Integral Field Spectroscopy of High-Redshift Star Forming Galaxies with Laser Guided Adaptive Optics: Evidence for Dispersion-Dominated Kinematics

We present early results from an ongoing study of the kinematic structure of star-forming galaxies at redshift z ~ 2 - 3 using integral-field spectroscopy of rest-frame optical nebular emission lines in combination with Keck laser guide star adaptive optics (LGSAO). We show kinematic maps of 3 target galaxies Q1623-BX453, Q0449-BX93, and DSF2237a-C2 located at redshifts z = 2.1820, 2.0067, and 3.3172 respectively, each of which is well-resolved with a PSF measuring approximately 0.11 - 0.15 arcsec (~ 900 - 1200 pc at z ~ 2-3) after cosmetic smoothing. Neither galaxy at z ~ 2 exhibits substantial kinematic structure on scales >~ 30 km/s; both are instead consistent with largely dispersion-dominated velocity fields with sigma ~ 80 km/s along any given line of sight into the galaxy. In contrast, DSF2237a-C2 presents a well-resolved gradient in velocity over a distance of ~ 4 kpc with peak-to-peak amplitude of 140 km/s. It is unlikely that DSF2237a-C2 represents a dynamically cold rotating disk of ionized gas as the local velocity dispersion of the galaxy (sigma = 79 km/s) is comparable to the observed shear. Using extant multi-wavelength spectroscopy and photometry we relate these kinematic data to physical properties such as stellar mass, gas fraction, star formation rate, and outflow kinematics and consider the applicability of current galaxy formation models.[Abridged]Comment: 19 pages, 10 figures (5 color); accepted for publication in ApJ. Version with full-resolution figures is available at http://www.astro.caltech.edu/~drlaw/Papers/OSIRIS_data1.pd

Portfolio Vol. V N 2

Koons, Marilynn. America Is . Poem. 4. Rucker, J.G. Nothing but the Beat . Prose. 5. Wyman, John. Pringle . Prose. 6. Tolan, Marace. Hands at Midnight . Poem. 7. Wright, Edward A. All in a Day\u27s Work . Prose. 8. Benson, Virginia. Now is the Time . Prose. 9. Moll, Wilhelm. The Dead Lover . Prose. 12. Flammt, Marga. Escape . Poem. 14. Rolph, Alice. Fancy\u27s Flight . Poem. 14. Vercoe, Mary. Future . Poem. 14. Klammt,Marga. Parting . Poem. 14. Anonymous. Denisoniana . Picture. 10. Benson, Virginia. Marquand-H.M. Pulham. Esquire . Prose. 15. Benson, Virginia. Junior Miss . Prose. 15. Reynolds, Virginia. Stubs of the Jungle . Prose. 16. Masquers. Thespiana . Prose. 17. Anonymous. How to Knit a Sweater, or, Eighteen Holes . Prose. 20

Characterization of a Chromosomally Encoded 2,4-Dichlorophenoxyacetic Acid/a-Ketoglutarate Dioxygenase from \u3ci\u3eBurkholderia\u3c/i\u3e sp. Strain RASC

The findings of previous studies indicate that the genes required for metabolism of the pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) are typically encoded on broad-host-range plasmids. However, characterization of plasmid-cured strains of Burkholderia sp. strain RASC, as well as mutants obtained by transposon mutagenesis, suggested that the 2,4-D catabolic genes were located on the chromosome of this strain. Mutants of Burkholderia strain RASC unable to degrade 2,4-D (2,4-D- strains) were obtained by insertional inactivation with Tn5. One such mutant (d1) was shown to have Tn5 inserted in tfdARASC, which encodes 2,4-D/alpha-ketoglutarate dioxygenase. This is the first reported example of a chromosomally encoded tfdA. The tfdARASC gene was cloned from a library of wild-type Burkholderia strain RASC DNA and shown to express 2,4-D/alpha-ketoglutarate dioxygenase activity in Escherichia coli. The DNA sequence of the gene was determined and shown to be similar, although not identical, to those of isofunctional genes from other bacteria. Moreover, the gene product (TfdARASC) was purified and shown to be similar in molecular weight, amino-terminal sequence, and reaction mechanism to the canonical TfdA of Alcaligenes eutrophus JMP134. The data presented here indicate that tfdA genes can be found on the chromosome of some bacterial species and suggest that these catabolic genes are rather mobile and may be transferred by means other than conjugation

