An applied noise model for low-loss EELS maps.

Electron energy-loss spectroscopy (EELS) performed in a scanning transmission electron microscope (STEM) is susceptible to noise, just like every other measurement. EELS measurements are also affected by signal blurring, related to the energy distribution of the electron beam and the detector point spread function (PSF). Moreover, the signal blurring caused by the detector introduces correlation effects, which smooth the noise.

Enhanced myocardial perfusion in late gestation fetal lambs with impaired left ventricular inflow.

Robust preclinical models of asymmetric ventricular loading in late gestation reflecting conditions such as hypoplastic left heart syndrome are lacking. We characterized the morphometry and microvascular function of the hypoplastic left ventricle (LV) and remaining right ventricle (RV) in a sham-controlled late gestation fetal lamb model of impaired left ventricular inflow (ILVI). Singleton fetuses were instrumented at ∼120 days gestational age (dGA; term is ∼147 days) with vascular catheters, an aortic flow probe and a deflated left atrial balloon.

Impact of Length Indexing of Deformation in Echocardiographic Evaluation of Right Ventricular Function.

Background: When assessing right ventricular (RV) function by echocardiography, some discordance between the deformational indices is predicted on the basis of the influence of RV length. RV free wall longitudinal strain (RVFWS) is relatively independent of RV length, whereas tricuspid annular plane systolic excursion (TAPSE) reflects the strain-length product. Systolic annular velocity (s'; distance over time) is also likely to be influenced by length.

Linear and Two-Dimensional Infrared Spectroscopy of the Multifunctional Vibrational Probe, 3-(4-Azidophenyl) Propiolonitrile. Deperturbing a Fermi Triad by Isotopic Substitution.

Infrared probes are chemical moieties whose vibrational modes are used to obtain spectroscopic information about structural dynamics of complex systems; in particular, of biomacromolecules. Here, we explore the vibrational spectroscopy and dynamics of a reagent, 3-(4-azidophenyl)propiolonitrile (AzPPN), for selectively tagging thiols in protein environments with a multifunctional infrared probe containing both, an azide and a nitrile chromophore. The linear infrared spectrum of AzPPN is heavily perturbed in the antisymmetric azide stretching region as a result of accidental Fermi resonances.

Survey on Cardiologists' Perspectives on Cardiac Point of Care Ultrasound (POCUS).

: Cardiac point of care ultrasound (POCUS) has been used with increasing frequency. As a result of this trend, this study sought to characterize cardiologists' perspectives on cardiac POCUS. An 18-question survey on demographics, cardiac POCUS clinical practice, education, and infrastructure was distributed by 16 academic medical centers.

In Vivo Cardiovascular Molecular Imaging: Contributions to Precision Medicine and Drug Development.

Conventional forms of noninvasive cardiovascular imaging that evaluate morphology, function, flow, and metabolism play a vital role in individual treatment decisions, often based on guidelines. Innovations in molecular imaging have enhanced our ability to spatially quantify the expression of a wider array of disease-related proteins, genes, or cell types, or the activity of specific pathogenic pathways. These techniques, which usually rely on design of targeted imaging probes, have already been used extensively in cancer medicine and have now become part of cardiovascular care in conditions such as amyloidosis and sarcoidosis.

Interleukin-2-secreting T helper cells promote extra-follicular B cell maturation via intrinsic regulation of a B cell mTOR-AKT-Blimp-1 axis.

During antigen-driven responses, B cells can differentiate at extra-follicular (EF) sites or initiate germinal centers (GCs) in processes that involve interactions with T cells. Here, we examined the roles of interleukin (IL)-2 secreted by T helper (Th) cells during cognate interactions with activated B cells. IL-2 boosted the expansion of EF plasma cells and the secretion of low-mutated immunoglobulin G (IgG).

Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE.

Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine.

Excitation of the Gyrotropic Mode in a Magnetic Vortex by Time-Varying Strain.

We demonstrate the excitation of the gyrotropic mode in a magnetostrictive vortex by time-varying strain. The vortex dynamics is driven by a time-varying voltage applied to the piezoelectric substrate and detected electrically by spin rectification at subthreshold values of rf current. When the frequency of the time-varying strain matches the gyrotropic frequency at a given in-plane magnetic field, the strain-induced in-plane magnetic anisotropy leads to a resonant excitation of the gyration dynamics in the magnetic vortex.

Integration of variant annotations using deep set networks boosts rare variant association testing.

Rare genetic variants can have strong effects on phenotypes, yet accounting for rare variants in genetic analyses is statistically challenging due to the limited number of allele carriers and the burden of multiple testing. While rich variant annotations promise to enable well-powered rare variant association tests, methods integrating variant annotations in a data-driven manner are lacking. Here we propose deep rare variant association testing (DeepRVAT), a model based on set neural networks that learns a trait-agnostic gene impairment score from rare variant annotations and phenotypes, enabling both gene discovery and trait prediction.

Terahertz magneto-optical sampling in quartz glass.

