Showing papers by "University College Dublin published in 2011"
TL;DR: A new program called Clustal Omega is described, which can align virtually any number of protein sequences quickly and that delivers accurate alignments, and which outperforms other packages in terms of execution time and quality.
Abstract: Multiple sequence alignments are fundamental to many sequence analysis methods. Most alignments are computed using the progressive alignment heuristic. These methods are starting to become a bottleneck in some analysis pipelines when faced with data sets of the size of many thousands of sequences. Some methods allow computation of larger data sets while sacrificing quality, and others produce high-quality alignments, but scale badly with the number of sequences. In this paper, we describe a new program called Clustal Omega, which can align virtually any number of protein sequences quickly and that delivers accurate alignments. The accuracy of the package on smaller test cases is similar to that of the high-quality aligners. On larger data sets, Clustal Omega outperforms other packages in terms of execution time and quality. Clustal Omega also has powerful features for adding sequences to and exploiting information in existing alignments, making use of the vast amount of precomputed information in public databases like Pfam.
12,489 citations
University of Amsterdam1, University of Toronto2, Centre Hospitalier Universitaire de Toulouse3, Cleveland Clinic4, Tohoku University5, Charles University in Prague6, University College Dublin7, University of Basel8, Icahn School of Medicine at Mount Sinai9, Lund University10, University College London11, University of California, San Francisco12, Mayo Clinic13, University of Texas Health Science Center at Houston14
TL;DR: These revisions simplify the McDonald Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
Abstract: New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
8,883 citations
TL;DR: It is shown that microplastic contaminates the shorelines at 18 sites worldwide representing six continents from the poles to the equator, with more material in densely populated areas, but no clear relationship between the abundance of miocroplastics and the mean size-distribution of natural particulates.
Abstract: Plastic debris 1900 fibers per wash. This suggests that a large proportion of microplastic fibers found in the marine environment may be derived from sewage as a consequence of washing of clothes. As the human population grows and people use more synthetic textiles, contamination of habitats and animals by microplastic is likely to increase.
2,903 citations
TL;DR: The ellipses are unbiased with respect to sample size, and their estimation via Bayesian inference allows robust comparison to be made among data sets comprising different sample sizes, which opens up more avenues for direct comparison of isotopic niches across communities.
Abstract: 1. The use of stable isotope data to infer characteristics of community structure and niche width of community members has become increasingly common. Although these developments have provided ecologists with new perspectives, their full impact has been hampered by an inability to statistically compare individual communities using descriptive metrics. 2. We solve these issues by reformulating the metrics in a Bayesian framework. This reformulation takes account of uncertainty in the sampled data and naturally incorporates error arising from the sampling process, propagating it through to the derived metrics. 3. Furthermore, we develop novel multivariate ellipse-based metrics as an alternative to the currently employed Convex Hull methods when applied to single community members. We show that unlike Convex Hulls, the ellipses are unbiased with respect to sample size, and their estimation via Bayesian inference allows robust comparison to be made among data sets comprising different sample sizes. 4. These new metrics, which we call SIBER (Stable Isotope Bayesian Ellipses in R), open up more avenues for direct comparison of isotopic niches across communities. The computational code to calculate the new metrics is implemented in the free-to-download package Stable Isotope Analysis for the R statistical environment.
2,226 citations
Seattle Children's1, National Health Service2, Beaumont Hospital3, University of Toronto4, University of Queensland5, Charles University in Prague6, Ludwig Maximilian University of Munich7, University College Dublin8, Case Western Reserve University9, Stanford University10, University of Paris11, University of Alabama at Birmingham12, Vertex Pharmaceuticals13, Queen's University Belfast14
TL;DR: Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks and substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride.
Abstract: Background Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis. Methods We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84 subjects, of whom 83 received at least one dose) or placebo (83, of whom 78 received at least one dose) for 48 weeks. The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second (FEV1). Results The change from baseline through week 24 in the percent of predicted FEV1 was greater by 10.6 percentage points in the ivacaftor group than in the placebo group (P<0.001). Effects on pulmonary function were noted by 2 weeks, and a significant treatment effect was maintained...
1,835 citations
TL;DR: The hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future.
Abstract: It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein (“hard”) corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP−protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once ...
1,582 citations
TL;DR: Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8+ T-cell-dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy.
