Novel ageing-biomarker discovery using data-intensive technologies

Ageing is accompanied by many visible characteristics. Other biological and physiological markers are also well-described e.g. loss of circulating sex hormones and increased inflammatory cytokines. Biomarkers for healthy ageing studies are presently predicated on existing knowledge of ageing traits. The increasing availability of data-intensive methods enables deep-analysis of biological samples for novel biomarkers. We have adopted two discrete approaches in MARK-AGE Work Package 7 for biomarker discovery; (1) microarray analyses and/or proteomics in cell systems e.g. endothelial progenitor cells or T cell ageing including a stress model; and (2) investigation of cellular material and plasma directly from tightly-defined proband subsets of different ages using proteomic, transcriptomic and miR array. The first approach provided longitudinal insight into endothelial progenitor and T cell ageing.This review describes the strategy and use of hypothesis-free, data-intensive approaches to explore cellular proteins, miR, mRNA and plasma proteins as healthy ageing biomarkers, using ageing models and directly within samples from adults of different ages. It considers the challenges associated with integrating multiple models and pilot studies as rational biomarkers for a large cohort study. From this approach, a number of high-throughput methods were developed to evaluate novel, putative biomarkers of ageing in the MARK-AGE cohort.

IUPHAR-DB:the IUPHAR database of G protein-coupled receptors and ion channels

The IUPHAR database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 nonsensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated-like ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of approximately one-third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. IUPHAR-DB provides a comprehensive description of the genes and their functions, with information on protein structure and interactions, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). In addition, the phenotypes resulting from altered gene expression (e.g. in genetically altered animals or in human genetic disorders) are described. The content of the database is peer reviewed by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR); the data are provided through manual curation of the primary literature by a network of over 60 subcommittees of NC-IUPHAR. Links to other bioinformatics resources, such as NCBI, Uniprot, HGNC and the rat and mouse genome databases are provided. IUPHAR-DB is freely available at http://www.iuphar-db.org. © 2008 The Author(s).

Discovering knowledge structures in mind maps of mental health risks

This thesis addressed the problem of risk analysis in mental healthcare, with respect to the GRiST project at Aston University. That project provides a risk-screening tool based on the knowledge of 46 experts, captured as mind maps that describe relationships between risks and patterns of behavioural cues. Mind mapping, though, fails to impose control over content, and is not considered to formally represent knowledge. In contrast, this thesis treated GRiSTs mind maps as a rich knowledge base in need of refinement; that process drew on existing techniques for designing databases and knowledge bases. Identifying well-defined mind map concepts, though, was hindered by spelling mistakes, and by ambiguity and lack of coverage in the tools used for researching words. A novel use of the Edit Distance overcame those problems, by assessing similarities between mind map texts, and between spelling mistakes and suggested corrections. That algorithm further identified stems, the shortest text string found in related word-forms. As opposed to existing approaches’ reliance on built-in linguistic knowledge, this thesis devised a novel, more flexible text-based technique. An additional tool, Correspondence Analysis, found patterns in word usage that allowed machines to determine likely intended meanings for ambiguous words. Correspondence Analysis further produced clusters of related concepts, which in turn drove the automatic generation of novel mind maps. Such maps underpinned adjuncts to the mind mapping software used by GRiST; one such new facility generated novel mind maps, to reflect the collected expert knowledge on any specified concept. Mind maps from GRiST are stored as XML, which suggested storing them in an XML database. In fact, the entire approach here is ”XML-centric”, in that all stages rely on XML as far as possible. A XML-based query language allows user to retrieve information from the mind map knowledge base. The approach, it was concluded, will prove valuable to mind mapping in general, and to detecting patterns in any type of digital information.

