Publications by authors named "Mark Bell"

The number of ground-nesting ducks in the marshes of Great Salt Lake (GSL), Utah has drastically decreased in the past few decades. One potential cause for this decline is the increase in climate extremes caused by global warming. From 2019 through 2023, GSL marshes experienced 1 year of historic spring rainfall (2019), 2 years of historic droughts (2021 and 2022), and 1 year of record snowfall (2023).

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Background: Sixty-five percent of people with severe asthma and a fractional exhaled nitric oxide (Feno) greater than or equal to 45 parts per billion (ppb) are nonadherent to inhaled corticosteroids (ICSs). Digital devices recording both time of use and inhaler technique identify nonadherence and ICS responsiveness but are not widely available. As the NEXThaler dose counter activates only at an inspiratory flow rate of 35 L/min, this may provide an alternative to identifying ICS responsiveness.

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The number of ground-nesting ducks in the wetlands of Great Salt Lake, Utah has drastically decreased in the past few decades. A potential cause for this decline is the increase of predator species and their abundances, which has caused most nests to fail from depredation. Ground-nesting ducks may be able to reduce the risk of nest depredation by selecting nest sites where local physical structures or vegetation provides olfactory or visual concealment.

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Chronic hepatitis B (CHB) most commonly occurs following infection in early childhood. Prevalence varies markedly around the globe. Country of birth is therefore a strong predictor of CHB risk in adults.

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The UK Government Web Archive (UKGWA) has been archiving government websites since 1996 and now holds regular snapshots of over 5000 sites. Currently, this material can be accessed through browsing or a simple keyword search interface on their website and has also been catalogued in The National Archives' online catalogue, Discovery. However, the scale of the UKGWA exposes the limits of the current search interface, and there is no facility to understand the archive in aggregate.

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We introduce a new chamfering paradigm, locally connecting pixels to produce path distances that approximate Euclidean space by building a small network (a replacement product) inside each pixel. These " RE -grid graphs" maintain near-Euclidean polygonal distance contours even in noisy data sets, making them useful tools for approximation when exact numerical solutions are unobtainable or impractical. The RE -grid graph creates a modular global architecture with lower pixel-to-pixel valency and simplified topology at the cost of increased computational complexity due to its internal structure.

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This article aims to provide an overview of drug discovery with a focus on application within dermatology. The term "drug" can be used to describe a wide variety of agents, including small molecules, cell therapies, and antibodies, which may be dosed intravenously, orally, topically, or by other routes of administration. We summarize the economics and risks involved in drug discovery.

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In order to study the role of S1PRs in inflammatory skin disease, S1PR modulators are dosed orally and topically in animal models of disease. The topical application of S1PR modulators in these models may, however, lead to systemic drug concentrations, which can complicate interpretation of the observed effects. We set out to design soft drug S1PR modulators as topical tool compounds to overcome this limitation.

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We describe an algorithm to compute trisections of orientable four-manifolds using arbitrary triangulations as input. This results in explicit complexity bounds for the trisection genus of a 4-manifold in terms of the number of pentachora (4-simplices) in a triangulation.

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The oral S1PR1 agonist ponesimod demonstrated substantial efficacy in a phase II clinical trial of psoriasis. Unfortunately, systemic side effects were observed, which included lymphopenia and transient bradycardia. We sought to develop a topical soft-drug S1PR1 agonist with an improved therapeutic index.

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The successful remediation of clinicians demonstrating poor performance in the workplace is essential to ensure the provision of safe patient care. Clinicians may develop performance problems for numerous reasons, including health, personal factors, the workplace environment, or outdated knowledge/skills. Performance problems are often complex involving multifactorial issues, encompassing knowledge, skills, and professional behaviors.

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Since the dawn of time, or at least the dawn of recombinant DNA technology (which for many of today's scientists is the same thing), investigators have been cloning and expressing heterologous proteins in a variety of different cells for a variety of different reasons. These range from cell biological studies looking at protein-protein interactions, post-translational modifications, and regulation, to laboratory-scale production in support of biochemical, biophysical, and structural studies, to large scale production of potential biotherapeutics. In parallel, fusion-tag technology has grown-up to facilitate microscale purification (pull-downs), protein visualization (epitope tags), enhanced expression and solubility (protein partners, e.

