Measurements of reactive nitrogen produced by tropical thunderstorms during BIBLE-C

The Biomass Burning and Lightning Experiment phase C (BIBLE-C) aircraft mission was carried out near Darwin, Australia (12°S, 131°E) in December 2000. This was the first aircraft experiment designed to estimate lightning NO production rates in the tropics, where production is considered to be most intense. During the two flights (flights 10 and 13 made on December 9 and 11-12, respectively) enhancements of NOx (NO + NO2) up to 1000 and 1600 parts per trillion by volume (pptv, 10-s data) were observed at altitudes between 11.5 and 14 km. The Geostationary Meteorological Satellite (GMS) cloud (brightness temperature) data and ground-based lightning measurements by the Global Positioning and Tracking System (GPATS) indicate that there were intensive lightning events over the coast of the Gulf of Carpentaria, which took place upstream from our measurement area 10 to 14 h prior to the measurements. For these two flights, air in which NOx exceeded 100 pptv extended over 620 × 140 and 400 × 170 km2 (wind direction x perpendicular direction), respectively, suggesting a significant impact of lightning NO production on NOx levels in the tropics. We estimate the amount of NOx observed between 11.5 and 14 km produced by the thunderstorms to be 3.3 and 1.8 × 1025 NO molecules for flights 10 and 13, respectively. By using the GPATS lightning flash count data, column NO production rates are estimated to be 1.9-4.4 and 21-49 × 1025 NO molecules per single flash for these two flight data sets. In these estimations, it is assumed that the column NO production between 0 and 16 km is greater than the observed values between 11.5 and 14 km by a factor of 3.2, which is derived using results reported by Pickering et al. (1998). There are however large uncertainties in the GPATS lightning data in this study and care must be made when the production rates are referred. Uncertainties in these estimates are discussed. The impact on the ozone production rate is also described. Copyright 2007 by the American Geophysical Union

Autoinjection of electrons into a wake field using a capillary with attached cone

Copyright 2009 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Physics of Plasmas, 16(12), 123103, 2009 and may be found at http://dx.doi.org/10.1063/1.327115

Spectrum modulation of relativistic electrons by laser wakefield

Copyright 2008 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Applied Physics Letters, 93(8), 081501, 2008 and may be found at http://dx.doi.org/10.1063/1.297123

Methods and rationale of the DISCOVER CKD global observational study

Background: Real-world data for patients with chronic kidney disease (CKD), specifically pertaining to clinical management, metabolic control, treatment patterns, quality of life (QoL) and dietary patterns, are limited. Understanding these gaps using real-world, routine care data will improve our understanding of the challenges and consequences faced by patients with CKD, and will facilitate the long-term goal of improving their management and prognosis. Methods: DISCOVER CKD follows an enriched hybrid study design, with both retrospective and prospective patient cohorts, integrating primary and secondary data from patients with CKD from China, Italy, Japan, Sweden, the UK and the USA. Data will be prospectively captured over a 3-year period from >1000 patients with CKD who will be followed up for at least 1 year via electronic case report form entry during routine clinical visits and also via a mobile/tablet-based application, enabling the capture of patient-reported outcomes (PROs). In-depth interviews will be conducted in a subset of ∼100 patients. Separately, secondary data will be retrospectively captured from >2 000 000 patients with CKD, extracted from existing datasets and registries. Results: The DISCOVER CKD program captures and will report on patient demographics, biomarker and laboratory measurements, medical histories, clinical outcomes, healthcare resource utilization, medications, dietary patterns, physical activity and PROs (including QoL and qualitative interviews). Conclusions: The DISCOVER CKD program will provide contemporary real-world insight to inform clinical practice and improve our understanding of the epidemiology and clinical and economic burden of CKD, as well as determinants of clinical outcomes and PROs from a range of geographical regions in a real-world CKD setting

Genetic deficiency of aldose reductase counteracts the development of diabetic nephropathy in C57BL/6 mice

