Entrepreneurship in Peace Operations

Journal of Civic Society," 6(01), (2010), pp. 1-21.A central question guides this article: To what extent can entrepreneurship be a force for change and transformation in war-torn areas? To address the question, this article introduces the topic of social entrepreneurship and illustrates how social entrepreneurs are serving as change agents in rebuilding and reconstructing areas devastated by conflict. The social enterprise of Kiva, the brainchild of social entrepreneurs Matthew Flannery and Jessica Jackley, provides an example. It is notable for its innovative idea—a Web-based, internet-facilitated micro-loan process that attracts individual investors worldwide in support of business entrepreneurs in the developing world. As a counter example to top-down, mandate-driven, organization-centric intervention strategies that many organizations pursue in peace operations, Kiva’s enduring legacy may very well be its bottom-up, entrepreneur-driven, network-centric model of change. Its most salient features are: a supply chain that ‘contractually’ connects all the partners in the loan process to minimize coordination problems and ensure that each step in the workflow sequentially adds value; processes and systems that guarantee work is transparent, efficient and accountable; a model of learning that enables global and local partners to co-create a complex, worldwide community-based learning system in support of entrepreneurship; and a rich network of social relations built from face-to-face and online interactions to help generate social capital needed for development

Using Stakeholder Value Analysis to Build Exploration Sustainability

Abstract: The sustainability of space exploration will depend in large part on its ability to consistently and reliably deliver valued benefits to societal stakeholders over an extended period. This on-going research studies the values of prospective stakeholders in the space exploration enterprise—both in the near term and with a perspective extending over decades. The immediate focus is human and robotic exploration of the Earth/Moon system, but extends to the exploration of Mars as well. Potential beneficiaries of space exploration are identified in broad societal sectors. An analysis of these stakeholders, their values and needs leads to the development of a comprehensive set of space exploration objectives that address those needs. The relative priority of exploration objectives is weighted using information about stakeholder characteristics, values, and their role and place in the exploration value stream. The weighted exploration objectives can then be used to assess the relative value of different technical system architectures, and to design exploration enterprise architecture, attributes and policy frameworks to enable value delivery to societal stakeholders. Ultimately, through stakeholders ’ continuing support, sustainable space exploration will be delivered. I

Pyrroloquinoline quinone prevents developmental programming of microbial dysbiosis and macrophage polarization to attenuate liver fibrosis in offspring of obese mice.

Increasingly, evidence suggests that exposure to maternal obesity creates an inflammatory environment in utero, exerting long-lasting postnatal signatures on the juvenile innate immune system and microbiome that may predispose offspring to development of fatty liver disease. We found that exposure to a maternal Western-style diet (WD) accelerated fibrogenesis in the liver of offspring and was associated with early recruitment of proinflammatory macrophages at 8-12 weeks and microbial dysbiosis as early as 3 weeks of age. We further demonstrated that bone marrow-derived macrophages (BMDMs) were polarized toward an inflammatory state at 8 weeks of age and that a potent antioxidant, pyrroloquinoline quinone (PQQ), reversed BMDM metabolic reprogramming from glycolytic toward oxidative metabolism by restoring trichloroacetic acid cycle function at isocitrate dehydrogenase. This resulted in reduced inflammation and inhibited collagen fibril formation in the liver at 20 weeks of age, even when PQQ was withdrawn at 3 weeks of age. Beginning at 3 weeks of age, WD-fed mice developed a decreased abundance of Parabacteroides and Lactobacillus, together with increased Ruminococcus and decreased tight junction gene expression by 20 weeks, whereas microbiota of mice exposed to PQQ retained compositional stability with age, which was associated with improved liver health. Conclusion: Exposure to a maternal WD induces early gut dysbiosis and disrupts intestinal tight junctions, resulting in BMDM polarization and induction of proinflammatory and profibrotic programs in the offspring that persist into adulthood. Disrupted macrophage and microbiota function can be attenuated by short-term maternal treatment with PQQ prior to weaning, suggesting that reshaping the early gut microbiota in combination with reprogramming macrophages during early weaning may alleviate the sustained proinflammatory environment, preventing the rapid progression of nonalcoholic fatty liver disease to nonalcoholic steatohepatitis in offspring of obese mothers. (Hepatology Communications 2018;2:313-328)

Gut microbiome, liver immunology, and liver diseases

The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology. The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota. The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens. Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases. Of immense importance is the step from high-throughput sequencing (correlation) to mechanistic studies (causality) and therapeutic intervention. Here, we review the gut microbiota, liver immunology, and the interaction between the gut and liver. In addition, the impairment in the gut–liver axis found in various liver diseases is reviewed here, with an emphasis on alcohol-associated liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and autoimmune liver disease (AILD). On the basis of growing evidence from these preclinical studies, we propose that the gut–liver axis paves the way for targeted therapeutic modalities for liver diseases