Taking advantage of an old concept, "illegitimate transcription", for a proposed novel method of genetic diagnosis of McArdle disease

McArdle disease is a metabolic disorder caused by pathogenic mutations in the PYGM gene. Timely diagnosis can sometimes be difficult with direct genomic analysis, which requires additional studies of cDNA from muscle transcripts. Although the "nonsense-mediated mRNA decay" (NMD) eliminates tissue-specific aberrant transcripts, there is some residual transcription of tissue-specific genes in virtually all cells, such as peripheral blood mononuclear cells (PBMCs).We studied a subset of the main types of PYGM mutations (deletions, missense, nonsense, silent, or splicing mutations) in cDNA from easily accessible cells (PBMCs) in 12 McArdle patients.Analysis of cDNA from PBMCs allowed detection of all mutations. Importantly, the effects of mutations with unknown pathogenicity (silent and splicing mutations) were characterized in PBMCs. Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation c.645G>A (p.K215=), whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies.We propose considering the use of PBMCs for detecting mutations that are thought to cause McArdle disease, particularly for studying their actual pathogenicity.

Causes of a Divided Discipline: Rethinking the Concept of Cause in International Relations theory

Kurki, M. (2006). Causes of a Divided Discipline: Rethinking the Concept of Cause in International Relations theory. Review of International Studies, 32 (2), 189-216. RAE2008

A Memory Model for Concept Hierarchy Representation and Commonsense Reasoning

Most associative memory models perform one level mapping between predefined sets of input and output patterns1 and are unable to represent hierarchical knowledge. Complex AI systems allow hierarchical representation of concepts, but generally do not have learning capabilities. In this paper, a memory model is proposed which forms concept hierarchy by learning sample relations between concepts. All concepts are represented in a concept layer. Relations between a concept and its defining lower level concepts, are chunked as cognitive codes represented in a coding layer. By updating memory contents in the concept layer through code firing in the coding layer, the system is able to perform an important class of commonsense reasoning, namely recognition and inheritance.

Is the Species Flock Concept Operational? The Antarctic Shelf Case

There has been a significant body of literature on species flock definition but not so much about practical means to appraise them. We here apply the five criteria of Eastman and McCune for detecting species flocks in four taxonomic components of the benthic fauna of the Antarctic shelf: teleost fishes, crinoids (feather stars), echinoids (sea urchins) and crustacean arthropods. Practical limitations led us to prioritize the three historical criteria (endemicity, monophyly, species richness) over the two ecological ones (ecological diversity and habitat dominance). We propose a new protocol which includes an iterative fine-tuning of the monophyly and endemicity criteria in order to discover unsuspected flocks. As a result nine « full » species flocks (fulfilling the five criteria) are briefly described. Eight other flocks fit the three historical criteria but need to be further investigated from the ecological point of view (here called « core flocks »). The approach also shows that some candidate taxonomic components are no species flocks at all. The present study contradicts the paradigm that marine species flocks are rare. The hypothesis according to which the Antarctic shelf acts as a species flocks generator is supported, and the approach indicates paths for further ecological studies and may serve as a starting point to investigate the processes leading to flock-like patterning of biodiversity. © 2013 Lecointre et al.

[Book review] Symmetry - A Unifying Concept, István Hargittai and Magdolna Hargittai

Tony Mann provides a review of the book: István Hargittai and Magdolna Hargittai, Symmetry - A Unifying Concept, 1994, Ten Speed Press, 222pp. ISBN: 089815-590-8. £14.99

Predicting toxic gas concentrations resulting from enclosure fires using local equivalence ratio concept linked to fire field models

A practical CFD method is presented in this study to predict the generation of toxic gases in enclosure fires. The model makes use of local combustion conditions to determine the yield of carbon monoxide, carbon dioxide, hydrocarbon, soot and oxygen. The local conditions used in the determination of these species are the local equivalence ratio (LER) and the local temperature. The heat released from combustion is calculated using the volumetric heat source model or the eddy dissipation model (EDM). The model is then used to simulate a range of reduced-scale and full-scale fire experiments. The model predictions for most of the predicted species are then shown to be in good agreement with the test results

The food multimix concept: potential of an innovative food based approach on nutritional status in pregnant women in resource-poor communities

RATIONALE & OBJECTIVES: The food multimix (FFM)concept states that limited food resources can be combined using scientific knowledge to meet nutrient needs of vulnerable groups at low cost utilizing the ‘nutrient strengths’ of individual or candidate foods in composite recipes within a cultural context. METHODS: The method employed the food-to-food approach for recipe development using traditional food ingredients. Recipes were subjected to proximate and micronutrient analysis and optimized to meet at tleast 40% of recommended daily intakes. End products including breads, porridge and soup were developed. RESULTS: FMM products were employed in a feeding trial among 120 healthy pregnant women in Gauteng, South Africa resulting in improvements in serum iron levels from baseline values of 14.59 (=/-7.67) umol/L and 14.02 (=/-8.13) umol/L for control and intervention groups (p=0.71), to 16.03 (=/-5.67) umol/L and 18.66 (=/-9.41) umol/L (p=0.19). The increases from baseline to post-intervention were however statistically significant within groups. Similarly Mean Cell Volume values improved from baseline as well as serum ferritin and transferritin levels. CONCLUSION: The FMM concept has potential value in feeding programs for vulnerable groups including pregnant and lactating mothers.

