Suspension mechanics: I. Inertial and non-Newtonian migration of neutrally buoyant rigid spheres in two-dimensional unidirectional flows; II. The effect of viscoelasticity on the creeping motion of a train of neutrally buoyant Newtonian drops through a circular tube

The lateral migration of neutrally buoyant rigid spheres in two-dimensional unidirectional flows was studied theoretically. The cases of both inertia-induced migration in a Newtonian fluid and normal stress-induced migration in a second-order fluid were considered. Analytical results for the lateral velocities were obtained, and the equilibrium positions and trajectories of the spheres compared favorably with the experimental data available in the literature. The effective viscosity was obtained for a dilute suspension of spheres which were simultaneously undergoing inertia-induced migration and translational Brownian motion in a plane Poiseuille flow. The migration of spheres suspended in a second-order fluid inside a screw extruder was also considered.

The creeping motion of neutrally buoyant concentrically located Newtonian drops through a circular tube was studied experimentally for drops which have an undeformed radius comparable to that of the tube. Both a Newtonian and a viscoelastic suspending fluid were used in order to determine the influence of viscoelasticity. The extra pressure drop due to the presence of the suspended drops, the shape and velocity of the drops, and the streamlines of the flow were obtained for various viscosity ratios, total flow rates, and drop sizes. The results were compared with existing theoretical and experimental data.

Horizontal Bloch line motion in magnetic bubble materials

The purpose of this work is to extend experimental and theoretical understanding of horizontal Bloch line (HBL) motion in magnetic bubble materials. The present theory of HBL motion is reviewed, and then extended to include transient effects in which the internal domain wall structure changes with time. This is accomplished by numerically solving the equations of motion for the internal azimuthal angle ɸ and the wall position q as functions of z, the coordinate perpendicular to the thin-film material, and time. The effects of HBL's on domain wall motion are investigated by comparing results from wall oscillation experiments with those from the theory. In these experiments, a bias field pulse is used to make a step change in equilibrium position of either bubble or stripe domain walls, and the wall response is measured by using transient photography. During the initial response, the dynamic wall structure closely resembles the initial static structure. The wall accelerates to a relatively high velocity (≈20 m/sec), resulting in a short (≈22 nsec ) section of initial rapid motion. An HBL gradually forms near one of the film surfaces as a result of local dynamic properties, and moves along the wall surface toward the film center. The presence of this structure produces low-frequency, triangular-shaped oscillations in which the experimental wall velocity is nearly constant, v_s≈ 5-8 m/sec. If the HBL reaches the opposite surface, i.e., if the average internal angle reaches an integer multiple of π, the momentum stored in the HBL is lost, and the wall chirality is reversed. This results in abrupt transitions to overdamped motion and changes in wall chirality, which are observed as a function of bias pulse amplitude. The pulse amplitude at which the n^th punch- through occurs just as the wall reaches equilibrium is given within 0.2 0e by H_n = (2v_sH'/γ)^1/2 • (nπ)^1/2 + H_sv), where H' is the effective field gradient from the surrounding domains, and H_sv is a small (less than 0.03 0e), effective drag field. Observations of wall oscillation in the presence of in-plane fields parallel to the wall show that HBL formation is suppressed by fields greater than about 40 0e (≈2πM_s), resulting in the high-frequency, sinusoidal oscillations associated with a simple internal wall structure.

Quantum squeezing of motion in a mechanical resonator

Quantum mechanics places limits on the minimum energy of a harmonic oscillator via the ever-present "zero-point" fluctuations of the quantum ground state. Through squeezing, however, it is possible to decrease the noise of a single motional quadrature below the zero-point level as long as noise is added to the orthogonal quadrature. While squeezing below the quantum noise level was achieved decades ago with light, quantum squeezing of the motion of a mechanical resonator is a more difficult prospect due to the large thermal occupations of megahertz-frequency mechanical devices even at typical dilution refrigerator temperatures of ~ 10 mK.

