1,845 research outputs found

    Operational Semantics of Process Monitors

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    CSPe is a specification language for runtime monitors that can directly express concurrency in a bottom-up manner that composes the system from simpler, interacting components. It includes constructs to explicitly flag failures to the monitor, which unlike deadlocks and livelocks in conventional process algebras, propagate globally and aborts the whole system's execution. Although CSPe has a trace semantics along with an implementation demonstrating acceptable performance, it lacks an operational semantics. An operational semantics is not only more accessible than trace semantics but also indispensable for ensuring the correctness of the implementation. Furthermore, a process algebra like CSPe admits multiple denotational semantics appropriate for different purposes, and an operational semantics is the basis for justifying such semantics' integrity and relevance. In this paper, we develop an SOS-style operational semantics for CSPe, which properly accounts for explicit failures and will serve as a basis for further study of its properties, its optimization, and its use in runtime verification

    Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium

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    Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs

    Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

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    The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

    Surfactant protein D modulates HIV infection of both T-cells and dendritic cells

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    Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo

    A pilot study comparing the metabolic profiles of elite-level athletes from different sporting disciplines

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    Background: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Methods: Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Results: Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. Conclusions: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications

    Targeting the TGF-β1 Pathway to Prevent Normal Tissue Injury After Cancer Therapy

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    Evidence supporting the critical role of transforming growth factor β1 in the development of normal tissue injury after cancer therapy is reviewed and the results of recent research aimed at preventing normal tissue injury by targeting the transforming growth factor β1 pathway are presented

    ARPES: A probe of electronic correlations

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    Angle-resolved photoemission spectroscopy (ARPES) is one of the most direct methods of studying the electronic structure of solids. By measuring the kinetic energy and angular distribution of the electrons photoemitted from a sample illuminated with sufficiently high-energy radiation, one can gain information on both the energy and momentum of the electrons propagating inside a material. This is of vital importance in elucidating the connection between electronic, magnetic, and chemical structure of solids, in particular for those complex systems which cannot be appropriately described within the independent-particle picture. Among the various classes of complex systems, of great interest are the transition metal oxides, which have been at the center stage in condensed matter physics for the last four decades. Following a general introduction to the topic, we will lay the theoretical basis needed to understand the pivotal role of ARPES in the study of such systems. After a brief overview on the state-of-the-art capabilities of the technique, we will review some of the most interesting and relevant case studies of the novel physics revealed by ARPES in 3d-, 4d- and 5d-based oxides.Comment: Chapter to appear in "Strongly Correlated Systems: Experimental Techniques", edited by A. Avella and F. Mancini, Springer Series in Solid-State Sciences (2013). A high-resolution version can be found at: http://www.phas.ubc.ca/~quantmat/ARPES/PUBLICATIONS/Reviews/ARPES_Springer.pdf. arXiv admin note: text overlap with arXiv:cond-mat/0307085, arXiv:cond-mat/020850

    Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

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    Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

    Plastic shrinkage cracking of concrete - Roles of osmotic suction

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    Plastic shrinkage cracking of concrete occurs when the stresses arising in the concrete, due to a combination of suction and restraints of deformation such as reinforcement or formwork, equal its strength. However, three different types of suctions should be distinguished, namely total, matric and osmotic suctions. Although the total suction comprises matric and osmotic suctions, it is often used interchangeably with matric suction, with the underlying unconfirmed assumption that either the osmotic suction or its effect is negligible. In this paper, after a discussion of the pore moisture suctions and strength of unsaturated early-age concrete, experimental investigations of the suctions arising in, and the tensile strength and shear strength of, fly ash mixed with solutions of different osmotic suctions are described. It was found that osmotic suction has negligible effect on the shear and tensile strength, and hence, by inference, the inter-particle stresses in the fly ash mixture and early-age concrete. This strongly suggests that the role played by osmotic suction in the plastic shrinkage cracking of concrete is minimal and, accordingly, justifies the focus of earlier researchers on matric suction only
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