Solid State Physics

Contains research objectives and reports on four research projects

Evaluating the Evidence for Transmission Distortion in Human Pedigrees

Children of a heterozygous parent are expected to carry either allele with equal probability. Exceptions can occur, however, due to meiotic drive, competition among gametes, or viability selection, which we collectively term “transmission distortion” (TD). Although there are several well-characterized examples of these phenomena, their existence in humans remains unknown. We therefore performed a genome-wide scan for TD by applying the transmission disequilibrium test (TDT) genome-wide to three large sets of human pedigrees of European descent: the Framingham Heart Study (FHS), a founder population of European origin (HUTT), and a subset of the Autism Genetic Resource Exchange (AGRE). Genotyping error is an important confounder in this type of analysis. In FHS and HUTT, despite extensive quality control, we did not find sufficient evidence to exclude genotyping error in the strongest signals. In AGRE, however, many signals extended across multiple SNPs, a pattern highly unlikely to arise from genotyping error. We identified several candidate regions in this data set, notably a locus in 10q26.13 displaying a genome-wide significant TDT in combined female and male transmissions and a signature of recent positive selection, as well as a paternal TD signal in 6p21.1, the same region in which a significant TD signal was previously observed in 30 European males. Neither region replicated in FHS, however, and the paternal signal was not visible in sperm competition assays or as allelic imbalance in sperm. In maternal transmissions, we detected no strong signals near centromeres or telomeres, the regions predicted to be most susceptible to female-specific meiotic drive, but we found a significant enrichment of top signals among genes involved in cell junctions. These results illustrate both the potential benefits and the challenges of using the TDT to study transmission distortion and provide candidates for investigation in future studies

Association of Lifestyle Factors With Abdominal Subcutaneous and Visceral Adiposity: The Framingham Heart Study

OBJECTIVE— The purpose of this study was to assess the relationship between lifestyle factors and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in a community-based setting

Dzyaloshinskii-Moriya Interaction and Spiral Order in Spin-orbit Coupled Optical Lattices

We show that the recent experimental realization of spin-orbit coupling in ultracold atomic gases can be used to study different types of spin spiral order and resulting multiferroic effects. Spin-orbit coupling in optical lattices can give rise to the Dzyaloshinskii-Moriya (DM) spin interaction which is essential for spin spiral order. By taking into account spin-orbit coupling and an external Zeeman field, we derive an effective spin model in the Mott insulator regime at half filling and demonstrate that the DM interaction in optical lattices can be made extremely strong with realistic experimental parameters. The rich finite temperature phase diagrams of the effective spin models for fermions and bosons are obtained via classical Monte Carlo simulations.Comment: 7 pages, 5 figure

Pathogenesis of pili annulati

Plucked scalp hairs and hair roots of pili annulati were examined to understand their pathogenesis. Stereoscopic examinations of hairs in transmitted light and/or reflected light and light microscopic surveys of the cross-sections of hairs confirmed that the cortical empty spaces appeared to be responsible to the unique dotted shiny appearance of the hairs seen by the unaided eyes under a refracted light. By transmission electron microscope, small vacuoles and dense bodies were observed in the cytoplasm of the differentiating cortical cells; subsequently, with increasing number of tonofilaments, an uneven distribution of free ribosomes occurred and abnormal spaces containing fine granular substances were formed in the cytoplasm of the cortical cells. Occasionally, extremely large cortical trichohyaline granules were found. In the keratinized hair, irregular empty spaces were present in the cortex of the abnormal hair segments. Histochemically, the keratinized cortex of the affected hairs always had more residual SH groups than the controls. Pili annulati may be a disorder of protein metabolism involving a partial dysfunction of cytoplasmic ribosomes, resulting in a lack of cortical keratin formation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47241/1/403_2004_Article_BF00440605.pd

Recent methods for polygenic analysis of genome-wide data implicate an important effect of common variants on cardiovascular disease risk

<p>Abstract</p> <p>Background</p> <p>Traditional genome-wide association studies are generally limited in their ability explain a large portion of genetic risk for most common diseases. We sought to use both traditional GWAS methods, as well as more recently developed polygenic genome-wide analysis techniques to identify subsets of single-nucleotide polymorphisms (SNPs) that may be involved in risk of cardiovascular disease, as well as estimate the heritability explained by common SNPs.</p> <p>Methods</p> <p>Using data from the Framingham SNP Health Association Resource (SHARe), three complimentary methods were applied to examine the genetic factors associated with the Framingham Risk Score, a widely accepted indicator of underlying cardiovascular disease risk. The first method adopted a traditional GWAS approach - independently testing each SNP for association with the Framingham Risk Score. The second two approaches involved polygenic methods with the intention of providing estimates of aggregate genetic risk and heritability.</p> <p>Results</p> <p>While no SNPs were independently associated with the Framingham Risk Score based on the results of the traditional GWAS analysis, we were able to identify cardiovascular disease-related SNPs as reported by previous studies. A predictive polygenic analysis was only able to explain approximately 1% of the genetic variance when predicting the 10-year risk of general cardiovascular disease. However, 20% to 30% of the variation in the Framingham Risk Score was explained using a recently developed method that considers the joint effect of all SNPs simultaneously.</p> <p>Conclusion</p> <p>The results of this study imply that common SNPs explain a large amount of the variation in the Framingham Risk Score and suggest that future, better-powered genome-wide association studies, possibly informed by knowledge of gene-pathways, will uncover more risk variants that will help to elucidate the genetic architecture of cardiovascular disease.</p

Electrical properties of ferroelectric YMnO3 films deposited on n-type Si (111) substrates

YMnO3 thin films were grown on n - type Si substrate by nebulized spray pyrolysis in Metal - Ferroelectric - Semiconductor (MFS) configuration. The C-V characteristics of the film in MFS structure exhibit hysteretic behavior consistent with the polarization charge switching direction, with the memory window decreasing with increase in temperature. The density of interface states decreases with the increase in the annealing temperature. Mapping of the silicon energy band gap with the interface states has been carried out. The leakage current measured in the accumulation region, is lower in well-crystallized thin films and obeys a space- charge limited conduction mechanism. The calculated activation energy from the dc leakage current characteristics of Arhennius plot reveals that the activation energy correspond to the oxygen vacancy motionComment: 26 pages, 1 table, 8 figures, submitted to submitted to J. Phys. D; applied physics on 5th feb 200

Blood pressure reduction and clinical outcomes with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: protocol for a systematic review and meta-regression analysis

Background Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) efficaciously reduce systolic blood pressure (BP), a well-established risk factor for myocardial infarction (MI). Both inhibit the renin-angiotensin system, albeit through different mechanisms, and produce similar reductions in BP. However, in parallel meta-analyses of ACEi and ARB trials, ACEis reduce risk of MI whereas ARBs do not—a phenomenon described as the ‘ARB-MI paradox’. In addition, ACEis reduce all-cause mortality, whereas ARBs do not, which appears to be independent of BP lowering. The divergent cardiovascular effects of ACE inhibitors and ARBs, despite similar BP reductions, are counter-intuitive. This systematic review aims to ascertain the extent to which clinical outcomes in randomised trials of ACEi and ARBs are attributable to reductions in systolic BP. Methods A comprehensive search of bibliographic databases will be performed to identify all randomised studies of agents of the ACEi and ARB class. Placebo and active comparator-controlled studies that report clinical outcomes, with greater than 500 person-years of follow-up in each study arm, will be included. Two independent reviewers will screen study records against a priori-defined eligibility criteria and perform data extraction. The Cochrane Risk of Bias Tool will be applied to all included studies. Studies retracted subsequent to initial publication will be excluded. Primary outcomes of interest include MI and all-cause mortality; secondary outcomes include stroke, heart failure, revascularisation and cardiovascular mortality. Meta-regression will be performed, evaluating the relationship between attained reduction in systolic BP and relative risk of each outcome, stratified by drug class. Where a BP-dependent effect exists (two-tailed p value < 0.05), relative risks, standardised per 10 mmHg difference in BP, will be reported for each study outcome. Publication bias will be examined using Funnel plots, and calculation of Egger’s statistic. Discussion This systematic review will provide a detailed synthesis of evidence regarding the relationship between BP reduction and clinical outcomes with ACEi and ARBs. Greater understanding of the dependency of the effect of each class on BP reduction will advance insight into the nature of the ARB-MI paradox and guide the future usage of these agents. Systematic review registration PROSPERO CRD4201707298

The Florey Adelaide Male Ageing Study (FAMAS): Design, procedures & participants

<p>Abstract</p> <p>Background</p> <p>The Florey Adelaide Male Ageing Study (FAMAS) examines the reproductive, physical and psychological health, and health service utilisation of the ageing male in Australia. We describe the rationale for the study, the methods used participant response rates, representativeness and attrition to date.</p> <p>Methods</p> <p>FAMAS is a longitudinal study involving approximately 1200 randomly selected men, aged 35–80 years and living in the north – west regions of Adelaide. Respondents were excluded at screening if they were considered incapable of participating because of immobility, language, or an inability to undertake the study procedures. Following a telephone call to randomly selected households, eligible participants were invited to attend a baseline clinic measuring a variety of biomedical and socio-demographic factors. Beginning in 2002, these clinics are scheduled to reoccur every five years. Follow-up questionnaires are completed annually. Participants are also invited to participate in sub-studies with selected collaborators.</p> <p>Results</p> <p>Of those eligible to participate, 45.1% ultimately attended a clinic. Non-responders were more likely to live alone, be current smokers, have a higheevalence of self-reported diabetes and stroke, and lower levels of hypercholesterolemia. Comparisons with the Census 2001 data showed that participants matched the population for most key demographics, although younger groups and never married men were under-represented and elderly participants were over-represented. To date, there has been an annual loss to follow-up of just over 1%.</p> <p>Conclusion</p> <p>FAMAS allows a detailed investigation into the effects of bio-psychosocial and behavioural factors on the health and ageing of a largely representative group of Australian men.</p

Protein disulphide isomerase-mediated grafting of cysteine-containing peptides onto over-bleached hair

The ability of Protein disulphide isomerase (PDI) to promote the grafting of two cysteine-containing peptides onto hair was investigated in order to develop an alternative treatment for over-bleached hair. The studied peptides were designed based on human keratin and human lung surfactant proteins and were linked to a fluorescent dye to facilitate visualisation of the grafting process and to assess hair penetration. The ability of the peptides to restore mechanical and thermal properties lost by repeated bleaching treatments was also studied. After eight bleaching treatments, hair samples displayed 42% less mechanical resistance, coupled with a decrease in α-helix denaturation enthalpies and temperatures. Hair surface damage following bleaching was visualized by scanning electron microscopy. Addition of PDI to the treatment formulations promoted peptide attachment to the hair via disulphide bonds, facilitating their penetration into the hair cortex, as observed by fluorescence microscopy. The proposed peptide treatment resulted in an increase in α-helix denaturation enthalpy in over-bleached hair, as well as an increase in both Young's modulus and tensile strength. Thus, mechanical and thermal properties were improved after the peptide treatment in the presence of PDI; suggesting that the formulations presented in this work are promising candidates for hair-care applications