264 research outputs found

    Deliberating stratospheric aerosols for climate geoengineering and the SPICE project

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    Increasing concerns about the narrowing window for averting dangerous climate change have prompted calls for research into geoengineering, alongside dialogue with the public regarding this as a possible response. We report results of the first public engagement study to explore the ethics and acceptability of stratospheric aerosol technology and a proposed field trial (the Stratospheric Particle Injection for Climate Engineering (SPICE) ‘pipe and balloon’ test bed) of components for an aerosol deployment mechanism. Although almost all of our participants were willing to allow the field trial to proceed, very few were comfortable with using stratospheric aerosols. This Perspective also discusses how these findings were used in a responsible innovation process for the SPICE project initiated by the UK’s research councils

    Number preferences in lotteries

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    We explore people's preferences for numbers in large proprietary data sets from two different lottery games. We find that choice is far from uniform, and exhibits some familiar and some new tendencies and biases. Players favor personally meaningful and situationally available numbers, and are attracted towards numbers in the center of the choice form. Frequent players avoid winning numbers from recent draws, whereas infrequent players chase these. Combinations of numbers are formed with an eye for aesthetics, and players tend to spread their numbers relatively evenly across the possible range

    PTHrP Induces Autocrine/Paracrine Proliferation of Bone Tumor Cells through Inhibition of Apoptosis

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    Giant Cell Tumor of Bone (GCT) is an aggressive skeletal tumor characterized by local bone destruction, high recurrence rates and metastatic potential. Previous work in our lab has shown that the neoplastic cell of GCT is a proliferating pre-osteoblastic stromal cell in which the transcription factor Runx2 plays a role in regulating protein expression. One of the proteins expressed by these cells is parathryroid hormone-related protein (PTHrP). The objectives of this study were to determine the role played by PTHrP in GCT of bone with a focus on cell proliferation and apoptosis. Primary stromal cell cultures from 5 patients with GCT of bone and one lung metastsis were used for cell-based experiments. Control cell lines included a renal cell carcinoma (RCC) cell line and a human fetal osteoblast cell line. Cells were exposed to optimized concentrations of a PTHrP neutralizing antibody and were analyzed with the use of cell proliferation and apoptosis assays including mitochondrial dehydrogenase assays, crystal violet assays, APO-1 ELISAs, caspase activity assays, flow cytometry and immunofluorescent immunohistochemistry. Neutralization of PTHrP in the cell environment inhibited cell proliferation in a consistent manner and induced apoptosis in the GCT stromal cells, with the exception of those obtained from a lung metastasis. Cell cycle progression was not significantly affected by PTHrP neutralization. These findings indicate that PTHrP plays an autocrine/paracrine neoplastic role in GCT by allowing the proliferating stromal cells to evade apoptosis, possibly through non-traditional caspase-independent pathways. Thus PTHrP neutralizing immunotherapy is an intriguing potential therapeutic strategy for this tumor

    Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life

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    Background: Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs) of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L.) Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. Results: In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica) and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. Conclusions: These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence

    Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

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    Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP). While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK) using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung) preferentially metastasize to bone

    Gecko CD59 Is Implicated in Proximodistal Identity during Tail Regeneration

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    Several adult reptiles, such as Gekko japonicus, have the ability to precisely re-create a missing tail after amputation. To ascertain the associated acquisition of positional information from blastemal cells and the underlying molecular mechanism of tail regeneration, a candidate molecule CD59 was isolated from gecko. CD59 transcripts displayed a graded expression in the adult gecko spinal cord with the highest level in the anterior segment, with a stable expression along the normal tail. After tail amputation, CD59 transcripts in the spinal cord proximal to the injury sites increased markedly at 1 day and 2 weeks; whereas in the regenerating blastema, strong CD59 positive signals were detected in the blastemal cells anterior to the blastema, with a gradual decrease along the proximodistal (PD) axis. When treated with RA following amputation, CD59 transcripts in the blastema were up-regulated. PD confrontation assays revealed that the proximal blastema engulfed the distal one after in vitro culture, and rabbit-anti human CD59 antibody was able to block this PD engulfment. Overexpression of the CD59 during tail regeneration causes distal blastemal cells to translocate to a more proximal location. Our results suggest that position identity is not restricted to amphibian limb regeneration, but has already been established in tail blastema of reptiles. The CD59, a cell surface molecule, acted as a determinant of proximal–distal cell identity

    Scholarly Impact: A Pluralistic Conceptualisation.

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    We critically assess a common approach to scholarly impact that relies almost exclusively on a single stakeholder (i.e., other academics). We argue that this approach is narrow and insufficient, and thereby threatens the credibility and long-term sustainability of the management research community. We offer a solution in the form of a broader and novel conceptual and measurement framework of scholarly impact: a pluralist perspective. It proposes actions that depart from the current win–lose and zero-sum views that lead to false trade-offs such as research versus practice, rigor versus relevance, and research versus service. Our proposed pluralist conceptualization can be instrumental in enabling business schools and other academic units to clarify their strategic direction in terms of which stakeholders they are trying to affect and why, the way future scholars are trained, and the design and implementation of faculty performance management systems. We argue that the adoption of a pluralist conceptualization of scholarly impact can increase motivation for engaged scholarship and design-science research that is more conducive to actionable knowledge as opposed to exclusive career-focused advances, enhance the relevance and value of our scholarship, and thereby help to narrow the much-lamented chasm between research and practice
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