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.

     

Exploration of a Library of 3,4‐(Methylenedioxy)aniline‐Derived Semicarbazones as Dual Inhibitors of Monoamine Oxidase and Acetylcholinesterase: Design,Synthesis, and Evaluation

A library of 3,4‐(methylenedioxy)aniline‐derived semicarbazones was designed, synthesized, and evaluated as monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors for the treatment of neurodegenerative diseases. Most of the new compounds selectively inhibited MAO‐B and AChE, with IC₅₀ values in the micro‐ or nanomolar ranges. Compound 16 , 1‐(2,6‐dichlorobenzylidene)‐4‐(benzo[1,3]dioxol‐5‐yl)semicarbazide presented a balanced multifunctional profile of MAO‐A (IC₅₀=4.52±0.032 μm ), MAO‐B (IC₅₀=0.059±0.002 μm ), and AChE (IC₅₀=0.0087±0.0002 μm ) inhibition without neurotoxicity. Kinetic studies revealed that compound 16 exhibits competitive and reversible inhibition against MAO‐A and MAO‐B, and mixed‐type inhibition against AChE. Molecular docking studies further revealed insight into the possible interactions within the enzyme–inhibitor complexes. The most active compounds were found to interact with the enzymes through hydrogen bonding and hydrophobic interactions. Additionally, in silico molecular properties and ADME properties of the synthesized compounds were calculated to explore their drug‐like characteristics.     

Isolation of directed evolution mutants of chloroperoxidase resistant to suicide inactivation by primary olefins

Wild-type chloroperoxidase catalyzes the efficient chiral epoxidation of secondary olefins but is rapidly inactivated in a mechanism-based suicide reaction when incubated with hydrogen peroxide and primary olefins. Directed evolution mutants of chloroperoxidase have now been isolated that are resistant to suicidal inactivation. Plasmid vectors containing error-prone copies of the chloroperoxidase gene and a hygromycin B resistance marker gene have been used to transform Caldariomyces fumago spheroplasts and produce mutant libraries. The mutant library clones were screened for their ability to resist mechanism-based inactivation by allylbenzene. Four generations of PCR-based random mutagenesis and screening yielded mutants that were completely resistant to the suicide-inactivation reaction. Rather surprisingly, the fourth generation mutant developed enhanced epoxidation activity in addition to resistance to allylbenzene inactivation. These initial results suggest that the directed evolution technique can be used to produce chloroperoxidase variants that can further exploit the potential of chloroperoxidase for the synthesis of chiral intermediates.     

Finite element method based machining simulation environment for analyzing part errors induced during milling of thin-walled components

The rigid body motion of the workpieces and their elastic–plastic deformations induced during high speed milling of thin-walled parts are the main root causes of part geometrical and dimensional variabilities; these are governed mainly from the choice of process plan parameters such as fixture layout design, operation sequence, selected tool path strategies and the values of cutting variables. Therefore, it becomes necessary to judge the validity of a given process plan before going into actual machining. This paper presents an overview of a comprehensive finite element method (FEM) based milling process plan verification model and associated tools, which by considering the effects of fixturing, operation sequence, tool path and cutting parameters simulates the milling process in a transient 3D virtual environment and predicts the part thin wall deflections and elastic–plastic deformations during machining. The advantages of the proposed model over previous works are: (i) Performs a computationally efficient transient thermo-mechanical coupled field milling simulation of complex prismatic parts comprising any combination of machining features like steps, slots, pockets, nested features, etc., using a feature based milling simulation approach; (ii) Predicts the workpiece non-linear behavior during machining due to its changing geometry, inelastic material properties and fixture–workpiece flexible contacts; (iii) Allows the modelling of the effects of initial residual stresses (residing inside the raw stock) on part deformations; (iv) Incorporates an integrated analytical machining load (cutting force components and average shear plane temperature) model; and (v) Provides a seamless interface to import an automatic programming tool file (APT file) generated by CAM packages like CATIA V5. The prediction accuracy of the model was validated experimentally and the obtained numerical and experimental results were found in good agreement.     

Tertiary treatment of distillery wastewater by nanofiltration

Tertiary treatment of aerobically treated distillery wastewater by nanofiltration was carried out in a spiral wound nanofiltration membrane module under different operating conditions. The results show that the percentage separation of organic and inorganic compounds was quite high, as reflected by the reduction of chemical oxygen demand (COD) and total dissolved solids (TDS) in the range of 96–99.5%, and 85–95% respectively. The color removal was in the range of 98–99.5%. The results of the effect of variation of the inlet concentration, feed circulation rate and pH conform to the mechanism of gel layer formation. Gel layer formation and Concentration polarization was found to play a major role in the treatment of distillery waste using nanofiltration (NF) membrane. It was observed that as concentration of feed solution increases the permeate flux was reduced. This change was higher compared to the separation of COD and TDS. The result indicates that the NF membrane showed very high performance efficiency for organic components (96–99.5%), as indicated by COD removal. In comparison, the separation of inorganic compounds was found to be in the range of 25–90% as estimated from relative separation of COD and TDS. The present study shows that nanofiltration is a promising technique for recovery of water from distillery waste, which could be used to achieve zero discharge status and solve a major environmental problem.     

Fabrication of co-PVDF/modacrylic/SiO2 nanofibrous membrane: Composite separator for safe and high performance lithium-ion batteries

Highly porous free-standing co-poly(vinylidene fluoride)/modacrylic/SiO₂ nanofibrous membrane was developed using electrically-assisted solution blow spinning method. The performance and the potential of the membrane as a lithium-ion battery separator were investigated. The addition of modacrylic enhanced the solution spinnability that resulted in defect-free membranes. Moreover, the presence of modacrylic enhanced the dimensional and thermal stabilities, while the addition of hydrophilic SiO₂ nanoparticle enhanced both mechanical property and ionic conductivity. Combustion test results illustrated that the presence of modacrylic provide flame retarding property over a set of different polymeric-based membranes. Electrochemical performance results showed that the developed membrane can increase the battery capacity compared with the commercial separator.     

A computer approach for reliability evaluation of telecommunicationnetworks with heterogeneous link-capacities

The authors present a computer approach to obtaining a survivability index called capacity related reliability (CRR) in large telecommunication networks where links have different capacities. The method is a two-step approach. The first step deals with composite path enumeration (CPE). A k-composite path is defined as the union of the set of edges in any k simple paths and relates link capacity and network connectivity. The CPE approach is an improvement over the algorithms proposed by the authors earlier (1991). In step two, k-composite paths information is manipulated to generate the CRR. The authors use CAREL (computer aided reliability evaluator) to solve this step. The technique is automated using C on the Encore Multimax System. The results on CRR for three networks with various values of minimum message capacity are presented. An exhaustive technique is used to verify these results. An informal proof of the CPE approach is also included     

Randomized controlled trial of effects of Escherichia coli antiserum on serum immunoglobulin G concentrations and morbidity and mortality rates in foals

OBJECTIVE: To determine whether administration of commercially available Escherichia coli antiserum to neonatal foals would affect serum IgG concentration or morbidity and mortality rates during the first 60 days of life. DESIGN: Randomized controlled trial. ANIMALS: 271 neonatal foals on 4 well-managed farms. PROCEDURE: Foals were randomly assigned to a treatment or control group. All foals were allowed to suckle colostrum normally. In addition, treatment-group foals were given E coli antiserum (10 micromilligrams) orally between 0 and 8 hours after birth. Serum samples were obtained between 18 and 36 hours after birth, and serum IgG concentration was determined. Foals were monitored for the first 60 days after birth, and causes of disease or death were recorded. RESULTS: Groups did not differ significantly in regard to breed, sex, month of birth, season of birth, age of dams, parity of dams, duration of gestation, or specific gravity of colostrum before suckling. In addition, groups did not differ significantly in regard to mean serum IgG concentration, prevalence of complete or partial failure of passive transfer of immunity, frequency or causes of disease, or frequency of death from infectious causes. CLINICAL IMPLICATIONS: In this group of foals on well-managed farms, administration of E coli antiserum did not alter serum IgG concentrations or morbidity and mortality rates during the first 60 days of life.     

Prevalence and predictors of sexual dysfunction in long-term survivors of marrow transplantation

PURPOSE: To describe the prevalence of sexual difficulties in men and women after marrow transplantation (MT), and to define medical, demographic, sexual, and psychologic predictors of sexual dysfunction 3 years after MT. PATIENTS AND METHODS: Four hundred seven adult MT patients were assessed pretransplantation. Survivors repeated measures of psychologic and sexual functioning at 1 and 3 years posttransplantation. RESULTS: Data were analyzed from 102 event-free 3-year survivors who defined themselves as sexually active. Men and women did not differ in sexual satisfaction pretransplantation. At 1 and 3 years posttransplantation, women reported significantly more sexual dysfunction than men. Eighty percent of women and 29% of men reported at least one sexual problem by 3 years after MT. No pretransplantation variables were significant predictors of 3-year sexual satisfaction for women. For men, pretransplantation variables of older age, poorer psychologic function, not being married, and lower sexual satisfaction predicted sexual dissatisfaction at 3 years (R2=.28; P < .001). Women who were more dissatisfied 3 years after MT did not receive hormone replacement therapy (HRT) at 1 -year posttransplantation and were less satisfied at 1 year, but not pretransplantation (R2=.35; P < .001). CONCLUSION: Sexual problems are significant in the lives of MT survivors, particularly for women. Although HRT before 1 year posttransplantation improves sexual function, it does not ensure sexual quality of life. Intervention for women is needed to apply hormonal, mechanical, and behavioral methods to prevent sexual difficulties as early after transplantation as possible.     

Visual selective attention after severe closed head injury

This study investigated the nature of selective attention deficits after severe closed head injury (CHI). Twenty participants with severe CHI (greater than 1 year postinjury) and 20 matched controls completed search and nonsearch visual selective attention tasks under conditions of low (Experiment 1) and high (Experiment 2) target-distractor similarity. In the search situations, participants searched visual displays that contained 1, 4, or 8 items for the targets. In the nonsearch situations, the location of the targets was visually cued with a peripheral arrow. The results revealed that in both the low and high target-distractor similarity search conditions. CHI participants required a longer time than controls to locate and identify the target. In contrast, in the nonsearch condition, CHI participants were able to successfully ignore irrelevant task information when target-distractor similarity was low. However, when target-distractor similarity was high, CHI participants had more difficulty than controls ignoring the irrelevant information. These results suggest that, in comparison to controls, CHI participants may be at a disadvantage in selective attention situations when visual search is required and when the discriminability between targets and distractors is difficult.