Comprehensibility of UML-based Formal Model – A Series of Controlled Experiments

This paper summarises two controlled experiments conducted on a model that integrates the use of semi-formal notation, the Unified Modelling Language (UML) and a formal notation, B. The experiments assessed the comprehensibility of the model, namely UML-B. The first experiment compared the comprehensibility of a UML-B model and a B model. In the second experiment, the model was compared with an Event-B model, a new generation of B. The experiments assessed the ability of the model to present information and to promote problem domain understanding. The measurement focused on the efficiency in performing the comprehension tasks. The experiments employed a cross-over design and were conducted on third-year and masters students. The results suggest that the integration of semi-formal and formal notations expedites the subjects’ comprehension tasks with accuracy even with limited hours of training

Sustainable management of miombo woodlands in the Northern part of Mozambique (Niassa National Reserve - NNR).

Poster presented at Commiting Science to Global Development. Lisbon (Portugal). 29-30 Sep 2009

Munc18c provides stimulus-selective regulation of GLUT4 but not fatty acid transporter trafficking in skeletal muscle

Insulin-, and contraction-induced GLUT4 and fatty acid (FA) transporter translocation may share common trafficking mechanisms. Our objective was to examine the effects of partial Munc18c ablation on muscle glucose and FA transport, FA oxidation, GLUT4 and FA transporter (FAT/CD36, FAB-Ppm, FATP1, FATP4) trafficking to the sarcolemma, and FAT/CD36 to mitochondria. In Munc18c(-/+) mice, insulin-stimulated glucose transport and GLUT4 sarcolemmal appearance were impaired, but were unaffected by contraction. Insulin- and contraction-stimulated FA transport, sarcolemmal FA transporter appearance, and contraction-mediated mitochondrial FAT/CD36 were increased normally in Munc18c(-/+) mice. Hence, Munc18c provides stimulus-specific regulation of GLUT4 trafficking, but not FA transporter trafficking

Relearning traditional knowledge to achieve sustainability: honey gathering in the miombo woodlands of northern Mozambique

Mozambique’s Niassa Reserve contains Africa’s best preserved miombo woodlands. Half of the households there gather wild honey from natural hives for consumption and income. However, most collectors used destructive techniques: setting fire to the grasses under the hive tree to create smoke and then felling the tree. Cutting trees to obtain honey was the principal source of tree mortality. Trees grow very slowly, about 0.25 cm diameter [dbh]/yr, meaning an average hive tree was nearly 200 years old. Furthermore, of the trees > 20 cm dbh of species important for nectar and hives, only about 15% had cavities. Although fire is intrinsic to miombo woodlands, the increased frequency resulting from anthropogenic sources impedes regeneration of some tree species as well as affecting bees, other wildlife and villages. A few people in the reserve had learned from earlier generations how to gather honey in a nondestructive way, using certain plant species to keep bees from stinging and climbing the trees using ropes to take the honey combs out of the hives. Traditional practices included leaving the larval combs behind so the colony continued to grow. Previously, the older men who had this knowledge had not been willing to share it with younger men. The project arranged for one of the traditional honey hunters to participate in an international conference on honey collection with other indigenous collectors from around the world. This helped him recognize the value of his knowledge. The project team then arranged for him to demonstrate these traditional techniques to groups of honey hunters in nine communities within the Reserve. A yearlater, monitoring revealed that many collectors had adopted these nondestructive techniques. They found them less time consuming, and appreciated that they allowed collectors to return to the same trees repeatedly to obtain honey. Sharing traditional knowledge made honey hunting compatible with the conservation of miombo woodlands

Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1 alpha) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats

Aims/hypothesis Reductions in peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1 alpha) levels have been associated with the skeletal muscle insulin resistance. However, in vivo, the therapeutic potential of PGC-1 alpha has met with failure, as supra-physiological overexpression of PGC-1 alpha induced insulin resistance, due to fatty acid translocase (FAT)-mediated lipid accumulation. Based on physiological and metabolic considerations, we hypothesised that a modest increase in PGC-1 alpha levels would limit FAT upregulation and improve lipid metabolism and insulin sensitivity, although these effects may differ in lean and insulin-resistant muscle. Methods Pgc-1 alpha was transfected into lean and obese Zucker rat muscles. Two weeks later we examined mitochondrial biogenesis, intramuscular lipids (triacylglycerol, diacylglycerol, ceramide), GLUT4 and FAT levels, insulin-stimulated glucose transport and signalling protein phosphorylation (thymoma viral proto-oncogene 2 [Akt2], Akt substrate of 160 kDa [AS160]), and fatty acid oxidation in subsarcolemmal and intermyofibrillar mitochondria. Results Electrotransfection yielded physiologically relevant increases in Pgc-1 alpha (also known as Ppargc1a) mRNA and protein (similar to 25%) in lean and obese muscle. This induced mitochondrial biogenesis, and increased FAT and GLUT4 levels, insulin-stimulated glucose transport, and Akt2 and AS160 phosphorylation in lean and obese animals, while bioactive intramuscular lipids were only reduced in obese muscle. Concurrently, PGC-1 alpha increased palmitate oxidation in subsarcolemmal, but not in intermyofibrillar mitochondria, in both groups. In obese compared with lean animals, the PGC-1 alpha-induced improvement in insulin-stimulated glucose transport was smaller, but intramuscular lipid reduction was greater. Conclusions/interpretations Increases in PGC-1 alpha levels, similar to those that can be induced by physiological stimuli, altered intramuscular lipids and improved fatty acid oxidation, insulin signalling and insulin-stimulated glucose transport, albeit to different extents in lean and insulin-resistant muscle. These positive effects are probably attributable to limiting the PGC-1 alpha-induced increase in FAT, thereby preventing bioactive lipid accumulation as has occurred in transgenic PGC-1 alpha animals

Caffeine-stimulated fatty acid oxidation is blunted in CD36 null mice

Aim: The increase in skeletal muscle fatty acid metabolism during exercise has been associated with the release of calcium. We examined whether this increase in fatty acid oxidation was attributable to a calcium-induced translocation of the fatty acid transporter CD36 to the sarcolemma, thereby providing an enhanced influx of fatty acids to increase their oxidation.Methods: Calcium release was triggered by caffeine (3 mM) to examine fatty acid oxidation in intact soleus muscles of WT and CD36-KO mice, while fatty acid transport and mitochondrial fatty acid oxidation were examined in giant vesicles and isolated mitochondria, respectively, from caffeine-perfused hindlimb muscles of WT and CD36-KO mice. Western blotting was used to examine calcium-induced signalling.Results: In WT, caffeine stimulated muscle palmitate oxidation (+136%), but this was blunted in CD36-KO mice (-70%). Dantrolene inhibited (WT) or abolished (CD36-KO) caffeine-induced palmitate oxidation. In muscle, caffeine-stimulated palmitate oxidation was not attributable to altered mitochondrial palmitate oxidation. Instead, in WT, caffeine increased palmitate transport (+55%) and the translocation of fatty acid transporters CD36, FABPpm, FATP1 and FATP4 (26-70%) to the sarcolemma. In CD36-KO mice, caffeine-stimulated FABPpm, and FATP1 and 4 translocations were normal, but palmitate transport was blunted (-70%), comparable to the reductions in muscle palmitate oxidation. Caffeine did not alter the calcium-/calmodulin-dependent protein kinase II phosphorylation but did increase the phosphorylation of AMPK and acetyl-CoA carboxylase comparably in WT and CD36-KO.Conclusion: These studies indicate that sarcolemmal CD36-mediated fatty acid transport is a primary mediator of the calcium-induced increase in muscle fatty acid oxidation

Energy representation for out-of-equilibrium Brownian-like systems: steady states and fluctuation relations

Stochastic dynamics in the energy representation is employed as a method to study non-equilibrium Brownian-like systems. It is shown that the equation of motion for the energy of such systems can be taken in the form of the Langevin equation with multiplicative noise. Properties of the steady states are examined by solving the Fokker-Planck equation for the energy distribution functions. The generalized integral fluctuation theorem is deduced for the systems characterized by the shifted probability flux operator. There are a number of entropy and fluctuation relations such as the Hatano-Sasa identity and the Jarzynski's equality that follow from this theorem.Comment: revtex4-1, 18 pages, extended discussion, references adde

Boundary lubrication properties of materials with expansive freezing

We have performed molecular dynamics simulations of solid-solid contacts lubricated by a model fluid displaying many of the properties of water, particularly its expansive freezing. Near the region where expansive freezing occurs, the lubricating film remains fluid, and the friction force decreases linearly as the shear velocity is reduced. No sign of stick-slip motion is observed even at the lowest velocities. We give a simple interpretation of these results, and suggest that in general good boundary lubrication properties will be found in the family of materials with expansive freezing.Comment: Version to appear in Phys. Rev. Let

In Vivo, Fatty Acid Translocase (CD36) Critically Regulates Skeletal Muscle Fuel Selection, Exercise Performance, and Training-induced Adaptation of Fatty Acid Oxidation

For ∼40 years it has been widely accepted that (i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is largely attributable to muscle mitochondrial biogenesis. These long standing concepts were developed prior to the recent recognition that fatty acid entry into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36-KO versus WT mice displayed reduced fatty acid transport (−21%) and oxidation (−25%), intramuscular lipids (less than or equal to −31%), and hepatic glycogen (−20%); but muscle glycogen, VO(2max), and mitochondrial content and enzymes did not differ. In acutely exercised (78% VO(2max)) CD36-KO mice, fatty acid transport (−41%), oxidation (−37%), and exercise duration (−44%) were reduced, whereas muscle and hepatic glycogen depletions were accelerated by 27–55%, revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and β-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise training (+44%) or by CD36 overexpression (+41%), increased FAO similarly (84–90%), either when mitochondrial biogenesis and FAO enzymes were up-regulated (exercise training) or when these were unaltered (CD36 overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance, and training-induced muscle FAO adaptation, challenging long held views of mechanisms involved in acute and adaptive regulation of muscle FAO

A lesson on interrogations from detainees: Predicting self-reported confessions and cooperation

The ability to predict confessions and cooperation from the elements of an interrogation was examined. Incarcerated men (N = 100) completed a 50-item questionnaire about their most recent police interrogation, and regression analyses were performed on self-reported decisions to confess and cooperate. Results showed that the likelihood of an interrogation resulting in a confession was greatest when evidence strength and score on a humanitarian interviewing scale were high, and when the detainee had few previous convictions or did not seek legal advice. We also found that the level of cooperation was greatest when the humanitarian interviewing score was high, and when previous convictions were low. The implications of the findings for interrogation practices are discussed