781 research outputs found
Post-licensing safety of fosamprenavir in HIV-infected children in Europe
Purpose: Fosamprenavir, combined with low-dose ritonavir (FPV/r), is indicated for treatment of HIV-infected children aged â„6 years in Europe. Our purpose was to assess the safety of licensed use of FPV/r in HIV-infected children reported to six cohorts in the European Pregnancy and Paediatric HIV Cohort Collaboration.
Methods: Retrospective analysis of individual patient data for all children aged 6â18 years taking the licensed dose of FPV up to 31/12/10. Adverse events (clinical events and absolute neutrophil counts, total cholesterol and triglycerides, and alanine transaminase) were summarised and DAIDS gradings characterised severity.
Results: Ninety-two HIV-infected children aged 6â18 years took the licensed dose, comprising 3% of the total number of children in follow-up in participating cohorts. Median age at antiretroviral therapy initiation was 6 years (interquartile range 1â11 years), and median age at start of FPV/r was 15 years (12â17 years). Estimated median time on an FPV-containing regimen was 52 months, with a total of
266.9 patient years of exposure overall. Half (54%) were on an FPV-containing regimen at last follow-up. Rates of grade 3/4 events were generally low for all biochemical toxicity markers, and no serious adverse events considered to be causally related to FPV/r were reported.
Conclusions: Results suggest that long-term licensed dose FPV-containing regimens appear to be generally well tolerated with few reported toxicities in HIV-infected children in Europe, although relatively infrequently prescribed. No serious events were reported
More than a century of bathymetric observations and present-day shallow sediment characterization in Belfast Bay, Maine, USA: implications for pockmark field longevity
This paper is not subject to U.S. copyright. The definitive version was published in Geo-Marine Letters 31 (2011): 237-248, doi:10.1007/s00367-011-0228-0.Mechanisms and timescales responsible for
pockmark formation and maintenance remain uncertain,
especially in areas lacking extensive thermogenic fluid
deposits (e.g., previously glaciated estuaries). This study
characterizes seafloor activity in the Belfast Bay, Maine
nearshore pockmark field using (1) three swath bathymetry
datasets collected between 1999 and 2008, complemented
by analyses of shallow box-core samples for radionuclide
activity and undrained shear strength, and (2) historical
bathymetric data (report and smooth sheets from 1872,
1947, 1948). In addition, because repeat swath bathymetry
surveys are an emerging data source, we present a selected
literature review of recent studies using such datasets for
seafloor change analysis. This study is the first to apply the
method to a pockmark field, and characterizes macro-scale
(>5 m) evolution of tens of square kilometers of highly
irregular seafloor. Presence/absence analysis yielded no
change in pockmark frequency or distribution over a 9-year
period (1999â2008). In that time pockmarks did not
detectably enlarge, truncate, elongate, or combine. Historical
data indicate that pockmark chains already existed in
the 19th century. Despite the lack of macroscopic changes
in the field, near-bed undrained shear-strength values of
less than 7 kPa and scattered downcore 137Cs signatures
indicate a highly disturbed setting. Integrating these
findings with independent geophysical and geochemical
observations made in the pockmark field, it can be
concluded that (1) large-scale sediment resuspension and
dispersion related to pockmark formation and failure do not
occur frequently within this field, and (2) pockmarks can
persevere in a dynamic estuarine setting that exhibits
minimal modern fluid venting. Although pockmarks are
conventionally thought to be long-lived features maintained
by a combination of fluid venting and minimal sediment
accumulation, this suggests that other mechanisms may be
equally active in maintaining such irregular seafloor
morphology. One such mechanism could be upwelling
within pockmarks induced by near-bed currents.Graduate support for Brothers came from a
Maine Economic Improvement Fund Dissertation Fellowship
Distinct Visual Working Memory Systems for View-Dependent and View-Invariant Representation
Background: How do people sustain a visual representation of the environment? Currently, many researchers argue that a single visual working memory system sustains non-spatial object information such as colors and shapes. However, previous studies tested visual working memory for two-dimensional objects only. In consequence, the nature of visual working memory for three-dimensional (3D) object representation remains unknown. Methodology/Principal Findings: Here, I show that when sustaining information about 3D objects, visual working memory clearly divides into two separate, specialized memory systems, rather than one system, as was previously thought. One memory system gradually accumulates sensory information, forming an increasingly precise view-dependent representation of the scene over the course of several seconds. A second memory system sustains view-invariant representations of 3D objects. The view-dependent memory system has a storage capacity of 3â4 representations and the view-invariant memory system has a storage capacity of 1â2 representations. These systems can operate independently from one another and do not compete for working memory storage resources. Conclusions/Significance: These results provide evidence that visual working memory sustains object information in two separate, specialized memory systems. One memory system sustains view-dependent representations of the scene, akin to the view-specific representations that guide place recognition during navigation in humans, rodents and insects. Th
The cell cycle of the planctomycete Gemmata obscuriglobus with respect to cell compartmentalization
Background: Gemmata obscuriglobus is a distinctive member of the divergent phylum Planctomycetes, all known members of which are peptidoglycan-less bacteria with a shared compartmentalized cell structure and divide by a budding process. G. obscuriglobus in addition shares the unique feature that its nucleoid DNA is surrounded by an envelope consisting of two membranes forming an analogous structure to the membrane-bounded nucleoid of eukaryotes and therefore G. obscuriglobus forms a special model for cell biology. Draft genome data for G. obscuriglobus as well as complete genome sequences available so far for other planctomycetes indicate that the key bacterial cell division protein FtsZ is not present in these planctomycetes, so the cell division process in planctomycetes is of special comparative interest. The membrane-bounded nature of the nucleoid in G. obscuriglobus also suggests that special mechanisms for the distribution of this nuclear body to the bud and for distribution of chromosomal DNA might exist during division. It was therefore of interest to examine the cell division cycle in G. obscuriglobus and the process of nucleoid distribution and nuclear body formation during division in this planctomycete bacterium via light and electron microscopy. Results: Using phase contrast and fluorescence light microscopy, and transmission electron microscopy, the cell division cycle of G. obscuriglobus was determined. During the budding process, the bud was formed and developed in size from one point of the mother cell perimeter until separation. The matured daughter cell acted as a new mother cell and started its own budding cycle while the mother cell can itself initiate budding repeatedly. Fluorescence microscopy of DAPI-stained cells of G. obscuriglobus suggested that translocation of the nucleoid and formation of the bud did not occur at the same time. Confocal laser scanning light microscopy applied to cells stained for membranes as well as DNA confirmed the behaviour of the nucleoid and nucleoid envelope during cell division. Electron microscopy of cryosubstituted cells confirmed deductions from light microscopy concerning nucleoid presence in relation to the stage of budding, and showed that the nucleoid was observed to occur in both mother and bud cells only at later budding stages. It further suggested that nucleoid envelope formed only after the nucleoid was translocated into the bud, since envelopes only appeared in more mature buds, while naked nucleoids occurred in smaller buds. Nucleoid envelope appeared to originate from the intracytoplasmic membranes (ICM) of both mother cell and bud. There was always a connecting passage between mother cell and bud during the budding process until separation of the two cells. The division cycle of the nucleated planctomycete G. obscuriglobus appears to be a complex process in which chromosomal DNA is transported to the daughter cell bud after initial formation of the bud, and this can be performed repeatedly by a single mother cell. Conclusion: The division cycle of the nucleated planctomycete G. obscuriglobus is a complex process in which chromosomal nucleoid DNA is transported to the daughter cell bud after initial formation of a bud without nucleoid. The new bud nucleoid is initially naked and not surrounded by membrane, but eventually acquires a complete nucleoid envelope consisting of two closely apposed membranes as occurs in the mother cell. The membranes of the new nucleoid envelope surrounding the bud nucleoid are derived from intracytoplasmic membranes of both the mother cell and the bud. The cell division of G. obscuriglobus displays some unique features not known in cells of either prokaryotes or eukaryotes
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Efficient, nonâtoxic anion transport by synthetic carriers in cells and epithelia
Transmembrane anion transporters (anionophores) have potential for new modes of biological activity, including therapeutic applications. In particular they might replace the activity of defective anion channels in conditions such as cystic fibrosis. However, data on the biological effects of anionophores are scarce, and it remains uncertain whether such molecules are fundamentally toxic. Here, we report a biological study of an extensive series of powerful anion carriers. Fifteen anionophores were assayed in single cells by monitoring anion transport in real time through fluorescence emission from halide-sensitive yellow fluorescent protein. A bis-(p-nitrophenyl)ureidodecalin shows especially promising activity, including deliverability, potency and persistence. Electrophysiological tests show strong effects in epithelia, close to those of natural anion channels. Toxicity assays yield negative results in three cell lines, suggesting that promotion of anion transport may not be deleterious to cells. We therefore conclude that synthetic anion carriers are realistic candidates for further investigation as treatments for cystic fibrosis.info:eu-repo/semantics/publishe
Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)
This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0âD*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4ââfb-1 collected at the ΄(4S) resonance during 1999â2000, we have reconstructed 38 candidate signal events in the mode B0âD*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0âD*+D*-)=[8.3±1.6(stat)±1.2(syst)]Ă10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation
Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at âs=10.6 GeV
This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qqÌ
continuum events near the ΄(4S) resonance are presented. Using 20.8 fb-1 of data on the ΄(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(BâDs+X)=(10.93±0.19±0.58±2.73)% and B(BâDs*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+âÏÏ+ branching fraction uncertainty. The production cross sections Ï(e+e-âDs+X)ĂB(Ds+âÏÏ+)=7.55±0.20±0.34pb and Ï(e+e-âDs*±X)ĂB(Ds+âÏÏ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the ΄(4S) mass. The branching fractions ÎŁB(BâDs(*)+D(*))=(5.07±0.14±0.30±1.27)% and ÎŁB(BâDs*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation
Search for rare quark-annihilation decays, B --> Ds(*) Phi
We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context
of the Standard Model, these decays are expected to be highly suppressed since
they proceed through annihilation of the b and u-bar quarks in the B- meson.
Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected
with the BABAR detector at SLAC. We find no evidence for these decays, and we
set Bayesian 90% confidence level upper limits on the branching fractions BF(B-
--> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results
are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid
Communications
Composition Influences the Pathway but not the Outcome of the Metabolic Response of Bacterioplankton to Resource Shifts
Bacterioplankton community metabolism is central to the functioning of aquatic ecosystems, and strongly reactive to changes in the environment, yet the processes underlying this response remain unclear. Here we explore the role that community composition plays in shaping the bacterial metabolic response to resource gradients that occur along aquatic ecotones in a complex watershed in Québec. Our results show that the response is mediated by complex shifts in community structure, and structural equation analysis confirmed two main pathways, one involving adjustments in the level of activity of existing phylotypes, and the other the replacement of the dominant phylotypes. These contrasting response pathways were not determined by the type or the intensity of the gradients involved, as we had hypothesized, but rather it would appear that some compositional configurations may be intrinsically more plastic than others. Our results suggest that community composition determines this overall level of community plasticity, but that composition itself may be driven by factors independent of the environmental gradients themselves, such that the response of bacterial communities to a given type of gradient may alternate between the adjustment and replacement pathways. We conclude that community composition influences the pathways of response in these bacterial communities, but not the metabolic outcome itself, which is driven by the environment, and which can be attained through multiple alternative configurations
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