Search results for: Lindner Volkhard

Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

Abstract:

Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

Procedia PDF Downloads 165

Authors: Paul G. Bolz, Paul G. Lindner, Frohmut Wellner, Christian Schulze, Joern Huebelt

Abstract:

Concrete, as a result of its use as a construction material, is not only subject to static loads but is also exposed to variables, time-variant, and oscillating stresses. In order to ensure the suitability of construction materials for resisting these cyclic stresses, different test methods are used for the systematic fatiguing of specimens, like the cyclic indirect tensile test. A procedure is presented that allows the estimation of the degradation of cylindrical concrete specimens during the cyclic indirect tensile test by measuring the dynamic modulus of elasticity in different states of the specimens’ fatigue process. Two methods are used in addition to the cyclic indirect tensile test in order to examine the dynamic modulus of elasticity of cylindrical concrete specimens. One of the methods is based on the analysis of eigenfrequencies, whilst the other one uses ultrasonic pulse measurements to estimate the material properties. A comparison between the dynamic moduli obtained using the three methods that operate in different frequency ranges shows good agreement. The concrete specimens’ fatigue process can therefore be monitored effectively and reliably.

Keywords: concrete, cyclic indirect tensile test, degradation, dynamic modulus of elasticity, eigenfrequency, fatigue, natural frequency, ultrasonic, ultrasound, Young’s modulus

Procedia PDF Downloads 144

Authors: Robert Lindner

Abstract:

In recent years a multitude of international efforts, including the United Nations’ aspirational 2030 Agenda for Sustainable Development, provided a new momentum to facilitate energy access and rural electrification projects to combat energy poverty in developing states in Asia. Rural electrification projects promise to facilitate other sustainable development aims, such as the empowerment of local communities through the creation of economic opportunities or increased disaster resilience. This study applies a multi-governance research framework to study the cases of the ongoing energy system transition in Myanmar and Cambodia. It explores what impact the international aid community, especially multilateral development banks and international development agencies, has on the governance of the transitions and how diverging aid donor interest shape policy making and project planning. The study is based on policy analysis and expert interviews, as well as extensive field research. It critically examines the current development trajectories and the strategies of the stakeholders involved. It concludes that institutional and technological competition between donors, as well as a lack of transparency and inclusion in the project planning and implementation phases, contributes to insufficient coordination in national energy policy making and project implementation at the local level. The study further discusses possible alternative approaches that might help to promote the spread of sustainable energy technologies.

Keywords: energy governance, developing countries, multi-level governance, energy transitions

Procedia PDF Downloads 80