3,081 research outputs found
A family of abundant plasma membrane-associated glycoproteins related to the arabinogalactan proteins is unique to flowering plants
We have identified a family of abundant peripheral plasma membrane glycoproteins that is unique to flowering plants. They are identified by a monoclonal antibody, MAC 207, that recognizes an epitope containing L-arabinose and D-glucuronic acid. Immunofluorescence and immunogold labeling studies locate the MAC 207 epitope to the outer surface of the plasma membrane both in protoplasts and in intact tissues. In some cells MAC 207 also binds to the vacuolar membrane, probably reflecting the movement of the plasma membrane glycoproteins in the endocytic pathway. The epitope recognized by MAC 207 is also present on a distinct soluble proteoglycan secreted into the growth medium by carrot (Daucus carota) suspension culture cells. Biochemical evidence identifies this neutral proteoglycan as a member of the large class of arabinogalactan proteins (AGPs), and suggests a structural relationship between it and the plasma membrane glycoproteins. AGPs have the property of binding to beta-glycans, and we therefore propose that one function of the AGP-related, plasma membrane-associated glycoproteins may be to act as cell surface attachment sites for cell wall matrix polysaccharides
Scale Dependence of Dark Energy Antigravity
We investigate the effects of negative pressure induced by dark energy
(cosmological constant or quintessence) on the dynamics at various
astrophysical scales. Negative pressure induces a repulsive term (antigravity)
in Newton's law which dominates on large scales. Assuming a value of the
cosmological constant consistent with the recent SnIa data we determine the
critical scale beyond which antigravity dominates the dynamics () and discuss some of the dynamical effects implied. We show that
dynamically induced mass estimates on the scale of the Local Group and beyond
are significantly modified due to negative pressure. We also briefly discuss
possible dynamical tests (eg effects on local Hubble flow) that can be applied
on relatively small scales (a few ) to determine the density and equation
of state of dark energy.Comment: Contributed talk at the 2nd Hellenic Cosmology Workshop at NOA
(Athens) Jan. 2001.To appear in the proceedings. Based on work done in
collaboration with M. Axenides and E. Florato
Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: A multicenter study
The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1β and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1β and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal−Wallis analysis of variance with Dunn’s multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences (P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1β determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected <2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface
Absence of Evidence for MHC–Dependent Mate Selection within HapMap Populations
The major histocompatibility complex (MHC) of immunity genes has been reported to influence mate choice in vertebrates, and a recent study presented genetic evidence for this effect in humans. Specifically, greater dissimilarity at the MHC locus was reported for European-American mates (parents in HapMap Phase 2 trios) than for non-mates. Here we show that the results depend on a few extreme data points, are not robust to conservative changes in the analysis procedure, and cannot be reproduced in an equivalent but independent set of European-American mates. Although some evidence suggests an avoidance of extreme MHC similarity between mates, rather than a preference for dissimilarity, limited sample sizes preclude a rigorous investigation. In summary, fine-scale molecular-genetic data do not conclusively support the hypothesis that mate selection in humans is influenced by the MHC locus
Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile
<p>Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.</p>
<p>Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).</p>
<p>Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.</p>
<p>Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.</p>
Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment
Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of 800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of 400 through 714 per QALY gained through 50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al
Challenges of Profile Likelihood Evaluation in Multi-Dimensional SUSY Scans
Statistical inference of the fundamental parameters of supersymmetric
theories is a challenging and active endeavor. Several sophisticated algorithms
have been employed to this end. While Markov-Chain Monte Carlo (MCMC) and
nested sampling techniques are geared towards Bayesian inference, they have
also been used to estimate frequentist confidence intervals based on the
profile likelihood ratio. We investigate the performance and appropriate
configuration of MultiNest, a nested sampling based algorithm, when used for
profile likelihood-based analyses both on toy models and on the parameter space
of the Constrained MSSM. We find that while the standard configuration is
appropriate for an accurate reconstruction of the Bayesian posterior, the
profile likelihood is poorly approximated. We identify a more appropriate
MultiNest configuration for profile likelihood analyses, which gives an
excellent exploration of the profile likelihood (albeit at a larger
computational cost), including the identification of the global maximum
likelihood value. We conclude that with the appropriate configuration MultiNest
is a suitable tool for profile likelihood studies, indicating previous claims
to the contrary are not well founded.Comment: 21 pages, 9 figures, 1 table; minor changes following referee report.
Matches version accepted by JHE
Reaction Time and Mortality from the Major Causes of Death:The NHANES-III Study
Studies examining the relation of information processing speed, as measured by reaction time, with mortality are scarce. We explored these associations in a representative sample of the US population
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