PTHR1 polymorphisms influence BMD variation through effects on the growing skeleton

We investigated whether polymorphisms in PTHR1 are associated with bone mineral density (BMD), to determine whether the association of this gene with BMD was due to effects on attainment of peak bone mass or effects on subsequent bone loss. The PTHR1 gene, including its 14 exons, their exon-intron boundaries, and 1,500 bp of its promoter region, was screened for polymorphisms by denaturing high-performance liquid chromatography (dHPLC) and sequencing in 36 osteoporotic cases. Eleven single-nucleotide polymorphisms (SNPs), one tetranucleotide repeat, and one tetranucleotide deletion were identified. A cohort of 634 families, including 1,236 men (39%) and 1,926 women (61%) ascertained with probands with low BMD (Z< -2.0) and the Children in Focus subset of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (785 unrelated individuals, mean age 118 months), were genotyped for the five most informative SNPs (minor allele frequency >5%) and the tetranucleotide repeat. In our osteoporosis families, association was noted between lumbar spine BMD and alleles of a known functional tetranucleotide repeat (U4) in the PTHR1 promoter region (P = 0.042) and between two and three marker haplotypes of PTHR1 polymorphisms with lumbar spine, femoral neck, and total hip BMD (P = 0.021-0.047). This association was restricted to the youngest tertile of the population (age 16-39 years, P = 0.013-0.048). A similar association was found for the ALSPAC cohort: two marker haplotypes of SNPs A48609T and C52813T were associated with height (P = 0.006) and total body less head BMD (P = 0.02), corrected for age and gender, confirming the family findings. These findings suggest a role for PTHR1 variation in determining peak BMD.

Catalyst engineering for lithium ion batteries: The catalytic role of Ge in enhancing the electrochemical performance of SnO2(GeO2)0.13/G anodes

The catalytic role of germanium (Ge) was investigated to improve the electrochemical performance of tin dioxide grown on graphene (SnO(2)/G) nanocomposites as an anode material of lithium ion batteries (LIBs). Germanium dioxide (GeO(20) and SnO(2) nanoparticles (<10 nm) were uniformly anchored on the graphene sheets via a simple single-step hydrothermal method. The synthesized SnO(2)(GeO(2))0.13/G nanocomposites can deliver a capacity of 1200 mA h g(-1) at a current density of 100 mA g(-1), which is much higher than the traditional theoretical specific capacity of such nanocomposites (∼ 702 mA h g(-1)). More importantly, the SnO(2)(GeO(2))0.13/G nanocomposites exhibited an improved rate, large current capability (885 mA h g(-1) at a discharge current of 2000 mA g(-1)) and excellent long cycling stability (almost 100% retention after 600 cycles). The enhanced electrochemical performance was attributed to the catalytic effect of Ge, which enabled the reversible reaction of metals (Sn and Ge) to metals oxide (SnO(2) and GeO(2)) during the charge/discharge processes. Our demonstrated approach towards nanocomposite catalyst engineering opens new avenues for next-generation high-performance rechargeable Li-ion batteries anode materials.

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: A Mendelian randomisation analysis

Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1α and IL-1β); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0·22 SD (95% CI 0·18–0·25; 12·5%; p=9·3 × 10−33), concentrations of interleukin 6 decreased by 0·02 SD (−0·04 to −0·01; −1·7%; p=3·5 × 10−3), and concentrations of C-reactive protein decreased by 0·03 SD (−0·04 to −0·02; −3·4%; p=7·7 × 10−14). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1·15 (1·08–1·22; p=1·8 × 10−6) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1·03 (1·02–1·04; p=3·9 × 10−10). Per-allele odds ratios were 0·97 (0·95–0·99; p=9·9 × 10−4) for rheumatoid arthritis, 0·99 (0·97–1·01; p=0·47) for type 2 diabetes, 1·00 (0·98–1·02; p=0·92) for ischaemic stroke, and 1·08 (1·04–1·12; p=1·8 × 10−5) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1α/β inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Funding UK Medical Research Council, British Heart Foundation, UK National Institute for Health Research, National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council, and European Commission Framework Programme 7.

Genetic analyses in a sample of individuals with high or low BMD shows association with multiple Wnt pathway genes

INTRODUCTION Although the high heritability of BMD variation has long been established, few genes have been conclusively shown to affect the variation of BMD in the general population. Extreme truncate selection has been proposed as a more powerful alternative to unselected cohort designs in quantitative trait association studies. We sought to test these theoretical predictions in studies of the bone densitometry measures BMD, BMC, and femoral neck area, by investigating their association with members of the Wnt pathway, some of which have previously been shown to be associated with BMD in much larger cohorts, in a moderate-sized extreme truncate selected cohort (absolute value BMD Z-scores = 1.5-4.0; n = 344). MATERIALS AND METHODS Ninety-six tag-single nucleotide polymorphism (SNPs) lying in 13 Wnt signaling pathway genes were selected to tag common genetic variation (minor allele frequency [MAF] > 5% with an r(2) > 0.8) within 5 kb of all exons of 13 Wnt signaling pathway genes. The genes studied included LRP1, LRP5, LRP6, Wnt3a, Wnt7b, Wnt10b, SFRP1, SFRP2, DKK1, DKK2, FZD7, WISP3, and SOST. Three hundred forty-four cases with either high or low BMD were genotyped by Illumina Goldengate microarray SNP genotyping methods. Association was tested either by Cochrane-Armitage test for dichotomous variables or by linear regression for quantitative traits. RESULTS Strong association was shown with LRP5, polymorphisms of which have previously been shown to influence total hip BMD (minimum p = 0.0006). In addition, polymorphisms of the Wnt antagonist, SFRP1, were significantly associated with BMD and BMC (minimum p = 0.00042). Previously reported associations of LRP1, LRP6, and SOST with BMD were confirmed. Two other Wnt pathway genes, Wnt3a and DKK2, also showed nominal association with BMD. CONCLUSIONS This study shows that polymorphisms of multiple members of the Wnt pathway are associated with BMD variation. Furthermore, this study shows in a practical trial that study designs involving extreme truncate selection and moderate sample sizes can robustly identify genes of relevant effect sizes involved in BMD variation in the general population. This has implications for the design of future genome-wide studies of quantitative bone phenotypes relevant to osteoporosis.

Polymorphism in codon 17 of the CTLA-4 gene (+49 A/G) is not associated with susceptibility to rheumatoid arthritis in British Caucasians

The role of the CTLA-4 antigen in the development of autoimmune diseases is well documented, with several autoimmune disorders showing association or linkage with the CTLA-4 locus. Its role in the aetiology of rheumatoid arthritis (RA) however, remains unclear, as the functional studies of the B7-CTLA-4 pathway in mouse models of RA and genetic studies in humans have given contrasting results. We have studied the single nucleotide polymorphism at position +49 (A/G) of the CTLA-4 gene, in a cohort of 421 RA cases and 452 healthy controls from the UK. Despite the high statistical power to detect even a weak susceptibility effect, no significant association was found. We also analysed the distribution of the allele and genotype frequencies with respect to the presence of the shared epitope (a known RA susceptibility factor) and found no statistically significant differences. We conclude that, although the importance of the B7-CTLA-4 interaction in the development of RA can not be excluded, the CTLA-4 gene is unlikely to be a predisposing factor to this disease.

Serum immunoglobulin G directed against porcine trypsin in the serum of cystic fibrosis children receiving porcine pancreatic enzyme supplements

Cystic fibrosis (CF) patients require pancreatic enzyme replacement therapy to correct pancreatic insufficiency. These enzymes are derived from porcine pancreas and are known to be antigenic. To determine the possible clinical consequences, a specific ELISA was developed to detect IgG antibody directed against porcine trypsin (PTAb) in the sera of CF patients. The assay was used to evaluate the occurrence of PTAb in a cross sectional study of 103 CF patients in relation to the introduction of porcine enzyme therapy, clinical status and genotype. Antibodies against porcine trypsin were detected in the sera of 63% of patients unrelated to the age of commencement or the duration of enzyme therapy. No differences were observed in the clinical status of CF patients who had developed PTAb (n = 65) and those who had no detectable PTAb (n = 38) as determined from: the current prescribed dose of porcine pancreatic enzyme capsules; Z scores for height and weight; and respiratory function tests. It is suggested that the PTAb commonly found in the sera of CF patients are of doubtful clinical significance but the prospect of PTAb contributing to immune complex disease should be examined further.

Revision of JANAF (1985) data for C2H2(g)

There is an error in the JANAF (1985) data on the standard enthalpy, Gibbs energy and equilibrium constant for the formation of C2H2 (g) from elements. The error has arisen on account of an incorrect expression used for computing these parameters from the heat capacity, entropy and the relative heat content. Presented in this paper are the corrected values of the enthalpy, the Gibbs energy of formation and the corresponding equilibrium constant.

Pedestrian self-reported exposure to distraction by smart phones while walking and crossing the road

Pedestrian crashes account for approximately 14% of road fatalities in Australia. Crossing the road, while a minor part of total walking, presents the highest crash risk because of potential interaction with motor vehicles. Crash risk is elevated by pedestrian illegal use of the road, which may be widespread (e.g. 20% of crossings at signalised intersections at a sample of sites, Brisbane) and enforcement is rare. Effective road crossing requires integration of multiple skills and judgements, any of which can be hindered by distraction. Observational studies suggest that pedestrians are increasingly likely to ‘multitask’, using mobile technology for entertainment and communication, elevating the risk of distraction while crossing. To investigate this, intercept interviews were conducted with a convenience sample of 211 pedestrians aged 18-65 years in Brisbane CBD. Self-reported frequency of using a smart phone for activities at two levels of distraction: cognitive only (voice calls); or cognitive and visual (text messages, internet access) while walking or crossing the road was collected. Results indicated that smart phone use for potentially distracting activities while walking and while crossing the road was high, especially among 18-30 year olds, who were significantly more likely than 31-44yo or 45-65yo to report smart phone use while crossing the road. For 18-30yo and the higher risk activity of crossing the road, 32% texted at high frequency levels and 27% used internet at high frequency levels. Risky levels of distracted crossing appear to be a growing safety issue for 18-30yo, with greater attention to appropriate interventions needed.

G(its)(2) VSR: An Information Theoretic Secure Verifiable Secret Redistribution Protocol for Long-term Archival Storage

Protocols for secure archival storage are becoming increasingly important as the use of digital storage for sensitive documents is gaining wider practice. Wong et al.[8] combined verifiable secret sharing with proactive secret sharing without reconstruction and proposed a verifiable secret redistribution protocol for long term storage. However their protocol requires that each of the receivers is honest during redistribution. We proposed[3] an extension to their protocol wherein we relaxed the requirement that all the recipients should be honest to the condition that only a simple majority amongst the recipients need to be honest during the re(distribution) processes. Further, both of these protocols make use of Feldman's approach for achieving integrity during the (redistribution processes. In this paper, we present a revised version of our earlier protocol, and its adaptation to incorporate Pedersen's approach instead of Feldman's thereby achieving information theoretic secrecy while retaining integrity guarantees.

Use of Petrifilm(R) 3M to assess coliform numbers on lamb carcasses.

Petrifilm(R) (6410) was used directly on lamb carcasses to enumerate coliforms. 10 sites on 30 carcasses were sampled at each of 4 separate meat processing establishments (works). Coliform counts obtained by this technique were statistically analysed using analysis of variance (ANOVA) to select the optimum sampling sites on the carcass and to assess contamination of the carcass by gut flora at a particular establishment. There was a large variation between sites and between works. In general, works 3 and 4 produced cleaner carcasses than works 2, which in turn was cleaner than works 1. Works 1, 2 and 4 used conventional dressing techniques and works 3 used the inverted dressing method, therefore, the coliform counts found at works 3 and 4 are achievable regardless of dressing technique. Coliform bacteria were most concentrated around the posterior pelvic rim and less prevalent at the carcass extremities. The posterior pelvic rim (sites 3 and 4) had higher (P < 0.05) coliform counts than the exterior ventral flank area (sites 5, 6, 7 and 8), which in turn had higher (P < 0.05) counts than the proximal hind and proximal fore limbs (sites 1, 2, 9 and 10) across all works. With in-line routine testing it is recommended that the majority of carcasses sampled should give coliform counts of <50 cfu/20 cm2 for sites 4 and 8. Reprinted with permission from Journal of Food Protection. Copyright held by the International Association of Food Protection, Des Moines, Iowa, USA. Authors affifiation. J.A.Guthrie & K.J.Dunlop International Food Institute of Queensland, Department of Primary Industries, Rockhampton and G.A.Saunders Veterinary Public Health Division, Livestock and Meat Authority of Queensland, Emerald.

Effective Use in Livestock Feeds of Mouldy and Weather-damaged Grain Containing Mycotoxins-Case Histories and Economic Assessments Pertaining to Pig and Poultry Industries of Queensland

Mould growth in field crops or stored grain reduces starch and lipid content, with consequent increases in fibre, and an overall reduction in digestible energy; palatability is often adversely affected. If these factors are allowed for, and mycotoxin concentrations are low, there are sound economic reasons for using this cheaper grain. Mycotoxins are common in stock feed but their effects on animal productivity are usually slight because either the concentration is too low or the animal is tolerant to the toxin. In Australia, aflatoxins occur in peanut by-products and in maize and sorghum if the grain is moist when stored. Zearalenone is found in maize and in sorghum and wheat in wetter regions. Nivalenol and deoxynivalenol are found in maize and wheat but at concentrations that rarely affect pigs, with chickens and cattle being even more tolerant. Other mycotoxins including cyclopiazonic acid, T-2 toxin, cytochalasins and tenuazonic acid are produced by Australian fungi in culture but are not found to be significant grain contaminants. Extremely mouldy sorghum containing Alternaria and Fusarium mycotoxins decreased feed conversion in pigs and chickens by up to 14%. However, E moniliforme- and Diplodia maydis-infected maize produced only slight reductions in feed intake by pigs and Ustilago- infected barley produced no ill effects. Use of these grains would substantially increase profits if the grain can be purchased cheaply.

Aavan meren täällä puolen : Arkkityyppiset piirteet ja amerikkalaisvaikutteet suosituimmissa suomalaisissa molli-iskelmissä

What are the musical features that turn a song into a hit? The aim of this research is to explore the musical features of hit tunes by studying the 224 most popular Finnish evergreens from the 1930s to the 1990s. It is remarkable, that 80-90% of Finnish oldies are in a minor key, though parallel major keys have also been widely employed within single pieces through, for example, modulations. Furthermore, melodies are usually diatonic, staying mostly in the same key. Consequently, chromatically altered tones in the melody and short modulations in the bridge sections become more prominent. I have concentrated in particular on the melodic lines in order to find the most typical melodic formulas from the data. These analyzed melodic formulas play an important role, because they serve as leading phrases and punchlines in songs. Analysis has revealed three major melodic formulas, which most often appear in the melodic lines of hit tunes. All of these formulas share common thematic ground, because they originate from the triadic tonic chord. Because the tonic chord is the most conventional opening chord in the verse parts, it is logical that these formulas occur most often in verses. The strong dominance of these formulas is very much a result of the rhythmic flexibility they possess; for instance, they can be found in every musical style from waltz to foxtrot. Alongside the major formulas lies a miscellaneous group of other tonic-related melodic formulas. One group of melodic formulas consists of melodic quotations. These quotations appear in a different musical context, for instance in a harmonically altered form, and are therefore often difficult to recognize as such. Yet despite the contextual manipulation, the distinctive character of the cited melody usually remains the same. Composers have also made use of certain popular chord-progressions in order to create new but familiar-sounding melodies. The most important individual progression in this case is what is known as a "circle of fifths" and its shortened, prolonged and altered versions. Because that progression is harmonically strong, it is also a contrastive tool used especially in chorus parts and middle sections (AABA). I have also paid attention to ragtime and jazz influences, which can be found in harmony parts and certain melody notes, which extend, suspend or alter the accompaning chords. Other influences from jazz and ragtime in the Finnish evergreen are evident in the use of typical Tin Pan Alley popular song forms. The most important is the AABA form, which dominates over the data along with the verse/chorus-type popular song form. To briefly illustrate the main results, the basic concept of the hit tune can be traced back to Tin Pan Alley songs, whereas the major stylistic aspects, such as minor keys and musical styles, bear influences from Russian, Western European, and Finnish traditions.

Archaeology of wings : Birds and people in the Baltic Sea region during the Stone Age

The prominent roles of birds, often mentioned in historical sources, are not well reflected in archaeological research. Absence or scarcity of bird bones in archaeological assemblages has been often seen as indication of a minor role of birds in the prehistoric economy or ideology, or explained by taphonomic loss. Few studies exist where birds form the basis for extensive archaeological interpretation. In this doctoral dissertation bird bone material from various Stone Age sites in the Baltic Sea region is investigated. The study period is approximately 7000-3400 BP, comprising mainly Neolithic cultures. The settlement material comes from Finland, Åland, Gotland, Saaremaa and Hiiumaa. Osteological materials are used for studying the economic and cultural importance of birds, fowling methods and principal fowling seasons. The bones were identified and earlier identifications partially checked with help of a reference material of modern skeletons. Fracture analysis was used in order to study the deposition history of bones at Ajvide settlement site. Birds in burials at two large cemeteries, Ajvide on Gotland and Zvejnieki in northern Latvia were investigated in order to study the roles of birds in burial practices. My study reveals that the economic importance of birds is at least seasonally often more prominent than usually thought, and varies greatly in different areas. Fowling has been most important in coastal areas, and especially during the breeding season. Waterbirds and grouse species were generally the most important groups in Finnish Stone Age economy. The identified species composition shows much resemblance to contemporary hunting with species such as the mallard and capercaillie commonly found. Burial materials and additional archaeological evidence from Gotland, Latvia and some other parts of northern Europe indicate that birds –e.g., jay, whooper swan, ducks – have been socially and ideologically important for the studied groups (indicating a place in the belief system, e.g. clan totemism). The burial finds indicate that some common ideas about waterbirds (perhaps as messengers or spirit helpers) might have existed in the northern European Stone Age.

The reliability of supply of feed grains in the northern region

Reliability of supply of feed grain has become a high priority issue for industry in the northern region. Expansion by major intensive livestock and industrial users of grain, combined with high inter-annual variability in seasonal conditions, has generated concern in the industry about reliability of supply. This paper reports on a modelling study undertaken to analyse the reliability of supply of feed grain in the northern region. Feed grain demand was calculated for major industries (cattle feedlots, pigs, poultry, dairy) based on their current size and rate of grain usage. Current demand was estimated to be 2.8Mt. With the development of new industrial users (ethanol) and by projecting the current growth rate of the various intensive livestock industries, it was estimated that demand would grow to 3.6Mt in three years time. Feed grain supply was estimated using shire scale yield prediction models for wheat and sorghum that had been calibrated against recent ABS production data. Other crops that contribute to a lesser extent to the total feed grain pool (barley, maize) were included by considering their production relative to the major winter and summer grains, with estimates based on available production records. This modelling approach allowed simulation of a 101-year time series of yield that showed the extent of the impact of inter-annual climate variability on yield levels. Production estimates were developed from this yield time series by including planted crop area. Area planted data were obtained from ABS and ABARE records. Total production amounts were adjusted to allow for any export and end uses that were not feed grain (flour, malt etc). The median feed grain supply for an average area planted was about 3.1Mt, but this varied greatly from year to year depending on seasonal conditions and area planted. These estimates indicated that supply would not meet current demand in about 30% of years if a median area crop were planted. Two thirds of the years with a supply shortfall were El Nino years. This proportion of years was halved (i.e. 15%) if the area planted increased to that associated with the best 10% of years. Should demand grow as projected in this study, there would be few years where it could be met if a median crop area was planted. With area planted similar to the best 10% of years, there would still be a shortfall in nearly 50% of all years (and 80% of El Nino years). The implications of these results on supply/demand and risk management and investment in research and development are briefly discussed.

Near infrared reflectance as a rapid and inexpensive surrogate measure for fatty acid composition and oil content in peanuts (Arachis hypogaea L.)

The fatty acid composition of ground nuts (Arachis hypogaea L.) commonly known as peanuts, is an important consideration when a new variety is being released. The composition impacts on nutrition and, importantly, self-life of peanut products. To select for suitable breeding material, it was necessary to develop a rapid, non-derstructive and cost-efficient method. Near infrared spectroscopy was chosen as that methodology. Calibrations were developed for two major fatty-acid components, oleic and linoleic acids and two minor components, palmitic and stearic acids, as well as total oil content. Partial least squares models indicated a high level of precision with a squared multiple correlation coefficient of greater than 0.90 for each constitutent. Standard errors for prediction for oleic, linoleic, palmitic, stearic acids and total oil content were 6.4%, 4.5%, 0.8%, 0.9% and 1.3% respectively. The results demonstrated that reasonable calibrations could be developed to predict oil composition and content of peanuts for a breeding programme.