Conditions for statistical determination of the neutrino mass spectrum in radiative emission of neutrino pairs in atoms

The photon spectrum in macrocoherent atomic deexcitation via radiative emission of neutrino pairs has been proposed as a sensitive probe of the neutrino mass spectrum, capable of competing with conventional neutrino experiments. In this paper we revisit this interesting proposal in order to quantify the requirements for statistical determination of some of the properties of the neutrino spectrum, in particular, the neutrino mass scale and the mass ordering. Our results are shown as the product of the experimental lifetime, the target volume, and the number density of atoms which have to be set in a coherence state with a given electric field in the target, needed for determination of these properties with a given confidence level

Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy

Background: Cationic solid lipid nanoparticles (SLNs) have been given considerable attention for therapeutic nucleic acid delivery owing to their advantages over viral and other nanoparticle delivery systems. However, poor delivery efficiency and complex formulations hinder the clinical translation of SLNs. Aim: The aim of this study was to formulate and characterize SLNs incorporating the cholesterol derivative cholesteryl oleate to produce SLN-nucleic acid complexes with reduced cytotoxicity and more efficient cellular uptake. Methods: Five cholesteryl oleate-containing formulations were prepared. Laser diffraction and laser Doppler microelectrophoresis were used to evaluate particle size and zeta potential, respectively. Nanoparticle morphology was analyzed using electron microscopy. Cytotoxicity and cellular uptake of lipoplexes were evaluated using flow cytometry and fluorescence microscopy. The gene inhibition capacity of the lipoplexes was assessed using siRNAs to block constitutive luciferase expression. Results: We obtained nanoparticles with a mean diameter of approximately 150-200 nm in size and zeta potential values of 25-40 mV. SLN formulations with intermediate concentrations of cholesteryl oleate exhibited good stability and spherical structures with no aggregation. No cell toxicity of any reference SLN was observed. Finally, cellular uptake experiments with DNAand RNA-SLNs were performed to select one reference with superior transient transfection efficiency that significantly decreased gene activity upon siRNA complexation. Conclusion: The results indicate that cholesteryl oleate-loaded SLNs are a safe and effective platform for nonviral nucleic acid delivery

Lessons for Research Policy and Practice: The Case of Co-enquiry Research With Rural Communities

This article explores the relationship between institutional funding for research and community-based or co-enquiry research practice. It examines the implementation of co-enquiry research in the COMBIOSERVE project, which was funded by the European Commission’s Seventh Framework Programme for research and innovation, between the years 2012 and 2015. Research partnerships between Latin American and European civil society organisations, research institutions, and Latin American rural communities are analysed. Challenges for effective collaboration in co-enquiry and lessons learned for research policy and practice are outlined. Based on our case study we suggest that: (1) the established values and practices of academia seem largely unfavourable towards alternative forms of research, such as co-enquiry; (2) the policies and administrative practices of this European Commission funding are unsuitable for adopting participatory forms of enquiry; and (3) the approach to research funding supports short engagements with communities whereas long-term collaborations are more desirable. Based on our case study, we propose more flexible funding models that support face-to-face meetings between researchers and communities from the time of proposal drafting, adaptation of research processes to local dynamics, adaptation of administrative processes to the capacities of all participants, and potential for long-term collaborations. Large-scale funding bodies such as European Commission research programmes are leaders in the evolution of research policy and practice. They have the power and the opportunity to publicly acknowledge the value of partnerships with civil society organisations and communities, actively support co-enquiry, and foment interest in innovative forms of research

A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules

A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules

Latitude dictates plant diversity effects on instream decomposition

Running waters contribute substantially to global carbon fluxes through decomposition of terrestrial plant litter by aquatic microorganisms and detritivores. Diversity of this litter may influence instream decomposition globally in ways that are not yet understood. We investigated latitudinal differences in decomposition of litter mixtures of low and high functional diversity in 40 streams on 6 continents and spanning 113 degrees of latitude. Despite important variability in our dataset, we found latitudinal differences in the effect of litter functional diversity on decomposition, which we explained as evolutionary adaptations of litter-consuming detritivores to resource availability. Specifically, a balanced diet effect appears to operate at lower latitudes versus a resource concentration effect at higher latitudes. The latitudinal pattern indicates that loss of plant functional diversity will have different consequences on carbon fluxes across the globe, with greater repercussions likely at low latitudes

Global Patterns and Controls of Nutrient Immobilization On Decomposing Cellulose In Riverine Ecosystems

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature