5,051 research outputs found

    Required Rates of Return for Corporate Investment Appraisal in the Presence of Growth Opportunities

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    Traditional methods of estimating required rates of return overstate hurdle rates in the presence of growth opportunities. We attempt to quantify this effect by developing a simple model which: (i) identifies those companies that have valuable growth opportunities; (ii) splits the value of shares into 'assets-in-place' and 'growth opportunities'; and (iii) splits the equity β into β for 'assets-in-place' and 'growth opportunities'. We find growth opportunities for UK companies over the 1990–2004 period to average 33% of equity value. Incorporating the effect of growth opportunities, the average cost of capital for investment purposes falls by 1.1 percentage points

    Stable isotope probing: Technical considerations when resolving ¹⁵N-labeled RNA in gradients

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    RNA based stable isotope probing (SIP) facilitates the detection and identification of active members of microbial populations that are involved in the assimilation of an isotopically labeled compound. ¹⁵N-RNA-SIP is a new method that has been discussed in recent literature but has not yet been tested. Herein, we define the limitations to using ¹⁵N-labeled substrates for SIP and propose modifications to compensate for some of these shortcomings. We have used ¹⁵N-RNA-SIP as a tool for analysing mixed bacterial populations that use nitrogen substrates. After incubating mixed microbial communities with ¹⁵N-ammonium chloride or ¹⁵N₂ we assessed the fractionation resolution of ¹⁵N-RNA by isopycnic centrifugation in caesium trifluoroacetate (CsTFA) gradients. We found that the more isotopic label incorporated, the further the buoyant density (BD) separation between ¹⁵N- and ¹⁴N-RNA, however it was not possible to resolve the labeled from unlabeled RNA definitively through gradient fractionation. Terminal-restriction fragment length polymorphism (T-RFLP) analysis of the extracted RNA and fluorescent in situ hybridisation (FISH) analysis of the enrichment cultures provided some insight into the organisms involved in nitrogen fixation. This approach is not without its limitations and will require further developments to assess its applicability to other nitrogen-fixing environments

    Activation of Akt at T308 and S473 in alcohol, tobacco and HPV-induced HNSCC:is there evidence to support a prognostic or diagnostic role?

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    BACKGROUND: Tobacco, alcohol and HPV infection are associated with increased risk of HNSCC. However, little is known about the underlying signaling events influencing risk. We aimed to investigate the relationship between these risk factors and Akt phosphorylation, to determine prognostic value. METHOD: VEGF-positive HNSCC biopsies, with known HPV status, were analyzed by immunohistochemistry (IHC) for Akt, phosphorylated at residues S473 and T308. Comparisons between the tissues were carried out using a Mann–Whitney U test. Associations between the variables and continuous immunohistochemical parameters were evaluated with general linear models. Patient characteristics and pAkt IHC score were analyzed for possible association with overall survival by Cox proportional hazard models. RESULTS: Immunohistochemistry revealed that cancer patients had significantly higher levels of pAkt T308 than S473 (P < 0.001). Smoking and alcohol were found to be independent risk factors for Akt phosphorylation at T308 (P = 0.022 and 0.027, respectively). Patients with tumors positive for HPV or pAkt S473 had a poorer prognosis (P = 0.005, and 0.004, respectively). Patients who were heavy drinkers were 49 times more likely to die than non-drinkers (P = 0.003). Patients with low pAkt T308 were more likely to be HPV positive (P = 0.028). Non-drinkers were also found to have lower levels of pAkt T308 and were more likely to have tumors positive for HPV than heavy drinkers (P = 0.044 and 0.007, respectively). CONCLUSION: This study suggests different mechanisms of carcinogenesis are initiated by smoking, alcohol and HPV. Our data propose higher phosphorylation of Akt at T308 as a reliable biomarker for smoking and alcohol induced HNSCC progression and higher phosphorylation of Akt at S473 as a prognostic factor for HNSCC

    Assessing the potential economic benefits to farmers from various GM crops becoming available in the European Union by 2025: results from an expert survey

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    This paper reports on a study that identified a range of crop-trait combinations that are: agronomically suited to the EU; provide advantages to arable farmers and consumers; and are either already available in international markets, or advancing along the development pipeline and likely to become available by 2025. An expert stakeholder panel was recruited and asked for their views, using the Delphi approach, on the impact of these crop-traits on enterprise competitiveness, through changes to yields, production costs and product prices. In terms of input traits, there was consensus that traits such as herbicide tolerant/insect resistant (HT/IR) maize, HT sugar beet and HT soya bean would provide positive benefits for farmers. Output-side traits such as winter-sown rape with reduced saturated fats, were seen as offering benefits to consumers, but were either likely to be restricted to niche markets, or offer relatively modest price premia to farmers growing them. Our analysis of the financial impact of the adoption of GM crops more widely in the EU, showed that the competitiveness of the agricultural sector could well be improved by this. However, such improvements would be relatively small-scale in that large-scale national natural advantages from either economic or environmental conditions is unlikely to be overturned

    Challenges facing immediate tourism leveraging: evidence from the London 2012 Olympic Games

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    Models of event leveraging identify strategies that organisers can use to increase the benefits that sport events bring to host destinations. Amongst these, leveraging tourism benefits during the event is a frequently cited strategy by which organisers can bring more money into a destination. To date, little work has been conducted on leveraging immediate tourism benefits from mega sport events. In addressing this issue, we reflect and present findings related to previously identified event leveraging theories that are determined by tourists’ activities at a host destination. These are (a) enticing visitor spending and (b) lengthening visitor stay. The aim of this paper is to evaluate the use of such leveraging strategies during the London 2012 Olympic Games to increase event-related tourism. Results from 15 interviews with key stakeholders demonstrate that the effectiveness of these leveraging strategies can be limited by a number of challenges: (1) limited strategies to entice visitor spending (2) limited interest in tourism attractions (3) lack of location attractiveness (4) the displacement effect and (5) the impact of the wider economic environment. Key challenges and opportunities are detailed, a discussion on the implications for event leveraging is provided and potential areas for future research are outlined

