Acid-Labile Traceless Click Linker for Protein Transduction

Intracellular delivery of active proteins presents an interesting approach in research and therapy. We created a protein transduction shuttle based on a new traceless click linker that combines the advantages of click reactions with implementation of reversible pH-sensitive bonds. The azidomethyl-methylmaleic anhydride (AzMMMan) linker was found compatible with different click chemistries, demonstrated in bioreversible protein modification with dyes, polyethylene glycol, or a transduction carrier. Linkages were stable at physiological pH but reversible at the mild acidic pH of endosomes or lysosomes. We show that pH-reversible attachment of a defined endosome-destabilizing three-arm oligo(ethane amino)amide carrier generates an effective shuttle for protein delivery. The cargo protein nlsEGFP, when coupled via the traceless AzMMMan linker, experiences efficient cellular uptake and endosomal escape into the cytosol, followed by import into the nucleus. In contrast, irreversible linkage to the same shuttle hampers nuclear delivery of nlsEGFP which after uptake remains trapped in the cytosol. Successful intracellular delivery of bioactive ß-galactosidase as a model enzyme was also demonstrated using the pH-controlled shuttle system

Shedding light on sporopollenin chemistry, with reference to UV reconstructions

Sporopollenin, which forms the outer wall of pollen and spores, contains a chemical signature of ultraviolet-B flux via concentrations of UV-B absorbing compounds (UACs), providing a proxy for reconstructing UV irradiance through time. Although Fourier transform infrared (FTIR) spectroscopy provides an efficient means of measuring UAC concentrations, nitrogen-containing compounds have the potential to bias the aromatic and hydroxyl bands used to quantify and standardise UAC abundances. Here, we explore the presence and possible influence of nitrogen in UV reconstruction via an FTIR study of Lycopodium spores from a natural shading gradient. We show that the UV-sensitive aromatic peak at 1510 cm− 1 is clearly distinguishable from the amide II peak at 1550 cm− 1, and the decrease in aromatic content with increased shading can be reconstructed using standardisation approaches that do not rely on the 3300 cm− 1 hydroxyl band. Isolation of the sporopollenin results in the loss of nitrogen-related peaks from the FTIR spectra, while the aromatic gradient remains. This confirms the lack of nitrogen in sporopollenin and its limited potential for impacting on palaeo-UV reconstructions. FTIR is therefore an appropriate tool for quantifying UACs in spores and pollen, and information on UV flux should be obtainable from fossil or processed samples

Implementation of an outdoor smoke-free policy at sports clubs: Critical situations and determinants influencing implementation

Background Outdoor smoke-free policies (SFPs) at sports clubs have significant potential to reduce adolescent smoking. However, the realization of this potential may be strongly dependent on how these policies are implemented in practice. The aim of this study is to explore the perceptions of key stakeholders at different sports clubs in the Netherlands concerning how outdoor SFPs are implemented in practice and which determinants influence implementation. Methods Semi-structured interviews were held with 46 key stakeholders at eight Dutch sports clubs (i.e., field hockey, soccer, tennis, korfball) with an outdoor SFP. A thematic approach was used for the analysis of the transcripts. Results Overall, respondents perceived the implementation of an outdoor SFP at sports clubs as feasible. The SFP is often enforced, people who smoke react positively when they are approached, the SFP has led to less (visible) smoking at the venue, and a nonsmoking norm is reinforced. However, we identified three ‘critical situations’ in which implementation is less than optimal: 1) when children are not present at the sports club, 2) when alcohol is involved, and 3) when people who smoke relocate to the entrance of the sports club. Several determinants influenced implementation in those critical situations: 1) determinants related to individual smokers and club members (i.e., support, communication towards people who smoke), 2) determinants related to the SFP itself (i.e., clarity of the policy), 3) determinants related to the sports club (i.e., communication of the policy, characteristics of the sports club), and 4) determinants related to the wider community (i.e., change of social norm with regard to smoking, support from local and national organizations). Conclusion Implementation of an outdoor SFP at sports clubs is feasible because there is a high level of support and experiences are mainly positive. Nevertheless, some situations present challenges to compliance and enforcement. We identified a number of determinants that may facilitate implementation of an outdoor SFP at sports clubs

Low-Dissipation Simulation Methods and Models for Turbulent Subsonic Flow

The simulation of turbulent flows by means of computational fluid dynamics is highly challenging. The costs of an accurate direct numerical simulation (DNS) are usually too high, and engineers typically resort to cheaper coarse-grained models of the flow, such as large-eddy simulation (LES). To be suitable for the computation of turbulence, methods should not numerically dissipate the turbulent flow structures. Therefore, energy-conserving discretizations are investigated, which do not dissipate energy and are inherently stable because the discrete convective terms cannot spuriously generate kinetic energy. They have been known for incompressible flow, but the development of such methods for compressible flow is more recent. This paper will focus on the latter: LES and DNS for turbulent subsonic flow. A new theoretical framework for the analysis of energy conservation in compressible flow is proposed, in a mathematical notation of square-root variables, inner products, and differential operator symmetries. As a result, the discrete equations exactly conserve not only the primary variables (mass, momentum and energy), but also the convective terms preserve (secondary) discrete kinetic and internal energy. Numerical experiments confirm that simulations are stable without the addition of artificial dissipation. Next, minimum-dissipation eddy-viscosity models are reviewed, which try to minimize the dissipation needed for preventing sub-grid scales from polluting the numerical solution. A new model suitable for anisotropic grids is proposed: the anisotropic minimum-dissipation model. This model appropriately switches off for laminar and transitional flow, and is consistent with the exact sub-filter tensor on anisotropic grids. The methods and models are first assessed on several academic test cases: channel flow, homogeneous decaying turbulence and the temporal mixing layer. As a practical application, accurate simulations of the transitional flow over a delta wing have been performed

