The Impact of Athletes As Ambassadors in Olympic and Sports marketing strategies in Spain

The role of athletes as ambassadors in sports marketing has gained significant attention in recent years, especially within the context of Olympic marketing strategies. This research aimed to explore the impact of athlete ambassadors on sports marketing strategies in Spain, with a particular focus on Olympic athletes. A mixed methods approach was adopted, combining qualitative interviews with sports marketing experts and quantitative surveys conducted among Spanish sports fans. The data were analyzed to assess the effectiveness of athletes in shaping brand image, influencing consumer behavior, and driving engagement with sports events and campaigns. The findings indicated that athletes, particularly those with strong national recognition, play a crucial role in enhancing brand visibility and fostering emotional connections with audiences. Additionally, athletes were found to positively impact the public perception of Olympic brands, contributing to higher levels of sponsorship and fan loyalty. The study concluded that athlete ambassadors are a powerful tool in Olympic and sports marketing strategies in Spain, offering opportunities for greater audience reach and deeper engagement with sports brands

Regulation of polarised growth in fungi

Polarised growth in fungi occurs through the delivery of secretory vesicles along tracks formed by cytoskeletal elements to specific sites on the cell surface where they dock with a multiprotein structure called the exocyst before fusing with the plasmamembrane. The budding yeast, Saccharomyces cerevisiae has provided a useful model to investigate the mechanisms involved and their control. Cortical markers, provided by bud site selection pathways during budding, the septin ring during cytokinesis or the stimulation of the pheromone response receptors during mating, act through upstream signalling pathways to localise Cdc24, the GEF for the rho family GTPase, Cdc42. Cdc42 in its GTP-bound activates a multiprotein protein complex called the polarisome which nucleates actin cables along which the secretory vesicles are transported to the cell surface. Hyphae can elongate at a rate orders of magnitude faster than the extension of a yeast bud, so understanding hyphal growth will require substantial modification of the yeast paradigm. The rapid rate of hyphal growth is driven by a structure called the Spitzenkörper, located just behind the growing tip and which is rich in secretory vesicles. It is thought that secretory vesicles are delivered to the apical region where they accumulate in the Spitzenkörper. The Spitzenkörper then acts as vesicle supply centre in which vesicles exit the Spitzenkörper in all directions, but because of its proximity, the tip receives a greater concentration of vesicles per unit area than subapical regions. There are no obvious equivalents to the bud site selection pathway to provide a spatial landmark for polarised growth in hyphae. However, an emerging model is the way that the site of polarised growth in the fission yeast, Schizosaccharomyces pombe, is marked by delivery of the kelch repeat protein, Tea1, along microtubules. The relationship of the Spitzenkörper to the polarisome and the mechanisms that promote its formation are key questions that form the focus of current research

KRAS driven expression signature has prognostic power superior to mutation status in non-small cell lung cancer

KRAS is the most frequently mutated oncogene in non-small cell lung cancer (NSCLC). However, the prognostic role of KRAS mutation status in NSCLC still remains controversial. We hypothesize that the expression changes of genes affected by KRAS mutation status will have the most prominent effect and could be used as a prognostic signature in lung cancer. We divided NSCLC patients with mutation and RNA-seq data into KRAS mutated and wild type groups. Mann-Whitney test was used to identify genes showing altered expression between these cohorts. Mean expression of the top five genes was designated as a "transcriptomic fingerprint" of the mutation. We evaluated the effect of this signature on clinical outcome in 2,437 NSCLC patients using univariate and multivariate Cox regression analysis. Mutation of KRAS was most common in adenocarcinoma. Mutation status and KRAS expression were not correlated to prognosis. The transcriptomic fingerprint of KRAS include FOXRED2, KRAS, TOP1, PEX3 and ABL2. The KRAS signature had a high prognostic power. Similar results were achieved when using the second and third set of strongest genes. Moreover, all cutoff values delivered significant prognostic power (p < 0.01). The KRAS signature also remained significant (p < 0.01) in a multivariate analysis including age, gender, smoking history and tumor stage. We generated a "surrogate signature" of KRAS mutation status in NSCLC patients by computationally linking genotype and gene expression. We show that secondary effects of a mutation can have a higher prognostic relevance than the primary genetic alteration itself

