The total assessment profile, volume 2

Appendices are presented which include discussions of interest formulas, factors in regionalization, parametric modeling of discounted benefit-sacrifice streams, engineering economic calculations, and product innovation. For Volume 1, see

The total assessment profile, volume 1

A methodology is described for the evaluation of societal impacts associated with the implementation of a new technology. Theoretical foundations for the methodology, called the total assessment profile, are established from both the economic and social science perspectives. The procedure provides for accountability of nonquantifiable factors and measures through the use of a comparative value matrix by assessing the impacts of the technology on the value system of the society

Natural products that reduce rotavirus infectivity identified by a cell-based moderate-throughput screening assay

BACKGROUND: There is widespread interest in the use of innate immune modulators as a defense strategy against infectious pathogens. Using rotavirus as a model system, we developed a cell-based, moderate-throughput screening (MTS) assay to identify compounds that reduce rotavirus infectivity in vitro, toward a long-term goal of discovering immunomodulatory agents that enhance innate responses to viral infection. RESULTS: A natural product library consisting of 280 compounds was screened in the assay and 15 compounds that significantly reduced infectivity without cytotoxicity were identified. Time course analysis of four compounds with previously characterized effects on inflammatory gene expression inhibited replication with pre-treatment times as minimal as 2 hours. Two of these four compounds, α-mangostin and 18-β-glycyrrhetinic acid, activated NFκB and induced IL-8 secretion. The assay is adaptable to other virus systems, and amenable to full automation and adaptation to a high-throughput format. CONCLUSION: Identification of several compounds with known effects on inflammatory and antiviral gene expression that confer resistance to rotavirus infection in vitro suggests the assay is an appropriate platform for discovery of compounds with potential to amplify innate antiviral responses

The identification of established modifiable mid-life risk factors for cardiovascular disease which contribute to cognitive decline: Korean Longitudinal Study of Aging (KLoSA)

INTRODUCTION: We explored how different chronic diseases, risk factors, and protective factors highly associated with cardiovascular diseases (CVD) are associated with dementia or Mild Cognitive Impairment (MCI) in Korean elders, with a focus on those that manifest in mid-life. METHODS: A CVD-free cohort (n = 4289) from the Korean Longitudinal Study of Aging was selected to perform Cox mixed-effects proportional hazard regressions. Eighteen control variables with strong associations to CVD were chosen as explanatory variables, and Mini-Mental State Examination (MMSE) score cut-off for dementia and MCI were used as outcome variables. RESULTS: The statistically significant (P < 0.05) adverse factors that contribute in developing dementia were age (aHR 1.07, 1.05-1.09), Centre for Epidemiological Studies Depression Scale (CESD-10) (aHR 1.17, 1.12-1.23), diagnosis with cerebrovascular disease (aHR 3.73, 1.81-7.66), living with diabetes (aHR 2.30, 1.22-4.35), and living with high blood pressure (HBP) (aHR 2.05, 1.09-3.87). In contrast, the statistically significant protective factors against developing dementia were current alcohol consumption (aHR 0.67, 0.46-0.99), higher educational attainment (aHR 0.36, 0.26-0.56), and regular exercise (aHR 0.37, 0.26-0.51). The factors with a statistically significant adverse association with progression to MCI were age (aHR 1.02, 1.01-1.03) and CESD-10 (aHR 1.17, 1.14-1.19). In contrast, the statistically significant protective factors against developing MCI were BMI (aHR 0.96, 0.94-0.98), higher educational attainment (aHR 0.33, 0.26-0.43), and regular exercise (aHR 0.83, 0.74-0.92). CONCLUSION: In lieu of the protective factor of MCI and dementia, implementing regular exercise routine well before mid-life and cognitive decline is significant, with adjustments made for those suffering from health conditions, so they can continue exercising despite their morbidity. Further attention in diabetes care and management is needed for patients who already show decline in cognitive ability as it is likely that their MCI impacts their ability to manage their existing chronic conditions, which may adversely affect their cognitive ability furthermore

Effects of hatchery rearing and sea ranching of parents on the life history traits of released salmon offspring

Life-history traits such as growth, survival, sea migration and age at sexual maturity in the sea were compared between Carlin-tagged hatchery-reared Atlantic salmon smolts (Salmo salar) originating from hatchery broodstocks (reared) or naturally ascending spawners captured (sea ranched). The ranched parents included both wild (born in nature) and reared individuals (released as parr or smolts). All smolts were reared in similar hatchery conditions, and they were tagged and released as two-year-olds in the Simojoki River in 1986-2007. The recapture rates did not differ between the progeny groups, although the tagged smolts of the reared parents were larger than those of ranched parents at time of release. The captive salmon with ranched parents were at average heavier during their second winter at sea, but not later. Salmon with ranched parents more frequently migrated to feed in the Main Basin of the Baltic Sea, further from the home river of the salmon stock. The proportions of multi-sea-winter returners were 30% and 69% in salmon with reared and ranched parents, respectively. The different patterns of migration and sea age at maturity of these parental progeny groups suggest that differences in the life history of brood fish may cause distinct, possibly even genetic differences in the progenies. (c) 2013 Elsevier B.V. All rights reserved

The subconvexity problem for \GL_{2}

Generalizing and unifying prior results, we solve the subconvexity problem for the $L$-functions of \GL_{1} and \GL_{2} automorphic representations over a fixed number field, uniformly in all aspects. A novel feature of the present method is the softness of our arguments; this is largely due to a consistent use of canonically normalized period relations, such as those supplied by the work of Waldspurger and Ichino--Ikeda.Comment: Almost final version to appear in Publ. Math IHES. References updated

Platelet Ice Under Arctic Pack Ice in Winter

The formation of platelet ice is well known to occur under Antarctic sea ice, where subice platelet layers form from supercooled ice shelf water. In the Arctic, however, platelet ice formation has not been extensively observed, and its formation and morphology currently remain enigmatic. Here, we present the first comprehensive, long‐term in situ observations of a decimeter thick subice platelet layer under free‐drifting pack ice of the Central Arctic in winter. Observations carried out with a remotely operated underwater vehicle (ROV) during the midwinter leg of the MOSAiC drift expedition provide clear evidence of the growth of platelet ice layers from supercooled water present in the ocean mixed layer. This platelet formation takes place under all ice types present during the surveys. Oceanographic data from autonomous observing platforms lead us to the conclusion that platelet ice formation is a widespread but yet overlooked feature of Arctic winter sea ice growth

Murine and Bovine γδ T Cells Enhance Innate Immunity against Brucella abortus Infections

γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ−/− mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα−/−, and GMCSF−/− mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ−/− mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections

Inducible Bronchus-Associated Lymphoid Tissue Elicited by a Protein Cage Nanoparticle Enhances Protectionin Mice against Diverse Respiratory Viruses

Destruction of the architectural and subsequently the functional integrity of the lung following pulmonary viral infections is attributable to both the extent of pathogen replication and to the host-generated inflammation associated with the recruitment of immune responses. The presence of antigenically disparate pulmonary viruses and the emergence of novel viruses assures the recurrence of lung damage with infection and resolution of each primary viral infection. Thus, there is a need to develop safe broad spectrum immunoprophylactic strategies capable of enhancing protective immune responses in the lung but which limits immune-mediated lung damage. The immunoprophylactic strategy described here utilizes a protein cage nanoparticle (PCN) to significantly accelerate clearance of diverse respiratory viruses after primary infection and also results in a host immune response that causes less lung damage

Modeling the role of the close- range effect and environmental variables in the occurrence and spread of Phragmites australis in four sites on the Finnish coast of the Gulf of Finland and the Archipelago Sea

Peer reviewe