Instrumented crutches for gait parameters evaluation

Most of the prototypes of instrumented crutches available in the literature require external motion capture devices to perform a gait analysis and to report the load applied on the crutches with respect to the gait cycle. Motion capture systems with markers require a controlled laboratory with cameras, instead IMU-based systems are more transportable, but the user must be instrumented. A new version of instrumented crutches, previously developed by the authors, allows one to measure the axial forces and to detect the gait phases during two-point assisted walking thanks to the cameras mounted on the lower part of the crutches

Body measurement estimations using 3D scanner for individuals with severe motor impairments

In biomechanics, a still unresolved question is how to estimate with enough accuracy the volume and mass of each body segment of a subject. This is important for several applications ranging from the rehabilitation of injured subjects to the study of athletic performances via the analysis of the dynamic inertia of each body segment. However, traditionally this evaluation is done by referring to anthropometric tables or by approximating the volumes using manual measurements. We propose a novel method based on the 3D reconstruction of the subject’s body using the commercial low-cost camera Kinect v2. The software developed performs body segment separation in a few minutes leveraging alpha shape approximation of 3D polyhedrons to quickly compute a Montecarlo volume estimation. The procedure was evaluated on a total of 30 healthy subjects and the resulting segments’ lengths and masses were compared with the literature

Structure-dependent optical and electrical transport properties of nanostructured Al-doped ZnO

The structure-property relation of nanostructured Al-doped ZnO thin films has been investigated in detail through a systematic variation of structure and morphology, with particular emphasis on how they affect optical and electrical properties. A variety of structures, ranging from compact polycristalline films to mesoporous, hierarchically organized cluster assemblies, are grown by Pulsed Laser Deposition at room temperature at different oxygen pressures. We investigate the dependence of functional properties on structure and morphology and show how the correlation between electrical and optical properties can be studied to evaluate energy gap, conduction band effective mass and transport mechanisms. Understanding these properties opens the way for specific applications in photovoltaic devices, where optimized combinations of conductivity, transparency and light scattering are required.Comment: 8 pages, 9 figure

Multi-wavelength Raman scattering of nanostructured Al-doped zinc oxide

In this work we present a detailed Raman scattering investigation of zinc oxide and aluminum-doped zinc oxide (AZO) films characterized by a variety of nanoscale structure and morphology and synthesized by pulsed laser deposition (PLD) under different oxygen pressure conditions. The comparison of Raman data for pure ZnO and AZO films with similar morphology at the nano/mesoscale allows to investigate the relation between Raman features (peak or band positions, width, relative intensity) and material properties such as local structural order, stoichiometry and doping. Moreover Raman measurements with three different excitation lines (532, 457 and 325 nm) point out a strong correlation between vibrational and electronic properties. This observation confirms the relevance of a multi-wavelength Raman investigation to obtain a complete structural characterization of advanced doped oxide materials.Comment: 27 pages, 7 figures, submitted to the Journal of Applied Physic

Integration of antimicrobial pectin-based edible coating and active modified atmosphere packaging to preserve the quality and microbial safety of fresh-cut persimmon (Diospyros kaki Thunb. cv. Rojo Brillante)

BACKGROUND: The greatest hurdle to the commercial marketing of fresh-cut fruits is related to their higher susceptibility to enzymatic browning, tissue softening, and microbial growth. The aim of this study was to test the efficacy of a pectin-based edible coating and low oxygen modified atmosphere packaging (MAP) to control enzymatic browning and reduce microbial growth of fresh-cut Rojo Brillante' persimmon. The survival of Escherichia coli, Salmonella enteritidis and Listeria monocytogenes artificially inoculated on fresh-cut fruit was also assessed. The pectin coating was amended with 500 IU mL(-1) nisin (NI) as antimicrobial agent and 10gkg(-1) citric acid and 10gkg(-1) calcium chloride as anti-browning and firming agents, respectively. Persimmon slices were dipped in the coating or in water (control) and packed under 5 kPa O-2 (MAP) or in ambient atmosphere for up to 9 days at 5 degrees C. Microbial growth, package gas composition, colour, firmness, polyphenol oxidase activity, visual quality and overall sensory flavour of persimmon slices were measured during storage. RESULTS: Coating application combined with active MAP significantly reduced the CO2 emission and O-2 consumption in the package. The coating was effective in reducing browning and also inhibited the growth of mesophilic aerobic bacteria. Coating also reduced the populations of E. coli, S. enteritidis and L. monocytogenes. CONCLUSION: The combination of the pectin-based edible coating and active MAP proved to be the most effective treatment to maintain the sensory and microbiological quality of persimmon slices for more than 9 days of storage. (c) 2016 Society of Chemical Industr