Abstract: Immune-regulated pathways influence multiple aspects of cancer development. In this article we demonstrate that both macrophage abundance and T-cell abundance in breast cancer represent prognostic indicators for recurrence-free and overall survival. We provide evidence that response to chemotherapy is in part regulated by these leukocytes; cytotoxic therapies induce mammary epithelial cells to produce monocyte/macrophage recruitment factors, including colony stimulating factor 1 (CSF1) and interleukin-34, which together enhance CSF1 receptor (CSF1R)–dependent macrophage infiltration. Blockade of macrophage recruitment with CSF1R-signaling antagonists, in combination with paclitaxel, improved survival of mammary tumor–bearing mice by slowing primary tumor development and reducing pulmonary metastasis. These improved aspects of mammary carcinogenesis were accompanied by decreased vessel density and appearance of antitumor immune programs fostering tumor suppression in a CD8 + T-cell–dependent manner. These data provide a rationale for targeting macrophage recruitment/response pathways, notably CSF1R, in combination with cytotoxic therapy, and identification of a breast cancer population likely to benefit from this novel therapeutic approach. Significance: These findings reveal that response to chemotherapy is in part regulated by the tumor immune microenvironment and that common cytotoxic drugs induce neoplastic cells to produce monocyte/macrophage recruitment factors, which in turn enhance macrophage infiltration into mammary adenocarcinomas. Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8 + T-cell–dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy. Cancer Discovery; 1(1); 54–67. ©2011 AACR . This article is highlighted in the In This Issue feature, p. 4
1,520 citations
University of California, Riverside1, Texas A&M University2, University College Dublin3, Pontifícia Universidade Católica do Rio Grande do Sul4, University of California, Berkeley5, Pepperdine University6, American Museum of Natural History7, Stellenbosch University8, Chaffey College9, La Trobe University10, Washington and Lee University11
TL;DR: Molecular phylogenetic analysis, calibrated with fossils, resolves the time frame of the mammalian radiation and diversification analyses suggest important roles for the Cretaceous Terrestrial Revolution and KPg mass extinction in opening up ecospace that promoted interordinal and intraordinal diversification, respectively.
Abstract: Previous analyses of relations, divergence times, and diversification patterns among extant mammalian families have relied on supertree methods and local molecular clocks. We constructed a molecular supermatrix for mammalian families and analyzed these data with likelihood-based methods and relaxed molecular clocks. Phylogenetic analyses resulted in a robust phylogeny with better resolution than phylogenies from supertree methods. Relaxed clock analyses support the long-fuse model of diversification and highlight the importance of including multiple fossil calibrations that are spread across the tree. Molecular time trees and diversification analyses suggest important roles for the Cretaceous Terrestrial Revolution and Cretaceous-Paleogene (KPg) mass extinction in opening up ecospace that promoted interordinal and intraordinal diversification, respectively. By contrast, diversification analyses provide no support for the hypothesis concerning the delayed rise of present-day mammals during the Eocene Period.
1,284 citations
TL;DR: It is shown that 84% of the 147 grassland plant species studied in 17 biodiversity experiments promoted ecosystem functioning at least once, and many species are needed to maintain multiple functions at multiple times and places in a changing world.
Abstract: Biodiversity is rapidly declining worldwide, and there is consensus that this can decrease ecosystem functioning and services. It remains unclear, though, whether few or many of the species in an ecosystem are needed to sustain the provisioning of ecosystem services. It has been hypothesized that most species would promote ecosystem services if many times, places, functions and environmental changes were considered; however, no previous study has considered all of these factors together. Here we show that 84% of the 147 grassland plant species studied in 17 biodiversity experiments promoted ecosystem functioning at least once. Different species promoted ecosystem functioning during different years, at different places, for different functions and under different environmental change scenarios. Furthermore, the species needed to provide one function during multiple years were not the same as those needed to provide multiple functions within one year. Our results indicate that even more species will be needed to maintain ecosystem functioning and services than previously suggested by studies that have either (1) considered only the number of species needed to promote one function under one set of environmental conditions, or (2) separately considered the importance of biodiversity for providing ecosystem functioning across multiple years, places, functions or environmental change scenarios. Therefore, although species may appear functionally redundant when one function is considered under one set of environmental conditions, many species are needed to maintain multiple functions at multiple times and places in a changing world.
