Engineered T cell receptors and their potential in molecular medicine

T cell receptors are among the most specific biological structures found in nature and are therefore excellent candidates for the molecular targeting of antigen. It is becoming increasingly apparent that common sets of T cell receptors are frequently used in humans to combat pathogen and cancer derived threats. Given that many of these conserved T cell receptors have high affinity for their target ligands, there is potential to amass virtual banks of “off-the-shelf” receptors for use in a wide range of immunotherapeutic strategies. Additionally, such T cell receptors could become basic blueprints for artificial enhancement through mutagenesis, thereby creating an even better 3-dimensional fit for their cognate targets. Indeed, preliminary approaches using both “natural” and “supernatural” T cell receptors have shown promise in treating autoimmunity and malignancy. This review will discuss these studies and other approaches through which T cell receptors can be exploited in immunodiagnostics, pathogen control and gene therapy.

Consumer search of the web: An exploratory analysis of antecedents of web search satisfaction

This article explores consumer Web-search satisfaction. It commences with a brief overview of the concepts consumer information search and consumer satisfaction. Consumer Web adoption issues are then briefly discussed and the importance of consumer search satisfaction is highlighted in relation to the adoption of the Web as an additional source of consumer information. Research hypotheses are developed and the methodology of a large scale consumer experiment to record consumer Web search behaviour is described. The hypotheses are tested and the data explored in relation to post-Web-search satisfaction. The results suggest that consumer post-Web-search satisfaction judgments may be derived from subconscious judgments of Web search efficiency, an empirical calculation of which is problematic in unlimited information environments such as the Web. The results are discussed and a future research agenda is briefly outlined.

Overcoming network overload and redundancy in inter-organizational networks:the roles of potential and latent ties

This paper builds on Granovetter's distinction between strong and weak ties [Granovetter, M. S. 1973. The strength of weak ties. Amer. J. Sociol. 78(6) 1360–1380] in order to respond to recent calls for a more dynamic and processual understanding of networks. The concepts of potential and latent tie are deductively identified, and their implications for understanding how and why networks emerge, evolve, and change are explored. A longitudinal empirical study conducted with companies operating in the European motorsport industry reveals that firms take strategic actions to search for potential ties and reactivate latent ties in order to solve problems of network redundancy and overload. Examples are given, and their characteristics are examined to provide theoretical elaboration of the relationship between the types of tie and network evolution. These conceptual and empirical insights move understanding of the managerial challenge of building effective networks beyond static structural contingency models of optimal network forms to highlight the processes and capabilities of dynamic relationship building and network development. In so doing, this paper highlights the interrelationship between search and redundancy and the scope for strategic action alongside path dependence and structural influences on network processes.

Does online information drive offline revenues? Only for specific products and consumer segments!

While many offline retailers have developed informational websites that offer information on products and prices, the key question for such informational websites is whether they can increase revenues via web-to-store shopping. The current paper draws on the information search literature to specify and test hypotheses regarding the offline revenue impact of adding an informational website. Explicitly considering marketing efforts, a latent class model distinguishes consumer segments with different short-term revenue effects, while a Vector Autoregressive model on these segments reveals different long-term marketing response. We find that the offline revenue impact of the informational website critically depends on the product category and customer segment. The lower online search costs are especially beneficial for sensory products and for customers distant from the store. Moreover, offline revenues increase most for customers with high web visit frequency. We find that customers in some segments buy more and more expensive products, suggesting that online search and offline purchases are complements. In contrast, customers in a particular segment reduce their shopping trips, suggesting their online activities partially substitute for experiential shopping in the physical store. Hence, offline retailers should use specific online activities to target specific product categories and customer segments.

Effectiveness of Title-Search vs. Full-Text Search in the Web

Search engines sometimes apply the search on the full text of documents or web-pages; but sometimes they can apply the search on selected parts of the documents only, e.g. their titles. Full-text search may consume a lot of computing resources and time. It may be possible to save resources by applying the search on the titles of documents only, assuming that a title of a document provides a concise representation of its content. We tested this assumption using Google search engine. We ran search queries that have been defined by users, distinguishing between two types of queries/users: queries of users who are familiar with the area of the search, and queries of users who are not familiar with the area of the search. We found that searches which use titles provide similar and sometimes even (slightly) better results compared to searches which use the full-text. These results hold for both types of queries/users. Moreover, we found an advantage in title-search when searching in unfamiliar areas because the general terms used in queries in unfamiliar areas match better with general terms which tend to be used in document titles.

