Tensor-Scalar Torsion

A theory of gravity with torsion is examined in which the torsion tensor is constructed from the exterior derivative of an antisymmetric rank two potential plus the dual of the gradient of a scalar field. Field equations for the theory are derived by demanding that the action be stationary under variations with respect to the metric, the antisymmetric potential, and the scalar field. A material action is introduced and the equations of motion are derived. The correct conservation law for rotational angular momentum plus spin is observed to hold in this theory.Comment: 10 pages, LaTeX, Mod. Phys. Lett. A accepte

Floating Bare Tether as Upper Atmosphere Probe

Use of a (bare) conductive tape electrically floating in LEO as an effective e-beam source that produces artificial auroras, and is free of problems that have marred standard beams, is considered. Ambient ions impacting the tape with KeV energies over most of its length liberate secondary electrons, which race down the magnetic field and excite neutrals in the E-layer, resulting in auroral emissions. The tether would operate at night-time with both a power supply and a plasma contactor off; power and contactor would be on at daytime for reboost. The optimal tape thickness yielding a minimum mass for an autonomous system is determined; the alternative use of an electric thruster for day reboost, depending on mission duration, is discussed. Measurements of emission brightness from the spacecraft could allow determination of the (neutral) density vertical profile in the critical E-layer; the flux and energy in the beam, varying along the tether, allow imaging line-of-sight integrated emissions that mix effects with altitude-dependent neutral density and lead to a brightness peak in the beam footprint at the E-layer. Difficulties in tomographic inversion, to determine the density profile, result from beam broadening, due to elastic collisions, which flattens the peak, and to the highly nonlinear functional dependency of line-of-sight brightness. Some dynamical issues are discussed

Phosphate Loading does not improve 30-km cycling time-trial performance in trained cyclists:phosphate and exercise performance

Phosphate is integral to numerous metabolic processes, several of which strongly predict exercise performance (i.e., cardiac function, oxygen transport, and oxidative metabolism). Evidence regarding phosphate loading is limited and equivocal, at least partly because studies have examined sodium phosphate supplements of varied molar mass (e.g., mono/di/tribasic, dodecahydrate), thus delivering highly variable absolute quantities of phosphate. Within a randomized cross-over design and in a singleblind manner, 16 well-trained cyclists (age 38 ± 16 years, mass 74.3 ± 10.8 kg, training 340 ± 171 min/week; mean ± SD) ingested either 3.5 g/day of dibasic sodium phosphate (Na2HPO4: 24.7 mmol/day phosphate; 49.4 mmol/day sodium) or a sodium chloride placebo (NaCl: 49.4 mmol/day sodium and chloride) for 4 days prior to each of two 30-km time trials, separated by a washout interval of 14 days. There was no evidence of any ergogenic benefit associated with phosphate loading. Time to complete the 30-km time trial did not differ following ingestion of sodium phosphate and sodium chloride (3,059 ± 531 s vs. 2,995 ± 467 s). Accordingly, neither absolute mean power output (221 ± 48 W vs. 226 ± 48 W) nor relative mean power output (3.02 ± 0.78 W/kg vs. 3.08 ± 0.71 W/kg) differed meaningfully between the respective intervention and placebo conditions. Measures of cardiovascular strain and ratings of perceived exertion were very closely matched between treatments (i.e., average heart rate 161 ± 11 beats per minute vs. 159 ± 12 beats per minute; Δ2 beats per minute; and ratings of perceived exertion 18 [14- 20] units vs. 17 [14-20] units). In conclusion, supplementing with relatively high absolute doses of phosphate (i.e., &gt;10 mmol daily for 4 days) exerted no ergogenic effects on trained cyclists completing 30-km time trials.</p

Mathematical modelling of adjuvant-enhanced active ingredient leaf uptake of pesticides

The global importance of effective and affordable pesticides to optimise crop yield and to support health of our growing population cannot be understated. But to develop new products or refine existing ones in response to climate and environmental changes is both time-intensive and expensive which is why the agrochemical industry is increasingly interested in using mechanistic models as part of their formulation development toolbox. In this work, we develop such a model to describe uptake of pesticide spray droplets across the leaf surface. We simplify the leaf structure by identifying the outer cuticle as the main barrier to uptake; the result is a novel, hybrid model in which two well-mixed compartments are separated by a membrane in which we describe the spatio-temporal distribution of the pesticide. This leads to a boundary value partial differential equation problem coupled to a pair of ordinary differential equation systems which we solve numerically. We also simplify the pesticide formulation into two key components: the Active Ingredient which produces the desired effect of the pesticide and an Adjuvant which is present in the formulation to facilitate effective absorption of the Active Ingredient into the leaf. This approach gives rise to concentration-dependent diffusion. We take an intuitive approach to parameter estimation using a small experimental data set and subsequently demonstrate the importance of the concentration-dependent diffusion in replicating the data. Finally, we demonstrate the need for further work to identify how the physicochemical properties of pesticides affect flow into and across the leaf surface

