Significant Penetration Research Articles

Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: remarkable brain delivery enhancement

Objective: Indinavir (IDV), an antiretroviral protease inhibitor used in treatment of HIV infection, has limited entry into brain due to efflux by the P-glycoprotein presented in blood–brain barrier. The aim of present study was to develop lactoferrin-treated nanoemulsion containing indinavir (Lf-IDV-NEs) for delivery to brain. Methods: Indinavir-loaded nanoemulsions (IDV-NEs) were prepared by high-speed homogenization method, and then lactoferrin was coupled to IDV-NEs by water soluble EDC method. Results: The hydrodynamic diameters, polydispersity index, and zeta potential of IDV-NEs were 112 ± 3.5 nm, 0.20 ± 0.02, and −33.2 ± 2.6 mV, respectively. From in vivo studies in animal model of rats, the AUC0–4 h of brain concentration–time profile of IDV-NEs and Lf-IDV-NEs were 1.6 and 4.1 times higher than free drug, respectively. The brain uptake clearance of IDV-NEs and Lf-IDV-NEs were, interestingly, 393- and 420-times higher than the free drug. Conclusions: It can be concluded that applying both lactoferrin-treated and non-treated nanoemulsions clearly leads to significant brain penetration enhancement of indinavir, an effect which is more pronounced in the case of Lf-IDV-NEs with the higher drug residence time in brain.

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

Due to the blood-brain barrier (BBB) limiting the exposure of therapeutics to the central nervous system (CNS), patients with brain malignancies are challenging to treat, typically have poor prognoses, and represent a significant unmet medical need. Preclinical data report osimertinib to have significant BBB penetration and emerging clinical data demonstrate encouraging activity against CNS malignancies. Here, we discuss the oncology drug candidates AZD3759 and AZD1390 as case examples of discovery projects designing in BBB penetrance. We demonstrate how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders.

PH triggered and charge attracted nanogel for simultaneous evaluation of penetration and toxicity against skin cancer: In-vitro and ex-vivo study.

The current research is focused to develop and investigate the toxicity and penetration potential of biocompatible chitosan nanogel encapsulating capecitabine by ionic interaction mechanism exhibiting pH triggered transdermal targeting. The nanogel (CPNL) was synthesized by ion gelation mechanism using Pluronic F 127 and surface decoration by Transcutol as non-ionic penetration enhancer. The CPNL possesses fine morphology and nano size range when evaluated by TEM, SEM and DLS analysis with cationic charge and slightly acidic pH assayed by zeta potential and pH analysis. It showed pH responsive drug release characteristics mimicking the skin cancer micro-environment. The MTT assay and apoptotic index of CPNL on HaCaT cell line elaborated optimal cell toxicity and retention on 24h of exposure. The ex-vivo skin penetration analysis exhibited noteworthy diffusion and penetration caliber through concentration depth profile, steady state flux and fluorescent skin imaging on porcine tissue. Overall outcomes suggested CPNL as a potent alternative biocompatible, transdermal nanotherapy against skin cancer displaying significant penetration caliber with enhance toxicity on cancerous cell.

Potential Impacts of Net-Zero Energy Buildings With Distributed Photovoltaic Power Generation on the U.S. Electrical Grid

