12,587 research outputs found
Quantum Gravity at the Planck Length
I describe our understanding of physics near the Planck length, in particular
the great progress in the last four years in string theory. These are lectures
presented at the 1998 SLAC Summer Institute.Comment: 33 pages, LaTeX, 11 epsf figure
The lattice Schwarzian KdV equation and its symmetries
In this paper we present a set of results on the symmetries of the lattice
Schwarzian Korteweg-de Vries (lSKdV) equation. We construct the Lie point
symmetries and, using its associated spectral problem, an infinite sequence of
generalized symmetries and master symmetries. We finally show that we can use
master symmetries of the lSKdV equation to construct non-autonomous
non-integrable generalized symmetries.Comment: 11 pages, no figures. Submitted to Jour. Phys. A, Special Issue SIDE
VI
Chronopharmacology of mitoxantrone (MX): Evodence for a circadian rhythm of its myelotoxicity from an animal model and a clinical pilot trial
Expanding perfect fluid generalizations of the C-metric
We reexamine Petrov type D gravitational fields generated by a perfect fluid
with spatially homogeneous energy density and in which the flow lines form a
timelike non-shearing and non-rotating congruence. It is shown that the
anisotropic such spacetimes, which comprise the vacuum C-metric as a limit
case, can have \emph{non-zero} expansion, contrary to the conclusion in the
original investigation by Barnes (Gen. Rel. Grav. 4, 105 (1973)). This class
consists of cosmological models with generically one and at most two Killing
vectors. We construct their line element and discuss some important properties.
The methods used in this investigation incite to deduce testable criteria
regarding shearfree normality and staticity op Petrov type spacetimes in
general, which we add in an appendix.Comment: 16 pages, extended and amended versio
Kinetic Antiferromagnetism in the Triangular Lattice
We show that the motion of a single hole in the infinite Hubbard model
with frustrated hopping leads to weak metallic antiferromagnetism of kinetic
origin. An intimate relationship is demonstrated between the simplest versions
of this problem in 1 and 2 dimensions, and two of the most subtle many body
problems, namely the Heisenberg Bethe ring in 1-d and the 2-dimensional
triangular lattice Heisenberg antiferromagnet.Comment: 10 pages, 2 figures, 5 supplementary figures; Figures fixe
Exact Static Cylindrical Solution to Conformal Weyl Gravity
We present the exact exterior solution for a static and neutral cylindrically
symmetric source in locally conformal invariant Weyl gravity. As a special case
the general relativity analogue still can be attained, however only as a
sub-family of solutions. Our solution contains a linear term that would thus
result in a potential that grows linearly over large distances. This may have
implications for exotic astrophysical structures as well as matter fields on
the extremely small scale.Comment: 8 pages, Physical Review
The Role of Heterologous Immunity in Mediating Natural Resistance to Infection in Human Subjects: A Dissertation
Heterologous immunity is a mechanism by which immunological memory within an individual, developed in response to a previous infection, plays a role in the immune response to a subsequent unrelated infection. In murine studies, heterologous immunity facilitated by cross-reactive CD8 T-cell responses can mediate either beneficial (protective immunity) or detrimental effects (e.g. enhanced lung and adipose immunopathology and enhanced viral titers) (Selin et al., 1998; Chen et al., 2001; Welsh and Selin, 2002; Nie et al., 2010; Welsh et al., 2010). Protective heterologous immunity results in enhanced clearance of virus during a subsequent infection with an unrelated pathogen. Such is the case when mice are immunized with lymphocytic choriomeningitis virus (LCMV) and subsequently challenged with Pichinde virus (PV) or vaccinia virus (VACV) (Selin et al., 1998). However, heterologous immunity may also mediate enhanced immunopathology as mice immunized with influenza A virus (IAV) and challenged with LCMV show increased viral titers and enhanced lung immunopathology (Chen et al., 2003).
The role heterologous immunity plays during infection is not limited to the murine system. In fact, there have now been several reports of enhanced immunopathology due to heterologous immunity during human infections, involving viruses such as IAV, Epstein-Barr Virus (EBV), hepatitis C virus (HCV), and dengue virus (DENV) (Mathew et al., 1998; Wedemeyer et al., 2001; Acierno et al., 2003; Nilges et al., 2003; Clute et al., 2005; Urbani et al., 2005). Interestingly, in all reported cases in humans, heterologous immunity mediated enhanced immunopathology.
Upon infection with EBV the clinical presentation can range from asymptomatic to severe, occasionally fatal, acute infectious mononucleosis (AIM) (Crawford et al., 2006b; Luzuriaga and Sullivan, 2010) which is marked by a massive CD8 lymphocytosis. This lympho-proliferative effect in AIM was shown to be partially mediated by reactivation of cross-reactive IAV-M1 58-66 (IAV-GIL) specific CD8 memory T-cells in HLA-A2 patients reacting to the EBV-BMLF1 280 (EBV-GLC) epitope (Clute et al., 2005).