The Kiloparsec-Scale Kinematics of High-Redshift Star-Forming Galaxies

We present the results of a spectroscopic survey of the kinematic structure of star-forming galaxies at redshift z ~ 2 - 3 using Keck/OSIRIS integral field spectroscopy. Our sample is comprised of 12 galaxies between redshifts z ~ 2.0 and 2.5 and one galaxy at z ~ 3.3 which are well detected in either HAlpha or [O III] emission. These observations were obtained in conjunction with the Keck laser guide star adaptive optics system, with a typical angular resolution after spatial smoothing ~ 0.15" (approximately 1 kpc at the redshift of the target sample). At most five of these 13 galaxies have spatially resolved velocity gradients consistent with rotation while the remaining galaxies have relatively featureless or irregular velocity fields. All of our galaxies show local velocity dispersions ~ 60 - 100 km/s, suggesting that (particularly for those galaxies with featureless velocity fields) rotation about a preferred axis may not be the dominant mechanism of physical support. While some galaxies show evidence for major mergers such evidence is unrelated to the kinematics of individual components (one of our strongest merger candidates also exhibits unambiguous rotational structure), refuting a simple bimodal disk/merger classification scheme. We discuss these data in light of complementary surveys and extant UV-IR spectroscopy and photometry, concluding that the dynamical importance of cold gas may be the primary factor governing the observed kinematics of z ~ 2 galaxies. We conclude by speculating on the importance of mechanisms for accreting low angular-momentum gas and the early formation of quasi-spheroidal systems in the young universe.(abridged)Comment: 34 pages, 13 figures. Revised version accepted for publication in the Astrophysical Journal. Version with full-resolution figures is available at http://www.astro.ucla.edu/~drlaw/Papers/OSIRIS_data2.pd

Shortened hinge design of Fab x sdAb-Fc bispecific antibodies enhances redirected T-Cell killing of tumor cells

T cell engager (TCE) antibodies have emerged as promising cancer therapeutics that link cytotoxic T-cells to tumor cells by simultaneously binding to CD3E on T-cells and to a tumor-associated antigen (TAA) expressed by tumor cells. We previously reported a novel bispecific format, the IgG-like Fab x sdAb-Fc (also known as half-IG_VH-h-CH2-CH3), combining a conventional antigen-binding fragment (Fab) with a single domain antibody (sdAb). Here, we evaluated this Fab x sdAb-Fc format as a T-cell redirecting bispecific antibody (TbsAbs) by targeting mEGFR on tumor cells and mCD3E on T cells. We focused our attention specifically on the hinge design of the sdAb arm of the bispecific antibody. Our data show that a TbsAb with a shorter hinge of 23 amino acids (TbsAb.short) showed a significantly better T cell redirected tumor cell elimination than the TbsAb with a longer, classical antibody hinge of 39 amino acids (TbsAb.long). Moreover, the TbsAb.short form mediated better T cell-tumor cell aggregation and increased CD69 and CD25 expression levels on T cells more than the TbsAb.long form. Taken together, our results indicate that already minor changes in the hinge design of TbsAbs can have significant impact on the anti-tumor activity of TbsAbs and may provide a new means to improve their potency

Planetary Construction Zones in Occultation: Discovery of an Extrasolar Ring System Transiting a Young Sun-like Star and Future Prospects for Detecting Eclipses by Circumsecondary and Circumplanetary Disks

