A cathode support structure for use in a magnetron oscillator experiment

A low temperature co-fired ceramic (LTCC) material system has been used to develop a protype field emission cathode structure for use in an experimental magnetron oscillator. The structure is designed for used with 30 gated field emission array (GFEA) die electrically connected through silver metal traces and electrical vias. To approximate a cylinder, the cathode structure (48 mm long and 13.7 mm in diameter) is comprised of 10 faceted plates which cover the GFEA dies. Slits in the facet plates allow electron injection. The GFEA die (3 mm × 8 mm) are placed in axial columns of 3 and spaced azimuthally around a cylindrical support structure in a staggered configuration resulting in 10 azimuthal locations. LTCC manufacturing techniques were developed in order to fabricate the newly designed cathode with seven layers wrapped to form the cylinder with electrical traces and vias. Two different cathode wrapping techniques and two different via filling techniques were studied and compared. Two different facet plate manufacturing techniques were studied. Finally, four different support stand configurations for firing the cylindrical structure were also compared with a square post stand having the best circularity and linearity measurements of the fired structure.     

Assembly and Characterization of Biocompatible Coenzyme Q10-Enriched Lipid Nanoparticles

Coenzyme Q₁₀ (CoQ₁₀) is a strongly hydrophobic lipid that functions in the electron transport chain and as an antioxidant. CoQ₁₀ was conferred with aqueous solubility by incorporation into nanoparticles containing phosphatidylcholine (PtdCho) and apolipoprotein (apo) A-I. These particles, termed CoQ₁₀ nanodisks (ND), contain 1.0 mg CoQ₁₀/5 mg PtdCho/2 mg apoA-I (97% CoQ₁₀ solubilization efficiency). UV/Vis absorbance spectroscopy of CoQ₁₀ ND revealed a characteristic absorbance peak centered at 275 nm. Incorporation of CoQ₁₀ into ND resulted in quenching of apoA-I tryptophan fluorescence emission. Gel filtration chromatography of CoQ₁₀ ND gave rise to a single major absorbance peak and HPLC of material extracted from this peak confirmed the presence of CoQ₁₀. Incubation of cultured cells with CoQ₁₀ ND, but not empty ND, resulted in a significant increase in the CoQ₁₀ content of mitochondria as well as enhanced oxidative phosphorylation, as observed by a ~24% increase in maximal oxygen consumption rate. Collectively, a facile method to solubilize significant quantities of CoQ₁₀ in lipid nanoparticles has been developed. The availability of CoQ₁₀ ND provides a novel means to investigate biochemical aspects of CoQ₁₀ uptake by cells and/or administer it to subjects deficient in this key lipid as a result of inborn errors of metabolism, statin therapy, or otherwise.     

Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells

The cAMP-dependent aquaporin-2 (AQP2) redistribution from intracellular vesicles into the plasma membrane of renal collecting duct principal cells induces water reabsorption and fine-tunes body water homeostasis. However, the mechanisms controlling the localization of AQP2 are not understood in detail. Using immortalized mouse medullary collecting duct (MCD4) and primary rat inner medullary collecting duct (IMCD) cells as model systems, we here discovered a key regulatory role of Aurora kinase A (AURKA) in the control of AQP2. The AURKA-selective inhibitor Aurora-A inhibitor I and novel derivatives as well as a structurally different inhibitor, Alisertib, prevented the cAMP-induced redistribution of AQP2. Aurora-A inhibitor I led to a depolymerization of actin stress fibers, which serve as tracks for the translocation of AQP2-bearing vesicles to the plasma membrane. The phosphorylation of cofilin-1 (CFL1) inactivates the actin-depolymerizing function of CFL1. Aurora-A inhibitor I decreased the CFL1 phosphorylation, accounting for the removal of the actin stress fibers and the inhibition of the redistribution of AQP2. Surprisingly, Alisertib caused an increase in actin stress fibers and did not affect CFL1 phosphorylation, indicating that AURKA exerts its control over AQP2 through different mechanisms. An involvement of AURKA and CFL1 in the control of the localization of AQP2 was hitherto unknown.     

