| 1. |
- Amara, Umme, et al.
(författare)
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Molecular Intercommunication between the Complement and Coagulation Systems
- 2010
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 185:9, s. 5628-5636
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Tidskriftsartikel (refereegranskat)abstract
- The complement system as well as the coagulation system has fundamental clinical implications in the context of life-threatening tissue injury and inflammation. Associations between both cascades have been proposed, but the precise molecular mechanisms remain unknown. The current study reports multiple links for various factors of the coagulation and fibrinolysis cascades with the central complement components C3 and C5 in vitro and ex vivo. Thrombin, human coagulation factors (F) XIa, Xa, and IXa, and plasmin were all found to effectively cleave C3 and C5. Mass spectrometric analyses identified the cleavage products as C3a and C5a, displaying identical molecular weights as the native anaphylatoxins C3a and C5a. Cleavage products also exhibited robust chemoattraction of human mast cells and neutrophils, respectively. Enzymatic activity for C3 cleavage by the investigated clotting and fibrinolysis factors is defined in the following order: FXa > plasmin > thrombin > FIXa > FXIa > control. Furthermore, FXa-induced cleavage of C3 was significantly suppressed in the presence of the selective FXa inhibitors fondaparinux and enoxaparin in a concentration-dependent manner. Addition of FXa to human serum or plasma activated complement ex vivo, represented by the generation of C3a, C5a, and the terminal complement complex, and decreased complement hemolytic serum activity that defines exact serum concentration that results in complement-mediated lysis of 50% of sensitized sheep erythrocytes. Furthermore, in plasma from patients with multiple injuries (n = 12), a very early appearance and correlation of coagulation (thrombin-antithrombin complexes) and the complement activation product C5a was found. The present data suggest that coagulation/fibrinolysis proteases may act as natural C3 and C5 convertases, generating biologically active anaphylatoxins, linking both cascades via multiple direct interactions in terms of a complex serine protease system. The Journal of Immunology, 2010, 185: 5628-5636.
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| 2. |
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| 3. |
- Balla, Prannay, et al.
(författare)
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Post-compression of picosecond pulses to four optical cycles
- 2020
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Ingår i: High Intensity Lasers and High Field Phenomena, HILAS 2020. - 9781557528209
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Konferensbidrag (refereegranskat)abstract
- We report post-compression of 1.2 ps pulses into the few-cycle regime via multi-pass spectral broadening. We achieve compression factors of 40 in single and 93 in a dual stage scheme using a compact setup.
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| 4. |
- Balla, Prannay, et al.
(författare)
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Postcompression of picosecond pulses into the few-cycle regime
- 2020
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Ingår i: Optics Letters. - 0146-9592. ; 45:9, s. 2572-2575
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Tidskriftsartikel (refereegranskat)abstract
- In this work,we demonstrate postcompression of 1.2 ps laser pulses to 13 fs via gas-based multipass spectral broadening. Our results yield a single-stage compression factor of about 40 at 200 W in-burst average power and a total compression factor >90 at reduced power. The employed scheme represents a route toward compact few-cycle sources driven by industrial-grade Yb:YAG lasers at high average power.
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| 5. |
- Bauer, Margit, et al.
(författare)
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Assessment of the in vivo biomechanical properties of the human uterine cervix in pregnancy using the aspiration test A feasibility study
- 2009
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Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 144, s. S77-S81
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To date no diagnostic tool is yet available to objectively assess the in vivo biomechanical properties of the uterine cervix during gestation. Methods: We show the first clinical application of an aspiration device to assess the in vivo biomechanical properties of the cervix in pregnancy with the aim to describe the physiological biomechanical changes throughout gestation in order to eventually detect pregnant women at risk for cervical insufficiency (CI). Results: Out of 15 aspiration measurements, 12 produced valid results. The stiffness values were in the range between 0.013 and 0.068 bar/mm. The results showed a good reproducibility of the aspiration test. In our previous test series on non-pregnant cervices our repetitive measurements showed a standard deviation of > 20% compared to <+/- 10% to our data on pregnant cervices. Stiffness values are decreasing with gestational age which indicates a progressive softening of cervical tissue towards the end of pregnancy. Three pregnant women had two subsequent measurements within a time interval of four weeks. Decreasing stiffness values in the range of 20% were recorded. Discussion: This preliminary study on the clinical practicability of aspiration tests showed promising results in terms of reproducibility (reliability) and clinical use (feasibility). Ongoing studies will provide further insights on its usefulness in clinical practice and in the detection of substantial changes of the cervix in pregnancy indicative for threatened preterm birth or cervical insufficiency.
