| 1. |
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| 2. |
- Kotmayer, L, et al.
(författare)
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Landscape of BCL2 Resistance Mutations in a Real-World Cohort of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax
- 2023
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
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Tidskriftsartikel (refereegranskat)abstract
- The oral, highly selective Bcl2 inhibitor venetoclax has substantially improved the therapeutic landscape of chronic lymphocytic leukemia (CLL). Despite the remarkable response rates in patients with relapsed/refractory (R/R) disease, acquired resistance is the leading cause of treatment failure, with somatic BCL2 mutations being the predominant genetic drivers underpinning venetoclax resistance. To assess the correlation between disease progression and the most common BCL2 mutations G101V and D103Y, sensitive (10−4) screening for the most common BCL2 mutations G101V and D103Y was performed in 67 R/R CLL patients during venetoclax single-agent or venetoclax–rituximab combination therapy. With a median follow-up time of 23 months, BCL2 G101V and D103Y were detected in 10.4% (7/67) and 11.9% (8/67) of the cases, respectively, with four patients harboring both resistance mutations. Ten out of eleven patients carrying BCL2 G101V and/or D103Y experienced relapse during the follow-up period, representing 43.5% of the cases (10/23) showing clinical signs of disease progression. All BCL2 G101V or D103Y variants were detected in patients receiving venetoclax as a continuous single-agent treatment while these mutations were not observed during or after fixed-duration venetoclax therapy. Targeted ultra-deep sequencing of BCL2 uncovered three additional variants in four patient samples obtained at relapse, suggesting convergent evolution and implying a cooperating role of BCL2 mutations in driving venetoclax resistance. This cohort is the largest R/R CLL patient population reported to date in which BCL2 resistance mutations were investigated. Our study demonstrates the feasibility and clinical value of sensitive screening for BCL2 resistance mutations in R/R CLL.
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| 3. |
- Szasz, R., et al.
(författare)
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Hysteretic Dynamics of Flashback in a Low-Swirl Stabilized Combustor
- 2017
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Ingår i: Combustion Science and Technology. - : Taylor & Francis. - 0010-2202 .- 1563-521X. ; 189:2, s. 266-289
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Tidskriftsartikel (refereegranskat)abstract
- The hysteretic behavior of flashback (FB) and flash forward (FF) in methane and natural gas flames, stabilized by a low swirl fuel injector, is investigated using high speed OH* chemiluminescence and particle image velocimetry. Due to the lack of vortex breakdown, the two mechanisms discussed are boundary layer and turbulence induced FB. Two hysteresis cycles were identified, one when FB is induced by increasing the equivalence ratio starting from lean conditions, and the other by decreasing the equivalence ratio starting from rich conditions. Impact of relevant parameters including Reynolds number (Re), equivalence ratio, fuel type, combustion chamber geometry, preheating, and mixing tube protrusions are investigated. As Re is increased, the equivalence ratio at which both rich and lean flashbacks occur approaches stoichiometric conditions. However, the range of the hysteresis cycle between FB and FF is independent on Re. The transition processes during FB and FF are quite variable and their duration is independent on Re. The mean duration of FB transition initiated from lean conditions is nearly twice longer than the rich branch and also longer than both the lean and rich FF. The geometry of the combustion chamber affected neither FB nor FF. However, preheating increased the equivalence ratio at which FB occurred but did not affect FF. Also, FB had significant effect on the mean flow field.
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| 4. |
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| 5. |
- Agoston, EI, et al.
(författare)
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Deconstructing Immune Cell Infiltration in Human Colorectal Cancer: A Systematic Spatiotemporal Evaluation
- 2022
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Cancer-related immunity has been identified as playing a key role in the outcome of colorectal cancer (CRC); however, the exact mechanisms are only partially understood. In this study, we evaluated a total of 242 surgical specimen of CRC patients using tissue microarrays and immunohistochemistry to evaluate tumor infiltrating immune cells (CD3, CD4, CD8, CD20, CD23, CD45 and CD56) and immune checkpoint markers (CTLA-4, PD-L1, PD-1) in systematically selected tumor regions and their corresponding lymph nodes, as well as in liver metastases. Additionally, an immune panel gene expression assay was performed on 12 primary tumors and 12 consecutive liver metastases. A higher number of natural killer cells and more mature B cells along with PD-1+ expressing cells were observed in the main tumor area as compared to metastases. A higher number of metastatic lymph nodes were associated with significantly lower B cell counts. With more advanced lymph node metastatic status, higher leukocyte—particularly T cell numbers—were observed. Eleven differentially expressed immune-related genes were found between primary tumors and liver metastases. Also, alterations of the innate immune response and the tumor necrosis factor superfamily pathways had been identified.
