715 research outputs found
Genetic steps to organ laterality in zebrafish.
All internal organs are asymmetric along the left-right axis. Here we report a genetic screen to discover mutations which perturb organ laterality. Our particular focus is upon whether, and how, organs are linked to each other as they achieve their laterally asymmetric positions. We generated mutations by ENU mutagenesis and examined F3 progeny using a cocktail of probes that reveal early primordia of heart, gut, liver and pancreas. From the 750 genomes examined, we isolated seven recessive mutations which affect the earliest left-right positioning of one or all of the organs. None of these mutations caused discernable defects elsewhere in the embryo at the stages examined. This is in contrast to those mutations we reported previously (Chen et al., 1997) which, along with left-right abnormalities, cause marked perturbation in gastrulation, body form or midline structures. We find that the mutations can be classified on the basis of whether they perturb relationships among organ laterality. In Class 1 mutations, none of the organs manifest any left-right asymmetry. The heart does not jog to the left and normally leftpredominant BMP4 in the early heart tube remains symmetric. The gut tends to remain midline. There frequently is a remarkable bilateral duplication of liver and pancreas. Embryos with Class 2 mutations have organotypic asymmetry but, in any given embryo, organ positions can be normal, reversed or randomized. Class 3 reveals a hitherto unsuspected gene that selectively affects laterality of heart. We find that visceral organ positions are predicted by the direction of the preceding cardiac jog. We interpret this as suggesting that normally there is linkage between cardiac and visceral organ laterality. Class 1 mutations, we suggest, effectively remove the global laterality signals, with the consequence that organ positions are effectively symmetrical. Embryos with Class 2 mutations do manifest linkage among organs, but it may be reversed, suggesting that the global signals may be present but incorrectly orientated in some of the embryos. That laterality decisions of organs may be independently perturbed, as in the Class 3 mutation, indicates that there are distinctive pathways for reception and organotypic interpretation of the global signals
Adjusting bone mass for differences in projected bone area and other confounding variables: an allometric perspective.
The traditional method of assessing bone mineral density (BMD; given by bone mineral content [BMC] divided by projected bone area [Ap], BMD = BMC/Ap) has come under strong criticism by various authors. Their criticism being that the projected bone "area" (Ap) will systematically underestimate the skeletal bone "volume" of taller subjects. To reduce the confounding effects of bone size, an alternative ratio has been proposed called bone mineral apparent density [BMAD = BMC/(Ap)3/2]. However, bone size is not the only confounding variable associated with BMC. Others include age, sex, body size, and maturation. To assess the dimensional relationship between BMC and projected bone area, independent of other confounding variables, we proposed and fitted a proportional allometric model to the BMC data of the L2-L4 vertebrae from a previously published study. The projected bone area exponents were greater than unity for both boys (1.43) and girls (1.02), but only the boy's fitted exponent was not different from that predicted by geometric similarity (1.5). Based on these exponents, it is not clear whether bone mass acquisition increases in proportion to the projected bone area (Ap) or an estimate of projected bone volume (Ap)3/2. However, by adopting the proposed methods, the analysis will automatically adjust BMC for differences in projected bone size and other confounding variables for the particular population being studied. Hence, the necessity to speculate as to the theoretical value of the exponent of Ap, although interesting, becomes redundant
Shocks and Thermal Conduction Fronts in Retracting Reconnected Flux Tubes
We present a model for plasma heating produced by time-dependent, spatially
localized reconnection within a flare current sheet separating skewed magnetic
fields. The reconnection creates flux tubes of new connectivity which
subsequently retract at Alfv\'enic speeds from the reconnection site. Heating
occurs in gas-dynamic shocks which develop inside these tubes. Here we present
generalized thin flux tube equations for the dynamics of reconnected flux
tubes, including pressure-driven parallel dynamics as well as temperature
dependent, anisotropic viscosity and thermal conductivity. The evolution of
tubes embedded in a uniform, skewed magnetic field, following reconnection in a
patch, is studied through numerical solutions of these equations, for solar
coronal conditions. Even though viscosity and thermal conductivity are
negligible in the quiet solar corona, the strong gas-dynamic shocks generated
by compressing plasma inside reconnected flux tubes generate large velocity and
temperature gradients along the tube, rendering the diffusive processes
dominant. They determine the thickness of the shock that evolves up to a
steady-state value, although this condition may not be reached in the short
times involved in a flare. For realistic solar coronal parameters, this
steady-state shock thickness might be as long as the entire flux tube. For
strong shocks at low Prandtl numbers, typical of the solar corona, the
gas-dynamic shock consists of an isothermal sub-shock where all the compression
and cooling occur, preceded by a thermal front where the temperature increases
and most of the heating occurs. We estimate the length of each of these
sub-regions and the speed of their propagation.Comment: 39 pages (AASTeX: 29 pages of text, 10 figures), accepted for
