2,081 research outputs found
Human papillomavirus viral load as a useful triage tool for non-16/18 high-risk human papillomavirus positive women: A prospective screening cohort study
ASCCP cervical cancer screening guidelines recommend triaging high-risk human papillomavirus (hrHPV) positive women with cytology and genotyping, but cytology is often unavailable in resource-limited areas. We compared the long-term risk of cervical cancer and precancers among type-specific hrHPV-positive women triaged by viral load to cytology and visual inspection with acetic acid (VIA).A cohort of 1742 Chinese women was screened with cytology, VIA, and Hybrid Capture 2 (HC2) test and followed for ten years. All HC2-positive samples were genotyped. Viral load was measured by HC2 relative light units/cutoff (RLU/CO). Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) for type-specific hrHPV viral load was estimated using Kaplan-Meier methods.Baseline hrHPV viral load stratified by specific genotypes was positively correlated with prevalent cytological lesions. Ten-year CIR of CIN2 + was associated with cytological lesions and viral load. Among HPV 16/18-positive women, ten-year CIR of CIN2 + was high, even with normal cytology (15.3%), normal VIA (32.4%), viral load with RLU/CO < 10 (23.6%) or RLU/CO < 100 (33.8%). Among non-16/18 hrHPV positive women, ten-year CIR of CIN2 + was significantly stratified by cytology grade of atypical squamous cell of undetermined significance or higher (2.0% VS. 34.6%), viral load cutoffs at 10 RLU/CO (5.1% VS. 27.2%), at 100 RLU/CO (11.0% VS. 35.5%), but not by VIA (19.1% VS. 19.0%).Our findings support the guidelines in referring all HPV16/18 positive women to colposcopy and suggest triaging non-16/18 hrHPV positive women using viral loads in resource-limited areas where cytology screening was inaccessible
Trapped lipopolysaccharide and LptD intermediates reveal lipopolysaccharide translocation steps across the Escherichia coli outer membrane
Lipopolysaccharide (LPS) is a main component of the outer membrane of Gram-negative bacteria, which is essential for the vitality of most Gram-negative bacteria and plays a critical role for drug resistance. LptD/E complex forms a N-terminal LPS transport slide, a hydrophobic intramembrane hole and the hydrophilic channel of the barrel, for LPS transport, lipid A insertion and core oligosaccharide and O-antigen polysaccharide translocation, respectively. However, there is no direct evidence to confirm that LptD/E transports LPS from the periplasm to the external leaflet of the outer membrane. By replacing LptD residues with an unnatural amino acid p-benzoyl-L-phenyalanine (pBPA) and UV-photo-cross-linking in E.coli, the translocon and LPS intermediates were obtained at the N-terminal domain, the intramembrane hole, the lumenal gate, the lumen of LptD channel, and the extracellular loop 1 and 4, providing the first direct evidence and “snapshots” to reveal LPS translocation steps across the outer membrane
The DArk Matter Particle Explorer mission
The DArk Matter Particle Explorer (DAMPE), one of the four scientific space
science missions within the framework of the Strategic Pioneer Program on Space
Science of the Chinese Academy of Sciences, is a general purpose high energy
cosmic-ray and gamma-ray observatory, which was successfully launched on
December 17th, 2015 from the Jiuquan Satellite Launch Center. The DAMPE
scientific objectives include the study of galactic cosmic rays up to
TeV and hundreds of TeV for electrons/gammas and nuclei respectively, and the
search for dark matter signatures in their spectra. In this paper we illustrate
the layout of the DAMPE instrument, and discuss the results of beam tests and
calibrations performed on ground. Finally we present the expected performance
in space and give an overview of the mission key scientific goals.Comment: 45 pages, including 29 figures and 6 tables. Published in Astropart.
Phy
Direct detection of a break in the teraelectronvolt cosmic-ray spectrum of electrons and positrons
High energy cosmic ray electrons plus positrons (CREs), which lose energy
quickly during their propagation, provide an ideal probe of Galactic
high-energy processes and may enable the observation of phenomena such as
dark-matter particle annihilation or decay. The CRE spectrum has been directly
measured up to TeV in previous balloon- or space-borne experiments,
and indirectly up to TeV by ground-based Cherenkov -ray
telescope arrays. Evidence for a spectral break in the TeV energy range has
been provided by indirect measurements of H.E.S.S., although the results were
qualified by sizeable systematic uncertainties. Here we report a direct
measurement of CREs in the energy range by the
DArk Matter Particle Explorer (DAMPE) with unprecedentedly high energy
resolution and low background. The majority of the spectrum can be properly
fitted by a smoothly broken power-law model rather than a single power-law
model. The direct detection of a spectral break at TeV confirms the
evidence found by H.E.S.S., clarifies the behavior of the CRE spectrum at
energies above 1 TeV and sheds light on the physical origin of the sub-TeV
CREs.Comment: 18 pages, 6 figures, Nature in press, doi:10.1038/nature2447
Internal alignment and position resolution of the silicon tracker of DAMPE determined with orbit data
The DArk Matter Particle Explorer (DAMPE) is a space-borne particle detector
designed to probe electrons and gamma-rays in the few GeV to 10 TeV energy
range, as well as cosmic-ray proton and nuclei components between 10 GeV and
100 TeV. The silicon-tungsten tracker-converter is a crucial component of
DAMPE. It allows the direction of incoming photons converting into
electron-positron pairs to be estimated, and the trajectory and charge (Z) of
cosmic-ray particles to be identified. It consists of 768 silicon micro-strip
sensors assembled in 6 double layers with a total active area of 6.6 m.
Silicon planes are interleaved with three layers of tungsten plates, resulting
in about one radiation length of material in the tracker. Internal alignment
parameters of the tracker have been determined on orbit, with non-showering
protons and helium nuclei. We describe the alignment procedure and present the
position resolution and alignment stability measurements
Multiple Nodeless Superconducting Gaps in (Ba0.6K0.4)Fe2As2 Superconductor from Angle-Resolved Photoemission Spectroscopy
High resolution angle-resolved photoemission measurements have been carried
out to study the superconducting gap in the (Ba0.6K0.4)Fe2As2 superconductor
with Tc=35 K. Two hole-like Fermi surface sheets around the G(0,0) point
exhibit different superconducting gaps. The inner Fermi surface sheet shows
larger (10-12 meV) and slightly momentum-dependent gap while the outer one has
smaller (7-8 meV) and nearly isotropic gap. The lack of gap node in both Fermi
surface sheets favours s-wave superconducting gap symmetry. Superconducting gap
opening is also observed at the M(pi,pi) point. The two Fermi surface spots
near the M point are gapped below Tc but the gap persists above Tc. The rich
and detailed superconducting gap information will provide key insights and
constraints in understanding pairing mechanism in the iron-based
superconductors.Comment: 11 pages, 4 figure
Common Features in Electronic Structure of the Fe-Based Layered Superconductors from Photoemission Spectroscopy
High resolution photoemission measurements have been carried out on
non-superconducting LaOFeAs parent compound and various superconducting
R(O1-xFx)FeAs (R=La, Ce and Pr) compounds. We found that the parent LaOFeAs
compound shows a metallic character. Through extensive measurements, we have
identified several common features in the electronic structure of these
Fe-based compounds: (1). 0.2 eV feature in the valence band; (2). A universal
13~16 meV feature; (3). A clear Fermi cutoff showing zero leading-edge shift in
the superconducting state;(4). Lack of superconducting coherence peak(s); (5).
Near EF spectral weight suppression with decreasing temperature. These
universal features can provide important information about band structure,
superconducting gap and pseudogap in these Fe-based materials.Comment: 5 pages,4 figure
Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial
Background: Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases. Methods: We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Patients aged 18 years or older who had radiotherapy-naive HER2-positive brain metastases (cohort A) or progressive disease after radiotherapy (cohort B), with an Eastern Cooperative Oncology Group performance status of 0–2, received pyrotinib 400 mg orally once daily, and capecitabine 1000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed intracranial objective response rate by investigator assessment according to the Response Evaluation Criteria In Solid Tumours (version 1.1). Activity and safety were analysed in patients with at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT03691051. Findings: Between Jan 29, 2019, and July 10, 2020, we enrolled 78 women: 51 (86%) of 59 patients in cohort A and 18 (95%) of 19 patients in cohort B had previous exposure to trastuzumab. Median follow-up duration was 15·7 months (IQR 9·7–19·0). The intracranial objective response rate was 74·6% (95% CI 61·6–85·0; 44 of 59 patients) in cohort A and 42·1% (20·3–66·5; eight of 19 patients) in cohort B. The most common grade 3 or worse treatment-emergent adverse event was diarrhoea (14 [24%] in cohort A and four [21%] in cohort B). Two (3%) patients in cohort A and three (16%) in cohort B had treatment-related serious adverse events. No treatment-related deaths occurred. Interpretation: To our knowledge, this is the first prospective study showing the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naive population. This combination deserves further validation in a randomised, controlled trial. Funding: National Cancer Centre Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals. Translation: For the Chinese translation of the abstract see Supplementary Materials section
Study of and and
We study the decays of and to the final states
and based on a single
baryon tag method using data samples of
and events collected with
the BESIII detector at the BEPCII collider. The decays to
are observed for the first time. The
measured branching fractions of and
are in good agreement with, and much
more precise, than the previously published results. The angular parameters for
these decays are also measured for the first time. The measured angular decay
parameter for , , is found to be negative, different to the other
decay processes in this measurement. In addition, the "12\% rule" and isospin
symmetry in the and and
systems are tested.Comment: 11 pages, 7 figures. This version is consistent with paper published
in Phys.Lett. B770 (2017) 217-22
- …