A hydrogen-bonded polar network in the core of the glucagon-like peptide-1 receptor is a fulcrum for biased agonism:lessons from class B crystal structuress

The glucagon-like peptide 1 (GLP-1) receptor is a class B G protein-coupled receptor (GPCR) that is a key target for treatments for type II diabetes and obesity. This receptor, like other class B GPCRs, displays biased agonism, though the physiologic significance of this is yet to be elucidated. Previous work has implicated R2.60190 , N3.43240 , Q7.49394 , and H6.52363 as key residues involved in peptide-mediated biased agonism, with R2.60190 , N3.43240 , and Q7.49394 predicted to form a polar interaction network. In this study, we used novel insight gained from recent crystal structures of the transmembrane domains of the glucagon and corticotropin releasing factor 1 (CRF1) receptors to develop improved models of the GLP-1 receptor that predict additional key molecular interactions with these amino acids. We have introduced E6.53364 A, N3.43240 Q, Q7.49493N, and N3.43240 Q/Q7.49 Q/Q7.49493N mutations to probe the role of predicted H-bonding and charge-charge interactions in driving cAMP, calcium, or extracellular signal-regulated kinase (ERK) signaling. A polar interaction between E6.53364 and R2.60190 was predicted to be important for GLP-1- and exendin-4-, but not oxyntomodulin-mediated cAMP formation and also ERK1/2 phosphorylation. In contrast, Q7.49394 , but not R2.60190 /E6.53364 was critical for calcium mobilization for all three peptides. Mutation of N3.43240 and Q7.49394 had differential effects on individual peptides, providing evidence for molecular differences in activation transition. Collectively, this work expands our understanding of peptide-mediated signaling from the GLP-1 receptor and the key role that the central polar network plays in these events.

Review on protection issues of low-voltage distribution network with multiple powerelectronic-converter-interfaced distribution energy resources

The realisation of an eventual low-voltage (LV) Smart Grid with a complete communication infrastructure is a gradual process. During this evolution the protection scheme of distribution networks should be continuously adapted and optimised to fit the protection and cost requirements at the time. This paper aims to review practices and research around the design of an effective, adaptive and economical distribution network protection scheme. The background of this topic is introduced and potential problems are defined from conventional protection theories and new Smart Grid technologies. Challenges are identified with possible solutions defined as a pathway to the ultimate flexible and reliable LV protection systems.

Semantic enabled sensor network design

Wireless Sensor Network (WSN) systems have become more and more popular in our modern life. They have been widely used in many areas, such as smart homes/buildings, context-aware devices, military applications, etc. Despite the increasing usage, there is a lack of formal description and automated verification for WSN system design. In this paper, we present an approach to support the rigorous verification of WSN modeling using the Semantic Web technology We use Web Ontology Language (OWL) and Semantic Web Rule Language (SWRL) to define a meta-ontology for the modeling of WSN systems. Furthermore, we apply ontology reasoners to perform automated verification on customized WSN models and their instances. We demonstrate and evaluate our approach through a Light Control System (LCS) as the case study.

A Bayesian neural network algorithm identifies patients in whom post-EVAR surveillance may be unnecessary

Lifelong surveillance is not cost-effective after endovascular aneurysm repair (EVAR), but is required to detect aortic complications which are fatal if untreated (type 1/3 endoleak, sac expansion, device migration). Aneurysm morphology determines the probability of aortic complications and therefore the need for surveillance, but existing analyses have proven incapable of identifying patients at sufficiently low risk to justify abandoning surveillance. This study aimed to improve the prediction of aortic complications, through the application of machine-learning techniques. Patients undergoing EVAR at 2 centres were studied from 2004–2010. Aneurysm morphology had previously been studied to derive the SGVI Score for predicting aortic complications. Bayesian Neural Networks were designed using the same data, to dichotomise patients into groups at low- or high-risk of aortic complications. Network training was performed only on patients treated at centre 1. External validation was performed by assessing network performance independently of network training, on patients treated at centre 2. Discrimination was assessed by Kaplan-Meier analysis to compare aortic complications in predicted low-risk versus predicted high-risk patients. 761 patients aged 75 +/− 7 years underwent EVAR in 2 centres. Mean follow-up was 36+/− 20 months. Neural networks were created incorporating neck angu- lation/length/diameter/volume; AAA diameter/area/volume/length/tortuosity; and common iliac tortuosity/diameter. A 19-feature network predicted aor- tic complications with excellent discrimination and external validation (5-year freedom from aortic complications in predicted low-risk vs predicted high-risk patients: 97.9% vs. 63%; p < 0.0001). A Bayesian Neural-Network algorithm can identify patients in whom it may be safe to abandon surveillance after EVAR. This proposal requires prospective study.

