PXR-mediated Metabolism During Pregnancy and Cholestasis

Nuclear receptors, including the pregnane x receptor (PXR) and the farnesoid x receptor (FXR), regulate the expression of genes that maintain bile acid (BA) homeostasis. Intrahepatic cholestasis of pregnancy (ICP) is a common gestational liver disease and BAs are implicated in its pathogenesis. Rodents exhibit maternal liver growth in order to meet the metabolic demands of pregnancy. This process is found to precede changes in body weight, occur in the presence of raised serum BAs and is likely to be driven by a placental lactogen. While the growth is normally achieved by hepatocyte hypertrophy, potentially harmful hyperplasia makes a major contribution in mice lacking Fxr. Consistent with reports of raised serum BAs in normal pregnant women, hepatic BAs are found in association with pro-cholestatic gene expression in normal pregnant mice. Gestation could be a state of reduced Fxr function because BA-fed and Fxr-/- mice do not develop raised hepatic BAs during pregnancy. Sequencing and functional assessment of PXR variants revealed that polymorphisms in this gene are unlikely to contribute to the aetiology of ICP. Surprisingly, Pxr-/- mice have enhanced hepatic metabolism and are resistant to toxicity caused by lithocholic acid (LCA). Furthermore, while hepatic Pxr is activated by intraperitoneal injection of LCA, it is not activated by physiologically relevant LCA-feeding. Summary: Pregnancy causes liver growth, raised hepatic BA and pro-cholestatic gene expression in normal mice. In humans, these adaptations may expose predisposed individuals to gestational liver disease. Genetic variation in PXR does not contribute to ICP and Pxr may play only a limited role in mediating hepatic responses to toxic BAs

Nonlinear Dynamics of Particles Excited by an Electric Curtain

The use of the electric curtain (EC) has been proposed for manipulation and control of particles in various applications. The EC studied in this paper is called the 2-phase EC, which consists of a series of long parallel electrodes embedded in a thin dielectric surface. The EC is driven by an oscillating electric potential of a sinusoidal form where the phase difference of the electric potential between neighboring electrodes is 180 degrees. We investigate the one- and two-dimensional nonlinear dynamics of a particle in an EC field. The form of the dimensionless equations of motion is codimension two, where the dimensionless control parameters are the interaction amplitude ($A$) and damping coefficient ($\beta$). Our focus on the one-dimensional EC is primarily on a case of fixed $\beta$ and relatively small $A$, which is characteristic of typical experimental conditions. We study the nonlinear behaviors of the one-dimensional EC through the analysis of bifurcations of fixed points. We analyze these bifurcations by using Floquet theory to determine the stability of the limit cycles associated with the fixed points in the Poincar\'e sections. Some of the bifurcations lead to chaotic trajectories where we then determine the strength of chaos in phase space by calculating the largest Lyapunov exponent. In the study of the two-dimensional EC we independently look at bifurcation diagrams of variations in $A$ with fixed $\beta$ and variations in $\beta$ with fixed $A$. Under certain values of $\beta$ and $A$, we find that no stable trajectories above the surface exists; such chaotic trajectories are described by a chaotic attractor, for which the the largest Lyapunov exponent is found. We show the well-known stable oscillations between two electrodes come into existence for variations in $A$ and the transitions between several distinct regimes of stable motion for variations in $\beta$

Spatiotemporally Periodic Driven System with Long-Range Interactions

It is well known that some driven systems undergo transitions when a system parameter is changed adiabatically around a critical value. This transition can be the result of a fundamental change in the structure of the phase space, called a bifurcation. Most of these transitions are well classified in the theory of bifurcations. Among the driven systems, spatiotemporally periodic (STP) potentials are noteworthy due to the intimate coupling between their time and spatial components. A paradigmatic example of such a system is the Kapitza pendulum, which is a pendulum with an oscillating suspension point. The Kapitza pendulum has the strange property that it will stand stably in the inverted position for certain driving frequencies and amplitudes. A particularly interesting and useful STP system is an array of parallel electrodes driven with an AC electrical potential such that adjacent electrodes are 180 degrees out of phase. Such an electrode array embedded in a surface is called an Electric Curtain (EC). As we will show, by using two ECs and a quadrupole trap it is posible to produce an electric potential simular in form to that of the Kapitza pendulum. Here I will present the results of four related pieces of work, each focused on understanding the behaviors STP systems, long-range interacting particles, and long-range interacting particles in STP systems. I will begin with a discussion on the experimental results of the EC as applied to the cleaning of solar panels in extraterrestrial environments, and as a way to produce a novel one-dimensional multiparticle STP potential. Then I will present a numerical investigation and dynamical systems analysis of the dynamics that may be possible in an EC. Moving to a simpler model in order to explore the rudimentary physics of coulomb interactions in a STP potential, I will show that the tools of statistical mechanics may be important to the study of such systems to understand transitions that fall outside of bifurcation theory. Though the Coulomb and, similarly, gravitational interactions of particles are prevalent in nature, these long-range interactions are not well understood from a statistical mechanics perspective because they are not extensive or additive. Finally, I will present a simple model for understanding long-range interacting pendula, finding interesting non-equilibrium behavior of the pendula angles. Namely, that a quasistationary clustered state can exist when the angles are initially ordered by their index

