Resonant Orbits in Triaxial Galaxies

Box orbits in triaxial potentials are generically thin, that is, they lie close in phase space to a resonant orbit satisfying a relation of the form l\omega_1 +m\omega_2+n\omega_3=0 between the three fundamental frequencies. Resonant orbits are confined to a membrane; they play roughly the same role, in three dimensions, that closed orbits play in two. Stable resonant orbits avoid the center of the potential; orbits that are thick enough to pass near the center are typically stochastic. Very near the center, where the gravitational potential is dominated by the black hole, resonant orbits continue to exist, including at least one family whose elongation is parallel to the long axes of the triaxial figure.Comment: 20 Latex pages, 11 Postscript figures. Submitted to The Astronomical Journa

Measurement of optical response of a detuned resonant sideband extraction gravitational wave detector

We report on the optical response of a suspended-mass detuned resonant sideband extraction (RSE) interferometer with power recycling. The purpose of the detuned RSE configuration is to manipulate and optimize the optical response of the interferometer to differential displacements (induced by gravitational waves) as a function of frequency, independently of other parameters of the interferometer. The design of our interferometer results in an optical gain with two peaks: an RSE optical resonance at around 4 kHz and a radiation pressure induced optical spring at around 41 Hz. We have developed a reliable procedure for acquiring lock and establishing the desired optical configuration. In this configuration, we have measured the optical response to differential displacement and found good agreement with predictions at both resonances and all other relevant frequencies. These results build confidence in both the theory and practical implementation of the more complex optical configuration being planned for Advanced LIGO

Wee1-Regulated Apoptosis Mediated by the Crk Adaptor Protein in Xenopus Egg Extracts

Many of the biochemical reactions of apoptotic cell death, including mitochondrial cytochrome c release and caspase activation, can be reconstituted in cell-free extracts derived from Xenopus eggs. In addition, because caspase activation does not occur until the egg extract has been incubated for several hours on the bench, upstream signaling processes occurring before full apoptosis are rendered accessible to biochemical manipulation. We reported previously that the adaptor protein Crk is required for apoptotic signaling in egg extracts (Evans, E.K., W. Lu, S.L. Strum, B.J. Mayer, and S. Kornbluth. 1997. EMBO (Eur. Mol. Biol. Organ.) J. 16:230–241). Moreover, we demonstrated that removal of Crk Src homology (SH)2 or SH3 interactors from the extracts prevented apoptosis. We now report the finding that the relevant Crk SH2-interacting protein, important for apoptotic signaling in the extract, is the well-known cell cycle regulator, Wee1. We have demonstrated a specific interaction between tyrosine-phosphorylated Wee1 and the Crk SH2 domain and have shown that recombinant Wee1 can restore apoptosis to an extract depleted of SH2 interactors. Moreover, exogenous Wee1 accelerated apoptosis in egg extracts, and this acceleration was largely dependent on the presence of endogenous Crk protein. As other Cdk inhibitors, such as roscovitine and Myt1, did not act like Wee1 to accelerate apoptosis, we propose that Wee1–Crk complexes signal in a novel apoptotic pathway, which may be unrelated to Wee1's role as a cell cycle regulator

Measurement of Optical Response of a Detuned Resonant Sideband Extraction Interferometer

We report on the optical response of a suspended-mass detuned resonant sideband extraction (RSE) interferometer with power recycling. The purpose of the detuned RSE configuration is to manipulate and optimize the optical response of the interferometer to differential displacements (induced by gravitational waves) as a function of frequency, independently of other parameters of the interferometer. The design of our interferometer results in an optical gain with two peaks: an RSE optical resonance at around 4 kHz and a radiation pressure induced optical spring at around 41 Hz. We have developed a reliable procedure for acquiring lock and establishing the desired optical configuration. In this configuration, we have measured the optical response to differential displacement and found good agreement with predictions at both resonances and all other relevant frequencies. These results build confidence in both the theory and practical implementation of the more complex optical configuration being planned for Advanced LIGO.Comment: 6 pages, 4 figures, for submission to Phys Rev Letter

Healing Multiculturalism: Middle-Ground Liberal Forgiveness in a Diverse Public Realm

This article examines debates about political forgiveness in liberal, pluralist societies. Although the concept of forgiveness is not usually taken up by liberals, I outline a plausible conception by exploring two recent approaches. The first, ‘unattached articulation’, concept requires no real emotional change on the forgiver’s part, but rather a form of civic restraint. In contrast, the second version highlights a strong form of empathy for perpetrators. In spite of their advantages, each concept proves too extreme. The problems are revealed by focusing on the case of the Harkis, who fought for the French during the Algerian war. Often still marginalised in French society, their case helps to highlight the conceivability of a ‘middle-ground’ or moderate concept of political forgiveness. Its core rests on the forgiver’s care for the social world. While this concept brings considerable challenges also, and is not inevitable in any particular case, it entails a more plausible combination of emotional and rational shifts in the forgiver’s world-view. Although the article does not recommend forgiveness by any person or group, it observes, recalling Arendt’s idea of amor mundi or ‘love of the world’, that political forgiveness may sustain a viable connection between diverse citizens’ public and non-public lives

CSF1R+ Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapies including single-agent immunotherapy and has a dense desmoplastic stroma, and most patients present with advanced metastatic disease. We reveal that macrophages are the dominant leukocyte population both in human PDAC stroma and autochthonous models, with an important functional contribution to the squamous subtype of human PDAC. We targeted macrophages in a genetic PDAC model using AZD7507, a potent selective inhibitor of CSF1R. AZD7507 caused shrinkage of established tumors and increased mouse survival in this difficult-to-treat model. Malignant cell proliferation diminished, with increased cell death and an enhanced T cell immune response. Loss of macrophages rewired other features of the TME, with global changes in gene expression akin to switching PDAC subtypes. These changes were markedly different to those elicited when neutrophils were targeted via CXCR2. These results suggest targeting the myeloid cell axis may be particularly efficacious in PDAC, especially with CSF1R inhibitors

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation