Emerging role of TRP channels in cell migration: from tumor vascularization to metastasis

Transient Receptor Potential (TRP) channels modulate intracellular Ca(2+) concentrations, controlling critical cytosolic and nuclear events that are involved in the initiation and progression of cancer. It is not, therefore, surprising that the expression of some TRP channels is altered during tumor growth and metastasis. Cell migration of both epithelial and endothelial cells is an essential step of the so-called metastatic cascade that leads to the spread of the disease within the body. It is in fact required for both tumor vascularization as well as for tumor cell invasion into adjacent tissues and intravasation into blood/lymphatic vessels. Studies from the last 15 years have unequivocally shown that the ion channles and the transport proteins also play important roles in cell migration. On the other hand, recent literature underlies a critical role for TRP channels in the migration process both in cancer cells as well as in tumor vascularization. This will be the main focus of our review. We will provide an overview of recent advances in this field describing TRP channels contribution to the vascular and cancer cell migration process, and we will systematically discuss relevant molecular mechanism involved

Garment Recommendations for Online and Offline Consumers

Recommender Systems have obvious influence in environments where data size exceeds the capabilities of any user to fully explore the available choices in the store (physical or on-line). Many algorithms and techniques have been used to help recommending useful and interesting items to users. If the user is unidentified, the process is even harder as there are no historical or other data to use as input. Association rules is a popular technique used for many purposes in Recommender Systems such as for building more robust systems, improving quality of recommendations; and even addressing fundamental limitations of recommender systems and, generally, large datasets, e.g. sparsity and cold start. At the same time, efforts have been made to fully understand if and how differently customers are behaving in an online and in a physical environment.This work tries to combine the two efforts. We use association rules to provide recommendations to customers, as well as understand who the customer is, what her needs are and what is her mentality when entering a physical store or the corresponding e-shop. To fulfill our goal, we used descriptive statistics along with Association Rules analysis of the POS transactional data on basket data level and historical data level

Tailoring Ru(II) and Os(II) luminophores to their application: from bioimaging and sensing to cytotoxic tools.

Transition metal luminophores show significant potential as multifunctional probes with applications in many fields extending from medicinal chemistry to bioimaging and biosensing. Conjugation of Ru(II)/ Os(II) luminophores to signal peptides is a useful strategy to reliably deliver the probes intracellularly and to specific organelles such as the nucleus and mitochondria. While conventional microscopy methods are used for cellular-imaging, biosensing techniques, can range from fluorescence lifetime imaging microscopy (FLIM) to simple fluorescence intensity-based measurements. This thesis explores the design and photophysical properties of biocompatibleprobes for imaging and sensing within the cellular environment. Chapter 1 reviews the literature and background to the thesis. Chapter 2 describes an achiral Os(II) complex, [Os(tpybenzCOOH)2] 2+ conjugated to the mitochondrial targeting peptide, MPP, at two conjugation sites. The novel bis-MPP conjugate showed NIR emission coincident with the biological window and an interesting approach to theranostics was proposed whereby switch in cell death mechanism (dark toxicity) is reflected in specific probe localisation observed via confocal microscopy. Chapter 3 describes the preparation of two polyarginine-based Os(II) conjugates and their uptake in live cells. While confocal imaging revealed probe- membrane interactions, Os-bisR8 was not taken up by cells, attributed to the large arginine-chains resulting in a significantly high cationic charge. In order to balance lipophilicity and overall cationic charge, Os-bisR4 was prepared and shown to be taken up by A549 lung carcinoma cells. Chapter 4 presents the preparation and characterization of novel ratiometric Ru(II)/ BODIPY core- shell nanoparticles. Single excitation at 480 nm resulted in dual emission corresponding to the BODIPY and Ru(II) particle component. The poly-L-lysine coated particles were studied in two cancerous cell lines as oxygen sensors. The changes in oxygen levels under hypoxic conditions were monitored using xy-lamda (xyλ) scanning microscopy. Chapter 5 investigated a series of novel Ru(biq) 2 (trzbenzCOOH)-conjugates (NLS,R8,MPP,PEG) in CHO and HeLa cell lines. All conjugates exhibited dark cytotoxicity and the origin of toxicity was studied in detail using the mitochondrial depolarization and caspase activity assays. This chapterhighlighted the importance of balancing lipophilicity and targeting ability in order to reduce overall probe toxicity