Molecular Similarity and Xenobiotic Metabolism

MetaPrint2D, a new software tool implementing a data-mining approach for predicting sites of xenobiotic metabolism has been developed. The algorithm is based on a statistical analysis of the occurrences of atom centred circular fingerprints in both substrates and metabolites. This approach has undergone extensive evaluation and been shown to be of comparable accuracy to current best-in-class tools, but is able to make much faster predictions, for the first time enabling chemists to explore the effects of structural modifications on a compound’s metabolism in a highly responsive and interactive manner.MetaPrint2D is able to assign a confidence score to the predictions it generates, based on the availability of relevant data and the degree to which a compound is modelled by the algorithm.In the course of the evaluation of MetaPrint2D a novel metric for assessing the performance of site of metabolism predictions has been introduced. This overcomes the bias introduced by molecule size and the number of sites of metabolism inherent to the most commonly reported metrics used to evaluate site of metabolism predictions.This data mining approach to site of metabolism prediction has been augmented by a set of reaction type definitions to produce MetaPrint2D-React, enabling prediction of the types of transformations a compound is likely to undergo and the metabolites that are formed. This approach has been evaluated against both historical data and metabolic schemes reported in a number of recently published studies. Results suggest that the ability of this method to predict metabolic transformations is highly dependent on the relevance of the training set data to the query compounds.MetaPrint2D has been released as an open source software library, and both MetaPrint2D and MetaPrint2D-React are available for chemists to use through the Unilever Centre for Molecular Science Informatics website.----Boehringer-Ingelhie

Preliminary Fairbanks Bee Pollinator Protection Plan

Master's Project (M.S.) University of Alaska Fairbanks, 2020Global declines in pollinator species have been documented in several studies across the United States, Canada, and Europe. Honeybees, bumble bees and Monarch butterflies have been hit particularly hard in the US. This Preliminary Fairbanks Bee Pollinator Protection Plan recommends ways to increase public awareness of the problems facing bees and other pollinators, methods to increase and protect pollinator habitat and steps to take to reduce the use of pesticides. The plan also includes a list of native and nonnative plants that grow well in the Fairbanks area and that are attractive to insect pollinators. Planting these species can greatly increase the local habitat for pollinators. In developing the plan, I evaluated 12 pollinator plans from other areas, learned about local pollinators and their habitat requirements, and surveyed local beekeepers. To create the goals, objectives and actions included in this plan, I combined ideas from each of these three sources plus ideas of my own. The plan is not intended to be implemented by any one individual or agency. Instead, the plan can be used by anyone interested in improving pollinator habitat. If you have a backyard, access to a community garden, or just a few pots or a windowsill, you can create pollinator habitat. In addition to individuals, there are many businesses, government agencies, non-profits and other organizations that may be interested in taking steps listed in the plan to benefit bees and other pollinators

Evaluating the Impact of Grafting on Local Tomato Production in Nebraska

Grafting has been successfully used in vegetable production for tomatoes, peppers, eggplants, cucumbers, and watermelon. Besides its usefulness for managing soil-borne diseases, grafting can improve nutrient uptake and yield. However, few studies have assessed the effects of grafting and soil fertility management on yield of open field-grown tomatoes in the Midwest. Therefore, the objective of this two-year research was to better document the effects of grafting heirloom and hybrid tomato cultivar onto hybrid tomato rootstocks on tomato yield and quality. The field experiments were located at the University of Nebraska Lincoln - East Campus in Lincoln, West Central Research and Extension Center in North Platte, and a farm trial at Perkarek’s Vegetable Farm near Dwight, Nebraska. Two determinant fresh market tomatoes, ‘Nebraska Wedding’ and ‘BHN-589’, were grafted onto two rootstocks, ‘Estamino’ and ‘Maxifort,’ with the non-grafted determinant market tomatoes as a control. During the second year of this study, fertilizer treatment was introduced with two N rates (0% and 100%). At the end of the growing season, ripe tomatoes were harvested on a weekly basis, and yield was determined by weighing all tomatoes from the five plants in each experimental unit. Overall, there was no consistent improvement in total yield for any of the grafting treatments, and the estimated total mean yield of BHN-589 was at least 50% more than Nebraska Wedding. Moreover, there was no interaction effect between grafting and fertilizing treatment within each location. Results from this study suggest the need for more assessment on the effect of tomato grafting under different environmental conditions