Characteristics of Bi-metallic Interfaces Formed During Direct Energy Deposition Additive Manufacturing Processing

Metallurgical and Materials Transactions B - Various additive manufacturing processes are being evaluated to reduce the time and cost for fabrication of low volume, complex, and multifunctional...     

Transcriptional and functional responses of Escherichia coli O157:H7 growing in the lettuce rhizoplane

Lettuce and spinach are increasingly implicated in foodborne illness outbreaks due to contamination by Escherichia coli O157:H7. While this bacterium has been shown to colonize and survive on lettuce leaf surfaces, little is known about its interaction with the roots of growing lettuce plants. In these studies, a microarray analyses, mutant construction and confocal microscopy were used to gain an understanding of structure and function of bacterial genes involved in the colonization and growth of E. coli O157:H7 on lettuce roots. After three days of interaction with lettuce roots, 94 and 109 E. coli O157:H7 genes were significantly up- and down-regulated at least 1.5 fold, respectively. While genes involved in biofilm modulation (ycfR and ybiM) were significantly up-regulated, 40 of 109 (37%) of genes involved in protein synthesis were significantly repressed. E. coli O157:H7 was 2 logs less efficient in lettuce root colonization than was E. coli K12. We also unambiguously showed that a ΔycfR mutant of E. coli O157:H7 was unable to attach to or colonize lettuce roots. Taken together these results indicate that bacterial genes involved in attachment and biofilm formation are likely important for contamination of lettuce plants with Shiga toxin-producing E. coli strains.     

Impaired hepatic autophagic activity in dairy cows with severe fatty liver is associated with inflammation and reduced liver function

The ability of liver to respond to changes in nutrient availability is essential for the maintenance of metabolic homeostasis. Autophagy encompasses mechanisms of cell survival, including capturing, degrading, and recycling of intracellular proteins and organelles in lysosomes. During negative nutrient status, autophagy provides substrates to sustain cellular metabolism and hence, tissue function. Severe negative energy balance in dairy cows is associated with fatty liver. The aim of this study was to investigate the hepatic autophagy status in dairy cows with severe fatty liver and to determine associations with biomarkers of liver function and inflammation. Liver and blood samples were collected from multiparous cows diagnosed as clinically healthy (n = 15) or with severe fatty liver (n = 15) at 3 to 9 d in milk. Liver tissue was biopsied by needle puncture, and serum samples were collected on 3 consecutive days via jugular venipuncture. Concentrations of free fatty acids and β-hydroxybutyrate were greater in cows with severe fatty liver. Milk production, dry matter intake, and concentration of glucose were all lower in cows with severe fatty liver. Activities of serum aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, and γ-glutamyl transferase were all greater in cows with severe fatty liver. Serum concentrations of haptoglobin and serum amyloid A were also markedly greater in cows with severe fatty liver. The mRNA expression of autophagosome formation-related gene ULK1 was lower in the liver of dairy cows with severe fatty liver. However, the expression of other autophagosome formation-related genes, beclin 1 (BECN1), phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), autophagy-related gene (ATG) 3, ATG5, and ATG12, did not differ. More important, ubiquitinated proteins, protein expression of sequestosome-1 (SQSTM1, also called p62), and microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3)-II was greater in cows with severe fatty liver. Transmission electron microscopy revealed an increased number of autophagosomes in the liver of dairy cows with severe fatty liver. Taken together, these results indicate that excessive lipid infiltration of the liver impairs autophagic activity that may lead to cellular damage and inflammation.     

The use of small angle neutron scattering with contrast matching and variable adsorbate partial pressures in the study of porosity in activated carbons

The porosity of a typical activated carbon is investigated with small angle neutron scattering (SANS), using the contrast matching technique, by changing the hydrogen/deuterium content of the absorbed liquid (toluene) to extract the carbon density at different scattering vector (Q) values and by measuring the p/p₀ dependence of the SANS, using fully deuterated toluene. The contrast matching data shows that the apparent density is Q-dependent, either because of pores opening near the carbon surface during the activation processor or changes in D-toluene density in nanoscale pores. For each p/p₀ value, evaluation of the Porod Invariant yields the fraction of empty pores. Hence, comparison with the adsorption isotherm, shows that the fully dry powder undergoes densification when liquid is added. An algebraic function is developed to fit the SANS signal at each p/p₀ value hence yielding the effective Kelvin radii of the liquid surfaces as a function of p/p₀. These values, when compared with the Kelvin equation, show that the resultant surface tension value is accurate for the larger pores but tends to increase for small (nanoscale) pores. The resultant pore size distribution is less model-dependent than for the traditional methods of analyzing the adsorption isotherms.     

Role of physical structures in bulk oils on lipid oxidation

Lipid oxidation is important to food manufacturers especially when they increase unsaturated lipids in their products to improve nutritional profiles. Unfortunately, the number of antioxidants available to food manufacturers to control oxidative rancidity is limited and the approval of new antioxidants is unlikely due to economic barriers in obtaining government approval for new food additives. Therefore, new antioxidant technologies are needed for food oils. This paper reviews the current knowledge of lipid oxidation in foods with emphasis on how physical properties of food systems impact oxidation chemistry. In particular, the role of association colloids in bulk oils on lipid oxidation chemistry is discussed in an attempt to understand mechanisms of oxidation. Increasing the understanding of how physical properties impact lipid oxidation could lead to the development of novel antioxidant technologies that not only protect the oil against oxidation and increase shelf-life but also allow food manufacturers to include more nutritionally beneficial fatty acids in their products.     

Computer Simulations and Network-Based Profiling of Binding and Allosteric Interactions of SARS-CoV-2 Spike Variant Complexes and the Host Receptor: Dissecting the Mechanistic Effects of the Delta and Omicron Mutations

In this study, we combine all-atom MD simulations and comprehensive mutational scanning of S-RBD complexes with the angiotensin-converting enzyme 2 (ACE2) host receptor in the native form as well as the S-RBD Delta and Omicron variants to (a) examine the differences in the dynamic signatures of the S-RBD complexes and (b) identify the critical binding hotspots and sensitivity of the mutational positions. We also examined the differences in allosteric interactions and communications in the S-RBD complexes for the Delta and Omicron variants. Through the perturbation-based scanning of the allosteric propensities of the SARS-CoV-2 S-RBD residues and dynamics-based network centrality and community analyses, we characterize the global mediating centers in the complexes and the nature of local stabilizing communities. We show that a constellation of mutational sites (G496S, Q498R, N501Y and Y505H) correspond to key binding energy hotspots and also contribute decisively to the key interfacial communities that mediate allosteric communications between S-RBD and ACE2. These Omicron mutations are responsible for both favorable local binding interactions and long-range allosteric interactions, providing key functional centers that mediate the high transmissibility of the virus. At the same time, our results show that other mutational sites could provide a “flexible shield” surrounding the stable community network, thereby allowing the Omicron virus to modulate immune evasion at different epitopes, while protecting the integrity of binding and allosteric interactions in the RBD–ACE2 complexes. This study suggests that the SARS-CoV-2 S protein may exploit the plasticity of the RBD to generate escape mutants, while engaging a small group of functional hotspots to mediate efficient local binding interactions and long-range allosteric communications with ACE2.     

Real options valuation of US federal renewable energy research,development, demonstration,and deployment

Benefits analysis of US Federal government research, development, demonstration, and deployment (RD³) programmes for renewable energy (RE) technology improvement typically employs a deterministic forecast of the cost and performance of renewable and non-renewable fuels. The benefits estimate for the programme derives from the difference between two forecasts, with and without the RD³ programme in place. Three deficiencies of this approach are that it ignores: (1) uncertainty in the cost of non-renewable energy (NRE); (2) the possibility of adjustment to the RD³ effort commensurate with the evolving state of the world; and (3) the underlying technical risk associated with RD³. In this paper, an intuitive approach to determining the option value of RE RD³ is developed. This approach seeks to tackle the first two deficiencies noted above by providing an estimate via a compound real option of an RE RD³ programme in a future with uncertain NRE costs. A binomial lattice reveals the economic intuition underlying the decision-making process, while a numerical example illustrates the option components embedded in a simplified representation of current US Federal RE RD³.