1,521 research outputs found

    Spatiotemporal perspectives on urban energy transitions: a comparative study of three cities in China

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    This paper develops an integrated framework to study the socio-spatial and temporal dimensions of urban energy transitions to investigate the development and spread of solar energy technologies in urban China. A comparative analysis of three case studies of solar energy transitions in the cities of Foshan (in Guangdong), Rizhao (in Shandong), and Wuxi (in Jiangsu) demonstrates the framework’s applicability. The results map each city’s trajectory towards low carbon energy. Transitions result from dynamic interactions among central and local governments, solar manufacturers, solar installers, and residents. Alongside industrial strategies, locally-specific factors have a determining influence on the eventual outcomes

    Nano-Fe<sup>0</sup> immobilized onto functionalized biochar gaining excellent stability during sorption and reduction of chloramphenicol via transforming to reusable magnetic composite

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    © 2017 Elsevier B.V. The widely used nanosized zero-valent iron (nZVI or nFe0) particles and their composite material lose reductive nature during application, and the stability of transformed composite material for repeatable application is not addressed to date. To shed light on this, nZVI was synthesized from scrap material and immobilized on functionalized biochar (fBC) to prepare nZVI-fBC composite. Comparative study between nZVI and nZVI-fBC composite on the removal of chlorinated antibiotic chloramphenicol from different water types was conducted. The results suggested that nZVI was solely responsible for reduction of chloramphenicol. Whereas nZVI-fBC could be applied once, within a few hours, for the reduction of chloramphenico (29–32.5%) and subsequently sorption (67.5–70.5%) by transforming to a fully magnetic composite (nFe3O4-fBC) gaining stability with synergistic sorption performance. In both cases, two reduction by-products were identified namely 2-chloro-N-[1,3-dihydroxy-1-(4-aminophenyl)propan-2-yl]acetamide (m/z 257) and dechlorinated N-[1,3-dihydroxy-1-(4-aminophenyl)propan-2-yl]acetamide (m/z 223). The complete removal of 3.1 ”M L−1 of chloramphenicol in different water was faster by nZVI-fBC (∌12–15 h) than by stable nFe3O4-fBC composite (∌18 h). Both nZVI-fBC and nFe3O4-fBC composites removed chloramphenicol in the order: deionized water > lake water > synthetic wastewater. nFe3O4-fBC showed excellent reusability after regeneration, with the regenerated nFe3O4-fBC composite (after 6 cycles of application) showing significant performance for methylene blue removal (∌287 mg g−1). Therefore, the transformed nFe3O4-fBC composite is a promising and reusable sorbent for the efficient removal of organic contaminants

    Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC

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    Regulation of cell volume is critical for many cellular and organismal functions, yet the molecular identity of a key player, the volume-regulated anion channel VRAC, has remained unknown. A genome-wide siRNA screen in mammalian cells identified LRRC8A as a VRAC component. LRRC8A formed heteromers with other LRRC8 multispan membrane proteins. Genomic disruption of LRRC8A ablated VRAC currents. Cells with disruption of all five LRRC8 genes required LRRC8A co-transfection with other LRRC8 isoforms to reconstitute VRAC currents. The isoform combination determined VRAC inactivation kinetics. Taurine flux and regulatory volume decrease also depended on LRRC8 proteins. Our work shows that VRAC defines a class of anion channels, suggests that VRAC is identical to the volume-sensitive organic osmolyte/anion channel VSOAC, and explains the heterogeneity of native VRAC currents

    Therapeutic complement targeting in ANCA-associated vasculitides and thrombotic microangiopathy

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    Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of systemic autoimmune disorders characterized by necrotizing inflammation of medium-to-small vessels, a relative paucity of immune deposits, and an association with detectable circulating ANCAs. AAVs include granulomatosis with polyangiitis (renamed from Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Until recently, AAVs have not been viewed as complement-mediated disorders. However, recent findings predominantly from animal studies demonstrated a crucial role of the complement system in the pathogenesis of AAVs. Complement activation or defects in its regulation have been described in an increasing number of acquired or genetically driven forms of thrombotic microangiopathy. Coinciding with this expanding spectrum of complement-mediated diseases, the question arises as to which AAV patients might benefit from a complement-targeted therapy. Therapies directed against the complement system point to the necessity of a genetic workup of genes of complement components and regulators in patients with AAV. Genetic testing together with pluripotent stem cells and bioinformatics tools may broaden our approach to the treatment of patients with aggressive forms of AAV

