Primary open angle glaucoma (POAG) features an optic neuropathy, elevated aqueous humor (AH) TGFβ2, and major risk factors of central corneal thickness (CCT), increasing age and intraocular pressure ...(IOP). We examined Tight skin (Tsk) mice to see if mutation of fibrillin-1, a repository for latent TGFβ, is associated with characteristics of human POAG. We measured: CCT by ocular coherence tomography (OCT); IOP; retinal ganglion cell (RGC) and optic nerve axon counts by microscopic techniques; visual electrophysiologic scotopic threshold responses (STR) and pattern electroretinogram (PERG); and AH TGFβ2 levels and activity by ELISA and MINK epithelial cell-based assays respectively. Tsk mice had open anterior chamber angles and compared with age-matched wild type (WT) mice: 23% thinner CCT (p < 0.003); IOP that was higher (p < 0.0001), more asymmetric (p = 0.047), rose with age (p = 0.04) and had a POAG-like frequency distribution. Tsk mice also had RGCs that were fewer (p < 0.04), declined with age (p = 0.0003) and showed increased apoptosis and glial activity; fewer optic nerve axons (p = 0.02); abnormal axons and glia; reduced STR (p < 0.002) and PERG (p < 0.007) visual responses; and higher AH TGFβ2 levels (p = 0.0002) and activity (p = 1E-11) especially with age. Tsk mice showed defining features of POAG, implicating aberrant fibrillin-1 homeostasis as a pathogenic contributor to emergence of a POAG phenotype.
Hepatocellular carcinoma (HCC) ranks worldwide as one of the most lethal cancers. In spite of the vast existing knowledge about HCC, the pathogenesis of HCC is not completely understood. Discovery of ...novel genes that contribute to HCC pathogenesis will provide new insights for better understanding and treating HCC. The relatively obscure gene midnolin has been studied for over two decades; however, its biological roles are largely unknown. Our study is the first to demonstrate the functional significance of midnolin in HCC/cancer: Midnolin expression correlates with poor prognosis in HCC patients, and suppression of midnolin severely inhibits tumorigenicity of HCC cells in vitro and in mice and disrupts retinoic acid/lipid metabolism in these cells.
Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery ...that the knockdown of midnolin suppresses liver cancer cell tumorigenicity and that this antitumorigenic effect is associated with modulation of lipid metabolism, we hypothesized that knockout of midnolin in vivo could potentially protect from nonalcoholic fatty liver disease (NAFLD) which has become the most common cause of chronic liver disease in the Western world. Accordingly, in the present study, we have developed and now report on the first functional global midnolin knockout mouse model. Although the overwhelming majority of global homozygous midnolin knockout mice demonstrated embryonic lethality, heterozygous knockout mice were observed to be similar to wild-type mice in their viability and were used to determine the effect of reduced midnolin expression on NAFLD. We found that global heterozygous midnolin knockout attenuated the severity of NAFLD in mice fed a Western-style diet, high in fat, cholesterol, and fructose, and this attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism. Collectively, our results support a role for midnolin in regulating cholesterol/lipid metabolism in the liver. Thus, midnolin may represent a novel therapeutic target for NAFLD. Finally, our observation that midnolin was essential for survival underscores the broad importance of this gene beyond its role in liver biology.
We have developed and now report on the first functional global midnolin knockout mouse model. We found that global heterozygous midnolin knockout attenuated the severity of nonalcoholic fatty liver disease (NAFLD) in mice fed a Western-style diet, high in fat, cholesterol, and fructose, and this attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism.
Blockchain technology has been recognized as one of the emerging technologies that can significantly innovate many industries. Major advantages of using blockchain technology includes reducing ...transaction costs, preventing data forgery and alteration, and further flexibility. The construction industry is generally considered as an industry that has great potentials for blockchain technology utilization mainly due to the high volume of transactions among various entities. Despite the perceived positive impact, there have been few cases of blockchain applications within the construction industry. This study is conducted with an aim of finding ways to apply blockchain technology to the construction industry. In order to identify potential application areas, construction lifecycle and project management knowledge areas are used in developing a survey questionnaire. Data collected from the survey is analyzed by employing importance performance analysis (IPA) method considering both applicability of the technology and anticipated impact from utilizing the technology. In relation to the construction project lifecycle, ‘Project Cost/Change Management’, ‘Contract Bidding and Formation’, and ‘Procurement Evaluation’ are emerged as top three candidates for blockchain application with high applicability and impact. Regarding the knowledge area, ‘Procurement Management’ and ‘Cost Management’ are identified as the main blockchain application areas with high applicability and impact. All the identified specific construction tasks with high applicability and impact are related to ‘Procurement’, ‘Contract’, and ‘Cost’. Therefore, it is reasonable to start focusing blockchain convergence efforts these areas and then expand them as the technology matures.
Inadequate cost management has widely been recognized as one of the most problematic areas in the Korean construction industry as many believes that public cost references are not reasonably ...reflecting the market conditions. 'Total Project Cost Management Guideline' developed by Ministry of Economy and Finance(MOEF) to govern public budget control has been identified as one of the main reasons for this problem. This study attempts to thoroughly review 'Total Project Cost Management Guideline' itself and quantitatively analyze the impact of it on project cost during procurement process. Different procurement methods are considered including turnkey & alternative, private contract, qualification examination, and lowest price bidding system in this quantitative impact analysis of 'Total Project Cost Management Guideline'. Analysis results shows that this governmental process works mainly as a constant cost-cutting tool throughout the procurement process. 국내 공공 건설공사 공사비 수준이 시장 상황을 합리적으로 반영하지 못하고 있는 인식이 산업 전반에 널리 펴져 있는 가운데, 총사업비 관리 프로세스 상의 과도한 공사비 조정이 공사비의 적정성 미확보에 대한 핵심 원인 중 하나로 지목되고 있다. 정부는 건설 프로젝트 총사업비 산정 및 관리 프로세스에서 삭감 위주의 정책을 펼치고 있으며, 산업계에서는 예정가격 대비 낙찰가격의 수준은 매우 낮다는 인식이 일반적이다. 본 연구에서는 총사업비 관리 프로세스를 개선하기 위한 목적으로 총사업비 산정 및 관리 프로세스에 대한 분석을 수행한다. 입·낙찰 방식별 총사업비가 단계별 조정되는 과정을 분석하고, 사업구상 단계 대비 낙찰가격의 수준에 대한 정량적 비교분석 결과를 도출한다.
