THE DYNAMIC CHROMATIN LANDSCAPE IN SACCHAROMYCES CEREVISIAE

The accurate and faithful segregation of chromosomes during mitosis is essential for cellular survival. Current paradigms of chromosome segregation focus on the mechanical contributions of the mitotic spindle without considering the biomechanical properties of the chromatin itself. In order to further our understanding of how the inherent physical properties of chromatin contribute to cellular processes like chromosome segregation, we have examined both histone and chromatin dynamics in the budding yeast Saccharomyces cerevisiae. During mitosis, the mitotic spindle exerts force on the pericentromeric chromatin, which adjusts structurally to accommodate this force. By measuring the fluorescence recovery after photobleaching (FRAP), we found that histones are more dynamic in the pericentromeric region as compared to the chromosome arm, and these increased recovery rates are dependent on spindle-based tension. The tension-dependent histone dynamics in the pericentromere are dependent on the chromatin remodeling activities of the Remodels the Structure of Chromatin (RSC) and Imitation Switch (ISWI) ATP-dependent chromatin remodeling complexes. Thus, balanced histone removal and reincorporation in the pericentromere provide a mechanism for accommodation of spindle-based tension and the maintenance of chromatin packaging. Having measured the dynamic nature of histone turnover within the chromatin polymer in response to spindle-based tension, we subsequently examined the spatio-temporal fluctuations of the chromatin polymer. We combined in vivo chromatin motion analysis and mathematical modeling to elucidate the physical properties of the chromatin polymer underlying dynamic fluctuations. The range of chromatin motion and its effective spring constants are found to vary along the length of the chromosome, in a manner dependent on tethering at the centromere. These polymer properties of the chromatin are dependent on both histone occupancy and cohesin packaging. As a whole, the work detailed in this dissertation contributes valuable insights into the importance of dynamic histone occupancy and chromatin motion in defining and maintaining the biomechanical polymer properties of chromosomes in vivo.Doctor of Philosoph

Microtubule dynamics drive enhanced chromatin motion and mobilize telomeres in response to DNA damage

Chromatin exhibits increased mobility on DNA damage, but the biophysical basis for this behavior remains unknown. To explore the mechanisms that drive DNA damage–induced chromosome mobility, we use single-particle tracking of tagged chromosomal loci during interphase in live yeast cells together with polymer models of chromatin chains. Telomeres become mobilized from sites on the nuclear envelope and the pericentromere expands after exposure to DNA-damaging agents. The magnitude of chromatin mobility induced by a single double-strand break requires active microtubule function. These findings reveal how relaxation of external tethers to the nuclear envelope and internal chromatin–chromatin tethers, together with microtubule dynamics, can mobilize the genome in response to DNA damage

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

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