FABRICATION, MEASUREMENTS, AND MODELING OF SEMICONDUCTOR RADIATION DETECTORS FOR IMAGING AND DETECTOR RESPONSE FUNCTIONS

In the first part of this dissertation, we cover the development of a diamond semiconductor alpha-tagging sensor for associated particle imaging to solve challenges with currently employed scintillators. The alpha-tagging sensor is a double-sided strip detector made from polycrystalline CVD diamond. The performance goals of the alpha-tagging sensor are 700-picosecond timing resolution and 0.5 mm spatial resolution. A literature review summarizes the methodology, goals, and challenges in associated particle imaging. The history and current state of alpha-tagging sensors, followed by the properties of diamond semiconductors are discussed to close the literature review. The materials and methods used to calibrate the detector readout, fabricate the sensor, perform simulations, take measurements, and conduct data analysis are discussed. The results of our simulations and measurements are described with challenges and interpretations. The first part of the dissertation is concluded with potential solutions to challenges with our diamond alpha-tagging sensor design, recommendations of work to help further verify or refute diamonds viability for alpha tagging in associated particle imaging. In the second part of this dissertation, we cover the development of a high-purity germanium detector response function for the Los Alamos National Laboratory Detector Response Function Toolkit. The goal is to accurately model the pulse-height spectra measured by semiconductor radiation detectors. The literature review provides information on high-purity germanium radiation detectors and semiconductor charge transport kinematics. The components of the electronic readout and their effect on radiation measurements are discussed. The literature review ends with a discussion on different methods for building detector response functions. In the methods section, we explain our methodology for building detector response functions. This includes models of radiation transport, electrostatics, charge transport, and electronic readout components. Within the methods section, there are results from individual components to demonstrate their functionality. The results section is reserved for demonstrating the use of the detector response function as a whole. We provide the modeled pulse-height spectra for different radiation sources and user input parameters. These are compared to experimentally measured datasets. The second part of the dissertation concludes with a discussion of the benefits, drawbacks, and future improvements that could be made

Surface control system for the 15 meter hoop-column antenna

The 15-meter hoop-column antenna fabricated by the Harris Corporation under contract to the NASA Langley Research Center is described. The antenna is a deployable and restowable structure consisting of a central telescoping column, a 15-meter-diameter folding hoop, and a mesh reflector surface. The hoop is supported and positioned by 48 quartz cords attached to the column above the hoop, and by 24 graphite cords from the base of the antenna column. The RF reflective surface is a gold plated molybdenum wire mesh supported on a graphite cord truss structure which is attached between the hoop and the column. The surface contour is controlled by 96 graphite cords from the antenna base to the rear of the truss assembly. The antenna is actually a quadaperture reflector with each quadrant of the surface mesh shaped to produce an offset parabolic reflector. Results of near-field and structural tests are given. Controls structures and electromagnetics interaction, surface control system requirements, mesh control adjustment, surface control system actuator assembly, surface control system electronics, the system interface unit, and control stations are discussed

Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier function and heat shock proteins in intestinal porcine epithelial cells

Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic, Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on cytoprotective HSP expression and gut barrier function, were investigated in a porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells polarized on a permeable filter exhibited villus-like cell phenotype with development of apical microvilli. Western blot analysis detected HSP expression in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG did not. For HSP72, only the supernatant of L. reuteri induced the expression, which was comparable to the heat shock treatment, which indicated that HSP72 expression was more stimulus-specific. The protective effect of lactobacilli was further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC) challenge. ETEC caused intestinal barrier destruction, as reflected by loss of cell-cell contact, reduced IPEC-J2 cell viability and transepithelial electrical resistance, and disruption of tight junction protein zonula occludens-1. In contrast, the L. reuteri treatment substantially counteracted these detrimental effects and preserved the barrier function. L. johnsonii and LGG also achieved barrier protection, partly by directly inhibiting ETEC attachment. Together, the results indicate that specific strains of Lactobacillus can enhance gut barrier function through cytoprotective HSP induction and fortify the cell protection against ETEC challenge through tight junction protein modulation and direct interaction with pathogens