A Survey of the Citation of Research in Modern Public Speaking Texts

In view of the quantity of research related to communication, the purpose of this study was to see, first, to what extent the results of this research are made available to beginning students of public address through their public speaking textbooks, and second, to seek to determine if, or to what extent, modern public speaking text writers make use of the often-praised inductive method of teaching

JRIF: Reactive Information Flow Control for Java

A reactive information flow (RIF) automaton for a value v specifies (i) allowed uses for v and (ii) the RIF automaton for any value that might be directly or indirectly derived from v. RIF automata thus specify how transforming a value alters how the result might be used. Such labels are more expressive than existing approaches for controlling downgrading. We devised a type system around RIF automata and incorporated it into Jif, a dialect of Java that supports a classic form of labels for information flow. By implementing a compiler for the resulting JRIF language, we demonstrate how easy it is to replace a classic information-flow type system by a more expressive RIF-based type system. We programmed two example applications in JRIF, and we discuss insights they provide into the benefits of RIF-based security labels.Supported in part by AFOSR grants F9550-06-0019 and FA9550-11-1-0137, National Science Foundation grants 0430161, 0964409, and CCF-0424422 (TRUST), ONR grants N00014-01- 1-0968 and N00014-09-1-0652, and grants from Microsoft

Long-range interacting pendula: A simple model for understanding complex dynamics of charged particles in an electronic curtain device

In this paper, we investigate the equilibrium and non-equilibrium properties of a model that shares several important characteristics with charged particles interacting in an Electric Curtain (EC) device. An EC comprises a periodic array of parallel electrodes, applied to each is an alternating electric potential. Depending on the applied potentials and the geometry of the electrodes, a wide variety of field structures above the plane of the electrodes are possible. The EC has multiple applications in the control and manipulation of small particles, but is under utilized in industry and science because of difficulties in predicting and understanding the particle dynamics. One particular challenge in understanding the dynamics is the many-body coulomb interactions. To better understand the role of the interactions, we study a one-dimensional analytically tractable model that encapsulates their long-range nature. Specifically, we study a Hamiltonian similar to that of the Hamiltonian mean field model but with the inclusion of an index dependent phase in the interaction term that, as we show, reflects the periodic structure of an EC field. We solve for the canonical partition function and also investigate some of the non-equilibrium behaviors. In the study of the non-equilibrium behaviors, we find an interesting property, namely that a quasistationary (lifetime diverges as the number of particles is increased) clustered state can exist when an initial configuration is ordered by the particle indices

Automatic partitioning of database applications

Database-backed applications are nearly ubiquitous in our daily lives. Applications that make many small accesses to the database create two challenges for developers: increased latency and wasted resources from numerous network round trips. A well-known technique to improve transactional database application performance is to convert part of the application into stored procedures that are executed on the database server. Unfortunately, this conversion is often difficult. In this paper we describe Pyxis, a system that takes database-backed applications and automatically partitions their code into two pieces, one of which is executed on the application server and the other on the database server. Pyxis profiles the application and server loads, statically analyzes the code's dependencies, and produces a partitioning that minimizes the number of control transfers as well as the amount of data sent during each transfer. Our experiments using TPC-C and TPC-W show that Pyxis is able to generate partitions with up to 3x reduction in latency and 1.7x improvement in throughput when compared to a traditional non-partitioned implementation and has comparable performance to that of a custom stored procedure implementation.National Science Foundation (U.S.). Graduate Research Fellowshi

Computational studies of multiple-particle nonlinear dynamics in a spatio-temporally periodic potential

The spatio-temporally periodic (STP) potential is interesting in Physics due to the intimate coupling between its time and spatial components. In this paper, we begin with a brief discussion of the dynamical behaviors of a single particle in a STP potential and then examine the dynamics of multiple particles interacting in a STP potential via the electric Coulomb potential. For the multiple particles\u27 case, we focus on the occurrence of bifurcations when the amplitude of the STP potential varies. It is found that the particle concentration of the system plays an important role; the type of bifurcations that occur and the number of attractors present in the Poincaré sections depend on whether the number of particles in the simulation is even or odd. In addition to the nonlinear dynamical approach, we also discuss dependence of the squared fractional deviation of particles\u27 kinetic energy of the multiple particle system on the amplitude of the STP potential which can be used to elucidate certain transitions of states; this approach is simple and useful particularly for experimental studies of complicated interacting systems. © 2014 AIP Publishing LLC