The Prospectus of the Invisible University

This exhibition and research project, helped by Hardingham, is an updating of the famous Locally Available World Unseen Network (L.A.W.u.N.) project that Greene began in the late-1960s while still in Archigram. The original aim, which has now been substantially revised and mutated, was to look at how newly emerging invisible, trans-spatial communication technologies could lead to a new form of Invisible University as a model for tertiary education. In the interim, much of what was once speculation has now come to pass through the advent of the internet, intranet, text messages, etc. – hence this latest presentation for the 2006 London Architecture Biennale showed what the revised version of the project was becoming. As such it involved taking over a newspaper shop, putting up advertising holdings and posters, holding impromptu workshops, and a number of other discrete outputs. The exhibition installation featured in the local press and raised a good deal of discussion. In terms of workload, Greene was responsible for 90% of the research and presentation material used in the exhibition installation and its ancillary outputs, and Hardingham for the other 10% involved in editing it. This latest research work has constantly been disseminated across the world through exhibitions and lectures, with for instance Greene talking about the Invisible University project in connection with the Archigram exhibition in Mito, Japan (December 2004). Elements of the project have also been exhibited at the Architectural Association, ICA, etc. The ongoing scheme for the Invisible University also featured as the subject for a specially invited interdisciplinary design workshop for the ESPRC Ideas Factory in Middlesbrough (May 2006), set up to look at ideas of designing for uncertainty; this event was jointly organised by Greene and Hardingham, and was then attended by many of Britain’s leading mathematicians and scientists

Why China? A study of why foreign hotel companies are rushing to develop new luxury hotels in China

Purpose: The purpose of this professional paper is to identify why China is currently the number one recipient of foreign investment from foreign multinational luxury hotel companies. Statement of Objective: An exploratory study will be conducted in support of the purpose. With such a lack of available information relating specifically to luxury hotel development in China; published data on the current economic, cultural, and tourism environment in China will be used to support conclusions made in regard to luxury hotel development by multinational hotel companies. Justification: Deng Xiaoping’s introduction of the Open Door Policy in 1978 opened the door to what would become decades of unprecedented economic growth in China’s history. Riding along the waves of new found economic liberty and the freedom to partner with foreign investors, China’s hotel investment community seized the opportunity to welcome outside investment. The hotel industry in China quickly developed from 137 properties in 1978 to 14,237 properties in 2009. One of the main catalysts of the rapid development seen in the hotel industry has been the expansion of multinational hotel groups into China (Zhang, Guillet, & Gao, 2011). The outlook for international tourism in China remains extremely positive. In a 2010 study conducted by the World Tourism Organization, China was listed as the fourth most popular international tourism destination (in terms of arrivals) with 133 million visitors. The number of international visitors to China is expected to increase to 137 million by 2020. As positive as these numbers seems, they are dwarfed in comparison to the 2+ billion people participating in leisure travel within China already. Currently, there is little information available on what makes China an attractive target for foreign multinational luxury hotel companies. This paper will serve to address the void of information relating to this specific issue

Chondroitin sulfate and joint disease

SummaryChondroitin sulfate is an important and major component of articular cartilage, where it occurs as part of the large proteoglycan, aggrecan. In the early stages of joint disease, both in animal models and in man, there are change in chondroitin sulfate that affect the chain length and the pattern of sulfation. These changes can be detected by monoclonal antibodies and appear to reflect part of the cellular response by the chondrocytes to damage to the articular cartilage matrix. The specificity of the changes show that the biosynthesis of chondroitin sulfate is under tight cellular control in chondrocytes and suggests that selected patterns of sulphation within chains are expressed to suit different biological functions

NMDA receptor-dependent glutamate excitotoxicity in human embryonic stem cell-derived neurons

AbstractThanks to the development of efficient differentiation strategies, human pluripotent stem cells (HPSC) offer the opportunity for modelling neuronal injury and dysfunction in human neurons in vitro. Critically, the effective use of HPSC-derived neural cells in disease-modelling and potentially cell replacement therapies hinges on an understanding of the biology of these cells, specifically their development, subtype specification and responses to neurotoxic signalling mediators. Here, we generated neurons from human embryonic stem cells and characterised the development of vulnerability to glutamate excitotoxicity, a key contributor to neuronal injury in several acute and chronic neurodegenerative disorders. Over two months of differentiation we observed a gradual increase in responsiveness of neurons to glutamate-induced Ca2+ influx, attributable to NMDA receptor activity. This increase was concomitant with an increase in expression of mRNA encoding NMDA and AMPA receptor subunits. Differentiated neurons were vulnerable to glutamate excitotoxicity in a dose-dependent manner, which was reduced by NMDA receptor antagonists

Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration

Glia, including astrocytes, are increasingly at the forefront of neurodegenerative research for their role in the modulation of neuronal function and survival. Improved understanding of underlying disease mechanisms, including the role of the cellular environment in neurodegeneration, is central to therapeutic development for these currently untreatable diseases. In these endeavours, experimental models that more closely reproduce the human condition have the potential to facilitate the transition between experimental studies in model organisms and patient trials. In this review we discuss the growing role of astrocytes in neurodegenerative diseases, and how astrocytes generated from human pluripotent stem cells represent a useful tool for analyzing astrocytic signalling and influence on neuronal function

Pro-survival signalling from the NMDA receptor

Ca(2+) influx through the NMDA subtype of ionotropic glutamate receptors plays a Jekyll and Hyde role in the mammalian central nervous system. While it mediates excitotoxic death triggered by stroke and other acute trauma, there is growing evidence that physiological levels of NMDA receptor activity promote survival. Understanding the mechanisms that underlie these opposing effects may lead to strategies to selectively block pro-death signalling, which could have considerable clinical benefits

In developing hippocampal neurons, NR2B-containing N-methyl-d-aspartate receptors (NMDARs) can mediate signaling to neuronal survival and synaptic potentiation, as well as neuronal death

It has been suggested that NR2B-containing NMDA receptors have a selective tendency to promote pro-death signalling and synaptic depression, compared to the survival promoting, synapse potentiating properties of NR2A-containing NMDA receptors. A preferential localization of NR2A-containing NMDA receptors at the synapse in maturing neurons could thus explain differences in synaptic vs. extrasynaptic NMDA receptor signalling. We have investigated whether NMDA receptors can mediate signalling to survival, death, and synaptic potentiation, in neurons at a developmental stage prior to significant NR2A expression and subunit-specific differences between synaptic and extrasynaptic NMDA receptors. We show that in developing hippocampal neurons, the progressive reduction in sensitivity of NMDA receptor currents to the NR2B antagonist ifenprodil applies to both synaptic and extrasynaptic locations. However, the reduction is less acute in extrasynaptic currents, indicating that NR2A does partition preferentially, but not exclusively, into synaptic locations at DIV>12. We then studied NMDA receptor signalling at DIV10, when both synaptic and extrasynaptic NMDA receptors are both overwhelmingly and equally NR2B-dominated. To analyse pro-survival signalling we studied the influence of synaptic NMDA receptor activity on staurosporine-induced apoptosis. Blockade of spontaneous NMDAR activity with MK-801, or ifenprodil exacerbated the apoptotic insult. Furthermore, MK-801 and ifenprodil both antagonized neuroprotection promoted by enhancing synaptic activity. Pro-death signalling induced by a toxic dose of NMDA is also blocked by NR2B-specific antagonists. Using a cell culture model of synaptic NMDA receptor-dependent synaptic potentiation, we find that this is mediated exclusively by NR2B-containing NMDARs, as implicated by NR2B-specific antagonists and the use of selective vs. non-selective doses of the NR2A-preferring antagonist NVP-AAM077. Therefore, within a single neuron, NR2B-NMDA receptors are able to mediate both survival and death signalling, as well as model of NMDA receptor-dependent synaptic potentiation. In this instance, subunit differences cannot account for the dichotomous nature of NMDA receptor signalling

Recovery of NMDA receptor currents from MK-801 blockade is accelerated by Mg2+ and memantine under conditions of agonist exposure

AbstractMK-801 is a use-dependent NMDA receptor open channel blocker with a very slow off-rate. These properties can be exploited to ‘pre-block’ a population of NMDARs, such as synaptic ones, enabling the selective activation of a different population, such as extrasynaptic NMDARs. However, the usefulness of this approach is dependent on the stability of MK-801 blockade after washout. We have revisited this issue, and confirm that recovery of NMDAR currents from MK-801 blockade is enhanced by channel opening by NMDA, and find that it is further increased when Mg2+ is also present. In the presence of Mg2+, 50% recovery from MK-801 blockade is achieved after 10′ of 100 μM NMDA, or 30′ of 15 μM NMDA exposure. In Mg2+-free medium, NMDA-induced MK-801 dissociation was found to be much slower. Memantine, another PCP-site antagonist, could substitute for Mg2+ in accelerating the unblock of MK-801 in the presence of NMDA. This suggests a model whereby, upon dissociation from its binding site in the pore, MK-801 is able to re-bind in a process antagonized by Mg2+ or another PCP-site antagonist. Finally we show that even when all NMDARs are pre-blocked by MK-801, incubation of neurons with 100 μM NMDA in the presence of Mg2+ for 2.5 h triggers sufficient unblocking to kill >80% of neurons. We conclude that while synaptic MK-801 ‘pre-block’ protocols are useful for pharmacologically assessing synaptic vs. extrasynaptic contributions to NMDAR currents, or studying short-term effects, it is problematic to use this technique to attempt to study the effects of long-term selective extrasynaptic NMDAR activation.This article is part of the Special Issue entitled ‘Glutamate Receptor-Dependent Synaptic Plasticity’