Design and evaluation of a consulting system for database design

Database design is a difficult problem for non-expert designers. It is desirable to assist such designers during the problem solving process by means of a knowledge based (KB) system. A number of prototype KB systems have been proposed, however there are many shortcomings. Few have incorporated sufficient expertise in modeling relationships, particularly higher order relationships. There has been no empirical study that experimentally tested the effectiveness of any of these KB tools. Problem solving behavior of non-experts, whom the systems were intended to assist, has not been one of the bases for system design. In this project a consulting system for conceptual database design that addresses the above short comings was developed and empirically validated.^ The system incorporates (a) findings on why non-experts commit errors and (b) heuristics for modeling relationships. Two approaches to knowledge base implementation--system restrictiveness and decisional guidance--were used and compared in this project. The Restrictive approach is proscriptive and limits the designer's choices at various design phases by forcing him/her to follow a specific design path. The Guidance system approach which is less restrictive, provides context specific, informative and suggestive guidance throughout the design process. The main objectives of the study are to evaluate (1) whether the knowledge-based system is more effective than a system without the knowledge-base and (2) which knowledge implementation--restrictive or guidance--strategy is more effective. To evaluate the effectiveness of the knowledge base itself, the two systems were compared with a system that does not incorporate the expertise (Control).^ The experimental procedure involved the student subjects solving a task without using the system (pre-treatment task) and another task using one of the three systems (experimental task). The experimental task scores of those subjects who performed satisfactorily in the pre-treatment task were analyzed. Results are (1) The knowledge based approach to database design support lead to more accurate solutions than the control system; (2) No significant difference between the two KB approaches; (3) Guidance approach led to best performance; and (4) The subjects perceived the Restrictive system easier to use than the Guidance system. ^

The role of market knowledge in recognizing and exploiting entrepreneurial opportunities in technology intensive firms

Entrepreneurial opportunity recognition is an increasingly prevalent phenomenon. Of particular interest is the ability of promising technology based ventures to recognize and exploit opportunities. Recent research drawing on the Austrian economic theory emphasizes the importance of knowledge, particularly market knowledge, behind opportunity recognition. While insightful, this research has tended to overlook those interrelationships that exist between different types of knowledge (technology and market knowledge) as well as between a firm’s knowledge base and its entrepreneurial orientation. Additional shortfalls of prior research include the ambiguous definitions provided for entrepreneurial opportunities, oversight of opportunity exploitation with an extensive focus on opportunity recognition only, and the lack of quantitative, empirical evidence on entrepreneurial opportunity recognition. ^ In this dissertation, these research gaps are addressed by integrating Schumpeterian opportunity development view with a Kirznerian opportunity discovery theory as well as insights from literature on entrepreneurial orientation. A sample of 85 new biotechnology ventures from the United States, Finland, and Sweden was analyzed. While leaders in all 85 companies were interviewed for the research in 2003-2004, 42 firms provided data in 2007. Data was analyzed using regression analysis. ^ The results show the value and importance of early market knowledge and technology knowledge as well as an entrepreneurial company posture for subsequent opportunity recognition. The highest numbers of new opportunities are recognized in firms where high levels of market knowledge are combined with high levels of technology knowledge (measured with a number of patents). A firm’s entrepreneurial orientation also enhances its opportunity recognition. Furthermore, the results show that new ventures with more market knowledge are able to gather more equity investments, license out more technologies, and achieve higher sales than new ventures with lower levels of market knowledge. Overall, the findings of this dissertation help further our understanding of the sources of entrepreneurial opportunities, and should encourage further research in this area. ^

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.

Efficient storage and domain-specific information discovery on semistructured documents

The increasing amount of available semistructured data demands efficient mechanisms to store, process, and search an enormous corpus of data to encourage its global adoption. Current techniques to store semistructured documents either map them to relational databases, or use a combination of flat files and indexes. These two approaches result in a mismatch between the tree-structure of semistructured data and the access characteristics of the underlying storage devices. Furthermore, the inefficiency of XML parsing methods has slowed down the large-scale adoption of XML into actual system implementations. The recent development of lazy parsing techniques is a major step towards improving this situation, but lazy parsers still have significant drawbacks that undermine the massive adoption of XML. ^ Once the processing (storage and parsing) issues for semistructured data have been addressed, another key challenge to leverage semistructured data is to perform effective information discovery on such data. Previous works have addressed this problem in a generic (i.e. domain independent) way, but this process can be improved if knowledge about the specific domain is taken into consideration. ^ This dissertation had two general goals: The first goal was to devise novel techniques to efficiently store and process semistructured documents. This goal had two specific aims: We proposed a method for storing semistructured documents that maps the physical characteristics of the documents to the geometrical layout of hard drives. We developed a Double-Lazy Parser for semistructured documents which introduces lazy behavior in both the pre-parsing and progressive parsing phases of the standard Document Object Model’s parsing mechanism. ^ The second goal was to construct a user-friendly and efficient engine for performing Information Discovery over domain-specific semistructured documents. This goal also had two aims: We presented a framework that exploits the domain-specific knowledge to improve the quality of the information discovery process by incorporating domain ontologies. We also proposed meaningful evaluation metrics to compare the results of search systems over semistructured documents. ^