This study evaluates the potential aggregate effects of net-zero energy building (NZEB) implementations on the electrical grid in a simulation-based analysis. To estimate the impact of NZEBs on the electrical grid, a simulation-based study of an office building with a grid-tied photovoltaic (PV) power generation system is conducted. This study assumes that net-metering is available for NZEBs such that the excess on-site PV generation can be fed to the electrical grid. The impact of electrical energy storage (EES) within NZEBs on the electrical grid is also considered in this study. Different levels of NZEB adoption are examined: 20%, 50%, and 100% of the U.S. office building stock. Results indicate that significant penetration of NZEBs could potentially affect the current U.S. electricity demand profiles by reducing purchased electricity from the electrical grid and by increasing exported electricity to the electrical grid during peak hours. Annual electricity consumption of simulated office NZEBs in the U.S. climate locations is in the range of around 94–132 kWh/m2 yr. Comparison of hourly electricity demand profiles for the actual U.S. demand versus the calculated net-demand on a national scales indicates that the peak percentage difference of the U.S. net-electricity demand includes about 10.7%, 15.2%, and 9.3% for 100% of the U.S. NZEB stock on representative summer, transition, and winter days, respectively. Using EES within NZEBs, the peak percentage differences are reduced and shifted to the afternoon, including 8.6%, 13.3%, and 6.3% for 100% of the U.S. NZEB stock on each representative day.

Microbubbles, Nanodroplets and Gas-Stabilizing Solid Particles for Ultrasound-Mediated Extravasation of Unencapsulated Drugs: An Exposure Parameter Optimization Study

Ultrasound-induced cavitation has been proposed as a strategy to tackle the challenge of inadequate extravasation, penetration and distribution of therapeutics into tumours. Here, the ability of microbubbles, droplets and solid gas-trapping particles to facilitate mass transport and extravasation of a model therapeutic agent following ultrasound-induced cavitation is investigated. Significant extravasation and penetration depths on the order of millimetres are achieved with all three agents, including the range of pressures and frequencies achievable with existing clinical ultrasound systems. Deeper but highly directional extravasation was achieved with frequencies of 1.6 and 3.3 MHz compared with 0.5 MHz. Increased extravasation was observed with increasing pulse length and exposure time, while an inverse relationship is observed with pulse repetition frequency. No significant cell death or any haemolytic activity in human blood was observed at clinically relevant concentrations for any of the agents. Overall, solid gas-trapping nanoparticles were found to enable the most extensive extravasation for the lowest input acoustic energy, followed by microbubbles and then droplets. The ability of these agents to produce sustained inertial cavitation activity whilst being small enough to follow the drug out of the circulation and into diseased tissue, combined with a good safety profile and the possibility of real-time monitoring, offers considerable potential for enhanced drug delivery of unmodified drugs in oncological and other biomedical applications.

The Analysis of Technical Trend in Islanding Operation, Harmonic Distortion, Stabilizing Frequency, and Voltage of Islanded Entities

This paper focuses on autonomous multi-islanded entities and the seamless reconnection to the main grid as the self-healing ability of the future power system. The minimization of power quality issues (mainly that of voltage, frequency, and harmonics) in such entities based on controllers, with or without intercommunication, is also an important part of this paper. The future power system, with the significant penetration of distributed generations (DGs), can rapidly respond to any problem occurring within it by separating into autonomous islanded entities to prevent the disconnection of DGs. As a result, high-quality and continuous power is supplied to consumers. Finally, future research that is necessary for the realization of the future power system is discussed.

The effect of perceived risk on the purchase intention of electric vehicles: an extension to the technology acceptance model

Electric cars will be the future of the transportation industry as it records a significant market penetration including Sri Lanka. The purchasing mechanism that drives customers to make purchasing decisions is a critical notion to investigate since it engages many connected factors. Accordingly, this study reviews how perceived risk factor influences purchase intention referring to electric vehicles in Sri Lanka. The review is based on the theoretical rationale and supportive empirical findings. A descriptive statistical review is presented to signify why Sri Lanka is considered as a context to be examined whilst empirical evidences are presented to support the arguments. The paper concludes with research propositions to examine how perceived risk influences the purchasing mechanism of electric vehicles whilst buying intention is referred to as a main notion within.

