Self-nanoemulsifying drug-delivery system for improved oral bioavailability of rosuvastatin using natural oil antihyperlipdemic.

PubMed

Abo Enin, Hadel A

2015-01-01

The aim is improving the antihyperlipidemic activity of Rosuvastatin Calcium (Rs) through improving its solubility using self-nanoemulsifying drug delivery system (SNEDDS) containing natural oil full of unsaturated fatty acid and omega 3. A 7 × 3(2) full factorial design was adopted for optimization of oil ratio, Surfactant: Co-surfactant (S:CoS) ratio and oil:S/CoS ratio. Ternary phase diagrams were constructed for optimizing the system with drug loading (10 and 20%). The optimized SNEDD systems were evaluated according to their physical evaluation and drug release. Furthermore, the anti-hyperlipidemia efficacy was compared with commercially marketed product on rates followed by clinical study. The system containing Tween 80:PEG 400 (3:1) and olive oil:garlic oil (1:1) as an oily phase has droplet size less than 100 nm, ZP (+23.43 ± 2.58 mV), PDI (<0.02) and cloud point (>90 °C). In vitro drug release studies showed remarkable enhancement of the Rs release from Rs-SNEDDS. The antihyperlipidemic effect of Rs-SNEDDS is greater than that of the commercial tablets and the pure drug on rates and in hyperlipidemic patients. Rs-SNEDDS is a promising drug delivery system for improving the drug solubility and antihyperlipidemic effect using natural oils as (olive oil and garlic oil).

A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release.

PubMed

Chuang, Er-Yuan; Lin, Chia-Chen; Chen, Ko-Jie; Wan, De-Hui; Lin, Kun-Ju; Ho, Yi-Cheng; Lin, Po-Yen; Sung, Hsing-Wen

2016-07-01

The nonspecific distribution of therapeutic agents and nontargeted heating commonly produce undesirable side effects during cancer treatment since the optimal timing of triggering the carrier systems is unknown. This work proposes a multifunctional liposomal system that can intracellularly and simultaneously deliver the therapeutic drug doxorubicin (DOX), heat, and a bubble-generating agent (ammonium bicarbonate, ABC) into targeted tumor cells to have a cytotoxic effect. Gold nanocages that are encapsulated in liposomes effectively convert near-infrared light irradiation into localized heat, which causes the decomposition of ABC and generates CO2 bubbles, rapidly triggering the release of DOX. Additionally, a hybridized Mucin-1 aptamer is conjugated on the surface of the test liposomes, which then function as a recognition probe to enhance the uptake of those liposomes by cells, and as a molecular beacon to signal when the internalized particles have been maximized, which is the optimal time for photothermally triggering the release of the drug following the systemic administration of the liposomes. Empirical results reveal that this combined treatment effectively controls targeted drug release in a spatially and temporally precise fashion and so significantly increases the potency of the drug while minimizing unwanted side effects, making it a promising treatment for cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation and characterization of a novel conformed bipolymer paclitaxel-nanoparticle using tea polysaccharides and zein.

PubMed

Li, Shuqin; Wang, Xiuming; Li, Weiwei; Yuan, Guoqi; Pan, Yuxiang; Chen, Haixia

2016-08-01

To improve the aqueous solubility of the anticancer agent paclitaxel (PTX), a newly conformed bipolymer paclitaxel-nanoparticle using tea polysaccharide (TPS) and zein was prepared and characterized. Tea polysaccharide was used as a biopolymer shell and zein was as the core and the optimal formula was subjected to the characteristic study by TEM, DSC, FTIR and in vitro release study. Results showed that the optimal particle was acquired with particle yield at 40.01%, drug loading at 0.12% and diameters around 165nm when the concentration of tea polysaccharide was set at 0.2%, and the amount of PTX:zein=1:10. The particle was a nanoparticle with spherical surface and the encapsulated PTX was in an amorphous form rather than cystalline form. PTX was interacted with zein and polysaccharide through O H and CO groups and it had a sustained release. The results suggested that the novel bipolymer might be a promising agent for PTX delivery and tea polysaccharide was demonstrated its function in drug delivery system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Octadecylamine-Mediated Versatile Coating of CoFe2O4 NPs for the Sustained Release of Anti-Inflammatory Drug Naproxen and in Vivo Target Selectivity.

PubMed

Georgiadou, Violetta; Makris, George; Papagiannopoulou, Dionysia; Vourlias, Georgios; Dendrinou-Samara, Catherine

2016-04-13

Magnetic nanoparticles (MNPs) can play a distinct role in magnetic drug delivery via their distribution to the targeted area. The preparation of such MNPs is a challenging multiplex task that requires the optimization of size, magnetic, and surface properties for the achievement of desirable target selectivity, along with the sustained drug release as a prerequisite. In that context, CoFe2O4 MNPs with a small size of ∼7 nm and moderate saturation magnetization of ∼60 emu g(-1) were solvothermally synthesized in the presence of octadecylamine (ODA) with a view to investigate the functionalization route effect on the drug release. Synthetic regulations allowed us to prepare MNPs with aminated (AmMNPs) and amine-free (FAmMNPs) surface. The addition of the nonsteroidal anti-inflammatory drug with a carboxylate donor, Naproxen (NAP), was achieved by direct coupling with the NH2 groups, rendered by ODA, through the formation of an amide bond in the case of AmMNPs. In the case of FAmMNPs, indirect coupling of NAP was performed through an intermediate linker (polyethylenimine) and on PEG-ylated MNPs. FT-IR, (1)H NMR, (13)C NMR, and UV-vis data confirmed the addition of NAP, whereas diverse drug-release behavior was observed for the different functionalization approaches. The biological behavior of the MNPs@NAP was evaluated in vitro in rat serum and in vivo in mice, after radiolabeling with a γ-emitting radionuclide, (99m)Tc. The in vivo fate of MNPs@NAP carriers was in straightforward relation with the direct or indirect coupling of NAP. Furthermore, an inflammation was induced intramuscularly, where the directly coupled (99m)Tc-MNPs@NAP carriers showed increased accumulation at the inflammation site.

Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential.

PubMed

Singh, Bhupinder; Khurana, Lalit; Bandyopadhyay, Shantanu; Kapil, Rishi; Katare, O O P

2011-11-01

Carvedilol, a widely prescribed cardiovascular drug for hypertension and congestive heart failure, exhibits low and variable bioavailability owing to poor absorption and extensive hepatic first-pass metabolism. The current research work, therefore, entails formulation development of liquid self-nano-emulsifying drug delivery systems (SNEDDS) to enhance the bioavailability of carvedilol by facilitating its transport via lymphatic circulation. The formulation constituents, i.e. lipids, surfactants, and co-surfactants, were selected on the basis of solubility studies. Pseudo-ternary phase diagrams were constructed to embark upon the selection of blend of lipidic (i.e. Capmul PG8) and hydrophilic components (i.e. Cremophor EL as surfactant and Transcutol HP as co-surfactant) for efficient and robust formulation of SNEDDS. The SNEDDS, systematically optimized employing a central composite design (CCD), were evaluated for various response variables viz drug release parameters, emulsification time, emulsion droplet size, and mean dissolution time. In vitro drug release studies depicted that the release from SNEDDS systems followed a non-Fickian kinetic behavior. The TEM imaging of the optimized formulation affirmed the uniform shape and nano size of the system. Accelerated studies of the optimized formulation indicated high stability of the formulation for 6 months. The in situ perfusion studies carried out in wistar rats construed several fold augmentation in the permeability and absorption potential of the optimized formulation vis-à-vis marketed formulation. Thus, the present studies ratified the potential of SNEDDS in augmenting the oral bioavailability of BCS class II drugs.

Application of Box-Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity.

PubMed

Baig, Mirza Salman; Ahad, Abdul; Aslam, Mohammed; Imam, Syed Sarim; Aqil, Mohd; Ali, Asgar

2016-04-01

The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Flavonoids released by carrot (Daucus carota) seedlings stimulate hyphal development of vesicular-arbuscular mycorrhizal fungi in the presence of optimal CO2 enrichment.

PubMed

Poulin, M J; Bel-Rhlid, R; Piché, Y; Chênevert, R

1993-10-01

Carbon dioxide has been previously identified as a critical volatile factor that stimulates hyphal growth ofGigaspora margarita, a vesiculararbuscular mycorrhizal fungus, and we determined the optimal concentration at 2.0%. The beneficial effect of CO2 on fungal development is also visible in the presence of stimulatory (quercetin, myricetin) or inhibitory (naringenin) flavonoids. Sterile root exudates from carrot seedlings stimulate the hyphal development ofG. margarita in the presence of optimal CO2 enrichment. Three flavonols (quercetin, kaempferol, rutin or quercetin 3-rutinoside) and two flavones (apigenin, luteolin) were identified in carrot root exudates by means of HPLC retention time. Flavonols like quercetin and kaempferol are known to have stimulatory effects on hyphal growth ofG. margarita.

Protein functionalized tramadol-loaded PLGA nanoparticles: preparation, optimization, stability and pharmacodynamic studies.

PubMed

Lalani, Jigar; Rathi, Mohan; Lalan, Manisha; Misra, Ambikanandan

2013-06-01

Poly (d,l-lactide-co-glycolide acid) (PLGA) Nanoparticles (NPs) with sustained drug release and enhanced circulation time presents widely explored non-invasive approach for drug delivery to brain. However, blood-brain barrier (BBB) limits the drug delivery to brain. This can be overcome by anchoring endogenous ligand like Transferrin (Tf) and Lactoferrin (Lf) on the surface of NPs, allowing efficient brain delivery via receptor-mediated endocytosis. The aim of the present investigation was preparation, optimization, characterization and comparative evaluation of targeting efficiency of Tf- vs. Lf-conjugated NPs. Tramadol-loaded PLGA NPs were prepared by nanoprecipitation techniques and optimized using 3(3) factorial design. The effect of polymer concentration, stabilizer concentration and organic:aqueous phase ratio were evaluated on particle size (PS) and entrapment efficiency (EE). The formulation was optimized based on desirability for lower PS (<150 nm) and higher EE (>70%). Optimized PLGA NPs were conjugated with Tf and Lf, characterized and evaluated for stability study. Pharmacodynamic study was performed in rat after intravenous administration. The optimized formulation had 100 mg of PLGA, 1% polyvinyl alcohol (PVA) and 1:2 acetone:water ratio. The Lf and Tf conjugation to PLGA NPs was estimated to 186 Tf and 185 Lf molecules per NPs. Lyophilization was optimized at 1:2 ratio of NPs:trehalose. The NPs were found stable for 6 months at refrigerated condition. Pharmacodynamic study demonstrated enhanced efficacy of ligand-conjugated NPs against unconjugated NPs. Conjugated NPs demonstrated significantly higher pharmacological effect over a period of 24 h. Furthermore Lf functionalized NPs exhibited better antinociceptive effect as compared to Tf functionalized NPs.

Deuterium retention and release behaviours of tungsten and deuterium co-deposited layers

NASA Astrophysics Data System (ADS)

Qiao, L.; Zhang, H. W.; Xu, J.; Chai, L. Q.; Hu, M.; Wang, P.

2018-04-01

Tungsten (W) layer deposited in argon and deuterium atmosphere by magnetron sputtering was used as a model system to study the deuterium (D) retention and release behavior in co-deposited W layer. After deposition several selected samples were exposed in deuterium plasma at 370 K with a flux of 4.0 × 1021 D/(m2 s) up to a fluence of 1.1 × 1025 D/m2. Structures of co-deposited W layers are investigated by field-emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD), and the corresponding D retention and release behaviors are studied as functions of deposition and exposure parameters using thermal desorption spectroscopy (TDS). Two main D release peaks were detected from TDS spectra located near 600 and 800 K in these W and D co-deposited layers, and total deuterium retention increased linearly as a function of W layer's thickness. After deuterium plasma exposure, the total D retention amount in W layer increases significantly and D release peak shifts to lower temperature. Clearly, despite the high density of defects expected in co-deposited W layers, the initial deuterium retention before exposure to the deuterium plasma is low even for the samples with a W&D layer. But due to the high densities of defects, during the deuterium plasma exposure the deuterium retention increases faster for co-deposited layer than for the bulk W sample.

Functionalized mesoporous materials for adsorption and release of different drug molecules: A comparative study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Gang; Otuonye, Amy N.; Blair, Elizabeth A.

2009-07-15

The adsorption capacity and release properties of mesoporous materials for drug molecules can be improved by functionalizing their surfaces with judiciously chosen organic groups. Functionalized ordered mesoporous materials containing various types of organic groups via a co-condensation synthetic method from 15% organosilane and by post-grafting organosilanes onto a pre-made mesoporous silica were synthesized. Comparative studies of their adsorption and release properties for various model drug molecules were then conducted. Functional groups including 3-aminopropyl, 3-mercaptopropyl, vinyl, and secondary amine groups were used to functionalize the mesoporous materials while rhodamine 6G and ibuprofen were utilized to investigate the materials' relative adsorption andmore » release properties. The self-assembly of the mesoporous materials was carried out in the presence of cetyltrimethylammonium bromide (CTAB) surfactant, which produced MCM-41 type materials with pore diameters of {approx}2.7-3.3 nm and moderate to high surface areas up to {approx}1000 m{sup 2}/g. The different functional groups introduced into the materials dictated their adsorption capacity and release properties. While mercaptopropyl and vinyl functionalized samples showed high adsorption capacity for rhodamine 6G, amine functionalized samples exhibited higher adsorption capacity for ibuprofen. While the diffusional release of ibuprofen was fitted on the Fickian diffusion model, the release of rhodamine 6G followed Super Case-II transport model. - Graphical abstract: The adsorption capacity and release properties of mesoporous materials for various drug molecules are tuned by functionalizing the surfaces of the materials with judiciously chosen organic groups. This work reports comparative studies of the adsorption and release properties of functionalized ordered mesoporous materials containing different hydrophobic and hydrophilic groups that are synthesized via a co-condensation and post-grafting methods for various model drug molecules.« less

Co-optimization of CO 2 -EOR and Storage Processes under Geological Uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ampomah, William; Balch, Robert; Will, Robert

This paper presents an integrated numerical framework to co-optimize EOR and CO 2 storage performance in the Farnsworth field unit (FWU), Ochiltree County, Texas. The framework includes a field-scale compositional reservoir flow model, an uncertainty quantification model and a neural network optimization process. The reservoir flow model has been constructed based on the field geophysical, geological, and engineering data. A laboratory fluid analysis was tuned to an equation of state and subsequently used to predict the thermodynamic minimum miscible pressure (MMP). A history match of primary and secondary recovery processes was conducted to estimate the reservoir and multiphase flow parametersmore » as the baseline case for analyzing the effect of recycling produced gas, infill drilling and water alternating gas (WAG) cycles on oil recovery and CO 2 storage. A multi-objective optimization model was defined for maximizing both oil recovery and CO 2 storage. The uncertainty quantification model comprising the Latin Hypercube sampling, Monte Carlo simulation, and sensitivity analysis, was used to study the effects of uncertain variables on the defined objective functions. Uncertain variables such as bottom hole injection pressure, WAG cycle, injection and production group rates, and gas-oil ratio among others were selected. The most significant variables were selected as control variables to be used for the optimization process. A neural network optimization algorithm was utilized to optimize the objective function both with and without geological uncertainty. The vertical permeability anisotropy (Kv/Kh) was selected as one of the uncertain parameters in the optimization process. The simulation results were compared to a scenario baseline case that predicted CO 2 storage of 74%. The results showed an improved approach for optimizing oil recovery and CO 2 storage in the FWU. The optimization process predicted more than 94% of CO 2 storage and most importantly about 28% of incremental oil recovery. The sensitivity analysis reduced the number of control variables to decrease computational time. A risk aversion factor was used to represent results at various confidence levels to assist management in the decision-making process. The defined objective functions were proved to be a robust approach to co-optimize oil recovery and CO 2 storage. The Farnsworth CO 2 project will serve as a benchmark for future CO 2–EOR or CCUS projects in the Anadarko basin or geologically similar basins throughout the world.« less

Co-optimization of CO 2 -EOR and Storage Processes under Geological Uncertainty

DOE PAGES

Ampomah, William; Balch, Robert; Will, Robert; ...

2017-07-01

This paper presents an integrated numerical framework to co-optimize EOR and CO 2 storage performance in the Farnsworth field unit (FWU), Ochiltree County, Texas. The framework includes a field-scale compositional reservoir flow model, an uncertainty quantification model and a neural network optimization process. The reservoir flow model has been constructed based on the field geophysical, geological, and engineering data. A laboratory fluid analysis was tuned to an equation of state and subsequently used to predict the thermodynamic minimum miscible pressure (MMP). A history match of primary and secondary recovery processes was conducted to estimate the reservoir and multiphase flow parametersmore » as the baseline case for analyzing the effect of recycling produced gas, infill drilling and water alternating gas (WAG) cycles on oil recovery and CO 2 storage. A multi-objective optimization model was defined for maximizing both oil recovery and CO 2 storage. The uncertainty quantification model comprising the Latin Hypercube sampling, Monte Carlo simulation, and sensitivity analysis, was used to study the effects of uncertain variables on the defined objective functions. Uncertain variables such as bottom hole injection pressure, WAG cycle, injection and production group rates, and gas-oil ratio among others were selected. The most significant variables were selected as control variables to be used for the optimization process. A neural network optimization algorithm was utilized to optimize the objective function both with and without geological uncertainty. The vertical permeability anisotropy (Kv/Kh) was selected as one of the uncertain parameters in the optimization process. The simulation results were compared to a scenario baseline case that predicted CO 2 storage of 74%. The results showed an improved approach for optimizing oil recovery and CO 2 storage in the FWU. The optimization process predicted more than 94% of CO 2 storage and most importantly about 28% of incremental oil recovery. The sensitivity analysis reduced the number of control variables to decrease computational time. A risk aversion factor was used to represent results at various confidence levels to assist management in the decision-making process. The defined objective functions were proved to be a robust approach to co-optimize oil recovery and CO 2 storage. The Farnsworth CO 2 project will serve as a benchmark for future CO 2–EOR or CCUS projects in the Anadarko basin or geologically similar basins throughout the world.« less

Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bilayered matrix tablet.

PubMed

Kang, Won-Ho; Nguyen, Hien Van; Park, Chulhun; Choi, Youn-Woong; Lee, Beom-Jin

2017-05-01

This study was designed to develop a once-daily controlled-release matrix tablet of aceclofenac 200mg (AFC-CR) with dual release characteristics and to investigate the role of an alkalizer in enhancing drug solubility and reducing the occurrence of gastroduodenal mucosal lesions. Two formulation approaches were employed, namely a monolithic matrix tablet and a bilayered tablet. In vitro dissolution studies of AFC-CR tablets were carried out in simulated intestinal fluid (pH6.8 buffer). The in vivo pharmacokinetic studies and drug safety of the immediate-release reference tablet Airtal® 100mg (Daewoong Co., Korea) and the optimized AFC-CR tablet were compared in beagle dogs under fasted condition. The optimally selected AFC-CR formulation displayed the desired dual release characteristics in simulated intestinal fluid with satisfactory micromeritic properties. The swelling action of the optimal matrix tablet, which was visualized by near-infrared (NIR) chemical imaging, occurred rapidly following hydration. Incorporation of sodium carbonate (Na 2 CO 3 ) was found to enhance the release rate of the AFC-CR bilayered tablets at early stages and increase the microenvironmental pH (pH M ). A pharmacokinetic study in beagle dogs indicated a higher drug plasma concentration and a sustained-release pattern for the AFC-CR tablet compared to the Airtal® tablet. AFC-CR was also superior to Airtal® in terms of in vivo drug safety, since no beagle dog receiving AFC-CR experienced gastrointestinal bleeding. The significant enhancement of drug safety was attributed to the size reduction and the increase of pH M of drug particles by means of incorporation of the alkalizer. These findings provide a scientific rationale for developing a novel controlled-release matrix tablet with enhanced patient compliance and better pain control. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing the Efficacy of Poly(N-isopropylacrylamide) for Drug Delivery Applications Using Molecular Dynamics Simulations.

PubMed

Moghadam, Soroush; Larson, Ronald G

2017-02-06

All-atom molecular dynamic simulations (AA-MD) are performed for aqueous solutions of hydrophobic drug molecules (phenytoin) with model polymer excipients, namely, (1) N-isopropylacrylamide, (pNIPAAm), (2) pNIPAAm-co-acrylamide (Am), and (3) pNIPAAm-co-dimethylacrylamide (DMA). After validating the force field parameters using the well-known lower critical solution behavior of pNIPAAm, we simulate the polymer-drug complex in water and its behavior at temperatures below (295 K) and above the LCST (310 K). Using radial distribution functions, we find that there is an optimum comonomer molar fraction of around 20-30% DMA at which interaction with phenytoin drug molecules is strongest, consistent with recent experimental findings. The results provide evidence that molecular simulations are able to provide guidance in the optimization of novel polymer excipients for drug release.

Microencapsulation of citronella oil for mosquito-repellent application: formulation and in vitro permeation studies.

PubMed

Solomon, B; Sahle, F F; Gebre-Mariam, T; Asres, K; Neubert, R H H

2012-01-01

Citronella oil (CO) has been reported to possess a mosquito-repellent action. However, its application in topical preparations is limited due to its rapid volatility. The objective of this study was therefore to reduce the rate of evaporation of the oil via microencapsulation. Microcapsules (MCs) were prepared using gelatin simple coacervation method and sodium sulfate (20%) as a coacervating agent. The MCs were hardened with a cross-linking agent, formaldehyde (37%). The effects of three variables, stirring rate, oil loading and the amount of cross-linking agent, on encapsulation efficiency (EE, %) were studied. Response surface methodology was employed to optimize the EE (%), and a polynomial regression model equation was generated. The effect of the amount of cross-linker was insignificant on EE (%). The response surface plot constructed for the polynomial equation provided an optimum area. The MCs under the optimized conditions provided EE of 60%. The optimized MCs were observed to have a sustained in vitro release profile (70% of the content was released at the 10th hour of the study) with minimum initial burst effect. Topical formulations of the microencapsulated oil and non-microencapsulated oil were prepared with different bases, white petrolatum, wool wax alcohol, hydrophilic ointment (USP) and PEG ointment (USP). In vitro membrane permeation of CO from the ointments was evaluated in Franz diffusion cells using cellulose acetate membrane at 32 °C, with the receptor compartment containing a water-ethanol solution (50:50). The receptor phase samples were analyzed with GC/MS, using citronellal as a reference standard. The results showed that microencapsulation decreased membrane permeation of the CO by at least 50%. The amount of CO permeated was dependent on the type of ointment base used; PEG base exhibited the highest degree of release. Therefore, microencapsulation reduces membrane permeation of CO while maintaining a constant supply of the oil. Copyright © 2011 Elsevier B.V. All rights reserved.

Different design of enzyme-triggered CO-releasing molecules (ET-CORMs) reveals quantitative differences in biological activities in terms of toxicity and inflammation.

PubMed

Stamellou, E; Storz, D; Botov, S; Ntasis, E; Wedel, J; Sollazzo, S; Krämer, B K; van Son, W; Seelen, M; Schmalz, H G; Schmidt, A; Hafner, M; Yard, B A

2014-01-01

Acyloxydiene-Fe(CO)3 complexes can act as enzyme-triggered CO-releasing molecules (ET-CORMs). Their biological activity strongly depends on the mother compound from which they are derived, i.e. cyclohexenone or cyclohexanedione, and on the position of the ester functionality they harbour. The present study addresses if the latter characteristic affects CO release, if cytotoxicity of ET-CORMs is mediated through iron release or inhibition of cell respiration and to what extent cyclohexenone and cyclohexanedione derived ET-CORMs differ in their ability to counteract TNF-α mediated inflammation. Irrespective of the formulation (DMSO or cyclodextrin), toxicity in HUVEC was significantly higher for ET-CORMs bearing the ester functionality at the outer (rac-4), as compared to the inner (rac-1) position of the cyclohexenone moiety. This was paralleled by an increased CO release from the former ET-CORM. Toxicity was not mediated via iron as EC50 values for rac-4 were significantly lower than for FeCl2 or FeCl3 and were not influenced by iron chelation. ATP depletion preceded toxicity suggesting impaired cell respiration as putative cause for cell death. In long-term HUVEC cultures inhibition of VCAM-1 expression by rac-1 waned in time, while for the cyclohexanedione derived rac-8 inhibition seems to increase. NFκB was inhibited by both rac-1 and rac-8 independent of IκBα degradation. Both ET-CORMs activated Nrf-2 and consequently induced the expression of HO-1. This study further provides a rational framework for designing acyloxydiene-Fe(CO)3 complexes as ET-CORMs with differential CO release and biological activities. We also provide a better understanding of how these complexes affect cell-biology in mechanistic terms.

Dissolution enhancement of atorvastatin calcium by co-grinding technique.

PubMed

Prabhu, Priyanka; Patravale, Vandana

2016-08-01

Atorvastatin calcium (AC) is a BCS class II drug which shows poor bioavailability due to inadequate dissolution. Solid dispersions present a promising option to enhance the solubility of poorly soluble drugs. Co-grinding with hydrophilic excipients is an easy and economical technique to improve the solubility of poorly soluble drugs and is free from usage of organic solvents. The aim of the present study was to explore novel carrier VBP-1 (organosulphur compound) for formulating a solid dispersion by using a simple, commercially viable co-grinding technique to enhance the dissolution of AC and to develop an oral formulation of the same. Composition of the solid dispersion was optimized based on the release profile in pH 1.2 buffer. The optimized solid dispersion was further characterized for flow properties, DSC, FTIR spectroscopy, XRD, contact angle, SEM studies and release profile in phosphate buffer pH 6.8. The developed solid dispersion gave similar release profile as the innovator formulation (Lipitor® tablets) in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed solid dispersion was formulated into hard gelatin capsules (size 3). The developed capsules were found to give similar release as the innovator formulation in both pH 1.2 buffer and phosphate buffer pH 6.8. The developed capsules were found to be stable for a period of 6 months. Anti-hyperlipidemic efficacy studies in rats showed higher reduction in cholesterol and triglyceride levels by the developed capsules in comparison to pure AC. In conclusion, novel carrier VBP-1 was successfully employed to enhance the dissolution of AC using co-grinding technique.

One-step formation of lipid-polyacrylic acid-calcium carbonate nanoparticles for co-delivery of doxorubicin and curcumin.

PubMed

Peng, Jianqing; Fumoto, Shintaro; Miyamoto, Hirotaka; Chen, Yi; Kuroda, Naotaka; Nishida, Koyo

2017-09-01

A doxorubicin (Dox) and curcumin (Cur) combination treatment regimen has been widely studied in pre-clinical research. However, the nanoparticles developed for this combination therapy require a consecutive drug loading process because of the different water-solubility of these drugs. This study provides a strategy for the "one-step" formation of nanoparticles encapsulating both Dox and Cur. We took advantage of polyacrylic acid (PAA) and calcium carbonate (CaCO 3 ) to realise a high drug entrapment efficiency (EE) and pH-sensitive drug release using a simplified preparation method. Optimisation of lipid ratios and concentrations of CaCO 3 was conducted. Under optimal conditions, the mean diameter of PEGylated lipid/PAA/CaCO 3 nanoparticles with encapsulated Cur and Dox (LPCCD) was less than 100 nm. An obvious pH-sensitive release of both drugs was observed, with different Dox and Cur release rates. Successful co-delivery of Cur and Dox was achieved via LPCCD on HepG2 cells. LPCCD altered the bio-distribution of Dox and Cur in vivo and decreased Dox-induced cardiotoxicity. The current investigation has developed an efficient ternary system for co-delivery of Dox and Cur to tumours, using a "one-step" formation resulting in nanoparticles possessing remarkable pH-sensitive drug release behaviour, which may be valuable for further clinical studies and eventual clinical application.

Modulation of hydrogel nanoparticle intracellular trafficking by multivalent surface engineering with tumor targeting peptide

NASA Astrophysics Data System (ADS)

Karamchand, Leshern; Kim, Gwangseong; Wang, Shouyan; Hah, Hoe Jin; Ray, Aniruddha; Jiddou, Ruba; Koo Lee, Yong-Eun; Philbert, Martin A.; Kopelman, Raoul

2013-10-01

Surface engineering of a hydrogel nanoparticle (NP) with the tumor-targeting ligand, F3 peptide, enhances both the NP's binding affinity for, and internalization by, nucleolin overexpressing tumor cells. Remarkably, the F3-functionalized NPs consistently exhibited significantly lower trafficking to the degradative lysosomes than the non-functionalized NPs, in the tumor cells, after internalization. This is attributed to the non-functionalized NPs, but not the F3-functionalized NPs, being co-internalized with Lysosome-associated Membrane Protein-1 (LAMP1) from the surface of the tumor cells. Furthermore, it is shown that the intracellular trafficking of the F3-functionalized NPs differs significantly from that of the molecular F3 peptides (untethered to NPs). This has important implications for designing effective, chemically-responsive, controlled-release and multifunctional nanodrugs for multi-drug-resistant cancers.Surface engineering of a hydrogel nanoparticle (NP) with the tumor-targeting ligand, F3 peptide, enhances both the NP's binding affinity for, and internalization by, nucleolin overexpressing tumor cells. Remarkably, the F3-functionalized NPs consistently exhibited significantly lower trafficking to the degradative lysosomes than the non-functionalized NPs, in the tumor cells, after internalization. This is attributed to the non-functionalized NPs, but not the F3-functionalized NPs, being co-internalized with Lysosome-associated Membrane Protein-1 (LAMP1) from the surface of the tumor cells. Furthermore, it is shown that the intracellular trafficking of the F3-functionalized NPs differs significantly from that of the molecular F3 peptides (untethered to NPs). This has important implications for designing effective, chemically-responsive, controlled-release and multifunctional nanodrugs for multi-drug-resistant cancers. Electronic supplementary information (ESI) available: Effect of Potassium depletion on F3 peptide subcellular localization, MTT cytotoxicity data for endocytic inhibitors, size and morphology characterizations of hydrogel PAA nanocarriers, and optimization data for nanocarrier surface functionalization with PEG molecules and F3 peptides. See DOI: 10.1039/c3nr00908d

Lithium-functionalized germanene: A promising media for CO2 capture

NASA Astrophysics Data System (ADS)

Mehdi Aghaei, S.; Monshi, M. M.; Torres, I.; Banakermani, M.; Calizo, I.

2018-02-01

Density functional theory (DFT) is employed to investigate the interactions of CO2 gas molecules with pristine and lithium-functionalized germanene. It is discovered that although a single CO2 molecule is weakly physisorbed on pristine germanene, a significant improvement on its adsorption energy is found by utilizing Li-functionalized germanene as the adsorbent. Excitingly, the moderate adsorption energy at high CO2 coverage secures an easy release step. Moreover, the structure of Li-functionalized germanene can be fully recovered after removal of CO2 gas molecules. Our results suggest that Li-functionalized germanene show promise for CO2 sensing and capture with a storage capacity of 12.57 mol/kg.

Preparation and characterization of cross-linked excipient of coprocessed xanthan gum-acacia gum as matrix for sustained release tablets

NASA Astrophysics Data System (ADS)

Surini, Silvia; Wati, Dina Risma; Syahdi, Rezi Riadhi

2018-02-01

Sustained release tablet is solid dosage form which is designed to release drugs slowly in the body. This research was intended to prepare and characterize the cross-linked excipients of co-processed xanthan gum-acacia gum (CL-Co-XGGA) as matrices for sustained release tablets with gliclazide as a model drug. CL-Co-XGGA excipients were cross-linked materials of co-processed excipients of xanthan gum-acacia gum (Co-XGGA) using sodium trimetaphosphate. Co-processed excipients of xanthan gum-acacia gum were prepared in the ratio of each excipient 1:2, 1:1 and 2:1. Co-XGGA and CL-Co-XGGA excipients were characterized physically, chemically and functionally. Then, the sustained release (SR) tablets were formulated by wet granulation method using CL-Co-XGGA excipients as matrices. Also, the dissolution study of the gliclazide SR tablets was carried out in phosphate buffer medium pH 7,4 containing sodium lauryl sulphate 0.2% for 12 hours. The results showed that the degree of substitution (DS) of CL-Co-XGGA 1:2, 1:1, 2:1 excipients were respectively 0.067, 0.082 and 0.08. Besides that, the excipients gel strengths were 14.03, 17.27 and 20,70 gF, respectively. The cross-linked excipients had improved flow properties and swelling capability compared to the Co-XGGA excipients. The results of the gliclazide SR tablets evaluations showed that all tablets were passed all tablet requirements. Moreover, the gliclazide release from SR tablets F1 - F6 revealed the sustained release profile, which was following zero order kinetics (F1, F2, F3, F6) and Higuchi kinetics (F4 and F5). It could be concluded that the obtained CL-Co-XGGA excipients might be used as matrices for sustained release tablets and could retard drug release up to 8 until 32 hours.

Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles.

PubMed

Jiao, Y Y; Ubrich, N; Marchand-Arvier, M; Vigneron, C; Hoffman, M; Maincent, P

2001-01-01

Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation efficiency and heparin release profiles were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation efficiency was observed when 5000 IU of heparin were incorporated in the first emulsion. High drug entrapment efficiency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (<14%). The use of the two types of Eudragit in combination with PCL and PLAGA increased the encapsulation efficiency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modified and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a significant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.

Cation Exchange Strategy for the Encapsulation of a Photoactive CO-Releasing Organometallic Molecule into Anionic Porous Frameworks.

PubMed

Carmona, Francisco J; Rojas, Sara; Sánchez, Purificación; Jeremias, Hélia; Marques, Ana R; Romão, Carlos C; Choquesillo-Lazarte, Duane; Navarro, Jorge A R; Maldonado, Carmen R; Barea, Elisa

2016-07-05

The encapsulation of the photoactive, nontoxic, water-soluble, and air-stable cationic CORM [Mn(tacn)(CO)3]Br (tacn = 1,4,7-triazacyclononane) in different inorganic porous matrixes, namely, the metalorganic framework bio-MOF-1, (NH2(CH3)2)2[Zn8(adeninate)4(BPDC)6]·8DMF·11H2O (BPDC = 4,4'-biphenyldicarboxylate), and the functionalized mesoporous silicas MCM-41-SO3H and SBA-15-SO3H, is achieved by a cation exchange strategy. The CO release from these loaded materials, under simulated physiological conditions, is triggered by visible light. The results show that the silica matrixes, which are unaltered under physiological conditions, slow the kinetics of CO release, allowing a more controlled CO supply. In contrast, bio-MOF-1 instability leads to the complete leaching of the CORM. Nevertheless, the degradation of the MOF matrix gives rise to an enhanced CO release rate, which is related to the presence of free adenine in the solution.

Enhanced bone regeneration using an insulin-loaded nano-hydroxyapatite/collagen/PLGA composite scaffold.

PubMed

Wang, Xing; Zhang, Guilan; Qi, Feng; Cheng, Yongfeng; Lu, Xuguang; Wang, Lu; Zhao, Jing; Zhao, Bin

2018-01-01

Insulin is widely considered as a classical hormone and drug in maintaining energy and glucose homeostasis. Recently, insulin has been increasingly recognized as an indispensable factor for osteogenesis and bone turnover, but its applications in bone regeneration have been restricted because of the short periods of activity and uncontrolled release. In this study, we incorporated insulin-loaded poly lactic-co-glycolic-acid (PLGA) nanospheres into nano-hydroxyapatite/collagen (nHAC) scaffolds and investigated the bioactivity of the composite scaffolds in vitro and in vivo. Bioactive insulin was successfully released from the nanospheres within the scaffold, and the release kinetics of insulin could be efficiently controlled by uniform-sized nanospheres. The physical characterizations of the composite scaffolds demonstrated that incorporation of nanospheres in nHAC scaffolds using this method did not significantly change the porosity, pore diameters, and compressive strengths of nHAC. In vitro, the insulin-loaded nHAC/PLGA composite scaffolds possessed favorable biological function for bone marrow mesenchymal stem cells adhesion and proliferation, as well as the differentiation into osteoblasts. In vivo, the optimized bone regenerative capability of this composite scaffold was confirmed in rabbit mandible critical size defects. These results demonstrated successful development of a functional insulin-PLGA-nHAC composite scaffold that enhances the bone regeneration capability of nHAC.

Genetic engineering of Synechocystis PCC6803 for the photoautotrophic production of the sweetener erythritol.

PubMed

van der Woude, Aniek D; Perez Gallego, Ruth; Vreugdenhil, Angie; Puthan Veetil, Vinod; Chroumpi, Tania; Hellingwerf, Klaas J

2016-04-08

Erythritol is a polyol that is used in the food and beverage industry. Due to its non-caloric and non-cariogenic properties, the popularity of this sweetener is increasing. Large scale production of erythritol is currently based on conversion of glucose by selected fungi. In this study, we describe a biotechnological process to produce erythritol from light and CO2, using engineered Synechocystis sp. PCC6803. By functionally expressing codon-optimized genes encoding the erythrose-4-phosphate phosphatase TM1254 and the erythrose reductase Gcy1p, or GLD1, this cyanobacterium can directly convert the Calvin cycle intermediate erythrose-4-phosphate into erythritol via a two-step process and release the polyol sugar in the extracellular medium. Further modifications targeted enzyme expression and pathway intermediates. After several optimization steps, the best strain, SEP024, produced up to 2.1 mM (256 mg/l) erythritol, excreted in the medium.

TMAP-7 simulation of D2 thermal release data from Be co-deposited layers

NASA Astrophysics Data System (ADS)

Baldwin, M. J.; Schwarz-Selinger, T.; Yu, J. H.; Doerner, R. P.

2013-07-01

The efficacy of (1) bake-out at 513 K and 623 K, and (2) thermal transient (10 ms) loading to up to 1000 K, is explored for reducing D inventory in 1 μm thick Be-D (D/Be ˜0.1) co-deposited layers formed at 323 K for experiment (1) and ˜500 K for experiment (2). D release data from co-deposits are obtained by thermal desorption and used to validate a model input into the Tritium Migration & Analysis Program 7 (TMAP). In (1), good agreement with experiment is found for a TMAP model encorporating traps of activation energies, 0.80 eV and 0.98 eV, whereas an additional 2 eV trap was required to model experiment (2). Thermal release is found to be trap limited, but simulations are optimal when surface recombination is taken into account. Results suggest that thick built-up co-deposited layers will hinder ITER inventory control, and that bake periods (˜1 day) will be more effective in inventory reduction than transient thermal loading.

Dexamethasone acetate encapsulation into Trojan particles.

PubMed

Gómez-Gaete, Carolina; Fattal, Elias; Silva, Lídia; Besnard, Madeleine; Tsapis, Nicolas

2008-05-22

We have combined the therapeutic potential of nanoparticles systems with the ease of manipulation of microparticles by developing a hybrid vector named Trojan particles. We aim to use this new delivery vehicle for intravitreal administration of dexamethasone. Initialy, dexamethasone acetate (DXA) encapsulation into biodegradable poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles was optimized. Then, Trojan particles were formulated by spray drying 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC), hyaluronic acid (HA) and different concentrations of nanoparticle suspensions. The effect of nanoparticles concentration on Trojan particle physical characteristics was investigated as well as the effect of the spray drying process on nanoparticles size. Finally, DXA in vitro release from nanoparticles and Trojan particles was evaluated under sink condition. SEM and confocal microscopy show that most of Trojan particles are spherical, hollow and possess an irregular surface due to the presence of nanoparticles. Neither Trojan particle tap density nor size distribution are significantly modified as a function of nanoparticles concentration. The mean nanoparticles size increase significantly after spray drying. Finally, the in vitro release of DXA shows that the excipient matrix provides protection to encapsulated nanoparticles by slowing drug release.

Monitoring CO2 Intrusion in shallow aquifer using complex electrical methods and a novel CO2 sensitive Lidar-based sensor

NASA Astrophysics Data System (ADS)

Leger, E.; Dafflon, B.; Thorpe, M.; Kreitinger, A.; Laura, D.; Haivala, J.; Peterson, J.; Spangler, L.; Hubbard, S. S.

