Enzyme activation by alternating magnetic field: Importance of the bioconjugation methodology

Iron oxide nanoparticles (NPs) are attractive materials for enzyme immobilization and, thanks to their superparamagnetism, can be accessed by remote stimuli. This can be exploited to activate molecules that are not remotely actuable. Here, we demonstrate that thermophilic enzymes chemically linked to NPs can be activated in a \u201cwireless\u201d fashion by an external alternate magnetic field (AMF). To this aim, we have conjugated, with different binding strategies, the thermophilic enzymes \u3b1-amylase and L-aspartate oxidase to iron oxide NPs obtaining NP-enzyme systems with activities depending on the different orientations and stretching of the enzymes. Since enzyme activation occurs without a significant rise of the \u201coverall\u201d temperature of the systems, we have speculated a local NP-enzyme heating that does not immediately interest the rest of the solution that remains at relatively low temperature, low enough to allow non-thermophilic enzymes to work together with the NP-conjugated thermophilic enzymes. Nanoactuation of thermophilic enzymes by AMF has potential applications in different fields. Indeed, multi-enzymatic processes with enzymes with different temperature optima could be carried out in the same reaction pot and thermolabile products could be efficiently produced by thermophilic enzymes without suffering for the high temperatures. Moreover, our findings represent a proof of concept of the possibility to achieve a fine-tuning of the enzyme-NP system with the aim to intervene in cell metabolism

Pre-hospital risk factors for inpatient death from severe febrile illness in Malian children.

BACKGROUND: Inpatient case fatality from severe malaria remains high in much of sub-Saharan Africa. The majority of these deaths occur within 24 hours of admission, suggesting that pre-hospital management may have an impact on the risk of case fatality. METHODS: Prospective cohort study, including questionnaire about pre-hospital treatment, of all 437 patients admitted with severe febrile illness (presumed to be severe malaria) to the paediatric ward in Sikasso Regional Hospital, Mali, in a two-month period. FINDINGS: The case fatality rate was 17.4%. Coma, hypoglycaemia and respiratory distress at admission were associated with significantly higher mortality. In multiple logistic regression models and in a survival analysis to examine pre-admission risk factors for case fatality, the only consistent and significant risk factor was sex. Girls were twice as likely to die as boys (AOR 2.00, 95% CI 1.08-3.70). There was a wide variety of pre-hospital treatments used, both modern and traditional. None had a consistent impact on the risk of death across different analyses. Reported use of traditional treatments was not associated with post-admission outcome. INTERPRETATION: Aside from well-recognised markers of severity, the main risk factor for death in this study was female sex, but this study cannot determine the reason why. Differences in pre-hospital treatments were not associated with case fatality

Do ethnobotanical and laboratory data predict clinical safety and efficacy of anti-malarial plants?

<p>Abstract</p> <p>Background</p> <p>Over 1200 plant species are reported in ethnobotanical studies for the treatment of malaria and fevers, so it is important to prioritize plants for further development of anti-malarials.</p> <p>Methods</p> <p>The “RITAM score” was designed to combine information from systematic literature searches of published ethnobotanical studies and laboratory pharmacological studies of efficacy and safety, in order to prioritize plants for further research. It was evaluated by correlating it with the results of clinical trials.</p> <p>Results and discussion</p> <p>The laboratory efficacy score correlated with clinical parasite clearance (r_s=0.7). The ethnobotanical component correlated weakly with clinical symptom clearance but not with parasite clearance. The safety component was difficult to validate as all plants entering clinical trials were generally considered safe, so there was no clinical data on toxic plants.</p> <p>Conclusion</p> <p>The RITAM score (especially the efficacy and safety components) can be used as part of the selection process for prioritising plants for further research as anti-malarial drug candidates. The validation in this study was limited by the very small number of available clinical studies, and the heterogeneity of patients included.</p

Determinants of woody encroachment and cover in African savannas

Savanna ecosystems are an integral part of the African landscape and sustain the livelihoods of millions of people. Woody encroachment in savannas is a widespread phenomenon but its causes are widely debated. We review the extensive literature on woody encroachment to help improve understanding of the possible causes and to highlight where and how future scientific efforts to fully understand these causes should be focused. Rainfall is the most important determinant of maximum woody cover across Africa, but fire and herbivory interact to reduce woody cover below the maximum at many locations. We postulate that woody encroachment is most likely driven by CO2 enrichment and propose a two-system conceptual framework, whereby mechanisms of woody encroachment differ depending on whether the savanna is a wet or dry system. In dry savannas, the increased water-use efficiency in plants relaxes precipitation-driven constraints and increases woody growth. In wet savannas, the increase of carbon allocation to tree roots results in faster recovery rates after disturbance and a greater likelihood of reaching sexual maturity. Our proposed framework can be tested using a mixture of experimental and earth observational techniques. At a local level, changes in precipitation, burning regimes or herbivory could be driving woody encroachment, but are unlikely to be the explanation of this continent-wide phenomenon

The Upgrade I of LHCb VELO -- towards an intelligent monitoring platform

The Large Hadron Collider beauty (LHCb) detector is designed to detect decays of b- and c- hadrons for the study of CP violation and rare decays. At the end of the LHC Run 2, many of the LHCb measurements remained statistically dominated. In order to increase the trigger yield for purely hadronic channels, the hardware trigger will be removed, and the detector will be read out at 40 MHz. This, in combination with the five-fold increase in luminosity, requires radical changes to LHCb's electronics, and, in some cases, the replacement of entire sub-detectors with state-of-the-art detector technologies. The Vertex Locator (VELO) surrounding the interaction region is used to reconstruct the collision points (primary vertices) and decay vertices of long-lived particles (secondary vertices). The upgraded VELO will be composed of 52 modules placed along the beam axis divided into two retractable halves. The modules will each be equipped with 4 silicon hybrid pixel tiles, each read out by 3 VeloPix ASICs. The total output data rate anticipated for the whole detector will be around 1.6 Tbit/s. The highest occupancy ASICs will have pixel hit rates of approximately 900 Mhit/s, with the corresponding output data rate of 15 Gbit/s. The LHCb upgrade detector will be the first detector to read out at the full LHC rate of 40 MHz. The VELO upgrade will utilize the latest detector technologies to read out at this rate while maintaining the required radiation-hard profile and minimizing the detector material

Complementary organic thin film transistor circuits fabricated directly on silicone substrates

The present work demonstrates organic circuits on a new class of substrate, silicone elastomers. The fabrication method relies on dry, additive processes performed at ultra-low substrate temperature (&lt;100 °C). P-type pentacene and n-type C60 organic thin-film transistors (TFTs) in a bottom gate, top contact architecture are prepared directly on polydimethylsiloxane (PDMS) membranes without any surface pre-treatment. Simple logic elements including complementary inverters and ambipolar transistors patterned on PDMS perform similarly to their counterparts fabricated on substrates thousands times stiffer. The processing options and mechanical compliance of the elastomeric substrate combined with organic device materials open new opportunities for compliant, lightweight, low-power and large area thin-film circuitry. © 2010 Elsevier B.V. All rights reserved