Kronwald, Marquardt, and Clerk (2013) propose a method of squeezing a single quadrature of mechanical motion below the level of its zero-point fluctuations, even when the mechanics starts out with a large thermal occupation. The scheme operates under the framework of cavity optomechanics, where an optical or microwave cavity is coupled to the mechanics in order to control and read out the mechanical state. In the proposal, two pump tones are applied to the cavity, each detuned from the cavity resonance by the mechanical frequency. The pump tones establish and couple the mechanics to a squeezed reservoir, producing arbitrarily-large, steady-state squeezing of the mechanical motion. In this dissertation, I describe two experiments related to the implementation of this proposal in an electromechanical system. I also expand on the theory presented in Kronwald et. al. to include the effects of squeezing in the presence of classical microwave noise, and without assumptions of perfect alignment of the pump frequencies.

In the first experiment, we produce a squeezed thermal state using the method of Kronwald et. al.. We perform back-action evading measurements of the mechanical squeezed state in order to probe the noise in both quadratures of the mechanics. Using this method, we detect single-quadrature fluctuations at the level of 1.09 +/- 0.06 times the quantum zero-point motion.

In the second experiment, we measure the spectral noise of the microwave cavity in the presence of the squeezing tones and fit a full model to the spectrum in order to deduce a quadrature variance of 0.80 +/- 0.03 times the zero-point level. These measurements provide the first evidence of quantum squeezing of motion in a mechanical resonator.

A computer-aided investigation of motion detection units in the fly

This work deals with two related areas: processing of visual information in the central nervous system, and the application of computer systems to research in neurophysiology.

Certain classes of interneurons in the brain and optic lobes of the blowfly Calliphora phaenicia were previously shown to be sensitive to the direction of motion of visual stimuli. These units were identified by visual field, preferred direction of motion, and anatomical location from which recorded. The present work is addressed to the questions: (1) is there interaction between pairs of these units, and (2) if such relationships can be found, what is their nature. To answer these questions, it is essential to record from two or more units simultaneously, and to use more than a single recording electrode if recording points are to be chosen independently. Accordingly, such techniques were developed and are described.

One must also have practical, convenient means for analyzing the large volumes of data so obtained. It is shown that use of an appropriately designed computer system is a profitable approach to this problem. Both hardware and software requirements for a suitable system are discussed and an approach to computer-aided data analysis developed. A description is given of members of a collection of application programs developed for analysis of neuro-physiological data and operated in the environment of and with support from an appropriate computer system. In particular, techniques developed for classification of multiple units recorded on the same electrode are illustrated as are methods for convenient graphical manipulation of data via a computer-driven display.

By means of multiple electrode techniques and the computer-aided data acquisition and analysis system, the path followed by one of the motion detection units was traced from open optic lobe through the brain and into the opposite lobe. It is further shown that this unit and its mirror image in the opposite lobe have a mutually inhibitory relationship. This relationship is investigated. The existence of interaction between other pairs of units is also shown. For pairs of units responding to motion in the same direction, the relationship is of an excitatory nature; for those responding to motion in opposed directions, it is inhibitory.

Experience gained from use of the computer system is discussed and a critical review of the current system is given. The most useful features of the system were found to be the fast response, the ability to go from one analysis technique to another rapidly and conveniently, and the interactive nature of the display system. The shortcomings of the system were problems in real-time use and the programming barrier—the fact that building new analysis techniques requires a high degree of programming knowledge and skill. It is concluded that computer system of the kind discussed will play an increasingly important role in studies of the central nervous system.