2016-12-01

While subsurface storage of CO2 in geological formations offers significant potential to mitigate atmospheric greenhouse gasses, approaches are needed to monitor the efficacy of the strategy as well as possible negative consequences, such as leakage of CO2 or brine into groundwater or release of fugitive gaseous CO2. Groundwater leakages can cause subsequent reactions that may also be deleterious. For example, a release of dissolved CO2 into shallow groundwatersystems can decrease groundwater pH which can potentiallymobilize naturally occurring trace metals and ions. In this perspective, detecting and assessing potential leak requires development of novel monitoring techniques.We present the results of using surface electrical resistivity tomography (ERT) and a novel CO2 sensitive Lidar-based sensor to monitor a controlled CO2 release at the ZeroEmission Research and Technology Center (Bozeman, Montana). Soil temperature and moisture sensors, wellbore water quality measurements as well as chamber-based CO2 flux measurements were used in addition to the ERT and a novel Lidar-based sensor to detect and assess potential leakage into groundwater, vadose zone and atmosphere. The three-week release wascarried out in the vadose and the saturated zones. Well sampling of pH and conductivity and surface CO2 fluxes and concentrations measurements were acquired during the release and are compared with complex electricalresistivity time-lapse measurements. The novel Lidar-based image of the CO2 plume were compared to chamber-based CO2 flux and concentration measurements. While a continuous increase in subsurface ERT and above ground CO2 was documented, joint analysis of the above and below ground data revealed distinct transport behavior in the vadose and saturated zones. Two type of transport were observed, one in the vadoze zone, monitored by CO2 flux chamber and ERT, and the other one in the saturated zone, were ERT and wellsampling were carried. The experiment suggests how a range of geophysical, remote sensing, hydrological and geochemical measurement approaches can be optimally configured to detect the distribution and explore behavior of possible CO2 leakages in distinct compartments, including groundwater, vadose zone, and atmosphere.

Electrospray ionization study of tricarbonyl fac-[Re(CO)3 (PO)(X)]-type complexes: influence of ancillary co-ligands in the release of carbon monoxide.

PubMed

Tisato, Francesco; Porchia, Marina; Shegani, Antoni; Maina, Theodosia; Papadopoulos, Minas S; Seraglia, Roberta; Traldi, Pietro

2018-05-08

fac-[Re(CO) 3 (PO)(X)]-type complexes (PO = chelated bidentate tertiary phosphine(1-), X = various neutral, mono-dentate ligands) represent a class of compounds that meets the synthetic criteria for the preparation of potential carbon monoxide (CO) release molecules (CORMs) for medicinal application. The aim of our investigation was to achieve qualitative information whether the nature of the ancillary X ligand might influence the release of CO. The release of CO has been investigated by means of product ion spectrometry of electrospray ionization-generated [M + H] + species, produced by multiple collisional experiments, using an ion trap mass spectrometer. Tandem mass spectrometry applied to the protonated species [Re(CO) 3 (PO)(X) + H] + of seven complexes (those including X = OH 2 (1), isonitrile (2, 3), imidazole (4), pyridine (5) and phosphine (6, 7) show initial loss of coordinated water (1) or pyridine (5), whereas the majority of investigated entries display initial, sequential release of CO groups. The energetics of CO release have been investigated by breakdown curves for selected collisionally-activated decomposition processes involving CO, and compared with those involving X groups. The nature of the co-ligand X drives the primary loss in the MS n processes of [Re(CO) 3 (PO)(X) + H] + compounds. When X = solvent, the energetics of these decompositions follow the trend H 2 O < MeOH < CO. In each case, loss of CO is a favored fragmentation route with associated energies following the trend: N-py ≤ P-phosphine < C-isonitrile. Overall, MS n pathways indicate that [Re(PO)] (Re with chelated PO phosphine) constitutes the residual moiety. This behavior indicates that the presence of a functionalized phosphine is essential for a sequential, controlled release of CO. This article is protected by copyright. All rights reserved.

Vegetation and climate controls on potential CO2, DOC and DON production in northern latitude soils

USGS Publications Warehouse

Neff, J.C.; Hooper, D.U.

2002-01-01

Climatic change may influence decomposition dynamics in arctic and boreal ecosystems, affecting both atmospheric CO2 levels, and the flux of dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) to aquatic systems. In this study, we investigated landscape-scale controls on potential production of these compounds using a one-year laboratory incubation at two temperatures (10?? and 30??C). We measured the release of CO2, DOC and DON from tundra soils collected from a variety of vegetation types and climatic regimes: tussock tundra at four sites along a latitudinal gradient from the interior to the north slope of Alaska, and soils from additional vegetation types at two of those sites (upland spruce at Fairbanks, and wet sedge and shrub tundra at Toolik Lake in northern Alaska). Vegetation type strongly influenced carbon fluxes. The highest CO2 and DOC release at the high incubation temperature occurred in the soils of shrub tundra communities. Tussock tundra soils exhibited the next highest DOC fluxes followed by spruce and wet sedge tundra soils, respectively. Of the fluxes, CO2 showed the greatest sensitivity to incubation temperatures and vegetation type, followed by DOC. DON fluxes were less variable. Total CO2 and total DOC release were positively correlated, with DOC fluxes approximately 10% of total CO2 fluxes. The ratio of CO2 production to DOC release varied significantly across vegetation types with Tussock soils producing an average of four times as much CO2 per unit DOC released compared to Spruce soils from the Fairbanks site. Sites in this study released 80-370 mg CO2-C g soil C-1 and 5-46 mg DOC g soil C-1 at high temperatures. The magnitude of these fluxes indicates that arctic carbon pools contain a large proportion of labile carbon that could be easily decomposed given optimal conditions. The size of this labile pool ranged between 9 and 41% of soil carbon on a g soil C basis, with most variation related to vegetation type rather than climate.

Selective adsorption of oppositely charged PNIPAAM on halloysite surfaces: a route to thermo-responsive nanocarriers.

PubMed

Cavallaro, Giuseppe; Lazzara, Giuseppe; Lisuzzo, Lorenzo; Milioto, Stefana; Parisi, Filippo

2018-08-10

Halloysite nanotubes were functionalized with stimuli-responsive macromolecules to generate smart nanohybrids. Poly(N-isopropylacrylamide)-co-methacrylic acid (PNIPAAM-co-MA) was selectively adsorbed into halloysite lumen by exploiting electrostatic interactions. Amine-terminated PNIPAAM polymer was also investigated that selectively interacts with the outer surface of the nanotubes. The adsorption site has a profound effect on the thermodynamic behavior and therefore temperature responsive features of the hybrid material. The drug release kinetics was investigated by using diclofenac as a non-steroidal anti-inflammatory drug model. The release kinetics depends on the nanoarchitecture of the PNIPAAM/halloysite based material. In particular, diclofenac release was slowed down above the LCST for PNIPAAM-co-MA/halloysite. Opposite trends occurred for halloysite functionalized with PNIPAAM at the outer surface. This work represents a further step toward the opportunity to extend and control the delivery conditions of active species, which represent a key point in technological applications.

Murai Reaction on Furfural Derivatives Enabled by Removable N,N'-Bidentate Directing Groups.

PubMed

Pezzetta, Cristofer; Veiros, Luis F; Oble, Julie; Poli, Giovanni

2017-06-22

Furfural and related compounds are industrially relevant building blocks obtained from lignocellulosic biomass. To enhance the added value of these renewable resources, a Ru-catalyzed hydrofurylation of alkenes, involving a directed C-H activation at C3 of the furan ring, was developed. A thorough experimental study revealed that a bidentate amino-imine directing group enabled the desired coupling. Removal of the directing group occurred during the purification step, directly releasing the C3-functionalized furfurals. Development of the reaction as well as optimization and scope of the method were described. A mechanism was proposed on the basis of DFT calculations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of rotatable central composite design in the preparation and optimization of poly(lactic-co-glycolic acid) nanoparticles for controlled delivery of paclitaxel.

PubMed

Kollipara, Sivacharan; Bende, Girish; Movva, Snehalatha; Saha, Ranendra

2010-11-01

Polymeric carrier systems of paclitaxel (PCT) offer advantages over only available formulation Taxol® in terms of enhancing therapeutic efficacy and eliminating adverse effects. The objective of the present study was to prepare poly (lactic-co-glycolic acid) nanoparticles containing PCT using emulsion solvent evaporation technique. Critical factors involved in the processing method were identified and optimized by scientific, efficient rotatable central composite design aiming at low mean particle size and high entrapment efficiency. Twenty different experiments were designed and each formulation was evaluated for mean particle size and entrapment efficiency. The optimized formulation was evaluated for in vitro drug release, and absorption characteristics were studied using in situ rat intestinal permeability study. Amount of polymer and duration of ultrasonication were found to have significant effect on mean particle size and entrapment efficiency. First-order interactions of amount of miglyol with amount of polymer were significant in case of mean particle size, whereas second-order interactions of polymer were significant in mean particle size and entrapment efficiency. The developed quadratic model showed high correlation (R(2) > 0.85) between predicted response and studied factors. The optimized formulation had low mean particle size (231.68 nm) and high entrapment efficiency (95.18%) with 4.88% drug content. The optimized formulation showed controlled release of PCT for more than 72 hours. In situ absorption study showed faster and enhanced extent of absorption of PCT from nanoparticles compared to pure drug. The poly (lactic-co-glycolic acid) nanoparticles containing PCT may be of clinical importance in enhancing its oral bioavailability.

Fine-tuning the release of molecular guests from mesoporous silicas by controlling the orientation and mobility of surface phenyl substituents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manzano, J. Sebastian; Singappuli-Arachchige, Dilini; Parikh, Bosky L.

Phenyl-functionalized mesoporous silica materials were used to explore the effect of non-covalent interactions on the release of Ibuprofen into simulated body fluid. Variations in orientation and conformational mobility of the surface phenyl groups were introduced by selecting different structural precursors: a rigid upright orientation was obtained using phenyl groups directly bound to surface Si atoms (Ph-MSN), mobile groups were produced by using ethylene linkers to connect phenyl groups to the surface (PhEt-MSN), and groups co-planar to the surface were obtained by synthesizing a phenylene-bridged periodic mesoporous organosilica (Ph-PMO). The Ibuprofen release profiles from these materials and non-functionalized mesoporous silica nanoparticlesmore » (MSN) were analyzed using an adsorption-diffusion model. The model provided kinetic and thermodynamic parameters that evidenced fundamental differences in drug-surface interactions between the materials. All phenyl-bearing materials show lower Ibuprofen initial release rates than bare MSN. The conformationally locked Ph-MSN and Ph-PMO have stronger interactions with the drug (negative ΔG of adsorption) than the flexible PhEt-MSN and bare MSN (positive ΔG of adsorption). These differences in strength of adsorption are consistent with differences between interaction geometries obtained from DFT calculations. B3LYP-D3-optimized models show that π-π interactions contribute more to drug adsorption than H-bonding with silanol groups. Here, the results suggest that the type and geometry of interactions control the kinetics and extent of drug release, and should therefore serve as a guide to design new drug delivery systems with precise release behaviors customized to any desired target.« less

Fine-tuning the release of molecular guests from mesoporous silicas by controlling the orientation and mobility of surface phenyl substituents

DOE PAGES

Manzano, J. Sebastian; Singappuli-Arachchige, Dilini; Parikh, Bosky L.; ...

2017-12-05

Phenyl-functionalized mesoporous silica materials were used to explore the effect of non-covalent interactions on the release of Ibuprofen into simulated body fluid. Variations in orientation and conformational mobility of the surface phenyl groups were introduced by selecting different structural precursors: a rigid upright orientation was obtained using phenyl groups directly bound to surface Si atoms (Ph-MSN), mobile groups were produced by using ethylene linkers to connect phenyl groups to the surface (PhEt-MSN), and groups co-planar to the surface were obtained by synthesizing a phenylene-bridged periodic mesoporous organosilica (Ph-PMO). The Ibuprofen release profiles from these materials and non-functionalized mesoporous silica nanoparticlesmore » (MSN) were analyzed using an adsorption-diffusion model. The model provided kinetic and thermodynamic parameters that evidenced fundamental differences in drug-surface interactions between the materials. All phenyl-bearing materials show lower Ibuprofen initial release rates than bare MSN. The conformationally locked Ph-MSN and Ph-PMO have stronger interactions with the drug (negative ΔG of adsorption) than the flexible PhEt-MSN and bare MSN (positive ΔG of adsorption). These differences in strength of adsorption are consistent with differences between interaction geometries obtained from DFT calculations. B3LYP-D3-optimized models show that π-π interactions contribute more to drug adsorption than H-bonding with silanol groups. Here, the results suggest that the type and geometry of interactions control the kinetics and extent of drug release, and should therefore serve as a guide to design new drug delivery systems with precise release behaviors customized to any desired target.« less

Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate.

PubMed

Mayer, Lori; Fink, Mary Kay; Sammarco, Carrie; Laing, Lisa

2018-04-01

Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

Co-combustion characteristics and blending optimization of tobacco stem and high-sulfur bituminous coal based on thermogravimetric and mass spectrometry analyses.

PubMed

Zhang, Kaihua; Zhang, Kai; Cao, Yan; Pan, Wei-ping

2013-03-01

Despite much research on co-combustion of tobacco stem and high-sulfur coal, their blending optimization has not been effectively found. This study investigated the combustion profiles of tobacco stem, high-sulfur bituminous coal and their blends by thermogravimetric analysis. Ignition and burnout performances, heat release performances, and gaseous pollutant emissions were also studied by thermogravimetric and mass spectrometry analyses. The results indicated that combustion of tobacco stem was more complicated than that of high-sulfur bituminous coal, mainly shown as fixed carbon in it was divided into two portions with one early burning and the other delay burning. Ignition and burnout performances, heat release performances, and gaseous pollutant emissions of the blends present variable trends with the increase of tobacco stem content. Taking into account the above three factors, a blending ratio of 0–20% tobacco stem content is conservatively proposed as optimum amount for blending. Copyright © 2012 Elsevier Ltd. All rights reserved.

Selenite-Releasing Bone Mineral Nanoparticles Retard Bone Tumor Growth and Improve Healthy Tissue Functions In Vivo.

PubMed

Wang, Yanhua; Hao, Hang; Liu, Haoming; Wang, Yifan; Li, Yan; Yang, Gaojie; Ma, Jun; Mao, Chuanbin; Zhang, Shengmin

2015-08-26

Selenite-doped bone mineral nanoparticles can retard the growth of osteosarcoma in a nude mice model, through sustained release of selenite ions. The selenite ions released from the nanoparticles through a degradation-mediated fashion inhibit tumor metastasis. Blood routine analysis indicates that selenite ions can also improve the functions of liver, kidney, and heart. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peroxisomal Malate Dehydrogenase Is Not Essential for Photorespiration in Arabidopsis But Its Absence Causes an Increase in the Stoichiometry of Photorespiratory CO2 Release1[W][OA

PubMed Central

Cousins, Asaph B.; Pracharoenwattana, Itsara; Zhou, Wenxu; Smith, Steven M.; Badger, Murray R.

2008-01-01

Peroxisomes are important for recycling carbon and nitrogen that would otherwise be lost during photorespiration. The reduction of hydroxypyruvate to glycerate catalyzed by hydroxypyruvate reductase (HPR) in the peroxisomes is thought to be facilitated by the production of NADH by peroxisomal malate dehydrogenase (PMDH). PMDH, which is encoded by two genes in Arabidopsis (Arabidopsis thaliana), reduces NAD+ to NADH via the oxidation of malate supplied from the cytoplasm to oxaloacetate. A double mutant lacking the expression of both PMDH genes was viable in air and had rates of photosynthesis only slightly lower than in the wild type. This is in contrast to other photorespiratory mutants, which have severely reduced rates of photosynthesis and require high CO2 to grow. The pmdh mutant had a higher O2-dependent CO2 compensation point than the wild type, implying that either Rubisco specificity had changed or that the rate of CO2 released per Rubisco oxygenation was increased in the pmdh plants. Rates of gross O2 evolution and uptake were similar in the pmdh and wild-type plants, indicating that chloroplast linear electron transport and photorespiratory O2 uptake were similar between genotypes. The CO2 postillumination burst and the rate of CO2 released during photorespiration were both greater in the pmdh mutant compared with the wild type, suggesting that the ratio of photorespiratory CO2 release to Rubisco oxygenation was altered in the pmdh mutant. Without PMDH in the peroxisome, the CO2 released per Rubisco oxygenation reaction can be increased by over 50%. In summary, PMDH is essential for maintaining optimal rates of photorespiration in air; however, in its absence, significant rates of photorespiration are still possible, indicating that there are additional mechanisms for supplying reductant to the peroxisomal HPR reaction or that the HPR reaction is altogether circumvented. PMID:18685043

Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson’s disease model

NASA Astrophysics Data System (ADS)

Sharma, Shrestha; Narang, Jasjeet K.; Ali, Javed; Baboota, Sanjula

2016-09-01

Purpose. Oxidative stress is the leading cause in the pathogenesis of Parkinson’s disease. Rutin is a naturally occurring strong antioxidant molecule with wide therapeutic applications. It suffers from the problem of low oral bioavailability which is due to its poor aqueous solubility. Methods. In order to increase the solubility self-nanoemulsifying drug delivery systems (SNEDDS) of rutin were prepared. The oil, surfactant and co-surfactant were selected based on solubility/miscibility studies. Optimization was done by a three-factor, four-level (34) Box-Behnken design. The independent factors were oil, surfactant and co-surfactant concentration and the dependent variables were globule size, self-emulsification time, % transmittance and cumulative percentage of drug release. The optimized SNEDDS formulation (RSE6) was evaluated for various release studies. Antioxidant activity was assessed by various in vitro tests such as 2,2-diphenyl-1-picrylhydrazyl and reducing power assay. Oxidative stress models which had Parkinson’s-type symptoms were used to determine the antioxidant potential of rutin SNEDDS in vivo. Permeation was assessed through confocal laser scanning microscopy. Results. An optimized SNEDDS formulation consisting of Sefsol + vitamin E-Solutol HS 15-Transcutol P at proportions of 25:35:17.5 (w/w) was prepared and characterized. The globule size and polydispersity index of the optimized formulation was found to be 16.08 ± 0.02 nm and 0.124 ± 0.01, respectively. A significant (p < 0.05) increase in the percentage of drug release was achieved in the case of the optimized formulation as compared to rutin suspension. Pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability. The optimized formulation had significant in vitro and in vivo antioxidant activity. Conclusion. Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing the oral bioavailability and efficacy of rutin, thus helping in ameliorating oxidative stress in neurodegenerative disorders like Parkinson’s disease.

CMAQ modeling in the nitrogen inventory study in the Nooksack-Abbotsford-Sumas Transboundary Region

EPA Science Inventory

Optimizing nitrogen (N) use for food production while minimizing the release of N and co-pollutants to the environment is an important challenge. The Nooksack-Abbotsford-Sumas Transboundary (NAS) Region, spanning a portion of the western interface of British Columbia, Washington...

Iron-Rich Carbonates as the Potential Source of Evolved CO2 Detected by the Sample Analysis at Mars (SAM) Instrument in Gale Crater

NASA Technical Reports Server (NTRS)

Sutter, B.; Heil, E.; Rampe, E. B.; Morris, R. V.; Ming, D. W.; Archer, P. D.; Eigenbrode, J. L.; Franz, H. B.; Glavin, D. P.; McAdam, A. C.;

Jet Mixing in a Reacting Cylindrical Crossflow

NASA Technical Reports Server (NTRS)

Leong, M. Y.; Samuelsen, G. S.; Holdeman, J. D.

1995-01-01

This paper addresses the mixing of air jets into the hot, fuel-rich products of a gas turbine primary zone. The mixing, as a result, occurs in a reacting environment with chemical conversion and substantial heat release. The geometry is a crossflow confined in a cylindrical duct with side-wall injection of jets issuing from round orifices. A specially designed reactor, operating on propane, presents a uniform mixture without swirl to mixing modules consisting of 8, 9, 10, and 12 holes at a momentum-flux ratio of 57 and a jet-to-mainstream mass-flow ratio of 2.5. Concentrations of O2, CO2, CO, and HC are obtained upstream, downstream, and within the orifice plane. O2 profiles indicate jet penetration while CO2, CO, and HC profiles depict the extent of reaction. Jet penetration is observed to be a function of the number of orifices and is found to affect the mixing in the reacting system. The results demonstrate that one module (the 12-hole) produces near-optimal penetration defined here as a jet penetration closest to the module half-radius, and hence the best uniform mixture at a plane one duct radius from the orifice leading edge.

Hybrid PCL/CaCO3 scaffolds with capabilities of carrying biologically active molecules: Synthesis, loading and in vivo applications.

PubMed

Saveleva, M S; Ivanov, A N; Kurtukova, M O; Atkin, V S; Ivanova, A G; Lyubun, G P; Martyukova, A V; Cherevko, E I; Sargsyan, A K; Fedonnikov, A S; Norkin, I A; Skirtach, A G; Gorin, D A; Parakhonskiy, B V

2018-04-01

Designing advanced biomaterials for tissue regeneration with drug delivery and release functionalities remains a challenge in regenerative medicine. In this research, we have developed novel composite scaffolds based on polymeric polycaprolactone fibers coated with porous calcium carbonate structures (PCL/CaCO 3 ) for tissue engineering and have shown their drug delivery and release in rats. In vivo biocompatibility tests of PCL/CaCO 3 scaffolds were complemented with in vivo drug release study, where tannic acid (TA) was used as a model drug. Release of TA from the scaffolds was realized by recrystallization of the porous vaterite phase of calcium carbonate into the crystalline calcite. Cell colonization and tissue vascularization as well as transplantability of developed PCL/CaCO 3 +TA scaffolds were observed. Detailed study of scaffold transformations during 21-day implantation period was followed by scanning electron microscopy and X-ray diffraction studies before and after in vivo implantation. The presented results demonstrate that PCL/CaCO 3 scaffolds are attractive candidates for implants in bone regeneration and tissue engineering with a possibility of loading biologically active molecules and controlled release. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasma immersion ion implantation for reducing metal ion release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz, C.; Garcia, J. A.; Maendl, S.

Plasma immersion ion implantation of Nitrogen and Oxygen on CoCrMo alloys was carried out to improve the tribological and corrosion behaviors of these biomedical alloys. In order to optimize the implantation results we were carried experiments at different temperatures. Tribocorrosion tests in bovine serum were used to measure Co, Cr and Mo releasing by using Inductively Coupled Plasma Mass Spectrometry analysis after tests. Also, X-ray Diffraction analysis were employed in order to explain any obtained difference in wear rate and corrosion tests. Wear tests reveals important decreases in rate of more than one order of magnitude for the best treatment.more » Moreover decreases in metal release were found for all the implanted samples, preserving the same corrosion resistance of the unimplanted samples. Finally this paper gathers an analysis, in terms of implantation parameters and achieved properties for industrial implementation of these treatments.« less

Functional implications of neurotransmitter co-release: glutamate and GABA share the load.

PubMed

Seal, Rebecca P; Edwards, Robert H

2006-02-01

For decades it has been thought that a neuron releases only one classical neurotransmitter from all of its processes. However, recent work has shown that most neuronal populations release more than one classical transmitter, and indeed that the transmitters can be segregated into different processes of the same neuron. Glutamate and gamma-aminobutyric acid, the major excitatory and inhibitory neurotransmitters in the mammalian central nervous system, appear to be co-released with most other transmitters, as well as with each other. The release of multiple transmitters by the same neuron enhances the spatial and temporal control of synaptic transmission. Moreover, dynamic regulation of neurotransmitter phenotypes increases the plasticity of neurotransmission, indicating potential avenues for therapeutic intervention.

Preparation and Optimization of Immediate Release/Sustained Release Bilayered Tablets of Loxoprofen Using Box-Behnken Design.

PubMed

Tak, Jin Wook; Gupta, Biki; Thapa, Raj Kumar; Woo, Kyu Bong; Kim, Sung Yub; Go, Toe Gyeong; Choi, Yongjoo; Choi, Ju Yeon; Jeong, Jee-Heon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2017-05-01

The aim of our current study was to characterize and optimize loxoprofen immediate release (IR)/sustained release (SR) tablet utilizing a three-factor, three-level Box-Behnken design (BBD) combined with a desirability function. The independent factors included ratio of drug in the IR layer to total drug (X 1 ), ratio of HPMC to drug in the SR layer (X 2 ), and ratio of Eudragit RL PO to drug in the SR layer (X 3 ). The dependent variables assessed were % drug released in distilled water at 30 min (Y 1 ), % drug released in pH 1.2 at 2 h (Y 2 ), and % drug released in pH 6.8 at 12 h (Y 3 ). The responses were fitted to suitable models and statistical validation was performed using analysis of variance. In addition, response surface graphs and contour plots were constructed to determine the effects of different factor level combinations on the responses. The optimized loxoprofen IR/SR tablets were successfully prepared with the determined amounts of ingredients that showed close agreement in the predicted and experimental values of tablet characterization and drug dissolution profile. Therefore, BBD can be utilized for successful optimization of loxoprofen IR/SR tablet, which can be regarded as a suitable substitute for the current marketed formulations.

Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

PubMed

Duque, Marcelo Dutra; Kreidel, Rogério Nepomuceno; Taqueda, Maria Elena Santos; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Consiglieri, Vladi Olga

2013-01-01

A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

Development of PMMA membranes functionalized with hydroxypropyl-beta-cyclodextrins for controlled drug delivery using a supercritical CO(2)-assisted technology.

PubMed

Temtem, M; Pompeu, D; Jaraquemada, G; Cabrita, E J; Casimiro, T; Aguiar-Ricardo, A

2009-07-06

Cyclodextrin-containing polymers have proved themselves to be useful for controlled release. Herein we describe the preparation of membranes of poly(methylmethacrylate) (PMMA) containing hydroxypropyl-beta-cyclodextrins (HP-beta-CDs) using a supercritical CO(2)-assisted phase inversion method, for potential application as drug delivery devices. Results are reported on the membrane preparation, physical properties, and drug elution profile of a model drug. The polymeric membranes were obtained with HP-beta-CD contents ranging from 0 to 33.4 wt%, by changing the composition of the casting solution, and were further impregnated with ibuprofen using supercritical carbon dioxide (scCO(2)) in batch mode. The influence of the membrane functionalization in the controlled release of ibuprofen was studied by performing in vitro experiments in buffer solution pH at 7.4. The release of the anti-inflammatory drug could be tuned by varying the cyclodextrin content on the membranes.

Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons.

PubMed

Kim, Jae-Ick; Ganesan, Subhashree; Luo, Sarah X; Wu, Yu-Wei; Park, Esther; Huang, Eric J; Chen, Lu; Ding, Jun B

2015-10-02

Midbrain dopamine neurons are an essential component of the basal ganglia circuitry, playing key roles in the control of fine movement and reward. Recently, it has been demonstrated that γ-aminobutyric acid (GABA), the chief inhibitory neurotransmitter, is co-released by dopamine neurons. Here, we show that GABA co-release in dopamine neurons does not use the conventional GABA-synthesizing enzymes, glutamate decarboxylases GAD65 and GAD67. Our experiments reveal an evolutionarily conserved GABA synthesis pathway mediated by aldehyde dehydrogenase 1a1 (ALDH1a1). Moreover, GABA co-release is modulated by ethanol (EtOH) at concentrations seen in blood alcohol after binge drinking, and diminished ALDH1a1 leads to enhanced alcohol consumption and preference. These findings provide insights into the functional role of GABA co-release in midbrain dopamine neurons, which may be essential for reward-based behavior and addiction. Copyright © 2015, American Association for the Advancement of Science.

Surface-functionalized, pH-responsive poly(lactic-co-glycolic acid)-based microparticles for intranasal vaccine delivery: Effect of surface modification with chitosan and mannan.

PubMed

Li, Ze; Xiong, Fangfang; He, Jintian; Dai, Xiaojing; Wang, Gaizhen

2016-12-01

In the present study, surface-functionalized, pH-responsive poly(lactic-co-glycolic acid) (PLGA) microparticles were investigated for nasal delivery of hepatitis B surface Antigen (HBsAg). pH-responsive PLGA, chitosan modified PLGA (CS-PLGA), mannan modified PLGA (MN-PLGA), mannan and chitosan co-modified PLGA (MN-CS-PLGA) microparticles were prepared utilizing a double-emulsion method. Antigen was released rapidly from four types of microparticles at pH5.0 and pH 6.0, but slowly released at pH 7.4. Mannan and chitosan surface modification enhanced intracellular microparticle uptake by macrophages. Following intracellular macrophage antigen uptake, antigen release occurred in three different patterns: fast release from PLGA and MN-PLGA microparticles in endosomes/lysosomes, slow release from CS-PLGA microparticles in cytoplasm and a combination of fast release and slow release patterns from MN-CS-PLGA microparticles. Furthermore, chitosan coating modification increased the residence time of CS-PLGA and MN-CS-PLGA microparticles in the nasal cavity. In vivo immunogenicity studies indicated that MN-CS-PLGA microparticles induced stronger humoral and cell-mediated immune responses compared with PLGA, MN-PLGA and CS-PLGA microparticles. These results suggest that surface modification of pH-responsive PLGA microparticles with mannan and chitosan is a promising tool for nasal delivery of HBsAg. Copyright © 2016. Published by Elsevier B.V.

Optimized preparation of in situ forming microparticles for the parenteral delivery of vinpocetine.

PubMed

Li, Jizhong; Chen, Fei; Hu, Chanjuan; He, Ling; Yan, Keshu; Zhou, Liying; Pan, Weisan

2008-06-01

A spherical symmetric design-response surface methodology was applied to optimize the preparation of vinpocetine-loaded poly(D,L-lactide-co-glycolide) PLGA in situ forming microparticles (ISM system). The influence of the ratio of PLGA to vinpocetine (w/w), the concentration of Tween 80 (w/v) and the volume of propylene glycol on the burst release, medium particle diameter and size distribution was evaluated. Scan electron microscopy of the optimized in situ microparticles exhibited spherical shape, and vinpocetine-loading mainly inside the microparticles. The data showed that the release of vinpocetine from in situ microparticles in vitro and in vivo lasted about 40 d. In vivo pharmacokinetic characteristics of the optimized in situ microparticles was assessed after they were intramuscularly injected into rats. HPLC method was used to determine the plasma concentration of vinpocetine. The absolute bioavailability of vinpocetine in the microparticles was 27.6% in rats, which suggested that PLGA in situ microparticles were a valuable system for the delivery of vinpocetine.

Self-Nanoemulsifying Drug Delivery System of Coenzyme (Q10) with Improved Dissolution, Bioavailability, and Protective Efficiency on Liver Fibrosis.

PubMed

Khattab, Abeer; Hassanin, Lobna; Zaki, Nashwah

2017-07-01

The aim of our investigation is to develop and characterize self-nanoemulsifying drug delivery systems (SNEDDS) of CoQ 10 to improve its water solubility, dissolution rate, and bioavailability, and then evaluate its biochemical and physiological effect on liver cirrhosis in rats compared with CoQ 10 powder. SNEDDS are isotropic and thermodynamically stable mixture of oil, surfactant, co-surfactant, and drug that form an oil/water nanoemulsion when added to aqueous phases with soft agitation. Upon administration, self-nanoemulsifying system becomes in contact with gastrointestinal fluid and forms o/w nanoemulsion by the aid of gastrointestinal motility. When the nanoemulsion is formed in the gastrointestinal tract, it presents the drug in a solubilized form inside small nano-sized droplets that provide a large surface area for enhancing the drug release and absorption. Solubility of CoQ 10 in various oils, surfactants, and co-surfactants were studied to identify the components of SNEDDS; pseudo-ternary phase diagrams were plotted to identify the efficient self-emulsifying regions. CoQ 10 -loaded SNEDDS were prepared using isopropyl myristate as oil; Cremophor El, Labrasol, or Tween80 as surfactant; and Transcutol as co-surfactant. The amount of CoQ 10 in each vehicle was 3%. The formulations that passed thermostability evaluation test were assessed for particle size analysis, morphological characterization, refractive index, zeta potential, viscosity, electroconductivity, drug release profile, as well as ex vivo permeability. Pharmacokinetics and hepatoprotective efficiency of the optimized SNEDDS of CoQ 10 compared with CoQ 10 suspension were performed. Results showed that all optimized formulae have the ability to form a good and stable nanoemulsion when diluted with water; the mean droplet size of all formulae was in the nanometric range (11.7-13.5 nm) with optimum polydispersity index values (0.2-0.21). All formulae showed negative zeta potential (-11.3 to -17.2), and maximum drug loading efficiency. One hundred percent of CoQ 10 was released from most formulae within 30 min. One hundred percent of CoQ 10 was permeated from all formulae through 10 h. The pharmacokinetic study in rabbits revealed a significant increase in bioavailability of CoQ 10 SNEDDS to 2.1-fold compared with CoQ 10 suspension after oral administration. Comparative effect of the optimized formulae on acute liver injury compared with CoQ 10 powder was also studied; it was found that all the liver biochemical markers as alanine transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), total protein (TP), and albumin were significantly improved at p < 0.05. Also, histochemical and histopthological studies confirm the biochemical results. Our results suggest the potential use of SNEDDS to increase the solubility of liphophilic drug as poorly water-soluble CoQ 10 and improve its oral absorption, so it can be more efficient to improve liver damage compared to CoQ 10 powder. These results demonstrated that CoQ 10 SNEDDS inhibited thioacetamide (TAA)-induced liver fibrosis mainly through suppression of collagen production.

Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy.

PubMed

Chacon, Jessica Ann; Pilon-Thomas, Shari; Sarnaik, Amod A; Radvanyi, Laszlo G

2013-09-01

Co-stimulation through members of the tumor necrosis factor receptor (TNFR) family appears to be critical for the generation of T cells with optimal effector-memory properties for adoptive cell therapy. Our work suggests that continuous 4-1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal therapeutic profile and that the administration of 4-1BB agonists upon adoptive cell transfer further improves antitumor T-cell functions.

Model-Free Optimal Tracking Control via Critic-Only Q-Learning.

PubMed

Luo, Biao; Liu, Derong; Huang, Tingwen; Wang, Ding

2016-10-01

Model-free control is an important and promising topic in control fields, which has attracted extensive attention in the past few years. In this paper, we aim to solve the model-free optimal tracking control problem of nonaffine nonlinear discrete-time systems. A critic-only Q-learning (CoQL) method is developed, which learns the optimal tracking control from real system data, and thus avoids solving the tracking Hamilton-Jacobi-Bellman equation. First, the Q-learning algorithm is proposed based on the augmented system, and its convergence is established. Using only one neural network for approximating the Q-function, the CoQL method is developed to implement the Q-learning algorithm. Furthermore, the convergence of the CoQL method is proved with the consideration of neural network approximation error. With the convergent Q-function obtained from the CoQL method, the adaptive optimal tracking control is designed based on the gradient descent scheme. Finally, the effectiveness of the developed CoQL method is demonstrated through simulation studies. The developed CoQL method learns with off-policy data and implements with a critic-only structure, thus it is easy to realize and overcome the inadequate exploration problem.

Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

PubMed

McRae, A; Hjorth, S; Mason, D; Dillon, L; Tice, T

1990-01-01

Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

Controlled release of GAG-binding enhanced transduction (GET) peptides for sustained and highly efficient intracellular delivery.

PubMed

Abu-Awwad, Hosam Al-Deen M; Thiagarajan, Lalitha; Dixon, James E

2017-07-15

Controlled release systems for therapeutic molecules are vital to allow the sustained local delivery of their activities which direct cell behaviour and enable novel regenerative strategies. Direct programming of cells using exogenously delivered transcription factors can by-pass growth factor signalling but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly, using GAG-binding domains which promote cell targeting, and cell penetrating peptides (CPPs) which allow cell entry. Herein we demonstrate that GET system can be used in controlled release systems to mediate sustained intracellular transduction over one week. We assessed the stability and activity of GET peptides in poly(dl-lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) prepared using a S/O/W double emulsion method. Efficient encapsulation (∼65%) and tailored protein release profiles could be achieved, however intracellular transduction was significantly inhibited post-release. To retain GET peptide activity we optimized a strategy of co-encapsulation of l-Histidine, which may form a complex with the PLGA degradation products under acidic conditions. Simulations of the polymer microclimate showed that hydrolytic acidic PLGA degradation products directly inhibited GET peptide transduction activity, and use of l-Histidine significantly enhanced released protein delivery. The ability to control the intracellular transduction of functional proteins into cells will facilitate new localized delivery methods and allow approaches to direct cellular behaviour for many regenerative medicine applications. The goal for regenerative medicine is to restore functional biological tissue by controlling and augmenting cellular behaviour. Either Transcription (TFs) or growth factors (GFs) can be presented to cells in spatio-temporal gradients for programming cell fate and gene expression. Here, we have created a sustained and controlled release system for GET (Glycosaminoglycan-enhanced transducing)-tagged proteins using S/O/W PLGA microparticle fabrication. We demonstrated that PLGA and its acidic degradants inhibit GET-mediated transduction, which can be overcome by using pH-activated l-Histidine. l-Histidine inhibits the electrostatic interaction of GET/PLGA and allows enhanced intracellular transduction. GET could provide a powerful tool to program cell behaviour either in gradients or with sustained delivery. We believe that our controlled release systems will allow application of GET for tissue regeneration directly by TF cellular programming. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Development and evaluation of co-formulated docetaxel and curcumin biodegradable nanoparticles for parenteral administration.

PubMed

Pawar, Harish; Wankhade, Shrikant Rameshrao; Yadav, Dharmendra K; Suresh, Sarasija

2016-09-01

Technology for development of biodegradable nanoparticles encapsulating combinations for enhanced efficacy. To develop docetaxel (DTX) and curcumin (CRM) co-encapsulated biodegradable nanoparticles for parenteral administration with potential for prolonged release and decreased toxicity. Modified emulsion solvent-evaporation technique was employed in the preparation of the nanoparticles optimized by the face centered-central composite design (FC-CCD). The uptake potential was studied in MCF-7 cells, while the toxicity was evaluated by in vitro hemolysis test. In vivo pharmacokinetic was evaluated in male Wistar rats. Co-encapsulated nanoparticles were developed of 219 nm size, 0.154 PDI, -13.74 mV zeta potential and 67.02% entrapment efficiency. Efficient uptake was observed by the nanoparticles in MCF-7 cells with decreased toxicity in comparison with the commercial DTX intravenous injection, Taxotere®. The nanoparticles exhibited biphasic release with initial burst release followed by sustained release for 5 days. The nanoparticles displayed a 4.3-fold increase in AUC (391.10 ± 32.94 versus 89.77 ± 10.58 μg/ml min) in comparison to Taxotere® with a 6.2-fold increase in MRT (24.78 ± 2.36 versus 3.58 ± 0.21 h). The nanoparticles exhibited increased uptake, prolonged in vitro and in vivo release, with decreased toxicity thus exhibiting potential for enhanced efficacy.

Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

PubMed Central

2013-01-01

Background and the aim of the study The objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology. Method A Box-Behnken design was made considering the mass ratio of drug to polymer (D/P), the volumetric proportion of the water to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the independent agents. PLGA-NPs were successfully prepared and the size (nm), entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from NPs post 1 and 8 hrs were assessed as the responses. Results The NPs were prepared in a spherical shape and the sizes range of 240 to 316 nm. The polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied between 14-62% and 2-6%, respectively. The optimized formulation with a desirability factor of 0.9 was selected and characterized. This formulation demonstrated the particle size of 270 nm, EE of 55%, DL of 3.9% and cumulative drug release of 79% after 12 hrs. In vitro release studies showed a burst release at the initial stage followed by a sustained release of sildenafil from NPs up to 12 hrs. The release kinetic of the optimized formulation was fitted to Higuchi model. Conclusions Sildenafil citrate NPs with small particle size, lipophilic feature, high entrapment efficiency and good loading capacity is produced by this method. Characterization of optimum formulation, provided by an evaluation of experimental data, showed no significant difference between calculated and measured data. PMID:24355133

Reconstruction of Atmospheric Tracer Releases with Optimal Resolution Features: Concentration Data Assimilation

NASA Astrophysics Data System (ADS)

Singh, Sarvesh Kumar; Turbelin, Gregory; Issartel, Jean-Pierre; Kumar, Pramod; Feiz, Amir Ali

2015-04-01

The fast growing urbanization, industrialization and military developments increase the risk towards the human environment and ecology. This is realized in several past mortality incidents, for instance, Chernobyl nuclear explosion (Ukraine), Bhopal gas leak (India), Fukushima-Daichi radionuclide release (Japan), etc. To reduce the threat and exposure to the hazardous contaminants, a fast and preliminary identification of unknown releases is required by the responsible authorities for the emergency preparedness and air quality analysis. Often, an early detection of such contaminants is pursued by a distributed sensor network. However, identifying the origin and strength of unknown releases following the sensor reported concentrations is a challenging task. This requires an optimal strategy to integrate the measured concentrations with the predictions given by the atmospheric dispersion models. This is an inverse problem. The measured concentrations are insufficient and atmospheric dispersion models suffer from inaccuracy due to the lack of process understanding, turbulence uncertainties, etc. These lead to a loss of information in the reconstruction process and thus, affect the resolution, stability and uniqueness of the retrieved source. An additional well known issue is the numerical artifact arisen at the measurement locations due to the strong concentration gradient and dissipative nature of the concentration. Thus, assimilation techniques are desired which can lead to an optimal retrieval of the unknown releases. In general, this is facilitated within the Bayesian inference and optimization framework with a suitable choice of a priori information, regularization constraints, measurement and background error statistics. An inversion technique is introduced here for an optimal reconstruction of unknown releases using limited concentration measurements. This is based on adjoint representation of the source-receptor relationship and utilization of a weight function which exhibits a priori information about the unknown releases apparent to the monitoring network. The properties of the weight function provide an optimal data resolution and model resolution to the retrieved source estimates. The retrieved source estimates are proved theoretically to be stable against the random measurement errors and their reliability can be interpreted in terms of the distribution of the weight functions. Further, the same framework can be extended for the identification of the point type releases by utilizing the maximum of the retrieved source estimates. The inversion technique has been evaluated with the several diffusion experiments, like, Idaho low wind diffusion experiment (1974), IIT Delhi tracer experiment (1991), European Tracer Experiment (1994), Fusion Field Trials (2007), etc. In case of point release experiments, the source parameters are mostly retrieved close to the true source parameters with least error. Primarily, the proposed technique overcomes two major difficulties incurred in the source reconstruction: (i) The initialization of the source parameters as required by the optimization based techniques. The converged solution depends on their initialization. (ii) The statistical knowledge about the measurement and background errors as required by the Bayesian inference based techniques. These are hypothetically assumed in case of no prior knowledge.

