1,625 research outputs found
Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression:implications for atherosclerosis research
Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE−/− mice, their M1/M2 phenotype, inflammatory status, and lipid metabolism signatures were compared. oxLDL accumulation was similar in PEMs and BMDMs. On protein expression level, BMDMs showed an M2-like CD206(high)CD11c(low) profile, while cholesterol loading led to enhanced CD11c expression and reduced MCP-1 secretion. In contrast, PEMs expressed low levels of CD206 and CD11c, and responded to cholesterol loading by increasing CD11c expression and MCP-1 secretion. mRNA expression of M1/M2 markers was higher in PEMS than BMDMs, while lipid metabolism genes were similarly expressed. Whole aorta flow cytometry showed an accumulation of M2-like CD206(high)CD11c(low) macrophages in advanced versus early atherosclerotic disease in ApoE−/− mice. In isolated lesions, mRNA levels of the M2 markers Socs2, CD206, Retnla, and IL4 were downregulated with increasing disease severity. Likewise, mRNA expression of lipid metabolism genes (SREBP2, ACSL1, SRB1, DGAT1, and cpt1a) was decreased in advanced versus early lesions. In conclusion, PEMs and BMDMs are phenotypically distinct and differ from macrophages in lesions with respect to expression of M1/M2 markers and lipid metabolism genes
To fly as a pilot after cardiac surgery
Aircrew are responsible for safe and reliable aircraft operations. Cardiovascular disease accounts for 50% of all pilot licences declined or withdrawn for medical reasons in Western Europe and is the most common cases of sudden incapacitation in flight. Aircrew retirement age is increasing (up to age 65) in a growing number of airlines and the burden of subclinical, but potentially significant, coronary atherosclerosis is unknown in qualified pilots above age 40. Safety considerations are paramount in aviation medicine, and the most dreaded cardiovascular complications are thromboembolic events and rhythm disturbances due to their potential for sudden incapacitation. In aviation, the current consensus risk threshold for an acceptable level of controlled risk of acute incapacitation is 1% (for dual pilot commercial operations), a percentage calculated using engineering principles to ensure the incidence of a fatal air accident is no greater than 1 per 107 h of flying. This is known as the '1% safety rule'. To fly as a pilot after cardiac surgery is possible; however, special attention to perioperative planning is mandatory. Choice of procedure is crucial for license renewal. Licensing restrictions are likely to apply and the postoperative follow-up requires a tight scheduling. The cardiac surgeon should always liaise and communicate with the pilot's aviation medicine examiner prior to and following cardiac surgery
Experiments in vortex avalanches
Avalanche dynamics is found in many phenomena spanning from earthquakes to
the evolution of species. It can be also found in vortex matter when a type II
superconductor is externally driven, for example, by increasing the magnetic
field. Vortex avalanches associated with thermal instabilities can be an
undesirable effect for applications, but "dynamically driven" avalanches
emerging from the competition between intervortex interactions and quenched
disorder constitute an interesting scenario to test theoretical ideas related
with non-equilibrium dynamics. However, differently from the equilibrium phases
of vortex matter in type II superconductors, the study of the corresponding
dynamical phases - in which avalanches can play a role - is still in its
infancy. In this paper we critically review relevant experiments performed in
the last decade or so, emphasizing the ability of different experimental
techniques to establish the nature and statistical properties of the observed
avalanche behavior.Comment: To be published in Reviews of Modern Physics April 2004. 17 page
Does field application of manure from sulfadiazine treated pigs affect the abundance and transferability of resistance genes?