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| 6. |
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| 7. |
- Burk, Anne-Maud, et al.
(författare)
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Early Complementopathy After Multiple Injuries in Humans.
- 2012
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Ingår i: Shock. - 1540-0514. ; 37:4, s. 348-354
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In the present study we hypothesized that multiple trauma results in immediate activation, consumption and dysfunction of the complement cascade and that the resulting severe "complementopathy" may be associated with morbidity and mortality.Therefore a prospective multicenter study with 25 healthy volunteers and 40 polytrauma patients (mean injury severity score [ISS] = 30.3 ± 2.9) was performed. After polytrauma serum was collected as early as possible at the scene, upon admission to the emergency room and 4, 12, 24, 120 and 240 hours post trauma and analysed for the complement profile. Complement hemolytic activity (CH-50) was massively reduced within the first 24 h after injury, recovered only 5 days after trauma and discriminated between lethal and non-lethal 28-day outcome. Serum levels of the complement activation products C3a and C5a were significantly elevated throughout the entire observation period and correlatedwith the severity of traumatic brain injury and survival. The soluble terminal complement complex SC5b-9 and mannose-binding lectin (MBL) showed a biphasic response after trauma. Key fluid phase inhibitors of complement, such as C4b-binding protein (C4BP) and factor I, were significantly diminished early after trauma.The present data indicate an almost synchronically rapid activation and dysfunction of complement suggesting a trauma-induced "complementopathy" early after injury. These events may participate to the impairment of the innate immune response observed after severe trauma.
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| 8. |
- Colvill, Emma, et al.
(författare)
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A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy : A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking
- 2016
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 119:1, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Purpose A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded. Results For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm γ-fail rate of <3% for all systems with adaptation for lung and prostate. Conclusions The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.
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| 9. |
- Lang, Karl A., et al.
(författare)
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Linking orogeny and orography in the Southern Alps of New Zealand : New observations from detrital fission-track thermochronology of the Waiho-1 borehole
- 2020
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Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 552
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Tidskriftsartikel (refereegranskat)abstract
- Numerical modeling coupling erosion with crustal deformation predicts that development of an orographic rain shadow may explain the asymmetric exhumation of convergent plate boundary orogens. This prediction is consistent with observations from the Southern Alps of New Zealand, where bedrock thermochronology indicates crustal exhumation has been concentrated along the wet, windward side of the mountains. While the spatial correspondence of exhumation and precipitation patterns is compelling, a robust evaluation of the link between orographic and orogenic processes further requires a temporal comparison between exhumation history, plate reconstructions and paleoclimatic records. We present a detailed exhumation history of the Southern Alps from detrital apatite and zircon fission-track thermochronology of the Waiho-1 borehole, a 3.6 km-thick sequence of proximal foreland basin sediments. Inverse thermal modeling of a 2062-grain dataset predicts two periods of rapid exhumation in the Early and Late Miocene. Rapid exhumation in the Early Miocene was synchronous with the development of transpression along the Alpine Fault and a ca. 20-22 Ma pulse of exhumation may reflect cooling during inversion of preexisting extensional basins. Rapid exhumation in the Late Miocene was not synchronous with a discrete change in plate convergence but increased exhumation rates after 7.4 Ma may instead reflect localization of plate boundary deformation along the Alpine Fault as orographic precipitation concentrated exhumation in the Alpine Fault hanging wall. We propose that, similar to prior interpretations from bedrock thermochronology, detrital thermochronology of the Southern Alps foreland basin is consistent with numerical model predictions linking asymmetric exhumation of the orogen to the growth of an orographic rain shadow.
