Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model

The Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is endowed with immunomodulatory properties that make it a potential candidate for anticancer therapeutic applications. By activating cytotoxic Th1 responses, HP-NAP inhibits the growth of bladder cancer and enhances the anti-tumor activity of oncolytic viruses in the treatment of metastatic breast cancer and neuroendocrine tumors. The possibility that HP-NAP exerts its anti-tumor effect also by modulating the activity of innate immune cells has not yet been explored. Taking advantage of the zebrafish model, we examined the therapeutic efficacy of HP-NAP against metastatic human melanoma, limiting the observational window to 9 days post-fertilization, well before the maturation of the adaptive immunity. Human melanoma cells were xenotransplanted into zebrafish embryos and tracked in the presence or absence of HP-NAP. The behavior and phenotype of macrophages and the impact of their drug-induced depletion were analyzed exploiting macrophage-expressed transgenes. HP-NAP administration efficiently inhibited tumor growth and metastasis and this was accompanied by strong recruitment of macrophages with a pro-inflammatory profile at the tumor site. The depletion of macrophages almost completely abrogated the ability of HP-NAP to counteract tumor growth. Our findings highlight the pivotal role of activated macrophages in counteracting melanoma growth and support the notion that HP-NAP might become a new biological therapeutic agent for the treatment of metastatic melanomas.     

Understanding selective oxidations

Functionalizing organic molecules is an important value-creating step throughout the entire chemical value-chain. Oxyfunctionalization of e.g. C-H or C=C bonds is one of the most important functionalization technologies used industrially. The major challenge in this field is the prevention of side reactions and/or the consecutive over-oxidation of the desired products. Despite its importance, a fundamental understanding of the intrinsic chemistry, and the subsequent design of a tailored engineering environment, is often missing. Industrial oxidation processes are indeed to a large extent based on empirical know-how. In this mini-review, we summarize some of our previous work to help to bridge this knowledge gap and elaborate on our ongoing research.     

Bifurcation analysis of a dynamic duopoly model with heterogeneous costs and behavioural rules

We develop a nonlinear dynamic Cournot duopoly model in discrete time, where two bounded rational quantity-setting firms, both endowed with naïve expectations, are heterogeneous as to their cost functions and output strategies. One of the two competing firms adopts best-reply behaviour, whereas the other adjusts its production according to the gradient of its profit. Although excessive reaction of the latter firm generally results in destabilization of the ‘Cournot–Nash’ equilibrium and brings about complex dynamic scenarios, this occurs via qualitatively different bifurcation routes, depending on the ratio between firms’ marginal costs. The paper also provides a preliminary exploration of the long-run sustainability of the heterogeneous duopoly competition, by investigating numerically the impact of fixed costs on firms’ survival, along different output trajectories.     

Realization and Preliminary Measurements on a 94 GHz SIS Mixer

In this paper we present the realization and a preliminary characterization of a SIS based receiver. It has been developed for the MASTER experiment that consists in a three-band SIS receiver (94, 225 and 345 GHz) for astrophysical observations through the atmospheric windows available at high altitude dry sites. The measurements performed establish an upper limit to the overall receiver noise temperature. A comparison has been tried with the MASTER requirements and with state of the art results. A noise figure of 110 K has been obtained at 94 GHz, about 22 times the quantum limit.     

Transfer of a nanoparticle product between different mixers using latent variable model inversion

An experimental nanoparticle preparation process by solvent displacement in passive mixers is considered. The problem under investigation is to estimate the operating conditions in a target device (Mixer B) in order to obtain a product of assigned properties that has already been manufactured in a source device of different geometry (Mixer A). A large historical database is available for Mixer A, whereas a limited historical database is available for Mixer B. The difference in device geometries causes a different mixing performance within the devices, which is very difficult to capture using mechanistic models. The problem is further complicated by the fact that Mixer B can only be run under an experimental setup that is different from the one under which the available historical dataset was obtained. A joint‐Y projection to latent structures (JY‐PLS) model inversion approach is used to transfer the nanoparticle product from Mixer A to Mixer B. The Mixer B operating conditions estimated by the model are tested experimentally and confirm the model predictions within the experimental uncertainty. Since the inversion of the JY‐PLS model generates an infinite number of solutions that all lie in the so‐called null space, experiments are carried out to provide (to the authors' knowledge) the first experimental validation of the theoretical concept of null space. Finally, by interpreting the JY‐PLS model parameters from first principles, the understanding of the system physics is improved. © 2013 American Institute of Chemical Engineers AIChE J, 60: 123–135, 2014     

Oligonucleotides‐decorated‐poly(N‐vinyl pyrrolidone) nanogels for gene delivery

Pulsed electron‐beam irradiation of a semi‐dilute poly(N‐vinyl pyrrolidone) (PVP) aqueous solution in the presence of acrylic acid has led to a carboxyl functionalized nanogel system. Nanoparticles hydrodynamic size and surface charge density, in water and as a function of pH, were investigated by dynamic light scattering and laser doppler velocimetry, respectively. Nanogels (NGs) were proved not to be cytotoxic at the cellular level. Indeed, they rapidly bypass the cellular membrane to accumulate in specific cell portions of the cytoplasm, in the perinuclear area. The availability of pendant carboxyl groups on the crosslinked PVP NGs core prompted us to attempt their decoration with a single strand oligonucleotide, which holds a terminal amino group. The recognition ability of the attached single helix of its complementary strand was investigated. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39774.     

