Protective coatings for chromium alloys Final summary report, Nov. 1, 1965 - Jul. 13, 1967

Aluminum protective coatings for chromium alloy

Complex Roles of Macrophages in Lipid Metabolism and Metabolic Disease: A Dissertation

The worldwide prevalence of obesity and metabolic disease is increasing at an exponential rate and current projections provide no indication of relief. This growing burden of obesity-related metabolic disorders, including type 2 diabetes mellitus (T2DM), highlights the importance of identifying how lifestyle choices, genetics and physiology play a role in metabolic disease and place obese individuals at a greater risk for obesity-related complications including insulin resistance (IR). This increased risk of IR, which is characterized by a decreased response to insulin in peripheral tissues including adipose tissue (AT) and liver, is associated with a chronic, low grade inflammatory state; however, the causative connections between obesity and inflammation remains in question. Experimental evidence suggests that adipocytes and macrophages can profoundly influence obesity-induced IR because adipocyte dysfunction leads to ectopic lipid deposition in peripheral insulin sensitive tissues, and obese AT is characterized by increased local inflammation and macrophage and other immune cell populations. Attempts to delineate the individual roles of macrophage-derived pro-inflammatory cytokines, like tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), have demonstrated causative roles in impaired systemic insulin sensitivity, adipocyte function and hepatic glucose and lipid metabolism in obese animal models. Thus, the attenuation of macrophage-derived inflammation is an evolving area of interest to provide insight into the underlying mechanism(s) leading to obesity-induced IR. Thus, in the first chapter of this thesis, I describe experiments to refine the current paradigm of obesity-induced AT inflammation by combining gene expression profiling with computational analysis of two anatomically distinct AT depots, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) to address whether the inflammatory signature of AT is influenced by diet-induced obesity (DIO). Microarray and qRT-PCR analysis data revealed that DIO mouse SAT is resistant to high fat diet (HFD)-induced inflammation and macrophage infiltration, and our data support the current model of obesity-induced visceral adipose tissue macrophage (VATM) enrichment. Our data demonstrated robust increases in VAT pro-inflammatory cytokine expression, which are consistent with the significant increases in macrophage-specific gene expression and consistent with previous reports in which VAT inflammation is enhanced and attributed to classically activated (M1) macrophage infiltration. However, these data are only observed relative to the expression of invariant housekeeping gene expression. When M1-specific genes are expressed relative to macrophage-specific standards like F4/80 expression, these inflammatory makers are unchanged. These data indicate that the changes in the overall inflammatory profile of DIO mouse VAT is because of quantitative changes in adipose tissue macrophage (ATM) number and not qualitative changes in activation state. These observations are consistent with the idea that infiltrating ATMs may have roles other than the previously described role in mediating inflammation in obese adipose tissue. Hepatic IR occurs partly as a consequence of adipocyte dysfunction because the liver becomes a reservoir for AT-derived fatty acids (FAs), which leads to obesity-related non-alcoholic fatty liver disease (NAFLD). In the second part of my thesis, I used clodronate liposome-mediated macrophage depletion to define the role of macrophages in hepatic lipid metabolism regulation. We discovered that i.p. administration of clodronate liposomes depletes Kupffer cells (KCs) in ob/ob mice without affecting VATM content, whereas clodronate liposomes depletes both KCs and VATMs in DIO mice. To this end, we established that clodronate liposome-mediated KC depletion, regardless of VATM content in obese mice, abrogated hepatic steatosis by reducing hepatic de novo lipogenic gene expression. The observed reductions in hepatic inflammation in macrophage-depleted obese mice led to the hypothesis that IL-1β may be responsible for obesity-induced increased hepatic triglyceride (TG) accumulation. We determined that IL-1β treatment increases fatty acid synthase (Fas) protein expression and TG accumulation in primary mouse hepatocytes. Pharmacological inhibition of interleukin-1 (IL-1) signaling by interleukin-1 receptor antagonist (IL-1Ra) administration recapitulated these results by reducing hepatic TG accumulation and lipogenic gene expression in DIO mice. Thus, these data highlight the importance of the inflammatory cytokine IL-1β in obesity-driven hepatic steatosis and suggests that liver inflammation controls hepatic lipogenesis in obesity. To this end, the studies described herein provide new insight and appreciation to the multi-functional nature of macrophages and clinical implications for anti-inflammatory therapy in obesity and NAFLD treatment. We demonstrate the complexities of macrophage-mediated functions in insulin sensitive tissues and a role for obesity-induced inflammatory cytokine IL-1β in hepatic lipid metabolism modulation, which is reversed via IL-1Ra intervention. The use of anti-inflammatory therapy to ameliorate obesity-associated NAFLD was perhaps the most important contribution to this body of work and is full of promise for future clinical application. It is likely that the future of therapeutics will be multi-faceted and combine therapeutic approaches to enhance glucose tolerance and overall health in obese, IR and T2DM patients

Simulación (fem) de la distribución de esfuerzos de contacto en sistemas recubiertos bajo repetidas indentaciones

