607 research outputs found

    Judicial Restraint?

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    An independent judiciary is one of the cornerstones of American democracy and the rule of law. But increasing challenges to the authority of judges have many in the legal community concerned about maintaining the rightful balance of power

    Towards a new understanding of decision-making by hematopoietic stem cells

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    Cells within the hematopoietic stem cell compartment selectively express receptors for cytokines that have a lineage(s) specific role; they include erythropoietin, macrophage colony-stimulating factor, granulocyte colony-stimulating factor, granulocyte/macrophage colony-stimulating factor and the ligand for the fms-like tyrosine kinase 3. These hematopoietic cytokines can instruct the lineage fate of hematopoietic stem and progenitor cells in addition to ensuring the survival and proliferation of cells that belong to a particular cell lineage(s). Expression of the receptors for macrophage colony-stimulating factor and granulocyte colony-stimulating factor is positively autoregulated and the presence of the cytokine is therefore likely to enforce a lineage bias within hematopoietic stem cells that express these receptors. In addition to the above roles, macrophage colony-stimulating factor and granulocyte/macrophage colony-stimulating factor are powerful chemoattractants. The multiple roles of some hematopoietic cytokines leads us towards modelling hematopoietic stem cell decision-making whereby these cells can ‘choose’ just one lineage fate and migrate to a niche that both reinforces the fate and guarantees the survival and expansion of cells as they develop

    Targeting the retinoic acid pathway to eradicate cancer stem cells

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    All-trans retinoic acid is a morphogen during embryogenesis and a teratogen. Cancer is an error of development, and the retinoic acid receptors (RAR) for all-trans retinoic acid play a role in cancer. Expression of the cytosolic aldehyde dehydrogenases, which mediate the last step to the synthesis of all-trans retinoic acid, is deregulated in various human cancers. Inhibiting these enzymes using a variety of agents reduced the proliferation of lung cancer cells, reduced the proliferation and induced apoptosis of ovarian, prostate, squamous, and uterine cancer cells, and sensitised breast, colorectal and ovarian cancer cells to chemotherapeutic agents. RARγ is an oncogene within some cases of AML, cholangiocarcinoma, colorectal cancer, clear cell renal cell carcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, prostate cancer, and ovarian cancer. Pan-RAR and RARγ antagonist inhibition of the action of RARγ led to necroptosis of human prostate and pediatric brain tumour cancer stem cells. Treatment of hepatocellular carcinoma cells with the flavenoid acacetin, which interferes with the action of RARγ, decreased cell growth and induced apoptosis. Targeting the retinoic acid pathway is promising regarding the development of new drugs to eradicate cancer stem cells

    Groupoid equivalence and the associated iterated crossed product

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    Given groupoids GG and HH and a (G,H)(G,H)-equivalence XX we may form the transformation groupoid G⋉X⋊HG\ltimes X\rtimes H. Given a separable groupoid dynamical system (A,G⋉X⋊H,ω)(A,G\ltimes X\rtimes H,\omega) we may restrict ω\omega to an action of G⋉XG\ltimes X on AA and form the crossed product A⋊G⋉XA\rtimes G\ltimes X. We show that there is an action of HH on A⋊G⋉XA\rtimes G\ltimes X and that the iterated crossed product (A⋊G⋉X)⋊H(A\rtimes G\ltimes X)\rtimes H is naturally isomorphic to the crossed product A⋊(G⋉X⋊H)A\rtimes (G\ltimes X\rtimes H).Comment: 18 pages; changed typo in titl

    Full Disclosure: Why Bank Transparency Matters

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    This report seeks to reinvigorate the debate on bank disclosure in the UK and to create a better understanding of why it should be demanded of banks. This analysis is carried out through detailed case studies comparing Charter One Bank in Chicago in the US where banks have disclosed local lending practices since 1975- with its parent company Royal Bank of Scotland in Manchester to review the level of information available and the impact that this has. To do this we evaluate the available information on small-business lending, bank branch availability and basic bank account opening in underserved areas of Manchester. Our analysis indicates that data on these factors is generally difficult to obtain, inconsistent, and in many cases incomplete

    Editorial: Targeted therapies for Aggressive Cancers

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    Automation and miniaturization of a microbial fermentation platform for the production of antibody fragments

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    Automation and miniaturization is currently a hot topic in many industries, and the Bioprocessing industry is no exception. The potential benefits of automating and miniaturizing our Microbial fermentation process development work include reducing our process development timelines by improving our throughput and making better use of available resources. With these aims in mind, two systems have been implemented in UCB’s fermentation process development laboratories, namely the Ambr250 Modular system from Sartorius and the Freedom Evo 200 from Tecan. It has been demonstrated that the Ambr250 modular system is comparable to 5L scale glass STR’s over a range of parameters including growth, titre and cell viability. The disposable nature of the system has resulted in a significant saving of man-days per experiment. In combination with this, the Tecan robot has been used to both automate plate based assays and to enable rapid purification of protein samples ready for further product quality analysis to support a QbD approach. In this work we have considered the challenges that will need to be addressed to reach the ultimate aim of a fully automated miniaturized Upstream Process development platform for E.coli

    A post-mortem of regional innovation policy failure : Scotland's Intermediate Technology Initiative (ITI)

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    Brown R., Gregson G. and Mason C. A post-mortem of regional innovation policy failure: Scotland's Intermediate Technology Initiative (ITI), Regional Studies. The Intermediate Technology Initiative (ITI) was one of the most ambitious ‘systemic’ regional innovation policy instruments developed in the UK in recent years. However, little of the ITI's anticipated outputs materialized and the programme was prematurely terminated. This paper examines the reasons for its failure, which largely centred on the programme's inappropriate design. The findings suggest that greater recognition needs to be given to the specificities of local entrepreneurial ecosystems when designing, aligning and executing systemic innovation policy instruments. It is argued that paying greater attention to policy failures could potentially help innovation scholars better understand how innovation systems function.PostprintPeer reviewe
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