6 research outputs found

    Business angels and early stage decision making criteria: empirical evidence from an emerging market

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    How do business angels assess a prospective entrepreneurial firm when they make an investment decision? This article examines a central question that informal venture capitalists have been struggling with for decades: What early stage decision making criteria do investors define and apply to reduce the volume of potential deals to a more manageable size? Based on semi-structured interviews with business angels in an emerging market, we show that investors are focused on the industry structure and product features, on the other side, our results also suggest a very strong support for the personality of the entrepreneur and management team. More specifically, entrepreneur trustworthiness is an essential element affecting an investor’s decision to close a deal. Business angels set requirements in terms of the entrepreneur’s equity stake in the start-up and monitoring tools to prevent the failure of investee firms. Our findings suggest that if there are warning signs that the project is in an existential crisis, most of the investors will reject their participation. We believe that our empirical results support both researchers and practitioners to establish a better understanding between the well-developed financial theories and the underresearched informal venture capital market in a Central and Eastern European country

    Transcription activity of rRNA genes correlates with a tendency towards intergenomic homogenization in Nicotiana allotetraploids

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    International audienceThis paper establishes relationships between two aspects of ribosomal DNA (rDNA) biology: epigenetic silencing of rDNA loci; and homogenization leading to concerted evolution. Here, we examined rDNA inheritance and expression patterns in three natural Nicotiana allopolyploids (closest living descendants of diploid parents are given), N. rustica (N. paniculata x N. undulata), N. tabacum (N. sylvestris x N. tomentosiformis) and N. arentsii (N. undulata x N. wigandioides), and synthetic F-1 hybrids and allopolyploids. The extent of interlocus rDNA homogenization decreased in the direction N. arentsii > N. tabacum > N. rustica. The persistence of parental rDNA units in one of the subgenomes was associated with their transcription inactivity and likely heterochromatization. Of synthetic hybrids and polyploids only N. paniculata x N. undulata showed strong uniparental transcriptional silencing of rDNA triggered already in F-1. Epigenetic patterns of expression established early in allopolyploid nucleus formation may render units susceptible or resistant to homogenization over longer time-frames. We propose that nucleolus-associated transcription leaves rDNA units vulnerable to homogenization, while epigenetically inactivated units, well-separated from the nucleolus, remain unconverted

    Passive Intestinal Absorption of Representative Plant Secondary Metabolites: A Physicochemical Study

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    Natural products are generally ingested as part of traditional herbal decoctions or in the current diet. However, in natural product research, the bioavailability of secondary metabolites is often poorly investigated. In this work, a systematic study was carried out in order to highlight the physicochemical parameters that mainly influence the passive intestinal absorption of natural products. For this, a representative set of natural products including alkaloids, coumarins, flavonoid aglycones and glycosides, and carboxylic acids was selected and their physicochemical properties were predicted using relevant Volsurf+ descriptors. The chemical space obtained with this unbiased method was then correlated with experimental passive intestinal permeability data, which highlighted the main influence of lipophilicity, global hydrophilicity, size, and the ionisation state on passive intestinal absorption of natural products. Since the pH range encountered in the intestine is wide, the influence of the ionisation was investigated deeper experimentally. The ionisation state of weakly ionisable natural products, such as flavonoid aglycones, alkaloids, and carboxylic acids, was found to prevent the passive intestinal absorption of such natural products completely. In addition, the impact of solubility issues on passive permeability results was evaluated in cases of poorly water-soluble natural products, such as flavonoid aglycones and coumarins. The biomimetic fasted state simulated fluid-version 2 was found to improve the apparent solubility of such poorly soluble natural products without influencing their permeability behaviours. The use of such a solubilising buffer was found to be well adapted to the hexadecane membrane-parallel artificial membrane permeability assay and can circumvent the solubility issues encountered with poorly soluble natural products in such an assay

    Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

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    Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11‚Äą154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3¬∑3 years (IQR 2¬∑8‚Äď3¬∑8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7¬∑3%] of 5558 vs 480 [8¬∑6%] of 5596; HR 0¬∑85 [95% CI 0¬∑74‚Äď0¬∑97], p=0¬∑013). The same effect was not observed in patients without PCI (p=0¬∑76, p interaction=0¬∑16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3¬∑1%] with ticagrelor vs 183 (3¬∑3%) with placebo; HR 0¬∑96 [95% CI 0¬∑78‚Äď1¬∑18], p=0¬∑68), as well as all-cause death (282 [5¬∑1%] vs 323 [5¬∑8%]; 0¬∑88 [0¬∑75‚Äď1¬∑03], p=0¬∑11). TIMI major bleeding occurred in 111 (2¬∑0%) of 5536 patients receiving ticagrelor and 62 (1¬∑1%) of 5564 patients receiving placebo (HR 2¬∑03 [95% CI 1¬∑48‚Äď2¬∑76], p<0¬∑0001), and fatal bleeding in 6 (0¬∑1%) of 5536 patients with ticagrelor and 6 (0¬∑1%) of 5564 with placebo (1¬∑13 [0¬∑36‚Äď3¬∑50], p=0¬∑83). Intracranial haemorrhage occurred in 33 (0¬∑6%) and 31 (0¬∑6%) patients (1¬∑21 [0¬∑74‚Äď1¬∑97], p=0¬∑45). Ticagrelor improved net clinical benefit: 519/5558 (9¬∑3%) versus 617/5596 (11¬∑0%), HR=0¬∑85, 95% CI 0¬∑75‚Äď0¬∑95, p=0¬∑005, in contrast to patients without PCI where it did not, p interaction=0¬∑012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk