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1,911 result(s) for "Campbell, Steven"
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Currencies of the Indian ocean world
This book is the first to trace the unique monetary history of the Indian Ocean World. Long-distance trade across the region was facilitated by a highly complex multi-currency system undergirded by shared ideas that transcended ethno-linguistic, religious and class divisions. Currencies also occupied key roles in local spiritual, aesthetic and affective practices. Foregrounding these tensions between the global/universalistic and the local/particularistic, the volume shows how this traditional currency system remained in place until the middle of the twentieth century, and how aspects of the system continue to inform monetary practices throughout the region. With case studies covering China, India, the Arabian Sea, the Red Sea, East Africa, Zanzibar, Madagascar and Mauritius from the thirteenth to the twenty-first centuries, this volume explores the central role currencies played in economic exchange as well as in establishing communal bonds, defining state power and expressing religious sentiments.
Renal cell carcinoma
Considerable progress has been made in the treatment of patients with renal cell carcinoma, with innovative surgical and systemic strategies revolutionising the management of this disease. In localised disease, partial nephrectomy for small tumours and radical nephrectomy for large tumours continue to be the gold-standard treatments, with emphasis on approaches that have reduced invasiveness and preserve renal function. Additionally, cytoreductive nephrectomy is often indicated before the start of systemic treatment in patients with metastatic disease as part of integrated management strategy. The effectiveness of immunotherapy, although previously widely used for treatment of metastatic renal cell carcinoma, is still controversial, and is mainly reserved for patients with good prognostic factors. Development of treatments that have specific targets in relevant biological pathways has been the main advance in treatment. Targeted drugs, including inhibitors of the vascular endothelial growth factor and mammalian target of rapamycin pathways, have shown robust effectiveness and offer new therapeutic options for the patients with metastatic disease.
Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants
Ascorbic acid is among the most abundant antioxidants in the lung, where it likely plays a key role in the mechanism by which particulate air pollution initiates a biological response. Because ascorbic acid is a highly redox active species, it engages in a far more complex web of reactions than a typical organic molecule, reacting with oxidants such as the hydroxyl radical as well as redox-active transition metals such as iron and copper. The literature provides a solid outline for this chemistry, but there are large disagreements about mechanisms, stoichiometries and reaction rates, particularly for the transition metal reactions. Here we synthesize the literature, develop a chemical kinetics model, and use seven sets of laboratory measurements to constrain mechanisms for the iron and copper reactions and derive key rate constants. We find that micromolar concentrations of iron(III) and copper(II) are more important sinks for ascorbic acid (both AH 2 and AH − ) than reactive oxygen species. The iron and copper reactions are catalytic rather than redox reactions, and have unit stoichiometries: Fe(III)/Cu(II) + AH 2 /AH −  + O 2 → Fe(III)/Cu(II) + H 2 O 2  + products. Rate constants are 5.7 × 10 4 and 4.7 × 10 4  M −2  s −1 for Fe(III) + AH 2 /AH − and 7.7 × 10 4 and 2.8 × 10 6  M −2  s −1 for Cu(II) + AH 2 /AH − , respectively.
HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism
Clear cell renal cell carcinoma (ccRCC) is histologically defined by its lipid and glycogen-rich cytoplasmic deposits. Alterations in the VHL tumor suppressor stabilizing the hypoxia-inducible factors (HIFs) are the most prevalent molecular features of clear cell tumors. The significance of lipid deposition remains undefined. We describe the mechanism of lipid deposition in ccRCC by identifying the rate-limiting component of mitochondrial fatty acid transport, carnitine palmitoyltransferase 1A ( CPT1A ), as a direct HIF target gene. CPT1A is repressed by HIF1 and HIF2, reducing fatty acid transport into the mitochondria, and forcing fatty acids to lipid droplets for storage. Droplet formation occurs independent of lipid source, but only when CPT1A is repressed. Functionally, repression of CPT1A is critical for tumor formation, as elevated CPT1A expression limits tumor growth. In human tumors, CPT1A expression and activity are decreased versus normal kidney; and poor patient outcome associates with lower expression of CPT1A in tumors in TCGA. Together, our studies identify HIF control of fatty acid metabolism as essential for ccRCC tumorigenesis. Clear cell renal cancers (ccRCC) display elevated intracellular lipid storage. Here the authors show that such lipid accumulation is due to the repression of carnitine palmitoyltransferase 1A (CPT1A) enzyme that impairs fatty acid (FA) transport into the mitochondrion resulting in reduced FA beta oxidation.
Low grade oncocytic tumors of the kidney: a clinically relevant approach for the workup and accurate diagnosis
Renal oncocytoma and chromophobe renal cell carcinoma were accepted as unique renal tumors in the late 1990s. Since their formal description, criteria for diagnosis have evolved and additional distinct tumor subtypes originally considered as one these two entities are now recognized. The last two decades have witnessed unprecedented interest in the spectrum of low grade oncocytic renal neoplasms in three specific areas: (1) histologic characterization of tumors with overlapping morphologic features between oncocytoma and chromophobe renal cell carcinoma; (2) description of potentially unique entities within this spectrum, such as eosinophilic vacuolated tumor and low-grade oncocytic tumor; and (3) better appreciation of the association between a subset of low grade oncocytic tumors and hereditary renal neoplasia. While this important work has been academically rewarding, the proposal of several histologic entities with overlapping morphologic and immunophenotypic features (which may require esoteric adjunctive immunohistochemical and/or molecular techniques for confirmation) has created frustration in the diagnostic pathology and urology community as information evolves regarding classification within this spectrum of renal neoplasia. Pathologists, including genitourinary subspecialists, are often uncertain as to the “best practice” diagnostic approach to such tumors. In this review, we present a practical clinically relevant algorithmic approach to classifying tumors within the low grade oncocytic family of renal neoplasia, including a proposal for compressing terminology for evolving categories where appropriate without sacrificing prognostic relevance.
Atmospheric conditions and composition that influence PM2.5 oxidative potential in Beijing, China
Epidemiological studies have consistently linked exposure to PM2.5 with adverse health effects. The oxidative potential (OP) of aerosol particles has been widely suggested as a measure of their potential toxicity. Several acellular chemical assays are now readily employed to measure OP; however, uncertainty remains regarding the atmospheric conditions and specific chemical components of PM2.5 that drive OP. A limited number of studies have simultaneously utilised multiple OP assays with a wide range of concurrent measurements and investigated the seasonality of PM2.5 OP. In this work, filter samples were collected in winter 2016 and summer 2017 during the atmospheric pollution and human health in a Chinese megacity campaign (APHH-Beijing), and PM2.5 OP was analysed using four acellular methods: ascorbic acid (AA), dithiothreitol (DTT), 2,7-dichlorofluorescin/hydrogen peroxidase (DCFH) and electron paramagnetic resonance spectroscopy (EPR). Each assay reflects different oxidising properties of PM2.5, including particle-bound reactive oxygen species (DCFH), superoxide radical production (EPR) and catalytic redox chemistry (DTT/AA), and a combination of these four assays provided a detailed overall picture of the oxidising properties of PM2.5 at a central site in Beijing. Positive correlations of OP (normalised per volume of air) of all four assays with overall PM2.5 mass were observed, with stronger correlations in winter compared to summer. In contrast, when OP assay values were normalised for particle mass, days with higher PM2.5 mass concentrations (µgm-3) were found to have lower mass-normalised OP values as measured by AA and DTT. This finding supports that total PM2.5 mass concentrations alone may not always be the best indicator for particle toxicity. Univariate analysis of OP values and an extensive range of additional measurements, 107 in total, including PM2.5 composition, gas-phase composition and meteorological data, provided detailed insight into the chemical components and atmospheric processes that determine PM2.5 OP variability. Multivariate statistical analyses highlighted associations of OP assay responses with varying chemical components in PM2.5 for both mass- and volume-normalised data. AA and DTT assays were well predicted by a small set of measurements in multiple linear regression (MLR) models and indicated fossil fuel combustion, vehicle emissions and biogenic secondary organic aerosol (SOA) as influential particle sources in the assay response. Mass MLR models of OP associated with compositional source profiles predicted OP almost as well as volume MLR models, illustrating the influence of mass composition on both particle-level OP and total volume OP. Univariate and multivariate analysis showed that different assays cover different chemical spaces, and through comparison of mass- and volume-normalised data we demonstrate that mass-normalised OP provides a more nuanced picture of compositional drivers and sources of OP compared to volume-normalised analysis. This study constitutes one of the most extensive and comprehensive composition datasets currently available and provides a unique opportunity to explore chemical variations in PM2.5 and how they affect both PM2.5 OP and the concentrations of particle-bound reactive oxygen species.