Multiscale Analysis of Metal Oxide Nanoparticles in Tissue: Insights into Biodistribution and Biotransformation

Metal oxide nanoparticles have emerged as exceptionally potent biomedical sensors and actuators due to their unique physicochemical features. Despite fascinating achievements, the current limited understanding of the molecular interplay between nanoparticles and the surrounding tissue remains a major obstacle in the rationalized development of nanomedicines, which is reflected in their poor clinical approval rate. This work reports on the nanoscopic characterization of inorganic nanoparticles in tissue by the example of complex metal oxide nanoparticle hybrids consisting of crystalline cerium oxide and the biodegradable ceramic bioglass. A validated analytical method based on semiquantitative X‐ray fluorescence and inductively coupled plasma spectrometry is used to assess nanoparticle biodistribution following intravenous and topical application. Then, a correlative multiscale analytical cascade based on a combination of microscopy and spectroscopy techniques shows that the topically applied hybrid nanoparticles remain at the initial site and are preferentially taken up into macrophages, form apatite on their surface, and lead to increased accumulation of lipids in their surroundings. Taken together, this work displays how modern analytical techniques can be harnessed to gain unprecedented insights into the biodistribution and biotransformation of complex inorganic nanoparticles. Such nanoscopic characterization is imperative for the rationalized engineering of safe and efficacious nanoparticle‐based systems

Fracturing ranked surfaces

Discretized landscapes can be mapped onto ranked surfaces, where every element (site or bond) has a unique rank associated with its corresponding relative height. By sequentially allocating these elements according to their ranks and systematically preventing the occupation of bridges, namely elements that, if occupied, would provide global connectivity, we disclose that bridges hide a new tricritical point at an occupation fraction $p=p_{c}$, where $p_{c}$ is the percolation threshold of random percolation. For any value of $p$ in the interval $p_{c}< p \leq 1$, our results show that the set of bridges has a fractal dimension $d_{BB} \approx 1.22$ in two dimensions. In the limit $p \rightarrow 1$, a self-similar fracture is revealed as a singly connected line that divides the system in two domains. We then unveil how several seemingly unrelated physical models tumble into the same universality class and also present results for higher dimensions

The labour supply effect of Education Maintenance Allowance and its implications for parental altruism

Education Maintenance Allowance (EMA) was a UK government cash transfer paid directly to children aged 16–18, in the first 2 years of post-compulsory full-time education. This paper uses the labour supply effect of EMA to infer the magnitude of the transfer response made by the parent, and so test for the presence of an ‘effectively altruistic’ head-of-household, who redistributes resources among household members so as to maximise overall welfare. Using data from the Longitudinal Study of Young People in England, an EMA payment of £30 per week is found to reduce teenagers’ labour supply by 3 h per week and probability of employment by 13 % points from a base of 43 %. We conclude that parents withdraw cash and in-kind transfers from their children to a value of between 22 and 86 % of what the child receives in EMA. This means we reject the hypothesis of an effectively altruistic head-of-household, and argue that making this cash transfer directly to the child produces higher child welfare than if the equivalent transfer were made to parents

Elite Influence? Religion, Economics, and the Rise of the Nazis

Adolf Hitler's seizure of power was one of the most consequential events of the twentieth century. Yet, our understanding of which factors fueled the astonishing rise of the Nazis remains highly incomplete. This paper shows that religion played an important role in the Nazi party's electoral success -- dwarfing all available socioeconomic variables. To obtain the first causal estimates we exploit plausibly exogenous variation in the geographic distribution of Catholics and Protestants due to a peace treaty in the sixteenth century. Even after allowing for sizeable violations of the exclusion restriction, the evidence indicates that Catholics were significantly less likely to vote for the Nazi Party than Protestants. Consistent with the historical record, our results are most naturally rationalized by a model in which the Catholic Church leaned on believers to vote for the democratic Zentrum Party, whereas the Protestant Church remained politically neutral

Optical properties of waveguide-coupled nanowires for sub-wavelength detection in microspectrometer applications

In this paper we experimentally investigate optical interactions between gold nanowires and fs-laser written waveguides in a view of applications for stationary-wave integrated Fourier-transform spectrometers in a movable mirror configuration. For this purpose we fabricated gold nanowires of widths in the range from 40 to 130 nm and of 25 nm in thickness directly on the surface of a borosilicate glass containing fs-laser written optical waveguides beneath. The outcoupling efficiency and the radiation pattern angular distribution were investigated at the wavelength of 850 nm, dependent on the geometrical size of the nanowires, the position of the waveguides under the surface, and the light polarization. We also report measured plasmonic scattering spectra of the nanowires in the wavelength range of 400 to 900 nm. Our findings show that the chosen geometries and material systems are promising candidates for the use in integrated focal plane array spectrometer devices. Finally, we demonstrate the successful operation of a waveguide spectrometer modified by a movable mirror with a stroke of more than 10 μmum

Multiscale Analysis of Metal Oxide Nanoparticles in Tissue: Insights into Biodistribution and Biotransformation

Metal oxide nanoparticles have emerged as exceptionally potent biomedical sensors and actuators due to their unique physicochemical features. Despite fascinating achievements, the current limited understanding of the molecular interplay between nanoparticles and the surrounding tissue remains a major obstacle in the rationalized development of nanomedicines, which is reflected in their poor clinical approval rate. This work reports on the nanoscopic characterization of inorganic nanoparticles in tissue by the example of complex metal oxide nanoparticle hybrids consisting of crystalline cerium oxide and the biodegradable ceramic bioglass. A validated analytical method based on semiquantitative X‐ray fluorescence and inductively coupled plasma spectrometry is used to assess nanoparticle biodistribution following intravenous and topical application. Then, a correlative multiscale analytical cascade based on a combination of microscopy and spectroscopy techniques shows that the topically applied hybrid nanoparticles remain at the initial site and are preferentially taken up into macrophages, form apatite on their surface, and lead to increased accumulation of lipids in their surroundings. Taken together, this work displays how modern analytical techniques can be harnessed to gain unprecedented insights into the biodistribution and biotransformation of complex inorganic nanoparticles. Such nanoscopic characterization is imperative for the rationalized engineering of safe and efficacious nanoparticle‐based systems