Role of Covalent Modification of Hyaluronan with Inter-Alpha Inhibitor Heavy Chains During Acute Lung Injury

Indiana University-Purdue University Indianapolis (IUPUI)The extracellular matrix (ECM) provides a structural and signaling platform for cells that comprise various organs, playing a critical role in tissue maintenance, injury, and repair. Hyaluronan (also known as hyaluronic acid, HA) is a ubiquitous ECM polysaccharide consisting of a repeating disaccharide backbone that can be covalently modified by the heavy chains (HC) of the serum protein inter-alpha-inhibitor (IαI) during inflammation. Known as the only covalent modification of HA, the HC linking of HA is exclusively mediated by the inflammation-induced secreted enzyme TNFα-stimulated gene-6 (TSG-6). Mice deficient for HC-HA formation, due to the lack of either TSG-6 or IαI, display reduced survival during systemic lipopolysaccharide (LPS)-induced endotoxic shock and its associated acute lung injury. We therefore hypothesized that HC-HA should play an important protective role against acute lung injury induced by intratracheal LPS or Pseudomonas aeruginosa (PA) gram-negative bacteria. We also identified that lung instillation of LPS or PA caused rapid induction of lung parenchymal HC-HA that was largely cleared during resolution of injury, indicative of a high rate of HA turnover and remodeling during reversible lung injury. However, using TSG-6 knockout mice, we determined that HC-HA exerted minimal protective effects against intratracheal LPS or PA-induced acute lung injury. To better address the differential roles of HC-HA during systemic versus localized intratracheal exposure to LPS, we characterized and compared the induction of HC-HA in plasma and lung in these two models. While lung parenchymal HC-HA formed in both injury models, intravascular HC-HA and TSG-6 were exclusively induced during systemic LPS exposure and were associated with improved outcomes, including decreased number of circulating neutrophils and plasma TNFα levels. Our results suggest that LPS induces HC-HA formation in various tissues depending on the route of exposure and that the specific intravascular induction of HCHA during systemic LPS exposure may have a protective role during endotoxic shock

Method Effects and the Need for Cognition Scale

Individual differences in the need for cognition are typically assessed using the 18-item Need for cognition scale (NCS) developed by Cacioppo and Petty (1982). However, in contrast to the unidimensional model proposed by the scale developers, recent factor analyses have introduced two -and three- dimensional models of the scale. Confirmatory factor analyses were used in this study to evaluate different measurement models based on data provided by 590 (236 males, 354 females) young adult members of the general public. Although some alternative models showed promise, a single factor model with method effects associated with positively and negatively worded items provided best fit. Implications for the asses sment of need for cognition are considered

A game-theoretic analysis of social responsibility conduct in two-echelon supply chains

This research investigates how two supply chain members, a downstream firm (F) and an upstream supplier (S), interact with each other with respect to corporate social responsibility (CSR) behavior and what impact exogenous parameters may have on this interaction. A game-theoretic analysis is conducted to obtain equilibriums for both simultaneous-move and sequential-move CSR games. Under certain assumptions, it is concluded that (1) there exists a mutual incentive between their CSR behavior, whereby a win–win performance in terms of both CSR and profitability is achieved as long as exogenous parameters exceed certain critical thresholds; (2) a higher consumer marginal social-benefit potential (MSBP) or a lower consumer marginal perception difficulty (MPD) helps to lower the critical thresholds of CSR budgets and CSR operational efficiency by S and F, making it easier to achieve the win–win performance; (3) an increase in one supply chain member\u27s CSR budget or CSR operational efficiency tends to make the supply chain easier to attain a win–win performance scenario; (4) if CSR decisions are made sequentially, a prior commitment to CSR activities from one supply chain member strengthens the mutual incentive and facilitates the realization of the win–win performance. Business implications of these research findings are also discussed

Visualizing chest X-ray dataset biases using GANs

Recent work demonstrates that images from various chest X-ray datasets contain visual features that are strongly correlated with protected demographic attributes like race and gender. This finding raises issues of fairness, since some of these factors may be used by downstream algorithms for clinical predictions. In this work, we propose a framework, using generative adversarial networks (GANs), to visualize what features are most different between X-rays belonging to two demographic subgroups.Comment: Medical Imaging with Deep Learning(MIDL) 202

Production costs, scope economies, and multi-client outsourcing under quantity competition

Two game models are developed based on production costs and scope economies to investigate the widely observed multi-client outsourcing (MCO) phenomenon. Analytical results demonstrate that outsourcers’ high in-house production costs and the advantage of scope economies motivate firms to outsource collectively to an independent vendor. Under certain conditions, if both firms make their outsourcing decisions simultaneously, collective outsourcing is one of the two equilibria; if both firms make decisions sequentially, collective outsourcing becomes the unique equilibrium. Furthermore, the comparative statics of the critical degree of scope economies are examined for the occurrence of MCO with regard to diverse market parameters. Finally, it is proved that market prices decrease as the degree of scope economies increases when MCO occurs. This research helps explain some widely observed phenomena such as malls, supply chain cities, and the China price

Social responsibility allocation in two-echelon supply chains: Insights from wholesale price contracts

Corporate social responsibility (CSR) is considered in a two-echelon supply chain consisting of an upstream supplier and a downstream firm that are bound by a wholesale price contract. CSR performance (the outcome of CSR conduct) of the whole supply chain is gauged by a global variable and the associated cost of achieving this CSR performance is only incurred by the supplier with an expectation of being shared with the downstream firm via the wholesale price contract. As such, the key issue is to determine who should be allocated as the responsibility holder with the right of offering the contract and how this right should be appropriately restricted. Game-theoretical analyses are carried out on six games, resulting from different interaction schemes between the supplier and the firm, to derive their corresponding equilibriums. Comparative institutional analyses are then conducted to determine the optimal social responsibility allocation based on both economic and CSR performance criteria. Main results are furnished in a series of propositions and their implications to the real-world business practice are discussed. The key findings are threefold: under the current model settings: (1) the optimal allocation scheme is to assign the supplier as the responsibility holder with appropriate restrictions on the corresponding rights to determine the wholesale price; (2) inherent conflict exists between the economic and CSR performance criteria and, hence, the two maxima cannot be achieved simultaneously; and (3) although integrative channel profit is not attainable, the system-wide profit will be improved by implementing optimal social responsibility allocation schemes

The archaeal ATPase PINA interacts with the helicase Hjm via its carboxyl terminal KH domain remodeling and processing replication fork and Holliday junction.

PINA is a novel ATPase and DNA helicase highly conserved in Archaea, the third domain of life. The PINA from Sulfolobus islandicus (SisPINA) forms a hexameric ring in crystal and solution. The protein is able to promote Holliday junction (HJ) migration and physically and functionally interacts with Hjc, the HJ specific endonuclease. Here, we show that SisPINA has direct physical interaction with Hjm (Hel308a), a helicase presumably targeting replication forks. In vitro biochemical analysis revealed that Hjm, Hjc, and SisPINA are able to coordinate HJ migration and cleavage in a concerted way. Deletion of the carboxyl 13 amino acid residues impaired the interaction between SisPINA and Hjm. Crystal structure analysis showed that the carboxyl 70 amino acid residues fold into a type II KH domain which, in other proteins, functions in binding RNA or ssDNA. The KH domain not only mediates the interactions of PINA with Hjm and Hjc but also regulates the hexameric assembly of PINA. Our results collectively suggest that SisPINA, Hjm and Hjc work together to function in replication fork regression, HJ formation and HJ cleavage

Graph Transformation Based Guidance for Web Navigation

With growing information volume and diverse user preferences on the web, the performance of web information retrieval has become a critical issue. Web navigation is dramatically influenced by the organizations of web contents. Hence, useful navigation guidance can considerably accelerate the information retrieval process. In this paper, web navigation is formulated as a Directed Group Steiner Forest (DGSF) problem in line graph representation of the website. A heuristic algorithm is proposed to tackle the DGSF problem and attain the suboptimal solution in polynomial time. Simulations are conducted to compare the mean searching time for the proposed DGSF-based navigation guidance and other approaches. The results suggest that the DGSF-based navigation guidance can significantly reduce the mean searching time, especially when the number of web pages is large while the number of destination pages is moderate. The discussion is also made for extending the model to take into account the websites owner’s interests and other concerns as well

The role of extension and forest characteristics in understanding the management decisions of new forest owners in Ireland

peer-reviewedMany European countries have seen significant changes in forest ownership structure, with the emergence of a cohort commonly referred to as new forest owners, mainly within the non-industrial, private forest (NIPF) owner group. The drivers of this change differ between countries but these owners frequently lack an existing knowledge base to draw on regarding forest management decisions and practices and may possess different objectives to traditional owners. As a result there is uncertainty concerning the management intentions of these owners. The provision of extension services is a recognised approach to supporting decision-making by NIPF owners but there have been relatively few studies that have sought to quantify the effectiveness of such initiatives in terms of management outcomes. In addition to measuring the outcome of extension initiatives, exploring the positive or negative outcomes can assist with the design of future initiatives. Ensuring that such initiatives are designed for appropriate phases in the forest life-cycle is important. This paper reports the results from a number of surveys that sought to explore the impact of an extension initiative, a thinning demonstration, on actual management outcomes and what characteristics of owners and their forests might explain observed management decisions. A retrospective pre-post test questionnaire was used at the demonstration to capture knowledge impacts and management intentions. A follow up survey was conducted 18 months later to investigate what, if any, practices had been undertaken. Data from a national household survey of land owners were also analysed to investigate whether the observations from the demonstration had significance for the wider population. The results suggest that the demonstration was successful in imparting knowledge to forest owners both in terms of self-reported learning and actual management outcomes. However, from an Irish perspective management decisions are dominated by forest age as the majority of the private estate is still in its first rotation. This presents a challenge to extension service personnel and to research seeking to explain management practices at a national level