Tuning PNA Properties by Chemical Modifications: Design Synthesis and Applications

The present Ph.D. Thesis concerns the development of modified chiral Peptide Nucleic Acids (PNAs) aimed at improving the affinity and the selectivity towards complementary DNA sequences for biomedical and food applications. In particular, PNA Molecular Beacons have been studied for HPLC analysis. PNAs based on arginine have been developed. Two types of microarrays, one with PNAs covalently linked to a silica surface, the other obtained by microcontact printing have been shown to be promising tools for selective DNA recognition. Finally PNAs embedding a pseudopeptide Nuclear Localization Sequence have been synthesized and tested in cell cultures, providing good evidence of internalization inside the nucleus.Il lavoro riportato in questa tesi di dottorato riguarda lo sviluppo di Acidi Peptido Nucleici (PNA) chirali al fine di migliorare l’affinità e selettività nel riconoscimento di DNA complementare per applicazioni biomediche e alimentari. In particolare sono stati studiati PNA Beacons per analisi in HPLC. Sono stati sviluppati PNA chirali a base di arginina. Due tipologie di microarrays sono state sviluppate, una in cui i PNA sonolegati covalentemente ad una superficie di silice, l’altra basata su una tecnologia di microcontact printing. Infine, sono stati sintetizzati PNA contenenti una sequenza pseudopeptidica di localizzazione nucleare, che somministrati in colture cellulari hanno mostrato una buona capacità di penetrazione nel nucleo

An experimental-numeric approach to manufacture semiconductor wafer using thick copper front metallization

AbstractThe presented work investigates about the deformation of semiconductor device induced by electrochemical deposited thick copper films. It enhances thermal and electric performances allowing to use copper interconnections without formations of intermetallic layers at the interfaces with consequent reliability improvement. Nevertheless, the induced deformation strongly affects manufacturability, criticizing the integration between different process steps. Experiment based on phase-shift Moiré principle has been performed to better understand the relation between warpage and temperature. Finite element model has been developed to reproduce the phenomenon in order to address the design and the process integration optimizing workability, electrical performances and reliability

Simulation of Dynamic Stresses on High Performance Engine Valve Spring System Considering Coil Clashing Effect

AbstractThe valve train plays a major role in the performance of internal combustion engines by controlling the combustion process and it is therefore one of the key aspects for increasing the efficiency of combustion engines. Considering the dynamics, the spring force must be high enough to reliably close the valve preventing from seating bouncing due to surge modes after the valve closure. On the other side, the spring force should be kept as low as possible in order to reduce the engine friction losses and consequently the fuel consumption. In the high-performance engines, the valve springs have to be designed and optimized for sustaining higher stresses with compact dimensions leading to critical material and manufacturing processes. This requires a reduction of moving masses and a strong focus on design and process optimization of the coil springs for reducing the mechanical load and the friction losses at low engine speed. At the same time, valve train should be reliable at high engine speed. The calculation of stresses and contact forces for moving parts under dynamic load is essential for durability analysis. A method to calculate the contact of moving masses is described and proposed to justify valve motions experimental results. To fully understand the failure mechanism of test bed reliability trials, the dynamic stresses have been calculated modeling the real springs' shape. The contact forces have been reproduced considering the coil clash effects and the dynamic behavior of the flexible spring

Analysis of Warpage Induced by Thick Copper Metal on Semiconductor Device

AbstractElectrochemical deposited (ECD) thick film copper on silicon substrate is one of the most challenging technological brick for semiconductor industry representing a relevant improvement from the state of art because of its excellent electrical and thermal conductivity compared with traditional compound such as aluminum. The main technological factor that makes challenging the industrial implementation of thick copper layer is the severe wafer warpage induced by Cu annealing process, which negatively impacts the wafer manufacturability. The aim of presented work is the understanding of warpage variation during annealing process of ECD thick (~20 µm) copper layer. Warpage has been experimental characterized at different temperature by means of Phase-Shift Moiré principle, according to different annealing profiles. A linear Finite Element Model (FEM) has been developed to predict the geometrically stress-curvature relation, comparing results with analytical models

Deep Learning Algorithm for Advanced Level-3 Inverse-Modeling of Silicon-Carbide Power MOSFET Devices

Inverse modelling with deep learning algorithms involves training deep architecture to predict device's parameters from its static behaviour. Inverse device modelling is suitable to reconstruct drifted physical parameters of devices temporally degraded or to retrieve physical configuration. There are many variables that can influence the performance of an inverse modelling method. In this work the authors propose a deep learning method trained for retrieving physical parameters of Level-3 model of Power Silicon-Carbide MOSFET (SiC Power MOS). The SiC devices are used in applications where classical silicon devices failed due to high-temperature or high switching capability. The key application of SiC power devices is in the automotive field (i.e. in the field of electrical vehicles). Due to physiological degradation or high-stressing environment, SiC Power MOS shows a significant drift of physical parameters which can be monitored by using inverse modelling. The aim of this work is to provide a possible deep learning-based solution for retrieving physical parameters of the SiC Power MOSFET. Preliminary results based on the retrieving of channel length of the device are reported. Channel length of power MOSFET is a key parameter involved in the static and dynamic behaviour of the device. The experimental results reported in this work confirmed the effectiveness of a multi-layer perceptron designed to retrieve this parameter.Comment: 13 pages, 8 figures, to be published on Journal of Physics: Conference Serie

Targeting CDK6 and BCL2 Exploits the MYB Addiction of Ph+ Acute Lymphoblastic Leukemia

Philadelphia chromosome–positive acute lymphoblastic leukemia (Phþ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Phþ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Phþ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced Phþ ALL cells rescues their impaired proliferation and survival. Levels of MYB and CDK6 were highly correlated in adult Phþ ALL (P ¼ 0.00008). Moreover, Phþ ALL cells exhibited a specific requirement for CDK6 but not CDK4 expression, most likely because, in these cells, CDK6 was predominantly localized in the nucleus, whereas CDK4 was almost exclusively cytoplasmic. Consistent with their essential role in Phþ ALL, pharmacologic inhibition of CDK6 and BCL2 markedly suppressed proliferation, colony formation, and survival of Phþ ALL cells ex vivo and in mice. In summary, these findings provide a proof-of-principle, rational strategy to target the MYB addiction of Phþ ALL. © 2017 American Association for Cancer Research

Power Semiconductor Devices and Packages: Solder Mechanical Characterization and Lifetime Prediction

Solder reliability is a key aspect for the packaging of low voltage power semiconductor device. The interconnections among package components, e.g. the silicon chip and copper leadframe, and between package itself and the external printed control board (PCB) should be properly designed to ensure the automotive durability requirements. In this framework, the proposed paper introduces an experimental-numeric characterization flow with the purpose to analyze solder visco-plasticity and fatigue during passive temperature cycle. The presented methodology has included solder mechanical characterization aimed to determine the parameters of Anand model which reproduces the solder visco-plastic behavior and the mechanical properties' temperature dependency. Finite element model has been employed to calculate the inelastic work which solder dissipates during each temperature cycle. Simulation results serve as input to predict solder lifetime according to an energetic method. Moreover, failure analyses have been performed to assess the failure mechanism and to check model correlation in terms of number of cycles to failure forecast

Implementation and Comparison of SiC and GaN switches for EV Fast Recharging Systems

Wide bandgap material-based devices allow faster switching frequency and exhibit smaller losses than traditional Si devices; nevertheless, a complete understanding of the functioning of these new devices remains poorly understood. A fast battery charger for electric vehicles based on a converter employing SiC and GaN devices is here reported Besides, these two technologies are experimentally compared, in the same layout, to highlights their performance in terms of electrical dynamic and electromagnetic compatibility

Suppression of Invasion and Metastasis of Triple-Negative Breast Cancer Lines by Pharmacological or Genetic Inhibition of Slug Activity

AbstractMost triple-negative breast cancers (TNBCs) exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT), a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1); thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA) or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic spread of TNBC cell lines. We show here that PCPA treatment induces the expression of E-cadherin and other epithelial markers and markedly suppresses migration and invasion of TNBC cell lines MDA-MB-231 and BT-549. These effects were phenocopied by Slug or LSD1 silencing. In two models of orthotopic breast cancer, PCPA treatment reduced local tumor growth and the number of lung metastases. In mice injected directly in the blood circulation with MDA-MB-231 cells, PCPA treatment or Slug silencing markedly inhibited bone metastases but had no effect on lung infiltration. Thus, blocking Slug activity may suppress the metastatic spread of TNBC and, perhaps, specifically inhibit homing/colonization to the bone