Using clusters of computers for large QU-GENE simulation experiments

The QU-GENE Computing Cluster (QCC) is a hardware and software solution to the automation and speedup of large QU-GENE (QUantitative GENEtics) simulation experiments that are designed to examine the properties of genetic models, particularly those that involve factorial combinations of treatment levels. QCC automates the management of the distribution of components of the simulation experiments among the networked single-processor computers to achieve the speedup.

Multi-fluorescent silica colloids for encoding large combinatorial libraries

Large chemical libraries can be synthesized on solid-support beads by the combinatorial split-and-mix method. A major challenge associated with this type of library synthesis is distinguishing between the beads and their attached compounds. A new method of encoding these solid-support beads, 'colloidal bar-coding', involves attaching fluorescent silica colloids ('reporters') to the beads as they pass through the compound synthesis, thereby creating a fluorescent bar code on each bead. In order to obtain sufficient reporter varieties to bar code extremely large libraries, many of the reporters must contain multiple fluorescent dyes. We describe here the synthesis and spectroscopic analysis of various mono- and multi-fluorescent silica particles for this purpose. It was found that by increasing the amount of a single dye introduced into the particle reaction mixture, mono- fluorescent silica particles of increasing intensities could be prepared. This increase was highly reproducible and was observed for six different fluorescent dyes. Multi-fluorescent silica particles containing up to six fluorescent dyes were also prepared. The resultant emission intensity of each dye in the multi-fluorescent particles was found to be dependent upon a number of factors; the hydrolysis rate of each silane-dye conjugate, the magnitude of the inherent emission intensity of each dye within the silica matrix, and energy transfer effects between dyes. We show that by varying the relative concentration of each silane-dye conjugate in the synthesis of multi-fluorescent particles, it is possible to change and optimize the resultant emission intensity of each dye to enable viewing in a fluorescence detection instrument.

Hydrophobicity of Templated Silica Xerogels for Molecular Sieving Applications

Silica xerogels were prepared by a sol-gel process catalyzed by acid with tetraethylorthosilicate, and using an organic covalent ligand template (methyltriethoxysilane) or a noncovalent template C6 surfactant (triethylhexylammonium bromide). The influence of hydrotreatment on the structure of templated xerogels is examined in terms of surface area, micropore volume, average pore size, and pore size distribution, and compared against a blank xerogel (nontemplated). The role of surface functional groups was evaluated using Si-29 nuclear magnetic resonance. The structural integrity of the xerogel was maintained to a large extent in samples that had a high contribution of Q(4) species (siloxane groups). Xerogel matrix densification occurred when there was a large concentration of Q(3) and Q(2) species (silanol groups), which also were responsible for increased hydrophilicity. The templated xerogels resulted in up to a 25% concentration of methyl functional groups (T-3 and T-2 species), leading to hydrophobic xerogels. The best results in terms of structural integrity and hydrophobicity were obtained with templated xerogels prepared with the C6 surfactant. The results in this study suggest that surfactant-enhanced condensation reactions lead to structures with a high contribution of Q(4) groups, which are not susceptible to water attack, but are strong enough to oppose matrix densification during rehydration.

Recurrent gains and losses of large (84-109 bp) repeats in the rDNA internal transcribed spacer 2 (ITS2) of rhipicephaline ticks

We studied the internal transcribed spacer 2 (ITS2) in twenty-two spp. of ticks from the subfamily Rhipicephalinae. A 104-109 base pair (bp) region was Imperfectly repeated In most ticks studied. Mapping the number of repeat copies on to a phylogeny from the ITS2 showed that there have been many Independent gains and losses of repeats. Comparison of the sequences of the repeat copies Indicated that in most taxa concerted evolution had played little if any role in the evolution of these regions, as the copies clustered by sequence position rather than species, In our putative secondary structure, each repeat copy can fold into a distinct and almost identical stem-loop complex; a gain or loss of a repeat copy apparently does not impair the function of the ITS2 in these ticks.

Changes in progesterone and testosterone during the breeding season of the large-footed myotis Myotis moluccarum (Microchiroptera : Vespertilionidae)

The reproductive biology of the large-footed myotis, Myotis moluccarum, was studied during the annual breeding season in southeast Queensland, Australia. Previous research has shown the species to be polyoestrous and monotoccous, producing two consecutive young with some degree of synchrony in late October to early November and again in late January to early February. Hormonal data was collected and observations of the female reproductive tract made in order to ascertain the reproductive cycle of this species. In July, when females were not pregnant, progesterone concentrations were 1.9 +/- 0.9 ng/ml. During the two gestation periods, progesterone concentrations increased progressively until late pregnancy at the end of October through to early November and again in late January to early February. During the latest stages of pregnancy, progesterone concentrations of 69.9 +/- 18.7 ng/ml were reached. It is suggested that a plasma progesterone concentration in excess of about 8 ng/ml indicates pregnancy in this species. Plasma testosterone concentration in males reached a peak of 43.1 +/- 9.81 ng/ml in July, and was then variable until December when levels declined significantly to 2.0 +/- 1.7 ng/ml.

Familial Paget's disease of bone: Nonlinkage to the PDB1 and PDB2 loci on chromosomes 6p and 18q in a large pedigree

Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. Susceptibility loci for Paget's disease of bone have been mapped to chromosome 6p21.3 (PDB1) and 18q121.1-q22 (PDB2) in different pedigrees, We have identified a large pedigree of over 250 individuals with 49 informative individuals affected with Paget's disease of bone; 31 of whom are available for genotypic analysis. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Linkage analysis has been performed with markers at PDB1; these data show significant exclusion of linkage with log,, of the odds ratio (LOD) scores < -2 in this region. Linkage analysis of microsatellite markers from the PDB2 region has excluded linkage with this region, with a 30 cM exclusion region (LOD score < -2.0) centered on D18S42, These data confirm the genetic heterogeneity of Paget's disease of bone. Our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree and will be identified using a microsatellite genomewide scan followed by positional cloning.

A segmentation-based and partial-volume-compensated method for an accurate measurement of lateral ventricular volumes on T-1-weighted magnetic resonance images

Lateral ventricular volumes based on segmented brain MR images can be significantly underestimated if partial volume effects are not considered. This is because a group of voxels in the neighborhood of lateral ventricles is often mis-classified as gray matter voxels due to partial volume effects. This group of voxels is actually a mixture of ventricular cerebro-spinal fluid and the white matter and therefore, a portion of it should be included as part of the lateral ventricular structure. In this note, we describe an automated method for the measurement of lateral ventricular volumes on segmented brain MR images. Image segmentation was carried in combination of intensity correction and thresholding. The method is featured with a procedure for addressing mis-classified voxels in the surrounding of lateral ventricles. A detailed analysis showed that lateral ventricular volumes could be underestimated by 10 to 30% depending upon the size of the lateral ventricular structure, if mis-classified voxels were not included. Validation of the method was done through comparison with the averaged manually traced volumes. Finally, the merit of the method is demonstrated in the evaluation of the rate of lateral ventricular enlargement. (C) 2001 Elsevier Science Inc. All rights reserved.

Effect of restricted feed intake on early reproductive development in Large White gilts

Forty-five Large White gilts were used to study the effect of energy intake from 28 to 176 d of age on body composition and reproductive development. From 28 to 60 d, the gilts were fed ad libitum a 16.6 MJ DE/kg, 24% crude protein and 1.3% total lysine diet. From 61 d of age three dietary treatments were used; 1) ad libitum access to feed (15.6 MJ DE/kg, 21% crude protein and 1.07% total lysine) (H), 2) feed offered at 75% (M) of the previous days intake of H, and 3) feed offered at 60% (L) of the previous days intake of H. ADG from 61 to 176 d of age was (p <0.05) affected by treatment. Although live weight at 176 d of age did not differ (p >0.1) the H gilts had higher (p <0.08) carcass weights than the M or L gilts. Back fat depths were similar (p >0.1) for all treatments at 115 d of age, however by 176 d of age M and H gilts were fatter (p <0.1) than L gilts. The mean lipid deposition (LD) from 115 to 176 d of age for L gilts (78.9 g/d) was less (p <0.05) than for M gilts (143.6 g/d) and H gilts (135.6 g/d). There were no differences between treatments for protein deposition (PD) over the same period. More (p <0.05) H gilts (n=8) attained puberty (first observed estrus) than either M gilts or L gilts (n=4 for both). Follicle numbers were similar (p >0.1) across treatments. For gilts that attained puberty, H gilts had fewer (p <0.05) follicles (13.5) than M gilts (19.7) and L gilts (21.3). For gilts with follicular development, H gilts had the heaviest (458.7 g) reproductive tract weight (RTW). However, for those that attained puberty, L gilts had the heaviest RTW. RTW were lowest for those with no follicular development. Energy restriction had a negative impact on puberty attainment, i.e. it took longer to reach puberty. However, for gilts that attained puberty, the number of follicles was greater for those on lower feed intakes. It would appear that rate of fat deposition, but not necessarily the total amount of fat, plays an important role in puberty attainment.

Large-conductance calcium-activated potassium channels in neonatal rat intracardiac ganglion neurons

The properties of single Ca2+-activated K+ (BK) channels in neonatal rat intracardiac neurons were investigated using the patch-clamp recording technique. In symmetrical 140 mM K+, the single-channel slope conductance was linear in the voltage range -60/+60 mV. and was 207+/-19 pS. Na+ ions were not measurably permeant through the open channel. Channel activity increased with the cytoplasmic free Ca2+ concentration ([Ca2+],) with a Hill plot giving a half-saturating [Ca2+] (K-0.5) of 1.35 muM and slope of congruent to3. The BK channel was inhibited reversibly by external tetraethylammonium (TEA) ions, charybdotoxin, and quinine and was resistant to block by 4-aminopyridine and apamin. Ionomycin (1-10 muM) increased BK channel activity in the cell-attached recording configuration. The resting activity was consistent with a [Ca2+](i)

Acoustic signature of the normal swallow: Characterization by age, gender, and bolus volume

Despite growing clinical use, cervical auscultation suffers from a lack of research-based data. One of the strongest criticisms of cervical auscultation is that there has been little research to demonstrate how dysphagic swallowing sounds are different from normal swallowing sounds, In order to answer this question, however, one first needs to document the acoustic characteristics of normal, nondysphagic swallowing sounds, This article provides the first normative database of normal swallowing sounds for the adult population. The current investigation documents the acoustic characteristics of normal swallowing sounds for individuals from 18 to more than 60 years of age over a range of thin liquid volumes. Previous research has shown the normal swallow to be a dynamic event. The normal swallow is sensitive to aging of the oropharyngeal system, and also to the volume of bolus swallowed. The current investigation found that the acoustic signals generated during swallowing were sensitive to an individual's age and to the volume of the bolus swallowed. There were also some gender-specific differences in the acoustic profile of the swallowing sound, It is anticipated that the results will provide a catalyst for further research into cervical auscultation.

CDT, GGT, and AST as markers of alcohol use: The WHO/ISBRA Collaborative Project

Background: Estimates of the performance of carbohydrate deficient transferrin (CDT) and gamma glutamyltransferase (GGT) as markers of alcohol consumption have varied widely. Studies have differed in design and subject characteristics. The WHO/ISBRA Collaborative Study allows assessment and comparison of CDT, GGT, and aspartate aminotransferase (AST) as markers of drinking in a large, well-characterized, multicenter sample. Methods: A total of 1863 subjects were recruited from five countries (Australia, Brazil, Canada, Finland, and Japan). Recruitment was stratified by alcohol use, age, and sex. Demographic characteristics, alcohol consumption, and presence of ICD-10 dependence were recorded using an interview schedule based on the AUDADIS, CDT was assayed using CDTect(TM) and GGT and AST by standard methods. Statistical techniques included receiver operating characteristic (ROC) analysis. Multiple regression was used to measure the impact of factors other than alcohol on test performance. Results: CDT and GGT had comparable performance on ROC analysis, with AST performing slightly less well. CDT was a slightly but significantly better marker of high-risk consumption in men. All were more effective for detection of high-risk rather than intermediate-risk drinking. CDT and GGT levels were influenced by body mass index, sex, age, and smoking status. Conclusions: CDT was little better than GGT in detecting high- or intermediate-risk alcohol consumption in this large, multicenter, predominantly community-based sample. As the two tests are relatively independent of each other, their combination is likely to provide better performance than either test alone, Test interpretation should take account sex, age. and body mass index.

Drop penetration into porous powder beds

The kinetics of drop penetration were studied by filming single drops of several different fluids (water, PEG200, PEG600, and HPC solutions) as they penetrated into loosely packed beds of glass ballotini, lactose, zinc oxide, and titanium dioxide powders. Measured times ranged from 0.45 to 126 s and depended on the powder particle size,viscosity, surface tensions, and contact angle. The experimental drop penetration times were compared to existing theoretical predictions by M. Denesuk et al. (J. Colloid Interface Sci. 158, 114, 1993) and S. Middleman (Modeling Axisymmetric Flows: Dynamics of Films, Jets, and Drops, Academic Press, San Diego, 1995) but did not agree. Loosely packed powder beds tend to have a heterogeneous bed structure containing large macrovoids which do not participate in liquid flow but are included implicitly in the existing approach to estimating powder pore size. A new two-phase model was proposed where the total volume of the macrovoids was assumed to be the difference between the bed porosity and the tap porosity. A new parameter, the effective porosity (epsilon)eff, was defined as the tap porosity multiplied by the fraction of pores that terminate at a macrovoid and are effectively blocked pores. The improved drop penetration model was much more successful at estimating the drop penetration time on all powders and the predicted times were generally within an order of magnitude of the experimental results. (C) 2002 Elsevier Science (USA).