Phosphorylation State-Dependent Regulation of SAPAP3 and mGluR5 Association

poster abstractThis study aims to characterize the interaction between SAP90/PSD-95-associated protein 3 (SAPAP3) and metabotropic Glutamate Receptor 5 (mGluR5); specifically focusing on how SAPAP3 phosphorylation state modulates association. SAPAP3 is a scaffolding protein localized to the postsynaptic density (PSD) of striatal neurons and SAPAP3 knockout mice have Obsessive-Compulsive Disorder-like symptoms. Here, we hypothesize that spinophilin modulates SAPAP3 phosphorylation and alterations in SAPAP3 phosphorylation regulate SAPAP3 binding to mGluR5. We will use in vitro and ex vivo studies to characterize the interaction between spinophilin and SAPAP3 and to determine the functional implications of SAPAP3 phosphorylation on mGluR5 binding. These data will enhance our understanding of molecular mechanisms that regulate SAPAP3 and mGluR5 function, two proteins with known roles in obsessive-compulsive disorder

Mineral resource information in support of national, regional and local planning : Gloucestershire (comprising Gloucestershire and South Gloucestershire)

This report is one of a series prepared by the British Geological Survey for various administrative areas in England for the Office of the Deputy Prime Minister’s research project Mineral Resource Information in Support of National, Regional and Local Planning. The accompanying map relates to the county of Gloucestershire, comprising Gloucestershire and South Gloucestershire, and delineates the mineral resources of current, or potential, economic interest in the area and the sites where minerals are or have been worked. It also relates these to national planning designations, which may represent constraints on the extraction of minerals. Three major elements of information are presented: • the geological distribution and importance of mineral resources; • the extent of mineral planning permissions and the location of current mineral workings; and • the extent of selected, nationally-designated planning constraints. This wide range of information, much of which is scattered and not always available in a consistent and convenient form, is presented on a digitally-generated summary map on the scale of 1:100 000. This scale is convenient for the overall display of the data and allows for a legible topographic base on which to depict the information. However, all the data are held digitally at larger scales using a Geographical Information System (GIS), which allows easy revision, updating and customisation of the information together with its possible integration with other datasets. The information will form part of a Summary of the Mineral Resources of the South West Region. The purpose of the work is to assist all interested parties involved in the preparation and review of development plans, both in relation to the extraction of minerals and the protection of mineral resources from sterilisation. It provides a knowledge base, in a consistent format, on the nature and extent of mineral resources and the environmental constraints, which may affect their extraction. An important objective is to provide baseline data for the long term. The results may also provide a starting point for discussions on specific planning proposals for mineral extraction or on proposals, which may sterilise resources. It is anticipated that the maps and report will also provide valuable background data for a much wider audience, including the different sectors of the minerals industry, other agencies and authorities (e.g. The Planning Inspectorate Agency, the Environment Agency, the Countryside Agency and English Nature), environmental interests and the general public. Basic mineral resource information is essential to support mineral exploration and development activities, for resource management and land-use planning, and to establish baseline data for environmental impact studies and environmental guidelines. It also enables a more sustainable pattern and standard of development to be achieved by valuing mineral resources as national assets. The mineral resources covered are sand and gravel, bedrock sand, crushed rock aggregate, building stone, hydrocarbons, and coal

Rational design of a polyurethane foam

Polyurethane (PU) foams are exceptionally versatile due to the nature of PU bond formation and the large variety of polymeric backbones and formulation components such as catalysts and surfactants. This versatility introduces a challenge, namely a near unlimited number of variables for formulating foams. In addition to this, PU foam development requires expert knowledge, not only in polyurethane chemistry but also in the art of evaluating the resulting foams. In this work, we demonstrate that a rational experimental design framework in conjunction with a design of experiments (DoE) approach reduces both the number of experiments required to understand the formulation space and reduces the need for tacit knowledge from a PU expert. We focus on an in-depth example where a catalyst and two surfactants of a known formulation are set as factors and foam physical properties are set as responses. An iterative DoE approach is used to generate a set of foams with substantially different cell morphology and hydrodynamic behaviour. We demonstrate that with 23 screening formulations and 16 final formulations, foam physical properties can be modelled from catalyst and surfactant loadings. This approach also allows for the exploration of relationships between the cell morphology of PU foam and its hydrodynamic behaviour

Mineral resource information in support of national, regional and local planning : Cheshire (comprising Cheshire, Boroughs of Halton and Warrington)

