Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

The synthesis of a sulfate-modified dendritic peptide amphiphile and its self-assembly into one-dimensional rod-like architectures in aqueous medium is reported. The influence of the ionic strength on the supramolecular polymerization was probed via circular dichroism spectroscopy and cryogenic transmission electron microscopy. Physiological salt concentrations efficiently screen the charges of the dendritic building block equipped with eight sulfate groups and trigger the formation of rigid supramolecular polymers. Since multivalent sulfated supramolecular structures mimic naturally occurring L-selectin ligands, the corresponding affinity was evaluated using a competitive SPR binding assay and benchmarked to an ethylene glycol-decorated supramolecular polymer

Fluorescent Polymer—Single‐Walled Carbon Nanotube Complexes with Charged and Noncharged Dendronized Perylene Bisimides for Bioimaging Studies

Fluorescent nanomaterials are expected to revolutionize medical diagnostic, imaging, and therapeutic tools due to their superior optical and structural properties. Their inefficient water solubility, cell permeability, biodistribution, and high toxicity, however, limit the full potential of their application. To overcome these obstacles, a water‐soluble, fluorescent, cytocompatible polymer—single‐walled carbon nanotube (SWNT) complex is introduced for bioimaging applications. The supramolecular complex consists of an alkylated polymer conjugated with neutral hydroxylated or charged sulfated dendronized perylene bisimides (PBIs) and SWNTs as a general immobilization platform. The polymer backbone solubilizes the SWNTs, decorates them with fluorescent PBIs, and strongly improves their cytocompatibility by wrapping around the SWNT scaffold. In photophysical measurements and biological in vitro studies, sulfated complexes exhibit superior optical properties, cellular uptake, and intracellular staining over their hydroxylated analogs. A toxicity assay confirms the highly improved cytocompatibility of the polymer‐wrapped SWNTs toward surfactant‐solubilized SWNTs. In microscopy studies the complexes allow for the direct imaging of the SWNTs' cellular uptake via the PBI and SWNT emission using the 1st and 2nd optical window for bioimaging. These findings render the polymer‐SWNT complexes with nanometer size, dual fluorescence, multiple charges, and high cytocompatibility as valuable systems for a broad range of fluorescence bioimaging studies

Enhancement of fluorescent properties of near-infrared dyes using clickable oligoglycerol dendrons

Near-infrared (NIR) fluorescent dyes are gaining increased attention due to their potential to serve as molecular probes for in vivo imaging. Here, we demonstrate that oligoglycerol dendrons effectively enhance the fluorescence properties of an NIR dye by increasing the solubility in water and the prevention of aggregate formation. First- and second-generation oligoglycerol dendrons were conjugated to an NIR dye via a dipolar-cycloaddition (click) reaction. The two new dye conjugates exhibited enhanced NIR fluorescent emission and considerably higher fluorescent quantum yields than the dye alone. The high photostability measured for one of the oligoglycerol-linked dyes, in comparison to commonly used fluorogenic dyes such as Cy5 and Cy7, was validated using fluorescence microscopy of macrophages

Transient Monte Carlo Simulations for the Optimisation and Characterisation of Monolithic Silicon Sensors

An ever-increasing demand for high-performance silicon sensors requires complex sensor designs that are challenging to simulate and model. The combination of electrostatic finite element simulations with a transient Monte Carlo approach provides simultaneous access to precise sensor modelling and high statistics. The high simulation statistics enable the inclusion of Landau fluctuations and production of secondary particles, which offers a realistic simulation scenario. The transient simulation approach is an important tool to achieve an accurate time-resolved description of the sensor, which is crucial in the face of novel detector prototypes with increasingly precise timing capabilities. The simulated time resolution as a function of operating parameters as well as the full transient pulse can be monitored and assessed, which offers a new perspective on the optimisation and characterisation of silicon sensors. In this paper, a combination of electrostatic finite-element simulations using 3D TCAD and transient Monte Carlo simulations with the Allpix Squared framework are presented for a monolithic CMOS pixel sensor with a small collection diode, that is characterised by a highly inhomogeneous, complex electric field. The results are compared to transient 3D TCAD simulations that offer a precise simulation of the transient behaviour but long computation times. Additionally, the simulations are benchmarked against test-beam data and good agreement is found for the performance parameters over a wide range of different operation conditions