Regrouping metric-space search index for search engine size adaptation

This work contributes to the development of search engines that self-adapt their size in response to fluctuations in workload. Deploying a search engine in an Infrastructure as a Service (IaaS) cloud facilitates allocating or deallocating computational resources to or from the engine. In this paper, we focus on the problem of regrouping the metric-space search index when the number of virtual machines used to run the search engine is modified to reflect changes in workload. We propose an algorithm for incrementally adjusting the index to fit the varying number of virtual machines. We tested its performance using a custom-build prototype search engine deployed in the Amazon EC2 cloud, while calibrating the results to compensate for the performance fluctuations of the platform. Our experiments show that, when compared with computing the index from scratch, the incremental algorithm speeds up the index computation 2–10 times while maintaining a similar search performance.

Predicting dyslexia using prereading skills:the role of sensorimotor and cognitive abilities

Background: It is well established that phonological awareness, print knowledge and rapid naming predict later reading difficulties. However, additional auditory, visual and motor difficulties have also been observed in dyslexic children. It is examined to what extent these difficulties can be used to predict later literacy difficulties. Method: An unselected sample of 267 children at school entry completed a wide battery of tasks associated with dyslexia. Their reading was tested 2, 3 and 4 years later and poor readers were identified (n = 42). Logistic regression and multiple case study approaches were used to examine the predictive validity of different tasks. Results: As expected, print knowledge, verbal short-term memory, phonological awareness and rapid naming were good predictors of later poor reading. Deficits in visual search and in auditory processing were also present in a large minority of the poor readers. Almost all poor readers showed deficits in at least one area at school entry, but there was no single deficit that characterised the majority of poor readers. Conclusions: Results are in line with Pennington’s (2006) multiple deficits view of dyslexia. They indicate that the causes of poor reading outcome are multiple, interacting and probabilistic, rather than deterministic. Keywords: Dyslexia; educational attainment; longitudinal studies; prediction; phonological processing.

The effects of attribute quality information and sources of information on consumers' perceptions and behavior: A model of Pre-purchase Information Utilization in Service Physical Environments

The search-experience-credence framework from economics of information, the human-environment relations models from environmental psychology, and the consumer evaluation process from services marketing provide a conceptual basis for testing the model of "Pre-purchase Information Utilization in Service Physical Environments." The model addresses the effects of informational signs, as a dimension of the service physical environment, on consumers' perceptions (perceived veracity and perceived performance risk), emotions (pleasure) and behavior (willingness to buy). The informational signs provide attribute quality information (search and experience) through non-personal sources of information (simulated word-of-mouth and non-personal advocate sources).^ This dissertation examines: (1) the hypothesized relationships addressed in the model of "Pre-purchase Information Utilization in Service Physical Environments" among informational signs, perceived veracity, perceived performance risk, pleasure, and willingness to buy, and (2) the effects of attribute quality information and sources of information on consumers' perceived veracity and perceived performance risk.^ This research is the first in-depth study about the role and effects of information in service physical environments. Using a 2 x 2 between subjects experimental research procedure, undergraduate students were exposed to the informational signs in a simulated service physical environment. The service physical environments were simulated through color photographic slides.^ The results of the study suggest that: (1) the relationship between informational signs and willingness to buy is mediated by perceived veracity, perceived performance risk and pleasure, (2) experience attribute information shows higher perceived veracity and lower perceived performance risk when compared to search attribute information, and (3) information provided through simulated word-of-mouth shows higher perceived veracity and lower perceived performance risk when compared to information provided through non-personal advocate sources. ^

Ranked search on data graphs

Graph-structured databases are widely prevalent, and the problem of effective search and retrieval from such graphs has been receiving much attention recently. For example, the Web can be naturally viewed as a graph. Likewise, a relational database can be viewed as a graph where tuples are modeled as vertices connected via foreign-key relationships. Keyword search querying has emerged as one of the most effective paradigms for information discovery, especially over HTML documents in the World Wide Web. One of the key advantages of keyword search querying is its simplicity—users do not have to learn a complex query language, and can issue queries without any prior knowledge about the structure of the underlying data. The purpose of this dissertation was to develop techniques for user-friendly, high quality and efficient searching of graph structured databases. Several ranked search methods on data graphs have been studied in the recent years. Given a top-k keyword search query on a graph and some ranking criteria, a keyword proximity search finds the top-k answers where each answer is a substructure of the graph containing all query keywords, which illustrates the relationship between the keyword present in the graph. We applied keyword proximity search on the web and the page graph of web documents to find top-k answers that satisfy user’s information need and increase user satisfaction. Another effective ranking mechanism applied on data graphs is the authority flow based ranking mechanism. Given a top- k keyword search query on a graph, an authority-flow based search finds the top-k answers where each answer is a node in the graph ranked according to its relevance and importance to the query. We developed techniques that improved the authority flow based search on data graphs by creating a framework to explain and reformulate them taking in to consideration user preferences and feedback. We also applied the proposed graph search techniques for Information Discovery over biological databases. Our algorithms were experimentally evaluated for performance and quality. The quality of our method was compared to current approaches by using user surveys.