Making the organization fly:organizational identification and citizenship in full-service and low-cost airlines

Recently, the service industry has seen a low-cost sector emerge alongside the traditional full-service sector. We explored whether these business models have different implications for employee cooperation, one factor that plays an important role in organizational functioning. Drawing on the social identity perspective, we argue that employees will identify less strongly with the lower-status, low-cost organizations, reducing their intrinsic motivation for such cooperation. We tested these relationships among employees in Thailand's airline industry. In line with expectations, flight attendants working for low-cost airlines (N = 77) perceived their organizations to have lower status than those working for the full-service airlines (N = 77), and this was associated with reduced organizational identification. This in turn predicted lower levels of organizational citizenship behaviour and a stronger desire for organizational exit. © 2010 Hogrefe Publishing.

Analysis of purchasing activity with discounted cash flow inventory models = Beszerzési tevékenység elemzése diszkontált pénzáramlású készletmodellel

A klasszikus tételnagyság probléma két fontosabb készletezési költséget ragad meg: rendelési és készlettartási költségek. Ebben a dolgozatban a vállalatok készpénz áramlásának a beszerzési tevékenységre gyakorolt hatását vizsgáljuk. Ebben az elemzésben a készpénzáramlási egyenlőséget használjuk, amely nagyban emlékeztet a készletegyenletekre. Eljárásunkban a beszerzési és rendelési folyamatot diszkontálva vizsgáljuk. A költségfüggvény lineáris készpénztartási, a pénzkiadás haszonlehetőség és lineáris kamatköltségből áll. Bemutatjuk a vizsgált modell optimális megoldását. Az optimális megoldást egy számpéldával illusztráljuk. = The classical economic order quantity model has two types of costs: ordering and inventory holding costs. In this paper we try to investigate the effect of purchasing activity on cash flow of a firm. In the examinations we use a cash flow identity similar to that of in inventory modeling. In our approach we analyze the purchasing and ordering process with discounted costs. The cost function of the model consists of linear cash holding, linear opportunity cost of spending cash, and linear interest costs. We show the optimal solution of the proposed model. The optimal solutions will be presented by numerical examples.

The network structure of Hungarian business clusters

This article investigates the attitudes to inter-firm co-operation in Hungary by analysing a special group of business networks: the business clusters. Following an overview of cluster policy, a wide range of selfproclaimed business clusters are identified. A small elite of these business networks evolves into successful, sustainable innovative business clusters. However, in the majority of cases, these consortia of interfirm co-operation are not based on a mutually satisfactory model, and as a consequence, many clusters do not survive in the longer term. The paper uses the concepts and models of social network theory in order to explain, why and under what circumstances inter-firm co-operation in clusters enhances the competitiveness of the network as a whole, or alternatively, under what circumstances the cluster remains dependent on Government subsidies. The empirical basis of the study is a thorough internet research about the Hungarian cluster movement; a questionnaire based expert survey among managers of clusters and member companies and a set of in-depth interviews among managers of self-proclaimed clusters. The last chapter analyises the applicability of social network theory in the analysis of business networks and a model involving the value chain is recommended.

Költség- és időcsökkentési eljárások alkalmazása a projekttervezésben és a nyomon követésben = Application of cost and time reduction procedures in project planning and the follow-up

