Perspectives in the development of hybrid bifunctional antitumour agents

In spite of the development of a large number of novel target-specific antitumour agents, the single-agent therapy is in general not able to provide an effective durable control of the malignant process. The limited efficacy of the available agents (both conventional cytotoxic and novel target-specific) reflects not only the expression of defence mechanisms, but also the complexity of tumour cell alterations and the redundancy of survival pathways, thus resulting in tumour cell ability to survive under stress conditions. A well-established strategy to improve the efficacy of antitumour therapy is the rational design of drug combinations aimed at achieving synergistic effects and overcoming drug resistance. An alternative strategy could be the use of agents designed to inhibit simultaneously multiple cellular targets relevant to tumour growth/survival. Among these novel agents are hybrid bifunctional drugs, i.e. compounds resulting by conjugation of different drugs or containing the pharmocophores of different drugs. This strategy has been pursued using various conventional or target-specific agents (with DNA damaging agents and histone deacetylase inhibitors as the most exploited compounds). A critical overview of the most representative compounds is provided with emphasis on the HDAC inhibitor-based hybrid agents. In spite of some promising results, the actual pharmacological advantages of the hybrid agents remain to be defined. This commentary summarizes the recent advances in this field and highlights the pharmacological basis for a rational design of hybrid bifunctional agents

Contrasting chaotic with stochastic dynamics via ordinal transition networks

We introduce a representation space to contrast chaotic with stochastic dynamics. Following the complex network representation of a time series through ordinal pattern transitions, we propose to assign each system a position in a two-dimensional plane defined by the permutation entropy of the network (global network quantifier) and the minimum value of the permutation entropy of the nodes (local network quantifier). The numerical analysis of representative chaotic maps and stochastic systems shows that the proposed approach is able to distinguish linear from non-linear dynamical systems by different planar locations. Additionally, we show that this characterization is robust when observational noise is considered. Experimental applications allow us to validate the numerical findings and to conclude that this approach is useful in practical contexts.We introduce a representation space to contrast chaotic with stochastic dynamics. Following the complex network representation of a time series through ordinal pattern transitions, we propose to assign each system a position in a two-dimensional plane defined by the permutation entropy of the network (global network quantifier) and the minimum value of the permutation entropy of the nodes (local network quantifier). The numerical analysis of representative chaotic maps and stochastic systems shows that the proposed approach is able to distinguish linear from non-linear dynamical systems by different planar locations. Additionally, we show that this characterization is robust when observational noise is considered. Experimental applications allow us to validate the numerical findings and to conclude that this approach is useful in practical contexts.Fil: Olivares, F.. Pontificia Universidad Católica de Valparaíso; ChileFil: Olivares, F.. Pontificia Universidad Católica de Valparaíso; ChileFil: Zanin, M.. Universidad Politécnica de Madrid; EspañaFil: Zanin, M.. Universidad Politécnica de Madrid; EspañaFil: Zunino, Luciano José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Ópticas. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones Ópticas. Universidad Nacional de La Plata. Centro de Investigaciones Ópticas; Argentina. Universidad Nacional de La Plata. Facultad de Ingeniería. Departamento de Ciencias Básicas; ArgentinaFil: Zunino, Luciano José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Ópticas. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones Ópticas. Universidad Nacional de La Plata. Centro de Investigaciones Ópticas; Argentina. Universidad Nacional de La Plata. Facultad de Ingeniería. Departamento de Ciencias Básicas; ArgentinaFil: Pérez, D.G.. Pontificia Universidad Católica de Valparaíso; ChileFil: Pérez, D.G.. Pontificia Universidad Católica de Valparaíso; Chil

Gas turbine prime movers fuelled by LNG as a future alternative for sustainable power in marine propulsion: current emission policy assessment and exhaust quality evaluation