1,268 citations
TL;DR: Protein Nanoparticle Interactions: Opportunities and Challenges
Abstract: Protein Nanoparticle Interactions: Opportunities and Challenges Morteza Mahmoudi,* Iseult Lynch, Mohammad Reza Ejtehadi, Marco P. Monopoli, Francesca Baldelli Bombelli, and Sophie Laurent National Cell Bank, Pasteur Institute of Iran, Tehran, Iran Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran School of Chemistry and Chemical Biology & Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland Department of Physics, Sharif University of Technology, Tehran, Iran School of Pharmacy, UEA, Norwich Research Park, Norwich,U.K. Department of General, Organic, and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, B-7000 Mons, Belgium
1,214 citations
TL;DR: This study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.
Abstract: The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 ± 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.
Papworth Hospital1, Katholieke Universiteit Leuven2, Charles University in Prague3, University of Amsterdam4, Aarhus University5, Wrocław Medical University6, Slovak Medical University7, University of Barcelona8, University of Toronto9, Hannover Medical School10, University College Dublin11, Complutense University of Madrid12, Medical University of Graz13, University of Paris-Sud14
TL;DR: Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions.
Abstract: Background—Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. Methods and Results—The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%– 60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and...
TL;DR: The results confirm that significant evolution of the corona occurs in the second biological solution, but that the final corona contains a "fingerprint" of its history, which could be evolved to map the transport pathways utilized by nanoparticles, and eventually to predict nanoparticle fate and behavior.
Abstract: The importance of the protein corona formed around nanoparticles upon entering a biological fluid has recently been highlighted. This corona is, when sufficiently long-lived, thought to govern the particles’ biological fate. However, even this long-lived “hard” corona evolves and re-equilibrates as particles pass from one biological fluid to another, and may be an important feature for long-term fate. Here we show the evolution of the protein corona as a result of transfer of nanoparticles from one biological fluid (plasma) into another (cytosolic fluid), a simple illustrative model for the uptake of nanoparticles into cells. While no direct comparison can be made to what would happen in, for example, the uptake pathway, the results confirm that significant evolution of the corona occurs in the second biological solution, but that the final corona contains a “fingerprint” of its history. This could be evolved to map the transport pathways utilized by nanoparticles, and eventually to predict nanoparticle f...
01 Jan 2011
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TL;DR: In this article, the authors consider the topological structure of two networks derived from Bitcoin's public transaction history and combine these structures with external information and techniques such as context discovery and flow analysis to investigate an alleged theft of Bitcoins.
Abstract: Anonymity in Bitcoin, a peer-to-peer electronic currency system, is a complicated issue. Within the system, users are identified by public-keys only. An attacker wishing to de-anonymize its users will attempt to construct the one-to-many mapping between users and public-keys and associate information external to the system with the users. Bitcoin tries to prevent this attack by storing the mapping of a user to his or her public-keys on that user's node only and by allowing each user to generate as many public-keys as required. In this chapter we consider the topological structure of two networks derived from Bitcoin's public transaction history. We show that the two networks have a non-trivial topological structure, provide complementary views of the Bitcoin system and have implications for anonymity. We combine these structures with external information and techniques such as context discovery and flow analysis to investigate an alleged theft of Bitcoins, which, at the time of the theft, had a market value of approximately half a million U.S. dollars.
TL;DR: In this article, the authors explore sustainable consumption and consider possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade the planet, and propose a macro-institutional approach to fostering sustainability.
Abstract: This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade the planet. Future research approaches to this interdisciplinary topic must be comprehensive and systematic and would benefit from a variety of different perspectives. There are several opportunities for further research; the authors explore three areas in detail. First, they consider the inconsistency between the attitudes and behaviors of consumers with respect to sustainability. Second, they broaden the agenda to explore the role of individual citizens in society. Third, they propose a macroinstitutional approach to fostering sustainability. For each of these separate, but interrelated, opportunities, the authors examine the area in detail and consider possible research avenues and public policy initiatives.
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TL;DR: The PDF4LHC working group as discussed by the authors provided an interim summary of the current recommendations for the use of parton distribution functions (PDFs) and of PDF uncertainties at the LHC, for cross section and cross section uncertainty calculations.
Abstract: This note provides an interim summary of the current recommendations of the PDF4LHC working group for the use of parton distribution functions (PDFs) and of PDF uncertainties at the LHC, for cross section and cross section uncertainty calculations. It also contains a succinct user guide to the computation of PDFs, uncertainties and correlations using available PDF sets. A companion note (the PDF4LHC Working Group Interim Report) summarizes predictions for benchmark cross sections at the LHC at NLO using modern PDFs currently available from 6 PDF fitting groups.
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TL;DR: In this paper, the power of personality traits both as predictors and as causes of academic and economic success, health, and criminal activity is explored, where the authors interpret personality as a construct derived from an economic model of preferences, constraints, and information.
Abstract: This paper explores the power of personality traits both as predictors and as causes of academic and economic success, health, and criminal activity. Measured personality is interpreted as a construct derived from an economic model of preferences, constraints, and information. Evidence is reviewed about the "situational specificity" of personality traits and preferences. An extreme version of the situationist view claims that there are no stable personality traits or preference parameters that persons carry across different situations. Those who hold this view claim that personality psychology has little relevance for economics. The biological and evolutionary origins of personality traits are explored. Personality measurement systems and relationships among the measures used by psychologists are examined. The predictive power of personality measures is compared with the predictive power of measures of cognition captured by IQ and achievement tests. For many outcomes, personality measures are just as predictive as cognitive measures, even after controlling for family background and cognition. Moreover, standard measures of cognition are heavily influenced by personality traits and incentives. Measured personality traits are positively correlated over the life cycle. However, they are not fixed and can be altered by experience and investment. Intervention studies, along with studies in biology and neuroscience, establish a causal basis for the observed effect of personality traits on economic and social outcomes. Personality traits are more malleable over the life cycle compared to cognition, which becomes highly rank stable around age 10. Interventions that change personality are promising avenues for addressing poverty and disadvantage.
TL;DR: These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations.
TL;DR: Future strategies to improve dairy cow fertility are needed for the benefit of the dairy industry and for cow welfare and should be based upon an integrative approach of these events.
TL;DR: A multistage vaccination strategy in which the early antigens Ag85B and 6-kDa early secretory antigenic target (ESAT-6) are combined with the latency-associated protein Rv2660c (H56 vaccine), which confers protective immunity characterized by a more efficient containment of late-stage infection.
Abstract: All tuberculosis vaccines currently in clinical trials are designed as prophylactic vaccines based on early expressed antigens. We have developed a multistage vaccination strategy in which the early antigens Ag85B and 6-kDa early secretory antigenic target (ESAT-6) are combined with the latency-associated protein Rv2660c (H56 vaccine). In CB6F1 mice we show that Rv2660c is stably expressed in late stages of infection despite an overall reduced transcription. The H56 vaccine promotes a T cell response against all protein components that is characterized by a high proportion of polyfunctional CD4(+) T cells. In three different pre-exposure mouse models, H56 confers protective immunity characterized by a more efficient containment of late-stage infection than the Ag85B-ESAT6 vaccine (H1) and BCG. In two mouse models of latent tuberculosis, we show that H56 vaccination after exposure is able to control reactivation and significantly lower the bacterial load compared to adjuvant control mice.
TL;DR: Evidence in humans is provided to support preclinical observations suggesting that inhibiting the β₂-adrenergic signaling pathway can reduce breast cancer progression and mortality.
Abstract: Purpose Preclinical studies have demonstrated that antagonism of β2-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer–specific mortality. Patients and Methods Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (β1/β2 antagonist; n = 70) or atenolol (β1 antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer–specific mortality were assessed. ...
TL;DR: Eight proteins, defects in which are associated with Meckel-Gruber syndrome and nephronophthisis ciliopathies, work together as two functional modules at the transition zone to establish basal body/transition zone connections with the membrane and barricade entry of non-ciliary components into this organelle.
Abstract: Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and related ciliopathies present with overlapping phenotypes and display considerable allelism between at least twelve different genes of largely unexplained function. We demonstrate that the conserved C. elegans B9 domain (MKS-1, MKSR-1, and MKSR-2), MKS-3/TMEM67, MKS-5/RPGRIP1L, MKS-6/CC2D2A, NPHP-1, and NPHP-4 proteins exhibit essential, collective functions at the transition zone (TZ), an underappreciated region at the base of all cilia characterized by Y-shaped assemblages that link axoneme microtubules to surrounding membrane. These TZ proteins functionally interact as members of two distinct modules, which together contribute to an early ciliogenic event. Specifically, MKS/MKSR/NPHP proteins establish basal body/TZ membrane attachments before or coinciding with intraflagellar transport–dependent axoneme extension and subsequently restrict accumulation of nonciliary components within the ciliary compartment. Together, our findings uncover a unified role for eight TZ-localized proteins in basal body anchoring and establishing a ciliary gate during ciliogenesis, and suggest that disrupting ciliary gate function contributes to phenotypic features of the MKS/NPHP disease spectrum.
