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Istruzioni essenziali per la compilazione dell’application form, a cura di Cristina Soave\ud
No full textAliphatic Nitro compounds as Key Starting Materials for the One-Pot Synthesis of Cyclic and Heterocyclic Fine Chemicals
Get PDFQuantum Cryptography in d-dimensional Hilbert spaces
No full textThe topic of this thesis is Quantum Cryptography. Based on the laws of Quantum Mechanics, this allows two parties to share a secure key, by using \ud
quantum states to carry classical information. Namely, the Quantum Key Distribution (QKD) process, completed with the classical algorithm One Time Pad, leads to an unconditionally secure cryptosystem.\ud
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Most QKD protocols, like the famous BB84, are realized on unidirectional quantum channels and have probabilistic character. Recently, a new protocol, named LM05, has been proposed, which works on bidirectional quantum channels and in a deterministic way.\ud
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This thesis is mainly concerned with protocols extending LM05 from binary to d-ary alphabets (d>2), by using multi-level quantum systems in d-dimensional Hilbert spaces.\ud
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The construction of such protocols relies on the notion of Mutually Unbiased Bases (MUB). But the total number of MUB in a Hilbert space of dimension d is known only if d is a prime power. Accordingly, the new protocols are realized under this assumption. \ud
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As a preliminary step, an explicit expression for MUB encompassing powers of both even and odd primes is discussed.\ud
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The first proposed extension, called EM09, uses shift operators on MUB to encode information and the usual quantum measurement to realize the control procedure. This guarantees maximal security for dimension d=3 against a powerful individual attack.\ud
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The second extension, named EM11, is characterized by an innovative control strategy based on a suitable unitary transformation rather than on quantum measurement. Such protocol only works for d an odd prime power, due to the particular choice of the control operator, which is proved to be the only possible with the required properties. The EM11 protocol leads to a relevant improvement. In fact, the security against the same attack is much better than in the EM09 and it increases in terms of the dimension d.\ud
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Some partial results are also obtained about the possible extensions of the probabilistic protocol called SARG04 to higher dimensions.\ud
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Finally, it is considered the use of the EM09 and EM11 protocols in the Quantum Direct Communication, where the meaningful message is transmitted without any encryption, as allowed by their deterministic character. In this context, the asymptotic security turns out to be optimal in dimension d=2 for EM09 and in dimension d=3 for EM11.\ud
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Tra terzieri, contrade e computer: riflessioni sulle modalità di ricostruzione del tessuto urbano di Cingoli nel XIV secolo.
No full textGenetic determinants of Human Survival and Longevity:\ud A cross-sectional association study in a population of\ud Central Italy
No full textAim of the present thesis is to test the association of functional common variants located within possible candidate genes with human survival and longevity.\ud
Furthermore, we attempt to replicate and extend previous findings obtained on APOE, TNF-alpha and TP53 functional polymorphisms.\ud
The study has been conducted according to a cross-sectional approach and the polymorphisms have been determined for 1072 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes.\ud
Since the search for longevity-determining genes in human has largely neglected the operation of genetic interactions, we also performed gene-gene interaction analysis to assess the contribute of epistatic phenomena to the definition of genetic architecture underlying the complex trait of human longevity
Mutational analysis of translational activities in bacteria
No full textProtein biosynthesis occurs on large macromolecular ribo-nucleoprotein complexes, the ribosomes, in a process termed translation.\ud
In prokaryotes transcription and translation are tightly coupled cellular processes; ribosomes initiate translation on mRNAs while they are still being transcribed.\ud
Translation initiation is the rate-limiting and most highly regulated step of the three phases of protein biosynthesis (initiation, elongation and termination). Protein synthesis\ud
begins with an initial binding to the 30S ribosomal subunit of the initiation factors: IF3, IF1 and IF2 (according to the presumed order in which they bind). The initiator fMet-tRNAfMet and mRNA bind stochastically to the ribosomal subunit without initially interacting with each other, yielding a “30S pre-initiation complex”, which can either\ud