In recent years, climate change has dramatically shown its effects in terms of fluctuations of temperatures because of increased global warming due to greenhouse gas emissions. Pollution control is strongly linked to atmospheric acidification and contaminants in combustion exhausts. In such a contest, marine propulsion is actually a key player that is accounting for a substantial contribution to pollution. Kyoto protocol’s obligations established decarbonisation as a compulsory commitment and contaminant constraints are defined by current emission policy and regulations both on a global and on a regional basis. In this paper, a study is carried out in order to develop a framework for current emission policy and assessment of exhausts due to constraints imposed on fuel choice. Gas fuelled marine propulsion, implemented through state-of-the-art GT areoderivative prime movers, powered by LNG, is analysed from the environmental point of view. The pollutant emissions from various size GT models are evaluated through both GT datasheets and commercial (as well as self-coded) software, in order to assess the validity of LNG as an alternative fuel option for future sustainable marine applications

Time-Sensitive Networking to Improve the Performance of Distributed Functional Safety Systems Implemented over Wi-Fi

Industry 4.0 has significantly improved the industrial manufacturing scenario in recent years. The Industrial Internet of Things (IIoT) enables the creation of globally interconnected smart factories, where constituent elements seamlessly exchange information. Industry 5.0 has further complemented these achievements, as it focuses on a human-centric approach where humans become part of this network of things, leading to a robust human–machine interaction. In this distributed, dynamic, and highly interconnected environment, functional safety is essential for adequately protecting people and machinery. The increasing availability of wireless networks makes it possible to implement distributed and flexible functional safety systems. However, such networks are known for introducing unwanted delays that can lead to safety performance degradation due to their inherent uncertainty. In this context, the Time-Sensitive Networking (TSN) standards present an attractive prospect for enhancing and ensuring acceptable behaviors. The research presented in this paper deals with the introduction of TSN to implement functional safety protocols for wireless networks. Among the available solutions, we selected Wi-Fi since it is a widespread network, often considered and deployed for industrial applications. The introduction of a reference functional safety protocol is detailed, along with an analysis of how TSN can enhance its behavior by evaluating relevant performance indexes. The evaluation pertains to a standard case study of an industrial warehouse, tested through practical simulations. The results demonstrate that TSN provides notable advantages, but it requires meticulous coordination with the Wi-Fi MAC layer protocol to guarantee improved performance

Time resolved PIV measurements of the unsteady wake migration in a LPT blade passage: effect of the wake passing frequency

A time resolved Particle Image Velocimetry (TR-PIV) system has been employed to investigate the unsteady propagation of upstream wakes in a low-pressure turbine cascade. Data are obtained in the steady state condition and for two passing wake reduced frequencies. The study is focused on the identification and split of the different dynamics responsible for deterministic and random oscillations, thus loss generation. A very large data set has been collected: for each condition, about 9000 instantaneous flow fields have been acquired at up to 2kHz in order to resolve with great detail the vortex shedding phenomenon characterizing the separation at steady condition as well as the propagation of the coherent structures induced by the incoming wake. Instantaneous vector maps, phase averaged velocity fields and Proper Orthogonal Decomposition (POD) have been used for the in depth characterization of the different phenomena. The paper takes advantage of the properties of POD that reduces the data set to a low number of modes that represent the most energetic dynamics of the system. It is clearly shown that the phase averaged flow field can be represented by a few number of POD modes related to the wake passing event for the unsteady cases. POD is also able to capture flow features affecting the instantaneous flow field not directly related to the wake passage (i.e. the vortex shedding phenomenon induced by the intermittent separation developing between adjacent wakes), that are smeared out in the phase averaged results. Once recognized the POD modes most involved in the unsteady flow field, a procedure for the quantification of the different contributions to the overall amount of losses is proposed

Feasibility of mini combined cycles for naval applications

The objective of energy production with low environmental impact will have, in the near future, high potential of development also for naval applications. The containment of pollutant emissions can be achieved by the combined use of an innovative mini gas-steam combined cycle with thermal energy cogeneration to feed the ship thermal utilities, in place of the current Diesel engine application, and liquefied natural gas as fuel (LNG). The present work is focused on the definition of the architecture of the plant, by selecting optimal distribution of pressure and temperature and repartition of power between Gas Turbine (GT), Steam Turbine (ST) and thermal utilities, as well as on the choice and sizing of the individual components. The main purpose is the definition of a compact, high efficiency, system. The proposed basic mini-cycle ranges from 2 MW to 10 MW electric power. Thanks to the combined heat and power cogeneration plant adopted, for an overall electrical efficiency of about 30%, a total return (thermal + electricity) of about 75% can be achieved. An example of plant providing large power, in a partially modular arrangement is also proposed

