SafeNet: A methodology for integrating general-purpose unsafe devices in safe-robot rehabilitation systems

Robot-assisted neurorehabilitation often involves networked systems of sensors (“sensory rooms”) and powerful devices in physical interaction with weak users. Safety is unquestionably a primary concern. Some lightweight robot platforms and devices designed on purpose include safety properties using redundant sensors or intrinsic safety design (e.g. compliance and backdrivability, limited exchange of energy). Nonetheless, the entire “sensory room” shall be required to be fail-safe and safely monitored as a system at large. Yet, sensor capabilities and control algorithms used in functional therapies require, in general, frequent updates or re-configurations, making a safety-grade release of such devices hardly sustainable in cost-effectiveness and development time. As such, promising integrated platforms for human-in-the-loop therapies could not find clinical application and manufacturing support because of lacking in the maintenance of global fail-safe properties.     

A genetic algorithm for energy-efficiency in job-shop scheduling

Many real-world scheduling problems are solved to obtain optimal solutions in term of processing time, cost, and quality as optimization objectives. Currently, energy-efficiency is also taken into consideration in these problems. However, this problem is NP-hard, so many search techniques are not able to obtain a solution in a reasonable time. In this paper, a genetic algorithm is developed to solve an extended version of the Job-shop Scheduling Problem in which machines can consume different amounts of energy to process tasks at different rates (speed scaling). This problem represents an extension of the classical job-shop scheduling problem, where each operation has to be executed by one machine and this machine can work at different speeds. The evaluation section shows that a powerful commercial tool for solving scheduling problems was not able to solve large instances in a reasonable time, meanwhile our genetic algorithm was able to solve all instances with a good solution quality.     

The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs

Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators.     

Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.     

Mechanical behavior of cold-water fish gelatin gels crosslinked with 1,4-butanediol diglycidyl ether

In this work, chemical crosslinking with 1,4-butanediol diglycidyl ether (BDDGE) is used as strategy to enhance mechanical performance of fish gelatin (FG) gels in order to meet the properties' range of mammalian gelatin physical gels. Joint analysis of free amino groups, swelling ratio, and total soluble material indicates that crosslinking degree increases with increasing FG concentration and it is favored by a 0.2 BDDGE/FG ratio. Increasing crosslinking degree enhances gel indentation strength and shear modulus (μ) while decreases fracture toughness (G_IC). Measured μ and G_IC values lies within the range exhibited by mammalian gelatin physical gels, but the relationship between these parameters is opposite. This is due to the different fracture mechanisms occurring in chemically crosslinked and physical gels.     

Composition of phospholipid fraction in raw chicken meat and pre-cooked chicken patties: influence of feeding fat sources and processing technology

The effect of dietary lipid sources (animal fat, AF vs. vegetable oil, VO) was investigated on the phospholipid (PL) fraction of raw chicken meat and pre-cooked chicken patties. PL classes were determined on extracted lipids by high-performance liquid chromatography (HPLC) connected with an evaporative light-scattering detector (ELSD). The HPLC-ELSD method showed good intraday repeatability (less than 5% for different PL) and limits of detection ranging from 0.006 mg/mL (phosphatidylethanolamine) to 0.045 mg/mL (sphingomyelin). Diet did not consistently influence PL in chicken breast. A significant difference was assessed in meat batter where total PL were at levels of 349.0 and 388.2 mg/100 g of product in batter from broilers fed AF and VO diet, respectively. Cooking oil absorption caused an important decrease in PL (lower than 300 mg/100 g of product in pre-fried patties). Diet was an effective means to control the PL fatty acid profile in chicken, particularly the levels of polyunsaturated fatty acids (PUFA). In minced breast and thigh and meat batter from birds fed a VO-supplemented diet, the relative amount of PUFA was 46, 81 and 28% higher than that determined in the corresponding samples obtained from broilers fed an AF-based diet.