Two-photon brightness of NIR-emitting, atomically precise DNA-stabilized silver nanoclusters.

Near-infrared (NIR) emitters with high two-photon absorption (2PA) cross-sections are of interest to enable imaging in the tissue transparency windows. This study explores the potential of DNA-stabilized silver nanoclusters (Ag -DNAs) as water-soluble two-photon absorbers. We investigate 2PA of four different atomically precise Ag -DNA species with far-red to NIR emission and varying nanocluster and ligand compositions.

Soil Moisture-Cloud-Precipitation Feedback in the Lower Atmosphere From Functional Decomposition of Satellite Observations.

The feedback of topsoil moisture (SM) content on convective clouds and precipitation is not well understood and represented in the current generation of weather and climate models. Here, we use functional decomposition of satellite-derived SM and cloud vertical profiles (CVP) to quantify the relationship between SM and the vertical distribution of cloud water in the central US. High-dimensional model representation is used to disentangle the contributions of SM and other land-surface and atmospheric variables to the CVP.

HANNA: hard-constraint neural network for consistent activity coefficient prediction.

We present the first hard-constraint neural network model for predicting activity coefficients (HANNA), a thermodynamic mixture property that is the basis for many applications in science and engineering. Unlike traditional neural networks, which ignore physical laws and result in inconsistent predictions, our model is designed to strictly adhere to all thermodynamic consistency criteria. By leveraging deep-set neural networks, HANNA maintains symmetry under the permutation of the components.

at Scientific Sessions 2023: Moving Toward Social Justice in Cardiovascular Health in the United States.

Attention to social justice is essential to improving cardiovascular health outcomes. In the absence of social justice, equitable cardiovascular health is impossible. This viewpoint provides a brief synopsis of the 2023 -sponsored session titled "Moving Towards Social Justice in Cardiovascular Health.

Global Results of Implantable Loop Recorder for Detection of Atrial Fibrillation After Stroke: Reveal LINQ Registry.

Background: We aimed to quantify the incidence of atrial fibrillation (AF) in patients with cryptogenic stroke globally, as well as separately in patients in and outside of Japan, using an implantable loop recorder from a prospective, observational, Reveal LINQ Registry.

Methods And Results: Patients developing cryptogenic stroke and monitored by implantable loop recorder for searching AF were studied. The primary end point was incidence of AF within 36 months after insertion.

Adverse Cardiovascular Effects of Nicotine Delivered by Chronic Electronic Cigarettes or Standard Cigarettes Captured by Cardiovascular Intrinsic Frequencies.

Background: Electronic cigarettes have gained popularity as a nicotine delivery system, which has been recommended by some as an aid to help people quit traditional smoking. The potential long-term effects of vaping on the cardiovascular system, as well as how their effects compare with those from standard cigarettes, are not well understood. The intrinsic frequency (IF) method is a systems approach for analysis of left ventricle and arterial function.

Machine-learned molecular mechanics force fields from large-scale quantum chemical data.

The development of reliable and extensible molecular mechanics (MM) force fields-fast, empirical models characterizing the potential energy surface of molecular systems-is indispensable for biomolecular simulation and computer-aided drug design. Here, we introduce a generalized and extensible machine-learned MM force field, espaloma-0.3, and an end-to-end differentiable framework using graph neural networks to overcome the limitations of traditional rule-based methods.

4f-Orbital mixing increases the magnetic susceptibility of Cp'Eu.

Traditional models of lanthanide electronic structure suggest that bonding is predominantly ionic, and that covalent orbital mixing is not an important factor in determining magnetic properties. Here, 4f orbital mixing and its impact on the magnetic susceptibility of Cp'Eu (Cp' = CHSiMe) was analyzed experimentally using magnetometry and X-ray absorption spectroscopy (XAS) methods at the C K-, Eu M-, and L-edges. Pre-edge features in the experimental and TDDFT-calculated C K-edge XAS spectra provided unequivocal evidence of C 2p and Eu 4f orbital mixing in the π-antibonding orbital of a' symmetry.

