Letter from Robert E. Prior to James B. Finley

Prior writes asking Finley to help bring about the pardon of his brother James, who is in prison and very ill. Governor Bebb is aware of the situation, but Finley will need to advocate for James\u27 release. Abstract Number - 1102https://digitalcommons.owu.edu/finley-letters/2086/thumbnail.jp

Letter from Robert E. Prior to James B. Finley

Prior writes concerning his incarcerated brother, James Prior, who is ill. In order to request a pardon for James from Governor Bebb, Prior needs two letters -- one from Finley attesting to the reformation of James\u27 character, and one from the attending physician at the prison, confirming that confinement is dangerous for James\u27 health. Abstract Number - 1121https://digitalcommons.owu.edu/finley-letters/2105/thumbnail.jp

Light Curve Templates and Galactic Distribution of RR Lyrae Stars from Sloan Digital Sky Survey Stripe 82

We present an improved analysis of halo substructure traced by RR Lyrae stars in the SDSS stripe 82 region. With the addition of SDSS-II data, a revised selection method based on new ugriz light curve templates results in a sample of 483 RR Lyrae stars that is essentially free of contamination. The main result from our first study persists: the spatial distribution of halo stars at galactocentric distances 5--100 kpc is highly inhomogeneous. At least 20% of halo stars within 30 kpc from the Galactic center can be statistically associated with substructure. We present strong direct evidence, based on both RR Lyrae stars and main sequence stars, that the halo stellar number density profile significantly steepens beyond a Galactocentric distance of ~30 kpc, and a larger fraction of the stars are associated with substructure. By using a novel method that simultaneously combines data for RR Lyrae and main sequence stars, and using photometric metallicity estimates for main sequence stars derived from deep co-added u-band data, we measure the metallicity of the Sagittarius dSph tidal stream (trailing arm) towards R.A.2h-3h and Dec~0 deg to be 0.3 dex higher ([Fe/H]=-1.2) than that of surrounding halo field stars. Together with a similar result for another major halo substructure, the Monoceros stream, these results support theoretical predictions that an early forming, smooth inner halo, is metal poor compared to high surface brightness material that have been accreted onto a later-forming outer halo. The mean metallicity of stars in the outer halo that are not associated with detectable clumps may still be more metal-poor than the bulk of inner-halo stars, as has been argued from other data sets.Comment: Submitted to ApJ, 68 pages, 26 figures, supplemental material (light curves, templates, animation) can be downloaded from http://www.astro.washington.edu/bsesar/S82_RRLyr.htm

Earliest rock fabric formed in the Solar System preserved in a chondrule rim

Rock fabrics – the preferred orientation of grains – provide a window into the history of rock formation, deformation and compaction. Chondritic meteorites are among the oldest materials in the Solar System1 and their fabrics should record a range of processes occurring in the nebula and in asteroids, but due to abundant fine-grained material these samples have largely resisted traditional in situ fabric analysis. Here we use high resolution electron backscatter diffraction to map the orientation of sub-micrometre grains in the Allende CV carbonaceous chondrite: the matrix material that is interstitial to the mm-sized spherical chondrules that give chondrites their name, and fine-grained rims which surround those chondrules. Although Allende matrix exhibits a bulk uniaxial fabric relating to a significant compressive event in the parent asteroid, we find that fine-grained rims preserve a spherically symmetric fabric centred on the chondrule. We define a method that quantitatively relates fabric intensity to net compression, and reconstruct an initial porosity for the rims of 70-80% - a value very close to model estimates for the earliest uncompacted aggregates2,3. We conclude that the chondrule rim textures formed in a nebula setting and may therefore be the first rock fabric to have formed in the Solar System