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| 10. |
- Lang, K. A., et al.
(författare)
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Sediment storage in the Southern Alps of New Zealand : New observations from tracer thermochronology
- 2018
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Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 493, s. 140-149
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Tidskriftsartikel (refereegranskat)abstract
- Careful study of the processes transporting sediment across Earth's surface is critical for robust interpretation of the sedimentary record. Here we consider the specific influence of cyclic glaciation on the export of sediment from mountain landscapes to ocean basins. Using detrital apatite fission-track tracer thermochronology, we present new observations of sediment provenance from six large river systems draining the eastern flank of the Southern Alps, New Zealand. Detrital cooling ages in all six rivers reflect erosion of partially-reset and fully-unreset bedrock exposed in lower catchment areas and indicate that sediment is not currently contributed in proportion to long-term (>10(6) yr) erosion patterns. Instead, detrital cooling ages are better explained by either localized erosion along the eastern mountain front or intermontane sediment storage. Of these two alternatives, only intermontane sediment storage is further consistent with suspended sediment flux measurements in eastern rivers. Our observations are consistent with prior interpretations of Holocene sediment retention, and contrast with tracer thermochronology from continental margin deposits indicating sediment was rapidly exported to the continental shelf during the late Pleistocene. Collectively, this evidence argues for a reactive sediment routing system east of the main drainage divide that responds to cyclic glaciation by retaining sediment onshore following deglaciation and evacuating sediment reservoirs offshore during the subsequent glacial advance. Our research demonstrates the importance of intermontane sediment storage on the transmission of high-frequency (similar to 10(4-5) yr) climate signals to offshore sedimentary archives while highlighting a novel approach to detailing sediment provenance in tectonically active mountain ranges.
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| 11. |
- Lang, Roberto M., et al.
(författare)
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Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults : An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16:3, s. 233-271
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Tidskriftsartikel (refereegranskat)abstract
- The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines.
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| 12. |
- Lang, Roberto M., et al.
(författare)
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Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults : An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging
- 2015
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Ingår i: Journal of the American Society of Echocardiography. - : Elsevier BV. - 0894-7317 .- 1097-6795. ; 28:1, s. 1-U170
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Tidskriftsartikel (refereegranskat)abstract
- The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines.
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| 13. |
- Luederitz, Christopher, et al.
(författare)
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Learning through Evaluation: A Tentative Evaluative Scheme for Sustainability Transition Experiments
- 2017
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Ingår i: Journal of Cleaner Production. - 0959-6526. ; 169, s. 61-76
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Tidskriftsartikel (refereegranskat)abstract
- Transitions towards sustainability are urgently needed to address the interconnected challenges of economic development, ecological integrity, and social justice, from local to global scales. Around the world, collaborative science-society initiatives are forming to conduct experiments in support of sustainability transitions. Such experiments, if carefully designed, provide significant learning opportunities for making progress on transition efforts. Yet, there is no broadly applicable evaluative scheme available to capture this critical information across a large number of cases, and to guide the design of transition experiments. To address this gap, the article develops such a scheme, in a tentative form, drawing on evaluative research and sustainability transitions scholarship, alongside insights from empirical cases. We critically discuss the scheme's key features of being generic, comprehensive, operational, and formative. Furthermore, we invite scholars and practitioners to apply, reflect and further develop the proposed tentative scheme – making evaluation and experiments objects of learning.
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| 14. |
- Matyschok, Jan, et al.
