Are transnational tobacco companies' market access strategies linked to economic development models? A case study of South Korea.

Transnational tobacco companies (TTCs) have used varied strategies to access previously closed markets. Using TTCs' efforts to enter the South Korean market from the late 1980s as a case study, this article asks whether there are common patterns in these strategies that relate to the broader economic development models adopted by targeted countries. An analytical review of the existing literature on TTCs' efforts to access emerging markets was conducted to develop hypotheses relating TTCs' strategies to countries' economic development models. A case study of Korea was then undertaken based on analysis of internal tobacco industry documents. Findings were consistent with the hypothesis that TTCs' strategies in Korea were linked to Korea's export-oriented economic development model and its hostile attitude towards foreign investment. A fuller understanding of TTCs' strategies for expansion globally can be derived by locating them within the economic development models of specific countries or regions. Of foremost importance is the need for governments to carefully balance economic and public health policies when considering liberalisation

Legislative History: An Act to Amend the Date to Determine Age for Kindergarten Eligibility (HP284)(LD 367)

https://digitalmaine.com/legishist113/1366/thumbnail.jp

Sometimes You Cannot Have It All: Party Switching and Affiliation Motivations as Substitutes

Existing research on when legislators switch parties reports inconsistent results about motivations for switching (e.g., office, ideology, and votes). I treat the motivations for party switching as substitutes and argue that many of the inconsistencies that persist can be explained by modelling the interactive effects between these motivations. For example, scholars differ in terms of whether they find that electoral considerations are an important determinant of party switching. The conflicting findings on the independent effects of electoral considerations are explained here by demonstrating that these effects are conditional on the level of office benefits a legislators enjoys, as well as the ideological distance between the legislator and party. More generally, the empirical analysis provides strong support for the substitution effect hypothesis. Thus, modelling interactive effects increases our understanding of party switching

MexEF-OprN Efflux Pump Exports the Pseudomonas Quinolone Signal (PQS) Precursor HHQ (4-hydroxy-2-heptylquinoline)

Bacterial cells have evolved the capacity to communicate between each other via small diffusible chemical signals termed autoinducers. Pseudomonas aeruginosa is an opportunistic pathogen involved, among others, in cystic fibrosis complications. Virulence of P. aeruginosa relies on its ability to produce a number of autoinducers, including 4-hydroxy-2-alkylquinolines (HAQ). In a cell density-dependent manner, accumulated signals induce the expression of multiple targets, especially virulence factors. This phenomenon, called quorum sensing, promotes bacterial capacity to cause disease. Furthermore, P. aeruginosa possesses many multidrug efflux pumps conferring adaptive resistance to antibiotics. Activity of some of these efflux pumps also influences quorum sensing. The present study demonstrates that the MexEF-OprN efflux pump modulates quorum sensing through secretion of a signalling molecule belonging to the HAQ family. Moreover, activation of MexEF-OprN reduces virulence factor expression and swarming motility. Since MexEF-OprN can be activated in infected hosts even in the absence of antibiotic selective pressure, it could promote establishment of chronic infections in the lungs of people suffering from cystic fibrosis, thus diminishing the immune response to virulence factors. Therapeutic drugs that affect multidrug efflux pumps and HAQ-mediated quorum sensing would be valuable tools to shut down bacterial virulence

Structural determinants of PINK1 topology and dual subcellular distribution

<p>Abstract</p> <p>Background</p> <p>PINK1 is a mitochondria-targeted kinase that constitutively localizes to both the mitochondria and the cytosol. The mechanism of how PINK1 achieves cytosolic localization following mitochondrial processing remains unknown. Understanding PINK1 subcellular localization will give us insights into PINK1 functions and how mutations in PINK1 lead to Parkinson's disease. We asked how the mitochondrial localization signal, the transmembrane domain, and the kinase domain participate in PINK1 localization.</p> <p>Results</p> <p>We confirmed that PINK1 mitochondrial targeting signal is responsible for mitochondrial localization. Once inside the mitochondria, we found that both PINK1 transmembrane and kinase domain are important for membrane tethering and cytosolic-facing topology. We also showed that PINK1 dual subcellular distribution requires both Hsp90 interaction with the kinase domain and the proteolysis at a cleavage site downstream of the transmembrane domain because removal of this cleavage site completely abolished cytosolic PINK1. In addition, the disruption of the Hsp90-PINK1 interaction increased mitochondrial PINK1 level.</p> <p>Conclusion</p> <p>Together, we believe that once PINK1 enters the mitochondria, PINK1 adopts a tethered topology because the transmembrane domain and the kinase domain prevent PINK1 forward movement into the mitochondria. Subsequent proteolysis downstream of the transmembrane domain then releases PINK1 for retrograde movement while PINK1 kinase domain interacts with Hsp90 chaperone. The significance of this dual localization could mean that PINK1 has compartmental-specific functions.</p

The connection between radio halos and cluster mergers and the statistical properties of the radio halo population

