Raman scattering of perovskite SmScO3 and NdScO3 single crystals

We report an investigation of perovskite-type SmScO3 and NdScO3 single crystals by Raman scattering in various scattering configurations and at different wavelengths. The reported Raman spectra, together with the phonon mode assignment, set the basis for the use of Raman scattering for the structural investigation of RE-scandates. Further to the phonon signature, a fluorescence signal is observed for both scandates and is particularly intense for NdScO3 when using a 488 or 514 nm excitation line. A comparison of Raman spectra of RE-scandates with literature Raman data on orthorhombic perovskites shows that the frequency of particular modes scales with the orthorhombic distortion in terms of the rotation (or tilt) angle of the ScO6 octahedr

Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).

We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome

Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome

Mutations in CCAAT/enhancer binding protein α (CEBPA) are seen in 5% to 14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPA mutations simultaneously carry 2 mutations (CEBPAdouble-mut), usually biallelic, whereas single heterozygous mutations (CEBPAsingle-mut) are less frequently seen. Using denaturing high-performance liquid chromatography and nucleotide sequencing, we identified among a cohort of 598 newly diagnosed AMLs a subset of 41 CEBPA mutant cases (28 CEBPAdouble-mut and 13 CEBPA single-mut cases) CEBPAdouble-mut associated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multi-variable analysis that included cytoge-netic risk, FZT3-ITD and NPM1 mutation, white blood cell count, and age. In contrast, CEBPA single-mut AMLs did not express a discriminating signature and could not be distinguished from wild-type cases as regards clinical outcome. These results demonstrate significant underlying heterogeneity within CEBPA mutation-positive AML with prognostic relevance

Astromineralogy of the 13 μm Feature in the Spectra of Oxygen-rich Asymptotic Giant Branch Stars. I. Corundum and Spinel

http://iopscience.iop.org/0004-637X/640/2/971/pdf/0004-637X_640_2_971.pdfAsymptotic giant branch (AGB) stars have several interesting infrared spectral features. Approximately half the oxygen-rich AGB stars to be investigated spectroscopically exhibit a feature at ~13 μm. The carrier of this feature has not yet been unequivocally identified but has been attributed to various dust species, including corundum (α-Al2O 3), spinel (MgAl2O4), and silica (SiO 2). In order to constrain the carrier of the 13 μm feature, we have used the one-dimensional radiative transfer code DUSTY to model the effects of composition and optical depth on the shape and strength of the emerging 13 μm feature from corundum and spinel grains. We have modeled various corundum, spinel, corundum-silicate, and spinel-silicate mixtures in dust shells surrounding O-rich AGB stars. These models demonstrate that (1) if corundum is present in these circumstellar dust shells, even at very low relative abundances, a ~13 μm feature should be observed; (2) corundum's weak ~21 μm feature will not be observed, even if it is responsible for the ~13 μm feature; (3) even at low relative abundances, spinel exhibits a feature at 16.8 μm that is not found in observations; and (4) the grains must be spherical. Other grain shapes (spheroids, ellipsoids, and hollow spheres) shift the features to longer wavelengths for both spinel and corundum. Our models show that spinel is unlikely to be the carrier of the 13 μm feature. The case for corundum as the carrier is strengthened but not yet proven.This work is supported in part by NASA grant APRA04-0000-0041

The intronic G13964C variant in p53 is not a high-risk mutation in familial breast cancer in Australia

BACKGROUND: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53 - G13964C - occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in breast cancer susceptibility. METHOD: We genotyped 71 familial breast cancer patients and 143 control individuals for the G13964C variant using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. RESULTS: Three (4.2%; 95% confidence interval [CI] 0–8.9%) G13964C heterozygotes were identified. The variant was also identified in 5 out of 143 (3.5%; 95% CI 0.6–6.4%) control individuals without breast cancer or a family history of breast cancer, however, which is no different to the proportion found in familial cases (P = 0.9). CONCLUSION: The present study would have had 80% power to detect an odds ratio of 4.4, and we therefore conclude that the G13946C polymorphism is not a 'high-risk' mutation for familial breast cancer

Candidate gene association study in pediatric acute lymphoblastic leukemia evaluated by Bayesian network based Bayesian multilevel analysis of relevance

Background: We carried out a candidate gene association study in pediatric acute lymphoblastic leukemia (ALL) to identify possible genetic risk factors in a Hungarian population. Methods: The results were evaluated with traditional statistical methods and with our newly developed Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA) method. We collected genomic DNA and clinical data from 543 children, who underwent chemotherapy due to ALL, and 529 healthy controls. Altogether 66 single nucleotide polymorphisms (SNPs) in 19 candidate genes were genotyped. Results: With logistic regression, we identified 6 SNPs in the ARID5B and IKZF1 genes associated with increased risk to B-cell ALL, and two SNPs in the STAT3 gene, which decreased the risk to hyperdiploid ALL. Because the associated SNPs were in linkage in each gene, these associations corresponded to one signal per gene. The odds ratio (OR) associated with the tag SNPs were: OR = 1.69, P = 2.22x10-7 for rs4132601 (IKZF1), OR = 1.53, P = 1.95x10-5 for rs10821936 (ARID5B) and OR = 0.64, P = 2.32x10-4 for rs12949918 (STAT3). With the BN-BMLA we confirmed the findings of the frequentist-based method and received additional information about the nature of the relations between the SNPs and the disease. E.g. the rs10821936 in ARID5B and rs17405722 in STAT3 showed a weak interaction, and in case of T-cell lineage sample group, the gender showed a weak interaction with three SNPs in three genes. In the hyperdiploid patient group the BN-BMLA detected a strong interaction among SNPs in the NOTCH1, STAT1, STAT3 and BCL2 genes. Evaluating the survival rate of the patients with ALL, the BN-BMLA showed that besides risk groups and subtypes, genetic variations in the BAX and CEBPA genes might also influence the probability of survival of the patients. Conclusions: In the present study we confirmed the roles of genetic variations in ARID5B and IKZF1 in the susceptibility to B-cell ALL. With the newly developed BN-BMLA method several gene-gene, gene-phenotype and phenotype-phenotype connections were revealed. We showed several advantageous features of the new method, and suggested that in gene association studies the BN-BMLA might be a useful supplementary to the traditional frequentist-based statistical method

Advances in the treatment of chronic myeloid leukemia

Although imatinib is firmly established as an effective therapy for newly diagnosed patients with chronic myeloid leukemia (CML), the field continues to advance on several fronts. In this minireview we cover recent results of second generation tyrosine kinase inhibitors in newly diagnosed patients, investigate the state of strategies to discontinue therapy and report on new small molecule inhibitors to tackle resistant disease, focusing on agents that target the T315I mutant of BCR-ABL. As a result of these advances, standard of care in frontline therapy has started to gravitate toward dasatinib and nilotinib, although more observation is needed to fully support this. Stopping therapy altogether remains a matter of clinical trials, and more must be learned about the mechanisms underlying the persistence of leukemic cells with treatment. However, there is good news for patients with the T315I mutation, as effective drugs such as ponatinib are on their way to regulatory approval. Despite these promising data, accelerated or blastic phase disease remains a challenge, possibly due to BCR-ABL-independent resistance

Morphological effects on IR band profiles: Experimental spectroscopic analysis with application to observed spectra of oxygen-rich AGB stars

To trace the source of the unique 13, 19.5, and 28 $\mu$m emission features in the spectra of oxygen-rich circumstellar shells around AGB stars, we have compared dust extinction spectra obtained by aerosol measurements. We have measured the extinction spectra for 19 oxide powder samples of eight different types, such as Ti-compounds (TiO, TiO$_2$, Ti$_2$O$_3$, Ti$_3$O$_5$, Al$_2$TiO$_5$, CaTiO$_3$), $\alpha$-, $\gamma$-, $\chi$-$\delta$-$\kappa$-Al$_2$O$_3$, and MgAl$_2$O$_4$ in the infrared region (10 - 50 $\mu$m) paying special attention to the morphological (size, shape, and agglomeration) effects and the differences in crystal structure. Anatase (TiO$_2$) particles with rounded edges are the possible 13, 19.5 and 28 $\mu$m band carriers as the main contributor in the spectra of AGB stars, and spherically shaped nano-sized spinel and Al$_2$TiO$_5$ dust grains are possibly associated with the anatase, enhancing the prominence of the 13 $\mu$m feature and providing additional features at 28 $\mu$m. The extinction data sets obtained by the aerosol and CsI pellet measurements have been made available for public use at http://elbe.astro.uni-jena.deComment: 17 pages, 8 figures, Accepted 24 March 2009 for publication in A&