25 research outputs found
ChemInform Abstract: trans-2,6-, 3,6- and 4,6-Diaza-5,6,6a,7,8,12b-hexahydrobenzo[c]phenanthrene-10,11-diols as Dopamine Agonists.
No full textHuman astrocytoma U138MG cells express predominantly type-A endothelin receptor
No full textAbstractEndothelin-1 (ET-1) binding to human astrocytoma U138MG cells was time-dependent, and bound [125I]ET-1 was difficult to dissociate. The Bmax and Kd values of [125I]ET-1 binding were 70 fmol/mg and 0.07 nM, respectively. Interestingly, different from other astrocytoma cells and astrocytes, the U138MG cells expressed predominantly ETA receptor as shown by RT-PCR results and binding studies. ET-1, FR139317, BQ123, PD142893 and Ro46–2005 inhibited specific [125I]ET-1 binding with Ki values of 0.10, 0.53, 4.3, 22, and 320 nM, respectively. ETB selective ligands ET-3 and IRL1620 were much less potent. The inhibitory effects of antagonists BQ123 and PD142893 on [125I]ET-1 binding diminished following the incubation time. ET-1 binding caused a modest stimulation in phosphatidylinositol hydrolysis with an EC50 value of 24 nM. In comparison to the human U373MG cells. ET-1-induced receptor internalization in U138MG cells was less efficient with 42% of bound ET-1 internalized after 30 min of incubation. These results imply that human astrocytoma cells/astrocytes are able to express either ETA or ETB receptor under different pathophysiological conditions
Cholecystokinin (CCK) antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors
No full textCCK antagonists: Investigations of the relationship between benzotript and glutamic acid-based antagonists
No full textAssessing the impact of algorithmic trading on markets: a simulation approach
No full textInnovative automated execution strategies like Algorithmic Trading gain significant market share on electronic market venues worldwide, although their impact on market outcome has not been investigated in depth yet. In order to assess the impact of such concepts, e.g. effects on the price formation or the volatility of prices, a simulation environment is presented that provides stylized implementations of algorithmic trading behavior and allows for modeling latency. As simulations allow for reproducing exactly the same basic situation, an assessment of the impact of algorithmic trading models can be conducted by comparing different simulation runs including and excluding a trader constituting an algorithmic trading model in its trading behavior. By this means the impact of Algorithmic Trading on different characteristics of market outcome can be assessed. The results indicate that large volumes to execute by the algorithmic trader have an increasing impact on market prices. On the other hand, lower latency appears to lower market volatility
Galaxy and Mass Assembly (GAMA) : merging galaxies and their properties
No full textWe derive the close pair fractions and volume merger rates for galaxies in the Galaxy and Mass Assembly (GAMA) survey with -23 <M-r <-17 (Omega(M) = 0.27, Omega(A) = 0.73, H-0 = 100 km s(-1) Mpc(-1)) at 0.01 <z <0.22 (look-back time of <2 Gyr). The merger fraction is approximately 1.5 per cent Gyr(-1) at all luminosities (assuming 50 per cent of pairs merge) and the volume merger rate is approximate to 3.5 x 10(-4) Mpc(-3) Gyr(-1). We examine how the merger rate varies by luminosity and morphology. Dry mergers (between red/spheroidal galaxies) are found to be uncommon and to decrease with decreasing luminosity. Fainter mergers are wet, between blue/discy galaxies. Damp mergers (one of each type) follow the average of dry and wetmergers. In the brighter luminosity bin (-23 <M-r <-20), the merger rate evolution is flat, irrespective of colour or morphology, out to z similar to 0.2. The makeup of the merging population does not appear to change over this redshift range. Galaxy growth by major mergers appears comparatively unimportant and dry mergers are unlikely to be significant in the buildup of the red sequence over the past 2 Gyr. We compare the colour, morphology, environmental density and degree of activity (BPT class, Baldwin, Phillips & Terlevich) of galaxies in pairs to those of more isolated objects in the same volume. Galaxies in close pairs tend to be both redder and slightly more spheroid dominated than the comparison sample. We suggest that this may be due to 'harassment' in multiple previous passes prior to the current close interaction. Galaxy pairs do not appear to prefer significantly denser environments. There is no evidence of an enhancement in the AGN fraction in pairs, compared to other galaxies in the same volume.Peer reviewe
Genetic variation in the chicken genome: insights in selection
No full text The chicken currently provides more than a quarter of the meat and nearly all eggs produced worldwide. For future improvements in production traits and animal welfare as well as to address future consumer demands it is necessary to understand the etiology and biology underlying production traits and diseases. The primary aim of the research described in this thesis was to investigate the utility of several molecular approaches to identify causative variants underlying a variety of traits in the chicken. The general introduction in chapter 1 provides an overview of the domestication history of the chicken - with a particular focus on commercial chicken breeds - and describes the importance to identify causative variants underlying production traits and diseases. Furthermore, several different molecular techniques and methods are introduced that are being used to detect causative variants underlying monogenic and polygenic traits. Linkage maps are essential for linkage analysis, important to study recombination rates and recombination hotspots within the genome and can assist in the sequence assembly of genomes. In chapter 2 we describe the construction of a new high-resolution linkage map of the chicken genome based on two chicken populations with a total of 1619 individuals. The two populations used are a purebred broiler line and a broiler x broiler cross. This high resolution allowed accurate identification of recombination hotspots in the chicken genome, including sex specific recombination. Furthermore, to improve the current reference genome (WASHUC2), 613 unmapped markers were included in the genome-wide assay that included a total of 17,790 SNPs. The resulting linkage map comprises 13,340 SNPs, of which 360 had not been assigned to a known chromosome on chicken genome build WASHUC2. The resulting linkage map is composed of 31 linkage groups, with a total length of 3,054 cM for the sex-average map of the combined population. Regional differences in recombination hotspots between the two mapping populations were observed for several chromosomes near the telomere of the p arm. The sex-specific analysis revealed that these regional differences were mainly caused by female-specific recombination hotspots in the broiler × broiler cross. In chapter 3 we describe the molecular characterization of the locus causing the late feathering phenotype; a monogenic trait in chicken that results in a delayed emergence of flight feathers at hatch. The late feathering phenotype is beneficial to breeders as it can be used for sex typing at hatch. The locus has, therefore, been extensively used in diverse commercial chicken breeds. However, a retrovirus closely linked to the late feathering allele causes a negative pleiotropic effect on egg production and causes viral infections. Within this chapter we describe the identification of a 180 kb tandem duplication in the late feathering allele using a quantitative PCR approach. The tandem duplication results in the partial duplication of two genes; the prolactin receptor and the gene encoding sperm flagellar protein 2. Sequence analysis revealed that the duplication is identical in broiler, white egg-layer, and brown egg-layer lines. This information was also used to design a molecular test to detect this duplication, particularly in heterozygous individuals. The recent advances in massive parallel sequencing technologies have enabled rapid and cost-effective detection of all genetic variants within genomes. The detection of all genetic variants within a genome has further increased our ability to identify causative variants underlying quantitative trait loci (QTL). In chapter 4, we combined a genome-wide association study with whole-genome resequencing to identify causative variants underlying the pulmonary hypertension syndrome (PHS), a polygenic trait in chicken. PHS is a metabolic disease that has been linked to intense selection on growth rate and feed conversion ratio of modern broilers (meat-type chicken). PHS has become one of the most frequent causes of mortality within the broiler industry and leads to substantial economic losses and reduced animal welfare. In total, 18 QTL regions were identified in the genome-wide association study. In order to detect causative variants underlying these QTL regions, we sequenced the genomes of twelve individuals. To maximize the detection of causative variants we selected the individuals based on extreme phenotypes for PHS. Within 8 QTL regions we identified a total of 10 genes that contain at least one variant that is predicted to affect protein function. Moreover, 7.62 million SNPs were detected within the twelve animals compared to the reference genome. These markers can be used in the development of future genome-wide assays. Genomic regions that have undergone selection should contain loci that influence important phenotypic traits and will, therefore, include causative variant(s) that could aid in further future improvement of production traits and disease resistance. In chapter 5, we applied hitch-hiking mapping to make a broad assessment of the effects of selection histories in domesticated chicken. Towards this end, we sampled commercial chickens representing all major breeding goals from multiple breeding companies. In addition, we sampled non-commercial chicken diversity by sampling almost all recognized traditional Dutch breeds and a representative sample of breeds from China. The broad sample of 67 commercial and non-commercial breeds were assessed for signatures of selection in the genome using information of 57,636 SNPs that were genotyped on pooled DNA samples. Our approach demonstrates the strength of including many different populations with similar, and breed groups with different selection histories to reduce stochastic effects based on single populations. The detection of regions of putative selection resulted in the identification of several candidate genes that could aid in further improvement of production traits and disease resistance. Finally, the general discussion in chapter 6 describes the main findings of this thesis. In this chapter recommendations are given for the best strategies to detect causative variants underlying monogenic or polygenic traits. All strategies can benefit substantially from the recent developments in massive parallel sequencing, although the high costs of this method currently prevent large scale studies. In order to perform powerful and cost-effective studies, several strategies are discussed that combine massive parallel sequencing with other existing methods and techniques. Furthermore, the limitations of the different strategies are addressed, as well as the improvements needed in the near future to identify causative variants underlying a variety of traits in, but not limited to, the chicken. </p
Bioinformatics' approaches to detect genetic variation in whole genome sequencing data
No full textCurrent genetic marker repositories are not sufficient or even are completely lacking for most farm animals. However, genetic markers are essential for the development of a research tool facilitating discovery of genetic factors that contribute to resistance to disease and the overall welfare and performance in farm animals. By large scale identification of Single Nucleotide Polymorphisms (SNPs) and Structural Variants (SVs) we aimed to contribute to the development of a repository of genetic variants for farm animals. For this purpose bioinformatics data pipelines were designed and validated to address the challenge of the cost effective identification of genetic markers in DNA sequencing data even in absence of a fully sequenced reference genome. To find SNPs in pig, we analysed publicly available whole genome shotgun sequencing datasets by sequence alignment and clustering. Sequence clusters were assigned to genomic locations using publicly available BAC sequencing and BAC mapping data. Within the sequence clusters thousands of SNPs were detected of which the genomic location is roughly known. For turkey and duck, species that both were lacking a sufficient sequence data repository for variant discovery, we applied next-generation sequencing (NGS) on a reduced genome representation of a pooled DNA sample. For turkey a genome reference was reconstructed from our sequencing data and available public sequencing data whereas in duck the reference genome constructed by a (NGS) project was used. SNPs obtained by our cost-effective SNP detection procedure still turned out to cover, at intervals, the whole turkey and duck genomes and are of sufficient quality to be used in genotyping studies. Allele frequencies, obtained by genotyping animal panels with a subset our SNPs, correlated well with those observed during SNP detection. The availability of two external duck SNP datasets allowed for the construction of a subset of SNPs which we had in common with these sets. Genotyping turned out that this subset was of outstanding quality and can be used for benchmarking other SNPs that we identified within duck. Ongoing developments in (NGS) allowed for paired end sequencing which is an extension on sequencing analysis that provides information about which pair of reads are coming from the outer ends of one sequenced DNA fragment. We applied this technique on a reduced genome representation of four chicken breeds to detect SVs. Paired end reads were mapped to the chicken reference genome and SVs were identified as abnormally aligned read pairs that have orientation or span sizes discordant from the reference genome. SV detection parameters, to distinguish true structural variants from false positives, were designed and optimized by validation of a small representative sample of SVs using PCR and traditional capillary sequencing. To conclude: we developed SNP repositories which fulfils a requirement for SNPs to perform linkage analysis, comparative genomics QTL studies and ultimately GWA studies in a range of farm animals. We also set the first step in developing a repository for SVs in chicken, a relatively new genetic marker in animal sciences. <br/
Stock Market Integration Between the Hong Kong SAR and the People's Republic of China - the Use of a Revised 'H' Share Model and Enhanced Institutional Support
No full textPhDBilateral, multilateral and regional linkages between stock exchanges generate
increased sources of funds, investor return and product choice. Such
associations can also lower transaction costs in both initial listing and
subsequent trading, increase liquidity more generally in the secondary market
and enhance investor protection and confidence in the stability and reputation
of the market and the status of companies listed on the market. This thesis
argues that the integration of the stock markets between The Special
Administrative Region of Hong Kong ("Hong Kong") and the People's
Republic of China (CTRC) is therefore a desirable objective and investigates
how a more successful and substantial degree of integration could be achieved
in this area.
Integration, in particular, requires harmonization of laws and regulations. In
1993,H shares issued by PRC companies were first allowed to cross-list on the
Hong Kong Stock Exchange. This listing was made possible by the
introduction of a new set of legal and operational rules promulgated in both the
PRC and Hong Kong.
This thesis expounds four models of integration, the H Share Model, the
System Harmonization Model, the Mixed Harmonization and Mutual
Recognition Model, and the Full Harmonization Model and argues that H share
regulations are an effective way to further integration despite problems
inherited from the PRC's 'pre-open door' policy.
In considering other potential models, the European Union and the United
States capital market are also considered as potential models for further
integration of the PRC and Hong Kong stock markets despite the inherent
limitations of the latter model.
It is also proposed that enhanced institutional support can be used as an
effective means of accelerating the integration process. Investigating both the
feasibility and possible implementation of market integration within an
appropriate institutional framework ensures an autonomous, legal and
independent environment separate from the political realm