publication in the Astrophysical Journa
Dynamical suppression of unwanted transition paths in multistate quantum systems
We introduce a method to suppress unwanted transition channels, even without
knowing their couplings, and achieve perfect population transfer in multistate
quantum systems by the application of composite pulse sequences. Unwanted
transition paths may be present due to imperfect light polarization, stray
electromagnetic fields, misalignment of quantization axis, spatial
inhomogeneity of trapping fields, off-resonant couplings, etc. Compensation of
simultaneous deviations in polarization, pulse area, and detuning is
demonstrated. The accuracy, the flexibility and the robustness of this
technique make it suitable for high-fidelity applications in quantum optics and
quantum information processing.Comment: 5 figure
The TIGA technique for detecting gravitational waves with a spherical antenna
We report the results of a theoretical and experimental study of a spherical
gravitational wave antenna. We show that it is possible to understand the data
from a spherical antenna with 6 radial resonant transducers attached to the
surface in the truncated icosahedral arrangement. We find that the errors
associated with small deviations from the ideal case are small compared to
other sources of error, such as a finite signal-to-noise ratio. An in situ
measurement technique is developed along with a general algorithm that
describes a procedure for determining the direction of an external force acting
on the antenna, including the force from a gravitational wave, using a
combination of the transducer responses. The practicality of these techniques
was verified on a room-temperature prototype antenna.Comment: 15 pages, 14 figures, submitted to Physical Review
Cosmological distance indicators
We review three distance measurement techniques beyond the local universe:
(1) gravitational lens time delays, (2) baryon acoustic oscillation (BAO), and
(3) HI intensity mapping. We describe the principles and theory behind each
method, the ingredients needed for measuring such distances, the current
observational results, and future prospects. Time delays from strongly lensed
quasars currently provide constraints on with < 4% uncertainty, and with
1% within reach from ongoing surveys and efforts. Recent exciting discoveries
of strongly lensed supernovae hold great promise for time-delay cosmography.
BAO features have been detected in redshift surveys up to z <~ 0.8 with
galaxies and z ~ 2 with Ly- forest, providing precise distance
measurements and with < 2% uncertainty in flat CDM. Future BAO
surveys will probe the distance scale with percent-level precision. HI
intensity mapping has great potential to map BAO distances at z ~ 0.8 and
beyond with precisions of a few percent. The next years ahead will be exciting
as various cosmological probes reach 1% uncertainty in determining , to
assess the current tension in measurements that could indicate new
physics.Comment: Review article accepted for publication in Space Science Reviews
(Springer), 45 pages, 10 figures. Chapter of a special collection resulting
from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in
the Space Ag
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Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib
Background: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. ClincalTrials.gov number: NCT02184195
Earth BioGenome Project: Sequencing life for the future of life.
Increasing our understanding of Earth's biodiversity and responsibly stewarding its resources are among the most crucial scientific and social challenges of the new millennium. These challenges require fundamental new knowledge of the organization, evolution, functions, and interactions among millions of the planet's organisms. Herein, we present a perspective on the Earth BioGenome Project (EBP), a moonshot for biology that aims to sequence, catalog, and characterize the genomes of all of Earth's eukaryotic biodiversity over a period of 10 years. The outcomes of the EBP will inform a broad range of major issues facing humanity, such as the impact of climate change on biodiversity, the conservation of endangered species and ecosystems, and the preservation and enhancement of ecosystem services. We describe hurdles that the project faces, including data-sharing policies that ensure a permanent, freely available resource for future scientific discovery while respecting access and benefit sharing guidelines of the Nagoya Protocol. We also describe scientific and organizational challenges in executing such an ambitious project, and the structure proposed to achieve the project's goals. The far-reaching potential benefits of creating an open digital repository of genomic information for life on Earth can be realized only by a coordinated international effort
Conformation-regulated mechanosensory control via titin domains in cardiac muscle
The giant filamentous protein titin is ideally positioned in the muscle sarcomere to sense mechanical stimuli and transform them into biochemical signals, such as those triggering cardiac hypertrophy. In this review, we ponder the evidence for signaling hotspots along the titin filament involved in mechanosensory control mechanisms. On the way, we distinguish between stress and strain as triggers of mechanical signaling events at the cardiac sarcomere. Whereas the Z-disk and M-band regions of titin may be prominently involved in sensing mechanical stress, signaling hotspots within the elastic I-band titin segment may respond primarily to mechanical strain. Common to both stress and strain sensor elements is their regulation by conformational changes in protein domains
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
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