Modulation of Biodistribution,Pharmacokinetics, and Photosensitivity with the Delivery Vehicle of a Bacteriochlorin Photosensitizer for Photodynamic Therapy

Intravenous (i.v.) formulations with various amounts of organic solvents [PEG₄₀₀, propylene glycol (PG), cremophor EL (CrEL)] were used to deliver a fluorinated sulfonamide bacteriochlorin to mice, rats, and minipigs. Biodistribution studies in mice showed that a low‐content CrEL formulation combines high bioavailability with high tumor‐to‐muscle and tumor‐to‐skin ratios. This formulation was also the most successful in the photodynamic therapy of mice with subcutaneously implanted CT26 murine colon adenocarcinoma tumors. Pharmacokinetic studies in mice and minipigs revealed that with the same low CrEL formulation, the half‐life of the photosensitizer in the central compartment was longer in minipigs. Differences in biodistribution with the various formulations, and in pharmacokinetics between the two animal species with the same formulation, are attributed to the interaction of the formulations with low‐density lipoproteins (LDLs). Skin photosensitivity studies in rats showed that 30 min exposure of the skin to a solar simulator 7 days after i.v. administration of the fluorinated sulfonamide bacteriochlorin at 1 mg kg^?1 did not elicit significant skin reactions.     

Heuristic approaches for the optimal wiring in large scale robotic skin design

This paper faces the problem of optimizing the wiring and the connections in a tactile skin for robots. The robotic skin is a device composed of a network of tactile sensors, whose wiring can be very complex: the control of this complexity is a key problem. In the considered robotic skin, skin elements are grouped into skin patches, which output tactile data that have to be read by a micro-controller. The logical connections between the sensors must be defined in order to route signals through the network. A finite set of micro-controllers is given and a set of constraints is imposed on the given assignment and routing. The considered problem has a combinatorial nature and it can be formulated as a Minimum Constrained Spanning Forest problem with costs on arcs that cannot be a priori defined as they are solution-dependent. The problem is NP-hard. The paper introduces a mathematical formulation and then proposes a Multi-Start Heuristic algorithm and an Ant Colony Optimization approach whose effectiveness is evaluated through experimental tests performed on both real and synthetically generated instances.     

Effect of shallow-angled skins on the structural performance of the large-scale wind turbine blade

Two shallow-angled symmetric and asymmetric skins, with off-axis fiber angles of less than 45°, were proposed and employed to a 5 MW wind turbine blade. For the symmetric configuration, shallow-angled skins were applied to both the pressure and suction sides of the blade, while, for the asymmetric configuration, only the pressure side was implemented with a shallow-angled skin, keeping the conventional 45-degree-angled skin for the suction side. The blade tip deflection, modal frequencies, buckling stability, and failure index were computed for off-axis fiber angles of 45°, 35°, and 25°. The use of shallow-angled skins improved blade bending stiffness and strength. The buckling resistance decreased for symmetric skins and remained unchanged for asymmetric skins; the former case was compensated for by increasing the core thickness. For both skin configurations, a reduction in the blade failure index of up to 18% and 38%, and mass reductions of up to 8% and 13% were demonstrated for the 35° and 25° shallow-angled skins, respectively.     

Patterns in melanocytic lesions: impact of the geometry on growth and transport inside the epidermis

In glabrous skin, nevi and melanomas exhibit pigmented stripes during clinical dermoscopic examination. They find their origin in the basal layer geometry which periodically exhibits ridges, alternatively large (limiting ridges) and thin (intermediate ridges). However, nevus and melanoma lesions differ by the localization of the pigmented stripes along furrows or ridges of the epidermis surface. Here, we propose a biomechanical model of avascular tumour growth which takes into account this specific geometry in the epidermis where both kinds of lesions first appear. Simulations show a periodic distribution of tumour cells inside the lesion, with a global contour stretched out along the ridges. In order to be as close as possible to clinical observations, we also consider the melanin transport by the keratinocytes. Our simulations show that reasonable assumptions on melanocytic cell repartition in the ridges favour the limiting ridges of the basal compared with the intermediate ones in agreement with nevus observations but not really with melanomas. It raises the question of cell aggregation and repartition of melanocytic cells in acral melanomas and requires further biological studies of these cells in situ.     

