Polymeric materials with noble metals nanoparticles

The general focus of this PhD project was the combination of gold and/or silver nanoparticles with a polymeric matrix. In particular, PVA films containing pectin-stabilized AgNP and gold nanostars (GNS) coated with HS-PEG or HS-PEG-COOH have been prepared. These materials proved to combine an intrinsic microbicidal activity, due to the release of Ag⁺ ions, with an on-demand action given by the photothermal response of GNS upon laser irradiation in the NIR bio-transparent window. Films containing GNS coated with HS-PEG-COOH, that act directly as cross-linking agents, are most promising for the development of medical devices for wound healing applications. In addition, the study of PEG coating of AuNP has been carried on, particularly by potentiometric titration, in order to investigate the effect of NP-binding on the acid-base properties of PEG thiols. After the determination of the protonation constants of a set of molecules with different mw, an experimental procedure for the titration of PEG-coated AuNP was set up. The first results on AuNP@HS-PEG-COOH show a reduction of the average acidity of the carboxylic groups, attributed to the interaction between the neighboring molecules confined on the NP surface. Eventually, a novel photothermal material has been produced by the inclusion of GNS in a sponge-like PDMS scaffold, obtained via a simple templating method which could also enable control over pore size and porosity. Very elastic, hydrophobic sponges have been obtained, both with and without PEGylated GNS embedded. Preliminary data from natural solar irradiation show a remarkable photothermal response of the PDMS@GNS samples; however, a finer control is required over irradiation parameters as well as new experimental setups to assess their performance as solar water evaporators and/or oil separation platforms

Magnus and Dyson Series for Master Integrals

We elaborate on the method of differential equations for evaluating Feynman integrals. We focus on systems of equations for master integrals having a linear dependence on the dimensional parameter. For these systems we identify the criteria to bring them in a canonical form, recently identified by Henn, where the dependence of the dimensional parameter is disentangled from the kinematics. The determination of the transformation and the computation of the solution are obtained by using Magnus and Dyson series expansion. We apply the method to planar and non-planar two-loop QED vertex diagrams for massive fermions, and to non-planar two-loop integrals contributing to 2 -> 2 scattering of massless particles. The extension to systems which are polynomial in the dimensional parameter is discussed as well.Comment: 32 pages, 6 figures, 2 ancillary files. v2: references added, typos corrected in the text and in the ancillary file

Advancement flap in the management of chronic anal fissure: A prospective study

Lateral internal sphincterotomy is the surgical treatment of choice of chronic anal fissure after failure of conservative measures. Several randomized trials identified an overall risk of incontinence of 10 % mostly for flatus. Fissurectomy is the most commonly used procedure to preserve the integrity of the anal sphincters. However, a possible complication is keyhole defect that may lead to faecal soiling. In this study, chronic anal fissure (CAF) was treated by fissurectomy and anal advancement flap to preserve the anatomo-functional integrity of sphincters and to reduce healing time and the risk of anal stenosis. In patients with hypertonia, surgical treatment was combined with chemical sphincterotomy by injection of botulinum toxin to enhance tissue perfusion. Forty eight patients with CAF underwent fissurectomy and anal advancement flap. In 22 subjects with hypertonia of the internal anal sphincter, intrasphincter injection of 30 UI of botulinum toxin at the completion of the surgical operation was used. All patients were followed up to 24 months. Since the first defecation, the intensity and duration of pain were significantly reduced. Two patients had urinary retention, five had infections and three had partial breakdowns. No anal stenosis, keyhole deformity or necrosis flap was recorded. At the 24 months follow-up visit, anal incontinence was similar to those detected preoperatively. Only four recurrences were detected at 18 and 20 months. After medical treatment failure, fissurectomy with advancement flap is a valid sphincter-conserving procedure for treatment of anterior or posterior CAF, regardless of hypertonia of the internal anal sphincter. © 2011 Springer-Verlag

