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Robotic technology and functional electrical stimulation (FES) have emerged as highly effective rehabilitative techniques for individuals with neuromuscular diseases, showcasting their ability to restore motor functions. Within the proposed study, we developed and tested a new hybrid controller combining an upper-limb exoskeleton with FES to enhance haptic feedback when performing task-oriented and bimanual movement, like pick-and-place, in a virtual environment. We investigated the performance of the proposed approach on eight unimpaired participants providing haptic feedback either only by the exoskeleton or by the hybrid system. The hybrid control presents two different modalities, assistive and resistive, to modulate the perception of the load. FES intensity is calibrated to the subjects’ biomechanical properties and it is adjusted in real-time according to the real-time motion of the upper limbs. Experimental results highlighted the ability of the hybrid control to improve kinematic performance: in both hybrid modalities subjects reduced the target matching error(values between 0.048±0.007 m and 0.06±0.006 m) without affecting the normal motion smoothness (SPARC values in the hybrid conditions range from −2.58±0.12 to −3.30±0.13). Moreover, the resistive approach resulted in greater metabolic consumption (1.04±0.03 W/kg), indicating a more realistic experience of lifting a virtual object through FES that increased the perceived weight. The innovation in our hybrid control relies on the modulation of muscular activation during manipulation tasks, which could be a promising approach in the clinical treatment of neuromuscular diseases.

The objective of this work was to develop a versatile strategy for preparing multifunctional composite films with tunable properties. Novel conductive composites based on the combination of single walled carbon nanotubes (SWCNTs) and biodegradable poly(butylene cyclohexanedicarboxylate/diglycolate) random copolymers (P(BCEmBDGn)) are here presented. In particular, synthesized PBCE homopolymer and two copolymers containing different amounts of ether–oxygen containing co-units, P(BCE90BDG10) and P(BCE70BDG30), have been considered as matrices of SWCNTs based composites. The effect of incorporation of different amounts of SWCNTs (0.1–0.5–0.75–1 wt%) on morphological, thermal, mechanical and electrical properties was deeply investigated. The morphology of the fracture surfaces is affected by the SWCNT presence, while the increase in the SWCNT content does not provide significant microstructure modifications. The thermal properties underlined that nanotubes can act as nucleating agents, favouring the polymer crystallization process. The mechanical behavior demonstrated that the introduction of carbon nanotubes both in the case of PBCE homopolymer and in random copolymers based formulations exerted a reinforcing effect. All composites exhibit high electrical conductivity in comparison to the neat polymers. This work demonstrates that this combinatorial approach can be used to develop materials with tunable and advanced functional properties.

A series of novel random copolymers of poly(propylene 1,4-cyclohexanedicarboxylate) (PPCE) containing neo -pentyl glycol sub-unit (P(PCExNCEy)) were synthesized and characterized in terms of molecular and solid-state properties. In addition, biodegradability studies in compost have been conducted. The copolymers displayed a high and similar thermal stability with respect to PPCE. At room temperature, all the copolymers appeared as semicrystalline materials: the main effect of copolymerization was a lowering of crystallinity degree (χc) and a decrease of the melting temperature compared to the parent homopolymer. In particular, Wide Angle X-Ray diffraction (WAXD) measurements indicated that P(PCExNCEy) copolymers are characterized by cocrystallization, PNCE counits cocrystallizing in PPCE crystalline phase. Final properties and biodegradation rate of the materials under study were strictly dependent on copolymer composition and χc. As a matter of fact, the elastic modulus and the elongation at break decreased and increased, respectively, as neopentyl glycol cyclohexanedicarboxylate (NCE) unit content was increased. The presence of a rigid-amorphous phase was evidenced by means of Dynamic Mechanical Thermal Analysis (DMTA) analysis in all the samples under investigation. Lastly, the biodegradation rate of P(PCExNCEy) copolymers was found to slightly increase with the increasing of NCE molar content.

Gene editing following designer nuclease cleavage in the presence of a DNA donor template can revert mutations in disease-causing genes. For optimal benefit, reversion of the point mutation in HBB leading to sickle cell disease (SCD) would permit precise homology-directed repair (HDR) while concurrently limiting on-target non-homologous end joining (NHEJ)-based HBB disruption. In this study, we directly compared the relative efficiency of co-delivery of a novel CRISPR/Cas9 ribonucleoprotein targeting HBB in association with recombinant adeno-associated virus 6 (rAAV6) versus single-stranded oligodeoxynucleotides (ssODNs) to introduce the sickle mutation (GTC or GTG; encoding E6V) or a silent change (GAA; encoding E6optE) in human CD34+ mobilized peripheral blood stem cells (mPBSCs) derived from healthy donors. In vitro, rAAV6 outperformed ssODN donor template delivery and mediated greater HDR correction, leading to both higher HDR rates and a higher HDR:NHEJ ratio. In contrast, at 12–14 weeks post-transplant into recipient, immunodeficient, NOD, B6, SCID Il2rγ−/− Kit(W41/W41) (NBSGW) mice, a ∼6-fold higher proportion of ssODN-modified cells persisted in vivo compared to recipients of rAAV6-modified mPBSCs. Together, our findings highlight that methodology for donor template delivery markedly impacts long-term persistence of HBB gene-modified mPBSCs, and they suggest that the ssODN platform is likely to be most amenable to direct clinical translation. Keywords: sickle cell disease, gene editing, rAAV6, ssODN, homology-directed repair, Crispr/Cas9, hemoglobin disorders, NHEJ versus HDR, in vivo engraftment, NBSGW41 mice, CD34, hematopoietic stem cells, stem cell cures

Poly(propylene isophthalate) (PPI), poly(propylene succinate) (PPS), and poly(propylene isophthalate/succinate) (PPI‐PPS) random copolymers were synthesized and characterized in terms of chemical structure and molecular weight. The thermal behavior was examined by TGA and DSC. All the polymers showed a good thermal stability. At room temperature, they appeared as semicrystalline materials, except 20PPI‐PPS and 30PPI‐PPS: the main effect of copolymerization was a lowering in the amount of crystallinity and a decrease of Tm with respect to homopolymers. A crystalline phase of PPI and PPS was evidenced at high content of PI or PS units, respectively. Amorphous samples were obtained after melt quenching and an increment of Tg, with the increment of PI units, was observed. This behavior was explained as due to the presence of stiff phenylene groups. The Wood equation described well Tg‐composition data. Lastly, the presence of a rigid‐amorphous phase was evidenced in copolymers, differently from the two homopolymers. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 310–321, 2007. [ABSTRACT FROM AUTHOR]

An anomalous enhancement of the segmental dynamics upon crystallization is observed by analyzing the dielectric relaxation of a random copolymer formed by stiff aromatic and flexible aliphatic co-monomeric units. The corresponding aliphatic homopolymer is characterized by a low glass transition temperature. The results show that the characteristic self-confinement inherent to semicrystalline polymer systems, which significantly slows down the segmental dynamics as compared to that of pure amorphous ones, is not only avoided but pushed in the opposite direction. Although the effect formally resembles that observed in liquids confined within non-interacting environments, X-ray measurements have shown that the origin in the present case must be sought in an enrichment of the amorphous phase with the most flexible co-monomer upon crystallization. [ABSTRACT FROM AUTHOR]