Zinc polycarboxylate dental cement for the controlled release of an active organic substance: proof of concept

The potential of employing zinc polycarboxylate dental cement as a controlled release material has been studied. Benzalkonium chloride was used as the active ingredient, and incorporated at concentrations of 1, 2 and 3% by mass within the cement. At these levels, there was no observable effect on the speed of setting. Release was followed using an ion-selective electrode to determine changes in chloride ion concentration with time. This technique showed that the additive was released when the cured cement was placed in water, with release occurring by a diffusion mechanism for the first 3 h, but continuing beyond that for up to 1 week. Diffusion coefficients were in the range 5.62 × 10(−6) cm(2) s(−1) (for 1% concentration) to 10.90 × 10(−6) cm(2) s(−1) (for 3% concentration). Up to 3% of the total loading of benzalkonium chloride was released from the zinc polycarboxylate after a week, which is similar to that found in previous studies with glass-ionomer cement. It is concluded that zinc polycarboxylate cement is capable of acting as a useful material for the controlled release of active organic compounds.

The food multimix concept: new innovative approach to meeting nutritional challenges in Sub-Saharan Africa

Food insecurity, chronic hunger, starvation and malnutrition continue to affect millions of individuals throughout the developing world, especially Sub-Saharan Africa. Various initiatives by African governments and International Agencies such as the UN, the industrial nations, the International Monetary Fund, the World Bank and the World Trade Organisation to boost economic development, have failed to provide the much-needed solution to these challenges. The impact of these economic shifts and the failures of structural adjustment programmes on the nutritional well-being and health of the most vulnerable members of poor communities cannot be over-emphasised. The use of ad hoc measures as an adjunct to community-based rural integrated projects have provided little success and will be unsustainable unless they are linked to harnessing available local resources. The present paper therefore focuses on exploring alternative ways of harnessing the scant agricultural resources by employing a scientific approach to food-related problem-solving. The food multimix (FMM) concept offers a scientific contribution alongside other attempts currently in use by the World Food Programme, WHO and FAO to meet the food insecurity challenges that confront most of the developing world in the twenty-first century. It is an innovative approach that makes better use of traditional food sources as a tool for meeting community nutritional needs. The FMM concept employs a food-based approach using traditional methods of food preparation and locally-available, cheap and affordable staples (fruits, pulses, vegetables and legumes) in the formulation of nutrient-enriched multimixes. Developed recipes can provide >= 40% of the daily nutritional requirements of vulnerable groups, including patients with HIV/AIDS and children undergoing nutrition rehabilitation. The FMM approach can also be used as a medium- to long-term adjunct to community-based rural integration projects aimed at health improvement and economic empowerment in Sub-Saharan Africa.

A Competence-Based Course Authoring Concept for Learning Platforms with Legacy Assignment Tools

This paper is concerned with several of the most important aspects of Competence-Based Learning (CBL): course authoring, assignments, and categorization of learning content. The latter is part of the so-called Bologna Process (BP) and can effectively be supported by integrating knowledge resources like, e.g., standardized skill and competence taxonomies into the target implementation approach, aiming at making effective use of an open integration architecture while fostering the interoperability of hybrid knowledge-based e-learning solutions. Modern scenarios ask for interoperable software solutions to seamlessly integrate existing e-learning infrastructures and legacy tools with innovative technologies while being cognitively efficient to handle. In this way, prospective users are enabled to use them without learning overheads. At the same time, methods of Learning Design (LD) in combination with CBL are getting more and more important for production and maintenance of easy to facilitate solutions. We present our approach of developing a competence-based course-authoring and assignment support software. It is bridging the gaps between contemporary Learning Management Systems (LMS) and established legacy learning infrastructures by embedding existing resources via Learning Tools Interoperability (LTI). Furthermore, the underlying conceptual architecture for this integration approach will be explained. In addition, a competence management structure based on knowledge technologies supporting standardized skill and competence taxonomies will be introduced. The overall goal is to develop a software solution which will not only flawlessly merge into a legacy platform and several other learning environments, but also remain intuitively usable. As a proof of concept, the so-called platform independent conceptual architecture model will be validated by a concrete use case scenario.