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- Holmfeldt, Linda, et al.
(författare)
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The genomic landscape of hypodiploid acute lymphoblastic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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- Htet, Cho Sandar, et al.
(författare)
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Effect of Local Structural Distortions on Antiferroelectric-Ferroelectric Phase Transition in Dilute Solid Solutions of K xNa1- xNbO3
- 2022
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 61:50, s. 20277-20287
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Tidskriftsartikel (refereegranskat)abstract
- The fundamental principles that govern antiferroelectric (AFE)-ferroelectric (FE) transitions are not well understood for many solid solutions of perovskite compounds. For example, crystal chemical considerations based on the average Goldschmidt tolerance factor or ionic polarizability do not precisely predict the boundary between the AFE and FE phases in dilute solid solutions of alkali niobates, such as KxNa1-xNbO3(x ≤ 0.02). Here, based on detailed structural analysis from neutron total scattering experiments, we provide insights about how the relative local distortions around the A- and B-sites of the ABO3perovskite structure affect the AFE/FE order of the average crystallographic phases in KxNa1-xNbO3. We show that a higher (lower) ratio of B-site-centered distortions over A-site-centered distortions drives transition toward a long-range FE (AFE) phase, which is based on a competition between the long-range polarizing field of the Nb-O dipoles and the disordering effect of local distortions around the A-site. Our study provides a predictive tool for designing complex solid-solution perovskites with tunable (anti)ferroelectric polarization properties, which can be of interest for various energy-related applications such as high-density energy storage and solid-state cooling.
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- Htet, Cho Sandar, et al.
(författare)
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Local structural mechanism for enhanced energy storage properties in heterovalent doped NaNbO3 ceramics
- 2024
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Ingår i: Journal of the European Ceramic Society. - 0955-2219. ; 44:3, s. 1597-1609
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, there is a growing interest for new lead-free oxides with reversible antiferroelectric (AFE)-ferroelectric (FE) phase transition for high-power energy-storage applications. NaNbO3-based ceramics are particularly attractive due to their easy synthesis and cost-effectiveness. In order to stabilize reversible AFE-FE phase transition, NaNbO3 is doped with a combination of heterovalent substitutions, although the underlying structural mechanism for the same is poorly understood. Here, we investigated local and average structures of Ca/Zr doped NaNbO3 using neutron total scattering. We show that Ca/Zr doping increases the average AFE phase (Pbma) fraction, however, the material remains as a composite of both FE (P21ma) and AFE regions. Analysis of local structure suggests that increase in the long-range AFE phase results from more extensive twinning of local FE regions, due to introduced charge disorder. We propose that enhanced energy-storage properties of Ca/Zr-doped NaNbO3 arises from localized twin boundary motion between the defect-induced pinning centers.
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- Kong, Jing, et al.
(författare)
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A Local Atomic Mechanism for Monoclinic-Tetragonal Phase Boundary Creation in Li-Doped Na0.5K0.5NbO3Ferroelectric Solid Solution
- 2022
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 61:10, s. 4335-4349
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Tidskriftsartikel (refereegranskat)abstract
- ABO3 perovskites display a wide range of phase transitions, which are driven by A/B-site centered polyhedral distortions and/or BO6 octahedral tilting. Since heterogeneous substitutions at the A/B-site can locally alter both polyhedral distortions and/or tilting, they are often used to create phase boundary regions in solid solutions of ABO3, where the functional properties are highly enhanced. However, the relationships between doping-induced atomistic structural changes and the creation of phase boundaries are not always clear. One prominent example of this is the Li-doped K0.5Na0.5NbO3 (KNNL), which is considered a promising alternative to traditional Pb-based ferroelectrics. Although the electromechanical properties of KNNL are enhanced for compositions near the morphotropic phase boundary (MPB), the atomistic mechanism for phase transitions is not well understood. Here, we combined neutron total scattering experiments and density functional theory to investigate the long-range average and short-range (∼10 Å) structural changes in KNNL. We show that the average monoclinic-to-tetragonal (M-T) transition across the MPB in KNNL can be described as an order-disorder-type change, which is driven by competition between a longer-range polarization field of monoclinic structural units and local distortions of the disordered AO12 polyhedra. The current study demonstrates a way to clarify dopant-induced local distortions near phase boundaries in complex solid solution systems, which will be important for the rational design of new environmentally sustainable ferroelectrics.
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- Marlton, Frederick P., et al.
(författare)
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Broad Distribution of Local Polar States Generates Large Electrothermal Properties in Pb-Free Relaxor Ferroelectrics
- 2021
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 33:22
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Tidskriftsartikel (refereegranskat)abstract
- Electrothermal energy conversion provides attractive solutions for global energy management, such as energy harvesting from waste heat using pyroelectric energy conversion (PEC) and efficient cooling of portable electronics or data servers using the electrocaloric effect. Relaxor ferroelectrics are attractive for electrothermal energy conversion because of their large pyroelectric coefficients over a wide temperature range. Although Pb-based relaxors are well-known, toxicity concerns have mandated the intense search for Pb-free alternatives. Here, we engineered (Ba,Ca)TiO3-based relaxors based on a multisite doping strategy, which show promising electrothermal performance, viz. a maximum PEC efficiency of 14% and electrocaloric refrigeration capacity of 115 J/kg. Using local-scale structural analysis, we provide an atomistic model for large electrothermal properties in the newly designed Pb-free ferroelectrics, whereby a temperature-independent continuous distribution of cation displacement directions creates easy pathways for microscopic polarization reorientation. This research provides key structural insight for future atomic-scale engineering of environmentally sustainable ferroelectrics in energy applications.
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- Morschhauser, F., et al.