The Molecular Basis of Lysine Acetylation: Addition, Removal, and Recognition

Acetyltransferases and deacetylases catalyze the addition and removal, respectively, of acetyl groups to the epsilon-amino group of protein lysine residues. This modification can affect the function of a protein through several means, including the recruitment of specific binding partners called acetyl-lysine readers. Acetyltransferases, deacetylases, and acetyl-lysine readers have emerged as crucial regulators of biological processes and prominent targets for the treatment of human disease. This work describes a combination of structural, biochemical, biophysical, cell-biological, and organismal studies undertaken on a set of proteins that cumulatively include all steps of the acetylation process: the acetyltransferase MEC-17, the deacetylase SIRT1, and the acetyl-lysine reader DPF2. Tubulin acetylation by MEC-17 is associated with stable, long-lived microtubule structures. We determined the crystal structure of the catalytic domain of human MEC-17 in complex with the cofactor acetyl-CoA. The structure in combination with an extensive enzymatic analysis of MEC-17 mutants identified residues for cofactor and substrate recognition and activity. A large, evolutionarily conserved hydrophobic surface patch distal to the active site was shown to be necessary for catalysis, suggesting that specificity is achieved by interactions with the alpha-tubulin substrate that extend outside of the modified surface loop. Experiments in C. elegans showed that while MEC-17 is required for touch sensitivity, MEC-17 enzymatic activity is dispensible for this behavior. SIRT1 deacetylates a wide range of substrates, including p53, NF-kappaB, FOXO transcription factors, and PGC-1-alpha, with roles in cellular processes ranging from energy metabolism to cell survival. SIRT1 activity is uniquely controlled by a C-terminal regulatory segment (CTR). Here we present crystal structures of the catalytic domain of human SIRT1 in complex with the CTR in an apo form and in complex with a cofactor and a pseudo-substrate peptide. The catalytic domain adopts the canonical sirtuin fold. The CTR forms a beta-hairpin structure that complements the beta-sheet of the NAD^+-binding domain, covering an essentially invariant, hydrophobic surface. A comparison of the apo and cofactor bound structures revealed conformational changes throughout catalysis, including a rotation of a smaller subdomain with respect to the larger NAD^+-binding subdomain. A biochemical analysis identified key residues in the active site, an inhibitory role for the CTR, and distinct structural features of the CTR that mediate binding and inhibition of the SIRT1 catalytic domain. DPF2 represses myeloid differentiation in acute myelogenous leukemia. Finally, we solved the crystal structure of the tandem PHD domain of human DPF2. We showed that DPF2 preferentially binds H3 tail peptides acetylated at Lys14, and binds H4 tail peptides with no preference for acetylation state. Through a structural and mutational analysis we identify the molecular basis of histone recognition. We propose a model for the role of DPF2 in AML and identify the DPF2 tandem PHD finger domain as a promising novel target for anti-leukemia therapeutics.

Studies of response to earthquake ground motion

A study is made of the accuracy of electronic digital computer calculations of ground displacement and response spectra from strong-motion earthquake accelerograms. This involves an investigation of methods of the preparatory reduction of accelerograms into a form useful for the digital computation and of the accuracy of subsequent digital calculations. Various checks are made for both the ground displacement and response spectra results, and it is concluded that the main errors are those involved in digitizing the original record. Differences resulting from various investigators digitizing the same experimental record may become as large as 100% of the maximum computed ground displacements. The spread of the results of ground displacement calculations is greater than that of the response spectra calculations. Standardized methods of adjustment and calculation are recommended, to minimize such errors.

Studies are made of the spread of response spectral values about their mean. The distribution is investigated experimentally by Monte Carlo techniques using an electric analog system with white noise excitation, and histograms are presented indicating the dependence of the distribution on the damping and period of the structure. Approximate distributions are obtained analytically by confirming and extending existing results with accurate digital computer calculations. A comparison of the experimental and analytical approaches indicates good agreement for low damping values where the approximations are valid. A family of distribution curves to be used in conjunction with existing average spectra is presented. The combination of analog and digital computations used with Monte Carlo techniques is a promising approach to the statistical problems of earthquake engineering.

Methods of analysis of very small earthquake ground motion records obtained simultaneously at different sites are discussed. The advantages of Fourier spectrum analysis for certain types of studies and methods of calculation of Fourier spectra are presented. The digitizing and analysis of several earthquake records is described and checks are made of the dependence of results on digitizing procedure, earthquake duration and integration step length. Possible dangers of a direct ratio comparison of Fourier spectra curves are pointed out and the necessity for some type of smoothing procedure before comparison is established. A standard method of analysis for the study of comparative ground motion at different sites is recommended.

I. Electronic processes in α-sulfur. II. Polaron motion in a D.C. electric field

Part I: The mobilities of photo-generated electrons and holes in orthorhombic sulfur are determined by drift mobility techniques. At room temperature electron mobilities between 0.4 cm²/V-sec and 4.8 cm²/V-sec and hole mobilities of about 5.0 cm²/V-sec are reported. The temperature dependence of the electron mobility is attributed to a level of traps whose effective depth is about 0.12 eV. This value is further supported by both the voltage dependence of the space-charge-limited, D.C. photocurrents and the photocurrent versus photon energy measurements.

