Synthesis and biological evaluation of gemcitabine-lipid conjugate (NEO6002)

A novel gemcitabine-lipid conjugate 5 was synthesized and tested for its in vivo efficacy and toxicity. Compound 5 was tested in BxPC-3 human pancreatic tumor model in SCID mice and exhibited promising activity and lower toxicity when compared with Gemzar.     

Human CD59 Incorporation into Porcine Endogenous Retrovirus Particles: Implications for the Use of Transgenic Pigs for Xenotransplantation

Transgenic pigs have been engineered to express human CD59 (hCD59) in order to suppress hyperacute rejection of xenotransplants in human recipients. In this study, porcine endogenous retrovirus (PERV) was produced in a porcine cell line expressing hCD59 in order to examine the effect of this complement control protein on PERV neutralization by human sera. hCD59 was found to be incorporated into PERV particles produced from engineered ST-IOWA cells. PERV incorporation of hCD59 resulted in a dramatic inhibition of complement-mediated virolysis by human serum. However, incorporation of hCD59 had no effect on neutralization of PERV by human serum, as measured in infectivity assays. Our results suggest that the use of organs from hCD59 transgenic pigs will inhibit complement-mediated virolysis, but will not compromise the protective effects of human sera on the neutralization of PERV particles.     

A populational survey of amino acids in Prosopis species from North and South America

Leaf extracts of 540 plants representing 24 species of the genus Prosopis from North and South America were analyzed by 2-D PC and high voltage electrophoresis for their protein and non-protein amino acids. In addition to the presence of the usual protein amino acids, most of the species examined contained high concentrations of the non-protein amino acids, pipecolic acid, 4-hydroxypipecolic acid and proline.     

Substrate specificity of king cobra (Ophiophagus hannah) venom L-amino acid oxidase

1. Substrate specificity of purified king cobra (Ophiophagus hannah) venom L-amino acid oxidase was investigated. 2. The enzyme was highly specific for the L-enantiomer of amino acid. Effective oxidation of L-amino acid by the enzyme requires the presence of a free primary alpha-amino group but the alpha-carboxylate group is not as critical for the catalysis. 3. The enzyme was very active against L-Lys, L-Phe, L-Leu, L-Tyr, L-Tryp, L-Arg, L-Met, L-ornithine, L-norleucine and L-norvaline and moderately active against L-His, L-cystine and L-Ileu. Other L-amino acids were oxidized slowly or not oxidized. 4. The data suggest the presence of a side chain binding site in the enzyme, and that the binding site comprises at least five 'subsites': the hydrophobic subsites a, b and c; and the two 'amino' binding subsites d and e. Subsite b appears to be able to accommodate two methylene/methyl carbons.     

Association study of the NRAMP1 gene promoter polymorphism and early-onset type 1 diabetes

Natural resistance-associated macrophage protein 1 (NRAMP1) has an important role in regulating macrophage functions that affect innate resistance as well as immune responses. We analyzed the microsatellite polymorphism in the promoter region of the human NRAMP1 gene in 206 type 1 diabetes patients and 200 normal children to determine whether this polymorphism might be associated with type 1 diabetes in the Japanese population. The frequency of allele 2 (180 bp) of the promoter microsatellite polymorphism of the NRAMP1gene was slightly lower in the early-onset population (2-10 years of age) of type 1 diabetes patients than in controls, although the difference did not reach statistical significance. The association study of the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene, located near the NRAMP1 gene, and type 1 diabetes showed that the CTLA-4 gene significantly contributed to the development of type 1 diabetes, whereas NRAMP1 had an additional effect on the onset of type 1 diabetes in the young population.     

Moment Feature Based Fast Feature Extraction Algorithm for Moving Object Detection Using Aerial Images

Fast and computationally less complex feature extraction for moving object detection using aerial images from unmanned aerial vehicles (UAVs) remains as an elusive goal in the field of computer vision research. The types of features used in current studies concerningmoving object detection are typically chosen based on improving detection rate rather than on providing fast and computationally less complex feature extraction methods. Because moving object detection using aerial images from UAVs involves motion as seen from a certain altitude, effective and fast feature extraction is a vital issue for optimum detection performance. This research proposes a two-layer bucket approach based on a new feature extraction algorithm referred to as the moment-based feature extraction algorithm (MFEA). Because a moment represents thecoherent intensity of pixels and motion estimation is a motion pixel intensity measurement, this research used this relation to develop the proposed algorithm. The experimental results reveal the successful performance of the proposed MFEA algorithm and the proposed methodology.     

Does service accessibility reduce socioeconomic differentials in maternity care seeking? Evidence from rural Bangladesh

Maternal mortality is a serious public health concern in Bangladesh. However, most deaths could be prevented through proper and timely care seeking and adequate management. Unfortunately, fewer than half of pregnant women in Bangladesh seek antenatal care, and only one in eight receive delivery care from medically trained providers. The specific objectives of this research are to examine the socioeconomic differentials of maternity care seeking, and to determine whether accessibility of health services reduces the socioeconomic differentials in maternity care seeking. A multi-level logistic regression method is employed to analyse longitudinal data collected from a sample of 1019 women from all over Bangladesh. The study finds significant socioeconomic disparities in both antenatal and delivery care seeking. Service accessibility, however, significantly reduces the socioeconomic differentials in delivery care seeking. Services need to be made accessible to reduce the inequality in maternity care seeking between rich and poor, empowered and non-empowered.     

Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population

Co-stimulatory molecules of CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and the newly identified inducible co-stimulator (ICOS) are expressed on cell surfaces and provide regulatory signals for T-cell activation. Their genes are candidate susceptibility genes for type 1 diabetes because they co-localize to Chromosome 2q33 with the IDDM12 locus. After determining the genomic structure and screening for polymorphisms of the ICOS gene, we performed association studies between newly identified polymorphisms of the ICOS gene, together with known polymorphisms of CD28 and CTLA-4 genes, and type 1 diabetes. The 49A/G dimorphism in exon 1 and the (AT)n in the 3' untranslated region of the CTLA-4 gene were significantly associated with type 1 diabetes. Evaluation of the CTLA-4 49A-3'(AT)n 86-bp haplotype frequency in patients and controls confirmed the results from the analysis of each polymorphic site. Dimorphism in intron 3 of the CD28 gene was associated with type 1 diabetes only in the early-onset group. In contrast, there was no association with the microsatellite polymorphisms in the ICOS gene or dimorphisms in the promotor region of CTLA-4. Of the three genes encoding co-stimulatory molecules, the CTLA-4 gene appears to confer risks for the development of type 1 diabetes.