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Introduction: One-quarter of the relapses in children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) occur very early (within 18 months, before completion of treatment), and prognosis in these patients is worse compared to cases that relapse after treatment has ended. Methods: In this study, we performed a genomic analysis of diagnosis–relapse pairs of 12 children who relapsed very early, followed by a deep-sequencing validation of all identified mutations. In addition, we included one case with a good initial treatment response and on-treatment relapse at the end of upfront therapy. Results: We observed a dynamic clonal evolution in all cases, with relapse almost exclusively originating from a subclone at diagnosis. We identified several driver mutations that may have influenced the outgrowth of a minor clone at diagnosis to become the major clone at relapse. For example, a minimal residual disease (MRD)-based standard-risk patient with ETV6-RUNX1-positive leukemia developed a relapse from a TP53-mutated subclone after loss of the wildtype allele. Furthermore, two patients with TCF3-PBX1-positive leukemia that developed a very early relapse carried E1099K WHSC1 mutations at diagnosis, a hotspot mutation that was recurrently encountered in other very early TCF3-PBX1-positive leukemia relapses as well. In addition to alterations in known relapse drivers, we found two cases with truncating mutations in the cohesin gene RAD21. Conclusion: Comprehensive genomic characterization of diagnosis–relapse pairs shows that very early relapses in BCP-ALL frequently arise from minor subclones at diagnosis. A detailed understanding of the therapeutic pressure driving these events may aid the development of improved therapies.

Contains fulltext : 218617.pdf (publisher's version ) (Open Access), Genomic alterations in relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) may provide insight into the role of specific genomic events in relapse development. Along this line, comparisons between the spectrum of alterations in relapses that arise in different upfront treatment protocols may provide valuable information on the association between the tumor genome, protocol components and outcome. Here, we performed a comprehensive characterization of relapsed BCP-ALL cases that developed in the context of 3 completed Dutch upfront studies, ALL8, ALL9, and ALL10. In total, 123 pediatric BCP-ALL relapses and 77 paired samples from primary diagnosis were analyzed for alterations in 22 recurrently affected genes. We found pronounced differences in relapse alterations between the 3 studies. Specifically, CREBBP mutations were observed predominantly in relapses after treatment with ALL8 and ALL10 which, in the latter group, were all detected in medium risk-treated patients. IKZF1 alterations were enriched 2.2-fold (p = 0.01) and 2.9-fold (p < 0.001) in ALL8 and ALL9 relapses compared to diagnosis, respectively, whereas no significant enrichment was found for relapses that were observed after treatment with ALL10. Furthermore, IKZF1 deletions were more frequently preserved from a major clone at diagnosis in relapses after ALL9 compared to relapses after ALL8 and ALL10 (p = 0.03). These data are in line with previous studies showing that the prognostic value of IKZF1 deletions differs between upfront protocols and is particularly strong in the ALL9 regimen. In conclusion, our data reveal a correlation between upfront treatment and the genetic composition of relapsed BCP-ALL.

Here we report the synthesis and structural, morphological, and photoluminescence analysis of white- and blue-light-emitting Dy3+- and Tm3+-doped Gd2Ti2O7 nanophosphors. Single-phase cubic Gd2Ti2O7 nanopowders consist of compact, dense aggregates of nanoparticles with an average size of similar to 25 nm for Dy3+-doped and similar to 50 nm for Tm3+-doped samples. The photoluminescence results indicated that ultraviolet (UV) light excitation of the Dy3+-doped sample resulted in direct generation of white light, while a dominant yellow emission was obtained under blue-light excitation. Intense blue light was obtained for Tm3+-doped Gd2Ti2O7 under UV excitation suggesting that this material could be used as a blue phosphor.

Zinc sulfide, both as a bulk material and in nanocrystalline form, is a valuable luminescent material with important applications. Doped ZnS nanoparticles of around 5 nm are the material of choice for optoelectronic applications running in the UV region owing to their significant quantum size effect. This paper concerns detailed structural, spectroscopic and crystal field studies of ZnS nanoparticles, both pure and doped with Mn2+ ions, successfully synthesized at room temperature using a simple reverse micelle technique in the Triton X-100/cyclohexane medium. The resulting ZnS sphalerite phase smallsize nanoparticles (3-5 nm) have a much larger energy band gap ( similar to 4.7 eV) than that reported for the bulk ZnS (3.6 eV), thus confirming a pronounced quantum confinement effect. The electron paramagnetic resonance data provided evidence for the existence of two distinct environments for Mn2+ ions: the interior (core) and near the surface of the nanoparticles. The presence of an Mn2+-characteristic orange emission centered at 600 nm confirmed that our samples were properly doped with Mn2+ ions, as the T-4(1)- GT (6)A(1) radiation transition could arise only on the basis of Mn2+ ions incorporated into the ZnS nanoparticles. To the best of our knowledge, our finding include the longest decay time component for the orange emission ever observed, timed at about 3.3 ms. The experimental excitation spectra were analyzed and the transitions assigned using the exchange charge model of theory of crystal field, which allowed to calculate the energy level scheme of the Mn2+ ions. The results presented in this paper provide us with detailed information about the ZnS sphalerite nanocrystals studied and can be readily applied to other similar systems. (C) 2013 Elsevier B.V. All rights reserved.

The emission rise time of Eu3+-doped SrY2O4 was investigated in the temperature range of 20-200 degrees C for application in luminescence thermometry. After pulsed excitation, the energy transfer between the adjacent Eu3+ ions causes a emission build-up from the D-5(0) level of Eu3+ and a notable emission rise occurs prior to decay. The emission rise-time values linearly decrease with temperature, providing an absolute sensitivity of 0.66 mu s degrees C-1 and a maximal relative sensitivity of 5.53% degrees C-1 at 200 degrees C, for samples containing 0.5 at% Eu3+ ions. It is shown that the time after excitation at which emission reaches a maximum (time-to-max) can also be exploited for temperature sensing, since it is easily measurable and shows a linear dependence with temperature.

The performance of Sm3+ doped TiO2 nanoparticles for luminescence temperature sensing was tested over a temperature range from room to 110 degrees C. The Sm3+ ions were incorporated into TiO2 nanocrystals using hydrolytic sol-gel route. Microstructural characterization of the obtained material was performed using transmission electron microscopy and x-ray diffraction measurements. Luminescence emission spectra of Sm3+ doped TiO2 nanoparticles consists of two distinct spectral regions: the high energy region associated with the trap emission of the TiO2 host, and the low energy region with well-resolved emission peaks of the Sm3+ ions. The ratio between Sm3+ emission and TiO2 trap emission shows strong temperature dependence, and is tested for temperature sensing. The relative sensor sensitivity was found to be higher than 1% degrees C-1 over given temperature range with the maximum value of 10.54% degrees C-1 at 57.5 degrees C. Lifetime data derived from the Sm3+ emission decay revealed that time-resolved measurements provide comparable quality of temperature sensing as corresponding ratiometric measurements, with a maximum relative sensitivity of 10.14% degrees C-1 at 66.5 degrees C.

Herein, temperature dependencies of emission and emission decay of Zn2SiO4:Mn2+ powder in the range from room temperature to 300 degrees C is reported. These dependencies allow temperature sensing from luminescence measurements, since Mn2+ emission intensity, emission band spectral position, and emission decay are rapidly changing over the entire temperature range. For fluorescence intensity ratio method, measurement that relays on emission intensity changes with temperature, sensitivity of 12.2% is found. In the case of lifetime thermometry, method that relays on emission decay changes with temperature, sensitivity of 0.48% is determined. Both sensitivity values are among the highest ever recorded for inorganic materials. (C) 2013 AIP Publishing LLC.

Phosphors are thermographic if their emission characteristics change with temperature. In this paper, we investigated the potential use of a europium-doped (1, 3 and 6 at.% Eu3+) yttrium-gadolinium oxide (Y0.75Gd0.25)(2)O-3 nanostructured matrix for phosphor thermometry and thermometry in high-energy radiation fields. Photoluminescence emission measurements were recorded in the temperature range from room temperature to 873 K, observing temperature changes in trivalent europium ion transitions from D-5(1) and D-5(0) energy levels. The results show that Eu3+-doped (Y0.75Gd0.25)(2)O-3 is a new promising high-temperature thermometric phosphor with a very good sensitivity of approximately 4.9x10(-3) K-1 at 823 K for a sample doped with 1 at.% Eu3+. It is shown that with this material the fluorescence intensity ratio method can be used for temperature measurements in high-energy radiation fields without the use of an optical excitation source. In this case a maximal sensitivity of 2.35x10(-3) K-1 is obtained.

Rare-earth orthovanadates are important hosts for the luminescence of rare earth activators with considerable practical applications in the artificial production of light. In this paper we investigated the possibility for GdVO4:Sm3+ usage in phosphor thermometry by observing the temperature changes of trivalent samarium transitions from F-4(3/2) and (4)G(5/2) energy levels to the ground state. A set of three samples of Sm3+-doped GdVO4 (0.5, 1 and 2 mol.% Sm3+ with respect to Gd3+ ions) was produced via solid state synthesis. The sample crystalline structure is confirmed from x-ray diffraction (XRD) measurements. Photoluminescence measurements were recorded in the temperature range 293-823 K and the fluorescence intensity ratio of the paired emissions bands was studied as a function of temperature. All three GdVO4:Sm3+ samples proved to have good potential for the development of thermographic phosphors, whereas the maximum sensitivity of approximately 4.5x10(-4) K-1 was found for the sample with 2 mol.% Sm3+ in the temperature region around 750 K.

Samarium doped LaYO3 nanocrystalline phosphor powders are obtained by polymer complex solution method. Stoichiometric quantities of La2O3, Y2O3 and for dopant ions Sm2O3 were dissolved in hot nitric acid. Polyethylene glycol was added in solutions in 1:1 mass ratio to corresponding metal nitrates to form gel. The gel is combusted and annealed at 800 degrees C for two hours to form nanopowder samples. Crystalline structure and phase purity is checked by X-ray diffraction and show that this material is synthesized in cubic bixbyite type structure for the first time. Luminescence properties of Sm3+ doped LaYOL3 exhibited characteristic orange-red emission coming from the intra-4f-shell (4)G(5/2) - GT H-6(J) electron transitions with emission decay of 1.5 ms. Energy level positions are derived from emission and excitation spectra.

In recent years there is an increasing interest in obtaining and investigating composite materials that comprise nanoparticles as fillers and polymers as matrix. Such composites may display combined features of both components, and sometimes even novel properties resulting from their mutual interactions. It is important that both unique size-dependent properties of nanoparticles and favorable properties of polymer material remain preserved in the composite. In this research we investigated the possibility of obtaining composite material using as polymer matrix poly (methyl methacrylate) - PMMA and Gd2O3:Eu3+ nanopowder as filler. Three samples, containing 1, 3 and 5 mass % of Gd2O3:Eu3+, are prepared with a dispersion casting method. The composites exhibited characteristic red emission coming from the D-5(0) - GT F-7(2) transition of Eu3+ ion in Gd2O3:Eu3+. The observed lifetime values, around 1.1 ms, are quite high and suggest successful encapsulation of dopant ions in polymer through gadolinium oxide host. Experimental intensity parameters, transition rates and quantum efficiency of the D-5(0) emission are calculated from emission spectra using Judd-Ofelt theory. Influence of Gd2O3:Eu3+ filler on the modification of glass transition and thermo-degradable properties of the polymer matrix is also investigated. Thermal analyses give evidence of unchanged thermal stability of polymer phase in the composites.

In the present work we explored the possibility of obtaining Y2O3:Eu3+ mu m-size particles by an ultrasonic spray pyrolysis method. As-prepared sample constitutes of spherical, hollow particles with an average size of 1 to 2 mu m. Pure, well crystalline, cubic Y2O3 is formed after additional thermal treatment at 800 degrees C for 2 h. A detailed optical investigation has been done with photoluminescence measurements in the energy and time domains. Experimental intensity parameters, transition rates and quantum efficiency of the D-5(0) emission are evaluated on the basis of Judd-Ofelt theory.

Nanostructured wollastonite was synthesized by a sol-gel method and then used as a filler for polypropylene (PP). The obtained wollastonite particles were investigated using XRD, TEM and FTIR techniques. Non-isothermal crystallization measurements revealed that the wollastonite filler reduced the crystallization temperature of the matrix. TGA analyses showed improved thermal stability of the nanocomposite with respect to that of the pure polypropylene. From the DMA tan delta curves, it was concluded that the introduction of the filler into the PP matrix induced a slight shift of the beta-transition (glass transition) towards higher temperature. The measurements of storage moduli showed that the nanocomposites have higher stiffness than the pure PP over the whole range of test temperature. An increase in stiffness was also confirmed by tensile measurements. (C) 2009 Elsevier Ltd. All rights reserved.

We present here the synthesis procedure for obtaining Zn2SiO4:M2+ (M = Mn, Ni, Co) powder based on the combination of so-gel and combustion methods. Combustion is performed both in a conventional furnace and in a microwave oven in order to evaluate the influence of combustion conditions on the properties of synthesized material. X-ray diffraction analysis confirmed that obtained material has crystallized in rhombohedral structure of Zn2SiO4 (willemite) with traces of ZnO. The effects of combustion conditions are investigated further by means of thermogravimetric analysis, differential thermal analysis, infrared spectroscopy, diffuse reflectance optical spectroscopy and photoluminescence spectroscopy. Based on these results we could conclude that microwave combustion synthesis can be successfully applied for Zn2SiO4-based products.