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| 6. |
- Alsam, A., et al.
(författare)
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Wind-Wave Interaction Effects on a Wind Farm Power Production
- 2017
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Ingår i: Journal of Energy Resources Technology. - : ASME International. - 0195-0738 .- 1528-8994. ; 139:5
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Tidskriftsartikel (refereegranskat)abstract
- In the current study, the effects of the nonlocally generated long sea surface waves (swells) on the power production of a 2 × 2 wind farm are investigated by using large-eddy simulations (LES) and actuator-line method (ALM). The short sea waves are modeled as a roughness height, while the wave-induced stress accounting for swell effects is added as an external source term to the momentum equations. The results show that the marine atmospheric boundary layers (MABLs) obtained in this study have similar characteristics as the MABLs observed during the swell conditions by many other studies. The current results indicate also that swells have significant impacts on the MABL. As a consequence of these changes in the MABL, swells moving faster than the wind and aligned with the local wind direction increase the power extraction rate.
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| 7. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Long-term safety and tolerability of lacosamide monotherapy in patients with epilepsy: Results from a multicenter, open-label trial
- 2021
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Ingår i: Epilepsia Open. - : Wiley. - 2470-9239. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective of this trial (SP1042; NCT02582866) was to assess long-term safety and tolerability of lacosamide monotherapy (200-600 mg/day) in adults with focal (partial-onset) seizures or generalized tonic-clonic seizures (without clear focal origin). This Phase III, long-term, open-label, multicenter, follow-up trial enrolled patients with epilepsy who were taking lacosamide in, and completed, the previous double-blind trial (SP0994; NCT01465997). Primary safety outcomes were treatment-emergent adverse events (TEAEs), discontinuations due to TEAEs, and serious TEAEs. One hundred and six patients were enrolled and received lacosamide: 84 (79.2%) completed the trial and 22 (20.8%) discontinued. The median duration of exposure was 854.0 days, with a median modal dose of 200 mg/day. Ninety-six (90.6%), 64 (60.4%), and 44 (41.5%) patients had >= 12, >= 24, and >= 36 months of lacosamide exposure, respectively. At least one TEAE was reported by 61 (57.5%) patients. The most common (>= 4%) TEAEs were headache (10 [9.4%]), nasopharyngitis (eight [7.5%]), and back pain (five [4.7%]). One (0.9%) patient discontinued due to a TEAE (sudden unexpected death in epilepsy; not considered drug-related), 14 (13.2%) patients reported serious TEAEs, and seven (6.6%) patients reported TEAEs that were considered drug-related. Overall, long-term lacosamide monotherapy was generally well tolerated up to 600 mg/day, with no new safety signals identified.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Grosshans, H., et al.
(författare)
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Sensitivity of VOF simulations of the liquid jet breakup to physical and numerical parameters
- 2016
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Ingår i: Computers & Fluids. - : Elsevier. - 0045-7930 .- 1879-0747. ; 136, s. 312-323
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Tidskriftsartikel (refereegranskat)abstract
- In this paper the characteristics of the primary breakup of a liquid jet is analyzed numerically. We applied the Volumes of Fluids (VOF) approach utilizing the Direction Averaged Curvature (DAC) model, to estimate the interface curvature, and the Direction Averaged Normal (DAN) model, to propagate the interface. While being used for the first time to predict liquid atomization, this methodology showed a high accuracy. The influence of varying the fluid properties, namely liquid-gas density and viscosity ratio, and injection conditions is discussed related to the required grid resolution. Resulting droplet sizes are compared to distributions obtained through the One-Dimensional Turbulence (ODT) model.