Smart IR780 Theranostic Nanocarrier for Tumor-Specific Therapy: Hyperthermia-Mediated Bubble-Generating and Folate-Targeted Liposomes.

PubMed

Guo, Fang; Yu, Meng; Wang, Jinping; Tan, Fengping; Li, Nan

2015-09-23

The therapeutic effectiveness of chemotherapy was hampered by dose-limiting toxicity and was optimal only when tumor cells were subjected to a maximum drug exposure. The purpose of this work was to design a dual-functional thermosensitive bubble-generating liposome (BTSL) combined with conjugated targeted ligand (folate, FA) and photothermal agent (IR780), to realize enhanced therapeutic and diagnostic functions. This drug carrier was proposed to target tumor cells owing to FA-specific binding, followed by triggering drug release due to the decomposition of encapsulated ammonium bicarbonate (NH4HCO3) (generated CO2 bubbles) by being subjected to near-infrared (near-IR) laser irradiation, creating permeable defects in the lipid bilayer that rapidly release drug. In vitro temperature-triggered release study indicated the BTSL system was sensitive to heat triggering, resulting in rapid drug release under hyperthermia. For in vitro cellular uptake experiments, different results were observed on human epidermoid carcinoma cells (KB cells) and human lung cancer cells (A549 cells) due to their different (positive or negative) response to FA receptor. Furthermore, in vivo biodistribution analysis and antitumor study indicated IR780-BTSL-FA could specifically target KB tumor cells, exhibiting longer circulation time than free drug. In the pharmacodynamics experiments, IR780-BTSL-FA efficiently inhibited tumor growth in nude mice with no evident side effect to normal tissues and organs. Results of this study demonstrated that the constructed smart theranostic nanocarrier IR780-BTSL-FA might contribute to establishment of tumor-selective and effective chemotherapy.

Postsynthetic Functionalization of Mg-MOF-74 with Tetraethylenepentamine: Structural Characterization and Enhanced CO2 Adsorption.

PubMed

Su, Xiao; Bromberg, Lev; Martis, Vladimir; Simeon, Fritz; Huq, Ashfia; Hatton, T Alan

2017-03-29

Postsynthetic functionalization of magnesium 2,5-dihydroxyterephthalate (Mg-MOF-74) with tetraethylenepentamine (TEPA) resulted in improved CO 2 adsorption performance under dry and humid conditions. XPS, elemental analysis, and neutron powder diffraction studies indicated that TEPA was incorporated throughout the MOF particle, although it coordinated preferentially with the unsaturated metal sites located in the immediate proximity to the surface. Neutron and X-ray powder diffraction analyses showed that the MOF structure was preserved after amine incorporation, with slight changes in the lattice parameters. The adsorption capacity of the functionalized amino-Mg-MOF-74 (TEPA-MOF) for CO 2 was as high as 26.9 wt % versus 23.4 wt % for the original MOF due to the extra binding sites provided by the multiunit amines. The degree of functionalization with the amines was found to be important in enhancing CO 2 adsorption, as the optimal surface coverage improved performance and stability under both pure CO 2 and CO 2 /H 2 O coadsorption, and with partially saturated surface coverage, optimal CO 2 capacity could be achieved under both wet and dry conditions by a synergistic binding of CO 2 to the amines as well as metal centers.

Substrate lability and plant activity controls greenhouse gas release from Neotropical peatland

NASA Astrophysics Data System (ADS)

Sjogersten, Sofie; Hoyos, Jorge; Lomax, Barry; Turner, Ben; Wright, Emma

2014-05-01

Almost one third of global CO2 emissions resulting from land use change and substantial CH4 emissions originate from tropical peatlands. However, our understanding of the controls of CO2 and CH4 release from tropical peatlands are limited. The aim of this study was to investigate the role of peat lability and the activity of the vegetation on gas release using a combination of field and laboratory experiments. We demonstrated that peat lability constrained CH4 production to the surface peat under anaerobic conditions. The presence of plants shifted the C balance from a C source to a C sink with respect to CO2 while the activity of the root system strongly influenced CH4 emissions through its impact on soil O2 inputs. Both field and laboratory data suggest a coupling between the photosynthetic activity of the vegetation and the release of both CO2 and CH4 following the circadian rhythm of the dominant plant functional types. Forest clearance for agriculture resulted in elevated CH4 release, which we attribute in part to the cessation of root O2 inputs to the peat. We conclude that high emissions of CO2 and CH4 from forested tropical peatlands are likely driven by labile C inputs from the vegetation but that root O2 release may limit CH4 emissions.

Temozolomide-loaded PLGA nanoparticles to treat glioblastoma cells: a biophysical and cell culture evaluation.

PubMed

Ananta, Jeyarama S; Paulmurugan, Ramasamy; Massoud, Tarik F

2016-01-01

Current chemotherapies for brain glioblastoma do not achieve sufficient drug concentrations within tumors. Polymeric nanoparticles have useful physicochemical properties that make them promising as nanoparticle platforms for glioblastoma drug delivery. Poly[lactic-co-glycolic acid] (PLGA) nanoparticles encapsulating temozolomide (TMZ) could improve localized delivery and sustained drug release to glioblastomas. We investigated three different procedures to encapsulate TMZ within PLGA nanoparticles. We studied the biophysical features of optimized nanocarriers, including their size, shape, surface properties, and release characteristics of TMZ. We evaluated the antiproliferative and cytotoxic effects of TMZ-loaded PLGA nanoparticles on U87 MG glioblastoma cells. A single emulsion technique using a TMZ saturated aqueous phase produced nanoparticles ≤200 nm in size allowing a maximal drug loading of 4.4% w/w of polymer. There was a bi-phasic drug release pattern, with 80% of TMZ released within the first 6 h. Nanoparticles accumulated in the cytoplasm after effective endocytosis. There was no significant difference in cytotoxic effect of TMZ encapsulated within PLGA nanoparticles and free TMZ. PLGA nanoparticles are not suitable as carriers of TMZ for glioblastoma drug delivery on account of the overall high IC50 values of glioblastoma cells to TMZ and poor loading and encapsulation efficiencies. Further biotechnological developments aimed at improving the loading of TMZ in PLGA nanoparticles or co-delivery of small molecule sensitizers to improve the response of human glioblastoma cells to TMZ are required for this approach to be considered and optimized for future clinical translation.

Nitrogen input inventory in the Nooksack-Abbotsford-Sumas Transboundary Region: Key component of an international nitrogen management study

EPA Science Inventory

Nitrogen (N) is an essential biological element, so optimizing N use for food production while minimizing the release of N and co-pollutants to the environment is an important challenge. The Nooksack-Abbotsford-Sumas Transboundary (NAS) Region, spanning a portion of the western...

Nitrogen input inventory in the Nooksack-Abbotsford-Sumas Transboundary Region: Key component of an international nitrogen management study.

EPA Science Inventory

Background/Question/Methods: Nitrogen (N) is an essential biological element, so optimizing N use for food production while minimizing the release of N and co-pollutants to the environment is an important challenge. The Nooksack-lower Fraser Valley, spanning a portion of the w...

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

PubMed

Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

2015-11-01

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Enzymatic hydrolysis optimization of microwave alkali pretreated wheat straw and ethanol production by yeast.

PubMed

Singh, Anita; Bishnoi, Narsi R

2012-03-01

Microwave alkali pretreated wheat straw was used for in-house enzyme production by Aspergillusflavus and Trichodermareesei. Produced enzymes were concentrated, pooled and assessed for the hydrolysis of pretreated wheat straw. Factors affecting hydrolysis were screened out by Placket-Burman design (PBD) and most significant factors were further optimized by Box-Behnken design (BBD). Under optimum conditions, 82% efficiency in hydrolysis yield was observed. After the optimization by response surface methodology (RSM), a model was proposed to predict the optimum value confirmed by the experimental results. The concentrated enzymatic hydrolyzate was fermented for ethanol production by Saccharomyces cerevisiae, Pichia stipitis and co-culture of both. The yield of ethanol was found to be 0.48 g(p)/g(s), 0.43 g(p)/g(s) and 0.40 g(p)/g(s) by S. cerevisiae, P. stipitis and by co-culture, respectively, using concentrated enzymatic hydrolyzate. During anaerobic fermentation 42.31 μmol/mL, 36.69 μmol/mL, 43.35 μmol/mL CO(2) was released by S. cerevisiae, P. stipitis and by co-culture, respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

Olivine dissolution in the presence of heterotrophic bacteria (Pseudomonas reactants) extracted from Icelandic groundwater of the CO2 injection pilot site

NASA Astrophysics Data System (ADS)

Shirokova, Liudmila; Pokrovsky, Oleg; Benezeth, Pascale; Gerard, Emmanuelle; Menez, Benedicte; Alfredsson, Helgi

2010-05-01

This work is aimed at experimental modeling of the effect of heterotrophic bacteria on dissolution of important rock-forming mineral, olivine, at the conditions of CO2 storage and sequestration. Heterotrophic aerobic gram-negative bacteria were extracted from deep underground water (HK31, 1700 m deep and, t = 25-30°C) of basaltic aquifer located within the Hellisheidi CO2 injection pilot site (Iceland). Following this sampling, we separated, using culture on nutrient agar plates, four different groups of gram-negative aerobic bacteria. The enzymatic activity of studied species has been evaluated using Biolog Ecoplates and their genetic identification was performed using 18-S RNA analysis. The optimal growth conditions of bacteria on Brain Hearth Broth nutrient have been determined as 5 to 37°C and growth media pH varied from 7.0-8.2. Culturing experiments allowed determining the optimal physico-chemical conditions for bacteria experiments in the presence of basic Ca, Mg-containing silicates. Olivine (Fo92) was chosen as typical mineral of basalt, widely considered in carbon dioxide sequestration mechanisms. Dissolution experiments were performed in constant-pH (7 to 9), bicarbonate-buffered (0.001 to 0.05 M) nutrient-diluted media in batch reactors at 0-30 bars of CO2 in the presence of various biomass of Pseudomonas reactants. The release rate of magnesium, silica and iron was measured as a function of time in the presence of live, actively growing, dead (autoclaved or glutaraldehyde-treated) cells and bacteria exometabolites. Both nutrient media diluted 10 times (to 100 mg DOC/L) and inert electrolyte (NaCl, no DOC) were used. Our preliminary results indicate that the pH and dissolved organic matter are the first-order parameters that control the element release from olivine at far from equilibrium conditions. The SEM investigation of reacted surfaces reveal formation of surface roughness with much stronger mineral alteration in the presence of live bacteria compared to experiments with dead biomass. Overall, this work allows better understanding of microbially-affected silicate dissolution in basaltic aquifers and provides a firm methodological basis for constructing the mixed-flow reactors for studying the interaction of heterotrophic bacteria with rock-forming silicates at the environmental conditions of CO2-storage.

Comb-like amphiphilic copolymers bearing acetal-functionalized backbones with the ability of acid-triggered hydrophobic-to-hydrophilic transition as effective nanocarriers for intracellular release of curcumin.

PubMed

Zhao, Junqiang; Wang, Haiyang; Liu, Jinjian; Deng, Liandong; Liu, Jianfeng; Dong, Anjie; Zhang, Jianhua

2013-11-11

The pH-responsive micelles have enormous potential as nanosized drug carriers for cancer therapy due to their physicochemical changes in response to the tumor intracellular acidic microenvironment. Herein, a series of comb-like amphiphilic copolymers bearing acetal-functionalized backbone were developed based on poly[(2,4,6-trimethoxybenzylidene-1,1,1-tris(hydroxymethyl) ethane methacrylate-co-poly(ethylene glycol) methyl ether methacrylate] [P(TTMA-co-mPEGMA)] as effective nanocarriers for intracellular curcumin (CUR) release. P(TTMA-co-mPEGMA) copolymers with different hydrophobic-hydrophilic ratios were prepared by one-step reversible addition fragmentation chain transfer (RAFT) copolymerization of TTMA and mPEGMA. Their molecular structures and chemical compositions were confirmed by (1)H NMR, Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). P(TTMA-co-mPEGMA) copolymers could self-assemble into nanosized micelles in aqueous solution and displayed low critical micelle concentration (CMC). All P(TTMA-co-mPEGMA) micelles displayed excellent drug loading capacity, due to the strong π-π conjugate action and hydrophobic interaction between the PTTMA and CUR. Moreover, the hydrophobic PTTMA chain could be selectively hydrolyzed into a hydrophilic backbone in the mildly acidic environment, leading to significant swelling and final disassembly of the micelles. These morphological changes of P(TTMA-co-mPEGMA) micelles with time at pH 5.0 were determined by DLS and TEM. The in vitro CUR release from the micelles exhibited a pH-dependent behavior. The release rate of CUR was significantly accelerated at mildly acidic pH of 4.0 and 5.0 compared to that at pH 7.4. Toxicity test revealed that the P(TTMA-co-mPEGMA) copolymers exhibited low cytotoxicity, whereas the CUR-loaded micelles maintained high cytotoxicity for HepG-2 and EC-109 cells. The results indicated that the novel P(TTMA-co-mPEGMA) micelles with low CMC, small and tunable sizes, high drug loading, pH-responsive drug release behavior, and good biocompatibility may have potential as hydrophobic drug delivery nanocarriers for cancer therapy with intelligent delivery.

Dynamic compression and volatile release of carbonates

NASA Technical Reports Server (NTRS)

Tyburczy, J. A.; Ahrens, T. J.

1984-01-01

Particle velocity profiles upon shock compression and isentropic releases were measured for polycrystalline calcite. The Solenhofen limestone release paths lie, close to the Hugoniot. Calcite 3 to 2 transition, upon release, was observed, but rarefaction shocks were not detected. The equation of state is used to predict the fraction of material devolatilized upon isentropic release as a function of shock pressure. The effect of ambient partial pressure of CO2 on the calculations is demonstrated and considered in models of atmospheric evolution by impact induced mineral devolatilization. The radiative characteristics of shocked calcite indicate that localization of thermal energy occurs under shock compression. Shock entropy calculations result in a minimum estimate of 90% devolatilization upon complete release from 10 GPa. Isentropic release paths from calculated continuum Hugoniot temperatures cross into the CaO (solid) + CO2 (vapor) field at improbably low pressures. It is found that release paths from measured shock temperatures cross into the melt plus vapor field at pressures greater than .5 GPa, which suggests that devolatilization is initiated at the shear banding sites.

Cyclosporine a loaded solid lipid nanoparticles: optimization of formulation, process variable and characterization.

PubMed

Varia, Jigisha K; Dodiya, Shamsunder S; Sawant, Krutika K

2008-01-01

Solid lipid nanoparticles (SLNs) loaded with Cyclosporine A using glyceryl monostearate (GMS) and glyceryl palmitostearate (GPS) as lipid matrices were prepared by melt-homogenization using high-pressure homogenizer. Various process parameters such as homogenization pressure, homogenization cycles and formulation parameters such as ratio of drug: lipid, emulsifier: lipid and emulsifier: co-emulsifier were optimized using particle size and entrapment efficiencies as the dependent variables. The mean particle size of optimized batches of the GMS SLN and GPS SLN were found to be 131 nm and 158 nm and their entrapment efficiencies were 83 +/- 3.08% and 97 +/- 2.59% respectively. To improve the handling processing and stability of the prepared SLNs, the SLN dispersions were spray dried and its effect on size and reconstitution parameters were evaluated. The spray drying of SLNs did not significantly alter the size of SLNs and they exhibited good redispersibility. Solid state studies such as Infra Red Spectroscopy and Differential Scanning Calorimetry indicated absence of any chemical interaction between Cyclosporine A and the lipids. Scanning Electron Microscopy of optimized formulations showed spherical shape with smooth and non porous surface. In vitro release studies revealed that GMS based SLNs released the drug faster (41.12% in 20 hours) than GPS SLNs (7.958% in 20 hours). Release of Cyclosporine A from GMS SLN followed Higuchi equation better than first order while release from GPS SLN followed first order better than Higuchi model.

Anion-activated, thermoreversible gelation system for the capture, release, and visual monitoring of CO2

NASA Astrophysics Data System (ADS)

Zhang, Xin; Lee, Songyi; Liu, Yifan; Lee, Minji; Yin, Jun; Sessler, Jonathan L.; Yoon, Juyoung

2014-04-01

Carbon dioxide (CO2) is an important green house gas. This is providing an incentive to develop new strategies to detect and capture CO2. Achieving both functions within a single molecular system represents an unmet challenge in terms of molecular design and could translate into enhanced ease of use. Here, we report an anion-activated chemosensor system, NAP-chol 1, that permits dissolved CO2 to be detected in organic media via simple color changes or through ratiometric differences in fluorescence intensity. NAP-chol 1 also acts as a super gelator for DMSO. The resulting gel is transformed into a homogeneous solution upon exposure to fluoride anions. Bubbling with CO2 regenerates the gel. Subsequent flushing with N2 or heating serves to release the CO2 and reform the sol form. This series of transformations is reversible and can be followed by easy-to-discern color changes. Thus, NAP-chol 1 allows for the capture and release of CO2 gas while acting as a three mode sensing system. In particular, it permits CO2 to be detected through reversible sol-gel transitions, simple changes in color, or ratiometric monitoring of the differences in the fluorescence features.

CO2 Capture Using Electric Fields: Low-Cost Electrochromic Film on Plastic for Net-Zero Energy Building

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2010-01-01

Broad Funding Opportunity Announcement Project: Two faculty members at Lehigh University created a new technique called supercapacitive swing adsorption (SSA) that uses electrical charges to encourage materials to capture and release CO2. Current CO2 capture methods include expensive processes that involve changes in temperature or pressure. Lehigh University’s approach uses electric fields to improve the ability of inexpensive carbon sorbents to trap CO2. Because this process uses electric fields and not electric current, the overall energy consumption is projected to be much lower than conventional methods. Lehigh University is now optimizing the materials to maximize CO2 capture and minimize themore » energy needed for the process.« less

In silico and in vitro methods to optimize the performance of experimental gastroretentive floating mini-tablets.

PubMed

Eberle, Veronika A; Häring, Armella; Schoelkopf, Joachim; Gane, Patrick A C; Huwyler, Jörg; Puchkov, Maxim

2016-01-01

Development of floating drug delivery systems (FDDS) is challenging. To facilitate this task, an evaluation method was proposed, which allows for a combined investigation of drug release and flotation. It was the aim of the study to use functionalized calcium carbonate (FCC)-based lipophilic mini-tablet formulations as a model system to design FDDS with a floating behavior characterized by no floating lag time, prolonged flotation and loss of floating capability after complete drug release. Release of the model drug caffeine from the mini-tablets was assessed in vitro by a custom-built stomach model. A cellular automata-based model was used to simulate tablet dissolution. Based on the in silico data, floating forces were calculated and analyzed as a function of caffeine release. Two floating behaviors were identified for mini-tablets: linear decrease of the floating force and maintaining of the floating capability until complete caffeine release. An optimal mini-tablet formulation with desired drug release time and floating behavior was developed and tested. A classification system for a range of varied floating behavior of FDDS was proposed. The FCC-based mini-tablets had an ideal floating behavior: duration of flotation is defined and floating capability decreases after completion of drug release.

Modular assembly of thick multifunctional cardiac patches

PubMed Central

Fleischer, Sharon; Shapira, Assaf; Feiner, Ron; Dvir, Tal

2017-01-01

In cardiac tissue engineering cells are seeded within porous biomaterial scaffolds to create functional cardiac patches. Here, we report on a bottom-up approach to assemble a modular tissue consisting of multiple layers with distinct structures and functions. Albumin electrospun fiber scaffolds were laser-patterned to create microgrooves for engineering aligned cardiac tissues exhibiting anisotropic electrical signal propagation. Microchannels were patterned within the scaffolds and seeded with endothelial cells to form closed lumens. Moreover, cage-like structures were patterned within the scaffolds and accommodated poly(lactic-co-glycolic acid) (PLGA) microparticulate systems that controlled the release of VEGF, which promotes vascularization, or dexamethasone, an anti-inflammatory agent. The structure, morphology, and function of each layer were characterized, and the tissue layers were grown separately in their optimal conditions. Before transplantation the tissue and microparticulate layers were integrated by an ECM-based biological glue to form thick 3D cardiac patches. Finally, the patches were transplanted in rats, and their vascularization was assessed. Because of the simple modularity of this approach, we believe that it could be used in the future to assemble other multicellular, thick, 3D, functional tissues. PMID:28167795

Characterization and mosquito repellent activity of citronella oil nanoemulsion.

PubMed

Sakulku, Usawadee; Nuchuchua, Onanong; Uawongyart, Napaporn; Puttipipatkhachorn, Satit; Soottitantawat, Apinan; Ruktanonchai, Uracha

2009-05-08

Encapsulated citronella oil nanoemulsion prepared by high pressure homogenization at varying amounts of surfactant and glycerol, was studied in terms of the droplet size, stability, release characteristics and in vivo mosquito protection. Transparent nanoemulsion can be obtained at optimal concentration of 2.5% surfactant and 100% glycerol. Physical appearance and the stability of the emulsion were greatly improved through an addition of glycerol, owing to its co-solvent and highly viscous property. The increasing emulsion droplet increased the oil retention. The release behavior could be attributed to the effect of droplet size and concentrations of surfactant and glycerol. By fitting to Higuchi's equation, an increase in glycerol and surfactant concentrations resulted in slow release of the oil. The release rate related well to the protection time where a decrease in release rate can prolong mosquito protection time.

A simple and rapid approach to evaluate the in vitro in vivo role of release controlling agent ethyl cellulose ether derivative polymer.

PubMed

Akhlaq, Muhammad; Khan, Gul Majid; Jan, Syed Umer; Wahab, Abdul; Hussain, Abid; Nawaz, Asif; Abdelkader, Hamdy

2014-11-01

Diclofenac sodium (DCL-Na) conventional oral tablets exhibit serious side effects when given for a longer period leading to noncompliance. Controlled release matrix tablets of diclofenac sodium were formulated using simple blending (F-1), solvent evaporation (F-2) and co-precipitation techniques (F-3). Ethocel® Standard 7 FP Premium Polymer (15%) was used as a release controlling agent. Drug release study was conducted in 7.4 pH phosphate buffer solutions as dissolution medium in vitro. Pharmacokinetic parameters were evaluated using albino rabbits. Solvent evaporation technique was found to be the best release controlling technique thereby prolonging the release rate up to 24 hours. Accelerated stability studies of the optimized test formulation (F-2) did not show any significant change (p<0.05) in the physicochemical characteristics and release rate when stored for six months. A simple and rapid method was developed for DCL-Na active moiety using HPLC-UV at 276nm. The optimized test tablets (F-2) significantly (p<0.05) exhibited peaks plasma concentration (cmax=237.66±1.98) and extended the peak time (tmax=4.63±0.24). Good in-vitro in vivo correlation was found (R(2)=0.9883) against drug absorption and drug release. The study showed that once-daily controlled release matrix tablets of DCL-Na were successfully developed using Ethocel® Standard 7 FP Premium.

Oxygen Release Induced Chemomechanical Breakdown of Layered Cathode Materials

DOE PAGES

Mu, Linqin; Lin, Ruoqian; Xu, Rong; ...

2018-04-18

Chemical and mechanical properties interplay on the nanometric scale and collectively govern the functionalities of battery materials. Understanding the relationship between the two can inform the design of battery materials with optimal chemomechanical properties for long-life lithium batteries. Herein, we report a mechanism of nanoscale mechanical breakdown in layered oxide cathode materials, originating from oxygen release at high states of charge under thermal abuse conditions. Here, we observe that the mechanical breakdown of charged Li 1-xNi 0.4Mn 0.4Co 0.2O 2 materials proceeds via a two-step pathway involving intergranular and intragranular crack formation. Owing to the oxygen release, sporadic phase transformationsmore » from the layered structure to the spinel and/or rocksalt structures introduce local stress, which initiates microcracks along grain boundaries and ultimately leads to the detachment of primary particles; i.e., intergranular crack formation. Furthermore, intragranular cracks (pores and exfoliations) form, likely due to the accumulation of oxygen vacancies and continuous phase transformations at the surfaces of primary particles. Finally, finite element modeling confirms our experimental observation that the crack formation is attributable to formation of oxygen vacancies, oxygen release, and phase transformations. This study is designed to directly observe the chemomechanical behavior of layered oxide cathode materials and provides a chemical basis for strengthening primary and secondary particles by stabilizing the oxygen anions in the lattice.« less

Oxygen Release Induced Chemomechanical Breakdown of Layered Cathode Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mu, Linqin; Lin, Ruoqian; Xu, Rong

Chemical and mechanical properties interplay on the nanometric scale and collectively govern the functionalities of battery materials. Understanding the relationship between the two can inform the design of battery materials with optimal chemomechanical properties for long-life lithium batteries. Herein, we report a mechanism of nanoscale mechanical breakdown in layered oxide cathode materials, originating from oxygen release at high states of charge under thermal abuse conditions. Here, we observe that the mechanical breakdown of charged Li 1-xNi 0.4Mn 0.4Co 0.2O 2 materials proceeds via a two-step pathway involving intergranular and intragranular crack formation. Owing to the oxygen release, sporadic phase transformationsmore » from the layered structure to the spinel and/or rocksalt structures introduce local stress, which initiates microcracks along grain boundaries and ultimately leads to the detachment of primary particles; i.e., intergranular crack formation. Furthermore, intragranular cracks (pores and exfoliations) form, likely due to the accumulation of oxygen vacancies and continuous phase transformations at the surfaces of primary particles. Finally, finite element modeling confirms our experimental observation that the crack formation is attributable to formation of oxygen vacancies, oxygen release, and phase transformations. This study is designed to directly observe the chemomechanical behavior of layered oxide cathode materials and provides a chemical basis for strengthening primary and secondary particles by stabilizing the oxygen anions in the lattice.« less

Olfactory bulb short axon cell release of GABA and dopamine produces a temporally biphasic inhibition-excitation response in external tufted cells

PubMed Central

Liu, Shaolin; Plachez, Celine; Shao, Zuoyi; Puche, Adam; Shipley, Michael T.

2013-01-01

Evidence for co-expression of two or more classic neurotransmitters in neurons has increased but less is known about co-transmission. Ventral tegmental area (VTA) neurons, co-release dopamine (DA), the excitatory transmitter glutamate and the inhibitory transmitter GABA onto target cells in the striatum. Olfactory bulb (OB) short axon cells (SACs) form interglomerular connections and co-express markers for dopamine (DA) and GABA. Using an optogenetic approach we provide evidence that mouse OB SACs release both GABA and DA onto external tufted cells (ETCs) in other glomeruli. Optical activation of channelrhodopsin specifically expressed in DAergic SACs produced a GABAA receptor-mediated monosynaptic inhibitory response followed by DA-D1-like receptor-mediated excitatory response in ETCs. The GABAA receptor-mediated hyperpolarization activates Ih current in ETCs; synaptically released DA increases Ih, which enhances post-inhibitory rebound spiking. Thus, the opposing actions of synaptically released GABA and DA are functionally integrated by Ih to generate an inhibition-to-excitation “switch” in ETCs. Consistent with the established role of Ih in ETC burst firing, we show that endogenous DA release increases ETC spontaneous bursting frequency. ETCs transmit sensory signals to mitral/tufted output neurons and drive intraglomerular inhibition to shape glomerulus output to downstream olfactory networks. GABA and DA co-transmission from SACs to ETCs may play a key role in regulating output coding across the glomerular array. PMID:23407950

Contrasting roles of DAP10 and KARAP/DAP12 signaling adaptors in activation of the RBL-2H3 leukemic mast cell line.

PubMed

Anfossi, Nicolas; Lucas, Mathias; Diefenbach, Andreas; Bühring, Hans-Jörg; Raulet, David; Tomasello, Elena; Vivier, Eric

2003-12-01

A common feature of hematopoietic activating immunoreceptors resides in their association at the cell surface with transmembrane signaling adaptors. Several adaptors, such as the CD3 molecules, FcRgamma and KARAP/DAP12, harbor intracytoplasmic immunoreceptor tyrosine-based activation motifs (ITAM) that activate Syk-family protein tyrosine kinases. In contrast, another transmembrane adaptor, DAP10, bears a YxxM motif that delivers signals by activation of lipid kinase pathways. We show here that the human signal-regulatory protein SIRPbeta1 can associate with both DAP10 and KARAP/DAP12 in a model of RBL-2H3 cell transfectants. In association with KARAP/DAP12, SIRPbeta1 complexes are capable of inducing serotonin release and tumor necrosis factor (TNF) secretion. By contrast,in the absence of KARAP/DAP12, engagement of SIRPbeta1:DAP10 complexes does not lead to detectable serotonin release or TNF secretion by RBL-2H3 transfectants. However, triggering of SIRPbeta1:DAP10 complexes co-stimulates RBL-2H3 effector function induced by sub-optimal stimulation of the endogenous FcepsilonRI complex. Therefore, we report here a cellular model in which the association of a cell surface receptor with various signaling adaptors dictates the co-stimulatory or the direct stimulatory properties of the complex.

Co-Optimization of CO 2-EOR and Storage Processes in Mature Oil Reservoirs

DOE PAGES

Ampomah, William; Balch, Robert S.; Grigg, Reid B.; ...

2016-08-02

This article presents an optimization methodology for CO 2 enhanced oil recovery in partially depleted reservoirs. A field-scale compositional reservoir flow model was developed for assessing the performance history of an active CO 2 flood and for optimizing both oil production and CO 2 storage in the Farnsworth Unit (FWU), Ochiltree County, Texas. A geological framework model constructed from geophysical, geological, and engineering data acquired from the FWU was the basis for all reservoir simulations and the optimization method. An equation of state was calibrated with laboratory fluid analyses and subsequently used to predict the thermodynamic minimum miscible pressure (MMP).more » Initial history calibrations of primary, secondary and tertiary recovery were conducted as the basis for the study. After a good match was achieved, an optimization approach consisting of a proxy or surrogate model was constructed with a polynomial response surface method (PRSM). The PRSM utilized an objective function that maximized both oil recovery and CO 2 storage. Experimental design was used to link uncertain parameters to the objective function. Control variables considered in this study included: water alternating gas cycle and ratio, production rates and bottom-hole pressure of injectors and producers. Other key parameters considered in the modeling process were CO 2 purchase, gas recycle and addition of infill wells and/or patterns. The PRSM proxy model was ‘trained’ or calibrated with a series of training simulations. This involved an iterative process until the surrogate model reached a specific validation criterion. A sensitivity analysis was first conducted to ascertain which of these control variables to retain in the surrogate model. A genetic algorithm with a mixed-integer capability optimization approach was employed to determine the optimum developmental strategy to maximize both oil recovery and CO 2 storage. The proxy model reduced the computational cost significantly. The validation criteria of the reduced order model ensured accuracy in the dynamic modeling results. The prediction outcome suggested robustness and reliability of the genetic algorithm for optimizing both oil recovery and CO 2 storage. The reservoir modeling approach used in this study illustrates an improved approach to optimizing oil production and CO 2 storage within partially depleted oil reservoirs such as FWU. Lastly, this study may serve as a benchmark for potential CO 2–EOR projects in the Anadarko basin and/or geologically similar basins throughout the world.« less

Co-Optimization of CO 2-EOR and Storage Processes in Mature Oil Reservoirs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ampomah, William; Balch, Robert S.; Grigg, Reid B.

This article presents an optimization methodology for CO 2 enhanced oil recovery in partially depleted reservoirs. A field-scale compositional reservoir flow model was developed for assessing the performance history of an active CO 2 flood and for optimizing both oil production and CO 2 storage in the Farnsworth Unit (FWU), Ochiltree County, Texas. A geological framework model constructed from geophysical, geological, and engineering data acquired from the FWU was the basis for all reservoir simulations and the optimization method. An equation of state was calibrated with laboratory fluid analyses and subsequently used to predict the thermodynamic minimum miscible pressure (MMP).more » Initial history calibrations of primary, secondary and tertiary recovery were conducted as the basis for the study. After a good match was achieved, an optimization approach consisting of a proxy or surrogate model was constructed with a polynomial response surface method (PRSM). The PRSM utilized an objective function that maximized both oil recovery and CO 2 storage. Experimental design was used to link uncertain parameters to the objective function. Control variables considered in this study included: water alternating gas cycle and ratio, production rates and bottom-hole pressure of injectors and producers. Other key parameters considered in the modeling process were CO 2 purchase, gas recycle and addition of infill wells and/or patterns. The PRSM proxy model was ‘trained’ or calibrated with a series of training simulations. This involved an iterative process until the surrogate model reached a specific validation criterion. A sensitivity analysis was first conducted to ascertain which of these control variables to retain in the surrogate model. A genetic algorithm with a mixed-integer capability optimization approach was employed to determine the optimum developmental strategy to maximize both oil recovery and CO 2 storage. The proxy model reduced the computational cost significantly. The validation criteria of the reduced order model ensured accuracy in the dynamic modeling results. The prediction outcome suggested robustness and reliability of the genetic algorithm for optimizing both oil recovery and CO 2 storage. The reservoir modeling approach used in this study illustrates an improved approach to optimizing oil production and CO 2 storage within partially depleted oil reservoirs such as FWU. Lastly, this study may serve as a benchmark for potential CO 2–EOR projects in the Anadarko basin and/or geologically similar basins throughout the world.« less

Release the Prisoners Game

ERIC Educational Resources Information Center

Van Hecke, Tanja

2011-01-01

This article presents the mathematical approach of the optimal strategy to win the "Release the prisoners" game and the integration of this analysis in a math class. Outline lesson plans at three different levels are given, where simulations are suggested as well as theoretical findings about the probability distribution function and its mean…

Formulation, characterization, and in vitro/ex vivo evaluation of quercetin-loaded microemulsion for topical application.

PubMed

Kajbafvala, Azar; Salabat, Alireza; Salimi, Anayatollah

2016-12-09

The aim of this study was to develop a new microemulsion formulation for topical application of poorly soluble drug named quercetin. In order to design suitable microemulsion system, the pseudo-ternary phase diagrams of microemulsion systems were constructed at different surfactant/co-surfactant ratios using tween 80 as surfactant, transcutol ® P as a co-surfactant and oleic acid as an oil phase. Some physicochemical properties such as droplet size, density, refractive index, electrical conductivity, pH, surface tension, and viscosity of the microemulsion systems were measured at 298.15 K. The average hydrodynamic droplet size of the optimized microemulsions was obtained by dynamic light scattering method. Morphology assessment of the optimized quercetin-loaded microemulsion by transmission electron microscopy analysis indicated that the particles have the size of about 25 nm and spherical with narrow size distribution. Equilibrium solubility, in vitro drug release at a 24 h time period, release kinetic evaluation as well as ex vivo permeation and retention of quercetin-loaded microemulsions through rat skin has been investigated. The obtained results showed a slow release behavior without any transdermal delivery. Most of the formulations fitted best with zero-order kinetic model with a non-Fickian mechanisms. This study illustrated that the proposed QU-microemulsion has a good potential for use in sunscreen formulations. [Formula: see text].

Fabrication of nonfouling, bactericidal, and bacteria corpse release multifunctional surface through surface-initiated RAFT polymerization.

PubMed

Wang, Bailiang; Ye, Zi; Tang, Yihong; Han, Yuemei; Lin, Quankui; Liu, Huihua; Chen, Hao; Nan, Kaihui

Infections after surgery or endophthalmitis are potentially blinding complications caused by bacterial adhesion and subsequent biofilm formation on the intraocular lens. Neither single-function anti-adhesion surface nor contacting killing surface can exhibit ideal antibacterial function. In this work, a novel (2-(dimethylamino)-ethyl methacrylate- co -2-methacryloyloxyethyl phosphorylcholine) (p (DMAEMA- co -MPC)) brush was synthesized by "grafting from" method through reversible-addition fragmentation chain transfer polymerization. 1-Bromoheptane was used to quaternize the p (DMAEMA- co -MPC) brush coating and to endow the surface with bactericidal function. The success of the surface functionalization was confirmed by atomic force microscopy, water contact angle, and spectroscopic ellipsometry. The quaternary ammonium salt units were employed as efficient disinfection that can eliminate bacteria through contact killing, whereas the 2-methacryloyloxyethyl phosphorylcholine units were introduced to suppress unwanted nonspecific adsorption. The functionalized poly(dimethyl siloxane) surfaces showed efficiency in reducing bovine serum albumin adsorption and in inhibiting bacteria adhesion and biofilm formation. The copolymer brushes also demonstrated excellent bactericidal function against gram-positive ( Staphylococcus aureus ) bacteria measured by bacteria live/dead staining and shake-flask culture methods. The surface biocompatibility was evaluated by morphology and activity measurement with human lens epithelial cells in vitro. The achievement of the p (DMAEMA + - co -MPC) copolymer brush coating with nonfouling, bactericidal, and bacteria corpse release properties can be used to modify intraocular lenses.

Fabrication of nonfouling, bactericidal, and bacteria corpse release multifunctional surface through surface-initiated RAFT polymerization

PubMed Central

Wang, Bailiang; Ye, Zi; Tang, Yihong; Han, Yuemei; Lin, Quankui; Liu, Huihua; Chen, Hao; Nan, Kaihui

2017-01-01

Infections after surgery or endophthalmitis are potentially blinding complications caused by bacterial adhesion and subsequent biofilm formation on the intraocular lens. Neither single-function anti-adhesion surface nor contacting killing surface can exhibit ideal antibacterial function. In this work, a novel (2-(dimethylamino)-ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine) (p (DMAEMA-co-MPC)) brush was synthesized by “grafting from” method through reversible–addition fragmentation chain transfer polymerization. 1-Bromoheptane was used to quaternize the p (DMAEMA-co-MPC) brush coating and to endow the surface with bactericidal function. The success of the surface functionalization was confirmed by atomic force microscopy, water contact angle, and spectroscopic ellipsometry. The quaternary ammonium salt units were employed as efficient disinfection that can eliminate bacteria through contact killing, whereas the 2-methacryloyloxyethyl phosphorylcholine units were introduced to suppress unwanted nonspecific adsorption. The functionalized poly(dimethyl siloxane) surfaces showed efficiency in reducing bovine serum albumin adsorption and in inhibiting bacteria adhesion and biofilm formation. The copolymer brushes also demonstrated excellent bactericidal function against gram-positive (Staphylococcus aureus) bacteria measured by bacteria live/dead staining and shake-flask culture methods. The surface biocompatibility was evaluated by morphology and activity measurement with human lens epithelial cells in vitro. The achievement of the p (DMAEMA+-co-MPC) copolymer brush coating with nonfouling, bactericidal, and bacteria corpse release properties can be used to modify intraocular lenses. PMID:28053527

Optimization of Microemulsion Based Transdermal Gel of Triamcinolone.

