Analysis of Migrating and Non-Migrating Tides of the Extended Unified Model in the Mesosphere and Lower Thermosphere

Atmospheric tides play a key role in coupling the lower, middle, and upper atmosphere/ionosphere. The tides reach large amplitudes in the mesosphere and lower thermosphere (MLT), where they can have significant fluxes of energy and momentum, and so strongly influence the coupling and dynamics. The tides must therefore be accurately represented in general circulation models (GCMs) that seek to model the coupling of atmospheric layers and impacts on the ionosphere. The tides consist of both migrating (sun-following) and non-migrating (not sun-following) components, both of which have important influences on the atmosphere. The Extended Unified Model (ExUM) is a recently developed version of the Met Office's GCM (the Unified Model) which has been extended to include the MLT. Here, we present the first in-depth analysis of migrating and non-migrating components in the ExUM. We show that the ExUM produces both non-migrating and migrating tides in the MLT of significant amplitude across a rich spectrum of spatial and temporal components. The dominant non-migrating components in the MLT are found to be DE3, DW2, and DW3 in the diurnal tide and S0, SW1, and SW3 in the semidiurnal tide. These components in the model can have monthly mean amplitudes at a height of 95 km as large as 35 m s−1/10 K. All the non-migrating components exhibit a strong seasonal variability in amplitude, and a significant short-term variability is evident. Both the migrating and non-migrating components exhibit notable variation with latitude. For example, the temperature and wind diurnal tides maximise at low latitudes and the semidiurnal tides include maxima at high latitudes. A comparison against published satellite and ground-based observations shows generally good agreement in latitudinal tidal structure, with more differences in seasonal tidal structure. Our results demonstrate the capability of the ExUM for modelling atmospheric migrating and non-migrating tides, and this lays the foundation for its future development into a whole atmosphere model. To this end, we make specific recommendations on further developments which would improve the capability of the model

Manipulating nanoscale structure to control functionality in printed organic photovoltaic, transistor and bioelectronic devices.

Printed electronics is simultaneously one of the most intensely studied emerging research areas in science and technology and one of the fastest growing commercial markets in the world today. For the past decade the potential for organic electronic (OE) materials to revolutionize this printed electronics space has been widely promoted. Such conviction in the potential of these carbon-based semiconducting materials arises from their ability to be dissolved in solution, and thus the exciting possibility of simply printing a range of multifunctional devices onto flexible substrates at high speeds for very low cost using standard roll-to-roll printing techniques. However, the transition from promising laboratory innovations to large scale prototypes requires precise control of nanoscale material and device structure across large areas during printing fabrication. Maintaining this nanoscale material control during printing presents a significant new challenge that demands the coupling of OE materials and devices with clever nanoscience fabrication approaches that are adapted to the limited thermodynamic levers available. In this review we present an update on the strategies and capabilities that are required in order to manipulate the nanoscale structure of large area printed organic photovoltaic (OPV), transistor and bioelectronics devices in order to control their device functionality. This discussion covers a range of efforts to manipulate the electroactive ink materials and their nanostructured assembly into devices, and also device processing strategies to tune the nanoscale material properties and assembly routes through printing fabrication. The review finishes by highlighting progress in printed OE devices that provide a feedback loop between laboratory nanoscience innovations and their feasibility in adapting to large scale printing fabrication. The ability to control material properties on the nanoscale whilst simultaneously printing functional devices on the square metre scale is prompting innovative developments in the targeted nanoscience required for OPV, transistor and biofunctional devices

