Preferred Formation of Minority Concomitant Polymorphs in 2D Self‐Assembly under Lateral Nanoconfinement

Control over polymorph formation in the crystallization of organic molecules remains a huge scientific challenge. Now, preferential formation is presented of one polymorph, formed by chiral molecules, in controlled two‐dimensional (2D) nanoconfinement conditions at a liquid–solid interface. So‐called nanocorrals to control concomitant polymorph formation were created in situ via a nanoshaving protocol at the interface between 1‐phenyloctane and covalently modified highly‐oriented pyrolytic graphite (HOPG). The preferentially formed polymorphs, which were less stable in the large‐scale monolayers, could be selected simply by varying the orientation of the square nanocorrals with respect to the HOPG lattice

Quantitative Phase Imaging with a Metalens

Quantitative phase imaging (QPI) recovers the exact wavefront of light from the intensity measured by a camera. Topographical maps of translucent microscopic bodies can be extracted from these quantified phase shifts. We demonstrate quantitative phase imaging at the tip of an optical fiber endoscope with a chromatic silicon nitride metalens. Our method leverages spectral multiplexing to recover phase from multiple defocus planes in a single capture. The half millimeter wide metalens shows phase imaging capability with a 280 field of view and 0.1{\lambda} sensitivity in experiments with an endoscopic fiber bundle. Since the spectral functionality is encoded directly in the imaging lens, no additional filters are needed. Key limitations in the scaling of a phase imaging system, such as multiple acquisition, interferometric alignment or mechanical scanning are completely mitigated in the proposed schem

Real Time Full-Color Imaging in a Meta-Optical Fiber Endoscope

Endoscopes are an important component for the development of minimally invasive surgeries. Their size is one of the most critical aspects, because smaller and less rigid endoscopes enable higher agility, facilitate larger accessibility, and induce less stress on the surrounding tissue. In all existing endoscopes, the size of the optics poses a major limitation in miniaturization of the imaging system. Not only is making small optics difficult, but their performance also degrades with downscaling. Meta-optics have recently emerged as a promising candidate to drastically miniaturize optics while achieving similar functionalities with significantly reduced size. Herein, we report an inverse-designed meta-optic, which combined with a coherent fiber bundle enables a 33% reduction in the rigid tip length over traditional gradient-index (GRIN) lenses. We use the meta-optic fiber endoscope (MOFIE) to demonstrate real-time video capture in full visible color, the spatial resolution of which is primarily limited by the fiber itself. Our work shows the potential of meta-optics for integration and miniaturization of biomedical devices towards minimally invasive surgery

Visualizing Chiral Interactions in Carbohydrates Adsorbed on Au(111) by High‐Resolution STM Imaging

Carbohydrates are the most abundant organic material on Earth and the structural “material of choice” in many living systems. Nevertheless, design and engineering of synthetic carbohydrate materials presently lag behind that for protein and nucleic acids. Bottom-up engineering of carbohydrate materials demands an atomic-level understanding of their molecular structures and interactions in condensed phases. Here, high-resolution scanning tunneling microscopy (STM) is used to visualize at submolecular resolution the three-dimensional structure of cellulose oligomers assembled on Au(1111) and the interactions that drive their assembly. The STM imaging, supported by ab initio calculations, reveals the orientation of all glycosidic bonds and pyranose rings in the oligomers, as well as details of intermolecular interactions between the oligomers. By comparing the assembly of D- and L-oligomers, these interactions are shown to be enantioselective, capable of driving spontaneous enantioseparation of cellulose chains from its unnatural enantiomer and promoting the formation of engineered carbohydrate assemblies in the condensed phases

A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments

PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of −20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics

Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Double layer crystallization of heptahelicene on noble metal surfaces

Resolution of enantiomers of chiral compounds via crystallization is the dominant method in chemical industry, but chiral recognition at the molecular level during this process is still poorly understood. Using single metal surfaces in ultrahigh vacuum as model system, the enantio-related transition from the monolayer structure into a double layer of the racemic mixture of heptahelicene has been studied with scanning tunneling microscopy. Submolecular resolution reveals enantiopure second layers on Ag(111) and almost enantiopure second layers on Au(111). In analogy to previous results on Cu(111), it is concluded that transition from the 2D first layer racemate into a layered racemate occurs

How ready is Rio de Janeiro to be a Smart City?

Urbanization will primarily occur in developing countries. The concept smart city promises to increase efficiency and improve infrastructure in cities to manage this increased density. However, successful smart city implementation in developing countries is hard due to complexity, high cost, instability, and lacking research. Therefore, a government needs to assess the city’s smart city readiness to better prepare for smart city adoption. The neglect of special circumstances in developing countries and the inadequate spectrum of influencing factors of existing readiness frameworks suggested the development of a new smart city readiness meta-model. This was then applied to the city of Rio de Janeiro in Brazil. Participants rated each of the model’s factors in a survey. The ratings were further validated by additional data from other research sources. The developed meta-model is composed of five readiness levels: technological, organizational, environmental, cultural, and EPEL (economic, political, ethical, and legal) readiness. Rio performs poorly across these levels’ factors. Fragmented technological infrastructure, poor collaboration between stakeholders, difficult financial situation as well as economic and political instability compromise the preparedness of Rio to become a smart city. This study’s results implicate that Rio’s government should include citizens from all neighborhoods, optimize resource use, and focus on a strategy that fosters collaboration between stakeholders. Besides, the created meta-model gives policymakers in developing countries a tool to assess their current state of smart city readiness. Evaluating beforehand how prepared the location is for implementation reduces risk and increases resource efficiency.A urbanização ocorrerá principalmente nos países em desenvolvimento. O conceito de cidade inteligente promete aumentar a eficiência e melhorar as infraestruturas nas cidades para gerir esta densidade acrescida. O êxito da implementação de cidades inteligentes nos países em desenvolvimento é complexo e problemático. Por conseguinte, um governo tem de avaliar a disponibilidade da cidade para se preparar melhor para a adoção da cidade inteligente. O espectro inadequado de fatores influenciadores dos atuais quadros de preparação sugeriu o desenvolvimento de um novo meta-modelo de preparação para a cidade inteligente. Tal foi então aplicado à cidade do Rio de Janeiro no Brasil. Os participantes classificaram cada um dos fatores do modelo num inquérito. As notações foram ainda validadas por dados adicionais de outras fontes de investigação. O meta-modelo desenvolvido é composto por cinco níveis de prontidão: preparação tecnológica, organizacional, ambiental, cultural e EPEL (preparação económica, política, ética e legal). O Rio tem um fraco desempenho em estes níveis. A infraestrutura tecnológica fragmentada, a má colaboração entre as partes interessadas, a difícil situação financeira, bem como a instabilidade económica e política comprometem a preparação do Rio para se tornar uma cidade inteligente. Os resultados deste estudo implicam que o Governo do Rio deve incluir cidadãos de todos os bairros, otimizar a utilização dos recursos e concentrar-se numa estratégia que promova a colaboração entre as partes interessadas. Além disso, o meta-modelo criado proporciona aos responsáveis políticos dos países em desenvolvimento uma ferramenta para avaliar o seu estado atual de preparação para a cidade inteligente