Synchrotron characterization of hexagonal and cubic lipidic phases loaded with azolate/phosphane gold(I) compounds: a new approach to the uploading of gold(I)-based drugs

none9Gold(I) phosphane compounds have recently attracted a renewed interest as potential new protagonists in cancer therapy. A class of phosphane gold(I) complexes containing azolate ligands has been successfully tested against several cancer cell lines and, in particular, against basal-like breast (BLB) cancer, a form characterized by strongly severe diagnosis and short life lapse after classic chemotherapy. Even though the anticancer activity of gold(I) phosphane compounds is thoroughly ascertained, no study has been devoted to the possibility of their delivery in nanovectors. Herein, nonlamellar lyotropic liquid crystalline lipid nanosystems, a promising class of smart materials, have been used to encapsulate gold(I) azolate/phosphane complexes. In particular, ((triphenylphosphine)-gold(I)-(4,5-dichloroimidazolyl-1H-1yl)) (C-I) and ((triphenylphosphine)-gold(I)-(4,5-dicyanoimidazolyl-1H-1yl)) (C-II) have been encapsulated in three different lipid matrices: monoolein (GMO), phytantriol (PHYT) and dioleoyl-phosphatidylethanolamine (DOPE). An integrated experimental approach involving X-ray diffraction and UV resonant Raman (UVRR) spectroscopy, based on synchrotron light and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, has been employed to establish the effects of drug encapsulation on the structure and phase behavior of the host mesophases. The results indicate that gold(I) complexes C-I and C-II are successfully encapsulated in the three lipid matrices as evidenced by the drug-induced phase transitions or by the changes in the mesophase lattice parameters observed in X-ray diffraction experiments and by the spectral changes occurring in UV resonant Raman spectra upon loading the lipid matrices with C-I and C-II.openPaola Astolfi, Michela Pisani, Elisabetta Giorgini, Barbara Rossi, Alessandro Damin, Francesco Vita, Oriano Francescangeli, Lorenzo Luciani, Rossana GalassiAstolfi, Paola; Pisani, Michela; Giorgini, Elisabetta; Rossi, Barbara; Damin, Alessandro; Vita, Francesco; Francescangeli, Oriano; Luciani, Lorenzo; Galassi, Rossan

Experimental study and computational modelling of cruzain cysteine protease inhibition by dipeptidyl nitriles

Chagas disease affects millions of people in Latin America. This disease is caused by the protozoan parasite Trypanossoma cruzi. The cysteine protease cruzain is a key enzyme for the survival and propagation of this parasite lifecycle. Nitrile-based inhibitors are efficient inhibitors of cruzain that bind by forming a covalent bond with this enzyme. Here, three nitrile-based inhibitors dubbed Neq0409, Neq0410 and Neq0570 were synthesized, and the thermodynamic profile of the bimolecular interaction with cruzain was determined using isothermal titration calorimetry (ITC). The result suggests the inhibition process is enthalpy driven, with a detrimental contribution of entropy. In addition, we have used hybrid Quantum Mechanical/Molecular Mechanical (QM/MM) and Molecular Dynamics (MD) simulations to investigate the reaction mechanism of reversible covalent modification of cruzain by Neq0409, Neq0410 and Neq0570. The computed free energy profile shows that the nucleophilic attack of Cys25 on the carbon C1 of inhibitiors and the proton transfer from His162 to N1 of the dipeptidyl nitrile inhibitor take place in a single step. The calculated free energy of the inhibiton reaction is in agreement with covalent experimental binding. Altogether, the results reported here suggests that nitrile-based inhibitors are good candidates for the development of reversible covalent inhibitors of cruzain and other cysteine proteases

Beyond the Guidelines: The Grey Zones of the Management ofGastric Cancer. Consensus Statements from the Gastric CancerItalian Network (GAIN)

The Grey Zones of the Management ofGastric Cancer. Consensus Statements from the Gastric CancerItalian Network (GAIN

Mapping agricultural land in Afghanistan’s opium provinces using a generalised deep learning model and medium resolution satellite imagery

Understanding the relationship between land use and opium production is critical for monitoring the dynamics of poppy cultivation and developing an effective counter narcotics policy in Afghanistan. However, mapping agricultural land accurately and rapidly is challenging, as current methods require resource-intensive and time consuming manual image-interpretation. Deep convolutional neural nets have been shown to greatly reduce the manual effort in mapping agriculture from satellite imagery but require large amounts of densely labelled training data for model training. Here we develop a generalised model using past images and labels from different medium resolution satellite sensors for fully automatic agricultural land classification using the latest medium resolution satellite imagery. The model (FCN-8) is first trained on Disaster Monitoring Constellation (DMC) satellite images from 2007 to 2009. The effect of shape, texture and spectral features on model performance are investigated along with normalisation in order to standardise input medium resolution imagery from DMC, Landsat-5, Landsat-8, and Sentinel-2 for transfer learning between sensors and across years. Textural features make the highest contribution to overall accuracy (∼73%) while the effect of shape is minimal. The model accuracy on new images, with no additional training, is comparable to visual image interpretation (overall > 95%, user accuracy > 91%, producer accuracy > 85%, and frequency weighted intersection over union > 67%). The model is robust and was used to map agriculture from archive images (1990) and can be used in other areas with similar landscapes. The model can be updated by fine tuning using smaller, sparsely labelled datasets in the future. The generalised model was used to map the change in agricultural area in Helmand Province, showing the expansion of agricultural land into former desert areas. Training generalised deep learning models using data from both new and long-term EO programmes, with little or no requirement for fine tuning, is an exciting opportunity for automating image classification across datasets and through time that can improve our understanding of the environment.Natural Environment Research Council (NERC): NE/M009009/

Aromatic and proteomic analyses corroborate the distinction between Mediterranean landraces and modern varieties of durum wheat

In this paper volatile organic compounds (VOCs) from durum wheat cultivars and landraces were analyzed using PTR-TOF-MS. The aim was to characterize the VOC's profile of the wholemeal flour and of the kernel to find out if any VOCs were specific to varieties and sample matrices. The VOC data is accompanied by SDS-PAGE analyses of the storage proteins (gliadins and glutenins). Statistical analyses was carried out both on the signals obtained by MS and on the protein profiles. The difference between the VOC profile of two cultivars or two preparations of the same sample - matrices, in this case kernel vs wholemeal flour - can be very subtle; the high resolution of PTR-TOF-MS - down to levels as low as pptv - made it possible to recognize these differences. The effects of grinding on the VOC profiles were analyzed using SIMPER and Tanglegram statistical methods. Our results show that it is possible describe samples using VOC profiles and protein data

Aromatic and proteomic analyses corroborate the distinction between Mediterranean landraces and modern varieties of durum wheat

In this paper volatile organic compounds (VOCs) from durum wheat cultivars and landraces were analyzed using PTR-TOF-MS. The aim was to characterize the VOC’s profile of the wholemeal flour and of the kernel to find out if any VOCs were specific to varieties and sample matrices. The VOC data is accompanied by SDS-PAGE analyses of the storage proteins (gliadins and glutenins). Statistical analyses was carried out both on the signals obtained by MS and on the protein profiles. The difference between the VOC profile of two cultivars or two preparations of the same sample - matrices, in this case kernel vs wholemeal flour - can be very subtle; the high resolution of PTR-TOF-MS - down to levels as low as pptv - made it possible to recognize these differences. The effects of grinding on the VOC profiles were analyzed using SIMPER and Tanglegram statistical methods. Our results show that it is possible describe samples using VOC profiles and protein data

Susceptibility of Human Melanoma Cells to Autologous Natural Killer (NK) Cell Killing: HLA-Related Effector Mechanisms and Role of Unlicensed NK Cells

BACKGROUND: Despite Natural Killer (NK) cells were originally defined as effectors of spontaneous cytotoxicity against tumors, extremely limited information is so far available in humans on their capability of killing cancer cells in an autologous setting. METHODOLOGY/PRINCIPAL FINDINGS: We have established a series of primary melanoma cell lines from surgically resected specimens and here showed that human melanoma cells were highly susceptible to lysis by activated autologous NK cells. A variety of NK cell activating receptors were involved in killing: particularly, DNAM-1 and NKp46 were the most frequently involved. Since self HLA class I molecules normally play a protective role from NK cell-mediated attack, we analyzed HLA class I expression on melanomas in comparison to autologous lymphocytes. We found that melanoma cells presented specific allelic losses in 50% of the patients analyzed. In addition, CD107a degranulation assays applied to NK cells expressing a single inhibitory receptor, revealed that, even when expressed, specific HLA class I molecules are present on melanoma cell surface in amount often insufficient to inhibit NK cell cytotoxicity. Remarkably, upon activation, also the so called "unlicensed" NK cells, i.e. NK cells not expressing inhibitory receptor specific for self HLA class I molecules, acquired the capability of efficiently killing autologous melanoma cells, thus additionally contributing to the lysis by a mechanism independent of HLA class I expression on melanoma cells. CONCLUSIONS/SIGNIFICANCE: We have investigated in details the mechanisms controlling the recognition and lysis of melanoma cells by autologous NK cells. In these autologous settings, we demonstrated an efficient in vitro killing upon NK cell activation by mechanisms that may be related or not to abnormalities of HLA class I expression on melanoma cells. These findings should be taken into account in the design of novel immunotherapy approaches against melanoma