High-order splitting methods for separable non-autonomous parabolic equations

We consider the numerical integration of non-autonomous separable parabolic equations using high order splitting methods with complex coefficients (methods with real coeffi- cients of order greater than two necessarily have negative coefficients). We propose to consider a class of methods that allows us to evaluate all time-dependent operators at real values of the time, leading to schemes which are stable and simple to implement. If the system can be considered as the perturbation of an exactly solvable problem and the flow of the dominant part is advanced using real coefficients, it is possible to build highly efficient methods for these problems. We show the performance of this class of methods on several numerical examples and present some new improved schemesThe authors thank the referees for their suggestions to improve the presentation of this work. The work of Sergio Blanes has been supported by Ministerio de Ciencia e Innovacion (Spain) under project MTM2010-18246-C03 and the Ministerio de Educacion, Cultura y Deporte, under Programa Nacional de Movilidad de Recursos Humanos del Plan Nacional de I-D+i 2008-2011 (PRX12/00547). The work of Muaz Seydaoglu has been supported by the Turkish Council of High Education through a grant for visiting the Instituto de Matematica Multidisciplinar at the Polytechnic University of Valencia where this work was carried out.Seydaoglu, M.; Blanes Zamora, S. (2014). High-order splitting methods for separable non-autonomous parabolic equations. Applied Numerical Mathematics. 84:22-32. https://doi.org/10.1016/j.apnum.2014.05.004S22328

Investigating patterns of straying and mixed stock exploitation of sea trout, Salmo trutta, in rivers sharing an estuary in south-west England

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.For effective management, information on the stock composition of a fishery is essential. Here, the utility of a resident trout, Salmon trutta L, microsatellite baseline to determine the origins of sea trout entering the rivers Tamar, Tavy and Lynher in south-west England is highlighted – all share a common estuary and have major runs of sea trout. There is a high degree of geographical structuring of the genetic variation in the baseline rivers. Testing with simulated and real data sets showed fish can be assigned to reporting group with a high degree of accuracy. Mixed stock analysis of >1000 sea trout showed that fish entering the Tamar and Tavy constituted mixed stocks. Significantly, in the Tamar, non-natal origin sea trout are restricted to the lower catchment. As well as providing insight into sea trout behaviour, this study also has important implications for the management of recreational rod and line fisheries.This research forms part of the Atlantic AquaticResource Conservation (AARC) project and was funded via the European Union 2007–2013 Atlantic Area Pro-gramme, an INTERREG III B initiat ive; additional funding for this project was provided by the Atlantic SalmonTrust

Multiple roles of GluN2B-containing NMDA receptors in synaptic plasticity in juvenile hippocampus

AbstractIn the CA1 area of the hippocampus N-methyl-d-aspartate receptors (NMDARs) mediate the induction of long-term depression (LTD), short-term potentiation (STP) and long-term potentiation (LTP). All of these forms of synaptic plasticity can be readily studied in juvenile hippocampal slices but the involvement of particular NMDAR subunits in the induction of these different forms of synaptic plasticity is currently unclear. Here, using NVP-AAM077, Ro 25-6981 and UBP145 to target GluN2A-, 2B- and 2D-containing NMDARs respectively, we show that GluN2B-containing NMDARs (GluN2B) are involved in the induction of LTD, STP and LTP in slices prepared from P14 rat hippocampus. A concentration of Ro (1 μM) that selectively blocks GluN2B-containing diheteromers is able to block LTD. It also inhibits a component of STP without affecting LTP. A higher concentration of Ro (10 μM), that also inhibits GluN2A/B triheteromers, blocks LTP. UBP145 selectively inhibits the Ro-sensitive component of STP whereas NVP inhibits LTP. These data are consistent with a role of GluN2B diheretomers in LTD, a role of both GluN2B- and GluN2D- containing NMDARs in STP and a role of GluN2A/B triheteromers in LTP.This article is part of the Special Issue entitled ‘Ionotropic glutamate receptors’

A novel de novo BRCA1 mutation in a Chinese woman with early onset breast cancer

Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. De novo mutations such as multiple exon deletion are rarely occurred in BRCA1 and BRCA2. During our mutation screening for BRCA1/2 genes to Chinese women with risk factors for hereditary breast/ovarian cancer, we identified a novel germline mutation, consisting of a deletion from exons 1 to 12 in BRCA1 gene, in a patient diagnosed with early onset triple negative breast cancer with no family history of cancer. None of her parents carried the mutation and molecular analysis showed that this novel de novo germline mutation resulted in down-regulation of BRCA1 gene expression

Dietary interventions for induction and maintenance of remission in inflammatory bowel disease

