Identification of molecular glues of the SLP76/14-3-3 protein-protein interaction.

The stabilisation of protein-protein interactions (PPIs) through molecular glues is a novel and promising approach in drug discovery. In stark contrast to research in protein-protein inhibition the field of stabilisation remains underdeveloped with comparatively few examples of small-molecule stabilisers of PPIs reported to date. At the same time identifying molecular glues has received recent sustained interest, especially in the fields of targeted protein degradation and 14-3-3 PPIs.

A comprehensive tool box for large animal studies of intervertebral disc degeneration.

Preclinical studies involving large animal models aim to recapitulate the clinical situation as much as possible and bridge the gap from benchtop to bedside. To date, studies investigating intervertebral disc (IVD) degeneration and regeneration in large animal models have utilized a wide spectrum of methodologies for outcome evaluation. This paper aims to consolidate available knowledge, expertise, and experience in large animal preclinical models of IVD degeneration to create a comprehensive tool box of anatomical and functional outcomes.

Effectiveness of cell adhesive additives in different supramolecular polymers.

Supramolecular motifs in elastomeric biomaterials facilitate the modular incorporation of additives with corresponding motifs. The influence of the elastomeric supramolecular base polymer on the presentation of additives has been sparsely examined, limiting the knowledge of transferability of effective functionalization between polymers. Here it was investigated if the polymer backbone and the additive influence biomaterial modification in two different types of hydrogen bonding supramolecular systems, that is, based on ureido-pyrimidinone or bis-urea units.

Polymorphism of a semi-crystalline diketopyrrolopyrrole-terthiophene polymer.

Few semiconducting polymers are known that possess more than one semi-crystalline structure. Guidelines for rationalizing or creating polymorphism in these materials do not exist. Two different semi-crystalline polymorphs, and , and an amorphous phase have recently been identified for alternating diketopyrrolopyrrole-quaterthiophene copolymers (PDPP4T).

Elucidating dynamic behavior of synthetic supramolecular polymers in water by hydrogen/deuterium exchange mass spectrometry.

A comprehensive understanding of the structure, self-assembly mechanism, and dynamics of one-dimensional supramolecular polymers in water is essential for their application as biomaterials. Although a plethora of techniques are available to study the first two properties, there is a paucity in possibilities to study dynamic exchange of monomers between supramolecular polymers in solution. We recently introduced hydrogen/deuterium exchange mass spectrometry (HDX-MS) to characterize the dynamic nature of synthetic supramolecular polymers with only a minimal perturbation of the chemical structure.

The role of sodium in stabilizing tin-lead (Sn-Pb) alloyed perovskite quantum dots.

Narrow-bandgap CsSn Pb I perovskite quantum dots (QDs) show great promise for optoelectronic applications owing to their reduced use of toxic Pb, improved phase stability, and tunable band gaps in the visible and near-infrared range. The use of small ions has been proven beneficial in enhancing the stability and photoluminescence quantum yield (PLQY) of perovskite QDs. The introduction of sodium (Na) has succeeded in boosting the PLQY of CsSnPbI QDs.

Microelectrode Arrays for Simultaneous Electrophysiology and Advanced Optical Microscopy.

Advanced optical imaging techniques address important biological questions in neuroscience, where structures such as synapses are below the resolution limit of a conventional microscope. At the same time, microelectrode arrays (MEAs) are indispensable in understanding the language of neurons. Here, the authors show transparent MEAs capable of recording action potentials from neurons and compatible with advanced microscopy.

Photo isomerization of -cyclooctene to -cyclooctene: Integration of a micro-flow reactor and separation by specific adsorption.

Liquid-phase adsorption has hardly been established in micro-flow, although this constitutes an industrially vital method for product separation. A micro-flow UV-photo isomerization process converts -cyclooctene partly into -cyclooctene, leaving an isomeric mixture. cyclooctene adsorption and thus separation was achieved in a fixed-bed micro-flow reactor, packed with AgNO/SiO powder, while the -isomer stays in the flow.

Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures.

Cells sense and respond to scaffold pore geometry and mechanical stimuli. Many fabrication methods used in bone tissue engineering render structures with poorly controlled pore geometries. Given that cell-scaffold interactions are complex, drawing a conclusion on how cells sense and respond to uncontrolled scaffold features under mechanical loading is difficult.

Global Fractional Flow Reserve Value Predicts 5-Year Outcomes in Patients With Coronary Atherosclerosis But Without Ischemia.

Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long-term clinical outcome of patients with stable coronary artery disease but no ischemia-inducing stenosis. Methods and Results We studied major adverse cardiovascular events (MACEs: all-cause death, myocardial infarction, and any revascularization) after 5 years in 1122 patients without significant stenosis (all FFR >0.

Nanoscopy for endosomal escape quantification.

The successful cytosolic delivery of nanoparticles is hampered by their endosomal entrapment and degradation. To push forward the smart development of nanoparticles we must reliably detect and quantify their endosomal escape process. However, the current methods employed are not quantitative enough at the nanoscale to achieve this.

On the Emergence Mechanism of Carrot Sprites.

We investigate the launch of negative upward streamers from sprite glows. This phenomenon is readily observed in high-speed observations of sprites and underlies the classification of sprites into carrot or column types. First, we describe how an attachment instability leads to a sharply defined region in the upper part of the streamer channel.

Hypoxic stress enhances extension and branching of dorsal root ganglion neuronal outgrowth.

Unlabelled: It has been shown that painful intervertebral discs (IVDs) were associated with a deeper innervation. However, the effect of the disc's degenerative microenvironment on neuronal outgrowth remains largely unknown. The focus of this study was to determine the influence of hypoxia on dorsal root ganglion (DRG) neurite outgrowth.

Hyperthermia-Triggered On-Demand Biomimetic Nanocarriers for Synergetic Photothermal and Chemotherapy.

Nanoparticle-based drug delivery systems with low side effects and enhanced efficacy hold great potential in the treatment of various malignancies, in particular cancer; however, they are still challenging to attain. Herein, an anticancer drug delivery system based on a cisplatin (CDDP) containing nanogel, functionalized with photothermal gold nanorods (GNRs) which are electrostatically decorated with doxorubicin (DOX) is reported. The nanoparticles are formed via the crosslinking reaction of hyaluronic acid with the ancillary anticarcinogen CDDP in the presence of DOX-decorated GNRs.

Recovery of Absolute Coronary Blood Flow and Microvascular Resistance After Chronic Total Occlusion Percutaneous Coronary Intervention: An Exploratory Study.

Background This study aimed to investigate longitudinal physiological changes in the recanalized coronary chronic total occlusion (CTO) vessel and its dependent myocardium after successful percutaneous coronary intervention (PCI). Methods and Results In this pilot study, 25 patients scheduled for elective CTO PCI with viable myocardium and angiographically visible collaterals were included. Absolute coronary blood flow and absolute microvascular resistance were measured invasively using continuous thermodilution.

Rheology of Crystallizing LLDPE.

Polymer crystallization occurs in many plastic manufacturing processes, from injection molding to film blowing. Linear low-density polyethylene (LLDPE) is one of the most commonly processed polymers, wherein the type and extent of short-chain branching (SCB) may be varied to influence crystallization. In this work, we report simultaneous measurements of the rheology and Raman spectra, using a Rheo-Raman microscope, for two industrial-grade LLDPEs undergoing crystallization.

Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical.

Chronic back and neck pain is a prevalent disability, often caused by degeneration of the intervertebral disc. Because current treatments for this condition are less than satisfactory, a great deal of effort is being applied to develop new solutions, including regenerative strategies. However, the path from initial promising idea to clinical use is fraught with many hurdles to overcome.