The effect of perceived risk on the purchase intention of electric vehicles: an extension to the technology acceptance model

Electric cars will be the future of the transportation industry as it records a significant market penetration including Sri Lanka. The purchasing mechanism that drives customers to make purchasing decisions is a critical notion to investigate since it engages many connected factors. Accordingly, this study reviews how perceived risk factor influences purchase intention referring to electric vehicles in Sri Lanka. The review is based on the theoretical rationale and supportive empirical findings. A descriptive statistical review is presented to signify why Sri Lanka is considered as a context to be examined whilst empirical evidences are presented to support the arguments. The paper concludes with research propositions to examine how perceived risk influences the purchasing mechanism of electric vehicles whilst buying intention is referred to as a main notion within.

Joints Properties of Aluminum Foams/Aluminum Plate by Transient Liquid Phase Bonding Process

Aluminum foams/aluminum plate was transient liquid phase diffusion bonded with Cu/Al/Cu composite interlayer, then the investigation on joint microstructure, element diffusion and joint strength was conducted at 565°C. The results showed that, there was a significant grain boundary penetration phenomenon near the interface and it was more seriously at the side of aluminum foams. The XRD results showed indicated that the main phases near the interface were α-Al, CuAl2, AlCu, Al4Cu9, Al2O3. By EDS line scanning, it indicated that the diffusion behavior of elements was different at three regions, compared with the edge region, the interface of the central region was better and the depth of element diffusion is larger, at the pore region, the liquefaction of interlayer was not successfully and the morphology was lamellar. Mechanical properties test showed that the largest shear strength of joint was 4.61 MPa when the duration was 40 min. Key words: Aluminum foams; transient liquid phase bonding; microstructure; element diffusion; shear strength

Adaptive Predictor Subset Selection Strategy for Enhanced Forecasting of Distributed PV Power Generation

Distributed photovoltaic (PV) solar power plants are playing an increasing role as a power generation resource in the modern electricity grid. However, PVs pose significant challenges to grid planners, operators, owners, investors, aggregators, and other stakeholders. This is due to the high uncertainty of the PV output power, which is caused by its entire dependence on intermittent environmental factors. This has brought a serious problem to the power industry to integrate and manage power grids containing significant penetration of PVs. Thus, an enhanced PV power forecast is very important to operate these power grids efficiently and reliably. Most previous methodologies have focused on predicting the aggregate amount of potential solar power generation at the national or regional scale and ignored the distributed PVs that are installed primarily for local electric supply. Furthermore, a few research groups have carried out predictor selection before training predictive models. This paper proposes an adaptive hybrid predictor subset selection (PSS) strategy to obtain the most relevant and nonredundant predictors for enhanced short-term forecasting of the power output of distributed PVs. In the proposed strategy, the binary genetic algorithm (BGA) is applied for the feature selection process and support vector regression (SVR) is used for measuring the fitness score of the predictors. In order to validate the effectiveness of the proposed strategy, it is applied to actual distributed PVs located in the Otaniemi area of Espoo, Finland. The findings are compared with those achieved by other PSS techniques. The proposed strategy enhances the quality and efficiency of the predictor subset selection, with minimal chosen predictors to achieve enhanced prediction accuracy. It outperforms the other prediction selection methods. Besides, a configuration of an adaptive forecasting model is introduced and the performance tests are presented to further validate the impact of the PSS results for the PV power prediction accuracy enhancement.

Generic Demand Model Considering the Impact of Prosumers for Future Grid Scenario Analysis

The increasing uptake of residential PV-battery systems is bound to significantly change demand patterns of future power systems and, consequently, their dynamic performance. In this paper, we propose a generic demand model that captures the aggregated effect of a large population of price-responsive users equipped with small-scale PV-battery systems, called prosumers , for market simulation in future grid scenario analysis. The model is formulated as a bi-level program in which the upper-level unit commitment problem minimizes the total generation cost, and the lower-level problem maximizes prosumers’ aggregate self-consumption. Unlike in the existing bi-level optimization frameworks that focus on the interaction between the wholesale market and an aggregator, the coupling is through the prosumers’ demand, not through the electricity price. That renders the proposed model market structure agnostic, making it suitable for future grid studies where the market structure is potentially unknown. As a case study, we perform steady-state voltage stability analysis of a simplified model of the Australian National Electricity Market with a significant penetration of renewable generation. The simulation results show that a high prosumer penetration changes the demand profile in ways that significantly improve the system loadability, which confirms the suitability of the proposed model for future grid studies.

