137 research outputs found
The relationship between Lp(a) and CVD outcomes: a systematic review
Summary of QUIPS quality assessment domains (60 studies). (DOCX 54Â kb
Re-thinking Regionalism: Europe and East Asia in Comparative Historical Perspective
Regionally-based processes of political and economic integration, security cooperation, and even social identification have become increasingly important and prominent parts of the international system. Nowhere have such processes gone further than in Western Europe. Somewhat surprisingly, similar patterns of regional integration have been steadily developing in East Asia - a region many observers consider unlikely to replicate the European experience. What are the factors that encourage regional political cooperation and economic integration? Are there common forces encouraging such outcomes in very different geographical areas and at very different moments in history? This paper uses an historically grounded comparative approach to examine the historical pre-conditions that underpinned the formation of the European Union, and then contrasts them with the situation in East Asia today. While the overall geopolitical and specific national contexts are very different, the East Asian experience may ultimately generate relationships and structures that are more like the European Union's than some of the sceptics imagine
What does regional studies study? From subnational to supra-national regional spaces or Grossraum of sovereign governance
This article makes a case for expanding the scope of current versions of “regional studies” to include greater emphasis upon transnational regions as of equal if not greater importance compared with an exclusive focus upon sub-national regions. The latter more restrictive approach is typically predicated on the continued centrality of state borders against which the dominant notion of regions as subnational entities is constituted and reiterated. Drawing upon a case study of the African Union our study provides a framework, a critically revised Grossraum theory, for addressing the emergence of a new pluralistic and multipolar world order characterised by supra-national regions and regional organizations. Traditional Schmittian notions of Grossraum are shown to be in need of substantial revision before they are able to adequately accommodate and explain the empirical details of our case study
Exploring Fold Space Preferences of New-born and Ancient Protein Superfamilies
The evolution of proteins is one of the fundamental processes that has delivered the diversity and complexity of life we see around ourselves today. While we tend to define protein evolution in terms of sequence level mutations, insertions and deletions, it is hard to translate these processes to a more complete picture incorporating a polypeptide's structure and function. By considering how protein structures change over time we can gain an entirely new appreciation of their long-term evolutionary dynamics. In this work we seek to identify how populations of proteins at different stages of evolution explore their possible structure space. We use an annotation of superfamily age to this space and explore the relationship between these ages and a diverse set of properties pertaining to a superfamily's sequence, structure and function. We note several marked differences between the populations of newly evolved and ancient structures, such as in their length distributions, secondary structure content and tertiary packing arrangements. In particular, many of these differences suggest a less elaborate structure for newly evolved superfamilies when compared with their ancient counterparts. We show that the structural preferences we report are not a residual effect of a more fundamental relationship with function. Furthermore, we demonstrate the robustness of our results, using significant variation in the algorithm used to estimate the ages. We present these age estimates as a useful tool to analyse protein populations. In particularly, we apply this in a comparison of domains containing greek key or jelly roll motifs
Isomeric recognition by ion/molecule reactions: The ionized phenol-cyclohexadienone case
Experimental and theoretical study of the gas-phase interaction between ionized nitrile sulfides and pyridine
Distinguishing Molecular Features and Clinical Characteristics of a Putative New Rhinovirus Species, Human Rhinovirus C (HRV C)
Background: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected
Toolbox for Non-Intrusive Structural and Functional Analysis of Recombinant VLP Based Vaccines: A Case Study with Hepatitis B Vaccine
Background: Fundamental to vaccine development, manufacturing consistency, and product stability is an understanding of the vaccine structure-activity relationship. With the virus-like particle (VLP) approach for recombinant vaccines gaining popularity, there is growing demand for tools that define their key characteristics. We assessed a suite of non-intrusive VLP epitope structure and function characterization tools by application to the Hepatitis B surface antigen (rHBsAg) VLP-based vaccine. Methodology: The epitope-specific immune reactivity of rHBsAg epitopes to a given monoclonal antibody was monitored by surface plasmon resonance (SPR) and quantitatively analyzed on rHBsAg VLPs in-solution or bound to adjuvant with a competitive enzyme-linked immunosorbent assay (ELISA). The structure of recombinant rHBsAg particles was examined by cryo transmission electron microscopy (cryoTEM) and in-solution atomic force microscopy (AFM). Principal Findings: SPR and competitive ELISA determined relative antigenicity in solution, in real time, with rapid turnaround, and without the need of dissolving the particulate aluminum based adjuvant. These methods demonstrated the nature of the clinically relevant epitopes of HBsAg as being responsive to heat and/or redox treatment. In-solution AFM and cryoTEM determined vaccine particle size distribution, shape, and morphology. Redox-treated rHBsAg enabled 3D reconstruction from CryoTEM images – confirming the previously proposed octahedral structure and the established lipidto-protei
Mathematical models for immunology:current state of the art and future research directions
The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years
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