EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer

PURPOSE: EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumor initiation, neovascularization, and metastasis in a wide range of epithelial and mesenchymal cancers; however, its role in colorectal cancer recurrence and progression is unclear.

EXPERIMENTAL DESIGN: EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumors (N = 338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive colorectal cancer cell line models.

RESULTS: Colorectal tumors displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III colorectal cancer tissues, in both univariate and multivariate analyses. Preclinically, we found that EphA2 was highly expressed in KRASMT colorectal cancer cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines, and downregulation of EphA2 using RNAi or recombinant EFNA1 suppressed migration and invasion of KRASMT colorectal cancer cells.

CONCLUSIONS: These data show that EpHA2 is a poor prognostic marker in stage II/III colorectal cancer, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. Clin Cancer Res; 22(1); 230-42. ©2015 AACR.

Fast line, arc/circle and leg detection from laser scan data in a player driver

A feature detection system has been developed for real-time identification of lines, circles and people legs from laser range data. A new method sutable for arc/circle detection is proposed: the Inscribed Angle Variance (IAV). Lines are detected using a recursive line fitting method.

Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone

It is recognized that some mutated cancer genes contribute to the development of many cancer types, whereas others are cancer type specific. For genes that are mutated in multiple cancer classes, mutations are usually similar in the different affected cancer types. Here, however, we report exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases of chondroblastoma (95%), we found p.Lys36Met alterations predominantly encoded in H3F3B, which is one of two genes for histone H3.3. In contrast, in 92% (49/53) of giant cell tumors of bone, we found histone H3.3 alterations exclusively in H3F3A, leading to p.Gly34Trp or, in one case, p.Gly34Leu alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding p.Lys27Met and p.Gly34Arg or p.Gly34Val alterations in childhood brain tumors, a remarkable picture of tumor type specificity for histone H3.3 driver alterations emerges, indicating that histone H3.3 residues, mutations and genes have distinct functions.

Licensing in an international triopoly

We study the effects of entry of two foreign firms on domestic welfare in the presence of licensing, when the incumbent is technologically superior to the entrants. We consider two different situations: (i) the cost-reducing innovation is licensed to both entrants; (ii) the cost- reducing innovation is licensed to just one of the entrants. We analyse three kind of license: (lump- sum) fixed-fee; (per-unit) royalty; and two-part tariff, that is a combination of a fixed-fee and a royalty. We prove that a two part tariff is never an optimal licensing scheme for the incumbent. Moreover, (i) when the technology is licensed to the two entrants, the optimal contract consists of a licensing with only output royalty; and (ii) when the technology is licensed to just one of the entrants, the optimal contract consists of a licensing with only a fixed-fee.

Per-unit royalty and fixed-fee licensing in a differentiated Stackelberg model

In the present paper we consider a differentiated Stackelberg model, when the leader firm engages in an R&D process that gives an endogenous cost-reducing innovation. The aim is to study the licensing of the cost-reduction by a per-unit royalty and a fixed-fee. We analyse the implications of these types of licensing contracts over the R&D effort, the profits of the firms, the consumer surplus and the social welfare. By using comparative static analysis, we conclude that the degree of the differentiation of the goods plays an important role in the results.

Digital interconnectivity as a driver for port and logistics competitiveness

Creating an innovative tool that takes advantage of digital interconnectivity between shipping agencies and husbandry services suppliers was the starting point. But the main purpose of this paper is to figure out if that represents a business opportunity. It describes the preliminary stages undertaken, as the connections with the main potential providers of the husbandry services. This was carried out as a qualitative research, based on interviews given by shipping agencies that contributed as a source of data about their activities but also to survey their acceptance of the concept that could change the way of doing business in this area.At the same time, inquiries have been made to build financial scenarios that show the costs and revenue streams allocated to this project. Considering the data collected from the main players in husbandry services and the different outcomes, the feasibility of this project is assessed. Even though the paradigm was well received by all the firms contacted, the development costs turn out to be the main threat to the project so further steps are advised.

