TOURIST ENTERPRISES FINANCING IN GREECE

The main purpose of our paper is to examine the financing framework of the Greek tourist enterprises. More specifically, in the first part of this paper we analyze the sector of the Greek tourism market in order to be able to define its operational framework. Then, we examine the structural problems of the sector and analyze the relevant Institutional financing framework. In the second part we work out a critical assessment of the tourist enterprises existing financial framework, focussing on the financial difficulties that they face. In the last part of our paper, we set out our proposals concerning the adoption of the appropriate tourism policy that will contribute to the supporting of the aforementioned firms and especially to their access to finance (through Developmental Laws, E.U’s programs, financial Institutions like Credit Guarantee Fund for Small and Very Small Enterprises, etc). The most important conclusions that come out of the whole analysis of our paper, show that the majority of Greek Tourist Industry are small enterprises that they have the same structural characteristics (e.g: seasonal bussiness, mainly situated in insular regions, stayed behind large companies in terms of productivity, technological experience, financial and other areas. Particularly, they often lack creditworthiness and have trouble securing funds needed for their business activities). Furthermore, tourist enterprises, like most small companies have only limited capital resources. So, they have to rely on banks and other financial institutions for their funds. Banks require sufficient collateral or a well-established surety for their debtors to secure a loan. The lack of such assets or appropriate surety makes it difficult for many small tourist business to obtain loans from financial houses. Thus, it is obvious that the pin pointing of the financial problems that the tourist enterprises face, facilitates the planing of the appropriate mix of tourism policy measures, that can lead to a more effective running of tourist enterprises and also contribute to the reinforcement of local entrepreneurship.

An integrated total quality strategy to endogenous tourism development

This paper is an attempt to define the content of the "Integrated Total Quality Strategy" as a tool of promoting the goals of the endogenous tourism development for countries like Greece where the dominant paradigm of mass tourism for summer holidays has reached its limits. We propose a differentiation strategy through total quality management based on the bottom up approach to sustainable development that promotes competitive advantage. It requires small scale operations, local participation, clustering, integrated approach and symbiosis between social and natural systems.peer-reviewe

Business clusters formation as a means of improving competitiveness in the tourism sector

Business Clusters became foreground of economic thought in the 90s due to Michael Porter’s research work, who argued that the most successful export companies belong to group of enterprises of the same industry that are geographically close to one another. This issue became even more acute because of the globalisation of the economy and the need to plan and implement policies aiming mainly at strengthening the competitiveness of small and medium sized enterprises. Tourism, as an economic activity, includes a wide range of small and medium enterprises engaging in various sectors of it. It is argued that business clusters within the field of tourism economics define de facto the competitiveness of a tourist destination. Business clusters of small and medium enterprises which operate in a tourism destination are a prerequisite contributing to its competitiveness. Especially in Greece, it is alleged that clusters can maximise the abilities offered by technology, new markets and other external factors and contribute to the strengthening of competitiveness in the tourism industry.peer-reviewe

microRNAs in the Lymphatic Endothelium : Master Regulators of Lineage Plasticity and Inflammation

microRNAs (miRNAs) are highly conserved, small non-coding RNAs that regulate gene expression at the posttranscriptional level. They have crucial roles in organismal development, homeostasis, and cellular responses to pathological stress. The lymphatic system is a large vascular network that actively regulates the immune response through antigen trafficking, cytokine secretion, and inducing peripheral tolerance. Here, we review the role of miRNAs in the lymphatic endothelium with a particular focus on their role in lymphatic endothelial cell (LEC) plasticity, inflammation, and regulatory function. We highlight the lineage plasticity of LECs during inflammation and the importance of understanding the regulatory role of miRNAs in these processes. We propose that targeting miRNA expression in lymphatic endothelium can be a novel strategy in treating human pathologies associated with lymphatic dysfunction

IL-36γ has proinflammatory effects on human endothelial cells

Interleukin-36 cytokines are predominantly expressed by epithelial cells. Significant upregulation of epidermal IL-36 is now a recognised characteristic of psoriatic skin inflammation. IL-36 is known to induce inflammatory responses in dendritic cells, fibroblasts and epithelial cells. Although vascular alterations are a hallmark of psoriatic lesions and dermal endothelial cells are well known to play a critical role in skin inflammation, the effects of IL-36 on endothelial cells are unexplored. We here show that endothelial cells including dermal microvascular cells express a functionally active IL-36 receptor. Adhesion molecules VCAM-1 and ICAM-1 are upregulated by IL-36γ stimulation and this is reversed by the presence of the endogenous IL-36 receptor antagonist. IL-36γ stimulated endothelial cells secrete the proinflammatory chemokines IL-8, CCL2 and CCL20. Chemotaxis assays showed increased migration of T cells following IL-36γ stimulation of endothelial cells. These results suggest a role for IL-36γ in the dermal vascular compartment and it is likely to enhance psoriatic skin inflammation by activating endothelial cells and promoting leukocyte recruitment. This article is protected by copyright. All rights reserved

MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells

Programmed death ligand-1 (PD-L1) is a critical regulator of T cell function contributing to peripheral immune tolerance. Although it has been shown that posttranscriptional regulatory mechanisms control PD-L1 expression in cancer, it remains unknown whether such regulatory loops operate also in non-transformed cells. Here we studied PD-L1 expression in human dermal lymphatic endothelial cells (HDLECs), which play key roles in immunity and cancer. Treatment of HDLECs with the pro-inflammatory cytokines IFN-γ and TNF-α synergistically upregulated PDL1 expression. IFN-γ and TNF-α also affected expression of several microRNAs (miRNAs) that have the potential to suppress PD-L1 expression. The most highly upregulated miRNA following IFN-γ and TNF-α treatment in HDLECs was miR- 155, which has a central role in the immune system and cancer. Induction of miR-155 was driven by TNF-α, the effect of which was significantly enhanced by IFN-γ. The PD-L1 3'- UTR contains two functional miR-155 binding sites. Endogenous miR-155 controlled the kinetics and maximal levels of PD-L1 induction upon IFN-γ and TNF-α treatment. We obtained similar findings in dermal fibroblasts, demonstrating that the IFN-γ/TNF-α/miR-155/PD-L1 pathway is not restricted to HDLECs. These results reveal miR- 155 as a critical component of an inflammationinduced regulatory loop controlling PD-L1 expression in primary cells

The Sensor Organism

Large-scale, distributed sensor networks are the projected weapon of choice for future pervasive computing applications such as, for example, envi- ronment monitoring, surveillance, (big) data mining and patient monitoring. However, state-of-the-art approaches face major challenges: specialized sen- sors are expensive and require careful calibration. Hardware sensors operating in uncertain, harsh environments eventually suffer from stress, ageing and phys- ical damage, which leads to unforeseen effects that can render the device and the data recorded useless. Highly-tuned data processing algorithms are often not scalable and are not robust against faulty sensors delivering wrong data. Gener- ally, systems can only adapt, if at all, in some predefined limited ways and are not capable of autonomously “inventing” new ways of adapting to unexpected changes in their internal and external environment

Mathematical modelling of activation-induced heterogeneity in TNF, IL6, NOS2, and IL1β expression reveals cell state transitions underpinning macrophage responses to LPS

Background: Despite extensive work on macrophage heterogeneity, the mechanisms driving activation induced heterogeneity (AIH) in macrophages remain poorly understood. Here, we aimed to develop mathematical models to explore theoretical cellular states underpinning the empirically observed responses of macrophages following lipopolysaccharide (LPS) challenge. Methods: We obtained empirical data following primary and secondary responses to LPS in two in vitro cellular models (bone marrow-derived macrophages or BMDMs, and RAW 264.7 cells) and single-cell protein measurements for four key inflammatory mediators: TNF, IL-6, pro-IL-1β, and NOS2, and used mathematical modelling to understand heterogeneity. Results: For these four factors, we showed that macrophage community AIH is dependent on LPS dose and that altered AIH kinetics in macrophages responding to a second LPS challenge underpin hypo-responsiveness to LPS. These empirical data can be explained by a mathematical three-state model including negative, positive, and non-responsive states (NRS), but they are also compatible with a four-state model that includes distinct reversibly NRS and non-responsive permanently states (NRPS). Our mathematical model, termed NoRM (Non-Responsive Macrophage) model identifies similarities and differences between BMDM and RAW 264.7 cell responses. In both cell types, transition rates between states in the NoRM model are distinct for each of the tested proteins and, crucially, macrophage hypo-responsiveness is underpinned by changes in transition rates to and from NRS. Conclusions: Overall, we provide a mathematical model for studying macrophage ecology and community dynamics that can be used to elucidate the role of phenotypically negative macrophage populations in AIH and, primary and secondary responses to LPS

Ionic modulation of immune checkpoint proteins

Despite extensive basic and clinical research on immune checkpoint regulatory pathways, little is known about the effects of the ionic tumour microenvironment on immune checkpoint expression and function. We screened effects of ion channel modulating compounds on indoleamine-2',3'-dioxygenase (IDO1) activity. Here, we describe a mechanistic link between Na+/K+ ATPase inhibition by cardiac glycosides and activity of IDO1, a well-characterized immune checkpoint. IDO1 catalyses the rate-limitig step of tryptophan catabolim and inhibits the immune response to the tumour by local depletion of tryptophan, an amino acid essential for anabolic functions in cancer and T cells