Tidal Modulation of a Lateral Shear Margin: Priestley Glacier, Antarctica

We use high resolution, ground-based observations of ice displacement to investigate ice deformation across the floating left-lateral shear margin of Priestley Glacier, Terra Nova Bay, Antarctica. Bare ice conditions allow us to fix survey marks directly to the glacier surface. A combination of continuous positioning of a local reference mark, and repeat positioning of a network of 33 stakes installed across a 2 km width of the shear margin are used to quantify shear strain rates and the ice response to tidal forcing over an 18-day period. Along-flow velocity observed at a continuous Global Navigation Satellite Systems (GNSS) station within the network varies by up to ∼30% of the mean speed (±28 m a−1) over diurnal tidal cycles, with faster flow during the falling tide and slower flow during the rising tide. Long-term deformation in the margin approximates simple shear with a small component of flow-parallel shortening. At shorter timescales, precise optical techniques allow high-resolution observations of across-flow bending in response to the ocean tide, including across-flow strains on the order of 10–5. An elastodynamic model informed by the field observations is used to simulate the across-flow motion and deformation. Flexure is concentrated in the shear margin, such that a non-homogeneous elastic modulus is implied to best account for the combined observations. The combined pattern of ice displacement and ice strain also depends on the extent of coupling between the ice and valley sidewall. These conclusions suggest that investigations of elastic properties made using vertical ice motion, but neglecting horizontal displacement and surface strain, will lead to incorrect conclusions about the elastic properties of ice and potentially over-simplified assumptions about the sidewall boundary condition

Ultrasonic and seismic constraints on crystallographic preferred orientations of the Priestley Glacier shear margin, Antarctica

Crystallographic preferred orientations (CPOs) are particularly important in controlling the mechanical properties of glacial shear margins. Logistical and safety considerations often make direct sampling of shear margins difficult, and geophysical measurements are commonly used to constrain the CPOs. We present here the first direct comparison of seismic and ultrasonic data with measured CPOs in a polar shear margin. The measured CPO from ice samples from a 58 m deep borehole in the left lateral shear margin of the Priestley Glacier, Antarctica, is dominated by horizontal c axes aligned sub-perpendicularly to flow. A vertical-seismic-profile experiment with hammer shots up to 50 m away from the borehole, in four different azimuthal directions, shows velocity anisotropy of both P waves and S waves. Matching P-wave data to the anisotropy corresponding to CPO models defined by horizontally aligned c axes gives two possible solutions for the c-axis azimuth, one of which matches the c-axis measurements. If both P-wave and S-wave data are used, there is one best fit for the azimuth and intensity of c-axis alignment that matches the measurements well. Azimuthal P-wave and S-wave ultrasonic data recorded in the laboratory on the ice core show clear anisotropy of P-wave and S-wave velocities in the horizontal plane that match that predicted from the CPO of the samples. With quality data, azimuthal increments of 30∘ or less will constrain well the orientation and intensity of c-axis alignment. Our experiments provide a good framework for planning seismic surveys aimed at constraining the anisotropy of shear margins

Microstructure and crystallographic preferred orientations of an azimuthally oriented ice core from a lateral shear margin: Priestley Glacier, Antarctica

A 58 m long azimuthally oriented ice core has been collected from the floating lateral sinistral shear margin of the lower Priestley Glacier, Terra Nova Bay, Antarctica. The crystallographic preferred orientations (CPO) and microstructures are described in order to correlate the geometry of anisotropy with constrained large-scale kinematics. Cryogenic Electron Backscatter Diffraction analysis shows a very strong fabric (c-axis primary eigenvalue ∼0.9) with c-axes aligned horizontally sub-perpendicular to flow, rotating nearly 40° clockwise (looking down) to the pole to shear throughout the core. The c-axis maximum is sub-perpendicular to vertical layers, with the pole to layering always clockwise of the c-axes. Priestley ice microstructures are defined by largely sub-polygonal grains and constant mean grain sizes with depth. Grain long axis shape preferred orientations (SPO) are almost always 1–20° clockwise of the c-axis maximum. A minor proportion of “oddly” oriented grains that are distinct from the main c-axis maximum, are present in some samples. These have horizontal c-axes rotated clockwise from the primary c-axis maximum and may define a weaker secondary maximum up to 30° clockwise of the primary maximum. Intragranular misorientations are measured along the core, and although the statistics are weak, this could suggest recrystallization by subgrain rotation to occur. These microstructures suggest subgrain rotation (SGR) and recrystallization by grain boundary migration recrystallization (GBM) are active in the Priestley Glacier shear margin. Vorticity analysis based on intragranular distortion indicates a vertical axis of rotation in the shear margin. The variability in c-axis maximum orientation with depth indicates the structural heterogeneity of the Priestley Glacier shear margin occurs at the meter to tens of meters scale. We suggest that CPO rotations could relate to rigid rotation of blocks of ice within the glacial shear margin. Rotation either post-dates CPO and SPO development or is occurring faster than CPO evolution can respond to a change in kinematics

