Recognition of double helical DNA by purine oligonucleotides via triple helix formation

Oligonucleotide-directed triple helix formation is one of the most versatile methods for the sequence specific recognition of double helical DNA. Chapter 2 describes affinity cleaving experiments carried out to assess the recognition potential for purine-rich oligonucleotides via the formation of triple helices. Purine-rich oligodeoxyribonucleotides were shown to bind specifically to purine tracts of double helical DNA in the major groove antiparallel to the purine strand of the duplex. Specificity was derived from the formation of reverse Hoogsteen G•GC, A•AT and T•AT triplets and binding was limited to mostly purine tracts. This triple helical structure was stabilized by multivalent cations, destabilized by high concentrations of monovalent cations and was insensitive to pH. A single mismatched base triplet was shown to destabilize a 15 mer triple helix by 1.0 kcal/mole at 25°C. In addition, stability appeared to be correlated to the number of G•GC triplets formed in the triple helix. This structure provides an additional framework as a basis for the design of new sequence specific DNA binding molecules.

In work described in Chapter 3, the triplet specificities and required strand orientations of two classes of DNA triple helices were combined to target double helical sequences containing all four base pairs by alternate strand triple helix formation. This allowed for the use of oligonucleotides containing only natural 3'-5' phosphodiester linkages to simultaneously bind both strands of double helical DNA in the major groove. The stabilities and structures of these alternate strand triple helices depended on whether the binding site sequence was 5'-(purine)_m (pyrimidine)_n-3' or 5'- (pyrimidine)_m (purine)_n-3'.

In Chapter 4, the ability of oligonucleotide-cerium(III) chelates to direct the transesterfication of RNA was investigated. Procedures were developed for the modification of DNA and RNA oligonucleotides with a hexadentate Schiff-base macrocyclic cerium(III) complex. In addition, oligoribonucleotides modified by covalent attachment of the metal complex through two different linker structures were prepared. The ability of these structures to direct transesterification to specific RNA phosphodiesters was assessed by gel electrophoresis. No reproducible cleavage of the RNA strand consistent with transesterification could be detected in any of these experiments.

Black holes in the early universe, in compact binaries, and as energy sources inside solar-type stars

This thesis consists of three separate studies of roles that black holes might play in our universe.

In the first part we formulate a statistical method for inferring the cosmological parameters of our universe from LIGO/VIRGO measurements of the gravitational waves produced by coalescing black-hole/neutron-star binaries. This method is based on the cosmological distance-redshift relation, with "luminosity distances" determined directly, and redshifts indirectly, from the gravitational waveforms. Using the current estimates of binary coalescence rates and projected "advanced" LIGO noise spectra, we conclude that by our method the Hubble constant should be measurable to within an error of a few percent. The errors for the mean density of the universe and the cosmological constant will depend strongly on the size of the universe, varying from about 10% for a "small" universe up to and beyond 100% for a "large" universe. We further study the effects of random gravitational lensing and find that it may strongly impair the determination of the cosmological constant.

In the second part of this thesis we disprove a conjecture that black holes cannot form in an early, inflationary era of our universe, because of a quantum-field-theory induced instability of the black-hole horizon. This instability was supposed to arise from the difference in temperatures of any black-hole horizon and the inflationary cosmological horizon; it was thought that this temperature difference would make every quantum state that is regular at the cosmological horizon be singular at the black-hole horizon. We disprove this conjecture by explicitly constructing a quantum vacuum state that is everywhere regular for a massless scalar field. We further show that this quantum state has all the nice thermal properties that one has come to expect of "good" vacuum states, both at the black-hole horizon and at the cosmological horizon.

In the third part of the thesis we study the evolution and implications of a hypothetical primordial black hole that might have found its way into the center of the Sun or any other solar-type star. As a foundation for our analysis, we generalize the mixing-length theory of convection to an optically thick, spherically symmetric accretion flow (and find in passing that the radial stretching of the inflowing fluid elements leads to a modification of the standard Schwarzschild criterion for convection). When the accretion is that of solar matter onto the primordial hole, the rotation of the Sun causes centrifugal hangup of the inflow near the hole, resulting in an "accretion torus" which produces an enhanced outflow of heat. We find, however, that the turbulent viscosity, which accompanies the convective transport of this heat, extracts angular momentum from the inflowing gas, thereby buffering the torus into a lower luminosity than one might have expected. As a result, the solar surface will not be influenced noticeably by the torus's luminosity until at most three days before the Sun is finally devoured by the black hole. As a simple consequence, accretion onto a black hole inside the Sun cannot be an answer to the solar neutrino puzzle.

