CBA Method Research Articles

SMAD3 deficiency causes immune dysregulation, colitis and colon tumorigenesis (66.13)

Abstract Introduction: TGFβ plays important role in T cell development, differentiation, tolerance and autoimmune diseases. However, recent studies have shown an important role for TGF-β1 and β3 in pathogenic helper T-cell (Th17) differentiation in the presence of IL-1β, IL-6 and IL-23. SMAD3 is mediates TGFβ signaling in many cell types including lymphocytes. Smad3 /- mice develop inflammation-induced colon cancer upon Helicobacter hepaticus infection suggesting that TGFβ1 signaling through SMAD3 is essential to prevent inflammation and progression to colon cancer. In this study we investigated the role of SMAD3 in inflammation using mice deficient in Smad3. Methods: Splenocytes are cultured in the presence of anti-CD3/CD28 beads, TGFβ1 and IL-2 for 3 days. Cytokines are determined by ELISA, CBA and MSD methods. Cells are stained with antibodies for CD4, CD25, CD62L and intracellular FOXP3 and Helios. Results: Smad3-/- mice exhibit inflammatory response upon infection with commensal bacterium H. hepaticus. We find that while SMAD3 signaling is important for inducible Treg cell generation and for their maintenance, deficiency of SMAD3 increases IL-6 and IL-17 levels suggesting a regulatory role for SMAD3 in Th17 cell differentiation. Conclusions: While SMAD3 signaling is important for iTreg cell generation and maintenance, it is not required for Th17 cell differentiation. In addition, we find that SMAD3 signaling negatively regulates Th17 differentiation through induction of FOXP3.

Calcineurin Aβ signalling is required for Treg-cell generation and prevention of T-cell activation and B-cell lymphomagenesis (100.13)

Abstract Introduction: Calcineurin (CN), a protein phosphatase activated by Ca2+-calmodulin, is involved in activation of NFAT. CN inhibitors such as cyclosporine A (CsA) and FK506 are potent inhibitors of T-cell responses and are commonly used to prevent graft rejection. Consistently, CNAβ-deficient mice exhibit defective thymocyte maturation in young mice. However, T cells undergo spontaneous activation in older Cnab-/- mice, and succumb to B-cell lymphomas. Methods: Splenocytes are cultured in the presence of anti-CD3/CD28 beads, TGFβ1 and IL-2 for 3 days. Cytokines in culture supernatants are determined by ELISA, CBA and MSD methods. Cells are stained with CD4, CD25, CD62L and intracellular FOXP3. Results: We observed that FOXP3+ Treg cells are decreased while mature activated T cells (CD62L-CD44+) are increased in KO mice compared to control mice. While TGFβ1 induced the expression of FOXP3 in WT cultures, it failed to induce FOXP3 in KO cultures. Cytokine profiles revealed that CNAβ is required to inhibit IL-4, IL-6, IL-10, IL-17 and IFNγ by TGFβ1. IHC analyses of lymphomas revealed that the lymphomas are of B cell origin and they do not express FOXP1, a marker for activated B cells (ABCs). Discussion: These data show that CNAβ is important for the development and homeostasis of mature T cells and Treg cells. The data also suggest that in the absence of CNAβ, a defective T-cell regulation results in activation of T cells, production of inflammatory cytokines and cause cancer.

A cost-benefit analysis for the economic growth in China

Currently, traditional development issues such as income inequality, depletion of natural resources, environmental pollution as well as retardation of infrastructure have occurred in China. In the future, more pressures would be imposed on China by the continuous fast development of industrialization, and with transfer of the world manufacture center to China. Sustainable development, including its economic, environmental and social elements, is a key goal of decisionmakers. This paper develops a methodology on cost benefit analysis of economic growth at macroscopic level to identify issues of China's sustainability. In order to address some important issues on how to make policies to improve the quality of economic growth, the CBA framework developed in this study analyses economic–ecological–social interaction, building three accounts that reflect three dimensions of sustainable development that includes 26 sub-models in all, and finally is integrated into an index as Net Progress Proceeds (NPP). The estimation methods of these submodels, such as cost of environmental pollution, depletion of natural resources and defensive expenditures are described in detail. Based on the framework and methods, this paper examines the costs and benefits of economic growth in three aspects of economy, ecology and society. The results illustrate that NPR of China's economic growth had been negative for a long time and has just became positive since year 2000 but was quite low. Even the best was only 1.6% in 2002 (the worst was −24.2% in 1982). Based on the comparison between three accounts, we can draw a conclusion that ecological cost is the dominant factor that affects China's NPR. The empirical results show that if no other innovative measures or policies are taken in the future the costs of growth would outweigh its benefits, resulting in un-sustainability. Basically, the long-term economic growth would be unsustainable due to increasing environmental damage and depletion of natural resources. There are a few limitations that we consider need to be improved in our CBA framework and method, nevertheless they have many options that can be explored by policy makers, to make the development path more sustainable.

A fuzzy multicriteria evaluation system for the assessment of tunnels vis-à-vis surface roads: the WPMA case—part II

The Fuzzy Multicriteria Evaluation System (FUMES) is applied on a real evaluation problem such as the Western Peripheral Motorway of Athens (WPMA). The lack of a formal development model of the study area suggested an evaluation strategy, which is characterized by the high uncertainty of the evaluation environment. This has resulted in using judgments when quantitative information on the performance of the tunnel or the surface road was not available. It also resulted in employing a relatively large number of alternative scenarios to deal with the different policy goals. The attempted impact analysis generated crisp and fuzzy scores for each competing alternative. The different scenarios under which the various alternatives were evaluated are of two types: socio-economic and policy scenarios. Subsequently, the criteria weights were computed using the Fuzzy Hierarchical Analysis and the different CBA and MCA methods were applied. Finally, the output of the evaluation determined that the surface road is the most ‘stable’ solution for all the ‘extrovert’ development scenarios, while the tunnel is more preferable for all the ‘introvert’ development scenarios.

Optically Active Phenyl-t-Butylphosphinothioic Acid as a Useful CSA for the Enantiomeric Excess Determination of Alcohols, Aminoalcohols and Related Compounds

Abstract There are rather few methods for determination of the enantiomeric excess of chiral alcohols, amines, thiols and related compounds.1 All these methods consist in the formation of. diastereomeric derivatives of the samples investigated with various chiral derivatizing agents (the CBA method) followed by the quantitative determination of their diastereomer composition using NMR or other techniques.