Framing infectious diseases and U.S. public opinion

The United States has been increasingly concerned with the transnational threat posed by infectious diseases. Effective policy implementation to contain the spread of these diseases requires active engagement and support of the American public. To influence American public opinion and enlist support for related domestic and foreign policies, both domestic agencies and international organizations have framed infectious diseases as security threats, human rights disasters, economic risks, and as medical dangers. This study investigates whether American attitudes and opinions about infectious diseases are influenced by how the issue is framed. It also asks which issue frame has been most influential in shaping public opinion about global infectious diseases when people are exposed to multiple frames. The impact of media frames on public perception of infectious diseases is examined through content analysis of newspaper reports. Stories on SARS, avian flu, and HIV/AIDS were sampled from coverage in The New York Times and The Washington Post between 1999 and 2007. Surveys of public opinion on infectious diseases in the same time period were also drawn from databases like Health Poll Search and iPoll. Statistical analysis tests the relationship between media framing of diseases and changes in public opinion. Results indicate that no one frame was persuasive across all diseases. The economic frame had a significant effect on public opinion about SARS, as did the biomedical frame in the case of avian flu. Both the security and human rights frames affected opinion and increased public support for policies intended to prevent or treat HIV/AIDS. The findings also address the debate on the role and importance of domestic public opinion as a factor in domestic and foreign policy decisions of governments in an increasingly interconnected world. The public is able to make reasonable evaluations of the frames and the domestic and foreign policy issues emphasized in the frames.

Grabbing Your Attention: The Impact of Finding a First Target in Multiple-Target Search

For over 50 years, the Satisfaction of Search effect, and more recently known as the Subsequent Search Miss (SSM) effect, has plagued the field of radiology. Defined as a decrease in additional target accuracy after detecting a prior target in a visual search, SSM errors are known to underlie both real-world search errors (e.g., a radiologist is more likely to miss a tumor if a different tumor was previously detected) and more simplified, lab-based search errors (e.g., an observer is more likely to miss a target ‘T’ if a different target ‘T’ was previously detected). Unfortunately, little was known about this phenomenon’s cognitive underpinnings and SSM errors have proven difficult to eliminate. However, more recently, experimental research has provided evidence for three different theories of SSM errors: the Satisfaction account, the Perceptual Set account, and the Resource Depletion account. A series of studies examined performance in a multiple-target visual search and aimed to provide support for the Resource Depletion account—a first target consumes cognitive resources leaving less available to process additional targets.

To assess a potential mechanism underlying SSM errors, eye movements were recorded in a multiple-target visual search and were used to explore whether a first target may result in an immediate decrease in second-target accuracy, which is known as an attentional blink. To determine whether other known attentional distractions amplified the effects of finding a first target has on second-target detection, distractors within the immediate vicinity of the targets (i.e., clutter) were measured and compared to accuracy for a second target. To better understand which characteristics of attention were impacted by detecting a first target, individual differences within four characteristics of attention were compared to second-target misses in a multiple-target visual search.

The results demonstrated that an attentional blink underlies SSM errors with a decrease in second-target accuracy from 135ms-405ms after detection or re-fixating a first target. The effects of clutter were exacerbated after finding a first target causing a greater decrease in second-target accuracy as clutter increased around a second-target. The attentional characteristics of modulation and vigilance were correlated with second- target misses and suggest that worse attentional modulation and vigilance are predictive of more second-target misses. Taken together, these result are used as the foundation to support a new theory of SSM errors, the Flux Capacitor theory. The Flux Capacitor theory predicts that once a target is found, it is maintained as an attentional template in working memory, which consumes attentional resources that could otherwise be used to detect additional targets. This theory not only proposes why attentional resources are consumed by a first target, but encompasses the research in support of all three SSM theories in an effort to establish a grand, unified theory of SSM errors.

