'Special K' and a loss of cell-to-cell adhesion in proximal tubule-derived epithelial cells: modulation of the adherens junction complex by ketamine

Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention

A multi-agent based system to enable strategic and operational design coordination

This paper presents two systems which individually focus on different aspects of design coordination, namely strategic and operational. The systems were developed in parallel and individually contain related models that represent specific frames from a Design Coordination Framework developed by Andreasen et al. [1]. The focus of the strategic design management system is the management of design tasks, decisions, information, goals and rationale within the design process, whereas the focus of the operational design coordination system is the coordination of tasks and activities with respect to the near-optimal utilisation of available resources. A common interface exists which enables the two systems to be integrated and used as a single system with the aim of managing both strategicand operational design coordination. Hence, the objective of this work is to enable the design process to be conducted in a timely and appropriate manner

Coordination approaches and systems - part II : an operational perspective

This is the second of two papers surveying research in coordination approaches and systems. This paper is concerned with operational coordination, which is aimed at coordinating activities such that the design process can be performed in a near optimal manner with respect to time, and the allocation and utilisation of resources. Aspects of coordination categorised as operational include resource management, scheduling and planning. The first of these two papers presents a review of coordination from a strategic perspective, which is concerned with the decision management aspects of coordination. Greater emphasis is now being placed on the significance of organising the design process as this affects time to market, product quality, cost, and consequently product success. The aim of this paper is to present a fundamental review of operational coordination approaches and systems. The 1990s has seen much progress being made towards a greater understanding and appreciation of coordination in various disciplines through the development of a wide range of approaches and systems. However, there remains a requirement to formally identify the key issues involved in coordination such that a widely accepted representation can be agreed upon. Consequently, research should continue to be supported in the exploration for a unified approach to coordination which will permit a broader and greater understanding of those aspects involved

A system for co-ordinating concurrent engineering

Design of large made-to-order products invariably involves design activities which are increasingly being distributed globally in order to reduce costs, gain competitive advantage and utilise external expertise and resources. Designers specialise within their domain producing solutions to design problems using the tools and techniques with which they are familiar. They possess a relatively local perception of where their expertise and actions are consumed within the design process. This is further compounded when design activities are geographically distributed, resulting with the increased disassociation between an individual designer's activities and the overall design process. The tools and techniques used by designers rarely facilitate concurrency, producing solutions within a particular discipline without using or sharing information from other disciplines, and seldom considering stages within the product's life-cycle other than conceptual, embodiment or detail [1, 2]. Conventional management and maintenance of consistency throughout the product model can subsequently become difficult to achieve since there are many factors that need to be simultaneously considered whilst making achange to the product model

Coordination approaches and systems - part I : a strategic perspective

This is the first part of a two-part paper presenting a fundamental review and summary of research of design coordination and cooperation technologies. The theme of this review is aimed at the research conducted within the decision management aspect of design coordination. The focus is therefore on the strategies involved in making decisions and how these strategies are used to satisfy design requirements. The paper reviews research within collaborative and coordinated design, project and workflow management, and, task and organization models. The research reviewed has attempted to identify fundamental coordination mechanisms from different domains, however it is concluded that domain independent mechanisms need to be augmented with domain specific mechanisms to facilitate coordination. Part II is a review of design coordination from an operational perspective

Assessment worlds colliding? Negotiating between discourses of assessment on an online open course

Using the badged open course, Taking your first steps into Higher Education, this case study examines how assessment on online open courses draws on concepts of assessment used within formal and informal learning. Our experience was that assessment used within open courses, such as massive open online courses, is primarily determined by the requirements of quality assurance processes to award a digital badge or statement of participation as well as what is technologically possible. However, this disregards much recent work in universities that use assessment in support of learning. We suggest that designers of online open courses should pay greater attention to the relationship of assessment and learning to improve participant course completion

Measurement of Antenna Surfaces from In- and Out-Of-Focus Beam Maps using Astronomical Sources

We present a technique for the accurate estimation of large-scale errors in an antenna surface using astronomical sources and detectors. The technique requires several out-of-focus images of a compact source and the signal-to-noise ratio needs to be good but not unreasonably high. For a given pattern of surface errors, the expected form of such images can be calculated directly. We show that it is possible to solve the inverse problem of finding the surface errors from the images in a stable manner using standard numerical techniques. To do this we describe the surface error as a linear combination of a suitable set of basis functions (we use Zernike polynomials). We present simulations illustrating the technique and in particular we investigate the effects of receiver noise and pointing errors. Measurements of the 15-m James Clerk Maxwell telescope made using this technique are presented as an example. The key result is that good measurements of errors on large spatial scales can be obtained if the input images have a signal-to-noise ratio of order 100 or more. The important advantage of this technique over transmitter-based holography is that it allows measurements at arbitrary elevation angles, so allowing one to characterise the large scale deformations in an antenna as a function of elevation.Comment: 6 pages, 5 figures (accepted by Astronomy & Astrophysics

ALMA Temporal Phase Stability and the Effectiveness of Water Vapor Radiometer

Atacama Large Millimeter/submillimeter Array (ALMA) will be the world largest mm/submm interferometer, and currently the Early Science is ongoing, together with the commissioning and science verification (CSV). Here we present a study of the temporal phase stability of the entire ALMA system from antennas to the correlator. We verified the temporal phase stability of ALMA using data, taken during the last two years of CSV activities. The data consist of integrations on strong point sources (i.e., bright quasars) at various frequency bands, and at various baseline lengths (up to 600 m). From the observations of strong quasars for a long time (from a few tens of minutes, up to an hour), we derived the 2-point Allan Standard Deviation after the atmospheric phase correction using the 183 GHz Water Vapor Radiometer (WVR) installed in each 12 m antenna, and confirmed that the phase stability of all the baselines reached the ALMA specification. Since we applied the WVR phase correction to all the data mentioned above, we also studied the effectiveness of the WVR phase correction at various frequencies, baseline lengths, and weather conditions. The phase stability often improves a factor of 2 - 3 after the correction, and sometimes a factor of 7 improvement can be obtained. However, the corrected data still displays an increasing phase fluctuation as a function of baseline length, suggesting that the dry component (e.g., N2 and O2) in the atmosphere also contributes the phase fluctuation in the data, although the imperfection of the WVR phase correction cannot be ruled out at this moment.Comment: Proc. SPIE 8444-125, in press (7 pages, 4 figures, 1 table

A spatial frequency account of the detriment that local processing of Navon letters has on face recognition

Five minutes of processing the local features of a Navon letter causes a detriment in subsequent face recognition performance (Macrae & H. Lewis, 2002). We hypothesise a perceptual after-effect explanation of this effect in which face recognition is less accurate after adapting to high spatial frequencies at high contrasts. Five experiments were conducted in which face recognition performance was compared after processing high contrast Navon stimuli. The standard recognition deficit was observed for processing the local features of Navon stimuli, but not if the stimuli were blurred (Experiment 1) or if they were of lower contrast (Experiment 2). A face recognition deficit was observed after processing small high contrast letters equivalent to local processing of Navon letters (Experiment 3). Experiments 4 and 5 demonstrated that recognition of bandpass filtered faces interacted with the type of Navon processing, whereby the recognition of low-pass filtered faces was better following local rather than global processing. These results suggest that the Navon effect on subsequent face recognition is a perceptual phenomenon