983 research outputs found
Risk-Benefit Profiles of Women Using Tamoxifen for Chemoprevention
Tamoxifen has been US Food and Drug Administration–approved for primary prevention of breast cancer since 1998 but has not been widely adopted, in part because of increased risk of serious side effects. Little is known about the risk-benefit profiles of women who use chemoprevention outside of a clinical trial. We examined characteristics associated with initiation and discontinuation of tamoxifen for primary prevention of breast cancer within a large cohort of women with a first-degree family history of breast cancer
Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies
Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent epitopes on gp120. In contrast to previously characterized glycan-dependent bNAbs that recognize high-mannose N-glycans, PGT121 binds complex-type N-glycans in glycan microarrays. We isolated the B-cell clone encoding PGT121, which segregates into PGT121-like and 10-1074–like groups distinguished by sequence, binding affinity, carbohydrate recognition, and neutralizing activity. Group 10-1074 exhibits remarkable potency and breadth but no detectable binding to protein-free glycans. Crystal structures of unliganded PGT121, 10-1074, and their likely germ-line precursor reveal that differential carbohydrate recognition maps to a cleft between complementarity determining region (CDR)H2 and CDRH3. This cleft was occupied by a complex-type N-glycan in a “liganded” PGT121 structure. Swapping glycan contact residues between PGT121 and 10-1074 confirmed their importance for neutralization. Although PGT121 binds complex-type N-glycans, PGT121 recognized high-mannose-only HIV envelopes in isolation and on virions. As HIV envelopes exhibit varying proportions of high-mannose- and complex-type N-glycans, these results suggest promiscuous carbohydrate interactions, an advantageous adaptation ensuring neutralization of all viruses within a given strain
Using effective medium theories to design tailored nanocomposite materials for optical systems
Modern optical systems are subject to very restrictive performance, size and cost requirements. Especially in portable systems size often is the most important factor, which necessitates elaborate designs to achieve the desired specifications. However, current designs already operate very close to the physical limits and further progress is difficult to achieve by changing only the complexity of the design. Another way of improving the performance is to tailor the optical properties of materials specifically to the application at hand. A class of novel, customizable materials that enables the tailoring of the optical properties, and promises to overcome many of the intrinsic disadvantages of polymers, are nanocomposites. However, despite considerable past research efforts, these types of materials are largely underutilized in optical systems. To shed light into this issue we, in this paper, discuss how nanocomposites can be modeled using effective medium theories. In the second part, we then investigate the fundamental requirements that have to be fulfilled to make nanocomposites suitable for optical applications, and show that it is indeed possible to fabricate such a material using existing methods. Furthermore, we show how nanocomposites can be used to tailor the refractive index and dispersion properties towards specific applications
Exoplanet Diversity in the Era of Space-based Direct Imaging Missions
This whitepaper discusses the diversity of exoplanets that could be detected
by future observations, so that comparative exoplanetology can be performed in
the upcoming era of large space-based flagship missions. The primary focus will
be on characterizing Earth-like worlds around Sun-like stars. However, we will
also be able to characterize companion planets in the system simultaneously.
This will not only provide a contextual picture with regards to our Solar
system, but also presents a unique opportunity to observe size dependent
planetary atmospheres at different orbital distances. We propose a preliminary
scheme based on chemical behavior of gases and condensates in a planet's
atmosphere that classifies them with respect to planetary radius and incident
stellar flux.Comment: A white paper submitted to the National Academy of Sciences Exoplanet
Science Strateg
Bose-Einstein Correlations of Three Charged Pions in Hadronic Z^0 Decays
Bose-Einstein Correlations (BEC) of three identical charged pions were
studied in 4 x 10^6 hadronic Z^0 decays recorded with the OPAL detector at LEP.
The genuine three-pion correlations, corrected for the Coulomb effect, were
separated from the known two-pion correlations by a new subtraction procedure.