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| 12. |
- Hodzic, Erdzan, et al.
(författare)
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A Large Eddy Simulation Study of Bluff Body Flame Dynamics Approaching Blow-Off
- 2017
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Ingår i: Combustion Science and Technology. - : Taylor & Francis. - 0010-2202 .- 1563-521X. ; 189:7, s. 1107-1137
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms leading to blowoff were investigated numerically by analyzing bluff body stabilized flame at two conditions: a condition far from blowoff to a condition just prior to blowoff. Large eddy simulations have been used to capture the time dependent, three-dimensional evolution of the field. The results were first validated to available experimental data, showing very good agreement for the flow and overall good agreement for the flame. Changes in the large-scale structures are investigated by means of proper orthogonal decomposition and the wavelet method, elucidating the underlying dynamics of the complex flow-flame interaction of a flame approaching blowoff. Our results reveal that, when the flame approaches blowoff conditions, significant changes are found in the large-scale structures responsible for entrainment of species into the recirculation zone located downstream of the bluff body. Possible causes of this shift in large-scale structures are also discussed, which may be useful for extending the blowoff limits of bluff body stabilized burners.
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| 13. |
- Parra-Santos, Teresa, et al.
(författare)
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An isothermal analysis of curved-vane and flat-vane swirlers for burners
- 2015
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Ingår i: Engineering Computations. - 0264-4401. ; 32:3, s. 668-686
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Tidskriftsartikel (refereegranskat)abstract
- Purpose - One current trend in burner technology is to obtain high efficiency while keeping low levels of NOx emissions. A swirling flow in combustion ensures a fixed position of a compact flame. Therefore, it is necessary to design efficient swirlers. Flow patterns are simulated for the different swirl devices proposed in this work. Two axial-swirlers are studied: one based on curve-vanes consisting of a straight line with an arc of a circle as the trailing edge and the other is the common flat-vanes. The purpose of this paper is to assess the accuracy of different swirl generators using a well-known benchmark test case. Design/methodology/approach - This work deals with modelling the swirler using two approaches: the general purpose Computational fluid dynamics (CFD) solver Ansys-Fluent (R) and the suite of libraries OpenFOAM (R) to solve the Reynolds Averaged Navier Stokes equations, showing there is a slight deviation between both approaches. Their performance involves analyzing not only the Swirl number but also the size of the recirculation zones in the test chamber. A subsequent process on the flow patterns was carried out to establish the intensity of segregation which provides insight into the quality of mixing. Findings - CFD models are feasible tools to predict flow features. It was found that numerical results tend to reduce the inner recirculation zone (IRZ) radial size. Further, an increase of the swirl number involves larger IRZ and a smaller outer recirculation zone (ORZ). The curved swirler displays a better axi-symmetric behaviour than flat vanes. There is weak influence of the chord vanes on the swirl number. The number of vanes is a compromise of head loses and guidance of the flow. Originality/value - The paper offers two different approaches to solve turbulent swirling flows. One based in a general contrasted commercial tool and other using open source code. Both models show similar performance. An innovative set up for an axial swirler different from the conventional flat vanes was proposed.
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| 14. |
- Parra, Teresa, et al.
(författare)
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Numerical modelling of flow pattern for high swirling flows
- 2015
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Ingår i: Efm14 - Experimental Fluid Mechanics 2014. - : EDP Sciences. - 2100-014X .- 2101-6275. ; 92, s. 02059-02059
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Konferensbidrag (refereegranskat)abstract
- This work focuses on the interaction of two coaxial swirling jets. High swirl burners are suitable for lean flames and produce low emissions. Computational Fluid Dynamics has been used to study the isothermal behaviour of two confined jets whose setup and operating conditions are those of the benchmark of Roback and Johnson. Numerical model is a Total Variation Diminishing and PISO is used to pressure velocity coupling. Transient analysis let identify the non-axisymmetric region of reverse flow. The center of instantaneous azimuthal velocities is not located in the axis of the chamber. The temporal sampling evidences this center spins around the axis of the device forming the precessing vortex core (PVC) whose Strouhal numbers are more than two for Swirl numbers of one. Influence of swirl number evidences strong swirl numbers are precursor of large vortex breakdown. Influence of conical diffusers evidence the reduction of secondary flows associated to boundary layer separation.
