Adaptable electro-optic detection of THz radiation using a laser-written bull's-eye antenna.

We report a nonlinear terahertz (THz) detection device based on a metallic bull's-eye plasmonic antenna. The antenna, fabricated with femtosecond laser direct writing and deposited on a nonlinear gallium phosphide (GaP) crystal, focuses incoming THz waveforms within the sub-wavelength bull's eye region to locally enhance the THz field. Additionally, the plasmonic structure minimizes diffraction effects allowing a relatively long interaction length between the transmitted THz field and the co-propagating near-infrared gating pulse used in an electro-optic sampling configuration.

Surface plasmons on silver gratings transform pyrolytic carbon into luminescent graphitized carbon dots.

Plasmonic catalysis holds the promise of opening new reaction pathways that are inaccessible thermally or via direct UV-vis electronic transitions. Here, energetic carriers produced via the decay of surface plasmons excited by visible light at 532 nm (2.33 eV, green) on a Ag-grating-bearing pyrolytic carbon residue drive its transformation into light-emitting graphitized carbon dots.

Laser-machined thin copper films on silicon as physical unclonable functions.

Physical unclonable functions (PUFs) are receiving significant attention with the rise of cryptography and the drive towards creating unique structures for security applications and anti-counterfeiting. Specifically, nanoparticle based PUFs can produce a high degree of randomness through their size, shape, spatial distribution, chemistry, and optical properties, rendering them very difficult to replicate. However, nanoparticle PUFs typically rely on complex preparation procedures involving chemical synthesis in solution, therefore requiring dispersion, and embedding within a host medium for application.

Engineered interfaces between perovskite LaLiTiO electrolyte and Li metal for solid-state batteries.

Perovskite LaLiTiO (LLTO) materials are promising solid-state electrolytes for lithium metal batteries (LMBs) due to their intrinsic fire-resistance, high bulk ionic conductivity, and wide electrochemical window. However, their commercialization is hampered by high interfacial resistance, dendrite formation, and instability against Li metal. To address these challenges, we first prepared highly dense LLTO pellets with enhanced microstructure and high bulk ionic conductivity of S cm at room temperature.

Biopredictive capability assessment of two dissolution/permeation assays, µFLUX™ and PermeaLoop™, using supersaturating formulations of Posaconazole.

The majority of new drug entities exhibits poor water solubility and therefore enabling formulations are often needed to ensure sufficient in vivo bioavailability upon oral administration. Several in vitro tools have been proposed for biopredictive screening of such drug formulations to facilitate formulation development. Among these, combined dissolution/permeation (D/P) assays have gained increasing interest in recent years, since they are presumed to better predict the absorption behavior as compared to single-compartment dissolution assays.

Systematic identification of novel cancer genes through analysis of deep shRNA perturbation screens.

Systematic perturbation screens provide comprehensive resources for the elucidation of cancer driver genes. The perturbation of many genes in relatively few cell lines in such functional screens necessitates the development of specialized computational tools with sufficient statistical power. Here we developed APSiC (Analysis of Perturbation Screens for identifying novel Cancer genes) to identify genetic drivers and effectors in perturbation screens even with few samples.

Fully unsupervised deep mode of action learning for phenotyping high-content cellular images.

Motivation: The identification and discovery of phenotypes from high content screening images is a challenging task. Earlier works use image analysis pipelines to extract biological features, supervised training methods or generate features with neural networks pretrained on non-cellular images. We introduce a novel unsupervised deep learning algorithm to cluster cellular images with similar Mode-of-Action (MOA) together using only the images' pixel intensity values as input.

ZNRF3 and RNF43 cooperate to safeguard metabolic liver zonation and hepatocyte proliferation.

AXIN2 and LGR5 mark intestinal stem cells (ISCs) that require WNT/β-Catenin signaling for constant homeostatic proliferation. In contrast, AXIN2/LGR5+ pericentral hepatocytes show low proliferation rates despite a WNT/β-Catenin activity gradient required for metabolic liver zonation. The mechanisms restricting proliferation in AXIN2+ hepatocytes and metabolic gene expression in AXIN2+ ISCs remained elusive.

Value of the TTM risk score for early prognostication of comatose patients after out-of-hospital cardiac arrest in a Swiss university hospital.

Comatose patients admitted to the intensive care unit (ICU) after out-of-hospital cardiac arrest frequently die after withdrawal of life support. Guidelines recommend scheduling prognostication no sooner than 96 hours after cardiac arrest, and strict withdrawal criteria leave many patients waiting for improvement for days without ever reaching a favourable outcome. In clinical practice, physicians are frequently confronted with vague living wills expressed by next of kin or an imprecise advance care directive soon after cardiac arrest.

Simultaneous Visualization of Wet Cells and Nanostructured Biomaterials in SEM using Ionic Liquids.

This work presents a successful methodology to image mammalian cells adhered to nanostructured titanium by using scanning electron microscopy (SEM) operating in low-vacuum mode following ionic liquid treatment. Human osteoblast-like Saos-2 cells were treated with a room-temperature ionic liquid, 1-ethyl-3-methylimidazolium tetrafluoroborate, and subsequently imaged on titanium by SEM. Titanium substrates were modified to create laser-induced periodic surface structures (LIPSS) for visualization at the submicron scale.

