226 research outputs found
Oncometabolite induced primary cilia loss in pheochromocytoma
No full textBarts and the London Charity Clinical Research Training Fellowships to Samuel M. O’Toole [grant number MRD0191]; Medical Research Council (MRC) [grant number MR/L002876/1].
UK Biotechnology and Biological Sciences Research Council (BBSRC) [grant
503 number BB/M0020611] and MRC [grant number MR/N009185/1] to Dr Tyson V. Shar
Intel Corp. v. Hamidi: Tresspas to Chattels, the Internet\u27s Greatest Antagonist?
No full textThis Casenote examines the recent California Court of Appeals decision in Intel Corp. v. Hamidi and argues that by departing from the strict common law requirements and upholding a permanent injunction on the grounds of trespass to chattels, the court destroyed the elements and reasons that underlie the tort of trespass to chattels, in essence creating a new tort. The author argues that in doing so the court rejected the traditional definition of trespass to chattels and paved the way for absurd judicial results that have the potential to result in enormous adverse consequences
Influence profile of wastewater chain in Amsterdam: Towards resilient system for phosphorus recovery and Valorisation
No full textThe wastewater system of Amsterdam offers an opportunity to recover phosphorus, and contribute to circular economy. However, it remains unclear where to intervene in system to maximize recovery and valorisation in a resilient and feasible way. The Design Structure Matrix method was tested to define the system architecture from Food-Water-Energy nexus perspective. Physical, phosphorus, and ownership dependencies between Infrastructure, Stakeholder, Resource and Cleantech domains (elements) of the wastewater system in Amsterdam are analyzed in a Multi-Domain Matrix model. Change Propagation Indicator quantified critical elements, and emergent changes. An Influence Profile unveiled four levels of system leverage: household, neighborhood, city-block, region. The stakeholders can engage into optimizations at each level, to generate individual and shared benefits. Hybrid infrastructure, plug&play solutions and modular approach to cleantech will harness up to 100% of phosphorus available. The method proved to be an effective tool for analysing complexity and engineering resilient solutions for the circular economy.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Sanitary Engineerin
Influence of cleantech interventions on wastewater chain and City of Amsterdam: Towards a resilient system for phosphorus recovery & valorisation
No full textThe wastewater chain of Amsterdam offers an opportunity to recover up to 100% of phosphorus per year, versus 47% currently recovered. However, for the stakeholders of Amsterdam (e.g. citizens, business) it remains difficult to scale-up existing solutions for resource recovery. Mainly, due to the limitations of the widelyused methods (e.g. mass flow, life-cycle analysis) to provide holistic assessment of the solutions and the changes they will propagate outside the wastewater chain (e.g. solid waste). In the current study, three existing phosphorus recovery Solutions applied at three scales of Amsterdam (city, neighborhood, house) were analyzed. The study showed that the house scale closed-loop solution has higher positive influence on resilience of the city. Moreover, the DSM indicators could be used to measure resilience of the city and constituent parts, given an influence of a specific Solution. The developed toolkit is applicable for analysis of other resources in the wastewater of Amsterdam.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Sanitary Engineerin
Spotřeba masa: Je naše svobodná volba ve skutečnosti taková?
No full textSpotřeba masa, její rámování v médiích a dopady na společnost jsou velmi zajímavé pro vědce, marketingové specialisty a širokou veřejnost. I když se zdá, že lidé vědí o závažných problémech spojených se spotřebou masa, celosvětově stále roste. Tato práce si klade za cíl prozkoumat, jak se vytváří určitý vztah mezi masem a jeho spotřebiteli, a co ovlivňuje tento proces. Práce opírá své závěry o literární rešerši, zaměřenou především na fenomén disociace masa a kultivaci médií, a kvalitativní sémiotickou analýzu televizních reklam vysílaných nejúspěšnějším producentem masa v USA, Tyson Foods Inc. Studie ukazuje, že symbolika vytvořená kolem masa se úzce souvisí s konkrétními požadovanými stavy mysli a životním stylem, zatímco spojení mezi masem a zvířaty zcela chybí. Dále dochází k závěru, že uvedená symbolika je postavena na určitých genderových rolích a kulturních charakteristikách přítomných ve společnosti. Autor věří, že tato zjištění mohou být zajímavá pro ty, kteří se snaží přetvořit roli masa v našem každodenním životě a zaměřit se na podporu udržitelnějších alternativ.Meat consumption, its framing in the media and its effects on society have been of high interest to various scholars, marketing specialists and the wider public. While people seem to be knowledgeable of certain problems connected to meat consumption, it continues growing worldwide. This paper aims to investigate how a particular relationship between meat and its consumers is being created, and what influences this process. The paper grounds its conclusions on literature review, primarily focused on the phenomena of meat dissociation and media cultivation, and qualitative semiotic analysis of TV commercials aired by the U.S. most successful meat producer Tyson Foods Inc. The study shows that symbolism created around meat is closely linked to particular desired states of mind and lifestyles, while the link between meat and animals is completely absent. It further concludes that the mentioned symbolism is built upon certain gender roles and cultural characteristics present in the society. The author believes that the findings can be of interest to those who aim to re-shape the role of meat in our daily lives and focus on the promotion of more sustainable alternatives
Abstract A31: Targeting APC loss using synthetic lethality in Colorectal Cancer
No full textAbstract
Background: Mutations in the tumor suppressor gene Adenomatous Polyposis Coli (APC) are found in 80% of sporadic colorectal cancer (CRC) tumors and are also responsible for the inherited form of CRC, Familial Adenomatous Polyposis (FAP). APC mutations typically occur early in the development of CRC, followed by mutations in KRAS, SMAD2/3/4 and TP53. The majority of mutations in APC occur in a region known as the mutation cluster region (MCR). This region is responsible for negatively regulating levels of B-catenin and therefore the level of Wnt signaling activation. In APC mutated tumors, B-catenin is not tightly regulated resulting in hyperactivation of the Wnt signaling pathway leading to uncontrolled cellular proliferation, differentiation, migration and apoptosis.
