Modeling of nanoparticle coatings for medical applications

Abstract Gold nanoparticles (AuNPs) have been shown to possess properties beneficial for the treatment of cancerous tumors by acting as radiosensitizers for both photon and ion radiation. Blood circulation time is usually increased by coating the AuNPs with poly(ethylene glycol) (PEG) ligands. The effectiveness of the PEG coating, however, depends on both the ligand surface density and length of the PEG molecules, making it important to understand the structure of the coating. In this paper the thickness, ligand surface density, and density of the PEG coating is studied with classical molecular dynamics using the software package MBN Explorer. AuNPs consisting of 135 atoms (approximately 1.4 nm diameter) in a water medium have been studied with the number of PEG ligands varying between 32 and 60. We find that the thickness of the coating is only weakly dependent on the surface ligand density and that the degree of water penetration is increased when there is a smaller number of attached ligands

Granivorous habit in olrog’s gull (<i>Larus atlanticus</i>): implications for its specialist status

En este trabajo se dan a conocer observaciones sobre hábitos de alimentación desconocidos para la Gaviota Cangrejera (<i>Larus atlanticus</i>) en el puerto Ingeniero White, Bahía Blanca, Buenos Aires, Argentina. Entre 2002 y 2005, 281 individuos fueron observados alimentándose de granos en las banquinas del acceso y playa de estacionamiento del puerto. Los grupos de alimentación variaron entre 2–51 individuos. En el 78% de los casos este comportamiento ocurrió durante la pleamar, cuando el acceso a sus presas del intermareal era restringido. El uso de recursos de origen humano apoya la hipótesis que Larus atlanticus posee cierta plasticidad trófica y que puede comportarse como generalista. Se presenta una síntesis del estado actual del conocimiento de la dieta de esta especie y se propone una explicación para las distintas observaciones obtenidas a lo largo de la costa argentina.We report on unknown feeding habits of the Olrog’s Gull (<i>Larus atlanticus</i>) in the area of Ingeniero White port, Bahía Blanca, Buenos Aires Province, Argentina. Between 2002 and 2005, 281 individuals were observed feeding on grains along the shoulder of the road and in a parking lot besides the port. Feeding groups were of 2–51 individuals. This behaviour was observed mostly (78%) during high tides, when access to intertidal prey is limited. The exploitation of human resources by Larus atlanticus supports the hypothesis that this species has some degree of trophic plasticity and could behave as a generalist. We briefly review the literature on its diet, proposing an explanation for the different observations obtained along the coast of Argentina

Sexual selection and blue tit (Parus caeruleus) crown coloration

Conspicuous, sexually dimorphic plumage in birds is most likely a consequence of sexual selection favouring more ornamented males at obtaining a territory and/or a mate. Recent comparative analyses suggest that, among socially monogamous species, extra-pair paternity has also contributed to the elaboration of male ornaments. If females prefer more ornamented males as social or extra-pair mates this could translate into strong directional selection for ornament elaboration, since these males might sire more offspring in their own brood (within-pair success) or in broods of other males (extra-pair success). In this thesis I study the expression of the UV/blue crown coloration in the blue tit (Parus caeruleus) and investigate whether this trait could be selected through increased male within- or extra-pair success. Blue tits are socially monogamous passerines with relatively high levels of extra-pair paternity, and males in this species display more ultraviolet(UV)/blue reflectant crown feathers than females. Based on three years of data I found that crown coloration could be a cue used by females to assess male age since blue tits became more UV-ornamented as they aged. Crown coloration, however, did not correlate with survival to the next breeding season, suggesting that more UV-ornamented males are not necessarily of higher quality. While crown UV-ornamentation increased between years, it declined in the course of a year due to feather wear and dirt accumulation and this could affect female perception of male attractiveness. However, although the decline in UV ornamentation between winter and spring was large, it had no effect on male reproductive success, and winter and spring colour were still positively correlated. Using genetic paternity analysis I could show that more UV-ornamented males do not benefit through increased within-pair or extra-pair success. On the contrary, less UV-ornamented, adult males sired most of the extra-pair offspring. Hence the most successful males of the population were adult males that resembled juveniles in their crown colour. Accordingly, females seem to recognise less UV-ornamented males as highly successful, since they biased brood sex ratio towards male offspring if paired to these males. The causality of these patterns was tested in a colour manipulation experiment, where I treated males to become more (UV+) or less (UV-) ornamented within the natural range of variation. Against expectations UV(+) males sired significantly more extra-pair offspring than UV(-) males while the proportion of within-pair offspring was unaffected by the manipulation. Brood sex ratios did not differ between treatments but depended on male colour before manipulation. While these results do suggest that crown colour plays a role in paternity and brood sex allocation, they do not provide experimental support for the observed correlational patterns. I discuss the discrepancy between observational and experimental data, emphasising potential problems with the experimental manipulation of structural plumage colour. Finally, given that more UV-ornamented males did not sire more offspring, I explore the possibility that they would benefit by pairing with high quality females. High quality females in other species are often more ornamented, and birds of high quality pair assortatively based on ornament expression. This was not the case in this blue tit population, since female colour did not appear to indicate relevant female qualities (fecundity, seasonal reproductive success) and blue tits did not mate assortatively by crown colour in any of the three study years. To conclude, selection seems to favour older, less UV-ornamented males in this population. Whether this is due to female preference is unclear. Alternatively I hypothesise that being less ornamented may enable males searching for extra pair copulations to intrude into other territories without eliciting aggression by territory owners, perhaps by mimicking juveniles. Detailed behavioural observations in the wild coupled with choice chamber experiments in captivity are necessary to test this idea

Characterizing the Variability of Stars with Early-release Kepler Data

We present a variability analysis of the early-release first quarter of data publicly released by the Kepler project. Using the stellar parameters from the Kepler Input Catalog, we have separated the sample into 129,000 dwarfs and 17,000 giants and further sub-divided the luminosity classes into temperature bins corresponding approximately to the spectral classes A, F, G, K, and M. Utilizing the inherent sampling and time baseline of the public data set (30 minute sampling and 33.5 day baseline), we have explored the variability of the stellar sample. The overall variability rate of the dwarfs is 25% for the entire sample, but can reach 100% for the brightest groups of stars in the sample. G dwarfs are found to be the most stable with a dispersion floor of σ ~ 0.04 mmag. At the precision of Kepler, >95% of the giant stars are variable with a noise floor of ~0.1 mmag, 0.3 mmag, and 10 mmag for the G giants, K giants, and M giants, respectively. The photometric dispersion of the giants is consistent with acoustic variations of the photosphere; the photometrically derived predicted radial velocity distribution for the K giants is in agreement with the measured radial velocity distribution. We have also briefly explored the variability fraction as a function of data set baseline (1-33 days), at the native 30 minute sampling of the public Kepler data. To within the limitations of the data, we find that the overall variability fractions increase as the data set baseline is increased from 1 day to 33 days, in particular for the most variable stars. The lower mass M dwarf, K dwarf, and G dwarf stars increase their variability more significantly than the higher mass F dwarf and A dwarf stars as the time baseline is increased, indicating that the variability of the lower mass stars is mostly characterized by timescales of weeks while the variability of the higher mass stars is mostly characterized by timescales of days. A study of the distribution of the variability as a function of galactic latitude suggests that sources closer to the galactic plane are more variable. This may be the result of sampling differing populations (i.e., ages) as a function of latitude or may be the result of higher background contamination that is inflating the variability fractions at lower latitudes. A comparison of the M dwarf statistics to the variability of 29 known bright M dwarfs indicates that the M dwarfs are primarily variable on timescales of weeks or longer presumably dominated by spots and binarity. On shorter timescales of hours, which are relevant for planetary transit detection, the stars are significantly less variable, with ~80% having 12 hr dispersions of 0.5 mmag or less

Developmental and Radiobiologic Characteristics of Canine Multinucleated, Osteoclast-Like Cells Generated in Vitro from Canine Bone Marrow

We report here our initial observations on the growth and morphology, and developmental radiosensitivity of giant, multinucleated, osteoclast-like cells (MN-OS} generated through in vitro cultivation of hematopoietic progenitor-enriched canine bone marrow samples. Maximum cell densities of 5.5 x 103 to 6.5 x 103 MN-OS per cm2 of growth area were achieved following 10 to 14 days of culture at 37°C. Acute gamma irradiation of the initial marrow inocula resulted in significant, dose-dependent perturbations of MN-OS formation, growth, and development. Attempts to estimate radiosensitivity of MN-OS progenitors from canine marrow yielded a range of DO values from a low of 212 cGy measured at six days of culture to higher values of 405 to 542 cGy following 10 to 22 days of culture. At the intermediate times of culture (10 to 14 days}, the radiation-induced responses were clearly biphasic, reflecting either (a) the presence of multiple subpopulations of MN-OS progenitors with varying degrees of radiosensitivity or (b) the inherent biphasic nature of MN-OS development involving early progenitor cell proliferation followed by maturation and subsequent fusion. Morphologically, MN-OS generated from irradiated marrow inocula appeared only marginally altered, with alterations expressed largely in a biphasic, dose-dependent fashion in terms of smaller cell size, reduced number of nuclei, increased expression of both surface microprojections, and a unique set of crystalloid cytoplasmic inclusions. Functionally, MN-OS appeared to be impaired by irradiation of marrow progenitors, as evidenced by failure to initiate resorptive attachments to devitalized bone spicules in vitro

Transport of secondary electrons through coatings of ion-irradiated metallic nanoparticles