Browning inhibition and microbial control in fresh-cut persimmon (Diospyros kaki Thunb. cv. Rojo Brillante) by apple pectin-based edible coatings

The aim of this study was to develop new edible coatings based on apple pectin with a combination of antioxidants and antimicrobial agents to control enzymatic browning and microbial growth of fresh-cut ‘Rojo Brillante’ persimmon. The survival of important food-borne human pathogens artificially inoculated on fresh-cut fruit was also assessed. Potassium sorbate (PS) at 2 or 4 g kg−1, sodium benzoate (SB) at 4 g kg−1, or nisin (NI) at 500 IU mL−1, were added to apple pectin coatings containing 10 g kg−1 citric acid and 10 g kg−1 calcium chloride as antioxidants. Persimmon slices were dipped in the coatings, the aqueous antioxidant solution (citric acid and calcium chloride) or water (control), packed in an ambient atmosphere and stored at 5 °C for up to 9 days. Microbial growth, colour, firmness, polyphenol oxidase (PPO) activity, visual quality and overall sensory flavour were measured during storage. Coated samples and those dipped in the antioxidant aqueous solution presented lower a* values than control samples, which indicated effective browning inhibition. Persimmon slices treated with coatings containing PS and SB reached the limit of marketability after 7 days of storage. At the end of storage, the overall fruit flavour was ranked above the limit of acceptability. Antimicrobial coatings inhibited growth of mesophilic aerobic bacteria, and those containing SB and NI were the most effective. No growth of moulds, yeasts and psychrophilic aerobic bacteria was detected during storage. All the treatments effectively reduced the populations of Escherichia coli and Salmonella enteritidis, NI-coating being the most effective. For Listeria monocytogenes, only the NI-coating effectively reduced the bacterial population

Inhibition of resistance-refractory P. falciparum kinase PKG delivers prophylactic, blood stage, and transmission-blocking antiplasmodial activity

The search for antimalarial chemotypes with modes of action unrelated to existing drugs has intensified with the recent failure of first-line therapies across Southeast Asia. Here, we show that the trisubstituted imidazole MMV030084 potently inhibits hepatocyte invasion by Plasmodium sporozoites, merozoite egress from asexual blood stage schizonts, and male gamete exflagellation. Metabolomic, phosphoproteomic, and chemoproteomic studies, validated with conditional knockdown parasites, molecular docking, and recombinant kinase assays, identified cGMP-dependent protein kinase (PKG) as the primary target of MMV030084. PKG is known to play essential roles in Plasmodium invasion of and egress from host cells, matching MMV030084's activity profile. Resistance selections and gene editing identified tyrosine kinase-like protein 3 as a low-level resistance mediator for PKG inhibitors, while PKG itself never mutated under pressure. These studies highlight PKG as a resistance-refractory antimalarial target throughout the Plasmodium life cycle and promote MMV030084 as a promising Plasmodium PKG-targeting chemotype

Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis

Visceral leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of visceral leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for visceral leishmaniasis

Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis

The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard of care for VL suffers from multiple issues and there is a limited pipeline of new candidate drugs. As such, there is a clear unmet medical need to identify new treatments. This paper describes the optimization of a phenotypic hit against Leishmania donovani, the major causative organism of VL. The key challenges were to balance solubility and metabolic stability while maintaining potency. Herein, strategies to address these shortcomings and enhance efficacy are discussed, culminating in the discovery of preclinical development candidate GSK3186899/DDD853651 (<b>1</b>) for VL

Drug-perturbation-based stratification of blood cancer

As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non-BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.Peer reviewe