dissociate into its individual components or undergo a conformational change consisting of at least two first order rearrangements that promotes codon-anticodon interaction and formation of the more stable “30S initiation complex” [...]. The transition from pre-initiation to the bona fide 30S IC is kinetically controlled by the initiation factors [...] and entails a conformational transition of the ribosomal subunit and a shift of the mRNA from the “standy-by” to the P-decoding site position. The 30S initiation complex can then be fixed by its association with the 50S ribosomal subunit to form a “70S initiation complex”. Joining of the 50S subunit with the 30S initiation complex causes a number of events: the activation of GTP hydrolysis by IF2 and a conformational change of this initiation factor; the dissociation of the initiation factors IF1 and IF3 and the stabilization of fMet-tRNAfMet in the P site [...]. The newly formed 70S initiation complex with fMettRNAfMet in the peptidyltransferase center of the 50S ribosomal subunit is now ready to enter the elongation phase of translatio
Innovative Functional Methods Useful for New Cellular Target Identification and for Receptor Ligand Characterization
No full textG-protein coupled receptors (GPCRs) are a large family of receptor proteins that play important roles in many physiological and pathological conditions. In drug discovery, they are one of the most important drug targets. In particular, adenosine receptors, classified as A1, A2A, A2B and A3 (A1AR, A2AAR, A2BAR, and A3AR) subtypes, have been actively studied as potential therapeutic targets in several disorders such as cardiovascular and CNS pathologies.\ud
The aim of the present work is the development of innovative and non-radioactive screening systems in order to study a large number of adenosine P1 receptor ligands. On the other hand, since new assays could be useful to contribute to receptor deorphanization, the task work has been focused to characterize the putative guanosine receptor and the novel dual uracil nucleotide/cysteinyl-leukotriene receptor, GPR17. In particular, functional cAMP and DELFIA GTP-Eu binding assays were used.\ud
The cAMP immuno-competitive assay, performed in homogeneous time resolved fluorescence (HTRF), was optimized and validated using as reference agonists NECA at A2AAR and A2BAR, and Cl-IBMECA at A3AR. Hence, after this assay validation, the biological profile of a series of 8-substituted 9-ethyladenines was assessed at A2AAR. Results showed that all compounds behave as A2AAR antagonists.\ud
On the other hand, an innovative luminescence cAMP assay, that uses a genetically modified form of firefly luciferase containing a cAMP-binding protein moiety, was developed for ARs. Two new improved plasmids containing the gene for the modified form of firefly luciferase were optimized and validated at ARs in order to verify their efficacy at Gαs and Gαi systems. In particular, the experiments were carried out by transiently expressing these new vectors at CHO cell line stably transfected with A2A and A3 ARs. Results showed that both plasmids can be used at ARs and since this assay demonstrated to be robust and reproducible, it was used as new tool to investigate the novel “dual” GPR17. Furthermore, the better evaluation of the “dual” nature of the human GPR17 could be carried out in 1321N1 cells since they do not constitutively express nucleotide and cysteinyl-leukotriene receptors. In particular, different transient transfection methods such as calcium phosphate, lipofectamine, fugene, arrest-InTM and microporation, have been investigated. Experiments were performed using also in parallel GFP as reporter gene and results analyzed by RT-PCR suggested that microporator as well as Arrest-In are both the best method to promote an enriched hgpr17 delivery into 1321N1 cell line.\ud
Moreover, DELFIA GTP-Eu binding assay was carried out using CHO-A3 membranes. The standardization of DELFIA GTP-Eu assay is a long process, in which the determination of the specific receptor buffer stimulation was the first crucial step investigated. The assay validation was carried out using know ligands and subsequently, a new series of 2-alkynyl-N6-methyl-5’-N-methylcarboxamidoAdo derivatives were screened and results suggested that they are full agonists at A3AR. Subsequently, the assay potentialities were extended at native tissue. In particular, rat brain membranes were prepared from Male Wistar rat and used to investigate putative guanosine receptor by testing known and novel ligands. Results obtained suggested the presence of a G-protein coupled receptor able to be activated by guanosine and some guanosine derivatives.\ud
The AGC is a family of kinase that is composed of 60 different enzymes including PKC isoforms, PKB/AKT, S6K and their upstream kinase, the phosphoinositide-dependent protein kinase 1 (PDK1). In particular, located in the small loop of the kinase domain is present a pocket called PIF-binding pocket that is involved in the regulation of the intrinsic activity of these kinases. The molecular mechanism of allosteric activation of PDK1 by small molecular weight prodrugs and their effects in C2C12 cells were evaluated. In particular experiments were carried out incubating C2C12 with PS423 and PS0403, small chemical entities synthesized by the PhosphoSites research group, and after cell insulin stimulation the PDK1 pathway was investigated. Results obtained suggested that these compounds were able to bind the PIF-binding pocket inhibiting the S6K phosphorylation without affecting the PKB activity. On the other hand, the in cell western was optimized at C2C12, as new assay to screen and to evaluate in a throughput way the effects of several PS-compounds on the S6K phosphorylation by PDK1. Results demonstrated that the in cell western is a robust, reproducible and easy to use assay to screen directly in the cell several compounds in the same experiments