Superconducting Films for Absorber-Coupled MKID Detectors for Sub-Millimeter and Far-Infrared Astronomy

We describe measurements of the properties, at dc, gigahertz, and terahertz frequencies, of thin (10 nm) aluminum films with 10 ohm/{rm square}$ normal state sheet resistance. Such films can be applied to construct microwave kinetic inductance detector arrays for submillimeter and far-infrared astronomical applications in which incident power excites quasiparticles directly in a superconducting resonator that is configured to present a matched-impedance to the high frequency radiation being detected. For films 10 nm thick, we report normal state sheet resistance, resistance-temperature curves for the superconducting transition, quality factor and kinetic inductance fraction for microwave resonators made from patterned films, and terahertz measurements of sheet impedance measured with a Fourier Transform Spectrometer. We compare properties with similar resonators made from niobium 600 nm thick

Oral Medication for Agitation of Psychiatric Origin: A Scoping Review of Randomized Controlled Trials

© 2017 Elsevier Inc. Background Understanding more about the efficacy and safety of oral second-generation antipsychotic medications in reducing the symptoms of acute agitation could improve the treatment of psychiatric emergencies. Objective The objective of this scoping review was to examine the evidence base underlying expert consensus panel recommendations for the use of oral second-generation antipsychotics to treat acute agitation in mentally ill patients. Methods The Cochrane Schizophrenia Group's Study-Based Register was searched for randomized controlled trials comparing oral second-generation antipsychotics, benzodiazepines, or first-generation antipsychotics with or without adjunctive benzodiazepines, irrespective of route of administration of the drug being compared. Six articles were included in the final review. Results Two oral second-generation antipsychotic medications were studied across the six included trials. While the studies had relatively small sample sizes, oral second-generation antipsychotics were similarly effective to intramuscular first-generation antipsychotics in treating symptoms of acute agitation and had similar side-effect profiles. Conclusions This scoping review identified six randomized trials investigating the use of oral second-generation antipsychotic medications in the reduction of acute agitation among patients experiencing psychiatric emergencies. Further research will be necessary to make clinical recommendations due to the overall dearth of randomized trials, as well as the small sample sizes of the included studies

1/N Effects in Non-Relativistic Gauge-Gravity Duality

We argue that higher-curvature terms in the gravitational Lagrangian lead, via non-relativistic gauge-gravity duality, to finite renormalization of the dynamical exponent of the dual conformal field theory. Our argument includes a proof of the non-renormalization of the Schrodinger and Lifshitz metrics beyond rescalings of their parameters, directly generalizing the AdS case. We use this effect to construct string-theory duals of non-relativistic critical systems with non-integer dynamical exponents, then use these duals to predict the viscosity/entropy ratios of these systems. The predicted values weakly violate the KSS bound.Comment: 26 pages, late

Renormalization-Scheme Dependence of Pade Summation in QCD

We study the renormalization-scheme (RS) dependence of Pade Approximants (PA's), and compare them with the Principle of Minimal Sensitivity (PMS) and the Effective Charge (ECH) approaches. Although the formulae provided by the PA, PMS and ECH predictions for higher-order terms in a QCD perturbation expansion differ in general, their predictions can be very close numerically for a wide range of renormalization schemes. Using the Bjorken sum rule as a test case, we find that Pade Summation (PS) reduces drastically the RS dependence of the Bjorken effective charge. We use these results to estimate the theoretical error due to the choice of RS in the extraction of $\alpha_s$ from the Bjorken sum rule, and use the available data at $Q^2=3 GeV^2$ to estimate $\alpha_s(M_Z) = 0.117^{+0.004}_{-0.007} \pm 0.002$, where the first error is experimental, and the second is theoretical.Comment: 12 pages (latex), including 6 embedded figures; uses epsfig.st

