572 research outputs found
Rotational and Vibrational Dynamics of Interstitial Molecular Hydrogen
The calculation of the hindered roton-phonon energy levels of a hydrogen
molecule in a confining potential with different symmetries is systematized for
the case when the rotational angular momentum is a good quantum number. One
goal of this program is to interpret the energy-resolved neutron time of flight
spectrum previously obtained for HC. This spectrum gives direct
information on the energy level spectrum of H molecules confined to the
octahedral interstitial sites of solid C. We treat this problem of
coupled translational and orientational degrees of freedom a) by construction
of an effective Hamiltonian to describe the splitting of the manifold of states
characterized by a given value of and having a fixed total number of phonon
excitations, b) by numerical solutions of the coupled translation-rotation
problem on a discrete mesh of points in position space, and c) by a group
theoretical symmetry analysis. Results obtained from these three different
approaches are mutually consistent. The results of our calculations explain
several hitherto uninterpreted aspects of the experimental observations, but
show that a truly satisfactory orientational potential for the interaction of
an H molecule with a surrounding array of C atoms has not yet been
developed.Comment: 53 pages, 9 figures, to appear in Phys. Rev B (in press). Phys. Rev.
B (in press
The Local Bubble and Interstellar Material Near the Sun
The properties of interstellar matter (ISM) at the Sun are regulated by our
location with respect to the Local Bubble (LB) void in the ISM. The LB is
bounded by associations of massive stars and fossil supernovae that have
disrupted natal ISM and driven intermediate velocity ISM into the LB interior
void. The Sun is located in such a driven ISM parcel. The Local Fluff has a
bulk velocity of 19 km/s in the LSR, and an upwind direction towards the center
of the gas and dust ring formed by the Loop I supernova remnant interaction
with the LB. When the ram pressure of the LIC is included in the total LIC
pressure, and if magnetic thermal and cosmic ray pressures are similar, the LIC
appears to be in pressure equilibrium with the local hot bubble plasma.Comment: Proceedings of Symposium on the Composition of Matter, honoring
Johannes Geiss on the occasion of his 80th birthday. Space Science Reviews
(in press
Lattice-switch Monte Carlo
We present a Monte Carlo method for the direct evaluation of the difference
between the free energies of two crystal structures. The method is built on a
lattice-switch transformation that maps a configuration of one structure onto a
candidate configuration of the other by `switching' one set of lattice vectors
for the other, while keeping the displacements with respect to the lattice
sites constant. The sampling of the displacement configurations is biased,
multicanonically, to favor paths leading to `gateway' arrangements for which
the Monte Carlo switch to the candidate configuration will be accepted. The
configurations of both structures can then be efficiently sampled in a single
process, and the difference between their free energies evaluated from their
measured probabilities. We explore and exploit the method in the context of
extensive studies of systems of hard spheres. We show that the efficiency of
the method is controlled by the extent to which the switch conserves correlated
microstructure. We also show how, microscopically, the procedure works: the
system finds gateway arrangements which fulfill the sampling bias
intelligently. We establish, with high precision, the differences between the
free energies of the two close packed structures (fcc and hcp) in both the
constant density and the constant pressure ensembles.Comment: 34 pages, 9 figures, RevTeX. To appear in Phys. Rev.
SIRT1-NOX4 Signaling Axis Regulates Cancer Cachexia
Approximately one third of cancer patients die due to complexities related to cachexia. However, the mechanisms of cachexia and the potential therapeutic interventions remain poorly studied. We observed a significant positive correlation between SIRT1 expression and muscle fiber cross-sectional area in pancreatic cancer patients. Rescuing Sirt1 expression by exogenous expression or pharmacological agents reverted cancer cell-induced myotube wasting in culture conditions and mouse models. RNA-seq and follow-up analyses showed cancer cell-mediated SIRT1 loss induced NF-κB signaling in cachectic muscles that enhanced the expression of FOXO transcription factors and NADPH oxidase 4 (Nox4), a key regulator of reactive oxygen species production. Additionally, we observed a negative correlation between NOX4 expression and skeletal muscle fiber cross-sectional area in pancreatic cancer patients. Knocking out Nox4 in skeletal muscles or pharmacological blockade of Nox4 activity abrogated tumor-induced cachexia in mice. Thus, we conclude that targeting the Sirt1-Nox4 axis in muscles is an effective therapeutic intervention for mitigating pancreatic cancer-induced cachexia
Stable isotope food-web analysis and mercury biomagnification in polar bears ( Ursus maritimus )
Mercury (Hg) biomagnification occurs in many ecosystems, resulting in a greater potential for toxicological effects in higher-level trophic feeders. However, Hg transport pathways through different food-web channels are not well known, particularly in high-latitude systems affected by the atmospheric Hg deposition associated with snow and ice. Here, we report on stable carbon and nitrogen isotope ratios, and Hg concentrations, determined for 26, late 19th and early 20th century, polar bear ( Ursus maritimus ) hair specimens, collected from catalogued museum collections. These data elucidate relationships between the high-latitude marine food-web structure and Hg concentrations in polar bears. The carbon isotope compositions of polar bear hairs suggest that polar bears derive nutrition from coupled food-web channels, based in pelagic and sympagic primary producers, whereas the nitrogen isotope compositions indicate that polar bears occupy > fourth-level trophic positions. Our results show a positive correlation between polar bear hair Hg concentrations and δ 15 N. Interpretation of the stable isotope data in combination with Hg concentrations tentatively suggests that polar bears participating in predominantly pelagic food webs exhibit higher mercury concentrations than polar bears participating in predominantly sympagic food webs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73930/1/j.1751-8369.2009.00114.x.pd
Practicing Imperfect Forgiveness
Forgiveness is typically regarded as a good thing - even a virtue - but acts of forgiveness can vary widely in value, depending on their context and motivation. Faced with this variation, philosophers have tended to reinforce everyday concepts of forgiveness with strict sets of conditions, creating ideals or paradigms of forgiveness. These are meant to distinguish good or praiseworthy instances of forgiveness from problematic instances and, in particular, to protect the self-respect of would-be forgivers. But paradigmatic forgiveness is problematic for a number of reasons, including its inattention to forgiveness as a gendered trait. We can account for the values and the risks associated with forgiving far better if we treat it as a moral practice and not an ideal
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.
BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)
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