Enhanced topical delivery of dexamethasone by β-cyclodextrin decorated thermoresponsive nanogels

Highly hydrophilic, responsive nanogels are attractive as potential systems for the topical delivery of bioactives encapsulated in their three-dimensional polymeric scaffold. Yet, these drug carrier systems suffer from drawbacks for efficient delivery of hydrophobic drugs. Addressing this, β-cyclodextrin (βCD) could be successfully introduced into the drug carrier systems by exploiting its unique affinity toward dexamethasone (DXM) as well as its role as topical penetration enhancer. The properties of βCD could be combined with those of thermoresponsive nanogels (tNGs) based on dendritic polyglycerol (dPG) as a crosslinker and linear thermoresponsive polyglycerol (tPG) inducing responsiveness to temperature changes. Electron paramagnetic resonance (EPR) studies localized the drug within the hydrophobic cavity of βCD by differences in its mobility and environmental polarity. In fact, the fabricated carriers combining a particulate delivery system with a conventional penetration enhancer, resulted in an efficient delivery of DXM to the epidermis and the dermis of human skin ex vivo (enhancement compared to commercial DXM cream: ∼2.5 fold in epidermis, ∼30 fold in dermis). Furthermore, DXM encapsulated in βCD tNGs applied to skin equivalents downregulated the expression of proinflammatory thymic stromal lymphopoietin (TSLP) and outperformed a commercially available DXM cream

Synergistic effects of iron and temperature on Antarctic phytoplankton and microzooplankton assemblages

© 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution 3.0 License. The definitive version was published in Biogeosciences 6 (2009): 3131-3147, doi: 10.5194/bg-6-3131-2009Iron availability and temperature are important limiting factors for the biota in many areas of the world ocean, and both have been predicted to change in future climate scenarios. However, the impacts of combined changes in these two key factors on microbial trophic dynamics and nutrient cycling are unknown. We examined the relative effects of iron addition (+1 nM) and increased temperature (+4°C) on plankton assemblages of the Ross Sea, Antarctica, a region characterized by annual algal blooms and an active microbial community. Increased iron and temperature individually had consistently significant but relatively minor positive effects on total phytoplankton abundance, phytoplankton and microzooplankton community composition, as well as photosynthetic parameters and nutrient drawdown. Unexpectedly, increased iron had a consistently negative impact on microzooplankton abundance, most likely a secondary response to changes in phytoplankton community composition. When iron and temperature were increased in concert, the resulting interactive effects were greatly magnified. This synergy between iron and temperature increases would not have been predictable by examining the effects of each variable individually. Our results suggest the possibility that if iron availability increases under future climate regimes, the impacts of predicted temperature increases on plankton assemblages in polar regions could be significantly enhanced. Such synergistic and antagonistic interactions between individual climate change variables highlight the importance of multivariate studies for marine global change experiments.This project was supported by US NSF grants ANT 0528715 to JMR, ANT 0741411, ANT 0741428 and OCE 0825319 to DAH, ANT 0338157 to WOS, ANT 0338097 to GRD, and ANT 0338350 to RBD

Operational experience with the GEM detector assembly lines for the CMS forward muon upgrade

The CMS Collaboration has been developing large-area triple-gas electron multiplier (GEM) detectors to be installed in the muon Endcap regions of the CMS experiment in 2019 to maintain forward muon trigger and tracking performance at the High-Luminosity upgrade of the Large Hadron Collider (LHC); 10 preproduction detectors were built at CERN to commission the first assembly line and the quality controls (QCs). These were installed in the CMS detector in early 2017 and participated in the 2017 LHC run. The collaboration has prepared several additional assembly and QC lines for distributed mass production of 160 GEM detectors at various sites worldwide. In 2017, these additional production sites have optimized construction techniques and QC procedures and validated them against common specifications by constructing additional preproduction detectors. Using the specific experience from one production site as an example, we discuss how the QCs make use of independent hardware and trained personnel to ensure fast and reliable production. Preliminary results on the construction status of CMS GEM detectors are presented with details of the assembly sites involvement

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum