Memory CD8+ T Cell Function during Mycobacterium Tuberculosis Infection: A Dissertation

T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the secondary (memory) response during Mtb challenge, an effect moderated by increased TCR affinity. To determine whether the expansion of polyclonal memory T cells is restrained following Mtb challenge, we used TCRb deep sequencing to track TB10.4-specific CD8+ T cells after vaccination and subsequent challenge in intact mice. Successful memory T cells, defined by their clonal expansion after Mtb challenge, express similar CDR3b sequences suggesting TCR selection by antigen. Thus, both TCR-dependent and independent factors affect the fitness of memory CD8+ responses. The impaired expansion of the majority of memory T cell clonotypes may explain why some TB vaccines have not provided better protection

Cuatro Vientos: A Reconsideration of Seven Prehistoric Sites in the Lower Rio Grande Plains of South Texas

With this report, Texas Department of Transportation (TxDOT) begins a reconsideration of approaches to the evaluation and treatment of those areas where surface lithic scatters are the main constituent of the archeological record. The reconsideration was inspired by the Cuatro Vientos project in Laredo, Webb County, Texas. The project and the ideas surrounding it developed slowly. The ideas continued to evolve through discussion between SWCA Environmental Consultants (SWCA) and TxDOT as additional work on the project occurred. Because this project proceeded in an idiosyncratic fashion, some words of explanation might be helpful. The following discussion provides an account of how the project developed and where future work might be heading

Vaccine-elicited memory CD4+ T cell expansion is impaired in the lungs during tuberculosis

Immunological memory is the key biological process that makes vaccines possible. Although tuberculosis vaccines elicit protective immunity in animals, few provide durable protection. To understand why protection is transient, we evaluated the ability of memory CD4+ T cells to expand, differentiate, and control Mycobacterium tuberculosis. Both naive and memory CD4+ T cells initially proliferated exponentially, and the accumulation of memory T cells in the lung correlated with early bacterial control. However, later during infection, memory CD4+ T cell proliferation was curtailed and no protection was observed. We show that memory CD4+ T cells are first activated in the LN and their recruitment to the lung attenuates bacterial growth. However, their interaction with Mtb-infected macrophages does not promote continued proliferation. We conclude that a lack of sustained expansion by memory-derived T cells in the lung limits the durability of their protection, linking their slower expansion with transient protection in vaccinated mice

A Resolved Ring of Debris Dust around the Solar Analog HD 107146

We present resolved images of the dust continuum emission from the debris disk around the young (80-200 Myr) solar-type star HD 107146 with CARMA at λ = 1.3 mm and the CSO at λ = 350 μ. Both images show that the dust emission extends over an approximately 10" diameter region. The high-resolution (3") CARMA image further reveals that the dust is distributed in a partial ring with significant decrease in a flux inward of 97 AU. Two prominent emission peaks appear within the ring separated by ~140° in the position angle. The morphology of the dust emission is suggestive of dust captured into a mean motion resonance, which would imply the presence of a planet at an orbital radius of ~45-75 AU

Exit time as a measure of ecological resilience

Ecological resilience is the magnitude of the largest perturbation from which a system can still recover to its original state. However, a transition into another state may often be invoked by a series of minor synergistic perturbations rather than a single big one. We show how resilience can be estimated in terms of average life expectancy, accounting for this natural regime of variability. We use time series to fit a model that captures the stochastic as well as the deterministic components. The model is then used to estimate the mean exit time from the basin of attraction. This approach offers a fresh angle to anticipating the chance of a critical transition at a time when high-resolution time series are becoming increasingly available.</p

Atmospheric phase correction using CARMA-PACS: high angular resolution observations of the FU Orionis star PP 13S*

We present 0".15 resolution observations of the 227 GHz continuum emission from the circumstellar disk around the FU Orionis star PP 13S*. The data were obtained with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) Paired Antenna Calibration System (C-PACS), which measures and corrects the atmospheric delay fluctuations on the longest baselines of the array in order to improve the sensitivity and angular resolution of the observations. A description of the C-PACS technique and the data reduction procedures are presented. C-PACS was applied to CARMA observations of PP 13S*, which led to a factor of 1.6 increase in the observed peak flux of the source, a 36% reduction in the noise of the image, and a 52% decrease in the measured size of the source major axis. The calibrated complex visibilities were fitted with a theoretical disk model to constrain the disk surface density. The total disk mass from the best-fit model corresponds to 0.06 M_⊙, which is larger than the median mass of a disk around a classical T Tauri star. The disk is optically thick at a wavelength of 1.3 mm for orbital radii less than 48 AU. At larger radii, the inferred surface density of the PP 13S* disk is an order of magnitude lower than that needed to develop a gravitational instability

The Little Paint Site: A Classic Toyah Camp on the South Llano River, Kimble County, Texas

On behalf of the Texas Department of Transportation (TxDOT), SWCA Environmental Consultants (SWCA) conducted testing and data recovery investigations at the Little Paint site (41KM226), a prehistoric multi-component site in the US 377 right-of-way along the South Llano River in Kimble County, Texas. While the site revealed Archaic and Late Prehistoric components, the earlier components were stratigraphically intermixed. Consequently, data recovery focused almost entirely on a discrete Toyah component, which, based on earlier test excavations conducted in August and September 2006, had previously been determined to be eligible for listing on the National Register of Historic Places and as a State Archeological Landmark. SWCA performed the investigations under Texas Antiquities Permits 4184 and 4318. Kevin A. Miller served as Principal Investigator. The excavations recovered approximately 102 m2 of a stratigraphically-discrete Toyah component consisting of rock-lined hearths, Perdiz points, Cliffton points, a bird-bone bead, bone-tempered ceramics, bifaces, scrapers (notably end scrapers on blade-flakes), various informal lithic tools, drills, awls, debitage, and faunal remains. Based on the assemblage, the site is interpreted as a Toyah basecamp as indicated by a diversity of tool forms and site furniture. The component has good integrity, is vertically and horizontally discrete, and contains a substantial amount of archaeological materials. The suite of 16 radiometric dates indicates intermittent Toyah occupations between 240 and 570 years ago, a time range that is generally consistent with recognized span of the Toyah assemblage. The archaeological assemblage and site structure, however, suggests a possible single Toyah occupation. While not a focal point of the data recovery investigations, the excavations also recovered mixed Archaic components below the Toyah component. Artifacts include diagnostic point styles that indicate Late Archaic to early Late Prehistoric occupations, representing 1,000 to 2,000 years of the regional cultural chronology compressed within a thin stratum. Based on the findings, the depositional conditions below the Toyah component, as was previously determined by the testing data, were found to be generally not conducive to the formation of stratigraphic separation of the successive occupations. This compression resulted in intermixing of components and poor integrity. Below the mixed Archaic zone, deeply buried Middle to Early Archaic deposits were identified. These retained a better potential for significant isolable strata, but these deeper deposits were beyond the project impacts and therefore were not the subject of mitigative efforts. The deeper deposits are preserved by avoidance. As previously determined and further substantiated by the data recovery investigations, the Little Paint site, because of the Toyah component and perhaps earlier deposits, is eligible for National Register of Historic Places listing under Criterion D, 36 CFR 60.4, and eligible for State Archeological Landmark designation under Criteria 1 and 2 of the Rules of Practice and Procedure for the Antiquities Code of Texas, 13 TAC 26.8. The excavations have mitigated the adverse effects of the US 377 bridge replacement by recovering the vast majority of the Toyah component within the area of potential effect of the roadway undertaking. No further archaeological work is recommended. Portions of the site outside of the right-of-way have not been fully evaluated. The artifacts and records from the project are curated at the Center for Archaeological Studies, Texas State University

Dynamically Driven Evolution of the Interstellar Medium in M51

Massive star formation occurs in giant molecular clouds (GMCs); an understanding of the evolution of GMCs is a prerequisite to develop theories of star formation and galaxy evolution. We report the highest-fidelity observations of the grand-design spiral galaxy M51 in carbon monoxide (CO) emission, revealing the evolution of GMCs vis-a-vis the large-scale galactic structure and dynamics. The most massive GMCs (giant molecular associations (GMAs)) are first assembled and then broken up as the gas flow through the spiral arms. The GMAs and their H_2 molecules are not fully dissociated into atomic gas as predicted in stellar feedback scenarios, but are fragmented into smaller GMCs upon leaving the spiral arms. The remnants of GMAs are detected as the chains of GMCs that emerge from the spiral arms into interarm regions. The kinematic shear within the spiral arms is sufficient to unbind the GMAs against self-gravity. We conclude that the evolution of GMCs is driven by large-scale galactic dynamics—their coagulation into GMAs is due to spiral arm streaming motions upon entering the arms, followed by fragmentation due to shear as they leave the arms on the downstream side. In M51, the majority of the gas remains molecular from arm entry through the interarm region and into the next spiral arm passage