GTSE1: a novel TEAD4-E2F1 target gene involved in cell protrusions formation in Triple Negative Breast Cancer

Dissemination of cancer cells from the primary tumors to distant organs represents the main cause of death in cancer patients. GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies including breast cancer where GTSE1 expression levels correlate with tumor grade, enhanced invasive potential and negative prognosis. Given the strong association between GTSE1 deregulation and bad clinical outcome the aim of this work was to clarify how GTSE1 is regulated in triple negative breast cancer and the molecular mechanism underlying GTSE1dependent cell movement. Here, I identified GTSE1 as a novel direct TEAD4 and E2F1 transcription factors target gene, highlighting a role for YAP and TAZ co-activators in GTSE1 transcriptional regulation. Frequently deregulated in cancers, TEAD4 and the co-activators YAP and TAZ have been reported to promote tumorigenesis, invasion and metastasis in breast cancer. I demonstrated that the effect of the TEAD transcription factor on cell migration and invasion is GTSE1-dependent. Moreover, I found that TEAD controls cell protrusions formation, required for cell migration, through GTSE1 protein, unveiling a relevant effector role for GTSE1 in the TEAD-dependent cellular functions

Characterization of mycobacterial enzymes as targets for potential antitubercular compounds.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, an aerobic pathogen that establishes its infection mainly in lungs. Even if it was considered for a very long period an illness of the past, new hotspots arose at the beginning of ’90 and it is still today a global emergency. According to the 2019 WHO global report, tuberculosis is one of the top 10 causes of death worldwide.10 million new cases were estimated only in 2019 and 1.5 million people died for the disease in the same year, overall cause of the multi-drug resistant and extensively drug resistant strains. To fight back this emergency it is necessary to identify new therapeutic TB drug targets and to develop more effective drugs. In this thesis I show how it is possible to design multi-target molecules that may inhibits the M. tuberculosis salicylate synthase MbtI and the virulence factor protein phosphatase PtpB, two interesting mycobacterial druggable targets

Multitargeting Compounds: A Promising Strategy to Overcome Multi-Drug Resistant Tuberculosis

Tuberculosis is still an urgent global health problem, mainly due to the spread of multi-drug resistant M. tuberculosis strains, which lead to the need of new more efficient drugs. A strategy to overcome the problem of the resistance insurgence could be the polypharmacology approach, to develop single molecules that act on different targets. Polypharmacology could have features that make it an approach more effective than the classical polypharmacy, in which different drugs with high affinity for one target are taken together. Firstly, for a compound that has multiple targets, the probability of development of resistance should be considerably reduced. Moreover, such compounds should have higher efficacy, and could show synergic effects. Lastly, the use of a single molecule should be conceivably associated with a lower risk of side effects, and problems of drug-drug interaction. Indeed, the multitargeting approach for the development of novel antitubercular drugs have gained great interest in recent years. This review article aims to provide an overview of the most recent and promising multitargeting antitubercular drug candidates

Characterization of convection-related parameters by Raman lidar: Selected case studies from the convective and orographically-induced precipitation study

An approach to determine the convective available potential energy (CAPE) and the convective inhibition (CIN) based on the use of data from a Raman lidar system is illustrated in this work. The use of Raman lidar data allows to provide high temporal resolution measurements (5 min) of CAPE and CIN and follow their evolution over extended time periods covering the full cycle of convective activity. Lidar-based measurements of CAPE and CIN are obtained from Raman lidar measurements of the temperature and water vapor mixing ratio profiles and the surface measurements of temperature, pressure and dew point temperature provided by a surface weather station. The approach is applied to the data collected by the Raman lidar system BASIL in the frame of COPS. Attention was focused on 15 July and 25-26 July 2007. Lidar-based measurements are in good agreement with simultaneous measurements from radiosondes and with estimates from different mesoscale models

Collaborating for Educational Improvement: Exploring cases of teacher collaboration for policy implementation

Teacher collaboration holds great promise for improving educational outcomes. Education policies commonly seek to foster teacher collaboration to bring about improvements in teacher learning, instructional quality, and improved student outcomes. Collaborative approaches including professional learning communities (PLCs), grade level teams, instructional coaching, and co-teaching are common in the reform landscape. Teachers’ collaboration is deeply enabled or constrained by school organization and the broader educational systems in which it is embedded. My dissertation studies employ an organizational and systems lens for exploring the embeddedness of teachers’ collaboration for policy implementation. Specifically, my studies explore two different policy contexts that utilize collaborative approaches for improvement: the inclusion of students with disabilities and ambitious mathematics instruction. Policies related to inclusion count on teachers’ collaboration as a means for ensuring that students with disabilities are appropriately supported in general education settings. With regard to math instruction, schools and districts commonly employ collaborative approaches to enhance teacher professional learning and ultimately enhance the quality of their math instruction. Findings from these studies suggest that using an organizational lens and exploring teachers’ practice in terms of collaboration can reveal important barriers and unintended consequences to collaboration for policy implementation. Together, my dissertation studies illuminate the organizational and social aspects of teacher collaborations for policy implementation that matter if collaboration is to be productive for supporting students in inclusive settings or improving teachers’ professional learning for math instruction

Characterization of the planetary boundary layer height and structure by Raman lidar: comparison of different approaches

Abstract. The planetary boundary layer (PBL) includes the portion of the atmosphere which is directly influenced by the presence of the earth's surface. Aerosol particles trapped within the PBL can be used as tracers to study the boundary-layer vertical structure and time variability. As a result of this, elastic backscatter signals collected by lidar systems can be used to determine the height and the internal structure of the PBL. The present analysis considers three different methods to estimate the PBL height. The first method is based on the determination of the first-order derivative of the logarithm of the range-corrected elastic lidar signals. Estimates of the PBL height for specific case studies obtained through this approach are compared with simultaneous estimates from the potential temperature profiles measured by radiosondes launched simultaneously to lidar operation. Additional estimates of the boundary layer height are based on the determination of the first-order derivative of the range-corrected rotational Raman lidar signals. This latter approach results to be successfully applicable also in the afternoon–evening decaying phase of the PBL, when the effectiveness of the approach based on the elastic lidar signals may be compromised or altered by the presence of the residual layer. Results from these different approaches are compared and discussed in the paper, with a specific focus on selected case studies collected by the University of Basilicata Raman lidar system BASIL during the Convective and Orographically-induced Precipitation Study (COPS)

Aharonov-Bohm Effect on Noncommutative Plane: A Coherent State Approach

We apply the coherent state approach to study Aharonov-Bohm effect in the field theory context. We verify that, contrarily to the commutative result, the scattering amplitude is ultraviolet finite. However, we have logarithmic singularities as the noncommutative parameter tends to zero. Thus, the inclusion of a quartic self-interaction for the scalar field is necessary to obtain a smooth commutative limit.Comment: 14 pages, 4 figures, minor correction