A Data-Driven Predictive Approach for Drug Delivery Using Machine Learning Techniques

In drug delivery, there is often a trade-off between effective killing of the pathogen, and harmful side effects associated with the treatment. Due to the difficulty in testing every dosing scenario experimentally, a computational approach will be helpful to assist with the prediction of effective drug delivery methods. In this paper, we have developed a data-driven predictive system, using machine learning techniques, to determine, in silico, the effectiveness of drug dosing. The system framework is scalable, autonomous, robust, and has the ability to predict the effectiveness of the current drug treatment and the subsequent drug-pathogen dynamics. The system consists of a dynamic model incorporating both the drug concentration and pathogen population into distinct states. These states are then analyzed using a temporal model to describe the drug-cell interactions over time. The dynamic drug-cell interactions are learned in an adaptive fashion and used to make sequential predictions on the effectiveness of the dosing strategy. Incorporated into the system is the ability to adjust the sensitivity and specificity of the learned models based on a threshold level determined by the operator for the specific application. As a proof-of-concept, the system was validated experimentally using the pathogen Giardia lamblia and the drug metronidazole in vitro

Nanoparticle biofabrication using English ivy (\u3cem\u3eHedera helix\u3c/em\u3e)

Background English ivy (Hedera helix) is well known for its adhesive properties and climbing ability. Essential to its ability to adhere to vertical surfaces is the secretion of a nanocomposite adhesive containing spherical nanoparticles, 60–85 nm in diameter, produced exclusively by root hairs present on adventitious roots. These organic nanoparticles have shown promise in biomedical and cosmetic applications, and represent a safer alternative to metal oxide nanoparticles currently available. Results It was discovered that the maximum adventitious root production was achieved by a 4 h application of 1 mg/ml indole-3 butyric acid (IBA) to juvenile English ivy shoot segments cultured in custom vessels. After incubation of the shoots under continuous light at 83 μmol/m2 s at 20°C for 2 weeks, the adventitious roots were harvested from the culture system and it was possible to isolate 90 mg of dry weight nanoparticles per 12 g of roots. The nanoparticle morphology was characterized by atomic force microscopy, and found to be similar to previous studies. Conclusions An enhanced system for the production of English ivy adventitious roots and their nanoparticles by modifying GA7 Magenta boxes and identifying the optimal concentration of IBA for adventitious root growth was developed. This system is the first such platform for growing and harvesting organic nanoparticles from plants, and represents an important step in the development of plant-based nanomanufacturing. It is a significant improvement on the exploitation of plant systems for the formation of metallic nanoparticles, and represents a pathway for the generation of bulk ivy nanoparticles for translation into biomedical applications

Nanoparticle biofabrication using English ivy (Hedera helix)

Background English ivy (Hedera helix) is well known for its adhesive properties and climbing ability. Essential to its ability to adhere to vertical surfaces is the secretion of a nanocomposite adhesive containing spherical nanoparticles, 60–85 nm in diameter, produced exclusively by root hairs present on adventitious roots. These organic nanoparticles have shown promise in biomedical and cosmetic applications, and represent a safer alternative to metal oxide nanoparticles currently available. Results It was discovered that the maximum adventitious root production was achieved by a 4 h application of 1 mg/ml indole-3 butyric acid (IBA) to juvenile English ivy shoot segments cultured in custom vessels. After incubation of the shoots under continuous light at 83 μmol/m2 s at 20°C for 2 weeks, the adventitious roots were harvested from the culture system and it was possible to isolate 90 mg of dry weight nanoparticles per 12 g of roots. The nanoparticle morphology was characterized by atomic force microscopy, and found to be similar to previous studies. Conclusions An enhanced system for the production of English ivy adventitious roots and their nanoparticles by modifying GA7 Magenta boxes and identifying the optimal concentration of IBA for adventitious root growth was developed. This system is the first such platform for growing and harvesting organic nanoparticles from plants, and represents an important step in the development of plant-based nanomanufacturing. It is a significant improvement on the exploitation of plant systems for the formation of metallic nanoparticles, and represents a pathway for the generation of bulk ivy nanoparticles for translation into biomedical applications. doi:10.1186/1477-3155-10-4

