Between 1960 and 1983 the Dutch economist Dr. Albert Winsemius (1910-1996) was the most influential economic adviser to the government of Singapore and one of the leading architects of Singapore’s... Show moreBetween 1960 and 1983 the Dutch economist Dr. Albert Winsemius (1910-1996) was the most influential economic adviser to the government of Singapore and one of the leading architects of Singapore’s highly successful development model. Winsemius' beliefs and recommendations chimed with the views of Singapore’s first-generation postcolonial political leaders and quickly grew in popular appeal once they started yielding impressive economic results. Winsemius’ uncompromising hostility to communism, and at the same time his sympathy toward moderate trade unionism, were of particular importance here.This research identifies strategies and policies that contributed to Singapore's development, and that can be traced to Albert Winsemius as a historical principal. It concludes that in essence, many of these successful strategies and policies were based on Winsemius’ experiences in his earlier life and career: the economic reconstruction in the Netherlands in the years after World War Two, in which he played a key role, his empathy toward the United States and the American way of life, his contacts with other right-wing governments, and his involvement during the Cold War in the production of arms. Show less
Patients with a congenital bicuspid aortic valve (BAV), a valve with two instead of three aortic leaflets, have an increased risk of developing thoracic aneurysms and aortic dissection. The... Show morePatients with a congenital bicuspid aortic valve (BAV), a valve with two instead of three aortic leaflets, have an increased risk of developing thoracic aneurysms and aortic dissection. The mechanisms underlying BAV-associated aortopathy are poorly understood. This study examined BAV-associated aortopathy in Nos3(-/-) mice, a model with congenital BAV formation. A combination of histological examination and in vivo ultrasound imaging was used to investigate aortic dilation and dissections in Nos3(-/-) mice. Moreover, cell lineage analysis and single-cell RNA sequencing were used to observe the molecular anomalies within vascular smooth muscle cells (VSMCs) of Nos3(-/-) mice. Spontaneous aortic dissections were found in ascending aortas located at the sinotubular junction in similar to 13% of Nos3(-/-) mice. Moreover, Nos3(-/-) mice were prone to developing aortic dilations in the proximal and distal ascending aorta during early adulthood. Lower volumes of elastic fibres were found within vessel walls of the ascending aortas of Nos3(-/-) mice, as well as incomplete coverage of the aortic inner media by neural crest cell (NCC)-derived VSMCs. VSMCs of Nos3(-/-) mice showed downregulation of 15 genes, of which seven were associated with aortic aneurysms and dissections in the human population. Elastin mRNA was most markedly downregulated, followed by fibulin-5 expression, both primary components of elastic fibres. This study demonstrates that, in addition to congenital BAV formation, disrupted endothelial-mediated nitric oxide (NO) signalling in Nos3(-/-) mice also causes aortic dilation and dissection, as a consequence of inhibited elastic fibre formation in VSMCs within the ascending aorta. Show less