A high pressure xenon time projection chamber for double beta decay

This thesis describes the design, construction and performance of a high-pressure, xenon, gas time projection chamber (TPC) for the study of double beta decay in ^(136) Xe. The TPC when operating at 5 atm can accommodate 28 moles of 60% enriched ^(136) Xe. The TPC has operated as a detector at Caltech since 1986. It is capable of reconstructing a charged particle trajectory and can easily distinguish between different kinds of charged particles. A gas purification and xenon gas recovery system were developed. The electronics for the 338 channels of readout was developed along with a data acquistion system. Currently, the detector is being prepared at the University of Neuchatel for installation in the low background laboratory situated in the St. Gotthard tunnel, Switzerland. In one year of runtime the detector should be sensitive to a 0ν lifetime of the order of 10^(24) y, which corresponds to a neutrino mass in the range 0.3 to 3.3 eV.

Dynamical stability of nascent neutron stars

This thesis presents a study of the dynamical stability of nascent neutron stars resulting from the accretion induced collapse of rapidly rotating white dwarfs.

Chapter 2 and part of Chapter 3 study the equilibrium models for these neutron stars. They are constructed by assuming that the neutron stars have the same masses, angular momenta, and specific angular momentum distributions as the pre-collapse white dwarfs. If the pre-collapse white dwarf is rapidly rotating, the collapsed object will contain a high density central core of size about 20 km, surrounded by a massive accretion torus extending to hundreds of kilometers from the rotation axis. The ratio of the rotational kinetic energy to gravitational binding energy, β, of these neutron stars is all found to be less than 0.27.

Chapter 3 studies the dynamical stability of these neutron stars by numerically evolving the linearized hydrodynamical equations. A dynamical bar-mode instability is observed when the β of the star is greater than the critical value β_d ≈ 0.25. It is expected that the unstable mode will persist until a substantial amount of angular momentum is carried away by gravitational radiation. The detectability of these sources is studied and it is estimated that LIGO II is unlikely to detect them unless the event rate is greater than 10^-6/year/galaxy.

All the calculations on the structure and stability of the neutron stars in Chapters 2 and 3 are carried out using Newtonian hydrodynamics and gravity. Chapter 4 studies the relativistic effects on the structure of these neutron stars. New techniques are developed and used to construct neutron star models to the first post-Newtonian (1PN) order. The structures of the 1PN models are qualitatively similar to the corresponding Newtonian models, but the values of β are somewhat smaller. The maximum β for these 1PN neutron stars is found to be 0.24, which is 8% smaller than the Newtonian result (0.26). However, relativistic effects will also change the critical value β_d. A detailed post-Newtonian stability analysis has yet to be carried out to study the relativistic effects on the dynamical stability of these neutron stars.

Electronic and kinetic processes in the Cu/CuCl double pulse laser

Kinetic and electronic processes in a Cu/CuCl double pulsed laser were investigated by measuring discharge and laser pulse characteristics, and by computer modeling. There are two time scales inherent to the operation of the Cu/CuCl laser. The first is during the interpulse afterglow (tens to hundreds of microseconds). The second is during the pumping pulse (tens of nanoseconds). It was found that the character of the pumping pulse is largely determined by the initial conditions provided by the interpulse afterglow. By tailoring the dissociation pulse to be long and low energy, and by conditioning the afterglow, one may select the desired initial conditions and thereby significantly improve laser performance. With a low energy dissociation pulse, the fraction of metastable copper obtained from a CuCl dissociation is low. By maintaining the afterglow, contributions to the metastable state from ion recombinations are prevented, and the plasma impedance remains low thereby increasing the rate of current rise during the pumping pulse. Computer models for the dissociation pulse, afterglow, pumping pulse and laser pulse reproduced experimentally observed behavior of laser pulse energy and power as a function of time delay, pumping pulse characteristics, and buffer gas pressure. The sensitivity of laser pulse properties on collisional processes (e.g., CuCl reassociation rates) was investigated.

Spin dynamics of pulsed nuclear magnetic double resonance in solids

In the first part of this thesis, experiments utilizing an NMR phase interferometric concept are presented. The spinor character of two-level systems is explicitly demonstrated by using this concept. Following this is the presentation of an experiment which uses this same idea to measure relaxation times of off-diagonal density matrix elements corresponding to magnetic-dipole-forbidden transitions in a ^(13)C-^1H, AX spin system. The theoretical background for these experiments and the spin dynamics of the interferometry are discussed also.