Outcome prediction with resting-state functional connectivity after cardiac arrest.

Predicting outcome in comatose patients after successful cardiopulmonary resuscitation is challenging. Our primary aim was to assess the potential contribution of resting-state-functional magnetic resonance imaging (RS-fMRI) in predicting neurological outcome. RS-fMRI was used to evaluate functional and effective connectivity within the default mode network in a cohort of 90 comatose patients and their impact on functional neurological outcome after 3 months.

DOT1L inhibition is lethal for multiple myeloma due to perturbation of the endoplasmic reticulum stress pathway.

The histone 3 lysine 79 (H3K79) methyltransferase (HMT) DOT1L is known to play a critical role for growth and survival of -rearranged leukemia. Serendipitous observations during high-throughput drug screens indicated that the use of DOT1L inhibitors might be expandable to multiple myeloma (MM). Through pharmacologic and genetic experiments, we could validate that DOT1L is essential for growth and viability of a subset of MM cell lines, in line with a recent report from another team.

Topography of MR lesions correlates with standardized EEG pattern in early comatose survivors after cardiac arrest.

Aim: Multimodal prognostication in comatose patients after cardiac arrest (CA) is complicated by the fact that different modalities are usually not independent. Here we set out to systematically correlate early EEG and MRI findings.

Methods: 89 adult patients from a prospective register who underwent at least one EEG and one MRI in the acute phase after CA were included.

Analysis of head and neck carcinoma progression reveals novel and relevant stage-specific changes associated with immortalisation and malignancy.

We report changes in the genomic landscape in the development of head and neck squamous cell carcinomas HNSCC from potentially premalignant lesions (PPOLS) to malignancy and lymph node metastases. Likely pathological mutations predominantly involved a relatively small set of genes reported previously (TP53, KMT2D, CDKN2A, PIK3CA, NOTCH1 and FAT1) but also other predicted cancer drivers (MGA, PABPC3, NR4A2, NCOR1 and MACF1). Notably, all these mutations arise early and are present in PPOLs.

Plasmonic colours predicted by deep learning.

Picosecond laser pulses have been used as a surface colouring technique for noble metals, where the colours result from plasmonic resonances in the metallic nanoparticles created and redeposited on the surface by ablation and deposition processes. This technology provides two datasets which we use to train artificial neural networks, data from the experiment itself (laser parameters vs. colours) and data from the corresponding numerical simulations (geometric parameters vs.

Next-generation characterization of the Cancer Cell Line Encyclopedia.

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers.

Correction of copy number induced false positives in CRISPR screens.

Cell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function viability screens. However, a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons, since the entire amplified region can exhibit lethal scores. These false-positive hits can either be discarded from further analysis, which in cancer models can represent a significant number of hits, or methods can be developed to rescue the true-positives within amplified regions.

Passivation of Plasmonic Colors on Bulk Silver by Atomic Layer Deposition of Aluminum Oxide.

We report the passivation of angle-independent plasmonic colors on bulk silver by atomic layer deposition (ALD) of thin films of aluminum oxide. The colors are rendered by silver nanoparticles produced by laser ablation and redeposition on silver. We then apply a two-step approach to aluminum oxide conformal film formation via ALD.

Midregional proatrial natriuretic peptide improves risk stratification after ischemic stroke.

Objective: To validate midregional proatrial natriuretic peptide (MR-proANP) for outcome prediction and diagnosis of cardioembolic stroke etiology compared to established clinical variables.

Methods: In this prospective multicenter cohort study, we quantified MR-proANP levels in ischemic stroke patients within 24 hours of onset. Primary outcome measures were 90-day mortality, unfavorable functional outcome (modified Rankin Scale score >2), and cardioembolic stroke etiology diagnosed during hospitalization.

Visible light driven plasmonic photochemistry on nano-textured silver.

Plasmon assisted generation of silver sulfate from dodecanethiol is demonstrated on a nano-textured silver substrate with a strong surface plasmon resonance in the visible range. The observed photo-physical processes are attributed to hot charge carriers that are generated from the excitation of surface plasmon resonances using 532 nm laser light. Excited charge carriers are responsible for cleaving the alkane chain, and for generating reactive oxygen species which rapidly photooxidize the exposed sulfur atoms.

Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening.

Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines.

Laser-induced plasmonic colours on metals.

Plasmonic resonances in metallic nanoparticles have been used since antiquity to colour glasses. The use of metal nanostructures for surface colourization has attracted considerable interest following recent developments in plasmonics. However, current top-down colourization methods are not ideally suited to large-scale industrial applications.

Resistance mechanisms to TP53-MDM2 inhibition identified by in vivo piggyBac transposon mutagenesis screen in an Arf mouse model.

Inhibitors of double minute 2 protein (MDM2)-tumor protein 53 (TP53) interaction are predicted to be effective in tumors in which the gene is wild type, by preventing TP53 protein degradation. One such setting is represented by the frequent deletion in human cancer that, through inactivation of , activates MDM2 protein, which in turn degrades TP53 tumor suppressor. Here we used piggyBac (PB) transposon insertional mutagenesis to anticipate resistance mechanisms occurring during treatment with the MDM2-TP53 inhibitor HDM201.