Wine tourism as a non-core business strategy for small wineries

In recent years, wineries have been implementing increasingly more wine tourism activities as complementary or supplementary services to enhance their wine products. This paper adopts an inductive research paradigm based on grounded investigation; more specifically, this paper begins with a case study and expands to involve further similar evidence. The findings of this study show that, for wineries, wine tourism represents a fundamental opportunity for communication (institutional and commercial), distribution (as a form of direct channel), and growth (to include tasting, catering, hospitality, and so on). Most importantly, for both scholars and managers, the results of the research highlight that wine tourism can become the main source of the business value, especially in the case of small wineries (an example of which is examined in the case study under analysis). In these situations, however, wine production still characterizes the business because, otherwise, there can be no wine tourism, but wine production is not realistically critical to the business in terms of survival, competitiveness, and development

Digital transformation and tourist experience co-design: big social data for planning cultural tourism

Digital transformation has completely changed the demand/offering interaction in the travel industry, as well as largely affecting the customer journey. In this direction, “big social data” and user-generated content have become key sources of well-timed and rich knowledge supporting data driven decision approaches addressed the managing of complex relationships. Based on this theoretical framework, the paper suggests how to apply “big social data” in the tourist experience co-design, providing an increased value for the visitors and a better decision making approach for managers. In this respect, the field analysis concentrated specifically on user-generated content regarding the Pompeii Archaeological Site (P.A.S.), to trace valuable insights for the tourist experience. Based on double stage of research – netnographic analysis and a supplementary online survey – the study aimed to detect: (a) tourist perception on the P.A.S.; (b) random chat on the part of internet users (tourists and other browsers, not necessarily visitors) on the topic of the P.A.S.; (c) the main characteristics of the P.A.S. that attract internet user attention; (d) the main topics debated by influencers/opinion leaders managing online discussions on the P.A.S. managerial and theoretical implications were investigated highlighting the main limitations of the study as well

Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Sells.

Neomorphic mutations in NADP-dependent isocitrate dehydrogenases (IDH1 and IDH2) contribute to tumorigenesis in several cancers. Although significant research has focused on the hypermethylation phenotypes associated with (D)2-hydroxyglutarate (D2HG) accumulation, the metabolic consequences of these mutations may also provide therapeutic opportunities. Here we apply flux-based approaches to genetically engineered cell lines with an endogenous IDH1 mutation to examine the metabolic impacts of increased D2HG production and altered IDH flux as a function of IDH1 mutation or expression. D2HG synthesis in IDH1-mutant cells consumes NADPH at rates similar to de novo lipogenesis. IDH1-mutant cells exhibit increased dependence on exogenous lipid sources for in vitro growth, as removal of medium lipids slows growth more dramatically in IDH1-mutant cells compared with those expressing wild-type or enzymatically inactive alleles. NADPH regeneration may be limiting for lipogenesis and potentially redox homeostasis in IDH1-mutant cells, highlighting critical links between cellular biosynthesis and redox metabolism

Sc substitution for Mg in MgB2: effects on Tc and Kohn anomaly

Here we report synthesis and characterization of Mg_{1-x}Sc_{x}B_{2} (0.12T_{c}>6 K. We find that the Sc doping moves the chemical potential through the 2D/3D electronic topological transition (ETT) in the sigma band where the ``shape resonance" of interband pairing occurs. In the 3D regime beyond the ETT we observe a hardening of the E_{2g} Raman mode with a significant line-width narrowing due to suppression of the Kohn anomaly over the range 0<q<2k_{F}.Comment: 8 pages, 4 EPS figures, to be published in Phys. Rev.

Digital transformation and tourist experience co-design: Big social data for planning cultural tourism

Digital transformation has completely changed the demand/offering interaction in the travel industry, as well as largely affecting the customer journey. In this direction, “big social data” and user-generated content have become key sources of well-timed and rich knowledge supporting data driven decision approaches addressed the managing of complex relationships. Based on this theoretical framework, the paper suggests how to apply “big social data” in the tourist experience co-design, providing an increased value for the visitors and a better decision making approach for managers. In this respect, the field analysis concentrated specifically on user-generated content regarding the Pompeii Archaeological Site (P.A.S.), to trace valuable insights for the tourist experience. Based on double stage of research – netnographic analysis and a supplementary online survey – the study aimed to detect: (a) tourist perception on the P.A.S.; (b) random chat on the part of internet users (tourists and other browsers, not necessarily visitors) on the topic of the P.A.S.; (c) the main characteristics of the P.A.S. that attract internet user attention; (d) the main topics debated by influencers/opinion leaders managing online discussions on the P.A.S. managerial and theoretical implications were investigated highlighting the main limitations of the study as well

Stable isotope-assisted untargeted metabolomics identifies ALDH1A1-driven erythronate accumulation in lung cancer cells

Using an untargeted stable isotope-assisted metabolomics approach, we identify erythronate as a metabolite that accumulates in several human cancer cell lines. Erythronate has been reported to be a detoxification product derived from off-target glycolytic metabolism. We use chemical inhibitors and genetic silencing to define the pentose phosphate pathway intermediate erythrose 4-phosphate (E4P) as the starting substrate for erythronate production. However, following enzyme assay-coupled protein fractionation and subsequent proteomics analysis, we identify aldehyde dehydrogenase 1A1 (ALDH1A1) as the predominant contributor to erythrose oxidation to erythronate in cell extracts. Through modulating ALDH1A1 expression in cancer cell lines, we provide additional support. We hence describe a possible alternative route to erythronate production involving the dephosphorylation of E4P to form erythrose, followed by its oxidation by ALDH1A1. Finally, we measure increased erythronate concentrations in tumors relative to adjacent normal tissues from lung cancer patients. These findings suggest the accumulation of erythronate to be an example of metabolic reprogramming in cancer cells, raising the possibility that elevated levels of erythronate may serve as a biomarker of certain types of cancer

Investigation of K14/K5 as a stem cell marker in the limbal region of the bovine cornea

Background: Identification of stem cells from a corneal epithelial cell population by specific molecular markers has been investigated previously. Expressions of P63, ABCG2 and K14/K5 have all been linked to mammalian corneal epithelial stem cells. Here we report on the limitations of K14/K5 as a limbal stem cell marker. Methodology/Principal Findings: K14/K5 expression was measured by immunohistochemistry, Western blotting and Real time PCR and compared between bovine epithelial cells in the limbus and central cornea. A functional study was also included to investigate changes in K5/14 expression within cultured limbal epithelial cells undergoing forced differentiation. K14 expression (or its partner K5) was detected in quiescent epithelial cells from both the limbal area and central cornea. K14 was localized predominantly to basal epithelial cells in the limbus and suprabasal epithelial cells in the central cornea. Western blotting revealed K14 expression in both limbus and central cornea (higher levels in the limbus). Similarly, quantitative real time PCR found K5, partner to K14, to be expressed in both the central cornea and limbus. Following forced differentiation in culture the limbal epithelial cells revealed an increase in K5/14 gene/protein expression levels in concert with a predictable rise in a known differentiation marker. Conclusions/Significance: K14 and its partner K5 are limited not only to the limbus but also to the central bovine cornea epithelial cells suggesting K14/K5 is not limbal specific in situ. Furthermore K14/K5 expression levels were not lowered (in fact they increased) within a limbal epithelial cell culture undergoing forced differentiation suggesting K14/K5 is an unreliable maker for undifferentiated cells ex vivo

Snapshots of human anatomy, locomotion, and behavior from Late Pleistocene footprints at Engare Sero, Tanzania

Fossil hominin footprints preserve data on a remarkably short time scale compared to most other fossil evidence, offering snapshots of organisms in their immediate ecological and behavioral contexts. Here, we report on our excavations and analyses of more than 400 Late Pleistocene human footprints from Engare Sero, Tanzania. The site represents the largest assemblage of footprints currently known from the human fossil record in Africa. Speed estimates show that the trackways reflect both walking and running behaviors. Estimates of group composition suggest that these footprints were made by a mixed-sex and mixed-age group, but one that consisted of mostly adult females. One group of similarly oriented trackways was attributed to 14 adult females who walked together at the same pace, with only two adult males and one juvenile accompanying them. In the context of modern ethnographic data, we suggest that these trackways may capture a unique snapshot of cooperative and sexually divided foraging behavior in Late Pleistocene humans

Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis

Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. PKM2 interaction with phosphotyrosine-containing proteins inhibits enzyme activity and increases availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small molecule PKM2 activators inhibit growth of xenograft tumors. Structural studies reveal that small molecule activators bind PKM2 at the subunit interaction interface, a site distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small molecule activation of PKM2 can interfere with anabolic metabolism