A válság okozta megszorítások a projektek költségvetését sem hagyták változatlanul. Nagyon sokszor nemcsak a jövőbeni projekttervek költségvetését kell átgondolni, hanem a már futó projektek költségvetését is újra kell szabni. E tanulmány ilyen esetekben nyújthat módszertani támogatást. A szerző ebben a kutatásban négy költség- és időcsökkentő módszert hasonlít össze. Ismerteti, hogy ezeket az eljárásokat milyen módon lehet ötvözni, illetve mikor, melyiket célszerű alkalmazni. Az eljárások között van olyan módszer, amely a hagyományos projektmenedzsment (pl. építési, beruházási projektek menedzselésének) eszköztárát gazdagítja, de találkozhatunk olyan eljárásokkal is, amelyek az agilis projektszemléleten alapuló módszerek körét szélesítik. A bemutatott módszerek nemcsak a hálótervezési, hanem a mátrixos projekttervezési eljárások esetén is alkalmazhatók. ____ Due to the effects of the crisis, budgets of present as well as future projects are decreasing steadily. In this study four different methods are introduced for minimising budget and time demands. These introduced methods support not only the traditional but also the agile project management. Furthermore these methods can be used not only in case of network planning, but also for matrix-based project planning.

An investigation of location effect on trip production using artificial neural networks

As traffic congestion exuberates and new roadway construction is severely constrained because of limited availability of land, high cost of land acquisition, and communities' opposition to the building of major roads, new solutions have to be sought to either make roadway use more efficient or reduce travel demand. There is a general agreement that travel demand is affected by land use patterns. However, traditional aggregate four-step models, which are the prevailing modeling approach presently, assume that traffic condition will not affect people's decision on whether to make a trip or not when trip generation is estimated. Existing survey data indicate, however, that differences exist in trip rates for different geographic areas. The reasons for such differences have not been carefully studied, and the success of quantifying the influence of land use on travel demand beyond employment, households, and their characteristics has been limited to be useful to the traditional four-step models. There may be a number of reasons, such as that the representation of influence of land use on travel demand is aggregated and is not explicit and that land use variables such as density and mix and accessibility as measured by travel time and congestion have not been adequately considered. This research employs the artificial neural network technique to investigate the potential effects of land use and accessibility on trip productions. Sixty two variables that may potentially influence trip production are studied. These variables include demographic, socioeconomic, land use and accessibility variables. Different architectures of ANN models are tested. Sensitivity analysis of the models shows that land use does have an effect on trip production, so does traffic condition. The ANN models are compared with linear regression models and cross-classification models using the same data. The results show that ANN models are better than the linear regression models and cross-classification models in terms of RMSE. Future work may focus on finding a representation of traffic condition with existing network data and population data which might be available when the variables are needed to in prediction.

Defense against node compromise in sensor network security

Recent advances in electronic and computer technologies lead to wide-spread deployment of wireless sensor networks (WSNs). WSNs have wide range applications, including military sensing and tracking, environment monitoring, smart environments, etc. Many WSNs have mission-critical tasks, such as military applications. Thus, the security issues in WSNs are kept in the foreground among research areas. Compared with other wireless networks, such as ad hoc, and cellular networks, security in WSNs is more complicated due to the constrained capabilities of sensor nodes and the properties of the deployment, such as large scale, hostile environment, etc. Security issues mainly come from attacks. In general, the attacks in WSNs can be classified as external attacks and internal attacks. In an external attack, the attacking node is not an authorized participant of the sensor network. Cryptography and other security methods can prevent some of external attacks. However, node compromise, the major and unique problem that leads to internal attacks, will eliminate all the efforts to prevent attacks. Knowing the probability of node compromise will help systems to detect and defend against it. Although there are some approaches that can be used to detect and defend against node compromise, few of them have the ability to estimate the probability of node compromise. Hence, we develop basic uniform, basic gradient, intelligent uniform and intelligent gradient models for node compromise distribution in order to adapt to different application environments by using probability theory. These models allow systems to estimate the probability of node compromise. Applying these models in system security designs can improve system security and decrease the overheads nearly in every security area. Moreover, based on these models, we design a novel secure routing algorithm to defend against the routing security issue that comes from the nodes that have already been compromised but have not been detected by the node compromise detecting mechanism. The routing paths in our algorithm detour those nodes which have already been detected as compromised nodes or have larger probabilities of being compromised. Simulation results show that our algorithm is effective to protect routing paths from node compromise whether detected or not.