(författare)
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Results of a phase I/II study of ocrelizumab, a fully humanized anti-CD20 mAb, in patients with relapsed/refractory follicular lymphoma
- 2010
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 21:9, s. 1870-1876
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ocrelizumab is a humanized anti-CD20 antibody with increased antibody-dependent cellular cytotoxicity compared with rituximab. This phase I/II study evaluated its safety and efficacy in patients with relapsed/refractory follicular lymphoma (FL) after prior rituximab therapy. Design and methods: Forty-seven patients were treated in three dose cohorts and received eight infusions every 3 weeks: cohort A, 200 mg/m(2) (n = 15); cohort B, 375 mg/m(2) (n = 16); cohort C, first dose 375 mg/m(2), seven subsequent doses of 750 mg/m(2) (n = 16). Patients were assessed for safety, efficacy, pharmacodynamics and pharmacokinetics. Results: The median patient age was 58 years, the majority had Ann Arbor stage III/IV disease and had received a median of 2 (range 1-6) prior regimens. Ocrelizumab was well tolerated with grade 3/4 toxicity occurring in 9% of patients. The most common toxicity was infusion-related reactions (74% patients), all grade 1/2 except one grade 3 event. The objective response rate was 38% and was similar in patients with low-affinity and high-affinity variants of the Fc gamma receptor IIIa (Fc gamma RIIIa). With follow-up of similar to 28 months, the median progression-free survival was 11.4 months. Conclusion: Ocrelizumab demonstrated activity in patients with relapsed/refractory FL following prior rituximab treatment, with safety similar to rituximab although adverse events appeared milder.
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- Park, Ji Hun, et al.
(författare)
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Composition-dependent spin exchange interaction for multiferroicity in perovskite Pb(Fe1/2Nb1/2)O3
- 2024
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Ingår i: Journal of Applied Physics. - 0021-8979. ; 135:20
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Tidskriftsartikel (refereegranskat)abstract
- The composition-dependent spin exchange interaction in a perovskite-structured Pb(Fe0.5−xNix)Nb1/2O3 system has been studied to understand its multiferroicity at room-temperature. Special emphasis was paid to the magnetic behavior in terms of magnetic moment, interatomic distance, and atomic ordering because they play a key role in the modulation of magnetic multiferroic behavior. We observed that 10 mol. % Ni incorporation led to multiferroic behavior with considerable ferrimagnetic properties (saturation magnetization of 0.6 emu/g and a coercive field of 20 Oe) coupled with the inherent properties of displacive ferroelectricity (spontaneous polarization of 20 μC/cm2). A subsequent increase in the Ni substitution degree degraded the ferroelectricity due to a phase transition from a non-centrosymmetric rhombohedral to a centrosymmetric cubic system. We have shown that magnetic spins with a pronounced magnetic moment along the [001] direction are ferrimagnetically arranged when the interatomic distance between the magnetic transition metals at the octahedral site is less than 4 Å, resulting in significant magnetic properties The objective of this study is to provide a general methodology for modulating magnetic orders in ferroelectric perovskite oxides.
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- Venkateshwarlu, Sarangi, et al.
(författare)
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Large electromechanical strain and unconventional domain switching near phase convergence in a Pb-free ferroelectric
- 2020
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Ingår i: Communications Physics. - : Springer Science and Business Media LLC. - 2399-3650. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- In many ferroelectrics, large electromechanical strains are observed near regions of composition- or temperature- driven phase coexistence. Phenomenologically, this is attributed to easy re-orientation of the polarization vector and/or phase transition, although their effects are highly convoluted and difficult to distinguish experimentally. Here, we used synchrotron X-ray scattering and digital image correlation to differentiate between the microscopic mechanisms leading to large electrostrains in an exemplary Pb-free piezoceramic Sn-doped barium calcium zirconate titanate. Large electrostrains of ~0.2% measured at room-temperature are attributed to an unconventional effect, wherein polarization switching is aided by a reversible phase transition near the tetragonal-orthorhombic phase boundary. Additionally, electrostrains of ~0.1% or more could be maintained from room temperature to 140 °C due to a succession of different microscopic mechanisms. In situ X-ray diffraction elucidates that while 90° domain reorientation is pertinent below the Curie temperature (TC), isotropic distortion of polar clusters is the dominant mechanism above TC.
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| 16. |
- Venkateshwarlu, Sarangi, et al.
(författare)
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Relaxor behavior and electrothermal properties of Sn- And Nb-modified (Ba,Ca)TiO3 Pb-free ferroelectric
- 2020
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Ingår i: Journal of Materials Research. - : Springer Science and Business Media LLC. - 0884-2914 .- 2044-5326. ; 35:8, s. 1017-1027
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Forskningsöversikt (refereegranskat)abstract
- Relaxor ferroelectrics have drawn attention for possible applications in solid-state cooling and thermal energy harvesting, owing to their electrothermal energy conversion properties. Here, we have synthesized and characterized the structure-property correlations of a new Sn- and Nb-doped (Ba,Ca)TiO3 relaxor ferroelectric with large pyroelectric and electrocaloric effects over a broad temperature range. We observed two peaks for the temperature-dependent pyroelectric coefficient: (i) -(δP/δT) ∼ 563 μC/(m2 K) at T ∼ 270 K and (ii) -(δP/δT) ∼ 1021 μC/(m2 K) at T ∼ 320 K. In addition, a broad peak for electrocaloric temperature change is observed near 320 K with a relative cooling power of 1/417 J/kg. These properties could be correlated to structural changes observed using X-ray diffraction at two different temperature ranges in the material. Analysis of high-energy X-ray scattering and specific heat capacity data revealed a transition from the cubic to tetragonal phase near Tm ∼ 320 K, whereas an additional increase in the tetragonality (c/a) of the polar phase is observed below Ts ∼ 270 K.
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