ALTERNATIVE POLYADENYLATION MODULATES EXPRESSION OF PRO-FIBROTIC PROTEINS AND CONTRIBUTES TO LUNG FIBROSIS

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects about 5 to 8 million individuals in the world. Despite the high prevalence, there is currently no cure for IPF, and the cause of this disease is still unclear. Our laboratory and collaborators have shown that nudix hydrolase 21 (NUDT21, which is also known as cleavage factor 25, CFIm25) is a key regulator of alternative polyadenylation (APA). NUDT21 depletion causes 3’UTR shortening via APA leading to enhanced mRNA stability and protein translation. This NUDT21 reduction promotes tumor growth in glioblastoma by enhancing expression of oncogenes. Cancer and IPF share cellular features, such as enhanced expression for pathological mediators and increased cell proliferation. However, whether APA plays a role in lung fibrosis is not known. Our results reveal that NUDT21 reduction is found in lung fibroblasts isolated from IPF patients. Depletion of NUDT21 causes 3’UTR shortening in pro-fibrotic genes, such as Wnt and TGFb1, leading to robust protein expression of the pathological genes and ultimately worsening of pulmonary fibrosis. Additionally, we found that TGFb1 depletes NUDT21 in fibroblasts by transcriptionally inducing miR203 through Smad3. Modulating NUDT21 by overexpression or antagomiR203 attenuated NUDT21 reduction-mediated fibrosis in vitro. The results of this dissertation are significant in that these findings broaden our understanding on the role of APA in fibrosis. The knowledge discovered in this project is potentially beneficial as these results may lead to identification of targets for novel therapies which can halt the progression of IPF

Metamaterial-Based Radiative Cooling: Towards Energy-Free All-Day Cooling

In the light of the ever increasing dangers of global warming, the efforts to reduce energy consumption by radiative cooling techniques have been designed, but are inefficient under strong sunlight during the daytime. With the advent of metamaterials and their selective control over optical properties, radiative cooling under direct sunlight is now possible. The key principles of metamaterial-based radiative cooling are: almost perfect reflection in the visible and near-infrared spectrum (0.3-3 mu m) and high thermal emission in the infrared atmospheric window region (8-13 mu m). Based on these two basic principles, studies have been conducted using various materials and structures to find the most efficient radiative cooling system. In this review, we analyze the materials and structures being used for radiative cooling, and suggest the future perspectives as a substitute in the current cooling industry.11Ysciescopu

Comparison of Mortality Outcomes in Acute Myocardial Infarction Patients With or Without Standard Modifiable Cardiovascular Risk Factors

Background: Acute myocardial infarction (AMI) cases have decreased in part due to the advent of targeted therapies for standard modifiable cardiovascular disease risk factors (SMuRF). Recent studies have reported that ST-elevation myocardial infarction (STEMI) patients without SMuRF (termed "SMuRF-less") may be increasing in prevalence and have worse outcomes than "SMuRF-positive" patients. As these studies have been limited to STEMI and comprised mainly Caucasian cohorts, we investigated the changes in the prevalence and mortality of both SMuRF-less STEMI and non-STEMI (NSTEMI) patients in a multiethnic Asian population. Methods: We evaluated 23,922 STEMI and 62,631 NSTEMI patients from a national multiethnic registry. Short-term cardiovascular and all-cause mortalities in SMuRF-less patients were compared to SMuRF-positive patients. Results: The proportions of SMuRF-less STEMI but not of NSTEMI have increased over the years. In hospitals, all-cause and cardiovascular mortality and 1-year cardiovascular mortality were significantly higher in SMuRF-less STEMI after adjustment for age, creatinine, and hemoglobin. However, this difference did not remain after adjusting for anterior infarction, cardiopulmonary resuscitation (CPR), and Killip class. There were no differences in mortality in SMuRF-less NSTEMI. In contrast to Chinese and Malay patients, SMuRF-less patients of South Asian descent had a two-fold higher risk of in-hospital all-cause mortality even after adjusting for features of increased disease severity. Conclusion: SMuRF-less patients had an increased risk of mortality with STEMI, suggesting that there may be unidentified nonstandard risk factors predisposing SMuRF-less patients to a worse prognosis. This group of patients may benefit from more intensive secondary prevention strategies to improve clinical outcomes

Association between smoking status and outcomes in myocardial infarction patients undergoing percutaneous coronary intervention

Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed the “smoker’s paradox.” Given the known detrimental effects of smoking on the cardiovascular system, it has been proposed that the beneficial effect of smoking on outcomes is due to age differences between smokers and non-smokers and is therefore a smoker’s pseudoparadox. The aim of this study was to evaluate the association between smoking status and clinical outcomes in ST-segment elevation (STEMI) and non-STEMI (NSTEMI) patients treated by percutaneous coronary intervention (PCI), using a national multi-ethnic Asian registry. In unadjusted analyses, current smokers had better clinical outcomes following STEMI and NSTEMI. However, after adjusting for age, the protective effect of smoking was lost, confirming a smoker’s pseudoparadox. Interestingly, although current smokers had increased risk for recurrent MI within 1 year after PCI in both STEMI and NSTEMI patients, there was no increase in mortality. In summary, we confirm the existence of a smoker’s pseudoparadox in a multi-ethnic Asian cohort of STEMI and NSTEMI patients and report increased risk of recurrent MI, but not mortality, in smokers

Association of body mass index, metabolic health status and clinical outcomes in acute myocardial infarction patients: a national registry-based study

IntroductionObesity is an important risk factor for acute myocardial infarction (AMI), but the interplay between metabolic health and obesity on AMI mortality has been controversial. In this study, we aimed to elucidate the risk of short- and long-term all-cause mortality by obesity and metabolic health in AMI patients using data from a multi-ethnic national AMI registry.MethodsA total of 73,382 AMI patients from the national Singapore Myocardial Infarction Registry (SMIR) were included. These patients were classified into four groups based on the presence or absence of metabolic diseases, diabetes mellitus, hyperlipidaemia, and hypertension, and obesity: (1) metabolically-healthy-normal-weight (MHN); (2) metabolically-healthy-obese (MHO); (3) metabolically-unhealthy-normal-weight (MUN); and (4) metabolically-unhealthy-obese (MUO).ResultsMHO patients had reduced unadjusted risk of all-cause in-hospital, 30-day, 1-year, 2-year, and 5-year mortality following the initial MI event. However, after adjusting for potential confounders, the protective effect from MHO on post-AMI mortality was lost. Furthermore, there was no reduced risk of recurrent MI or stroke within 1-year from onset of AMI by the MHO status. However, the risk of 1-year mortality was higher in female and Malay AMI patients with MHO compared to MHN even after adjusting for confounders.ConclusionIn AMI patients with or without metabolic diseases, the presence of obesity did not affect mortality. The exception to this finding were female and Malay MHO who had worse long-term AMI mortality outcomes when compared to MHN suggesting that the presence of obesity in female and Malay patients may confer worsened outcomes

Decoding accuracy in supplementary motor cortex correlates with perceptual sensitivity to tactile roughness

Perceptual sensitivity to tactile roughness varies across individuals for the same degree of roughness. A number of neurophysiological studies have investigated the neural substrates of tactile roughness perception, but the neural processing underlying the strong individual differences in perceptual roughness sensitivity remains unknown. In this study, we explored the human brain activation patterns associated with the behavioral discriminability of surface texture roughness using functional magnetic resonance imaging (fMRI). First, a wholebrain searchlight multi-voxel pattern analysis (MVPA) was used to find brain regions from which we could decode roughness information. The searchlight MVPA revealed four brain regions showing significant decoding results: the supplementary motor area (SMA), contralateral postcentral gyrus (S1), and superior portion of the bilateral temporal pole (STP). Next, we evaluated the behavioral roughness discrimination sensitivity of each individual using the just-noticeable difference (JND) and correlated this with the decoding accuracy in each of the four regions. We found that only the SMA showed a significant correlation between neuronal decoding accuracy and JND across individuals; Participants with a smaller JND (i.e., better discrimination ability) exhibited higher decoding accuracy from their voxel response patterns in the SMA. Our findings suggest that multivariate voxel response patterns presented in the SMA represent individual perceptual sensitivity to tactile roughness and people with greater perceptual sensitivity to tactile roughness are likely to have more distinct neural representations of different roughness levels in their SMA. © 2015 Kim et al.close0

초고집적 광 회로를 위한 능동 유효 메타매질 연구

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Metamaterial-Based Radiative Cooling: Towards Energy-Free All-Day Cooling

In the light of the ever increasing dangers of global warming, the efforts to reduce energy consumption by radiative cooling techniques have been designed, but are inefficient under strong sunlight during the daytime. With the advent of metamaterials and their selective control over optical properties, radiative cooling under direct sunlight is now possible. The key principles of metamaterial-based radiative cooling are: almost perfect reflection in the visible and near-infrared spectrum (0.3–3 µm) and high thermal emission in the infrared atmospheric window region (8–13 µm). Based on these two basic principles, studies have been conducted using various materials and structures to find the most efficient radiative cooling system. In this review, we analyze the materials and structures being used for radiative cooling, and suggest the future perspectives as a substitute in the current cooling industry

Ultra-Highly-Integrated Waveguide Based On Active Meta-Materials

Photonic devices are promising research areas that leading the technical innovation paradigm. It is rapidly developing with the development of the latest nano-fabrication technologies. Meta-materials, which are designed nano-pattern array to have designed optical properties, have been investigated to achieve the miniaturization of photonic devices. The use of meta-materials allows for miniaturization and that enables ultra-highly integrated photonic devices. Here, we attempt a novel nano-fabrication approach to achieve ultra-compact waveguide device. Firstly, we fabricate a nano-cavity in the commercial waveguide vertically to control the permittivity (ε) at the optical telecom wavelength (1300-1550 nm). And then we deposit the meta-materials based on phase change material (PCM) Ge-Sb-Te (GST), VO2. PCM has a property that changes in permittivity depending on the phase state and can control by electrical signals. In here, we can consider to being planar planes with an effective permittivity ( ) based on the ‘Maxwell-Garnett approximation’ [1]. This approach can sharply control of the waveguide by PCM-filling inside the waveguide, and directly control the optical path or filter, thereby enabling the ultra-high-density and active property of optical waveguide. Our approach can apply to diverse fields that require active optical properties devices. Acknowledgments This work was supported by the Electronics and Telecommunications Research Institute, grant-funded by the Korean government (18ZB1100, Development of Basic Technologies for 3D Photo-Electronics). References [1] Introduction to the Maxwell Garnett approximation: tutorial (2016).2