Solar and Heliospheric Observatory (SOHO) (1995)

SOHO is the most comprehensive space mission ever devoted to the study of the Sun and its nearby cosmic environment known as the heliosphere. It was launched in December 1995 and is currently funded at least through the end of 2016. SOHO's twelve instruments observe and measure structures and processes occurring inside as well as outside the Sun, and which reach well beyond Earth's orbit into the heliosphere. While designed to study the "quiet" Sun, the new capabilities and combination of several SOHO instruments have revolutionized space weather research. This article gives a brief mission overview, summarizes selected highlight results, and describes SOHO's contributions to space weather research. These include cotemporaneous EUV imaging of activity in the Sun's corona and white light imaging of coronal mass ejections in the extended corona, magnetometry in the Sun's atmosphere, imaging of far side activity, measurements to predict solar proton storms, and monitoring solar wind plasma at the L1 Lagrangian point, 1.5 million kilometers upstream of Earth

A machine learning case–control classifier for schizophrenia based on DNA methylation in blood

Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case–control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported. Using the first two SPLS-DA dimensions we calculated a “risk distance” to identify individuals with the highest probability of SZ. The model was then evaluated on an independent HM450 data set on 353 SZ cases and 322 non-psychiatric controls. Our CoRSIV-based model classified 303 individuals as cases with a positive predictive value (PPV) of 80%, far surpassing the performance of a model based on polygenic risk score (PRS). Importantly, risk distance (based on CoRSIV methylation) was not associated with medication use, arguing against reverse causality. Risk distance and PRS were positively correlated (Pearson r = 0.28, P = 1.28 × 10−12), and mediational analysis suggested that genetic effects on SZ are partially mediated by altered methylation at CoRSIVs. Our results indicate two innate dimensions of SZ risk: one based on genetic, and the other on systemic epigenetic variants

New Symmetries in Crystals and Handed Structures

For over a century, the structure of materials has been described by a combination of rotations, rotation-inversions and translational symmetries. By recognizing the reversal of static structural rotations between clockwise and counterclockwise directions as a distinct symmetry operation, here we show that there are many more structural symmetries than are currently recognized in right- or left-handed handed helices, spirals, and in antidistorted structures composed equally of rotations of both handedness. For example, though a helix or spiral cannot possess conventional mirror or inversion symmetries, they can possess them in combination with the rotation reversal symmetry. Similarly, we show that many antidistorted perovskites possess twice the number of symmetry elements as conventionally identified. These new symmetries predict new forms for "roto" properties that relate to static rotations, such as rotoelectricity, piezorotation, and rotomagnetism. They also enable symmetry-based search for new phenomena, such as multiferroicity involving a coupling of spins, electric polarization and static rotations. This work is relevant to structure-property relationships in all material structures with static rotations such as minerals, polymers, proteins, and engineered structures.Comment: 15 Pages, 4 figures, 3 Tables; Fig. 2b has error

A Compromise between Neutrino Masses and Collider Signatures in the Type-II Seesaw Model

A natural extension of the standard $SU(2)_{\rm L} \times U(1)_{\rm Y}$ gauge model to accommodate massive neutrinos is to introduce one Higgs triplet and three right-handed Majorana neutrinos, leading to a $6\times 6$ neutrino mass matrix which contains three $3\times 3$ sub-matrices $M_{\rm L}$, $M_{\rm D}$ and $M_{\rm R}$. We show that three light Majorana neutrinos (i.e., the mass eigenstates of $\nu_e$, $\nu_\mu$ and $\nu_\tau$) are exactly massless in this model, if and only if $M_{\rm L} = M_{\rm D} M_{\rm R}^{-1} M_{\rm D}^T$ exactly holds. This no-go theorem implies that small but non-vanishing neutrino masses may result from a significant but incomplete cancellation between $M_{\rm L}$ and $M_{\rm D} M_{\rm R}^{-1} M_{\rm D}^T$ terms in the Type-II seesaw formula, provided three right-handed Majorana neutrinos are of ${\cal O}(1)$ TeV and experimentally detectable at the LHC. We propose three simple Type-II seesaw scenarios with the $A_4 \times U(1)_{\rm X}$ flavor symmetry to interpret the observed neutrino mass spectrum and neutrino mixing pattern. Such a TeV-scale neutrino model can be tested in two complementary ways: (1) searching for possible collider signatures of lepton number violation induced by the right-handed Majorana neutrinos and doubly-charged Higgs particles; and (2) searching for possible consequences of unitarity violation of the $3\times 3$ neutrino mixing matrix in the future long-baseline neutrino oscillation experiments.Comment: RevTeX 19 pages, no figure