    On the selection and design of proteins and peptide derivatives for the production of photoluminescent, red-emitting gold quantum clusters

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    Novel pathways of the synthesis of photoluminescent gold quantum clusters (AuQCs) using biomolecules as reactants provide biocompatible products for biological imaging techniques. In order to rationalize the rules for the preparation of red-emitting AuQCs in aqueous phase using proteins or peptides, the role of different organic structural units was investigated. Three systems were studied: proteins, peptides, and amino acid mixtures, respectively. We have found that cysteine and tyrosine are indispensable residues. The SH/S-S ratio in a single molecule is not a critical factor in the synthesis, but on the other hand, the stoichiometry of cysteine residues and the gold precursor is crucial. These observations indicate the importance of proper chemical behavior of all species in a wide size range extending from the atomic distances (in the AuI-S semi ring) to nanometer distances covering the larger sizes of proteins assuring the hierarchical structure of the whole self-assembled system

    Efficacy and Safety of Viltolarsen in Boys With Duchenne Muscular Dystrophy: Results From the Phase 2, Open-Label, 4-Year Extension Study

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    Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations, resulting in absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, significantly increased dystrophin levels in patients with DMD. Presented here are completed study results of \u3e 4 years of functional outcomes in viltolarsen-treated patients compared to a historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study [CINRG DNHS]). Objective: To evaluate the efficacy and safety of viltolarsen for an additional 192 weeks in boys with DMD. Methods: This phase 2, open-label, 192-week long-term extension (LTE) study (NCT03167255) evaluated the efficacy and safety of viltolarsen in participants aged 4 to \u3c 10 years at baseline with DMD amenable to exon 53 skipping. All 16 participants from the initial 24-week study enrolled into this LTE. Timed function tests were compared to the CINRG DNHS group. All participants received glucocorticoid treatment. The primary efficacy outcome was time to stand from supine (TTSTAND). Secondary efficacy outcomes included additional timed function tests. Safety was continuously assessed. Results: For the primary efficacy outcome (TTSTAND), viltolarsen-treated patients showed stabilization of motor function over the first two years and significant slowing of disease progression over the following two years compared with the CINRG DNHS control group which declined. Viltolarsen was well tolerated, with most reported treatment-emergent adverse events being mild or moderate. No participants discontinued drug during the study. Conclusions: Based on the results of this 4-year LTE, viltolarsen can be an important treatment strategy for DMD patients amenable to exon 53 skipping

    DRAM-3 modulates autophagy and promotes cell survival in the absence of glucose

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    Macroautophagy is a membrane-trafficking process that delivers cytoplasmic constituents to lysosomes for degradation. The process operates under basal conditions as a mechanism to turnover damaged or misfolded proteins and organelles. As a result, it has a major role in preserving cellular integrity and viability. In addition to this basal function, macroautophagy can also be modulated in response to various forms of cellular stress, and the rate and cargoes of macroautophagy can be tailored to facilitate appropriate cellular responses in particular situations. The macroautophagy machinery is regulated by a group of evolutionarily conserved autophagy-related (ATG) proteins and by several other autophagy regulators, which either have tissue-restricted expression or operate in specific contexts. We report here the characterization of a novel autophagy regulator that we have termed DRAM-3 due to its significant homology to damage-regulated autophagy modulator (DRAM-1). DRAM-3 is expressed in a broad spectrum of normal tissues and tumor cells, but different from DRAM-1, DRAM-3 is not induced by p53 or DNA-damaging agents. Immunofluorescence studies revealed that DRAM-3 localizes to lysosomes/autolysosomes, endosomes and the plasma membrane, but not the endoplasmic reticulum, phagophores, autophagosomes or Golgi, indicating significant overlap with DRAM-1 localization and with organelles associated with macroautophagy. In this regard, we further proceed to show that DRAM-3 expression causes accumulation of autophagosomes under basal conditions and enhances autophagic flux. Reciprocally, CRISPR/Cas9-mediated disruption of DRAM-3 impairs autophagic flux confirming that DRAM-3 is a modulator of macroautophagy. As macroautophagy can be cytoprotective under starvation conditions, we also tested whether DRAM-3 could promote survival on nutrient deprivation. This revealed that DRAM-3 can repress cell death and promote long-term clonogenic survival of cells grown in the absence of glucose. Interestingly, however, this effect is macroautophagy-independent. In summary, these findings constitute the primary characterization of DRAM-3 as a modulator of both macroautophagy and cell survival under starvation conditions