PubMed

Jagdale, Swati; Chaudhari, Bhagyashree

2017-01-01

Triamcinolone is a long acting corticosteroid used in the treatment of arthritis, eczema, psoriasis and similar conditions which cause inflammation. Triamcinolone has half-life of 88min. Prolonged oral use is associated with gastrointestinal adverse effects as peptic ulcer, abdominal distention and ulcerative esophagitis as described in various patents. Microemulgel offers advantage of better stability, better loading capacity and controlled release especially for drug with short half life. Objective of the present study was to optimize microemulgel based transdermal delivery of triamcinolone. Saturated solubility of triamcinolone in various oils, surfactants and co-surfactants is estimated. Pseudo-ternary phase diagrams were constructed to determine the region of transparent microemulsion. Microemulsion was evaluated for globule size (FE-SEM, zetasizer), % transmittance, pH, viscosity, conductivity etc. Design of experiment was used to optimize microemulsion based gel. Carbopol 971P and HPMC K100M were used as independent variables. Microemulsion based gel was evaluated for in-vitro as well as ex-vivo parameters. Microemulsion was formulated with oleic acid, lauroglycol FCC and propylene glycol. PDI 0.197 indicated microemulsion is mono-disperse. 32 factorial design gave batch F8 as optimized. Design expert suggested drug release; gel viscosity and bio-adhesive strength were three significant dependant factors affecting the transdermal delivery. F8 showed drug release 92.62.16±1.22% through egg membrane, 95.23±1.44% through goat skin after 8hr and Korsmeyer-Peppas release model was followed. It can be concluded that a stable, effective controlled release transdermal microemulgel was optimised for triamcinolone. This would be a promising tool to deliver triamcinolone with enhanced bioavailability and reduced dosing frequency. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

pH responsive alginate polymeric rafts for controlled drug release by using box behnken response surface design

PubMed Central

Abbas, Ghulam; Hanif, Muhammad; Khan, Mahtab Ahmad

2017-01-01

Abstract Aim of the present work was to develop alginate raft forming tablets for controlled release pantoprazole sodium sesquihydrate (PSS). Box behnken design was used to optimize 15 formulations with three independent and three dependent variables. Physical tests of all formulations were within pharmacopoeial limits. Raft was characterized by their strength, thickness, resilience, acid neutralizing capacity, floating lag time and total floating time. Raft strength, thickness and resilience of optimized formulation AR9 were 7.43 ± 0.019 g, 5.8 ± 0.245 cm and greater than 480 min, respectively. Buffering and neutralizing capacity were 11.2 ± 1.01 and 6.5 ± 0.56 meq, respectively. Dissolution studies were performed by using simulated gastric fluid pH 1.2 and cumulative percentage release of optimized formulation AR9 was found 98%. First order release kinetics were followed and non-fickian diffusion was observed as value of n was greater than 0.45 in korsmeyer-peppas model. PSS, polymers, tablets and rafts were further characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). FTIR spectra of PSS, polymers and raft of optimized formulation AR9 showed peaks at 3223.09, 1688.17, 1586.67, 1302.64 and 1027.74 cm−1 due to –OH stretching, ester carbonyl group (C=O) stretching, existence of water and carboxylic group in raft, C–N stretching and –OH bending vibration showed no interaction between them. XRD showed diffraction lines indicates crystalline nature of PSS. DSC thermogram showed endothermic peaks at 250 °C for PSS. The developed raft was suitable for controlled release delivery of PSS. PMID:29491774

Universal Strategy for Ultrathin Pt-M (M = Fe, Co, Ni) Nanowires for Efficient Catalytic Hydrogen Generation.

PubMed

Bai, Shuxing; Huang, Bolong; Shao, Qi; Huang, Xiaoqing

2018-06-25

Methanol (CH 3 OH) reformation with water (H 2 O) to in situ release hydrogen (H 2 ) is regarded as a hopeful H 2 production approach for polymer electrolyte membrane fuel cells, while developing highly efficient CH 3 OH reformation catalysts still remains a great challenge. Herein, a series of Pt-based ultrafine nanowires (UNWs) with high surface atom ratio are used as highly active and stable catalysts for CH 3 OH reformation to H 2 . By tuning Pt 3 M (M = Fe, Co, Ni), support and the composition of the Pt x Fe UNWs, the optimized Pt 4 Fe UNWs/Al 2 O 3 exhibits excellent catalytic behaviors with the high H 2 turnover frequency reaching to 2035.8 h -1 , more than 4 times higher than that of Pt UNWs/Al 2 O 3 . The reaction mechanism investigated by diffuse reflectance infrared Fourier transform spectroscopy turns out that the production of H 2 undergoes the CH 3 OH decomposition to *CO and gas-shift reaction of *CO with H 2 O. Combing with the XPS result and the density functional theory calculations, the high CH 3 OH reformation activity of Pt 4 Fe UNWs/Al 2 O 3 is attributable to synergism between Pt and Fe, which facilitates H 2 desorption and intermediate HCOO* and *COO formations via the reaction between *CO and OH - .

Valence electronic structure of cobalt phthalocyanine from an optimally tuned range-separated hybrid functional.

PubMed

Brumboiu, Iulia Emilia; Prokopiou, Georgia; Kronik, Leeor; Brena, Barbara

2017-07-28

We analyse the valence electronic structure of cobalt phthalocyanine (CoPc) by means of optimally tuning a range-separated hybrid functional. The tuning is performed by modifying both the amount of short-range exact exchange (α) included in the hybrid functional and the range-separation parameter (γ), with two strategies employed for finding the optimal γ for each α. The influence of these two parameters on the structural, electronic, and magnetic properties of CoPc is thoroughly investigated. The electronic structure is found to be very sensitive to the amount and range in which the exact exchange is included. The electronic structure obtained using the optimal parameters is compared to gas-phase photo-electron data and GW calculations, with the unoccupied states additionally compared with inverse photo-electron spectroscopy measurements. The calculated spectrum with tuned γ, determined for the optimal value of α = 0.1, yields a very good agreement with both experimental results and with GW calculations that well-reproduce the experimental data.

PCL foamed scaffolds loaded with 5-fluorouracil anti-cancer drug prepared by an eco-friendly route.

PubMed

Salerno, Aurelio; Domingo, Concepción; Saurina, Javier

2017-06-01

This study describes a new preparation method, which combines freeze drying and supercritical CO 2 foaming approaches, for the preparation of drug delivery scaffolds of polycaprolactone loaded with 5-fluorouracil, an anti-cancer drug, with low solubility in scCO 2 . It is a principal objective of this work to design a scCO 2 strategy to reduce 5-Fu solubility limitations in its homogeneous distribution into a PCL scaffold through the design of an innovative processing method. The design of this process is considered valuable for the development of clean technology in pharmacy and medicine, since most of the active agents have a null solubility in scCO 2 ·Supercritical CO 2 is used as a blowing agent to induce polymer foaming by means of the low temperature pressure quench process. The resulting samples have been prepared under different operational conditions focused on enhancing the performance of the release process. In this case, design of experiments (DOE) was considered for a more comprehensive and systematic optimization of the product. In particular, drug amount, equals to 4.8 or 9.1wt%, process temperature, of 45 or 50°C and depressurization rate, equals to 0.1MPas -1 or 2MPas -1 were selected as the factors to be investigated by a three-factor at two-level full factorial design. Samples were characterized to establish porosity data, drug loading percentage and, especially, release profile chromatographically monitored. Results from DOE have concluded which are the best samples providing a sustained drug release for several days, which may be of great interest to develop materials for tissue engineering and sustained release applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Crimpy enables discrimination of pre and postsynaptic pools of a BMP at the Drosophila NMJ

PubMed Central

James, Rebecca E.; Hoover, Kendall M.; Bulgari, Dinara; McLaughlin, Colleen N.; Wilson, Christopher G.; Wharton, Kristi A.; Levitan, Edwin S.; Broihier, Heather T.

2014-01-01

Summary Distinct pools of the BMP Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, while muscle-derived Gbb regulates NMJ growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's pro-neurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling. In addition to trafficking Gbb to DCVs, we propose that Gbb/Cmpy co-release from presynaptic terminals defines a neuronal pro-transmission signal. PMID:25453556

CO Emission from an Impinging Non-Premixed Flame

PubMed Central

Chien, Y.C.; Escofet-Martin, D.; Dunn-Rankin, D.

2017-01-01

Carbon monoxide (CO) results from the incomplete oxidation of hydrocarbon fuels. While CO can be desirable in some syngas processes, it is a dangerous emission from fires, gas heaters, gas stoves, or furnaces where insufficient oxygen in the core reaction prevents complete oxidation of fuel to carbon dioxide and water, particularly when the reaction is interrupted by interaction with relatively cool solid boundaries. This research examines the physico-thermo-chemical processes responsible for carbon monoxide release from a small laminar non-premixed methane/air flame impinging on a nearby surface. We measure the changes in CO emission as correlated with variations in flame structure observed using planar laser induced fluorescence (PLIF of OH and 2-photon CO), and two-line OH PLIF thermometry, as a function of burner-to-plate distance. In particular, this work combines the use of OH and CO PLIF, and PLIF thermometry to describe the relative locations of the CO rich region, the peak heat release zone as indicated by chemiluminescence and OH gradients, and the extended oxidative zone in the impinging flames. The results show that CO release correlates strongly with stagnating flow-driven changes in the location and extent of high concentration regions of OH in surface-impinging diffusion flames. PMID:28989179

Anion-activated, thermoreversible gelation system for the capture, release, and visual monitoring of CO2

PubMed Central

Zhang, Xin; Lee, Songyi; Liu, Yifan; Lee, Minji; Yin, Jun; Sessler, Jonathan L.; Yoon, Juyoung

2014-01-01

Carbon dioxide (CO2) is an important green house gas. This is providing an incentive to develop new strategies to detect and capture CO2. Achieving both functions within a single molecular system represents an unmet challenge in terms of molecular design and could translate into enhanced ease of use. Here, we report an anion-activated chemosensor system, NAP-chol 1, that permits dissolved CO2 to be detected in organic media via simple color changes or through ratiometric differences in fluorescence intensity. NAP-chol 1 also acts as a super gelator for DMSO. The resulting gel is transformed into a homogeneous solution upon exposure to fluoride anions. Bubbling with CO2 regenerates the gel. Subsequent flushing with N2 or heating serves to release the CO2 and reform the sol form. This series of transformations is reversible and can be followed by easy-to-discern color changes. Thus, NAP-chol 1 allows for the capture and release of CO2 gas while acting as a three mode sensing system. In particular, it permits CO2 to be detected through reversible sol-gel transitions, simple changes in color, or ratiometric monitoring of the differences in the fluorescence features. PMID:24699626

The mid-Cretaceous super plume, carbon dioxide, and global warming

NASA Technical Reports Server (NTRS)

Caldeira, Ken; Rampino, Michael R.

1991-01-01

Carbon-dioxide releases associated with a mid-Cretaceous super plume and the emplacement of the Ontong-Java Plateau have been suggested as a principal cause of the mid-Cretaceous global warming. A carbonate-silicate cycle model is developed to quantify the possible climatic effects of these CO2 releases, utilizing four different formulations for the rate of silicate-rock weathering as a function of atmospheric CO2. CO2 emissions resulting from super-plume tectonics could have produced atmospheric CO2 levels from 3.7 to 14.7 times the modern preindustrial value of 285 ppm. Based on the temperature sensitivity to CO2 increases used in the weathering-rate formulations, this would cause a global warming of from 2.8 to 7.7 C over today's glogal mean temperature. Altered continental positions and higher sea level may have been contributed about 4.8 C to mid-Cretaceous warming. Thus, the combined effects of paleogeographic changes and super-plume related CO2 emissions could be in the range of 7.6 to 12.5 C, within the 6 to 14 C range previously estimated for mid-Cretaceous warming. CO2 releases from oceanic plateaus alone are unlikely to have been directly responsible for more than 20 percent of the mid-Cretaceous increase in atmospheric CO2.

Development of WRF-CO2 4DVAR Data Assimilation System

NASA Astrophysics Data System (ADS)

Zheng, T.; French, N. H. F.

2016-12-01

Four dimensional variational (4DVar) assimilation systems have been widely used for CO2 inverse modeling at global scale. At regional scale, however, 4DVar assimilation systems have been lacking. At present, most regional CO2 inverse models use Lagrangian particle backward trajectory tools to compute influence function in an analytical/synthesis framework. To provide a 4DVar based alternative, we developed WRF-CO2 4DVAR based on Weather Research and Forecasting (WRF), its chemistry extension (WRF-Chem), and its data assimilation system (WRFDA/WRFPLUS). Different from WRFDA, WRF-CO2 4DVAR does not optimize meteorology initial condition, instead it solves for the optimized CO2 surface fluxes (sources/sink) constrained by atmospheric CO2 observations. Based on WRFPLUS, we developed tangent linear and adjoint code for CO2 emission, advection, vertical mixing in boundary layer, and convective transport. Furthermore, we implemented an incremental algorithm to solve for optimized CO2 emission scaling factors by iteratively minimizing the cost function in a Bayes framework. The model sensitivity (of atmospheric CO2 with respect to emission scaling factor) calculated by tangent linear and adjoint model agrees well with that calculated by finite difference, indicating the validity of the newly developed code. The effectiveness of WRF-CO2 4DVar for inverse modeling is tested using forward-model generated pseudo-observation data in two experiments: first-guess CO2 fluxes has a 50% overestimation in the first case and 50% underestimation in the second. In both cases, WRF-CO2 4DVar reduces cost function to less than 10-4 of its initial values in less than 20 iterations and successfully recovers the true values of emission scaling factors. We expect future applications of WRF-CO2 4DVar with satellite observations will provide insights for CO2 regional inverse modeling, including the impacts of model transport error in vertical mixing.

Optimizing an experimental design for an electromagnetic experiment

NASA Astrophysics Data System (ADS)

Roux, Estelle; Garcia, Xavier

2013-04-01

Most of geophysical studies focus on data acquisition and analysis, but another aspect which is gaining importance is the discussion on acquisition of suitable datasets. This can be done through the design of an optimal experiment. Optimizing an experimental design implies a compromise between maximizing the information we get about the target and reducing the cost of the experiment, considering a wide range of constraints (logistical, financial, experimental …). We are currently developing a method to design an optimal controlled-source electromagnetic (CSEM) experiment to detect a potential CO2 reservoir and monitor this reservoir during and after CO2 injection. Our statistical algorithm combines the use of linearized inverse theory (to evaluate the quality of one given design via the objective function) and stochastic optimization methods like genetic algorithm (to examine a wide range of possible surveys). The particularity of our method is that it uses a multi-objective genetic algorithm that searches for designs that fit several objective functions simultaneously. One main advantage of this kind of technique to design an experiment is that it does not require the acquisition of any data and can thus be easily conducted before any geophysical survey. Our new experimental design algorithm has been tested with a realistic one-dimensional resistivity model of the Earth in the region of study (northern Spain CO2 sequestration test site). We show that a small number of well distributed observations have the potential to resolve the target. This simple test also points out the importance of a well chosen objective function. Finally, in the context of CO2 sequestration that motivates this study, we might be interested in maximizing the information we get about the reservoir layer. In that case, we show how the combination of two different objective functions considerably improve its resolution.

TGF-beta1 release from biodegradable polymer microparticles: its effects on marrow stromal osteoblast function

NASA Technical Reports Server (NTRS)

Lu, L.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

2001-01-01

BACKGROUND: Controlled release of transforming growth factor-beta1 (TGF-beta1) to a bone defect may be beneficial for the induction of a bone regeneration cascade. The objectives of this work were to assess the feasibility of using biodegradable polymer microparticles as carriers for controlled TGF-beta1 delivery and the effects of released TGF-beta1 on the proliferation and differentiation of marrow stromal cells in vitro. METHODS: Recombinant human TGF-beta1 was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Fluorescein isothiocynate-labeled bovine serum albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content (0, 1, or 5% by weight [wt%]) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for as long as 28 days. Rat marrow stromal cells were seeded on a biodegradable poly(propylene fumarate) (PPF) substrate. The dose response and biological activity of released TGF-beta1 was determined after 3 days in culture. The effects of TGF-beta1 released from PLGA/PEG microparticles on marrow stromal cell proliferation and osteoblastic differentiation were assessed during a 21-day period. RESULTS: TGF-beta1 was encapsulated along with FITC-BSA into PLGA/PEG blend microparticles and released in a multiphasic fashion including an initial burst for as long as 28 days in vitro. Increasing the initial PEG content resulted in a decreased cumulative mass of released proteins. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. The degradation of PLGA was increased at higher PEG content and significantly accelerated at acidic pH conditions. Rat marrow stromal cells cultured on PPF substrates showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating that the activity of TGF-beta1 was retained during microparticle fabrication and after growth factor release. At an optimal TGF-beta1 dosage of 1.0 ng/ml after 3 days, the released TGF-beta1 enhanced the proliferation and osteoblastic differentiation of marrow stromal cells over 21 days of culture, with increased total cell number, alkaline phosphatase activity, and osteocalcin production. CONCLUSIONS: PLGA/PEG blend microparticles can serve as delivery vehicles for controlled release of TGF-beta1, and the released growth factor enhances marrow stromal cell proliferation and osteoblastic differentiation in vitro. CLINICAL RELEVANCE: Controlled release of TGF-beta1 from PLGA/PEG microparticles is representative of emerging tissue engineering technologies that may modulate cellular responses to encourage bone regeneration at a skeletal defect site.

Co-delivery of chemotherapeutics and proteins for synergistic therapy.

PubMed

He, Chaoliang; Tang, Zhaohui; Tian, Huayu; Chen, Xuesi

2016-03-01

Combination therapy with chemotherapeutics and protein therapeutics, typically cytokines and antibodies, has been a type of crucial approaches for synergistic cancer treatment. However, conventional approaches by simultaneous administration of free chemotherapeutic drugs and proteins lead to limitations for further optimizing the synergistic effects, due to the distinct in vivo pharmacokinetics and distribution of small drugs and proteins, insufficient tumor selectivity and tumor accumulation, unpredictable drug/protein ratios at tumor sites, short half-lives, and serious systemic adverse effects. Consequently, to obtain optimal synergistic anti-tumor efficacy, considerable efforts have been devoted to develop the co-delivery systems for co-incorporating chemotherapeutics and proteins into a single carrier system and subsequently releasing the dual or multiple payloads at desired target sites in a more controllable manner. The co-delivery systems result in markedly enhanced blood stability and in vivo half-lives of the small drugs and proteins, elevated tumor accumulation, as well as the capability of delivering the multiple agents to the same target sites with rational drug/protein ratios, which may facilitate maximizing the synergistic effects and therefore lead to optimal antitumor efficacy. This review emphasizes the recent advances in the co-delivery systems for chemotherapeutics and proteins, typically cytokines and antibodies, for systemic or localized synergistic cancer treatment. Moreover, the proposed mechanisms responsible for the synergy of chemotherapeutic drugs and proteins are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of the effect of sulfate, alkalinity and disinfector on iron release of iron pipe and iron corrosion scale characteristics under water quality changing condition using response surface methodology

NASA Astrophysics Data System (ADS)

Yang, Fan; Shi, Baoyou; Zhang, Weiyu; Guo, Jianbo; Wu, Nana; Liu, Xinyuan

2018-02-01

The response surface methodology (RSM), particularly Box-Behnken design model, was used in this study to evaluate the sulfate, alkalinity and free chlorine on iron release of pipe with groundwater supply history and its iron corrosion scale characteristics under water quality changing experiment. The RSM results together with response surface contour plots indicated that the iron release of pipe section reactors was positively related with Larson Ratio and free chlorine. The thin Corrosion scales with groundwater supply history upon collection site contained Fe3O4 (18%), α-FeOOH (64%), FeCO3 (9%), β-FeOOH (8%) and γ-FeOOH (5%), besides their averaged amorphous iron oxide content was 13.6%. After the RSM water quality changing experiment, Fe3O4, amorphous iron oxide and intermediate iron products (FeCO3, Green Rust (GR)) content on scale of Cl2Rs increased, while their α-FeOOH contents decreased and β-FeOOH disappeared. The high iron released Cl2Rs receiving higher LR water (1.40-2.04) contained highest FeCO3 (20%) and amorphous iron oxide (42%), while the low iron release Cl2Rs receiving lower LR water (0.52-0.73) had higher GR(6.5%) and the amorphous iron oxide (23.7%). In high LR water (>0.73), the thin and non-protective corrosion scale containing higher amorphous iron oxide, Fe(II) derived from new produced Fe3O4 or FeCO3 or GR was easy for oxidants and sulfate ions penetration, and had higher iron release. However the same unstable corrosion scale didn’t have much iron release in low LR water (≤0.73). RSM experiment indicated that iron release of these unstable corrosion scales had close relationship with water quality (Larson Ratio and disinfectant). Optimizing the water quality of new source water and using reasonable water purification measures can help to eliminate the red water case.

Spatial and temporal variations of diffuse CO2 degassing at El Hierro volcanic system: Relation to the 2011-2012 submarine eruption

NASA Astrophysics Data System (ADS)

Melián, Gladys; Hernández, Pedro A.; Padrón, Eleazar; Pérez, Nemesio M.; Barrancos, José; Padilla, Germán.; Dionis, Samara; Rodríguez, Fátima; Calvo, David; Nolasco, Dacil

2014-09-01

We report herein the results of extensive diffuse CO2 emission surveys performed on El Hierro Island in the period 1998-2012. More than 17,000 measurements of the diffuse CO2 efflux were carried out, most of them during the volcanic unrest period that started in July 2011. Two significant precursory signals based on geochemical and geodetical studies suggest that a magma intrusion processes might have started before 2011 in El Hierro Island. During the preeruptive and eruptive periods, the time series of the diffuse CO2 emission released by the whole island experienced two significant increases. The first started almost 2 weeks before the onset of the submarine eruption, reflecting a clear geochemical anomaly in CO2 emission, most likely due to increasing release of deep-seated magmatic gases to the surface. The second one, between 24 October and 27 November 2011, started before the most energetic seismic events of the volcanic-seismic unrest. The data presented here demonstrate that combined continuous monitoring studies and discrete surveys of diffuse CO2 emission provide important information to optimize the early warning system in volcano monitoring programs and to monitor the evolution of an ongoing volcanic eruption, even though it is a submarine eruption.

Novel Approach for in Situ Recovery of Lithium Carbonate from Spent Lithium Ion Batteries Using Vacuum Metallurgy.

PubMed

Xiao, Jiefeng; Li, Jia; Xu, Zhenming

2017-10-17

Lithium is a rare metal because of geographical scarcity and technical barrier. Recycling lithium resource from spent lithium ion batteries (LIBs) is significant for lithium deficiency and environmental protection. A novel approach for recycling lithium element as Li 2 CO 3 from spent LIBs is proposed. First, the electrode materials preobtained by mechanical separation are pyrolyzed under enclosed vacuum condition. During this process the Li is released as Li 2 CO 3 from the crystal structure of lithium transition metal oxides due to the collapse of the oxygen framework. An optimal Li recovery rate of 81.90% is achieved at 973 K for 30 min with a solid-to-liquid ratio of 25 g L -1 , and the purity rate of Li 2 CO 3 is 99.7%. The collapsed mechanism is then presented to explain the release of lithium element during the vacuum pyrolysis. Three types of spent LIBs including LiMn 2 O 4 , LiCoO 2 , and LiCo x Mn y Ni z O 2 are processed to prove the validity of in situ recycling Li 2 CO 3 from spent LIBs under enclosed vacuum condition. Finally, an economic assessment is taken to prove that this recycling process is positive.

Performance evaluation of a slow-release packing material-embedded functional microorganisms for biofiltration.

PubMed

Zhu, Rencheng; Li, Shunyi; Wu, Zhenjun; Dumont, Éric

2017-04-01

A composite packing material (CM-5) was prepared in this study, mainly consisting of compost with functional microorganisms, calcium carbonate (CaCO 3 ), perlite, cement and plant fiber. To get stronger compressive strength, mass ratios of these components were optimized based on single factor experiments, and finally adding amounts of perlite, cement, plant fiber, CaCO 3 , compost and binder at 18%, 18%, 7%, 13%, 17% and 27%, respectively. According to the optimum proportion, CM-5 was extruded in cylindrical shape (12 mm in diameter and 20 mm in length) with a bulk density of 470 kg m -3 , a moisture retention capacity of 49% and the microbial counts of × 10 5 CFU g -1 of packing material. The cumulative release rates of total organic carbon (TOC) and total nitrogen (TN) from CM-5 were 3.1% and 6.5%, respectively, after 19 times extraction in distilled water. To evaluate the H 2 S removal capacity, CM-5 was compared with an organic (corncob) and an inorganic (ceramsite) packing material in three biofilters. The results showed that CM-5 had higher H 2 S removal capacity compared with corncob and ceramsite. CM-5 could avoid the large fluctuation of pH value and pressure drop during the operation. The maximum H 2 S removal capacity of CM-5 was 12.9 g m -3  h -1 and the removal efficiency could maintain over 95.4% when the inlet H 2 S loading rate was lower than 11.3 g m -3  h -1 without any addition of nutrients and pH buffer substances. Besides, only 2-3 days were needed for the recovery of biofiltration performance after about two weeks of idle period.

Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres-Focus on Feature Selection.

PubMed

Zawbaa, Hossam M; Szlȩk, Jakub; Grosan, Crina; Jachowicz, Renata; Mendyk, Aleksander

2016-01-01

Poly-lactide-co-glycolide (PLGA) is a copolymer of lactic and glycolic acid. Drug release from PLGA microspheres depends not only on polymer properties but also on drug type, particle size, morphology of microspheres, release conditions, etc. Selecting a subset of relevant properties for PLGA is a challenging machine learning task as there are over three hundred features to consider. In this work, we formulate the selection of critical attributes for PLGA as a multiobjective optimization problem with the aim of minimizing the error of predicting the dissolution profile while reducing the number of attributes selected. Four bio-inspired optimization algorithms: antlion optimization, binary version of antlion optimization, grey wolf optimization, and social spider optimization are used to select the optimal feature set for predicting the dissolution profile of PLGA. Besides these, LASSO algorithm is also used for comparisons. Selection of crucial variables is performed under the assumption that both predictability and model simplicity are of equal importance to the final result. During the feature selection process, a set of input variables is employed to find minimum generalization error across different predictive models and their settings/architectures. The methodology is evaluated using predictive modeling for which various tools are chosen, such as Cubist, random forests, artificial neural networks (monotonic MLP, deep learning MLP), multivariate adaptive regression splines, classification and regression tree, and hybrid systems of fuzzy logic and evolutionary computations (fugeR). The experimental results are compared with the results reported by Szlȩk. We obtain a normalized root mean square error (NRMSE) of 15.97% versus 15.4%, and the number of selected input features is smaller, nine versus eleven.

Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres—Focus on Feature Selection

PubMed Central

Zawbaa, Hossam M.; Szlȩk, Jakub; Grosan, Crina; Jachowicz, Renata; Mendyk, Aleksander

2016-01-01

Poly-lactide-co-glycolide (PLGA) is a copolymer of lactic and glycolic acid. Drug release from PLGA microspheres depends not only on polymer properties but also on drug type, particle size, morphology of microspheres, release conditions, etc. Selecting a subset of relevant properties for PLGA is a challenging machine learning task as there are over three hundred features to consider. In this work, we formulate the selection of critical attributes for PLGA as a multiobjective optimization problem with the aim of minimizing the error of predicting the dissolution profile while reducing the number of attributes selected. Four bio-inspired optimization algorithms: antlion optimization, binary version of antlion optimization, grey wolf optimization, and social spider optimization are used to select the optimal feature set for predicting the dissolution profile of PLGA. Besides these, LASSO algorithm is also used for comparisons. Selection of crucial variables is performed under the assumption that both predictability and model simplicity are of equal importance to the final result. During the feature selection process, a set of input variables is employed to find minimum generalization error across different predictive models and their settings/architectures. The methodology is evaluated using predictive modeling for which various tools are chosen, such as Cubist, random forests, artificial neural networks (monotonic MLP, deep learning MLP), multivariate adaptive regression splines, classification and regression tree, and hybrid systems of fuzzy logic and evolutionary computations (fugeR). The experimental results are compared with the results reported by Szlȩk. We obtain a normalized root mean square error (NRMSE) of 15.97% versus 15.4%, and the number of selected input features is smaller, nine versus eleven. PMID:27315205

Optimization of encapsulation of a synthetic long peptide in PLGA nanoparticles: low-burst release is crucial for efficient CD8(+) T cell activation.

PubMed

Silva, A L; Rosalia, R A; Sazak, A; Carstens, M G; Ossendorp, F; Oostendorp, J; Jiskoot, W

2013-04-01

Overlapping synthetic long peptides (SLPs) hold great promise for immunotherapy of cancer. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are being developed as delivery systems to improve the potency of peptide-based therapeutic cancer vaccines. Our aim was to optimize PLGA NP for SLP delivery with respect to encapsulation and release, using OVA24, a 24-residue long synthetic antigenic peptide covering a CTL epitope of ovalbumin (SIINFEKL), as a model antigen. Peptide-loaded PLGA NPs were prepared by a double emulsion/solvent evaporation technique. Using standard conditions (acidic inner aqueous phase), we observed that either encapsulation was very low (1-30%), or burst release extremely high (>70%) upon resuspension of NP in physiological buffers. By adjusting formulation and process parameters, we uncovered that the pH of the first emulsion was critical to efficient encapsulation and controlled release. In particular, an alkaline inner aqueous phase resulted in circa 330 nm sized NP with approximately 40% encapsulation efficiency and low (<10%) burst release. These NP showed enhanced MHC class I restricted T cell activation in vitro when compared to high-burst releasing NP and soluble OVA24, proving that efficient entrapment of the antigen is crucial to induce a potent cellular immune response. Copyright © 2012 Elsevier B.V. All rights reserved.

Capreomycin oleate microparticles for intramuscular administration: Preparation, in vitro release and preliminary in vivo evaluation.

PubMed

Cambronero-Rojas, Adrián; Torres-Vergara, Pablo; Godoy, Ricardo; von Plessing, Carlos; Sepúlveda, Jacqueline; Gómez-Gaete, Carolina

2015-07-10

Capreomycin sulfate (CS) is a second-line drug used for the treatment of multidrug-resistant tuberculosis (MDR-TB). The adverse effects profile and uncomfortable administration scheme of CS has led to the development of formulations based on liposomes and polymeric microparticles. However, as CS is a water-soluble peptide that does not encapsulate properly into hydrophobic particulate matrices, it was necessary to reduce its aqueous solubility by forming the pharmacologically active capreomycin oleate (CO) ion pair. The aim of this research was to develop a new formulation of CO for intramuscular injection, based on biodegradable microparticles that encapsulate CO in order to provide a controlled release of the drug with reduced local and systemic adverse effects. The CO-loaded microparticles prepared by spray drying or solvent emulsion-evaporation were characterized in their morphology, encapsulation efficiency, in vitro/in vivo kinetics and tissue tolerance. Through scanning electron microscopy it was confirmed that the microparticles were monodisperse and spherical, with an optimal size for intramuscular administration. The interaction between CO and the components of the microparticle matrix was confirmed on both formulations by X-ray powder diffraction and differential scanning calorimetry analyses. The encapsulation efficiencies for the spray-dried and emulsion-evaporation microparticles were 92% and 56%, respectively. The in vitro kinetics performed on both formulations demonstrated a controlled and continuous release of CO from the microparticles, which was successfully reproduced on an in vivo rodent model. The results of the histological analysis demonstrated that none of the formulations produced significant tissue damage on the site of injection. Therefore, the results suggest that injectable CO microparticles obtained by spray drying and solvent emulsion-evaporation could represent an interesting therapeutic alternative for the treatment of MDR-TB. Copyright © 2015 Elsevier B.V. All rights reserved.

Characteristics of CO2 release from forest soil in the mountains near Beijing.

PubMed

Sun, Xiang Yang; Gao, Cheng Da; Zhang, Lin; Li, Su Yan; Qiao, Yong

2011-04-01

CO2 release from forest soil is a key driver of carbon cycling between the soil and atmosphere ecosystem. The rate of CO2 released from soil was measured in three forest stands (in the mountainous region near Beijing, China) by the alkaline absorption method from 2004 to 2006. The rate of CO2 released did not differ among the three stands. The CO2 release rate ranged from - 341 to 1,193 mg m(-2) h(-1), and the mean value over all three forests and sampling times was 286 mg m(-2) h(-1). CO2 release was positively correlated with soil water content and the soil temperature. Diurnally, CO2 release was higher in the day than at night. Seasonally, CO2 release was highest in early autumn and lowest in winter; in winter, negative values of CO2 release suggested that CO2 was absorbed by soil.

Prediction of dexamethasone release from PLGA microspheres prepared with polymer blends using a design of experiment approach.

PubMed

Gu, Bing; Burgess, Diane J

2015-11-10

Hydrophobic drug release from poly (lactic-co-glycolic acid) (PLGA) microspheres typically exhibits a tri-phasic profile with a burst release phase followed by a lag phase and a secondary release phase. High burst release can be associated with adverse effects and the efficacy of the formulation cannot be ensured during a long lag phase. Accordingly, the development of a long-acting microsphere product requires optimization of all drug release phases. The purpose of the current study was to investigate whether a blend of low and high molecular weight polymers can be used to reduce the burst release and eliminate/minimize the lag phase. A single emulsion solvent evaporation method was used to prepare microspheres using blends of two PLGA polymers (PLGA5050 (25 kDa) and PLGA9010 (113 kDa)). A central composite design approach was applied to investigate the effect of formulation composition on dexamethasone release from these microspheres. Mathematical models obtained from this design of experiments study were utilized to generate a design space with maximized microsphere drug loading and reduced burst release. Specifically, a drug loading close to 15% can be achieved and a burst release less than 10% when a composition of 80% PLGA9010 and 90 mg of dexamethasone is used. In order to better describe the lag phase, a heat map was generated based on dexamethasone release from the PLGA microsphere/PVA hydrogel composite coatings. Using the heat map an optimized formulation with minimum lag phase was selected. The microspheres were also characterized for particle size/size distribution, thermal properties and morphology. The particle size was demonstrated to be related to the polymer concentration and the ratio of the two polymers but not to the dexamethasone concentration. Copyright © 2015 Elsevier B.V. All rights reserved.

Single-Dose Electrospun Nanoparticles-in-Nanofibers Wound Dressings with Enhanced Epithelialization, Collagen Deposition, and Granulation Properties.

PubMed

Ali, Isra H; Khalil, Islam A; El-Sherbiny, Ibrahim M

2016-06-15

Phenytoin (Ph), an antiepileptic drug, was reported to exhibit high wound healing activity. However, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop new single-dose electrospun nanoparticles-in-nanofibers (NPs-in-NFs) wound dressings that allow a well-controlled release of Ph. These NPs-in-NFs systems are based on enhanced chitosan (CS)/poly(ethylene oxide) (PEO) electrospun nanofibers (NFs) incorporating optimized Ph-loaded nanocarriers. First, a study was conducted to investigate Ph loading efficiency into polymeric nanocarriers of different types; pluronic nanomicelles and poly(lactic-co-glycolic) acids nanoparticles (PLGA NPs). The drug release profile from the nanocarriers was further optimized via lecithin coating. Second, different electrospinning parameters were manipulated to fabricate beads-free homogeneous NFs with optimized polymer ratios. Plain and Ph-loaded nanocarriers were characterized using Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Both entrapment efficiency of Ph (EE%) and its release profile in phosphate buffer saline (PBS; pH 5.5), simulating the wound environment, were studied. Biodegradability, swelling, vapor permeability, and porosity of the developed Ph-loaded NPs-in-NFs wound dressings were investigated. Morphology of the NPs-in-NFs was also studied using SEM and confocal laser microscopy (CLSM). Besides, the release profiles of Ph from the optimized NPs-in-NFs were assessed. The newly developed wound dressings were evaluated in vitro for their cytotoxicity using human fibroblasts and in vivo using a wound healing mice model. Nanocarriers with particle size ranging from 100 to 180 nm were successfully prepared. All nanocarriers attained a high drug entrapment efficiency exceeding 94% and showed promising sustained release profiles compared to free Ph. Results also demonstrated that NFs incorporating the optimized lecithin-coated Ph-loaded PLGA NPs could be the most promising candidate for efficient wound healing. These NPs-in-NFs systems conferred a well-controlled and sustained release of Ph over 9 days. Moreover, they showed the best re-epithelization and healing quality during the in vivo study with minimal inflammatory and necrotic cells formation.

Improving the controlled release of water-insoluble emodin from amino-functionalized mesoporous silica

NASA Astrophysics Data System (ADS)

Xu, Yunqiang; Wang, Chunfeng; Zhou, Guowei; Wu, Yue; Chen, Jing

2012-06-01

Several types of amino-functionalized mesoporous silica, including F5-SBA-15, F10-SBA-15, and F15-SBA-15 were prepared through co-condensation of tetraethoxysilane (TEOS) and (3-aminopropyl)triethoxysilane (APTES) in varying molar ratios (5 mol%, 10 mol%, and 15 mol%) via a hydrothermal process. The materials obtained were characterized by means of small-angle X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption, Fourier transformed infrared spectra, and X-ray photoelectron spectroscopy. Increasing APTES molar ratios decreased the degree of orderliness of the functionalized mesoporous silica. Pure and amino-functionalized SBA-15 samples were employed as supports for the controlled release of water-insoluble drug emodin. Loading experiments showed that drug loading capacities mainly depended on the surface areas and pore diameters of the carriers. Controlled release profiles of emodin-loaded samples were studied in phosphate buffered saline (PBS, pH 7.4), and results indicated that the emodin release rate could be controlled by surface amino-functionalized carriers. Emodin loaded on functionalized mesoporous supports exhibited a lower release rate than that of loaded on pure SBA-15, emodin loaded on F10-SBA-15 showed the smallest release amount (71.74 wt%) after stirring in PBS for 60 h. Findings suggest that functionalized mesoporous SBA-15 is a promising carrier for achieving prolonged release time periods.

[Effect of slow-release aminophylline on pulmonary function in obstructive respiratory disease(author's transl)].

PubMed

Wiessmann, K J

1975-09-05

The effects on pulmonary function of a slow-release preparation of an oral broncholytic drug (containing 350 mg aminophylline, released over eight hours) was tested on 26 patients in a double-blind trial. There was a marked reduction of airway resistance and stimulation of breathing with decreased dynamic work of breathing. Distinctly improved alveolar function was demonstrated especially in a fall of arterial CO2 tension, but in some cases there was probably an increase in distribution abnormality. Central haemodynamic changes with a decreased in pulmonary artery pressure and changes in the other values lasted for more than ten hours on the first day of treatment, and were demonstrable on the fourth day even before the drug was taken that day. The criteria of an effective broncholytic slow-release drug with sustained effect were thus fulfilled.

Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound.

PubMed

Bazan-Peregrino, Miriam; Rifai, Bassel; Carlisle, Robert C; Choi, James; Arvanitis, Costas D; Seymour, Leonard W; Coussios, Constantin C

2013-07-10

Oncolytic viruses (OV) and ultrasound-enhanced drug delivery are powerful novel technologies. OV selectively self-amplify and kill cancer cells but their clinical use has been restricted by limited delivery from the bloodstream into the tumor. Ultrasound has been previously exploited for targeted release of OV in vivo, but its use to induce cavitation, microbubble oscillations, for enhanced OV tumor extravasation and delivery has not been previously reported. By identifying and optimizing the underlying physical mechanism, this work demonstrates that focused ultrasound significantly enhances the delivery and biodistribution of systemically administered OV co-injected with microbubbles. Up to a fiftyfold increase in tumor transgene expression was achieved, without any observable tissue damage. Ultrasound exposure parameters were optimized as a function of tumor reperfusion time to sustain inertial cavitation, a type of microbubble activity, throughout the exposure. Passive detection of acoustic emissions during treatment confirmed inertial cavitation as the mechanism responsible for enhanced delivery and enabled real-time monitoring of successful viral delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

Engineered collagen hydrogels for the sustained release of biomolecules and imaging agents: promoting the growth of human gingival cells.

PubMed

Choi, Jonghoon; Park, Hoyoung; Kim, Taeho; Jeong, Yoon; Oh, Myoung Hwan; Hyeon, Taeghwan; Gilad, Assaf A; Lee, Kwan Hyi

2014-01-01

We present here the in vitro release profiles of either fluorescently labeled biomolecules or computed tomography contrast nanoagents from engineered collagen hydrogels under physiological conditions. The collagen constructs were designed as potential biocompatible inserts into wounded human gingiva. The collagen hydrogels were fabricated under a variety of conditions in order to optimize the release profile of biomolecules and nanoparticles for the desired duration and amount. The collagen constructs containing biomolecules/nanoconstructs were incubated under physiological conditions (ie, 37°C and 5% CO2) for 24 hours, and the release profile was tuned from 20% to 70% of initially loaded materials by varying the gelation conditions of the collagen constructs. The amounts of released biomolecules and nanoparticles were quantified respectively by measuring the intensity of fluorescence and X-ray scattering. The collagen hydrogel we fabricated may serve as an efficient platform for the controlled release of biomolecules and imaging agents in human gingiva to facilitate the regeneration of oral tissues.

