Abstract-Vascular cell adhesion molecule-1 (VCAM-1/Vcam1) is a cytokine-inducible member of the immunoglobulin gene superfamily that is expressed by arterial endothelial cells in regions predisposed to atherosclerosis and at borders of atherosclerotic plaques. To determine whether VCAM-1 expression regulates atherosclerotic lesion formation, we crossed Vcam1 domain 4 -deficient (D4D) mice, which partially circumvent the embryonic lethality of Vcam1 null mice, with apolipoprotein E null (Apoe Ϫ/Ϫ ) mice, which spontaneously develop hypercholesterolemia and atherosclerosis. In the Apoe Ϫ/Ϫ background, mice homozygous for the Vcam1 D4D allele had markedly reduced arterial VCAM-1 expression, monocyte adherence in the aortic root, and fatty streak formation. A therosclerosis begins as a focal process at specific regions of the vasculature, so-called lesion-prone areas, where hemodynamic flow is altered. The arterial endothelium expresses numerous adhesion molecules, such as P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), at these lesion-prone areas before lesion development 1,2 and at the borders of atherosclerotic lesions. 2,3 Whereas ICAM-1 is also abundantly expressed at lesion-prone areas in wild-type mice with normal cholesterol levels, 1,2 VCAM-1, a cytokine-inducible member of the immunoglobulin gene superfamily, 4 is specifically upregulated in arterial endothelial cells at lesion-prone areas in hypercholesterolemic mice and rabbits. 1,2,5 This specific upregulation of VCAM-1 at lesion-prone areas in hypercholesterolemic animals suggests that VCAM-1 may regulate monocyte adhesion in early atherogenesis.To circumvent the embryonic lethality of Vcam1 null mice, 6,7 mutant mice were generated with a targeted disruption of the exon encoding the fourth immunoglobulin domain of VCAM-1, which codes for an ␣ 4 integrin binding site. 8 Domain 4 -deficient (D4D) mice (Vcam1 D4D/D4D ) express only a 6-immunoglobulin domain form of Vcam1, with VCAM-1 mRNA and protein levels Ͻ10% of those found in wild-type mice. 8 Reduced expression of VCAM-1 protein resulted in decreased embryonic survival of Vcam1 D4D/D4D mice. 8 The frequency of embryonic survival was strain dependent, ranging from 29% in 129-C57BL/6 hybrids to 6% of expected in C57BL/6 Vcam1 D4D/D4D mice. 8 When Vcam1 D4D/D4D of mixed genetic background were bred with LDL receptor-deficient (Ldlr Ϫ/Ϫ ) mice, the aortic surface area occupied by atherosclerosis was reduced by 40% compared with that of Ldlr Ϫ/Ϫ mice. 8 In the present study, Vcam1 D4D/D4D mice were bred with hypercholesterolemic apoE null (Apoe Ϫ/Ϫ ) mice 9 to determine whether relative deficiency in VCAM-1 would also attenuate lesion formation in the apoE-deficient background. Mice homozygous for the Vcam1 D4D allele (Apoe Ϫ/Ϫ and Vcam1 D4D/D4D) had markedly reduced arterial VCAM-1 expression, monocyte adherence, and an 84% decrease in aortic root lesion area. We also demonstrate a significant Vcam1 gene-dosage effect on these parameters. Our da...

Background: Taiwan experiences typhoons annually and the heavy rain accompanies a typhoon often causes flooding and damage. Local decision-makers invest heavily in flood-prevention measures thus need to allocate resources wisely to minimize the destruction. As floods periodically cause tremendous damage to lives and property, passing on the learning of previous generations becomes important. Disaster education is therefore critical in the region. However, the current disaster education curriculum follows a traditional education methodology focusing on theoretical and conceptual knowledge and teaching. An alternative methodology is needed to motivate students and to deliver practical experience in disaster education. Method: This study adopted a persuasive technology game-initiated-learning (GIL) and developed a Flood Protection game to understanding the following: (1) students' motivation for learning, (2) their ability to play the game, and (3) their focus on disaster topics. To evaluate their levels of motivation, students' reactions were analyzed and categorized into four specific expressions: discussion, question, laughter, and screaming. Students' game playing ability was analyzed and categorized into four stages: explore, aware, fluent, and known. Finally, the content of students' discussions and questions were analyzed to assess their interest in disaster education. Results: Students' levels of motivation were found to be high (an average of 2.3 instances of discussion, 0.7 instances of question, 1.3 instances of laughter, and 0.8 instances of screaming were observed per minute during the game); their ability to play the game was sufficient (79% of students completed the game having reached the "known" stage); and the content of their discussions and questions was closely related to disaster knowledge (73% of the 256 discussions and questions related closely to flood and disaster knowledge). Conclusions: From this research, we find that GIL is a persuasive design in flood protection training. Students with low motivation in conventional learning environments were triggered after playing the game. It enhanced students' motivation to learn more about flooding. In short, the game does benefit flood disaster education, indicating that a well-designed game may promote students' motivation in disaster education and cause behavior change.

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