Characterization of CD45+ Primary Fibroblasts in Interstitial Lung Disease

The role of cells of the hematopoietic lineage in fibrosis associated with interstitial lung disease (ILD) is controversial; whether monocytes solely differentiate into macrophages that activate resident fibroblasts, or if they can also differentiate into fibrocytes (CD45+/Col I+ cells) that then differentiate into fibroblasts has been debated. By using systemic bleomycin to induce fibrosis in a bone marrow transplant and transgenic mouse models, as well as using human lung tissue from a patient with scleroderma-associated ILD, we studied the contribution of the hematopoietic lineage to the fibroblast population using flow cytometry and single cell RNA sequencing. Further, our studies revealed reasons why fibrocytes are lost when fibroblast cultures are passaged. Finally, we evaluated how treatment of mice with a novel, water-soluble version of caveolin scaffolding domain (CSD) called WCSD affects fibrocyte accumulation and fibrosis in our animal model. We found that during fibrosis, fibrocytes increase in number and in their expression of Col I both in the lung tissue and in the bronchiolar lavage fluid (BAL). The appearance of Col I in CD45+ precursors occurs after their recruitment into the lung. Interestingly, fibrocytes express higher levels of monocyte/macrophage markers (CD45, CD16, CD68, CD206) than do CD45+/Col I- cells. In vitro experiments demonstrated that CD45+/Col I+ cells are at first predominant in fibroblast cultures, but then are lost progressively during passage. Furthermore, these fibrocytes do not appear to grow in vitro in the absence of CD45-/Col I+ fibroblasts. Treating mice with WCSD inhibited fibrocyte accumulation as well as overall collagen I, Tenascin C, α-sma, and HSP47 levels and vascular leakage. The decreased fibrocyte accumulation may result both from decreased precursor recruitment due at least in part to decreased vascular permeability and from decreased differentiation of fibrocytes from CD45+/Col I- precursor monocytes. In summary, CD45+ cells accumulate in lung tissue during fibrosis and contribute to pathological remodeling by differentiating into myofibroblasts that overexpress ECM proteins and myofibroblast markers. Their contribution to fibrosis can be inhibited by WCSD which serves as a surrogate for caveolin-1, a protein known to be reduced in expression in multiple cell types from patients with fibrotic lung disease

The solvent dependence of enzymatic selectivity

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1996.Includes bibliographical references (leaves 86-97).by Charles R. Wescott.Ph.D

Distribution, structure, and function of marine ecological communities in the northern California Current upwelling ecosystem

Within systems characterized by substantial spatial and temporal variability, abundances of organisms tend to be higher in localized areas. Within the northern California Current system, the identification of such marine, biological hotspots would be of great importance to resource managers, conservationists, and research planners, and is consequently a growing area of research. Furthermore, in order to understand how ecosystems function and persist, it is necessary to know how ecological communities are distributed. The overall goal of this study is to provide further understanding regarding the functioning of marine ecosystems in such highly variable environments and to provide information about the distribution and structure of marine communities. Sampling was conducted during June and August of 2000 and 2002 as part of the U.S. GLOBEC mesoscale surveys from Newport, Oregon in the north to Crescent City, California in the south. A geostatistical approach was used to create surfaces used in a GIS to determine the distribution of various community characteristics. Two biological hotspots were identified and determined to persist in space and time, yet differed with respect to biological and physical features and in the amount of area covered. Various community analyses, including nonmetric multidimensional scaling, indicator species analysis, and cluster analysis were used to determine various community properties associated with the hotspots and non-hotspot regions. Results indicate that nekton biological hotspots in the northern California Current persist across differing environmental and biological conditions, although upwelling-based hotspots may be more susceptible to climatic conditions than retention-based hotspots. Analyses of the distribution of the functional groups within the region indicate that the predominant biological activity is spatially nonrandom and occurs within persistent, localized areas. Analyses of species associations suggest a moderate degree of redundancy. The presence of such complementary species within functional groups may confer the stability observed within these systems. The finding that large regional areas are composed of smaller, localized hotspots where a predominant amount of biological activity is occurring, suggests that the evaluation of large marine ecosystems may lead to erroneous or misleading results if they do not consider the more persistent, localized biological hotspots

A Multi-wavelength Study of the Sunyaev-Zel'dovich Effect in the Triple-Merger Cluster MACS J0717.5+3745 with MUSTANG and Bolocam

We present 90, 140, and 268GHz sub-arcminute resolution imaging of the Sunyaev-Zel'dovich effect (SZE) in MACSJ0717.5+3745. Our 90GHz SZE data result in a sensitive, 34uJy/bm map at 13" resolution using MUSTANG. Our 140 and 268GHz SZE imaging, with resolutions of 58" and 31" and sensitivities of 1.8 and 3.3mJy/beam respectively, was obtained using Bolocam. We compare these maps to a 2-dimensional pressure map derived from Chandra X-ray observations. Our MUSTANG data confirm previous indications from Chandra of a pressure enhancement due to shock-heated, >20keV gas immediately adjacent to extended radio emission seen in low-frequency radio maps. The MUSTANG data also detect pressure substructure that is not well-constrained by the X-ray data in the remnant core of a merging subcluster. We find that the small-scale pressure enhancements in the MUSTANG data amount to ~2% of the total pressure measured in the 140GHz Bolocam observations. The X-ray template also fails on larger scales to accurately describe the Bolocam data, particularly at the location of a subcluster known to have a high line of sight optical velocity (~3200km/s). Our Bolocam data are adequately described when we add an additional component - not described by a thermal SZE spectrum - coincident with this subcluster. Using flux densities extracted from our model fits, and marginalizing over the temperature constraints for the region, we fit a thermal+kinetic SZE spectrum to our data and find the subcluster has a best-fit line of sight proper velocity of 3600+3440/-2160km/s. This agrees with the optical velocity estimates for the subcluster. The probability of velocity<0 given our measurements is 2.1%. Repeating this analysis using flux densities measured non-parametrically results in a 3.4% probability of a velocity<=0. We note that this tantalizing result for the kinetic SZE is on resolved, subcluster scales.Comment: 10 Figures, 18 pages. this version corrects issues with the previous arXiv versio

Object-oriented modeling of the communications networks of the MAGTF

The Marine Air-Ground Task Force (MAGTF) is supported by a communications system comprised of heterogenous links and widely shared network resources. In this work, we describe our approach to modeling the MAGTF communications network. This model employs a new concept of workload modeling which we have developed. We provide a mathematical development of our measures of effectiveness and show how our model will be used to seek improvement in MAGTF communications performanceWarfighting Center—Studies and Analysis MCCDC, Quantico, VAhttp://archive.org/details/objectorientedmo00bailM9545091WRR1AK2NAApproved for public release; distribution is unlimited

Ewing Brass Quintet: Herb Koerselman, Trumpet; Kirby Reese, Trumpet; Don Peterson, Horn; Charles Stokes, Trombone; Ed Livingston, Tuba; March 27, 1977

Hayden AuditoriumSunday EveningMarch 27, 19778:00 p.m

Ewing Brass Quintet: Herb Koerselman, Trumpet; Kirby Reese, Trumpet; Philip Hillstrom, Horn; Charles Stokes, Trombone; Ed Livingston, Tuba; April 13, 1976

Center for the Visual Arts, Art GalleryTuesday EveningApril 13, 19768:15 p.m