A cross validation of Consumer-Based Brand Equity (CBBE) with Private Labels in Spain

Molinillo,S., Ekinci, Y., Japutra, A. (2014)'A cross validation of Consumer-Based Brand Equity (CBBE) with Private Labels in Spain'. in Martínez-López, Gázquez-Abad, J.C. and Sethuraman, R. J.A. (eds.) Advances in National Brand and Private Label Marketing. Second International Conference, 2015. Springer Proceedings in Business and Economics, pp. 113-125In recent years a number of Consumer-Based Brand Equity (CBBE) models and measurement scales have been introduced in the branding literature. However, examinations of brand equity in Private Labels (PL) are rather limited. This study aims to compare the validity of the two prominent CBBE models those introduced by Yoo and Donthu (2001) and Nam et al. (2011). In order to test the models and make this comparison, the study collected data from 236 respondents who rated private labels in Spain. A list of 30 different fashion and sportswear PL was introduced to respondents. These brands do not make any reference to the retail store in which they are sold. Research findings suggest that the extended CBBE model introduced by Nam et al. (2011) and Ciftci et al. (2014) is more reliable and valid than Yoo and Donthu’s model for assessing PL. Theoretical contributions and managerial implications are discussed.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor of cancer cell migration and proliferation

<p>Abstract</p> <p>Background</p> <p>Human growth factor receptor bound protein 7 (Grb7) is an adapter protein that mediates the coupling of tyrosine kinases with their downstream signaling pathways. Grb7 is frequently overexpressed in invasive and metastatic human cancers and is implicated in cancer progression via its interaction with the ErbB2 receptor and focal adhesion kinase (FAK) that play critical roles in cell proliferation and migration. It is thus a prime target for the development of novel anti-cancer therapies. Recently, an inhibitory peptide (G7-18NATE) has been developed which binds specifically to the Grb7 SH2 domain and is able to attenuate cancer cell proliferation and migration in various cancer cell lines.</p> <p>Results</p> <p>As a first step towards understanding how Grb7 may be inhibited by G7-18NATE, we solved the crystal structure of the Grb7 SH2 domain to 2.1 Å resolution. We describe the details of the peptide binding site underlying target specificity, as well as the dimer interface of Grb 7 SH2. Dimer formation of Grb7 was determined to be in the μM range using analytical ultracentrifugation for both full-length Grb7 and the SH2 domain alone, suggesting the SH2 domain forms the basis of a physiological dimer. ITC measurements of the interaction of the G7-18NATE peptide with the Grb7 SH2 domain revealed that it binds with a binding affinity of K_d= ~35.7 μM and NMR spectroscopy titration experiments revealed that peptide binding causes perturbations to both the ligand binding surface of the Grb7 SH2 domain as well as to the dimer interface, suggesting that dimerisation of Grb7 is impacted on by peptide binding.</p> <p>Conclusion</p> <p>Together the data allow us to propose a model of the Grb7 SH2 domain/G7-18NATE interaction and to rationalize the basis for the observed binding specificity and affinity. We propose that the current study will assist with the development of second generation Grb7 SH2 domain inhibitors, potentially leading to novel inhibitors of cancer cell migration and invasion.</p

Trace-gas metabolic versatility of the facultative methanotroph Methylocella silvestris

The climate-active gas methane is generated both by biological processes and by thermogenic decomposition of fossil organic material, which forms methane and short-chain alkanes, principally ethane, propane and butane1, 2. In addition to natural sources, environments are exposed to anthropogenic inputs of all these gases from oil and gas extraction and distribution. The gases provide carbon and/or energy for a diverse range of microorganisms that can metabolize them in both anoxic3 and oxic zones. Aerobic methanotrophs, which can assimilate methane, have been considered to be entirely distinct from utilizers of short-chain alkanes, and studies of environments exposed to mixtures of methane and multi-carbon alkanes have assumed that disparate groups of microorganisms are responsible for the metabolism of these gases. Here we describe the mechanism by which a single bacterial strain, Methylocella silvestris, can use methane or propane as a carbon and energy source, documenting a methanotroph that can utilize a short-chain alkane as an alternative to methane. Furthermore, during growth on a mixture of these gases, efficient consumption of both gases occurred at the same time. Two soluble di-iron centre monooxygenase (SDIMO) gene clusters were identified and were found to be differentially expressed during bacterial growth on these gases, although both were required for efficient propane utilization. This report of a methanotroph expressing an additional SDIMO that seems to be uniquely involved in short-chain alkane metabolism suggests that such metabolic flexibility may be important in many environments where methane and short-chain alkanes co-occur

