Cardiovascular Mechanisms of Action of Anthocyanins May Be Associated with the Impact of Microbial Metabolites on Heme Oxygenase-1 in Vascular Smooth Muscle Cells

Anthocyanins are reported to have cardio-protective effects, although their mechanisms of action remain elusive. We aimed to explore the effects of microbial metabolites common to anthocyanins and other flavonoids on vascular smooth muscle heme oxygenase-1 (HO-1) expression. Thirteen phenolic metabolites identified by previous anthocyanin human feeding studies, as well as 28 unique mixtures of metabolites and their known precursor structures were explored for their activity on HO-1 protein expression in rat aortic smooth muscle cells (RASMCs). No phenolic metabolites were active when treated in isolation; however, five mixtures of phenolic metabolites significantly increased HO-1 protein expression (127.4-116.6%, p ≤ 0.03). The present study demonstrates that phenolic metabolites of anthocyanins differentially affect HO-1 activity, often having additive, synergistic or nullifying effects

Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the ESBRA 2017 Congress.

The symposium, "Role of Nutrition in Alcoholic Liver Disease", was held at the European Society for Biomedical Research on Alcoholism Congress on 9 October 2017 in Crete, Greece. The goal of the symposium was to highlight recent advances and developments in the field of alcohol and nutrition. The symposium was focused on experimental and clinical aspects in relation to the role of different types of dietary nutrients and malnutrition in the pathogenesis of alcoholic liver disease (ALD). The following is a summary of key research presented at this session. The speakers discussed the role of dietary fats and carbohydrates in the development and progression of alcohol-induced multi-organ pathology in animal models of ALD, analyzed novel nutrition-related therapeutics (specifically, betaine and zinc) in the treatment of ALD, and addressed clinical relevance of malnutrition and nutrition support in ALD. This summary of the symposium will benefit junior and senior faculty currently investigating alcohol-induced organ pathology as well as undergraduate, graduate, and post-graduate students and fellows

Redox-dependent Franck–Condon blockade and Avalanche Transport in a Graphene–Fullerene single-molecule transistor

We report transport measurements on a graphene–fullerene single-molecule transistor. The device architecture where a functionalized C60 binds to graphene nanoelectrodes results in strong electron–vibron coupling and weak vibron relaxation. Using a combined approach of transport spectroscopy, Raman spectroscopy, and DFT calculations, we demonstrate center-of-mass oscillations, redox-dependent Franck–Condon blockade, and a transport regime characterized by avalanche tunnelling in a single-molecule transistor

Mapping nanoscale electrostatic field fluctuations around graphene dislocation cores using four-dimensional scanning transmission electron microscopy (4D-STEM)

Defects in crystalline lattices cause modulation of the atomic density, and this leads to variations in the associated electrostatics at the nanoscale. Mapping these spatially varying charge fluctuations using transmission electron microscopy has typically been challenging due to complicated contrast transfer inherent to conventional phase contrast imaging. To overcome this, we used four-dimensional scanning transmission electron microscopy (4D-STEM) to measure electrostatic fields near point dislocations in a monolayer. The asymmetry of the atomic density in a (1,0) edge dislocation core in graphene yields a local enhancement of the electric field in part of the dislocation core. Through experiment and simulation, the increased electric field magnitude is shown to arise from "long-range" interactions from beyond the nearest atomic neighbor. These results provide insights into the use of 4D-STEM to quantify electrostatics in thin materials and map out the lateral potential variations that are important for molecular and atomic bonding through Coulombic interactions

A 1D microphysical cloud model for Earth, and Earth-like exoplanets. Liquid water and water ice clouds in the convective troposphere

One significant difference between the atmospheres of stars and exoplanets is the presence of condensed particles (clouds or hazes) in the atmosphere of the latter. The main goal of this paper is to develop a self-consistent microphysical cloud model for 1D atmospheric codes, which can reproduce some observed properties of Earth, such as the average albedo, surface temperature, and global energy budget. The cloud model is designed to be computationally efficient, simple to implement, and applicable for a wide range of atmospheric parameters for planets in the habitable zone. We use a 1D, cloud-free, radiative-convective, and photochemical equilibrium code originally developed by Kasting, Pavlov, Segura, and collaborators as basis for our cloudy atmosphere model. The cloud model is based on models used by the meteorology community for Earth's clouds. The free parameters of the model are the relative humidity and number density of condensation nuclei, and the precipitation efficiency. In a 1D model, the cloud coverage cannot be self-consistently determined, thus we treat it as a free parameter. We apply this model to Earth (aerosol number density 100 cm^-3, relative humidity 77 %, liquid cloud fraction 40 %, and ice cloud fraction 25 %) and find that a precipitation efficiency of 0.8 is needed to reproduce the albedo, average surface temperature and global energy budget of Earth. We perform simulations to determine how the albedo and the climate of a planet is influenced by the free parameters of the cloud model. We find that the planetary climate is most sensitive to changes in the liquid water cloud fraction and precipitation efficiency. The advantage of our cloud model is that the cloud height and the droplet sizes are self-consistently calculated, both of which influence the climate and albedo of exoplanets.Comment: To appear in Icaru

Graphene-porphyrin single-molecule transistors

We demonstrate a robust graphene-molecule-graphene transistor architecture. We observe remarkably reproducible single electron charging, which we attribute to insensitivity of the molecular junction to the atomic configuration of the graphene electrodes. The stability of the graphene electrodes allow for high-bias transport spectroscopy and the observation of multiple redox states at room-temperature

National trends in hyperglycemia and diabetic ketoacidosis in children, adolescents, and young adults with type 1 diabetes: a challenge due to age or stage of development, or is new thinking about service provision needed?

OBJECTIVE Adolescence is associated with high-risk hyperglycemia. This study examines the phenomenon in a life course context. RESEARCH DESIGN AND METHODS A total of 93,125 people with type 1 diabetes aged 5 to 30 years were identified from the National Diabetes Audit and/or the National Paediatric Diabetes Audit for England and Wales for 2017/2018–2019/2020. For each audit year, the latest HbA1c and hospital admissions for diabetic ketoacidosis (DKA) were identified. Data were analyzed in sequential cohorts by year of age. RESULTS In childhood, unreported HbA1c measurement is uncommon; however, for 19-year-olds, it increases to 22.3% for men and 17.3% for women, and then reduces to 17.9% and 13.1%, respectively, for 30-year-olds. Median HbA1c for 9-year-olds is 7.6% (60 mmol/mol) (interquartile range 7.1–8.4%, 54–68 mmol/mol) in boys and 7.7% (61 mmol/mol) (8.0–8.4%, 64–68 mmol/mol) in girls, increasing to 8.7% (72 mmol/mol) (7.5–10.3%, 59–89 mmol/mol) and 8.9% (74 mmol/mol) (7.7–10.6%, 61–92 mmol/mol), respectively, for 19-year-olds before falling to 8.4% (68 mmol/mol) (7.4–9.7%, 57–83 mmol/mol) and 8.2% (66 mmol/mol) (7.3–9.7%, 56–82 mmol/mol), respectively, for 30-year-olds. Annual hospitalization for DKA rose steadily in age from 6 years (2.0% for boys, 1.4% for girls) and peaked at 19 years for men (7.9%) and 18 years for women (12.7%), reducing to 4.3% for men and 5.4% for women at age 30 years. For all ages over 9 years, the prevalence of DKA was higher in female individuals. CONCLUSIONS HbA1c and the prevalence of DKA increase through adolescence and then decline. Measurement of HbA1c, a marker of clinical review, falls abruptly in the late teenage years. Age-appropriate services are needed to overcome these issues

Towards comprehensive syntactic and semantic annotations of the clinical narrative

Objective: To create annotated clinical narratives with layers of syntactic and semantic labels to facilitate advances in clinical natural language processing (NLP). To develop NLP algorithms and open source components. Methods: Manual annotation of a clinical narrative corpus of 127 606 tokens following the Treebank schema for syntactic information, PropBank schema for predicate-argument structures, and the Unified Medical Language System (UMLS) schema for semantic information. NLP components were developed. Results: The final corpus consists of 13 091 sentences containing 1772 distinct predicate lemmas. Of the 766 newly created PropBank frames, 74 are verbs. There are 28 539 named entity (NE) annotations spread over 15 UMLS semantic groups, one UMLS semantic type, and the Person semantic category. The most frequent annotations belong to the UMLS semantic groups of Procedures (15.71%), Disorders (14.74%), Concepts and Ideas (15.10%), Anatomy (12.80%), Chemicals and Drugs (7.49%), and the UMLS semantic type of Sign or Symptom (12.46%). Inter-annotator agreement results: Treebank (0.926), PropBank (0.891–0.931), NE (0.697–0.750). The part-of-speech tagger, constituency parser, dependency parser, and semantic role labeler are built from the corpus and released open source. A significant limitation uncovered by this project is the need for the NLP community to develop a widely agreed-upon schema for the annotation of clinical concepts and their relations. Conclusions: This project takes a foundational step towards bringing the field of clinical NLP up to par with NLP in the general domain. The corpus creation and NLP components provide a resource for research and application development that would have been previously impossible