Integrating olive grove maintenance and energy biomass recovery with a single-pass pruning and harvesting machine

In Italy, olive tree groves may offer up to a million tonnes of dry biomass per year as pruning residue. Searching for a cost-effective way to tap this potential, the authors tested a new machine, capable of recovering pruning residue at the same time as pruning. The pre-commercial prototype was tested on four different plots and compared to a simpler tractor-base mechanical pruning unit. The authors conducted detailed time-studies in order to determine machine productivity and residue recovery cost. The integrated machine can treat between 0.2 and 0.6 ha h⁻¹, producing between 0.33 and 1.03 tonnes of fresh residue hour⁻¹. Its integrated residue recovery function does not slow the pruning, which actually proceeds faster than with the tractor-base unit, due to the more efficient multiple-disc cutting bar. The marginal cost of residue recovery hovers around 40-45 € fresh tonne⁻¹. However, the new machine must not be considered just as a biomass harvester, but rather as a mechanical pruning unit with an integrated biomass recovery function. Its main benefit derives from the capacity of performing a very effective mechanical pruning, and the residue recovery function is a secondary benefit yet unavailable on standard pruning machines. Its deployment must be seen in the context of a general effort to modernize olive grove management and to develop an integrated biomass production system, rather than as a further attempt to build a specialised biomass supply chain.     

Hemoglobin adducts of benzo[a]pyrene diolepoxide in newspaper vendors: association with traffic exhaust

Benzo[a]pyrene diol epoxide adducts with hemoglobin (Hb) were measured to detect human exposure to environmental benzo[a]pyrene from traffic exhaust. Benzo[a]pyrene tetrahydrotetrols (BPTs) released from Hb after acid hydrolysis were quantitated by gas chromatography-mass spectrometry after immunoaffinity chromatography. Fifty three newspaper vendors were enrolled. The median adduct concentration was 0.3 fmol BPTs/mg Hb in high density traffic-exposed vendors and < or = 0.1 fmol BPTs/mg Hb in those exposed to low density traffic; the difference was not significant (P = 0.09). Among non-smokers, adducts were detectable in 60% of high exposure subjects (median 0.3 fmol BPTs/mg Hb) and in 28% of those with low exposure (median < or = 0.1 fmol/mg Hb). This difference was significant (P = 0.02). In low exposure smokers the median of adducts was 0.26 fmol BPTs/mg Hb, while in low exposure non-smokers it was < or = 0.1 fmol BPTs/mg Hb (P = 0.08, not significant). Adduct concentration was no different for low and high density traffic-exposed smokers (P = 0.82). The data indicate a significant difference in adduct concentration related to traffic exhaust exposure among non-smokers.     

Using modified foragers to harvest short-rotation poplar plantations

In Italy, short rotation coppice (SRC) has become very popular in recent years, with over 4000 ha already planted – almost exclusively with clonal poplar. Commercial harvesting operations are dominated by modified foragers, equipped with dedicated SRC headers. At present, contractors use two main header types: German Claas HS-2 and Italian GBE. The former fits smaller foragers with a power below 300 kW, the latter is used on larger harvest units. This study models the performance of modified foragers on a range of short-rotation poplar plantations. Data were collected from 45 operations, covering a total of 118 ha and producing over 4400 green tonnes of wood chips. The average yield of the fields harvested during the trials was about 23 gt ha^?1 year^?1 (at a moisture content of 59%), and machine productivity ranged from 9 to 70 green tonnes per scheduled machine hour (gt SMH^?1), with an average value of 35 gt SMH^?1. A model was developed to predict harvesting performance and cost, showing that harvesting cost can be maintained below the 15 € gt^?1 (2 € GJ^?1) level, if field stocking exceeds 40 gt ha^?1.     

Relating safety, productivity and company type for motor-manual logging operations in the Italian Alps

The study compared the performance of four different logging crews with respect to productivity, organization and safety. To this purpose, the authors developed a data collection method capable of providing a quantitative analysis of risk-taking behavior. Four crews were tested under the same working conditions, representative of close-to-nature alpine forestry. Motor-manual working methods were applied, since these methods are still prevalent in the specific study area, despite the growing popularity of mechanical processors. Crews from public companies showed a significantly lower frequency of risk-taking behavior. The best safety performance was offered by the only (public) crew that had been administered formal safety training. The study seems to deny the common prejudice that safety practice is inversely proportional to productivity. Instead, productivity is increased by introducing more efficient working methods and equipment. The quantitative analysis of risk-taking behavior developed in this study can be applied to a number of industrial fields besides forestry. Characterizing risk-taking behavior for a given case may eventually lead to the development of custom-made training programmes, which may address problem areas while avoiding that the message is weakened by the inclusion of redundant information. In the specific case of logging crews in the central Alps, the study suggests that current training courses may be weak on ergonomics, and advocates a staged training programme, focusing first on accident reduction and then expanding to the prevention of chronic illness.