346 research outputs found

    Development of planar langmuir probes for supersonic plasma flows

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    Langmuir probes are a long established tool for the investigation and char- acterization of plasmas. Diagnostic use of planar Langmuir probes in sta- tionary low temperature plasmas is a well understood and long established technique. When the plasma possesses a drift velocity greater than the ion sound speed the flow is considered to be supersonic. Under such conditions the theory for Langmuir probes is less than satisfactory. Where the flow is supersonic the Mach probe theory of Hudis and Lidsky [1] can be applied for a magnetized plasma. However in the case of an unmagnetized plasma there is no satisfactory theory. It has been observed that in orientating a planar Langmuir probe parallel to the direction of flow, the ion current due to the flow is eliminated. Under such conditions the behaviour of the plasma’s in- teraction with the probe bears close resemblance to the conditions seen in plasma immersion ion implantation (PIII). This thesis describes the adaptation’s made to PIII analytical model’s to take advantage of these similarities and its use to then describe the ion current of planar Langmuir probes in unmagnetized plasmas possessing a supersonic flow. In adapting a suitable analytical model for planar Langmuir probes under such conditions, extensive use of both 1D and 2D hybrid particle in cell (PIC) simulations have been made. Additionally the work required the development of a 2D hybrid PIC code where the probe is embedded within the grid. This allowed the investigation of the impact of edge effects on the analytical model’s performance. The theory for and structure of the 2D code is also presented as part of this work. Three different probe orientations are considered, firstly the parallel case, the other two concerns the near parallel cases of the probe surface orientated both into and away from the direction of flow. The model’s performance under these conditions is evaluated and discussed. Finally the use of this model in allowing a planar Langmuir probe to act as a Mach probe is also considered. In testing the success of the analytical model against experimental data, comparisons are made between the models results and those of the 2D hybrid PIC. The experimental results used for this work were for xenon plasma with a range of moderately supersonic velocities and a highly supersonic silver laser ablated plasma plume

    CCL2 nitration is a negative regulator of chemokine-mediated inflammation.

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    Chemokines promote leukocyte recruitment during inflammation. The oxidative burst is an important effector mechanism, this leads to the generation of reactive nitrogen species (RNS), including peroxynitrite (ONOO). The current study was performed to determine the potential for nitration to alter the chemical and biological properties of the prototypical CC chemokine, CCL2. Immunofluorescence was performed to assess the presence of RNS in kidney biopsies. Co-localisation was observed between RNS-modified tyrosine residues and the chemokine CCL2 in diseased kidneys. Nitration reduced the potential of CCL2 to stimulate monocyte migration in diffusion gradient chemotaxis assays (p < 0.05). This was consistent with a trend towards reduced affinity of the nitrated chemokine for its cognate receptor CCR2b. The nitrated chemokine was unable to induce transendothelial monocyte migration in vitro and failed to promote leukocyte recruitment when added to murine air pouches (p < 0.05). This could potentially be attributed to reduced glycosaminoglycan binding ability, as surface plasmon resonance spectroscopy showed that nitration reduced heparan sulphate binding by CCL2. Importantly, intravenous administration of nitrated CCL2 also inhibited the normal recruitment of leukocytes to murine air pouches filled with unmodified CCL2. Together these data suggest that nitration of CCL2 during inflammation provides a mechanism to limit and resolve acute inflammation

    Outcomes of patients with atypical haemolytic uraemic syndrome with native and transplanted kidneys treated with eculizumab: a pooled post hoc analysis

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    Atypical hemolytic uremic syndrome (aHUS) often leads to end-stage renal disease (ESRD) and kidney transplantation; graft loss rates are high due to disease recurrence. A post hoc analysis of four prospective clinical trials in aHUS was performed to evaluate eculizumab, a terminal complement inhibitor, in patients with native or transplanted kidneys. The trials included 26-week treatment and extension periods. Dialysis, transplant, and graft loss were evaluated. Study endpoints included complete thrombotic microangiopathy (TMA) response, TMA event-free status, hematologic and renal parameters, and adverse events. Of 100 patients, 74 had native kidneys and 26 in the transplant subgroup had a collective history of 38 grafts. No patients lost grafts and only one with preexisting ESRD received a transplant on treatment. Efficacy endpoints were achieved similarly in both subgroups. After 26 weeks, mean absolute estimated glomerular filtration rate increased from baseline to 61 and 37 mL/min/1.73 m2 in native (n=71; P<0.0001) and transplanted kidney (n=25; P=0.0092) subgroups. Two patients (one/subgroup) developed meningococcal infections; both recovered, one continued therapy. Eculizumab was well tolerated. Eculizumab improved hematologic and renal outcomes in both subgroups. In patients with histories of multiple graft losses, eculizumab protected kidney function. (ClinicalTrials. gov numbers : NCT00844545, NCT00844844, NCT00838513, NCT00844428, NCT01193348, and NCT01194973) This article is protected by copyright. All rights reserved

    Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland

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    Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange–treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody–targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody–mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample siz
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