Listing 1 - 8 of 8 |
Sort by
|
Choose an application
Asthma --- Bronchial hyperactivity --- Dendritic cells --- Intracellular signaling peptides and proteins --- immunology --- physiology
Choose an application
Guanine Nucleotide Exchange Factors --- Intestinal Mucosa --- Intracellular Signaling Peptides and Proteins --- Inflammation --- immunology --- Inflammation.
Choose an application
Hirschsprung Disease --- Carrier Proteins --- Intracellular Signaling Peptides and Proteins --- genetics --- metabolism --- metabolism
Choose an application
The objective of this thesis is to identify the determinants of the failure of Initial Coin Offerings (ICOs). ICOs are a new, innovative form of corporate financing: The company sells digital tokens to investors, who can then participate in the company's future development. Intermediaries like banks are no longer required. ICOs have been enjoying a lot of popularity lately. However, the market suffers from high uncertainty and asymmetric information. Therefore, further research is needed. Some studies have already analyzed the determinants of the success (esp. the amount raised) of ICOs. This thesis instead, aims to identify the determinants of failure. These are to be determined with multivariate data analysis. It is suggested to indicate the dependent variable of the failure of an ICO by the listing and/or the trading activity of its token on a secondary exchange.
ICO --- Initial Coin Offering --- Corporate Financing --- Crypto --- Signaling Theory --- Sciences économiques & de gestion > Comptabilité & audit
Choose an application
Herpesviridae --- Cattle diseases --- Herpesviridae infections --- Malignant catarrh --- Intercellular signaling peptides and proteins --- Immune Evasion. --- genetics --- Herpesviridae Infections. --- Cattle Diseases. --- Malignant Catarrh. --- genetics. --- Intercellular Signaling Peptides and Proteins. --- Cattle Diseases --- Herpesviridae Infections
Choose an application
Abnormalities, Multiple --- Craniofacial Abnormalities --- Intellectual Disability --- Intracellular Signaling Peptides and Proteins --- Nuclear Proteins --- Gigantism --- genetics --- genetics --- genetics --- genetics --- genetics --- blood
Choose an application
This thesis presents an overview about the interplay of cybersecurity investment, information asymmetry and information gathering. It investigates the impact of asymmetric information between consumer, vendor and hacker. To determine the effect, this thesis draws upon the cybersecurity models of Al- Humaigani and Dunn (2003), Gordon and Loeb (2002) and Huang, Hu, and Behara (2008). Thereupon, possible solution methods for asymmetric information are analysed. These are in particular information sharing and bug bounty programs. The influence of information sharing on investment is modelled based on network theory. In order to make the quality of a software assessable, bug bounty programs work as a signaling device. Both information gathering programs reduce asymmetric information. While information sharing is more focussed on asymmetries between consumers, bug bounty programs help to reduce asymmetry between vendor and consumer. The magnitude of the effect is dependent on the characteristics of the model, such as risk-averseness.
Choose an application
Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide, with patients presenting an overall 5-year survival lower than 15%. NSCLC is characterized by a multitude of tumor-promoting genetic alterations, such as mutations in KRAS, EGFR and TP53 genes. The high heterogeneity and plasticity of lung cancers is one of the main reasons for the failure of current treatment strategies. Importantly, genomic amplification of RICTOR frequently occurs in lung cancer. RICTOR is the defining component of mTOR complex 2 (mTORC2). Moreover, RICTOR-dependent activation of mTORC2 is essential to support lung cancer cell survival and tumor growth in vivo. Despite high therapeutic potential, directly targeting mTORC2 activity in patients remains challenging. Therefore, targeting mTORC2-dependent liabilities may represent a better option for the development of anticancer treatments. Preliminary work from our lab and results from the literature have positioned mTORC2 signaling at the crossroad between translation and metabolism. Hence, deciphering the mechanisms linking mTORC2-dependent translation to the acquisition of specific metabolic liabilities will highlight new therapeutic strategies for the treatment of lung cancer. In this study, I focused on understanding the molecular mechanisms that sustain the rewiring of cancer cell metabolism in the clinically relevant context of RICTOR-overexpressing (RICTOR OE) lung cancer. Using several models, I first evidenced an active role for RICTOR/mTORC2 in the regulation of cancer associated mRNA translation. Preliminary data from the lab indicated that RICTOR silencing in human lung cancer cells was associated with a negative enrichment of hypoxia signatures. Therefore, I first assessed the expression of the different hypoxia-inducible factors (HIF-1α, HIF-2α and HIF-1β) in RICTOR-depleted lung cancer cells. Strikingly, I found that expression of the transcription factor HIF-1β was significantly and consistently decreased upon RICTOR silencing. Importantly, RICTOR-dependent modulation of HIF-1β expression occurred at protein level and was observed in multiple cancer cell lines, highlighting HIF-1β as a potential RICTOR-dependent translational target in lung cancer. Using pharmacological and genetic inhibition of mTOR signaling (RICTOR, RAPTOR and SIN1 siRNAs; mTOR, AKT and PKC inhibitors) I further showed that RICTOR controlled HIF-1β expression through an mTOR-PKC signaling axis, independently of AKT activity. Finally, I demonstrated that HIF-1β levels correlated with mTORC2 activation in vivo, in a mouse model of RICTOR OE. Taken together, my results highlight HIF-1β as a clinically relevant target and support targeting of hypoxia-mediated metabolism as a potential therapeutic approach for the treatment of lung cancer.
lung cancer --- mRNA translation --- metabolism --- mTORC2 --- RICTOR --- HIF1beta --- HIF-1β --- signaling pathways --- Sciences du vivant > Biochimie, biophysique & biologie moléculaire
Listing 1 - 8 of 8 |
Sort by
|