347 research outputs found

    Airlines Entry and Exit and the Impact on Air Traffic Management: An Analytical Framework for Zero-Sum and Positive-Sum Outcomes

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    Passenger airline service can have a significant impact on a metropolitan region's economy in terms of direct spending and employment, as well as on indirect spending related to industries such as tourism and the service sector. In the past decade passenger service levels have changed considerably in many markets because of a wide variety of events including increased competition, terrorism, and a downturn in the economy. Airlines have responded to these challenges in a variety of ways. Some of the traditional network carriers have been forced into bankruptcy in an attempt to reduce costs and compete more effectively with low cost carriers. In contrast, the low cost carriers have expanded service and entered new markets at a rapid pace.This paper examines the economic evolutionary process whereby a dominant carrier competes intensely in one market against a similar airline and retreats in another where new, lower-cost entrant expands service. Literature is examined for evidence pertaining to the market's response to a network carrier's financial distress, its impact on airport service levels, and implications for local economies. A zero sum case is explained using a recent example. A positive sum case is explored, where the positive contributions of the entering carrier exceed those left behind by the resident carrier. In the process, depending on the types of gains and nature of the evolving airlines' network, the patterns of air traffic may also change. Using these experiences, an analytical framework is proposed that attempts to explain the emergent behavior of low cost carriers when they enter new markets. In addition, the impact of these changes on the air traffic management system is also examined

    Understanding the town centre customer experience (TCCE)

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    This research enhances the understanding of consumer behaviour and customer experience in the context of town centres. First, it defines town centre customer experience (TCCE) as a multifaceted journey that combines interactions with a diverse range of public and private organisations, including retailers and social and community elements; this results in a unique experience co-created with the consumer across a series of functional and experiential touchpoints. Second, combining qualitative and quantitative insights, this research reveals a series of specific functional and experiential TCCE touchpoints, which underpin the consumer internal response (motivation to visit) and outward behaviour (desire to stay and revisit intentions) in the town centre. In addition to enhancing town centre and customer experience knowledge, these findings offer important new insights to those managing town centres and seeking to retain customer loyalty in the high street. Above all, these findings can help identify the touchpoints that need to be reinforced and/or improved to differentiate a town from its competing centres and to create tailored marketing strategies. Taken together, such initiatives have the potential to positively impact the revitalisation of the high street and the town centre economy

    Giant lobelias exemplify convergent evolution

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    Giant lobeliads on tropical mountains in East Africa and Hawaii have highly unusual, giant-rosette growth forms that appear to be convergent on each other and on those of several independently evolved groups of Asteraceae and other families. A recent phylogenetic analysis by Antonelli, based on sequencing the widest selection of lobeliads to date, raises doubts about this paradigmatic example of convergent evolution. Here I address the kinds of evidence needed to test for convergent evolution and argue that the analysis by Antonelli fails on four points. Antonelli's analysis makes several important contributions to our understanding of lobeliad evolution and geographic spread, but his claim regarding convergence appears to be invalid. Giant lobeliads in Hawaii and Africa represent paradigmatic examples of convergent evolution

    DPOAEs in Children With Sickle Cell Disease

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    The purpose of this study was to investigate distortion product otoacoustic emissions (DPOAEs) in young normal-hearing children with sickle cell disease (SCD). It was hypothesized that the prevalence of DPOAEs and response amplitudes would be lower than those in children with normal hemoglobin due to suspected compromised cochlear function as a result of vaso-occlusive events characteristic of SCD. Twenty African-American children with SCD and 15 African-American children with normal hemoglobin participated. Distortion product OAEs were evoked by thirteen primary tone pairs with f2 frequencies ranging from 1000 to 4500 Hz. The primary tones were presented at and L1 and L2 levels of 70 and 60 dB SPL (high) and 50 and 40 dB SPL (low), respectively. The findings of this study were completely unexpected and contrary to our original hypotheses. The likelihood of detecting a DPOAE response was not related to the clinical status of the children. Distortion product OAE amplitudes were significantly larger for children with SCD (p = .01). Educational Objectives: After completing this article the reader will (1) have a basic knowledge of the audiometric complications of sickle cell disease and (2) appreciate the differences in DPOAEs between young normal-hearing children with sickle cell DPOAEs in Children With Sickle Cell Disease 3 disease and young normal-hearing children with normal hemoglobin

    Directed evolution of an orthogonal nucleoside analog kinase via fluorescence-activated cell sorting

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    Nucleoside analogs (NAs) represent an important category of prodrugs for the treatment of viral infections and cancer, yet the biological potency of many analogs is compromised by their inefficient activation through cellular 2′-deoxyribonucleoside kinases (dNKs). We herein report the directed evolution and characterization of an orthogonal NA kinase for 3′-deoxythymidine (ddT), using a new FACS-based screening protocol in combination with a fluorescent analog of ddT. Four rounds of random mutagenesis and DNA shuffling of Drosophila melanogaster 2′-deoxynucleoside kinase, followed by FACS analysis, yielded an orthogonal ddT kinase with a 6-fold higher activity for the NA and a 20-fold kcat/KM preference for ddT over thymidine, an overall 10 000-fold change in substrate specificity. The contributions of individual amino acid substitutions in the ddT kinase were evaluated by reverse engineering, enabling a detailed structure–function analysis to rationalize the observed changes in performance. Based on our results, kinase engineering with fluorescent NAs and FACS should prove a highly versatile method for evolving selective kinase:NA pairs and for studying fundamental aspects of the structure–function relationship in dNKs

