Construction and Investigation of Metallochromic Dyes

Novel fluorophores were synthesized, characterized, and examined with respect to their metal-binding properties. These compounds (Figure 1) consist of a heteroaromatic core substituted with two triazole rings, synthesized via copper-catalyzed azide-alkyne cycloaddition. Binding of a metal ion is achieved through coordination between two nitrogens (one in the triazole ring, and one in the heteroaromatic core). For practical purposes, these sensors must be soluble in water. This is accomplished through the use of a water-soluble side chain; in this case, one with a branched oligoethylene glycol substituent. This bulky side-chain decreases fluorescence quenching from intermolecular aggregation, resulting in metal ion sensors that are brightly fluorescent, even in water. Figure 1 Metal ion sensors. R represents tri(ethylene glycol) monomethyl ether, X represents H, F, or Cl, and Y represents O, S, or Se. These molecules are designed so that they serve as the binding receptor and the sensing element. We are then able to tune the structure of the core molecule, thereby adjusting the metal-binding activity, as well as the optical properties. In Figure 1, the series of molecules on the left is tunable through halogen substitution of the phenazine core. On the right, variation of the chalcogen heteroatom serves the same purpose. Increasing understanding of this kind of structure-property relationship is vital for the future construction of highly sensitive and selective fluorescent sensors. The results show that of the phenazine-containing compounds, those that are more electron-poor (halogen-substituted) are not able to efficiently bind metal ions in aqueous solution. A similar effect is seen with the benzochalcogendiazole compounds, with binding affinity increasing moving down the group, parallel to the decreasing electronegativity of the chalcogen atom. The heteroaromatic core also plays a significant role in the selectivity; the phenazine compound functions as a selective silver sensor, while the benzochalcogendiazole compounds respond to copper, silver, and nickel. The response to each metal is unique, and statistical analysis of the resulting data enables differentiation of these three metals with a single molecule

Enhancements in Mass Transfer for Carbon Capture Solvents Part I: Homogeneous Catalyst

The novel small molecule carbonic anhydrase (CA) mimic [CoIII(Salphen-COO−)Cl]HNEt3 (1), was synthesized as an additive for increasing CO2 absorption rates in amine-based post-combustion carbon capture processes (CCS), and its efficacy was verified. 1 was designed for use in a kinetically slow but thermally stable blended solvent, containing the primary amines 1-amino-2-propanol (A2P) and 2-amino-2-methyl-1-propanol (AMP). Together, the A2P/AMP solvent and 1 reduce the overall energy penalty associated with CO2 capture from coal-derived flue gas, relative to the baseline solvent MEA. 1 is also effective at increasing absorption kinetics of kinetically fast solvents, such as MEA, which can reduce capital costs by requiring a smaller absorber tower. The transition from catalyst testing under idealized laboratory conditions, to process relevant lab- and bench-scale testing adds many additional variables that are not well understood and rarely discussed. The stepwise testing of both 1 and the novel A2P/AMP solvent blend is described through a transition process that identifies many of these process and evaluation challenges not often addressed when designing a chemical or catalytic additive for industrial CCS systems, where consideration of solvent chemistry is typically the primary goal

Complete Genome Sequence of the Aerobic CO-Oxidizing Thermophile Thermomicrobium roseum

In order to enrich the phylogenetic diversity represented in the available sequenced bacterial genomes and as part of an “Assembling the Tree of Life” project, we determined the genome sequence of Thermomicrobium roseum DSM 5159. T. roseum DSM 5159 is a red-pigmented, rod-shaped, Gram-negative extreme thermophile isolated from a hot spring that possesses both an atypical cell wall composition and an unusual cell membrane that is composed entirely of long-chain 1,2-diols. Its genome is composed of two circular DNA elements, one of 2,006,217 bp (referred to as the chromosome) and one of 919,596 bp (referred to as the megaplasmid). Strikingly, though few standard housekeeping genes are found on the megaplasmid, it does encode a complete system for chemotaxis including both chemosensory components and an entire flagellar apparatus. This is the first known example of a complete flagellar system being encoded on a plasmid and suggests a straightforward means for lateral transfer of flagellum-based motility. Phylogenomic analyses support the recent rRNA-based analyses that led to T. roseum being removed from the phylum Thermomicrobia and assigned to the phylum Chloroflexi. Because T. roseum is a deep-branching member of this phylum, analysis of its genome provides insights into the evolution of the Chloroflexi. In addition, even though this species is not photosynthetic, analysis of the genome provides some insight into the origins of photosynthesis in the Chloroflexi. Metabolic pathway reconstructions and experimental studies revealed new aspects of the biology of this species. For example, we present evidence that T. roseum oxidizes CO aerobically, making it the first thermophile known to do so. In addition, we propose that glycosylation of its carotenoids plays a crucial role in the adaptation of the cell membrane to this bacterium's thermophilic lifestyle. Analyses of published metagenomic sequences from two hot springs similar to the one from which this strain was isolated, show that close relatives of T. roseum DSM 5159 are present but have some key differences from the strain sequenced

