LINDSAY Virtual Nephron: From Physics to Physiology

The LINDSAY Virtual Human is a project that aims to design and simulate a human being in a virtual environment [1].  LINDSAY Composer is one of the components of the LINDSAY Virtual Human; it is a dedicated application that acts as a highly versatile simulation environment. The LINDSAY Virtual Nephron is a summer project that aimed to recreate the most basic functionality within a human nephron, while simultaneously ensuring that the mechanisms within the model were both accurate and reusable in other simulations. Using LINDSAY Composer as a test environment, two basic behaviours were developed for the virtual nephron: a tool to accommodate for ubiquitous flow, and selective permeability in the vessels of the nephron. The former is used to ensure that entities flowing through a complex vessel can navigate smoothly within the vessel walls. This was achieved using ray casting, a method for detection of nearby physical structures and adjusting the entity’s path to flow along the vessel in accordance with its distance from the vessel, as well as any forces acting on the entity. The latter selectively allows entities to pass from one vessel to another. Focus was placed on the relationship between ADH and water levels in the reabsorption model, osmotic pressure affected ADH release, which in turn altered membrane permeability. These simple functions were found to produce reasonably realistic behaviours for the entities in the simulation without the need for strictly defined behaviours through hard coding and scripted actions that are typical of most existing simulations. This allows the simulation to be highly modular and adaptable, in turn making it possible for these mechanisms to be reused and adapted for simulations in other regions of the body (such as circulation and digestion)

An undergraduate perspective on LINDSAY Composer: bridging the gap between software engineering and physiology

LINDSAY Composer is a project aiming to capitalise on advances in computer technology, providing a fully immersive and interactive platform for modelling physiological systems. Allowing its users to design models using a set of customisable, shared components, LINDSAY Composer permits for a diverse range of systems to be simulated, as well as allowing for these systems to interact with one another. We present three undergraduate projects here, reflecting on the adaptability of LINDSAY Composer; the program has allowed for novel user-interactions to be implemented, alongside two simulations, the nephron and reflex arc, to be modelled with high accuracy and performance. Despite being disjoint, these projects are all designed within LINDSAY Composer and are built upon the same basic components. Their unique functions and behaviours are implemented as specialised components that confer system-specific behaviours, illustrating the Composer's potential applicability in educational and clinical settings as a platform for providing a straightforward means of visualising any system of the user's choosing, as well as its capacity to adapt to ever-changing technological paradigms

Antecedents Of Information Systems Habit In Sporadic Use Of Learning Systems: Personalization And Peer Effects

Research on Information Systems (IS) habit formation has been focused mostly on IS habit’s effect on IS continuance. Antecedents of IS habit formation, as reported in the literature, are primarily on users’ prior behavior and comprehensiveness of usage. Most of the literature focus on analyzing the relationship between users’ IS usage behavior and IS habit. Limited work has been reported to investigate genuine and practical ways to develop IS habit, as well as to address the issue of sporadic IS usage, which leads to different interpretations on IS habit and continuance. This study purports to address the theoretical gap on issues related to IS habit antecedents and sporadic IS usage habit in the educational context. Adopting an empirical survey in universities’ (sub-degree and postgraduate settings) learning systems usage, data from cross-sectional survey on learning systems usage on per-course basis is analyzed. Theoretically, our results suggest that IT functionality design (personalization) and social factor (peer effect) have strong and positive relationship on IS habit with respect to the sporadic usage nature of course based learning systems. Practically, we suggest some dimensions for teachers on curriculum design that facilitate IS habit development, e.g., maintaining an online community with substantial student peer input at the early stage of a course

Non-enzymatic roles of human RAD51 at stalled replication forks

The central recombination enzyme RAD51 has been implicated in replication fork processing and restart in response to replication stress. Here, we use a separation-of-function allele of RAD51 that retains DNA binding, but not D-loop activity, to reveal mechanistic aspects of RAD51’s roles in the response to replication stress. Here, we find that cells lacking RAD51’s enzymatic activity protect replication forks from MRE11-dependent degradation, as expected from previous studies. Unexpectedly, we find that RAD51’s strand exchange activity is not required to convert stalled forks to a form that can be degraded by DNA2. Such conversion was shown previously to require replication fork regression, supporting a model in which fork regression depends on a non-enzymatic function of RAD51. We also show RAD51 promotes replication restart by both strand exchange-dependent and strand exchange-independent mechanisms