Engineered collagen hydrogels for the sustained release of biomolecules and imaging agents: promoting the growth of human gingival cells

PubMed Central

Choi, Jonghoon; Park, Hoyoung; Kim, Taeho; Jeong, Yoon; Oh, Myoung Hwan; Hyeon, Taeghwan; Gilad, Assaf A; Lee, Kwan Hyi

2014-01-01

We present here the in vitro release profiles of either fluorescently labeled biomolecules or computed tomography contrast nanoagents from engineered collagen hydrogels under physiological conditions. The collagen constructs were designed as potential biocompatible inserts into wounded human gingiva. The collagen hydrogels were fabricated under a variety of conditions in order to optimize the release profile of biomolecules and nanoparticles for the desired duration and amount. The collagen constructs containing biomolecules/nanoconstructs were incubated under physiological conditions (ie, 37°C and 5% CO2) for 24 hours, and the release profile was tuned from 20% to 70% of initially loaded materials by varying the gelation conditions of the collagen constructs. The amounts of released biomolecules and nanoparticles were quantified respectively by measuring the intensity of fluorescence and X-ray scattering. The collagen hydrogel we fabricated may serve as an efficient platform for the controlled release of biomolecules and imaging agents in human gingiva to facilitate the regeneration of oral tissues. PMID:25429215

A facile and efficient single-step approach for the fabrication of vancomycin functionalized polymer-based monolith as chiral stationary phase for nano-liquid chromatography.

PubMed

Xu, Dongsheng; Shao, Huikai; Luo, Rongying; Wang, Qiqin; Sánchez-López, Elena; Fanali, Salvatore; Marina, Maria Luisa; Jiang, Zhengjin

2018-07-06

A facile single-step preparation strategy for fabricating vancomycin functionalized organic polymer-based monolith within 100μm fused-silica capillary was developed. The synthetic chiral functional monomer, i.e 2-isocyanatoethyl methacrylate (ICNEML) derivative of vancomycin, was co-polymerized with the cross-linker ethylene dimethacrylate (EDMA) in the presence of methanol and dimethyl sulfoxide as the selected porogens. The co-polymerization conditions were systematically optimized in order to obtain satisfactory column performance. Adequate permeability, stability and column morphology were observed for the optimized poly(ICNEML-vancomycin-co-EDMA) monolith. A series of chiral drugs were evaluated on the monolith in either polar organic-phase or reversed-phase modes. After the optimization of separation conditions, baseline or partial enantioseparation were obtained for series of drugs including thalidomide, colchicine, carteolol, salbutamol, clenbuterol and several other β-blockers. The proposed single-step approach not only resulted in a vancomycin functionalized organic polymer-based monolith with acceptable performance, but also significantly simplified the preparation procedure by reducing time and labor. Copyright © 2018 Elsevier B.V. All rights reserved.

PEGylated Lipid bilayer coated mesoporous silica nanoparticles for co-delivery of paclitaxel and curcumin: Design, characterization and its cytotoxic effect.

PubMed

Lin, Jiahao; Cai, Qiang; Tang, Yinian; Xu, Yanjun; Wang, Qian; Li, Tingting; Xu, Huihao; Wang, Shuaiyu; Fan, Kai; Liu, Zhongjie; Jin, Yipeng; Lin, Degui

2018-01-30

Highly ordered mesoporous silica nanoparticles (MSNs) with pore diameter of 2.754nm and particle size of 115±15nm were prepared with etching method. Homogeneous PEGylated lipid bilayer with 10-15nm thickness was coated around the surface of MSNs using film hydration method. Systematic optimization and characterization of co-encapsulation process of paclitaxel (Tax) and curcumin (Cur) into PEGylated lipid bilayer coated mesoporous silica nanoparticles (PLMSNs) were performed carrying out single factor test, associated with Box-Behnken Design. The concentration of encapsulated drugs was measured by reversed phase high performance liquid chromatography (RP-HPLC) method. Optimal factor settings were as follows: 50mg MSNs, ratio of MSNs to lipid (w/w)=1:1.11, and ratio of lipid to CHO (w/w)=3.93:1. The average experimental EE Tax , EE Cur and stability score value were (77.48±2.73) %, (30.70±3.56) % and 4 point respectively based on the conditions mentioned above. Morphology determination of Tax-Cur-PLMSNs revealed that the composite nanoparticles were spherical particals with uniform dispersion. In vitro release experiment indicated that PLMSNs improved dissolution of Tax compared to Tax powder suspension and exhibited sustained release property. Tax-Cur-PLMSNs manifested definite and persistently promoted cytotoxic effect against canine breast cancer cells. This prolonged and enhanced activity of Tax-Cur-PLMSNs might contribute to its sustained release effect. Copyright © 2017. Published by Elsevier B.V.

Design of aromatic-containing cell-penetrating peptide mimics with structurally modified π electronics.

PubMed

deRonde, Brittany M; Birke, Alexander; Tew, Gregory N

2015-02-09

Cell-penetrating peptides (CPPs) and their synthetic mimics (CPPMs) represent a class of molecules that facilitate the intracellular delivery of various cargo. Previous studies indicated that the presence of aromatic functionalities improved CPPM activity. Given that aromatic functionalities play prominent roles in membrane biology and participate in various π interactions, we explored whether these interactions could be optimized for improved CPPM activity. CPPMs were synthesized by ring-opening metathesis polymerization by using monomers that contained aromatic rings substituted with electron-donating and electron-withdrawing groups and covered an electrostatic potential range from -29.69 to +15.57 kcal mol(-1) . These groups altered the quadrupole moments of the aromatic systems and were used to test if such structural modifications changed CPPM activity. CPPMs were added to dye-loaded vesicles and the release of carboxyfluorescein was monitored as a function of polymer concentration. Changes in the effective polymer concentration to release 50% of the dye (effective concentration, EC50 ) were monitored. Results from this assay showed that the strength of the electron-donating and electron-withdrawing groups incorporated in the CPPMs did not alter polymer EC50 values or activity. This suggests that other design parameters may have a stronger impact on CPPM activity. In addition, these results indicate that a wide range of aromatic groups can be incorporated without negatively impacting polymer activity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Statistical Evaluation and Optimization of Factors Affecting the Leaching Performance of Copper Flotation Waste

PubMed Central

Çoruh, Semra; Elevli, Sermin; Geyikçi, Feza

2012-01-01

Copper flotation waste is an industrial by-product material produced from the process of manufacturing copper. The main concern with respect to landfilling of copper flotation waste is the release of elements (e.g., salts and heavy metals) when in contact with water, that is, leaching. Copper flotation waste generally contains a significant amount of Cu together with trace elements of other toxic metals, such as Zn, Co, and Pb. The release of heavy metals into the environment has resulted in a number of environmental problems. The aim of this study is to investigate the leaching characteristics of copper flotation waste by use of the Box-Behnken experimental design approach. In order to obtain the optimized condition of leachability, a second-order model was examined. The best leaching conditions achieved were as follows: pH = 9, stirring time = 5 min, and temperature = 41.5°C. PMID:22629194

Statistical evaluation and optimization of factors affecting the leaching performance of copper flotation waste.

PubMed

Coruh, Semra; Elevli, Sermin; Geyikçi, Feza

2012-01-01

Copper flotation waste is an industrial by-product material produced from the process of manufacturing copper. The main concern with respect to landfilling of copper flotation waste is the release of elements (e.g., salts and heavy metals) when in contact with water, that is, leaching. Copper flotation waste generally contains a significant amount of Cu together with trace elements of other toxic metals, such as Zn, Co, and Pb. The release of heavy metals into the environment has resulted in a number of environmental problems. The aim of this study is to investigate the leaching characteristics of copper flotation waste by use of the Box-Behnken experimental design approach. In order to obtain the optimized condition of leachability, a second-order model was examined. The best leaching conditions achieved were as follows: pH = 9, stirring time = 5 min, and temperature = 41.5 °C.

Fuzzy Energy and Reserve Co-optimization With High Penetration of Renewable Energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Cong; Botterud, Audun; Zhou, Zhi

In this study, we propose a fuzzy-based energy and reserve co-optimization model with consideration of high penetration of renewable energy. Under the assumption of a fixed uncertainty set of renewables, a two-stage robust model is proposed for clearing energy and reserves in the first stage and checking the feasibility and robustness of re-dispatches in the second stage. Fuzzy sets and their membership functions are introduced into the optimization model to represent the satisfaction degree of the variable uncertainty sets. The lower bound of the uncertainty set is expressed as fuzzy membership functions. The solutions are obtained by transforming the fuzzymore » mathematical programming formulation into traditional mixed integer linear programming problems.« less

Fuzzy Energy and Reserve Co-optimization With High Penetration of Renewable Energy

DOE PAGES

Liu, Cong; Botterud, Audun; Zhou, Zhi; ...

2016-10-21

In this study, we propose a fuzzy-based energy and reserve co-optimization model with consideration of high penetration of renewable energy. Under the assumption of a fixed uncertainty set of renewables, a two-stage robust model is proposed for clearing energy and reserves in the first stage and checking the feasibility and robustness of re-dispatches in the second stage. Fuzzy sets and their membership functions are introduced into the optimization model to represent the satisfaction degree of the variable uncertainty sets. The lower bound of the uncertainty set is expressed as fuzzy membership functions. The solutions are obtained by transforming the fuzzymore » mathematical programming formulation into traditional mixed integer linear programming problems.« less

Formulation and Optimization of Candesartan Cilexetil Nano Lipid Carrier: In Vitro and In Vivo Evaluation.

PubMed

Paudel, Anjan; Ameeduzzafar; Imam, Syed Sarim; Fazil, Mohd; Khan, Shahroz; Hafeez, Abdul; Ahmad, Farhan Jalees; Ali, Asgar

2017-01-01

The objective of this study was to formulate and optimize Candesartan Cilexetil (CC) loaded nanostructured lipid carriers (NLCs) for enhanced oral bioavailability. Glycerol monostearate (GMS), Oleic acid, Tween 80 and Span 40 were selected as a solid lipid, liquid lipid, surfactant and co- surfactant, respectively. The CC-NLCs were prepared by hot emulsion probe sonication technique and optimized using experimental design approach. The formulated CC-NLCs were evaluated for various physicochemical parameters and further optimized formulation (CC-NLC-Opt) was assessed for in vivo pharmacokinetic and pharmacodynamic activity. The optimized formulation (CC-NLC-Opt) showed particle size (183.5±5.89nm), PDI (0.228±0.13), zeta potential (-28.2±0.99mV), and entrapment efficiency (88.9±3.69%). The comparative in vitro release study revealed that CC-NLC-Opt showed significantly better (p<0.05) release and enhanced permeation as compared to CC-suspension. The in vivo pharmacokinetic study gave many folds increase in oral bioavailability than CC suspension, which was further confirmed by antihypertensive activity in a murine model. Thus, the results of ex vivo permeation, pharmacokinetic study and pharmacodynamics study suggest the potential of CC-NLCs for improved oral delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Carbon dioxide absorber and regeneration assemblies useful for power plant flue gas

DOEpatents

Vimalchand, Pannalal; Liu, Guohai; Peng, Wan Wang

2012-11-06

Disclosed are apparatus and method to treat large amounts of flue gas from a pulverized coal combustion power plant. The flue gas is contacted with solid sorbents to selectively absorb CO.sub.2, which is then released as a nearly pure CO.sub.2 gas stream upon regeneration at higher temperature. The method is capable of handling the necessary sorbent circulation rates of tens of millions of lbs/hr to separate CO.sub.2 from a power plant's flue gas stream. Because pressurizing large amounts of flue gas is cost prohibitive, the method of this invention minimizes the overall pressure drop in the absorption section to less than 25 inches of water column. The internal circulation of sorbent within the absorber assembly in the proposed method not only minimizes temperature increases in the absorber to less than 25.degree. F., but also increases the CO.sub.2 concentration in the sorbent to near saturation levels. Saturating the sorbent with CO.sub.2 in the absorber section minimizes the heat energy needed for sorbent regeneration. The commercial embodiments of the proposed method can be optimized for sorbents with slower or faster absorption kinetics, low or high heat release rates, low or high saturation capacities and slower or faster regeneration kinetics.

CO2 adsorption on diatomaceous earth modified with cetyltrimethylammonium bromide and functionalized with tetraethylenepentamine: Optimization and kinetics.

PubMed

Pornaroonthama, Phuwadej; Thouchprasitchai, Nutthavich; Pongstabodee, Sangobtip

2015-07-01

The carbon dioxide (CO2) adsorbent diatomaceous earth (DE) was modified with cetyltrimethylammonium bromide (CTAB) and functionalized with varying levels of tetraethylenepentamine (TEPA). The CO2 absorption at atmospheric pressure was optimized by varying the TEPA-loading level (0-40% (w/w)), operating temperature (40-80 °C) and water vapor concentration (0-16% (v/v)) in a 10% (v/v) CO2 feed stream in helium balance using a full 2(3) factorial design. The TEPA/CTAB-DE adsorbents were characterized by X-ray diffractometry, Fourier transform infrared spectrometry and thermogravimetric analyses. The CO2 adsorption capacity increased as each of these three factors increased. The TEPA loading level-water concentration interaction had a positive influence on the CO2 adsorption while the operating temperature-water concentration interaction was antagonistic. The optimal condition for CO2 adsorption on 40%TEPA/CTAB-DE, evaluated via a factorial design response surface method (RSM), was a temperature of 58-68 °C and a water vapor concentration of 9.5-14% (v/v), with a maximum CO2 adsorption capacity of 149.4 mg g(-1) at 63.5 °C and 12% (v/v) water vapor concentration in the feed. Validation and sensitivity tests revealed that the estimated CO2 adsorption capacity was within ±4% of the experimental values, suggesting that the RSM model was satisfied and acceptable. From three kinetic models (pseudo-first-order, pseudo-second-order model and Avrami's equation), assessed using an error function (Err) and the coefficient of determination (R(2)), Avrami's equation was the most appropriate to describe the kinetics of CO2 adsorption on the 40%TEPA/CTAB-DE adsorbent and suggested that more than one reaction pathway occurred in the CO2 adsorption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation and Properties of a Novel Semi-IPN Slow-Release Fertilizer with the Function of Water Retention.

PubMed

Xiang, Yang; Ru, Xudong; Shi, Jinguo; Song, Jiang; Zhao, Haidong; Liu, Yaqing; Guo, Dongdong; Lu, Xin

2017-12-20

A new semi-interpenetrating polymer network (semi-IPN) slow-release fertilizer (SISRF) with water absorbency, based on the kaolin-g-poly(acrylic acid-co-acrylic amide) (kaolin-g-P(AA-co-AM)) network and linear urea-formaldehyde oligomers (UF), was prepared by solution polymerization. Nutrients phosphorus and potassium were supplied by adding dipotassium hydrogen phosphate during the preparation process. The structure and properties of SISRF were characterized by various characterization methods. SISRF showed excellent water absorbency of 68 g g -1 in tap water. The slow-release behavior of nutrients and water-retention capacity of SISRF were also measured. Meanwhile, the swelling kinetics was well described by a pseudo-second-order kinetics model. Results suggested the formation of SISRF with simultaneously good slow-release and water-retention capacity, which was expected to apply in modern agriculture and horticulture.

Facile Preparation of Drug-Loaded Tristearin Encapsulated Superparamagnetic Iron Oxide Nanoparticles Using Coaxial Electrospray Processing.

PubMed

Rasekh, Manoochehr; Ahmad, Zeeshan; Cross, Richard; Hernández-Gil, Javier; Wilton-Ely, James D E T; Miller, Philip W

2017-06-05

Naturally occurring polymers are promising biocompatible materials that have many applications for emerging therapies, drug delivery systems, and diagnostic agents. The handling and processing of such materials still constitutes a major challenge, which can limit the full exploitation of their properties. This study explores an ambient environment processing technique: coaxial electrospray (CO-ES) to encapsulate genistein (an isoflavonoid and model drug), superparamagnetic iron oxide nanoparticles (SPIONs, 10-15 nm), and a fluorophore (BODIPY) into a layered (triglyceride tristearin shell) particulate system, with a view to constructing a theranostic agent. Mode mapping of CO-ES led to an optimized atomization engineering window for stable jetting, leading to encapsulation of SPIONs within particles of diameter 0.65-1.2 μm and drug encapsulation efficiencies of around 92%. Electron microscopy was used to image the encapsulated SPIONs and confirm core-shell triglyceride encapsulation in addition to further physicochemical characterization (AFM, FTIR, DSC, and TGA). Cell viability assays (MTT, HeLa cells) were used to determine optimal SPION loaded particles (∼1 mg/mL), while in vitro release profile experiments (PBS, pH = 7.4) demonstrate a triphasic release profile. Further cell studies confirmed cell uptake and internalization at selected time points (t = 1, 2, and 4 h). The results suggest potential for using the CO-ES technique as an efficient way to encapsulate SPIONs together with sensitive drugs for the development of multimodal particles that have potential application for combined imaging and therapy.

Assessment of hemodynamic load components affecting optimization of cardiac resynchronization therapy by lumped parameter mode.

PubMed

Xu, Ke; Butlin, Mark; Avolio, Alberto P

2012-01-01

Timing of biventricular pacing devices employed in cardiac resynchronization therapy (CRT) is a critical determinant of efficacy of the procedure. Optimization is done by maximizing function in terms of arterial pressure (BP) or cardiac output (CO). However, BP and CO are also determined by the hemodynamic load of the pulmonary and systemic vasculature. This study aims to use a lumped parameter circulatory model to assess the influence of the arterial load on the atrio-ventricular (AV) and inter-ventricular (VV) delay for optimal CRT performance.

Micelles of enzymatically synthesized PEG-poly(amine-co-ester) block copolymers as pH-responsive nanocarriers for docetaxel delivery.

PubMed

Zhang, Xiaofang; Liu, Bo; Yang, Zhe; Zhang, Chao; Li, Hao; Luo, Xingen; Luo, Huiyan; Gao, Di; Jiang, Qing; Liu, Jie; Jiang, Zhaozhong

2014-03-01

A series of PEGylated poly(amine-co-ester) terpolymers were successfully synthesized in one step via lipase-catalyzed copolymerization of ω-pentadecalactone (PDL), diethyl sebacate (DES), and N-methyldiethanolamine (MDEA) comonomers in the presence of poly(ethylene glycol) methyl ether as a chain-terminating agent. The resultant amphiphilic poly(ethylene glycol)-poly(PDL-co-MDEA-co-sebacate) (PEG-PPMS) block copolymers consisted of hydrophilic PEG chain segments and hydrophobic random PPMS chain segments, which self-assembled in aqueous medium to form stable, nanosized micelles at physiological pH of 7.4. Upon decreasing the medium pH from 7.4 to 5.0, the copolymer micelles swell significantly due to protonation of the amino groups in the micelle PPMS cores. Correspondingly, docetaxel (DTX)-encapsulated PEG2K-PPMS copolymer micelles showed gradual sustained drug release at pH of 7.4, but remarkably accelerated DTX release at acidic pH of 5.0. The drug-loaded micelle particles were readily internalized by SK-BR-3 cancer cells and, compared to free DTX drug, DTX-loaded micelles of the copolymers with optimal compositions exhibited enhanced potency against the cells. Biodegradable PEG-PPMS copolymer micelles represent a new type of promising, pH-responsive nanocarriers for anticancer drug delivery, and the drug release rate from the micelles can be systematically controlled by both pH and the copolymer composition. Copyright © 2013 Elsevier B.V. All rights reserved.

Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model.

PubMed

Brisbois, Elizabeth J; Bayliss, Jill; Wu, Jianfeng; Major, Terry C; Xi, Chuanwu; Wang, Stewart C; Bartlett, Robert H; Handa, Hitesh; Meyerhoff, Mark E

2014-10-01

Nitric oxide (NO) has many biological roles (e.g. antimicrobial agent, promoter of angiogenesis, prevention of platelet activation) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2±0.7wt.%) and Tecophilic SP-60D-20 (22.5±1.1wt.%)) were doped with 25wt.% DBHD/N2O2 and 10wt.% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with the lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rate of the PLGA additive, thereby providing a more acidic environment that increases the rate of NO release from the NO donor. The optimal NO releasing and control SG-80A patches were then applied to scald burn wounds that were infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24h (∼4 log reduction). The NO release patches are also able to reduce the level of transforming growth factor-β in comparison to controls, which can enhance re-epithelialization, decrease scarring and reduce migration of bacteria. The combined DBHD/N2O2 and PLGA-doped polymer patches, which could be replaced periodically throughout the wound healing process, demonstrate the potential to reduce risk of bacterial infection and promote the overall wound healing process. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model

PubMed Central

Brisbois, Elizabeth J.; Bayliss, Jill; Wu, Jianfeng; Major, Terry C.; Xi, Chuanwu; Wang, Stewart C.; Bartlett, Robert H.; Handa, Hitesh; Meyerhoff, Mark E.

2014-01-01

Nitric oxide (NO) has many biological roles (e.g., antimicrobial agent, promoter of angiogenesis, prevention of platelet activation, etc.) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2 ± 0.7 wt %) and Tecophillic SP-60D-20 (22.5 ± 1.1 wt%)) were doped with 25 wt% DBHD/N2O2 and 10 wt% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rate of the PLGA additive, thereby providing a more acidic environment that increases the rate of NO release from the NO donor. The optimal NO releasing and control SG-80A patches were then applied to scald burn wounds that were infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24 h (~4 log reduction). The NO release patches are also able to reduce the TGF-β levels, in comparison to controls, which can enhance reepithelialization, decrease scarring, and reduce migration of bacteria. The combined DBHD/N2O2 and PLGA-doped polymer patches, which could be replaced periodically throughout the wound healing process, demonstrate the potential to reduce risk of bacterial infection and promote the overall wound healing process. PMID:24980058

Grating-patterned FeCo coated surface acoustic wave device for sensing magnetic field

NASA Astrophysics Data System (ADS)

Wang, Wen; Jia, Yana; Xue, Xufeng; Liang, Yong; Du, Zhaofu

2018-01-01

This study addresses the theoretical and experimental investigations of grating-patterned magnetostrictive FeCo coated surface acoustic wave (SAW) device for sensing magnetic field. The proposed sensor is composed of a configuration of differential dual-delay-line oscillators, and a magnetostrictive FeCo grating array deposited along the SAW propagation path of the sensing device, which suppresses effectively the hysteresis effect by releasing the internal binding force in FeCo. The magnetostrictive strain and ΔE effect from the FeCo coating modulates the SAW propagation characteristic, and the corresponding shift in differential oscillation frequency was utilized to evaluate the measurant. A theoretical model is performed to investigate the wave propagation in layered structure of FeCo/LiNbO3 in the effect of magnetostrictive, and allowing determining the optimal structure. The experimental results indicate that higher sensitivity, excellent linearity, and lower hysteresis error over the typical FeCo thin-film coated sensor were achieved from the grating-patterned FeCo coated sensor successfully.

Co-production of bio-ethanol, xylonic acid and slow-release nitrogen fertilizer from low-cost straw pulping solid residue.

PubMed

Huang, Chen; Ragauskas, Arthur J; Wu, Xinxing; Huang, Yang; Zhou, Xuelian; He, Juan; Huang, Caoxing; Lai, Chenhuan; Li, Xin; Yong, Qiang

2018-02-01

A novel bio-refinery sequence yielding varieties of co-products was developed using straw pulping solid residue. This process utilizes neutral sulfite pretreatment which under optimal conditions (160 °C and 3% (w/v) sulfite charge) provides 64.3% delignification while retaining 90% of cellulose and 67.3% of xylan. The pretreated solids exhibited excellent enzymatic digestibility, with saccharification yields of 86.9% and 81.1% for cellulose and xylan, respectively. After pretreatment, the process of semi-simultaneous saccharification and fermentation (S-SSF) and bio-catalysis was investigated. The results revealed that decreased ethanol yields were achieved when solid loading increased from 5% to 30%. An acceptable ethanol yield of 76.8% was obtained at 20% solid loading. After fermentation, bio-catalysis of xylose remaining in fermentation broth resulted in near 100% xylonic acid (XA) yield at varied solid loadings. To complete the co-product portfolio, oxidation ammoniation of the dissolved lignin successfully transformed it into biodegradable slow-release nitrogen fertilizer with excellent agricultural properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Docetaxel-loaded polylactic acid-co-glycolic acid nanoparticles: formulation, physicochemical characterization and cytotoxicity studies.

PubMed

Pradhan, Roshan; Poudel, Bijay Kumar; Ramasamy, Thiruganesh; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2013-08-01

In the present study, we developed novel docetaxel (DTX)-loaded polylactic acid-co-glycolic acid (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate (SLS) and poloxamer 407, the anionic and non-ionic surfactants respectively for stabilization. The NPs were prepared by emulsification/solvent evaporation method. The combination of these surfactants at weight ratio of 1:0.5 was able to produce uniformly distributed small sized NPs and demonstrated the better stability of NP dispersion with high encapsulation efficiency (85.9 +/- 0.6%). The drug/polymer ratio and phase ratio were 2:10 and 1:10, respectively. The optimized formulation of DTX-loaded PLGA NPs had a particle size and polydispersity index of 104.2 +/- 1.5 nm and 0.152 +/- 0.006, respectively, which was further supported by TEM image. In vitro release study was carried out with dialysis membrane and showed 32% drug release in 192 h. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.481, which suggested the drug was released by anomalous or non-Fickian diffusion. In addition, DTX-loaded PLGA NPs in 72 h, displayed approximately 75% cell viability reduction at 10 microg/ml DTX concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of DTX into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

Co-administration of delta- and mu-opioid receptor agonists promotes peripheral opioid receptor function

PubMed Central

Schramm, Cicely L.; Honda, Christopher N.

2010-01-01

Enhancement of peripheral opioid analgesia following tissue injury or inflammation in animal models is well-documented, but clinical results of peripheral opioid therapy remain inconsistent. Previous studies in the central nervous system have shown that co-administration of μ- and δ-opioid receptor agonists can enhance analgesic outcomes; however, less is known about the functional consequences of opioid receptor interactions in the periphery. The present study examines the effects of intraplantar injection of the μ- and δ-opioid receptor agonists, morphine and deltorphin, alone and in combination on behavioral tests of nociception in naïve rats and on potassium-evoked release of CGRP from sciatic nerves of naïve rats. Neither drug alone affected nociceptive behaviors or CGRP release. Two separate measures of mechanical nociceptive sensitivity remained unchanged after co-administration of the two drugs. In contrast, when deltorphin was co-injected with morphine, dose-dependent and peripherally-restricted increases in paw withdrawal latencies to radiant heat were observed. Similarly, concentration-dependent inhibition of CGRP release was observed when deltorphin and morphine were administered in sequence prior to potassium stimulation. However, no inhibition was observed when morphine was administered prior to deltorphin. All combined opioid effects were blocked by co-application of antagonists. Deltorphin exposure also enhanced the in vivo and in vitro effects of another μ-opioid receptor agonist, DAMGO. Together, these results suggest that under normal conditions, δ-opioid receptor agonists enhance the effect of μ-opioid receptor agonists in the periphery, and local co-administration of δ- and μ-opioid receptor agonists may improve results of peripheral opioid therapy for the treatment of pain. PMID:20970925

Local Approximation and Hierarchical Methods for Stochastic Optimization

NASA Astrophysics Data System (ADS)

Cheng, Bolong

In this thesis, we present local and hierarchical approximation methods for two classes of stochastic optimization problems: optimal learning and Markov decision processes. For the optimal learning problem class, we introduce a locally linear model with radial basis function for estimating the posterior mean of the unknown objective function. The method uses a compact representation of the function which avoids storing the entire history, as is typically required by nonparametric methods. We derive a knowledge gradient policy with the locally parametric model, which maximizes the expected value of information. We show the policy is asymptotically optimal in theory, and experimental works suggests that the method can reliably find the optimal solution on a range of test functions. For the Markov decision processes problem class, we are motivated by an application where we want to co-optimize a battery for multiple revenue, in particular energy arbitrage and frequency regulation. The nature of this problem requires the battery to make charging and discharging decisions at different time scales while accounting for the stochastic information such as load demand, electricity prices, and regulation signals. Computing the exact optimal policy becomes intractable due to the large state space and the number of time steps. We propose two methods to circumvent the computation bottleneck. First, we propose a nested MDP model that structure the co-optimization problem into smaller sub-problems with reduced state space. This new model allows us to understand how the battery behaves down to the two-second dynamics (that of the frequency regulation market). Second, we introduce a low-rank value function approximation for backward dynamic programming. This new method only requires computing the exact value function for a small subset of the state space and approximate the entire value function via low-rank matrix completion. We test these methods on historical price data from the PJM Interconnect and show that it outperforms the baseline approach used in the industry.

Localised controlled release of simvastatin from porous chitosan-gelatin scaffolds engrafted with simvastatin loaded PLGA-microparticles for bone tissue engineering application.

PubMed

Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Daly, Jacqueline; Chiono, Valeria; Mattu, Clara; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

2016-02-01

Localised controlled release of simvastatin from porous freeze-dried chitosan-gelatin (CH-G) scaffolds was investigated by incorporating simvastatin loaded poly-(dl-lactide-co-glycolide) acid (PLGA) microparticles (MSIMs) into the scaffolds. MSIMs at 10% w/w simvastatin loading were prepared using a single emulsion-solvent evaporation method. The MSIM optimal amount to be incorporated into the scaffolds was selected by analysing the effect of embedding increasing amounts of blank PLGA microparticles (BL-MPs) on the scaffold physical properties and on the in vitro cell viability using a clonal human osteoblastic cell line (hFOB). Increasing the BL-MP content from 0% to 33.3% w/w showed a significant decrease in swelling degree (from 1245±56% to 570±35%). Scaffold pore size and distribution changed significantly as a function of BL-MP loading. Compressive modulus of scaffolds increased with increasing BL-MP amount up to 16.6% w/w (23.0±1.0kPa). No significant difference in cell viability was observed with increasing BL-MP loading. Based on these results, a content of 16.6% w/w MSIM particles was incorporated successfully in CH-G scaffolds, showing a controlled localised release of simvastatin able to influence the hFOB cell proliferation and the osteoblastic differentiation after 11 days. Copyright © 2015 Elsevier B.V. All rights reserved.

Multifunctional phosphate-based inorganic-organic hybrid nanoparticles.

PubMed

Heck, Joachim G; Napp, Joanna; Simonato, Sara; Möllmer, Jens; Lange, Marcus; Reichardt, Holger M; Staudt, Reiner; Alves, Frauke; Feldmann, Claus

2015-06-17

Phosphate-based inorganic-organic hybrid nanoparticles (IOH-NPs) with the general composition [M](2+)[Rfunction(O)PO3](2-) (M = ZrO, Mg2O; R = functional organic group) show multipurpose and multifunctional properties. If [Rfunction(O)PO3](2-) is a fluorescent dye anion ([RdyeOPO3](2-)), the IOH-NPs show blue, green, red, and near-infrared fluorescence. This is shown for [ZrO](2+)[PUP](2-), [ZrO](2+)[MFP](2-), [ZrO](2+)[RRP](2-), and [ZrO](2+)[DUT](2-) (PUP = phenylumbelliferon phosphate, MFP = methylfluorescein phosphate, RRP = resorufin phosphate, DUT = Dyomics-647 uridine triphosphate). With pharmaceutical agents as functional anions ([RdrugOPO3](2-)), drug transport and release of anti-inflammatory ([ZrO](2+)[BMP](2-)) and antitumor agents ([ZrO](2+)[FdUMP](2-)) with an up to 80% load of active drug is possible (BMP = betamethason phosphate, FdUMP = 5'-fluoro-2'-deoxyuridine 5'-monophosphate). A combination of fluorescent dye and drug anions is possible as well and shown for [ZrO](2+)[BMP](2-)0.996[DUT](2-)0.004. Merging of functional anions, in general, results in [ZrO](2+)([RdrugOPO3]1-x[RdyeOPO3]x)(2-) nanoparticles and is highly relevant for theranostics. Amine-based functional anions in [MgO](2+)[RaminePO3](2-) IOH-NPs, finally, show CO2 sorption (up to 180 mg g(-1)) and can be used for CO2/N2 separation (selectivity up to α = 23). This includes aminomethyl phosphonate [AMP](2-), 1-aminoethyl phosphonate [1AEP](2-), 2-aminoethyl phosphonate [2AEP](2-), aminopropyl phosphonate [APP](2-), and aminobutyl phosphonate [ABP](2-). All [M](2+)[Rfunction(O)PO3](2-) IOH-NPs are prepared via noncomplex synthesis in water, which facilitates practical handling and which is optimal for biomedical application. In sum, all IOH-NPs have very similar chemical compositions but can address a variety of different functions, including fluorescence, drug delivery, and CO2 sorption.

A novel ropivacaine-loaded in situ forming implant prolongs the effect of local analgesia in rats

PubMed Central

Lu, Lei; Zhang, Wei; Wu, Xin; Wang, Xiaoyu; Zhang, Min; Zhu, Quangang; Ding, Xueying; Xu, Zhiyun

2012-01-01

Introduction Prolonged postoperative analgesia cannot be achieved by a single injection of local anesthetic solution. The objective of this study was to optimize the formulation of a ropivacaine hydrochloride (Ropi-HCl) loaded in situ forming implant (ISI) by addition of different co-solvents, and evaluate the in vitro release of Ropi-HCl, and the analgesic effect and toxicity of the optimized formulation in rats. Material and methods Triacetin (TA), benzyl benzoate (BB) and polyethylene glycol 400 (PEG 400) were used as additives and added to the solvent of N-methyl-2-pyrrolidone (NMP). Drug release to the surface and inner structural properties of the formed implant were evaluated by scanning electron microscopy (SEM). The analgesic effect was determined by injection near the rat sciatic nerve. Results The solvent system added with TA or BB significantly decreased the burst release, whereas PEG 400 increased the Ropi-HCl burst release from the formulation. Over 70% of the incorporated Ropi-HCl was released from all formulations in 14 days in the in vitro assay. The SEM showed that the surface of NMP-BB formulation was less porous and more homogeneous, compared with the other formulations. Compared with Ropi-HCl injection, the optimized formulation (NMP-BB) significantly prolonged the analgesic effect in 48 h (p < 0.05), with a mild degree of motor block from 3 h to 12 h. Histological evaluation of the injection site revealed only mild inflammatory infiltration without obvious pathological nerve alterations. Conclusions The biodegradable Ropi-HCl-loaded ISI system with NMP-BB may prove to be an attractive and safe alternative for the delivery of parenteral local anesthetics to prolong pain relief. PMID:24049519

High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.

PubMed

Cun, Dongmei; Jensen, Ditte Krohn; Maltesen, Morten Jonas; Bunker, Matthew; Whiteside, Paul; Scurr, David; Foged, Camilla; Nielsen, Hanne Mørck

2011-01-01

Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. Copyright © 2010 Elsevier B.V. All rights reserved.

The evolution of imperfect floral mimicry

PubMed Central

Vereecken, Nicolas J.; Schiestl, Florian P.

2008-01-01

The theory of mimicry predicts that selection favors signal refinement in mimics to optimally match the signals released by their specific model species. We provide here chemical and behavioral evidence that a sexually deceptive orchid benefits from its mimetic imperfection to its co-occurring and specific bee model by triggering a stronger response in male bees, which react more intensively to the similar, but novel, scent stimulus provided by the orchid. PMID:18508972

The evolution of imperfect floral mimicry.

PubMed

Vereecken, Nicolas J; Schiestl, Florian P

2008-05-27

The theory of mimicry predicts that selection favors signal refinement in mimics to optimally match the signals released by their specific model species. We provide here chemical and behavioral evidence that a sexually deceptive orchid benefits from its mimetic imperfection to its co-occurring and specific bee model by triggering a stronger response in male bees, which react more intensively to the similar, but novel, scent stimulus provided by the orchid.

Studies on self-nanoemulsifying drug delivery system of flurbiprofen employing long, medium and short chain triglycerides.

PubMed

Daar, Junaid; Khan, Ahmad; Khan, Jallat; Khan, Amjad; Khan, Gul Majid

2017-03-01

The aim of the study was to successfully design, formulate and evaluate self-nanoemulsifying drug delivery system (SNEDDS) of poorly aqueous soluble drug viz. flurbiprofen using long (LCT), medium (MCT) and short chain triglycerides (SCT). The SNEDDS are thermodynamically stable lipid based drug delivery systems which consist of mixture of oil, surfactant and co-surfactant. Upon aqueous dilution, this mixture produces nano-emulsion spontaneously on slight agitation. The excipients intended to be used were screened for their potential to dissolve the drug and to form clear dispersion upon aqueous dilution. Labrafil M 1944 CS, capryol-90 and triacetin were selected as long, medium and short chain triglycerides, respectively, as lipids while tween-80 and polyethylene glycol-400 (PEG-400)/ethanol (3:1 ratio) were selected as surfactant and co-surfactant, respectively. The excipients were studied at every possible combination ratios using pseudo-ternary diagram. The LCT, MCT and SCT-SNEDDS were optimized using thermodynamic studies, percentage transmittance value, viscosity, refractive index (RI), electrical conductivity, globule size analysis and in-vitro drug release studies. The drug release profiles of optimized SNEDDS were then compared with market product at different pH mediums. The LCT-SNEDDS was considered to be superior for enhancement of the drug bioavailability when compared with other SNEDDS formulations and market product.

Co-existence of Functionally Different Vesicular Neurotransmitter Transporters.

PubMed

Münster-Wandowski, Agnieszka; Zander, Johannes-Friedrich; Richter, Karin; Ahnert-Hilger, Gudrun

2016-01-01

The vesicular transmitter transporters VGLUT, VGAT, VMAT2 and VAChT, define phenotype and physiological properties of neuronal subtypes. VGLUTs concentrate the excitatory amino acid glutamate, VGAT the inhibitory amino acid GABA, VMAT2 monoamines, and VAChT acetylcholine (ACh) into synaptic vesicle (SV). Following membrane depolarization SV release their content into the synaptic cleft. A strict segregation of vesicular transporters is mandatory for the precise functioning of synaptic communication and of neuronal circuits. In the last years, evidence accumulates that subsets of neurons express more than one of these transporters leading to synaptic co-release of different and functionally opposing transmitters and modulation of synaptic plasticity. Synaptic co-existence of transporters may change during pathological scenarios in order to ameliorate misbalances in neuronal activity. In addition, evidence increases that transporters also co-exist on the same vesicle providing another layer of regulation. Generally, vesicular transmitter loading relies on an electrochemical gradient ΔμH(+) driven by the proton ATPase rendering the lumen of the vesicle with respect to the cytosol positive (Δψ) and acidic (ΔpH). While the activity of VGLUT mainly depends on the Δψ component, VMAT, VGAT and VAChT work best at a high ΔpH. Thus, a vesicular synergy of transporters depending on the combination may increase or decrease the filling of SV with the principal transmitter. We provide an overview on synaptic co-existence of vesicular transmitter transporters including changes in the excitatory/inhibitory balance under pathological conditions. Additionally, we discuss functional aspects of vesicular synergy of transmitter transporters.

Co-existence of Functionally Different Vesicular Neurotransmitter Transporters

PubMed Central

Münster-Wandowski, Agnieszka; Zander, Johannes-Friedrich; Richter, Karin; Ahnert-Hilger, Gudrun

2016-01-01

The vesicular transmitter transporters VGLUT, VGAT, VMAT2 and VAChT, define phenotype and physiological properties of neuronal subtypes. VGLUTs concentrate the excitatory amino acid glutamate, VGAT the inhibitory amino acid GABA, VMAT2 monoamines, and VAChT acetylcholine (ACh) into synaptic vesicle (SV). Following membrane depolarization SV release their content into the synaptic cleft. A strict segregation of vesicular transporters is mandatory for the precise functioning of synaptic communication and of neuronal circuits. In the last years, evidence accumulates that subsets of neurons express more than one of these transporters leading to synaptic co-release of different and functionally opposing transmitters and modulation of synaptic plasticity. Synaptic co-existence of transporters may change during pathological scenarios in order to ameliorate misbalances in neuronal activity. In addition, evidence increases that transporters also co-exist on the same vesicle providing another layer of regulation. Generally, vesicular transmitter loading relies on an electrochemical gradient ΔμH+ driven by the proton ATPase rendering the lumen of the vesicle with respect to the cytosol positive (Δψ) and acidic (ΔpH). While the activity of VGLUT mainly depends on the Δψ component, VMAT, VGAT and VAChT work best at a high ΔpH. Thus, a vesicular synergy of transporters depending on the combination may increase or decrease the filling of SV with the principal transmitter. We provide an overview on synaptic co-existence of vesicular transmitter transporters including changes in the excitatory/inhibitory balance under pathological conditions. Additionally, we discuss functional aspects of vesicular synergy of transmitter transporters. PMID:26909036

A Voltage-Responsive Free-Blockage Controlled-Release System Based on Hydrophobicity Switching.

