Smart Tourism Destinations: Can the Destination Management Organizations Exploit Benefits of the ICTs? Evidences from a Multiple Case Study

Recent developments of ICTs enable new ways to experience tourism and conducted to the concept of smart tourism. The adoption of cutting-edge technologies and its combination with innovative organizational models fosters cooperation, knowledge sharing, and open innovation among service providers in tourism destination. Moreover, it offers innovative services to visitors. In few words, they become smart tourism destinations. In this paper, we report first results of the SMARTCAL project aimed at conceiving a digital platform assisting Destination Management Organizations (DMOs) in providing smart tourism services. A DMO is the organization charged with managing the tourism offer of a collaborative network, made up of service providers acting in a destination. In this paper, we adopted a multiple case studies approach to analyze five Italian DMOs. Our aims were to investigate (1) if, and how, successful DMOs were able to offer smart tourism services to visitors; (2) if the ICTs adoption level was related to the collaboration level among DMO partners. First results highlighted that use of smart technologies was still in an embryonic stage of development, and it did not depend from collaboration levels

Directed Neural Differentiation of Mouse Embryonic Stem Cells Is a Sensitive System for the Identification of Novel Hox Gene Effectors

The evolutionarily conserved Hox family of homeodomain transcription factors plays fundamental roles in regulating cell specification along the anterior posterior axis during development of all bilaterian animals by controlling cell fate choices in a highly localized, extracellular signal and cell context dependent manner. Some studies have established downstream target genes in specific systems but their identification is insufficient to explain either the ability of Hox genes to direct homeotic transformations or the breadth of their patterning potential. To begin delineating Hox gene function in neural development we used a mouse ES cell based system that combines efficient neural differentiation with inducible Hoxb1 expression. Gene expression profiling suggested that Hoxb1 acted as both activator and repressor in the short term but predominantly as a repressor in the long run. Activated and repressed genes segregated in distinct processes suggesting that, in the context examined, Hoxb1 blocked differentiation while activating genes related to early developmental processes, wnt and cell surface receptor linked signal transduction and cell-to-cell communication. To further elucidate aspects of Hoxb1 function we used loss and gain of function approaches in the mouse and chick embryos. We show that Hoxb1 acts as an activator to establish the full expression domain of CRABPI and II in rhombomere 4 and as a repressor to restrict expression of Lhx5 and Lhx9. Thus the Hoxb1 patterning activity includes the regulation of the cellular response to retinoic acid and the delay of the expression of genes that commit cells to neural differentiation. The results of this study show that ES neural differentiation and inducible Hox gene expression can be used as a sensitive model system to systematically identify Hox novel target genes, delineate their interactions with signaling pathways in dictating cell fate and define the extent of functional overlap among different Hox genes

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Modeling a mobile group recommender system for tourism with intelligent agents and gamification

To provide recommendations to groups of people is a complex task, especially due to the group’s heterogeneity and conflicting preferences and personalities. This heterogeneity is even deeper in occasional groups formed for predefined tour packages in tourism. Group Recommender Systems (GRS) are being designed for helping in situations like those. However, many limitations can still be found, either on their time-consuming configurations and excessive intrusiveness to build the tourists’ profile, or in their lack of concern for the tourists’ interests during the planning and tours, like feeling a greater liberty, diminish the sense of fear/being lost, increase their sense of companionship, and promote the social interaction among them without losing a personalized experience. In this paper, we propose a conceptual model that intends to enhance GRS for tourism by using gamification techniques, intelligent agents modeled with the tourists’ context and profile, such as psychological and socio-cultural aspects, and dialogue games between the agents for the post-recommendation process. Some important aspects of a GRS for tourism are also discussed, opening the way for the proposed conceptual model, which we believe will help to solve the identified limitations.This work was supported by the GrouPlanner Project (POCI-01-0145-FEDER-29178) and by National Funds through the FCT –Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within the Projects UID/CEC/00319/2019 and UID/EEA/00760/2019

A note on multiple flow equilibria

A set of ordinary differential equations describing a mechanical system subject to forcing and dissipation is considered. A topological argument is employed to show that if all time-dependent solutions of the governing equations are bounded, the equations admit N steady solutions, where N is a positive odd integer and where at least ( N −1)/2 of the steady solutions are unstable. The results are discussed in the context of atmospheric flows, and it is shown that truncated forms of the quasigeostrophic equations of dynamic meteorology and of Budyko-Sellers climate models satisfy the hypotheses of the theorem.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43139/1/24_2004_Article_BF00881609.pd

BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells

Hoxb1 Controls Anteroposterior Identity of Vestibular Projection Neurons

The vestibular nuclear complex (VNC) consists of a collection of sensory relay nuclei that integrates and relays information essential for coordination of eye movements, balance, and posture. Spanning the majority of the hindbrain alar plate, the rhombomere (r) origin and projection pattern of the VNC have been characterized in descriptive works using neuroanatomical tracing. However, neither the molecular identity nor developmental regulation of individual nucleus of the VNC has been determined. To begin to address this issue, we found that Hoxb1 is required for the anterior-posterior (AP) identity of precursors that contribute to the lateral vestibular nucleus (LVN). Using a gene-targeted Hoxb1-GFP reporter in the mouse, we show that the LVN precursors originate exclusively from r4 and project to the spinal cord in the stereotypic pattern of the lateral vestibulospinal tract that provides input into spinal motoneurons driving extensor muscles of the limb. The r4-derived LVN precursors express the transcription factors Phox2a and Lbx1, and the glutamatergic marker Vglut2, which together defines them as dB2 neurons. Loss of Hoxb1 function does not alter the glutamatergic phenotype of dB2 neurons, but alters their stereotyped spinal cord projection. Moreover, at the expense of Phox2a, the glutamatergic determinants Lmx1b and Tlx3 were ectopically expressed by dB2 neurons. Our study suggests that the Hox genes determine the AP identity and diversity of vestibular precursors, including their output target, by coordinating the expression of neurotransmitter determinant and target selection properties along the AP axis

Biomedical Discovery Acceleration, with Applications to Craniofacial Development

The profusion of high-throughput instruments and the explosion of new results in the scientific literature, particularly in molecular biomedicine, is both a blessing and a curse to the bench researcher. Even knowledgeable and experienced scientists can benefit from computational tools that help navigate this vast and rapidly evolving terrain. In this paper, we describe a novel computational approach to this challenge, a knowledge-based system that combines reading, reasoning, and reporting methods to facilitate analysis of experimental data. Reading methods extract information from external resources, either by parsing structured data or using biomedical language processing to extract information from unstructured data, and track knowledge provenance. Reasoning methods enrich the knowledge that results from reading by, for example, noting two genes that are annotated to the same ontology term or database entry. Reasoning is also used to combine all sources into a knowledge network that represents the integration of all sorts of relationships between a pair of genes, and to calculate a combined reliability score. Reporting methods combine the knowledge network with a congruent network constructed from experimental data and visualize the combined network in a tool that facilitates the knowledge-based analysis of that data. An implementation of this approach, called the Hanalyzer, is demonstrated on a large-scale gene expression array dataset relevant to craniofacial development. The use of the tool was critical in the creation of hypotheses regarding the roles of four genes never previously characterized as involved in craniofacial development; each of these hypotheses was validated by further experimental work