Linking Old Librarianship to New: Aligning 5-Steps of The Innovator's DNA in Creating Thematic Discovery Systems for the Everglades

This poster presentation from the May 2015 Florida Library Association Conference, along with the Everglades Explorer discovery portal at http://ee.fiu.edu, demonstrates how traditional bibliographic and curatorial principles can be applied to: 1) selection, cross-walking and aggregation of metadata linking end-users to wide-spread digital resources from multiple silos; 2) harvesting of select PDFs, HTML and media for web archiving and access; 3) selection of CMS domains, sub-domains and folders for targeted searching using an API. Choosing content for this discovery portal is comparable to past scholarly practice of creating and publishing subject bibliographies, except metadata and data are housed in relational databases. This new and yet traditional capacity coincides with: Growth of bibliographic utilities (MarcEdit); Evolution of open-source discovery systems (eXtensible Catalog); Development of target-capable web crawling and archiving systems (Archive-it); and specialized search APIs (Google). At the same time, historical and technical changes – specifically the increasing fluidity and re-purposing of syndicated metadata – make this possible. It equally stems from the expansion of freely accessible digitized legacy and born-digital resources. Innovation principles helped frame the process by which the thematic Everglades discovery portal was created at Florida International University. The path -- to providing for more effective searching and co-location of digital scientific, educational and historical material related to the Everglades -- is contextualized through five concepts found within Dyer and Christensen’s “The Innovator’s DNA: Mastering the five skills of disruptive innovators (2011). The project also aligns with Ranganathan’s Laws of Library Science, especially the 4th Law -- to "save the time of the user.”

The role of market knowledge in recognizing and exploiting entrepreneurial opportunities in technology intensive firms

Entrepreneurial opportunity recognition is an increasingly prevalent phenomenon. Of particular interest is the ability of promising technology based ventures to recognize and exploit opportunities. Recent research drawing on the Austrian economic theory emphasizes the importance of knowledge, particularly market knowledge, behind opportunity recognition. While insightful, this research has tended to overlook those interrelationships that exist between different types of knowledge (technology and market knowledge) as well as between a firm’s knowledge base and its entrepreneurial orientation. Additional shortfalls of prior research include the ambiguous definitions provided for entrepreneurial opportunities, oversight of opportunity exploitation with an extensive focus on opportunity recognition only, and the lack of quantitative, empirical evidence on entrepreneurial opportunity recognition. In this dissertation, these research gaps are addressed by integrating Schumpeterian opportunity development view with a Kirznerian opportunity discovery theory as well as insights from literature on entrepreneurial orientation. A sample of 85 new biotechnology ventures from the United States, Finland, and Sweden was analyzed. While leaders in all 85 companies were interviewed for the research in 2003-2004, 42 firms provided data in 2007. Data was analyzed using regression analysis. The results show the value and importance of early market knowledge and technology knowledge as well as an entrepreneurial company posture for subsequent opportunity recognition. The highest numbers of new opportunities are recognized in firms where high levels of market knowledge are combined with high levels of technology knowledge (measured with a number of patents). A firm’s entrepreneurial orientation also enhances its opportunity recognition. Furthermore, the results show that new ventures with more market knowledge are able to gather more equity investments, license out more technologies, and achieve higher sales than new ventures with lower levels of market knowledge. Overall, the findings of this dissertation help further our understanding of the sources of entrepreneurial opportunities, and should encourage further research in this area.

Efficient Storage and Domain-Specific Information Discovery on Semistructured Documents

The increasing amount of available semistructured data demands efficient mechanisms to store, process, and search an enormous corpus of data to encourage its global adoption. Current techniques to store semistructured documents either map them to relational databases, or use a combination of flat files and indexes. These two approaches result in a mismatch between the tree-structure of semistructured data and the access characteristics of the underlying storage devices. Furthermore, the inefficiency of XML parsing methods has slowed down the large-scale adoption of XML into actual system implementations. The recent development of lazy parsing techniques is a major step towards improving this situation, but lazy parsers still have significant drawbacks that undermine the massive adoption of XML. Once the processing (storage and parsing) issues for semistructured data have been addressed, another key challenge to leverage semistructured data is to perform effective information discovery on such data. Previous works have addressed this problem in a generic (i.e. domain independent) way, but this process can be improved if knowledge about the specific domain is taken into consideration. This dissertation had two general goals: The first goal was to devise novel techniques to efficiently store and process semistructured documents. This goal had two specific aims: We proposed a method for storing semistructured documents that maps the physical characteristics of the documents to the geometrical layout of hard drives. We developed a Double-Lazy Parser for semistructured documents which introduces lazy behavior in both the pre-parsing and progressive parsing phases of the standard Document Object Model's parsing mechanism. The second goal was to construct a user-friendly and efficient engine for performing Information Discovery over domain-specific semistructured documents. This goal also had two aims: We presented a framework that exploits the domain-specific knowledge to improve the quality of the information discovery process by incorporating domain ontologies. We also proposed meaningful evaluation metrics to compare the results of search systems over semistructured documents.

Design and evaluation of a consulting system for database design

Database design is a difficult problem for non-expert designers. It is desirable to assist such designers during the problem solving process by means of a knowledge based (KB) system. Although a number of prototype KB systems have been proposed, there are many shortcomings. Firstly, few have incorporated sufficient expertise in modeling relationships, particularly higher order relationships. Secondly, there does not seem to be any published empirical study that experimentally tested the effectiveness of any of these KB tools. Thirdly, problem solving behavior of non-experts, whom the systems were intended to assist, has not been one of the bases for system design. In this project, a consulting system, called CODA, for conceptual database design that addresses the above short comings was developed and empirically validated. More specifically, the CODA system incorporates (a) findings on why non-experts commit errors and (b) heuristics for modeling relationships. Two approaches to knowledge base implementation were used and compared in this project, namely system restrictiveness and decisional guidance (Silver 1990). The Restrictive system uses a proscriptive approach and limits the designer's choices at various design phases by forcing him/her to follow a specific design path. The Guidance system approach, which is less restrictive, involves providing context specific, informative and suggestive guidance throughout the design process. Both the approaches would prevent erroneous design decisions. The main objectives of the study are to evaluate (1) whether the knowledge-based system is more effective than the system without a knowledge-base and (2) which approach to knowledge implementation - whether Restrictive or Guidance - is more effective. To evaluate the effectiveness of the knowledge base itself, the systems were compared with a system that does not incorporate the expertise (Control). An experimental procedure using student subjects was used to test the effectiveness of the systems. The subjects solved a task without using the system (pre-treatment task) and another task using one of the three systems, viz. Control, Guidance or Restrictive (experimental task). Analysis of experimental task scores of those subjects who performed satisfactorily in the pre-treatment task revealed that the knowledge based approach to database design support lead to more accurate solutions than the control system. Among the two KB approaches, Guidance approach was found to lead to better performance when compared to the Control system. It was found that the subjects perceived the Restrictive system easier to use than the Guidance system.

Database of the GLAMAP project

A uniform chronology for foraminifera-based sea surface temperature records has been established in more than 120 sediment cores obtained from the equatorial and eastern Atlantic up to the Arctic Ocean. The chronostratigraphy of the last 30,000 years is mainly based on published d18O records and 14C ages from accelerator mass spectrometry, converted into calendar-year ages. The high-precision age control provides the database necessary for the uniform reconstruction of the climate interval of the Last Glacial Maximum within the GLAMAP-2000 project.

Primary data sets of the hydrographic atlas of the Southern Ocean

The general knowledge of the hydrographic structure of the Southern Ocean is still rather incomplete since observations particularly in the ice covered regions are cumbersome to be carried out. But we know from the available information that thermohaline processes have large amplitudes and cover a wide range of scales in this part of the world ocean. The modification of water masses around Antarctica have indeed a worldwide impact, these processes ultimately determine the cold state of the present climate in the world ocean. We have converted efforts of the German and Russian polar research institutions to collect and validate the presently available temperature, salinity and oxygen data of the ocean south of 30°S latitude. We have carried out this work in spite of the fact that the hydrographic programme of the World Ocean Circulation Experiment (WOCE) will provide more new information in due time, but its contribution to the high latitudes of the Southern Ocean is quite sparse. The modified picture of the hydrographic structure of the Southern Ocean presented in this atlas may serve the oceanographic community in many ways and help to unravel the role of this ocean in the global climate system. This atlas could only be prepared with the altruistic assistance of many colleagues from various institutions worldwide who have provided us with their data and their advice. Their generous help is gratefully acknowledged. During two years scientists from the Arctic and Antarctic Research Institute in St. Petersburg and the Alfred Wegener Institute for Polar and Marine Research in Bremerhaven have cooperated in a fruitful way to establish the atlas and the archive of about 38749 validated hydrographic stations. We hope that both sources of information will be widely applied for future ocean studies and will serve as a reference state for global change considerations.