In this Letter, we demonstrate terahertz (THz) magnetic field detection in fused silica with sensitivity that can be easily controlled by sample tilting (for both amplitude and polarization). The proposed technique remains in the linear regime at magnetic fields exceeding 0.3 T (0.

Emerging Pathway to a Precision Medicine Approach for Angina With Nonobstructive Coronary Arteries in Women.

Women are disproportionately affected by symptoms of angina with nonobstructive coronary arteries (ANOCA) which is associated with significant mortality and economic impact. Although distinct endotypes of ANOCA have been defined, it is underdiagnosed and is often incompletely characterized when identified. Patients are often unresponsive to traditional therapeutic options, which are typically antianginal, and the current ability to guide treatment modification by specific pathways is limited.

An Analysis of PIK3CA Hotspot Mutations and Response to Neoadjuvant Therapy in Patients with Breast Cancer from Four Prospective Clinical Trials.

Purpose: The PI3K signaling pathway is frequently dysregulated in breast cancer, and mutations in PIK3CA are relevant for therapy resistance in HER2-positive (HER2pos) breast cancer. Mutations in exons 9 or 20 may have different impacts on response to neoadjuvant chemotherapy-based treatment regimens.

Experimental Design: We investigated PIK3CA mutations in 1,691 patients with early breast cancer who were randomized into four neoadjuvant multicenter trials: GeparQuattro (NCT00288002), GeparQuinto (NCT00567554), GeparSixto (NCT01426880), and GeparSepto (NCT01583426).

Quantifying Diaphragm Blood Flow With Contrast-Enhanced Ultrasound in Humans.

Background: Despite the known interplay between blood flow and function, to our knowledge, there is currently no minimally invasive method to monitor diaphragm hemodynamics. We used contrast-enhanced ultrasound to quantify relative diaphragm blood flow (Q˙) in humans and assessed the technique's efficacy and reliability during graded inspiratory pressure threshold loading. We hypothesized that: (1) Q˙ would linearly increase with pressure generation, and (2) that there would be good test-retest reliability and interanalyzer reproducibility.

Viability of Human Arterial Grafts Monitored by Comet Assay.

An analytical method for studying DNA degradation by electrophoresis after cell lysis and visualization of DNA fragments with fluorescent dye, comet assay, was used to evaluate the viability of the endothelial layer of human arterial grafts with the aim of identifying the procedure that will least damage the tissue before cryopreservation. Four groups of samples were studied: cryopreserved arterial grafts that were thawed in two different ways, slowly lasting 2 hours or rapidly for approx. 7 minutes.

DFT-Assisted Investigation of the Electric Field and Charge Density Distribution of Pristine and Defective 2D WSe by Differential Phase Contrast Imaging.

Most properties of solid materials are defined by their internal electric field and charge density distributions which so far are difficult to measure with high spatial resolution. Especially for 2D materials, the atomic electric fields influence the optoelectronic properties. In this study, the atomic-scale electric field and charge density distribution of WSe bi- and trilayers are revealed using an emerging microscopy technique, differential phase contrast (DPC) imaging in scanning transmission electron microscopy (STEM).

Removal of endothelial surface-associated von villebrand factor suppresses accelerate datherosclerosis after myocardial infarction.

Background: Thromboinflammation involving platelet adhesion to endothelial surface-associated von Willebrand factor (VWF) has been implicated in the accelerated progression of non-culprit plaques after MI. The aim of this study was to use arterial endothelial molecular imaging to mechanistically evaluate endothelial-associated VWF as a therapeutic target for reducing remote plaque activation after myocardial infarction (MI).

Methods: Hyperlipidemic mice deficient for the low-density lipoprotein receptor and Apobec-1 underwent closed-chest MI and were treated chronically with either: (i) recombinant ADAMTS13 which is responsible for proteolytic removal of VWF from the endothelial surface, (ii) N-acetylcysteine (NAC) which removes VWF by disulfide bond reduction, (iii) function-blocking anti-factor XI (FXI) antibody, or (iv) no therapy.

Insulin signalling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons.

Mitochondrial quality control failure is frequently observed in neurodegenerative diseases. The detection of damaged mitochondria by stabilization of PTEN-induced kinase 1 (PINK1) requires transport of Pink1 messenger RNA (mRNA) by tethering it to the mitochondrial surface. Here, we report that inhibition of AMP-activated protein kinase (AMPK) by activation of the insulin signalling cascade prevents Pink1 mRNA binding to mitochondria.

Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy.

The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic T cell therapies remains a time- and cost-intensive endeavor. Current approaches to identify tumor-reactive TCRs analyze tumor mutations to predict T cell activating (neo)antigens and use these to either enrich tumor infiltrating lymphocyte (TIL) cultures or validate individual TCRs for transgenic autologous therapies. Here we combined high-throughput TCR cloning and reactivity validation to train predicTCR, a machine learning classifier that identifies individual tumor-reactive TILs in an antigen-agnostic manner based on single-TIL RNA sequencing.