PubMed

Jiao, Xiangyu; Sun, Ruijuan; Cheng, Yaya; Li, Fengyu; Du, Xin; Wen, Yongqiang; Song, Yanlin; Zhang, Xueji

2017-05-19

Controlled-release systems based on mesoporous silica nanomaterials (MSNs) have drawn great attention owing to their potential biomedical applications. Various switches have been designed to control the release of cargoes through the construction of physical blocking units on the surface of MSNs. However, such physical blockages are limited by poor sealing ability and low biocompatibility, and most of them lack closure ability. Herein, a voltage-responsive controlled-release system was constructed by functionalizing the nanopore of MSNs with ferrocene. The system realized free-blockage controlled release and achieved pulsatile release. The nanopores of the ferrocene-functionalized MSNs were hydrophobic enough to prevent invasion of the solution. Once a suitable voltage was applied, the nanopores became hydrophilic, which was followed by invasion of the solution and the release of the cargos. Moreover, pulsatile release was realized, which avoided unexpected release after the stimulus disappeared. Thus, we believe that our studies provide new insight into highly effective blockage for MSNs. Furthermore, the voltage-responsive release system is expected to find use in electrical stimulation combination therapy and bioelectricity-responsive release. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimal Design of Biomass Utilization System for Rural Area Includes Technical and Economic Dimensions

NASA Astrophysics Data System (ADS)

Morioka, Yasuki; Nakata, Toshihiko

In order to design optimal biomass utilization system for rural area, OMNIBUS (The Optimization Model for Neo-Integrated Biomass Utilization System) has been developed. OMNIBUS can derive the optimal system configuration to meet different objective function, such as current account balance, amount of biomass energy supply, and CO2 emission. Most of biomass resources in a focused region e.g. wood biomass, livestock biomass, and crop residues are considered in the model. Conversion technologies considered are energy utilization technologies e.g. direct combustion and methane fermentation, and material utilization technologies e.g. composting and carbonization. Case study in Miyakojima, Okinawa prefecture, has been carried out for several objective functions and constraint conditions. Considering economics of the utilization system as a priority requirement, composting and combustion heat utilization are mainly chosen in the optimal system configuration. However gasification power plant and methane fermentation are included in optimal solutions, only when both biomass energy utilization and CO2 reduction have been set as higher priorities. External benefit of CO2 reduction has large impacts on the system configuration. Provided marginal external benefit of more than 50,000 JPY/t-C, external benefit becomes greater than the revenue from electricity and compost etc. Considering technological learning in the future, expensive technologies such as gasification power plant and methane fermentation will have economic feasibility as well as market competitiveness.

Development and statistical optimization of nefopam hydrochloride loaded nanospheres for neuropathic pain using Box-Behnken design.

PubMed

Sukhbir, S; Yashpal, S; Sandeep, A

2016-09-01

Nefopam hydrochloride (NFH) is a non-opioid centrally acting analgesic drug used to treat chronic condition such as neuropathic pain. In current research, sustained release nefopam hydrochloride loaded nanospheres (NFH-NS) were auspiciously synthesized using binary mixture of eudragit RL 100 and RS 100 with sorbitan monooleate as surfactant by quasi solvent diffusion technique and optimized by 3 5 Box-Behnken designs to evaluate the effects of process and formulation variables. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetric (DSC) and X-ray diffraction (XRD) affirmed absence of drug-polymer incompatibility and confirmed formation of nanospheres. Desirability function scrutinized by design-expert software for optimized formulation was 0.920. Optimized batch of NFH-NS had mean particle size 328.36 nm ± 2.23, % entrapment efficiency (% EE) 84.97 ± 1.23, % process yield 83.60 ± 1.31 and % drug loading (% DL) 21.41 ± 0.89. Dynamic light scattering (DLS), zeta potential analysis and scanning electron microscopy (SEM) validated size, charge and shape of nanospheres, respectively. In-vitro drug release study revealed biphasic release pattern from optimized nanospheres. Korsmeyer Peppas found excellent kinetics model with release exponent less than 0.45. Chronic constricted injury (CCI) model of optimized NFH-NS in Wistar rats produced significant difference in neuropathic pain behavior ( p  < 0.05) as compared to free NFH over 10 h indicating sustained action. Long term and accelerated stability testing of optimized NFH-NS revealed degradation rate constant 1.695 × 10 -4 and shelf-life 621 days at 25 ± 2 °C/60% ± 5% RH.

A "Reverse-Schur" Approach to Optimization With Linear PDE Constraints: Application to Biomolecule Analysis and Design.

PubMed

Bardhan, Jaydeep P; Altman, Michael D; Tidor, B; White, Jacob K

2009-01-01

We present a partial-differential-equation (PDE)-constrained approach for optimizing a molecule's electrostatic interactions with a target molecule. The approach, which we call reverse-Schur co-optimization, can be more than two orders of magnitude faster than the traditional approach to electrostatic optimization. The efficiency of the co-optimization approach may enhance the value of electrostatic optimization for ligand-design efforts-in such projects, it is often desirable to screen many candidate ligands for their viability, and the optimization of electrostatic interactions can improve ligand binding affinity and specificity. The theoretical basis for electrostatic optimization derives from linear-response theory, most commonly continuum models, and simple assumptions about molecular binding processes. Although the theory has been used successfully to study a wide variety of molecular binding events, its implications have not yet been fully explored, in part due to the computational expense associated with the optimization. The co-optimization algorithm achieves improved performance by solving the optimization and electrostatic simulation problems simultaneously, and is applicable to both unconstrained and constrained optimization problems. Reverse-Schur co-optimization resembles other well-known techniques for solving optimization problems with PDE constraints. Model problems as well as realistic examples validate the reverse-Schur method, and demonstrate that our technique and alternative PDE-constrained methods scale very favorably compared to the standard approach. Regularization, which ordinarily requires an explicit representation of the objective function, can be included using an approximate Hessian calculated using the new BIBEE/P (boundary-integral-based electrostatics estimation by preconditioning) method.

A “Reverse-Schur” Approach to Optimization With Linear PDE Constraints: Application to Biomolecule Analysis and Design

PubMed Central

Bardhan, Jaydeep P.; Altman, Michael D.

2009-01-01

We present a partial-differential-equation (PDE)-constrained approach for optimizing a molecule’s electrostatic interactions with a target molecule. The approach, which we call reverse-Schur co-optimization, can be more than two orders of magnitude faster than the traditional approach to electrostatic optimization. The efficiency of the co-optimization approach may enhance the value of electrostatic optimization for ligand-design efforts–in such projects, it is often desirable to screen many candidate ligands for their viability, and the optimization of electrostatic interactions can improve ligand binding affinity and specificity. The theoretical basis for electrostatic optimization derives from linear-response theory, most commonly continuum models, and simple assumptions about molecular binding processes. Although the theory has been used successfully to study a wide variety of molecular binding events, its implications have not yet been fully explored, in part due to the computational expense associated with the optimization. The co-optimization algorithm achieves improved performance by solving the optimization and electrostatic simulation problems simultaneously, and is applicable to both unconstrained and constrained optimization problems. Reverse-Schur co-optimization resembles other well-known techniques for solving optimization problems with PDE constraints. Model problems as well as realistic examples validate the reverse-Schur method, and demonstrate that our technique and alternative PDE-constrained methods scale very favorably compared to the standard approach. Regularization, which ordinarily requires an explicit representation of the objective function, can be included using an approximate Hessian calculated using the new BIBEE/P (boundary-integral-based electrostatics estimation by preconditioning) method. PMID:23055839

Constraining gross primary production and ecosystem respiration estimates for North America using atmospheric observations of carbonyl sulfide (OCS) and CO2

NASA Astrophysics Data System (ADS)

He, W.; Ju, W.; Chen, H.; Peters, W.; van der Velde, I.; Baker, I. T.; Andrews, A. E.; Zhang, Y.; Launois, T.; Campbell, J. E.; Suntharalingam, P.; Montzka, S. A.

2016-12-01

Carbonyl sulfide (OCS) is a promising novel atmospheric tracer for studying carbon cycle processes. OCS shares a similar pathway as CO2 during photosynthesis but not released through a respiration-like process, thus could be used to partition Gross Primary Production (GPP) from Net Ecosystem-atmosphere CO2 Exchange (NEE). This study uses joint atmospheric observations of OCS and CO2 to constrain GPP and ecosystem respiration (Re). Flask data from tower and aircraft sites over North America are collected. We employ our recently developed CarbonTracker (CT)-Lagrange carbon assimilation system, which is based on the CT framework and the Weather Research and Forecasting - Stochastic Time-Inverted Lagrangian Transport (WRF-STILT) model, and the Simple Biosphere model with simulated OCS (SiB3-OCS) that provides prior GPP, Re and plant uptake fluxes of OCS. Derived plant OCS fluxes from both process model and GPP-scaled model are tested in our inversion. To investigate the ability of OCS to constrain GPP and understand the uncertainty propagated from OCS modeling errors to constrained fluxes in a dual-tracer system including OCS and CO2, two inversion schemes are implemented and compared: (1) a two-step scheme, which firstly optimizes GPP using OCS observations, and then simultaneously optimizes GPP and Re using CO2 observations with OCS-constrained GPP in the first step as prior; (2) a joint scheme, which simultaneously optimizes GPP and Re using OCS and CO2 observations. We will evaluate the result using an estimated GPP from space-borne solar-induced fluorescence observations and a data-driven GPP upscaled from FLUXNET data with a statistical model (Jung et al., 2011). Preliminary result for the year 2010 shows the joint inversion makes simulated mole fractions more consistent with observations for both OCS and CO2. However, the uncertainty of OCS simulation is larger than that of CO2. The two-step and joint schemes perform similarly in improving the consistence with observations for OCS, implicating that OCS could provide independent constraint in joint inversion. Optimization makes less total GPP and Re but more NEE, when testing with prior CO2 fluxes from two biosphere models. This study gives an in-depth insight into the role of joint atmospheric OCS and CO2 observations in constraining CO2 fluxes.

Fast-Scan Cyclic Voltammetry (FSCV) Detection of Endogenous Octopamine in Drosophila melanogaster Ventral Nerve Cord.

PubMed

Pyakurel, Poojan; Privman Champaloux, Eve; Venton, B Jill

2016-08-17

Octopamine is an endogenous biogenic amine neurotransmitter, neurohormone, and neuromodulator in invertebrates and has functional analogy with norepinephrine in vertebrates. Fast-scan cyclic voltammetry (FSCV) can detect rapid changes in neurotransmitters, but FSCV has not been optimized for octopamine detection in situ. The goal of this study was to characterize octopamine release in the ventral nerve cord of Drosophila larvae for the first time. A FSCV waveform was optimized so that the potential for octopamine oxidation would not be near the switching potential where interferences can occur. Endogenous octopamine release was stimulated by genetically inserting either the ATP sensitive channel, P2X2, or the red-light sensitive channelrhodopsin, CsChrimson, into cells expressing tyrosine decarboxylase (TDC), an octopamine synthesis enzyme. To ensure that release is due to octopamine and not the precursor tyramine, the octopamine synthesis inhibitor disulfiram was applied, and the signal decreased by 80%. Stimulated release was vesicular, and a 2 s continuous light stimulation of CsChrimson evoked 0.22 ± 0.03 μM of octopamine release in the larval ventral nerve cord. Repeated stimulations were stable with 2 or 5 min interstimulation times. With pulsed stimulations, the release was dependent on the frequency of applied light pulse. An octopamine transporter has not been identified, and blockers of the dopamine transporter and serotonin transporter had no significant effect on the clearance time of octopamine, suggesting that they do not take up octopamine. This study shows that octopamine can be monitored in Drosophila, facilitating future studies of how octopamine release functions in the insect brain.

Cell system engineering to produce extracellular polyhydroxyalkanoate depolymerase with targeted applications.

PubMed

Martínez, Virginia; Dinjaski, Nina; de Eugenio, Laura I; de la Peña, Fernando; Prieto, María Auxiliadora

2014-11-01

Novel platforms based on the application of bacterial cell systems as factories for production of new bioproducts open avenues and dramatically expand the catalogue of existing biomaterials. Herein, we designed the strategy based on in vivo production of extracellular Pseudomonas fluorescens GK13 (PhaZGK13) depolymerase to degrade previously biosynthesized polyhydroxyalkanotes (PHAs) or to obtain 3-hydroxyalkanoic acids (HAs). With this aim, extracellular PhaZGK13 was produced in recombinant strains and the optimal conditions for controlled release of HAs and oligomers by growing cells were set up with a particle suspension of (14)C-labelled PHA, being maximal after 24h of incubation. Genetic modification of key factors involved in fatty acids metabolism revealed the influence of an active β-oxidation pathway on the extracellular degradation of PHA and subsequent HAs isolation. The highest HAs production was obtained using Pseudomonas putida KT2442 fadB mutant (0.27mg/mL) due to the reduced ability of this strain to metabolize the degradation products. The system was applied to produce new added value HAs harboring thioester groups in the side chain from the functionalized mcl-PHA, PHACOS. Remarkably, hydrolyzed PHACOS showed greater potential to inhibit Staphylococcus aureus(T) growth when compared to that of degradation products of non functionalized polyhydroxyoctanoate-co-hexanoate P(HO-co-HH). Copyright © 2014 Elsevier B.V. All rights reserved.

Loteprednol Etabonate Nanoparticles: Optimization via Box-Behnken Design Response Surface Methodology and Physicochemical Characterization.

PubMed

Sah, Abhishek K; Suresh, Preeti K

2017-01-01

Abstract: The objective of the present work was to prepare and optimize the loteprednoletabonate (LE) loaded poly (D,L-lactide co-glycolide) (PLGA) polymer based nanoparticle carrier. The review on recent patents (US9006241, US20130224302A1, US2012/0028947A1) assisted in the selection of drug and polymer for designing nanoparticles for ocular delivery applications. The nanoparticles were prepared by solvent evaporation followed by high speed homogenization. Biodegradable polymer PLGA (50:50) grade was utilized to develop various formulations with different drug:polymer ratio. A Box-Behnken design with 33 factorial design was selected for the present study and 17 runs were carried out in totality. The influence of various process variables (viz., polymer concentration, homogenization speed and sonication time) on the characteristics of nanoparticles including the in vitro drug release profile were studied. The nanoparticulate formulations were evaluated for mean spherical diameter, polydispersity index (PDI), zeta potential, surface morphology, drug entrapment and in-vitro drug release profile. The entrapment efficiency, drug loading and mean particle size were found to be 96.31±1.68 %, 35.46±0.35 % and 167.6±2.1 nm respectively. The investigated process and formulation variables were found to have significant effect on the particle size, drug loading (DL), entrapment efficiency (EE), and in vitro drug release profile. A biphasic in vitro drug release profile was apparent from the optimized nanoparticles (NPs) for 24 hours. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Eutrophication assessment and bioremediation strategy using seaweeds co-cultured with aquatic animals in an enclosed bay in China.

PubMed

Wu, Hailong; Huo, Yuanzi; Hu, Ming; Wei, Zhangliang; He, Peimin

2015-06-15

Intensive mariculture results in a rise in nutrient concentrations, then leads to serious eutrophication in coastal waters. Based on the sampling data obtained between August 2012 and July 2013, the eutrophication status in Yantian Bay was assessed, and the proportion of marine animals co-cultured with seaweeds was evaluated. The nutritional quality index (NQI) ranged from 4.37 to 13.20, indicating serious eutrophication conditions. The annual average ratio of nitrogen/phosphorus (N/P) was 25.19, indicating a nitrogen surplus in this system. DIN was selected as the best parameter to balance seaweed absorption and marine animal DIN production. Gracilaria lemaneiformis and Laminaria japonica were selected as co-cultured seaweeds. The optimal proportion of G. lemaneiformis production was assessed as 20074.14 tonnes. The optimal proportion of L. japonica production was evaluated as 15890.68 tonnes. High-temperature adapted seaweeds should be introduced for removing nutrients releasing by farmed aquatic animals in the summer in Yantian Bay. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional proteomics within the genus Lactobacillus.

PubMed

De Angelis, Maria; Calasso, Maria; Cavallo, Noemi; Di Cagno, Raffaella; Gobbetti, Marco

2016-03-01

Lactobacillus are mainly used for the manufacture of fermented dairy, sourdough, meat, and vegetable foods or used as probiotics. Under optimal processing conditions, Lactobacillus strains contribute to food functionality through their enzyme portfolio and the release of metabolites. An extensive genomic diversity analysis was conducted to elucidate the core features of the genus Lactobacillus, and to provide a better comprehension of niche adaptation of the strains. However, proteomics is an indispensable "omics" science to elucidate the proteome diversity, and the mechanisms of regulation and adaptation of Lactobacillus strains. This review focuses on the novel and comprehensive knowledge of functional proteomics and metaproteomics of Lactobacillus species. A large list of proteomic case studies of different Lactobacillus species is provided to illustrate the adaptability of the main metabolic pathways (e.g., carbohydrate transport and metabolism, pyruvate metabolism, proteolytic system, amino acid metabolism, and protein synthesis) to various life conditions. These investigations have highlighted that lactobacilli modulate the level of a complex panel of proteins to growth/survive in different ecological niches. In addition to the general regulation and stress response, specific metabolic pathways can be switched on and off, modifying the behavior of the strains. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conversion of sustained release omeprazole loaded buccal films into fast dissolving strips using supercritical carbon dioxide (scCO2) processing, for potential paediatric drug delivery.

PubMed

Khan, Sajjad; Trivedi, Vivek; Mitchell, John; Boateng, Joshua S

2016-10-10

This study involves the development of thin oral solvent cast films for the potential delivery of the proton pump inhibitor, omeprazole (OME) via the buccal mucosa for paediatric patients. OME containing films were prepared from ethanolic gels (1% w/w) of metolose (MET) with polyethylene glycol (PEG 400) (0.5% w/w) as plasticiser, and L-arginine (l-arg) (0.2% w/w) as a stabilizer and dried in an oven at 40°C. The blank and drug loaded films were divided into two groups, one group was subjected to supercritical carbon dioxide (scCO2) treatment and the other group untreated. The untreated and scCO2 treated films were then characterised using differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, hydration (swelling), mucoadhesion and in vitro drug dissolution studies. Treatment of the solvent cast films with scCO2 caused significant changes to the functional and physical properties of the MET films. The original drug loaded MET films showed a sustained release of OME (1h), whereas scCO2 treatment of the formulations resulted in fast dissolving films with >90% drug release within 15min. Copyright © 2016 Elsevier B.V. All rights reserved.

Individualized optimal release angles in discus throwing.

PubMed

Leigh, Steve; Liu, Hui; Hubbard, Mont; Yu, Bing

2010-02-10

The purpose of this study was to determine individualized optimal release angles for elite discus throwers. Three-dimensional coordinate data were obtained for at least 10 competitive trials for each subject. Regression relationships between release speed and release angle, and between aerodynamic distance and release angle were determined for each subject. These relationships were linear with subject-specific characteristics. The subject-specific relationships between release speed and release angle may be due to subjects' technical and physical characteristics. The subject-specific relationships between aerodynamic distance and release angle may be due to interactions between the release angle, the angle of attack, and the aerodynamic distance. Optimal release angles were estimated for each subject using the regression relationships and equations of projectile motion. The estimated optimal release angle was different for different subjects, and ranged from 35 degrees to 44 degrees . The results of this study demonstrate that the optimal release angle for discus throwing is thrower-specific. The release angles used by elite discus throwers in competition are not necessarily optimal for all discus throwers, or even themselves. The results of this study provide significant information for understanding the biomechanics of discus throwing techniques. Copyright 2009 Elsevier Ltd. All rights reserved.

Mesoporous silica nanoparticles for efficient rivastigmine hydrogen tartrate delivery into SY5Y cells.

PubMed

Karimzadeh, Mahmonir; Rashidi, Ladan; Ganji, Fariba

2017-04-01

Rivastigmine hydrogen tartrate (RT) is a molecule with both hydrophilic and hydrophobic properties used for the treatment of the Alzheimer's disease. In this work, the larger pore size of mesoporous silica nanoparticles (P1-MSN) was synthesized and then, P1-MSN were functionalized by succinic anhydride (S-P1-MSN) and 3-aminopropyltriethoxysilane (APTES) (AP-CO-P1-MSN) using the grafting and co-condensation methods, respectively. A new method was used for the functionalization of P1-MSN by succinic anhydride at room temperature. Nanoparticles were characterized by special instrumental analysis and loaded by RT. Maximum entrapment efficiency and RT loading percentage into P1-MSN, AP-CO-P1-MSN and S-P1-MSN were respectively obtained as 21.26 and 25.5%, 41.5 and 49.8%, and 11.9 and 14.28% for 24 h. In the simulated gastric and body fluids, the release rate of RT-loaded AP-CO-P1-MSN (AP-CO-P1-MSN-RT) was lower than that of other RT-loaded nanoparticles. In oral pathway, the sustained release of RT was observed in AP-CO-P1-MSN-RT. Moreover, no cytotoxicity effect was observed for P1-MSN, but the cells treated by AP-CO-P1-MSN showed a reduction in SY5Y cell viability due to easy entrance of these nanoparticles and their accumulation in different parts of the cell as observed by TEM.

Characteristics of Artemether-Loaded Poly(lactic-co-glycolic) Acid Microparticles Fabricated by Coaxial Electrospray: Validation of Enhanced Encapsulation Efficiency and Bioavailability.

PubMed

Mangrio, Farhana Akbar; Dwivedi, Pankaj; Han, Shuya; Zhao, Gang; Gao, Dayong; Si, Ting; Xu, Ronald X

2017-12-04

Artemether is one of the most effective drugs for the treatment of chloroquine-resistant and Plasmodium falciparum strains of malaria. However, its therapeutic potency is hindered by its poor bioavailability. To overcome this limitation, we have encapsulated artemether in poly(lactic-co-glycolic) acid (PLGA) core-shell microparticles (MPs) using the coaxial electrospray method. With optimized process parameters including liquid flow rates and applied electric voltages, experiments are systematically carried out to generate a stable cone-jet mode to produce artemether-loaded PLGA-MPs with an average size of 2 μm, an encapsulation efficiency of 78 ± 5.6%, and a loading efficiency of 11.7%. The in vitro release study demonstrates the sustained release of artemether from the core-shell structure in comparison with that of plain artemether and that of MPs produced by single-axial electrospray without any relevant cytotoxicity. The in vivo studies are performed to evaluate the pharmacokinetic characteristics of the artemether-loaded PLGA-MPs. Our study implies that artemether can be effectively encapsulated in a protective shell of PLGA for controlled release kinetics and enhanced oral bioavailability.

Automated parameterization of intermolecular pair potentials using global optimization techniques

NASA Astrophysics Data System (ADS)

Krämer, Andreas; Hülsmann, Marco; Köddermann, Thorsten; Reith, Dirk

2014-12-01

In this work, different global optimization techniques are assessed for the automated development of molecular force fields, as used in molecular dynamics and Monte Carlo simulations. The quest of finding suitable force field parameters is treated as a mathematical minimization problem. Intricate problem characteristics such as extremely costly and even abortive simulations, noisy simulation results, and especially multiple local minima naturally lead to the use of sophisticated global optimization algorithms. Five diverse algorithms (pure random search, recursive random search, CMA-ES, differential evolution, and taboo search) are compared to our own tailor-made solution named CoSMoS. CoSMoS is an automated workflow. It models the parameters' influence on the simulation observables to detect a globally optimal set of parameters. It is shown how and why this approach is superior to other algorithms. Applied to suitable test functions and simulations for phosgene, CoSMoS effectively reduces the number of required simulations and real time for the optimization task.

Effects of optimized root water uptake parameterization schemes on water and heat flux simulation in a maize agroecosystem

NASA Astrophysics Data System (ADS)

Cai, Fu; Ming, Huiqing; Mi, Na; Xie, Yanbing; Zhang, Yushu; Li, Rongping

2017-04-01

As root water uptake (RWU) is an important link in the water and heat exchange between plants and ambient air, improving its parameterization is key to enhancing the performance of land surface model simulations. Although different types of RWU functions have been adopted in land surface models, there is no evidence as to which scheme most applicable to maize farmland ecosystems. Based on the 2007-09 data collected at the farmland ecosystem field station in Jinzhou, the RWU function in the Common Land Model (CoLM) was optimized with scheme options in light of factors determining whether roots absorb water from a certain soil layer ( W x ) and whether the baseline cumulative root efficiency required for maximum plant transpiration ( W c ) is reached. The sensibility of the parameters of the optimization scheme was investigated, and then the effects of the optimized RWU function on water and heat flux simulation were evaluated. The results indicate that the model simulation was not sensitive to W x but was significantly impacted by W c . With the original model, soil humidity was somewhat underestimated for precipitation-free days; soil temperature was simulated with obvious interannual and seasonal differences and remarkable underestimations for the maize late-growth stage; and sensible and latent heat fluxes were overestimated and underestimated, respectively, for years with relatively less precipitation, and both were simulated with high accuracy for years with relatively more precipitation. The optimized RWU process resulted in a significant improvement of CoLM's performance in simulating soil humidity, temperature, sensible heat, and latent heat, for dry years. In conclusion, the optimized RWU scheme available for the CoLM model is applicable to the simulation of water and heat flux for maize farmland ecosystems in arid areas.

Optimizing Monitoring Designs under Alternative Objectives

DOE PAGES

Gastelum, Jason A.; USA, Richland Washington; Porter, Ellen A.; ...

2014-12-31

This paper describes an approach to identify monitoring designs that optimize detection of CO2 leakage from a carbon capture and sequestration (CCS) reservoir and compares the results generated under two alternative objective functions. The first objective function minimizes the expected time to first detection of CO2 leakage, the second more conservative objective function minimizes the maximum time to leakage detection across the set of realizations. The approach applies a simulated annealing algorithm that searches the solution space by iteratively mutating the incumbent monitoring design. The approach takes into account uncertainty by evaluating the performance of potential monitoring designs across amore » set of simulated leakage realizations. The approach relies on a flexible two-tiered signature to infer that CO2 leakage has occurred. This research is part of the National Risk Assessment Partnership, a U.S. Department of Energy (DOE) project tasked with conducting risk and uncertainty analysis in the areas of reservoir performance, natural leakage pathways, wellbore integrity, groundwater protection, monitoring, and systems level modeling.« less

The relationship between functional sciatic nerve block duration and the rate of release of lidocaine from a controlled-release matrix.

PubMed

Gerner, Peter; Wang, Chi-Fei; Lee, Byung-Sang; Suzuki, Suzuko; Degirolami, Umberto; Gandhi, Ankur; Knaack, David; Strichartz, Gary

2010-07-01

Nerve blocks of long duration are often desirable in perioperative and postoperative situations. The relationship between the duration of such blocks and the rate at which a local anesthetic is released is important to know for developing a localized drug delivery system that will optimize block duration. Lidocaine concentration was varied in 1 series of formulations (OSB-L) containing a constant amount of release rate modifier. In another series (OST-R), the release rate modifier was varied while the lidocaine content was held constant. Release kinetics were measured in vitro and correlated to the in vivo duration of antinociceptive and motor block effects when the formulation was implanted next to the rat sciatic nerve. In parallel studies, rats receiving different formulations of slow-release lidocaine were fixed by intracardiac perfusion with 4% paraformaldehyde and nerve-muscle tissue taken for histopathological analysis. In this study, we have demonstrated that the most important variable for effecting functional nerve block, i.e., the blockade of impulses in the relevant fibers of the sciatic nerve, is the rate of lidocaine release at that time. For the OSB-L formulations (lidocaine concentrations of 1.875%, 3.75%, 7.5%, and 15% at a constant release rate modifier of 5%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 0.91 +/- 0.28 and 1.75 +/- 0.61 mg/h, respectively. For the OST-R formulations (16% lidocaine with release rate modifier concentrations of 1.875%, 3.75%, 7.5%, and 15%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 2.33 +/- 1.39 and 4.34 +/- 1.09 mg/h, respectively. The OSB-L formulations showed a dose-dependent increase in block duration proportional to an increase in initial lidocaine concentration, whereas the OST-R formulations showed a nonmonotonic relationship between release rate modifier concentration and block duration. The histopathological studies at 24 hours, 3, 5, or 7 days, and 4 weeks after the implantation revealed inflammatory reactions with degrees correlated with lidocaine content, but limited to the connective tissue and muscle immediately surrounding the implanted material. Despite these observed inflammatory reactions, nociceptive and motor block function returned to normal, preimplantation values in all animals. Increasing initial lidocaine content proportionately increased the duration of functional sciatic nerve block. However, decreasing the release rate per se does not give a proportional increase in block duration. Instead, there seems to be an optimal, intermediate release rate for achieving the maximum duration of block.

Formulation and characterization of ORMOSIL particles loaded with budesonide for local colonic delivery.

PubMed

Petrovska-Jovanovska, Vesna; Geskovski, Nikola; Crcarevska, Maja Simonoska; Memed, Oya; Petruševski, Gjorgji; Chachorovska, Marina; Petrusevska, Marija; Poceva-Panovska, Ana; Mladenovska, Kristina; Ugarkovic, Sonja; Glavas-Dodov, Marija

2015-04-30

In this study, hybrid silica xerogel particles were developed as carriers of budesonide (BDS) for efficient local treatment of inflammatory bowel diseases (IBD). Organically modified silica particles (ORMOSILs) were prepared by co-condensation of 3-aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) by an ambient temperature acid catalysed sol-gel process followed by spray-drying. Formulation for preparation of BDS-loaded particles was optimized and their physicochemical parameters and drug release profiles were evaluated in vitro. Optimal formulation had a small particle size (mean diameter of 1.45±0.02μm) with unimodal narrow size distribution and high encapsulation efficiency (98.0 ± 1.85%). Due to the positive surface charge originated from amino group of APTES, ORMOSILs showed excessive mucoadhesiveness in comparison to native TEOS particles. The drug release decreased with increasing pH from 2.0 to 7.4. In order to avoid undesirable erroneous performance in the upper GI tract, particles were additionally coated with Eudragit(®) FS 30D, as a barrier to the drug release at pH range from 2.0 to 7.0. After Eudragit(®) FS 30D coating, the release of BDS in acidic media was sustained, while no significant differences in drug release were observed at pH 7.4. In conclusion, pH-responsive ORMOSILs showed great potential for efficient BDS delivery to the colon region. Copyright © 2015 Elsevier B.V. All rights reserved.

Controlling Release Kinetics of PLG Microspheres Using a Manufacturing Technique

NASA Astrophysics Data System (ADS)

Berchane, Nader

2005-11-01

Controlled drug delivery offers numerous advantages compared with conventional free dosage forms, in particular: improved efficacy and patient compliance. Emulsification is a widely used technique to entrap drugs in biodegradable microspheres for controlled drug delivery. The size of the formed microspheres has a significant influence on drug release kinetics. Despite the advantages of controlled drug delivery, previous attempts to achieve predetermined release rates have seen limited success. This study develops a tool to tailor desired release kinetics by combining microsphere batches of specified mean diameter and size distribution. A fluid mechanics based correlation that predicts the average size of Poly(Lactide-co-Glycolide) [PLG] microspheres from the manufacturing technique, is constructed and validated by comparison with experimental results. The microspheres produced are accurately represented by the Rosin-Rammler mathematical distribution function. A mathematical model is formulated that incorporates the microsphere distribution function to predict the release kinetics from mono-dispersed and poly-dispersed populations. Through this mathematical model, different release kinetics can be achieved by combining different sized populations in different ratios. The resulting design tool should prove useful for the pharmaceutical industry to achieve designer release kinetics.

Optimal Preventive Maintenance Schedule based on Lifecycle Cost and Time-Dependent Reliability

DTIC Science & Technology

2011-11-10

Page 1 of 16 UNCLASSIFIED: Distribution Statement A. Approved for public release. 12IDM-0064 Optimal Preventive Maintenance Schedule based... 1 . INTRODUCTION Customers and product manufacturers demand continued functionality of complex equipment and processes. Degradation of material...Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response

Adaptive Decision Making Using Probabilistic Programming and Stochastic Optimization

DTIC Science & Technology

2018-01-01

world optimization problems (and hence 16 Approved for Public Release (PA); Distribution Unlimited Pred. demand (uncertain; discrete ...simplify the setting, we further assume that the demands are discrete , taking on values d1, . . . , dk with probabilities (conditional on x) (pθ)i ≡ p...Tyrrell Rockafellar. Implicit functions and solution mappings. Springer Monogr. Math ., 2009. Anthony V Fiacco and Yo Ishizuka. Sensitivity and stability

A novel model of motor learning capable of developing an optimal movement control law online from scratch.

PubMed

Shimansky, Yury P; Kang, Tao; He, Jiping

2004-02-01

A computational model of a learning system (LS) is described that acquires knowledge and skill necessary for optimal control of a multisegmental limb dynamics (controlled object or CO), starting from "knowing" only the dimensionality of the object's state space. It is based on an optimal control problem setup different from that of reinforcement learning. The LS solves the optimal control problem online while practicing the manipulation of CO. The system's functional architecture comprises several adaptive components, each of which incorporates a number of mapping functions approximated based on artificial neural nets. Besides the internal model of the CO's dynamics and adaptive controller that computes the control law, the LS includes a new type of internal model, the minimal cost (IM(mc)) of moving the controlled object between a pair of states. That internal model appears critical for the LS's capacity to develop an optimal movement trajectory. The IM(mc) interacts with the adaptive controller in a cooperative manner. The controller provides an initial approximation of an optimal control action, which is further optimized in real time based on the IM(mc). The IM(mc) in turn provides information for updating the controller. The LS's performance was tested on the task of center-out reaching to eight randomly selected targets with a 2DOF limb model. The LS reached an optimal level of performance in a few tens of trials. It also quickly adapted to movement perturbations produced by two different types of external force field. The results suggest that the proposed design of a self-optimized control system can serve as a basis for the modeling of motor learning that includes the formation and adaptive modification of the plan of a goal-directed movement.

Provider Experiences with Prison Care and Aftercare for Women with Co-occurring Mental Health and Substance Use Disorders: Treatment, Resource, and Systems Integration Challenges.

PubMed

Johnson, Jennifer E; Schonbrun, Yael Chatav; Peabody, Marlanea E; Shefner, Ruth T; Fernandes, Karen M; Rosen, Rochelle K; Zlotnick, Caron

2015-10-01

Incarcerated women with co-occurring mental health and substance use disorders (COD) face complex psychosocial challenges at community reentry. This study used qualitative methods to evaluate the perspectives of 14 prison and aftercare providers about service delivery challenges and treatment needs of reentering women with COD. Providers viewed the needs of women prisoners with COD as distinct from those of women with substance use alone and from men with COD. Providers described optimal aftercare for women with COD as including contact with the same provider before and after release, access to services within 24-72 hours after release, assistance with managing multiple social service agencies, assistance with relationship issues, and long-term follow-up. Providers also described larger service system and societal issues, including systems integration and ways in which a lack of prison and community aftercare resources impacted quality of care and reentry outcomes. Practice and policy implications are provided.

Provider Experiences with Prison Care and Aftercare for Women with Co-occurring Mental Health and Substance Use Disorders: Treatment, Resource, and Systems Integration Challenges

PubMed Central

Johnson, Jennifer E.; Schonbrun, Yael Chatav; Peabody, Marlanea E.; Shefner, Ruth T.; Fernandes, Karen M.; Rosen, Rochelle K.; Zlotnick, Caron

2014-01-01

Incarcerated women with co-occurring mental health and substance use disorders (COD) face complex psychosocial challenges at community reentry. This study used qualitative methods to evaluate the perspectives of 14 prison and aftercare providers about service delivery challenges and treatment needs of reentering women with COD. Providers viewed the needs of women prisoners with COD as distinct from those of women with substance use alone and from men with COD. Providers described optimal aftercare for women with COD as including contact with the same provider before and after release, access to services within 24–72 hours after release, assistance with managing multiple social service agencies, assistance with relationship issues, and long-term follow-up. Providers also described larger service system and societal issues, including systems integration and ways in which a lack of prison and community aftercare resources impacted quality of care and reentry outcomes. Practice and policy implications are provided. PMID:24595815

Development of a sustained fluoride delivery system.

PubMed

Baturina, Olga; Tufekci, Eser; Guney-Altay, Ozge; Khan, Shadeed M; Wnek, Gary E; Lindauer, Steven J

2010-11-01

To develop a novel delivery system by which fluoride incorporated into elastomeric rings, such as those used to ligate orthodontic wires, will be released in a controlled and constant manner. Polyethylene co-vinyl acetate (PEVA) was used as the model elastomer. Samples (N = 3) were prepared by incorporating 0.02 to 0.4 g of sodium fluoride (NaF) into previously prepared PEVA solution. Another group of samples prepared in the same manner were additionally dip-coated in PEVA to create an overcoat. Fluoride release studies were conducted in vitro using an ion selective electrode over a period of 45 days. The amount of fluoride released was compared to the optimal therapeutic dose of 0.7 microg F(-)/ring/d. Only coated samples with the highest fluoride content (group D, 0.4 g of NaF) were able to release fluoride at therapeutic levels. When fluoride release from coated and uncoated samples with the same amount of NaF were compared, it was shown that the dip-coating technique resulted in a fluoride release in a controlled manner while eliminating the initial burst effect. This novel fluoride delivery matrix provided fluoride release at a therapeutically effective rate and profile.

In vitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-oped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive

PubMed Central

Handa, Hitesh; Brisbois, Elizabeth J.; Major, Terry C.; Refahiyat, Lahdan; Amoako, Kagya A.; Annich, Gail M.; Bartlett, Robert H.; Meyerhoff, Mark E.

2013-01-01

Nitric oxide (NO) is an endogenous vasodilator as well as natural inhibitor of platelet adhesion and activation that can be released from a NO donor species, such as diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) within a polymer coating. In this study, various Food and Drug Administration approved poly(lactic-co-glycolic acid) (PLGA) species were evaluated as additives to promote a prolonged NO release from DBHD/N2O2 within a plasticized poly(vinyl chloride) (PVC) matrix. When using an ester-capped PLGA additive with a slow hydrolysis time, the resulting coatings continuously release between 7–18×10-10 mol cm-2 min-1 NO for 14 d at 37°C in PBS buffer. The corresponding pH changes within the polymer films were visualized using pH sensitive indicators and are shown to correlate with the extended NO release pattern. The optimal combined diazeniumdiolate/PLGA-doped NO release (NOrel) PVC coating was evaluated in vitro and its effect on the hemodynamics was also studied within a 4 h in vivo extracorporeal circulation (ECC) rabbit model of thrombogenicity. Four out of 7 control circuits clotted within 3 h, whereas all the NOrel coated circuits were patent after 4 h. Platelet counts on the NOrel ECC were preserved (79 ± 11% compared to 54 ± 6% controls). The NOrel coatings showed a significant decrease in the thrombus area as compared to the controls. Results suggest that by using ester-capped PLGAs as additives to a conventional plasticized PVC material containing a lipophilic diazeniumdiolates, the NO release can be prolonged for up to 2 weeks by controlling the pH within the organic phase of the coating. PMID:23914297

Optimal function explains forest responses to global change

Treesearch

Roderick Dewar; Oskar Franklin; Annikki Makela; Ross E. McMurtrie; Harry T. Valentine

2009-01-01

Plant responses to global changes in carbon dioxide (CO2), nitrogen, and water availability are critical to future atmospheric CO2 concentrations, hydrology, and hence climate. Our understanding of those responses is incomplete, however. Multiple-resource manipulation experiments and empirical observations have revealed a...

