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Higher oxygen content and transport characterize high-altitude ethnic Tibetan women with the highest lifetime reproductive success
We chose the ânatural laboratoryâ provided by high-altitude native ethnic Tibetan women who had completed childbearing to examine the hypothesis that multiple oxygen delivery traits were associated with lifetime reproductive success and had genomic associations. Four hundred seventeen (417) women aged 46 to 86 y residing at â„3,500 m in Upper Mustang, Nepal, provided information on reproductive histories, sociocultural factors, physiological measurements, and DNA samples for this observational cohort study. Simultaneously assessing multiple traits identified combinations associated with lifetime reproductive success measured as the number of livebirths. Women with the most livebirths had distinctive hematological and cardiovascular traits. A hemoglobin concentration near the sample mode and a high percent of oxygen saturation of hemoglobin raised arterial oxygen concentration without risking elevated blood viscosity. We propose ongoing stabilizing selection on hemoglobin concentration because extreme values predicted fewer livebirths and directional selection favoring higher oxygen saturation because higher values had more predicted livebirths. EPAS1, an oxygen homeostasis locus with strong signals of positive natural selection and a high frequency of variants occurring only among populations indigenous to the Tibetan Plateau, associated with hemoglobin concentration. High blood flow into the lungs, wide left ventricles, and low hypoxic heart rate responses aided effective convective oxygen transport to tissues. Women with physiologies closer to unstressed, low altitude values had the highest lifetime reproductive success. This example of ethnic Tibetan women residing at high altitudes in Nepal links reproductive fitness with trait combinations increasing oxygen delivery under severe hypoxic stress and demonstrates ongoing natural selection
Design of 280 GHz feedhorn-coupled TES arrays for the balloon-borne polarimeter SPIDER
We describe 280 GHz bolometric detector arrays that instrument the
balloon-borne polarimeter SPIDER. A primary science goal of SPIDER is to
measure the large-scale B-mode polarization of the cosmic microwave background
in search of the cosmic-inflation, gravitational-wave signature. 280 GHz
channels aid this science goal by constraining the level of B-mode
contamination from galactic dust emission. We present the focal plane unit
design, which consists of a 1616 array of conical, corrugated feedhorns
coupled to a monolithic detector array fabricated on a 150 mm diameter silicon
wafer. Detector arrays are capable of polarimetric sensing via waveguide
probe-coupling to a multiplexed array of transition-edge-sensor (TES)
bolometers. The SPIDER receiver has three focal plane units at 280 GHz, which
in total contains 765 spatial pixels and 1,530 polarization sensitive
bolometers. By fabrication and measurement of single feedhorns, we demonstrate
14.7 FHWM Gaussian-shaped beams with 1% ellipticity in a 30%
fractional bandwidth centered at 280 GHz. We present electromagnetic
simulations of the detection circuit, which show 94% band-averaged,
single-polarization coupling efficiency, 3% reflection and 3% radiative loss.
Lastly, we demonstrate a low thermal conductance bolometer, which is
well-described by a simple TES model and exhibits an electrical noise
equivalent power (NEP) = 2.6 10 W/,
consistent with the phonon noise prediction.Comment: Proceedings of SPIE Astronomical Telescopes + Instrumentation 201
Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation
Research detailing the normal vascular adaptions to high altitude is minimal and
often confounded by pathology (e.g. chronic mountain sickness) and methodological issues.
We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged ( 2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders(Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation(FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intimaâmedia thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO2 â) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3â4 (acute high altitude) and 12â14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlandersâ FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2 vs. 6.6 ± 0.3 m sâ1; P = 0.001). These changes persisted at days 12â14, and after allometricallyscaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio ( 19%, P 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO2 â increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation
evident during acute (n = 11, r=â0.53) and chronic (n = 7, r=â0.69; P 0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n=11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspiredO2 fraction (FIO2 )=0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7±1.6 vs. 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α1-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high-altitude exposure appears to be associated with arterial remodelling
A Study of Muon Neutrino Disappearance Using the Fermilab Main Injector Neutrino Beam
We report the results of a search for muon-neutrino disappearance by the Main
Injector Neutrino Oscillation Search. The experiment uses two detectors
separated by 734 km to observe a beam of neutrinos created by the Neutrinos at
the Main Injector facility at Fermi National Accelerator Laboratory. The data
were collected in the first 282 days of beam operations and correspond to an
exposure of 1.27e20 protons on target. Based on measurements in the Near
Detector, in the absence of neutrino oscillations we expected 336 +/- 14
muon-neutrino charged-current interactions at the Far Detector but observed
215. This deficit of events corresponds to a significance of 5.2 standard
deviations. The deficit is energy dependent and is consistent with two-flavor
neutrino oscillations according to delta m-squared = 2.74e-3 +0.44/-0.26e-3
eV^2 and sin^2(2 theta) > 0.87 at 68% confidence level.Comment: In submission to Phys. Rev.
Measurement of neutrino velocity with the MINOS detectors and NuMI neutrino beam
The velocity of a ~3 GeV neutrino beam is measured by comparing detection times at the near and far detectors of the MINOS experiment, separated by 734 km. A total of 473 far detector neutrino events was used to measure (v-c)/c=5.12.910-5 (at 68% C.L.). By correlating the measured energies of 258 charged-current neutrino events to their arrival times at the far detector, a limit is imposed on the neutrino mass of mnu<50 MeV/c2 (99% C.L.)
Measurement of the Atmospheric Muon Charge Ratio at TeV Energies with MINOS
The 5.4 kton MINOS far detector has been taking charge-separated cosmic ray
muon data since the beginning of August, 2003 at a depth of 2070
meters-water-equivalent in the Soudan Underground Laboratory, Minnesota, USA.
The data with both forward and reversed magnetic field running configurations
were combined to minimize systematic errors in the determination of the
underground muon charge ratio. When averaged, two independent analyses find the
charge ratio underground to be 1.374 +/- 0.004 (stat.) +0.012 -0.010(sys.).
Using the map of the Soudan rock overburden, the muon momenta as measured
underground were projected to the corresponding values at the surface in the
energy range 1-7 TeV. Within this range of energies at the surface, the MINOS
data are consistent with the charge ratio being energy independent at the two
standard deviation level. When the MINOS results are compared with measurements
at lower energies, a clear rise in the charge ratio in the energy range 0.3 --
1.0 TeV is apparent. A qualitative model shows that the rise is consistent with
an increasing contribution of kaon decays to the muon charge ratio.Comment: 16 pages, 17 figure
First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector
The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nu” and [overline nu ]” charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nu” and [overline nu ]” interactions are separated. The ratio of [overline nu ]” to nu” events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nu” and [overline nu ]”
Herniation Pits in Human Mummies: A CT Investigation in the Capuchin Catacombs of Palermo, Sicily
Herniation pits (HPs) of the femoral neck were first described in a radiological publication in 1982 as round to oval radiolucencies in the proximal superior quadrant of the femoral neck on anteroposterior radiographs of adults. In following early clinical publications, HPs were generally recognized as an incidental finding. In contrast, in current clinical literature they are mentioned in the context of femoroacetabular impingement (FAI) of the hip joint, which is known to cause osteoarthritis (OA). The significance of HPs in chronic skeletal disorders such as OA is still unclear, but they are discussed as a possible radiological indicator for FAI in a large part of clinical studies
CORE: A Phylogenetically-Curated 16S rDNA Database of the Core Oral Microbiome
Comparing bacterial 16S rDNA sequences to GenBank and other large public databases via BLAST often provides results of little use for identification and taxonomic assignment of the organisms of interest. The human microbiome, and in particular the oral microbiome, includes many taxa, and accurate identification of sequence data is essential for studies of these communities. For this purpose, a phylogenetically curated 16S rDNA database of the core oral microbiome, CORE, was developed. The goal was to include a comprehensive and minimally redundant representation of the bacteria that regularly reside in the human oral cavity with computationally robust classification at the level of species and genus. Clades of cultivated and uncultivated taxa were formed based on sequence analyses using multiple criteria, including maximum-likelihood-based topology and bootstrap support, genetic distance, and previous naming. A number of classification inconsistencies for previously named species, especially at the level of genus, were resolved. The performance of the CORE database for identifying clinical sequences was compared to that of three publicly available databases, GenBank nr/nt, RDP and HOMD, using a set of sequencing reads that had not been used in creation of the database. CORE offered improved performance compared to other public databases for identification of human oral bacterial 16S sequences by a number of criteria. In addition, the CORE database and phylogenetic tree provide a framework for measures of community divergence, and the focused size of the database offers advantages of efficiency for BLAST searching of large datasets. The CORE database is available as a searchable interface and for download at http://microbiome.osu.edu
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