Calibration of muon reconstruction algorithms using an external muon tracking system at the Sudbury Neutrino Observatory

To help constrain the algorithms used in reconstructing high-energy muon events incident on the Sudbury Neutrino Observatory (SNO), a muon tracking system was installed. The system consisted of four planes of wire chambers, which were triggered by scintillator panels. The system was integrated with SNO's main data acquisition system and took data for a total of 95 live days. Using cosmic-ray events reconstructed in both the wire chambers and in SNO's water Cherenkov detector, the external muon tracking system was able to constrain the uncertainty on the muon direction to better than 0.6°

Precision medicine driven by cancer systems biology

Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors. Mutation hotspots, structural modeling, UV signature, and genomic as well as non-genomic mechanisms of disease initiation and progression are taken into consideration to identify resistance mutations and novel drug targets. A comprehensive precision medicine profile of a malignant melanoma patient illustrates future rational drug targeting strategies. Network analysis emphasizes an important role of epigenetic and metabolic master regulators in oncogenesis. Co-occurrence of driver mutations in signaling, metabolic, and epigenetic factors highlights how cumulative alterations of our genomes and epigenomes progressively lead to uncontrolled cell proliferation. Precision insights have the ability to identify independent molecular pathways suitable for drug targeting. Synergistic treatment combinations of orthogonal modalities including immunotherapy, mitogen-activated protein kinase inhibitors, epigenetic inhibitors, and metabolic inhibitors have the potential to overcome immune evasion, side effects, and drug resistance

Interleukin-4 Alters Early Phagosome Phenotype by Modulating Class I PI3K Dependent Lipid Remodeling and Protein Recruitment

Phagocytosis is a complex process that involves membranelipid remodeling and the attraction and retention of key effector proteins. Phagosome phenotype depends on the type of receptor engaged and can be influenced by extracellular signals. Interleukin 4 (IL-4) is a cytokine that induces the alternative activation of macrophages (MΦs) upon prolonged exposure, triggering a different cell phenotype that has an altered phagocytic capacity. In contrast, the direct effects of IL-4 during phagocytosis remain unknown. Here, we investigate the impact of short-term IL-4 exposure (1 hour) during phagocytosis of IgG-opsonized yeast particles by MΦs. By time-lapse confocal microscopy of GFP-tagged lipid-sensing probes, we show that IL-4 increases the negative charge of the phagosomal membrane by prolonging the presence of the negatively charged second messenger PI(3,4,5)P3. Biochemical assays reveal an enhanced PI3K/Akt activity upon phagocytosis in the presence of IL-4. Blocking the specific class I PI3K after the onset of phagocytosis completely abrogates the IL-4-induced changes in lipid remodeling and concomitant membrane charge. Finally, we show that IL-4 direct signaling leads to a significantly prolonged retention profile of the signaling molecules Rac1 and Rab5 to the phagosomal membrane in a PI3K-dependent manner. This protracted early phagosome phenotype suggests an altered maturation, which is supported by the delayed phagosome acidification measured in the presence of IL-4. Our findings reveal that molecular differences in IL-4 levels, in the extracellular microenvironment, influence the coordination of lipid remodeling and protein recruitment, which determine phagosome phenotype and, eventually, fate. Endosomal and phagosomal membranes provide topological constraints to signaling molecules. Therefore, changes in the phagosome phenotype modulated by extracellular factors may represent an additional mechanism that regulates the outcome of phagocytosis and could have significant impact on the net biochemical output of a cell