    Molecular phylogenetics reveal multiple tertiary vicariance origins of the African rain forest trees

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    Background - Tropical rain forests are the most diverse terrestrial ecosystems on the planet. How this diversity evolved remains largely unexplained. In Africa, rain forests are situated in two geographically isolated regions: the West-Central Guineo-Congolian region and the coastal and montane regions of East Africa. These regions have strong floristic affinities with each other, suggesting a former connection via an Eocene pan-African rain forest. High levels of endemism observed in both regions have been hypothesized to be the result of either 1) a single break-up followed by a long isolation or 2) multiple fragmentation and reconnection since the Oligocene. To test these hypotheses the evolutionary history of endemic taxa within a rain forest restricted African lineage of the plant family Annonaceae was studied. Molecular phylogenies and divergence dates were estimated using a Bayesian relaxed uncorrelated molecular clock assumption accounting for both calibration and phylogenetic uncertainties. Results - Our results provide strong evidence that East African endemic lineages of Annonaceae have multiple origins dated to significantly different times spanning the Oligocene and Miocene epochs. Moreover, these successive origins (c. 33, 16 and 8 million years ¿ Myr) coincide with known periods of aridification and geological activity in Africa that would have recurrently isolated the Guineo-Congolian rain forest from the East African one. All East African taxa were found to have diversified prior to Pleistocene times. Conclusion - Molecular phylogenetic dating analyses of this large pan-African clade of Annonaceae unravels an interesting pattern of diversification for rain forest restricted trees co-occurring in West/Central and East African rain forests. Our results suggest that repeated reconnections between the West/Central and East African rain forest blocks allowed for biotic exchange while the break-ups induced speciation via vicariance, enhancing the levels of endemicity. These results provide an explanation for present day distribution patterns and origins of endemicity for African rain forest trees. Moreover, given the pre-Pleistocene origins of all the studied endemic East African genera and species, these results also offer important insights for setting conservation priorities in these highly diversified but threatene

    How cigarette smoking may increase the risk of anxiety symptoms and anxiety disorders : a critical review of biological pathways

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    Multiple studies have demonstrated an association between cigarette smoking and increased anxiety symptoms or disorders, with early life exposures potentially predisposing to enhanced anxiety responses in later life. Explanatory models support a potential role for neurotransmitter systems, inflammation, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophins and neurogenesis, and epigenetic effects, in anxiety pathogenesis. All of these pathways are affected by exposure to cigarette smoke components, including nicotine and free radicals. This review critically examines and summarizes the literature exploring the role of these systems in increased anxiety and how exposure to cigarette smoke may contribute to this pathology at a biological level. Further, this review explores the effects of cigarette smoke on normal neurodevelopment and anxiety control, suggesting how exposure in early life (prenatal, infancy, and adolescence) may predispose to higher anxiety in later life. A large heterogenous literature was reviewed that detailed the association between cigarette smoking and anxiety symptoms and disorders with structural brain changes, inflammation, and cell-mediated immune markers, markers of oxidative and nitrosative stress, mitochondrial function, neurotransmitter systems, neurotrophins and neurogenesis. Some preliminary data were found for potential epigenetic effects. The literature provides some support for a potential interaction between cigarette smoking, anxiety symptoms and disorders, and the above pathways; however, limitations exist particularly in delineating causative effects. The literature also provides insight into potential effects of cigarette smoke, in particular nicotine, on neurodevelopment. The potential treatment implications of these findings are discussed in regards to future therapeutic targets for anxiety. The aforementioned pathways may help mediate increased anxiety seen in people who smoke. Further research into the specific actions of nicotine and other cigarette components on these pathways, and how these pathways interact, may provide insights that lead to new treatment for anxiety and a greater understanding of anxiety pathogenesis

    Epigenetics and developmental programming of welfare and production traits in farm animals

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    The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the ‘developmental origins of health and disease’ or ‘DOHaD’ hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems

    Nicotinic Receptors Underlying Nicotine Dependence: Evidence from Transgenic Mouse Models.

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    Nicotine underlies the reinforcing properties of tobacco cigarettes and e-cigarettes. After inhalation and absorption, nicotine binds to various nicotinic acetylcholine receptor (nAChR) subtypes localized on the pre- and postsynaptic membranes of cells, which subsequently leads to the modulation of cellular function and neurotransmitter signaling. In this chapter, we begin by briefly reviewing the current understanding of nicotine's actions on nAChRs and highlight considerations regarding nAChR subtype localization and pharmacodynamics. Thereafter, we discuss the seminal discoveries derived from genetically modified mouse models, which have greatly contributed to our understanding of nicotine's effects on the reward-related mesolimbic pathway and the aversion-related habenulo-interpeduncular pathway. Thereafter, emerging areas of research focusing on modulation of nAChR expression and/or function are considered. Taken together, these discoveries have provided a foundational understanding of various genetic, neurobiological, and behavioral factors underlying the motivation to use nicotine and related dependence processes, which are thereby advancing drug discovery efforts to promote long-term abstinence
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