Chiral symmetry restoration in linear sigma models with different numbers of quark flavors

Chiral symmetry restoration at nonzero temperature is studied in the framework of the O(4) linear sigma model and the U(N_f)_r x U(N_f)_l linear sigma model with N_f=2,3, and 4 quark flavors. We investigate the temperature dependence of the masses of the scalar and pseudoscalar mesons, and the non-strange, strange, and charm condensates within the Hartree approximation as derived from the Cornwall-Jackiw-Tomboulis formalism. We find that the masses of the non-strange and strange mesons at nonzero temperature depend sensitively on the particular symmetry of the model and the number of light quark flavors N_f. On the other hand, due to the large charm quark mass, neither do charmed mesons significantly affect the properties of the other mesons, nor do their masses change appreciably in the temperature range around the chiral symmetry restoration temperature. In the chiral limit, the transition temperatures for chiral symmetry restoration are surprisingly close to those found in lattice QCD.Comment: 28 pages, 8 figure

Influence of the U(1)_A Anomaly on the QCD Phase Transition

The SU(3)_{r} \times SU(3)_{\ell} linear sigma model is used to study the chiral symmetry restoring phase transition of QCD at nonzero temperature. The line of second order phase transitions separating the first order and smooth crossover regions is located in the plane of the strange and nonstrange quark masses. It is found that if the U(1)_{A} symmetry is explicitly broken by the U(1)_{A} anomaly then there is a smooth crossover to the chirally symmetric phase for physical values of the quark masses. If the U(1)_{A} anomaly is absent, then there is a phase transition provided that the \sigma meson mass is at least 600 MeV. In both cases, the region of first order phase transitions in the quark mass plane is enlarged as the mass of the \sigma meson is increased.Comment: 5 pages, 3 figures, Revtex, discussion extended and references added. To appear in PR

The Potential of Systems Biology to Discover Antibacterial Mechanisms of Plant Phenolics

Drug resistance of bacterial pathogens is a growing problem that can be addressed through the discovery of compounds with novel mechanisms of antibacterial activity. Natural products, including plant phenolic compounds, are one source of diverse chemical structures that could inhibit bacteria through novel mechanisms. However, evaluating novel antibacterial mechanisms of action can be difficult and is uncommon in assessments of plant phenolic compounds. With systems biology approaches, though, antibacterial mechanisms can be assessed without the bias of target-directed bioassays to enable the discovery of novel mechanism(s) of action against drug resistant microorganisms. This review article summarizes the current knowledge of antibacterial mechanisms of action of plant phenolic compounds and discusses relevant methodology

Naturally occurring nanoparticles from English ivy: an alternative to metal-based nanoparticles for UV protection

<p>Abstract</p> <p>Background</p> <p>Over the last decade safety concerns have arisen about the use of metal-based nanoparticles in the cosmetics field. Metal-based nanoparticles have been linked to both environmental and animal toxicity in a variety of studies. Perhaps the greatest concern involves the large amounts of TiO₂nanoparticles that are used in commercial sunscreens. As an alternative to using these potentially hazardous metal-based nanoparticles, we have isolated organic nanoparticles from English ivy (<it>Hedera helix</it>). In this study, ivy nanoparticles were evaluated for their potential use in sunscreens based on four criteria: 1) ability to absorb and scatter ultraviolet light, 2) toxicity to mammalian cells, 3) biodegradability, and 4) potential for diffusion through skin.</p> <p>Results</p> <p>Purified ivy nanoparticles were first tested for their UV protective effects using a standard spectrophotometric assay. Next the cell toxicity of the ivy nanoparticles was compared to TiO₂nanoparticles using HeLa cells. The biodegradability of these nanoparticles was also determined through several digestion techniques. Finally, a mathematical model was developed to determine the potential for ivy nanoparticles to penetrate through human skin. The results indicated that the ivy nanoparticles were more efficient in blocking UV light, less toxic to mammalian cells, easily biodegradable, and had a limited potential to penetrate through human skin. When compared to TiO₂nanoparticles, the ivy nanoparticles showed decreased cell toxicity, and were easily degradable, indicating that they provided a safer alternative to these nanoparticles.</p> <p>Conclusions</p> <p>With the data collected from this study, we have demonstrated the great potential of ivy nanoparticles as a sunscreen protective agent, and their increased safety over commonly used metal oxide nanoparticles.</p

