Metabolically stressed kidney is in part characterized by infiltrating macrophages and macrophage-derived TGF-β1 that promote the synthesis of various ECM molecules. TGF-β1 strongly enhances the expression of the ge...Metabolically stressed kidney is in part characterized by infiltrating macrophages and macrophage-derived TGF-β1 that promote the synthesis of various ECM molecules. TGF-β1 strongly enhances the expression of the gene TGFBI that encodes a cell-adhesion class, proapoptotic ECM protein called BIGH3. We hypothesized that in a diabetic environment a relationship between infiltrating macrophages, macrophage-derived TGF-β1, and BIGH3 protein promotes renal cell death. To investigate this hypothesis, we used our mouse model of diabetic complications. Mice on a high-fat diet developed hypercholesterolemia, and exposure to streptozotocin rendered hypercholesterolemic mice diabetic. Immunohistochemical images show increased macrophage infiltration and BIGH3 protein in the kidney cortices of hypercholesterolemic and diabetic mice. Macrophages induced a two-fold increase in BIGH3 expression and an 86% increase in renal proximal tubule epithelial cell apoptosis. TGF-β1 antibody and TGF-β1 receptor chemical antagonist blocked macrophage-induced apoptosis. BIGH3 antibody completely blocked apoptosis that was induced by TGF-β1, and blocked apoptosis induced by exogenous recombinant BIGH3. These results uncover a distinctive interplay of macrophage-derived TGF-β1, BIGH3 protein, and apoptosis, and indicate that BIGH3 is central in a novel pathway that promotes diabetic nephropathy. Macrophage TGF-β1 and BIGH3 are identified as prediabetic biomarkers, and potential therapeutic targets for intervention in prediabetic and diabetic individuals.展开更多
Learning-based techniques have recently been shown to be effective for denoising Monte Carlo rendering methods. However, there remains a quality gap to state-of-the-art handcrafted denoisers. In this paper, we propose...Learning-based techniques have recently been shown to be effective for denoising Monte Carlo rendering methods. However, there remains a quality gap to state-of-the-art handcrafted denoisers. In this paper, we propose a deep residual learning based method that outperforms both state-of-the-art handcrafted denoisers and learning-based denoisers.Unlike the indirect nature of existing learning-based methods(which e.g., estimate the parameters and kernel weights of an explicit feature based filter), we directly map the noisy input pixels to the smoothed output. Using this direct mapping formulation, we demonstrate that even a simple-and-standard ResNet and three common auxiliary features(depth, normal,and albedo) are sufficient to achieve high-quality denoising. This minimal requirement on auxiliary data simplifies both training and integration of our method into most production rendering pipelines. We have evaluated our method on unseen images created by a different renderer. Consistently superior quality denoising is obtained in all cases.展开更多
In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody leve...In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody levels of the cohort fluctuated, the antibody levels of 93% of the patients with NPC were raised and maintained at high levels for up to 10 years prior to diagnosis. This suggests that the serologic window affords an opportunity to monitor tumor progression during the preclinical stage of NPC development, facilitating early NPC detection. We reviewed the clinical records of the 171 patients with NPC in the prospective study to assess the efficacy of early NPC detection by serologic screening and clinical examination. Of the 171 patients, 51 had Stage I tumor (44 were among the 73 patients detected by clinical examination and 7 were among the 98 patients presented to outpatient department). Initial serologic screening predicted 58 (95.1%) of the 61 patients detected within 2 years. The risk of the screened population (58/3093) raised 13 times relative to cohort (61/42 048) during this period. Clinical examination detected all the 58 predicted cases, and 35 (60.3%) of which were diagnosed with Stage I tumor. The serologic prediction rate fell to 33.6% (37/110) 2 to 16 years after screening. The proportion of cases detected by clinical examination fell to 40.5% (15/37). The proportion of Stage I tumors among the cases detected by clinical examination during both periods remained at about 60%. We concluded that early detection of NPC can be accomplished by repeated serologic screening to maintain high prediction rates and by promptly examining screened subjects to detect tumors before the symptoms develop.展开更多