TL;DR: De novo lipogenesis has pathogenic and prognostic significance for HCC and inhibitors of lipogenic signaling, including those that inhibit the AKT pathway, might be useful as therapeutics for patients with liver cancer.
TL;DR: In this paper, the authors provide an update on recent laboratory research and commercial developments in fast pyrolysis and upgrading techniques, which is a relatively mature technology and is on the verge of commercialisation.
Abstract: Robust alternative technology choices are required in the paradigm shift from the current crude oil-reliant transport fuel platform to a sustainable, more flexible transport infrastructure. In this vein, fast pyrolysis of biomass and upgrading of the product is deemed to have potential as a technology solution. The objective of this review is to provide an update on recent laboratory research and commercial developments in fast pyrolysis and upgrading techniques. Fast pyrolysis is a relatively mature technology and is on the verge of commercialisation. While upgrading of bio-oils is currently confined to laboratory and pilot scale, an increased understanding of upgrading processes has been achieved in recent times.
TL;DR: This review summarizes the recent application of both thermal and non-thermal processing technologies on bioactive content of exotic fruits and their products and discusses the impact of processing conditions on the stability of bioactive compounds in exotic fruits.
TL;DR: The majority of the structural features of the IgG glycome were consistent with previous studies, but sialylation was somewhat higher than reported previously, indicating that the final glycan structures are not a simple result of competing enzymatic activities, but a carefully regulated outcome designed to meet the prevailing physiological needs.
TL;DR: This viewpoint examines currently available evidence favouring the concept of a causal link between psoriasis and cardiovascular disease: systemic inflammation may cause insulin resistance, which in turn triggers endothelial cell dysfunction, leading to atherosclerosis and finally myocardial infarction or stroke.
Abstract: There is increasing awareness that psoriasis is more than 'skin deep'. Several recent reviews focussed on biomarkers indicating the systemic dimension of psoriasis and the aspect of comorbidity psoriasis shares with other chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. Of emerging significance is the relationship to cardiovascular disease, as this contributes substantially to the patients' increased mortality. In this viewpoint, we examine currently available evidence favouring the concept of a causal link between psoriasis and cardiovascular disease: systemic inflammation may cause insulin resistance, which in turn triggers endothelial cell dysfunction, leading to atherosclerosis and finally myocardial infarction or stroke. While this 'psoriatic march' is not yet formally proven, it raises clinically and academically relevant questions, and gains support by recent observations of numerous investigators.
TL;DR: Two separate gamma-ray flares from a young and energetic pulsar powers the well-known Crab Nebula are described and it is suggested that the gamma rays were emitted via synchrotron radiation from peta–electron-volt electrons in a region smaller than 1.4 × 10−2 parsecs.
Abstract: A young and energetic pulsar powers the well-known Crab Nebula. Here, we describe two separate gamma-ray (photon energy greater than 100 mega-electron volts) flares from this source detected by the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. The first flare occurred in February 2009 and lasted approximately 16 days. The second flare was detected in September 2010 and lasted approximately 4 days. During these outbursts, the gamma-ray flux from the nebula increased by factors of four and six, respectively. The brevity of the flares implies that the gamma rays were emitted via synchrotron radiation from peta-electron-volt (10(15) electron volts) electrons in a region smaller than 1.4 × 10(-2) parsecs. These are the highest-energy particles that can be associated with a discrete astronomical source, and they pose challenges to particle acceleration theory.
TL;DR: In this paper, an array of nanomagnets in a kagome lattice structure should support the creation and separation of oppositely charged monopoles, which are connected by Dirac strings of flipped dipoles.
Abstract: An array of nanomagnets in a kagome lattice structure should support the creation and separation of oppositely charged monopoles, which are connected by Dirac strings of flipped dipoles. And indeed, such monopoles and their Dirac strings can be observed at room temperature.