Short-term wind power prediction based on extreme learning machine with error correction

Introduction: Large-scale integration of wind generation brings great challenges to the secure operation of the power systems due to the intermittence nature of wind. The fluctuation of the wind generation has a great impact on the unit commitment. Thus accurate wind power forecasting plays a key role in dealing with the challenges of power system operation under uncertainties in an economical and technical way. Methods: In this paper, a combined approach based on Extreme Learning Machine (ELM) and an error correction model is proposed to predict wind power in the short-term time scale. Firstly an ELM is utilized to forecast the short-term wind power. Then the ultra-short-term wind power forecasting is acquired based on processing the short-term forecasting error by persistence method. Results: For short-term forecasting, the Extreme Learning Machine (ELM) doesn’t perform well. The overall NRMSE (Normalized Root Mean Square Error) of forecasting results for 66 days is 21.09 %. For the ultra-short term forecasting after error correction, most of forecasting errors lie in the interval of [−10 MW, 10 MW]. The error distribution is concentrated and almost unbiased. The overall NRMSE is 5.76 %. Conclusion: The ultra-short-term wind power forecasting accuracy is further improved by using error correction in terms of normalized root mean squared error (NRMSE)

Brag2 differentially regulates β1- and β3-integrin-dependent adhesion in endothelial cells and is involved in developmental and pathological angiogenesis

β1-Integrins are essential for angiogenesis. The mechanisms regulating integrin function in endothelial cells (EC) and their contribution to angiogenesis remain elusive. Brag2 is a guanine nucleotide exchange factor for the small Arf-GTPases Arf5 and Arf6. The role of Brag2 in EC and angiogenesis and the underlying molecular mechanisms remain unclear. siRNA-mediated Brag2-silencing reduced EC angiogenic sprouting and migration. Brag2-siRNA transfection differentially affected α5β1- and αVβ3-integrin function: specifically, Brag2-silencing increased focal/fibrillar adhesions and adhesion on β1-integrin ligands (fibronectin and collagen), while reducing the adhesion on the αVβ3-integrin ligand, vitronectin. Consistent with these results, Brag2-silencing enhanced surface expression of α5β1-integrin, while reducing surface expression of αVβ3-integrin. Mechanistically, Brag2-mediated αVβ3-integrin-recycling and β1-integrin endocytosis and specifically of the active/matrix-bound α5β1-integrin present in fibrillar/focal adhesions (FA), suggesting that Brag2 contributes to the disassembly of FA via β1-integrin endocytosis. Arf5 and Arf6 are promoting downstream of Brag2 angiogenic sprouting, β1-integrin endocytosis and the regulation of FA. In vivo silencing of the Brag2-orthologues in zebrafish embryos using morpholinos perturbed vascular development. Furthermore, in vivo intravitreal injection of plasmids containing Brag2-shRNA reduced pathological ischemia-induced retinal and choroidal neovascularization. These data reveal that Brag2 is essential for developmental and pathological angiogenesis by promoting EC sprouting through regulation of adhesion by mediating β1-integrin internalization and link for the first time the process of β1-integrin endocytosis with angiogenesis.Deutsche Forschungsgemeinschaft. Transregional Collaborative Research Centre. (SFB/TR23)Deutsche Forschungsgemeinschaft. Transregional Collaborative Research Centre. (Project A2)Deutsche Forschungsgemeinschaft. Transregional Collaborative Research Centre.(Project Z5)Else Kroner-Fresenius-Stiftung (2013_A2

Inhibiting Phase Transfer of Protein Nanoparticles by Surface Camouflage-A Versatile and Efficient Protein Encapsulation Strategy

Engineering a system with a high mass fraction of active ingredients, especially water-soluble proteins, is still an ongoing challenge. In this work, we developed a versatile surface camouflage strategy that can engineer systems with an ultrahigh mass fraction of proteins. By formulating protein molecules into nanoparticles, the demand of molecular modification was transformed into a surface camouflage of protein nanoparticles. Thanks to electrostatic attractions and van der Waals interactions, we camouflaged the surface of protein nanoparticles through the adsorption of carrier materials. The adsorption of carrier materials successfully inhibited the phase transfer of insulin, albumin, β-lactoglobulin, and ovalbumin nanoparticles. As a result, the obtained microcomposites featured with a record of protein encapsulation efficiencies near 100% and a record of protein mass fraction of 77%. After the encapsulation in microcomposites, the insulin revealed a hypoglycemic effect for at least 14 d with one single injection, while that of insulin solution was only ∼4 h.Peer reviewe

Role of VEGFR2 in Mediating Endoplasmic Reticulum Stress Under Glucose Deprivation and Determining Cell Death, Oxidative Stress, and Inflammatory Factor Expression

Retinal pigment epithelium (RPE), a postmitotic monolayer located between the neuroretina and choroid, supports the retina and is closely associated with vision loss diseases such as age-related macular degeneration (AMD) upon dysfunction. Although environmental stresses are known to play critical roles in AMD pathogenesis and the roles of other stresses have been well investigated, glucose deprivation, which can arise from choriocapillary flow voids, has yet to be fully explored. In this study, we examined the involvement of VEGFR2 in glucose deprivation-mediated cell death and the underlying mechanisms. We found that VEGFR2 levels are a determinant for RPE cell death, a critical factor for dry AMD, under glucose deprivation. RNA sequencing analysis showed that upon VEGFR2 knockdown under glucose starvation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are reduced. Consistently, VEGFR2 overexpression increased ER stress under the same condition. Although VEGFR2 was less expressed compared to EGFR1 and c-Met in RPE cells, it could elicit a higher level of ER stress induced by glucose starvation. Finally, downregulated VEGFR2 attenuated the oxidative stress and inflammatory factor expression, two downstream targets of ER stress. Our study, for the first time, has demonstrated a novel role of VEGFR2 in RPE cells under glucose deprivation, thus providing valuable insights into the mechanisms of AMD pathogenesis and suggesting that VEGFR2 might be a potential therapeutic target for AMD prevention, which may impede its progression

Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation

Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine–induced Parkinson’s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3β phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC–PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions

A miR-327–FGF10–FGFR2-mediated autocrine signaling mechanism controls white fat browning

Understanding the molecular mechanisms regulating beige adipocyte formation may lead to the development of new therapies to combat obesity. Here, we report a miRNA-based autocrine regulatory pathway that controls differentiation of preadipocytes into beige adipocytes. We identify miR-327 as one of the most downregulated miRNAs targeting growth factors in the stromal-vascular fraction (SVF) under conditions that promote white adipose tissue (WAT) browning in mice. Gain- and loss-of-function experiments reveal that miR-327 targets FGF10 to prevent beige adipocyte differentiation. Pharmacological and physiological β-adrenergic stimulation upregulates FGF10 levels and promotes preadipocyte differentiation into beige adipocytes. In vivo local delivery of miR-327 to WATs significantly compromises the beige phenotype and thermogenesis. Contrarily, systemic inhibition of miR-327 in mice induces browning and increases whole-body metabolic rate under thermoneutral conditions. Our data provide mechanistic insight into an autocrine regulatory signaling loop that regulates beige adipocyte formation and suggests that the miR-327–FGF10–FGFR2 signaling axis may be a therapeutic targets for treatment of obesity and metabolic diseases

Impairment of angiogenesis by fatty acid synthase inhibition Involves mTOR malonylation

The role of fatty acid synthesis in endothelial cells (ECs) remains incompletely characterized. We report that fatty acid synthase knockdown (FASNKD) in ECs impedes vessel sprouting by reducing proliferation. Endothelial loss of FASN impaired angiogenesis in vivo, while FASN blockade reduced pathological ocular neovascularization, at >10-fold lower doses than used for anti-cancer treatment. Impaired angiogenesis was not due to energy stress, redox imbalance, or palmitate depletion. Rather, FASNKD elevated malonyl-CoA levels, causing malonylation (a post-translational modification) of mTOR at lysine 1218 (K1218). mTOR K-1218 malonylation impaired mTOR complex 1 (mTORC1) kinase activity, thereby reducing phosphorylation of downstream targets (p70S6K/4EBP1). Silencing acetyl-CoA carboxylase 1 (an enzyme producing malonyl-CoA) normalized malonyl-CoA levels and reactivated mTOR in FASNKD ECs. Mutagenesis unveiled the importance of mTOR K1218 malonylation for angiogenesis. This study unveils a novel role of FASN in metabolite signaling that contributes to explaining the anti-angiogenic effect of FASN blockade

Genomic imprinting and DNA epigenetic modification in human liver and carcinogenesis : regulation of the IGF2 and H19 genes

Genomic imprinting, which is an non-classical genetic event discovered approximately a decade ago, has been shown to be involved in the mammalian development and several kinds of human diseases. Epigenetic modifications, such as DNA methylation, are believed to be markers functioning as the imprinting signals. With more and more studies focused in this field, imprinting alteration has been found to be involved in some of the genetic diseases inherited tumor syndromes and sporadic tumors. However, the molecular mechanism involved is still unclear. The human IGF2 gene is located on chromosome llpl5.5 and encodes a protein product of 67 amino acids functioning as a fetal growth factor and a cell mitogen. In fetal tissues, only the paternal allele is expressed while the maternal one is silent. The Hl9 gene is located approximately 200 kb downstream of IGF2. In most of the tissues, only the maternal allele is expressed. The Hl9 and IGF2 genes are believed to be not only physically linked but also correlated by utilizing the same enhancer. Among different forms of epigenetic modifications of DNA, methylation is believed to be the best candidate for the imprinting signal, and evidence has been shown that DNA methylation is involved in the regulation of both IGF2 and Hl9. In this study, promoter activities, general and promoter-specific imprinting, expression levels and DNA methylation status of the two genes were investigated in normal human livers and primary liver tumors, hepatoblastoma and hepatocellular carcinoma. Results show that the four promoters of IGF2 are under a tight but dynamic control in a developmental-specific way. The P3 and Pl promoters are activated in fetal and adult livers respectively, each producing approximately 70% and 50% of the total IGF2 transcripts. Methylation studies show that developmental and sequence-specific DNA methylation may be involved in the regulation of the promoter activities. The P2 and the P4 promoters are active throughout development with relatively minor changes in expression levels before and after birth. In adult, a relaxation of the imprinting from the P4 promoter can be seen by usage of the two parental alleles randomly. In both hepatoblastoma and hepatocellular carcinoma, promoter Pl is found significantly silenced and this turns out to be an important feature of liver tumors. P3 activity is upregulated in subgroups of both tumors with altered total expression levels of IGF2 and Hl9. The loss of imprinting of IGF2 can be found occasionally in both kinds of tumors. In conclusion, the aberrant IGF2 regulation, including disrupted promoter control by silencing of P1 and altered promoter-specific DNA methylation, is an frequent phenomenon in human liver cancers. Since the IGF2 gene is regulated in a tight but dynamic, developmental-specific way, any disruption during this procedure may affect the normal liver development. Therefore, the molecular basis of the aberrant IGF2 regulation is worth looking into to understand the molecular tumorigenesis of human liver cancers. ISBN 91-628-2566-