Measurement of the production cross section of prompt j/psi mesons in association with a W (+/-) boson in pp collisions root s=7 TeV with the ATLAS detector

ATLAS Collaboration, for complete list of authors see http://dx.doi.org/10.1007/JHEP04(2014)172</p

Identification of Microbial and Proteomic Biomarkers in Early Childhood Caries

The purpose of this study was to provide a univariate and multivariate analysis of genomic microbial data and salivary mass-spectrometry proteomic profiles for dental caries outcomes. In order to determine potential useful biomarkers for dental caries, a multivariate classification analysis was employed to build predictive models capable of classifying microbial and salivary sample profiles with generalization performance. We used high-throughput methodologies including multiplexed microbial arrays and SELDI-TOF-MS profiling to characterize the oral flora and salivary proteome in 204 children aged 1–8 years (n = 118 caries-free, n = 86 caries-active). The population received little dental care and was deemed at high risk for childhood caries. Findings of the study indicate that models incorporating both microbial and proteomic data are superior to models of only microbial or salivary data alone. Comparison of results for the combined and independent data suggests that the combination of proteomic and microbial sources is beneficial for the classification accuracy and that combined data lead to improved predictive models for caries-active and caries-free patients. The best predictive model had a 6% test error, >92% sensitivity, and >95% specificity. These findings suggest that further characterization of the oral microflora and the salivary proteome associated with health and caries may provide clinically useful biomarkers to better predict future caries experience

Measurement of the production of a W boson in association with a charm quark in pp collisions at root s=7 TeV with the ATLAS detector

ATLAS Collaboration, for complete list of authors see http://dx.doi.org/10.1007/JHEP05(2014)068</p

Single Cell Transcriptomics Implicate Novel Monocyte and T Cell Immune Dysregulation in Sarcoidosis

Sarcoidosis is a systemic inflammatory disease characterized by infiltration of immune cells into granulomas. Previous gene expression studies using heterogeneous cell mixtures lack insight into cell-type-specific immune dysregulation. We performed the first single-cell RNA-sequencing study of sarcoidosis in peripheral immune cells in 48 patients and controls. Following unbiased clustering, differentially expressed genes were identified for 18 cell types and bioinformatically assessed for function and pathway enrichment. Our results reveal persistent activation of circulating classical monocytes with subsequent upregulation of trafficking molecules. Specifically, classical monocytes upregulated distinct markers of activation including adhesion molecules, pattern recognition receptors, and chemokine receptors, as well as enrichment of immunoregulatory pathways HMGB1, mTOR, and ephrin receptor signaling. Predictive modeling implicated TGFβ and mTOR signaling as drivers of persistent monocyte activation. Additionally, sarcoidosis T cell subsets displayed patterns of dysregulation. CD4 naïve T cells were enriched for markers of apoptosis and Th17/T(reg) differentiation, while effector T cells showed enrichment of anergy-related pathways. Differentially expressed genes in regulatory T cells suggested dysfunctional p53, cell death, and TNFR2 signaling. Using more sensitive technology and more precise units of measure, we identify cell-type specific, novel inflammatory and regulatory pathways. Based on our findings, we suggest a novel model involving four convergent arms of dysregulation: persistent hyperactivation of innate and adaptive immunity via classical monocytes and CD4 naïve T cells, regulatory T cell dysfunction, and effector T cell anergy. We further our understanding of the immunopathology of sarcoidosis and point to novel therapeutic targets

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Owner-Level Taxes and Business Activity

In some classes of models, taxes at the owner level are "neutral" and have no effect on firm activity. However, this tax neutrality is sensitive to assumptions and no longer holds in more complex models. We review recent research that incorporates greater complexity in studying the link between taxes and business activity - particularly entrepreneurship. Dividend taxes on owners of large firms affect firm activity in models that include agency conflicts between owners and managers. Similarly, after incorporating entrepreneurs' occupational choice into the model, taxes are no longer neutral. By forsaking lucrative alternative careers, skilled entrepreneurs tend to have high opportunity costs, which make the choice of attempting to start a business of first order importance. Moreover, in models where it is assumed that capital flows across borders without cost, taxes on domestic business owners do not alter business activity because foreign capital seamlessly compensates for tax-induced declines in investments. This theoretical notion is contradicted by the strong "home bias" observed in business ownership, in particular for small firms and startups without easy access to international capital markets. Recent empirical work has emphasized that taxes have heterogeneous effects on mature firms, entrepreneurial startups, and owner-managed small firms. Lowering dividend taxes on firms with dispersed ownership has been shown to shift capital from mature firms into rapidly growing firms. Moreover, capital gains taxation tends to reduce the number of innovative startups and diminish venture capital activity, while high owner-level taxes encourage small business activity and non-entrepreneurial self-employment because such firms have more opportunities to avoid or evade taxes. To obtain efficient incentives in entrepreneurial startups, contractual terms are required that ex ante guarantee that all providers of critical inputs, especially equity constrained entrepreneurs, are entitled to a share of the resulting capital value firm. Unless properly designed, owner-level taxes prevent such ex ante contracting and thus lower the likelihood of eventual success

Transition, Integration and Convergence. The Case of Romania

This volume comprises several studies and papers published in the last decades. They have been selected and ranged so that to provide a minimum of coherence concerning the phases which Romania has crossed in her way to the advanced socio-economic system of European type: transition to the market economy, accession to the EU, the economic convergence in the three fundamental domains: institutions, real economy, and nominal economy. The readers may find in this volume a description of debates, difficulties and solutions adopted for building-up the market economy by a state being in a profound transformation from weak transition institutions towards hard democratic institutions. Because the transition to the market economy and the association of Romania with the EU and then the integration presenting strategic political decisions, I have included in this work two studies devoted to the political forces state and political parties that elaborated and applied these strategic decisions underlining their structure, role and function and their transformation. Integration into the EU of a country like Romania, which emerged from a different system comparing with the West-European one, has proved to be difficult and lasting many years because of the structural transformations. In five chapters I am referring to the essential characteristics of the integration process, such as: market liberalization, competitiveness of the local (national) firms on the national and EU markets, institutional reforms so that the institutions of candidate countries have to become compatible with those of the EU and finally the perspective assessment to find out the real and nominal convergence. Putting into practice the EU competitivity and cohesion principles, Romania has good prospects to close, in a reasonable time, the economic gap and to be admitted into the Euro Zone. Although the real convergence of Romania with the EU requires higher growth rates for the former, a new approach is compulsory to take into consideration the environment quality, the natural resources and the equity between the present and the future generations as natural resource consumers. Just these problems have determined me to include in this volume the last two chapters which, on the one hand, try to prove the necessity of the economy growth harmonization with the environment evolution as well as the saving of the energy resources, and, on the other hand, to point out the main ways to be followed and instruments to be used