GlycoPep Grader: A web-based utility for assigning the composition of N-linked glycopeptides

GlycoPep Grader (GPG) is a freely-available software tool designed to accelerate the process of accurately determining glycopeptide composition from tandem mass spectrometric data. GPG relies on the identification of unique dissociation patterns shown for high mannose, hybrid, and complex N-linked glycoprotein types, including patterns specific to those structures containing fucose or sialic acid residues. The novel GPG scoring algorithm scores potential candidate compositions of the same nominal mass against MS/MS data through evaluation of the Y1 ion and other peptide-containing product ions, across multiple charge states, when applicable. In addition to evaluating the peptide portions of a given glycopeptide, the GPG algorithm predicts and scores product ions that result from unique neutral losses of terminal glycans. GPG has been applied to a variety of glycoproteins, including RNase B, asialofetuin and transferrin, and the HIV envelope glycoprotein, CON-S gp140 CFI. The GPG software is implemented predominantly in PostgreSQL, with PHP as the presentation tier, and is publically accessible online. Thus far, the algorithm has identified the correct compositional assignment from multiple candidate N-glycopeptides in all tests performed

The Obliteration of Truth by Management: Badiou, St. Paul and the Question of Economic Managerialism in Education

This paper considers the questions that Badiou’s theory of the subject poses to cultures of economic managerialism within education. His argument that radical change is possible, for people and the situations they inhabit, provides a stark challenge to the stifling nature of much current educational climate. In 'Saint Paul: The Foundation of Universalism', Badiou describes the current universalism of capitalism, monetary homogeneity and the rule of the count. Badiou argues that the politics of identity are all too easily subsumed by the prerogatives of the marketplace and unable to present, therefore, a critique of the status quo. These processes are, he argues, without the potential for truth. What are the implications of Badiou’s claim that education is the arranging of ‘the forms of knowledge in such a way that truth may come to pierce a hole in them’ (Badiou, 2005, p. 9)? In this paper, I argue that Badiou’s theory opens up space for a kind of thinking about education that resists its colonisation by cultures of management and marketisation and leads educationalists to consider the emancipatory potential of education in a new light

Modal Ω-Logic: Automata, Neo-Logicism, and Set-Theoretic Realism

This essay examines the philosophical significance of $\Omega$-logic in Zermelo-Fraenkel set theory with choice (ZFC). The duality between coalgebra and algebra permits Boolean-valued algebraic models of ZFC to be interpreted as coalgebras. The modal profile of $\Omega$-logical validity can then be countenanced within a coalgebraic logic, and $\Omega$-logical validity can be defined via deterministic automata. I argue that the philosophical significance of the foregoing is two-fold. First, because the epistemic and modal profiles of $\Omega$-logical validity correspond to those of second-order logical consequence, $\Omega$-logical validity is genuinely logical, and thus vindicates a neo-logicist conception of mathematical truth in the set-theoretic multiverse. Second, the foregoing provides a modal-computational account of the interpretation of mathematical vocabulary, adducing in favor of a realist conception of the cumulative hierarchy of sets

Refuting the challenges of the developmental shift of polarity of GABA actions: GABA more exciting than ever!

During brain development, there is a progressive reduction of intracellular chloride associated with a shift in GABA polarity: GABA depolarizes and occasionally excites immature neurons, subsequently hyperpolarizing them at later stages of development. This sequence, which has been observed in a wide range of animal species, brain structures and preparations, is thought to play an important role in activity-dependent formation and modulation of functional circuits. This sequence has also been considerably reinforced recently with new data pointing to an evolutionary preserved rule. In a recent 'Hypothesis and Theory Article', the excitatory action of GABA in early brain development is suggested to be "an experimental artefact" (Bregestovski and Bernard, 2012). The authors suggest that the excitatory action of GABA is due to an inadequate/insufficient energy supply in glucose-perfused slices and/or to the damage produced by the slicing procedure. However, these observations have been repeatedly contradicted by many groups and are inconsistent with a large body of evidence including the fact that the developmental shift is neither restricted to slices nor to rodents. We summarize the overwhelming evidence in support of both excitatory GABA during development, and the implications this has in developmental neurobiology. \ua9 2012 Ben-ari, Woodin, Sernagor, Cancedda, Vinay, Rivera,Legendre, Luhmann, Bordey, Wenner, Fukuda, Pol, Jean-luc and Cherubini

Genomic analysis of human lung fibroblasts exposed to vanadium pentoxide to identify candidate genes for occupational bronchitis

BACKGROUND: Exposure to vanadium pentoxide (V(2)O(5)) is a cause of occupational bronchitis. We evaluated gene expression profiles in cultured human lung fibroblasts exposed to V(2)O(5 )in vitro in order to identify candidate genes that could play a role in inflammation, fibrosis, and repair during the pathogenesis of V(2)O(5)-induced bronchitis. METHODS: Normal human lung fibroblasts were exposed to V(2)O(5 )in a time course experiment. Gene expression was measured at various time points over a 24 hr period using the Affymetrix Human Genome U133A 2.0 Array. Selected genes that were significantly changed in the microarray experiment were validated by RT-PCR. RESULTS: V(2)O(5 )altered more than 1,400 genes, of which ~300 were induced while >1,100 genes were suppressed. Gene ontology categories (GO) categories unique to induced genes included inflammatory response and immune response, while GO catogories unique to suppressed genes included ubiquitin cycle and cell cycle. A dozen genes were validated by RT-PCR, including growth factors (HBEGF, VEGF, CTGF), chemokines (IL8, CXCL9, CXCL10), oxidative stress response genes (SOD2, PIPOX, OXR1), and DNA-binding proteins (GAS1, STAT1). CONCLUSION: Our study identified a variety of genes that could play pivotal roles in inflammation, fibrosis and repair during V(2)O(5)-induced bronchitis. The induction of genes that mediate inflammation and immune responses, as well as suppression of genes involved in growth arrest appear to be important to the lung fibrotic reaction to V(2)O(5)