(författare)
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Compact, high-repetition-rate OPCPA system for high harmonic generation
- 2014
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Ingår i: Frontiers in Ultrafast Optics : Biomedical, Scientific, and Industrial Applications XIV - Biomedical, Scientific, and Industrial Applications XIV. - : SPIE. - 9780819498854 ; 8972
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Konferensbidrag (refereegranskat)abstract
- A compact, high-repetition rate optical parametric chirped pulse amplifier system emitting CEP-stable, few-cycle pulses with 10 μJ of pulse energy is reported for the purpose of high-order harmonic generation. The system is seeded from a commercially available, CEP-stabilized Ti:sapphire oscillator, delivering an octave-spanning spectrum from 600-1200 nm. The oscillator output serves on the one hand as broadband signal for the parametric amplification process and on the other hand as narrowband seed for an Ytterbium-based fiber preamplifier with subsequent main amplifiers and frequency doubling. Broadband parametric amplification up to 17 μJ at 200 kHz repetition rate was achieved in two 5 mm BBO crystals using non-collinear phase matching in the Poynting-vector-walk-off geometry. Efficient pulse compression down to 6.3 fs is achieved with chirped mirrors leading to a peak power exceeding 800 MW. We observed after warm-up time a stability of < 0.5 % rms over 100 min. Drifts of the CE-phase in the parametric amplifier part could be compensated by a slow feedback to the set point of the oscillator phase lock. The CEP stability was measured to be better than 80 mrad over 15 min (3 ms integration time). The experimentally observed output spectra and energies could be well reproduced by simulations of the parametric amplification process based on a (2+1)-dimensional nonlinear propagation code, providing important insight for future repetition rate scaling of OPCPA systems. The system is well-suited for attosecond science experiments which benefit from the high repetition rate. First results for high-order harmonic generation in argon will be presented.
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| 15. |
- Matyschok, Jan, et al.
(författare)
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Temporal and spatial effects inside a compact and CEP stabilized, few-cycle OPCPA system at high repetition rates
- 2013
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Ingår i: Optics Express. - 1094-4087. ; 21:24, s. 29656-29665
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Tidskriftsartikel (refereegranskat)abstract
- We present a compact and ultra-stable few-cycle OPCPA system. In two non-collinear parametric amplification stages pulse energies up to 17 mu J at 200 kHz repetition rate are obtained. Recompression of the broadband pulses down to 6.3 fs is performed with chirped mirrors leading to peak powers above 800 MW. The parametric amplification processes were studied in detail employing (2 + 1) dimensional numerical simulations and compared to experimental observations in terms of spectral shapes, pulse energy, spatial effects as well as delay dependent nonlinear mixing products. This gives new insights into the parametric process and design guidelines for high repetition rate OPCPA systems. (C) 2013 Optical Society of America
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| 16. |
- Morgner, Uwe, et al.
(författare)
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Few-cycle and phase stable OPCPA systems with high repetition rate
- 2015
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Ingår i: CLEO : Science and Innovations, CLEO-SI 2015 - Science and Innovations, CLEO-SI 2015. - 9781557529688
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Konferensbidrag (refereegranskat)abstract
- We present different approaches for high repetition rate, few-cycle pulse generation with μJ-level energy from compact OPCPA systems. The sources are based on octave spanning Ti:Sa oscillators with all-optical synchronization to state-of-the-art Ytterbium based amplifiers.
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| 17. |
- Niedzielska, Magdalena, et al.
(författare)
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Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-β Production.