The interplay of microscopic and mesoscopic structure in complex networks

Not all nodes in a network are created equal. Differences and similarities exist at both individual node and group levels. Disentangling single node from group properties is crucial for network modeling and structural inference. Based on unbiased generative probabilistic exponential random graph models and employing distributive message passing techniques, we present an efficient algorithm that allows one to separate the contributions of individual nodes and groups of nodes to the network structure. This leads to improved detection accuracy of latent class structure in real world data sets compared to models that focus on group structure alone. Furthermore, the inclusion of hitherto neglected group specific effects in models used to assess the statistical significance of small subgraph (motif) distributions in networks may be sufficient to explain most of the observed statistics. We show the predictive power of such generative models in forecasting putative gene-disease associations in the Online Mendelian Inheritance in Man (OMIM) database. The approach is suitable for both directed and undirected uni-partite as well as for bipartite networks

Vitamin D and subsequent all-age and premature mortality: a systematic review

&lt;br&gt;Background: All-cause mortality in the population &#60; 65 years is 30% higher in Glasgow than in equally deprived Liverpool and Manchester. We investigated a hypothesis that low vitamin D in this population may be associated with premature mortality via a systematic review and meta-analysis.&lt;/br&gt; &lt;br&gt;Methods: Medline, EMBASE, Web of Science, the Cochrane Library and grey literature sources were searched until February 2012 for relevant studies. Summary statistics were combined in an age-stratified meta-analysis.&lt;/br&gt; &lt;br&gt;Results: Nine studies were included in the meta-analysis, representing 24,297 participants, 5,324 of whom died during follow-up. The pooled hazard ratio for low compared to high vitamin D demonstrated a significant inverse association (HR 1.19, 95% CI 1.12-1.27) between vitamin D levels and all-cause mortality after adjustment for available confounders. In an age-stratified meta-analysis, the hazard ratio for older participants was 1.25 (95% CI 1.14-1.36) and for younger participants 1.12 (95% CI 1.01-1.24).&lt;/br&gt; &lt;br&gt;Conclusions: Low vitamin D status is inversely associated with all-cause mortality but the risk is higher amongst older individuals and the relationship is prone to residual confounding. Further studies investigating the association between vitamin D deficiency and all-cause mortality in younger adults with adjustment for all important confounders (or using randomised trials of supplementation) are required to clarify this relationship.&lt;/br&gt

Measuring maternal mortality : an overview of opportunities and options for developing countries

Background:There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015. Methods: Since the launch of the Safe Motherhood Initiative in 1987, new opportunities for data capture have arisen and new methods have been developed, tested and used. This paper provides a pragmatic overview of these methods and the optimal measurement strategies for different developing country contexts. Results: There are significant recent advances in the measurement of maternal mortality, yet also room for further improvement, particularly in assessing the magnitude and direction of biases and their implications for different data uses. Some of the innovations in measurement provide efficient mechanisms for gathering the requisite primary data at a reasonably low cost. No method, however, has zero costs. Investment is needed in measurement strategies for maternal mortality suited to the needs and resources of a country, and which also strengthen the technical capacity to generate and use credible estimates. Conclusion: Ownership of information is necessary for it to be acted upon: what you count is what you do. Difficulties with measurement must not be allowed to discourage efforts to reduce maternal mortality. Countries must be encouraged and enabled to count maternal deaths and act.WJG is funded partially by the University of Aberdeen. OMRC is partially funded by the London School of Hygiene and Tropical Medicine. CS and SA are partially funded by Johns Hopkins University. CAZ is funded by the Health Metrics Network at the World Health Organization. WJG, OMRC, CS and SA are also partially supported through an international research program, Immpact, funded by the Bill & Melinda Gates Foundation, the Department for International Development, the European Commission and USAID