In-Flight Observation of Positron Annihilation by ILDAS.

We report a 511-keV photon flux enhancement that was observed inside a thundercloud and is a result of positron annihilation. The observation was made with the In-flight Lightning Damage Assessment System (ILDAS) on board of an A340 test aircraft. The aircraft was intentionally flying through a thunderstorm at 12-km altitude over Northern Australia in January 2016.

Association of Variability in Body Mass Index and Metabolic Health With Cardiometabolic Disease Risk.

Background Metabolic syndrome is associated with high risk of cardiovascular disease, although risk may differ according to the specific conditions present and variability in those conditions. Methods and Results We defined obesity (body mass index [BMI] ≥30 kg/m) and metabolic health (<2 nonobesity National Cholesterol Education Program Adult Treatment Panel III conditions) among 3632 Framingham Heart Study offspring cohort participants (mean age, 50.8 years; 53.

Early adulthood housing transitions in Amsterdam: Understanding dependence and independence between generations.

The housing context has a profound influence on how different generations within families negotiate dependence and independence. This article investigates the nature of intergenerational relations during early adulthood housing transitions. We consider an original dataset of qualitative interviews with young adults and their parents living in and around Amsterdam, where recent housing market liberalisation is challenging home-leaving norms.

Diameter in ultra-small scale-free random graphs.

It is well known that many random graphs with infinite variance degrees are ultra-small. More precisely, for configuration models and preferential attachment models where the proportion of vertices of degree at least k is approximately k with τ ∈ (2,3), typical distances between pairs of vertices in a graph of size n are asymptotic to and , respectively. In this paper, we investigate the behavior of the diameter in such models.

Symptomatic Carotid Plaques Demonstrate Less Leaky Plaque Microvasculature Compared With the Contralateral Side: A Dynamic Contrast-Enhanced Magnetic Resonance Imaging Study.

Background Rupture of a vulnerable carotid atherosclerotic plaque is an important underlying cause of ischemic stroke. Increased leaky plaque microvasculature may contribute to plaque vulnerability. These immature microvessels may facilitate entrance of inflammatory cells into the plaque.

Atrial Fibrillation Detection Using a Novel Cardiac Ambulatory Monitor Based on Photo-Plethysmography at the Wrist.

Background Long-term continuous cardiac monitoring would aid in the early diagnosis and management of atrial fibrillation ( AF ). This study examined the accuracy of a novel approach for AF detection using photo-plethysmography signals measured from a wrist-based wearable device. Methods and Results ECG and contemporaneous pulse data were collected from 2 cohorts of AF patients: AF patients (n=20) undergoing electrical cardioversion ( ECV ) and AF patients (n=40) that were prescribed for 24 hours ECG Holter in outpatient settings ( HOL ).

LOFAR Lightning Imaging: Mapping Lightning With Nanosecond Precision.

Lightning mapping technology has proven instrumental in understanding lightning. In this work we present a pipeline that can use lightning observed by the LOw-Frequency ARray (LOFAR) radio telescope to construct a 3-D map of the flash. We show that LOFAR has unparalleled precision, on the order of meters, even for lightning flashes that are over 20 km outside the area enclosed by LOFAR antennas (∼3,200 km), and can potentially locate over 10,000 sources per lightning flash.

Salt concentration dependence of the mechanical properties of LiPF/poly(propylene glycol) acrylate electrolyte at a graphitic carbon interface: A reactive molecular dynamics study.

This reactive molecular dynamics study explores the salt concentration dependence of the viscoelastic and mechanical failure properties of a poly(propylene glycol)/LiPF-based solid polymer electrolyte (SPE) at a graphitic carbon electrode interface. To account for the finite-size effect of interface-confined SPE films, the properties of two distinct film thicknesses are compared with the respective bulk properties. Additionally, the effect of uniaxial compression in the interface-normal direction on free energy profiles of Li-ion SPE-desolvation is studied.