Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome)

Abstract Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9.

Project 2.7 Leveraging R&D Investment for the Australian built environment : Phase 2 Case Study Report Part 4 - CADD, BIM and IPD

This report discusses findings of a case study into "CADD, BIM and IPD" undertaken as a part of the retrospective analysis component of Sustainable Built Environment National Research Centre (SBEnrc) Project 2.7 Leveraging R&D investment for the Australian Built Environment. This case study investigated the evolution that has taken place in the Queensland Department of Public Works Division of Project Services during the last 20 years from: the initial implementation of computer aided design and documentation(CADD); to the experimentation with building information modelling (BIM) from the mid 2000’s; embedding integrated practice (IP); to current steps towards integrated project delivery (IPD) with the integration of contractors in the design/delivery process. This case study should be read in conjunction with Part 1 of this suite of reports.

Project 2.7 Leveraging R&D Investment for the Australian built environment : Phase 2 Case Study Report Part 2 - Road Construction Safety

This report discusses findings of a case study into "Road Construction Safety" undertaken as a part of the retrospective analysis component of Sustainable Built Environment National Research Centre (SBEnrc) Project 2.7 Leveraging R&D investment for the Australian Built Environment. The Queensland Department of Transport and Main Roads (QTMR) has taken a leadership role in developing a safer working environment for road construction workers. In the past decades, a range of initiatives have been introduced to contribute to improved performance in this area. Several initiatives have been undertaken by QTMR as part of their overarching commitment to safety. Three such initiatives form the basis for this case study investigation, in order to better illustrate the nature of R&D investment and its impact on day-to-day operations and the supply chain. These are the development and implementation of: (i) the Mechanical Traffic Aid: (ii) the Thermal Imaging Camera; and (iii) the Trailer-based CCTV (camera). This case study should be read in conjunction with Part 1 of this suite of reports.

Vibrational spectroscopic characterization of the phosphate mineral kulanite Ba(Fe2+,Mn2+,Mg)2(Al,Fe3+)2(PO4)3(OH)3

The mineral kulanite BaFe2Al2(PO4)3(OH)3, a barium iron aluminum phosphate, has been studied by using a combination of electron microscopy and vibrational spectroscopy. Scanning electron microscopy with EDX shows the mineral is homogenous with no other phases present. The Raman spectrum is dominated by an intense band at 1022 cm−1 assigned to the PO43-ν1 symmetric stretching mode. Low intensity Raman bands at 1076, 1110, 1146, 1182 cm−1 are attributed to the PO43-ν3 antisymmetric stretching vibrations. The infrared spectrum shows a complex spectral profile with overlapping bands. Multiple phosphate bending vibrations supports the concept of a reduction in symmetry of the phosphate anion. Raman spectrum at 3211, 3513 and 3533 cm−1 are assigned to the stretching vibrations of the OH units. Vibrational spectroscopy enables aspects on the molecular structure of kulanite to be assessed.

Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3

Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum, namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3. The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs.

Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests

Background Accurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region. Methods The pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates, the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008), for 34 PfHRP2-detecting RDTs. Results Sequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However, no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified. Conclusions The results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.

Minnie’s Bow-Toons seasons 2 and 3

Minnie’s Bow-Toons follows the adventures of Minnie Mouse and her best friend Daisy Duck as they run Minnie's Bow-tique, a specialty shop stocked only with colorful bows and bowties. In the third season Minnie, Daisy and their assistant Cuckoo Loca opens a pet grooming salon adjacent to the Bow-tique. In the fourth season Minnie, Daisy and Cuckoo Loca travel around the world, visiting cities like London, Venice and Tokyo.

Crystal structures and hydrogen-bonding in the co-crystalline adducts of 3,5-dinitrobenzoic acid with 4-aminosalicylic acid and 2-hydroxy-3-(1H-indol-3-yl)propenoic acid

The structures of the cocrystalline adducts of 3,5-dinitrobenzoic acid (3,5-DNBA) with 4-aminosalicylic acid (PASA), the 1:1 partial hydrate, C7H4N2O6 .C7H7NO3 . 2H2O, (I) and 2-hydroxy-3-(1H-indol-3-yl)propenoic acid (HIPA) and the 1:1:1 d6-dimethylsulfoxide solvate, C7H4N2O6 . C11H9NO3 . C2D6OS, (II) are reported. The crystal substructure of (I) comprises two centrosymmetric hydrogen-bonded R2/2(8) homodimers, one with 3,5-DNBA, the other with PASA, and an R2/2(8) 3,5-DNBA-PASA heterodimer. In the crystal, inter-unit amine N-H...O and water O-H...O hydrogen bonds generate a three-dimensional supramolecular structure. In (II), the asymmetric unit consists of the three constituent molecules which form an essentially planar cyclic hydrogen-bonded heterotrimer unit [graph set R2/3(17)] through carboxyl, hydroxy and amino groups. These units associate across a crystallographic inversion centre through the HIPA carboxylic acid group in an R2/2~(8) hydrogen-bonding association, giving a zero-dimensional structure lying parallel to (100). In both structures, pi--pi interactions are present [minimum ring centroid separations: 3.6471(18)A in (I) and 3.5819(10)A in (II)].

Ethyl 1-(2-cyanoethyl)-3,5-dimethyl-1H-indole-2-carboxylate

The title compound, C16H18N2O2, is an important precursor in the synthesis of 1,2,3,4-tetrahydropyrazinoindoles, which show excellent antihistamine, antihypertensive and central nervous system depressant properties. The carbethoxy group attached to C2 and the planar cyanoethyl group attached to N1 make dihedral angles of 11.0(4) and 75.0(3)degrees, respectively, with the mean plane of the indole ring, The C-C=N chain is linear with a bond angle of 179.3 (4)degrees.

Phase Equilibria in the System $Al_{2}O_{3}-CaO-CoO$ and Gibbs Energy of Formation of $Ca_{3}CoAl_{4}O_{10}$

The floating-zone method with different growth ambiences has been used to selectively obtain hexagonal or orthorhombic DyMnO3 single crystals. The crystals were characterized by x-ray powder diffraction of ground specimens and a structure refinement as well as electron diffraction. We report magnetic susceptibility, magnetization and specific heat studies of this multiferroic compound in both the hexagonal and the orthorhombic structure. The hexagonal DyMnO3 shows magnetic ordering of Mn3+ (S = 2) spins on a triangular Mn lattice at T-N(Mn) = 57 K characterized by a cusp in the specific heat. This transition is not apparent in the magnetic susceptibility due to the frustration on the Mn triangular lattice and the dominating paramagnetic susceptibility of the Dy3+ (S = 9/2) spins. At T-N(Dy) = 3 K, a partial antiferromagnetic order of Dy moments has been observed. In comparison, the magnetic data for orthorhombic DyMnO3 display three transitions. The data broadly agree with results from earlier neutron diffraction experiments, which allows for the following assignment: a transition from an incommensurate antiferromagnetic ordering of Mn3+ spins at T-N(Mn) = 39 K, a lock-in transition at Tlock-in = 16 K and a second antiferromagnetic transition at T-N(Dy) = 5 K due to the ordering of Dy moments. Both the hexagonal and the orthorhombic crystals show magnetic anisotropy and complex magnetic properties due to 4f-4f and 4f-3d couplings.

A high yield synthesis of (±)-5,8-dimethoxy-2-α-hydroxyethyl-3,4-dihydronaphthalene, a key intermediate in anthracyclinone synthesis

The dimethoxytetralol gives on Vilsmeier reaction the dihydronaphthaldehyde (yield,92%), which on Grignard reaction with MeMgI affords the title compound (yield,�100%), the reactions constituting a high yield synthesis of this important anthracyclinone intermediate.

1H NMR and a study of the anomalous temperature dependence of the 35Cl NQR frequencies in 2-chloro-3-pyridinol

A 35Cl NQR study of 2-chloro-3-pyridinol showed the presence of four NQR signals at 77 K. One of the lines showed a positive temperature coefficient of the NQR frequency. 1H NMR studies showed the presence of intramolecular hydrogen bonding, and the anomalous NQR temperature dependence has been explained in terms of Bayer and hydrogen bond effects. The room temperature x-ray structure and the low-temperature NQR data suggest the presence of a phase transition.

High resolution genetic and physical mapping of the I-3 region of tomato chromosome 7 reveals almost continuous microsynteny with grape chromosome 12 but interspersed microsynteny with duplications on Arabidopsis chromosomes 1, 2 and 3

The tomato I-3 gene introgressed from the Lycopersicon pennellii accession LA716 confers resistance to race 3 of the fusarium wilt pathogen Fusarium oxysporum f. sp. lycopersici. We have improved the high-resolution map of the I-3 region of tomato chromosome 7 with the development and mapping of 31 new PCR-based markers. Recombinants recovered from L. esculentum cv. M82 × IL7-2 F2 and (IL7-2 × IL7-4) × M82 TC1F2 mapping populations, together with recombinants recovered from a previous M82 × IL7-3 F2 mapping population, were used to position these markers. A significantly higher recombination frequency was observed in the (IL7-2 × IL7-4) × M82 TC1F2 mapping population based on a reconstituted L. pennellii chromosome 7 compared to the other two mapping populations based on smaller segments of L. pennellii chromosome 7. A BAC contig consisting of L. esculentum cv. Heinz 1706 BACs covering the I-3 region has also been established. The new high-resolution map places the I-3 gene within a 0.38 cM interval between the molecular markers RGA332 and bP23/gPT with an estimated physical size of 50-60 kb. The I-3 region was found to display almost continuous microsynteny with grape chromosome 12 but interspersed microsynteny with Arabidopsis thaliana chromosomes 1, 2 and 3. An S-receptor-like kinase gene family present in the I-3 region of tomato chromosome 7 was found to be present in the microsyntenous region of grape chromosome 12 but was absent altogether from the A. thaliana genome.

Crystallization Kinetics and Electrical Relaxation of BaO-0.5Li(2)O-4.5B(2)O(3) Glasses

Transparent glasses in the composition BaO-0.5Li(2)O-4.5B(2)O(3) (BLBO) were fabricated via the conventional melt-quenching technique. X-ray powder diffraction combined with differential scanning calorimetric (DSC) studies carried out on the as-quenched samples confirmed their amorphous and glassy nature, respectively. The crystallization behavior of these glasses has been studied by isothermal and nonisothermal methods using DSC. Crystallization kinetic parameters were evaluated from the Johnson-Mehl-Avrami equation. The value of the Avrami exponent (n) was found to be 3.6 +/- 0.1, suggesting that the process involves three-dimensional bulk crystallization. The average value of activation energy associated with the crystallization of BLBO glasses was 317 +/- 10 kJ/mol. Transparent glass-ceramics were fabricated by controlled heat-treatment of the as-quenched glasses at 845 K/40 min. The dielectric constants for BLBO glasses and glass-ceramics in the 100 Hz-10 MHz frequency range were measured as a function of the temperature (300-925 K). The electrical relaxation and dc conductivity characteristics were rationalized using electric modulus formalism. The imaginary part of the electric modulus spectra was modeled using an approximate solution of the Kohlrausch-Williams-Watts relation. The temperature-dependent behavior of stretched exponent (beta) was discussed for the as-quenched and heat-treated BLBO glasses.

Ethyl 2-acetyl-3-(4-chloroanilino)butanoate

The title compound, C14H18ClNO3, adopts an extended conformation, with all of the main chain torsion angles associated with the ester and amino groups trans. In the crystal, inversion dimers linked by pairs of N-H center dot center dot center dot O hydrogen bonds are observed.