The importance of conflict characteristics for the diffusion of international mediation

This article argues that similar conflict characteristics form links between crises, which signal the relevant actors – that is, the belligerents and the potential mediator(s) – that a comparable approach in terms of third-party mediation could be suitable across these disputes – even if the relevant parties are not the same. Specifically, demand (antagonists) and supply-side actors (mediators) are likely to employ the heuristic of learning from and emulating the mediation behavior in similar crises. The empirical analysis, using data from the International Crisis Behavior project, shows that comparable patterns in violence, arguably the most visible and salient conflict characteristic, are associated with mediation traveling across crises; other dispute characteristics incorporated into spatial lags are not, however. Hence, particularly as domestic/unit-level (monadic) influences are controlled for, the effect of common exposure is taken into account, and different estimation strategies are used, the results emphasize that there is a genuine diffusion process via common levels of violence in the context of international mediation. </jats:p

Blockade of Aquaporin 1 Inhibits Proliferation, Motility, and Metastatic Potential of Mesothelioma In Vitro but not in an In Vivo Model

Copyright © 2015 Sonja Klebe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background. Malignant mesothelioma (MM) is an aggressive tumor of the serosal membranes, mostly the pleura. It is related to asbestos exposure and has a poor prognosis. MM has a long latency period, and incidence is predicted to remain stable or increase until 2020. Currently, no biomarkers for a specific targeted therapy are available. Previously, we observed that expression of aquaporin 1 (AQP1) was an indicator of prognosis in two independent cohorts. Here we determine whether AQP1 inhibition has therapeutic potential in the treatment of MM. Methods. Functional studies were performed with H226 cells and primary MM cells harvested from pleural effusions. AQP1 expression and mesothelial phenotype was determined by immunohistochemistry. AQP1 function was inhibited by a pharmacological blocker (AqB050) or AQP1-specific siRNA. Cell proliferation, migration, and anchorage-independent cell growth were assessed. A nude mouse heterotopic xenograft model of MM was utilised for the in vivo studies. Results. Inhibition of AQP1 significantly decreases cell proliferation, metastatic potential, and motility without inducing nonspecific cytotoxicity or increasing apoptosis. In vivo blockade of AQP1 had no biologically significant effect on growth of established tumours. Conclusions. Targeted blockade of AQP1 restricts MM growth and migration in vitro. Further work is warranted to fully evaluate treatment potential in vivo

Are chest compressions safe for the patient reconstructed with sternal plates? Evaluating the safety of cardiopulmonary resuscitation using a human cadaveric model

<p>Abstract</p> <p>Background</p> <p>Plate and screw fixation is a recent addition to the sternal wound treatment armamentarium. Patients undergoing cardiac and major vascular surgery have a higher risk of postoperative arrest than other elective patients. Those who undergo sternotomy for either cardiac or major vascular procedures are at a higher risk of postoperative arrest. Sternal plate design allows quick access to the mediastinum facilitating open cardiac massage, but chest compressions are the mainstay of re-establishing cardiac output in the event of arrest. The response of sternal plates and the chest wall to compressions when plated has not been studied. The safety of performing this maneuver is unknown. This study intends to demonstrate compressions are safe after sternal plating.</p> <p>Methods</p> <p>We investigated the effect of chest compressions on the plated sternum using a human cadaveric model. Cadavers were plated, an arrest was simulated, and an experienced physician performed a simulated resuscitation. Intrathoracic pressure was monitored throughout to ensure the plates encountered an appropriate degree of force. The hardware and viscera were evaluated for failure and trauma respectively.</p> <p>Results</p> <p>No hardware failure or obvious visceral trauma was observed. Rib fractures beyond the boundaries of the plates were noted but the incidence was comparable to control and to the fracture incidence after resuscitation previously cited in the literature.</p> <p>Conclusions</p> <p>From this work we believe chest compressions are safe for the patient with sternal plates when proper plating technique is used. We advocate the use of this life-saving maneuver as part of an ACLS resuscitation in the event of an arrest for rapidly re-establishing circulation.</p

Macrophage coordination of the interferon lambda immune response

Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria, and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14+ monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes

The Fight against the Influenza A Virus H1N1: Synthesis, Molecular Modeling, and Biological Evaluation of Benzofurazan Derivatives as Viral RNA Polymerase Inhibitors

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