China's construction industry is facing significant challenges in achieving sustainable development and digital operations. Integrating building information modeling (BIM) and sustainable construction is a good method for achieving these goals. However, barriers impact the applications of BIM technology to sustainable buildings, resulting in significant cost loss and time. As such, it is important to identify the constraints, hindering the application of BIM technology in sustainable buildings. This study used the factor analysis method, exploratory factor analysis (EFA), and structural equation modeling (SEM) to investigate the key constraints and conducted a questionnaire survey with 389 respondents to investigate the applications of BIM technology in sustainable building projects. The results showed that there were four main constraining factors: "Public participation", "technology application", "economic cost", and "application management"; "public participation" was particularly important. The study offers practical and managerial implications based on the findings for local government and the private sector and thus can improve the implementation of BIM technology in sustainable buildings and contribute to the accomplishment of China's sustainable development goals.
Background
Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of functional ubiquitin protein ligase E3A (UBE3A). In neurons, UBE3A expression is tightly regulated by a mechanism of imprinting which suppresses the expression of the paternal UBE3A allele. Promising treatment strategies for AS are directed at activating paternal UBE3A gene expression. However, for such strategies to be successful, it is important to know when such a treatment should start, and how much UBE3A expression is needed for normal embryonic brain development.
Methods
Using a conditional mouse model of AS, we further delineated the critical period for UBE3A expression during early brain development. Ube3a gene expression was induced around the second week of gestation and mouse phenotypes were assessed using a behavioral test battery. To investigate the requirements of embryonic UBE3A expression, we made use of mice in which the paternal Ube3a allele was deleted.
Results
We observed a full behavioral rescue of the AS mouse model phenotypes when Ube3a gene reactivation was induced around the start of the last week of mouse embryonic development. We found that full silencing of the paternal Ube3a allele was not completed till the first week after birth but that deletion of the paternal Ube3a allele had no significant effect on the assessed phenotypes.
Limitations
Direct translation to human is limited, as we do not precisely know how human and mouse brain development aligns over gestational time. Moreover, many of the assessed phenotypes have limited translational value, as the underlying brain regions involved in these tasks are largely unknown.
Conclusions
Our findings provide further important insights in the requirement of UBE3A expression during brain development. We found that loss of up to 50% of UBE3A protein during prenatal mouse brain development does not significantly impact the assessed mouse behavioral phenotypes. Together with previous findings, our results indicate that the most critical function for mouse UBE3A lies in the early postnatal period between birth and P21.
Highlights d Complex spikes can promote or reduce the symmetry of left and right movements d Cerebellar areas promoting symmetry are spatially distinct from those reducing it d Simple spikes regulate impact of the complex spikes on symmetric movements d Intracerebellar contralateral projections characterize areas promoting symmetry
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