Computational Studies of Smell and Taste Receptors

Smell and taste are among the basic senses with which we perceive the world around us. In addition to enabling recognition of chemical moieties that provide social or nutritional clues, taste and smell receptors are expressed in many extraoral tissues, including the gastrointestinal, respiratory, and reproductive systems. It is, therefore, likely that taste and smell receptors have additional physiological roles, which are currently under intensive study. Most of the taste modalities, as well as olfaction, are mediated by G-protein coupled receptors (GPCRs). Recent breakthroughs in crystallography and signaling studies of GPCRs (celebrated by the 2012 Nobel Prize in Chemistry to Robert Lefkowitz and Brian Kobilka) provide excellent opportunities for applying this information towards furthering our understanding of taste and smell signaling. No crystal structures of odorant or taste receptors are currently available. However, computational techniques, many of which stem from the pioneering contributions of the 2013 Nobel Prize in Chemistry laureates, Martin Karplus, Michael Levitt, and Arieh Warshel, can shed light on the function of taste and olfactory GPCRs. In this review, we highlight examples of iterative combinations of simulation and experiment that were successfully applied toward delineating binding modes of tastants and odorants and toward predicting additional ligands. Further studies are required in order to answer remaining questions regarding receptor promiscuity versus selectivity, the details of receptor coupling to G-proteins, and the roles of oligomerization and of allosteric modulation in taste and smell transduction.     

Imperfect in-vehicle collision avoidance warning systems can aid drivers

An experiment was conducted to determine the effects of an in-vehicle collision avoidance warning system (IVCAWS) on driver performance. A driving simulator was driven by 135 licensed drivers. Of these, 120 received alerts from the IVCAWS when their headway to a lead car was less than 2 s, and the other 15 (the control group) received no alerts. Drivers received varied alert interfaces: auditory, visual, and multimodal. The system had varied levels of reliability, determined by both false alarm rate and failure of the IVCAWS to alert to short headway. Results indicated that the IVCAWS led to safer (longer) headway maintenance. High false alarm rates induced drivers to slow down unnecessarily; large numbers of missed alerts did not have any significant impact on drivers. Driver acceptance of the system was mixed. Interface played a role in driver reliance on the system, with the multimodal interfaces generating least reliance. Actual or potential applications of this research include IVCAWS interface selection for greater system efficacy and user acceptance and the advisability of implementation, even of imperfect systems, for drivers who seek to maintain a safer headway.     

Energy saving strategies for parallel applications with point-to-point communication phases

Although high-performance computing traditionally focuses on the efficient execution of large-scale applications, both energy and power have become critical concerns when approaching exascale. Drastic increases in the power consumption of supercomputers affect significantly their operating costs and failure rates. In modern microprocessor architectures, equipped with dynamic voltage and frequency scaling (DVFS) and CPU clock modulation (throttling), the power consumption may be controlled in software. Additionally, network interconnect, such as Infiniband, may be exploited to maximize energy savings while the application performance loss and frequency switching overheads must be carefully balanced. This paper advocates for a runtime assessment of such overheads by means of characterizing point-to-point communications into phases followed by analyzing the time gaps between the communication calls. Certain communication and architectural parameters are taken into consideration in the three proposed frequency scaling strategies, which differ with respect to their treatment of the time gaps. The experimental results are presented for NAS parallel benchmark problems as well as for the realistic parallel electronic structure calculations performed by the widely used quantum chemistry package GAMESS. For the latter, three different process-to-core mappings were studied as to their energy savings under the proposed frequency scaling strategies and under the existing state-of-the-art techniques. Close to the maximum energy savings were obtained with a low performance loss of 2% on the given platform.     

A single-molecule potentiometer

Controlling electron transport through a single-molecule device is key to the realization of nanoscale electronic components. A design requirement for single molecule electrical devices is that the molecule must be both structurally and electrically connected to the metallic electrodes. Typically, the mechanical and electrical contacts are achieved by the same chemical moiety. In this study, we demonstrate that the structural role may be played by one group (for example, a sulfide) while the electrical role may be played by another (a conjugated chain of C═C π-bonds). We can specify the electrical conductance through the molecule by modulating to which particular site on the oligoene chain the electrode binds. The result is a device that functions as a potentiometer at the single-molecule level.     

Catalytic upgrading of 4-methylaniosle as a representative of lignin-derived pyrolysis bio-oil: Process evaluation and optimization via coupled application of design of experiment and artificial neural networks

Catalytic upgrading of 4-methylanisole as a representative of lignin-derived pyrolysis bio-oil was investigated over Pt/γ-Al₂O₃ catalyst. The catalytic upgrading process was conducted at different operating condition to determine the detailed reactions network. Additionally, artificial neural network and design of experiment were applied by feeding the reaction temperature, operating pressure and space velocity to predict 4-methylanisole conversion, main products selectivity, reactions rate and reactions network. The main products of 4-methylanisole upgrading were toluene, phenol derivatives, cyclohexanone, 4-methylcyclohexanone, and 2-tert-butyl-4-methylphenol. The major classes of reactions during the upgrading process were hydrogenolysis, hydrodeoxygenation, alkylation, and hydrogenation. For optimization of experimental data obtained at suggested conditions by design of experiment, the response surface methodology was applied. Artificial neural network model was used to investigate the kinetics behavior of the system due to the complex nature of system. A combination of the response surface methodology, artificial neural network, and design of experiment has revealed its ability to solve a quadratic polynomial model. The coefficients of determination were close to 1, and the mean square error of the artificial neural network model was close to 0 which showed the high accuracy of model predictions. It was inferred that during the upgrading process of 4-methylanisole, increasing temperature and pressure and setting space velocity at the minimum value are the reasons to come close to the optimum reaction rate. The comparison of experimental results with simulated data from the artificial neural network and the response surface methodology models illustrated that the developed model can create an applicable situation for practical design of large-scale production of valuable fuels from renewable resources.     

Attachment, maternal sensitivity, and infant temperament during the first year of life.

Families were examined at 6, 9, and 12 months in an intensive longitudinal study that included Home Behavior Attachment Q-sorts, laboratory Strange Situation assessment, home observations of infant temperament behavior on 24 occasions, observations of maternal parenting sensitivity on 12 occasions, and maternal reports of infant temperament. Maternal sensitivity was modestly related to Q-sort security and unrelated to Strange Situation classification. In contrast, observed infant temperament was more strongly related to both maternal sensitivity and Q-sort security. The relation between home and laboratory assessment of attachment security, which was at the level found in prior work ( e.g., B. E. Vaughn & E. Waters, 1990 ), remained after the effects of observed and mother reported infant temperament were partialed. Our data highlight the need to consider other factors besides maternal sensitivity in the explanation of variability in the attachment status of l-year-olds. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hapten Design for Antibody-Catalyzed Decarboxylation and Ring-Opening Reactions of Benzisoxazoles

Three benzisoxazole haptens designed to elicit antibody binding sites with widely differing polarity have been synthesized and used to induce antibodies in mice. Monoclonal antibodies were prepared using hybridoma technology, and screened for catalysis of the ring-opening isomerization and/or decarboxylation of a series of related benzisoxazoles and their 3-carboxy-derivatives. No catalysis of decarboxylation was observed, but 4 of a total of 47 antibodies obtained against the three haptens catalyzed the isomerization process. Of 12 antibodies raised against the 3-acetylbenzisoxazole structure 5 none was catalytically active; but one of 24 raised against a 3-isopropenylbenzisoxazole 6 increased the rate of ring-opening of 6-nitrobenzisoxazole, and 5 of 11 antibodies raised against a benzisoxazole 7 with a 3-amidinium group were moderately active against either 6-nitro or 6-acylaminobenzisoxazoles. Competitive binding studies suggest that at least some of the antibodies induced by the isopropenyl hapten do possess a recognizably hydrophobic binding site.     

Bordeaux-R interactions with surfactants: thermochromic investigations of proton ionisation in cationic, nonionic and anionic surfactant solutions

Apparent thermodynamic parameters for the hydroxy proton ionisation of Bordeaux-R were obtained in micellar solutions using the thermochromic method. The effect of addition of the surfactants CTAB, TX-100 and SDS was investigated in buffered solutions in the pH range of 6–13. Ionisation constants in water and in the presence of surfactants were determined spectrophotometrically and the p K ' of Bordeaux-R in water was found to be 10.90 in the absence of surfactant. However, at concentrations above critical micelle concentration, p K ' dropped to 10.14 with CTAB, increased to 11.29 with TX-100 but was insensitive to SDS addition. Standard enthalpies and entropies of ionisation were obtained using the thermochromic method. This method, in conjunction with p K and spectral measurements and comparison with different azo dyes, has been shown to provide detailed information on the mechanism of dye–surfactant interaction.     

偶然荷载结构抗连续倒塌的设计方法

对于结构抗连续倒塌的设计研究,国外的设计规范中相继作了相关的抗倒塌要求规定,但是这些规范给出的只是概念性的要求,没有可操作可实施的设计方法,国内的设计规范此方面的研究还是空白。因此目前结构设计难以实现抗连续倒塌的性能设计。本文采用静力非线性有限元倒塌分析法,进行连续倒塌计算分析,提出与中国设计规范背景相适宜的、具有可操作性的抗连续倒塌设计方法。     

Stacking sequence optimization for constant stiffness laminates based on a continuous optimization approach

In this paper, an optimization procedure based on multi-phase topology optimization is developed to determine the optimal stacking sequence of laminates made up of conventional plies oriented at ?45°, 0°, 45 and 90°. The formulation relies on the SFP (Shape Functions with Penalization) parameterization, in which the discrete optimization problem is replaced by a continuous approach with a penalty to exclude intermediate values of the design variables. In this approach, the material stiffness of each physical ply is expressed as a weighted sum over the stiffness of the candidate plies corresponding to ?45°, 0°, 45 and 90° orientations. In SFP, two design variables are needed for each physical ply in the laminate to parameterize the problem with respect to the 4 candidate orientations. Even if only constant stiffness laminates of constant thickness are considered in this paper, specific design rules used in aeronautics for composite panels (i.e., no more than a maximum number of consecutive plies with the same orientation in the stacking sequence) are however formulated and taken into account in the optimization problem. The methodology is demonstrated on an application. It is discussed how the different design rules can affect the solution.