This report is one of a series prepared by the British Geological Survey for various administrative areas in England for the Office of the Deputy Prime Minister’s research project Mineral Resource Information in Support of National, Regional and Local Planning. The accompanying map relates to the county of Cheshire (comprising Cheshire, Boroughs of Halton and Warrington), and delineates the mineral resources of current, or potential, economic interest in the area and the sites where minerals are or have been worked. It also relates these to national planning designations, which may represent constraints on the extraction of minerals. Three major elements of information are presented: • the geological distribution and importance of mineral resources; • the extent of mineral planning permissions and the location of current mineral workings; and • the extent of selected, nationally-designated planning constraints. This wide range of information, much of which is scattered and not always available in a consistent and convenient form, is presented on a digitally-generated summary map on the scale of 1:100 000. This scale is convenient for the overall display of the data and allows for a legible topographic base on which to depict the information. However, all the data are held digitally at larger scales using a Geographical Information System (GIS), which allows easy revision, updating and customisation of the information together with its possible integration with other datasets. The information will form part of a Summary of the Mineral Resources of the North West Region. The purpose of the work is to assist all interested parties involved in the preparation and review of development plans, both in relation to the extraction of minerals and the protection of mineral resources from sterilisation. It provides a knowledge base, in a consistent format, on the nature and extent of mineral resources and the environmental constraints, which may affect their extraction. An important objective is to provide baseline data for the long term. The results may also provide a starting point for discussion on specific planning proposals for minerals extraction or on proposals, which may sterilise resources. It is anticipated that the map and report will also provide valuable background data for a much wider audience, including the different sectors of the minerals industry, other agencies and authorities (e.g. The Planning Inspectorate Agency, the Environment Agency, The Countryside Agency and English Nature), environmental interests and the general public. Basic mineral resource information is essential to support mineral exploration and development activities, for resource management and land-use planning, and to establish baseline data for environmental impact studies and environmental guidelines. It also enables a more sustainable pattern and standard of development to be achieved by valuing mineral resources as national assets. The mineral resources covered are sand and gravel, crushed rock aggregate, silica sand, salt, brick clay, building stones, peat, coal, hydrocarbons and metalliferous mineralisation

Gender differences in the prevalence of impaired fasting glycaemia and impaired glucose tolerance in Mauritius. Does sex matter?

Objective: To examine gender differences in the characteristics and prevalence of various categories of glucose tolerance in a population study in Mauritius.Research design and methods: In 1998, a community-based cross-sectional survey was conducted in Mauritius. Categories of glucose metabolism were determined in 5388 adults, with an oral glucose tolerance test given to those who did not have previously diagnosed diabetes (n = 4036). Other cardiovascular risk factors were assessed among those without known diabetes.Results: For men and women the prevalence of diabetes (22.0 vs. 21.8%, respectively) and the prevalence of coexisting impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (3.2 vs. 2.9%) were similar. However, men were twice as likely as women to have isolated IFG [5.1% (4.2&ndash;6.0) vs. 2.9% (2.3&ndash;3.5)], despite being younger, thinner and with lower plasma insulin but higher lipids. Conversely, the prevalence of isolated IGT was lower in men [9.0% (7.9&ndash;10.2) vs. 13.9% (12.6&ndash;15.1)]. Among non-diabetic individuals, fasting glucose was higher in men than women, whereas 2-h glucose was higher in women. In people without diabetes, women had significantly higher body mass index, beta cell function (HOMA-B), fasting and 2-h insulin than men and significantly lower waist-hip ratios, waist circumference, insulin sensitivity (HOMA-S) and triglycerides.Conclusion: In Mauritius, the distribution of impaired glucose metabolism differs by sex. The observation that IFG is more prevalent in men and IGT more prevalent in women raises important questions about their underlying aetiology and the ability of the current glucose thresholds to equally identify men and women at high-risk of developing diabetes. IFG should be seen as a complimentary category of abnormal glucose tolerance, rather than a replacement for IGT.<br /

Automatic recognition of child speech for robotic applications in noisy environments

Automatic speech recognition (ASR) allows a natural and intuitive interface for robotic educational applications for children. However there are a number of challenges to overcome to allow such an interface to operate robustly in realistic settings, including the intrinsic difficulties of recognising child speech and high levels of background noise often present in classrooms. As part of the EU EASEL project we have provided several contributions to address these challenges, implementing our own ASR module for use in robotics applications. We used the latest deep neural network algorithms which provide a leap in performance over the traditional GMM approach, and apply data augmentation methods to improve robustness to noise and speaker variation. We provide a close integration between the ASR module and the rest of the dialogue system, allowing the ASR to receive in real-time the language models relevant to the current section of the dialogue, greatly improving the accuracy. We integrated our ASR module into an interactive, multimodal system using a small humanoid robot to help children learn about exercise and energy. The system was installed at a public museum event as part of a research study where 320 children (aged 3 to 14) interacted with the robot, with our ASR achieving 90% accuracy for fluent and near-fluent speech

Multiple full-length NS3 molecules are required for optimal unwinding of oligonucleotide DNA in vitro