PH-sensitive Eudragit® L 100 nanoparticles promote cutaneous penetration and drug release on the skin

Nanoparticles (NPs) are promising carriers for dermal and transdermal drug delivery. However, the underlying dynamics of drug release from the NPs, especially, how the physiological changes of diseased skin influence the drug release, remain poorly understood. We utilized electron paramagnetic resonance (EPR) and confocal laser scanning microscopy (CLSM) to comprehensively investigate the penetration behavior of a spin-labeled dexamethasone (DxPCA)-loaded pH-sensitive Eudragit® L 100 NP on intact and barrier-disrupted skins. The EPR investigation showed that a rapid in vitro DxPCA release from the NPs was triggered above pH 5.9. It also demonstrated that the NPs considerably improved the cutaneous penetration of the model drug in comparison to a commercial cream. Besides, as compared to the intact skin, a faster drug release and a higher drug penetration into the viable skin layers were obtained with barrier-disrupted skin. In accordance, CLSM studies confirmed that the NPs enhanced the penetration of the lipophilic model drug Nile red (NR) across the skin, whose penetration depth into glabrous skin was 160 μm. Moreover, a significant transfollicular penetration of NR from the NPs was observed. In conclusion, the pH-sensitive Eudragit® L 100 NPs improved the cutaneous penetration and controlled the release of a lipophilic drug, especially on barrier-disrupted skin. This may allow targeted drug delivery to lesional skin, avoiding side effects.

On the outlook for solar thermal hydrogen production in South Africa

Global warming and tightening environmental legislation is putting pressure on divesting from fossil fuel in the energy sector, with the transport sector likely to see the biggest changes. Current alternative energy sources are electric vehicles and hydrogen. Conventional hydrogen production technologies are fossil fuel based, emitting significant amounts of CO2 into the atmosphere. This paper explores various ways to integrate solar thermal technologies into hydrogen production to generate carbon free hydrogen in South Africa. South Africa's abundant solar resource indicates that the country may become a significant player in the hydrogen market. However, the high capital cost associated with solar thermal energy put solar thermal hydrogen at a price disadvantage against conventional production technologies. Significant market penetration for solar thermal hydrogen is not expected within the next decade, but cost reduction due to improved manufacturing techniques and larger manufacturing volumes might close the gap in the long term.

Network-constrained unit commitment under significant wind penetration: A multistage robust approach with non-fixed recourse

Generation scheduling in future smart grids will face significant uncertainty due to their considerable reliance on intermittent renewable-based generation such as wind power. Adaptive robust optimization provides a suitable framework to handle wind-related uncertainty in generation scheduling. However, available robust models feature relevant practical limitations including 1) the potential lack of physical implementability stemming from disregarding the nonanticipativity of the dispatch process, 2) the potential suboptimality or even infeasibility due to the use of fixed-recourse schemes, and 3) the intractable computational burden associated with a scenario-based counterpart. This paper presents a new multistage robust unit commitment approach with non-fixed recourse relying on the formulation of an alternative two-stage robust model. As a result, the least-cost generation schedule ensuring dispatch nonanticipativity is attained by solving a trilevel program of similar complexity as compared with available formulations neglecting this aspect. Moreover, an enhanced column-and-constraint generation algorithm is devised whereby lexicographic optimization is applied to accelerate the finite convergence to optimality. Numerical simulations including a practical out-of-sample validation procedure reveal that the proposed approach is 1) computationally effective even for a benchmark that is well beyond the capability of a recently published method, and 2) superior in terms of solution quality over existing two-stage robust models disregarding dispatch nonanticipativity.