As the field is increased from 10 kV/cm to 30 kV/cm a second mechanism for electron transport becomes appreciable and eventually dominates. Evidence that this is due to impurity band conduction at an appreciably lower mobility (4.10^-4 cm²/V-sec) is presented. No low mobility hole current could be detected. When fields exceeding 30 kV/cm for electron transport and 35 kV/cm for hole transport are applied, avalanche phenomena are observed. The results obtained are consistent with recent energy gap studies in sulfur.

The theory of the transport of photo-generated carriers is modified to include the case of appreciable thermos-regeneration from the traps in one transit time.

Part II: An explicit formula for the electric field E necessary to accelerate an electron to a steady-state velocity v in a polarizable crystal at arbitrary temperature is determined via two methods utilizing Feynman Path Integrals. No approximation is made regarding the magnitude of the velocity or the strength of the field. However, the actual electron-lattice Coulombic interaction is approximated by a distribution of harmonic oscillator potentials. One may be able to find the “best possible” distribution of oscillators using a variational principle, but we have not been able to find the expected criterion. However, our result is relatively insensitive to the actual distribution of oscillators used, and our E-v relationship exhibits the physical behavior expected for the polaron. Threshold fields for ejecting the electron for the polaron state are calculated for several substances using numerical results for a simple oscillator distribution.

Investigation of strong earthquake ground motion

The pattern of energy release during the Imperial Valley, California, earthquake of 1940 is studied by analysing the El Centro strong motion seismograph record and records from the Tinemaha seismograph station, 546 km from the epicenter. The earthquake was a multiple event sequence with at least 4 events recorded at El Centro in the first 25 seconds, followed by 9 events recorded in the next 5 minutes. Clear P, S and surface waves were observed on the strong motion record. Although the main part of the earthquake energy was released during the first 15 seconds, some of the later events were as large as M = 5.8 and thus are important for earthquake engineering studies. The moment calculated using Fourier analysis of surface waves agrees with the moment estimated from field measurements of fault offset after the earthquake. The earthquake engineering significance of the complex pattern of energy release is discussed. It is concluded that a cumulative increase in amplitudes of building vibration resulting from the present sequence of shocks would be significant only for structures with relatively long natural period of vibration. However, progressive weakening effects may also lead to greater damage for multiple event earthquakes.

The model with surface Love waves propagating through a single layer as a surface wave guide is studied. It is expected that the derived properties for this simple model illustrate well several phenomena associated with strong earthquake ground motion. First, it is shown that a surface layer, or several layers, will cause the main part of the high frequency energy, radiated from the nearby earthquake, to be confined to the layer as a wave guide. The existence of the surface layer will thus increase the rate of the energy transfer into the man-made structures on or near the surface of the layer. Secondly, the surface amplitude of the guided SH waves will decrease if the energy of the wave is essentially confined to the layer and if the wave propagates towards an increasing layer thickness. It is also shown that the constructive interference of SH waves will cause the zeroes and the peaks in the Fourier amplitude spectrum of the surface ground motion to be continuously displaced towards the longer periods as the distance from the source of the energy release increases.

Influence of local geology on earthquake ground motion

As a simplified approach for estimating theoretically the influence of local subsoils upon the ground motion during an earthquake, the problem of an idealized layered system subjected to vertically incident plane body waves was studied. Both the technique of steady-state analysis and the technique of transient analysis have been used to analyze the problem.

In the steady-state analysis, a recursion formula has been derived for obtaining the response of a layered system to sinusoidally steady-state input. Several conclusions are drawn concerning the nature of the amplification spectrum of a nonviscous layered system having its layer stiffnesses increasing with depth. Numerical examples are given to demonstrate the effect of layer parameters on the amplification spectrum of a layered system.

In the transient analysis, two modified shear beam models have been established for obtaining approximately the response of a layered system to earthquake-like excitation. The method of continuous modal analysis was adopted for approximate analysis of the models, with energy dissipation in the layers, if any, taken into account. Numerical examples are given to demonstrate the accuracy of the models and the effect of a layered system in modifying the input motion.

Conditions are established, under which the theory is applicable to predict the influence of local subsoils on the ground motion during an earthquake. To demonstrate the applicability of the models to actual cases, three examples of actually recorded earthquake events are examined. It is concluded that significant modification of the incoming seismic waves, as predicted by the theory, is likely to occur in well defined soft subsoils during an earthquake, provided that certain conditions concerning the nature of the incoming seismic waves are satisfied.

Real-Time Bayesian Analysis of Ground Motion Envelopes for Earthquake Early Warning

Current earthquake early warning systems usually make magnitude and location predictions and send out a warning to the users based on those predictions. We describe an algorithm that assesses the validity of the predictions in real-time. Our algorithm monitors the envelopes of horizontal and vertical acceleration, velocity, and displacement. We compare the observed envelopes with the ones predicted by Cua & Heaton's envelope ground motion prediction equations (Cua 2005). We define a "test function" as the logarithm of the ratio between observed and predicted envelopes at every second in real-time. Once the envelopes deviate beyond an acceptable threshold, we declare a misfit. Kurtosis and skewness of a time evolving test function are used to rapidly identify a misfit. Real-time kurtosis and skewness calculations are also inputs to both probabilistic (Logistic Regression and Bayesian Logistic Regression) and nonprobabilistic (Least Squares and Linear Discriminant Analysis) models that ultimately decide if there is an unacceptable level of misfit. This algorithm is designed to work at a wide range of amplitude scales. When tested with synthetic and actual seismic signals from past events, it works for both small and large events.

Proton magnetic resonance studies of ribonucleic acid complexes. I. Complexes of biological bases and oligonucleotides with RNA. II. Template recognition and the degeneracy of the genetic code

Part I. Complexes of Biological Bases and Oligonucleotides with RNA

The physical nature of complexes of several biological bases and oligonucleotides with single-stranded ribonucleic acids have been studied by high resolution proton magnetic resonance spectroscopy. The importance of various forces in the stabilization of these complexes is also discussed.

Previous work has shown that purine forms an intercalated complex with single-stranded nucleic acids. This complex formation led to severe and stereospecific broadening of the purine resonances. From the field dependence of the linewidths, T₁ measurements of the purine protons and nuclear Overhauser enhancement experiments, the mechanism for the line broadening was ascertained to be dipole-dipole interactions between the purine protons and the ribose protons of the nucleic acid.

The interactions of ethidium bromide (EB) with several RNA residues have been studied. EB forms vertically stacked aggregates with itself as well as with uridine, 3'-uridine monophosphate and 5'-uridine monophosphate and forms an intercalated complex with uridylyl (3' → 5') uridine and polyuridylic acid (poly U). The geometry of EB in the intercalated complex has also been determined.

The effect of chain length of oligo-A-nucleotides on their mode of interaction with poly U in D₂0 at neutral pD have also been studied. Below room temperatures, ApA and ApApA form a rigid triple-stranded complex involving a stoichiometry of one adenine to two uracil bases, presumably via specific adenine-uracil base pairing and cooperative base stacking of the adenine bases. While no evidence was obtained for the interaction of ApA with poly U above room temperature, ApApA exhibited complex formation of a 1:1 nature with poly U by forming Watson-Crick base pairs. The thermodynamics of these systems are discussed.

Part II. Template Recognition and the Degeneracy of the Genetic Code

The interaction of ApApG and poly U was studied as a model system for the codon-anticodon interaction of tRNA and mRNA in vivo. ApApG was shown to interact with poly U below ~20°C. The interaction was of a 1:1 nature which exhibited the Hoogsteen bonding scheme. The three bases of ApApG are in an anti conformation and the guanosine base appears to be in the lactim tautomeric form in the complex.

Due to the inadequacies of previous models for the degeneracy of the genetic code in explaining the observed interactions of ApApG with poly U, the "tautomeric doublet" model is proposed as a possible explanation of the degenerate interactions of tRNA with mRNA during protein synthesis in vivo.