Dynamic Programming Approaches for Estimating and Applying Large-scale Discrete Choice Models

People go through their life making all kinds of decisions, and some of these decisions affect their demand for transportation, for example, their choices of where to live and where to work, how and when to travel and which route to take. Transport related choices are typically time dependent and characterized by large number of alternatives that can be spatially correlated. This thesis deals with models that can be used to analyze and predict discrete choices in large-scale networks. The proposed models and methods are highly relevant for, but not limited to, transport applications. We model decisions as sequences of choices within the dynamic discrete choice framework, also known as parametric Markov decision processes. Such models are known to be difficult to estimate and to apply to make predictions because dynamic programming problems need to be solved in order to compute choice probabilities. In this thesis we show that it is possible to explore the network structure and the flexibility of dynamic programming so that the dynamic discrete choice modeling approach is not only useful to model time dependent choices, but also makes it easier to model large-scale static choices. The thesis consists of seven articles containing a number of models and methods for estimating, applying and testing large-scale discrete choice models. In the following we group the contributions under three themes: route choice modeling, large-scale multivariate extreme value (MEV) model estimation and nonlinear optimization algorithms. Five articles are related to route choice modeling. We propose different dynamic discrete choice models that allow paths to be correlated based on the MEV and mixed logit models. The resulting route choice models become expensive to estimate and we deal with this challenge by proposing innovative methods that allow to reduce the estimation cost. For example, we propose a decomposition method that not only opens up for possibility of mixing, but also speeds up the estimation for simple logit models, which has implications also for traffic simulation. Moreover, we compare the utility maximization and regret minimization decision rules, and we propose a misspecification test for logit-based route choice models. The second theme is related to the estimation of static discrete choice models with large choice sets. We establish that a class of MEV models can be reformulated as dynamic discrete choice models on the networks of correlation structures. These dynamic models can then be estimated quickly using dynamic programming techniques and an efficient nonlinear optimization algorithm. Finally, the third theme focuses on structured quasi-Newton techniques for estimating discrete choice models by maximum likelihood. We examine and adapt switching methods that can be easily integrated into usual optimization algorithms (line search and trust region) to accelerate the estimation process. The proposed dynamic discrete choice models and estimation methods can be used in various discrete choice applications. In the area of big data analytics, models that can deal with large choice sets and sequential choices are important. Our research can therefore be of interest in various demand analysis applications (predictive analytics) or can be integrated with optimization models (prescriptive analytics). Furthermore, our studies indicate the potential of dynamic programming techniques in this context, even for static models, which opens up a variety of future research directions.

D6.6 – Summary, Analysis, Road-mapping and Production of Training materials

This deliverable summarizes, validates and explains the purpose and concept behind the RAGE knowledge and innovation management platform as a self-sustainable Ecosystem, supporting innovation processes in the Applied Gaming (AG) industry. The Ecosystem portal will be developed with particular consideration of the demand and requirements of small and medium sized game developing companies, education providers and related stakeholders like AG researchers and AG end-users. The innovation potential of the new platform underlies the following factors: a huge, mostly entire collection of community specific knowledge (e.g., content like media objects, software components and best practices), a structured approach of knowledge access, search and browse, collaboration tools as well as social network analysis tools to foster efficient knowledge creation and transformation processes into marketable technology assets. The deliverable provides an overview of the current status and the remaining work to come, preceding the final version in month 48 of the RAGE project.

A Sense of Wonder: Enhancing Access to Folktales through Task and Facet Analysis

Discusses the approach taken in Phase 1 of a three-phase project Folktales, Facets and FRBR [funded by a grant from OCLC/ALISE]. This project works with the special collection of folktales at the Center for Children’s Books (CCB) at the University of Illinois at Urbana-Champaign, and the scholars who use this collection. The project aims to enhance the effectiveness and efficiency of folktale access through deep understanding of user needs. Phase 1 included facet analysis of the bibliographic records for a sample of 100 folktale books in the CCB, and task analysis of interviews with four CCB-affiliated faculty. Describes the information tasks, information seeking obstacles, and desired features for a discovery and access tool related to folktales for this initial group of scholarly users of folktales.

Direction, legitimacy and structuration in technological innovation systems upscaling-insights from roadmaps for deepwater offshore wind energy

This research investigates strategies aiming to accelerate the up-scaling of low- carbon innovations. We adopt the technological innovation systems (TIS) perspective to focus on structuration or system building processes, including key innovative activities. We analyze national roadmaps that have been developed for offshore wind energy in deep waters - more than 50 meters deep where most of the potential is expected but whose technologyis more immature . in Europe. The roadmaps analysis not only reveals how actors expect the TIS grow but also enables the understanding about the critical functions at this stage, such as direction of search and legitimacy.