Amplified Cold Transduction in Native Nociceptors by M-Channel Inhibition

Topically applied camphor elicits a sensation of cool, but nothing is known about how it affects cold temperature sensing. We found that camphor sensitizes a subpopulation of menthol-sensitive native cutaneous nociceptors in the mouse to cold, but desensitizes and partially blocks heterologously expressed TRPM8(transient receptor potential cation channel subfamily M member 8). In contrast, camphor reduces potassium outward currents in cultured sensory neurons and, in cold nociceptors, the cold-sensitizing effects of camphor and menthol are additive. Using a membrane potential dye-based screening assay and heterologously expressed potassium channels, we found that the effects of camphor are mediated by inhibition of K(v)7.2/3 channels subtypes that generate the M-current in neurons. In line with this finding, the specific M-current blocker XE991 reproduced the cold-sensitizing effect of camphor in nociceptors. However, the M-channel blocking effects of XE991 and camphor are not sufficient to initiate cold transduction but require a cold-activated inward current generated by TRPM8. The cold-sensitizing effects of XE991 and camphor are largest in high-threshold cold nociceptors. Low-threshold corneal cold thermoreceptors that express high levels of TRPM8 and lack potassium channels are not affected by camphor. We also found that menthol-like camphor-potently inhibits K(v)7.2/3 channels. The apparent functional synergism arising from TRPM8 activation and M-current block can improve the effectiveness of topical coolants and cooling lotions, and may also enhance TRPM8-mediated analgesia

3D Hydrogels Containing Interconnected Microchannels of Subcellular Size for Capturing Human Pathogenic Acanthamoeba Castellanii

3D Hydrogels Containing Interconnected Microchannels of Subcellular Size for Capturing Human Pathogenic Acanthamoeba Castellani

Developing a Monolithic Silicon Sensor in a 65 nm CMOS Imaging Technology for Future Lepton Collider Vertex Detectors

Monolithic CMOS sensors in a 65 nm imaging technology are being investigated by the CERN EP Strategic R&D Programme on Technologies for Future Experiments for an application in particle physics. The appeal of monolithic detectors lies in the fact that both sensor volume and readout electronics are integrated in the same silicon wafer, providing a reduction in production effort, costs and scattering material. The Tangerine Project WP1 at DESY participates in the Strategic R&D Programme and is focused on the development of a monolithic active pixel sensor with a time and spatial resolution compatible with the requirements for a future lepton collider vertex detector. By fulfilling these requirements, the Tangerine detector is suitable as well to be used as telescope planes for the DESY-II Test Beam facility. The project comprises all aspects of sensor development, from the electronics engineering and the sensor design using simulations, to laboratory and test beam investigations of prototypes. Generic TCAD Device and Monte-Carlo simulations are used to establish an understanding of the technology and provide important insight into performance parameters of the sensor. Testing prototypes in laboratory and test beam facilities allows for the characterization of their response to different conditions. By combining results from all these studies it is possible to optimize the sensor layout. This contribution presents results from generic TCAD and Monte-Carlo simulations, and measurements performed with test chips of the first sensor submission.Comment: 7 pages, 8 figures, submitted to IEEE Xplore as conference record for 2022 IEEE NSS/MIC/RTS

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report.

In an era of mass migration, social scientists, populist parties and social movements raise concerns over the future of immigration-destination societies. What impacts does this have on policy and social solidarity? Comparative cross-national research, relying mostly on secondary data, has findings in different directions. There is a threat of selective model reporting and lack of replicability. The heterogeneity of countries obscures attempts to clearly define data-generating models. P-hacking and HARKing lurk among standard research practices in this area.This project employs crowdsourcing to address these issues. It draws on replication, deliberation, meta-analysis and harnessing the power of many minds at once. The Crowdsourced Replication Initiative carries two main goals, (a) to better investigate the linkage between immigration and social policy preferences across countries, and (b) to develop crowdsourcing as a social science method. The Executive Report provides short reviews of the area of social policy preferences and immigration, and the methods and impetus behind crowdsourcing plus a description of the entire project. Three main areas of findings will appear in three papers, that are registered as PAPs or in process