An analysis of quantum Fokker-Planck models : a Wigner function approach

The analysis of dissipative transport equations within the framework of open quantum systems with Fokker-Planck-type scattering is carried out from the perspective of a Wigner function approach. In particular, the well-posedness of the self-consistent whole-space problem in 3D is analyzed: existence of solutions, uniqueness and asymptotic behavior in time, where we adopt the viewpoint of mild solutions in this paper. Also, the admissibility of a density matrix formulation in Lindblad form with Fokker-Planck dissipation mechanisms is discussed. We remark that our solution concept allows to carry out the analysis directly on the level of the kinetic equation instead of on the level of the density operator

Global climate change and food supply chains: policies for collective adaptation

According to climate model predictions, most parts of Latin America and the Caribbean (LAC) will see significant temperature increases and changes in precipitation by 2050. In Guatemala, Colombia, and Jamaica, for example, such shifts will pose serious challenges for food supply chains in the face of increasing demand. If crop production is allowed to fall behind, this will not only lower national income and private sector growth but also jeopardize the food security and livelihoods of thousands of smallholder farmers. Policy makers must begin now to minimize the socio-economic impacts of climate change through a coordinated effort to identify pro-active options for adaptation, which take into account the different impacts and degrees of vulnerability across locations, crops, supply chains, and cultures

Cambio climático mundial y cadenas de suministro de alimentos: políticas para la adaptación colectiva

Según predicciones de modelos climáticos, la mayor parte de América Latina y el Caribe (ALC) experimentará aumentos significativos de temperatura y cambios en la precipitación para el 2050. En Guatemala, Colombia y Jamaica, por ejemplo, estos cambios plantearán serios desafíos para las cadenas de suministro de alimentos frente a la creciente demanda. Si se deja rezagar la producción de cultivos, esto no solamente reducirá los ingresos nacionales y el crecimiento del sector privado, sino que además pondrá en riesgo la seguridad alimentaria y los medios de vida de miles de pequeños agricultores. Los responsables de formular las políticas deben empezar desde ahora a minimizar los impactos socioeconómicos del cambio climático mediante un esfuerzo coordinado para identificar opciones proactivas de adaptación, que tengan en cuenta los diferentes grados de vulnerabilidad en todas partes, cultivos, cadenas de suministro y culturas

Bottleneck and selection in the germline and maternal age influence transmission of mitochondrial DNA in human pedigrees.

Heteroplasmy-the presence of multiple mitochondrial DNA (mtDNA) haplotypes in an individual-can lead to numerous mitochondrial diseases. The presentation of such diseases depends on the frequency of the heteroplasmic variant in tissues, which, in turn, depends on the dynamics of mtDNA transmissions during germline and somatic development. Thus, understanding and predicting these dynamics between generations and within individuals is medically relevant. Here, we study patterns of heteroplasmy in 2 tissues from each of 345 humans in 96 multigenerational families, each with, at least, 2 siblings (a total of 249 mother-child transmissions). This experimental design has allowed us to estimate the timing of mtDNA mutations, drift, and selection with unprecedented precision. Our results are remarkably concordant between 2 complementary population-genetic approaches. We find evidence for a severe germline bottleneck (7-10 mtDNA segregating units) that occurs independently in different oocyte lineages from the same mother, while somatic bottlenecks are less severe. We demonstrate that divergence between mother and offspring increases with the mother's age at childbirth, likely due to continued drift of heteroplasmy frequencies in oocytes under meiotic arrest. We show that this period is also accompanied by mutation accumulation leading to more de novo mutations in children born to older mothers. We show that heteroplasmic variants at intermediate frequencies can segregate for many generations in the human population, despite the strong germline bottleneck. We show that selection acts during germline development to keep the frequency of putatively deleterious variants from rising. Our findings have important applications for clinical genetics and genetic counseling

Human Vault Nanoparticle Targeted Delivery of Antiretroviral Drugs to Inhibit Human Immunodeficiency Virus Type 1 Infection.

"Vaults" are ubiquitously expressed endogenous ribonucleoprotein nanoparticles with potential utility for targeted drug delivery. Here, we show that recombinant human vault nanoparticles are readily engulfed by certain key human peripheral blood mononuclear cells (PBMC), predominately dendritic cells, monocytes/macrophages, and activated T cells. As these cell types are the primary targets for human immunodeficiency virus type 1 (HIV-1) infection, we examined the utility of recombinant human vaults for targeted delivery of antiretroviral drugs. We chemically modified three different antiretroviral drugs, zidovudine, tenofovir, and elvitegravir, for direct conjugation to vaults. Tested in infection assays, drug-conjugated vaults inhibited HIV-1 infection of PBMC with equivalent activity to free drugs, indicating vault delivery and drug release in the cytoplasm of HIV-1-susceptible cells. The ability to deliver functional drugs via vault nanoparticle conjugates suggests their potential utility for targeted drug delivery against HIV-1

Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

<p>Abstract</p> <p>Background</p> <p>The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as <it>in vitro </it>and <it>in vivo </it>toxicity.</p> <p>Results</p> <p>The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an <it>ex vivo </it>rectal explant model.</p> <p>Conclusions</p> <p>Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products.</p

Workshop report: Playing out transformative adaptation in Usambara, Tanzania

This report documents the information collected during the participatory workshop hosted by The CGIAR Research Program on Climate Change, Agriculture and Food Security (CCAFS) in partnership with the Selian Agricultural Research Institute (SARI) and Lushoto District Office in the CCAFS site of Usambara Tanzania. This workshop was conducted as part of the CCAFS project “Playing out transformative adaptation in CCAFS benchmark sites in East-Africa: ‘When, where, how and with whom?’ which seeks to identify and understand, through integrated agricultural research, the adaptation process in the CCAFS benchmark site of Usambara, Tanzania. The workshop included farmers from various villages in the CCAFS site, who discussed agricultural practices and perceptions of climate change/variability. The workshop started off with an introduction/icebreaker, after which historical calendars, a discussion of crop suitability and baseline data and gender questions followed. Finally a vision for the future was made, in which the groups were asked to say what they would like to see in the future concerning climate change, food security and gender. The introduction/icebreaker and the general presentation of results were done in a large group but smaller groups were formed to do the historical calendars and to discuss crop suitability and baseline data as well as the gender questions. Most of the small groups were divided by gender, typically with two men’s groups and two women’s groups. In general it can be stated that the farmer is aware of a changing climate and the (negative) consequences this brings about. Furthermore there are differences in perspectives between men and women on the division of tasks and on the household decisionmaking process. Concerning the vision of the future, many farmers let us know that they would like to see more extended information and capacitation on climate change adaptation and mitigation strategies