\u3cem\u3eOAS1\u3c/em\u3e Polymorphisms Are Associated with Susceptibility to West Nile Encephalitis in Horses

West Nile virus, first identified within the United States in 1999, has since spread across the continental states and infected birds, humans and domestic animals, resulting in numerous deaths. Previous studies in mice identified the Oas1b gene, a member of the OAS/RNASEL innate immune system, as a determining factor for resistance to West Nile virus (WNV) infection. A recent case-control association study described mutations of human OAS1 associated with clinical susceptibility to WNV infection. Similar studies in horses, a particularly susceptible species, have been lacking, in part, because of the difficulty in collecting populations sufficiently homogenous in their infection and disease states. The equine OAS gene cluster most closely resembles the human cluster, with single copies of OAS1, OAS3 and OAS2 in the same orientation. With naturally occurring susceptible and resistant sub-populations to lethal West Nile encephalitis, we undertook a case-control association study to investigate whether, similar to humans (OAS1) and mice (Oas1b), equine OAS1 plays a role in resistance to severe WNV infection. We identified naturally occurring single nucleotide mutations in equine (Equus caballus) OAS1 and RNASEL genes and, using Fisher\u27s Exact test, we provide evidence that mutations in equine OAS1 contribute to host susceptibility. Virtually all of the associated OAS1 polymorphisms were located within the interferon-inducible promoter, suggesting that differences in OAS1 gene expression may determine the host\u27s ability to resist clinical manifestations associated with WNV infection

Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization.

NLRP3 induces caspase-1-dependent pyroptotic cell death to drive inflammation. Aberrant activity of NLRP3 occurs in many human diseases. NLRP3 activation induces ASC polymerization into a single, micron-scale perinuclear punctum. Higher resolution imaging of this signaling platform is needed to understand how it induces pyroptosis. Here, we apply correlative cryo-light microscopy and cryo-electron tomography to visualize ASC/caspase-1 in NLRP3-activated cells. The puncta are composed of branched ASC filaments, with a tubular core formed by the pyrin domain. Ribosomes and Golgi-like or endosomal vesicles permeate the filament network, consistent with roles for these organelles in NLRP3 activation. Mitochondria are not associated with ASC but have outer-membrane discontinuities the same size as gasdermin D pores, consistent with our data showing gasdermin D associates with mitochondria and contributes to mitochondrial depolarization

Dihydrodinophysistoxin-1 Produced by Dinophysis norvegica in the Gulf of Maine, USA and Its Accumulation in Shellfish

Dihydrodinophysistoxin-1 (dihydro-DTX1, (M-H)−m/z 819.5), described previously from a marine sponge but never identified as to its biological source or described in shellfish, was detected in multiple species of commercial shellfish collected from the central coast of the Gulf of Maine, USA in 2016 and in 2018 during blooms of the dinoflagellate Dinophysis norvegica. Toxin screening by protein phosphatase inhibition (PPIA) first detected the presence of diarrhetic shellfish poisoning-like bioactivity; however, confirmatory analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) failed to detect okadaic acid (OA, (M-H)−m/z 803.5), dinophysistoxin-1 (DTX1, (M-H)−m/z 817.5), or dinophysistoxin-2 (DTX2, (M-H)−m/z 803.5) in samples collected during the bloom. Bioactivity-guided fractionation followed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) tentatively identified dihydro-DTX1 in the PPIA active fraction. LC-MS/MS measurements showed an absence of OA, DTX1, and DTX2, but confirmed the presence of dihydro-DTX1 in shellfish during blooms of D. norvegica in both years, with results correlating well with PPIA testing. Two laboratory cultures of D. norvegica isolated from the 2018 bloom were found to produce dihydro-DTX1 as the sole DSP toxin, confirming the source of this compound in shellfish. Estimated concentrations of dihydro-DTX1 were \u3e0.16 ppm in multiple shellfish species (max. 1.1 ppm) during the blooms in 2016 and 2018. Assuming an equivalent potency and molar response to DTX1, the authority initiated precautionary shellfish harvesting closures in both years. To date, no illnesses have been associated with the presence of dihydro-DTX1 in shellfish in the Gulf of Maine region and studies are underway to determine the potency of this new toxin relative to the currently regulated DSP toxins in order to develop appropriate management guidance

Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials

BACKGROUND: Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in an ad hoc way, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts. METHODS/DESIGN: The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies. DISCUSSION: Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention. TRIAL REGISTRATION: The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial

Machine learning active-nematic hydrodynamics

Hydrodynamic theories effectively describe many-body systems out of equilibrium in terms of a few macroscopic parameters. However, such hydrodynamic parameters are difficult to derive from microscopics. Seldom is this challenge more apparent than in active matter where the energy cascade mechanisms responsible for autonomous large-scale dynamics are poorly understood. Here, we use active nematics to demonstrate that neural networks can extract the spatio-temporal variation of hydrodynamic parameters directly from experiments. Our algorithms analyze microtubule-kinesin and actin-myosin experiments as computer vision problems. Unlike existing methods, neural networks can determine how multiple parameters such as activity and elastic constants vary with ATP and motor concentration. In addition, we can forecast the evolution of these chaotic many-body systems solely from image-sequences of their past by combining autoencoder and recurrent networks with residual architecture. Our study paves the way for artificial-intelligence characterization and control of coupled chaotic fields in diverse physical and biological systems even when no knowledge of the underlying dynamics exists.Comment: SI Movie 1: https://www.youtube.com/watch?v=9WzIT7OG9pY SI Movie 2: https://youtu.be/Trc4RyU7-dw SI Movie 3: https://youtu.be/Epm_P_EakH

The SAMI Galaxy Survey: A Range in S0 Properties Indicating Multiple Formation Pathways

It has been proposed that S0 galaxies are either fading spirals or the result of galaxy mergers. The relative contribution of each pathway, and the environments in which they occur remains unknown. Here we investigate stellar and gas kinematics of 219 S0s in the SAMI Survey to look for signs of multiple formation pathways occurring across the full range of environments. We identify a large range of rotational support in their stellar kinematics, which correspond to ranges in their physical structure. We find that pressure-supported S0s with $v/{\sigma}$ below 0.5 tend to be more compact and feature misaligned stellar and gas components, suggesting an external origin for their gas. We postulate that these S0s are consistent with being formed through a merger process. Meanwhile, comparisons of ellipticity, stellar mass and S\'ersic index distributions with spiral galaxies shows that the rotationally supported S0s with $v/{\sigma}$ above 0.5 are more consistent with a faded spiral origin. In addition, a simulated merger pathway involving a compact elliptical and gas-rich satellite results in an S0 that lies within the pressure-supported group. We conclude that two S0 formation pathways are active, with mergers dominating in isolated galaxies and small groups, and the faded spiral pathway being most prominent in large groups ($10^{13} < M_{halo} < 10^{14}$).Comment: 14 pages, 12 figures, accepted for publication in MNRA

The SAMI galaxy survey: Can we trust aperture corrections to predict star formation?

In the low-redshift Universe (z < 0.3), our view of galaxy evolution is primarily based on fibre optic spectroscopy surveys. Elaborate methods have been developed to address aperture effects when fixed aperture sizes only probe the inner regions for galaxies of ever decreasing redshift or increasing physical size. These aperture corrections rely on assumptions about the physical properties of galaxies. The adequacy of these aperture corrections can be tested with integral-field spectroscopic data. We use integral-field spectra drawn from 1212 galaxies observed as part of the SAMI Galaxy Survey to investigate the validity of two aperture correction methods that attempt to estimate a galaxy's total instantaneous star formation rate. We show that biases arise when assuming that instantaneous star formation is traced by broad-band imaging, and when the aperture correction is built only from spectra of the nuclear region of galaxies. These biases may be significant depending on the selection criteria of a survey sample. Understanding the sensitivities of these aperture corrections is essential for correct handling of systematic errors in galaxy evolution studies