Electron Capture Dissociation Mass Spectrometry of Tyrosine Nitrated Peptides

In vivo protein nitration is associated with many disease conditions that involve oxidative stress and inflammatory response. The modification involves addition of a nitro group at the position ortho to the phenol group of tyrosine to give 3-nitrotyrosine. To understand the mechanisms and consequences of protein nitration, it is necessary to develop methods for identification of nitrotyrosine-containing proteins and localization of the sites of modification.Here, we have investigated the electron capture dissociation (ECD) and collision-induced association (CID) behavior of 3-nitrotyrosine-containing peptides. The presence of nitration did not affect the CID behavior of the peptides. For the doubly-charged peptides, addition of nitration severely inhibited the production of ECD sequence fragments. However, ECD of the triply-charged nitrated peptides resulted in some singly-charged sequence fragments. ECD of the nitrated peptides is characterized by multiple losses of small neutral species including hydroxyl radicals, water and ammonia. The origin of the neutral losses has been investigated by use of activated ion (AI) ECD. Loss of ammonia appears to be the result of non-covalent interactions between the nitro group and protonated lysine side-chains

Hidden Voices: Disabled Women's Experiences of Violence and Support Over the Life Course

Violence against women is a worldwide social and human rights problem that cuts across cultural, geographic, religious, social, and economic boundaries. It affects women in countries around the world, regardless of class, religion, disability, age, or sexual identity. International evidence shows that approximately three in five women experienced physical and/or sexual violence by an intimate partner. However, across the globe, women and girls with impairments or life-limiting illnesses are more susceptible to different forms of violence across a range of environments and by different perpetrators including professionals and family members as well as partners. However, they are likely to be seriously disadvantaged in gaining information and support to escape the abusive relationships. This article stems from the United Kingdom part of a comparative study with three other countries (Austria, Germany, and Iceland) funded by the European Commission (EC; 2013-2015). It presents preliminary findings, generated from life history interviews, about disabled women's experiences of violence and access to support (both formal and informal) over their life course and their aspirations for the prevention of violence in the future. The article includes examples of impairment-specific violence that non-disabled women do not experience. By bringing the voices of disabled women into the public domain, the article will facilitate a historically marginalized group to contribute to the debate about disability, violence, and support

Towards a ‘Long View’: Historical Perspectives on the Scaling and Replication of Social Ventures

Social ventures are now widely regarded as playing an essential role in addressing persistent and pervasive societal challenges. This insight has prompted an active search for readily-scaleable and replicable business models. However, relatively little consideration has been given to the longer-term growth and performance of these hybrid organizational forms. This paper examines how historically-informed research might enhance our understanding of growth processes. It considers the conceptualization of organizational growth in social ventures and the relevance of prevailing constructs. The explanatory potential of ‘long view’ approaches examined by applying three constructs, opportunity recognition, entrepreneurial adjustment, and institutional structure, in a comparative historical analysis of two British social ventures

Native and foreign born as predictors of pediatric asthma in an Asian immigrant population: a cross sectional survey

<p>Abstract</p> <p>Background</p> <p>Asthma prevalence is lower in less developed countries and among some recent immigrant populations in the US, but the reasons for this are not clear. One possibility is that early childhood infections are protective against asthma.</p> <p>Methods</p> <p>We surveyed Asian immigrant children (n = 204; age 4–18) to assess the relationship between asthma and native or foreign place of birth. We included questions about environmental exposures, demographic variables and family history of asthma to test whether they might explain effects of place of birth on asthma.</p> <p>Results</p> <p>The native and foreign born groups were similar in most respects. Analysis of association with diagnosed asthma for all ages together resulted in two logistic regression models. Both retained born in the US (ORs were 3.2 and 4.3; p < 0.01) and family history of asthma (ORs were 6.4 and 7.2; p < 0.001). One model retained living near heavy motor traffic (OR = 2.6; p = 0.012). The other retained language (OR = 3.2; p = 0.003). However, for older children (11–18 years of age) being born in the US lost some of its predictive power.</p> <p>Conclusion</p> <p>Our findings are consistent with early childhood infections that are prevalent outside the US protecting against asthma.</p

Resilience, redundancy and low-carbon living: co-producing individual and community learning

There is an acknowledged need for buildings and communities to be more resilient in the face of unpredictable effects of climate change, economic crises and energy supplies. The notion and social practices involving redundancy (the ability to switch between numerous available choices beyond optimal design) are explored as an aspect of resilience theory. Practice and Social Learning theories are used as a lens through which to explore the available redundancy in housing and home environments to help prevent performance failure through unexpected circumstances or in response to varying user needs. Findings from an in depth UK housing case study show how redundancy is linked with the capacity to share resources and to learn both individually and collectively as a community. Such learning in relation to resilient low-carbon living is shown to be co-produced effectively through participatory action research. The benefits of introducing extra redundancy in housing design and community development to accommodate varied user’s understanding and preferences are discussed in relation to future proofing, value and scalar issues. Recommendations include better understanding of the design, time and monetary contribution needed to implement social or technical redundancy. These costs should be evaluated in context of savings made through greater resilience achieved