Strategies to achieve deep reductions in metropolitan transportation GHG emissions: the case of Philadelphia

ABSTRACTThis paper investigates strategies that could achieve an 80% reduction in transportation emissions from current levels by 2050 in the City of Philadelphia. The baseline daily lifecycle emissions generated by road transportation in the Greater Philadelphia Region in 2012 were quantified using trip information from the 2012 Household Travel Survey (HTS). Emissions were projected to the year 2050 accounting for population growth and trends in vehicle technology for both the Greater Philadelphia Region and the City of Philadelphia. The impacts of vehicle technology and shifts in travel modes on greenhouse gas (GHG) emissions in 2050 were quantified using a scenario approach. The analysis of 12 different scenarios suggests that 80% reduction in emissions is technically feasible through a combination of active transportation, cleaner fuels for public transit vehicles, and a significant market penetration of battery-electric vehicles. The additional electricity demand associated with greater use of electric vehicles could amount to 10.8 TWh/year. The use of plug-in hybrid electric vehicles (PHEV) shows promising results due to high reductions in GHG emissions at a potentially manageable cost.

Renewable building blocks for polyurethanes

Abstract For the past 60+ years, polyurethane chemistry has been used to make a wide variety of everyday consumer products such as mattresses, automotive interior parts and foam insulation. Today, the vast majority of polyurethane products are made entirely from petroleum. Although polyols made from natural oils have made inroads during the past decade, cost and performance, as well as the presence of a large-scale established infrastructure around petroleum-based materials, remain as barriers to significant market penetration. Promising new developments such as sugar-derived raw materials have the potential to shift the balance of cost and performance, but they are at an early stage. While not a comprehensive review of the large volume of academic literature on renewable polyurethane chemistry, this article discusses several routes to renewable, commercially viable building blocks for polyurethanes, considering both established and emerging technology.

Dermal peptide delivery using enhancer molecules and colloidal carrier systems. Part III: Tetrapeptide GEKG

Dermal application of peptides as drugs is an interesting and growing field in therapeutics. Besides therapy, they are increasingly used as cosmetic agents. Peptide delivery into the skin is highly challenging since they provide disadvantageous properties like a high molecular weight, hydrophilicity, polarity and susceptibility to enzymatic degradation. The aim of the presented study was to improve the bioavailability of a dermal administered tetrapeptide GEKG (amino acid sequence in one-letter notation). A nano-sized carrier system (microemulsion, ME) of w/o type was therefore developed since ME provide excellent penetration enhancing properties. Furthermore, enhancers were used to increase the penetration capacity of GEKG. The penetration of GEKG from the ME and enhancer-containing emulsions was compared to the penetration from a standard formulation. For this purpose ex vivo penetration studies with human skin were performed, which provide insights into dermal penetration and also localization and distribution of the active substances in each skin layer as well as the influence of vehicle variations.Experiments with three incubation times (30, 100, 300 min) and 5000 ppm GEKG in the formulations clearly show that the nano-sized carrier system is significantly better suited to transport GEKG rapidly into upper and deeper vital skin layers as well as through the skin compared to the standard cream. Studies with o/w emulsions containing 5% glyceryl caprylate/caprate 2.0× or 1.5× as enhancer and 50 ppm peptide revealed only a tendency to increased penetration into the SC and for the formulation with glyceryl caprylate/caprate 1.5× into the vital epidermis compared to the standard cream without additional enhancer. Significant better penetration rates were observed for the ME with 50 ppm GEKG.It can be concluded that liquid nano-sized systems are significantly more effective as carriers for extremely hydrophilic peptides used in cosmetics and also in therapeutics than classic cosmetic emulsions or enhancer-containing emulsions. Chemical compoundsTetrapeptide-21 (CAS: 960608-17-7)glyceryl caprylate/caprate (CAS: 73398-61-5)sorbitan oleate (CAS: 1338-43-8)polyglyceryl-4 laurate (CAS: 75798-42-4)butylene glycol (CAS: 107-88-0)isopropyl palmitate (CAS: 142-91-6)