Experimental Studies and Dynamics Modeling Analysis of the Swimming and Diving of Whirligig Beetles (Coleoptera: Gyrinidae)

Whirligig beetles (Coleoptera, Gyrinidae) can fly through the air, swiftly swim on the surface of water, and quickly dive across the air-water interface. The propulsive efficiency of the species is believed to be one of the highest measured for a thrust generating apparatus within the animal kingdom. The goals of this research were to understand the distinctive biological mechanisms that allow the beetles to swim and dive, while searching for potential bio-inspired robotics applications. Through static and dynamic measurements obtained using a combination of microscopy and high-speed imaging, parameters associated with the morphology and beating kinematics of the whirligig beetle\u27s legs in swimming and diving were obtained. Using data obtained from these experiments, dynamics models of both swimming and diving were developed. Through analysis of simulations conducted using these models it was possible to determine several key principles associated with the swimming and diving processes. First, we determined that curved swimming trajectories were more energy efficient than linear trajectories, which explains why they are more often observed in nature. Second, we concluded that the hind legs were able to propel the beetle farther than the middle legs, and also that the hind legs were able to generate a larger angular velocity than the middle legs. However, analysis of circular swimming trajectories showed that the middle legs were important in maintaining stable trajectories, and thus were necessary for steering. Finally, we discovered that in order for the beetle to transition from swimming to diving, the legs must change the plane in which they beat, which provides the force required to alter the tilt angle of the body necessary to break the surface tension of water. We have further examined how the principles learned from this study may be applied to the design of bio-inspired swimming/diving robots. DOI: 10.1371/journal.pcbi.100279

Topological String Defect Formation During the Chiral Phase Transition

We extend and generalize the seminal work of Brandenberger, Huang and Zhang on the formation of strings during chiral phase transitions(berger) and discuss the formation of abelian and non-abelian topological strings during such transitions in the early Universe and in the high energy heavy-ion collisions. Chiral symmetry as well as deconfinement are restored in the core of these defects. Formation of a dense network of string defects is likely to play an important role in the dynamics following the chiral phase transition. We speculate that such a network can give rise to non-azimuthal distribution of transverse energy in heavy-ion collisions.Comment: 10 pages, 4 figures, minor correction

Characterization of physicochemical properties of ivy nanoparticles for cosmetic application

Background Naturally occurring nanoparticles isolated from English ivy (Hedera helix) have previously been proposed as an alternative to metallic nanoparticles as sunscreen fillers due to their effective UV extinction property, low toxicity and potential biodegradability. Methods This study focused on analyzing the physicochemical properties of the ivy nanoparticles, specifically, those parameters which are crucial for use as sunscreen fillers, such as pH, temperature, and UV irradiation. The visual transparency and cytotoxicity of ivy nanoparticles were also investigated comparing them with other metal oxide nanoparticles. Results Results from this study demonstrated that, after treatment at 100°C, there was a clear increase in the UV extinction spectra of the ivy nanoparticles caused by the partial decomposition. In addition, the UVA extinction spectra of the ivy nanoparticles gradually reduced slightly with the decrease of pH values in solvents. Prolonged UV irradiation indicated that the influence of UV light on the stability of the ivy nanoparticle was limited and time-independent. Compared to TiO2 and ZnO nanoparticles, ivy nanoparticles showed better visual transparency. Methylthiazol tetrazolium assay demonstrated that ivy nanoparticles exhibited lower cytotoxicity than the other two types of nanoparticles. Results also suggested that protein played an important role in modulating the three-dimensional structure of the ivy nanoparticles. Conclusions Based on the results from this study it can be concluded that the ivy nanoparticles are able to maintain their UV protective capability at wide range of temperature and pH values, further demonstrating their potential as an alternative to replace currently available metal oxide nanoparticles in sunscreen applications. doi:10.1186/1477-3155-11-