A static traffic assignment model combined with an artificial neural network delay model

As traffic congestion continues to worsen in large urban areas, solutions are urgently sought. However, transportation planning models, which estimate traffic volumes on transportation network links, are often unable to realistically consider travel time delays at intersections. Introducing signal controls in models often result in significant and unstable changes in network attributes, which, in turn, leads to instability of models. Ignoring the effect of delays at intersections makes the model output inaccurate and unable to predict travel time. To represent traffic conditions in a network more accurately, planning models should be capable of arriving at a network solution based on travel costs that are consistent with the intersection delays due to signal controls. This research attempts to achieve this goal by optimizing signal controls and estimating intersection delays accordingly, which are then used in traffic assignment. Simultaneous optimization of traffic routing and signal controls has not been accomplished in real-world applications of traffic assignment. To this end, a delay model dealing with five major types of intersections has been developed using artificial neural networks (ANNs). An ANN architecture consists of interconnecting artificial neurons. The architecture may either be used to gain an understanding of biological neural networks, or for solving artificial intelligence problems without necessarily creating a model of a real biological system. The ANN delay model has been trained using extensive simulations based on TRANSYT-7F signal optimizations. The delay estimates by the ANN delay model have percentage root-mean-squared errors (%RMSE) that are less than 25.6%, which is satisfactory for planning purposes. Larger prediction errors are typically associated with severely oversaturated conditions. A combined system has also been developed that includes the artificial neural network (ANN) delay estimating model and a user-equilibrium (UE) traffic assignment model. The combined system employs the Frank-Wolfe method to achieve a convergent solution. Because the ANN delay model provides no derivatives of the delay function, a Mesh Adaptive Direct Search (MADS) method is applied to assist in and expedite the iterative process of the Frank-Wolfe method. The performance of the combined system confirms that the convergence of the solution is achieved, although the global optimum may not be guaranteed.

Design strategies for an artificial neural network based algorithm for automatic incident detection on major arterial streets

Traffic incidents are non-recurring events that can cause a temporary reduction in roadway capacity. They have been recognized as a major contributor to traffic congestion on our nation’s highway systems. To alleviate their impacts on capacity, automatic incident detection (AID) has been applied as an incident management strategy to reduce the total incident duration. AID relies on an algorithm to identify the occurrence of incidents by analyzing real-time traffic data collected from surveillance detectors. Significant research has been performed to develop AID algorithms for incident detection on freeways; however, similar research on major arterial streets remains largely at the initial stage of development and testing. This dissertation research aims to identify design strategies for the deployment of an Artificial Neural Network (ANN) based AID algorithm for major arterial streets. A section of the US-1 corridor in Miami-Dade County, Florida was coded in the CORSIM microscopic simulation model to generate data for both model calibration and validation. To better capture the relationship between the traffic data and the corresponding incident status, Discrete Wavelet Transform (DWT) and data normalization were applied to the simulated data. Multiple ANN models were then developed for different detector configurations, historical data usage, and the selection of traffic flow parameters. To assess the performance of different design alternatives, the model outputs were compared based on both detection rate (DR) and false alarm rate (FAR). The results show that the best models were able to achieve a high DR of between 90% and 95%, a mean time to detect (MTTD) of 55-85 seconds, and a FAR below 4%. The results also show that a detector configuration including only the mid-block and upstream detectors performs almost as well as one that also includes a downstream detector. In addition, DWT was found to be able to improve model performance, and the use of historical data from previous time cycles improved the detection rate. Speed was found to have the most significant impact on the detection rate, while volume was found to contribute the least. The results from this research provide useful insights on the design of AID for arterial street applications.

Realization of Differentiated Quality of Service for Wideband Code Division Multiple Access Core Network

The development of 3G (the 3rd generation telecommunication) value-added services brings higher requirements of Quality of Service (QoS). Wideband Code Division Multiple Access (WCDMA) is one of three 3G standards, and enhancement of QoS for WCDMA Core Network (CN) becomes more and more important for users and carriers. The dissertation focuses on enhancement of QoS for WCDMA CN. The purpose is to realize the DiffServ (Differentiated Services) model of QoS for WCDMA CN. Based on the parallelism characteristic of Network Processors (NPs), the NP programming model is classified as Pool of Threads (POTs) and Hyper Task Chaining (HTC). In this study, an integrated programming model that combines both of the two models was designed. This model has highly efficient and flexible features, and also solves the problems of sharing conflicts and packet ordering. We used this model as the programming model to realize DiffServ QoS for WCDMA CN. ^ The realization mechanism of the DiffServ model mainly consists of buffer management, packet scheduling and packet classification algorithms based on NPs. First, we proposed an adaptive buffer management algorithm called Packet Adaptive Fair Dropping (PAFD), which takes into consideration of both fairness and throughput, and has smooth service curves. Then, an improved packet scheduling algorithm called Priority-based Weighted Fair Queuing (PWFQ) was introduced to ensure the fairness of packet scheduling and reduce queue time of data packets. At the same time, the delay and jitter are also maintained in a small range. Thirdly, a multi-dimensional packet classification algorithm called Classification Based on Network Processors (CBNPs) was designed. It effectively reduces the memory access and storage space, and provides less time and space complexity. ^ Lastly, an integrated hardware and software system of the DiffServ model of QoS for WCDMA CN was proposed. It was implemented on the NP IXP2400. According to the corresponding experiment results, the proposed system significantly enhanced QoS for WCDMA CN. It extensively improves consistent response time, display distortion and sound image synchronization, and thus increases network efficiency and saves network resource.^

Improving Analytical Travel Time Estimation for Transportation Planning Models

This dissertation aimed to improve travel time estimation for the purpose of transportation planning by developing a travel time estimation method that incorporates the effects of signal timing plans, which were difficult to consider in planning models. For this purpose, an analytical model has been developed. The model parameters were calibrated based on data from CORSIM microscopic simulation, with signal timing plans optimized using the TRANSYT-7F software. Independent variables in the model are link length, free-flow speed, and traffic volumes from the competing turning movements. The developed model has three advantages compared to traditional link-based or node-based models. First, the model considers the influence of signal timing plans for a variety of traffic volume combinations without requiring signal timing information as input. Second, the model describes the non-uniform spatial distribution of delay along a link, this being able to estimate the impacts of queues at different upstream locations of an intersection and attribute delays to a subject link and upstream link. Third, the model shows promise of improving the accuracy of travel time prediction. The mean absolute percentage error (MAPE) of the model is 13% for a set of field data from Minnesota Department of Transportation (MDOT); this is close to the MAPE of uniform delay in the HCM 2000 method (11%). The HCM is the industrial accepted analytical model in the existing literature, but it requires signal timing information as input for calculating delays. The developed model also outperforms the HCM 2000 method for a set of Miami-Dade County data that represent congested traffic conditions, with a MAPE of 29%, compared to 31% of the HCM 2000 method. The advantages of the proposed model make it feasible for application to a large network without the burden of signal timing input, while improving the accuracy of travel time estimation. An assignment model with the developed travel time estimation method has been implemented in a South Florida planning model, which improved assignment results.

An integrated multi-agent framework for optimizing time, cost and environmental impact of construction processes

Environmentally conscious construction has received a significant amount of research attention during the last decades. Even though construction literature is rich in studies that emphasize the importance of environmental impact during the construction phase, most of the previous studies failed to combine environmental analysis with other project performance criteria in construction. This is mainly because most of the studies have overlooked the multi-objective nature of construction projects. In order to achieve environmentally conscious construction, multi-objectives and their relationships need to be successfully analyzed in the complex construction environment. The complex construction system is composed of changing project conditions that have an impact on the relationship between time, cost and environmental impact (TCEI) of construction operations. Yet, this impact is still unknown by construction professionals. Studying this impact is vital to fulfill multiple project objectives and achieve environmentally conscious construction. This research proposes an analytical framework to analyze the impact of changing project conditions on the relationship of TCEI. This study includes green house gas (GHG) emissions as an environmental impact category. The methodology utilizes multi-agent systems, multi-objective optimization, analytical network process, and system dynamics tools to study the relationships of TCEI and support decision-making under the influence of project conditions. Life cycle assessment (LCA) is applied to the evaluation of environmental impact in terms of GHG. The mixed method approach allowed for the collection and analysis of qualitative and quantitative data. Structured interviews of professionals in the highway construction field were conducted to gain their perspectives in decision-making under the influence of certain project conditions, while the quantitative data were collected from the Florida Department of Transportation (FDOT) for highway resurfacing projects. The data collected were used to test the framework. The framework yielded statistically significant results in simulating project conditions and optimizing TCEI. The results showed that the change in project conditions had a significant impact on the TCEI optimal solutions. The correlation between TCEI suggested that they affected each other positively, but in different strengths. The findings of the study will assist contractors to visualize the impact of their decision on the relationship of TCEI.