Improved synthesis and polymerase recognition of 7-deaza-7-modified α-l-threofuranosyl guanosine analogs.

Threofuranosyl nucleic acid (TNA), an artificial genetic polymer known for its nuclease resistance and acid stability, has grown in popularity as a genetically-encoded material for applications in synthetic biology and biomedicine. TNA oligonucleotide synthesis requires enzymatic or solid phase synthesis pathways that rely on monomer building blocks that are not commercially available and can only be obtained by chemical synthesis. Here we present a synthetic route to 7-deaza-7-modified tGTP and phosphoramidite analogs that is operationally simpler than our previously described strategy.

Cardiomyopathy in Patients With Acute Ischemic Stroke and Methamphetamine Use: Relevance for Cardioembolic Stroke and Outcome.

Background: Methamphetamine use has emerged as a major risk factor for cardiovascular and cerebrovascular disease in young adults. The aim of this study was to investigate a possible association of methamphetamine use with cardioembolic stroke.

Methods And Results: We performed a retrospective study of patients with acute ischemic stroke admitted at our medical center between 2019 and 2022.

Increasing the functional density of threose nucleic acid.

Chemical strategies that augment genetic polymers with amino acid residues that are overrepresented on the paratope surface of an antibody offer a promising route for enhancing the binding properties of nucleic acid aptamers. Here, we describe the chemical synthesis of α-l-threofuranosyl cytidine nucleoside triphosphate (tCTP) carrying either a benzyl or phenylpropyl side chain at the pyrimidine C-5 position. Polymerase recognition studies indicate that both substrates are readily incorporated into a full-length α-l-threofuranosyl nucleic acid (TNA) product by extension of a DNA primer-template duplex with an engineered TNA polymerase.

Reversible Cl/Cl redox in a spinel MnO electrode.

A unique prospect of using halides as charge carriers is the possibility of the halides undergoing anodic redox behaviors when serving as charge carriers for the charge-neutrality compensation of electrodes. However, the anodic conversion of halides to neutral halogen species has often been irreversible at room temperature due to the emergence of diatomic halogen gaseous products. Here, we report that chloride ions can be reversibly converted to near-neutral atomic chlorine species in the MnO electrode at room temperature in a highly concentrated chloride-based aqueous electrolyte.

Efficacy and Adherence Rates of a Novel Community-Informed Virtual World-Based Cardiac Rehabilitation Program: Protocol for the Randomized Controlled Trial.

Background: Innovative restructuring of cardiac rehabilitation (CR) delivery remains critical to reduce barriers and improve access to diverse populations. is a novel virtual world technology-based CR program delivered through the virtual world platform, Second Life, which previously demonstrated high acceptability as an extension of traditional center-based CR. This study aims to evaluate efficacy and adherence of the virtual world-based CR program compared with center-based CR within a community-informed, implementation science framework.

Electron count and ligand composition influence the optical and chiroptical signatures of far-red and NIR-emissive DNA-stabilized silver nanoclusters.

Near-infrared (NIR) emissive DNA-stabilized silver nanoclusters (Ag-DNAs) are promising fluorophores in the biological tissue transparency windows. Hundreds of NIR-emissive Ag-DNAs have recently been discovered, but their structure-property relationships remain poorly understood. Here, we investigate 19 different far-red and NIR emissive Ag-DNA species stabilized by 10-base DNA templates, including well-studied emitters whose compositions and chiroptical properties have never been reported before.

Biomechanical and Mechanobiological Drivers of the Transition From PostCapillary Pulmonary Hypertension to Combined Pre-/PostCapillary Pulmonary Hypertension.

