bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL‐10 and the resolution of infections
Authors: Filippi CM , von Herrath MG 
Published: December 2007

AbstractChronic viral infections pose serious health concerns, as secondary complications such as immunodeficiencies and cancers are common. Treating such infections with conventional vaccine approaches has proved to be difficult. Studies in animals and humans suggest that vaccine failure is probably due to exhaustion of antiviral T cell responses, which occurs in a number of chronic infections. Attempts to elucidate the causes of impairment of antiviral immunity have pointed to a role for the immunomodulatory cytokine IL‐10 in the ability of viruses to establish persistence. Induction of IL‐10 production by the host during chronic infection appears to be one of the viral means to alter the class of the antiviral immune response and induce generalized immune suppression. Recent work by us and others suggests that it is possible to resuscitate antiviral immunity by interfering with the IL‐10 signalling pathway. Targeting IL‐10 thus constitutes a promising alternative to conventional vaccine strategies which have not proved to be successful in treating chronic infections. In addition, sterile cure may be achieved with minimal side‐effects by combining agents that alter the IL‐10 signalling pathway with other compounds, such as antiviral drugs or interferon, but also agents neutralizing other crucial elements of T cell exhaustion, such as PD‐1. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Stress proteins in CNS inflammation
Authors: van Noort JM 
Published: December 2007

AbstractStress proteins or heat shock proteins (HSPs) are ubiquitous cellular components that have long been known to act as molecular chaperones. By assisting proper folding and transport of proteins, and by assisting in the degradation of aberrant proteins, they play key roles in cellular metabolism. The frequent accumulation of insoluble protein aggregates during chronic neurodegenerative disorders suggests failure of HSP functions to be a common denominator among such diseases. Recent developments have clarified that functions of HSPs extend well beyond their role in protein folding and degradation alone. Stress‐inducible HSPs also regulate apoptosis, antigen presentation, inflammatory signalling pathways and, intriguingly, also serve as extracellular mediators of inflammation. Several receptors have been identified for extracellular HSPs, which control inflammatory pathways similar to those activated by cytokines and chemokines. In this review, both the traditional and the exciting novel functions of HSPs are discussed, with a focus on their relevance for neurodegeneration and neuroinflammation. Recent advances in this field suggest that HSPs represent attractive novel targets as well as therapeutic entities for CNS disorders. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The immunology of sepsis
Authors: Sriskandan S , Altmann DM 
Published: December 2007

AbstractSepsis, the systemic inflammatory response to infection, is considered the major cause of death among critically ill patients in the developed world. While there is a general view that this reflects contributions from both the pathogen and the host with respect to an inappropriate inflammatory response, there is a lack of agreement as to the key immune mechanisms. This has been reflected in the diverse range of immunotherapies tested in clinical trials, often with rather marginal effects. The case has been made for a pathogenic role of excessive immunity, the so‐called ‘cytokine storm’, and for a role of too little immunity through immune paralysis. Apoptosis is implicated as a key mechanism in both this immune paralysis and the multi‐organ failure that is a feature of severe sepsis. A number of polymorphisms have been implicated in susceptibility to sepsis, including cytokine genes, HLA class II and caspase‐12. In this review we focus in particular on the role of group A streptococci in severe sepsis. Here the effect of bacterial superantigens appears to be a correlate of inflammatory activation, although the precise evolutionary role of the superantigens remains unclear. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Immune activation and inflammation in HIV‐1 infection: causes and consequences
Authors: Appay V , Sauce D 
Published: December 2007

AbstractThorough research on HIV is progressively enabling us to understand the intricate mechanisms that link HIV‐1 infection to the onset of immunodeficiency. The infection and depletion of CD4+ T cells represent the most fundamental events in HIV‐1 infection. However, in recent years, the role played by chronic immune activation and inflammation in HIV pathogenesis has become increasingly apparent: quite paradoxically, immune activation levels are directly associated with HIV‐1 disease progression. In addition, HIV‐1‐infected patients present intriguing similarities with individuals of old age: their immune systems are characterized by a loss of regenerative capacity and an accumulation of ageing T cells. In this review, we discuss the potential reasons for the establishment of sustained immune activation and inflammation from the early stages of HIV‐1 infection, as well as the long‐term consequences of this process on the host immune system and health. A simplified model of HIV pathogenesis is proposed, which links together the three major facets of HIV‐1 infection: the massive depletion of CD4+ T cells, the paradoxical immune activation and the exhaustion of regenerative capacity. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cellular and molecular mechanisms of fibrosis
Authors: Wynn TA 
Published: December 2007

AbstractFibrosis is defined by the overgrowth, hardening, and/or scarring of various tissues and is attributed to excess deposition of extracellular matrix components including collagen. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury. Although current treatments for fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis typically target the inflammatory response, there is accumulating evidence that the mechanisms driving fibrogenesis are distinct from those regulating inflammation. In fact, some studies have suggested that ongoing inflammation is needed to reverse established and progressive fibrosis. The key cellular mediator of fibrosis is the myofibroblast, which when activated serves as the primary collagen‐producing cell. Myofibroblasts are generated from a variety of sources including resident mesenchymal cells, epithelial and endothelial cells in processes termed epithelial/endothelial‐mesenchymal (EMT/EndMT) transition, as well as from circulating fibroblast‐like cells called fibrocytes that are derived from bone‐marrow stem cells. Myofibroblasts are activated by a variety of mechanisms, including paracrine signals derived from lymphocytes and macrophages, autocrine factors secreted by myofibroblasts, and pathogen‐associated molecular patterns (PAMPS) produced by pathogenic organisms that interact with pattern recognition receptors (i.e. TLRs) on fibroblasts. Cytokines (IL‐13, IL‐21, TGF‐β1), chemokines (MCP‐1, MIP‐1β), angiogenic factors (VEGF), growth factors (PDGF), peroxisome proliferator‐activated receptors (PPARs), acute phase proteins (SAP), caspases, and components of the renin–angiotensin–aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs. This review explores our current understanding of the cellular and molecular mechanisms of fibrogenesis. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Macrophage activation by endogenous danger signals
Authors: Zhang X , Mosser DM 
Published: December 2007

AbstractMacrophages are cells that function as a first line of defence against invading microorganisms. One of the hallmarks of macrophages is their ability to become activated in response to exogenous ‘danger signals’. Most microbes have molecular patterns (PAMPS) that are recognized by macrophages and trigger this activation response. There are many aspects of the activation response to PAMPS that are recapitulated when macrophages encounter endogenous danger signals. In response to damaged or stressed self, macrophages undergo physiological changes that include the initiation of signal transduction cascades from germline‐encoded receptors, resulting in the elaboration of chemokines, cytokines and toxic mediators. This response to endogenous mediators can enhance inflammation, and thereby contribute to autoimmune pathologies. Often the overall inflammatory response is the result of cooperative activation signals from both exogenous and endogenous signals. Macrophage activation plays a critical role, not only in the initiation of the inflammatory response but also in the resolution of this response. The clearance of granulocytes and the elaboration of anti‐inflammatory mediators by macrophages contribute to the dissolution of the inflammatory response. Thus, macrophages are a key player in the initiation, propagation and resolution of inflammation. This review summarizes our understanding of the role of macrophages in inflammation. We pay particular attention to the endogenous danger signals that macrophages may encounter and the responses that these signals induce. The molecular mechanisms responsible for these responses and the diseases that result from inappropriately controlled macrophage activation are also examined. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Innate and adaptive mechanisms to control of pathological intestinal inflammation
Authors: Kelsall BL 
Published: December 2007

AbstractThe intestine is the home of a tremendous number of commensal organisms that have a primary role in host metabolism. As a consquence, the gut mucosa has evolved multiple layers of protection. This review highlights both innate and adaptive mechanisms that prevent bacterial invasion and abnormal intestinal inflamamation, how a failure of these mechanisms may be involved in the pathogenesis of inflammatory bowel diseases, and discusses new findings implicating dendritic cells as central to the induction of active mucosal tolerance to commensal bacteria. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The role of natural killer T cells in lung inflammation
Authors: Boyton R 
Published: December 2007

AbstractInvariant NK T cells (iNKT) bridge the innate and adaptive immune response, being characterized by the ability to use invariant T cell receptors to recognize glycolipid antigens presented by CD1d, leading to an explosive cytokine effector response. As such it has been proposed that iNKT cells perform important roles as both effector and regulatory cells in a wide range of disease settings. These roles have been characterized in experiments depending on the use of iNKT‐null mice, due to lack of either CD1d expression or Jα18 and the use of CD1d tetramers loaded with the model glycolipid antigen, α‐galactosylceramide (αGalCer). Several studies have examined lung disease, infectious and allergic, in humans and mice. While the lung itself does not carry an exceptionally large population of iNKT cells (compared with, say, the liver), it does appear to be a site at which these cells can exert a profound effect. Several models of bacterial, fungal and viral murine lung infection have been investigated that have sometimes produced conflicting results. Abrogation of iNKT cell function in knockouts is often associated with disease exacerbation, indicating a regulatory role in lung infection. Studies in murine asthma models and in patients have similarly probed the role of iNKT cells in these settings. While there are again somewhat contradictory findings, evidence suggests a likely role for iNKT cells in mediating airway hyper‐responsiveness (AHR), but probably not in Th2 polarization or lung eosinophilia. In marginally different models, administration of αGalCer has either ameliorated or exacerbated AHR. Different studies of BAL from human asthma patients show variously that there is either a very enlarged population of iNKT cells in the asthmatic lung, or that there is no significant difference from controls. Taken together, there are some observations that argue compellingly for an important role of iNKT cells in the lung, but resolution of some of the contradictory findings may await the development of reagents capable of providing alternative readouts of iNKT activation in these diverse disease settings. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Innate immunity in inflammatory bowel disease: a disease hypothesis
Authors: Marks DJB , Segal AW 
Published: December 2007

