Back to the future:re-establishing guinea pig in vivo asthma models

Research using animal models of asthma is currently dominated by mouse models. This has been driven by the comprehensive knowledge on inflammatory and immune reactions in mice, as well as tools to produce genetically modified mice. Many of the identified therapeutic targets influencing airway hyper-responsiveness and inflammation in mouse models, have however been disappointing when tested clinically in asthma. It is therefore a great need for new animal models that more closely resemble human asthma. The guinea pig has for decades been used in asthma research and a comprehensive table of different protocols for asthma models is presented. The studies have primarily been focused on the pharmacological aspects of the disease, where the guinea pig undoubtedly is superior to mice. Further reasons are the anatomical and physiological similarities between human and guinea pig airways compared with that of the mouse, especially with respect to airway branching, neurophysiology, pulmonary circulation and smooth muscle distribution, as well as mast cell localization and mediator secretion. Lack of reagents and specific molecular tools to study inflammatory and immunological reactions in the guinea pig has however greatly diminished its use in asthma research. The aim in this position paper is to review and summarize what we know about different aspects of the use of guinea pig in vivo models for asthma research. The associated aim is to highlight the unmet needs that have to be addressed in the future

Machining simulations and their use in industry

Machining simulations is a challenge both with respect to demands on robust numerical methods as well as modelling issues. The paper outlines some of the challenges but also current use of simulations at Sandvik Coromant.Godkänd; 2005; 20091015 (ysko

A Web-Enabled Visualization Toolkit for Geovisual Analytics

We introduce a framework and class library (GAV Flash) implemented in Adobe’s ActionScript, designed with the intention to significantly shorten the time and effort needed to develop customized web-enabled applications for visual analytics or geovisual analytics tasks. Through an atomic layered component architecture, GAV Flash provides a collection of common geo- and information visualization representations extended with motion behavior including scatter matrix, extended parallel coordinates, table lens, choropleth map and treemap, integrated in a multiple, timelinked layout. Versatile interaction methods are drawn from many data visualization research areas and optimized for dynamic web visualization of spatio-temporal and multivariate data. Based on layered component thinking and the use of programming interface mechanism the GAV Flash architecture is open and facilitates the creation of new or improved versions of existing components so that ideas can be tried out or optimized rapidly in a fully functional environment. Following the Visual Analytics mantra, a mechanism “snapshot ” for saving the explorative results of a reasoning process is developed that aids collaboration and publication of gained insight and knowledge embedded as dynamic visualizations in blogs or web pages with associative metadata or “storytelling”

Tolerance analysis of surface-to-surface contacts using finite element analysis

The accuracy of a cutting tool is dependent on the surface-to-surface contact between the tool body and the insert. Depending on the application, the forces generated during a cutting operation will change in both magnitude and direction. This will alter the contact locations between the tool body and carbide insert thus affecting on both tool life and key characteristics such as cutting performance and productivity. In this article, a methodology is presented to analyse contact variation in the interface between the tool body and the carbide insert. Results presented in this paper can be used for tolerance allocation of surface-to-surface contacts

New methods for in-process identification of modal parameters in milling

Chatter vibrations encountered in machining can degrade surface finish and damage the machining hardware. Since chatter originates from unstable interaction of the machining process and the machining structure, information about vibration parameters of the machining structure should be used to predict combinations of cutting parameters that allow stable machining. While modal test methods, for example those with impact hammers, are widely used to identify structural parameters; the need for sophisticated test equipment is prohibitive in their use. Furthermore, dynamic properties of critical components of a machine tool may change as they get affected by cutting loads, material removal and spindle rotation. Recently few algorithms have been proposed that identify the in-process dynamic parameters by frequency measurements, thus avoiding these problems. In this paper, some of these algorithms are reviewed and their capabilities and limitations in processing am experimental data set are compared and discussed. © 2018 The Authors. Published by Elsevier Ltd

Unaltered neurocardiovascular reactions to mental stress after renal sympathetic denervation

Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at rest remains controversial. Mental stress (MS) induces transient changes in sympathetic nerve activity, heart rate (HR) and blood pressure (BP). It is not known whether RDN modifies these changes. Purpose: The main objective was to assess the effect of RDN on MSNA and BP alterations during MS. Methods: In 14 patients (11 included in analysis) with resistant hypertension multi-unit MSNA, BP (Finometer ®) and HR were assessed at rest and during forced arithmetics at baseline and 6 months after RDN. Results: Systolic office BP decreased significantly 6 months after RDN (185 ± 29 vs.175 ± 33 mmHG; p = 0.04). No significant changes in MSNA at rest (68 ± 5 vs 73 ± 5 bursts/100hb; p = 0.43) were noted and no significant stress-induced change in group averaged sympathetic activity was found pre- (101 ± 24%; p = 0.9) or post-intervention (108 ± 26%; p = 0.37). Stress was associated with significant increases in mean arterial BP (p < 0.01) and HR (p < 0.01) at baseline, reactions which remained unaltered after intervention. We did not note any correlation between sympathetic nerve activity and BP changes after RDN. Conclusion: Thus, in our group of resistant hypertensives we find no support for the hypothesis that the BP-lowering effect of RDN depends on altered neurovascular responses to stress

A Modified Johnson-Cook Model for Ferritic-Pearlitic Steel in Dynamic Strain Aging Regime

In this study, the flow stress behavior of ferritic-pearlitic steel (C45E steel) is investigated through isothermal compression testing at different strain rates (1 s&#8722;1, 5 s&#8722;1, and 60 s&#8722;1) and temperatures ranging from 200 to 700 &#176;C. The stress-strain curves obtained from experimental testing were post-processed to obtain true stress-true plastic strain curves. To fit the experimental data to well-known material models, Johnson-Cook (J-C) model was investigated and found to have a poor fit. Analysis of the flow stress as a function of temperature and strain rate showed that among other deformation mechanisms dynamic strain aging mechanism was active between the temperature range 200 and 400 &#176;C for varying strain rates and J-C model is unable to capture this phenomenon. This lead to the need to modify the J-C model for the material under investigation. Therefore, the original J-C model parameters A, B and n are modified using the polynomial equation to capture its dependence on temperature and strain rate. The results show the ability of the modified J-C model to describe the flow behavior satisfactorily while dynamic strain aging was operative

Brain structural and functional correlates to defense-related inhibition of muscle sympathetic nerve activity in man

An individual’s blood pressure (BP) reactivity to stress is linked to increased risk of hypertension and cardiovascular disease. However, inter- and intra-individual BP variability makes understanding the coupling between stress, BP reactivity, and long-term outcomes challenging. Previous microneurographic studies of sympathetic signaling to muscle vasculature (i.e. muscle sympathetic nerve activity, MSNA) have established a neural predictor for an individual’s BP reactivity during short-lasting stress. Unfortunately, this method is invasive, technically demanding, and time-consuming and thus not optimal for widespread use. Potential central nervous system correlates have not been investigated. We used MagnetoEncephaloGraphy and Magnetic Resonance Imaging to search for neural correlates to sympathetic response profiles within the central autonomic network and sensorimotor (Rolandic) regions in 20 healthy young males. The main correlates include (a) Rolandic beta rebound and an anterior cingulate cortex (ACC) response elicited by sudden stimulation and (b) cortical thickness in the ACC. Our findings highlight the involvement of the ACC in reactions to stress entailing peripheral sympathetic responses to environmental stimuli. The Rolandic response furthermore indicates a surprisingly strong link between somatosensory and autonomic processes. Our results thus demonstrate the potential in using non-invasive neuroimaging-based measures of stress-related MSNA reactions, previously assessed only using invasive microneurography

Back to the future: re-establishing guinea pig in vivo asthma models

Research using animal models of asthma is currently dominated by mouse models. This has been driven by the comprehensive knowledge on inflammatory and immune reactions in mice, as well as tools to produce genetically modified mice. Many of the identified therapeutic targets influencing airway hyper-responsiveness and inflammation in mouse models, have however been disappointing when tested clinically in asthma. It is therefore a great need for new animal models that more closely resemble human asthma. The guinea pig has for decades been used in asthma research and a comprehensive table of different protocols for asthma models is presented. The studies have primarily been focused on the pharmacological aspects of the disease, where the guinea pig undoubtedly is superior to mice. Further reasons are the anatomical and physiological similarities between human and guinea pig airways compared with that of the mouse, especially with respect to airway branching, neurophysiology, pulmonary circulation and smooth muscle distribution, as well as mast cell localization and mediator secretion. Lack of reagents and specific molecular tools to study inflammatory and immunological reactions in the guinea pig has however greatly diminished its use in asthma research. The aim in this position paper is to review and summarize what we know about different aspects of the use of guinea pig in vivo models for asthma research. The associated aim is to highlight the unmet needs that have to be addressed in the future