Aim: We aim to use the concept of synthetic lethality to identify novel therapeutic targets for the treatment of APC mutated CRC.
Results: In order to identify novel therapeutic targets for the treatment of APC mutated CRC, we have generated an in vitro model of APC mutant CRC using a lentiviral CRISPR-cas9 system. Using the APC wildtype colorectal carcinoma cell line RKO, we targeted the cells with a guide RNA targeting the start of the final exon of APC, which covers 80% of the coding region. These cell lines allow us to identify targets, which are synthetically lethal with the APC mutation. To identify novel potential drug targets, we have used two parallel screening approaches. Firstly, we have screened our cell lines with a library of siRNA silencing over 700 kinases. Typically kinases are easy to target pharmaceutically, with many kinase inhibitors already clinically available. Upon analysis, we have identified seven genes which show synthetic lethality with the APC mutation, whilst not harming the control wildtype APC cells. In parallel, we have screened over 1000 FDA-approved compounds to identify drugs which cause increased selective lethality in APC mutant cells. From screening our FDA-approved compounds, we have identified a number of compounds which display synthetic lethality with the APC mutation.
Conclusions: We have identified seven genes as potential therapeutic targets and a number of FDA-approved compounds, which could potentially be new selective therapies for 80% of CRC patients. Currently we are validating these findings and investigating the mechanism of synthetic lethality with APC mutation. To further validate our findings we are also exploring whether these results extend to other CRC cell lines with different mutational backgrounds, this will help us access how many patients may benefit from our novel therapeutic targets.
Acknowledgments: We would like to thank Bowel and Cancer Research and The Rosetree Trust for co-funding this project.
Citation Format: Hannah Shailes, Gemma Bridge, Daniel Foxler, Tyson V. Sharp, Andrew Silver, Sarah A. Martin. Targeting APC loss using synthetic lethality in Colorectal Cancer [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr A31.</jats:p
MicroRNA-mediated gene silencing: are we close to a unifying model?
No full textAbstractMicroRNAs (miRNAs) comprise a group of small non-coding RNA –21 nucleotides in length. They act as post-transcriptional regulators of gene expression by forming base pairing interactions with target messenger RNA (mRNA). At least 1000 miRNAs are predicted to be expressed in humans and are encoded for in the genome of almost all organisms. Functional studies indicate that every cellular process studied thus far is regulated at some level by miRNAs. Given this expansive role, it is not surprising that disruption of this crucial pathway underlies the initiation of, or in the least, contributes to the development and progression of numerous human diseases and physiological disorders. This review will focus on the latest developments in uncovering the mechanism(s) of miRNA-mediated silencing with specific reference to the function of terminal effector proteins, how translation of target mRNA is inhibited and whether we are moving towards understanding this fundamental gene silencing paradigm.</jats:p
A Year in the Works: A Record of Engineering and Management Experience at Freese and Nichols, Inc.
No full textThis manuscript presents the author's experience as a fulltime graduate engineer at Freese and Nichols, Inc. (FNI), a professional engineering an servicebased consulting firm, as a Record of Study (ROS) for the Doctor of Engineering (DE) degree at Texas A&M University. Through the course of the internship, the author was to familiarize himself with FNI organizational procedures and fulfill established internship objectives concerning technical, managerial, strategic, and societal achievement. In meeting the above requirements, the author describes the history and key aspects of the FNI business, discusses established managerial procedures at FNI, presents direct work experience on projects during the DE internship period, and presents outcomes towards the internship objectives. FNI has a storied history, and the FNI business model centers around its ability to sell its employees time on projects; it requires technical expertise and client relationships that facilitate selection for the work. FNI's organizational structure and managerial procedures are designed to emphasize the company's differentiated strategy towards high quality customer service. The author worked on several projects throughout the internship; however, the primary role was via the Highlands Bond Program, which involved the design of multiple water resources structures. Through the awareness of the FNI business concept and these projects, the key outcomes of the DE internship were noted, as numbered below. 1) The author fulfilled all internship objectives. 2) As a function of the projects, technical/engineering skills were applied and learned, and a greater appreciation for the interconnectedness of technical disciplines was developed. 3) The author concluded that the Assistant Project Manager (APM) role, of which the author served while on the internship, offers significant managerial and strategic benefits to FNI, and that the role can facilitate faster individual growth and greater project ownership. 4) Strategically, all projects are important in a business, even if they are less technically advanced. 5) Recommendations that could potentially improve the engineering programs at Texas A&M include a) providing greater emphasis on developing the soft skills of engineering, and b) potentially adding dam management/design and pipeline/pump station design to the water resources portions of the Texas A&M Curriculum. 6) The author noted that FNI is a well-managed company, and that his observations during the DE internship reinforced this statement
Touching Freud's dog: H.D.'s tactile poetics
No full text"Do not touch me", Frau Emmy warns Freud in 1889. "Do not touch", Freud echoes in 1933. This time, he is referring to his pet chow, Yofi, warning H.D. that "she snaps - she is very difficult with strangers". Examining the prohibition in light of work by Jacques Derrida and Jean-Luc Nancy, this article charts the withdrawal that always interrupts touch. Despite Freud's taboo, however, H.D.'s writing seeks to make contact in strange and unnerving ways. Developing Julia Kristeva's account of the semiotic, this paper proposes a literature of touch. Reading H.D.'s poems, alongside Tribute to Freud, and her letters, the author demonstrates that H.D.'s poetics are always haunted by the very (im)possibility of contact
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