Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia

Children with Down syndrome (DS) have a greatly increased risk of acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia (ALL). Both DS-AMKL and the related transient myeloproliferative disorder (TMD) have GATA1 mutations as obligatory, early events. To identify mutations contributing to leukemogenesis in DS-ALL, we undertook sequencing of candidate genes, including FLT3, RAS, PTPN11, BRAF, and JAK2. Sequencing of the JAK2 pseudokinase domain identified a specific, acquired mutation, JAK2R683, in 12 (28%) of 42 DS-ALL cases. Functional studies of the common JAK2R683G mutation in murine Ba/F3 cells showed growth factor independence and constitutive activation of the JAK/STAT signaling pathway. High-resolution SNP array analysis of 9 DS-ALL cases identified additional submicroscopic deletions in key genes, including ETV6, CDKN2A, and PAX5. These results infer a complex molecular pathogenesis for DS-ALL leukemogenesis, with trisomy 21 as an initiating or first hit and with chromosome aneuploidy, gene deletions, and activating JAK2 mutations as complementary genetic events. (Blood. 2009; 113: 646-648)

Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma.

Multiple myeloma is characterized by genomic alterations frequently involving gains and losses of chromosomes. Single nucleotide polymorphism (SNP)-based mapping arrays allow the identification of copy number changes at the sub-megabase level and the identification of loss of heterozygosity (LOH) due to monosomy and uniparental disomy (UPD). We have found that SNP-based mapping array data and fluorescence in situ hybridization (FISH) copy number data correlated well, making the technique robust as a tool to investigate myeloma genomics. The most frequently identified alterations are located at 1p, 1q, 6q, 8p, 13, and 16q. LOH is found in these large regions and also in smaller regions throughout the genome with a median size of 1 Mb. We have identified that UPD is prevalent in myeloma and occurs through a number of mechanisms including mitotic nondisjunction and mitotic recombination. For the first time in myeloma, integration of mapping and expression data has allowed us to reduce the complexity of standard gene expression data and identify candidate genes important in both the transition from normal to monoclonal gammopathy of unknown significance (MGUS) to myeloma and in different subgroups within myeloma. We have documented these genes, providing a focus for further studies to identify and characterize those that are key in the pathogenesis of myeloma.

Generic SoC QR Array Processor for Adaptive Beamforming

A generic architecture for implementing a QR array processor in silicon is presented. This improves on previous research by considerably simplifying the derivation of timing schedules for a QR system implemented as a folded linear array, where account has to be taken of processor cell latency and timing at the detailed circuit level. The architecture and scheduling derived have been used to create a generator for the rapid design of System-on-a-Chip (SoC) cores for QR decomposition. This is demonstrated through the design of a single-chip architecture for implementing an adaptive beamformer for radar applications. Published as IEEE Trans Circuits and Systems Part II, Analog and Digital Signal Processing, April 2003 NOT Express Briefs. Parts 1 and II of Journal reorganised since then into Regular Papers and Express briefs

Photodiodes array as potential diagnostic for measuring short bursts of K-alpha radiation from Ti targets irradiated with 45 fs laser pulses

We report on a study comparing absolute K-alpha yield from Ti foils measured with a calibrated system of an X-ray CCD coupled to a curved LiF Von-Hamos crystal spectrometer to the difference in the signals measured simultaneously with two similar photodiodes fitted with two different filters. Our data indicate that a combination of photodiodes with different filters could be developed into an alternative and inexpensive diagnostic for monitoring single shot pulsed emission in a narrow band of X-ray region.

The complex array of bradykinin-related peptides (BRPs) in the peptidome of pickerel frog (Rana palustris) skin secretion is the product of transcriptional economy.

Previous peptidomic analyses of the defensive skin secretion from the North American pickerel frog, Rana palustris, have established the presence of canonical bradykinin and multiple bradykinin-related peptides (BRPs). As a consequence of the multiplicity of peptides identified and their diverse primary structures, it was speculated that they must represent the products of expression of multiple genes. Here, we present unequivocal evidence that the majority of BRPs (11/13) identified in skin secretion by the peptidomic approach can be generated by differential site-specific protease cleavage from a single common precursor of 321 amino acid residues, named skin kininogen 1, whose primary structure was deduced from cloned skin secretion-derived cDNA. The organization of skin kininogen 1 consists of a hydrophobic signal peptide followed by eight non-identical domains each encoding a single copy of either canonical bradykinin or a BRP. Two additional splice variants, encoding precursors of 233 (skin kininogen 2) or 189 amino acid residues (skin kininogen 3), were also cloned and were found to lack BRP-encoding domains 5 and 6 or 4, 5 and 6, respectively. Thus, generation of peptidome diversity in amphibian defensive skin secretions can be achieved in part by differential protease cleavage of relatively large and multiple-encoding domain precursors reflecting a high degree of transcriptional economy.

Australia Telescope Compact Array 1.2cm Observations of the Massive Star Forming Region G305.2+0.2

We report on Australia Telescope Compact Array observations of the massive star-forming region G305.2+0.2 at 1.2 cm. We detected emission in five molecules towards G305A, confirming its hot core nature. We determined a rotational temperature of 26 K for methanol. A non-local thermodynamic equilibrium excitation calculation suggests a kinematic temperature of the order of 200 K. A time-dependent chemical model is also used to model the gas-phase chemistry of the hot core associated with G305A. A comparison with the observations suggest an age of between 2 × 104 and 1.5 × 105 yr. We also report on a feature to the south-east of G305A which may show weak Class I methanol maser emission in the line at 24.933 GHz. The more evolved source G305B does not show emission in any of the line tracers, but strong Class I methanol maser emission at 24.933 GHz is found 3 arcsec to the east. Radio continuum emission at 18.496 GHz is detected towards two H ii regions. The implications of the non-detection of radio continuum emission towards G305A and G305B are also discussed.

Intragenic SNP haplotypes associated with 84dup18 mutation in TNFRSF11A in four FEO pedigrees suggest three independent origins for this mutation.

Familial expansile osteolysis (FEO) is a rare disorder causing bone dysplasia. The clinical features of FEO include early-onset hearing loss, tooth destruction, and progressive lytic expansion within limb bones causing pain, fracture, and deformity. An 18-bp duplication in the first exon of the TNFRSF11A gene encoding RANK has been previously identified in four FEO pedigrees. Despite having the identical mutation, phenotypic variations among affected individuals of the same and different pedigrees were noted. Another 18-bp duplication, one base proximal to the duplication previously reported, was subsequently found in two unrelated FEO patients. Finally, mutations overlapping with the mutations found in the FEO pedigrees have been found in ESH and early-onset PDB pedigrees. An Iranian FEO pedigree that contains six affected individuals dispersed in three generations has previously been introduced; here, the clinical features of the proband are reported in greater detail, and the genetic defect of the pedigree is presented. Direct sequencing of the entire coding region and upstream and downstream noncoding regions of TNFRSF11A in her DNA revealed the same 18-bp duplication mutation as previously found in the four FEO pedigrees. Additionally, eight sequence variations as compared to the TNFRSF11A reference sequence were identified, and a haplotype linked to the mutation based on these variations was defined. Although the mutation in the Iranian and four of the previously described FEO pedigrees was the same, haplotypes based on the intragenic SNPs suggest that the mutations do not share a common descent.

Low-power systolic array processor architecture for FSBM video motion estimation

A novel power-efficient systolic array architecture is proposed for full search block matching (FSBM) motion estimation, where the partial distortion elimination algorithm is used to dynamically switch off the computation of eliminated partial candidate blocks. The RTL-level simulation shows that the proposed architecture can reduce the power consumption of the computation part of the algorithm to about 60% of that of the conventional 2D systolic arrays.

Retro-transceiver array using monopole antennas

In this paper, we show how a self-tracking antenna array constructed using gimel /4 monopoles can be constructed, which is capable of receiving with gain over an entire 360 degrees azimuthal cut. It is also shown how the self-tacking receive unit can be used in conjunction with a self-phased transmitter so that self-steered spatially selective receive and transmit functions ran be formed simultaneously. The resulting array is capable of maintaining spatially selective receive and transmit functions to a roaming target without prior knowledge of its physical location.