Expanded GHOST database

In this study we review a global set of alkenone- and foraminiferal Mg/Ca-derived sea surface temperatures (SST) records from the Holocene and compare them with a suite of published Eemian SST records based on the same approach. For the Holocene, the alkenone SST records belong to the actualized GHOST database (Kim, J.-H., Schneider R.R., 2004). The actualized GHOST database not only confirms the SST changes previously described but also documents the Holocene temperature evolution in new oceanic regions such as the Northwestern Atlantic, the eastern equatorial Pacific, and the Southern Ocean. A comparison of Holocene SST records stemming from the two commonly applied paleothermometry methods reveals contrasting - sometimes divergent - SST evolution, particularly at low latitudes where SST records are abundant enough to infer systematic discrepancies at a regional scale. Opposite SST trends at particular locations could be explained by out-of-phase trends in seasonal insolation during the Holocene. This hypothesis assumes that a strong contrast in the ecological responses of coccolithophores and planktonic foraminifera to winter and summer oceanographic conditions is the ultimate reason for seasonal differences in the origin of the temperature signal provided by these organisms. As a simple test for this hypothesis, Eemian SST records are considered because the Holocene and Eemian time periods experienced comparable changes in orbital configurations, but had a higher magnitude in insolation variance during the Eemian. For several regions, SST changes during both interglacials were of a similar sign, but with higher magnitudes during the Eemian as compared to the Holocene. This observation suggests that the ecological mechanism shaping SST trends during the Holocene was comparable during the penultimate interglacial period. Although this "ecology hypothesis" fails to explain all of the available results, we argue that any other mechanism would fail to satisfactorily explain the observed SST discrepancies among proxies.

Health Knowledge, Attitudes, and Practices among Street Children in LMICs

Background: Worldwide, it is estimated that there are up to 150 million street children. Street children are an understudied, vulnerable population. While many studies have characterized street children’s physical health, few have addressed the circumstances and barriers to their utilization of health services.

Methods: A systematic literature review was conducted to understand the barriers and facilitators that street children face when accessing healthcare in low and middle income countries. Six databases were used to search for peer review literature and one database and Google Search engine were used to find grey literature (theses, dissertations, reports, etc.). There were no exclusions based on study design. Studies were eligible for inclusion if the study population included street children, the study location was a low and middle income country defined by the World Bank, AND whose subject pertained to healthcare.

In addition, a cross-sectional study was conducted between May 2015 and August 2015 with the goal of understanding knowledge, attitudes, and health seeking practices of street children residing in Battambang, Cambodia. Time location and purposive sampling were used to recruit community (control) and street children. Both boys and girls between the ages of 10 and 18 were recruited. Data was collected through a verbally administered survey. The knowledge, attitudes and health seeking practices of community and street children were compared to determine potential differences in healthcare utilization.

Results: Of the 2933 abstracts screened for inclusion in the systematic literature review, eleven articles met all the inclusion criteria and were found to be relevant. Cost and perceived stigma appeared to be the largest barriers street children faced when attempting to seek care. Street children preferred to receive care from a hospital. However, negative experiences and mistreatment by health providers deterred children from going there. Instead, street children would often self treat and/or purchase medicine from a pharmacy or drug vendor. Family and peer support were found to be important for facilitating treatment.

The survey found similar results to the systematic review. Forty one community and thirty four street children were included in the analysis. Both community and street children reported the hospital as their top choice for care. When asked if someone went with them to seek care, both community and street children reported that family members, usually mothers, accompanied them. Community and street children both reported perceived stigma. All children had good knowledge of preventative care.

Conclusions: While most current services lack the proper accommodations for street children, there is a great potential to adapt them to better address street children’s needs. Street children need health services that are sensitive to their situation. Subsidies in health service costs or provision of credit may be ways to reduce constraints street children face when deciding to seek healthcare. Health worker education and interventions to reduce stigma are needed to create a positive environment in which street children are admitted and treated for health concerns.