The Pursuit of Efficient Copyright Licensing : How Some Rights Reserved Attempts to Solve the Problems of All Rights Reserved

This dissertation analyses the growing pool of copyrighted works, which are offered to the public using Creative Commons licensing. The study consist of analysis of the novel licensing system, the licensors, and the changes of the "all rights reserved" —paradigm of copyright law. Copyright law reserves all rights to the creator until seventy years have passed since her demise. Many claim that this endangers communal interests. Quite often the creators are willing to release some rights. This, however, is very difficult to do and needs help of specialized lawyers. The study finds that the innovative Creative Commons licensing scheme is well suited for low value - high volume licensing. It helps to reduce transaction costs on several le¬vels. However, CC licensing is not a "silver bullet". Privacy, moral rights, the problems of license interpretation and license compatibility with other open licenses and collecting societies remain unsolved. The study consists of seven chapters. The first chapter introduces the research topic and research questions. The second and third chapters inspect the Creative Commons licensing scheme's technical, economic and legal aspects. The fourth and fifth chapters examine the incentives of the licensors who use open licenses and describe certain open business models. The sixth chapter studies the role of collecting societies and whether two institutions, Creative Commons and collecting societies can coexist. The final chapter summarizes the findings. The dissertation contributes to the existing literature in several ways. There is a wide range of prior research on open source licensing. However, there is an urgent need for an extensive study of the Creative Commons licensing and its actual and potential impact on the creative ecosystem.

Creating a global consciousness throught the driver model of curriculum development

The purpose of this study was to investigate the effect a human link through the One World Youth Project has on a global education program, if a human connection through the program enhances a student's ability to develop a critical consciousness of global issues, and the etTectiveness of thc constructivist-based Driver Model of Curriculum Development, which served as the curriculum model in this study. An action based research cycle was chosen as this study's research methodology and incorporated 5 qualitative data collection instruments: a) interviews and questionnaires, b) artifacts, c) teacher journal, d) critical friend's observation forms, and e) my critical friend's postobservation interviews. The data were conected from 4 student participants and my critical friend during all stages of the action research cycle. The results of this study provide educators with data on the impact of human connections in a global education program, the effects these connections have on students, and the effectiveness of the Driver Model of Curriculum Development. This study also provides practical activities and strategies that could be used by educators to develop their own global education programs. The United Nations drafted the Millennium Development Goals in an effort to improve the lives of billions of people across the globe. The eight goals were developed with the support of all member nations since all human beings are global citizens who have a responsibility to make the world a better place. Students need to develop a critical consciousness of global issues so that they can work with others to eliminate them. Students who are taught to restate the opinions of others win not be prepared to inherit a world full of challenges that will require new innovative ideas to foster positive change.

Lovell's Business and Professional Directory of the Province of Ontario, for 1882, Alphabetically arranged as to Places, Names, Business and Professions, with a Classified Business Directory of the City of Montreal (1882)

Business directory for the Province of Ontario for the year 1882.

Dominion of Canada and Colony of Newfoundland Gazetteer and Classified Business Directory (1899)

Business directory for Canada and Newfoundland for the year 1899

Brand Associations of Minor Hockey Tournaments: Understanding the Rep Hockey Parents' Perspective

Tournaments and other hockey-related activities have been calculated to be a significant driver of tourist dollars for many regions across Canada. The competition to attract teams to participate in tournaments, which benefit the tournament organizers and the communities in which they reside, is significant. Consequently, the purpose of the study was to assess the brand associations that representative (rep) minor hockey parents from Ontario’s Greater Golden Horseshoe Region perceive as relevant when considering ideal tournaments for their child to participate in. Brand associations have been classified as the attributes, benefits, or attitudes one uses to develop a perception of a product or service. To investigate the current study, 30 interviews were conducted using a laddering interview technique. Findings indicate that there are seven attributes and nine benefits that impact a tournament’s brand association including: competition, tournament operations, accommodations, bonding, fun, parity, and time management. The interrelationship between the identified attributes and benefits is discussed while recommendations and directions for future research are presented.

Thesaurus of english words and phrases classified and arranged so asto facilitate the expression of ideas and assiet in literary composition

UANL

The Ex Post Profitability of Licensing Thechnology.

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A Practical Grammar in Which Words, Phrases, and Sentences are Classified According to Their Offices and...

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