Orientalism and intelligence analysis: deconstructing Anglo-American notions of the ‘Arab’

Despite revived notions of a ‘cultural divide’ between East and West, Edward's Said's ‘Orientalism’ has received little attention from scholars of intelligence and diplomacy. This article brings to light for the first time a number of recently declassified documents of a different nature to usual assessments produced by Anglo-American analytic bodies: those focussed primarily on the issue of ‘national character’. Using and critiquing Said's thesis of Western ‘Orientalism’ it reveals some critical and enduring conceptualizations articulated by the diplomatic and intelligence community about Arab culture such as the role of Islam, rhetoric, political motivation and notions of ‘honour’. Such a critical approach demonstrates how diplomatic and intelligence history can also be a history of culture, ideas and institutional mentalité.

Carbon monoxide protects against oxidant-induced apoptosis via inhibition of Kv2.1

Oxidative stress induces neuronal apoptosis and is implicated in cerebral ischemia, head trauma, and age-related neurodegenerative diseases. An early step in this process is the loss of intracellular K(+) via K(+) channels, and evidence indicates that K(v)2.1 is of particular importance in this regard, being rapidly inserted into the plasma membrane in response to apoptotic stimuli. An additional feature of neuronal oxidative stress is the up-regulation of the inducible enzyme heme oxygenase-1 (HO-1), which catabolizes heme to generate biliverdin, Fe(2+), and carbon monoxide (CO). CO provides neuronal protection against stresses such as stroke and excitotoxicity, although the underlying mechanisms are not yet elucidated. Here, we demonstrate that CO reversibly inhibits K(v)2.1. Channel inhibition by CO involves reactive oxygen species and protein kinase G activity. Overexpression of K(v)2.1 in HEK293 cells increases their vulnerability to oxidant-induced apoptosis, and this is reversed by CO. In hippocampal neurons, CO selectively inhibits K(v)2.1, reverses the dramatic oxidant-induced increase in K(+) current density, and provides marked protection against oxidant-induced apoptosis. Our results provide a novel mechanism to account for the neuroprotective effects of CO against oxidative apoptosis, which has potential for therapeutic exploitation to provide neuronal protection in situations of oxidative stress.

Carbon monoxide inhibition of Cav3.2 T-type Ca2+ channels reveals tonic modulation by thioredoxin

T-type Ca2+ channels play diverse roles in tissues such as sensory neurons, vascular smooth muscle, and cancers, where increased expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1) is often found. Here, we report regulation of T-type Ca2+ channels by carbon monoxide (CO) a HO-1 by-product. CO (applied as CORM-2) caused a concentration-dependent, poorly reversible inhibition of all T-type channel isoforms (Cav3.1-3.3, IC50 ∼3 μM) expressed in HEK293 cells, and native T-type channels in NG108-15 cells and primary rat sensory neurons. No recognized CO-sensitive signaling pathway could account for the CO inhibition of Cav3.2. Instead, CO sensitivity was mediated by an extracellular redox-sensitive site, which was also highly sensitive to thioredoxin (Trx). Trx depletion (using auranofin, 2-5 μM) reduced Cav3.2 currents and their CO sensitivity by >50% but increased sensitivity to dithiothreitol ∼3-fold. By contrast, Cav3.1 and Cav3.3 channels, and their sensitivity to CO, were unaffected in identical experiments. Our data propose a novel signaling pathway in which Trx acts as a tonic, endogenous regulator of Cav3.2 channels, while HO-1-derived CO disrupts this regulation, causing channel inhibition. CO modulation of T-type channels has widespread implications for diverse physiological and pathophysiological mechanisms, such as excitability, contractility, and proliferation

The development of the Virtual Construction Simulator 3: an interactive simulation environment for construction management education

This paper discusses the development of the Virtual Construction Simulator (VCS) 3 - a simulation game-based educational tool for teaching construction schedule planning and management. The VCS3 simulation game engages students in learning the concepts of planning and managing construction schedules through goal driven exploration, employed strategies, and immediate feedback. Through the planning and simulation mode, students learn the difference between the as-planned and as-built schedules resulting from varying factors such as resource availability, weather and labor productivity. This paper focuses on the development of the VCS3 and its construction physics model. Challenges inherent in the process of identifying variables and their relationships to reliably represent and simulate the dynamic nature of planning and managing of construction projects are also addressed.