Este trabajo busca estudiar campos de esfuerzos obtenidos en un sistema recubierto (sustrato dúctil y un recubrimiento rígido) cuando se aplican repetidas indentaciones. Para esto, fue realizada una simulación FEM a través del software ABAQUS, considerando una malla bidimensional axisimétrica y un indentador esférico para la indentación, el cual aplica una carga normal de 50N. Los resultados permitieron observar que los valores de esfuerzos radiales en el borde del contacto no presentaron grandes diferencias a pesar de aumentar el número de ciclos de indentación, lo que sugiere que, después de la primera indentación el sistema conserva un comportamiento elástico haciendo necesario altos ciclos de carga para la falla del sistema

Análisis de simulación de esfuerzos y deformación plástica durante el contacto y deslizamiento de dos cuerpos

El objetivo se centra en estudiar el comportamiento de los esfuerzos equivalentes y la deformación plástica obtenidos como consecuencia de la aplicación de carga normal y desplazamiento tangencial de un penetrador rígido sobre un sustrato de aluminio. La simulación por el Método de los Elementos Finitos (MEF), utilizando el software ABAQUS, fue usado para evaluar los esfuerzos y los campos de deformaciones. El fenómeno fue simulado con una malla bidimensional, asumiendo el estado plano de deformaciones. Los resultados fueron obtenidos para diferentes valores de coeficiente de fricción entre el indentador rígido y la probeta de aluminio de comportamiento elasto-plástico

Análisis de simulación de esfuerzos y deformación plástica durante el contacto y deslizamiento de dos cuerpos

El objetivo se centra en estudiar el comportamiento de los esfuerzos equivalentes y la deformación plástica obtenidos como consecuencia de la aplicación de carga normal y desplazamiento tangencial de un penetrador rígido sobre un sustrato de aluminio. La simulación por el Método de los Elementos Finitos (MEF), utilizando el software ABAQUS, fue usado para evaluar los esfuerzos y los campos de deformaciones. El fenómeno fue simulado con una malla bidimensional, asumiendo el estado plano de deformaciones. Los resultados fueron obtenidos para diferentes valores de coeficiente de fricción entre el indentador rígido y la probeta de aluminio de comportamiento elasto-plástico

Simulación (fem) de la distribución de esfuerzos de contacto en sistemas recubiertos bajo repetidas indentaciones

Este trabajo busca estudiar campos de esfuerzos obtenidos en un sistema recubierto (sustrato dúctil y un recubrimiento rígido) cuando se aplican repetidas indentaciones. Para esto, fue realizada una simulación FEM a través del software ABAQUS, considerando una malla bidimensional axisimétrica y un indentador esférico para la indentación, el cual aplica una carga normal de 50N. Los resultados permitieron observar que los valores de esfuerzos radiales en el borde del contacto no presentaron grandes diferencias a pesar de aumentar el número de ciclos de indentación, lo que sugiere que, después de la primera indentación el sistema conserva un comportamiento elástico haciendo necesario altos ciclos de carga para la falla del sistema

2-(2-methyl-2-nitrovinyl)furan but not furvina interfere with staphylococcus aureus agr quorum-sensing system and potentiate the action of fusidic acid against biofilms

Quorum sensing (QS) plays an essential role in the production of virulence factors, in biofilm formation and antimicrobial resistance. Consequently, inhibiting QS is being consid-ered a promising target for antipathogenic/anti-virulence therapies. This study aims to screen 2-nitrovinylfuran derivatives structurally related to Furvina (a broad-spectrum antibiotic already used for therapeutic purposes) for their effects on QS and in biofilm prevention/control. Furvina and four 2-nitrovinylfuran derivatives (compounds 1–4) were tested to assess the ability to interfere with QS of Staphylococcus aureus using bioreporter strains (S. aureus ALC1742 and ALC1743). The activity of Furvina and the most promising quorum-sensing inhibitor (QSI) was evaluated in biofilm prevention and in biofilm control (combined with fusidic acid). The biofilms were further characterized in terms of biofilm mass, viability and membrane integrity. Compound 2 caused the most significant QS inhibition with reductions between 60% and 80%. Molecular docking simulations indicate that this compound interacts preferentially with the protein hydrophobic cleft in the LytTR domain of AgrA pocket. Metabolic inactivations of 40% for S. aureus ALC1742 and 20% for S. aureus ALC1743 were reached. A 24 h-old biofilm formed in the presence of the QSI increased the metabolic inactivation by fusidic acid to 80%, for both strains. The overall results highlight the effects of compound 2 as well as the potential of combining QSI with in-use antibiotics for the management of skin and soft tissues infections

Current Trends in Digital Twin Development, Maintenance, and Operation:An Interview Study

Digital twins (DT) are often defined as a pairing of a physical entity and a corresponding virtual entity mimicking certain aspects of the former depending on the use-case. In recent years, this concept has facilitated numerous use-cases ranging from design to validation and predictive maintenance of large and small high-tech systems. Although growing in popularity in both industry and academia, digital twins and the methodologies for developing and maintaining them differ vastly. To better understand these differences and similarities, we performed a semi-structured interview research study with 19 professionals from industry and academia who are closely associated with different lifecycle stages of the corresponding digital twins. In this paper, we present our analysis and findings from this study, which is based on eight research questions (RQ). We present our findings per research question. In general, we identified an overall lack of uniformity in terms of the understanding of digital twins and used tools, techniques, and methodologies for their development and maintenance. Furthermore, considering that digital twins are software intensive systems, we recognize a significant growth potential for adopting more software engineering practices, processes, and expertise in various stages of a digital twin's lifecycle