Infall, Outflow, Rotation, and Turbulent Motions of Dense Gas within NGC 1333 IRAS 4

Millimeter wavelength observations are presented of NGC 1333 IRAS 4, a group of highly-embedded young stellar objects in Perseus, that reveal motions of infall, outflow, rotation, and turbulence in the dense gas around its two brightest continuum objects, 4A and 4B. These data have finest angular resolution of approximately 2" (0.0034 pc) and finest velocity resolution of 0.13 km/s. Infall motions are seen from inverse P-Cygni profiles observed in H2CO 3_12-2_11 toward both objects, but also in CS 3-2 and N2H+ 1-0 toward 4A, providing the least ambiguous evidence for such motions toward low-mass protostellar objects. Outflow motions are probed by bright line wings of H2CO 3_12-2_11 and CS 3-2 observed at positions offset from 4A and 4B, likely tracing dense cavity walls. Rotational motions of dense gas are traced by a systematic variation of the N2H+ line velocities, and such variations are found around 4A but not around 4B. Turbulent motions appear reduced with scale, given N2H+ line widths around both 4A and 4B that are narrower by factors of 2 or 3 than those seen from single-dish observations. Minimum observed line widths of approximately 0.2 km/s provide a new low, upper bound to the velocity dispersion of the parent core to IRAS 4, and demonstrate that turbulence within regions of clustered star formation can be reduced significantly. A third continuum object in the region, 4B', shows no detectable line emission in any of the observed molecular species.Comment: LateX, 51 pages, 9 figures, accepted by Ap

Toward stronger theory in critical public health: Insights from debates surrounding posthumanism

The “posthumanist turn” in critical theory comprises efforts to recognize and analyze the interdependence of human existence with non-human entities, including other animals, spaces, and technologies. Scholarship aligned to and debating posthumanism pertains to public health, but has yet to be clearly articulated for a public health audience. This commentary and an appended glossary illustrate the relevance of these ideas for enhancing critical theory in public health. Keywords: Social Sciences, Humanities, Technology, Animals, Public HealthCanadian Institutes of Health Researc

IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System

PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471

Motion processing with wide-field neurons in the retino-tecto-rotundal pathway

The retino-tecto-rotundal pathway is the main visual pathway in non-mammalian vertebrates and has been found to be highly involved in visual processing. Despite the extensive receptive fields of tectal and rotundal wide-field neurons, pattern discrimination tasks suggest a system with high spatial resolution. In this paper, we address the problem of how global processing performed by motion-sensitive wide-field neurons can be brought into agreement with the concept of a local analysis of visual stimuli. As a solution to this problem, we propose a firing-rate model of the retino-tecto-rotundal pathway which describes how spatiotemporal information can be organized and retained by tectal and rotundal wide-field neurons while processing Fourier-based motion in absence of periodic receptive-field structures. The model incorporates anatomical and electrophysiological experimental data on tectal and rotundal neurons, and the basic response characteristics of tectal and rotundal neurons to moving stimuli are captured by the model cells. We show that local velocity estimates may be derived from rotundal-cell responses via superposition in a subsequent processing step. Experimentally testable predictions which are both specific and characteristic to the model are provided. Thus, a conclusive explanation can be given of how the retino-tecto-rotundal pathway enables the animal to detect and localize moving objects or to estimate its self-motion parameters