1,329 research outputs found
Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles
BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection
First-trimester or second-trimester screening, or both, for Down's syndrome
BACKGROUND: It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters.METHODS: Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency).RESULTS: First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening.CONCLUSIONS: First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates
Access to interpreting services in England: secondary analysis of national data
Background:
Overcoming language barriers to health care is a global challenge. There is great linguistic diversity in the major cities in the UK with more than 300 languages, excluding dialects, spoken by children in London alone. However, there is dearth of data on the number of non-English speakers for planning effective interpreting services. The aim was to estimate the number of people requiring language support amongst the minority ethnic communities in England.
Methods:
Secondary analysis of national representative sample of subjects recruited to the Health Surveys for England 1999 and 2004.
Results:
298,432 individuals from the four main minority ethnic communities (Indian, Pakistani, Bangladeshi and Chinese) who may be unable to communicate effectively with a health professional. This represents 2,520,885 general practice consultations per year where interpreting services might be required.
Conclusion:
Effective interpreting services are required to improve access and health outcomes of non-English speakers and thereby facilitate a reduction in health inequalities
Laser cooling of a diatomic molecule
It has been roughly three decades since laser cooling techniques produced
ultracold atoms, leading to rapid advances in a vast array of fields.
Unfortunately laser cooling has not yet been extended to molecules because of
their complex internal structure. However, this complexity makes molecules
potentially useful for many applications. For example, heteronuclear molecules
possess permanent electric dipole moments which lead to long-range, tunable,
anisotropic dipole-dipole interactions. The combination of the dipole-dipole
interaction and the precise control over molecular degrees of freedom possible
at ultracold temperatures make ultracold molecules attractive candidates for
use in quantum simulation of condensed matter systems and quantum computation.
Also ultracold molecules may provide unique opportunities for studying chemical
dynamics and for tests of fundamental symmetries. Here we experimentally
demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using
an optical cycling scheme requiring only three lasers, we have observed both
Sisyphus and Doppler cooling forces which have substantially reduced the
transverse temperature of a SrF molecular beam. Currently the only technique
for producing ultracold molecules is by binding together ultracold alkali atoms
through Feshbach resonance or photoassociation. By contrast, different proposed
applications for ultracold molecules require a variety of molecular
energy-level structures. Our method provides a new route to ultracold
temperatures for molecules. In particular it bridges the gap between ultracold
temperatures and the ~1 K temperatures attainable with directly cooled
molecules (e.g. cryogenic buffer gas cooling or decelerated supersonic beams).
Ultimately our technique should enable the production of large samples of
molecules at ultracold temperatures for species that are chemically distinct
from bialkalis.Comment: 10 pages, 7 figure
Regional performance variation in external validation of four prediction models for severity of COVID-19 at hospital admission: An observational multi-centre cohort study
Background Prediction models should be externally validated to assess their performance before implementation. Several prediction models for coronavirus disease-19 (COVID-19) have been published. This observational cohort study aimed to validate published models of severity for hospitalized patients with COVID-19 using clinical and laboratory predictors. Methods Prediction models fitting relevant inclusion criteria were chosen for validation. The outcome was either mortality or a composite outcome of mortality and ICU admission (severe disease). 1295 patients admitted with symptoms of COVID-19 at Kings Cross Hospital (KCH) in London, United Kingdom, and 307 patients at Oslo University Hospital (OUH) in Oslo, Norway were included. The performance of the models was assessed in terms of discrimination and calibration. Results We identified two models for prediction of mortality (referred to as Xie and Zhang1) and two models for prediction of severe disease (Allenbach and Zhang2). The performance of the models was variable. For prediction of mortality Xie had good discrimination at OUH with an area under the receiver-operating characteristic (AUROC) 0.87 [95% confidence interval (CI) 0.79–0.95] and acceptable discrimination at KCH, AUROC 0.79 [0.76–0.82]. In prediction of severe disease, Allenbach had acceptable discrimination (OUH AUROC 0.81 [0.74–0.88] and KCH AUROC 0.72 [0.68–0.75]). The Zhang models had moderate to poor discrimination. Initial calibration was poor for all models but improved with recalibration. Conclusions The performance of the four prediction models was variable. The Xie model had the best discrimination for mortality, while the Allenbach model had acceptable results for prediction of severe disease
Numerical approximations for the tempered fractional Laplacian: Error analysis and applications
In this paper, we propose an accurate finite difference method to discretize
the -dimensional (for ) tempered integral fractional Laplacian and
apply it to study the tempered effects on the solution of problems arising in
various applications. Compared to other existing methods, our method has higher
accuracy and simpler implementation. Our numerical method has an accuracy of
, for if (or if ) with
, suggesting the minimum consistency conditions. The accuracy can
be improved to , for if
(or if ). Numerical experiments confirm our analytical results and provide
insights in solving the tempered fractional Poisson problem. It suggests that
to achieve the second order of accuracy, our method only requires the solution
for any . Moreover, if the solution
of tempered fractional Poisson problems satisfies for and , our method has the accuracy
of . Since our method yields a (multilevel) Toeplitz stiffness
matrix, one can design fast algorithms via the fast Fourier transform for
efficient simulations. Finally, we apply it together with fast algorithms to
study the tempered effects on the solutions of various tempered fractional
PDEs, including the Allen-Cahn equation and Gray-Scott equations.Comment: 21 pages, 11 figures, 3 table
Comparison of s- and d-wave gap symmetry in nonequilibrium superconductivity
Recent application of ultrafast pump/probe optical techniques to
superconductors has renewed interest in nonequilibrium superconductivity and
the predictions that would be available for novel superconductors, such as the
high-Tc cuprates. We have reexamined two of the classical models which have
been used in the past to interpret nonequilibrium experiments with some
success: the mu* model of Owen and Scalapino and the T* model of Parker.
Predictions depend on pairing symmetry. For instance, the gap suppression due
to excess quasiparticle density n in the mu* model, varies as n^{3/2} in d-wave
as opposed to n for s-wave. Finally, we consider these models in the context of
S-I-N tunneling and optical excitation experiments. While we confirm that
recent pump/probe experiments in YBCO, as presently interpreted, are in
conflict with d-wave pairing, we refute the further claim that they agree with
s-wave.Comment: 14 pages, 11 figure
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