La scissione. Aspetti strategici ed economici

Analisi delle situazioni operative in cui può essere applicata la scissione. Analisi dei principali aspetti procedurali e tributari, con particolare riferimrnto all'elusività dell'operazione. Analisi dei bilanci di scissione secondo i principi contabili nazionali ed internazioanl

Motion Planning Algorithm in a Y-Graph

We present an explicit algorithm for two robots to move autonomously and without collisions on a track shaped like the letter Y. Configuration spaces are of practical relevance in designing safe control schemes for automated guided vehicles. The topological complexity of a configuration space is the minimal number of continuous instructions required to move robots between any initial configuration to any final one without collisions. Using techniques from topological robotics, we calculate the topological complexity of two robots moving on a Y-track and exhibit an optimal algorithm realizing this exact number of instructions given by the topological complexity

Weak lensing predictions for coupled dark energy cosmologies at non-linear scales

We present non-linear weak lensing predictions for coupled dark energy models using the CoDECS simulations. We calculate the shear correlation function and error covariance expected for these models, for forthcoming ground-based (such as DES) and space-based (Euclid) weak lensing surveys. We obtain predictions for the discriminatory power of a ground-based survey similar to DES and a space-based survey such as Euclid in distinguishing between $\Lambda$CDM and coupled dark energy models; we show that using the non-linear lensing signal we could discriminate between $\Lambda$CDM and exponential constant coupling models with $\beta_0\geq0.1$ at $4\sigma$ confidence level with a DES-like survey, and $\beta_0\geq0.05$ at $5\sigma$ confidence level with Euclid. We also demonstrate that estimating the coupled dark energy models' non-linear power spectrum, using the $\Lambda$CDM Halofit fitting formula, results in biases in the shear correlation function that exceed the survey errors.Comment: 9 pages, 5 figures, v2: accepted for publication in MNRA

Recombinant protein production by large-scale transient gene expression in mammalian cells: state of the art and future perspectives

The expansion of the biologics pipeline depends on the identification of candidate proteins for clinical trials. Speed is one of the critical issues, and the rapid production of high quality, research-grade material for preclinical studies by transient gene expression (TGE) is addressing this factor in an impressive way: following DNA transfection, the production phase for TGE is usually 2-10days. Recombinant proteins (r-proteins) produced by TGE can therefore enter the drug development and screening process in a very short time--weeks. With "classical” approaches to protein expression from mammalian cells, it takes months to establish a productive host cell line. This article summarizes efforts in industry and academia to use TGE to produce tens to hundreds of milligrams of r-proteins for either fundamental research or preclinical studie

Applicazioni di analisi ordinale: il teorema di Kruskal.

Si fornisce una caratterizzazione del teorema di Kruskal con la tecnica dell'analisi ordinale, uno dei principali strumenti della teoria della dimostrazione

Reduced glutamine concentration improves protein production in growth-arrested CHO-DG44 and HEK-293E cells

For most cultivated mammalian cells, glutamine is an essential medium component. However, glutamine consumption results in the production of ammonia, a cytotoxic byproduct. Here we investigated the effect of glutamine reduction on recombinant protein production and ammonia accumulation in transiently transfected CHO and HEK-293E cells maintained under conditions of growth arrest. Maximum transient recombinant protein yields were observed in HEK-293E cultures without glutamine and in CHO cultures with 2mM glutamine. The initial concentration of glutamine correlated with the level of ammonia accumulation in each culture. For both a stable CHO-derived cell line and a polyclonal population of recombinant CHO cells grown under conditions of mild hypothermia, the highest volumetric protein productivity was observed in cultures without glutamine. Here, the level of ammonia accumulation also corresponded to the initial glutamine concentration. Our data demonstrate that reduction of glutamine in the medium is an effective approach to improve protein production in both transiently and stably transfected mammalian cells when applying conditions that reduce or arrest the growth of these cell

Accurate and efficient target prediction using a potency-sensitive influence-relevance voter

BackgroundA number of algorithms have been proposed to predict the biological targets of diverse molecules. Some are structure-based, but the most common are ligand-based and use chemical fingerprints and the notion of chemical similarity. These methods tend to be computationally faster than others, making them particularly attractive tools as the amount of available data grows.ResultsUsing a ChEMBL-derived database covering 490,760 molecule-protein interactions and 3236 protein targets, we conduct a large-scale assessment of the performance of several target-prediction algorithms at predicting drug-target activity. We assess algorithm performance using three validation procedures: standard tenfold cross-validation, tenfold cross-validation in a simulated screen that includes random inactive molecules, and validation on an external test set composed of molecules not present in our database.ConclusionsWe present two improvements over current practice. First, using a modified version of the influence-relevance voter (IRV), we show that using molecule potency data can improve target prediction. Second, we demonstrate that random inactive molecules added during training can boost the accuracy of several algorithms in realistic target-prediction experiments. Our potency-sensitive version of the IRV (PS-IRV) obtains the best results on large test sets in most of the experiments. Models and software are publicly accessible through the chemoinformatics portal at http://chemdb.ics.uci.edu/

Hyperosmolarity enhances transient recombinant protein yield in Chinese hamster ovary cells

The effect of hyperosmolarity on transient recombinant protein production in Chinese hamster ovary (CHO) cells was investigated. Addition of 90mM NaCl to the production medium ProCHO5 increased the volumetric yield of recombinant antibody up to 4-fold relative to transfection in ProCHO5 alone. Volumetric yields up to 50mgl−1 were achieved in a 6day batch culture of 3l. In addition, hyperosmolarity reduced cell growth and increased cell size. The addition of salt to cultures of transiently transfected CHO cells is a simple and cost-effective method to increase TGE yields in this hos

Study of the improved Sf9 transient gene expression process

Insect cells have been widely used for the production of recombinant proteins using recombinant baculovirus for gene delivery [1]. To simplify protein production in insect cells, we have previously described a method, based on transient gene expression (TGE) with cultures of suspension-adapted Sf9 cells using polyethylenimine (PEI) for DNA delivery [2]. Expression of GFP has been realized at high efficiency and a tumor necrosis factor receptor-Fc fusion protein (TNFR-Fc) was produced at a level of 40 mg/L. However, the efficiency of the insect cells TGE system has not been studied and further opti- mization may improve protein titers. Here, we studied the efficiency of PEI for plasmid delivery in Sf9 cells