The large relative sizes of circumstellar and circumplanetary disks imply that they might be seen in eclipse in stellar light curves. We estimate that a survey of ~10^4 young (~10 Myr old) post-accretion pre-MS stars monitored for ~10 years should yield at least a few deep eclipses from circumplanetary disks and disks surrounding low mass companion stars. We present photometric and spectroscopic data for a pre-MS K5 star (1SWASP J140747.93-394542.6), a newly discovered ~0.9 Msun member of the ~16 Myr-old Upper Cen-Lup subgroup of Sco-Cen at a kinematic distance of 128 pc. SuperWASP and ASAS light curves for this star show a remarkably long, deep, and complex eclipse event centered on 29 April 2007. At least 5 multi-day dimming events of >0.5 mag are identified, with a >3.3 mag deep eclipse bracketed by two pairs of ~1 mag eclipses symmetrically occurring +-12 days and +-26 days before and after. Hence, significant dimming of the star was taking place on and off over at least a ~54 day period in 2007, and a strong >1 mag dimming event occurred over a ~12 day span. We place a firm lower limit on the period of 850 days (i.e. the orbital radius of the eclipser must be >1.7 AU and orbital velocity must be <22 km/s). The shape of the light curve is similar to the lop-sided eclipses of the Be star EE Cep. We suspect that this new star is being eclipsed by a low-mass object orbited by a dense inner disk, girded by at least 3 dusty rings of lower optical depth. Between these rings are at least two annuli of near-zero optical depth (i.e. gaps), possibly cleared out by planets or moons, depending on the nature of the secondary. For possible periods in the range 2.33-200 yr, the estimated total ring mass is ~8-0.4 Mmoon (if the rings have optical opacity similar to Saturn's rings), and the edge of the outermost detected ring has orbital radius ~0.4-0.09 AU.Comment: Astronomical Journal, in press, 13 figure

Differences in axial segment reorientation during standing turns predict multiple falls in older adults

Author's version of an article in the journal: Gait and Posture. Also available from the publisher at: http://dx.doi.org/10.1016/j.gaitpost.2012.05.013Background: The assessment of standing turning performance is proposed to predict fall risk in older adults. This study investigated differences in segmental coordination during a 360° standing turn task between older community-dwelling fallers and non-fallers. Methods: Thirty-five older adults age mean (SD) of 71 (5.4) years performed 360° standing turns. Head, trunk and pelvis position relative to the laboratory and each other were recorded using a Vicon motion analysis system. Fall incidence was monitored by monthly questionnaire over the following 12 months and used to identify non-faller, single faller and multiple faller groups. Results: Multiple fallers were found to have significantly different values, when compared to non-fallers, for pelvis onset (p=. 0.002); mean angular separation in the transverse plane between the head and trunk (p=. 0.018); peak angular separation in the transverse plane between the trunk and pelvis (p=. 0.013); and mean angular separation between the trunk and pelvis (p<. 0.001). Conclusions: Older adults who subsequently experience multiple falls show a simplified turning pattern to assist in balance control. This may be a predictor for those at increased risk of falling

Anti-Lysophosphatidic Acid Antibodies Improve Traumatic Brain Injury Outcomes

BACKGROUND: Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. FINDINGS: Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. CONCLUSIONS: This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction

An HST/WFC3-IR Morphological Survey of Galaxies at z = 1.5-3.6: II. The Relation between Morphology and Gas-Phase Kinematics

We analyze rest-frame optical morphologies and gas-phase kinematics as traced by rest-frame far-UV and optical spectra for a sample of 204 star forming galaxies in the redshift range z ~ 2-3 drawn from the Keck Baryonic Structure Survey (KBSS). We find that spectroscopic properties and gas-phase kinematics are closely linked to morphology: compact galaxies with semi-major axis radii r <~ 2 kpc are substantially more likely than their larger counterparts to exhibit LyA in emission. Although LyA emission strength varies widely within galaxies of a given morphological type, all but one of 19 galaxies with LyA equivalent width W_LyA > 20 Angstroms have compact and/or multiple-component morphologies with r <= 2.5 kpc. The velocity structure of absorption lines in the galactic continuum spectra also varies as a function of morphology. Galaxies of all morphological types drive similarly strong outflows (as traced by the blue wing of interstellar absorption line features), but the outflows of larger galaxies are less highly ionized and exhibit larger optical depth at the systemic redshift that may correspond to a decreasing efficiency of feedback in evacuating gas from the galaxy. This v ~ 0 km/s gas is responsible both for shifting the mean absorption line redshift and attenuating W_LyA (via a longer resonant scattering path) in galaxies with larger rest-optical half light radii. In contrast to galaxies at lower redshifts, there is no evidence for a correlation between outflow velocity and inclination, suggesting that outflows from these puffy and irregular systems may be poorly collimated. (Abbrev.)Comment: 18 pages, 11 figures. Revised version accepted for publication in ApJ. Version with full-resolution figures is available at http://di.utoronto.ca/~drlaw/Papers/wfc3_uvspec.pd

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes