Molecular basis of gene-environment interactions in the pathogenesis of asthma and COPD

The origins of respiratory disease, such as asthma in childhood and COPD in later life are unclear. Maternal smoking during pregnancy and low birth weight is associated with increased risk of asthma, poor lung function in adults and COPD in old age. Exposure to oxidative stress and poor nutrition in utero is thought to cause damage to the lung and alter the normal course of lung development.Glutathione S-transferases (GST) are potent antioxidants. In this work, genetic polymorphisms that alter GST enzyme activity were genotyped in a family-based childhood asthma cohort (341 families, n = 1508) and analysed to investigate whether they alter the risk of developing asthma when individuals are exposed to environmental tobacco smoke. Real-time PCR based copy number variation methodology was developed to genotype the common gene deletion polymorphism of GSTT1 and GSTM1 genes, for other GST genes (GSTP1 and GSTO2) SNP haplotypes were constructed. A rare GSTO2 haplotype was negatively associated with asthma susceptibility, atopy severity, and FEV1 values. Asthmatic children with a GSTT1 gene deletion, or a common GSTP1 haplotype, developed more severe asthma compared to individuals with a GSTT1 gene or non-carriers of the GSTP1 haplotype. Total IgE levels were increased in GSTT1*0 individuals when exposed to tobacco smoke in early life, suggesting a gene-environment interaction. GSTO2 may be a shared susceptibility locus for asthma in childhood and COPD in later life.Animal models of maternal protein-restriction during pregnancy can induce hypertension, diabetes and endothelial dysfunction in offspring and in some of these models alterations to lung gene expression and lung architecture have been reported. This work established that a rat model of maternal dietary protein-restriction during pregnancy known to induce hypertension in the offspring, results in persistent alterations to the expression of genes in the lungs of adult offspring (120 days), including genes involved in glucocorticoid action (Hsd11b2), growth (Igf1 & 2 and Pcdh1) and alveolar development (Tp53). Lung microRNA expression profiles were also altered in response to exposure to protein restriction in utero. These findings suggest a role for nutritional programming in respiratory disease susceptibility in later life and a role for microRNAs in the study of the developmental origins of health and disease in general. Further work will include the investigation of epigenetic mechanisms that control nutritional programming in lungs of animals exposed to protein-restriction in utero.This work has demonstrated that GST polymorphism is a risk factor for childhood asthma and certain genotypes can offer some protection against the development of severe asthma. There was little evidence to suggest that GST polymorphism modulates the effects of smoke exposure in early life. In addition, we have demonstrated that maternal diets that are poor in nutrition could predispose her offspring to respiratory disease in later life by altering the course of normal lung development in early life or response to environmental stimuli in later life

Sub-wavelength lithography over extended areas

We demonstrate a systematic approach to sub-wavelength resolution lithographic image formation on films covering areas larger than a wavelength squared. For example, it is possible to make a lithographic pattern with a feature size resolution of $\lambda/[2(N+1)]$ by using a particular $2 M$-photon, multi-mode entangled state, where $N < M$, and banks of birefringent plates. By preparing a statistically mixed such a state one can form any pixel pattern on a $(N+1) 2^{M-N} \times (N+1) 2^{M-N}$ pixel grid occupying a square with a side of $L=2^{M-N-1}$ wavelengths. Hence, there is a trade-off between the exposed area, the minimum lithographic feature size resolution, and the number of photons used for the exposure. We also show that the proposed method will work even under non-ideal conditions, albeit with somewhat poorer performance.Comment: 8 pages, 8 figures, 1 table. Written in RevTe

Spatial distribution of photoelectrons participating in formation of x-ray absorption spectra

Interpretation of x-ray absorption near-edge structure (XANES) experiments is often done via analyzing the role of particular atoms in the formation of specific peaks in the calculated spectrum. Typically, this is achieved by calculating the spectrum for a series of trial structures where various atoms are moved and/or removed. A more quantitative approach is presented here, based on comparing the probabilities that a XANES photoelectron of a given energy can be found near particular atoms. Such a photoelectron probability density can be consistently defined as a sum over squares of wave functions which describe participating photoelectron diffraction processes, weighted by their normalized cross sections. A fine structure in the energy dependence of these probabilities can be extracted and compared to XANES spectrum. As an illustration of this novel technique, we analyze the photoelectron probability density at the Ti K pre-edge of TiS2 and at the Ti K-edge of rutile TiO2.Comment: Journal abstract available on-line at http://link.aps.org/abstract/PRB/v65/e20511

A first step towards service-dominant logic as a new approach to overcome challenges in business intelligence

High expectations are set for Business Intelligence (BI), yet it fails to consistently deliver accordingly: there are numerous reports of BI challenges and failures. Existing approaches to address BI challenges are largely found to be ineffective, highlighting the need for a new approach. This paper examines how BI is perceived or understood and establishes that, firstly, BI is inherently grounded in Goods-Dominant (G-D) logic and secondly, that this can be linked to the challenges that are experienced within BI. A recommendation is made for a shift to Service-Dominant (S-D) logic as a new avenue of exploration to assist in overcoming BI’s prevailing challenges. Identifying the inherent G-D logic in BI provides the first step necessary in making this shift. Research findings are based on an interpretive case study of a South African Banking institution as well as a literature review.http://www.sajems.org/am201

Boost operators in Coulomb-gauge QCD: the pion form factor and Fock expansions in phi radiative decays

In this article we rederive the Boost operators in Coulomb-Gauge Yang-Mills theory employing the path-integral formalism and write down the complete operators for QCD. We immediately apply them to note that what are usually called the pion square, quartic... charge radii, defined from derivatives of the pion form factor at zero squared momentum transfer, are completely blurred out by relativistic and interaction corrections, so that it is not clear at all how to interpret these quantities in terms of the pion charge distribution. The form factor therefore measures matrix elements of powers of the QCD boost and Moeller operators, weighted by the charge density in the target's rest frame. In addition we remark that the decomposition of the eta' wavefunction in quarkonium, gluonium, ... components attempted by the KLOE collaboration combining data from phi radiative decays, requires corrections due to the velocity of the final state meson recoiling against a photon. This will be especially important if such decompositions are to be attempted with data from J/psi decays.Comment: 14 pages, 4 figure

Affine symmetry in mechanics of collective and internal modes. Part II. Quantum models

Discussed is the quantized version of the classical description of collective and internal affine modes as developed in Part I. We perform the Schr\"odinger quantization and reduce effectively the quantized problem from $n^{2}$ to $n$ degrees of freedom. Some possible applications in nuclear physics and other quantum many-body problems are suggested. Discussed is also the possibility of half-integer angular momentum in composed systems of spin-less particles

Zitterbewegung in External Magnetic Field: Classic versus Quantum Approach

We investigate variations of the Zitterbewegung frequency of electron due to an external static and uniform magnetic field employing the expectation value quantum approach, and compare our results with the classical model of spinning particles. We demonstrate that these two so far compatible approaches are not in agreement in the presence of an external uniform static magnetic field, in which the classical approach breaks the usual symmetry of free particles and antiparticles states, i.e. it leads to CP violation. Hence, regarding the Zitterbewegung frequency of electron, the classical approach in the presence of an external magnetic field is unlikely to correctly describe the spin of electron, while the quantum approach does, as expected. We also show that the results obtained via the expectation value are in close agreement with the quantum approach of the Heisenberg picture derived in the literature. However, the method we use is capable of being compared with the classical approach regarding the spin aspects. The classical interpretation of spin produced by the altered Zitterbewegung frequency, in the presence of an external magnetic field, are discussed.Comment: 16 pages, no figure