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

The compensational boundary method to calculate the projected contact area of nanoindentation in atomistic simulations

The atomistic simulation of nanoidentation has become a powerful method to probe the mechanical behaviour and properties of small volumes of materials. It is crucial to calculate the projected contact area (PCA) accurately in order to obtain a reliable value of nanoindentation hardness. In this work, atomistic simulations of nanoindentation were performed on the Cu(111) and Ag(111) surfaces, and a new compensational boundary method is proposed to calculate the PCA. Compared with other available methods, this method provides a clear physical implication, and works well independently of the contact depth and the deformation behaviour of the material. It is also concluded that the widely-used experimental Oliver–Pharr (O–P) method significantly underestimates the PCA in atomistic simulations, and does not work for shallow nanoindentation at the nanoscale

Molecular dynamics study of the interactions of incident N or Ti atoms with the TiN(001) surface

The interaction processes between incident N or Ti atoms and the TiN(001) surface are simulated by classical molecular dynamics based on the second nearest-neighbor modified embedded-atom method potentials. The simulations are carried out for substrate temperatures between 300–700 K and kinetic energies of the incident atoms within the range of 0.5–10 eV. When N atoms impact against the surface, adsorption, resputtering and reflection of particles are observed; several unique atomic mechanisms are identified to account for these interactions, in which the adsorption could occur due to the atomic exchange process while the resputtering and reflection may simultaneously occur. The impact position of incident N atoms on the surface plays an important role in determining the interaction modes. Their occurrence probabilities are dependent on the kinetic energy of incident N atoms but independent on the substrate temperature. When Ti atoms are the incident particles, adsorption is the predominant interaction mode between particles and the surface. This results in the much smaller initial sticking coefficient of N atoms on the TiN(001) surface compared with that of Ti atoms. Stoichiometric TiN is promoted by N/Ti flux ratios larger than one

RELIABILITY ASSESSMENT OF LOW VOLTAGE CUSTOMERS IN POWER SUPPLY SYSTEM

ABSTRAC

Adipose-derived mesenchymal stem cells improve glucose homeostasis in high-fat diet-induced obese mice

Introduction Effective therapies for obesity and diabetes are still lacking. The aim of this study was to evaluate whether a single intravenous infusion of syngeneic adipose-derived mesenchymal stem cells (ASCs) can reduce obesity, lower insulin resistance, and improve glucose homeostasis in a high-fat diet-induced obese (DIO) mouse model. Methods Seven-week-old C57BL/6 mice were fed a high-fat diet for 20 weeks to generate the DIO mouse model. Mice were given a single intravenous infusion of ex vivo expanded syngeneic ASCs at 2 × 10 6 cells per mouse. DIO or CHOW mice injected with saline were used as controls. Body weights, blood glucose levels, glucose, and insulin tolerance test results were obtained before and 2 and 6 weeks after cell infusion. Triglyceride (TG), high-density lipoprotein (HDL), and insulin levels in serum were measured. Expressions of genes related to insulin resistance, including peroxisome proliferator-activated receptor γ (PPARγ) and insulin receptor (InsR), and inflammation (IL-6, F4/80, and nucleotide-binding oligomerization domain containing 2, or NOD2), were measured in livers at mRNA level by real-time-polymerase chain reaction analysis. Beta-cell mass in pancrheases from CHOW, DIO, and DIO + ASC mice was quantified. GFP + ASCs were injected, and the presence of GFP + cells in livers and pancreases was determined. Results DIO mice that had received ASCs showed reduced body weights, reduced blood glucose levels, and increased glucose tolerance. ASC treatment was found to reduce TG levels and increase serum HDL levels. In livers, less fat cell deposition was observed, as were increased expression of InsR and PPARγ and reduction in expressions of IL-6 and F4/80. Treated mice showed well-preserved pancreatic β-cell mass with reduced expression of F4/80 and TNF-α compared with DIO controls. GFP + cells were found in liver and pancreas tissues at 1 and 2 weeks after cell injection. Conclusions ASC therapy is effective in lowering blood glucose levels and increasing glucose tolerance in DIO mice. The protective effects of ASCs arise at least in part from suppression of inflammation in the liver. In addition, ASCs are associated with better-preserved pancreatic β-cell mass

A Numerical Analysis Research on Earlier Behavior of Molten Droplet Covered with Vapor Film at the Stage of Triggering and Propagation in Steam Explosion