Optimal Scheduling of Power System Incorporating the Flexibility of Thermal Units

Due to the randomness, volatility and intermittent nature of wind power, power systems with significant wind penetration face serious “curtailment” problems. The flexibility of a power system is an important factor that affects the large-scale consumption of wind power. Based on this fact, this paper takes into account the economics and flexibility of the system, and proposes an optimal scheduling method that takes the flexibility of each thermal power unit into account. Firstly, a comprehensive evaluation index system of thermal power unit flexibility is designed by an analytic hierarchy process and entropy method. The system covers the technical indexes and economic characteristics of thermal power units and is able to quantitatively evaluate the different types of thermal power units in the system. Secondly, a multi-objective optimization scheduling model involving the overall flexibility of the unit and the total power generation cost is established. Finally, the correctness and effectiveness of the proposed indicators and models are verified by a case study.

Low-Bandgap Conjugated Polymer Dots for Near-Infrared Fluorescence Imaging

Low-bandgap conjugated polymers attract significant research interests because of their broad light absorption spectra in the red and near-infrared regions, making them desirable materials for solar photovoltaics. To date, low-bandgap conjugated polymers yield some of the best power conversion efficiencies offered by polymer solar cells. In addition to their applications as solar photovoltaic materials, nanoparticles of these polymers may be potentially beneficial for cell imaging because of their red and near-infrared absorption features, which are required for significant light penetration into biological samples. In this work, conjugated polymer dots (CPdots) of PCPDTBT, PSBTBT, PTB7, PCDTBT, and PBDTTPD are prepared in aqueous solution using nanoprecipitation. The maximum fluorescence wavelengths of these CPdots range from 800 to 1000 nm. The CPdots exhibit an average zeta potential of −30 mV, giving rise to colloidal stability of these nanoparticles. Dynamic light scattering results show that the CPd...

OA108] Quantitative analysis of ventilation SPECT applied to krypton and technegas

Purpose Assessment of the state of the lungs by ventilation perfusion (V/Q) Single Photon Emission Computed Tomography combined with Computed Tomography (SPECT/CT) has proved its value as a clinical tool. Physicians study both ventilation and perfusion images, but also the ratio image of these two. However, the interpretation of these images is qualitative. For the ventilation images quantitative measures were investigated in the case of Krypton-81 m and Technegas (Tc-99 m labelled graphite particles). Krypton is a gaseous ventilation tracer and distributes similarly to air. However, it is not widely available and relatively expensive. Technegas is cheaper and has wider availability, but is an aerosol, which may result in hot spots in obstructed airways. Methods Dual-isotope ventilation SPECT/CT with both Technegas(140 keV) and Krypton(190 keV) simultaneously was obtained for 11 patients with medium and low energy general purpose collimators including a follow-up. This resulted in 38 ventilation studies in total. Reconstruction was performed with and without attenuation and scatter correction. The penetration index and the heterogeneity index (with and without band filtering for relevant clinical sizes) were calculated for the right and left lung. Scatterplots of the intensities of the Krypton and Technegas images were made and statistical outliers were detected. Results Significant lower penetration indexes for Technegas were found for the medium energy collimators, but were not seen for the low energy collimators. The higher heterogeneity indexes for Technegas were significant in all cases except for the uncorrected medium energy collimators data. Band filtering of the heterogeneity index improved the statistical significance of the differences. The scatterplots showed that all patients suffered from Technegas-outliers in one or both lungs, indicating the presence of hot spots. The visually identified hot spots could be mapped to the outliers seen in the scatterplots. Conclusions The applied quantitative analysis revealed that there are significant differences between Krypton and Technegas as a ventilation tracer for patients with severe COPD. The penetration index may have limited clinical relevance, since it does not capture complicated activity distributions. However, the heterogeneity index with band filtering is potentially a useful quantitative clinical measure.