Did Nile flooding sink two ancient cities?

The discovery of the two cities of Herakleion and East Canopus under the waters of the Bay of Abu Qir (east of Alexandria, Egypt) stirred worldwide attention when it was first announced in the summer of 2000. Their disappearance some 1,250 years ago has been ascribed by Stanley, Goddio and Schnepp to a strong Nile flood that caused riverbank failure and the destruction of the two cities, rather than to the action of earthquakes, as was first proposed when the ruins were discovered. But I believe that this interpretation is flawed, because no flood could have reached the Abu Qir Bay at the time of the disappearance of the two cities, as the Canopic branch of the Nile, along whose banks they were situated, had dried to a trickle more than 200 years earlier.     

Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase

Cysteinyl leukotrienes are key mediators in inflammation and have an important role in acute and chronic inflammatory diseases of the cardiovascular and respiratory systems, in particular bronchial asthma. In the biosynthesis of cysteinyl leukotrienes, conversion of arachidonic acid forms the unstable epoxide leukotriene A4 (LTA4). This intermediate is conjugated with glutathione (GSH) to produce leukotriene C4 (LTC4) in a reaction catalysed by LTC4 synthase: this reaction is the key step in cysteinyl leukotriene formation. Here we present the crystal structure of the human LTC4 synthase in its apo and GSH-complexed forms to 2.00 and 2.15 A resolution, respectively. The structure reveals a homotrimer, where each monomer is composed of four transmembrane segments. The structure of the enzyme in complex with substrate reveals that the active site enforces a horseshoe-shaped conformation on GSH, and effectively positions the thiol group for activation by a nearby arginine at the membrane-enzyme interface. In addition, the structure provides a model for how the omega-end of the lipophilic co-substrate is pinned at one end of a hydrophobic cleft, providing a molecular 'ruler' to align the reactive epoxide at the thiol of glutathione. This provides new structural insights into the mechanism of LTC4 formation, and also suggests that the observed binding and activation of GSH might be common for a family of homologous proteins important for inflammatory and detoxification responses.     

Genome sequencing in microfabricated high-density picolitre reactors

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.     

Effect of deep cryogenic treatment on the properties of 80CrMo12 5 tool steel

The effect of deep cryogenic treatment on the mechanical properties of 80CrMo12 5 tool steel was investigated. Moreover, the effects of stabilization (holding at room temperature for some periods before deep cryogenic treatment) and tempering before deep cryogenic treatment were studied. The results show that deep cryogenic treatment can eliminate the retained austenite, making a better carbide distribution and a higher carbide amount. As a result, a remarkable improvement in wear resistance of cryogenically treated specimens is observed. Moreover, the ultimate tensile strength increases, and the toughness of the sample decreases. It is also found that both stabilization and tempering before deep cryogenic treatment decrease the wear resistance, hardness, and carbides homogeneity compared to the deep cryogenically treated samples. It is concluded that deep cryogenic treatment should be performed without any delay on samples after quenching to reach the highest wear resistance and hardness.     

Monitoring of Policy Implementation: Convergent Mobile and Fixed Technologies as Emergent Enablers

Based on the viable system model (VSM), a system viability refers to the capability of a system to exist and maintain its sustainability within an environment. In this framework, monitoring function supports the gathering of relevant information directly from the operating units and feeding them into the formal control function. In turn, the control function uses the information to produce reports for the higher level functions of intelligence and policymaking, which later utilise these information for their decision making. Given its role, monitoring function supports the viability of a system, especially in large-scale policy-based system. However, studies on the functions of a system monitoring are generally lacking, leading to the lack of understanding on how to conduct monitoring in a viable system implementation. The objectives of this study are a) to discuss the role of monitoring in a viable system framework, and b) to conceptualize the function of monitoring within a policy-based system that is enabled by technologies. To achieve these objectives, this study reviews the literature on monitoring (in relation to VSM framework), on research process in general, as well as on technology adoption. This conceptual exploration generates an emergent viable system model that can guide future researchers in conducting an action research of monitoring function implementation.     

Diagnosing Business Incubation for Social Purpose: A Viable System Model Approach

Systemic Practice and Action Research - Business incubation is one of the means that promotes the overall business and economic growth of a particular location. However, to date, the role of...     

Specific immune responses induced by a multi-epitope antigen of hepatitis C virus in mice and rabbits

Five highly conserved and immunogenic epitopes of hepatitis C virus (HCV) have been chosen to form a multi-epitope antigen gene and fused with β-galactosidase gene to express a hybrid GZ-PCX antigen, which could be specifically recognized by human HCV sera. High level of anti-GZ-PCX IgG has been induced when mice or rabbits were immunized with GZ-PCX antigen emulsificated with complete Freund’s adjuvant or mixed with killed attenuatedSalmonella typhimurium SL3261. The specific anti-GZ-PCX IgG reached a high titer of 10^-6, which remained for several months. Specific cytotoxic T lymphocyte (CTL) effects, delayed type hypersensitivity reaction (DTH) and proliferation of peripheral lymphocytes have been induced by GZ-PCX antigen or synthetic peptides. High level of anti-GZ-PCX slgG has been detected in mice’s intestinal washing fluids, which indicates that the antigen induced mucosal immunity as well as systematic immunity. The studies show that the HCV multi-epitope antigen induces high level of specific immune responses without obvious toxicity, which might be able to provide protectivity to any HCV genotypes and isolates.     

Functions and Inter-Relationships of Operating Agencies in Policy Implementation from a Viable System Perspective

Existence of supporting entities and their cohesive operations are important elements in industry development policy undertaken in emerging economies, which are characterized by heavy government interventions and involved many agencies and institutions. One of the models that emphasizes on cohesiveness as a precondition for viability is the viable system model (VSM). In this study, we adopt the VSM in combination with theories of innovation and innovation system as our conceptual framework to describe and explain the functions and relational structure that exist among agencies/institutions and that of the agencies with their environment elements within one policy level system implementation. We select a biotechnology industry development policy for our analysis, the implementation of which has been designated as a strategic vehicle to support the economic development goals of an emerging economy. The findings, which generate a model of the policy-level system implementation, explain the operating agencies’ functions and their inter-relationships. The emergent model provides policy makers and implementers recommendations for improvements, as well as offers future researchers potential for comparison between existing performance of a policy implementation against its expected performance targets. The study concludes that the biotechnology industry development is an effort by the Malaysian government to institutionalize biotechnology businesses and industry. The perspective of systems thinking, in combination with theories of institutionalization, innovation and innovation system, provide important foundations in explaining technology-based industry development. All these findings highlight that the knowledge gain in explaining and interpreting the problem in focus is worthwhile, although the use of VSM as a research tool demands considerable efforts.     

Developing a Cybernetics Approach to Analysing Inclusive Growth Constraints

Inclusive and sustainable economic growth supports the transformation of society towards a better quality of life and well-being. Therefore, it is crucial to diagnose the binding factors to growth. However, existing frameworks of growth diagnostics and inclusive growth analytics, which are widely used to analyse growth problems, mainly focused on a snapshot of growth constraints of a selected location at a particular point of time. Applications of these frameworks are not fully capable of addressing the dynamic nature of growth. Moreover, most existing applications of growth frameworks are mainly predictive studies, thus they do not fully support the effort of identifying the root cause of growth problem. This calls for a more comprehensive approach to diagnosing growth problems. Building upon the existing growth diagnostics and inclusive growth analytics frameworks, as well as on cybernetics and systems-based approach, we develop a cybernetics approach to analysing inclusive growth constraints. This approach enables analysis of the dynamic nature of growth, which supports the identification of growth constraint variables and mapping of their relationships, based on data gathered about the location.