332 research outputs found
Molecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablation
The goal of the current work was to profile positive (mTORC1 activation, autocrine/paracrine growth factors) and negative [AMPK, unfolded protein response (UPR)] pathways that might regulate overload-induced mTORC1 (mTOR complex 1) activation with the hypothesis that a number of negative regulators of mTORC1 will be engaged during a supraphysiological model of hypertrophy. To achieve this, mTORC1- IRS-1/2 signaling, BiP/CHOP/IRE1, and AMPK activation were determined in rat plantaris muscle following synergist ablation (SA). SA resulted in significant increases in muscle mass of 4% per day throughout the 21 days of the experiment. The expression of the insulin-like growth factors (IGF) were high throughout the 21st day of overload. However, IGF signaling was limited, since IRS-1 and -2 were undetectable in the overloaded muscle from day 3 to day 9. The decreases in IRS-1/2 protein were paralleled by increases in GRB10 Ser501/503 and S6K1 Thr389 phosphorylation, two mTORC1 targets that can destabilize IRS proteins. PKB Ser473 phosphorylation was higher from 3– 6 days, and this was associated with increased TSC2 Thr939 phosphorylation. The phosphorylation of TSC2 Thr1345 (an AMPK site) was also elevated, whereas phosphorylation at the other PKB site, Thr1462, was unchanged at 6 days. In agreement with the phosphorylation of Thr1345, SA led to activation of AMPK1 during the initial growth phase, lasting the first 9 days before returning to baseline by day 12. The UPR markers CHOP and BiP were elevated over the first 12 days following ablation, whereas IRE1 levels decreased. These data suggest that during supraphysiological muscle loading at least three potential molecular brakes engage to downregulate mTORC1. m
Numerical Ricci-flat metrics on K3
We develop numerical algorithms for solving the Einstein equation on
Calabi-Yau manifolds at arbitrary values of their complex structure and Kahler
parameters. We show that Kahler geometry can be exploited for significant gains
in computational efficiency. As a proof of principle, we apply our methods to a
one-parameter family of K3 surfaces constructed as blow-ups of the T^4/Z_2
orbifold with many discrete symmetries. High-resolution metrics may be obtained
on a time scale of days using a desktop computer. We compute various geometric
and spectral quantities from our numerical metrics. Using similar resources we
expect our methods to practically extend to Calabi-Yau three-folds with a high
degree of discrete symmetry, although we expect the general three-fold to
remain a challenge due to memory requirements.Comment: 38 pages, 10 figures; program code and animations of figures
downloadable from http://schwinger.harvard.edu/~wiseman/K3/ ; v2 minor
corrections, references adde
Decreased mass specific respiration under experimental warming is robust to the microbial biomass method employed
Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Blackwell for personal use, not for redistribution. The definitive version was published in Ecology Letters 12 (2009): E15-E18, doi:10.1111/j.1461-0248.2009.01332.x.Hartley et al. question whether reduction in Rmass, under experimental warming, arises because of
the biomass method. We show the method they treat as independent yields the same result. We
describe why the substrate-depletion hypothesis cannot alone explain observed responses, and
urge caution in the interpretation of the seasonal data.This research was supported by the Office of Science (BER), U.S. Department of Energy, the
Andrew W. Mellon Foundation and U.S. National Science Foundation grants to the Coweeta
LTER program
Does wage rank affect employees' well-being?
How do workers make wage comparisons? Both an experimental study and an analysis of 16,000 British employees are reported. Satisfaction and well-being levels are shown to depend on more than simple relative pay. They depend upon the ordinal rank of an individual's wage within a comparison group. âRankâ itself thus seems to matter to human beings. Moreover, consistent with psychological theory, quits in a workplace are correlated with pay distribution skewness
The Risks of Rewards in Health Care: How Pay-for-performance Could Threaten, or Bolster, Medical Professionalism
The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs
The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised
Relativity, rank and the utility of income
This is the accepted version of the following article: Rablen, M. D. (2008), Relativity, Rank and the Utility of Income. The Economic Journal, 118: 801â821, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/j.1468-0297.2008.02143.x/abstract.Relative utility has become an important concept in several disjoint areas of economics. I present a cardinal model of income utility based on the supposition that agents care about their rank in the income distribution and that utility is subject to adaptation over time. Utility levels correspond to the Leyden Individual Welfare Function while utility differences yield a version of the prospect theory value function, thereby providing a new and shared derivation of each. I offer an explanation of some long-standing paradoxes in the wellbeing literature and an insight into the links between relative comparisons and loss aversion.ESR
Minimising the error in eigenvalue calculations involving the Boltzmann transport equation using goal-based adaptivity on unstructured meshes
Upper limits on the strength of periodic gravitational waves from PSR J1939+2134
The first science run of the LIGO and GEO gravitational wave detectors
presented the opportunity to test methods of searching for gravitational waves
from known pulsars. Here we present new direct upper limits on the strength of
waves from the pulsar PSR J1939+2134 using two independent analysis methods,
one in the frequency domain using frequentist statistics and one in the time
domain using Bayesian inference. Both methods show that the strain amplitude at
Earth from this pulsar is less than a few times .Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo
Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July
200
Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers
We study frequency dependent (FD) input-output schemes for signal-recycling
interferometers, the baseline design of Advanced LIGO and the current
configuration of GEO 600. Complementary to a recent proposal by Harms et al. to
use FD input squeezing and ordinary homodyne detection, we explore a scheme
which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are
sub-optimal among all possible input-output schemes, provide a global noise
suppression by the power squeeze factor, while being realizable by using
detuned Fabry-Perot cavities as input/output filters. At high frequencies, the
two schemes are shown to be equivalent, while at low frequencies our scheme
gives better performance than that of Harms et al., and is nearly fully
optimal. We then study the sensitivity improvement achievable by these schemes
in Advanced LIGO era (with 30-m filter cavities and current estimates of
filter-mirror losses and thermal noise), for neutron star binary inspirals, and
for narrowband GW sources such as low-mass X-ray binaries and known radio
pulsars. Optical losses are shown to be a major obstacle for the actual
implementation of these techniques in Advanced LIGO. On time scales of
third-generation interferometers, like EURO/LIGO-III (~2012), with
kilometer-scale filter cavities, a signal-recycling interferometer with the FD
readout scheme explored in this paper can have performances comparable to
existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi
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