Floating bare tether as upper atmosphere probe

Use of a conductive bare tape electrically floating in low Earth orbit as an effective electron beam source to produce artificial auroral effects, free of problems that mard tandard beams, is considered. Ambient ions impacting the tape with keV energies over most of its length liberate secondary electrons that race down the magnetic field, excite neutrals in the E layer, and result in auroral emissions. The tether would operate with both a power supply and a plasma contactor off at nighttime; power and contactor would be on at daytime for reboost. Tomographic analysis of auroral emissions from the footprint of the beam, as observed from the spacecraft, can provide density profiles of dominant neutral species in the E layer. A characteristic tether system, at altitude 300 km and moderate orbital inclination, would involve an aluminum tape with a length of 20 km, a width of 15 mm, and a thickness of 0.2 mm for a full-system mass around 1200 kg, with two thirds going into the power subsystem

Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics

[EN] The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm(2) were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm(2) were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical enhancer because it allowed faster delivery of the drug. The DPK method was sufficiently sensitive to detect subtle vehicle-induced effects on the skin permeation of propranolol. The shorter duration of these experiments and their ability to provide mechanistic information about partition between vehicle and skin and diffusivity through skin place them as practical and potentially insightful approach to quantify and, ultimately, optimize topical bioavailability.This research was funded by Ministerio de Ciencia e Innovación (AP2007-03456) and the Universidad CEU Cardenal Herrera.Calatayud-Pascual, M.; Sebastian-Morelló, M.; Balaguer-Fernandez, C.; Delgado-Charro, M.; Lopez-Castellano, A.; Merino Sanjuán, V. (2018). Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics. Pharmaceutics. 10(4):1-15. https://doi.org/10.3390/pharmaceutics10040265S11510

Structural basis for assembly of vertical single β-barrel viruses

The vertical double beta-barrel major capsid protein (MCP) fold, fingerprint of the PRD1-adeno viral lineage, is widespread in many viruses infecting organisms across the three domains of life. The discovery of PRD1-like viruses with two MCPs challenged the known assembly principles. Here, we present the cryo-electron microscopy (cryo-EM) structures of the archaeal, halophilic, internal membrane-containing Haloarcula californiae icosahedral virus 1 (HCIV-1) and Haloarcula hispanica icosahedral virus 2 (HHIV-2) at 3.7 and 3.8 angstrom resolution, respectively. Our structures reveal proteins located beneath the morphologically distinct two- and three-tower capsomers and homopentameric membrane proteins at the vertices that orchestrate the positioning of pre-formed vertical single beta-barrel MCP heterodimers. The cryo-EM based structures together with the proteomics data provide insights into the assembly mechanism of this type of viruses and into those with membrane-less double beta-barrel MCPs.Peer reviewe

A mechanistic approach to modelling the formation of a drug reservoir in the skin

It has been shown that prolonged systemic presence of a drug can cause a build-up of that drug in the skin. This drug ‘reservoir’, if properly understood, could provide useful information about recent drug-taking history of the patient. We create a pair of coupled mathematical models which combine to explore the potential for a drug reservoir to establish based on the kinetic properties of the drug. The first compartmental model is used to characterise time-dependent drug concentrations in plasma and tissue following a customisable drug regimen. Outputs from this model provide boundary conditions for the second, spatio-temporal model of drug build-up in the skin. We focus on drugs that are highly bound as this will restrict their potential to move freely into the skin but which are lipophilic so that, in the unbound form, they would demonstrate an affinity to the outer layers of the skin. Buprenorphine, a drug used to treat opiate addiction, is one example of a drug satisfying these properties. In the discussion we highlight how our study might be used to inform future experimental design and data collection to provide relevant parameter estimates for reservoir formation and its potential to contribute to enhanced drug monitoring techniques.</p

Dermatopharmacokinetics: factors influencing drug clearance from the stratum corneum

PURPOSE: The dermatopharmacokinetic methodology, in which tape stripping of the stratum corneum (SC) is used to access the amount of drug accumulated in the skin barrier, has been proposed for the quantification of topical drug bioavailability. This investigation examined the clearance phase of a model drug from the SC after a short application of an infinite dose. METHODS: A saturated solution of ibuprofen in propylene glycol/water was applied to the forearm of human volunteers for 30 min. The formulation was then removed and the drug profile across the SC was assessed immediately, and over the next 4 h. RESULTS: The clearance phase depends only on drug diffusivity in the SC. However, the expected, progressive "flattening" of the concentration profiles with increasing time post-formulation removal was not observed. It was subsequently deduced, using infrared spectroscopy, that the rapid percutaneous diffusion of propylene glycol, relative to ibuprofen, resulted in the transient maintenance of a saturated drug concentration at the SC surface even after removal of the original formulation. CONCLUSIONS: The important role of formulation excipients in topical delivery is demonstrated, and the local disposition of cosolvents within the SC may impact significantly on drug dermatopharmacokinetics and local bioavailability