National Science Foundation of China [30770490]; 973 Program of China [2009CB941601]; Science Planning Program of Fujian Province [2009J1010]; Natural Science Foundation of Fujian Province [2009J01180]; Fujian Provincial Department of Science and TechnoloThe aim of the study was to investigate the effects of genetic deficiency of aldose reductase in mice on the development of key endpoints of diabetic nephropathy. A line of Ar (also known as Akr1b3)-knockout (KO) mice, a line of Ar-bitransgenic mice and control C57BL/6 mice were used in the study. The KO and bitransgenic mice were deficient for Ar in the renal glomeruli and all other tissues, with the exception of, in the bitransgenic mice, a human AR cDNA knockin-transgene that directed collecting-tubule epithelial-cell-specific AR expression. Diabetes was induced in 8-week-old male mice with streptozotocin. Mice were further maintained for 17 weeks then killed. A number of serum and urinary variables were determined for these 25-week-old mice. Periodic acid-Schiff staining, western blots, immunohistochemistry and protein kinase C (PKC) activity assays were performed for histological analyses, and to determine the levels of collagen IV and TGF-beta 1 and PKC activities in renal cortical tissues. Diabetes-induced extracellular matrix accumulation and collagen IV overproduction were completely prevented in diabetic Ar-KO and bitransgenic mice. Ar deficiency also completely or partially prevented diabetes-induced activation of renal cortical PKC, TGF-beta 1 and glomerular hypertrophy. Loss of Ar results in a 43% reduction in urine albumin excretion in the diabetic Ar-KO mice and a 48% reduction in the diabetic bitransgenic mice (p < 0.01). Genetic deficiency of Ar significantly ameliorated development of key endpoints linked with early diabetic nephropathy in vivo. Robust and specific inhibition of aldose reductase might be an effective strategy for the prevention and treatment of diabetic nephropathy

Activin A Induces Langerhans Cell Differentiation In Vitro and in Human Skin Explants

Langerhans cells (LC) represent a well characterized subset of dendritic cells located in the epidermis of skin and mucosae. In vivo, they originate from resident and blood-borne precursors in the presence of keratinocyte-derived TGFβ. Ιn vitro, LC can be generated from monocytes in the presence of GM-CSF, IL-4 and TGFβ. However, the signals that induce LC during an inflammatory reaction are not fully investigated. Here we report that Activin A, a TGFβ family member induced by pro-inflammatory cytokines and involved in skin morphogenesis and wound healing, induces the differentiation of human monocytes into LC in the absence of TGFβ. Activin A-induced LC are Langerin+, Birbeck granules+, E-cadherin+, CLA+ and CCR6+ and possess typical APC functions. In human skin explants, intradermal injection of Activin A increased the number of CD1a+ and Langerin+ cells in both the epidermis and dermis by promoting the differentiation of resident precursor cells. High levels of Activin A were present in the upper epidermal layers and in the dermis of Lichen Planus biopsies in association with a marked infiltration of CD1a+ and Langerin+ cells. This study reports that Activin A induces the differentiation of circulating CD14+ cells into LC. Since Activin A is abundantly produced during inflammatory conditions which are also characterized by increased numbers of LC, we propose that this cytokine represents a new pathway, alternative to TGFβ, responsible for LC differentiation during inflammatory/autoimmune conditions

The role of dendritic cells in the immunopathogenesis of psoriasis

Psoriasis vulgaris is a chronic inflammatory skin disease that is marked by a complex interplay of dendritic cells (DCs), T-cells, cytokines, and downstream transcription factors as part of a self-sustaining type 1 cytokine network. As integral players of the immune system, DCs represent antigen-presenting cells that are crucial for efficient activation of T-cells and B-cells. DCs have also been linked to distinct chronic inflammatory conditions, including psoriasis. In the setting of psoriasis therapy, DC/T cell interactions serve as a potential target for biologic response modifiers. Here we describe the major DC subsets as well as the immunologic involvement of DCs within the context of psoriatic lesions