Combined pre-/postcapillary pulmonary hypertension (Cpc-PH), a complication of left heart failure, is associated with higher mortality rates than isolated postcapillary pulmonary hypertension alone. Currently, knowledge gaps persist on the mechanisms responsible for the progression of isolated postcapillary pulmonary hypertension (Ipc-PH) to Cpc-PH. Here, we review the biomechanical and mechanobiological impact of left heart failure on pulmonary circulation, including mechanotransduction of these pathological forces, which lead to altered biological signaling and detrimental remodeling, driving the progression to Cpc-PH.

Optimizing Earthquake Nowcasting With Machine Learning: The Role of Strain Hardening in the Earthquake Cycle.

Nowcasting is a term originating from economics, finance, and meteorology. It refers to the process of determining the uncertain state of the economy, markets or the weather at the current time by indirect means. In this paper, we describe a simple two-parameter data analysis that reveals hidden order in otherwise seemingly chaotic earthquake seismicity.

Electrophilic halogenations of propargyl alcohols: paths to α-haloenones, β-haloenones and mixed β,β-dihaloenones.

The Meyer-Schuster rearrangement of propargyl alcohols or alkynols leading to α,β-unsaturated carbonyl compounds is well known. Yet, electrophilic halogenations of the same alkynols and their alkoxy, ester and halo derivatives are inconspicuous. This review on the halogenation reactions of propargyl alcohols and derivatives intends to give a perspective from its humble direct halogenation beginning to the present involving metal catalysis.

Hotspots of Predictability: Identifying Regions of High Precipitation Predictability at Seasonal Timescales From Limited Time Series Observations.

Precipitation prediction at seasonal timescales is important for planning and management of water resources as well as preparedness for hazards such as floods, droughts and wildfires. Quantifying predictability is quite challenging as a consequence of a large number of potential drivers, varying antecedent conditions, and small sample size of high-quality observations available at seasonal timescales, that in turn, increases prediction uncertainty and the risk of model overfitting. Here, we introduce a generalized probabilistic framework to account for these issues and assess predictability under uncertainty.

Hospital-Level Variation in Ticagrelor Use in Patients With Acute Coronary Syndrome.

Background Despite improved outcomes associated with ticagrelor compared with clopidogrel in acute coronary syndrome (ACS), many studies have demonstrated slow adoption of ticagrelor in the United States because of its increased cost. Less is known about how ticagrelor is adopted when there is no added cost consideration. Our objectives were to determine patterns of use of ticagrelor, hospital-level adoption of ticagrelor use, and factors associated with its use after ACS in a publicly funded health care system.

Magnetic resonance imaging of tumor-associated-macrophages (TAMs) with a nanoparticle contrast agent.

In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited "snapshot" in time of a dynamic and potentially heterogeneous tumor immune microenvironment.

Alchemical absolute protein-ligand binding free energies for drug design.

The recent advances in relative protein-ligand binding free energy calculations have shown the value of alchemical methods in drug discovery. Accurately assessing absolute binding free energies, although highly desired, remains a challenging endeavour, mostly limited to small model cases. Here, we demonstrate accurate first principles based absolute binding free energy estimates for 128 pharmaceutically relevant targets.

Self-cleaving ribozymes: substrate specificity and synthetic biology applications.

Various self-cleaving ribozymes appearing in nature catalyze the sequence-specific intramolecular cleavage of RNA and can be engineered to catalyze cleavage of appropriate substrates in an intermolecular fashion, thus acting as true catalysts. The mechanisms of the small, self-cleaving ribozymes have been extensively studied and reviewed previously. Self-cleaving ribozymes can possess high catalytic activity and high substrate specificity; however, substrate specificity is also engineerable within the constraints of the ribozyme structure.

Temperature artifacts in protein structures bias ligand-binding predictions.

X-ray crystallography is the gold standard to resolve conformational ensembles that are significant for protein function, ligand discovery, and computational methods development. However, relevant conformational states may be missed at common cryogenic (cryo) data-collection temperatures but can be populated at room temperature. To assess the impact of temperature on making structural and computational discoveries, we systematically investigated protein conformational changes in response to temperature and ligand binding in a structural and computational workhorse, the T4 lysozyme L99A cavity.