文摘Metabolically stressed kidney is in part characterized by infiltrating macrophages and macrophage-derived TGF-β1 that promote the synthesis of various ECM molecules. TGF-β1 strongly enhances the expression of the gene TGFBI that encodes a cell-adhesion class, proapoptotic ECM protein called BIGH3. We hypothesized that in a diabetic environment a relationship between infiltrating macrophages, macrophage-derived TGF-β1, and BIGH3 protein promotes renal cell death. To investigate this hypothesis, we used our mouse model of diabetic complications. Mice on a high-fat diet developed hypercholesterolemia, and exposure to streptozotocin rendered hypercholesterolemic mice diabetic. Immunohistochemical images show increased macrophage infiltration and BIGH3 protein in the kidney cortices of hypercholesterolemic and diabetic mice. Macrophages induced a two-fold increase in BIGH3 expression and an 86% increase in renal proximal tubule epithelial cell apoptosis. TGF-β1 antibody and TGF-β1 receptor chemical antagonist blocked macrophage-induced apoptosis. BIGH3 antibody completely blocked apoptosis that was induced by TGF-β1, and blocked apoptosis induced by exogenous recombinant BIGH3. These results uncover a distinctive interplay of macrophage-derived TGF-β1, BIGH3 protein, and apoptosis, and indicate that BIGH3 is central in a novel pathway that promotes diabetic nephropathy. Macrophage TGF-β1 and BIGH3 are identified as prediabetic biomarkers, and potential therapeutic targets for intervention in prediabetic and diabetic individuals.
基金supported by the Research Grants Council of the Hong Kong Special Administrative Region, under RGC General Research Fund (Project No. CUHK14217516)
文摘Learning-based techniques have recently been shown to be effective for denoising Monte Carlo rendering methods. However, there remains a quality gap to state-of-the-art handcrafted denoisers. In this paper, we propose a deep residual learning based method that outperforms both state-of-the-art handcrafted denoisers and learning-based denoisers.Unlike the indirect nature of existing learning-based methods(which e.g., estimate the parameters and kernel weights of an explicit feature based filter), we directly map the noisy input pixels to the smoothed output. Using this direct mapping formulation, we demonstrate that even a simple-and-standard ResNet and three common auxiliary features(depth, normal,and albedo) are sufficient to achieve high-quality denoising. This minimal requirement on auxiliary data simplifies both training and integration of our method into most production rendering pipelines. We have evaluated our method on unseen images created by a different renderer. Consistently superior quality denoising is obtained in all cases.
基金supported by National Natural Science Foundation of China (No. 75-61-02-13, 85-914-01-08, 96-906-01-03)
文摘In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody levels of the cohort fluctuated, the antibody levels of 93% of the patients with NPC were raised and maintained at high levels for up to 10 years prior to diagnosis. This suggests that the serologic window affords an opportunity to monitor tumor progression during the preclinical stage of NPC development, facilitating early NPC detection. We reviewed the clinical records of the 171 patients with NPC in the prospective study to assess the efficacy of early NPC detection by serologic screening and clinical examination. Of the 171 patients, 51 had Stage I tumor (44 were among the 73 patients detected by clinical examination and 7 were among the 98 patients presented to outpatient department). Initial serologic screening predicted 58 (95.1%) of the 61 patients detected within 2 years. The risk of the screened population (58/3093) raised 13 times relative to cohort (61/42 048) during this period. Clinical examination detected all the 58 predicted cases, and 35 (60.3%) of which were diagnosed with Stage I tumor. The serologic prediction rate fell to 33.6% (37/110) 2 to 16 years after screening. The proportion of cases detected by clinical examination fell to 40.5% (15/37). The proportion of Stage I tumors among the cases detected by clinical examination during both periods remained at about 60%. We concluded that early detection of NPC can be accomplished by repeated serologic screening to maintain high prediction rates and by promptly examining screened subjects to detect tumors before the symptoms develop.