Preparation,characterisation and structure of rabbit (Hyla rabbit) skin gelatine

Rabbit skin was used as a raw material to prepare gelatine. The yield of extracted rabbit skin gelatine was 8.49 ± 0.91% based on a wet weight basis. The bloom strength of 6.67% rabbit gelatine was 457.57 ± 3.302 g, and its gelling and melting temperatures were 27.8 and 34.4 °C, respectively. Sodium dodecyl sulphate‐polyacrylamide gel electrophoresis analysis demonstrated that the content of the subunit components (α chain, β and γ components) of the rabbit skin gelatine achieved 97.915%. Amino acid composition analysis indicated that the total amino acid contents (proline plus hydroxyproline) in the rabbit gelatine were 222 residues per 1000 residues. The high content of the subunit components and amino acids could contribute to the gelatine's suitable gel properties. Rabbit gelatine had nearly all of the characteristic absorption peaks of collagen from rabbit skin, and the loss of the triple helical structure and damage to part of the hydrogen bonds occurred during the conversion of collagen to gelatine.     

Determining elastic properties of skin by measuring surface waves from an impulse mechanical stimulus using phase-sensitive optical coherence tomography

The mechanical properties of skin are important tissue parameters that are useful for understanding skin patho-physiology, which can aid disease diagnosis and treatment. This paper presents an innovative method that employs phase-sensitive spectral-domain optical coherence tomography (PhS-OCT) to characterize the biomechanical properties of skin by measuring surface waves induced by short impulses from a home-made shaker. Experiments are carried out on single and double-layer agar–agar phantoms, of different concentrations and thickness, and on in vivo human skin, at the forearm and the palm. For each experiment, the surface wave phase-velocity dispersion curves were calculated, from which the elasticity of each layer of the sample was determined. It is demonstrated that the experimental results agree well with previous work. This study provides a novel combination of PhS-OCT technology with a simple and an inexpensive mechanical impulse surface wave stimulation that can be used to non-invasively evaluate the mechanical properties of skin in vivo, and may offer potential use in clinical situations.     

How to identify water from thickener aqueous solutions by touch

Water detection is one of the most crucial psychological processes for many animals. However, nobody knows the perception mechanism of water through our tactile sense. In the present study, we found that a characteristic frictional stimulus with large acceleration is one of the cues to differentiate water from water contaminated with thickener. When subjects applied small amounts of water to a glass plate, strong stick-slip phenomena with a friction force of 0.46 ± 0.30 N and a vertical force of 0.57 ± 0.36 N were observed at the skin surface, as shown in previous studies. Surprisingly, periodic shears with acceleration seven times greater than gravitational acceleration occurred during the application process. Finite-element analyses predicted that these strong stimuli could activate tactile receptors: Meissner''s corpuscle and Pacinians. When such stimuli were applied to the fingertips by an ultrasonic vibrator, a water-like tactile texture was perceived by some subjects, even though no liquid was present between the fingertip and the vibrator surface. These findings could potentially be applied in the following areas: materials science, information technology, medical treatment and entertainment.     

Angiotensin-I converting enzyme inhibitory and antioxidant activity of bioactive peptides produced by enzymatic hydrolysis of skin from grass carp (Ctenopharyngodon idella)

Grass carp skin pieces were homogenized in water and hydrolyzed by Alcalase®, collagenase, proteinase K, and/or trypsin at their optimum conditions. Samples were taken at various degrees of hydrolysis and were evaluated for antioxidant, antimicrobial, and angiotensin-converting enzyme inhibitory activities. Alcalase and collagenase completely hydrolyzed the skin with different rates, and released peptides with antioxidant and angiotensin-converting enzyme-inhibitory activity. These activities increased linearly with increasing degrees of hydrolysis. Subsequent incubation of the collagenase hydrolysates with trypsin slightly increased the antioxidant activity. Proteinase K, although only partially hydrolyzing the skin, also catalyzed the release of peptides with antioxidant and angiotensin-converting enzyme-inhibitory activities. These results show that skin by-products from grass carp can be a source of bioactive peptides produced by a one-step reaction. Such hydrolysates may be applied in food products to prolong shelf life and provide beneficial effects on blood pressure.     

Design of deployable bistable structures for morphing skin and its structural optimization

The morphing skin is the surface of a deployable frame which can change its shape to present optimal performance in all stages of a task for an aerospace vehicle. This article proposes a deployable frame with low kinematic error and high stability. Mechanical design and optimization of the deployable mechanism are developed, and specifically the analysis model of the deployable mechanism is established by the use of extendable units. The genetic algorithm is employed to find the optimal geometric parameters of the foldable structure. Furthermore, the design method of a bistable compliant mechanism is investigated to achieve the bistability. An example of a morphing leading edge (MLE) is analysed using the proposed method. The results show that the position errors converge to the optimal solution which supplies the minimum value. Numerical analysis indicates that the mechanism can provide two bistable positions for the actual use of the MLE.