Commissioning of the vacuum system of the KATRIN Main Spectrometer
The KATRIN experiment will probe the neutrino mass by measuring the
beta-electron energy spectrum near the endpoint of tritium beta-decay. An
integral energy analysis will be performed by an electro-static spectrometer
(Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a
volume of 1240 m^3, and a complex inner electrode system with about 120000
individual parts. The strong magnetic field that guides the beta-electrons is
provided by super-conducting solenoids at both ends of the spectrometer. Its
influence on turbo-molecular pumps and vacuum gauges had to be considered. A
system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter
strips has been deployed and was tested during the commissioning of the
spectrometer. In this paper the configuration, the commissioning with bake-out
at 300{\deg}C, and the performance of this system are presented in detail. The
vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is
demonstrated that the performance of the system is already close to these
stringent functional requirements for the KATRIN experiment, which will start
at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure
Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
BACKGROUND: The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status. METHODS: Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer. RESULTS: In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation = 3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable weight (±2.5 kg), long-term weight gain >10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR) = 1.42; 95% confidence interval 1.22-1.65] in ever HRT users (HR = 1.23; 1.04-1.44), in never HRT users (HR = 1.40; 1.16-1.68) and in oestrogen-and-progesterone-receptor-positive (ER+PR+) breast cancer (HR = 1.46; 1.15-1.85). CONCLUSION: Long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer
Measurement of the Total Active 8B Solar Neutrino Flux at the Sudbury Neutrino Observatory with Enhanced Neutral Current Sensitivity
The Sudbury Neutrino Observatory (SNO) has precisely determined the total
active (nu_x) 8B solar neutrino flux without assumptions about the energy
dependence of the nu_e survival probability. The measurements were made with
dissolved NaCl in the heavy water to enhance the sensitivity and signature for
neutral-current interactions. The flux is found to be 5.21 +/- 0.27 (stat) +/-
0.38 (syst) x10^6 cm^{-2}s^{-1}, in agreement with previous measurements and
standard solar models. A global analysis of these and other solar and reactor
neutrino results yields Delta m^{2} = 7.1^{+1.2}_{-0.6}x10^{-5} ev^2 and theta
= 32.5^{+2.4}_{-2.3} degrees. Maximal mixing is rejected at the equivalent of
5.4 standard deviations.Comment: Submitted to Phys. Rev. Let
CardioClassifier: disease- and gene-specific computational decision support for clinical genome interpretation
Purpose Internationally adopted variant interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) are generic and require disease-specific refinement. Here we developed CardioClassifier (http://www.cardioclassifier.org), a semiautomated decision-support tool for inherited cardiac conditions (ICCs). Methods CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. Combining disease- and gene-specific knowledge with variant observations in large cohorts of cases and controls, we refined 14 computational ACMG criteria and created three ICC-specific rules. Results We benchmarked CardioClassifier on 57 expertly curated variants and show full retrieval of all computational data, concordantly activating 87.3% of rules. A generic annotation tool identified fewer than half as many clinically actionable variants (64/219 vs. 156/219, Fisher’s P = 1.1 × 10−18), with important false positives, illustrating the critical importance of disease and gene-specific annotations. CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data. Conclusion CardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines
Electron Antineutrino Search at the Sudbury Neutrino Observatory
Upper limits on the \nuebar flux at the Sudbury Neutrino Observatory have
been set based on the \nuebar charged-current reaction on deuterium. The
reaction produces a positron and two neutrons in coincidence. This distinctive
signature allows a search with very low background for \nuebar's from the Sun
and other potential sources. Both differential and integral limits on the
\nuebar flux have been placed in the energy range from 4 -- 14.8 MeV. For an
energy-independent \nu_e --> \nuebar conversion mechanism, the integral limit
on the flux of solar \nuebar's in the energy range from 4 -- 14.8 MeV is found
to be \Phi_\nuebar <= 3.4 x 10^4 cm^{-2} s^{-1} (90% C.L.), which corresponds
to 0.81% of the standard solar model 8B \nu_e flux of 5.05 x 10^6 cm^{-2}
s^{-1}, and is consistent with the more sensitive limit from KamLAND in the 8.3
-- 14.8 MeV range of 3.7 x 10^2 cm^{-2} s^{-1} (90% C.L.). In the energy range
from 4 -- 8 MeV, a search for \nuebar's is conducted using coincidences in
which only the two neutrons are detected. Assuming a \nuebar spectrum for the
neutron induced fission of naturally occurring elements, a flux limit of
Phi_\nuebar <= 2.0 x 10^6 cm^{-2} s^{-1}(90% C.L.) is obtained.Comment: submitted to Phys. Rev.
Lowering the radioactivity of the photomultiplier tubes for the XENON1T dark matter experiment
The low-background, VUV-sensitive 3-inch diameter photomultiplier tube R11410
has been developed by Hamamatsu for dark matter direct detection experiments
using liquid xenon as the target material. We present the results from the
joint effort between the XENON collaboration and the Hamamatsu company to
produce a highly radio-pure photosensor (version R11410-21) for the XENON1T
dark matter experiment. After introducing the photosensor and its components,
we show the methods and results of the radioactive contamination measurements
of the individual materials employed in the photomultiplier production. We then
discuss the adopted strategies to reduce the radioactivity of the various PMT
versions. Finally, we detail the results from screening 216 tubes with
ultra-low background germanium detectors, as well as their implications for the
expected electronic and nuclear recoil background of the XENON1T experiment.Comment: 10 pages, 5 figure
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