Free fatty acid receptors:structural models and elucidation of ligand binding interactions

BACKGROUND: The free fatty acid receptors (FFAs), including FFA1 (orphan name: GPR40), FFA2 (GPR43) and FFA3 (GPR41) are G protein-coupled receptors (GPCRs) involved in energy and metabolic homeostasis. Understanding the structural basis of ligand binding at FFAs is an essential step toward designing potent and selective small molecule modulators.

RESULTS: We analyse earlier homology models of FFAs in light of the newly published FFA1 crystal structure co-crystallized with TAK-875, an ago-allosteric ligand, focusing on the architecture of the extracellular binding cavity and agonist-receptor interactions. The previous low-resolution homology models of FFAs were helpful in highlighting the location of the ligand binding site and the key residues for ligand anchoring. However, homology models were not accurate in establishing the nature of all ligand-receptor contacts and the precise ligand-binding mode. From analysis of structural models and mutagenesis, it appears that the position of helices 3, 4 and 5 is crucial in ligand docking. The FFA1-based homology models of FFA2 and FFA3 were constructed and used to compare the FFA subtypes. From docking studies we propose an alternative binding mode for orthosteric agonists at FFA1 and FFA2, involving the interhelical space between helices 4 and 5. This binding mode can explain mutagenesis results for residues at positions 4.56 and 5.42. The novel FFAs structural models highlight higher aromaticity of the FFA2 binding cavity and higher hydrophilicity of the FFA3 binding cavity. The role of the residues at the second extracellular loop used in mutagenesis is reanalysed. The third positively-charged residue in the binding cavity of FFAs, located in helix 2, is identified and predicted to coordinate allosteric modulators.

CONCLUSIONS: The novel structural models of FFAs provide information on specific modes of ligand binding at FFA subtypes and new suggestions for mutagenesis and ligand modification, guiding the development of novel orthosteric and allosteric chemical probes to validate the importance of FFAs in metabolic and inflammatory conditions. Using our FFA homology modelling experience, a strategy to model a GPCR, which is phylogenetically distant from GPCRs with the available crystal structures, is discussed.

Testing the channel-based model of duration perception

The channel-based model of duration perception postulates the existence of neural mechanisms that respond selectively to a narrow range of stimulus durations centred on their preferred duration (Heron et al Proceedings of the Royal Society B 279 690–698). In principle the channel-based model could
explain recent reports of adaptation-induced, visual duration compression effects (Johnston et al Current Biology 16 472–479; Curran and Benton Cognition 122 252–257); from this perspective duration compression is a consequence of the adapting stimuli being presented for a longer duration than the test stimuli. In the current experiment observers adapted to a sequence of moving random dot patterns at the same retinal position, each 340ms in duration and separated by a variable (500–1000ms) interval. Following adaptation observers judged the duration of a 600ms test stimulus at the same location. The test stimulus moved in the same, or opposite, direction as the adaptor. Contrary to the channel-based
model’s prediction, test stimulus duration appeared compressed, rather than expanded, when it moved in the same direction as the adaptor. That test stimulus duration was not distorted when moving in the opposite direction further suggests that visual timing mechanisms are influenced by additional neural processing associated with the stimulus being timed.

HOTVal Toolkit

**************************************************************************** Scroll down to "Additional Files" to access the HOTVal Toolkit. **************************************************************************** HOTVal is a hotel valuation spreadsheet based on a regression model discussed in the Center for Real Estate and Finance at Cornell called Cornell Hotel Indices: Second Quarter 2012: The Trend is Our Friend by Crocker H. Liu, Adam D. Nowak, and Robert M. White, Jr. The model which will be continually updated, provides a rough estimation of the value of a hotel property once the user inputs information on whether the hotel is a large or small hotel, the year and quarter of the valuation, the state where the property is located, the number of rooms, the number of floors, the land area of the hotel property, the actual age of the hotel and whether the hotel is located in a Gateway city. For the first three inputs as well as the last input, if the user clicks on a cell highlighted in yellow, a pull down menu will appear to expedite inputting. The model is provided as a free public service by The Center for Real Estate and Finance at the School of Hotel Administration at Cornell University to academics and practitioners on an as-is, best-effort basis with no warranties or claims regarding its usefulness or implications. The estimates should be considered preliminary and subject to revision. *This October 2016 version updates the previous Hotel Valuation model, published in 2012 , provides valuation estimates up to and including the third quarter of 2016.

