Mapping the Spread of Malaria Drug Resistance

Tim Anderson discusses a new study of molecular variation in alleles at the dihydropteroate synthase locus, which underlies resistance to sulfadoxine, in over 5,000 parasites from 50 locations

Technical Note:A Novel Servo-Driven Dual-Roller Handrim Wheelchair Ergometer

The measurement of handrim wheelchair propulsion characteristics and performance in the field is complicated due to the non-stationary nature of wheelchair driving. In contrast, the laboratory provides a constrained and standardisable environment to conduct measurements and experiments. Apart from wheelchair treadmills, dynamometers or ergometers for handrim wheelchairs are often custom-made, one-of-a-kind, expensive, and sparsely documented in the research literature. To facilitate standardised and comparable lab-based measurements in research, as well as in clinical settings and adapted sports, a new wheelchair ergometer was developed. The ergometer with instrumented dual rollers allows for the performance analysis of individuals in their personal handrim wheelchair and facilitates capacity assessment, training and skill acquisition in rehabilitation or adapted sports. The ergometer contains two servomotors, one for each rear wheel roller, that allow for the simulation of translational inertia and resistive forces as encountered during wheelchair propulsion based on force input and a simple mechanical model of wheelchair propulsion. A load cell configuration for left and right roller enables the measurement of effective user-generated torque and force on the handrim and the concomitant timing patterns. Preliminary results are discussed

Biomechanical and physiological differences between synchronous and asynchronous low intensity handcycling during practice-based learning in able-bodied men

BACKGROUND: Originally, the cranks of a handcycle were mounted with a 180° phase shift (asynchronous). However, as handcycling became more popular, the crank mode switched to a parallel mounting (synchronous) over the years. Differences between both modes have been investigated, however, not into great detail for propulsion technique or practice effects. Our aim is to compare both crank modes from a biomechanical and physiological perspective, hence considering force and power production as a cause of physiological outcome measures. This is done within a practice protocol, as it is expected that motor learning takes place in the early stages of handcycling in novices. METHODS: Twelve able-bodied male novices volunteered to take part. The experiment consisted of a pre-test, three practice sessions and a post-test, which was subsequently repeated for both crank modes in a counterbalanced manner. In each session the participants handcycled for 3 × 4 minutes on a leveled motorized treadmill at 1.94 m/s. Inbetween sessions were 2 days of rest. 3D forces, handlebar and crank angle were measured on the left hand side. Kinematic markers were placed on the handcycle to monitor the movement on the treadmill. Lastly, breath-by-breath spirometry combined with heart-rate were continuously measured. The effects of crank mode and practice-based learning were analyzed using a two way repeated measures ANOVA, with synchronous vs asynchronous and pre-test vs post-test as within-subject factors. RESULTS: In the pre-test, asynchronous handcycling was less efficient than synchronous handcycling in terms of physiological strain, force production and timing. At the post-test, the metabolic costs were comparable for both modes. The force production was, also after practice, more efficient in the synchronous mode. External power production, crank rotation velocity and the distance travelled back and forwards on the treadmill suggest that asynchronous handcycling is more constant throughout the cycle. CONCLUSIONS: As the metabolic costs were reduced in the asynchronous mode, we would advise to include a practice period, when comparing both modes in scientific experiments. For handcycle users, we would currently advise a synchronous set-up for daily use, as the force production is more effective in the synchronous mode, even after practice

Resonances in a spring-pendulum: algorithms for equivariant singularity theory

A spring-pendulum in resonance is a time-independent Hamiltonian model system for formal reduction to one degree of freedom, where some symmetry (reversibility) is maintained. The reduction is handled by equivariant singularity theory with a distinguished parameter, yielding an integrable approximation of the Poincaré map. This makes a concise description of certain bifurcations possible. The computation of reparametrizations from normal form to the actual system is performed by Gröbner basis techniques.

Identification of plastic constitutive parameters at large deformations from three dimensional displacement fields

The aim of this paper is to provide a general procedure to extract the constitutive parameters of a plasticity model starting from displacement measurements and using the Virtual Fields Method. This is a classical inverse problem which has been already investigated in the literature, however several new features are developed here. First of all the procedure applies to a general three-dimensional displacement field which leads to large plastic deformations, no assumptions are made such as plane stress or plane strain although only pressure-independent plasticity is considered. Moreover the equilibrium equation is written in terms of the deviatoric stress tensor that can be directly computed from the strain field without iterations. Thanks to this, the identification routine is much faster compared to other inverse methods such as finite element updating. The proposed method can be a valid tool to study complex phenomena which involve severe plastic deformation and where the state of stress is completely triaxial, e.g. strain localization or necking occurrence. The procedure has been validated using a three dimensional displacement field obtained from a simulated experiment. The main potentialities as well as a first sensitivity study on the influence of measurement errors are illustrated

Polaronic states with Spin-Charge-Coupled Excitation in a 1D Mott Insulator K-TCNQ

We discuss photogenerated midgap states of a one-dimensional (1D) dimerized Mott insulator, potassium-tetracyanoquinodimethane (K-TCNQ). Two types of phonon modes are taken into account: intermolecular and intramolecular vibrations. We treat these phonon modes adiabatically and analyze a theoretical model by using the density-matrix renormalization group (DMRG). Our numerical results demonstrate that the intermolecular lattice distortion is necessary to reproduce the photoinduced midgap absorption in K-TCNQ. We find two types of midgap states. One is a usual polaronic state characterized by a localized elementary excitation. The other is superposition of two types of excitations, a doped-carrier state and a triplet-dimer state, which can be generally observed in 1D dimerized Mott insulators, not limited to K-TCNQ.Comment: 6 pages, 8 figures, to appear in J. Phys. Soc. Jpn. Vol.77, No.7 (2008

Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase

BACKGROUND: For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally.The two key enzymatiques systems required for the production of these monocarboxylates are lactate dehydrogenase (LDH; EC1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA and oxydative phosphorylation. RESULTS: In this article, we show, with monoclonal antibodies applied to post-mortem human brain tissues, that the typically glycolytic isoenzyme of lactate dehydrogenase (LDH-5; also called LDHA or LDHM) is selectively present in astrocytes, and not in neurons, whereas pyruvate dehydrogenase (PDH) is mainly detected in neurons and barely in astrocytes. At the regional level, the distribution of the LDH-5 immunoreactive astrocytes is laminar and corresponds to regions of maximal 2-deoxyglucose uptake in the occipital cortex and hippocampus. In hippocampus, we observed that the distribution of the oxidative enzyme PDH was enriched in the neurons of the stratum pyramidale and stratum granulosum of CA1 through CA4, whereas the glycolytic enzyme LDH-5 was enriched in astrocytes of the stratum moleculare, the alveus and the white matter, revealing not only cellular, but also regional, selective distributions. The fact that LDH-5 immunoreactivity was high in astrocytes and occurred in regions where the highest uptake of 2-deoxyglucose was observed suggests that glucose uptake followed by lactate production may principally occur in these regions. CONCLUSION: These observations reveal a metabolic segregation, not only at the cellular but also at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons

MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium

Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validation. With miRNA microarray we identified forty-seven upregulated and ten downregulated miRNAs in hypercholesterolemic rat hearts compared to the normocholesterolemic group. Eleven mRNAs with at least 4 interacting upregulated miRNAs were selected by a network theoretical approach, out of which 3 mRNAs (beta-2 adrenergic receptor [Adrb2], calcineurin B type 1 [Ppp3r1] and calcium/calmodulin-dependent serine protein kinase [Cask]) were validated with qRT-PCR and Western blot. In hypercholesterolemic hearts, the expression of Adrb2 mRNA was significantly decreased. ADRB2 and PPP3R1 protein were significantly downregulated in hypercholesterolemic hearts. The direct interaction of Adrb2 with upregulated miRNAs was demonstrated by luciferase reporter assay. Gene ontology analysis revealed that the majority of the predicted mRNA changes may contribute to the hypercholesterolemia-induced cardiac dysfunction. In summary, the present unbiased target prediction approach based on global cardiac miRNA expression profiling revealed for the first time in the literature that both the mRNA and protein product of Adrb2 and PPP3R1 protein are decreased in the hypercholesterolemic heart

Praktijkervaringen met waterberging in natuur(ontwikkelings)gebieden : hoofdrapport pilotprogramma waterberging en natuur

In 2002 is het “Pilotprogramma Waterberging-Natuur”gestart. Het hoofddoel van het pilotprogramma was waterbeheerders, terreinbeherende instanties en provincies te ondersteunen in het koppelen van de functies waterberging en natuur. Daarbij is het pilotprogramma primair gericht geweest op het opdoen en verspreiden van ervaringskennis. Dit rapport geeft een overzicht van de belangrijkste resultaten van het pilotprogramma waterberging-natuur. Naast dit hoofdrapport is er per pilot een achtergrondrapport beschikbaar waar in meer detail wordt ingegaan op aanpak van de monitoring en de resultaten. Een samenwerking tussen vele partijen: WUR, Deltares, Natuurmonumenten, Staatsbosbeheer, RU Groningen, Twentse Vogelwerkgroep, waterschappen, Rijkswaterstaat en LNV (Natuur, Kennis