Deceleration unit for a drop tower

Cílem této práce bylo navrhnout vhodný zádržný systém pro pádovou věž, která se bude nacházet v areálu ČVUT. Práce zahrnuje základní rešerši pádových věží a jejich zádržných systémů, základní konstrukční návrh zádržného systému a základní pevnostní analýzu. Na základě provedené rešerše a pevnostní analýzy bylo zjištěno, že nejvhodnějším řešením zádržného systému je volba zapichovacího hrotu.The aim of this work was to design a suitable deceleration unit for the drop tower, which will be located in the area of CTU. The thesis includes basic research on drop towers and their deceleration units, basic design of the deceleration unit and basic strength analysis. Based on the research and carried out strength analysis, it was found out, that the most suitable solution of the deceleration unit was the choice of a deceleration spike

TRAIL Delivered by Mesenchymal Stromal/Stem Cells Counteracts Tumor Development in Orthotopic Ewing Sarcoma Models.

Ewing sarcoma (EWS) is the second most frequent pediatric malignant bone tumor. EWS patients have not seen any major therapeutic progress in the last thirty years, in particular in the case of metastatic disease, which requires new therapeutic strategies. The pro-apoptotic cytokine TNF-Related Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while sparing normal cells, making it a promising therapeutic tool in several types of cancer. However, certain EWS cell lines appear resistant to recombinant human (rh) TRAIL-induced apoptosis. We therefore hypothesized that a TRAIL presentation at the surface of the carrier cells might overcome this resistance and trigger apoptosis. For this purpose, human adipose mesenchymal stromal/stem cells (MSC) transfected in a stable manner to express full-length human TRAIL were co-cultured with several human EWS cell lines, inducing apoptosis by cell-to-cell contact even in cell lines initially resistant to rhTRAIL or AMG655, an antibody agonist to the death receptor, DR5. In vivo, TRAIL delivered by MSCs was able to counteract tumor progression in two orthotopic models of Ewing sarcoma, associated with caspase activation, indicating that a cell-based delivery of a potent apoptosis-inducing factor could be relevant in EWS. This article is protected by copyright. All rights reserved

Design improvements of a roller rig

Kladkový stav je zařízení, který se používá pro simulaci jízdy kolejového vozidla po kolejích. Nachází se na Ústavu automobilů, spalovacích motorů a kolejových vozidel v laboratořích na Julisce. Cílem této práce je úprava kladkového stavu, která do simulace projetí obloukem zakomponuje i působení odstředivých sil. Vypracování návrhu rámové konstrukce a pohonu, který umožní simulaci odstředivých sil působících na podvozek, provedení základní pevnostní kontroly a vytvoření sestavného výkresu mechanismu.Roller rig is a device that is used to simulate ride of a rail vehicle on rails. It is located at the Department of Automotive, Combustion Engine and Railway Engineering in laboratories at Juliska. The aim of this work is to adjust the roller rig, which incorporates the effect of centrifugal forces into the simulation of the ride through the arc. Design of a frame construction and propulsion, which will allow simulation of centrifugal forces acting on the chassis, performing a basic strength check and creating an assembly drawing of the mechanism

3D Microfluidic Bone Tumor Microenvironment Comprised of Hydroxyapatite/Fibrin Composite

Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate the interactions between the TME and HA using a microfluidic platform designed for culturing tumor cells in 3D bone-mimetic composite of HA and fibrin. We developed a bone metastasis TME model from colorectal cancer (SW620) and gastric cancer (MKN74) cells, which has very poor prognosis but rarely been investigated. The microfluidic platform enabled straightforward formation of 3D TME composed the hydrogel and multiple cell types. This facilitated monitoring of the effect of HA concentration and culture time on the TME. In 3D bone mimicking culture, we found that HA rich microenvironment affects cell viability, proliferation and cancer cell cytoplasmic volume in a manner dependent on the different metastatic cancer cell types and culture duration indicating the spatial heterogeneity (different origin of metastatic cancer) and temporal heterogeneity (growth time of cancer) of TME. We also found that both SW620 and MKN72 cells exhibited significantly reduced migration at higher HA concentration in our platform indicating inhibitory effect of HA in both cancer cells migration. Next, we quantitatively analyzed angiogenic sprouts induced by paracrine factors that secreted by TME and showed paracrine signals from tumor and stromal cell with a high HA concentration resulted in the formation of fewer sprouts. Finally we reconstituted vascularized TME allowing direct interaction between angiogenic sprouts and tumor-stroma microspheroids in a bone-mimicking microenvironment composing a tunable HA/fibrin composite. Our multifarious approach could be applied to drug screening and mechanistic studies of the metastasis, growth, and progression of bone tumors

Inkludering av nyankomne flyktninger i det norske samfunnet

When refugees arrive in a new country, they face a range of challenges and obstacles that can affect their integration and success. From language barriers and cultural differences to challenges in getting recognition for their qualifications, the path to successful integration is often demanding and complex. In this context, the introduction program plays a role in supporting refugees in their transition to the new society. The purpose of this study is to investigate the significance of participating in the introduction program for refugees from non-Western countries in terms of their qualifications and success in the labor market. The study uses a literature review as a method to explore relevant research, focusing on addressing the research question through analysis of selected articles. The systematic approach provides a comprehensive understanding of the topic and contributes to new insights. Through the analysis of three scholarly articles, the study identified key themes from the perspectives of employers, refugees, and helpers. The results show a clear "focus on refugee integration," "collaboration among different stakeholders," "the importance of tailoring the introduction program to individual needs," and "challenges and barriers in the integration process." The study provides a good understanding of the challenges and opportunities in the integration of refugees into Norwegian society through participation in the introduction program. It emphasizes the importance of individual adaptation, improved collaboration, and support to ensure an effective integration process for refugees in the labor market. Keywords: Refugees, introduction program, integration, labor market, and qualifications

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras

Mislocalization of the E3 Ligase, beta-Transducin Repeat-containing Protein 1 (beta-TrCP1), in Glioblastoma Uncouples Negative Feedback between the Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase 1 (PHLPP1) and Akt

The PH domain leucine-rich repeat protein phosphatase, PHLPP, plays a central role in controlling the amplitude of growth factor signaling by directly dephosphorylating and thereby inactivating Akt. The cellular levels of PHLPP1 have recently been shown to be enhanced by its substrate, activated Akt, via modulation of a phosphodegron recognized by the E3 ligase β-TrCP1, thus providing a negative feedback loop to tightly control cellular Akt output. Here we show that this feedback loop is lost in aggressive glioblastoma but not less aggressive astrocytoma. Overexpression and pharmacological studies reveal that loss of the feedback loop does not result from a defect in PHLPP1 protein or in the upstream kinases that control its phosphodegron. Rather, the defect arises from altered localization of β-TrCP1; in astrocytoma cell lines and in normal brain tissue the E3 ligase is predominantly cytoplasmic, whereas in glioblastoma cell lines and patient-derived tumor neurospheres, the E3 ligase is confined to the nucleus and thus spatially separated from PHLPP1, which is cytoplasmic. Restoring the localization of β-TrCP1 to the cytosol of glioblastoma cells rescues the ability of Akt to regulate PHLPP1 stability. Additionally, we show that the degradation of another β-TrCP1 substrate, β-catenin, is impaired and accumulates in the cytosol of glioblastoma cell lines. Our findings reveal that the cellular localization of β-TrCP1 is altered in glioblastoma, resulting in dysregulation of PHLPP1 and other substrates such as β-catenin