The structure and energetics of Cr(CO)6 and Cr(CO)5

NASA Technical Reports Server (NTRS)

Barnes, Leslie A.; Liu, Bowen; Lindh, Roland

1992-01-01

The geometric structure of Cr(CO)6 is optimized at the modified coupled pair functional (MCPF), single and double excitation coupled-cluster (CCSD) and CCSD(T) levels of theory (including a perturbational estimate for connected triple excitations), and the force constants for the totally symmetric representation are determined. The geometry of Cr(CO)5 is partially optimized at the MCPF, CCSD, and CCSD(T) levels of theory. Comparison with experimental data shows that the CCSD(T) method gives the best results for the structures and force constants, and that remaining errors are probably due to deficiencies in the one-particle basis sets used for CO. The total binding energies of Cr(CO)6 and Cr(CO)5 are also determined at the MCPF, CCSD, and CCSD(T) levels of theory. The CCSD(T) method gives a much larger total binding energy than either the MCPF or CCSD methods. An analysis of the basis set superposition error (BSSE) at the MCPF level of treatment points out limitations in the one-particle basis used. Calculations using larger basis sets reduce the BSSE, but the total binding energy of Cr(CO)6 is still significantly smaller than the experimental value, although the first CO bond dissociation energy of Cr(CO)6 is well described. An investigation of 3s3p correlation reveals only a small effect. In the largest basis set, the total CO binding energy of Cr(CO)6 is estimated to be 140 kcal/mol at the CCSD(T) level of theory, or about 86 percent of the experimental value. The remaining discrepancy between the experimental and theoretical value is probably due to limitations in the one-particle basis, rather than limitations in the correlation treatment. In particular an additional d function and an f function on each C and O are needed to obtain quantitative results. This is underscored by the fact that even using a very large primitive set (1042 primitive functions contracted to 300 basis functions), the superposition error for the total binding energy of Cr(CO)6 is 22 kcal/mol at the MCPF level of treatment.

Tailoring sub-micron PLGA particle release profiles via centrifugal fractioning

PubMed Central

Dutta, Dipankar; Salifu, Mariama; Sirianni, Rachael W.; Stabenfeldt, Sarah E.

2016-01-01

Poly(D,L-lactic-co-glycolic) acid (PLGA)-based submicron particles are uniquely posed to overcome limitations of conventional drug delivery systems. However, tailoring cargo/payload release profiles from PLGA micro/nanoparticles typically requires optimization of the multi-parameter formulation, where small changes may cause drastic shifts in the resulting release profiles. In this study, we aimed to establish whether refining the average diameter of submicron particle populations after formulation alters protein release profiles. PLGA particles were first produced via double emulsion-solvent evaporation method to encapsulate bovine serum albumin. Particles were then subjected to centrifugal fractioning protocols varying in both spin time and force to determine encapsulation efficiency and release profile of differently sized populations that originated from a single batch. We found the average particle diameter was related to marked alterations in encapsulation efficiencies (range: 36.4–49.4%), burst release (range: 15.8–49.1%), and time for total cargo release (range: 38–78 days). Our data corroborate previous reports relating PLGA particle size with such release characteristics, however, this is the first study, to our knowledge, to directly compare particle population size while holding all formulation parameters constant. In summary, centrifugal fractioning to selectively control the population distribution of sub-micron PLGA particles represents a feasible tool to tailor release characteristics. PMID:26517011

A novel accelerated in vitro release method to evaluate the release of thymopentin from PLGA microspheres.

PubMed

Xie, Xiangyang; Li, Zhiping; Zhang, Ling; Chi, Qiang; Yang, Yanfang; Zhang, Hui; Yang, Yang; Mei, Xingguo

2015-01-01

A novel accelerated method of good correlations with "real-time" release to evaluate in vitro thymopentin release from poly (D, L-lactide-co-glycolide) (PLGA) microsphere was developed. Thymopentin-loaded microspheres were made from three types of PLGA, and peptide release was studied in various conditions. Incomplete release of peptide (<60%) from microspheres was found in accelerated testing with two typical release media. This problem was circumvented by adding organic solvents to the release media and varying the temperature in the media heating process. Release media containing three kinds of organic solvents at 50 °C were tested, respectively, and hydro-alcoholic solution was selected for further study. After the surfactant concentration (0.06%, W/V) and ethanol concentration (20%, V/V) were fixed, a gradient heating program, consisting of three stages and each stage with a different temperature, was introduced to enhance the correlations between the short- and long-term release. After adjusting the heating time of each stage, a good correlation (R(2) = 9896, formulation 8 K; R(2) = 0.9898, formulation 13 K; R(2) = 0.9886, formulation 28 K) between accelerated and "real-time" release was obtained. By optimizing the conditions as ethanol concentration and temperature gradients, this accelerated method may be appropriate for similar peptide formulations that not well correlate with "real-time" release.

CO binding improves the structural, functional, physical and anti-oxidation properties of the PEGylated hemoglobin.

PubMed

Wang, Qingqing; Hu, Tao; Sun, Lijing; Ji, Shaoyang; Zhao, Dawei; Liu, Jiaxin; Ma, Guanghui; Su, Zhiguo

2015-02-01

PEGylated hemoglobin (Hb) is a promising oxygen therapeutic agent for clinical application. However, it suffered from structural perturbation, functional instability and methemoglobin (metHb) formation. To improve the structural, functional, physical and anti-oxidation properties of the PEGylated Hb. PEGylation of Hb with CO binding (HbCO) was conducted using maleimide and acylation chemistry, respectively. Physical and chemical parameters were measured for Hb samples. The circular dichroism spectra, dynamic light scattering and analytical ultracentrifugation were used to investigate the structure and conformation of PEGylated HbCO. CO binding can inhibit the autoxidation of the PEGylated Hb, structurally stabilize its tetramer and improve its thermal and pH stability. Importantly, the circular dichroism spectra showed that CO binding can decrease the structural perturbation of Hb induced by PEGylation. The PEGylated HbCO with CO release showed slightly higher oxygen-delivery capacity than the PEGylated Hb. The PEGylated HbCO did not show metHb formation after 30-day storage at 4°C. CO binding structurally stabilized the PEGylated Hb, abolished its metHb formation, and significantly increased its physical stability. In particular, it also avoided the perturbation of PEG chains on the heme microenvironment. The functional property of the PEGylated HbCO can be maintained during its long-term storage, which is of great significance for field transfusion.

Can observed ecosystem responses to elevated CO2 and N fertilisation be explained by optimal plant C allocation?

NASA Astrophysics Data System (ADS)

Stocker, Benjamin; Prentice, I. Colin

2016-04-01

The degree to which nitrogen availability limits the terrestrial C sink under rising CO2 is a key uncertainty in carbon cycle and climate change projections. Results from ecosystem manipulation studies and meta-analyses suggest that plant C allocation to roots adjusts dynamically under varying degrees of nitrogen availability and other soil fertility parameters. In addition, the ratio of biomass production to GPP appears to decline under nutrient scarcity. This reflects increasing plant C export into the soil and to symbionts (Cex) with decreasing nutrient availability. Cex is consumed by an array of soil organisms and may imply an improvement of nutrient availability to the plant. These concepts are left unaccounted for in Earth system models. We present a model for the coupled cycles of C and N in grassland ecosystems to explore optimal plant C allocation under rising CO2 and its implications for the ecosystem C balance. The model follows a balanced growth approach, accounting for the trade-offs between leaf versus root growth and Cex in balancing C fixation and N uptake. We further model a plant-controlled rate of biological N fixation (BNF) by assuming that Cex is consumed by N2-fixing processes if the ratio of Nup:Cex falls below the inverse of the C cost of N2-fixation. The model is applied at two temperate grassland sites (SwissFACE and BioCON), subjected to factorial treatments of elevated CO2 (FACE) and N fertilization. Preliminary simulation results indicate initially increased N limitation, evident by increased relative allocation to roots and Cex. Depending on the initial state of N availability, this implies a varying degree of aboveground growth enhancement, generally consistent with observed responses. On a longer time scale, ecosystems are progressively released from N limitation due tighter N cycling. Allowing for plant-controlled BNF implies a quicker release from N limitation and an adjustment to more open N cycling. In both cases, optimal plant C allocation implies a sustained growth enhancement but a decreased ratio of biomass productivity to GPP. Flexible allocation, C cost of N uptake, and flexible N retention imply plant control on N availability. Thereby, plant control on BNF is essential to determine the ultimate growth enhancement under elevated CO2 and whether this implies higher N losses and N2O emissions.

pH-responsive drug delivery system based on AIE luminogen functionalized layered zirconium phosphate nano-platelets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Dongdong, E-mail: lidongdong@jlu.edu.cn; Zhang, Yuping; Zhou, Bingbing

2015-05-15

Aggregation-induced emission (AIE) luminogen, quaternary tetraphenylethene cation (TPEN), was successfully incorporated into layered α-zirconium phosphate (α-ZrP) by using co-precipitation method to form inorganic–organic hybrid materials. The obtained materials show the characteristic hexagonal platelet shape with the interlayer distance did not reveal significant difference compared with pure α-ZrP. In addition, the obtained hybrid materials emit strong blue emission centered at 476 nm in aqueous media due to the electrostatic interactions of TPEN with the anionic framework of α-ZrP, which largely restrict their intramolecular rotation. More importantly, the materials provide a pH dependent release of doxorubicin (DOX), suggesting that AIE luminogen functionalizedmore » α-ZrP may be used as an imaging guided and pH-responsive delivery system for targeting therapy. - Graphical abstract: AIE luminogen was successfully incorporated into layered α-zirconium phosphate by a co-precipitation method to form inorganic–organic hybrid materials, showing a pH dependent release of DOX. - Highlights: • AIE luminogen cation was incorporated into layered α-ZrP by co-precipitation method. • The obtained material emits strong blue emission upon UV irradiation. • The material exhibits pH dependent release of DOX. • The AIE functionalized α-ZrP has potential applications in imaging guided therapy.« less

An Accelerated Release Method of Risperidone Loaded PLGA Microspheres with Good IVIVC.

PubMed

Hu, Xiaoqin; Zhang, Jianwei; Tang, Xuemei; Li, Mingyuan; Ma, Siyu; Liu, Cheng; Gao, Yue; Zhang, Yue; Liu, Yan; Yu, Fanglin; Yang, Yang; Guo, Jia; Li, Zhiping; Mei, Xingguo

2018-01-01

A long release period lasting several days or several weeks is always needed and thereby it is tedious and time consuming to screen formulations of such microspheres with so long release period and evaluate their release profiles in vitro with conventional long-term or "real-time" release method. So, an accelerated release testing of such system is necessary for formulation design as well as quality control purpose. The purpose of this study is to obtain an accelerated release method of risperidone loaded poly(lactic-co-glycolic acid) (PLGA) microspheres with good in vitro/in vivo correlation (IVIVC). Two formulations of risperidone loaded PLGA microspheres used for evaluating IVIVC were prepared by O/W method. The accelerated release condition was optimized by investigating the effect of pH, osmotic pressure, temperature and ethanol concentration on the release of risperidone from microspheres and the in vitro accelerated release profiles of risperidone from PLGA microspheres were obtained under this optimized accelerated release condition. The plasma concentration of risperidone were also detected after subcutaneous injection of risperidone loaded microspheres to rats. The in vivo cumulative absorption profiles were then calculated using Wagner-Nelson model, Loo- Riegelman model and numerical convolution model, respectively. The correlation between in vitro accelerated release and in vivo cumulative absorption were finally evaluated with Least Square Method. It was shown that temperature and ethanol concentration significantly affected the release of risperidone from the microspheres while pH and osmotic pressure of release media slightly affected the release behavior of risperidone. The in vitro release of risperidone from microspheres were finally undergone in PBS (pH7.0, 300mosm) with 20% (V/V) ethanol at 45°C. The sustained and complete release of risperidone was observed in both formulations under the accelerated release condition although these two release profiles were dissimilar. The correlation coefficients (R2) of IVIVC were all above 0.95 and the slopes were all between 0.9564 and 1.1868 in spite of fitted model and microsphere formulation. An in vitro accelerated release method of risperidone microspheres with good IVIVC was established in this paper and this accelerated release method was supposed to have great potential in both in vivo performance prediction and quality control for risperidone loaded PLGA microspheres. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Robust Team-Optimal and Leader-Follower Policies for Decision Making in C3 (Command, Control and Communications) Systems.

DTIC Science & Technology

1984-07-01

edition , Moscow: Nooka Publishing Co.. 1977; toelith translation of the Ilt edition : t ine with a specific cost structure, we have obtained Functional...651-666, September 1981. [131 L. W. Kantorovich and G. P. Akilov, Functional Analysis, 2nd edition , Moscow: Nauka Publishing Co., 1977; English...translation of the ist edition : Functional Analysis in Normed Spaces, New York: MacMillan, 1964. [14] J. Marschak and R. Radner, Economic Theory of Teams

An entropy-assisted musculoskeletal shoulder model.

PubMed

Xu, Xu; Lin, Jia-Hua; McGorry, Raymond W

2017-04-01

Optimization combined with a musculoskeletal shoulder model has been used to estimate mechanical loading of musculoskeletal elements around the shoulder. Traditionally, the objective function is to minimize the summation of the total activities of the muscles with forces, moments, and stability constraints. Such an objective function, however, tends to neglect the antagonist muscle co-contraction. In this study, an objective function including an entropy term is proposed to address muscle co-contractions. A musculoskeletal shoulder model is developed to apply the proposed objective function. To find the optimal weight for the entropy term, an experiment was conducted. In the experiment, participants generated various 3-D shoulder moments in six shoulder postures. The surface EMG of 8 shoulder muscles was measured and compared with the predicted muscle activities based on the proposed objective function using Bhattacharyya distance and concordance ratio under different weight of the entropy term. The results show that a small weight of the entropy term can improve the predictability of the model in terms of muscle activities. Such a result suggests that the concept of entropy could be helpful for further understanding the mechanism of muscle co-contractions as well as developing a shoulder biomechanical model with greater validity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development, optimization, and in vitro characterization of dasatinib-loaded PEG functionalized chitosan capped gold nanoparticles using Box-Behnken experimental design.

PubMed

Adena, Sandeep Kumar Reddy; Upadhyay, Mansi; Vardhan, Harsh; Mishra, Brahmeshwar

2018-03-01

The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs). Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett-Burman design (PBD) followed by Box-Behnken experimental design (BBD) were employed to optimize the process parameters. Polynomial equations, contour, and 3D response surface plots were generated to relate the factors and responses. The optimized DSB-PEG-Ch-GNPs were characterized by FTIR, XRD, HR-SEM, EDX, TEM, SAED, AFM, DLS, and ZP. The results of the optimized DSB-PEG-Ch-GNPs showed particle size (PS) of 24.39 ± 1.82 nm, apparent drug content (ADC) of 72.06 ± 0.86%, and zeta potential (ZP) of -13.91 ± 1.21 mV. The responses observed and the predicted values of the optimized process were found to be close. The shape and surface morphology studies showed that the resulting DSB-PEG-Ch-GNPs were spherical and smooth. The stability and in vitro drug release studies confirmed that the optimized formulation was stable at different conditions of storage and exhibited a sustained drug release of the drug of up to 76% in 48 h and followed Korsmeyer-Peppas release kinetic model. A process for preparing gold nanoparticles using chitosan, anchoring PEG to the particle surface, and entrapping dasatinib in the chitosan-PEG surface corona was optimized.

One-pot preparation of a sulfamethoxazole functionalized affinity monolithic column for selective isolation and purification of trypsin.

PubMed

Xiao, Yuan; Guo, Jialiang; Ran, Danni; Duan, Qianqian; Crommen, Jacques; Jiang, Zhengjin

2015-06-26

A facile and efficient "one-pot" copolymerization strategy was used for the preparation of sulfonamide drug (SA) functionalized monolithic columns. Two novel SA-immobilized methacrylate monolithic columns, i.e. poly(GMA-SMX-co-EDMA) and poly(GMA-SAA-co-EDMA) were prepared by one-pot in situ copolymerization of the drug ligand (sulfamethoxazole (SMX) or sulfanilamide (SAA)), the monomer (glycidyl methacrylate, GMA) and the cross-linker (ethylene dimethacrylate, EDMA) within 100 μm i.d. capillaries under optimized polymerization conditions. The physicochemical properties and column performance of the fabricated monolithic columns were characterized by elemental analysis, scanning electron microscopy and micro-HPLC. Satisfactory column permeability, efficiency and separation performance were obtained on the optimized poly(GMA-SMX-co-EDMA) monolithic column for small molecules, such as a standard test mixture and eight aromatic ketones. Notably, it was found that the poly(GMA-SMX-co-EDMA) monolith showed a selective affinity to trypsin, while the poly(GMA-SAA-co-EDMA) monolith containing sulfanilamide did not exhibit such affinity at all. This research not only provides a novel monolith for the selective isolation and purification of trypsin, but it also offers the possibility to easily prepare novel drug functionalized methacrylate monoliths through a one-pot copolymerization strategy. Copyright © 2015 Elsevier B.V. All rights reserved.

Borophene as a Promising Material for Charge-Modulated Switchable CO2 Capture.

PubMed

Tan, Xin; Tahini, Hassan A; Smith, Sean C

2017-06-14

Ideal carbon dioxide (CO 2 ) capture materials for practical applications should bind CO 2 molecules neither too weakly to limit good loading kinetics nor too strongly to limit facile release. Although charge-modulated switchable CO 2 capture has been proposed to be a controllable, highly selective, and reversible CO 2 capture strategy, the development of a practical gas-adsorbent material remains a great challenge. In this study, by means of density functional theory (DFT) calculations, we have examined the possibility of conductive borophene nanosheets as promising sorbent materials for charge-modulated switchable CO 2 capture. Our results reveal that the binding strength of CO 2 molecules on negatively charged borophene can be significantly enhanced by injecting extra electrons into the adsorbent. At saturation CO 2 capture coverage, the negatively charged borophene achieves CO 2 capture capacities up to 6.73 × 10 14 cm -2 . In contrast to the other CO 2 capture methods, the CO 2 capture/release processes on negatively charged borophene are reversible with fast kinetics and can be easily controlled via switching on/off the charges carried by borophene nanosheets. Moreover, these negatively charged borophene nanosheets are highly selective for separating CO 2 from mixtures with CH 4 , H 2 , and/or N 2 . This theoretical exploration will provide helpful guidance for identifying experimentally feasible, controllable, highly selective, and high-capacity CO 2 capture materials with ideal thermodynamics and reversibility.

β-Cyclodextrin hydrogels for the ocular release of antibacterial thiosemicarbazones.

PubMed

Glisoni, Romina J; García-Fernández, María J; Pino, Marylú; Gutkind, Gabriel; Moglioni, Albertina G; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Sosnik, Alejandro

2013-04-02

Two types of hydrophilic networks with conjugated beta-cyclodextrin (β-CD) were developed with the aim of engineering useful platforms for the localized release of an antimicrobial 5,6-dimethoxy-1-indanone N4-allyl thiosemicarbazone (TSC) in the eye and its potential application in ophthalmic diseases. Poly(2-hydroxyethyl methacrylate) soft contact lenses (SCLs) displaying β-CD, namely pHEMA-co-β-CD, and super-hydrophilic hydrogels (SHHs) of directly cross-linked hydroxypropyl-β-CD were synthesized and characterized regarding their structure (ATR/FT-IR), drug loading capacity, swelling and in vitro release in artificial lacrimal fluid. Incorporation of TSC to the networks was carried out both during polymerization (DP method) and after synthesis (PP method). The first method led to similar drug loads in all the hydrogels, with minor drug loss during the washing steps to remove unreacted monomers, while the second method evidenced the influence of structural parameters on the loading efficiency (proportion of CD units, mesh size, swelling degree). Both systems provided a controlled TSC release for at least two weeks, TSC concentrations (up to 4000μg/g dry hydrogel) being within an optimal therapeutic window for the antimicrobial ocular treatment. Microbiological tests against P. aeruginosa and S. aureus confirmed the ability of TSC-loaded pHEMA-co-β-CD network to inhibit bacterial growth. Copyright © 2012 Elsevier Ltd. All rights reserved.

Integrating research, clinical care, and education in academic health science centers.

PubMed

King, Gillian; Thomson, Nicole; Rothstein, Mitchell; Kingsnorth, Shauna; Parker, Kathryn

2016-10-10

Purpose One of the major issues faced by academic health science centers (AHSCs) is the need for mechanisms to foster the integration of research, clinical, and educational activities to achieve the vision of evidence-informed decision making (EIDM) and optimal client care. The paper aims to discuss this issue. Design/methodology/approach This paper synthesizes literature on organizational learning and collaboration, evidence-informed organizational decision making, and learning-based organizations to derive insights concerning the nature of effective workplace learning in AHSCs. Findings An evidence-informed model of collaborative workplace learning is proposed to aid the alignment of research, clinical, and educational functions in AHSCs. The model articulates relationships among AHSC academic functions and sub-functions, cross-functional activities, and collaborative learning processes, emphasizing the importance of cross-functional activities in enhancing collaborative learning processes and optimizing EIDM and client care. Cross-functional activities involving clinicians, researchers, and educators are hypothesized to be a primary vehicle for integration, supported by a learning-oriented workplace culture. These activities are distinct from interprofessional teams, which are clinical in nature. Four collaborative learning processes are specified that are enhanced in cross-functional activities or teamwork: co-constructing meaning, co-learning, co-producing knowledge, and co-using knowledge. Practical implications The model provides an aspirational vision and insight into the importance of cross-functional activities in enhancing workplace learning. The paper discusses the conceptual and empirical basis to the model, its contributions and limitations, and implications for AHSCs. Originality/value The model's potential utility for health care is discussed, with implications for organizational culture and the promotion of cross-functional activities.

Application of hydroxyapatite nanoparticles in development of an enhanced formulation for delivering sustained release of triamcinolone acetonide

PubMed Central

Koocheki, Saeid; Madaeni, Sayed Siavash; Niroomandi, Parisa

2011-01-01

We report an analysis of in vitro and in vivo drug release from an in situ formulation consisting of triamcinolone acetonide (TR) and poly(d,l-lactide-co-glycolide) (PLGA) and the additives glycofurol (GL) and hydroxyapatite nanoparticles (HA). We found that these additives enhanced drug release rate. We used the Taguchi method to predict optimum formulation variables to minimize the initial burst. This method decreased the burst rate from 8% to 1.3%. PLGA-HA acted as a strong buffer, thereby preventing tissue inflammation at the injection site caused by the acidic degradation products of PLGA. Characterization of the optimized formulation by a variety of techniques, including scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Fourier transform near infrared spectroscopy, revealed that the crystalline structure of TR was converted to an amorphous form. Therefore, this hydrophobic agent can serve as an additive to modify drug release rates. Data generated by in vitro and in vivo experiments were in good agreement. PMID:21589650

Control optimization of a lifting body entry problem by an improved and a modified method of perturbation function. Ph.D. Thesis - Houston Univ.

NASA Technical Reports Server (NTRS)

Garcia, F., Jr.

1974-01-01

A study of the solution problem of a complex entry optimization was studied. The problem was transformed into a two-point boundary value problem by using classical calculus of variation methods. Two perturbation methods were devised. These methods attempted to desensitize the contingency of the solution of this type of problem on the required initial co-state estimates. Also numerical results are presented for the optimal solution resulting from a number of different initial co-states estimates. The perturbation methods were compared. It is found that they are an improvement over existing methods.

Contribution to the optimal shape design of two-dimensional internal flows with embedded shocks

NASA Technical Reports Server (NTRS)

Iollo, Angelo; Salas, Manuel D.

1995-01-01

We explore the practicability of optimal shape design for flows modeled by the Euler equations. We define a functional whose minimum represents the optimality condition. The gradient of the functional with respect to the geometry is calculated with the Lagrange multipliers, which are determined by solving a co-state equation. The optimization problem is then examined by comparing the performance of several gradient-based optimization algorithms. In this formulation, the flow field can be computed to an arbitrary order of accuracy. Finally, some results for internal flows with embedded shocks are presented, including a case for which the solution to the inverse problem does not belong to the design space.

Respiration of resting honeybees

PubMed Central

Kovac, Helmut; Stabentheiner, Anton; Hetz, Stefan K.; Petz, Markus; Crailsheim, Karl

2011-01-01

The relation between the respiratory activity of resting honeybees and ambient temperature (Ta) was investigated in the range of 5–40 °C. Bees were kept in a temperature controlled flow through respirometer chamber where their locomotor and endothermic activity, as well as abdominal ventilatory movements was recorded by infrared thermography. Surprisingly, true resting bees were often weakly endothermic (thorax surface up to 2.8 °C warmer than abdomen) at a Ta of 14–30 °C. Above 33 °C many bees cooled their body via evaporation from their mouthparts. A novel mathematical model allows description of the relationship of resting (standard) metabolic rate and temperature across the entire functional temperature range of bees. In chill coma (<11 °C) bees were ectothermic and CO2 release was mostly continuous. CO2 release rate (nl s−1) decreased from 9.3 at 9.7 °C to 5.4 at 5 °C. At a Ta of >11 °C CO2 was released discontinuously. In the bees’ active temperature range mean CO2 production rate (nl s−1) increased sigmoidally (10.6 at 14.1 °C, 24.1 at 26.5 °C, and 55.2 at 38.1 °C), coming to a halt towards the upper lethal temperature. This was primarily accomplished by an exponential increase in gas exchange frequency (0.54 and 3.1 breaths min−1 at 14.1 and 38.1 °C) but not in released CO2 volume per respiratory cycle (1487 and 1083 nl cycle−1 at 14.1 and 38.1 °C). Emission of CO2 bursts was mostly (98%) accompanied by abdominal ventilation movements even in small CO2 bursts. Larger bursts coincided with a longer duration of active ventilation. An increased amount of CO2 expelled per unit time of ventilation indicates a higher efficiency of ventilation at high ambient temperatures. PMID:17707395

Tapping the Bioactivity Potential of Residual Stream from Its Pretreatments May Be a Green Strategy for Low-Cost Bioconversion of Rice Straw.

PubMed

Chen, Xingxuan; Wang, Xiahui; Xue, Yiyun; Zhang, Tian-Ao; Hu, Jiajun; Tsang, Yiu Fai; Gao, Min-Tian

2018-04-16

In this study, it was found that the residual stream from pretreatments of rice straw exhibited high antioxidant activity. Assays based on the Folin-Ciocalteu colorimetric method confirmed that the residual stream contained large amounts of phenolic compounds. Three antioxidant assays were employed to evaluate the bioactivity of the residual stream. Strong linear correlations existed among the release of phenolic compounds, saccharification efficiency, and antioxidant activity. The alkaline pretreatment provided a much greater release of phenolic compounds, especially phenolic acids, compared to the acid pretreatment, and consequently, it had stronger linear correlations than the acid pretreatment. Antibacterial experiments demonstrated the ability of the phenolic compounds in the residual stream to inhibit the growth of microorganisms, indicating the potential of these compounds as antimicrobial agents. To discuss the possibility of the co-production of antimicrobial agents and biofuels/biochemicals, both acid and alkaline pretreatments were optimized using response surface methodology. Under the optimal conditions, 285.7 g glucose could be produced from 1 kg rice straw with the co-production of 3.84 g FA and 6.98 g p-CA after alkaline pretreatment. These results show that the recovery of phenolic compounds from the residual stream could be a green strategy for the low-cost bioconversion of rice straw.

Investigation on influence of Wurster coating process parameters for the development of delayed release minitablets of Naproxen.

PubMed

Shah, Neha; Mehta, Tejal; Aware, Rahul; Shetty, Vasant

2017-12-01

The present work aims at studying process parameters affecting coating of minitablets (3 mm in diameter) through Wurster coating process. Minitablets of Naproxen with high drug loading were manufactured using 3 mm multi-tip punches. The release profile of core pellets (published) and minitablets was compared with that of marketed formulation. The core formulation of minitablets was found to show similarity in dissolution profile with marketed formulation and hence was further carried forward for functional coating over it. Wurster processing was implemented to pursue functional coating over core formulation. Different process parameters were screened and control strategy was applied for factors significantly affecting the process. Modified Plackett Burman Design was applied for studying important factors. Based on the significant factors and minimum level of coating required for functionalization, optimized process was executed. Final coated batch was evaluated for coating thickness, surface morphology, and drug release study.

A review on optimization production and upgrading biogas through CO2 removal using various techniques.

PubMed

Andriani, Dian; Wresta, Arini; Atmaja, Tinton Dwi; Saepudin, Aep

2014-02-01

Biogas from anaerobic digestion of organic materials is a renewable energy resource that consists mainly of CH4 and CO2. Trace components that are often present in biogas are water vapor, hydrogen sulfide, siloxanes, hydrocarbons, ammonia, oxygen, carbon monoxide, and nitrogen. Considering the biogas is a clean and renewable form of energy that could well substitute the conventional source of energy (fossil fuels), the optimization of this type of energy becomes substantial. Various optimization techniques in biogas production process had been developed, including pretreatment, biotechnological approaches, co-digestion as well as the use of serial digester. For some application, the certain purity degree of biogas is needed. The presence of CO2 and other trace components in biogas could affect engine performance adversely. Reducing CO2 content will significantly upgrade the quality of biogas and enhancing the calorific value. Upgrading is generally performed in order to meet the standards for use as vehicle fuel or for injection in the natural gas grid. Different methods for biogas upgrading are used. They differ in functioning, the necessary quality conditions of the incoming gas, and the efficiency. Biogas can be purified from CO2 using pressure swing adsorption, membrane separation, physical or chemical CO2 absorption. This paper reviews the various techniques, which could be used to optimize the biogas production as well as to upgrade the biogas quality.

Supercritical CO2 foamed polycaprolactone scaffolds for controlled delivery of 5-fluorouracil, nicotinamide and triflusal.

PubMed

Salerno, Aurelio; Saurina, Javier; Domingo, Concepción

2015-12-30

The manufacture of porous polycaprolactone (PCL) scaffolds containing three different drugs, namely 5-fluorouracil, nicotinamide and triflusal, was investigated in this work with the aim of obtaining bioactive systems with controlled drug delivery capabilities. The scaffolds were prepared by means of a supercritical CO2 (scCO2) foaming technique by optimizing the drug loading process. This was achieved by dissolving the drugs in organic solvents miscible with scCO2 and by mixing these drug/solvent solutions with PCL powder. The as prepared mixtures were further compressed to eliminate air bubbles and finally processed by the scCO2 foaming technique. ScCO2 saturation and foaming conditions were optimized to create the porosity within the samples and to allow for the concomitant removal of the organic solvents. Physical and chemical properties of porous scaffolds, as well as drug content and delivery profiles, were studied by HPLC. The results of this study demonstrated that the composition of the starting PCL/drug/solvent mixtures affected polymer crystallization, scaffold morphology and pore structure features. Furthermore, it was found that drug loading efficiency depended on both initial solution composition and drug solubility in scCO2. Nevertheless, in the case of highly scCO2-soluble drugs, such as triflusal, loading efficiency was improved by adding a proper amount of free drug inside of the pressure vessel. The drug delivery study indicated that release profiles depended mainly upon scaffolds composition and pore structure features. Copyright © 2015 Elsevier B.V. All rights reserved.

Membrane Vesicles Released by Intestinal Epithelial Cells Infected with Rotavirus Inhibit T-Cell Function

PubMed Central

Barreto, Alfonso; Rodríguez, Luz-Stella; Rojas, Olga Lucía; Wolf, Marie; Greenberg, Harry B.; Franco, Manuel A.

2010-01-01

Abstract Rotavirus (RV) predominantly replicates in intestinal epithelial cells (IEC), and “danger signals” released by these cells may modulate viral immunity. We have recently shown that human model IEC (Caco-2 cells) infected with rhesus-RV release a non-inflammatory group of immunomodulators that includes heat shock proteins (HSPs) and TGF-β1. Here we show that both proteins are released in part in association with membrane vesicles (MV) obtained from filtrated Caco-2 supernatants concentrated by ultracentrifugation. These MV express markers of exosomes (CD63 and others), but not of the endoplasmic reticulum (ER) or nuclei. Larger quantities of proteins associated with MV were released by RV-infected cells than by non-infected cells. VP6 co-immunoprecipitated with CD63 present in these MV, and VP6 co-localized with CD63 in RV-infected cells, suggesting that this viral protein is associated with the MV, and that this association occurs intracellularly. CD63 present in MV preparations from stool samples from 36 children with gastroenteritis due or not due to RV were analyzed. VP6 co-immunoprecipitated with CD63 in 3/8 stool samples from RV-infected children, suggesting that these MV are released by RV-infected cells in vivo. Moreover, fractions that contained MV from RV-infected cells induced death and inhibited proliferation of CD4+ T cells to a greater extent than fractions from non-infected cells. These effects were in part due to TGF-β, because they were reversed by treatment of the T cells with the TGF-β-receptor inhibitor ALK5i. MV from RV-infected and non-infected cells were heterogeneous, with morphologies and typical flotation densities described for exosomes (between 1.10 and 1.18 g/mL), and denser vesicles (>1.24 g/mL). Both types of MV from RV-infected cells were more efficient at inhibiting T-cell function than were those from non-infected cells. We propose that RV infection of IEC releases MV that modulate viral immunity. PMID:21142445

A Reversed Photosynthesis-like Process for Light-Triggered CO2 Capture, Release, and Conversion.

PubMed

Wang, Dingguan; Liao, Shenglong; Zhang, Shiming; Wang, Yapei

2017-06-22

Materials for CO 2 capture have been extensively exploited for climate governance and gas separation. However, their regeneration is facing the problems of high energy cost and secondary CO 2 contamination. Herein, a reversed photosynthesis-like process is proposed, in which CO 2 is absorbed in darkness while being released under light illumination. The process is likely supplementary to natural photosynthesis of plants, in which, on the contrary, CO 2 is released during the night. Remarkably, the material used here is able to capture 9.6 wt.% CO 2 according to its active component. Repeatable CO 2 capture at room temperature and release under light irradiation ensures its convenient and cost-effective regeneration. Furthermore, CO 2 released from the system is successfully converted into a stable compound in tandem with specific catalysts. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nitric Oxide Releasing Coronary Stent: A New Approach Using Layer-by-Layer Coating and Liposomal Encapsulation.

PubMed

Elnaggar, Mahmoud A; Seo, Seong Ho; Gobaa, Samy; Lim, Kyung Seob; Bae, In-Ho; Jeong, Myung Ho; Han, Dong Keun; Joung, Yoon Ki

2016-11-01

The sustained or controlled release of nitric oxide (NO) can be the most promising approach for the suppression or prevention of restenosis and thrombosis caused by stent implantation. The aim of this study is to investigate the feasibility in the potential use of layer-by-layer (LBL) coating with a NO donor-containing liposomes to control the release rate of NO from a metallic stent. Microscopic observation and surface characterizations of LBL-modified stents demonstrate successful LBL coating with liposomes on a stent. Release profiles of NO show that the release rate is sustained up to 5 d. In vitro cell study demonstrates that NO release significantly enhances endothelial cell proliferation, whereas it markedly inhibits smooth muscle cell proliferation. Finally, in vivo study conducted with a porcine coronary injury model proves the therapeutic efficacy of the NO-releasing stents coated by liposomal LBL technique, supported by improved results in luminal healing, inflammation, and neointimal thickening except thrombo-resistant effect. As a result, all these results demonstrate that highly optimized release rate and therapeutic dose of NO can be achieved by LBL coating and liposomal encapsulation, followed by significantly efficacious outcome in vivo. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of elevated atmospheric Co2 and tropospheric O3 on nutrient dynamics: decomposition of leaf litter in trembling aspen and paper birch communities. Plant Soil. 299:65–82.

Treesearch

Lingli Liu; John S. King; Christian P. Giardina

2007-01-01

Atmospheric changes could strongly influence how terrestrial ecosystems function by altering nutrient cycling. We examined how the dynamics of nutrient release from leaf litter responded to two important atmospheric changes: rising atmospheric Co2 and tropospheric O3. We evaluated the independent and combined effects of...

In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers

PubMed Central

Li, Di; Ding, Jian Xun; Tang, Zhao Hui; Sun, Hai; Zhuang, Xiu Li; Xu, Jing Zhe; Chen, Xue Si

2012-01-01

Four monomethoxy poly(ethylene glycol)-poly(L-lactide-co-glycolide)2 (mPEG-P( LA-co-GA)2) copolymers were synthesized by ring-opening polymerization of L-lactide and glycolide with double hydroxyl functionalized mPEG (mPEG-(OH)2) as macroinitiator and stannous octoate as catalyst. The copolymers self-assembled into nanoscale micellar/vesicular aggregations in phosphate buffer at pH 7.4. Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into the micellar/vesicular nanoparticles, yielding micellar/vesicular nanomedicines. The in vitro release behaviors could be adjusted by content of hydrophobic polyester and pH of the release medium. In vitro cell experiments showed that the intracellular DOX release could be adjusted by content of P(LA-co-GA), and the nanomedicines displayed effective proliferation inhibition against Henrietta Lacks’s cells with different culture times. Hemolysis tests indicated that the copolymers were hemocompatible, and the presence of copolymers could reduce the hemolysis ratio of DOX significantly. These results suggested that the novel anticancer nanomedicines based on DOX and amphiphilic Y-shaped copolymers were attractive candidates as tumor tissular and intracellular targeting drug delivery systems in vivo, with enhanced stability during circulation and accelerated drug release at the target sites. PMID:22701317

Layer-by-layer polyelectrolyte-polyester hybrid microcapsules for encapsulation and delivery of hydrophobic drugs.

PubMed

Luo, Rongcong; Venkatraman, Subbu S; Neu, Björn

2013-07-08

A two-step process is developed to form layer-by-layer (LbL) polyelectrolyte microcapsules, which are able to encapsulate and deliver hydrophobic drugs. Spherical porous calcium carbonate (CaCO3) microparticles were used as templates and coated with a poly(lactic acid-co-glycolic acid) (PLGA) layer containing hydrophobic compounds via an in situ precipitation gelling process. PLGA layers that precipitated from N-methyl-2-pyrrolidone (NMP) had a lower loading and smoother surface than those precipitated from acetone. The difference may be due to different viscosities and solvent exchange dynamics. In the second step, the successful coating of multilayer polyelectrolytes poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) onto the PLGA coated CaCO3 microparticles was confirmed with AFM and ζ-potential studies. The release of a model hydrophobic drug, ibuprofen, from these hybrid microcapsules with different numbers of PAH/PSS layers was investigated. It was found that the release of ibuprofen decreases with increasing layer numbers demonstrating the possibility to control the release of ibuprofen with these novel hybrid microcapsules. Besides loading of hydrophobic drugs, the interior of these microcapsules can also be loaded with hydrophilic compounds and functional nanoparticles as demonstrated by loading with Fe3O4 nanoparticles, forming magnetically responsive dual drug releasing carriers.

D-Optimal Experimental Design for Contaminant Source Identification

NASA Astrophysics Data System (ADS)

Sai Baba, A. K.; Alexanderian, A.

2016-12-01

Contaminant source identification seeks to estimate the release history of a conservative solute given point concentration measurements at some time after the release. This can be mathematically expressed as an inverse problem, with a linear observation operator or a parameter-to-observation map, which we tackle using a Bayesian approach. Acquisition of experimental data can be laborious and expensive. The goal is to control the experimental parameters - in our case, the sparsity of the sensors, to maximize the information gain subject to some physical or budget constraints. This is known as optimal experimental design (OED). D-optimal experimental design seeks to maximize the expected information gain, and has long been considered the gold standard in the statistics community. Our goal is to develop scalable methods for D-optimal experimental designs involving large-scale PDE constrained problems with high-dimensional parameter fields. A major challenge for the OED, is that a nonlinear optimization algorithm for the D-optimality criterion requires repeated evaluation of objective function and gradient involving the determinant of large and dense matrices - this cost can be prohibitively expensive for applications of interest. We propose novel randomized matrix techniques that bring down the computational costs of the objective function and gradient evaluations by several orders of magnitude compared to the naive approach. The effect of randomized estimators on the accuracy and the convergence of the optimization solver will be discussed. The features and benefits of our new approach will be demonstrated on a challenging model problem from contaminant source identification involving the inference of the initial condition from spatio-temporal observations in a time-dependent advection-diffusion problem.

CO and NO emissions from pellet stoves: an experimental study

NASA Astrophysics Data System (ADS)

Petrocelli, D.; Lezzi, A. M.

2014-04-01

This work presents a report on an experimental investigation on pellet stoves aimed to fully understand which parameters influence CO and NO emissions and how it is possible to find and choose the optimal point of working. Tests are performed on three pellet stoves varying heating power, combustion chamber size and burner pot geometry. After a brief review on the factors which influence the production of these pollutants, we present and discuss the results of experimental tests aimed to ascertain how the geometry of the combustion chamber and the distribution of primary and secondary air, can modify the quantity of CO and NO in the flue gas. Experimental tests show that production of CO is strongly affected by the excess air and by its distribution: in particular, it is critical an effective control of air distribution. In these devices a low-level of CO emissions does require a proper setup to operate in the optimal range of excess air that minimizes CO production. In order to simplify the optimization process, we propose the use of instantaneous data of CO and O2 concentration, instead of average values, because they allow a quick identification of the optimal point. It is shown that the optimal range of operation can be enlarged as a consequence of proper burner pot design. Finally, it is shown that NO emissions are not a critical issue, since they are well below threshold enforced by law, are not influenced by the distribution of air in the combustion chamber, and their behavior as a function of air excess is the same for all the geometries investigated here.

