Metodi per l'estrazione di caratteristiche di molecole mediante la microscopia a forza atomica

Questo lavoro si propone di estrarre informazioni su molecole biologiche fissate su un substrato utilizzando la microscopia AFM. Il limite naturale di questa microscopia è dato dagli effetti distorsivi della convoluzione punta-campione. Per superare questo limite, il presente lavoro propone un aproccio inverso rispetto a quelli classici; Invece di operare direttamente sull’imaging molecolare si costruisce un modello della molecola e viene simulata la microscopia, introducendo le distorsioni tipiche dell’AFM. Il confronto (basato sulla mutua informazione) viene reiterato raffinando ad ogni iterazione i parametri iniziali. La simulazione della microscopia afm comprende la ricostruzione del tip

Embedding Classical Variational Methods in Quantum Circuits

We introduce a novel quantum-classical variational method that extends the quantum devices capabilities to approximate ground states of interacting quantum systems. The proposed method enhances parameterized quantum circuit ansatzes implemented on quantum devices with classical variational functions, such as neural-network quantum states. The quantum hardware is used as a high-accuracy solver on the most correlated degrees of freedom, while the remaining contributions are treated on a classical device. Our approach is completely variational, providing a well-defined route to systematically improve the accuracy by increasing the number of variational parameters, and performs a global optimization of the two partitions at the same time. We demonstrate the effectiveness of the protocol on spin chains and small molecules and provide insights into its accuracy and computational cost. We prove that our method is able to converge to exact diagonalization results via the addition of classical degrees of freedom, while the quantum circuit is kept fixed in both depth and width.Comment: 11 pages, 6 figure

An efficient quantum algorithm for the time evolution of parameterized circuits

We introduce a novel hybrid algorithm to simulate the real-time evolution of quantum systems using parameterized quantum circuits. The method, named "projected - Variational Quantum Dynamics" (p-VQD) realizes an iterative, global projection of the exact time evolution onto the parameterized manifold. In the small time-step limit, this is equivalent to the McLachlan's variational principle. Our approach is efficient in the sense that it exhibits an optimal linear scaling with the total number of variational parameters. Furthermore, it is global in the sense that it uses the variational principle to optimize all parameters at once. The global nature of our approach then significantly extends the scope of existing efficient variational methods, that instead typically rely on the iterative optimization of a restricted subset of variational parameters. Through numerical experiments, we also show that our approach is particularly advantageous over existing global optimization algorithms based on the time-dependent variational principle that, due to a demanding quadratic scaling with parameter numbers, are unsuitable for large parameterized quantum circuits.Comment: 7+4 pages, 8 figures; Manuscript revised for publication. Method: added Section 2.2, Results: added Figure 6, Appendix: added Appendix E with Figure

Sequence of penalties method to study excited states using VQE

We propose an extension of the Variational Quantum Eigensolver (VQE) that leads to more accurate energy estimations and can be used to study excited states. The method is based on the introduction of a sequence of increasing penalties in the cost function. This approach does not require circuit modifications and thus can be applied with no additional depth cost. Through numerical simulations, we show that we are able to produce variational states with desired physical properties, such as total spin and charge. We assess its performance both on classical simulators and on currently available quantum devices, calculating the potential energy curves of small molecular systems in different physical configurations. Finally, we compare our method to the original VQE and to another extension, obtaining a better agreement with exact simulations for both energy and targeted physical quantities.Comment: 11 pages, 9 figures, accepted in IOP Quantum Science and Technolog

Studio del funzionamento dell'impianto di depurazione di Conselve

Oggetto della tesi è lo studio dell'impianto di depurazione di Conselveope

Boosting infrared energy transfer in 3D nanoporous gold antennas

The applications of plasmonics to energy transfer from free-space radiation to molecules are currently limited to the visible region of the electromagnetic spectrum due to the intrinsic optical properties of bulk noble metals that support strong electromagnetic field confinement only close to their plasma frequency in the visible/ultraviolet range. In this work, we show that nanoporous gold can be exploited as a plasmonic material for the mid-infrared region to obtain strong electromagnetic field confinement, co-localized with target molecules into the nanopores and resonant with their vibrational frequency. The effective optical response of the nanoporous metal enables the penetration of optical fields deep into the nanopores, where molecules can be loaded thus achieving a more efficient light–matter coupling if compared to bulk gold. In order to realize plasmonic resonators made of nanoporous gold, we develop a nanofabrication method based on polymeric templates for metal deposition and we obtain antenna arrays resonating at mid-infrared wavelengths selected by design. We then coat the antennas with a thin (3 nm) silica layer acting as the target dielectric layer for optical energy transfer. We study the strength of the light–matter coupling at the vibrational absorption frequency of silica at 1240 cm−1 through the analysis of the experimental Fano lineshape that is benchmarked against identical structures made of bulk gold. The boost in the optical energy transfer from free-space mid-infrared radiation to molecular vibrations in nanoporous 3D nanoantenna arrays can open new application routes for plasmon-enhanced physical–chemical reactions

