76 research outputs found

    Next-POI Recommendations Matching User's Visit Behaviour

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    AbstractWe consider the urban tourism scenario, which is characterized by limited availability of information about individuals' past behaviour. Our system goal is to identify relevant next Points of Interest (POIs) recommendations. We propose a technique that addresses the domain requirements by using clusters of users' visits trajectories that show similar visit behaviour. Previous analysis clustered visit trajectories by aggregating trajectories that contain similar POIs. We compare our approach with a next-item recommendation state-of-the-art Neighbour-based model. The results show that customizing recommendations for clusters of users' with similar behaviour yields superior performance on different quality dimensions of the recommendation

    CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's lymphoma and tumor-supportive follicular T helper cells

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    CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin's lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 with high avidity. CXCR5, physiologically expressed on mature B and Tfh cells, is also highly expressed on nodal B-NHLs. Anti-CXCR5 CAR-T cells eradicate B-NHL cells and lymphoma-supportive Tfh cells more potently than CD19 CAR-T cells in vitro, and they efficiently inhibit lymphoma growth in a murine xenograft model. Administration of anti-murine CXCR5 CAR-T cells in syngeneic mice specifically depletes endogenous and malignant B and Tfh cells without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 CAR-T cells provide a promising treatment strategy for nodal B-NHLs through the simultaneous elimination of lymphoma B cells and Tfh cells of the tumor-supporting TME

    Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

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    Drainage of central nervous system (CNS) antigens to the brain-draining cervical lymph nodes (CLN) is likely crucial in the initiation and control of autoimmune responses during multiple sclerosis (MS). We demonstrate neuronal antigens within CLN of MS patients. In monkeys and mice with experimental autoimmune encephalomyelitis (EAE) and in mouse models with non-inflammatory CNS damage, the type and extent of CNS damage was associated with the frequencies of CNS antigens within the cervical lymph nodes. In addition, CNS antigens drained to the spinal-cord-draining lumbar lymph nodes. In human MS CLN, neuronal antigens were present in pro-inflammatory antigen-presenting cells (APC), whereas the majority of myelin-containing cells were anti-inflammatory. This may reflect a different origin of the cells or different drainage mechanisms. Indeed, neuronal antigen-containing cells in human CLN did not express the lymph node homing receptor CCR7, whereas myelin antigen-containing cells in situ and in vitro did. Nevertheless, CLN from EAE-affected CCR7-deficient mice contained equal amounts of myelin and neuronal antigens as wild-type mice. We conclude that the type and frequencies of CNS antigens within the CLN are determined by the type and extent of CNS damage. Furthermore, the presence of myelin and neuronal antigens in functionally distinct APC populations within MS CLN suggests that differential immune responses can be evoked

    Transcriptional repression of NFKBIA triggers constitutive IKK- and proteasome-independent p65/RelA activation in senescence

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    The IκB kinase (IKK)‐NF‐κB pathway is activated as part of the DNA damage response and controls both inflammation and resistance to apoptosis. How these distinct functions are achieved remained unknown. We demonstrate here that DNA double‐strand breaks elicit two subsequent phases of NF‐κB activation in vivo and in vitro, which are mechanistically and functionally distinct. RNA‐sequencing reveals that the first‐phase controls anti‐apoptotic gene expression, while the second drives expression of senescence‐associated secretory phenotype (SASP) genes. The rapidly activated first phase is driven by the ATM‐PARP1‐TRAF6‐IKK cascade, which triggers proteasomal destruction of inhibitory IκBα, and is terminated through IκBα re‐expression from the NFKBIA gene. The second phase, which is activated days later in senescent cells, is on the other hand independent of IKK and the proteasome. An altered phosphorylation status of NF‐κB family member p65/RelA, in part mediated by GSK3β, results in transcriptional silencing of NFKBIA and IKK‐independent, constitutive activation of NF‐κB in senescence. Collectively, our study reveals a novel physiological mechanism of NF‐κB activation with important implications for genotoxic cancer treatment

    Smart technologies for personalized experiences: a case study in the hospitality domain

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    Recent advances in the field of technology have led to the emergence of innovative technological smart solutions providing unprecedented opportunities for application in the tourism and hospitality industry.With intensified competition in the tourism market place, it has become paramount for businesses to explore the potential of technologies, not only to optimize existing processes but facilitate the creation of more meaningful and personalized services and experiences. This study aims to bridge the current knowledge gap between smart technologies and experience personalization to understand how smart mobile technologies can facilitate personalized experiences in the context of the hospitality industry. By adopting a qualitative case study approach, this paper makes a two-fold contribution; it a) identifies the requirements of smart technologies for experience creation, including information aggregation, ubiquitous mobile connectedness and real time synchronization and b) highlights how smart technology integration can lead to two distinct levels of personalized tourism experiences. The paper concludes with the development of a model depicting the dynamic process of experience personalization and a discussion of the strategic implications for tourism and hospitality management and research

    Developing Student Engagement in China Through Collaborative Action Research

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    As its market and society open up, China has transformed itself from a closed agrarian socialist economy to an urban state and an economic force. This has released accumulated tourism demand, led to the development of a diversified industry, and the spread of university and vocational courses in this field. However, the industry faces challenges to recruit and retain staff, with tourism education in higher education blamed for the shortfall in numbers and quality of candidates with suitable purpose, knowledge, and passion to serve. This chapter provides a background to the development of and problems facing tourism education in China, and suggests how to support student engagement and hence the future workforce

    Die rechtliche Stellung der Minderheiten in Serbien

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    Sarajewo und das Kriegsjahrzehnt auf dem Balkan, 1908-1918

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