The second part of this thesis deals with NMR dipolar modulated chemical shift spectroscopy, with which internuclear bond lengths and bond angles with respect to the chemical shift principal axis frame are determined from polycrystalline samples. Experiments using benzene and calcium formate verify the validity of the technique in heteronuclear (^(13)C-^1H) systems. Similar experiments on powdered trichloroacetic acid confirm the validity in homonuclear (^1H- ^1H) systems. The theory and spin dynamics are explored in detail, and the effects of a number of multiple pulse sequences are discussed.

The last part deals with an experiment measuring the ^(13)C chemical shift tensor in K_2Pt(CN)_4Br_(0.3) • 3H_2O, a one-dimensional conductor. The ^(13)C spectra are strongly affected by ^(14)N quadrupolar interactions via the ^(13)C - ^(14)N dipolar interaction. Single crystal rotation spectra are shown.

An appendix discussing the design, construction, and performance of a single-coil double resonance NMR sample probe is included.

New Insights from Aperiodic Variability of Young Stars

Nearly all young stars are variable, with the variability traditionally divided into two classes: periodic variables and aperiodic or "irregular" variables. Periodic variables have been studied extensively, typically using periodograms, while aperiodic variables have received much less attention due to a lack of standard statistical tools. However, aperiodic variability can serve as a powerful probe of young star accretion physics and inner circumstellar disk structure. For my dissertation, I analyzed data from a large-scale, long-term survey of the nearby North America Nebula complex, using Palomar Transient Factory photometric time series collected on a nightly or every few night cadence over several years. This survey is the most thorough exploration of variability in a sample of thousands of young stars over time baselines of days to years, revealing a rich array of lightcurve shapes, amplitudes, and timescales.

I have constrained the timescale distribution of all young variables, periodic and aperiodic, on timescales from less than a day to ~100 days. I have shown that the distribution of timescales for aperiodic variables peaks at a few days, with relatively few (~15%) sources dominated by variability on tens of days or longer. My constraints on aperiodic timescale distributions are based on two new tools, magnitude- vs. time-difference (Δm-Δt) plots and peak-finding plots, for describing aperiodic lightcurves; this thesis provides simulations of their performance and presents recommendations on how to apply them to aperiodic signals in other time series data sets. In addition, I have measured the error introduced into colors or SEDs from combining photometry of variable sources taken at different epochs. These are the first quantitative results to be presented on the distributions in amplitude and time scale for young aperiodic variables, particularly those varying on timescales of weeks to months.

Double injection: high frequency noise and temperature dependence

Noise measurements from 140°K to 350°K ambient temperature and between 10kHz and 22MHz performed on a double injection silicon diode as a function of operating point indicate that the high frequency noise depends linearly on the ambient temperature T and on the differential conductance g measured at the same frequency. The noise is represented quantitatively by〈i^2〉 = α•4kTgΔf. A new interpretation demands Nyquist noise with α ≡ 1 in these devices at high frequencies. This is in accord with an equivalent circuit derived for the double injection process. The effects of diode geometry on the static I-V characteristic as well as on the ac properties are illustrated. Investigation of the temperature dependence of double injection yields measurements of the temperature variation of the common high-level lifetime τ(τ ∝ T^2), the hole conductivity mobility µ_p (µ_p ∝ T^(-2.18)) and the electron conductivity mobility µ_n(µ_n ∝ T^(-1.75)).

Effects of self energy of the ions on the double layer structure and properties at the dielectric interface

Although numerous theoretical efforts have been put forth, a systematic, unified and predictive theoretical framework that is able to capture all the essential physics of the interfacial behaviors of ions, such as the Hofmeister series effect, Jones-Ray effect and the salt effect on the bubble coalescence remain an outstanding challenge. The most common approach to treating electrostatic interactions in the presence of salt ions is the Poisson-Boltzmann (PB) theory. However, there are many systems for which the PB theory fails to offer even a qualitative explanation of the behavior, especially for ions distributed in the vicinity of an interface with dielectric contrast between the two media (like the water-vapor/oil interface). A key factor missing in the PB theory is the self energy of the ion.

