339 research outputs found
Production of Intermediate or Medium Carbon Ferro Chrome at FACOR
FACOR has foreseen the need to develop the intermediate carbon ferro chrome alloy to meet the demands of alloy and stainless steel manufacturers.The paper describes the decarbonisation of liquid high carbon ferro chrome in. an AOD convertor with respect to : (a) Theoretical
aspects and fundamentals, (b) Plant and equipment, (c) Process of making intermediate carbon ferro chromium., (d) Advantages of the processto improve the quality with respect to titanium, silicon, hydrogen and nitrogen in intermediate carbon ferro chromium
Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain.
BACKGROUND: Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, and demyelinating disease of the central nervous system (CNS). Several cytokines are thought to be involved in the regulation of MS pathogenesis. We recently identified interleukin (IL)-9 as a cytokine reducing inflammation and protecting from neurodegeneration in relapsing-remitting MS patients. However, the expression of IL-9 in CNS, and the mechanisms underlying the effect of IL-9 on CNS infiltrating immune cells have never been investigated. METHODS: To address this question, we first analyzed the expression levels of IL-9 in post-mortem cerebrospinal fluid of MS patients and the in situ expression of IL-9 in post-mortem MS brain samples by immunohistochemistry. A complementary investigation focused on identifying which immune cells express IL-9 receptor (IL-9R) by flow cytometry, western blot, and immunohistochemistry. Finally, we explored the effect of IL-9 on IL-9-responsive cells, analyzing the induced signaling pathways and functional properties. RESULTS: We found that macrophages, microglia, and CD4 T lymphocytes were the cells expressing the highest levels of IL-9 in the MS brain. Of the immune cells circulating in the blood, monocytes/macrophages were the most responsive to IL-9. We validated the expression of IL-9R by macrophages/microglia in post-mortem brain sections of MS patients. IL-9 induced activation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 and reduced the expression of activation markers, such as CD45, CD14, CD68, and CD11b in inflammatory macrophages stimulated in vitro with lipopolysaccharide and interferon (IFN)-Îł. Similarly, in situ the number of activated CD68+ macrophages was significantly reduced in areas with high levels of IL-9. Moreover, in the same conditions, IL-9 increased the secretion of the anti-inflammatory cytokine, transforming growth factor (TGF)-ÎČ. CONCLUSIONS: These results reveal a new cytokine expressed in the CNS, with a role in the context of MS. We have demonstrated that IL-9 and its receptor are both expressed in CNS. Moreover, we found that IL-9 decreases the activation state and promotes the anti-inflammatory properties of human macrophages. This mechanism may contribute to the beneficial effects of IL-9 that are observed in MS, and may be therapeutically potentiated by modulating IL-9 expression in MS
Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain
Background: Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, and demyelinating disease of the central nervous system (CNS). Several cytokines are thought to be involved in the regulation of MS pathogenesis. We recently identified interleukin (IL)-9 as a cytokine reducing inflammation and protecting from neurodegeneration in relapsing-remitting MS patients. However, the expression of IL-9 in CNS, and the mechanisms underlying the effect of IL-9 on CNS infiltrating immune cells have never been investigated. Methods: To address this question, we first analyzed the expression levels of IL-9 in post-mortem cerebrospinal fluid of MS patients and the in situ expression of IL-9 in post-mortem MS brain samples by immunohistochemistry. A complementary investigation focused on identifying which immune cells express IL-9 receptor (IL-9R) by flow cytometry, western blot, and immunohistochemistry. Finally, we explored the effect of IL-9 on IL-9-responsive cells, analyzing the induced signaling pathways and functional properties. Results: We found that macrophages, microglia, and CD4 T lymphocytes were the cells expressing the highest levels of IL-9 in the MS brain. Of the immune cells circulating in the blood, monocytes/macrophages were the most responsive to IL-9. We validated the expression of IL-9R by macrophages/microglia in post-mortem brain sections of MS patients. IL-9 induced activation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 and reduced the expression of activation markers, such as CD45, CD14, CD68, and CD11b in inflammatory macrophages stimulated in vitro with lipopolysaccharide and interferon (IFN)-Îł. Similarly, in situ the number of activated CD68+ macrophages was significantly reduced in areas with high levels of IL-9. Moreover, in the same conditions, IL-9 increased the secretion of the anti-inflammatory cytokine, transforming growth factor (TGF)-ÎČ. Conclusions: These results reveal a new cytokine expressed in the CNS, with a role in the context of MS. We have demonstrated that IL-9 and its receptor are both expressed in CNS. Moreover, we found that IL-9 decreases the activation state and promotes the anti-inflammatory properties of human macrophages. This mechanism may contribute to the beneficial effects of IL-9 that are observed in MS, and may be therapeutically potentiated by modulating IL-9 expression in MS
Surface and Interface Properties of 10â12 Unit Cells Thick Sputter Deposited Epitaxial CeO 2
Ultrathin and continuous epitaxial films with relaxed lattice strain can potentially maintain more of its bulk physical and chemical properties and are useful as buffer layers. We study surface, interface, and microstructural properties of ultrathin (âŒ10â12 unit cells thick) epitaxial ceria films grown on single crystal YSZ substrates. The out-of -plane and in-plane lattice parameters indicate relaxation in the continuous film due to misfit dislocations seen by high-resolution transmission electron microscopy (HRTEM) and substrate roughness of âŒ1-2 unit cells, confirmed by atomic force microscopy and HRTEM. A combination of secondary sputtering, lattice mismatch, substrate roughness, and surface reduction creating secondary phase was likely the cause of surface roughness which should be reduced to a minimum level for effective use of it as buffer layers
Pembrolizumab in Combination with Ipilimumab as Second-Line or Later Therapy for Advanced NonâSmall-Cell Lung Cancer: KEYNOTE-021 Cohorts D and H
Objectives
Combination immunotherapy may result in improved antitumor activity compared with single-agent treatment. We report results from dose-finding and dose-expansion cohorts of the phase 1/2 KEYNOTE-021 study that evaluated combination therapy with antiâprogrammed death 1 (PD-1) antibody pembrolizumab plus antiâcytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in patients with previously treated advanced nonâsmall-cell lung cancer (NSCLC).