Interestingly, EBV infects ~90% of individuals globally by the third decade of life, establishing a life-long infection (Henle et al., 1969). However, it is unknown why 5-10% of adults remain EBV-sero-negative (EBV-SN), despite the fact that the virus infects the vast majority of the population and is actively shed at high titers even during chronic infection (Hadinoto et al., 2009). Here, we show that EBV-SN HLA-A2+ adults possess cross-reactive IAV-GIL/EBV-GLC memory CD8 T-cells that show highly unique properties. These IAV-GIL cross-reactive memory CD8 T-cells preferentially expand and produce cytokines to EBV antigens at high functional avidity. Additionally, they are capable of lysing EBV-infected targets and show the potential to enter the mucosal epithelial tissue, where infection is thought to initiate, by CD103 expression. This protective capacity of these cross-reactive memory CD8 T-cells may be explained by a unique T-cell receptor (TCR) repertoire that differs by both organization and CDR3 usage from that in EBV-seropositive (EBV-SP) donors.
The composition of the CD8 T-cell repertoire is a dynamic process that begins during the stochastic positive selection of the T-cell pool during development in the thymus. Thus, upon egress to the periphery a naïve T-cell pool, or repertoire, is formed that is variable even between genetically identical individuals. This T-cell repertoire is not static, as each new infection leaves its mark on the repertoire once again by stochastically selecting and expanding best-fit effectors and memory populations to battle each new infection while at the same time deleting older memory CD8 T-cells to make room for the new memory cells (Selin et al., 1999). These events induce an altered repertoire that is unique to each individual at each infection. It is this dynamic and variable organization of the T-cell repertoire that leads to private specificity even between genetically identical individuals upon infection with the same pathogens and thus a different fate (Kim et al., 2005; Cornberg et al., 2006a; Nie et al., 2010). It is this private specificity of the TCR repertoire that helps explain why individuals with the same epitope specific cross-reactive response, but composed of different cross-reactive T-cell clones, can either develop AIM or never become infected with EBV.
Our results suggest that heterologous immunity may protect EBV-SN adults against the establishment of productive EBV infection, and potentially be the first demonstration of protective T-cell heterologous immunity between unrelated pathogens in humans. Our results also suggest that CD8 T-cell immunity can be sterilizing and that an individual’s TCR repertoire ultimately determines their fate during infection.
To conclusively show that heterologous immunity is actively protecting EBV-SN adults from the establishment of a productive EBV infection, one would have to deliberately expose an individual to the virus. Clearly, this is not an acceptable risk, and it could endanger the health of an individual. A humanized mouse model could allow one to address this question.
However, before we can even attempt to address the question of heterologous immunity mediating protection from EBV infection in humanized mice, we must first determine whether these mice can be infected with, and build an immune response to the two viruses we are studying, EBV and IAV. We show here that these mice can indeed be infected with and also mount an immune response to EBV. Additionally, these mice can also be infected with IAV. However, at this time the immune responses that are made to these viruses in our established humanized mouse model are not substantial enough to fully mimic a human immune response capable of testing our hypothesis of heterologous immunity mediating protection from EBV infection.
Although the immune response in these mice to EBV and IAV infection is not suitable for the testing of our model the data are promising, as the humanized mouse model is constantly improving. Hopefully, with constant improvements being made there will be a model that will duplicate a human immune system in its entirety.
This thesis will be divided into 5 major chapters. The first chapter will provide an introduction to both general T-cell biology and also to the role of heterologous immunity in viral infection. The second chapter will provide the details of the experimental procedures that were performed to test our hypothesis. The third chapter will describe the main scientific investigation of the role of heterologous immunity in providing natural resistance to infection in human subjects. This chapter will also consist of the data that will be compiled into a manuscript for publication in a peer-reviewed journal. The fourth chapter will consist of work performed pertaining to the establishment of a humanized mouse model of EBV and IAV infection. The establishment of this model is important for us to be able to show causation for protection from EBV infection mediated by heterologous immunity
Photo-excited zero-resistance states in the GaAs/AlGaAs system
The microwave-excited high mobility two-dimensional electron system exhibits,
at liquid helium temperatures, vanishing resistance in the vicinity of , where , m is an
effective mass, e is the charge, and \textit{f} is the microwave frequency.
Here, we summarize some experimental results.Comment: 7 color figures, 5 page
Fast and robust two-qubit gates for scalable ion trap quantum computing
We propose a new concept for a two-qubit gate operating on a pair of trapped
ions based on laser coherent control techniques. The gate is insensitive to the
temperature of the ions, works also outside the Lamb-Dicke regime, requires no
individual addressing by lasers, and can be orders of magnitude faster than the
trap period
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