Extracellular membrane vesicles from Limosilactobacillus reuteri strengthen the intestinal epithelial integrity, modulate cytokine responses and antagonize activation of TRPV1

Bacterial extracellular membrane vesicles (MV) are potent mediators of microbe-host signals, and they are not only important in host-pathogen interactions but also for the interactions between mutualistic bacteria and their hosts. Studies of MV derived from probiotics could enhance the understanding of these universal signal entities, and here we have studied MV derived from Limosilactobacillus reuteri DSM 17938 and BG-R46. The production of MV increased with cultivation time and after oxygen stress. Mass spectrometry-based proteomics analyses revealed that the MV carried a large number of bacterial cell surface proteins, several predicted to be involved in host-bacteria interactions. A 5 '-nucleotidase, which catalyze the conversion of AMP into the signal molecule adenosine, was one of these and analysis of enzymatic activity showed that L. reuteri BG-R46 derived MV exhibited the highest activity. We also detected the TLR2 activator lipoteichoic acid on the MV. In models for host interactions, we first observed that L. reuteri MV were internalized by Caco-2/HT29-MTX epithelial cells, and in a dose-dependent manner decreased the leakage caused by enterotoxigenic Escherichia coli by up to 65%. Furthermore, the MV upregulated IL-1 beta and IL-6 from peripheral blood mononuclear cells (PBMC), but also dampened IFN-gamma and TNF-alpha responses in PBMC challenged with Staphylococcus aureus. Finally, we showed that MV from the L. reuteri strains have an antagonistic effect on the pain receptor transient receptor potential vanilloid 1 in a model with primary dorsal root ganglion cells from rats. In summary, we have shown that these mobile nanometer scale MV reproduce several biological effects of L. reuteri cells and that the production parameters and selection of strain have an impact on the activity of the MV. This could potentially provide key information for development of innovative and more efficient probiotic products

Непрямий метод визначення діаграми випромінювання антени з невідомим параболоїдним профілем

Lactobacillus reuteri is a symbiont that inhabits the gastrointestinal (GI) tract of mammals, and several strains are used as probiotics. After introduction of probiotic strains in a complex ecosystem like the GI tract, keeping track of them is a challenge. The main objectives of this study were to introduce reporter proteins that would enable in vivo and in vitro detection of L. reuteri and increase knowledge about its interactions with the host. We describe for the first time cloning of codon-optimized reporter genes encoding click beetle red luciferase (CBRluc) and red fluorescent protein mCherry in L. reuteri strains ATCC PTA 6475 and R2LC. The plasmid persistence of mCherry-expressing lactobacilli was evaluated by both flow cytometry (FCM) and conventional plate count (PC), and the plasmid loss rates measured by FCM were lower overall than those determined by PC. Neutralization of pH and longer induction duration significantly improved the mCherry signal. The persistency, dose-dependent signal intensity and localization of the recombinant bacteria in the GI tract of mice were studied with an in vivo imaging system (IVIS), which allowed us to detect fluorescence from 6475-CBRluc-mCherry given at a dose of 1x10(10) CFU and luminescence signals at doses ranging from 1x10(5) to 1x10(10) CFU. Both 6475-CBRluc-mCherry and R2LC-CBRluc were localized in the colon 1 and 2 h after ingestion, but the majority of the latter were still found in the stomach, possibly reflecting niche specificity for R2LC. Finally, an in vitro experiment showed that mCherry-producing R2LC adhered efficiently to the intra cellular junctions of cultured IPEC-J2 cells. In conclusion, the two reporter genes CBRluc and mCherry were shown to be suitable markers for biophotonic imaging (BPI) of L. reuteri and may provide useful tools for future studies of in vivo and in vitro interactions between the bacteria and the host

