Development and Validation of an Artificial Mechanical Skin Model for the Study of Interactions between Skin and Microneedles

Microneedles are small needle‐like structures that are almost invisible to the naked eye. They have an immense potential to serve as a valuable tool in many medical applications, such as painless vaccination. Microneedles work by breaking through the stratum corneum, the outermost barrier layer of the skin, and providing a direct path for drug delivery into the skin. A lot of research has been presented over the past two decades on the applications of microneedles, yet the fundamental mechanism of how they interact, pressure, and penetrate the skin in its native state is worth examining further. As such, a major difficulty with understanding the mechanism of microneedle–skin interaction is the lack of an artificial mechanical human skin model to use as a standardized substrate. In this research news, the development of an artificial mechanical skin model based on a thorough mechanical study of fresh human and porcine skin samples is presented. The artificial mechanical skin model can be used to study the mechanical interactions between microneedles and skin, but not diffusion of molecules across skin. This model can assist in improving the performance of microneedles by enhancing the reproducibility of microneedle depth insertions for optimal drug delivery and biosensing.

     

Polymeric Nanoparticle-Based Photodynamic Therapy for Chronic Periodontitis in Vivo

Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT—in planktonic and biofilm phases—with MB or MB-NP (25 µg/mL) at 20 J/cm² in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm²) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment.     

Thermal Upgrading of Nickeliferous Pyrrhotite Tailings for the Recovery of Nickel in the Form of Ferronickel Alloy

Metallurgical and Materials Transactions B - Production of ferronickel alloy by thermal treatment of nickeliferous pyrrhotite (Pyrr) tailings was studied by both thermodynamic assessment and...     

Thermo-mechanical and metallurgical aspects in friction stir processing of AZ31 Mg alloy—A numerical and experimental investigation

Friction stir processing of AZ31 Mg alloy was investigated by numerical modeling and experiments. A CFD based, fully coupled, 3D, thermo-mechanical model was built to better understand the effect of process parameters on temperature, material flow and strain rate. In order to account for material softening phenomena at elevated temperatures and extremely high strain rates that occur during the FSP process, experimentally measured peak temperatures were utilized to introduce a correction function in the flow stress constitutive relation. The numerical results showed that rotational speed as compared to translational speed had a more dominant effect on temperature field and strain rate. In addition, the asymmetric material flow around the tool axis caused higher peak temperature and strain rate on the advancing side (AS), while the material in the path of tool pin was swept around the retreating side (RS). FSP experiments confirmed peak temperatures measured at sheet surface near shoulder perimeter on AS were always higher than corresponding RS peak temperatures, under the selected range of process parameters. In addition to thermo-mechanical aspects, the metallurgical characteristics of FSP i.e. mainly the grain size evolution was studied by optical and electron microscopy. Experiments revealed that the coarse bimodal microstructure of as-received AZ31 Mg was subdivided into a defect-free, fine grain microstructure at the rotational speed of 1000 rpm, while a defect-free but a relatively coarse and bimodal microstructure evolved in the material at rotational speeds higher than 1000 rpm. Furthermore, in the selected range of process parameters the increases in translational speed resulted in finer grain sizes without the formation of voids or defects.     

Purification of metallurgical silicon using iron as an impurity getter part I: Growth and separation of Si

The purification of metallurgical grade silicon (MG-Si) using a combination of solvent refining and physical separation is studied. MG-Si was alloyed with iron and solidified under different cooling rates in order to grow pure Si dendrites from the alloy. The Si dendrites were then separated using a gravity-based method. The separation method relies on the significantly different densities of Si and FeSi₂, and it uses a heavy liquid with specific gravity between the two phases to float the light Si particles to the surface of the liquid, while the heavy iron silicide sinks. The effects of the particle size and cooling rate on the yield and separation efficiency of the Si phase were investigated by quantifying the fraction of Si in the sinks and floats. The results demonstrate that the crushing size of the particles prior to separation should be approximately the same as the width of the dendrites in order to maximize the separation efficiency while simultaneously lowering the grinding cost.     

Weighting fuzzy classification rules using receiver operating characteristics (ROC) analysis

In fuzzy rule-based classification systems, rule weight has often been used to improve the classification accuracy. In past research, a number of heuristic methods for rule weight specification have been proposed. In this paper, a method of fuzzy rule weight specification using Receiver Operating Characteristic (ROC) analysis is proposed. In order to specify the weight of a fuzzy rule, using 2-class ROC analysis, the threshold that the rule achieves its maximum accuracy is found. This threshold is used as the weight of the rule. The proposed method is compared with existing ones through computer simulations on some well-known classification problems with continuous attributes. Simulation results show that the proposed method performs better than existing methods of fuzzy rule weight specification.     

An optimal algorithm for two robots path planning problem on the grid

This paper is a study on the problem of path planning for two robots on a grid. We consider the objective of minimizing the maximum path length which corresponds to minimizing the arrival time of the last robot at its goal position. We propose an optimal algorithm that solves the problem in linear time with respect to the size of the grid. We show that the algorithm is complete; meaning that it is sure to find an optimal solution or report if any does not exist.     

Phosphoinositide 3-kinase induces scattering and tubulogenesis in epithelial cells through a novel pathway

Hepatocyte growth factor/scatter factor (HGF/SF) treatment of the Madin-Darby canine kidney epithelial cell line causes scattering of cells grown in monolayer culture and the formation of branching tubules by cells grown in collagen gels. HGF/SF causes prolonged activation of both the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase 2 (ERK2) and the phosphoinositide 3-OH kinase (PI 3-kinase) target protein kinase B (PKB)/Akt; inhibition of either the MAP kinase pathway by the MAP kinase/ERK kinase inhibitor PD98059 or the PI 3-kinase pathway by LY294002 blocks HGF/SF induction of scattering, although in morphologically distinct ways. Expression of constitutively activated PI 3-kinase, Ras, or R-Ras will cause scattering, but activated Raf will not, indicating that activation of the MAP kinase pathway is not sufficient for this response. Downstream of PI 3-kinase, activated PKB/Akt and Rac are both unable to induce scattering, implicating a novel pathway. Scattering induced by Ras or PI 3-kinase is sensitive to PD98059, as well as to LY294002, suggesting that basal MAP kinase activity is required, but not sufficient, for the scattering response. Induction of MDCK cell tubulogenesis in collagen gels by HGF/SF is inhibited by PD98059; expression of activated Ras and Raf causes disorganized growth in this system, but activated PI 3-kinase or R-Ras causes branching tubule formation similar to that seen with HGF/SF treatment. These data indicate that multiple signaling pathways acting downstream of Met and Ras are needed for these morphological effects; scattering is induced primarily by the PI 3-kinase pathway, which acts through effectors other than PKB/Akt or Rac and requires at least basal MAP kinase function. Elevated PI 3-kinase activity induces tubulogenesis, but total inhibition and excess activation of the MAP kinase pathway both oppose this effect.