Effectiveness of Pyriproxyfen and Olyset Duo in Controlling Insecticide Resistant Mosquito Populations in Burkina Faso

The escalation of Long-Lasting Insecticidal Nets (LLINs) mass distribution marked the beginning of a period of malaria decline in sub-Saharan Africa. However, the emergence and spread of insecticide resistance in malaria mosquitoes is a threat to the effectiveness and sustainability of this vector control method. In this context, it is necessary to design and evaluate new compounds and methods that attenuate or even reverse the insecticide resistance trend. Olyset Duo is a novel LLIN that combines the insecticide properties of permethrin and the chemosterilising effect of pyriproxyfen (PPF). The rationale is that resistant mosquitoes that survive the contact with the net would not be able to transfer the resistance genes to the offspring, eventually influencing the resistant phenotype of the mosquito population. In the first part of this study the sterilising and sub-lethal effect of PPF and Olyset Duo was evaluated by a range of bioassays with laboratory and wild mosquito populations. PPF significantly affected the longevity, oogenesis, oviposition and hatching rate of susceptible and resistant mosquitoes, although the effect was partially diminished on the resistant colonies. The possible reasons and implications of PPF performance under controlled conditions are discussed. The second part of this thesis was done within the context of an Olyset Duo Randomised Controlled Trial (RCT) set in Banfora District, Burkina Faso. The RCT had a stepped-wedge design which ensured that Olyset Duo nets gradually replaced Olyset nets in randomly allocated cluster of villages until the Olyset Duo coverage was total. Wild mosquitoes collected in sentinel sites with Olyset Duo showed evident signs of reproductive impairment even after 1 year of deployment. Insecticide resistance strength was monitored during the RCT in several sentinel sites, and time-response data showed an overall reduction of permethrin resistance strength after the distribution of Olyset Duo. This is the most detailed study on the effect of Olyset Duo on key entomological factors of wild mosquito populations. The standardised protocols as well as the dataset obtained are valuable information for ongoing evaluation of Olyset Duo and PPF as a tool for controlling malaria mosquitoes and as a potential alternative for insecticide resistance management

Deep Learning Hamiltonians from Disordered Image Data in Quantum Materials

The capabilities of image probe experiments are rapidly expanding, providing new information about quantum materials on unprecedented length and time scales. Many such materials feature inhomogeneous electronic properties with intricate pattern formation on the observable surface. This rich spatial structure contains information about interactions, dimensionality, and disorder -- a spatial encoding of the Hamiltonian driving the pattern formation. Image recognition techniques from machine learning are an excellent tool for interpreting information encoded in the spatial relationships in such images. Here, we develop a deep learning framework for using the rich information available in these spatial correlations in order to discover the underlying Hamiltonian driving the patterns. We first vet the method on a known case, scanning near-field optical microscopy on a thin film of VO2. We then apply our trained convolutional neural network architecture to new optical microscope images of a different VO2 film as it goes through the metal-insulator transition. We find that a two-dimensional Hamiltonian with both interactions and random field disorder is required to explain the intricate, fractal intertwining of metal and insulator domains during the transition. This detailed knowledge about the underlying Hamiltonian paves the way to using the model to control the pattern formation via, e.g., tailored hysteresis protocols. We also introduce a distribution-based confidence measure on the results of a multi-label classifier, which does not rely on adversarial training. In addition, we propose a new machine learning based criterion for diagnosing a physical system's proximity to criticality

Voltage-Induced Ferromagnetic Resonance in Magnetic Tunnel Junctions

We demonstrate excitation of ferromagnetic resonance in CoFeB/MgO/CoFeB magnetic tunnel junctions (MTJs) by the combined action of voltage-controlled magnetic anisotropy (VCMA) and spin transfer torque (ST). Our measurements reveal that GHz-frequency VCMA torque and ST in low-resistance MTJs have similar magnitudes, and thus that both torques are equally important for understanding high-frequency voltage-driven magnetization dynamics in MTJs. As an example, we show that VCMA can increase the sensitivity of an MTJ-based microwave signal detector to the sensitivity level of semiconductor Schottky diodes.Comment: 5 pages; supplementary material adde

Plasmodium falciparum metacaspase PfMCA-1 triggers a z-VAD-fmk inhibitable protease to promote cell death.

Activation of proteolytic cell death pathways may circumvent drug resistance in deadly protozoan parasites such as Plasmodium falciparum and Leishmania. To this end, it is important to define the cell death pathway(s) in parasites and thus characterize proteases such as metacaspases (MCA), which have been reported to induce cell death in plants and Leishmania parasites. We, therefore, investigated whether the cell death function of MCA is conserved in different protozoan parasite species such as Plasmodium falciparum and Leishmania major, focusing on the substrate specificity and functional role in cell survival as compared to Saccharomyces cerevisae. Our results show that, similarly to Leishmania, Plasmodium MCA exhibits a calcium-dependent, arginine-specific protease activity and its expression in yeast induced growth inhibition as well as an 82% increase in cell death under oxidative stress, a situation encountered by parasites during the host or when exposed to drugs such as artemisins. Furthermore, we show that MCA cell death pathways in both Plasmodium and Leishmania, involve a z-VAD-fmk inhibitable protease. Our data provide evidence that MCA from both Leishmania and Plasmodium falciparum is able to induce cell death in stress conditions, where it specifically activates a downstream enzyme as part of a cell death pathway. This enzymatic activity is also induced by the antimalarial drug chloroquine in erythrocytic stages of Plasmodium falciparum. Interestingly, we found that blocking parasite cell death influences their drug sensitivity, a result which could be used to create therapeutic strategies that by-pass drug resistance mechanisms by acting directly on the innate pathways of protozoan cell death

A Novel In Vivo Approach to Assess Radial and Axial Distensibility of Large and Intermediate Pulmonary Artery Branches

Pulmonary arteries (PAs) distend to accommodate increases in cardiac output. PA distensibility protects the right ventricle (RV) from excessive increases in pressure. Loss of PA distensibility plays a critical role in the fatal progression of pulmonary arterial hypertension (PAH) toward RV failure. However, it is unclear how PA distensibility is distributed across the generations of PA branches, mainly because of the lack of appropriate in vivo methods to measure distensibility of vessels other than the large, conduit PAs. In this study, we propose a novel approach to assess the distensibility of individual PA branches. The metric of PA distensibility we used is the slope of the stretch ratio-pressure relationship. To measure distensibility, we combined invasive measurements of mean PA pressure with angiographic imaging of the PA network of six healthy female dogs. Stacks of 2D images of the PAs, obtained from either contrast enhanced magnetic resonance angiography (CE-MRA) or computed tomography digital subtraction angiography (CT-DSA), were used to reconstruct 3D surface models of the PA network, from the first bifurcation down to the sixth generation of branches. For each branch of the PA, we calculated radial and longitudinal stretch between baseline and a pressurized state obtained via acute embolization of the pulmonary vasculature. Our results indicated that large and intermediate PA branches have a radial distensibility consistently close to 2%/mmHg. Our axial distensibility data, albeit affected by larger variability, suggested that the PAs distal to the first generation may not significantly elongate in vivo, presumably due to spatial constraints. Results from both angiographic techniques were comparable to data from established phase-contrast (PC) magnetic resonance imaging (MRI) and ex vivo mechanical tests, which can only be used in the first branch generation. Our novel method can be used to characterize PA distensibility in PAH patients undergoing clinical right heart catheterization (RHC) in combination with MRI

Magnetic stray fields in nanoscale magnetic tunnel junctions

The magnetic stray field is an unavoidable consequence of ferromagnetic devices and sensors leading to a natural asymmetry in magnetic properties. Such asymmetry is particularly undesirable for magnetic random access memory applications where the free layer can exhibit bias. Using atomistic dipole-dipole calculations we numerically simulate the stray magnetic field emanating from the magnetic layers of a magnetic memory device with different geometries. We find that edge effects dominate the overall stray magnetic field in patterned devices and that a conventional synthetic antiferromagnet structure is only partially able to compensate the field at the free layer position. A granular reference layer is seen to provide near-field flux closure while additional patterning defects add significant complexity to the stray field in nanoscale devices. Finally we find that the stray field from a nanoscale antiferromagnet is surprisingly non-zero arising from the imperfect cancellation of magnetic sublattices due to edge defects. Our findings provide an outline of the role of different layer structures and defects in the effective stray magnetic field in nanoscale magnetic random access memory devices and atomistic calculations provide a useful tools to study the stray field effects arising from a wide range of defects