FGFR2 as a molecular target in endometrial cancer

Although molecularly targeted therapies have been effective in some cancer types, no targeted therapy is approved for use in endometrial cancer. The recent identification of activating mutations in fibroblast growth factor receptor 2 (FGFR2) in endometrial tumors has generated a new avenue for the development of targeted therapeutic agents. The majority of the mutations identified are identical to germline mutations in FGFR2 and FGFR3 that cause craniosynostosis and hypochondroplasia syndromes and result in both ligand-independent and ligand-dependent receptor activation. Mutations that predominantly occur in the endometrioid subtype of endometrial cancer, are mutually exclusive with KRAS mutation, but occur in the presence of PTEN abrogation. In vitro studies have shown that endometrial cancer cell lines with activating FGFR2 mutations are selectively sensitive to a pan-FGFR inhibitor, PD173074. Several agents with activity against FGFRs are currently in clinical trials. Investigation of these agents in endometrial cancer patients with activating FGFR2 mutations is warranted.

Targeting mutant fibroblast growth factor receptors in cancer

Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials evaluating multikinase inhibitors with anti-FGFR activity and a new generation of specific pan-FGFR inhibitors.

SAP webflow made configurable: unifying workflow templates into a configurable model

To facilitate the implementation of workflows, enterprise and workflow system vendors typically provide workflow templates for their software. Each of these templates depicts a variant of how the software supports a certain business process, allowing the user to save the effort of creating models and links to system components from scratch by selecting and activating the appropriate template. A combination of the strengths from different templates is however only achievable by manually adapting the templates which is cumbersome. We therefore suggest in this paper to combine different workflow templates into a single configurable workflow template. Using the workflow modeling language of SAP’s WebFlow engine, we show how such a configurable workflow modeling language can be created by identifying the configurable elements in the original language. Requirements imposed on configurations inhibit invalid configurations. Based on a default configuration such configurable templates can be used as easy as the traditional templates. The suggested approach is also applicable to other workflow modeling languages

A Virtual Evaluation Track for Cross Language Link Discovery

The Wikipedia has become the most popular online source of encyclopedic information. The English Wikipedia collection, as well as some other languages collections, is extensively linked. However, as a multilingual collection the Wikipedia is only very weakly linked. There are few cross-language links or cross-dialect links (see, for example, Chinese dialects). In order to link the multilingual-Wikipedia as a single collection, automated cross language link discovery systems are needed – systems that identify anchor-texts in one language and targets in another. The evaluation of Link Discovery approaches within the English version of the Wikipedia has been examined in the INEX Link the-Wiki track since 2007, whilst both CLEF and NTCIR emphasized the investigation and the evaluation of cross-language information retrieval. In this position paper we propose a new virtual evaluation track: Cross Language Link Discovery (CLLD). The track will initially examine cross language linking of Wikipedia articles. This virtual track will not be tied to any one forum; instead we hope it can be connected to each of (at least): CLEF, NTCIR, and INEX as it will cover ground currently studied by each. The aim is to establish a virtual evaluation environment supporting continuous assessment and evaluation, and a forum for the exchange of research ideas. It will be free from the difficulties of scheduling and synchronizing groups of collaborating researchers and alleviate the necessity to travel across the globe in order to share knowledge. We aim to electronically publish peer-reviewed publications arising from CLLD in a similar fashion: online, with open access, and without fixed submission deadlines.

Query expansion using term relationships in language models for information retrieval

Language Modeling (LM) has been successfully applied to Information Retrieval (IR). However, most of the existing LM approaches only rely on term occurrences in documents, queries and document collections. In traditional unigram based models, terms (or words) are usually considered to be independent. In some recent studies, dependence models have been proposed to incorporate term relationships into LM, so that links can be created between words in the same sentence, and term relationships (e.g. synonymy) can be used to expand the document model. In this study, we further extend this family of dependence models in the following two ways: (1) Term relationships are used to expand query model instead of document model, so that query expansion process can be naturally implemented; (2) We exploit more sophisticated inferential relationships extracted with Information Flow (IF). Information flow relationships are not simply pairwise term relationships as those used in previous studies, but are between a set of terms and another term. They allow for context-dependent query expansion. Our experiments conducted on TREC collections show that we can obtain large and significant improvements with our approach. This study shows that LM is an appropriate framework to implement effective query expansion.

