Radiosynthesis and preclinical evaluation of a carbon-11 labeled PET ligand for imaging metabotropic glutamate receptor 7.

Metabotropic glutamate receptor 7 (mGlu) is a G protein-coupled receptor that is preferentially found in the active zone of neurotransmitter release in the central nervous system (CNS). mGlu plays a vital role in memory, learning, and neuronal development, rendering it a potential target for treating epilepsy, depression, and anxiety. The development of noninvasive imaging ligands targeting mGlu could help elucidate the functional significance of mGlu and accelerate drug discovery for neurological and psychiatric disorders.

Development of a Candidate C-Labeled Selective Phosphodiesterase 1 Radioligand for Positron Emission Tomography.

Phosphodiesterases (PDEs) constitute a superfamily of phosphohydrolytic enzymes that regulate intracellular second messenger signaling by hydrolyzing cyclic adenosine monophosphate and cyclic guanosine monophosphate. Among the 11 subfamilies of PDEs, phosphodiesterase 1 (PDE1) stands out due to its broad implications in central and peripheral pathologies. There are three subtypes of PDE1: PDE1A, PDE1B, and PDE1C.

A Scalable, High-Efficiency, Low-Energy-Spread Laser Wakefield Accelerator Using a Tri-Plateau Plasma Channel.

The emergence of multi-petawatt laser facilities is expected to push forward the maximum energy gain that can be achieved in a single stage of a laser wakefield acceleration (LWFA) to tens of giga-electron volts, which begs the question-is it likely to impact particle physics by providing a truly compact particle collider? Colliders have very stringent requirements on beam energy, acceleration efficiency, and beam quality. In this article, we propose an LWFA scheme that can for the first time simultaneously achieve hitherto unrealized acceleration efficiency from the laser to the electron beam of >20% and a sub-1% energy spread using a stepwise plasma structure and a nonlinearly chirped laser pulse. Three-dimensional high-fidelity simulations show that the nonlinear chirp can effectively mitigate the laser waveform distortion and lengthen the acceleration distance.

Potential for visualization of intracellular pH gradient in the brain using PET imaging.

Intracellular pH is a valuable index for predicting neuronal damage and injury. However, no PET probe is currently available for monitoring intracellular pH . In this study, we developed a new approach for visualizing the hydrolysis rate of monoacylglycerol lipase, which is widely distributed in neurons and astrocytes throughout the brain.

Polyallylamine Binds to Aβ Amyloid and Inhibits Antibody Recognition.

Protein amyloids have attracted attention for their application as functional amyloid materials because of their strong properties, such as high resistance to chemical or biological degradation, despite their medical issues. Amyloids can be used for various applications by modifying the amyloid surface with functional materials, such as proteins and polymers. In this study, we investigated the effect of polyallylamine (PAA), a functional cationic polymer as a candidate for amyloid modification, on the amyloids formed from amyloid β (Aβ) peptide.

Preclinical Evaluation of Novel Positron Emission Tomography (PET) Probes for Imaging Leucine-Rich Repeat Kinase 2 (LRRK2).

Parkinson's disease (PD) is one of the most highly debilitating neurodegenerative disorders, which affects millions of people worldwide, and leucine-rich repeat kinase 2 (LRRK2) mutations have been involved in the pathogenesis of PD. Developing a potent LRRK2 positron emission tomography (PET) tracer would allow for in vivo visualization of LRRK2 distribution and expression in PD patients. In this work, we present the facile synthesis of two potent and selective LRRK2 radioligands [C] ([C]PF-06447475) and [F] ([F]PF-06455943).

Dephasingless laser wakefield acceleration in the bubble regime.

Laser wakefield accelerators (LWFAs) have electric fields that are orders of magnitude larger than those of conventional accelerators, promising an attractive, small-scale alternative for next-generation light sources and lepton colliders. The maximum energy gain in a single-stage LWFA is limited by dephasing, which occurs when the trapped particles outrun the accelerating phase of the wakefield. Here, we demonstrate that a single space-time structured laser pulse can be used for ionization injection and electron acceleration over many dephasing lengths in the bubble regime.

Development of Novel C-Labeled Selective Orexin-2 Receptor Radioligands for Positron Emission Tomography Imaging.

Orexin 2 receptors (OXR) represent a vital subtype of orexin receptors intricately involved in the regulation of wakefulness, arousal, and sleep-wake cycles. Despite their importance, there are currently no positron emission tomography (PET) tracers available for imaging the OXR in vivo. Herein, we report [C] ([C]OX-2201) and [C] ([C]OX-2202) as novel PET ligands.

Periosteal flaps allow for single stage reconstruction of larger full thickness eyelid defects: a retrospective study.

Full-thickness lower eyelid defects after Mohs micrographic surgery are frequently referred out to oculoplastic surgery for reconstruction. Reconstructive options include wedge closure with or without canthotomy/cantholysis and tarsoconjunctival sliding flaps. Defects > 50% of the eyelid margin have traditionally required the two-stage Hughes flap, leaving the patient with monocular vision for 3-6 weeks until pedicle division.

Nintedanib administration after the onset of acute exacerbation of interstitial lung disease in the real world.

Nintedanib reduces the decline in forced vital capacity and extends the time to the first acute exacerbation of interstitial lung disease (AE-ILD). However, the effect of additional nintedanib administration after AE-ILD onset is unknown. This study aimed to investigate the efficacy and safety of nintedanib administration after AE-ILD development.

