38 research outputs found
Companions of Stars: From Other Stars to Brown Dwarfs to Planets: The Discovery of the First Methane Brown Dwarf
The discovery of the first methane brown dwarf provides a framework for
describing the important advances in both fundamental physics and astrophysics
that are due to the study of companions of stars. I present a few highlights of
the history of this subject along with details of the discovery of the brown
dwarf Gliese 229B. The nature of companions of stars is discussed with an
attempt to avoid biases induced by anthropocentric nomenclature. With the newer
types of remote reconnaissance of nearby stars and their systems of companions,
an exciting and perhaps even more profound set of contributions to science is
within reach in the near future. This includes an exploration of the diversity
of planets in the universe and perhaps soon the first solid evidence for
biological activity outside our Solar System.Comment: 31 pages, 13 figure
A tetravalent live attenuated dengue virus vaccine stimulates balanced immunity to multiple serotypes in humans
The four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development
Onset of Superfluidity in 4He Films Adsorbed on Disordered Substrates
We have studied 4He films adsorbed in two porous glasses, aerogel and Vycor,
using high precision torsional oscillator and DC calorimetry techniques. Our
investigation focused on the onset of superfluidity at low temperatures as the
4He coverage is increased. Torsional oscillator measurements of the 4He-aerogel
system were used to determine the superfluid density of films with transition
temperatures as low as 20 mK. Heat capacity measurements of the 4He-Vycor
system probed the excitation spectrum of both non-superfluid and superfluid
films for temperatures down to 10 mK. Both sets of measurements suggest that
the critical coverage for the onset of superfluidity corresponds to a mobility
edge in the chemical potential, so that the onset transition is the bosonic
analog of a superconductor-insulator transition. The superfluid density
measurements, however, are not in agreement with the scaling theory of an onset
transition from a gapless, Bose glass phase to a superfluid. The heat capacity
measurements show that the non-superfluid phase is better characterized as an
insulator with a gap.Comment: 15 pages (RevTex), 21 figures (postscript
A Solvable Regime of Disorder and Interactions in Ballistic Nanostructures, Part I: Consequences for Coulomb Blockade
We provide a framework for analyzing the problem of interacting electrons in
a ballistic quantum dot with chaotic boundary conditions within an energy
(the Thouless energy) of the Fermi energy. Within this window we show that the
interactions can be characterized by Landau Fermi liquid parameters. When ,
the dimensionless conductance of the dot, is large, we find that the disordered
interacting problem can be solved in a saddle-point approximation which becomes
exact as (as in a large-N theory). The infinite theory shows a
transition to a strong-coupling phase characterized by the same order parameter
as in the Pomeranchuk transition in clean systems (a spontaneous
interaction-induced Fermi surface distortion), but smeared and pinned by
disorder. At finite , the two phases and critical point evolve into three
regimes in the plane -- weak- and strong-coupling regimes separated
by crossover lines from a quantum-critical regime controlled by the quantum
critical point. In the strong-coupling and quantum-critical regions, the
quasiparticle acquires a width of the same order as the level spacing
within a few 's of the Fermi energy due to coupling to collective
excitations. In the strong coupling regime if is odd, the dot will (if
isolated) cross over from the orthogonal to unitary ensemble for an
exponentially small external flux, or will (if strongly coupled to leads) break
time-reversal symmetry spontaneously.Comment: 33 pages, 14 figures. Very minor changes. We have clarified that we
are treating charge-channel instabilities in spinful systems, leaving
spin-channel instabilities for future work. No substantive results are
change
Human CD4 + T Cell Responses to an Attenuated Tetravalent Dengue Vaccine Parallel Those Induced by Natural Infection in Magnitude, HLA Restriction, and Antigen Specificity
Dengue virus (DENV) is responsible for growing numbers of infections worldwide and has proven to be a significant challenge for vaccine development. We previously demonstrated that CD8+ T cell responses elicited by a dengue live attenuated virus (DLAV) vaccine resemble those observed after natural infection. In this study, we screened peripheral blood mononuclear cells (PBMCs) from donors vaccinated with a tetravalent DLAV vaccine (TV005) with pools of dengue virus-derived predicted major histocompatibility complex (MHC) class II binding peptides. The definition of CD4+ T cell responses after live vaccination is important because CD4+ T cells are known contributors to host immunity, including cytokine production, help for CD8+ T and B cells, and direct cytotoxicity against infected cells. While responses to all antigens were observed, DENV-specific CD4+ T cells were focused predominantly on the capsid and nonstructural NS3 and NS5 antigens. Importantly, CD4+ T cell responses in vaccinees were similar in magnitude and breadth to those after natural infection, recognized the same antigen hierarchy, and had similar profiles of HLA restriction. We conclude that TV005 vaccination has the capacity to elicit CD4+ cell responses closely mirroring those observed in a population associated with natural immunity