The transport of low-energy electrons through the coating of a radiosensitizing metallic nanoparticle under fast ion irradiation is analyzed theoretically and numerically. As a case study, we consider a poly(ethylene glycol)-coated gold nanoparticle of diameter 1.6~nm excited by a carbon ion in the Bragg peak region in water as well as by more energetic carbon ions. The diffusion equation for low-energy electrons emitted from a finite-size spherical source representing the surface of the metal core is solved to obtain the electron number density as a function of radial distance and time. Information on the atomistic structure and composition of the coating is obtained from molecular dynamics simulations performed with the MBN Explorer software package. Two mechanisms of low-energy electron production by the metallic core are considered: the relaxation of plasmon excitations and collective excitations of valence $d$ electrons in individual atoms of gold. Diffusion coefficients and characteristic lifetimes of electrons propagating in gold, water, and poly(ethylene glycol) are obtained from relativistic partial wave analysis and the dielectric formalism, respectively. On this basis, the number of electrons released through the organic coating into the surrounding aqueous medium and the number of hydroxyl radicals produced are evaluated. The largest increase of the radical yield due to low-energy electrons is observed when the nanoparticle is excited by an ion with energy significantly exceeding that in the Bragg peak region. It is also shown that the water content of the coating, especially near the surface of the metal core, is crucial for the production of hydroxyl radicals.Comment: a contribution to the Special Issue "Atomic Cluster Collisions" of the European Physical Journal

LaCrO3 heteroepitaxy on SrTiO3(001) by molecular beam epitaxy

Stoichiometric, epitaxial LaCrO3 films have been grown on TiO2-terminated SrTiO3(001) substrates by molecular beam epitaxy using O2 as the oxidant. Film growth occurred in a layer-by-layer fashion, giving rise to structurally excellent films and surfaces which preserve the step-terrace structure of the substrate. The critical thickness is in excess of 500 {\AA}. Near-surface Cr(III) is highly susceptible to further oxidation to Cr(V), leading to the formation of a disordered phase upon exposure to atomic oxygen. Recovery of the original epitaxial LaCrO3 phase is readily achieved by vacuum annealing.Comment: 10 pages, 4 figure

Simulating long-term impacts of cover crops and climate change on crop production and environmental outcomes in the Midwestern United States

It is critical to evaluate conservation practices that protect soil and water resources from climate change in the Midwestern United States, a region that produces one-quarter of the world’s soybeans and one-third of the world’s maize. An over-winter cover crop in a maize–soybean rotation offers multiple potential benefits that can reduce the impacts of higher temperatures and more variable rainfall; some of the anticipated changes for the Midwest. In this experiment we used the Agricultural Production Systems sIMulator (APSIM) to understand how winter rye cover crops impact crop production and environmental outcomes, given future climate change. We first tested APSIM with data from a long-term maize–soybean rotation with and without winter rye cover crop field site. Our modeling work predicted that the winter rye cover crop has a neutral effect on maize and soybean yields over the 45 year simulation period but increases in minimum and maximum temperatures were associated with reduced yields of 1.6–2.7% by decade. Soil carbon decreased in both the cover crop and no cover crop simulations, although the cover crop is able to significantly offset (3% less loss over 45 years) this decline compared to the no cover crop simulation. Our predictions showed that the cover crop led to an 11–29% reduction in erosion and up to a 34% decrease in nitrous oxide emissions (N2O). However, the cover crop is unable to offset future predicted yield declines and does not increase the overall carbon balance relative to current soil conditions

Principal Stratum Strategy: Potential Role in Drug Development

A randomized trial allows estimation of the causal effect of an intervention compared to a control in the overall population and in subpopulations defined by baseline characteristics. Often, however, clinical questions also arise regarding the treatment effect in subpopulations of patients, which would experience clinical or disease related events post-randomization. Events that occur after treatment initiation and potentially affect the interpretation or the existence of the measurements are called {\it intercurrent events} in the ICH E9(R1) guideline. If the intercurrent event is a consequence of treatment, randomization alone is no longer sufficient to meaningfully estimate the treatment effect. Analyses comparing the subgroups of patients without the intercurrent events for intervention and control will not estimate a causal effect. This is well known, but post-hoc analyses of this kind are commonly performed in drug development. An alternative approach is the principal stratum strategy, which classifies subjects according to their potential occurrence of an intercurrent event on both study arms. We illustrate with examples that questions formulated through principal strata occur naturally in drug development and argue that approaching these questions with the ICH E9(R1) estimand framework has the potential to lead to more transparent assumptions as well as more adequate analyses and conclusions. In addition, we provide an overview of assumptions required for estimation of effects in principal strata. Most of these assumptions are unverifiable and should hence be based on solid scientific understanding. Sensitivity analyses are needed to assess robustness of conclusions