Thiolene-Based Microfluidic Flow Cells for Surface Plasmon Resonance Imaging

Thiolene-based microfluidic devices have been coupled with surface plasmon resonance imaging (SPRI) to provide an integrated platform to study interfacial interactions in both aqueous and organic solutions. In this work, we develop a photolithographic method that interfaces commercially available thiolene resin to gold and glass substrates to generate microfluidic channels with excellent adhesion that leave the underlying sensor surface free from contamination and readily available for surface modification through self-assembly. These devices can sustain high flow rates and have excellent solvent compatibility even with several organic solvents. To demonstrate the versatility of these devices, we have conducted nanomolar detection of streptavidin-biotin interactions using in situ SPRI. (C) 2011 American Institute of Physics. [doi:10.1063/1.3596395

Environmental Factors Affecting Large-Bodied Coral Reef Fish Assemblages in the Mariana Archipelago

Large-bodied reef fishes represent an economically and ecologically important segment of the coral reef fish assemblage. Many of these individuals supply the bulk of the reproductive output for their population and have a disproportionate effect on their environment (e.g. as apex predators or bioeroding herbivores). Large-bodied reef fishes also tend to be at greatest risk of overfishing, and their loss can result in a myriad of either cascading (direct) or indirect trophic and other effects. While many studies have investigated habitat characteristics affecting populations of small-bodied reef fishes, few have explored the relationship between large-bodied species and their environment. Here, we describe the distribution of the large-bodied reef fishes in the Mariana Archipelago with an emphasis on the environmental factors associated with their distribution. Of the factors considered in this study, a negative association with human population density showed the highest relative influence on the distribution of large-bodied reef fishes; however, depth, water temperature, and distance to deep water also were important. These findings provide new information on the ecology of large-bodied reef fishes can inform discussions concerning essential fish habitat and ecosystem-based management for these species and highlight important knowledge gaps worthy of additional research

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

The influence of oxygen isotope exchange between CO2 and H2O in natural CO2-rich spring waters: implications for geothermometry

Oxygen isotope ratio (δ18O) value deviations from the Meteoric Water Line with no significant change in the hydrogen isotope (δ2H) composition have been reported in naturally occurring CO2-rich waters from around the world. Here we review the effects of oxygen isotope exchange with CO2, high temperature equilibration with bedrock minerals and mineral dissolution and precipitation reactions on the CO2-rich water isotopic composition. We present two case studies from Daylesford (Australia) and Pah Tempe (Utah, USA) mineral springs, where we use a numerical geochemical modelling approach to resolve the influence of low temperature water-rock interactions and CO2 equilibration on the observed oxygen isotope ranges observed in the mineral waters. In both cases, we find that mineral dissolution – precipitation reactions are unlikely to have a significant effect on the groundwater isotopic compositions, and that the observed δ18O values in natural CO2 springs can be simply explained by equilibrium fractionation between water and free phase CO2. Traditionally, the interaction of CO2 and water in a natural CO2-rich groundwater setting has only been associated with water 18O depletion and this is the first study to consider 18O enrichment. We establish that in a natural setting, CO2 and water equilibration can result in water 18O depletion or enrichment, and that the change in the oxygen isotope composition ultimately depends on the initial CO2 and water δ18O values. Our new conceptual model therefore provides a mechanism to explain water 18O enrichment at ambient temperatures. This finding is critical for the use of δ18O in groundwater geothermometry and for the interpretation of natural water circulation depths: we argue that in some cases, natural waters previously interpreted as geothermal based on their oxygen isotope composition may actually have acquired their isotopic signature through interaction with CO2 at ambient temperatures

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Towards the asymmetric synthesis of (+)-maritidine

Two new routes towards the asymmetric synthesis of (+)-maritidine have been proposed and investigated. In both of our routes, the aim was to synthesise the 5,10b-ethanophenanthridone core structure of the target via the tricyclic dihydrodibenzofuran core structure present in galanthamine type compounds. Synthesis of the product in this way would allow formation of the quaternary stereocentre 10b using the efficient and facially selective intramolecular Heck reaction used by multiple groups in the synthesis of galanthamine. Route one attempted the ring opening oxidation of the benzofuran moiety to its respective para-quinone using hypervalent iodine reagents such as (diacetoxyiodo)benzene. From here, reduction of the quinone would be followed by the formation of the final ring structure. Unfortunately, the oxidation only served to form an unwanted tricyclic orthoquinone. The second route employed was inspired by a bidirectional system from Treu et al. for conversion between galanthamine and crinine type alkaloids. Their retro-Michael-Michael reaction however, formed an acyclic intermediate, losing the relevant stereochemistry for the target molecule. We aimed to oxidise the allylc position of the tricyclic scaffold and form a tetracyclic pyrollidine. This intermediate would then be able to undergo a retro-Michael reaction, leaving the stereochemistry of the quaternary centre intact. Progress was made to this end and an advanced intermediate of this route synthesised

Processing and Characterisation of Metal Foams as Filters for Space Radioisotope Power Systems

The University of Leicester is designing and building a Radioisotope Thermal electric Generator (RTG) and Radioisotope Heater Unit (RHU) with a consortium of companies and collaborative network. Both the RTGs and RHUs have a similar inner containment architecture in which they include a containment vessel that encompasses the radioisotopic ceramic fuel, known as the cladding. To stop the vessel from failing due to over pressurisation due to gaseous helium and oxygen release from the fuel, a frit vent is employed. The frit vent uses a porous material to stop radioactive fines from escaping the containment vessel while also releasing the internal gases at a specific flow rate. The work presented in this thesis was undertaken to determine a suitable material and manufacturing route for the frit vent, to complete the next phase of the ESA ISO scale. This was achieved through the manufacture and characterisation of surrogate frit vents. Copper frit vents were manufactured by employing two different methodologies: the space holder and loose powder sintering route. A systematic frit vent characterisation was undertaken through the development of a bulk sample image analysis tool for determination of filtration performance, and design and manufacture of a helium pressure-drop rig for testing against the helium flow criterion. Frit vents were initially manufactured via the traditional loose powder sintering route, in which they successfully passed the filtration criteria but failed the critical RTG helium flow criterion by around an order of magnitude. An experimental powder mixing study was undertaken to determine the mixing conditions required to attain uniformly dispersed PMMA space holder, resulting in the development of a dispersion image analysis tool. Through the utilisation of the space holder route, frit vents were successfully manufactured to meet filtration and helium flow criterion determined from previous US RTG studies for a fixed frit geometry.</p

Slowly rotating black holes in quartic generalized quasi-topological gravity

Abstract We study slowly rotating black hole solutions in the six independent theories of Quartic Generalized Quasi-topological Gravity in four dimensions. Unlike in the static case for which all six theories yield the same solution, for rotating black holes we obtain distinct results for five out of the six theories. Working to leading order in the rotation parameter, we find that the equations characterizing these black holes can be reduced to second order for each theory, similar to what has already been done for Einstein Cubic Gravity. We construct approximate and numerical solutions to these equations, and study how physical properties of the solutions such as the angular velocity, photon sphere, black hole shadow, and innermost stable circular orbit are modified, working to leading order in the coupling constant.</jats:p