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Atomic-level simulations are widely used to study biomolecules and their dynamics. A common goal in such studies is to compare simulations of a molecular system under several conditions—for example, with various mutations or bound ligands—in order to identify differences between the molecular conformations adopted under these conditions. However, the large amount of data produced by simulations of ever larger and more complex systems often renders it difficult to identify the structural features that are relevant to a particular biochemical phenomenon. We present a flexible software package named Python ENSemble Analysis (PENSA) that enables a comprehensive and thorough investigation into biomolecular conformational ensembles. It provides featurization and feature transformations that allow for a complete representation of biomolecules such as proteins and nucleic acids, including water and ion binding sites, thus avoiding the bias that would come with manual feature selection. PENSA implements methods to systematically compare the distributions of molecular features across ensembles to find the significant differences between them and identify regions of interest. It also includes a novel approach to quantify the state-specific information between two regions of a biomolecule, which allows, for example, tracing information flow to identify allosteric pathways. PENSA also comes with convenient tools for loading data and visualizing results, making them quick to process and easy to interpret. PENSA is an open-source Python library maintained at https://github.com/drorlab/pensa along with an example workflow and a tutorial. We demonstrate its usefulness in real-world examples by showing how it helps us determine molecular mechanisms efficiently. [ABSTRACT FROM AUTHOR]

This paper presents a lens-free imaging approach utilizing an array of light sources, capable of measuring the dielectric properties of many particles simultaneously. This method employs coplanar electrodes to induce velocity changes in flowing particles through dielectrophoretic forces, allowing the inference of individual particle properties from differential velocity changes. Both positive and negative forces are detectable. The light source utilized in this system is composed of LEDs with a wavelength of 470 nm, while detection is performed using a 256-element optical array detector. Measurements with 10 μm polystyrene beads demonstrate this method can resolve changes equivalent to a Clausius–Mossotti factor of 0.18. Simulations in this work, using values from the literature, predict that Clausius–Mossotti factor differences of 0.18 are sufficient to differentiate viable from nonviable cells and cancerous from multidrug-resistant cancerous cells. We demonstrate that for Chinese hamster ovary (CHO) cells, the method can collect a dielectric response spectrum for a large number of cells in several minutes. We demonstrate that for CHO cells, Clausius–Mossotti factor differences of 0.18 can be discriminated. Due to its simple detection apparatus and the utilization of high-throughput, wide, clog-resistant channels, this method holds promise for a wide range of applications. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular magnetic resonance (CMR) imaging shows promise in estimating pulmonary capillary wedge pressure (PCWP) non‐invasively. At the population level, the prognostic role of CMR‐modelled PCWP remains unknown. Furthermore, the relationship between CMR‐modelled PCWP and established risk factors for cardiovascular disease has not been well characterized. Objective: The main aim of this study was to investigate the prognostic value of CMR‐modelled PCWP at the population level. Methods: Employing data from the imaging substudy of the UK Biobank, a very large prospective population‐based cohort study, CMR‐modelled PCWP was calculated using a model incorporating left atrial volume, left ventricular mass and sex. Logistic regression explored the relationships between typical cardiovascular risk factors and raised CMR‐modelled PCWP (≥15 mmHg). Cox regression was used to examine the impact of typical risk factors and CMR‐modelled PCWP on heart failure (HF) and major adverse cardiovascular events (MACE). Results: Data from 39 163 participants were included in the study. Median age of all participants was 64 years (inter‐quartile range: 58 to 70), and 47% were males. Clinical characteristics independently associated with raised CMR‐modelled PCWP included hypertension [odds ratio (OR) 1.57, 95% confidence interval (CI) 1.44–1.70, P < 0.001], body mass index (BMI) [OR 1.57, 95% CI 1.52–1.62, per standard deviation (SD) increment, P < 0.001], male sex (OR 1.37, 95% CI 1.26–1.47, P < 0.001), age (OR 1.33, 95% CI 1.27–1.41, per decade increment, P < 0.001) and regular alcohol consumption (OR 1.10, 95% CI 1.02–1.19, P = 0.012). After adjusting for potential confounders, CMR‐modelled PCWP was independently associated with incident HF [hazard ratio (HR) 2.91, 95% CI 2.07–4.07, P < 0.001] and MACE (HR 1.48, 95% CI 1.16–1.89, P = 0.002). Conclusions: Raised CMR‐modelled PCWP is an independent risk factor for incident HF and MACE. CMR‐modelled PCWP should be incorporated into routine CMR reports to guide HF diagnosis and further management. [ABSTRACT FROM AUTHOR]

In this paper, we present a microfluidic flow cytometer for simultaneous imaging and dielectric characterization of individual biological cells within a flow. Utilizing a combination of dielectrophoresis (DEP) and high-speed imaging, this system offers a dual-modality approach to analyze both cell morphology and dielectric properties, enhancing the ability to analyze, characterize, and discriminate cells in a heterogeneous population. A high-speed camera is used to capture images of and track multiple cells in real-time as they flow through a microfluidic channel. A wide channel is used, enabling analysis of many cells in parallel. A coplanar electrode array perpendicular to cell flow is incorporated at the bottom of the channel to perform dielectrophoresis-based dielectric characterization. A frequency-dependent voltage applied to the array produces a non-uniform electric field, translating cells to higher or lower velocity depending on their dielectric polarizability. In this paper, we demonstrate how cell size, obtained by optical imaging, and DEP response, obtained by particle tracking, can be used to discriminate viable and non-viable Chinese hamster ovary cells in a heterogeneous cell culture. Multiphysics electrostatic-fluid dynamics simulation is used to develop a relationship between cell incoming velocity, differential velocity, size, and the cell's polarizability, which can subsequently be used to evaluate its physiological state. Measurement of a mixture of polystyrene microspheres is used to evaluate the accuracy of the cytometer. [ABSTRACT FROM AUTHOR]

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (-)-2(S)-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening.

Biogenic volatile organic compounds (BVOCs) from the Amazon forest region represent the largest source of organic carbon emissions to the atmosphere globally. These BVOC emissions dominantly consist of volatile and intermediate-volatility terpenoid compounds that undergo chemical transformations in the atmosphere to form oxygenated condensable gases and secondary organic aerosol (SOA). We collected quartz filter samples with 12 h time resolution and performed hourly in situ measurements with a semi-volatile thermal desorption aerosol gas chromatograph (SV-TAG) at a rural site ("T3") located to the west of the urban center of Manaus, Brazil as part of the Green Ocean Amazon (GoAmazon2014/5) field campaign to measure intermediate-volatility and semi-volatile BVOCs and their oxidation products during the wet and dry seasons. We speciated and quantified 30 sesquiterpenes and 4 diterpenes with mean concentrations in the range 0.01-6.04 ngm-3 (1-670ppqv). We estimate that sesquiterpenes contribute approximately 14 and 12% to the total reactive loss of O3 via reaction with isoprene or terpenes during the wet and dry seasons, respectively. This is reduced from ~ 50-70 % for within-canopy reactive O3 loss attributed to the ozonolysis of highly reactive sesquiterpenes (e.g., β-caryophyllene) that are reacted away before reaching our measurement site. We further identify a suite of their oxidation products in the gas and particle phases and explore their role in biogenic SOA formation in the central Amazon region. Synthesized authentic standards were also used to quantify gas- and particle-phase oxidation products derived from β-caryophyllene. Using tracer-based scaling methods for these products, we roughly estimate that sesquiterpene oxidation contributes at least 0.4-5 % (median 1 %) of total submicron OA mass. However, this is likely a low-end estimate, as evidence for additional unaccounted sesquiterpenes and their oxidation products clearly exists. By comparing our field data to laboratory-based sesquiterpene oxidation experiments we confirm that more than 40 additional observed compounds produced through sesquiterpene oxidation are present in Amazonian SOA, warranting further efforts towards more complete quantification.

The 2018 Program with Abstracts volume for the Western Association of Vertebrate Paleontologists 52nd Annual Meeting held at Dixie State University, St. George, Utah, USA.