AbstractCrohn's disease arises from a defective interaction between the highly concentrated mass of bacteria in the gastrointestinal tract and the underlying tissues. It has generally been believed to result from an excessively exuberant inflammatory response or from ‘autoimmunity’. Recent evidence has emerged that the problem is instead a failure of the way in which the body responds to the penetration of bacteria and other bowel contents through the intestinal mucosal barrier. Rather than Crohn's disease being caused by excessive inflammation, the primary mechanism is actually that of an immunodeficiency. Failure of inflammatory mediator production leads to insufficient recruitment of neutrophils, resulting in inadequate removal of bacteria and other debris. This impairment of acute inflammation can be compensated in some circumstances by signalling through NOD2. If not cleared, the foreign material in the bowel wall is taken up within macrophages, eliciting a granulomatous reaction and the local and systemic sequelae so characteristic of Crohn's disease. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Molecular and cellular themes in inflammation and immunology
Authors: Herrington CS , Hall PA 
Published: December 2007

AbstractThis issue of the Journal of Pathology contains a series of cutting‐edge review articles that deal with the broad issue of inflammatory and immunological disease mechanisms. Of necessity, these reviews deal with selected topics but the mixture of articles on specific signalling pathways and mediators with articles addressing individual organ systems provides a broad overview of the field. These contributions provide insight into current areas of debate in inflammation and immunology. In particular, they highlight current interest in the interface between innate and adaptive immunity and present intriguing prospects for future therapeutic developments in a variety of disease areas. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Development of nonlinear constitutive laws for anisotropic and asymmetric fiber reinforced composites
Authors: Kim Ji Hoon , Lee Myoung‐Gyu , Ryou Hansun , Chung Kwansoo , Youn Jae Ryoun , Kang Tae Jin 
Published: December 2007

AbstractA plane‐stress constitutive law was developed to describe the inelastic nonlinear, anisotropic, and asymmetric mechanical behavior of fiber reinforced composites under the elasto‐plasticity framework, in particular, based on the kinematic hardening model. A yield criterion that describes anisotropic and asymmetric yield behavior was proposed, while the anisotropic translation of the yield surface was assumed to account for the directional difference of hardening behavior. The proposed constitutive equation was then implemented into the commercial FE program ABAQUS with the aid of the user material subroutine. Experimental procedures to characterize the material parameters of the proposed constitutive equation were presented for 3D braided glass/Kevlar fiber reinforced composites. Verification performed for three point bending tests showed good agreements. POLYM. COMPOS., 2008. © 2007 Society of Plastics Engineers
Fiber orientation in injection molding with rotating flow
Authors: Silva Cristina A. , Viana Júlio C. , van Hattum Ferrie W.J. , Cunha António M. 
Published: December 2007

AbstractThe development of fiber orientation in injection molding was manipulated by a special molding tool, the RCEM mold, which imposes a rotation action by one of the cavity surfaces during the filling stage. Center‐gated disc moldings were produced from glass fiber reinforced polypropylene with different cavity rotation velocities, inducing distinct distributions and levels of fiber orientation. The morphologies of the moldings were characterized by optical and electronic microscopy. The through‐thickness profiles of fiber orientation were assessed by means of the orientation tensor, and the relationship between the processing thermo‐mechanical environment and the fiber orientation was established. At high rotation velocities, the resulting fiber orientation pattern is mainly controlled by the rotational motion, inducing a much more homogeneous through‐the‐thickness fiber orientation distribution, with a preferential alignment on the circumferential direction. POLYM. ENG. SCI., 2008. © 2007 Society of Plastics Engineers
Influence of molecular weight on the electrification of linear polyethylenes during extrusion: Identification of two different mechanisms for charge generation
Authors: Rodríguez‐González Francisco , Pérez‐González José , de Vargas Lourdes , Moreno Edgard , González‐Santos Germán 
Published: December 2007