    The Journal of Nutrition Nutrition and Disease Postprandial Hyperglycemia Impairs Vascular Endothelial Function in Healthy Men by Inducing Lipid Peroxidation and Increasing Asymmetric Dimethylarginine:Arginine 1-3

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    Abstract Postprandial hyperglycemia induces vascular endothelial dysfunction (VED) and increases future cardiovascular disease risk. We hypothesized that postprandial hyperglycemia would decrease vascular function in healthy men by inducing oxidative stress and proinflammatory responses and increasing asymmetric dimethylarginine:arginine (ADMA:arginine), a biomarker that is predictive of reduced NO biosynthesis. In a randomized, cross-over design, healthy men (n = 16; 21.6 6 0.8 y) ingested glucose or fructose (75 g) after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose and insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine, and ADMA were measured at regular intervals during the 3-h postprandial period. Baseline FMD did not differ between trials (P . 0.05). Postprandial Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation. Postprandial alterations in arginine and ADMA: arginine also suggest that acute hyperglycemia may induce VED by decreasing NO bioavailability through an oxidative stressdependent mechanism. Additional work is warranted to define whether inhibiting lipid peroxidation and restoring arginine metabolism would mitigate hyperglycemia-mediated decreases in vascular function

    Developing a methodology for three-dimensional correlation of PET–CT images and whole-mount histopathology in non-small-cell lung cancer

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    Background: Understanding the three-dimensional (3D) volumetric relationship between imaging and functional or histopathologic heterogeneity of tumours is a key concept in the development of image-guided radiotherapy. Our aim was to develop a methodologic framework to enable the reconstruction of resected lung specimens containing non-small-cell lung cancer (NSCLC), to register the result in 3D with diagnostic imaging, and to import the reconstruction into a radiation treatment planning system. Methods and Results: We recruited 12 patients for an investigation of radiology-pathology correlation (RPC) in NSCLC. Before resection, imaging by positron emission tomography (PET) or computed tomography (CT) was obtained. Resected specimens were formalin-fixed for 1-24 hours before sectioning at 3-mm to 10-mm intervals. To try to retain the original shape, we embedded the specimens in agar before sectioning. Consecutive sections were laid out for photography and manually adjusted to maintain shape. Following embedding, the tissue blocks underwent whole-mount sectioning (4-ÎŒm sections) and staining with hematoxylin and eosin. Large histopathology slides were used to whole-mount entire sections for digitization. The correct sequence was maintained to assist in subsequent reconstruction. Using Photoshop (Adobe Systems Incorporated, San Jose, CA, U.S.A.), contours were placed on the photographic images to represent the external borders of the section and the extent of macroscopic disease. Sections were stacked in sequence and manually oriented in Photoshop. The macroscopic tumour contours were then transferred to MATLAB (The Mathworks, Natick, MA, U.S.A.) and stacked, producing 3D surface renderings of the resected specimen and embedded gross tumour. To evaluate the microscopic extent of disease, customized "tile-based" and commercial confocal panoramic laser scanning (TISSUEscope: Biomedical Photometrics, Waterloo, ON) systems were used to generate digital images of whole-mount histopathology sections. Using the digital whole-mount images and imaging software, we contoured the gross and microscopic extent of disease. Two methods of registering pathology and imaging were used. First, selected PET and CT images were transferred into Photoshop, where they were contoured, stacked, and reconstructed. After importing the pathology and the imaging contours to MATLAB, the contours were reconstructed, manually rotated, and rigidly registered. In the second method, MATLAB tumour renderings were exported to a software platform for manual registration with the original PET and CT images in multiple planes. Data from this software platform were then exported to the Pinnacle radiation treatment planning system in DICOM (Digital Imaging and Communications in Medicine) format. Conclusions: There is no one definitive method for 3D volumetric RPC in NSCLC. An innovative approach to the 3D reconstruction of resected NSCLC specimens incorporates agar embedding of the specimen and whole-mount digital histopathology. The reconstructions can be rigidly and manually registered to imaging modalities such as CT and PET and exported to a radiation treatment planning system
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