Distinct B cell subsets in Peyer's patches convey probiotic effects by Limosilactobacillus reuteri

Background: Intestinal Peyer's patches (PPs) form unique niches for bacteria-immune cell interactions that direct host immunity and shape the microbiome. Here we investigate how peroral administration of probiotic bacterium Limosilactobacillus reuteri R2LC affects B lymphocytes and IgA induction in the PPs, as well as the downstream consequences on intestinal microbiota and susceptibility to inflammation.Results: The B cells of PPs were separated by size to circumvent activation-dependent cell identification biases due to dynamic expression of markers, which resulted in two phenotypically, transcriptionally, and spatially distinct subsets: small IgD(+)/GL7(-)/S1PR1(+)/Bcl6, CCR6-expressing pre-germinal center (GC)-like B cells with innate-like functions located subepithelially, and large GL7(+)/S1PR1(-)/Ki67(+)/Bcl6, CD69-expressing B cells with strong metabolic activity found in the GC. Peroral L. reuteri administration expanded both B cell subsets and enhanced the innate-like properties of pre-GC-like B cells while retaining them in the sub-epithelial compartment by increased sphingosine-1-phosphate/S1PR1 signaling. Furthermore, L. reuteri promoted GC-like B cell differentiation, which involved expansion of the GC area and autocrine TGF beta-1 activation. Consequently, PD-1-T follicular helper cell-dependent IgA induction and production was increased by L. reuteri, which shifted the intestinal microbiome and protected against dextran-sulfate-sodium induced colitis and dysbiosis.Conclusions: The Peyer's patches sense, enhance and transmit probiotic signals by increasing the numbers and effector functions of distinct B cell subsets, resulting in increased IgA production, altered intestinal microbiota, and protection against inflammation

FMD vaccine matching: Inter laboratory study for improved understanding of r1 values

Foot-and-mouth disease virus (FMDV) is a highly variable RNA virus existing as seven different serotypes. The antigenic variability between and within serotypes can limit the cross-reactivity and therefore the in vivo cross-protection of vaccines. Selection of appropriate vaccine strains is crucial in the control of FMD. Determination of indirect relationships (r1-value) between potential vaccine strains and field strains based on antibody responses against both are routinely used for vaccine matching purposes. Aiming at the investigation of the repeatability, reproducibility and comparability of r1-value determination within and between laboratories and serological tests, a small scale vaccine matching ring test for FMDV serotype A was organized. Well-characterized serum pools from cattle vaccinated with a monovalent A24/Cruzeiro/Brazil/55 (A24) FMD vaccine with known in vivo protection status (homologous and heterologous) were distributed to four laboratories to determine r1-values for the heterologous FMD strains A81/Argentina/87, A/Argentina/2000 and A/Argentina/2001 using the virus neutralization tests (VNT) and liquid phase blocking ELISA (LPBE). Within laboratories, the repeatability of r1-value determination was high for both antibody assays. VNT resulted in reproducible and comparable r1-values between laboratories, indicative of a lack of antigenic relatedness between the A24 strain and the heterologous strains tested in this work, thus corresponding to some of the in vivo findings with these strains. Using LPBE, similar trends in r1-values were observed in all laboratories, but the overall reproducibility was lower than with VNT. Inconsistencies between laboratories may at least in part be attributed to differences in LPBE protocols as well as the in preexisting information generated in each laboratory (such as antibody titer-protection correlation curves). To gain more insight in the LPBE-derived r1-values standard bovine control sera were included in the antibody assays performed in each laboratory and a standardization exercise was performed.Fil: Willems, Tom. No especifíca;Fil: De Vleeschauwer, Annebel. No especifíca;Fil: Pérez Filgueira, Daniel Mariano. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Virologia E Innovaciones Tecnologicas. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Virologia E Innovaciones Tecnologicas.; ArgentinaFil: Li, Yanmin. No especifíca;Fil: Ludi, Anna. No especifíca;Fil: Lefebvre, David. No especifíca;Fil: Wilsden, Ginette. No especifíca;Fil: Statham, Bob. No especifíca;Fil: Haas, Bernd. Federal Research Institute for Animal Health; AlemaniaFil: Mattion, Nora Marta. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; ArgentinaFil: Robiolo, Blanca. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; ArgentinaFil: Beascoechea Perez, Claudia. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Maradei, Eduardo. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Smitsaart, Eliana. Biogénesis Bagó; ArgentinaFil: la Torre, Jose Leonardo. Ministerio de Produccion y Trabajo. Secretaria de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virologia Animal. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Virologia Animal.; ArgentinaFil: De Clercq, Kris. No especifíca