Celtic censure: representing Wales in eighteenth-century Germany

Drawing on Pierre Bourdieu's notion of regionalist discourse as the performative legitimation of specific frontiers, this article examines how the English traveller Samuel Jackson Pratt mediated a picture of the Welsh to late eighteenth-century readers in his Gleanings Through Wales, Holland and Westphalia (1795). This process of mediation was further complicated by the translation of this work into German as the Aehrenlese auf einer Reise durch Wallis, which appeared with the Leipzig publisher Lincke in 1798. While this work made an important contribution to German Celtophilia in the Romantic period, the German translator was careful to omit its more Sternean passages, in favour of factual narrative. Pratt's account of his travel through Wales, mediated in turn to a German audience through its Leipzig translator, therefore embodies several layers of cultural transfer that generate a complex and multifaceted image of Wales at the close of the eighteenth century

A new 500 kb haplotype associated with high CD8+ T-lymphocyte numbers predicts a less severe expression of hereditary hemochromatosis

<p>Abstract</p> <p>Background</p> <p>Hereditary Hemochromatosis(HH) is a common genetic disorder of iron overload where the large majority of patients are homozygous for one ancestral mutation in the <it>HFE </it>gene. In spite of this remarkable genetic homogeneity, the condition is clinically heterogeneous, varying from a severe disease to an asymptomatic phenotype with only abnormal biochemical parameters. The recent recognition of the variable penetrance of the HH mutation in different large population studies demands the need to search for new modifiers of its phenotypic expression. The present study follows previous observations that MHC class-I linked genetic markers, associated with the setting of CD8+ T-lymphocyte numbers, could be clinically relevant modifiers of the phenotypic expression in HH, and aimed to find new markers that could be used as more reliable prognostic variables.</p> <p>Methods</p> <p>Haplotype analysis, including seven genetic markers within a 1 Mb region around the microsatellite D6S105 was performed in a group of 56 previously characterized C282Y homozygous Portuguese patients. Parameters analyzed in this study were total body iron stores, clinical manifestations related with HH and immunological parameters (total lymphocyte numbers, CD4+ and CD8+ T-lymphocyte numbers). An independent group of 10 C282Y homozygous patients from Vancouver, Canada, were also included in this study and analyzed for the same parameters.</p> <p>Results</p> <p>A highly conserved ancestral haplotype defined by the SNP markers PGBD1-A, ZNF193-A, ZNF165-T (designated as A-A-T) was found associated with both abnormally low CD8+ T-lymphocyte numbers and the development of a severe clinical expression of HH. In a small proportion of patients, another conserved haplotype defined by the SNP markers PGBD1-G, ZNF193-G, ZNF165-G (designated as G-G-G) was found associated with high CD8+ T-lymphocyte numbers and a milder clinical expression. Remarkably, the two conserved haplotypes defined in Portuguese patients were also observed in the geographically different population of Canadian patients, also predicting CD8+ T-lymphocyte numbers and the severity of disease.</p> <p>Conclusion</p> <p>These results may have important implications not only for approaching the question of the penetrance of the hemochromatosis gene in different world populations but also to further narrow the region of interest to find a candidate gene involved in the setting of CD8+ T-lymphocyte numbers in humans.</p

Synthetic routes, characterization and photophysical properties of luminescent, surface functionalized nanodiamonds

The functionalization of small diameter (ca. 50 nm) polycarboxylated nanodiamond particles using amide coupling methodologies in both water and acetonitrile solvent has been investigated. In this manner, the surfaces of nanodiamond particles were adorned with different luminescent moieties, including a green fluorescent 1,8-naphthalimide species (Nap-1), and a red emitting ruthenium(II) tris-bipyridine complex (Ru-1), as well as dual functionalization with both luminophores. Comprehensive characterization of the surface functionalized nanodiamonds has been achieved using a combination of dynamic light scattering, nanoparticle tracking analysis, transmission electron microscopy, X-ray photoelectron spectroscopy, zeta potential measurements, microwave plasma atomic emission spectroscopy and time-resolved photophysics. The tendency of the functionalized nanodiamonds to aggregate reflects the degree of surface substitution, yielding small aggregates with typical particle sizes ca. 150 nm. This is likely to be driven by the reduction of the zeta potential, concomitant with the conversion of surface charged carboxylate groups to neutral amide functions. The results show that luminescent nanodiamond materials can be synthesised with tuneable photophysical properties