Evaluation framework for focused link discovery

Information has no value unless it is accessible. Information must be connected together so a knowledge network can then be built. Such a knowledge base is a key resource for Internet users to interlink information from documents. Information retrieval, a key technology for knowledge management, guarantees access to large corpora of unstructured text. Collaborative knowledge management systems such as Wikipedia are becoming more popular than ever; however, their link creation function is not optimized for discovering possible links in the collection and the quality of automatically generated links has never been quantified. This research begins with an evaluation forum which is intended to cope with the experiments of focused link discovery in a collaborative way as well as with the investigation of the link discovery application. The research focus was on the evaluation strategy: the evaluation framework proposal, including rules, formats, pooling, validation, assessment and evaluation has proved to be efficient, reusable for further extension and efficient for conducting evaluation. The collection-split approach is used to re-construct the Wikipedia collection into a split collection comprising single passage files. This split collection is proved to be feasible for improving relevant passages discovery and is devoted to being a corpus for focused link discovery. Following these experiments, a mobile client-side prototype built on iPhone is developed to resolve the mobile Search issue by using focused link discovery technology. According to the interview survey, the proposed mobile interactive UI does improve the experience of mobile information seeking. Based on this evaluation framework, a novel cross-language link discovery proposal using multiple text collections is developed. A dynamic evaluation approach is proposed to enhance both the collaborative effort and the interacting experience between submission and evaluation. A realistic evaluation scheme has been implemented at NTCIR for cross-language link discovery tasks.

Comparative Studies Simplified in GPFlow

We present a novel, web-accessible scientific workflow system which makes large-scale comparative studies accessible without programming or excessive configuration requirements. GPFlow allows a workflow defined on single input values to be automatically lifted to operate over collections of input values and supports the formation and processing of collections of values without the need for explicit iteration constructs. We introduce a new model for collection processing based on key aggregation and slicing which guarantees processing integrity and facilitates automatic association of inputs, allowing scientific users to manage the combinatorial explosion of data values inherent in large scale comparative studies. The approach is demonstrated using a core task from comparative genomics, and builds upon our previous work in supporting combined interactive and batch operation, through a lightweight web-based user interface.

The knock-on from the knock-off : recent shifts within Australian mass market fashion design practice

Australia’s mass market fashion labels have traditionally benefitted from their peripheral location to the world’s fashion centres. Operating a season behind, Australian mass market designers and buyers were well-placed to watch trends play out overseas before testing them in the Australian marketplace. For this reason, often a designer’s role was to source and oversee the manufacture of ‘knock-offs’, or close copies of Northern hemisphere mass market garments. Both Weller (2007) and Walsh (2009) have commented on this practice. The knock-on effect from this continues to be a cautious, derivative fashion sensibility within Australian mass market fashion design, where any new trend or product is first tested and proved overseas months earlier. However, there is evidence that this is changing. The rapid online dissemination of global fashion trends, coupled with the Australian consumer’s willingness to shop online, has meant that the ‘knock-off’ is less viable. For this reason, a number of mass market companies are moving away from the practice of direct sourcing and are developing product in-house under a Northern hemisphere model. This shift is also witnessed in the trend for mass market companies to develop collections in partnership with independent Australian designers. This paper explores the current and potential effects of these shifts within Australian mass market design practice, and discusses how they may impact on designers, consumers and on the wider culture of Australian fashion.

Clusterin facilitates COMMD1 and I-kB degradation to enhance NF-kB activity in prostate cancer cells

Secretory clusterin (sCLU) is a stress-activated, cytoprotective chaperone that confers broad-spectrum cancer treatment resistance, and its targeted inhibitor (OGX-011) is currently in phase II trials for prostate, lung, and breast cancer. However, the molecular mechanisms by which sCLU inhibits treatment-induced apoptosis in prostate cancer remain incompletely defined. We report that sCLU increases NF-κB nuclear translocation and transcriptional activity by serving as a ubiquitin-binding protein that enhances COMMD1 and I-κB proteasomal degradation by interacting with members of the SCF-βTrCP E3 ligase family. Knockdown of sCLU in prostate cancer cells stabilizes COMMD1 and I-κB, thereby sequestrating NF-κB in the cytoplasm and decreasing NF-κB transcriptional activity. Comparative microarray profiling of sCLU-overexpressing and sCLU-knockdown prostate cancer cells confirmed that the expression of many NF-κB–regulated genes positively correlates with sCLU levels. We propose that elevated levels of sCLU promote prostate cancer cell survival by facilitating degradation of COMMD1 and I-κB, thereby activating the canonical NF-κB pathway.

A semantics-based approach to querying process model repositories

As business process management technology matures, organisations acquire more and more business process models. The resulting collections can consist of hundreds, even thousands of models and their management poses real challenges. One of these challenges concerns model retrieval where support should be provided for the formulation and efficient execution of business process model queries. As queries based on only structural information cannot deal with all querying requirements in practice, there should be support for queries that require knowledge of process model semantics. In this paper we formally define a process model query language that is based on semantic relationships between tasks. This query language is independent of the particular process modelling notation used, but we will demonstrate how it can be used in the context of Petri nets by showing how the semantic relationships can be determined for these nets in such a way that state space explosion is avoided as much as possible. An experiment with three large process model repositories shows that queries expressed in our language can be evaluated efficiently.

Crowded Diphosphinomethane Ligands in Catalysis: [(R2PCH2PR′2-κ2P)-NiR″]+ Cations for Ethylene Polymerization without Activators

The preparation of a series of nickel dichloride complexes with bulky diphosphinomethane chelate ligands R2PCH2PR′2 is reported. Reaction with the appropriate Grignard reagent leads to the corresponding dimethyl and dibenzyl complexes. Cationic monomethyl and mono-η3-benzyl complexes are generated from these dialkyl complexes by protonation with [H(OEt2)2]+[B(3,5-(CF3)2C6H3)4]−, while the complex [(dtbpm κ2P)Ni(η3-CH(CH2Ph)Ph]+[B(3,5-(CF3)2C6H3)4]−is obtained from protonation of the Ni(0) olefin complex (dtbpm-κ2P)N(η2-trans-stilbene). Crystal structures of examples of dichlorides, dimethyl, dibenzyl, cationic methyl, and cationic η3-benzyl complexes are reported. Solutions of the cations polymerize ethylene under mild conditions and without the necessity of an activating agent, to form polyethylene having high molecular weights and low degrees of chain branching. In comparison to the Ni methyl cations, the η3-benzyl cation complexes are more stable and somewhat less active but still very efficient in C2H4 polymerization. The effect on the resulting polyethylene of varying the substituents R, R′ on the phosphine ligand has been examined, and a clear trend for longer chain PE with less branching in the presence of more bulky substituents on the diphosphine has been found. Density functional calculations have been used to examine the rapid suprafacial η3 to η3 haptotropic shift processes of the[(R2PCH2PR′2)Ni] fragment and the η3−η1 change of the coordination mode of the benzyl group required for polymerization in those cations.

The relationship between academic library usage and educational performance in Kuwait

University libraries play an important role in contributing to student and faculty members’ academic achievement. This study examines perceptions of university library usage to consider factors that influence achievement of students, academics and administrators. A thorough review of relevant literature examined approaches to determining user satisfaction of students and faculty, and factors that influence library usage. It highlighted the value of usage on educational performance. It enabled development of a theoretical framework leading to the Factors of Academic Library Usage (FALU) model, which was developed to investigate the effect of usage factors. FALU was tested in Kuwait university libraries. The study used validated questionnaires from 792 students, 143 academics and 121 administrators to measure five library factors. Interviews were conducted across the three University libraries. The findings are useful in measuring the correlation between the current academic library usage and educational performance.

Designing an immersive environment for public use

Bystander is a multi-user, immersive, interactive environment intended for public display in a museum or art gallery. It is designed to make available heritage collections in novel and culturally responsible ways. We use its development as a case study to examine the role played in that process by a range of tools and techniques from participatory design traditions. We describe how different tools were used within the design process, specifically: the ways in which the potential audience members were both included and represented; the prototypes that have been constructed as a way of envisioning how the final work might be experienced; and how these tools have been brought together in ongoing designing and evaluation. We close the paper with some reflections on the extension of participatory commitments into still-emerging areas of technology design that prioritise the design of spaces for human experience and reflective interaction.

Patterns and transitions of query reformulation during web searching

Purpose – To investigate and identify the patterns of interaction between searchers and search engine during web searching. Design/methodology/approach – The authors examined 2,465,145 interactions from 534,507 users of Dogpile.com submitted on May 6, 2005, and compared query reformulation patterns. They investigated the type of query modifications and query modification transitions within sessions. Findings – The paper identifies three strong query reformulation transition patterns: between specialization and generalization; between video and audio, and between content change and system assistance. In addition, the findings show that web and images content were the most popular media collections. Originality/value – This research sheds light on the more complex aspects of web searching involving query modifications.

Exploring Indigenous social attitudes and priorities in Australia

Given significant government attention to, and expenditure on, Indigenous equity in Australia, this article addresses a core problem: the lack of a sound understanding of Indigenous social attitudes and priorities. An account of cultural theory raises the likelihood of difference in outlook between Indigenous and non-Indigenous people, including those making and implementing policy. Yet, years of scholarly research and official statistical collections have overlooked potentially critical aspects of Indigineity. Suggestions of difference emerge from reference to the 2007 Australian Survey of Social Attitudes (AuSSA). If the attitudes recorded a small sample in this instrument manifest in the Indigenous population at large, policy priorities and directions should be reviewed and possibly revised. Despite inherent methodological difficulties, the article calls for targeted social attitude research among Australia's Indigenous peoples so that future policy can be better oriented and calibrated. The national benefits would outweigh the costs via better directed policy making.