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Detailed kinetic and computational investigation of the enantio- and diastereoselective allylation of aldehydes 1 with allyltrichlorosilanes 5, employing the pyridine N-oxides METHOX (9) and QUINOX (10) as chiral organocatalysts, indicate that the reaction can proceed through a dissociative (cationic) or associative (neutral) mechanism: METHOX apparently favors a pentacoordinate cationic transition state, while the less sterically demanding QUINOX is likely to operate via a hexacoordinate neutral complex. In both pathways, only one molecule of the catalyst is involved in the rate- and selectivity-determining step, which is supported by both experimental and computational data.

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The geographic distribution of life on Earth supports a general pattern of increase in biodiversity with increasing temperature. However, some previous analyses of the 540-million-year Phanerozoic fossil record found a contrary relationship, with paleodiversity declining when the planet warms. These contradictory findings are hard to reconcile theoretically.

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The chemoenzymatic synthesis of a Lewis basic phosphine-phosphine oxide organocatalyst from a cis-dihydrodiol metabolite of bromobenzene proceeds via a palladium-catalysed carbon-phosphorus bond coupling and a novel room temperature Arbuzov [2,3]-sigmatropic rearrangement of an allylic diphenylphosphinite. Allylation of aromatic aldehydes were catalysed by the Lewis basic organocatalyst giving homoallylic alcohols in up to 57% ee. This compound also functioned as a ligand for rhodium-catalysed asymmetric hydrogenation of acetamidoacrylate giving reduction products with ee values of up to 84%.

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Metriorhynchid crocodylomorphs were the only group of archosaurs to fully adapt to a pelagic lifestyle. During the Jurassic and Early Cretaceous, this group diversified into a variety of ecological and morphological types, from large super-predators with a broad short snout and serrated teeth to specialized piscivores/teuthophages with an elongate tubular snout and uncarinated teeth. Here, we use an integrated repertoire of geometric morphometric (form), biomechanical finite-element analysis (FEA; function) and phylogenetic data to examine the nature of craniofacial evolution in this clade.

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Polyamines are endogenous molecules involved in cell damage following neurological insults, although it is unclear whether polyamines reduce or exacerbate this damage. We used a developmental seizure model in which we exposed Xenopus laevis tadpoles to pentylenetetrazole (PTZ), a known convulsant. We found that, after an initial PTZ exposure, seizure onset times were delayed in response to a second PTZ exposure 4 h later.

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Background: Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the Xenopus laevis tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits.

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Background: Physician reimbursement laws for diagnostic interpretive services require that only those services provided contemporaneously and /or contribute directly to patient care can be billed for. Despite these regulations, cardiologists and radiologists in many hospitals continue to bill for ECG and plain film diagnostic services performed in the emergency department (ED). The reimbursement value of this care, which is disconnected in time and place from the ED patient encounter, is unknown.

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Asymmetric Baeyer-Villiger reaction of symmetrical cyclobutanones 1a-j with urea-hydrogen peroxide (UHP) can be catalyzed by a complex of Pd(II) and the new terpene-derived P, N-ligand 7. The resulting lactones 2a-j were obtained in high yields and with good enantioselectivity (< or =81% ee).

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The organocatalytic enantioselective formation of vinyl-substituted all-carbon quaternary stereocenters via nucleophilic vinylic substitution by alpha-substituted-alpha-cyanoacetates is presented. The reaction proceeds well for different alpha-substituted-alpha-cyanoacetates and beta-chloroalkenones using a dimeric cinchona alkaloid phase-transfer catalyst giving the products in good yield and with enantioselectivities up to 98% ee.

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The organocatalytic allylic C-C bond-forming addition of activated alkylidenes to acrolein has been achieved with good yield and regio- and enantioselectivity. Chiral tertiary amines in the form of cinchona alkaloid catalysts are used to give allyl intermediates that exhibit unusual alpha-selectivity in the C-C bond-forming step. The products are transformed into a large range of intermediates that are difficult to access via alternative methods, using different oxidative and reductive protocols.

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Organocatalytic allylic C-C bond-forming addition of activated alkylidenes to alkyl and aryl nitroalkenes has been achieved with high diastereo- and enantioselectivity. Chiral tertiary amine catalysts are used to give allyl intermediates which exhibit gamma-selectivity in the C-C bond forming step. The reactions proceed with up to >99:1 syn:anti ratio for both the alkyl- and aryl nitroalkenes with up 96% and 98% ee, respectively.

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[reaction: see text]. Allylation of aromatic aldehydes with allyltrichlorosilane is catalyzed by the new terpene-derived pyridine N-oxide (+)-METHOX (< or =5 mol %) in MeCN with high enantioselectivities (< or =96% ee) and conversion rates; this catalyst retains high selectivity even at room temperature.

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