Custo histórico versus justo valor

Oriêntador: Mestre Carlos Pedro

A Multiple Criteria Utility-based Approa h for the Unit Commitment with Wind Power and Pumped Storage Hydro

The integration of wind power in eletricity generation brings new challenges to unit commitment due to the random nature of wind speed. For this particular optimisation problem, wind uncertainty has been handled in practice by means of conservative stochastic scenario-based optimisation models, or through additional operating reserve settings. However, generation companies may have different attitudes towards operating costs, load curtailment, or waste of wind energy, when considering the risk caused by wind power variability. Therefore, alternative and possibly more adequate approaches should be explored. This work is divided in two main parts. Firstly we survey the main formulations presented in the literature for the integration of wind power in the unit commitment problem (UCP) and present an alternative model for the wind-thermal unit commitment. We make use of the utility theory concepts to develop a multi-criteria stochastic model. The objectives considered are the minimisation of costs, load curtailment and waste of wind energy. Those are represented by individual utility functions and aggregated in a single additive utility function. This last function is adequately linearised leading to a mixed-integer linear program (MILP) model that can be tackled by general-purpose solvers in order to find the most preferred solution. In the second part we discuss the integration of pumped-storage hydro (PSH) units in the UCP with large wind penetration. Those units can provide extra flexibility by using wind energy to pump and store water in the form of potential energy that can be generated after during peak load periods. PSH units are added to the first model, yielding a MILP model with wind-hydro-thermal coordination. Results showed that the proposed methodology is able to reflect the risk profiles of decision makers for both models. By including PSH units, the results are significantly improved.

Example Based Image Analysis and Synthesis

Image analysis and graphics synthesis can be achieved with learning techniques using directly image examples without physically-based, 3D models. In our technique: -- the mapping from novel images to a vector of "pose" and "expression" parameters can be learned from a small set of example images using a function approximation technique that we call an analysis network; -- the inverse mapping from input "pose" and "expression" parameters to output images can be synthesized from a small set of example images and used to produce new images using a similar synthesis network. The techniques described here have several applications in computer graphics, special effects, interactive multimedia and very low bandwidth teleconferencing.

Space physics for graduate students: an activities-based approach

The geospace environment is controlled largely by events on the Sun, such as solar flares and coronal mass ejections, which generate significant geomagnetic and upper atmospheric disturbances. The study of this Sun-Earth system, which has become known as space weather, has both intrinsic scientific interest and practical applications. Adverse conditions in space can damage satellites and disrupt communications, navigation, and electric power grids, as well as endanger astronauts. The Center for Integrated Space Weather Modeling (CISM), a Science and Technology Center (STC) funded by the U.S. National Science Foundation (see http://www.bu.edu/cism/), is developing a suite of integrated physics-based computer models that describe the space environment from the Sun to the Earth for use in both research and operations [Hughes and Hudson, 2004, p. 1241]. To further this mission, advanced education and training programs sponsored by CISM encourage students to view space weather as a system that encompasses the Sun, the solar wind, the magnetosphere, and the ionosphere/thermosphere. This holds especially true for participants in the CISM space weather summer school [Simpson, 2004].

Comparing tube models for predicting the linear rheology of branched polymer melts

The hierarchical and "bob" (or branch-on-branch) models are tube-based computational models recently developed for predicting the linear rheology of general mixtures of polydisperse branched polymers. These two models are based on a similar tube-theory framework but differ in their numerical implementation and details of relaxation mechanisms. We present a detailed overview of the similarities and differences of these models and examine the effects of these differences on the predictions of the linear viscoelastic properties of a set of representative branched polymer samples in order to give a general picture of the performance of these models. Our analysis confirms that the hierarchical and bob models quantitatively predict the linear rheology of a wide range of branched polymer melts but also indicate that there is still no unique solution to cover all types of branched polymers without case-by-case adjustment of parameters such as the dilution exponent alpha and the factor p(2) which defines the hopping distance of a branch point relative to the tube diameter. An updated version of the hierarchical model, which shows improved computational efficiency and refined relaxation mechanisms, is introduced and used in these analyses.

B-spline neural network based digital baseband predistorter solution using the inverse of De Boor algorithm

In this paper a new nonlinear digital baseband predistorter design is introduced based on direct learning, together with a new Wiener system modeling approach for the high power amplifiers (HPA) based on the B-spline neural network. The contribution is twofold. Firstly, by assuming that the nonlinearity in the HPA is mainly dependent on the input signal amplitude the complex valued nonlinear static function is represented by two real valued B-spline neural networks, one for the amplitude distortion and another for the phase shift. The Gauss-Newton algorithm is applied for the parameter estimation, in which the De Boor recursion is employed to calculate both the B-spline curve and the first order derivatives. Secondly, we derive the predistorter algorithm calculating the inverse of the complex valued nonlinear static function according to B-spline neural network based Wiener models. The inverse of the amplitude and phase shift distortion are then computed and compensated using the identified phase shift model. Numerical examples have been employed to demonstrate the efficacy of the proposed approaches.

A 27 day persistence model of near-Earth solar wind conditions: a long lead-time forecast and a benchmark for dynamical models

Geomagnetic activity has long been known to exhibit approximately 27 day periodicity, resulting from solar wind structures repeating each solar rotation. Thus a very simple near-Earth solar wind forecast is 27 day persistence, wherein the near-Earth solar wind conditions today are assumed to be identical to those 27 days previously. Effective use of such a persistence model as a forecast tool, however, requires the performance and uncertainty to be fully characterized. The first half of this study determines which solar wind parameters can be reliably forecast by persistence and how the forecast skill varies with the solar cycle. The second half of the study shows how persistence can provide a useful benchmark for more sophisticated forecast schemes, namely physics-based numerical models. Point-by-point assessment methods, such as correlation and mean-square error, find persistence skill comparable to numerical models during solar minimum, despite the 27 day lead time of persistence forecasts, versus 2–5 days for numerical schemes. At solar maximum, however, the dynamic nature of the corona means 27 day persistence is no longer a good approximation and skill scores suggest persistence is out-performed by numerical models for almost all solar wind parameters. But point-by-point assessment techniques are not always a reliable indicator of usefulness as a forecast tool. An event-based assessment method, which focusses key solar wind structures, finds persistence to be the most valuable forecast throughout the solar cycle. This reiterates the fact that the means of assessing the “best” forecast model must be specifically tailored to its intended use.

Models of human behaviour in social-ecological systems

Environmental change research often relies on simplistic, static models of human behaviour in social-ecological systems. This limits understanding of how social-ecological change occurs. Integrative, process-based behavioural models, which include feedbacks between action, and social and ecological system structures and dynamics, can inform dynamic policy assessment in which decision making is internalised in the model. These models focus on dynamics rather than states. They stimulate new questions and foster interdisciplinarity between and within the natural and social sciences.

Ethics education in management accounting studies: evidence from business schools in Ghana

Management accounting in recent times, and perhaps rightly so, has begun to gain recognition as a profession separate and complimentary to financial accounting. Evidence exists to suggest that management accountants are exposed to a unique set of ethical challenges within industry and that a significant high number of management accountants have engaged in unethical practices in performing their jobs. For the accounting profession as a whole, the growing number of corporate failures has created a credibility crisis that requires a deliberate intervention to mitigate. If this is not addressed sooner, the accounting profession stands the risk of losing relevance. Scholarship on ethical issues in accounting practice have either focused mostly on financial accounting or have sought to combine ethical issues for financial and management accounting. Various arguments have been made in recent times of the need to treat ethical issues in behavioural studies as context-specific and therefore separate ethical considerations in management accounting from financial accounting. This study adopts an approach, following various literature, that effective ethics education can help practitioners deal appropriately with ethical issues at the work place, and explores students’ and faculty members’perceptions on current practices in ethics education. As expected, faculty and students differ significantly on a wide range of issues on ethics education in management accounting. Based on the insights provided from this study, appropriate recommendations have been made to improve ethics education in management accounting.

Accountants and valuations in Australian family court proceedings

This paper investigates issues related to the role of accountants in presenting expert evidence in the form of share valuations in Family Court of Australia proceedings. By providing a background to the valuation rules applied by the Family Court and examining relevant cases, the paper emphasises that considerable ambiguity exists. The paper highlights some of the inconsistencies that are evident from reported decisions and stresses the difficulties that judges have experienced with valuations presented by accountants in Family Court cases. It is evident that the courts, despite the legal precedents, continue to have considerable difficulty with valuation issues and methodologies. By exploring issues related to accounting based valuations in the context of Australian family law cases, the present paper examines accounting in a particular social and institutional setting. The paper is interdisciplinary in nature, in that issues extending over accounting, finance and legal boundaries are considered.

Simulation models of obesity : a review of the literature and implications for research and policy

Simulation models (SMs) combine information from a variety of sources to provide a useful tool for examining how the effects of obesity unfold over time and impact population health. SMs can aid in the understanding of the complex interaction of the drivers of diet and activity and their relation to health outcomes. As emphasized in a recently released report of the Institute or Medicine, SMs can be especially useful for considering the potential impact of an array of policies that will be required to tackle the obesity problem. The purpose of this paper is to present an overview of existing SMs for obesity. First, a background section introduces the different types of models, explains how models are constructed, shows the utility of SMs and discusses their strengths and weaknesses. Using these typologies, we then briefly review extant obesity SMs. We categorize these models according to their focus: health and economic outcomes, trends in obesity as a function of past trends, physiologically based behavioural models, environmental contributors to obesity and policy interventions. Finally, we suggest directions for future research.

Historical antecedents shaping corporate reporting in Iran

This research paper examines the evolution of corporate reporting and governance in Iran over the last century. The approach adopted was to provide an historical perspective to examine the environment within which Iranian corporate reporting has emerged and been shaped. An historical framework allows the study to focus on the evolution and development of corporate reporting practice in Iran. By adopting an historical framework, this study is able to inform future research based on models that adopt an evolutionary approach to the assessment of environmental factors on economic systems. The conclusion reached in this study is that socio-economic and political changes during the century have been opportune as drivers of corporate reporting in Iran. The study makes an incremental contribution to the existing accounting history literature for Asia / Middle East / developing countries.