Lacunar fractal photon sieves

We present a new family of diffractive lenses whose structure is based on the combination of two concepts: photon sieve and fractal zone plates with variable lacunarity. The focusing properties of different members of this family are examined. It is shown that the sieves provide a smoothing effect on the higher order foci of a conventional lacunar fractal zone plate. However, the characteristic self-similar axial response of the fractal zone plates is always preserved.Comment: 7 pages, 5 figure

Variability of the transport of anthropogenic CO2 at the Greenland-Portugal OVIDE section:Controlling mechanisms

The interannual to decadal variability in the transport of anthropogenic CO2 (Cant) across the subpolar North Atlantic (SPNA) is investigated, using summer data of the FOUREX and OVIDE high-resolution transoceanic sections, from Greenland to Portugal, occupied six times from 1997 to 2010. The transport of Cant across this section, Tcant hereafter, is northward, with a mean value of 254 ± 29 kmol s-1 over the 1997-2010 period. We find that Tcant undergoes interannual variability, masking any trend different from 0 for this period. In order to understand the mechanisms controlling the variability of Tcant across the SPNA, we propose a new method that quantifies the transport of Cant caused by the diapycnal and isopycnal circulation. The diapycnal component yields a large northward transport of Cant (400 ± 29 kmol s-1) that is partially compensated by a southward transport of Cant caused by the isopycnal component (-171 ± 11 kmol s-1), mainly localized in the Irminger Sea. Most importantly, the diapycnal component is found to be the main driver of the variability of Tcant across the SPNA. Both the Meridional Overturning Circulation (computed in density coordinates, MOCσ) and the Cant increase in the water column have an important effect on the variability of the diapycnal component and of Tcant itself. Based on this analysis, we propose a simplified estimator for the variability of T cant based on the intensity of the MOCσ and on the difference of Cant between the upper and lower limb of the MOCσ (ΔCant). This estimator shows a good consistency with the diapycnal component of T cant, and help to disentangle the effect of the variability of both the circulation and the Cant increase on the Tcant variability. We find that ΔCant keeps increasing over the past decade, and it is very likely that the continuous Cant increase in the water masses will cause an increase in Tcant across the SPNA at long timescale. Nevertheless, at the timescale analyzed here (1997-2010), the MOCσ controls the T cant variability, blurring any Tcant trend. Extrapolating the observed ΔCant increase rate and considering the predicted slow-down of 25% of the MOCσ, Tcant across the SPNA is expected to increase by 430 kmol s-1 during the 21st century. Consequently, an increase in the storage rate of Cant in the SPNA could be envisaged

A high-resolution aeromagnetic survey over the Cape Roberts Rift Basin: Correlations with seismic reflection and magnetic susceptibility log data

A high-resolution aeromagnetic survey (altitude 125 m asl, spacing 500 m , area 800 km2) was carried out in 1994 offshore of Cape Roberts by the GITARA (German ITalian Aeromagnetic Research in Antarctica) Group. The availability from drilling of whole-core physical properties logs for magnetic susceptibility, P-wave velocity and density/porosity data allows new insights to be inferred from reprocessed and reviewed HRAM aeromagnetic data. Aeromagnetic data have been reprocessed to image with greater detail the structural framework along the western flank of the Victoria Land Basin. New processing includes 2D Werner and 3D Euler deconvolution, the production of maps of the maximum horizontal gradient of pseudo-gravity, and 2D, 3D modelling. Magnetic trends and anomalies are discussed in conjunction with now available drilling results from the CRP, existing bathymetric data and recently published interpretations of a multichannel seismic reflection survey