Does Revlon Matter? A Empirical and Theoretical Study

We empirically examine whether and how the doctrine of enhanced judicial scrutiny that emerged from Revlon and its progeny actually affects M&A transactions. Combining hand-coding and machine-learning techniques, we assemble data from the proxy statements of publicly announced mergers between 2003 and 2017 into a dataset of 1,913 unique transactions. Of these, 1,167 transactions were subject to the Revlon standard, and 553 were not. After subjecting this sample to empirical analysis, our results show that Revlon does indeed matter for companies incorporated in Delaware. We find that in Delaware, Revlon deals are more intensely negotiated, involve more bidders, and result in higher transaction premiums than non-Revlon deals. However, these results do not hold for target companies incorporated in other jurisdictions that have adopted the Revlon doctrine. Our results shed light on the implications of the current state of uncertainty surrounding Revlon and provide some direction for courts going forward. We theorize that Revlon is a monitoring standard whose effectiveness depends upon the judiciary’s credible commitment to intervene in biased transactions. The precise contours of the doctrine are unimportant as long as the judiciary retains a substantive avenue for intervention. Recent Delaware decisions in C&J and Corwin have been criticized for overly restricting Revlon, but we suggest that such concerns are overstated so long as Delaware judges continue to monitor the substance of transactions. Thus, in applying these decisions, Delaware judges should focus not on procedural aspects but the substantive component of transactions, which Revlon initially sought to regulate

Hybridised multigrid preconditioners for a compatible finite element dynamical core

Compatible finite element discretisations for the atmospheric equations of motion have recently attracted considerable interest. Semi-implicit timestepping methods require the repeated solution of a large saddle-point system of linear equations. Preconditioning this system is challenging since the velocity mass matrix is non-diagonal, leading to a dense Schur complement. Hybridisable discretisations overcome this issue: weakly enforcing continuity of the velocity field with Lagrange multipliers leads to a sparse system of equations, which has a similar structure to the pressure Schur complement in traditional approaches. We describe how the hybridised sparse system can be preconditioned with a non-nested two-level preconditioner. To solve the coarse system, we use the multigrid pressure solver that is employed in the approximate Schur complement method previously proposed by the some of the authors. Our approach significantly reduces the number of solver iterations. The method shows excellent performance and scales to large numbers of cores in the Met Office next-generation climate- and weather prediction model LFRic.Comment: 24 pages, 13 figures, 5 tables; accepted for publication in Quarterly Journal of the Royal Meteorological Societ

Future Directions for Whole Atmosphere Modeling:Developments in the Context of Space Weather

Coupled Sun‐to‐Earth models represent a key part of the future development of space weather forecasting. With respect to predicting the state of the thermosphere and ionosphere, there has been a recent paradigm shift; it is now clear that any self‐respecting model of this region needs to include some representation of forcing from the lower atmosphere, as well as solar and geomagnetic forcing. Here we assess existing modeling capability and set out a roadmap for the important next steps needed to ensure further advances. These steps include a model verification strategy, analysis of the impact of non‐hydrostatic dynamical cores, and a cost‐benefit analysis of model chemistry for weather and climate applications

SciClone: Inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy

Structural basis for substrate specificity of the alpha-D-phosphohexomutase superfamily

Abstract only availablePhosphoacetylglucosamine mutase (PAGM) is a human enzyme that is the key to the formation of the essential metabolite UDP-N-acetylglucosamine. Bacterial phosphoglucomutase (PGM) from Acetobacter xylinum catalyzes the interconversion of glucose 1-phosphate and glucose 6-phosphate. PAGM and PGM are members of the alpha-D-phosphohexomutase superfamily which all catalyze intramolecular phosphoryl transfer on sugar substrates. These two analogs are similar in their mechanism, but dissimilar in their substrate specificity, not only to each other, but also to other well characterized (structurally and mechanistically) members of their superfamily. Protein expression and purification techniques were used to attempt to produce crystals to determine the three dimensional structures of human PAGM and bacterial PGM by X-ray diffraction in order to clarify the structural explanation for substrate specificity within the alpha-D-phosphohexomutase superfamily.Life Sciences Undergraduate Research Opportunity Progra

Using DNA Metabarcoding to Identify the Floral Composition of Honey:A New Tool for Investigating Honey Bee Foraging Preferences