We discuss the statistical properties of the radio halo population in galaxy clusters. Radio bi-modality is observed in galaxy clusters: a fraction of clusters host giant radio halos while the majority of clusters do not show evidence of diffuse cluster-scale radio emission. The radio bi-modality has a correspondence in terms of dynamical state of the hosting clusters showing that merging clusters host radio halos and follow the well known radio--X-ray correlation, while more relaxed clusters do not host radio halos and populate a region well separated from that correlation. These evidences can be understood in the framework of a scenario where merger-driven turbulence re-accelerate the radio emitting electrons. We discuss the main statistical expectations of this scenario underlining the important role of upcoming LOFAR surveys to test present models.Comment: 11 pages, 2 figures, Invited talk at the conference "Diffuse Relativistic Plasmas", Bangalore, 1-4 March 2011; accepted for publication in the Journal of Astrophysics and Astronom

Derivation of High Purity Neuronal Progenitors from Human Embryonic Stem Cells

The availability of human neuronal progenitors (hNPs) in high purity would greatly facilitate neuronal drug discovery and developmental studies, as well as cell replacement strategies for neurodegenerative diseases and conditions, such as spinal cord injury, stroke, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Here we describe for the first time a method for producing hNPs in large quantity and high purity from human embryonic stem cells (hESCs) in feeder-free conditions, without the use of exogenous noggin, sonic hedgehog or analogs, rendering the process clinically compliant. The resulting population displays characteristic neuronal-specific markers. When allowed to spontaneously differentiate into neuronal subtypes in vitro, cholinergic, serotonergic, dopaminergic and/or noradrenergic, and medium spiny striatal neurons were observed. When transplanted into the injured spinal cord the hNPs survived, integrated into host tissue, and matured into a variety of neuronal subtypes. Our method of deriving neuronal progenitors from hESCs renders the process amenable to therapeutic and commercial use

Sleeping sickness and its relationship with development and biodiversity conservation in the Luangwa valley, Zambia

The Luangwa Valley has a long historical association with Human African trypanosomiasis (HAT) and is a recognised geographical focus of this disease. It is also internationally acclaimed for its high biodiversity and contains many valuable habitats. Local inhabitants of the valley have developed sustainable land use systems in co-existence with wildlife over centuries, based on non-livestock keeping practices largely due to the threat from African Animal Trypanosomiasis. Historical epidemics of human sleeping sickness have influenced how and where communities have settled and have had a profound impact on development in the Valley. Historical attempts to control trypanosomiasis have also had a negative impact on conservation of biodiversity. Centralised control over wildlife utilisation has marginalised local communities from managing the wildlife resource. To some extent this has been reversed by the implementation of community based natural resource management programmes in the latter half of the 20th century and the Luangwa Valley provides some of the earliest examples of such programmes. More recently, there has been significant uncontrolled migration of people into the mid-Luangwa Valley driven by pressure on resources in the eastern plateau region, encouragement from local chiefs and economic development in the tourist centre of Mfuwe. This has brought changing land-use patterns, most notably agricultural development through livestock keeping and cotton production. These changes threaten to alter the endemically stable patterns of HAT transmission and could have significant impacts on ecosystem health and ecosystem services. In this paper we review the history of HAT in the context of conservation and development and consider the impacts current changes may have on this complex social-ecological system. We conclude that improved understanding is required to identify specific circumstances where win-win trade-offs can be achieved between the conservation of biodiversity and the reduction of disease in the human population.Ecosystem Services for Poverty Alleviation (ESPA

hTERT promoter activity and CpG methylation in HPV-induced carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Activation of telomerase resulting from deregulated hTERT expression is a key event during high-risk human papillomavirus (hrHPV)-induced cervical carcinogenesis. In the present study we examined hTERT promoter activity and its relation to DNA methylation as one of the potential mechanisms underlying deregulated hTERT transcription in hrHPV-transformed cells.</p> <p>Methods</p> <p>Using luciferase reporter assays we analyzed hTERT promoter activity in primary keratinocytes, HPV16- and HPV18-immortalized keratinocyte cell lines and cervical cancer cell lines. In the same cells as well as cervical specimens we determined hTERT methylation by bisulfite sequencing analysis of the region spanning -442 to +566 (relative to the ATG) and quantitative methylation specific PCR (qMSP) analysis of two regions flanking the hTERT core promoter.</p> <p>Results</p> <p>We found that in most telomerase positive cells increased hTERT core promoter activity coincided with increased hTERT mRNA expression. On the other hand basal hTERT promoter activity was also detected in telomerase negative cells with no or strongly reduced hTERT mRNA expression levels. In both telomerase positive and negative cells regulatory sequences flanking both ends of the core promoter markedly repressed exogenous promoter activity.</p> <p>By extensive bisulfite sequencing a strong increase in CpG methylation was detected in hTERT positive cells compared to cells with no or strongly reduced hTERT expression. Subsequent qMSP analysis of a larger set of cervical tissue specimens revealed methylation of both regions analyzed in 100% of cervical carcinomas and 38% of the high-grade precursor lesions, compared to 9% of low grade precursor lesions and 5% of normal controls.</p> <p>Conclusions</p> <p>Methylation of transcriptionally repressive sequences in the hTERT promoter and proximal exonic sequences is correlated to deregulated hTERT transcription in HPV-immortalized cells and cervical cancer cells. The detection of DNA methylation at these repressive regions may provide an attractive biomarker for early detection of cervical cancer.</p