The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.     

How does a bank's involvement interplay with a firm's capacity investment? An analysis and comparison of different consortium structures

As nonrecourse project finance (rather than financing on a sovereign basis) is becoming more prevalent worldwide, financing institutions have to collaborate more closely with firms to optimize capacity‐investment and financing decisions. Under this background, this paper presents a stylized Stackelberg games model, taking into account the firm's capacity investment as well as the bank's interest rate and funding ratio decisions. Consortium structures between bank and firm are formalized into five modes based on industry practice, namely, the integrated consortium, pure shareholder funding, bank as leader, full coordination, and bank as follower. The optimality and equilibrium of each of the five modes are analytically derived, and their existence and uniqueness are demonstrated. Valuable economic insights are obtained through both modeling analysis and numerical experiments, with the main findings including the following: (i) a lack of bank financing leads to insufficient capacity investment and poor consortium performance; (ii) interest rate and funding ratio play important but different roles in the bank's risk management; (iii) the bank's proactivity in leading and coordinating the consortium is critical for the two parties’ overall performance; and (iv) if the bank is the follower, the firm's capacity decision is irrelevant to the bank's loan contract, and the consortium cannot be coordinated to the first‐best level of performance.     

Evaluation of the electrical integrity of E-textiles subjected to environmental conditions

E-textiles contain electrically conductive elements and electronic devices that are integrated in textile substrate. Wearable e-textiles are expected to perform like textiles in terms of breathability, conformability, and comfort despite the presence of the electrically conductive elements and electronics. E-textiles are also expected to provide reliable data and signal processing like electronic devices while they are subjected to normal wear and tear under different environmental conditions. The goal of this research was to investigate the electrical integrity of e-textiles while they are subjected to environmental conditions. Different woven samples of electronic-improved outer tactical vest with two narrow conductive traces woven in the warp direction were subjected to range of temperatures and humidity, including extreme conditions. The effects of formation parameters (e-yarn type, number of e-yarns/trace, and weldability), temperature, and humidity on the integrity of the e-textiles were studied. It was found that resistance of networks was affected by changes in air temperature and humidity and the quality of the weld had the greatest impact on electrical integrity of the conductive network. This impact was pronounced in more extreme environmental conditions, which revealed that there was a strong interaction between the weldability, temperature, and humidity.     

Porosity measurements in suspension plasma sprayed YSZ coatings using NMR cryoporometry and X-ray microscopy

A large variety of coatings are used to protect structural engineering materials from corrosion, wear, and erosion, and to provide thermal insulation. In this work, yttria-stabilized zirconia coatings produced by suspension plasma spraying were investigated with respect to their microstructure and especially their porosity, as the porosity affects the thermal insulation of the underlying component. To determine porosity, pore size distribution, and pore shape, the coatings were investigated using novel advanced characterization techniques like NMR cryoporometry and X-ray microscopy. In general, the porosity is inhomogeneously distributed and the coatings showed a large variety of pore sizes ranging from a few nanometers to micrometers.     

The application of decision support tools and the influence of local data in prioritizing barrier removal in lower Michigan,USA

Web-based decision support tools (DSTs) can be useful to facilitate decision-making processes for managing complex natural resource systems. However, the alignment of DSTs with the objectives in governmental policies or management plans and the influence of limited local data on the outputs of these tools may reduce the use of DSTs by decision makers. In this study, we examined the outcomes of web-based DSTs when different types of local data were incorporated and demonstrated a way to incorporate outputs from multiple DSTs or local inventories to benefit barrier removal decisions. Restoring habitat connectivity in rivers in northwest lower Michigan, USA, was used as a case study due to the abundance of local inventory data and web-based DSTs. We found that, when compared to prioritizations made using local data, some DSTs could produce similar outcomes (in barriers selected, cost, and the benefit for migratory fish) with limited data, but the trade-offs among users' objectives might influence the cost and effectiveness of DSTs' outputs. Improving the ability of DSTs to incorporate objectives consistent with policy and stakeholders' values (e.g., restore certain species or sedimentation control) across management scales can help close the gap between tool recommendations and management decisions while making the barrier removal prioritization process transparent and efficient.     

Azaaurones as Potent Antimycobacterial Agents Active against MDR- and XDR-TB

Herein we report the screening of a small library of aurones and their isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm , whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC₉₉ values ranging from 0.4 to 2.0 μm . In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical M. tuberculosis isolates. The antimycobacterial mechanism of action of these compounds remains to be determined; however, a preliminary mechanistic study confirmed that they do not inhibit the mycobacterial cytochrome bc1 complex. Additionally, microsomal metabolic stability and metabolite identification studies revealed that N-acetylazaaurones are deacetylated to their azaaurone counterparts. Overall, these results demonstrate that azaaurones and their N-acetyl counterparts represent a new entry in the toolbox of chemotypes capable of inhibiting M. tuberculosis growth.     

Status of Mysis diluviana in Lake Ontario in 2013: Lower abundance but higher fecundity than in the 1990s

Mysis diluviana is a major component of prey fish diets in the Great Lakes, so annual production of M. diluviana is important for understanding and modeling energy flow through Great Lakes food webs. However, only three lake-wide measurements of M. diluviana annual production in Lake Ontario are currently available (1971, 1990, 1995). During 2013, lake-wide coverage of Lake Ontario was achieved during four periods from April to November. Annual mean density and biomass of M. diluviana in 2013 were 99?#/m² (SE: 8) and 318?mg?dw/m² (SE: 28) – approximately half of values observed in 1990s. M. diluviana comprised 13–30% of offshore zooplankton biomass in each period. Reproduction peaked in fall, with mean brood size of 32 embryos (range: 11–49), at least 10% larger than in 1990s. Generation time was two years from embryo to initial reproduction. Growth rates were 0.052?mm/d for the age-0 cohort and 0.027?mm/d for the age-1 cohort. Age-0 growth rate was significantly higher than in 1980s–90s (0.035?mm/d). Annual production in 2013 was 0.85?g?dw/m²/yr (SE: 0.03) which was 30–40% of values observed in 1990 and 1995 (2.23 and 2.53?g/m²/yr). Annual production to biomass ratio (P/B) in 2013 was 2.65?/yr which was 80–85% of values observed in 1990 and 1995 (3.24 and 3.11?/yr), but this difference was not statistically significant. Our results suggest that changes in annual production over time can be estimated using changes in biomass over time and a mean P/B ratio.     

Mechanical Properties of an Fe‐Based SAM2×5‐630 Metallic Glass Matrix Composite with Tungsten Particle Additions

We present the role of tungsten additions on the mechanical properties of a Fe‐based structural amorphous metal (SAM2×5‐630) containing crystalline tungsten. Matrix cracking by microindentation is inhibited by the addition of tungsten and indicates that tungsten improves the fracture toughness. Response surfaces from nanoindentation arrays indicate that the hardness and modulus of the matrix phase are increased by tungsten additions. Bulk composites with 30 vol% tungsten subjected to 4‐point flexure exhibited brittle fracture behavior and the characteristic strength and Weibull modulus were 165 and 8.7 MPa, respectively. The addition of tungsten did not cause devitrification of the matrix phase.