When the molten fuel with high temperature falls into the cavity water, it will be dispersed into droplets which are covered with vapor films due to the rapid heat transfer with phase transition. This situation cannot be simply described by liquid-liquid or gas-liquid systems. And there are no sufficient experimental studies on the behavior of droplet covered with vapor film because of the rapid reaction and the difficulty in capture of the film configuration. In this paper, a multiphase code with the volume of fluid (VOF) method is used to simulate the earlier behavior of droplet when vapor film exits. The earlier behavior is defined as behavior of the droplet before its disintegration. Thermal effect and pure hydrodynamic effect are, respectively, considered. The simulation results indicate that the film thickness and material density have significant effect on the earlier behavior of droplet. The situation assumed in Ciccarelli and Frost’s model (1994) is observed in current simulation of earlier thermal droplet behavior. The effect of triggering pressure pulse on earlier hydrodynamic behavior is also discussed and it indicates that vapor film has little effect on the hydrodynamic droplet deformation when the intensity of the pressure pulse is very high

C-di-GMP regulates <i>Pseudomonas aeruginosa</i> stress response to tellurite during both planktonic and biofilm modes of growth

Stress response plays an important role on microbial adaptation under hostile environmental conditions. It is generally unclear how the signaling transduction pathway mediates a stress response in planktonic and biofilm modes of microbial communities simultaneously. Here, we showed that metalloid tellurite (TeO(3)(2–)) exposure induced the intracellular content of the secondary messenger cyclic di-GMP (c-di-GMP) of Pseudomonas aeruginosa. Two diguanylate cyclases (DGCs), SadC and SiaD, were responsible for the increased intracellular content of c-di-GMP. Enhanced c-di-GMP levels by TeO(3)(2–) further increased P. aeruginosa biofilm formation and resistance to TeO(3)(2–). P. aeruginosa ΔsadCΔsiaD and PAO1/p(lac)-yhjH mutants with low intracellular c-di-GMP content were more sensitive to TeO(3)(2–) exposure and had low relative fitness compared to the wild-type PAO1 planktonic and biofilm cultures exposed to TeO(3)(2–). Our study provided evidence that c-di-GMP level can play an important role in mediating stress response in microbial communities during both planktonic and biofilm modes of growth

Formation mechanism of a smooth, defect-free surface of fused silica optics using rapid CO2 laser polishing

Surface defects introduced by conventional mechanical processing methods can induce irreversible damage and reduce the service life of optics applied in high-power lasers. Compared to mechanical processing, laser polishing with moving beam spot is a noncontact processing method, which is able to form a defect-free surface. This work aims to explore the mechanism of forming a smooth, defect-free fused silica surface by high-power density laser polishing with coupled multiple beams. The underlying mechanisms of laser polishing was revealed by numerical simulations and the theoretical results were verified by experiments. The simulated polishing depth and machined surface morphology were in close agreement with the experimental results. To obtain the optimized polishing quality, the effects of laser polishing parameters (e.g. overlap rate, pulse width and polishing times) on the polishing quality were experimentally investigated. It was found that the processing efficiency of fused silica materials by carbon dioxide (CO2) laser polishing could reach 8.68 mm2 s−1, and the surface roughness (Ra) was better than 25 nm. Besides, the cracks on pristine fused silica surfaces introduced by initial grinding process were completely removed by laser polishing to achieve a defect-free surface. The maximum laser polishing rate can reach 3.88 μm s−1, much higher than that of the traditional mechanical polishing methods. The rapid CO2 laser polishing can effectively achieve smooth, defect-free surface, which is of great significance to improve the surface quality of fused silica optics applied in high-power laser facilities

Quantum confined peptide assemblies with tunable visible to near-infrared spectral range

Quantum confined materials have been extensively studied for photoluminescent applications. Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materials in bio-imaging and bio-machine interface faces critical restrictions. Here, we present aromatic cyclo-dipeptides that dimerize into quantum dots, which serve as building blocks to further self-assemble into quantum confined supramolecular structures with diverse morphologies and photoluminescence properties. Especially, the emission can be tuned from the visible region to the near-infrared region (420 nm to 820 nm) by modulating the self-assembly process. Moreover, no obvious cytotoxic effect is observed for these nanostructures, and their utilization for in vivo imaging and as phosphors for light-emitting diodes is demonstrated. The data reveal that the morphologies and optical properties of the aromatic cyclo-dipeptide self-assemblies can be tuned, making them potential candidates for supramolecular quantum confined materials providing biocompatible alternatives for broad biomedical and opto-electric applications