Explore the vast range of titles available.

Encryption protocols are exploited and broken, and organizations have been found to have poor encryption practices. The purpose of this research project is to determine if current encryption protocols are safe and if organizations are capable of properly implementing encryption. The research project found that while current encryption protocols may sometimes have vulnerabilities, those vulnerabilities are quickly patched. Eventually, current encryption protocols will be made obsolete by advancing technologies. In the present, many organizations have demonstrated an inability to apply good encryption practices, which makes them unlikely to be prepared for future advancements in encryption.

Basalts are windows into the mantle from which they were derived, and their eruption at the surface provides an opportunity to probe the conditions in the mantle that lead to their formation including temperature, water content, and oxidation state. In this thesis, Quaternary basalts from three localities in the Basin and Range (western Basin and Range, the Mojave Desert, Yellowstone/Snake River Plain) are examined to evaluate how temperature and dissolved water content vary as a function of mantle source (i.e., subduction-modified lithosphere, asthenosphere, mantle plume). In Chapters 2 and 3, basalts that contain mantle xenoliths were, which requires rapid transit through the crust and precludes prolonged storage in crustal magma chambers. Instead, the hypothesis of rapid phenocryst growth of olivine during ascent along fractures was evaluated. A second hypothesis that was tested is whether the most Mg-rich olivine analyzed in each sample matches the expected liquidus composition for a basalt with the whole-rock composition. For all samples that passed olivine-melt liquidus tests, olivine-melt thermometry and hygrometry were applied at the liquidus. This gives the temperature and melt water content at the onset of phenocryst growth. In Chapter 2, the hypothesis of rapid phenocryst growth during ascent was tested for a suite of 10 basalts from the Big Pine volcanic field, CA, one of which contains mantle xenoliths. Olivine and clinopyroxene phenocrysts display diffusion-limited growth textures, which is consistent with rapid phenocryst growth during ascent. When the most Mg-rich olivine composition in each sample is paired with the whole-rock composition, all olivine-melt equilibrium tests are passed. Application of olivine-melt thermometry and hygrometry at the liquidus gives temperatures (~1250-1100 °C) that vary with MgO content (~13-7 wt%), and water contents that range from ~1.5-3.0, which matches those analyzed in olivine-hosted melt inclusions from the literature. In Chapter 3, alkaline lavas from the Mojave Desert (Cima volcanic field and Dish Hill, CA) were targeted due to their mantle xenoliths. Several of the xenolith-bearing samples are notable for their low MgO content (as low as 5 wt%) and are not direct partial melts of mantle. Thus, an outstanding question is how they were able to carry mantle xenoliths to the surface, if they first underwent fractional crystallization. Although evidence of rapid phenocryst growth is present in all samples, the most Mg-rich olivine in each sample fails olivine-melt equilibrium tests. The only hypothesis that could not be disproven is that magma mixing between two (or more) melts occurred rapidly during ascent along fractures, one of which is a high-MgO melt with entrained mantle xenoliths. In Chapter 4, Quaternary basalts adjacent to the active Yellowstone volcanic field and along the Snake River Plain were examined. Despite the absence of any mantle xenoliths, the most Mg-rich olivine analyzed in 15 of 16 basalts pass olivine-melt equilibrium tests. Application of olivine-melt thermometry and hygrometry give temperatures of ~1200-1130°C and water contents ≤ 1.8 wt% (which match H2O analyses in olivine-hosted melt inclusions from the literature). The YS/SRP basalts are not anomalously hot, have modest melt water contents, and relatively low Mg# values, which is consistent a larger volume of melt.In Chapter 5 olivine-melt equilibrium experiments were performed to evaluate chemical equilibrium in an undercooled Big Pine basalt that experienced a kinetic delay to nucleation. All experiments indicate chemical equilibrium is preserved despite textural disequilibrium in undercooled experiments.

This article examines selected school-based prevention programs that represent a dual focus of risk attenuation and competency promotion and exemplify a shift from risk to resilience in the prevention of antisocial behavior. A rationale explaining why a resilience framework broadens and reframes our understanding of variables associated with the onset, escalation, and desistance of antisocial behavior is presented. Empirically validated classroom, school-wide and multisetting approaches are evaluated in relation to nine critical resiliency mechanisms hypothesized to protect against and deter antisocial behavior. Characteristics of improved outcomes are identified and conclusions drawn for enhancing future efforts. Given the multiple personal difficulties and negative societal repercussions associated with antisocial behavior, there is an urgent need for preventive school-based efforts that increase resilience in this critical population.

Smokers with more than a 10-pack-year history of smoking who were part of an ongoing study had CT scans and lung-function tests. Approximately 1 in 12 had interstitial abnormalities; these patients had less emphysema and lower total lung capacities than did patients without such changes. The relationship between exposure to tobacco smoke and chronic obstructive pulmonary disease (COPD) is well described. 1 Two manifestations of COPD include emphysematous destruction of the lung parenchyma and elevated measures of total lung capacity. 2 However, there is increasing awareness that smoking may also result in areas of increased lung density — termed interstitial lung abnormalities — on high-resolution computed tomography (HRCT). 3 , 4 The extent to which interstitial lung abnormalities may be associated with a lesser amount of emphysema and lower measures of total lung capacity than anticipated on the basis of known smoking exposure is unclear. We determined the relationship . . .

Mast cells (MC) are key drivers of allergic and inflammatory diseases. Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 is an immunoregulatory receptor found on MCs. While it is recognized that engaging Siglecs with antibodies mediates inhibition across immune cells, the mechanisms that govern this agonism are not understood. Here we generated Siglec-6 mAb clones (AK01 to AK18) to better understand Siglec-6-mediated agonism. Siglec-6 mAbs displayed epitope-dependent receptor internalization and inhibitory activity. We identified a Siglec-6 mAb (AK04) that required Fc-mediated interaction for receptor internalization and induced inhibition and antibody-dependent cellular phagocytosis against MCs. AK04-mediated MC inhibition required Siglec-6 immunoreceptor tyrosine-based inhibitory motif (ITIM) and ITIM-like domains and was associated with receptor cluster formation containing inhibitory phosphatases. Treatment of humanized mice with AK04 inhibited systemic anaphylaxis with a single dose and reduced MCs with chronic dosing. Our findings suggest Siglec-6 activity is epitope dependent and highlight an agonistic Siglec-6 mAb as a potential therapeutic approach in allergic disease. An agonistic Siglec-6 antibody that binds to a membrane-distal domain of Siglec-6 is identified that induces inhibition and reduction of mast cells and suppresses anaphylaxis in a humanized mouse model.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection 1 , 2 , yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases. A cross-reactive antibody and T cell response is identified in a large portion of patients with multisystem inflammatory syndrome in children.

Physical activity is a modifiable lifestyle factor that is associated with a decreased risk for the development of breast cancer. While the exact mechanisms for the reduction in cancer risk due to physical activity are largely unknown, it is postulated that the biological reduction in cancer risk is driven by improvements in inflammation and immune function with exercise. Hematopoietic stem cells (HSCs) are the progenitor for all of the cells of the immune system and are involved in cancer immunosurveillance through differentiation into cytotoxic cell population. In this study, we investigate the role of physical activity (PA) in a spontaneously occurring model of breast cancer over time, with a focus on tumor incidence, circulating and tumor-infiltrating immune cells as well gene expression profiles of tumors and hematopoietic stem cells. Furthermore, we show that, in addition to a direct effect of PA on the immune cells of tumor-bearing mice, PA reduces the oxidative stress in HSCs of wildtype and tumor-bearing mice, and by doing so, alters the differentiation of the HSCs towards T cells in order to enhance cancer immunosurveillance.Physical activity is a modifiable lifestyle factor that is associated with a decreased risk for the development of breast cancer. While the exact mechanisms for the reduction in cancer risk due to physical activity are largely unknown, it is postulated that the biological reduction in cancer risk is driven by improvements in inflammation and immune function with exercise. Hematopoietic stem cells (HSCs) are the progenitor for all of the cells of the immune system and are involved in cancer immunosurveillance through differentiation into cytotoxic cell population. In this study, we investigate the role of physical activity (PA) in a spontaneously occurring model of breast cancer over time, with a focus on tumor incidence, circulating and tumor-infiltrating immune cells as well gene expression profiles of tumors and hematopoietic stem cells. Furthermore, we show that, in addition to a direct effect of PA on the immune cells of tumor-bearing mice, PA reduces the oxidative stress in HSCs of wildtype and tumor-bearing mice, and by doing so, alters the differentiation of the HSCs towards T cells in order to enhance cancer immunosurveillance.

During aging, adipose tissue within the bone marrow expands while the trabecular red marrow contracts. The impact of these changes on blood cell formation remains unclear. To address this question, we performed single-cell and single-nuclei transcriptomic analysis on adipose-rich yellow bone marrow (BMY) and adipose-poor trabecular red marrow (BMR) from human subjects undergoing lower limb amputations. Surprisingly, we discovered two distinct hematopoietic niches, in which BMY contains a higher number of monocytes and progenitor cells expressing genes associated with inflammation. To further investigate these niches, we developed an in-vitro organoid system that maintains features of the human bone marrow. We find cells from BMY are distinct in their expression of the leptin receptor, and respond to leptin stimulation with enhanced proliferation, leading to increased monocyte production. These findings suggest that the age-associated expansion of bone marrow adipose tissue drives a pro-inflammatory state by stimulating monocyte production from a spatially distinct, leptin-responsive hematopoietic stem/progenitor cell population. This study reveals that adipose tissue within the human bone marrow is a niche for hematopoietic stem and progenitor cells that can give rise to pro-inflammatory monocytes through leptin signaling. Expansion of bone marrow adipose tissue with age and stress may thus underlie inflammageing.