Automated radiosynthesis and in vivo evaluation of F-labeled analog of the photosensitizer ADPM06 for planning photodynamic therapy.

Background: A family of BF-chelated tetraaryl-azadipyrromethenes was developed as non-porphyrin photosensitizers for photodynamic therapy. Among the developed photosensitizers, ADPM06 exhibited excellent photochemical and photophysical properties. Molecular imaging is a useful tool for photodynamic therapy planning and monitoring.

Concentric hypertrophy geometry is a significant determinant of impaired global longitudinal strain in patients with normal cardiac structure and function.

Background: In recent years, the assessment of global longitudinal strain (GLS) derived by speckle-tracking analysis has become a clinically feasible alternative to left ventricular (LV) ejection fraction (LVEF) for the assessment of myocardial function. However, the determinant factors of impaired GLS in structurally and functionally normal patients are unclarified. The objective of this study was to elucidate the determinant factors of impaired GLS in structurally and functionally normal patients.

Mapping the self-generated magnetic fields due to thermal Weibel instability.

The origin of the seed magnetic field that is amplified by the galactic dynamo is an open question in plasma astrophysics. Aside from primordial sources and the Biermann battery mechanism, plasma instabilities have also been proposed as a possible source of seed magnetic fields. Among them, thermal Weibel instability driven by temperature anisotropy has attracted broad interests due to its ubiquity in both laboratory and astrophysical plasmas.

Analysis of the enzymatic degradation of lysozyme fibrils using a combination method of non-denaturing gel electrophoresis and double staining with Coomassie Brilliant Blue G-250 and R-250 dyes.

The Amyloid fibrils of proteins are involved in various diseases, such as Alzheimer's disease. To suppress such amyloid fibrils, it is essential to develop methods to elucidate their enzymatic degradation process. Lysozyme in egg white has been well studied as a model protein of amyloid fibrils.

Diversity and Career Goals of Graduating Allopathic Medical Students Pursuing Careers in Dermatology.

Importance: Dermatology is one of the least diverse specialties, while patients from minority racial and ethnic groups and other underserved populations continue to face numerous dermatology-specific health and health care access disparities in the US.

Objectives: To examine the demographic characteristics and intended career goals of graduating US allopathic medical students pursuing careers in dermatology compared with those pursuing other specialties and whether these differ by sex, race and ethnicity, and/or sexual orientation.

Design, Setting, And Participants: This secondary analysis of a repeated cross-sectional study included 58 077 graduating allopathic medical students using data from the 2016 to 2019 Association of American Medical Colleges Graduation Questionnaires.

Imaging of Transmembrane AMPA Receptor Regulatory Proteins by Positron Emission Tomography.

The transmembrane α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptor regulatory protein γ-8 (TARP γ-8) constitutes an auxiliary subunit of AMPA receptors, which mediates various brain functions including learning and memory. TARP γ-8 has emerged as a promising therapeutic target for central nervous system disorders. Despite considerable efforts, previously reported TARP γ-8 PET radioligands, such as [C]TARP-1903 and [C]TARP-1811 series, were plagued by limited brain uptake and/or high nonspecific binding in vivo.

Generation of ultrahigh-brightness pre-bunched beams from a plasma cathode for X-ray free-electron lasers.

The longitudinal coherence of X-ray free-electron lasers (XFELs) in the self-amplified spontaneous emission regime could be substantially improved if the high brightness electron beam could be pre-bunched on the radiated wavelength-scale. Here, we show that it is indeed possible to realize such current modulated electron beam at angstrom scale by exciting a nonlinear wake across a periodically modulated plasma-density downramp/plasma cathode. The density modulation turns on and off the injection of electrons in the wake while downramp provides a unique longitudinal mapping between the electrons' initial injection positions and their final trapped positions inside the wake.

Inflammasome assembly is required for intracellular formation of β2-microglobulin amyloid fibrils, leading to IL-1β secretion.

Introduction: Dialysis-related amyloidosis (DRA) caused by β2-microgloblin (B2M) fibrils is a serious complication for patients with kidney failure on long-term dialysis. Deposition of B2M amyloid fibrils is thought to be due not only to serum extracellular B2M but also to infiltrating inflammatory cells, which may have an important role in B2M amyloid deposition in osteoarticular tissues in patients with DRA. Here, we asked whether B2M amyloid fibrils activate the inflammasome and contribute to formation and deposition of amyloid fibrils in cells.

Differences in interaction lead to the formation of different types of insulin amyloid.

Insulin balls, localized insulin amyloids formed at the site of repeated insulin injections in patients with diabetes, cause poor glycemic control and cytotoxicity. Our previous study has shown that insulin forms two types of amyloids; toxic amyloid formed from the intact insulin ((i)-amyloid) and less-toxic amyloid formed in the presence of the reducing reagent TCEP ((r)-amyloid), suggesting insulin amyloid polymorphism. However, the differences in the formation mechanism and cytotoxicity expression are still unclear.

Ultrabright Electron Bunch Injection in a Plasma Wakefield Driven by a Superluminal Flying Focus Electron Beam.

We propose a new method for self-injection of high-quality electron bunches in the plasma wakefield structure in the blowout regime utilizing a "flying focus" produced by a drive beam with an energy chirp. In a flying focus the speed of the density centroid of the drive bunch can be superluminal or subluminal by utilizing the chromatic dependence of the focusing optics. We first derive the focal velocity and the characteristic length of the focal spot in terms of the focal length and an energy chirp.