Background Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic mucosal inflammation, frequent hospitalizations, adverse health economics, and compromised quality of life. Diet has been hypothesised to influence IBD activity. Objectives To evaluate the efficacy and safety of dietary interventions on IBD outcomes. Search methods We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, Web of Science, Clinicaltrials.gov and the WHO ICTRP from inception to 31 January 2019. We also scanned reference lists of included studies, relevant reviews and guidelines. Selection criteria We included randomized controlled trials (RCTs) that compared the effects of dietary manipulations to other diets in participants with IBD. Studies that exclusively focused on enteral nutrition, oral nutrient supplementation, medical foods, probiotics, and parenteral nutrition were excluded. Data collection and analysis Two review authors independently performed study selection, extracted data and assessed bias using the risk of bias tool. We conducted meta‐analyses where possible using a random‐effects model and calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We assessed the certainty of evidence using GRADE. Main results The review included 18 RCTs with 1878 participants. The studies assessed different dietary interventions for active CD (six studies), inactive CD (seven studies), active UC (one study) and inactive UC (four studies). Dietary interventions involved either the consumption of low amounts or complete exclusion of one or more food groups known to trigger IBD symptoms. There was limited scope for data pooling as the interventions and control diets were diverse. The studies were mostly inadequately powered. Fourteen studies were rated as high risk of bias. The other studies were rated as unclear risk of bias. The effect of high fiber, low refined carbohydrates, low microparticle diet, low calcium diet, symptoms‐guided diet and highly restricted organic diet on clinical remission in active CD is uncertain. At 4 weeks, remission was induced in: 100% (4/4) of participants in the low refined carbohydrates diet group compared to 0% (0/3) of participants in the control group (RR 7.20, 95% CI 0.53 to 97.83; 7 participants; 1 study; very low certainty evidence). At 16 weeks, 44% (23/52) of participants in the low microparticle diet achieved clinical remission compared to 25% (13/51) of control‐group participants (RR 3.13, 95% CI 0.22 to 43.84; 103 participants; 2 studies; I² = 73%; very low certainty evidence). Fifty per cent (16/32) of participants in the symptoms‐guided diet group achieved clinical remission compared to 0% (0/19) of control group participants (RR 20.00, 95% CI 1.27 to 315.40; 51 participants ; 1 study; very low certainty evidence) (follow‐up unclear). At 24 weeks, 50% (4/8) of participants in the highly restricted organic diet achieved clinical remission compared to 50% (5/10) of participants in the control group (RR 1.00, 95% CI 0.39 to 2.53; 18 participants; 1 study; very low certainty evidence). At 16 weeks, 37% (16/43) participants following a low calcium diet achieved clinical remission compared to 30% (12/40) in the control group (RR 1.24, 95% CI 0.67 to 2.29; 83 participants; 1 study; very low certainty evidence). The effect of low refined carbohydrate diets, symptoms‐guided diets and low red processed meat diets on relapse in inactive CD is uncertain. At 12 to 24 months, 67% (176/264) of participants in low refined carbohydrate diet relapsed compared to 64% (193/303) in the control group (RR 1.04, 95% CI 0.87 to 1.25; 567 participants; 3 studies; I² = 35%; low certainty evidence). At 6 to 24 months, 48% (24/50) of participants in the symptoms‐guided diet group relapsed compared to 83% (40/48) participants in the control diet (RR 0.53, 95% CI 0.28 to 1.01; 98 participants ; 2 studies; I² = 54%; low certainty evidence). At 48 weeks, 66% (63/96) of participants in the low red and processed meat diet group relapsed compared to 63% (75/118) of the control group (RR 1.03, 95% CI 0.85 to 1.26; 214 participants; 1 study; low certainty evidence). At 12 months, 0% (0/16) of participants on an exclusion diet comprised of low disaccharides / grains / saturated fats / red and processed meat experienced clinical relapse compared to 26% (10/38) of participants on a control group (RR 0.11, 95% CI 0.01 to 1.76; 54 participants; 1 study; very low certainty evidence). The effect of a symptoms‐guided diet on clinical remission in active UC is uncertain. At six weeks, 36% (4/11) of symptoms‐guided diet participants achieved remission compared to 0% (0/10) of usual diet participants (RR 8.25, 95% CI 0.50 to 136.33; 21 participants; 1 study; very low certainty evidence). The effect of the Alberta‐based anti‐inflammatory diet, the Carrageenan‐free diet or milk‐free diet on relapse rates in inactive UC is uncertain. At 6 months, 36% (5/14) of participants in the Alberta‐based anti‐inflammatory diet group relapsed compared to 29% (4/14) of participants in the control group (RR 1.25, 95% CI 0.42 to 3.70; 28 participants; 1 study; very low certainty evidence). Thirty per cent (3/10) of participants following the carrageenan‐free diet for 12 months relapsed compared to 60% (3/5) of the participants in the control group (RR 0.50, 95% CI 0.15 to 1.64; 15 participants; 1 study; very low certainty evidence). At 12 months, 59% (23/39) of milk free diet participants relapsed compared to 68% (26/38) of control diet participants (RR 0.83, 95% CI 0.60 to 1.15; 77 participants; 2 studies; I² = 0%; low certainty evidence). None of the included studies reported on diet‐related adverse events

Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.

Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit in autism, intellectual disability, Lennox Gastaut and West Syndromes. Here, we investigated several such mutations using a near-complete, hybrid 3D model of the human NMDAR and studied their consequences with kinetic modelling and electrophysiology. The mutants revealed reductions in glutamate potency; increased receptor desensitisation; and ablation of voltage-dependent Mg block. In addition, we provide new views on Mg and NMDA channel blocker binding sites. We demonstrate that these mutants have significant impact on excitatory transmission in developing neurons, revealing profound changes that could underlie their associated neurological disorders. Of note, the NMDAR channel mutant GluN2B unusually allowed Mg permeation, whereas nearby N615I reduced Ca permeability. By identifying the binding site for an NMDAR antagonist that is used in the clinic to rescue gain-of-function phenotypes, we show that drug binding may be modified by some GluN2B disease-causing mutations

Gustatory Perception and Fat Body Energy Metabolism Are Jointly Affected by Vitellogenin and Juvenile Hormone in Honey Bees

Honey bees (Apis mellifera) provide a system for studying social and food-related behavior. A caste of workers performs age-related tasks: young bees (nurses) usually feed the brood and other adult bees inside the nest, while older bees (foragers) forage outside for pollen, a protein/lipid source, or nectar, a carbohydrate source. The workers' transition from nursing to foraging and their foraging preferences correlate with differences in gustatory perception, metabolic gene expression, and endocrine physiology including the endocrine factors vitellogenin (Vg) and juvenile hormone (JH). However, the understanding of connections among social behavior, energy metabolism, and endocrine factors is incomplete. We used RNA interference (RNAi) to perturb the gene network of Vg and JH to learn more about these connections through effects on gustation, gene transcripts, and physiology. The RNAi perturbation was achieved by single and double knockdown of the genes ultraspiracle (usp) and vg, which encode a putative JH receptor and Vg, respectively. The double knockdown enhanced gustatory perception and elevated hemolymph glucose, trehalose, and JH. We also observed transcriptional responses in insulin like peptide 1 (ilp1), the adipokinetic hormone receptor (AKHR), and cGMP-dependent protein kinase (PKG, or “foraging gene” Amfor). Our study demonstrates that the Vg–JH regulatory module controls changes in carbohydrate metabolism, but not lipid metabolism, when worker bees shift from nursing to foraging. The module is also placed upstream of ilp1, AKHR, and PKG for the first time. As insulin, adipokinetic hormone (AKH), and PKG pathways influence metabolism and gustation in many animals, we propose that honey bees have conserved pathways in carbohydrate metabolism and conserved connections between energy metabolism and gustatory perception. Thus, perhaps the bee can make general contributions to the understanding of food-related behavior and metabolic disorders

Pleistocene terrace deposition related to tectonically controlled surface uplift: an example of the Kyrenia Range lineament in the northern part of Cyprus

AbstractIn this study, we consider how surface uplift of a narrow mountain range has interacted with glacial-related sea-level cyclicity and climatic change to produce a series of marine and non-marine terrace systems. The terrace deposits of the Kyrenia Range record rapid surface uplift of a long-lived tectonic lineament during the early Pleistocene, followed by continued surface uplift at a reduced rate during mid-late Pleistocene. Six terrace depositional systems are distinguished and correlated along the northern and southern flanks of the range, termed K0 to K5. The oldest and highest (K0 terrace system) is present only within the central part of the range. The K2–K5 terrace systems formed later, at sequentially lower levels away from the range. The earliest stage of surface uplift (K0 terrace system) comprises lacustrine carbonates interbedded with mass-flow facies (early Pleistocene?). The subsequent terrace system (K1) is made up of colluvial conglomerate and aeolian dune facies on both flanks of the range. The later terrace systems (K2 to K5) each begin with a basal marine deposit, interpreted as a marine transgression. Deltaic conglomerates prograded during inferred global interglacial stages. Overlying aeolian dune facies represent marine regressions, probably related to global glacial stages. Each terrace depositional system was uplifted and preserved, followed by subsequent deposits at progressively lower topographic levels. Climatic variation during interglacial–glacial cycles and autocyclic processes also exerted an influence on deposition, particularly on short-period fluvial and aeolian deposition

Musicking with an interactive musical system: The effects of task motivation and user interface mode on non-musicians' creative engagement

Creative engagement with novel musical interfaces can be rewarding for non-musicians. However, designing novel musical interfaces for non-musicians can be challenging because they lack conceptual and technical musical skills. In this paper we explore the effects of task motivation (experiential goal vs utilitarian goal) and user interface mode (whether the content is editable, and whether content can be replayed), on non-musicians’ creative engagement with novel musical interfaces. We show through an empirical study of twenty-four parti- cipants that an experiential exploratory goal encourages users’ creative engagement compared to a utilitarian creative goal. We found that being able to replay records is less important when participants have an experiential exploratory goal than when they have a utilitarian creative goal. Results also indicate that allowing people to replay their musical ideas increased some aspects of their creative engagement which was further increased when they were able to edit their creations. We also found that creative engagement increased when the in- terface supported users in planning ahead. A descriptive model of non-musician’s creative engagement with musical interfaces is proposed including three modes of musicking. An optimal trajectory of creative engagement through these modes is suggested and a description of inferred motivations, output, status and activities during creative processes is discussed. Design implications are proposed for supporting novices’ creative engagement taking into consideration their motivation and skills, and supporting insight and real-time activity