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| 15. |
- Pignatelli, F., et al.
(författare)
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Impact of pilot flame and hydrogen enrichment on turbulent methane/hydrogen/air swirling premixed flames in a model gas turbine combustor
- 2024
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Ingår i: Experimental Thermal and Fluid Science. - 0894-1777. ; 152
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Tidskriftsartikel (refereegranskat)abstract
- This work investigates the impact of pilot flame and fuel composition on the structures and stabilization of swirling turbulent premixed methane/hydrogen/air flames in a lab-scale gas turbine model combustor. Simultaneous measurements of the velocity field and OH radicals distribution in the combustor were conducted using particle imaging velocimetry (PIV) and planar laser-induced fluorescence (PLIF) methods, respectively. Flames under stable and close to lean blow-off (LBO) conditions were studied for two fuel mixtures, with a hydrogen mole ratio of 0 and 50 % in the hydrogen/methane mixture, respectively. The studied flames were at a constant Reynolds number of 20,000 with different equivalence ratios. Two pilot-to-global fuel ratios were investigated (2 % and 6 %) while keeping the pilot-to-global air ratio constant at 2 %. Data for non-piloted flames were also acquired for comparison. The pilot flames were shown to extend the operability range. The LBO equivalence ratio of the main flame decreased with increasing fuel mass flow rate in the pilot flames due to the increased amount of hot gases with high concentrations of OH radicals in the outer recirculation zone (ORZ), which significantly enhanced the stabilization of the main flame. The stable flame reaction zone was in the high-speed shear layer between the ORZ and the inner recirculation zone (IRZ). When approaching LBO, the reaction zone was pushed downstream to the IRZ and subsequently decreased the size of IRZ, indicating a strong flow/flame interaction. Hydrogen enrichment was shown to reduce the LBO equivalence ratio. When close to LBO, the OH radicals in the hydrogen-enriched flames were observed in isolated pockets due to differential diffusion, which enhanced resilience to LBO. The flame front curvature, mean progress variable, and flame surface density were calculated from the acquired OH-PLIF data to quantify the impact of fuel composition and pilot flames on the flame structures.
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| 16. |
- Pignatelli, F., et al.
(författare)
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Pilot impact on turbulent premixed methane/air and hydrogen-enriched methane/air flames in a laboratory-scale gas turbine model combustor
- 2022
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Ingår i: International Journal of Hydrogen Energy. - : Elsevier BV. - 0360-3199. ; 47:60, s. 25404-25417
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Tidskriftsartikel (refereegranskat)abstract
- The impact of pilot flame operation on the combustion of pure methane and hydrogen-enriched methane (H2/CH4: 50/50 in vol%) fuels was investigated in a gas turbine model combustor under atmospheric conditions. The burner assembly was designed to mimic the geometry of an industrial burner, the Siemens DLE Burner, in which a concentric annular ring equipped with pilot flame burners is implemented in the dome of the combustor. Two pilot burner configurations have been investigated: a non-premixed and a partially premixed pilot arrangement. The performance of the pilot burners was evaluated for varying Reynolds number (Re) and H2 enrichment. High-speed OH∗ chemiluminescence imaging, as well as simultaneous planar laser-induced fluorescence measurements of the OH radicals and formaldehyde (CH2O) were used for evaluating the dynamics and structures of the flames for different conditions. Furthermore, emission measurements were carried out to determine the influence of hydrogen dilution on the NOx and CO emission levels. The main findings are (a) the effect of the pilot flame is sensitive to the Reynolds number of the main flame and the type of the pilot flame, (b) the stability range becomes narrower with increasing hydrogen ratio, due to the tendency to flashback, (c) non-premixed pilot flames lower the NOx and increase the CO emissions, albeit rather small differences in the emissions have been detected, and (d) the NOx and CO emissions become significantly lower with increasing hydrogen ratio.
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