A significant genuine three-pion BEC enhancement near threshold was observed
having an emitter source radius of r_3 = 0.580 +/- 0.004 (stat.) +/- 0.029
(syst.) fm and a strength of \lambda_3 = 0.504 +/- 0.010 (stat.) +/- 0.041
(syst.). The Coulomb correction was found to increase the \lambda_3 value by
\~9% and to reduce r_3 by ~6%. The measured \lambda_3 corresponds to a value of
0.707 +/- 0.014 (stat.) +/- 0.078 (syst.) when one takes into account the
three-pion sample purity. A relation between the two-pion and the three-pion
source parameters is discussed.Comment: 19 pages, LaTeX, 5 eps figures included, accepted by Eur. Phys. J.
Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice
A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens
Highlights from the Pierre Auger Observatory
The Pierre Auger Observatory is the world's largest cosmic ray observatory.
Our current exposure reaches nearly 40,000 km str and provides us with an
unprecedented quality data set. The performance and stability of the detectors
and their enhancements are described. Data analyses have led to a number of
major breakthroughs. Among these we discuss the energy spectrum and the
searches for large-scale anisotropies. We present analyses of our X
data and show how it can be interpreted in terms of mass composition. We also
describe some new analyses that extract mass sensitive parameters from the 100%
duty cycle SD data. A coherent interpretation of all these recent results opens
new directions. The consequences regarding the cosmic ray composition and the
properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray
Conference, Rio de Janeiro 201
A search for point sources of EeV photons
Measurements of air showers made using the hybrid technique developed with
the fluorescence and surface detectors of the Pierre Auger Observatory allow a
sensitive search for point sources of EeV photons anywhere in the exposed sky.
A multivariate analysis reduces the background of hadronic cosmic rays. The
search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an
energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been
detected. An upper limit on the photon flux has been derived for every
direction. The mean value of the energy flux limit that results from this,
assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial
direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in
which EeV cosmic ray protons are emitted by non-transient sources in the
Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical
Journa
Reconstruction of inclined air showers detected with the Pierre Auger Observatory
We describe the method devised to reconstruct inclined cosmic-ray air showers
with zenith angles greater than detected with the surface array of
the Pierre Auger Observatory. The measured signals at the ground level are
fitted to muon density distributions predicted with atmospheric cascade models
to obtain the relative shower size as an overall normalization parameter. The
method is evaluated using simulated showers to test its performance. The energy
of the cosmic rays is calibrated using a sub-sample of events reconstructed
with both the fluorescence and surface array techniques. The reconstruction
method described here provides the basis of complementary analyses including an
independent measurement of the energy spectrum of ultra-high energy cosmic rays
using very inclined events collected by the Pierre Auger Observatory.Comment: 27 pages, 19 figures, accepted for publication in Journal of
Cosmology and Astroparticle Physics (JCAP
Subcellular localization and tissue specific expression of amidase 1 from Arabidopsis thaliana
Amidase 1 (AMI1) from Arabidopsis thaliana converts indole-3-acetamide (IAM), into indole-3-acetic acid (IAA). AMI1 is part of a small isogene family comprising seven members in A. thaliana encoding proteins which share a conserved glycine- and serine-rich amidase-signature. One member of this family has been characterized as an N-acylethanolamine-cleaving fatty acid amidohydrolase (FAAH) and two other members are part of the preprotein translocon of the outer envelope of chloroplasts (Toc complex) or mitochondria (Tom complex) and presumably lack enzymatic activity. Among the hitherto characterized proteins of this family, AMI1 is the only member with indole-3-acetamide hydrolase activity, and IAM is the preferred substrate while N-acylethanolamines and oleamide are not hydrolyzed significantly, thus suggesting a role of AMI1 in auxin biosynthesis. Whereas the enzymatic function of AMI1 has been determined in vitro, the subcellular localization of the enzyme remained unclear. By using different GFP-fusion constructs and an A. thaliana transient expression system, we show a cytoplasmic localization of AMI1. In addition, RT-PCR and anti-amidase antisera were used to examine tissue specific expression of AMI1 at the transcriptional and translational level, respectively. AMI1-expression is strongest in places of highest IAA content in the plant. Thus, it is concluded that AMI1 may be involved in de novo IAA synthesis in A. thaliana
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