Rapid Synthesis of Highly Substituted 1,6-Naphthyridines Via Heteroaryl Ditriflates.

We report the discovery of a convenient and efficient method for the synthesis of highly substituted 1,6-naphthyridines. A tandem nitrile hydration/cyclization procedure was developed to access 1,6-naphthyridine-5,7-diones under mild conditions. Subsequently, we have found that ditriflation of these intermediates provides 1,6-naphthyridine-5,7-ditriflates which are bench-stable but highly reactive intermediates that can be engaged in one-pot difunctionalization reactions leading to diverse drug-like products in rapid fashion.

Temporal convolutional networks and data rebalancing for clinical length of stay and mortality prediction.

It is critical for hospitals to accurately predict patient length of stay (LOS) and mortality in real-time. We evaluate temporal convolutional networks (TCNs) and data rebalancing methods to predict LOS and mortality. This is a retrospective cohort study utilizing the MIMIC-III database.

On collaborative reinforcement learning to optimize the redistribution of critical medical supplies throughout the COVID-19 pandemic.

Objective: This work investigates how reinforcement learning and deep learning models can facilitate the near-optimal redistribution of medical equipment in order to bolster public health responses to future crises similar to the COVID-19 pandemic.

Materials And Methods: The system presented is simulated with disease impact statistics from the Institute of Health Metrics, Centers for Disease Control and Prevention, and Census Bureau. We present a robust pipeline for data preprocessing, future demand inference, and a redistribution algorithm that can be adopted across broad scales and applications.

The toxin goniodomin, produced by Alexandrium spp., is identical to goniodomin A.

In 1968 Burkholder and associates (J. Antibiot. (Tokyo)1968, 21, 659-664) isolated the antifungal toxin goniodomin from an unidentified Puerto Rican dinoflagellate and partially characterized its structure.

Maternal Central Blood Pressure Is Associated with Fetal Middle Cerebral Artery Dopplers.

Cardiovascular adaptations to pregnancy involve physiological mechanisms that increase cardiac output, decrease total vascular resistance, and decrease both systolic and diastolic blood pressure (BP). These maternal hemodynamic changes modulate uteroplacental blood flow and fetal-placental Doppler indices. Our objective was to create maternal cardiac profiles of pregnant women using non-invasive measurements of central BP to identify changes in maternal-fetal hemodynamics as a surrogate to fetal status.

Maternal Fontan procedure is a predictor of a small-for-gestational-age neonate: a 10-year retrospective study.

Background: Women with single ventricle cardiac physiologic condition who have undergone Fontan procedures are surviving well into reproductive age and historically have been discouraged from pregnancy, despite the paucity of data regarding maternal and neonatal outcomes.

Objective: Our primary objective was to investigate, in a large cohort, the maternal and neonatal outcomes of pregnant women who have undergone the Fontan procedure and to understand maternal and neonatal sequelae of their pregnancies.

Study Design: This single-center retrospective cohort study involves pregnant women with a Fontan palliation who delivered at UCLA Medical Center over a 10-year period (2007-2017).

NOTCH1 is a mechanosensor in adult arteries.

Endothelial cells transduce mechanical forces from blood flow into intracellular signals required for vascular homeostasis. Here we show that endothelial NOTCH1 is responsive to shear stress, and is necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. NOTCH1 receptor localizes downstream of flow and canonical NOTCH signaling scales with the magnitude of fluid shear stress.

The SAR of brain penetration for a series of heteroaryl urea FAAH inhibitors.

The SAR of brain penetration for a series of heteroaryl piperazinyl- and piperadinyl-urea fatty acid amide hydrolase (FAAH) inhibitors is described. Brain/plasma (B/P) ratios ranging from >4:1 to as low as 0.02:1 were obtained through relatively simple structural changes to various regions of the heteroaryl urea scaffold.

Preclinical Characterization of the FAAH Inhibitor JNJ-42165279.

The pre-clinical characterization of the aryl piperazinyl urea inhibitor of fatty acid amide hydrolase (FAAH) JNJ-42165279 is described. JNJ-42165279 covalently inactivates the FAAH enzyme, but is highly selective with regard to other enzymes, ion channels, transporters, and receptors. JNJ-42165279 exhibited excellent ADME and pharmacodynamic properties as evidenced by its ability to block FAAH in the brain and periphery of rats and thereby cause an elevation of the concentrations of anandamide (AEA), oleoyl ethanolamide (OEA), and palmitoyl ethanolamide (PEA).

Heteroarylureas with spirocyclic diamine cores as inhibitors of fatty acid amide hydrolase.

A series of mechanism based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with spirocyclic diamine cores is described. A potent member of this class, (37), was found to inhibit FAAH centrally, elevate the brain levels of three fatty acid ethanolamides [FAAs: anandamide (AEA), oleoyl ethanolamide (OEA) and palmitoyl ethanolamide (PEA)], and was moderately efficacious in a rat model of neuropathic pain.

Ultrasensitive gas-phase chemical sensing based on functionalized photonic crystal nanobeam cavities.

Photonic crystal nanobeam cavities with high-quality factors are very sensitive to the changes of the dielectric properties of their surroundings. Utilizing this high sensitivity and by applying chemical functionalization, an ultrasensitive chemical sensor for gases based on a nanobeam cavity was demonstrated. A limit of detection of 1.

Heteroaryl urea inhibitors of fatty acid amide hydrolase: structure-mutagenicity relationships for arylamine metabolites.

The structure-activity relationships for a series of heteroaryl urea inhibitors of fatty acid amide hydrolase (FAAH) are described. Members of this class of inhibitors have been shown to inactivate FAAH by covalent modification of an active site serine with subsequent release of an aromatic amine from the urea electrophile. Systematic Ames II testing guided the optimization of urea substituents by defining the structure-mutagenicity relationships for the released aromatic amine metabolites.

Ulcerative disease outbreak in crayfish Orconectes propinquus linked to Saprolegnia australis in big Muskellunge Lake, Wisconsin.

Crayfish populations in the area of the North Temperate Lakes Long Term Ecological Research (LTER) project, Wisconsin, USA, have been monitored for >25 yr. In 2005, native crayfish Orconectes propinquus from Big Muskellunge Lake were found with ulcerated lesions in the cuticle. In 2006, lesions occurred in 9.