In this thesis, we develop a self-consistent theory that treats the electrostatic self energy (including both the short-range Born solvation energy and the long-range image charge interactions), the nonelectrostatic contribution of the self energy, the ion-ion correlation and the screening effect systematically in a single framework. By assuming a finite charge spread of the ion instead of using the point-charge model, the self energy obtained by our theory is free of the divergence problems and gives a continuous self energy across the interface. This continuous feature allows ions on the water side and the vapor/oil side of the interface to be treated in a unified framework. The theory involves a minimum set of parameters of the ion, such as the valency, radius, polarizability of the ions, and the dielectric constants of the medium, that are both intrinsic and readily available. The general theory is first applied to study the thermodynamic property of the bulk electrolyte solution, which shows good agreement with the experiment result for predicting the activity coefficient and osmotic coefficient.

Next, we address the effect of local Born solvation energy on the bulk thermodynamics and interfacial properties of electrolyte solution mixtures. We show that difference in the solvation energy between the cations and anions naturally gives rise to local charge separation near the interface, and a finite Galvani potential between two coexisting solutions. The miscibility of the mixture can either increases or decreases depending on the competition between the solvation energy and translation entropy of the ions. The interfacial tension shows a non-monotonic dependence on the salt concentration: it increases linearly with the salt concentration at higher concentrations, and decreases approximately as the square root of the salt concentration for dilute solutions, which is in agreement with the Jones-Ray effect observed in experiment.

Next, we investigate the image effects on the double layer structure and interfacial properties near a single charged plate. We show that the image charge repulsion creates a depletion boundary layer that cannot be captured by a regular perturbation approach. The correct weak-coupling theory must include the self-energy of the ion due to the image charge interaction. The image force qualitatively alters the double layer structure and properties, and gives rise to many non-PB effects, such as nonmonotonic dependence of the surface energy on concentration and charge inversion. The image charge effect is then studied for electrolyte solutions between two plates. For two neutral plates, we show that depletion of the salt ions by the image charge repulsion results in short-range attractive and long-range repulsive forces. If cations and anions are of different valency, the asymmetric depletion leads to the formation of an induced electrical double layer. For two charged plates, the competition between the surface charge and the image charge effect can give rise to like- charge attraction.

Then, we study the inhomogeneous screening effect near the dielectric interface due to the anisotropic and nonuniform ion distribution. We show that the double layer structure and interfacial properties is drastically affected by the inhomogeneous screening if the bulk Debye screening length is comparable or smaller than the Bjerrum length. The width of the depletion layer is characterized by the Bjerrum length, independent of the salt concentration. We predict that the negative adsorption of ions at the interface increases linearly with the salt concentration, which cannot be captured by either the bulk screening approximation or the WKB approximation. For asymmetric salt, the inhomogeneous screening enhances the charge separation in the induced double layer and significantly increases the value of the surface potential.

Finally, to account for the ion specificity, we study the self energy of a single ion across the dielectric interface. The ion is considered to be polarizable: its charge distribution can be self-adjusted to the local dielectric environment to minimize the self energy. Using intrinsic parameters of the ions, such as the valency, radius, and polarizability, we predict the specific ion effect on the interfacial affinity of halogen anions at the water/air interface, and the strong adsorption of hydrophobic ions at the water/oil interface, in agreement with experiments and atomistic simulations.

The theory developed in this work represents the most systematic theoretical technique for weak-coupling electrolytes. We expect the theory to be more useful for studying a wide range of structural and dynamic properties in physicochemical, colloidal, soft-matter and biophysical systems.

Topological strings, double affine Hecke algebras, and exceptional knot homology

In this thesis, we consider two main subjects: refined, composite invariants and exceptional knot homologies of torus knots. The main technical tools are double affine Hecke algebras ("DAHA") and various insights from topological string theory.

In particular, we define and study the composite DAHA-superpolynomials of torus knots, which depend on pairs of Young diagrams and generalize the composite HOMFLY-PT polynomials from the full HOMFLY-PT skein of the annulus. We also describe a rich structure of differentials that act on homological knot invariants for exceptional groups. These follow from the physics of BPS states and the adjacencies/spectra of singularities associated with Landau-Ginzburg potentials. At the end, we construct two DAHA-hyperpolynomials which are closely related to the Deligne-Gross exceptional series of root systems.

In addition to these main themes, we also provide new results connecting DAHA-Jones polynomials to quantum torus knot invariants for Cartan types A and D, as well as the first appearance of quantum E6 knot invariants in the literature.