Relaxation dynamics through a conical intersection: Quantum and quantum–classical studies

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Investigating the photodynamics of trans-azobenzene with coupled trajectories

In this work, we present the first implementation of the coupled-trajectory Tully surface hopping (CT-TSH) suitable for applications to molecular systems. We combine CT-TSH with the semiempirical Floating Occupation Molecular Orbitals-Configuration Interaction (FOMO-CI) electronic structure method to investigate the photoisomerization dynamics of trans-azobenzene. Our study shows that CT-TSH can capture correctly decoherence effects in this system, yielding consistent electronic and nuclear dynamics in agreement with (standard) decoherence-corrected TSH. Specifically, CT-TSH is derived from the exact factorization and the electronic coefficients’ evolution is directly influenced by the coupling of trajectories, resulting in the improvement of internal consistency if compared to standard TSH

Exact Factorization of the Electron-Nuclear Wavefunction:Fundamentals and Algorithms

This Chapter provides an overview on the exact factorization of the electron-nuclear wavefunction, from the presentation of the fundamental theory to its application in the domain of photochemistry. The exact factorization is presented in relation to the more standard Born-Oppenheimer picture, often employed to interpret and simulate excited-state processes that are at the heart of photochemistry. Numerical studies on a two-mode two-state model system are reported focusing on the photo-excitation process by an ultrashort laser pulse and on the subsequent relaxation dynamics through a conical intersection. The aim here is to analyze the time-dependent potentials of the theory and to introduce the concept of nuclear trajectories in the context of the exact factorization. Various applications in photochemistry are then presented, namely the cis-trans photo-isomerization of 2-cis-penta-2,4-dieniminium cation, the photo-dissociation of IBr with the inclusion of spin-orbit coupling, different examples of proton-coupled electron transfer. Those studies are performed by applying the nonadiabatic coupled-trajectory algorithms derived from the exact factorization.</p

Investigating the Photodynamics of trans-Azobenzene with Coupled Trajectories

In this work, we present the first implementation of coupled-trajectory Tully surface hopping (CT-TSH) suitable for applications to molecular systems. We combine CT-TSH with the semiempirical floating occupation molecular orbital-configuration interaction electronic structure method to investigate the photoisomerization dynamics of trans-azobenzene. Our study shows that CT-TSH can capture correctly decoherence effects in this system, yielding consistent electronic and nuclear dynamics in agreement with (standard) decoherence-corrected TSH. Specifically, CT-TSH is derived from the exact factorization and the electronic coefficients' evolution is directly influenced by the coupling of trajectories, resulting in the improvement of internal consistency if compared to standard TSH

Current management of intrahepatic cholangiocarcinoma: from resection to palliative treatments

Intrahepatic cholangiocarcinoma (ICC) is the second most common liver primary tumour after hepatocellular carcinoma and represents 20% of all the cholangiocarcinomas. Its incidence is increasing and mortality rates are rising. Surgical resection is the only option to cure the disease, despite the high recurrence rates reported to be up to 80%. Intrahepatic recurrences may be still treated with curative intent in a small percentage of the patients. Unfortunately, due to lack of specific symptoms, most patients are diagnosed in a late stage of disease and often unsuitable for resection. Liver transplantation for ICC is still controversial. After the first published poor results, improving outcomes have been reported in highly selected cases, including locally advanced ICC treated with neoadjuvant chemotherapy, when successful in controlling tumour progression. Thus, liver transplantation should be considered a possible option within study protocols. When surgical management is not possible, palliative treatments include chemotherapy, radiotherapy and loco-regional treatments such as radiofrequency ablation, trans-arterial chemoembolization or radioembolization

Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers?

Over the past 15 years, several biological and pathological characteristics proved their significance in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) prognostic stratification. However, the identification of new non-invasive disease biomarkers, relying on the most important disease mechanisms, is still necessary. In recent years, plasmatic circulating small extracellular vesicles (S-EVs) gathered great importance both as stable biomarker carriers and active players in tumorigenesis. In the present work, we performed a comprehensive study on the proteomic composition of plasmatic S-EVs of pediatric ALCL patients compared to healthy donors (HDs). By using a mass spectrometry-based proteomics approach, we identified 50 proteins significantly overrepresented in S-EVs of ALCL patients. Gene Ontology enrichment analysis disclosed cellular components and molecular functions connected with S-EV origin and vesicular trafficking, whereas cell adhesion, glycosaminoglycan metabolic process, extracellular matrix organization, collagen fibril organization and acute phase response were the most enriched biological processes. Of importance, consistently with the presence of nucleophosmin (NPM)-ALK fusion protein in ALCL cells, a topological enrichment analysis based on Reactome- and Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived networks highlighted a dramatic increase in proteins of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in ALCL S-EVs, which included heat shock protein 90-kDa isoform alpha 1 (HSP90AA1), osteopontin (SPP1/OPN) and tenascin C (TNC). These results were validated by Western blotting analysis on a panel of ALCL and HD cases. Further research is warranted to better define the role of these S-EV proteins as diagnostic and, possibly, prognostic parameters at diagnosis and for ALCL disease monitoring

Liposomal delivery of a Pin1 inhibitor complexed with cyclodextrins as new therapy for high-grade serous ovarian cancer.

Pin1, a prolyl isomerase that sustains tumor progression, is overexpressed in different types of malignancies. Functional inactivation of Pin1 restrains tumor growth and leaves normal cells unaffected making it an ideal pharmaceutical target. Although many studies on Pin1 have focused on malignancies that are influenced by sex hormones, studies in ovarian cancer have lagged behind. Here, we show that Pin1 is an important therapeutic target in high-grade serous epithelial ovarian cancer. Knock down of Pin1 in ovarian cancer cell lines induces apoptosis and restrains tumor growth in a syngeneic mouse model. Since specific and non-covalent Pin1 inhibitors are still limited, the first liposomal formulation of a Pin1 inhibitor was designed. The drug was efficiently encapsulated in modified cyclodextrins and remotely loaded into pegylated liposomes. This liposomal formulation accumulates preferentially in the tumor and has a desirable pharmacokinetic profile. The liposomal inhibitor was able to alter Pin1 cancer driving-pathways trough the induction of proteasome-dependent degradation of Pin1 and was found to be effective in curbing ovarian tumor growth in vivo