Identifying the floral composition of honey provides a method for investigating the plants that honey bees visit. We compared melissopalynology, where pollen grains retrieved from honey are identified morphologically, with a DNA metabarcoding approach using the rbcL DNA barcode marker and 454-pyrosequencing. We compared nine honeys supplied by beekeepers in the UK. DNA metabarcoding and melissopalynology were able to detect the most abundant floral components of honey. There was 92% correspondence for the plant taxa that had an abundance of over 20%. However, the level of similarity when all taxa were compared was lower, ranging from 22–45%, and there was little correspondence between the relative abundance of taxa found using the two techniques. DNA metabarcoding provided much greater repeatability, with a 64% taxa match compared to 28% with melissopalynology. DNA metabarcoding has the advantage over melissopalynology in that it does not require a high level of taxonomic expertise, a greater sample size can be screened and it provides greater resolution for some plant families. However, it does not provide a quantitative approach and pollen present in low levels are less likely to be detected. We investigated the plants that were frequently used by honey bees by examining the results obtained from both techniques. Plants with a broad taxonomic range were detected, covering 46 families and 25 orders, but a relatively small number of plants were consistently seen across multiple honey samples. Frequently found herbaceous species were Rubus fruticosus, Filipendula ulmaria, Taraxacum officinale, Trifolium spp., Brassica spp. and the non-native, invasive, Impatiens glandulifera. Tree pollen was frequently seen belonging to Castanea sativa, Crataegus monogyna and species of Malus, Salix and Quercus. We conclude that although honey bees are considered to be supergeneralists in their foraging choices, there are certain key species or plant groups that are particularly important in the honey bees environment. The reasons for this require further investigation in order to better understand honey bee nutritional requirements. DNA metabarcoding can be easily and widely used to investigate floral visitation in honey bees and can be adapted for use with other insects. It provides a starting point for investigating how we can better provide for the insects that we rely upon for pollination

Personalized ctDNA micro-panels can monitor and predict clinical outcomes for patients with triple-negative breast cancer

Circulating tumor DNA (ctDNA) in peripheral blood has been used to predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, previous approaches typically use large comprehensive panels of genes commonly mutated across all breast cancers. Given the reduction in sequencing costs and decreased turnaround times associated with panel generation, the objective of this study was to assess the use of custom micro-panels for tracking disease and predicting clinical outcomes for patients with TNBC. Paired tumor-normal samples from patients with TNBC were obtained at diagnosis (T0) and whole exome sequencing (WES) was performed to identify somatic variants associated with individual tumors. Custom micro-panels of 4-6 variants were created for each individual enrolled in the study. Peripheral blood was obtained at baseline, during Cycle 1 Day 3, at time of surgery, and in 3-6 month intervals after surgery to assess variant allele fraction (VAF) at different timepoints during disease course. The VAF was compared to clinical outcomes to evaluate the ability of custom micro-panels to predict pathological response, disease-free intervals, and patient relapse. A cohort of 50 individuals were evaluated for up to 48 months post-diagnosis of TNBC. In total, there were 33 patients who did not achieve pathological complete response (pCR) and seven patients developed clinical relapse. For all patients who developed clinical relapse and had peripheral blood obtained ≤ 6 months prior to relapse (n = 4), the custom ctDNA micro-panels identified molecular relapse at an average of 4.3 months prior to clinical relapse. The custom ctDNA panel results were moderately associated with pCR such that during disease monitoring, only 11% of patients with pCR had a molecular relapse, whereas 47% of patients without pCR had a molecular relapse (Chi-Square; p-value = 0.10). In this study, we show that a custom micro-panel of 4-6 markers can be effectively used to predict outcomes and monitor remission for patients with TNBC. These custom micro-panels show high sensitivity for detecting molecular relapse in advance of clinical relapse. The use of these panels could improve patient outcomes through early detection of relapse with preemptive intervention prior to symptom onset