Materials and Methods
Eligibility criteria stipulated histologically/cytologically confirmed advanced NSCLC and treatment failure on â„1 prior systemic therapy (platinum-based chemotherapy or targeted therapy for patients with EGFR/ALK aberrations). In the dose-finding cohort, patients initially received pembrolizumab 10âmg/kg plus ipilimumab 1 or 3âmg/kg once every 3 weeks for 4 cycles followed by pembrolizumab 10âmg/kg monotherapy for up to 2 years. Based on emerging published data, subsequent patients received pembrolizumab 2âmg/kg plus ipilimumab 1âmg/kg. Objective response rate (ORR; primary efficacy endpoint) was assessed per RECIST version 1.1 by blinded, independent central review. Phase 2 hypothesis that ORR would be greater than the 20% rate for historical controls was evaluated using the exact binomial test.
Results
Fifty-one patients were enrolled; 71% received â„2 prior lines of therapy. No dose-limiting toxicities occurred at any dose level. Among patients who received pembrolizumab 2âmg/kg plus ipilimumab 1âmg/kg (nâ=â44), ORR was 30% (95% CI, 17%â45%), but not statistically significantly >20% (Pâ=â0.0858). Median progression-free survival in this group was 4.1 (95% CI, 1.4â5.8) months; median overall survival was 10.9 (95% CI, 6.1â23.7) months. With pembrolizumab 2 mg/kg plus ipilimumab 1 mg/kg, incidences of treatment-related adverse events, grade 3â5 treatment-related adverse events, and immune-mediated adverse events and infusion reactions were 64%, 29% and 42%, respectively.
Conclusions
In patients with heavily pretreated advanced NSCLC, pembrolizumab plus ipilimumab showed evidence of antitumor activity, but was associated with meaningful toxicity
Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects
In gravitational-wave detection, special emphasis is put onto searches that
focus on cosmic events detected by other types of astrophysical observatories.
The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical
telescopes and neutrino observatories, provide a trigger time for analyzing
gravitational wave data coincident with the event. In certain cases the
expected frequency range, source energetics, directional and progenitor
information is also available. Beyond allowing the recognition of gravitational
waveforms with amplitudes closer to the noise floor of the detector, these
triggered searches should also lead to rich science results even before the
onset of Advanced LIGO. In this paper we provide a broad review of LIGO's
astrophysically triggered searches and the sources they target
First LIGO search for gravitational wave bursts from cosmic (super)strings
We report on a matched-filter search for gravitational wave bursts from
cosmic string cusps using LIGO data from the fourth science run (S4) which took
place in February and March 2005. No gravitational waves were detected in 14.9
days of data from times when all three LIGO detectors were operating. We
interpret the result in terms of a frequentist upper limit on the rate of
gravitational wave bursts and use the limits on the rate to constrain the
parameter space (string tension, reconnection probability, and loop sizes) of
cosmic string models.Comment: 11 pages, 3 figures. Replaced with version submitted to PR
A Joint Search for Gravitational Wave Bursts with AURIGA and LIGO
The first simultaneous operation of the AURIGA detector and the LIGO
observatory was an opportunity to explore real data, joint analysis methods
between two very different types of gravitational wave detectors: resonant bars
and interferometers. This paper describes a coincident gravitational wave burst
search, where data from the LIGO interferometers are cross-correlated at the
time of AURIGA candidate events to identify coherent transients. The analysis
pipeline is tuned with two thresholds, on the signal-to-noise ratio of AURIGA
candidate events and on the significance of the cross-correlation test in LIGO.
The false alarm rate is estimated by introducing time shifts between data sets
and the network detection efficiency is measured with simulated signals with
power in the narrower AURIGA band. In the absence of a detection, we discuss
how to set an upper limit on the rate of gravitational waves and to interpret
it according to different source models. Due to the short amount of analyzed
data and to the high rate of non-Gaussian transients in the detectors noise at
the time, the relevance of this study is methodological: this was the first
joint search for gravitational wave bursts among detectors with such different
spectral sensitivity and the first opportunity for the resonant and
interferometric communities to unify languages and techniques in the pursuit of
their common goal.Comment: 18 pages, IOP, 12 EPS figure
Search for gravitational-wave bursts in LIGO data from the fourth science run
The fourth science run of the LIGO and GEO 600 gravitational-wave detectors,
carried out in early 2005, collected data with significantly lower noise than
previous science runs. We report on a search for short-duration
gravitational-wave bursts with arbitrary waveform in the 64-1600 Hz frequency
range appearing in all three LIGO interferometers. Signal consistency tests,
data quality cuts, and auxiliary-channel vetoes are applied to reduce the rate
of spurious triggers. No gravitational-wave signals are detected in 15.5 days
of live observation time; we set a frequentist upper limit of 0.15 per day (at
90% confidence level) on the rate of bursts with large enough amplitudes to be
detected reliably. The amplitude sensitivity of the search, characterized using
Monte Carlo simulations, is several times better than that of previous
searches. We also provide rough estimates of the distances at which
representative supernova and binary black hole merger signals could be detected
with 50% efficiency by this analysis.Comment: Corrected amplitude sensitivities (7% change on average); 30 pages,
submitted to Classical and Quantum Gravit
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