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- Mogilenko, Denis A., et al.
(författare)
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Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR
- 2019
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 177:5, s. 1201-
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Tidskriftsartikel (refereegranskat)abstract
- Innate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-like receptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatory signals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect the immune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DCs) are exacerbated by a high-fatty-acid (FA) metabolic environment. FAs suppress the TLR-induced hexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changes enhance mitochondria! reactive oxygen species (mtROS) production and, in turn, the unfolded protein response (UPR), leading to a distinct transcriptomic signature with IL-23 as hallmark. Interestingly, chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response. Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23 expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innate immunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR.
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| 3. |
- Paget, Christophe, 1971-
(författare)
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Active Health Monitoring of Aerospace Composite Structures by Embedded Piezoceramic Transducers
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objectives of the thesis work were to study theinteraction between embedded piezoceramic transducers andcomposite structures as well as determine techniques tosimplify the Lamb waves analysis. Firstly, this studyconsidered the design of the embedded piezoceramic transducers.Secondly, the effect of the embedded transducer on thecomposite strength as well as the influence of the mechanicallyloaded composite on the characteristics of the embeddedtransducer were investigated. Finally, to simplify the analysisof such complex Lamb wave responses, two techniques weredeveloped. They were based on the wavelet technique and amodelling technique, respectively.The design of the embedded piezoceramic transducers wasimproved by reducing the stress concentrations in the compositeas well as in all components constituting the piezoceramictransducer, that is, the piezoceramic element, interconnectorand conductive adhesive. The numerical analysis showed that thethickness of the interconnector had no significant influence onthe stress state of the piezoceramic transducer. It was alsofound that a compliant conductive adhesive reduced the stressconcentration located at the edge of the piezoceramic element.The structural integrity of composites embedded with theimproved piezoceramic transducer was investigated. Theexperiments, performed in tensile and compressive staticloading, indicated that the strength of the composite was notsignificantly reduced by the embedded piezoceramic transducer.Further investigations were conducted to evaluate theperformance of the improved piezoceramic transducer used as aLamb wave generator embedded in composites subjected tomechanical loading. The tests were conducted in tensile andcompressive static loading as well as fatigue loading. Thestudy showed a large working range of the embedded piezoceramictransducer. A post processing technique based on the waveletswas further assessed in the detection of damage and in thedamage size evaluation. A new wavelet basis was developedspecially for processing the Lamb wave response. This method,focused on the wavelet coefficients from the decomposition Lambwave response, showed promising results in evaluating thedamage size. The wavelets offered a sensitive tool to detectsmall damage, compared to other detection methods, improvingthe damage detection capabilities. The other technique wasdevoted to the simplification of the generated Lamb waves bythe use of multi-element transducers. The transducers weredesigned using both a normal-mode expansion and a FE-method.This technique allowed reducing the effect of a Lamb wave modetowards another. This technique was successfully implemented ina damage detection system in composites.Keywords:Embedded piezoceramic, transducer, composite,structural integrity, health monitoring, damage detection, Lambwaves, wavelets, normal-mode expansion, FE-method
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| 5. |
- Vernerey, Dewi, et al.
(författare)
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Prognostic nomogram and score to predict overall survival in locally advanced untreated pancreatic cancer (PROLAP)
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115:3, s. 281-289
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Tidskriftsartikel (refereegranskat)abstract
- Background: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP).Methods: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besanc, on Hospital, France.Results: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index = 0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P<0.0001). The score ability to discriminate OS was externally confirmed in 63 (59%) patients with complete clinical data derived from a data set of 106 consecutive LAPC patients; median OS of 18.3, 14.1 and 7.6 months for the three groups (log-rank P<0.0001).Conclusions: The PROLAP nomogram and score can accurately predict OS before initiation of induction chemotherapy in LAPC-untreated patients. They may help to optimise clinical trials design and might offer the opportunity to define risk-adapted strategies for LAPC management in the future.
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