Obstructions to Pin Structures on Kleinian Manifolds

We develop various topological notions on four-manifolds of Kleinian signature $(- - + +)$. In particular, we extend the concept of `Kleinian metric homotopy' to non-orientable manifolds. We then derive the topological obstructions to pin-Klein cobordism, for all of the pin groups. Finally, we discuss various examples and applications which arise from this work.Comment: 20 pages, Latex, 2 xfigures available from Andrew Chamblin at [email protected]

BOUNDARY CONDITIONS FOR THE SCALAR FIELD IN THE PRESENCE OF SIGNATURE CHANGE

We show that, contrary to recent criticism, our previous work yields a reasonable class of solutions for the massless scalar field in the presence of signature change.Comment: 11 pages, Plain Tex, no figure

Implementing a Business Process Management System Using ADEPT: A Real-World Case Study

This article describes how the agent-based design of ADEPT (advanced decision environment for processed tasks) and implementation philosophy was used to prototype a business process management system for a real-world application. The application illustrated is based on the British Telecom (BT) business process of providing a quote to a customer for installing a network to deliver a specified type of telecommunication service. Particular emphasis is placed upon the techniques developed for specifying services, allowing heterogeneous information models to interoperate, allowing rich and flexible interagent negotiation to occur, and on the issues related to interfacing agent-based systems and humans. This article builds upon the companion article (Applied Artificial Intelligence Vol.14, no 2, pgs. 145-189) that provides details of the rationale and design of the ADEPT technology deployed in this application

Spin Structures on Kleinian Manifolds

We derive the topological obstruction to spin-Klein cobordism. This result has implications for signature change in general relativity, and for the $N=2$ superstring.Comment: 8 page

Initial Value Problems and Signature Change

We make a rigorous study of classical field equations on a 2-dimensional signature changing spacetime using the techniques of operator theory. Boundary conditions at the surface of signature change are determined by forming self-adjoint extensions of the Schr\"odinger Hamiltonian. We show that the initial value problem for the Klein--Gordon equation on this spacetime is ill-posed in the sense that its solutions are unstable. Furthermore, if the initial data is smooth and compactly supported away from the surface of signature change, the solution has divergent $L^2$-norm after finite time.Comment: 33 pages, LaTeX The introduction has been altered, and new work (relating our previous results to continuous signature change) has been include

On metric-connection compatibility and the signature change of space-time

We discuss and investigate the problem of existence of metric-compatible linear connections for a given space-time metric which is, generally, assumed to be semi-pseudo-Riemannian. We prove that under sufficiently general conditions such connections exist iff the rank and signature of the metric are constant. On this base we analyze possible changes of the space-time signature.Comment: 18 standard LaTeX 2e pages. The packages AMS-LaTeX and amsfonts are require

Challenges of Incorporating Digital Health Technology Outcomes in a Clinical Trial: Experiences from PD STAT.

Digital health technologies (DHTs) have great potential for use as clinical trial outcomes; however, practical issues need to be addressed in order to maximise their benefit. We describe our experience of incorporating two DHTs as secondary/exploratory outcome measures in PD STAT, a randomised clinical trial of simvastatin in people with Parkinson's disease. We found much higher rates of missing data in the DHTs than the traditional outcome measures, in particular due to technical and software difficulties. We discuss methods to address these obstacles in terms of protocol design, workforce training and data management

Challenges of Incorporating Digital Health Technology Outcomes in a Clinical Trial: Experiences from PD STAT

\ua9 2022 - The authors. Published by IOS Press.Digital health technologies (DHTs) have great potential for use as clinical trial outcomes; however, practical issues need to be addressed in order to maximise their benefit. We describe our experience of incorporating two DHTs as secondary/exploratory outcome measures in PD STAT, a randomised clinical trial of simvastatin in people with Parkinson\u27s disease. We found much higher rates of missing data in the DHTs than the traditional outcome measures, in particular due to technical and software difficulties. We discuss methods to address these obstacles in terms of protocol design, workforce training and data management

Type I Interferon regulates cytokine-delayed neutrophil apoptosis, reactive oxygen species production and chemokine expression via activation of p38 MAPK

ABSTRACTInterferons (IFNs) are key regulators of a number of inflammatory conditions in which neutrophils play an important role in pathology, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), where Type I IFNs are implicated in disease pathology. However, IFNs are usually generated in vivo together with other cytokines that also have immunoregulatory functions but such interactions are poorly-defined experimentally. We measured the effects of Type-I IFN (IFNα), elevated in both RA and SLE, on the functions of healthy neutrophils incubated in vitro in the absence and presence of pro-inflammatory cytokines typically elevated in inflammatory diseases (TNFα, GM-CSF). IFNα alone had no effect on neutrophil apoptosis, however it did abrogate the anti-apoptotic effect of GM-CSF (18h, p&lt; 0.01). The enhanced stabilty of the anti-apoptotic protein Mcl-1 and delayed activation of caspase activation normally regulated by GM-CSF were blocked by IFNα: this effect was mediated, in part, by activation of p38 MAPK, increased turnover of the anti-apoptotic protein Mcl-1 and cleavage of caspases. IFNα alone also primed ROS production alone and maintained the transient priming effect of TNF for up to 4h: it also down-regulated GM-CSF and TNFα-activated expression of CXCL1, CXCL2, CXCL3, CXCL8, CCL3 and CCL4, but in contrast increased the expression of CXCL10. These novel data identify complex regulatory signalling networks in which Type I IFNs profoundly alter the response of neutrophils to inflammatory cytokines. This is likely to have important consequences in vivo and may explain the complexity and heterogeneity of inflammatory diseases such as RA, in which multiple cytokine cascades have been activated.</jats:p