NS3 (nonstructural protein 3) from the hepatitis C virus is a 3′ → 5′ helicase classified in helicase superfamily 2. The optimally active form of this helicase remains uncertain. We have used unwinding assays in the presence of a protein trap to investigate the first cycle of unwinding by full-length NS3. When the enzyme was in excess of the substrate, NS3 (500 nM) unwound &gt;80% of a DNA substrate containing a 15-nucleotide overhang and a 30-bp duplex (45:30-mer; 1 nM). This result indicated that the active form of NS3 that was bound to the DNA prior to initiation of the reaction was capable of processive DNA unwinding. Unwinding with varying ratios of NS3 to 45:30-mer allowed us to investigate the active form of NS3 during the first unwinding cycle. When the substrate concentration slightly exceeded that of the enzyme, little or no unwinding was observed, indicating that if a monomeric form of the protein is active, then it exhibits very low processivity. Binding of NS3 to the 45:30-mer was measured by electrophoretic mobility shift assays, resulting in KD = 2.7 ± 0.4 nM. Binding to individual regions of the substrate was investigated by measuring the KD for a 15-mer oligonucleotide as well as a 30-mer duplex. NS3 bound tightly to the 15-mer (KD = 1.3 ± 0.2 nM) and, surprisingly, fairly tightly to the double-stranded 30-mer (KD = 11.3 ± 1.3 nM). However, NS3 was not able to rapidly unwind a blunt-end duplex. Thus, under conditions of optimal unwinding, the 45:30-mer is initially saturated with the enzyme, including the duplex region. The unwinding data are discussed in terms of a model whereby multiple molecules of NS3 bound to the single-stranded DNA portion of the substrate are required for optimal unwinding

Mineral resource information in support of national, regional and local planning : Devon (comprising Devon, Plymouth, Torbay, Dartmoor National Park and part of Exmoor National Park)

This report is one of a series prepared by the British Geological Survey for various administrative areas in England for the Office of the Deputy Prime Minister’s research project Mineral Resource Information in Support of National, Regional and Local Planning. The accompanying maps relate to the county of Devon and delineates the mineral resources of current, or potential, economic interest in the area and the sites where minerals are or have been worked. It also relates these to national planning designations, which may represent constraints on the extraction of minerals. Three major elements of information are presented: • the geological distribution and importance of mineral resources; • the extent of mineral planning permissions and the location of current mineral workings; and • the extent of selected, nationally-designated planning constraints. This wide range of information, much of which is scattered and not always available in a consistent and convenient form, is presented on two digitally-generated summary map on the scale of 1:100 000. This scale is convenient for the overall display of the data and allows for a legible topographic base on which to depict the information. However, all the data are held digitally at larger scales using a Geographical Information System (GIS), which allows easy revision, updating and customisation of the information together with its possible integration with other datasets. The information will form part of a Summary of the Mineral Resources of the South West Region. The purpose of the work is to assist all interested parties involved in the preparation and review of development plans, both in relation to the extraction of minerals and the protection of mineral resources from sterilisation. It provides a knowledge base, in a consistent format, on the nature and extent of mineral resources and the environmental constraints, which may affect their extraction. An important objective is to provide baseline data for the long term. The results may also provide a starting point for discussion on specific planning proposals for minerals extraction or on proposals, which may sterilise resources. It is anticipated that the map and report will also provide valuable background data for a much wider audience, including the different sectors of the minerals industry, other agencies and authorities (e.g. The Planning Inspectorate Agency, the Environment Agency, The Countryside Agency and English Nature), environmental interests and the general public. Basic mineral resource information is essential to support mineral exploration and development activities, for resource management and land-use planning, and to establish baseline data for environmental impact studies and environmental guidelines. It also enables a more sustainable pattern and standard of development to be achieved by valuing mineral resources as national assets. The mineral resources covered are sand and gravel, crushed rock aggregate, brick clay, kaolin, ball clay, building stones, hydrocarbons and metalliferous mineralisation

Effect of osteoarthritis on the repeatability of patella tendon angle measurement in dogs

Objective: To evaluate the influence of osteoarthritis on the measurement of patella tendon angle (PTA) and determine intraobserver and interobserver variability. Study design: Retrospective clinical study. Sample population: Eighty‐seven mediolateral radiographs that were obtained prior to tibial tuberosity advancement. Methods: Radiographic osteoarthritis was scored by 2 observers using guidelines derived from the International Elbow Working Group Protocol. Patella tendon angle was measured by 3 observers on 3 occasions, with at least 7 days between measurements. The data were statistically analyzed via weighted κ and Kruskal‐Wallis testing. Results: A fair strength of agreement was found among observers scoring osteoarthritis, with the same grades in 48% of radiographs. The intraobserver average bias between PTA measurements 1 and 3 ranged from −0.38° to −0.94°. Interobserver bias in angle measurement ranged from −0.92° to −2.00°. Observer 1 had the narrowest range of PTA differences (12.1°), and observer 3 had the highest range of PTA differences (23.5°). Observer 2 had the lowest mean bias (−0.38°). The mean bias was lowest between observers 1 and 2 (−0.92°) and highest between observers 1 and 3 (−2.0°). The mean intraobserver standard deviation of the PTA measurement differences was 2.90°, and interobserver standard deviation of the PTA measurement differences was 2.26°. The degree of osteoarthritis did not influence PTA measurements or their variability. Conclusion: The current study did not find evidence of an influence of osteoarthritis on PTA or on the repeatability of measurements. Clinical significance: Our findings suggest that osteoarthritis should not affect the radiographic planning for tibial tuberosity advancement surgery. The high variances in PTA measurement in less experienced observers may influence the clinical outcome of surgery