AbstractThe phenomenon of electrification is the accumulation of electric charge in a material. Polymers may become electrified when subjected to intense friction during their processing or under working conditions and the accumulated electric charge may change their adhesion and friction properties. In this work, a study of the influence of molecular weight and chain mobility on the electrification of linear low‐density polyethylenes under continuous extrusion is presented. The use of different die materials, polymer processing additives, as well as slip and no slip flow conditions allowed the identification of two different mechanisms for electric charge generation in the melts; namely, the stripping of an electrical double layer acting in the absence of slip, and dynamic frictional electrification, or tribocharging acting under strong slip conditions. The magnitude of the electric charge was found to increase with polymer molecular weight and die length, and exhibited a local maximum as a function of the average velocity of the melt in both cases. The height of the maximum increased along with the molecular mobility. The experimental results were compared with the numerical solution of the equation of continuity for charge transport and it is shown that it does not describe the experimental results because it does not consider the additional mechanism of charge generation introduced by strong slip at the die wall. POLYM. ENG. SCI., 2008. © 2007 Society of Plastics Engineers
Reversible thermal gelation of soft semi‐crystalline polyethylene microparticles with surface interactions in squalane
Authors: Ling Gerald H. , Shaw Montgomery T. 
Published: December 2007

AbstractThe effect of temperature on the steady‐shear viscosity of a soft semi‐crystalline crosslinked‐polyethylene microparticle suspension in squalane was studied using rotational rheometry. The results show a sharp increase in the viscosity of the system occurring at about 86°C. The magnitude of this spike is dependent on the concentration of the suspension and is reproducible over multiple heating and cooling cycles. This phenomenon has been attributed to the melting of the crystalline regions within the particles, causing them to swell by soaking up squalane. The Mooney equation was used to model the viscosity data based on swelling data obtained from separate experiments. The results showed that the model is inadequate for describing the observed phenomenon, suggesting the possibility of additional interactions existing among the particles. POLYM. ENG. SCI., 2008. © 2007 Society of Plastics Engineers
Conventional and nanometric nucleating agents in poly(ϵ‐caprolactone) foaming: Crystals vs. bubbles nucleation
Authors: Marrazzo Carlo , Di Maio Ernesto , Iannace Salvatore 
Published: December 2007

AbstractThe aim of this article was to investigate the nucleating ability of different nucleating agents for the foaming of poly(ε‐caprolactone), a biodegradable, semicrystalline polymer. In particular, the efficiency of the nucleating agent in inducing the formation of the gaseous phase has been compared to the efficiency in inducing the formation of the crystalline phase. In effect, in foaming of semicrystalline polymers, bubble nucleation and crystal nucleation are concurrent and somehow interacting phenomena. Here, these two aspects have been evidenced and clarified. Foams were prepared by using a batch process with the pressure quench method, with nitrogen and carbon dioxide as the blowing agents. Conventional and novel nucleating agents were used: talc has been compared to several novel nanometric particles of different geometries and dimensions, such as titanium dioxide and alumina powders, exfoliated and intercalated clays, and carbon nanotubes. Foam densities and morphologies, in terms of number of cells per initial unit volume, were measured and found to depend both on crystalline phase nucleation and gaseous phase nucleation. In fact, the different nucleating agents, depending on shape, dimension, and surface functionalization, selectively nucleated the crystallites and/or the bubbles, affecting, respectively, bubble growth (and, hence, final foam density) and bubble nucleation (and, hence, cell number density—morphology). POLYM. ENG. SCI., 2008. © 2007 Society of Plastics Engineers
Sharkskin and oscillating melt fracture: Why in slit and capillary dies and not in annular dies?
Authors: Delgadillo‐Velázquez O. , Georgiou G. , Sentmanat M. , Hatzikiriakos S.G. 
Published: December 2007

AbstractThe sharkskin and stick‐slip polymer extrusion instabilities are studied primarily as functions of the type of die geometry. Experimental observations concerning the flow curves, the critical wall shear stress for the onset of the instabilities, the pressure and flow rate oscillations, and the effects of geometry and operating conditions are presented for linear low‐density polyethylenes. It is found that sharkskin and stick‐slip instabilities are present in the capillary and slit extrusion. However, annular extrusion stick‐slip and sharkskin are absent at high ratios of the inside‐to‐outside diameter of the annular die. This observation also explains the absence of these phenomena in other polymer processing operations such as film blowing. These phenomena are explained in terms of the surface‐to‐volume ratio of the extrudates, that is, if this ratio is high, sharkskin and stick‐slip are absent. POLYM. ENG. SCI., 2008. © 2007 Society of Plastics Engineers