Thermochromic materials undergo temperature-dependent colour changes. Although there are several origins of thermochromism, two distinct types of thermochromism are common in thermochromic mixtures. Melt-lightened thermochromism occurs when the colour density of a mixture decreases with increasing temperature, and is usually associated with colour loss upon mixture melting. Melt-darkened thermochromism occurs when the colour density of a mixture increases with increasing temperature, and is usually associated conversion from a decoloured solid state to a coloured melt. Three-component thermochromic systems generally consist of a leuco dye (minor component), a phenolic colour developer (intermediate component), and a high melting-point organic solvent (dominant component). In these systems, the colouring behaviour is controlled by competing binary interactions, with the dye:developer interaction responsible for colour formation and the developer:solvent interaction responsible for colour erasure. In the present study, three-component mixtures composed of CVL (dye), long-chain alkyl gallates (phenolic developer), and long-chain alkyl alcohols (long-chain solvent) were examined. The thermochromic behaviour (i.e., melt-lightened vs. melt-darkened thermochromism) of these mixtures was examined as a function of the matching of the alkyl chain length of the gallate developer and alcohol solvent. When the alkyl chain lengths were well matched, the developer:solvent interaction dominated in the solid state and melt-darkened thermochromism was observed. When the alkyl chain lengths were poorly matched, the dye:developer interaction dominated in the solid state, and melt-lightened thermochromism was observed. The colour density of the molten state was determined by the developer:dye molar ratio, with high molar ratios yielding coloured melts and low molar ratios yielding decoloured melts. Additional studies employing chemically dissimilar developers and solvents (e.g., bisphenol A with 1-hexadecanol) yielded mixtures that displayed optimal melt-lightened thermochromism. The high solid-state colour density due to weak developer:solvent interactions provides further evidence that competing binary interactions are responsible for the colouring behaviour observed for three-component thermochromic systems. Ternary thermochromic phase diagrams were used to define compositional regions of optimal thermochromic behaviour (i.e., high colour contrast), providing a useful experimental tool for the rapid identification of ideal sample compositions. Additionally, an examination of the properties of thermally erasable ink-jet printer inks was carried out during the present study. / An assessment of the thermochromic behaviour of three-component chemical systems comprising a colour-changing leuco dye, an electron-accepting phenolic developer, and a long-chain alkyl alcohol solid solvent.

Single nucleotide polymorphisms (SNPs) have been increasingly popular for a wide range of genetic studies. A high-throughput genotyping technologies usually involves a statistical genotype calling algorithm. Most calling algorithms in the literature, using methods such as k-means and mixturemodels, rely on elliptical structures of the genotyping data; they may fail when the minor allele homozygous cluster is small or absent, or when the data have extreme tails or linear patterns. We propose an automatic genotype calling algorithm by further developing a linear grouping algorithm (Van Aelst et al., 2006). The proposed algorithm clusters unnormalized data points around lines as against around centroids. In addition, we associate a quality value, silhouette width, with each DNA sample and a whole plate as well. This algorithm shows promise for genotyping data generated from TaqMan technology (Applied Biosystems). A key feature of the proposed algorithm is that it applies to unnormalized fluorescent signals when the TaqMan SNP assay is used. The algorithm could also be potentially adapted to other fluorescence-based SNP genotyping technologies such as Invader Assay. Motivated by the SNP genotyping problem, we propose a partial likelihood approach to linear clustering which explores potential linear clusters in a data set. Instead of fully modelling the data, we assume only the signed orthogonal distance from each data point to a hyperplane is normally distributed. Its relationships with several existing clustering methods are discussed. Some existing methods to determine the number of components in a data set are adapted to this linear clustering setting. Several simulated and real data sets are analyzed for comparison and illustration purpose. We also investigate some asymptotic properties of the partial likelihood approach. A Bayesian version of this methodology is helpful if some clusters are sparse but there is strong prior information about their approximate locations or properties. We propose a Bayesian hierarchical approach which is particularly appropriate for identifying sparse linear clusters. We show that the sparse cluster in SNP genotyping datasets can be successfully identified after a careful specification of the prior distributions.

In resource polymorphism, ecological opportunity and selective predatory pressure can be considered key factors in phenotypic divergence. In post-glacial lakes of Scandinavia, the European whitefish (Coregonus lavaretus L.) is a common species and has repeatedly diverged along the benthic - pelagic resource axis. Recent studies suggest that predation by northern pike (Esox lucius L.) induces rapid divergence in whitefish, leading to two reproductively isolated ecotypes: a dwarf planktivore and a giant benthivore. In lakes where pike is absent, whitefish are only found as monomorphic populations. In this study I estimated growth rates in two monomorphic and two polymorphic populations having giant and dwarf ecotypes. The aim was to use growth rates as a tool to distinguish between juvenile giants and dwarfs, but also to find out if a population's resource use was reflected in the growth rate. Scales were used to calculate growth rate, where like trees, variations in seasonal growth could be observed in a ring-like structure. Growth rates differed between the morphs, and mirrored their use of resources. The two monomorphic populations had the highest average growth rate the first six years (40.1 and 35.5 mm/year), and quickly reached maximum size. Dwarfs and giants in the dimorphic systems had equal growth the first two years, after which giants grew at a substantially higher rate. Categorization between juvenile giants and dwarfs could be done if an individual had passed its third growth season.

GPCRs are known to form dimeric structures, and this affects their pharmacological properties. The ?2AR and AT1aR are GPCRs that are involved the regulation of the adrenergic and renin-angiotensin systems. The ?2AR is polymorphic at position 164, affecting its responsiveness to adrenergic ligands. Both receptors have been shown to form dimers, but little is known on how dimerization affects their trafficking and signalling following ligand treatments. Plasma membrane localization, arrestin-2 recruitment, and G-protein interactions were determined between receptor dimers using molecular biological techniques. This study demonstrates that the formation of heterodimers can change the expected response to ligand treatments, along with associated trafficking events. It was determined that ligands bind to dimers, resulting in conformational changes to the dimeric complexes. Both the ?2AR and AT1aR are targeted in cardiovascular disease and this research demonstrates the importance of dimerization when prescribing drug therapies to avoid potential unwanted drug side effects.

A series of experiments was completed in which the morphology, anatomy and biochemistry of two Melilotus species, Melilotus alba and Melilotus officinalis, were studied. The purposes of the study were to illustrate whether the variability of specimens was due to polymorphism or speciation and to isolate the factors that have separated these specimens as competitors.The effects of impaction and scarification on the germination of M. alba and M. officinalis seeds were studied, as were the effects of light and temperature stimuli on germination and growth The rate of plant maturation and the chronology of flowering for the two species were investigated. Maturation differences were minor, but the chronologies of flowering deviated markedly.The techniques of one- and two-directional thin layer chromatography were used to separate the free amino acids in Melilotus seed extract preparations. The technique of polyacrylamide gel electrophoresis was used to separate the proteins in these preparations. In every experiment, the two Melilotus "species" were genus specific with no species variables in terms of the amino acid and protein complements.

Background: There are a number of biological pathways that affect our ingestive behaviours, including energy homeostasis, food reward, and taste. Given that carbohydrates such as sugars, provide energy and a sweet taste, examining candidate genes in each pathway may help explain differences in carbohydrate consumption behaviours. Objective: To determine whether variations in genes encoding a glucose transporter (GLUT2), a dopamine receptor (DRD2), and sweet taste receptor (TAS1R2) are associated with differences in sugar consumption in two distinct populations. Methods: Population 1 included diabetes-free young adults where dietary intake was assessed using a one month 196-item food frequency questionnaire (FFQ). Population 2 consisted of individuals with type 2 diabetes. Dietary intake was assessed using 3-day food records administered 2 weeks apart; food record 1 (FR1) and 2 (FR2). Subjects were genotyped for the Thr110Ile variation in GLUT2 (n1=587; n2=100), the C957T variation in DRD2 (n1=313; n2=100), and the Ser9Cys and Ile191Val variations in TAS1R2 (n1=1037; n2=100) using real-time PCR. Results: In comparison to individuals homozygous for the GLUT2 Thr allele, consumption of sugars was higher among Ile carriers in population 1 (133 ± 5 vs 118 ± 3 g/d, p=0.006) and population 2 on two separate food records (FR1: 112 ± 9 vs 87 ± 5 g/d, p=0.02; FR2: 105 ± 8 vs 78 ± 4 g/d, p=0.002). For the C957T variation in population 1, we detected a significant DRD2xSex interaction with the consumption of sucrose decreasing with each T allele among men (p=0.03) and a heterosis mode of inheritance among women where heterozygotes consumed the most (p=0.01). For TAS1R2, we detected a significant TAS1R2xBMI interaction and among overweight individuals, carriers of the Val allele consumed less sugars than those with the Ile/Ile genotype (103 ± 6 vs122 ± 6 g/d, p=0.01). In population 2, carriers of the Val allele consumed less sugars than individuals with the Ile/Ile genotype (83 ± 6 vs 99 ± 6 g/d, p=0.04) on FR2. Conclusions: Our findings demonstrate that genetic variation in GLUT2, DRD2 and TAS1R2 affect habitual sugar consumption and suggest that selection of dietary sugars can be influenced by different biological pathways.

No description available.

Single nucleotide polymorphisms (SNPs) have been increasingly popular for a wide range of genetic studies. A high-throughput genotyping technologies usually involves a statistical genotype calling algorithm. Most calling algorithms in the literature, using methods such as k-means and mixturemodels, rely on elliptical structures of the genotyping data; they may fail when the minor allele homozygous cluster is small or absent, or when the data have extreme tails or linear patterns. We propose an automatic genotype calling algorithm by further developing a linear grouping algorithm (Van Aelst et al., 2006). The proposed algorithm clusters unnormalized data points around lines as against around centroids. In addition, we associate a quality value, silhouette width, with each DNA sample and a whole plate as well. This algorithm shows promise for genotyping data generated from TaqMan technology (Applied Biosystems). A key feature of the proposed algorithm is that it applies to unnormalized fluorescent signals when the TaqMan SNP assay is used. The algorithm could also be potentially adapted to other fluorescence-based SNP genotyping technologies such as Invader Assay. Motivated by the SNP genotyping problem, we propose a partial likelihood approach to linear clustering which explores potential linear clusters in a data set. Instead of fully modelling the data, we assume only the signed orthogonal distance from each data point to a hyperplane is normally distributed. Its relationships with several existing clustering methods are discussed. Some existing methods to determine the number of components in a data set are adapted to this linear clustering setting. Several simulated and real data sets are analyzed for comparison and illustration purpose. We also investigate some asymptotic properties of the partial likelihood approach. A Bayesian version of this methodology is helpful if some clusters are sparse but there is strong prior information about their approximate locations or properties. We propose a Bayesian hierarchical approach which is particularly appropriate for identifying sparse linear clusters. We show that the sparse cluster in SNP genotyping datasets can be successfully identified after a careful specification of the prior distributions.

Polymorphism can influence every aspect of the properties of a solid including the shelf life, dissolution rate, solubility, formulation properties and processing properties of a solid drug. A deeper understanding of polymorphism and related solid state properties would ensure an improved quality of the materials used throughout drug preparation, dosage form formulation and clinical trials. Therefore, determination of the existence of polymorphs and pseudopolymorphs, characterization of different solid state forms and their respective properties, and controlling the existing form in the resulting formulation all form part of a rapidly growing field within pharmaceutical research and industry. Carbamazepine (CBZ) was the model drug used in this study. FT-Raman spectroscopy was chosen as a main investigative technique in this study to evaluate its potential in monitoring (pseudo)polymorphic conversions in aqueous suspensions in the absence or presence of various pharmaceutical excipients. Partial least squares analysis (PLS) was used for quantitative analysis of the spectral data. Earlier it has been found that CBZ converts rapidly to the dihydrate (DH) when exposed to humidity or water, and this has been reported to be the main reason for the sometimes observed greatly decreased bioavailability of marketed CBZ tablets. In this study, the conversion kinetics of CBZ (forms I, II and III) to DH in aqueous suspension were found to be first order kinetics with an unconverted portion (R� [greater than or equal to] 0.95), where the crystal morphology appeared to play a more important role in its conversion kinetics than the polymorphic form. The influence of pharmaceutical excipients on the conversion of CBZ in aqueous suspension was also explored. For excipients such as methylcellulose (MC), hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) which have both a low solubility parameter (< 27.0 MPa[1/2]) and strong hydrogen bonding groups, complete inhibition of the conversion of CBZ was possible even at a very low concentration (0.1 % w/v). Raman spectroscopy showed its high applicability in investigating CBZ conversion kinetics and screening of excipient effects in aqueous environment. It was demonstrated that Raman has a robust nature in quantitative analysis since problems such as different particle size, morphology, and spatial distribution of the two solid state forms of the drug seemed not to have significant influence on Raman scattering. This study has also clarified the relative importance of many contributing factors (type of crystalline form (CBZ or DH), crystal morphology, surface area, and excipient interactions with drug particles) influencing the in vitro dissolution of CBZ. The solid state characterization approach taken in this study will provide a deeper insight into the dissolution performance of drugs and should thus lead to a better understanding of in vitro/in vivo behavior of drugs.

HSCR has been felt to be a polygeneic disease on the basis of an incompletely penetrant sex modified transmission, which may be either autosomal dominant or recessive in different kindred. During the 1990's several of the genes involved in this transmission have come to light. Other genes remain to be discovered.