610 research outputs found
Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance
An effective prophylactic hepatitis B virus (HBV) vaccine has long been available but is ineffective for chronic infection. The primary cause of chronic hepatitis B (CHB) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to HBV antigens. The resulting defective CD4+/CD8+ T cell response, poor cytokine production, insufficient neutralizing anti-body (nAb) and poor response to HBsAg vaccination characterize CHB infection. The objective of this study was to develop virus-like-particles (VLPs) that elicit nAb to prevent viral spread and prime CD4+/CD8+ T cells to eradicate intracellular HBV. Eight neutralizing B cell epitopes from the envelope PreS1 region were consolidated onto a species-variant of the HBV core protein, the woodchuck hepatitis core antigen (WHcAg). PreS1-specific B cell epitopes were chosen because of preferential expression on HBV virions. Because WHcAg and HBcAg are not crossreactive at the B cell level and only partially cross-reactive at the CD4+/CD8+ T cell level, CD4+ T cells specific for WHcAg-unique T cell sites can provide cognate T-B cell help for anti-PreS1 Ab production that is not curtailed by immune tolerance. Immunization of immune tolerant HBV transgenic (Tg) mice with PreS1-WHc VLPs elicited levels of high titer anti-PreS1 nAbs equivalent to wildtype mice. Passive transfer of PreS1 nAbs into human-liver chimeric mice prevented acute infection and cleared serum HBV from mice previously infected with HBV in a model of CHB. At the T cell level, PreS1-WHc VLPs and hybrid WHcAg/HBcAg DNA immunogens elicited HBcAg-specific CD4+ Th and CD8+ CTL responses
Passive acoustic monitoring complements traditional methods for assessing marine habitat enhancement outcomes
Habitat enhancement, often accomplished through the introduction of artificial structures, is a common strategy used by marine resource managers to provide habitat subsidies, protect sensitive habitat, and create new fishing opportunities. Traditional monitoring methods for assessing habitat enhancement outcomes face numerous limitations, including dependence on environmental conditions and trade-offs between sampling frequency and duration. Passive acoustic monitoring (PAM) is not subject to these same limitations and offers many advantages as a complement to traditional monitoring methods. Our team opportunistically monitored the soundscape and community development of a newly deployed artificial reef and compared it to that of a nearby established artificial reef using PAM and underwater time-lapse videos. Specifically, we compared the sound pressure level (SPL) timeseries, dusk peak in SPL, and dusk power spectrum between the two artificial reefs to evaluate whether and on what timescale the soundscapes converged. Additionally, we tracked temporal patterns in species-specific vocalizations to identify the trajectory of community development on the new reef. Lastly, we compared the qualitative conclusions drawn from PAM to previously published results from video monitoring of the same two artificial reefs. PAM identified minimal difference in mean low-frequency SPL between the two reefs at the onset of monitoring. Though the timeseries correlation, dusk SPL, and dusk power spectra all varied across sampling periods, there were periods of low-frequency soundscape alignment at four and eleven months following artificial reef deployment, associated with the presence of fish chorusing. The high-frequency timeseries on each reef were well correlated during all sampling periods, despite an initial SPL difference of 17 dB. Throughout monitoring, high-frequency sound levels became more similar between the reefs but did not converge. While video monitoring suggested that demersal species did not colonize the reef until five months post-deployment, patterns in species-specific vocalizations suggested that toadfish (Opsanus sp.) a cryptic, demersal species may have colonized the new reef within two weeks. Our findings demonstrate that passive acoustic monitoring is a useful complement to traditional methodologies and can provide a more holistic view of community development than visual monitoring alone
Finite element simulation of three-dimensional free-surface flow problems
An adaptive finite element algorithm is described for the stable solution of three-dimensional free-surface-flow problems based primarily on the use of node movement. The algorithm also includes a discrete remeshing procedure which enhances its accuracy and robustness. The spatial discretisation allows an isoparametric piecewise-quadratic approximation of the domain geometry for accurate resolution of the curved free surface.
The technique is illustrated through an implementation for surface-tension-dominated viscous flows modelled in terms of the Stokes equations with suitable boundary conditions on the deforming free surface. Two three-dimensional test problems are used to demonstrate the performance of the method: a liquid bridge problem and the formation of a fluid droplet
Can forest management based on natural disturbances maintain ecological resilience?
Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance
Partial Dynamical Symmetry in the Symplectic Shell Model
We present an example of a partial dynamical symmetry (PDS) in an interacting
fermion system and demonstrate the close relationship of the associated
Hamiltonians with a realistic quadrupole-quadrupole interaction, thus shedding
new light on this important interaction. Specifically, in the framework of the
symplectic shell model of nuclei, we prove the existence of a family of
fermionic Hamiltonians with partial SU(3) symmetry. We outline the construction
process for the PDS eigenstates with good symmetry and give analytic
expressions for the energies of these states and E2 transition strengths
between them. Characteristics of both pure and mixed-symmetry PDS eigenstates
are discussed and the resulting spectra and transition strengths are compared
to those of real nuclei. The PDS concept is shown to be relevant to the
description of prolate, oblate, as well as triaxially deformed nuclei.
Similarities and differences between the fermion case and the previously
established partial SU(3) symmetry in the Interacting Boson Model are
considered.Comment: 9 figure
Surto epidêmico de gastrenterite, com identificação do provável alimento veiculador da infecção
Neutrino Interferometry In Curved Spacetime
Gravitational lensing introduces the possibility of multiple (macroscopic)
paths from an astrophysical neutrino source to a detector. Such a multiplicity
of paths can allow for quantum mechanical interference to take place that is
qualitatively different to neutrino oscillations in flat space. After an
illustrative example clarifying some under-appreciated subtleties of the phase
calculation, we derive the form of the quantum mechanical phase for a neutrino
mass eigenstate propagating non-radially through a Schwarzschild metric. We
subsequently determine the form of the interference pattern seen at a detector.
We show that the neutrino signal from a supernova could exhibit the
interference effects we discuss were it lensed by an object in a suitable mass
range. We finally conclude, however, that -- given current neutrino detector
technology -- the probability of such lensing occurring for a
(neutrino-detectable) supernova is tiny in the immediate future.Comment: 25 pages, 1 .eps figure. Updated version -- with simplified notation
-- accepted for publication in Phys.Rev.D. Extra author adde
The Refederalization of American Health Care
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69090/2/10.1177_107755878704400103.pd
Effects of watershed land use on nitrogen concentrations and δ15 Nitrogen in groundwater
Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Biogeochemistry 77 (2006): 199-215, doi:10.1007/s10533-005-1036-2.Eutrophication is a major agent of change affecting freshwater, estuarine, and marine
systems. It is largely driven by transportation of nitrogen from natural and anthropogenic
sources. Research is needed to quantify this nitrogen delivery and to link the delivery to
specific land-derived sources. In this study we measured nitrogen concentrations and δ15N
values in seepage water entering three freshwater ponds and six estuaries on Cape Cod,
Massachusetts and assessed how they varied with different types of land use. Nitrate
concentrations and δ15N values in groundwater reflected land use in developed and pristine
watersheds. In particular, watersheds with larger populations delivered larger nitrate loads with
higher δ15N values to receiving waters. The enriched δ15N values confirmed nitrogen loading
model results identifying wastewater contributions from septic tanks as the major N source.
Furthermore, it was apparent that N coastal sources had a relatively larger impact on the N
loads and isotopic signatures than did inland N sources further upstream in the watersheds.
This finding suggests that management priorities could focus on coastal sources as a first
course of action. This would require management constraints on a much smaller population.This work was supported
by funds from the Woods Hole Oceanographic Institution Sea Grant Program, from the
Cooperative Institute for Coastal and Estuarine Environmental Technology, from
Massachusetts Department of Environmental Protection to Applied Science Associates,
Narragansett, RI, as well as from Palmer/McLeod and NOAA National Estuarine Research
Reserve Fellowships to Kevin Kroeger. This work is the result of research sponsored by NOAA
National Sea Grant College Program Office, Department of Commerce, under Grant No.
NA86RG0075, Woods Hole Oceanographic Institution Sea Grant Project No. R/M-40
Active Galactic Nuclei at the Crossroads of Astrophysics
Over the last five decades, AGN studies have produced a number of spectacular
examples of synergies and multifaceted approaches in astrophysics. The field of
AGN research now spans the entire spectral range and covers more than twelve
orders of magnitude in the spatial and temporal domains. The next generation of
astrophysical facilities will open up new possibilities for AGN studies,
especially in the areas of high-resolution and high-fidelity imaging and
spectroscopy of nuclear regions in the X-ray, optical, and radio bands. These
studies will address in detail a number of critical issues in AGN research such
as processes in the immediate vicinity of supermassive black holes, physical
conditions of broad-line and narrow-line regions, formation and evolution of
accretion disks and relativistic outflows, and the connection between nuclear
activity and galaxy evolution.Comment: 16 pages, 5 figures; review contribution; "Exploring the Cosmic
Frontier: Astrophysical Instruments for the 21st Century", ESO Astrophysical
Symposia Serie
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