- 2015
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 195:4, s. 1753-1762
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Tidskriftsartikel (refereegranskat)abstract
- Plasmacytoid dendritic cells (pDCs) efficiently produce large amounts of type I IFN in response to TLR7 and TLR9 ligands, whereas conventional DCs (cDCs) predominantly secrete high levels of the cytokines IL-10 and IL-12. The molecular basis underlying this distinct phenotype is not well understood. In this study, we identified the MAPK phosphatase Dusp9/MKP-4 by transcriptome analysis as selectively expressed in pDCs, but not cDCs. We confirmed the constitutive expression of Dusp9 at the protein level in pDCs generated in vitro by culture with Flt3 ligand and ex vivo in sorted splenic pDCs. Dusp9 expression was low in B220(-) bone marrow precursors and was upregulated during pDC differentiation, concomitant with established pDC markers. Higher expression of Dusp9 in pDCs correlated with impaired phosphorylation of the MAPK ERK1/2 upon TLR9 stimulation. Notably, Dusp9 was not expressed at detectable levels in human pDCs, although these displayed similarly impaired activation of ERK1/2 MAPK compared with cDCs. Enforced retroviral expression of Dusp9 in mouse GM-CSF-induced cDCs increased the expression of TLR9-induced IL-12p40 and IFN-β, but not of IL-10. Conditional deletion of Dusp9 in pDCs was effectively achieved in Dusp9(flox/flox); CD11c-Cre mice at the mRNA and protein levels. However, the lack of Dusp9 in pDC did not restore ERK1/2 activation after TLR9 stimulation and only weakly affected IFN-β and IL-12p40 production. Taken together, our results suggest that expression of Dusp9 is sufficient to impair ERK1/2 activation and enhance IFN-β expression. However, despite selective expression in pDCs, Dusp9 is not essential for high-level IFN-β production by these cells.
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| 18. |
- Rabe, Patrick, et al.
(författare)
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X-ray free-electron laser studies reveal correlated motion during isopenicillin N synthase catalysis
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:34
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Tidskriftsartikel (refereegranskat)abstract
- Isopenicillin N synthase (IPNS) catalyzes the unique reaction of L-delta-(alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.
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| 19. |
- Schober, Sebastian Johannes, et al.
(författare)
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No Improvement of Survival for Alveolar Rhabdomyosarcoma Patients After HLA-Matched Versus -Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Compared to Standard-of-Care Therapy
- 2022
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPatients with stage IV alveolar rhabdomyosarcoma (RMA) have a 5-year-survival rate not exceeding 30%. Here, we assess the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for these patients in comparison to standard-of-care regimens. We also compare the use of HLA-mismatched vs. HLA-matched grafts after reduced vs. myeloablative conditioning regimens, respectively. Patients and MethodsIn this retrospective analysis, we compare event-free survival (EFS), overall survival (OS), and toxicity of HLA-mismatched vs. -matched transplanted patients in uni- and multivariate analyses (total: n = 50, HLA-matched: n = 15, HLA-mismatched: n = 35). Here, the factors age at diagnosis, age at allo-HSCT, sex, Oberlin score, disease status at allo-HSCT, and HLA graft type are assessed. For 29 primarily transplanted patients, three matched non-transplanted patients per one transplanted patient were identified from the CWS registry. Outcomes were respectively compared for OS and EFS. Matching criteria included sex, age at diagnosis, favorable/unfavorable primary tumor site, and metastatic sites. ResultsMedian EFS and OS did not differ significantly between HLA-mismatched and -matched patients. In the mismatched group, incidence of acute GvHD was 0.87 (grade III-IV: 0.14) vs. 0.80 in HLA-matched patients (grade III-IV: 0.20). Transplant-related mortality (TRM) of all patients was 0.20 and did not differ significantly between HLA-mismatched and -matched groups. A proportion of 0.58 relapsed or progressed and died of disease (HLA-mismatched: 0.66, HLA-matched: 0.53) whereas 0.18 were alive in complete remission (CR) at data collection. Multivariate and competing risk analyses confirmed CR and very good partial response (VGPR) status prior to allo-HSCT as the only decisive predictor for OS (p < 0.001). Matched-pair survival analyses of primarily transplanted patients vs. matched non-transplanted patients also identified disease status prior to allo-HSCT (CR, VGPR) as the only significant predictor for EFS. Here, OS was not affected, however. ConclusionIn this retrospective analysis, only a subgroup of patients with good response at allo-HSCT survived. There was no survival benefit of allo-transplanted patients compared to matched controls, suggesting the absence of a clinically relevant graft-versus-RMA effect in the current setting. The results of this analysis do not support further implementation of allo-HSCT in RMA stage IV patients.
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| 20. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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