5,053 research outputs found
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: polĂticas para la adaptaciĂłn 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 desafĂos para las cadenas de suministro de alimentos frente a la creciente demanda. Si se deja rezagar la producciĂłn 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 polĂticas deben empezar desde
ahora a minimizar los impactos socioeconómicos del cambio climático mediante un esfuerzo coordinado para identificar opciones
proactivas de adaptaciĂłn, que tengan en cuenta los diferentes grados de vulnerabilidad en todas partes, cultivos, cadenas de suministro y
culturas
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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
Optimizing Beam Transport in Rapidly Compressing Beams on the Neutralized Drift Compression Experiment - II
The Neutralized Drift Compression Experiment-II (NDCX-II) is an induction
linac that generates intense pulses of 1.2 MeV helium ions for heating matter
to extreme conditions. Here, we present recent results on optimizing beam
transport. The NDCX-II beamline includes a 1-meter-long drift section
downstream of the last transport solenoid, which is filled with
charge-neutralizing plasma that enables rapid longitudinal compression of an
intense ion beam against space-charge forces. The transport section on NDCX-II
consists of 28 solenoids. Finding optimal field settings for a group of
solenoids requires knowledge of the envelope parameters of the beam. Imaging
the beam on scintillator gives the radius of the beam, but the envelope angle
dr/dz is not measured directly. We demonstrate how the parameters of the beam
envelope (r, dr/dz, and emittance) can be reconstructed from a series of images
taken at varying B-field strengths of a solenoid upstream of the scintillator.
We use this technique to evaluate emittance at several points in the NDCX-II
beamline and for optimizing the trajectory of the beam at the entry of the
plasma-filled drift section
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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
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