuming a binary population with spinning components and Gaussian distribution of masses representing a prototypical neutron star - black hole system with m1 ~ 1.35 Msol and m2 ~ 5 Msol, we calculate the 90%-confidence upper limit on the rate of coalescence of these systems to be 15.9 yr^-1 L_10^-1, where L_10 is 10^10 times the blue light luminosity of the Sun.Comment: 18 pages, 8 figure

Publisher’s Note: First cross-correlation analysis of interferometric and resonant-bar gravitational-wave data for stochastic backgrounds [Phys. Rev. DPRVDAQ0556-2821 76, 022001 (2007)]

This paper was published online on 9 July 2007 with incorrect affiliation numbering in the author list. The affiliations have been corrected as of 23 July 2007. The text is correct in the printed version of the journal

Publisher’s Note: First cross-correlation analysis of interferometric and resonant-bar gravitational-wave data for stochastic backgrounds [Phys. Rev. D 76, 022001 (2007)]

This paper was published online on 9 July 2007 with a formatting error in the fiftieth affiliation in the author list. The affiliation should read as ‘‘University of Western Australia, Crawley, WA 6009, Australia.’’ The affiliation has been corrected as of 4 March 2008. The affiliation is incorrect in the printed version of the journal

Upper limits on gravitational wave emission from 78 radio pulsars

We present upper limits on the gravitational wave emission from 78 radio pulsars based on data from the third and fourth science runs of the LIGO and GEO 600 gravitational wave detectors. The data from both runs have been combined coherently to maximize sensitivity. For the first time, pulsars within binary (or multiple) systems have been included in the search by taking into account the signal modulation due to their orbits. Our upper limits are therefore the first measured for 56 of these pulsars. For the remaining 22, our results improve on previous upper limits by up to a factor of 10. For example, our tightest upper limit on the gravitational strain is 2.6×10-25 for PSR J1603-7202, and the equatorial ellipticity of PSR J2124–3358 is less than 10-6. Furthermore, our strain upper limit for the Crab pulsar is only 2.2 times greater than the fiducial spin-down limit