On the correct formula for the lifetime broadened superconducting density of states

We argue that the well known Dynes formula [Dynes R C {\it et al.} 1978 {\it Phys. Rev. Lett.} {\bf 41} 1509] for the superconducting quasiparticle density of states, which tries to incorporate the lifetime broadening in an approximate way, cannot be justified microscopically for conventional superconductors. Instead, we propose a new simple formula in which the energy gap has a finite imaginary part $-\Delta_2$ and the quasiparticle energy is real. We prove that in the quasiparticle approximation 2$\Delta_2$ gives the quasiparticle decay rate at the gap edge for conventional superconductors. This conclusion does not depend on the nature of interactions that cause the quasiparticle decay. The new formula is tested on the case of a strong coupling superconductor Pb$_{0.9}$Bi$_{0.1}$ and an excellent agreement with theoretical predictions is obtained. While both the Dynes formula and the one proposed in this work give good fits and fit parameters for Pb$_{0.9}$Bi$_{0.1}$, only the latter formula can be justified microscopically.Comment: 6 pages, 4 figure

How sports clubs decide to adopt an outdoor smoke-free policy:A qualitative study applying the Garbage Can Model

Background Outdoor smoke-free policies (SFPs) at sports clubs can contribute to protecting people from second-hand smoke (SHS). However, in absence of national legislation, it is uncertain whether and how sports clubs decide to adopt an SFP. The aim of this study was to explore the decision-making process at sports clubs in relation to the adoption of an outdoor SFP. Methods Semi-structured interviews were held with key stakeholders at 20 Dutch sports clubs (in field hockey, football, tennis, or korfball) with an outdoor SFP. Thematic analysis was applied, and themes were defined in line with the four streams of the Garbage Can Model (GCM). Results We identified four motivating factors for sports clubs to start the decision-making process: 1) SHS as a problem, 2) intolerance of smoking behavior, 3) advantages of an outdoor SFP, and 4) external pressure to become smoke-free. The decision-making process involved a variety of participants, but the board, influential club members, and smokers usually played major roles. Decisions were discussed during both formal and informal choice opportunities, but only made during formal choice opportunities. With regard to solutions, sports clubs adopted a partial or total outdoor SFP. In addition, sports clubs followed different strategies with regard to the decision-making process, which we classified along two dimensions: 1) autocratic vs. democratic and 2) fast vs. slow. Conclusion A number of factors motivated sports clubs to start the decision-making process. These factors were mainly linked to a strong non-smoking norm. Decision-making involved different participants, with a key role for the board, influential club members, and smokers. Governments and other external organizations may contribute to SFP adoption at sports clubs in several ways. They may advise clubs on strategies of decision-making and how to involve smokers in this process

Nonlinear quantum logic with colliding graphene plasmons

Graphene has emerged as a promising platform to bring nonlinear quantum optics to the nanoscale, where a large intrinsic optical nonlinearity enables long-lived and actively tunable plasmon polaritons to strongly interact. Here we theoretically study the collision between two counter-propagating plasmons in a graphene nanoribbon, where transversal subwavelength confinement endows propagating plasmons with %large effective masses a flat band dispersion that enhances their interaction. This scenario presents interesting possibilities towards the implementation of multi-mode polaritonic gates that circumvent limitations imposed by the Shapiro no-go theorem for photonic gates in nonlinear optical fibers. As a paradigmatic example we demonstrate the feasibility of a high fidelity conditional $\pi$ phase shift (CZ), where the gate performance is fundamentally limited only by the single plasmon lifetime. These results open new exciting avenues towards quantum information and many-body applications with strongly-interacting polaritons.Comment: 13 pages, 4 figure

The association of adolescents' smoking with the physical activity levels of their friends

Funding Information: This study is part of the SILNE-R project (Enhancing the Effectiveness of Programs and Strategies to Prevent Smoking by Adolescents: A Realist Evaluation Comparing Seven European Countries), which is supported by the European Union‘s Horizon 2020 research and innovation programme, under grant agreement 635,056. The funder was not involved and did not have any input in the design, analysis and reporting of this study. Publisher Copyright: © 2023Background: Smoking is inversely related to people's Physical Activity Level (PAL). As the behavior of friends may affect the choices and behavior of adolescents, having friends with a high PAL may potentially protect against adolescent smoking. This study aims to assess whether adolescents' smoking is associated with the PAL of their friends. Methods: SILNE-R survey data of 11.918 adolescents from 55 different schools in 7 European cities was used to determine weekly smoking, individual PAL, PAL of friends, school PAL, and smoking of friends. Multilevel, multivariable logistic regression analysis were used to assess the association between the PAL of friends and weekly smoking. Several socio-demographic variables were included as covariates in the analysis. Results: Our results indicated that 10.8% of the respondents was smoking weekly. Weekly smoking was most common among adolescents whose friends had a PAL of 0–42.0 min per day (14.5%). Respondents were significantly more likely to be smoking weekly if their friends were on average 0–42 min vs. 80–180 min physically active (OR 1.27 [95% CI 1.04–1.55]). This association existed independently of the individual PAL of respondents. Stratification for smoking of friends yielded equal results, although the association appeared to be somewhat stronger for those with smoking friends (OR 1.38 [95% CI 1.06–1.82]). Conclusion: Adolescents are less likely to smoke weekly if they associate with friends who spend >80 min per day on physical activity. Initiatives aimed at the prevention of smoking among adolescents may benefit from organizing group-based physical activity programs.publishersversionpublishe