Pichia pastoris: an eukariotic system for the expression of recombinant therapeutic molecules

L’ideazione di farmaci antitumorali che riconoscono recettori o antigeni della superficie cellulare, come le Immunotossine, rappresentano un approccio promettente per il trattamento di pazienti affetti da cancro. La capacità di indurre l’apoptosi dell’Immunotossina IL4PE40 deriva dal frammento di 40 kDa della tossina PE (Pseudomonas esotossina A) e la sua specificità dalla forma permutata dell’interleuchina-4. IL4PE40 prodotta da E. coli è estratta dai corpi d’inclusione e purificata nella sua forma attiva tramite cromatografia di affinità. Comunque, la translazione clinica di molecole terapeutiche prodotte da E. coli è spesso difficoltosa, a causa di contaminazioni da endotossine e di protocolli laboriosi per la purificazione dei corpi d’inclusione che rendono difficile la riproducibilità della procedura di isolamento. Per superare questi svantaggi, ho clonato il gene di IL4PE40 in un vettore d’espressione per il lievito Pastoris pastoris. In letteratura è riportato che P. pastoris è in grado di secernere grammi per litro di proteine eterologhe in un terreno povero di proteine, economico e chimicamente definito. La presenza di un peptide segnale all’N-terminale della proteina ricombinante permette la secrezione della proteina nativa nel terreno di coltura. Inoltre il basso livello di secrezione di proteine endogene nel terreno di coltura, facilita i passaggi di purificazione del prodotto finale. Nel mio lavoro la resa di IL4PE40 prodotta dal lievito è stata ottimizzata dal utilizzo del “codon usage” del lievito e dall’analisi di diverse condizioni di induzione. Dopo l’ottimizzazione P. pastoris è in grado di produrre 120 µg di Immunotossina da un litro di coltura; questo quantità è lontana dai risultati ottenuti in altri lavori con proteine non tossiche. Inoltre, benché dopo l’ottimizzazione la resa sia aumentata, le proteine ottenute da colture ottimizzate di P. pastoris mostrano un considerevole livello di degradazione. La translocazione della proteina tossica nel citosol durante la biosintesi potrebbe portare ad una dminuzione della produzione. Inoltre, sembra che nel terreno del lievito siano presenti proteasi in grado di degradare la molecola ricombinante. Saggi di degradazione con la PE nativa e dati della letteratura suggeriscono che diverse proteasi (serine e subtilisine) potrebbero cooperare nella degradazione di IL4PE40. Nella mia tesi sono inoltre descritti esperimenti pianificati per superare queste limitazioni.Rationally designed anticancer agents targeting cell-surface antigens or receptors, such as Immunotoxins, represent a promising approach for treating cancer patients. The Immunotoxin IL4PE40 derives its activity to induce apoptosis from the 40 kDa PE fragment (Pseudomonas exotoxin A) and its specificity from the permuted form of interleukin-4. IL4PE40 produced in E. coli was extracted from inclusion bodies and purified by affinity chromatography, in its active form. However, the clinical translation of therapeutic molecules produced in E. coli is often difficult, due to endotoxin contaminations and laborious protocols of inclusion bodies purification that make hard the reproducibility of the isolation procedures. To overcome these disadvantages, I cloned the IL4PE40 gene into a yeast expression vector for use in the Pichia pastoris yeast. In the literature it is reported that P. pastoris can secrete grams per liter of foreign proteins in a protein-poor medium that is inexpensive and chemically defined. The presence of a signal peptide at the N-terminus of the recombinant protein allows the secretion of native protein within the culture medium. In addition, the low level of endogenous proteins secreted in the culture medium facilitates the purification steps of the final product. In my work the yield of IL4PE40 produced by yeast was optimized by yeast codon usage and by testing different induction conditions. After optimization the yeast P. pastoris was able to produce 120 µg of full-length Immunotoxin from 1 liter of culture, which is far from results obtained with non-toxic proteins by other workers. Moreover, although after optimization the yield increased, proteins obtained from optimized cultures of P. pastoris show a considerable level of degradation. The translocation of toxic fusion proteins in the cytosol during biosynthesis may lead to such low protein production. Additionally, it appears that proteases cleaving the recombinant molecules cold be present in the yeast medium. Preliminary cleavage assays with native PE and literature data suggest that several proteases (serine proteases and subtilisins) could cooperate in the IL4PE40 cleavage. Planned experiments to overcome these limitations are also described in my thesis