Impact of siRNA Overhangs for Dendrimer-Mediated siRNA Delivery and Gene Silencing

Wed, 06/29/2022 - 05:51 By Anonymous

Titolo: Impact of siRNA Overhangs for Dendrimer-Mediated siRNA Delivery and Gene Silencing
Abstract: Small interfering RNA (siRNA) have attracted considerable attention, as compelling therapeutics providing safe and competent delivery systems are available. Dendrimers are emerging as appealing siRNA delivery vectors thanks to their unique, well-defined architecture and the resulting cooperativity and multivalency confined within a nanostructure. We have recently disclosed the structurally flexible fifth-generation TEA-core PAMAM dendrimer (G5) as an effective nanocarrier for delivery of sticky siRNA bearing long complementary sequence overhangs (dA)n/(dT)n (n = 5 or 7). Here, using combined experimental/computational approaches, we successfully clarified (i) the underlying mechanisms of interaction between the dendrimer nanovector G5 and siRNA molecules bearing either complementary or noncomplementary sequence overhangs of different length and chemistry and (ii) the impact of siRNA overhangs contributing toward the improved delivery potency. Using siRNA with complementary overhangs offer the best action in term of gene silencing through the formation of concatemers, that is, supramolecular structures resulting from synergistic and cooperative binding via (dA)n/(dT)n bridges (n = 5 or 7). On the other hand, although siRNA bearing long, noncomplementary overhangs (dA)n/(dA)n or (dT)n/(dT)n (n = 5 or 7) are endowed with considerably higher gene silencing potency than normal siRNA with (dT)2/(dT)2, they remain less effective than their sticky siRNA counterparts. The observed gene silencing potency depends on length, nature, and flexibility of the overhangs, which behave as a sort of clamps that hold and interact with the dendrimer nanovectors, thus impacting siRNA delivery performance and, ultimately, gene silencing. Our findings can be instrumental in designing siRNA entities with enhanced capability to achieve effective RNA interference for therapeutic applications.

Sensitivity To Novel Tyrosine Kinase Inhibitors of Highly Resistant Single and Polymutant Bcr-abl1: A Combined Approach

Wed, 06/29/2022 - 05:51 By Anonymous

Titolo: Sensitivity To Novel Tyrosine Kinase Inhibitors of Highly Resistant Single and Polymutant Bcr-abl1: A Combined Approach
Abstract: In this paper we discuss the results of the coupled in silico/experimental approach to the resistance phenomena in cancer targeted therapy of tyrosin kinase mutations.

Fuelling power plants by natural gas: An analysis of energy efficiency, economical aspects and environmental footprint based on detailed process simulation of the whole carbon capture and storage system

Wed, 06/29/2022 - 05:51 By Anonymous

Titolo: Fuelling power plants by natural gas: An analysis of energy efficiency, economical aspects and environmental footprint based on detailed process simulation of the whole carbon capture and storage system
Abstract: In view of the low-carbon transformation of the power sector, natural gas-fired power generation is the only technology, among fossil resources, that will continue to provide an important source of flexibility for the power system in the coming years. However, the carbon dioxide emissions produced by the operation of such plants call for carbon capture and storage equipment, whose deployment needs to be assessed and compared with the main renewable technologies: wind power and photovoltaics. This work uses process simulation in order to assess two different carbon capture processes: a traditional one, based on monoethanolamine, and an innovative one, based on hot potassium carbonate. Process simulation is also used for the transportation of carbon dioxide to the sequestration site. Mass and energy balances from the simulations are then used for the calculation of the Energy Return on Energy Invested, the Levelized Cost of Energy and as inputs for the Life Cycle Assessments of both alternative designs. The life cycle analyses of the considered power technologies exhibited higher contributions due to fossil-based power plants towards climate-related impact categories, while renewable sources were revealed to be more burdensome for the exploitation of mineral resources. The calculated Energy Return on Energy Invested for gas-fired power plants with carbon capture and storage is between 5.2 and 12.4, comparable with the values of photovoltaics and wind power. On the other hand, their Levelized Cost of Energy is between 10.2 and 20.0 eurocent per kilowatt-hour, much higher than that of renewables. The conclusion is that, at present, the sustainability of gas-fired power stations equipped with carbon capture and storage should be carefully considered and not taken for granted.

Novel Approach to Material Selection: A Joint Venture of Multiscale Simulations and LCA

Wed, 06/29/2022 - 05:51 By Anonymous

Titolo: Novel Approach to Material Selection: A Joint Venture of Multiscale Simulations and LCA
Abstract: Since the sustainability related to materials and processes has become a relevant criterion within the products design procedures, a novel approach to materials choice has been adopted in order to minimize the impacts related to the products life cycle. The selection of innovative materials for specific applications has been adopted by numerous manufacturers belonging to different areas, including marine engine constructors sector which was formerly dominated by metallic alloys. Indeed, the introduction of nano-engineered thermoplastic polymers (NETPs) as the main constituent of marine engine non-structural components, provided an enhancement towards the reduction of cost and weights as well as simplified maintenance and inspection operations. However, the substitution of former material doesn’t come without any drawbacks, since an in-depth investigation on compelling alternatives is mandatory. In this regard, computer multiscale simulations established as a valuable support to identify the influence of several molecular structures on the parameters that most affect the performances required by specific product purposes.
In this work, we present a case study for the material substitution of a four-stroke marine engine plastic cylinder head cover, commonly made of aluminium alloys. Accordingly, different NETPs have been computationally evaluated and ranked in order to find the best compromise between mechanical properties and material costs. To reach this goal, a multiscale molecular modelling approach has been adopted in which the results from the atomistic scale have been used as inputs for the simulation of the final product performed with Finite Elements Method (FEM).

Finally, in order to have a complete scenario of the replacement of aluminium with the selected NETP, a detailed Life Cycle Assessment related to the different material products has been performed in order to identify the most sustainable product design using a cradle to grave life cycle perspective on openLCA v1.8.0. While performing Life Cycle Inventory, we were able to embed data provided by the actual suppliers and manufacturers, including geographical specific contributions, waste production, energy consumption and processing details. Well-established impact categories have been adopted for Life Cycle Impact Analysis in order to abide by the state-of-the-art of LCA practice. Finally, the main contributions to the whole product life cycle have been identified, highlighting the critical phases with the aim of applying the essential improvement for reducing the product-related impacts.

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