    And Then He Asked Me

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    arrangement for Regular Music of song by Jeremy Peyton Jones, text from James Joyc

    The NIRSPEC Brown Dwarf Spectroscopic Survey II: High-Resolution J-Band Spectra of M, L and T Dwarfs

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    We present a sequence of high resolution (R~20,000 or 15 km/s) infrared spectra of stars and brown dwarfs spanning spectral types M2.5 to T6. Observations of 16 objects were obtained using eight echelle orders to cover part of the J-band from 1.165-1.323 micron with NIRSPEC on the Keck II telescope. By comparing opacity plots and line lists, over 200 weak features in the J-band are identified with either FeH or H2O transitions. Absorption by FeH attains maximum strength in the mid-L dwarfs, while H2O absorption becomes systematically stronger towards later spectral types. Narrow resolved features broaden markedly after the M to L transition. Our high resolution spectra also reveal that the disappearance of neutral Al lines at the boundary between M and L dwarfs is remarkably abrupt, presumably because of the formation of grains. Neutral Fe lines can be traced to mid-L dwarfs before Fe is removed by condensation. The neutral potassium (K I) doublets that dominate the J-band have pressure broadened wings that continue to broaden from ~50 km/s (FWHM) at mid-M to ~500 km/s at mid-T. In contrast however, the measured pseudo-equivalent widths of these same lines reach a maximum in the mid-L dwarfs. The young L2 dwarf, G196-3B, exhibits narrow potassium lines without extensive pressure-broadened wings, indicative of a lower gravity atmosphere. Kelu-1AB, another L2, has exceptionally broad infrared lines, including FeH and H2O features, confirming its status as a rapid rotator. In contrast to other late T objects, the peculiar T6 dwarf 2MASS 0937+29 displays a complete absence of potassium even at high resolution, which may be a metallicity effect or a result of a cooler, higher-gravity atmosphere.Comment: 53 pages, 21 figures, data will be available at http://www.astro.ucla.edu/~mclean/BDSSarchive

    Going Down

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    arrangement for Irregular Music of song by Jeremy Peyton Jones, text by David Gal

    Tuning

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    arrangement for Irregular Music of song by Jeremy Peyton Jones, text by David Gal

    The alternate GNB3 splice variant, Gβ3s, exhibits an altered signalling response to EGF stimulation, which leads to enhanced cell migration

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    It has recently been reported that the duplication of the GNB3 gene has been shown to be directly linked to an obesity phenotype, both in humans and also in a humanised mouse model. Moreover, the common human GNB3 c.825C&gt;T polymorphism (rs5443) causes this ubiquitously expressed gene to be aberrantly spliced approximately 50% of the time leading to the production of both a normal Gβ3 protein and a truncated, possibly less stable subunit, known as Gβ3s. The presence of the GNB3 825T allele has previously been shown to be associated with predisposition to hypertension, obesity, various cancers, Alzheimers, age related cognitive function, erectile dysfunction as well as a marker for pharmacogenetic drug action. Great controversy, however, currently exists as to whether these phenotypes associated with the 825T allele are a) mainly due to the presence of the smaller, possibly more active, Gβ3s subunit or b) merely down to the haploinsufficiency of the normal GNB3 transcript, due to its frequent aberrant splicing. In order to try and address these two conflicting hypothesis, we report on the identification and characterisation of signalling alterations unique to the presence of Gβ3s protein subunit. Moreover we also show the physiological consequences associated with altered signalling, directly induced by the Gβ3s subunit. For this, we used both an EBV transformed lymphoblast cell line homozygote for GNB3 825T/825T (TT) and a stable Gβ3s expressing recombinant COS-7 clone. In both of these cell lines that express the Gβ3s subunit, we found enhanced cytosolic calcium influx upon stimulation with EGF, TGFα and VEGF ligands, as compared to “normal” GNB3 controls with the 825C/825C (CC) genotype. This aberrant calcium influx also led to an increase in ERK, but not AKT1, phosphorylation. Despite the lack of AKT1 activation, we paradoxically observed a significant increase in phosphorylation of its downstream substrates, namely mTOR and p70S6k (KS6B2). Moreover we observed a decrease in phospho FoxO3a only in Gβ3s expressing cells, but not in the “normal” GNB3 (CC) control cell line. The presence of the Gβ3s subunit also appeared to alter the distinct localisation patterns of both Foxo3a and AKT1, while also increasing the colocalisation of mTOR and p70S6K. Subsequent growth factor stimulation studies revealed that EGF treatment, of Gβ3s expressing cells, appeared to cause a significant decrease in cAMP levels, which, in turn resulted in both enhanced caveolin-1a phosphorylation, and an increase in actin stress fibre formation. The identification of these distinct Gβ3s specific signalling alterations were indicative of a more aggressive migratory phenotype. This led us to further investigate and confirm that the presence of the Gβ3s subunit also appears to cause significantly enhanced migration and robust scratch wound healing kinetics, as compared to cells harbouring only the normal copy of the gene. These data therefore present convincing evidence that the Gβ3s subunit is stable, functional and its presence can significantly alter signalling pathways, in different cell types
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