Increased Recruitment but Impaired Function of Leukocytes during Inflammation in Mouse Models of Type 1 and Type 2 Diabetes

BACKGROUND: Patients suffering from diabetes show defective bacterial clearance. This study investigates the effects of elevated plasma glucose levels during diabetes on leukocyte recruitment and function in established models of inflammation. METHODOLOGY/PRINCIPAL FINDINGS: Diabetes was induced in C57Bl/6 mice by intravenous alloxan (causing severe hyperglycemia), or by high fat diet (moderate hyperglycemia). Leukocyte recruitment was studied in anaesthetized mice using intravital microscopy of exposed cremaster muscles, where numbers of rolling, adherent and emigrated leukocytes were quantified before and during exposure to the inflammatory chemokine MIP-2 (0.5 nM). During basal conditions, prior to addition of chemokine, the adherent and emigrated leukocytes were increased in both alloxan- (62±18% and 85±21%, respectively) and high fat diet-induced (77±25% and 86±17%, respectively) diabetes compared to control mice. MIP-2 induced leukocyte emigration in all groups, albeit significantly more cells emigrated in alloxan-treated mice (15.3±1.0) compared to control (8.0±1.1) mice. Bacterial clearance was followed for 10 days after subcutaneous injection of bioluminescent S. aureus using non-invasive IVIS imaging, and the inflammatory response was assessed by Myeloperoxidase-ELISA and confocal imaging. The phagocytic ability of leukocytes was assessed using LPS-coated fluorescent beads and flow cytometry. Despite efficient leukocyte recruitment, alloxan-treated mice demonstrated an impaired ability to clear bacterial infection, which we found correlated to a 50% decreased phagocytic ability of leukocytes in diabetic mice. CONCLUSIONS/SIGNIFICANCE: These results indicate that reduced ability to clear bacterial infections observed during experimentally induced diabetes is not due to reduced leukocyte recruitment since sustained hyperglycemia results in increased levels of adherent and emigrated leukocytes in mouse models of type 1 and type 2 diabetes. Instead, decreased phagocytic ability observed for leukocytes isolated from diabetic mice might account for the impaired bacterial clearance

Re-storying and visualizing the changing entrepreneurial identities of Bill Gates and Richard Branson.

The storytelling in textual and visual re-constructions of Bill Gates and Richard Branson by their organizations produces entrepreneurial identities bound into particular social power-knowledge relations. Our purpose is to examine how these organizations, and their critics, mobilize storytelling in acts of re-storying (enlivening) or re-narrating (branding a monologic) practices using Internet technologies to invite viewers to frame the world of entrepreneurship. We use visual discourse and storytelling methods to analyze how Microsoft and Virgin Group use various kinds of entrepreneurial images and textual narratives to re-narrate and produce particular brands of capitalism. These organizations' scoptic regimes of representation are contested in counter-visualizing and counterstory practices of external stakeholders. We suggest that the image and textual practices of storytelling have changed as both entrepreneurs court philanthropic and social entrepreneur identity markers. Our contribution to entrepreneurial identity is to apply double and multiple narrations, the appropriation of another's narrative words (or images) into another's narrative, and relate such storytelling moves to visuality