Why business angels reject investment opportunities: Is it personal?

A major focus of research on business angels has examined their decision-making processes and investment criteria. As business angels reject most of the opportunities that they receive, this article explores the reasons informing such decisions. In view of angel heterogeneity, investment opportunities might be expected to be rejected for differing reasons. Two sources of data are used to examine this issue. Face-to-face interviews with 30 business angels in Scotland and Northern Ireland provided information on typical ‘deal killers’. This was complemented by an Internet survey of United Kingdom that attracted responses from 238 UK business angels. The findings confirm that the main reason for rejection relates to the entrepreneur/management team. However, angel characteristics do not explain the number of reasons given for opportunity rejection nor do they predict the reasons for rejecting investment opportunities. This could be related to the increasing trend for business angels to join organised groups which, in turn, leads to the development of a shared repertoire of investment approaches. We suggest the concept of ‘communities-of-practice’ as an explanation for this finding

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

The Role of Interleukin-1 and Interleukin-18 in Pro-Inflammatory and Anti-Viral Responses to Rhinovirus in Primary Bronchial Epithelial Cells

Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1α), interleukin-1beta (IL-1β) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1β and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1β and IL-1α, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses

Calcium phosphates and silicon: exploring methods of incorporation

Background: Bioinorganics have been explored as additives to ceramic bone graft substitutes with the aim to improve their performance in repair and regeneration of large bone defects. Silicon (Si), an essential trace element involved in the processes related to bone formation and remodeling, was shown not only to enhance osteoblasts proliferation but also to stimulate the differentiation of mesenchymal stem cells (MSCs) and preosteoblasts into the osteogenic lineage. In this study, the added value of Si to calcium phosphate (CaP) coatings was evaluated. Methods: Tissue culture plastic well plates were coated with a thin CaP layer to which traces amounts of Si were added, either by adsorption or by incorporation through coprecipitation. The physicochemical and structural properties of the coatings were characterized and the dissolution behavior was evaluated. The adsorption/incorporation of Si was successfully achieved and incorporated ions were released from the CaP coatings. Human MSCs were cultured on the coatings to examine the effects of Si on cell proliferation and osteogenic differentiation. For the statistical analysis, a one-way ANOVA with Bonferroni post-hoc test was performed. Results: The results showed that human MSCs (hMSCs) responded to the presence of Si in the CaP coatings, in a dosedependent manner. An increase in the expression of markers of osteogenic differentiation by human MSCs was observed as a result of the increase in Si concentration. Conclusions: The incorporation/adsorption of Si into CaP coatings was successfully achieved and hMSCs responded with an increase in osteogenic genes expression with the increase of Si concentration. Furthermore, hMSCs cultured on CaP-I coatings expressed higher levels of ALP and OP, indicating that this may be the preferred method of incorporation of bioinorganics into CaPsPortuguese Foundation for Science and Technology (FCT) for providing Ana I. Rodrigues her PhD scholarship (Grant No. SFRH/BD/69962/2010). This work was partially supported by national funds through the FCT under the scope of the project OSTEOSYNTHESIS project (PTDC/CTM-BIO/0814/2012) and by the European Regional Development Fund (FEDER) through the “COMPETE” - Operational Programme for Competitiveness factors (FCOMP-01-0124-FEDER-028491).info:eu-repo/semantics/publishedVersio

IL-1α/IL-1R1 expression in chronic obstructive pulmonary disease and mechanistic relevance to smoke-induced neutrophilia in mice.

Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide. Despite this, the cellular and molecular mechanisms that contribute to COPD pathogenesis are still poorly understood

Toothache and associated factors in Brazilian adults: a cross-sectional population-based study

Extent: 8p.Background: Toothache is a dental public health problem and one of the predictors of dental attendance and it is strongly associated with the life quality of individuals. In spite of this, there are few population-based epidemiological studies on this theme. Objective: To estimate the prevalence of toothache and associated factors in adults of Lages, Southern Brazil. Methods: A cross-sectional population-based study was carried out in a sample of 2,022 adults aged 20 to 59 years living in the urban area of a medium sized city in Southern Brazil. A questionnaire including socioeconomic, demographic, smoking, alcohol, and use of dental service variables was applied at adults household. Toothache occurred six months previous of the interview was considered the outcome. Poisson regression analyses were performed following a theoretical hierarchical framework. All analysis was adjusted by the sample design effect. Results: The response rate was 98.6%. The prevalence of toothache was 18.0% (95% CI 16.0; 20.1). The following variables were associated with toothache after adjustment: female (PR = 1.3 95% CI 1.3; 2.0), black skin colour vs. whites (PR = 1.5 95% CI 1.1, 1.9), low per capita income (PR = 1.7 95% CI 1.2, 2.3), smokers (PR = 1.5 95% CI 1.2, 1.9) and those who reported alcohol problems (PR = 1.4 95% CI 1.1; 1.9). To be 40 years of age (PR = 0.5 95% CI 0.4, 0.7) and use dental service in the last year (RR = 0.5 95% CI 0.4, 0.6) were protective factors for toothache. Conclusion: The prevalence of toothache in adults of Lages can be considered a major problem of dental public health.Mirian Kuhnen, Marco A Peres, Anelise V Masiero and Karen G Pere

Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study

<p>Abstract</p> <p>Background</p> <p>Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD). Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD.</p> <p>Methods</p> <p>The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells), and CD1a+ cells (Langerhans cells). The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD <it>versus </it>control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE), and dendritic cells extracted from mice chronically exposed to cigarette smoke.</p> <p>Results</p> <p>In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2%) exhibited enhanced survival <it>in vitro </it>when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1), and B cell lymphoma leukemia-x(L) (Bcl-xL), predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not impaired.</p> <p>Conclusions</p> <p>These data indicate that COPD is associated with increased numbers of cells bearing markers associated with Langerhans cells and mature dendritic cells, and that cigarette smoke promotes survival signals and augments survival of dendritic cells. Although CSE suppressed dendritic cell CCR7 expression, migration towards a CCR7 ligand was not diminished, suggesting that reduced CCR7-dependent migration is unlikely to be an important mechanism for dendritic cell retention in the lungs of smokers with COPD.</p