Nitrogen fertilization raises CO2 efflux from inorganic carbon: A global assessment.

PubMed

Zamanian, Kazem; Zarebanadkouki, Mohsen; Kuzyakov, Yakov

2018-07-01

Nitrogen (N) fertilization is an indispensable agricultural practice worldwide, serving the survival of half of the global population. Nitrogen transformation (e.g., nitrification) in soil as well as plant N uptake releases protons and increases soil acidification. Neutralizing this acidity in carbonate-containing soils (7.49 × 10 9  ha; ca. 54% of the global land surface area) leads to a CO 2 release corresponding to 0.21 kg C per kg of applied N. We here for the first time raise this problem of acidification of carbonate-containing soils and assess the global CO 2 release from pedogenic and geogenic carbonates in the upper 1 m soil depth. Based on a global N-fertilization map and the distribution of soils containing CaCO 3 , we calculated the CO 2 amount released annually from the acidification of such soils to be 7.48 × 10 12  g C/year. This level of continuous CO 2 release will remain constant at least until soils are fertilized by N. Moreover, we estimated that about 273 × 10 12  g CO 2 -C are released annually in the same process of CaCO 3 neutralization but involving liming of acid soils. These two CO 2 sources correspond to 3% of global CO 2 emissions by fossil fuel combustion or 30% of CO 2 by land-use changes. Importantly, the duration of CO 2 release after land-use changes usually lasts only 1-3 decades before a new C equilibrium is reached in soil. In contrast, the CO 2 released by CaCO 3 acidification cannot reach equilibrium, as long as N fertilizer is applied until it becomes completely neutralized. As the CaCO 3 amounts in soils, if present, are nearly unlimited, their complete dissolution and CO 2 release will take centuries or even millennia. This emphasizes the necessity of preventing soil acidification in N-fertilized soils as an effective strategy to inhibit millennia of CO 2 efflux to the atmosphere. Hence, N fertilization should be strictly calculated based on plant-demand, and overfertilization should be avoided not only because N is a source of local and regional eutrophication, but also because of the continuous CO 2 release by global acidification. © 2018 John Wiley & Sons Ltd.

Sustained release of diltiazem HCl tableted after co-spray drying and physical mixing with PVAc and PVP.

PubMed

Al-Zoubi, Nizar; Al-Obaidi, Ghada; Tashtoush, Bassam; Malamataris, Stavros

2016-01-01

In this work, aqueous diltiazem HCl and polyvinyl-pyrrolidone (PVP) solutions were mixed with Kollicoat SR 30D and spray dried to microparticles of different drug:excipient ratio and PVP content. Co-spray dried products and physical mixtures of drug, Kollidon SR and PVP were tableted. Spray drying process, co-spray dried products and compressibility/compactability of co-spray dried and physical mixtures, as well as drug release and water uptake of matrix-tablets was evaluated. Simple power equation fitted drug release and water uptake (R(2) > 0.909 and 0.938, respectively) and correlations between them were examined. Co-spray dried products with PVP content lower than in physical mixtures result in slower release, while at equal PVP content (19 and 29% w/w of excipient) in similar release (f2 > 50). Increase of PVP content increases release rate and co-spray drying might be an alternative, when physical mixing is inadequate. Co-spray dried products show better compressibility/compatibility but higher stickiness to the die-wall compared to physical mixtures. SEM observations and comparison of release and swelling showed that distribution of tableted component affects only the swelling, while PVP content for both co-spray dried and physical mixes is major reason for release alterations and an aid for drug release control.

A high-throughput microparticle microarray platform for dendritic cell-targeting vaccines.

PubMed

Acharya, Abhinav P; Clare-Salzler, Michael J; Keselowsky, Benjamin G

2009-09-01

Immunogenomic approaches combined with advances in adjuvant immunology are guiding progress toward rational design of vaccines. Furthermore, drug delivery platforms (e.g., synthetic particles) are demonstrating promise for increasing vaccine efficacy. Currently there are scores of known antigenic epitopes and adjuvants, and numerous synthetic delivery systems accessible for formulation of vaccines for various applications. However, the lack of an efficient means to test immune cell responses to the abundant combinations available represents a significant blockade on the development of new vaccines. In order to overcome this barrier, we report fabrication of a new class of microarray consisting of antigen/adjuvant-loadable poly(D,L lactide-co-glycolide) microparticles (PLGA MPs), identified as a promising carrier for immunotherapeutics, which are co-localized with dendritic cells (DCs), key regulators of the immune system and prime targets for vaccines. The intention is to utilize this high-throughput platform to optimize particle-based vaccines designed to target DCs in vivo for immune system-related disorders, such as autoimmune diseases, cancer and infection. Fabrication of DC/MP arrays leverages the use of standard contact printing miniarraying equipment in conjunction with surface modification to achieve co-localization of particles/cells on isolated islands while providing background non-adhesive surfaces to prevent off-island cell migration. We optimized MP overspotting pin diameter, accounting for alignment error, to allow construction of large, high-fidelity arrays. Reproducible, quantitative delivery of as few as 16+/-2 MPs per spot was demonstrated and two-component MP dosing arrays were constructed, achieving MP delivery which was independent of formulation, with minimal cross-contamination. Furthermore, quantification of spotted, surface-adsorbed MP degradation was demonstrated, potentially useful for optimizing MP release properties. Finally, we demonstrate DC co-localization with PLGA MPs on isolated islands and that DCs do not migrate between islands for up to 24 h. Using this platform, we intend to analyze modulation of DC function by providing multi-parameter combinatorial cues in the form of proteins, peptides and other immuno-modulatory molecules encapsulated in or tethered on MPs. Critically, the miniaturization attained enables high-throughput investigation of rare cell populations by reducing the requirement for cells and reagents by many-fold, facilitating advances in personalized vaccines which target DCs in vivo.

H2O and CO2 devolatilization in subduction zones: implications for the global water and carbon cycles (Invited)

NASA Astrophysics Data System (ADS)

van Keken, P. E.; Hacker, B. R.; Syracuse, E. M.; Abers, G. A.

2010-12-01

Subduction of sediments and altered oceanic crust functions as a major carbon sink. Upon subduction the carbon may be released by progressive metamorphic reactions, which can be strongly enhanced by free fluids. Quantification of the CO2 release from subducting slabs is important to determine the provenance of CO2 that is released by the volcanic arc and to constrain the flux of carbon to the deeper mantle. In recent work we used a global set of high resolution thermal models of subduction zones to predict the flux of H2O from the subducting slab (van Keken, Hacker, Syracuse, Abers, Subduction factory 4: Depth-dependent flux of H2O from subducting slabs worldwide, J. Geophys. Res., under review) which provides a new estimate of the dehydration efficiency of the global subducting system. It was found that mineralogically bound water can pass efficiently through old and fast subduction zones (such as in the western Pacific) but that warm subduction zones (such as Cascadia) see nearly complete dehydration of the subducting slab. The top of the slab is sufficiently hot in all subduction zones that the upper crust dehydrates significantly. The degree and depth of dehydration is highly diverse and strongly depends on (p,T) and bulk rock composition. On average about one third of subducted H2O reaches 240 km depth, carried principally and roughly equally in the gabbro and peridotite sections. The present-day global flux of H2O to the deep mantle translates to an addition of about one ocean mass over the age of the Earth. We extend the slab devolatilization work to carbon by providing an update to Gorman et al. (Geochem. Geophys. Geosyst, 2006), who quantified the effects of free fluids on CO2 release. The thermal conditions were based on three end-member subduction zones with linear interpolation to provide a global CO2 flux. We use the new high resolution and global set of models to provide higher resolution predictions for the provenance and pathways of CO2 release to the mantle wedge and a more robust prediction of the global CO2 flux in subduction.

High-throughput screening of PLGA thin films utilizing hydrophobic fluorescent dyes for hydrophobic drug compounds.

PubMed

Steele, Terry W J; Huang, Charlotte L; Kumar, Saranya; Widjaja, Effendi; Chiang Boey, Freddy Yin; Loo, Joachim S C; Venkatraman, Subbu S

2011-10-01

Hydrophobic, antirestenotic drugs such as paclitaxel (PCTX) and rapamycin are often incorporated into thin film coatings for local delivery using implantable medical devices and polymers such as drug-eluting stents and balloons. Selecting the optimum coating formulation through screening the release profile of these drugs in thin films is time consuming and labor intensive. We describe here a high-throughput assay utilizing three model hydrophobic fluorescent compounds: fluorescein diacetate (FDAc), coumarin-6, and rhodamine 6G that were incorporated into poly(d,l-lactide-co-glycolide) (PLGA) and PLGA-polyethylene glycol films. Raman microscopy determined the hydrophobic fluorescent dye distribution within the PLGA thin films in comparison with that of PCTX. Their subsequent release was screened in a high-throughput assay and directly compared with HPLC quantification of PCTX release. It was observed that PCTX controlled-release kinetics could be mimicked by a hydrophobic dye that had similar octanol-water partition coefficient values and homogeneous dissolution in a PLGA matrix as the drug. In particular, FDAc was found to be the optimal hydrophobic dye at modeling the burst release as well as the total amount of PCTX released over a period of 30 days. Copyright © 2011 Wiley-Liss, Inc.

High probability neurotransmitter release sites represent an energy efficient design

PubMed Central

Lu, Zhongmin; Chouhan, Amit K.; Borycz, Jolanta A.; Lu, Zhiyuan; Rossano, Adam J; Brain, Keith L.; Zhou, You; Meinertzhagen, Ian A.; Macleod, Gregory T.

2016-01-01

Nerve terminals contain multiple sites specialized for the release of neurotransmitters. Release usually occurs with low probability, a design thought to confer many advantages. High probability release sites are not uncommon but their advantages are not well understood. Here we test the hypothesis that high probability release sites represent an energy efficient design. We examined release site probabilities and energy efficiency at the terminals of two glutamatergic motor neurons synapsing on the same muscle fiber in Drosophila larvae. Through electrophysiological and ultrastructural measurements we calculated release site probabilities to differ considerably between terminals (0.33 vs. 0.11). We estimated the energy required to release and recycle glutamate from the same measurements. The energy required to remove calcium and sodium ions subsequent to nerve excitation was estimated through microfluorimetric and morphological measurements. We calculated energy efficiency as the number of glutamate molecules released per ATP molecule hydrolyzed, and high probability release site terminals were found to be more efficient (0.13 vs. 0.06). Our analytical model indicates that energy efficiency is optimal (~0.15) at high release site probabilities (~0.76). As limitations in energy supply constrain neural function, high probability release sites might ameliorate such constraints by demanding less energy. Energy efficiency can be viewed as one aspect of nerve terminal function, in balance with others, because high efficiency terminals depress significantly during episodic bursts of activity. PMID:27593375

3D Printed Silicone-Hydrogel Scaffold with Enhanced Physicochemical Properties.

PubMed

Mohanty, Soumyaranjan; Alm, Martin; Hemmingsen, Mette; Dolatshahi-Pirouz, Alireza; Trifol, Jon; Thomsen, Peter; Dufva, Martin; Wolff, Anders; Emnéus, Jenny

2016-04-11

Scaffolds with multiple functionalities have attracted widespread attention in the field of tissue engineering due to their ability to control cell behavior through various cues, including mechanical, chemical, and electrical. Fabrication of such scaffolds from clinically approved materials is currently a huge challenge. The goal of this work was to fabricate a tissue engineering scaffold from clinically approved materials with the capability of delivering biomolecules and direct cell fate. We have used a simple 3D printing approach, that combines polymer casting with supercritical fluid technology to produce 3D interpenetrating polymer network (IPN) scaffold of silicone-poly(2-hydroxyethyl methacrylate)-co-poly(ethylene glycol) methyl ether acrylate (pHEMA-co-PEGMEA). The pHEMA-co-PEGMEA IPN materials were employed to support growth of human mesenchymal stem cells (hMSC), resulting in high cell viability and metabolic activity over a 3 weeks period. In addition, the IPN scaffolds support 3D tissue formation inside the porous scaffold with well spread cell morphology on the surface of the scaffold. As a proof of concept, sustained doxycycline (DOX) release from pHEMA-co-PEGMEA IPN was demonstrated and the biological activity of released drug from IPN was confirmed using a DOX regulated green fluorescent reporter (GFP) gene expression assay with HeLa cells. Given its unique mechanical and drug releasing characteristics, IPN scaffolds may be used for directing stem cell differentiation by releasing various chemicals from its hydrogel network.

Quantitative analysis of serotonin secreted by human embryonic stem cells-derived serotonergic neurons via pH-mediated online stacking-CE-ESI-MRM.

PubMed

Zhong, Xuefei; Hao, Ling; Lu, Jianfeng; Ye, Hui; Zhang, Su-Chun; Li, Lingjun

2016-04-01

A CE-ESI-MRM-based assay was developed for targeted analysis of serotonin released by human embryonic stem cells-derived serotonergic neurons in a chemically defined environment. A discontinuous electrolyte system was optimized for pH-mediated online stacking of serotonin. Combining with a liquid-liquid extraction procedure, LOD of serotonin in the Krebs'-Ringer's solution by CE-ESI-MS/MS on a 3D ion trap MS was0.15 ng/mL. The quantitative results confirmed the serotonergic identity of the in vitro developed neurons and the capacity of these neurons to release serotonin in response to stimulus. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres.

PubMed

Prabhu, Sunil; Sullivan, Jennifer L; Betageri, Guru V

2002-01-01

The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.

Optimized Vertex Method and Hybrid Reliability

NASA Technical Reports Server (NTRS)

Smith, Steven A.; Krishnamurthy, T.; Mason, B. H.

2002-01-01

A method of calculating the fuzzy response of a system is presented. This method, called the Optimized Vertex Method (OVM), is based upon the vertex method but requires considerably fewer function evaluations. The method is demonstrated by calculating the response membership function of strain-energy release rate for a bonded joint with a crack. The possibility of failure of the bonded joint was determined over a range of loads. After completing the possibilistic analysis, the possibilistic (fuzzy) membership functions were transformed to probability density functions and the probability of failure of the bonded joint was calculated. This approach is called a possibility-based hybrid reliability assessment. The possibility and probability of failure are presented and compared to a Monte Carlo Simulation (MCS) of the bonded joint.

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer

PubMed Central

Zhang, Bo; Song, Yunmei; Wang, Tianqi; Yang, Shaomei; Zhang, Jing; Liu, Yongjun; Zhang, Na; Garg, Sanjay

2017-01-01

Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug–phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs. PMID:28435264

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer.

PubMed

Zhang, Bo; Song, Yunmei; Wang, Tianqi; Yang, Shaomei; Zhang, Jing; Liu, Yongjun; Zhang, Na; Garg, Sanjay

2017-01-01

Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug-phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs.

Photocontrol of Drug Release from Supramolecular Hydrogels with Green Light.

PubMed

Karcher, Johannes; Pianowski, Zbigniew

2018-06-26

Photoresponsive smart materials transform light energy into sophisticated functions. They find increasing biomedical applications in light-induced drug release and photopharmacology, as they can locally provide the desired therapeutic effect due to precise spatiotemporal dosage control. However, the majority of reported studies rely on cytotoxic UV light that poorly penetrates tissues. Here we report the first drug-releasing system based on photochromic low molecular weight supramolecular hydrogels that is triggered with visible light. We demonstrated green-light-induced release of structurally unmodified antibiotic, anticancer, and anti-inflammatory drugs under physiological conditions. Using the antibiotic-loaded gel, we selectively inhibited bacterial growth with green light. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design.

PubMed

Morovati, Amirhosein; Ghaffari, Alireza; Erfani Jabarian, Lale; Mehramizi, Ali

2017-01-01

Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex ® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release "%" in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X 1 : Cetyl alcohol, X 2 : Starch 1500 ® , X 3 : HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X 1 : 37.10, X 2 : 2, X 3 : 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500 ® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too.

Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design

PubMed Central

Morovati, Amirhosein; Ghaffari, Alireza; Erfani jabarian, Lale; Mehramizi, Ali

2017-01-01

Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release “%” in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X1: Cetyl alcohol, X2: Starch 1500®, X3: HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X1: 37.10, X2: 2, X3: 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too. PMID:29552045

Simulation of acid mine drainage generation around Küre VMS Deposits, Northern Turkey

NASA Astrophysics Data System (ADS)

Demirel, Cansu; Kurt, Mehmet Ali; Çelik Balci, Nurgül

2015-04-01

This study investigated comparative leaching characteristics of acidophilic bacterial strains under shifting environmental conditions at proposed two stages as formation stage or post acidic mine drainage (AMD) generation. At the first stage, initial reactions associated with AMD generation was simulated in shaking flasks containing massive pyritic chalcopyrite ore by using a pure strain Acidithiobacillus ferrooxidans and a mixed culture of Acidithiobacillus sp. mostly dominated by A. ferrooxidans and A. thiooxidans at 26oC. At the second stage, long term bioleaching experiments were carried out with the same strains at 26oC and 40oC to investigate the leaching characteristics of pyritic chalcopyrite ore under elevated heavy metal and temperature conditions. During the experiments, physicochemical characteristics (e.i. Eh, pH, EC) metal (Fe, Co, Cu, Zn) and sulfate concentration of the experimental solution were monitored during 180 days. Significant acid generation and sulfate release were determined during bioleaching of the ore by mixed acidophilic cultures containing both iron and sulfur oxidizers. In the early stage of the experiments, heavy metal release from the ore was caused by generation of acid due to accelerated bacterial oxidation of the ore. Generally high concentrations of Co and Cu were released into the solution from the experiments conducted by pure cultures of Acidithiobacillus ferrooxidans whereas high Zn and Fe was released into the solution from the mixed culture experiments. In the later stage of AMD generation and post AMD, chemical oxidation is accelerated causing excessive amounts of contamination, even exceeding the amounts resulted from bacterial oxidation by mixed cultures. Acidithibacillus ferrooxidans was found to be more effective in leaching Cu, Fe and Co at higher temperatures in contrary to mixed acidophiles that are more prone to operate at optimal moderate conditions. Moreover, decreasing Fe values are noted in bioleaching experiments with mixed acidophiles at higher temperatures. Further depleted Fe(III) values coinciding with decreasing pH may point to precipitation of secondary phases (i.e. jarosite). This study revealed that the metals (Fe, Cu, Co and Zn) released during short term leaching of the ore (34 days) are generally caused by acid produced by dissolution reactions rather than oxidation. In the long term experiments a more complex biogeochemical reactions (oxidation and dissolution) take place in conjunction. Key words: Bioleaching, AMD, heavy metal release, environment, acidophilic bacteria, Küre copper ore deposits, volcanogenic massive sulfide deposits

Location Isn’t Everything: Timing of Spawning Aggregations Optimizes Larval Replenishment

PubMed Central

Donahue, Megan J.; Karnauskas, Mandy; Toews, Carl; Paris, Claire B.

2015-01-01

Many species of reef fishes form large spawning aggregations that are highly predictable in space and time. Prior research has suggested that aggregating fish derive fitness benefits not just from mating at high density but, also, from oceanographic features of the spatial locations where aggregations occur. Using a probabilistic biophysical model of larval dispersal coupled to a fine resolution hydrodynamic model of the Florida Straits, we develop a stochastic landscape of larval fitness. Tracking virtual larvae from release to settlement and incorporating changes in larval behavior through ontogeny, we found that larval success was sensitive to the timing of spawning. Indeed, propagules released during the observed spawning period had higher larval success rates than those released outside the observed spawning period. In contrast, larval success rates were relatively insensitive to the spatial position of the release site. In addition, minimum (rather than mean) larval survival was maximized during the observed spawning period, indicating a reproductive strategy that minimizes the probability of recruitment failure. Given this landscape of larval fitness, we take an inverse optimization approach to define a biological objective function that reflects a tradeoff between the mean and variance of larval success in a temporally variable environment. Using this objective function, we suggest that the length of the spawning period can provide insight into the tradeoff between reproductive risk and reward. PMID:26103162

Sequencing biological acidification of waste-activated sludge aiming to optimize phosphorus dissolution and recovery.

PubMed

Guilayn, Felipe; Braak, Etienne; Piveteau, Simon; Daumer, Marie-Line

2017-06-01

Phosphorus (P) recovery in wastewater treatment plants (WWTP) as pure crystals such as struvite (MgNH 4 PO 4 .6H 2 O), potassium struvite (KMgPO 4 .6H 2 O) and calcium phosphates (e.g. Ca 3 (PO 4 ) 2 ) is an already feasible technique that permits the production of green and marketable fertilizers and the reduction of operational costs. Commercial crystallizers can recovery more than 90% of soluble P. However, most of the P in WWTP sludge is unavailable for the processes (not dissolved). P solubilization and separation are thus the limiting steps in P-crystallization. With an innovative two-step sequencing acidification strategy, the current study has aimed to improve biological P solubilization on waste-activated sludge (WAS) from a full-scale plant. In the first step (P-release), low charges of organic waste were used as co-substrates of WAS pre-fermentation, seeking to produce volatile fatty acids to feed the P-release by Polyphosphate-accumulating organisms, while keeping its optimal metabolic pH (6-7). In this phase, milk serum, WWTP grease, urban organic waste and collective restaurant waste were individually applied as co-substrates. In the second step (P-dissolution), pH 4 was aimed at as it allows the dissolution of the most common precipitated species of P. Biological acidification was performed by white sugar addition, as a carbohydrate-rich organic waste model, which was compared to chemical acidification by HCl (12M) addition. With short retention times (48-96 h) and without inoculum application, all experiences succeeded on P solubilization (37-55% of soluble P), principally when carbohydrate-rich co-substrates were applied. Concentrations from 270 to 450 mg [Formula: see text] were achieved. [Formula: see text].

Does Size Matter? Atmospheric CO2 May Be a Stronger Driver of Stomatal Closing Rate Than Stomatal Size in Taxa That Diversified under Low CO2.

PubMed

Elliott-Kingston, Caroline; Haworth, Matthew; Yearsley, Jon M; Batke, Sven P; Lawson, Tracy; McElwain, Jennifer C

2016-01-01

One strategy for plants to optimize stomatal function is to open and close their stomata quickly in response to environmental signals. It is generally assumed that small stomata can alter aperture faster than large stomata. We tested the hypothesis that species with small stomata close faster than species with larger stomata in response to darkness by comparing rate of stomatal closure across an evolutionary range of species including ferns, cycads, conifers, and angiosperms under controlled ambient conditions (380 ppm CO2; 20.9% O2). The two species with fastest half-closure time and the two species with slowest half-closure time had large stomata while the remaining three species had small stomata, implying that closing rate was not correlated with stomatal size in these species. Neither was response time correlated with stomatal density, phylogeny, functional group, or life strategy. Our results suggest that past atmospheric CO2 concentration during time of taxa diversification may influence stomatal response time. We show that species which last diversified under low or declining atmospheric CO2 concentration close stomata faster than species that last diversified in a high CO2 world. Low atmospheric [CO2] during taxa diversification may have placed a selection pressure on plants to accelerate stomatal closing to maintain adequate internal CO2 and optimize water use efficiency.

Does Size Matter? Atmospheric CO2 May Be a Stronger Driver of Stomatal Closing Rate Than Stomatal Size in Taxa That Diversified under Low CO2

PubMed Central

Elliott-Kingston, Caroline; Haworth, Matthew; Yearsley, Jon M.; Batke, Sven P.; Lawson, Tracy; McElwain, Jennifer C.

2016-01-01

One strategy for plants to optimize stomatal function is to open and close their stomata quickly in response to environmental signals. It is generally assumed that small stomata can alter aperture faster than large stomata. We tested the hypothesis that species with small stomata close faster than species with larger stomata in response to darkness by comparing rate of stomatal closure across an evolutionary range of species including ferns, cycads, conifers, and angiosperms under controlled ambient conditions (380 ppm CO2; 20.9% O2). The two species with fastest half-closure time and the two species with slowest half-closure time had large stomata while the remaining three species had small stomata, implying that closing rate was not correlated with stomatal size in these species. Neither was response time correlated with stomatal density, phylogeny, functional group, or life strategy. Our results suggest that past atmospheric CO2 concentration during time of taxa diversification may influence stomatal response time. We show that species which last diversified under low or declining atmospheric CO2 concentration close stomata faster than species that last diversified in a high CO2 world. Low atmospheric [CO2] during taxa diversification may have placed a selection pressure on plants to accelerate stomatal closing to maintain adequate internal CO2 and optimize water use efficiency. PMID:27605929

Development of a low cost unmanned aircraft system for atmospheric carbon dioxide leak detection

NASA Astrophysics Data System (ADS)

Mitchell, Taylor Austin

Carbon sequestration, the storage of carbon dioxide gas underground, has the potential to reduce global warming by removing a greenhouse gas from the atmosphere. These storage sites, however, must first be monitored to detect if carbon dioxide is leaking back out to the atmosphere. As an alternative to traditional large ground-based sensor networks to monitor CO2 levels for leaks, unmanned aircraft offer the potential to perform in-situ atmospheric leak detection over large areas for a fraction of the cost. This project developed a proof-of-concept sensor system to map relative carbon dioxide levels to detect potential leaks. The sensor system included a Sensair K-30 FR CO2 sensor, GPS, and altimeter connected an Arduino microcontroller which logged data to an onboard SD card. Ground tests were performed to verify and calibrate the system including wind tunnel tests to determine the optimal configuration of the system for the quickest response time (4-8 seconds based upon flowrate). Tests were then conducted over a controlled release of CO 2 in addition to over controlled rangeland fires which released carbon dioxide over a large area as would be expected from a carbon sequestration source. 3D maps of carbon dioxide were developed from the system telemetry that clearly illustrated increased CO2 levels from the fires. These tests demonstrated the system's ability to detect increased carbon dioxide concentrations in the atmosphere.

CO-Releasing Molecules Have Nonheme Targets in Bacteria: Transcriptomic, Mathematical Modeling and Biochemical Analyses of CORM-3 [Ru(CO)3Cl(glycinate)] Actions on a Heme-Deficient Mutant of Escherichia coli

PubMed Central

Wilson, Jayne Louise; Wareham, Lauren K.; McLean, Samantha; Begg, Ronald; Greaves, Sarah; Mann, Brian E.; Sanguinetti, Guido

2015-01-01

Abstract Aims: Carbon monoxide-releasing molecules (CORMs) are being developed with the ultimate goal of safely utilizing the therapeutic potential of CO clinically, including applications in antimicrobial therapy. Hemes are generally considered the prime targets of CO and CORMs, so we tested this hypothesis using heme-deficient bacteria, applying cellular, transcriptomic, and biochemical tools. Results: CORM-3 [Ru(CO)3Cl(glycinate)] readily penetrated Escherichia coli hemA bacteria and was inhibitory to these and Lactococcus lactis, even though they lack all detectable hemes. Transcriptomic analyses, coupled with mathematical modeling of transcription factor activities, revealed that the response to CORM-3 in hemA bacteria is multifaceted but characterized by markedly elevated expression of iron acquisition and utilization mechanisms, global stress responses, and zinc management processes. Cell membranes are disturbed by CORM-3. Innovation: This work has demonstrated for the first time that CORM-3 (and to a lesser extent its inactivated counterpart) has multiple cellular targets other than hemes. A full understanding of the actions of CORMs is vital to understand their toxic effects. Conclusion: This work has furthered our understanding of the key targets of CORM-3 in bacteria and raises the possibility that the widely reported antimicrobial effects cannot be attributed to classical biochemical targets of CO. This is a vital step in exploiting the potential, already demonstrated, for using optimized CORMs in antimicrobial therapy. Antioxid. Redox Signal. 23, 148–162. PMID:25811604

Introducing and Validating the New Aura CO Product Derived from Joined TES and MLS Measurements

NASA Astrophysics Data System (ADS)

Luo, M.; Schwartz, M. J.; Read, W. G.; Herman, R. L.; Kulawik, S. S.; Worden, J.; Livesey, N. J.; Bowman, K. W.; Sweeney, C.

2014-12-01

The new Aura CO product consists of CO vertical profiles derived from TES and MLS measurements. This product has been released to the public. We describe the algorithms for generating the product and the evaluations of it using in-situ measurements. TES and MLS standalone CO profile retrievals are sensitive respectively to lower-mid troposphere and upper troposphere and above. We pair TES nadir and MLS limb tangent locations within 6-8 min and less than 220 km. The paired radiance measurements of the two instruments per location are optimally combined to retrieve a single CO profile along with other interfering species. This combined CO profile has improved vertical resolution and vertical range over the two standalone products, especially in the upper-troposphere/lower-stratosphere. For example, the degree of freedom for signal (DOFS) between surface and 50hPa for TES alone is < 2, and for the combined CO profiles is 2-4. We will present the comparison results between the Aura CO and AirCore, HIPPO, and MOZAIC observations. The new Aura CO product provides a unique data set to studies on tropospheric transport of air pollutants and troposphere-stratospheric exchange processes.

Novel drug delivering conduit for peripheral nerve regeneration

NASA Astrophysics Data System (ADS)

Labroo, Pratima; Shea, Jill; Edwards, Kyle; Ho, Scott; Davis, Brett; Sant, Himanshu; Goodwin, Isak; Gale, Bruce; Agarwal, Jay

2017-12-01

Objective. This paper describes the design of a novel drug delivery apparatus integrated with a poly lactic-co-glycolic acid (PLGA) based nerve guide conduit for controlled local delivery of nerve growth factor (NGF) and application in peripheral nerve gap injury. Approach. An NGF dosage curve was acquired to determine the minimum in vitro concentration for optimal neurite outgrowth of dorsal root ganglion (DRG) cells; PLGA based drug delivery devices were then designed and tested in vitro and in vivo across 15 mm rat sciatic nerve gap injury model. Main results. The drug delivery nerve guide was able to release NGF for 28 d at concentrations (0.1-10 ng ml-1) that were shown to enhance DRG neurite growth. Furthermore, the released NGF was bioactive and able to enhance DRG neurite growth. Following these tests, optimized NGF-releasing nerve conduits were implanted across 15 mm sciatic nerve gaps in a rat model, where they demonstrated significant myelination and muscle innervation in vivo as compared to empty nerve conduits (p  <  0.05). This drug delivery nerve guide can release NGF for extended periods of time and enhance axon growth in vitro and in vivo and has the potential to improve nerve regeneration following a peripheral nerve injury. Significance. This integrated drug delivering nerve guide simplifies the design process and provides increased versatility for releasing a variety of different growth factors. This innovative device has the potential for broad applicability and allows for easier customization to change the type of drugs and dosage of individual drugs without devising a completely new biomaterial-drug conjugate each time.

In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Baowei; Shah, Saumil S.; Shin, Yongsoon

We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in a pH 9.0 NaHCO(3)-Na(2)CO(3) buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH(2)-FMSmore » can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents.« less

Carbon monoxide – physiology, detection and controlled release

PubMed Central

Heinemann, Stefan H.; Hoshi, Toshinori; Westerhausen, Matthias

2014-01-01

Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs, are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed. PMID:24556640

Grafting of GMA and some comonomers onto chitosan for controlled release of diclofenac sodium.

PubMed

Sharma, Rajeev Kr; Lalita; Singh, Anirudh P; Chauhan, Ghanshyam S

2014-03-01

In order to develop pH sensitive hydrogels for controlled drug release we have graft copolymerized glycidyl methacrylate (GMA) with comonomers acrylic acid, acrylamide and acrylonitrile, onto chitosan (Ch) by using potassium persulphate (KPS) as free radical initiator in aqueous solution. The optimum percent grafting for GMA was recorded for 1g chitosan at [KPS]=25.00 × 10(-3)mol/L, [GMA]=0.756 × 10(-3)mol/L, reaction temperature=60 °C and reaction time=1h in 20 mL H2O. Binary monomers were grafted for five different concentrations at optimum grafting conditions evaluated for GMA alone onto chitosan. The graft copolymers were characterized by FTIR, XRD, TGA and SEM. The swelling properties of chitosan and graft copolymers were investigated at different pH to define their end uses in sustained release of an anti-inflammatory drug, diclofenac sodium. Percent drug release w.r.t. drug loaded in polymeric sample was studied as function of time in buffer solutions of pH 2.0 and 7.4. In vitro release data was analyzed using Fick's Law. Chitosan grafted with binary monomers, GMA-co-AAm and GMA-co-AN showed very good results for sustained release of drug at 7.4 pH. Copyright © 2014 Elsevier B.V. All rights reserved.

Electrochemical capture and release of carbon dioxide

DOE PAGES

Rheinhardt, Joseph H.; Singh, Poonam; Tarakeshwar, Pilarisetty; ...

2017-01-18

Understanding the chemistry of carbon dioxide is key to affecting changes in atmospheric concentrations. One area of intense interest is CO 2 capture in chemically reversible cycles relevant to carbon capture technologies. Most CO 2 capture methods involve thermal cycles in which a nucleophilic agent captures CO 2 from impure gas streams (e.g., flue gas), followed by a thermal process in which pure CO 2 is released. Several reviews have detailed progress in these approaches. A less explored strategy uses electrochemical cycles to capture CO 2 and release it in pure form. These cycles typically rely on electrochemical generation ofmore » nucleophiles that attack CO 2 at the electrophilic carbon atom, forming a CO 2 adduct. Then, CO 2 is released in pure form via a subsequent electrochemical step. In this Perspective, we describe electrochemical cycles for CO 2 capture and release, emphasizing electrogenerated nucleophiles. As a result, we also discuss some advantages and disadvantages inherent in this general approach.« less

Can increased nitrogen uptake at elevated CO2 be explained by an hypothesis of optimal root function?

NASA Astrophysics Data System (ADS)

McMurtrie, R. E.; Norby, R. J.; Näsholm, T.; Iversen, C.; Dewar, R. C.; Medlyn, B. E.

2011-12-01

Forest free-air CO2 enrichment (FACE) experiments have shown that annual nitrogen (N) uptake increases when trees are grown at elevated CO2 (eCO2) and that increased N uptake is critical for a sustained growth response to eCO2. Processes contributing to increased N uptake at eCO2 may include: accelerated decomposition of soil organic matter due to enhanced root carbon (C) exudation (so-called rhizosphere priming); increased C allocation to fine roots and increased root production at depth, both of which enhance N acquisition; differences in soil N availability with depth; changes in the abundance of N in chemical forms with differing mobility in soil; and reduced N concentrations, reduced maintenance respiration rates, and increased longevities of deeper roots. These processes have been synthesised in a model of annual N uptake in relation to the spatial distribution of roots. We hypothesise that fine roots are distributed spatially in order to maximise annual N uptake. The optimisation hypothesis leads to equations for the optimal vertical distribution of root biomass in relation to the distribution of available soil N and for maximum annual N uptake. We show how maximum N uptake and rooting depth are related to total root mass, and compare the optimal solution with an empirical function that has been fitted to root-distribution data from all terrestrial biomes. Finally, the model is used to explore the consequences of rhizosphere priming at eCO2 as observed at the Duke forest FACE experiment (Drake et al. 2011, Ecology Letters 14: 349-357) and of increasing N limitation over time as observed at the Oak Ridge FACE experiment (Norby et al. 2010, Proc. Nat. Acad. Sci. USA 107: 19368-19373).

Dendritic cells for active immunotherapy: optimizing design and manufacture in order to develop commercially and clinically viable products.

PubMed

Nicolette, C A; Healey, D; Tcherepanova, I; Whelton, P; Monesmith, T; Coombs, L; Finke, L H; Whiteside, T; Miesowicz, F

2007-09-27

Dendritic cell (DC) active immunotherapy is potentially efficacious in a broad array of malignant disease settings. However, challenges remain in optimizing DC-based therapy for maximum clinical efficacy within manufacturing processes that permit quality control and scale-up of consistent products. In this review we discuss the critical issues that must be addressed in order to optimize DC-based product design and manufacture, and highlight the DC based platforms currently addressing these issues. Variables in DC-based product design include the type of antigenic payload used, DC maturation steps and activation processes, and functional assays. Issues to consider in development include: (a) minimizing the invasiveness of patient biological material collection; (b) minimizing handling and manipulations of tissue at the clinical site; (c) centralized product manufacturing and standardized processing and capacity for commercial-scale production; (d) rapid product release turnaround time; (e) the ability to manufacture sufficient product from limited starting material; and (f) standardized release criteria for DC phenotype and function. Improvements in the design and manufacture of DC products have resulted in a handful of promising leads currently in clinical development.

A protein/antibiotic releasing poly(lactic-co-glycolic acid)/lecithin scaffold for bone repair applications.

PubMed

Shi, Xuetao; Wang, Yingjun; Ren, Li; Huang, Wei; Wang, Dong-An

2009-05-21

Novel poly(lactic-co-glycolic acid) (PLGA)-hybridizing-lecithin scaffolds loaded with drug or protein were prepared with water/oil/water techniques and sintering microspheres technique. In such fabricated composite scaffolds (abbreviated "PLGA/Lec-SMS"), the introduction of lecithin component has been proven capable of largely enhancing Gentamicin (GS) and protein (Bovine Serum Albumin) encapsulation efficiency. The in vitro GS and BSA releasing profiles of PLGA/Lec-SMS system were plotted basing over 60 days' and 18 days' data collection, respectively. It indicates a sustained releasing tendency despite a burst at the very beginning. The antibacterial properties of GS-laden scaffolds were determined in vitro, and the antibacterial activity of scaffolds was enhanced by incorporating lecithin into PLGA bulks. Additionally, mesenchymal stem cells (MSCs) were seeded onto PLGA-SMS and PLGA/Lec-SMS in vitro. The outcome confirmed PLGA/Lec(5%)-SMS functions to improve MSC proliferation and also to enhance general ALP production and calcium secretion which is the vital markers for osteogenesis. In conclusion, this newly designed antibiotic releasing PLGA/Lec-SMS is promising for bone-repairing therapeutics.

Oral bioavailability enhancement of raloxifene by developing microemulsion using D-optimal mixture design: optimization and in-vivo pharmacokinetic study.

PubMed

Shah, Nirmal; Seth, Avinashkumar; Balaraman, R; Sailor, Girish; Javia, Ankur; Gohil, Dipti

2018-04-01

The objective of this work was to utilize a potential of microemulsion for the improvement in oral bioavailability of raloxifene hydrochloride, a BCS class-II drug with 2% bioavailability. Drug-loaded microemulsion was prepared by water titration method using Capmul MCM C8, Tween 20, and Polyethylene glycol 400 as oil, surfactant, and co-surfactant respectively. The pseudo-ternary phase diagram was constructed between oil and surfactants mixture to obtain appropriate components and their concentration ranges that result in large existence area of microemulsion. D-optimal mixture design was utilized as a statistical tool for optimization of microemulsion considering oil, S mix , and water as independent variables with percentage transmittance and globule size as dependent variables. The optimized formulation showed 100 ± 0.1% transmittance and 17.85 ± 2.78 nm globule size which was identically equal with the predicted values of dependent variables given by the design expert software. The optimized microemulsion showed pronounced enhancement in release rate compared to plain drug suspension following diffusion controlled release mechanism by the Higuchi model. The formulation showed zeta potential of value -5.88 ± 1.14 mV that imparts good stability to drug loaded microemulsion dispersion. Surface morphology study with transmission electron microscope showed discrete spherical nano sized globules with smooth surface. In-vivo pharmacokinetic study of optimized microemulsion formulation in Wistar rats showed 4.29-fold enhancements in bioavailability. Stability study showed adequate results for various parameters checked up to six months. These results reveal the potential of microemulsion for significant improvement in oral bioavailability of poorly soluble raloxifene hydrochloride.

Dexamethasone-Loaded, PEGylated, Vertically Aligned, Multiwalled Carbon Nanotubes for Potential Ischemic Stroke Intervention.

PubMed

Komane, Patrick P; Kumar, Pradeep; Marimuthu, Thashree; Toit, Lisa C du; Kondiah, Pierre P D; Choonara, Yahya E; Pillay, Viness

2018-06-10

The complete synthesis, optimization, purification, functionalization and evaluation of vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) was reported for potential application in dexamethasone delivery to the ischemic brain tissue. The conditions for high yield were optimized and carbon nanotubes functionalized and PEGylated prior to dexamethasone loading. Morphological changes were confirmed by SEM and TEM. Addition of functional groups to MWCNTs was demonstrated by FTIR. Thermal stability reduced following MWCNTs functionalization as demonstrated in TGA. The presence of carbon at 2θ of 25° and iron at 2θ of 45° in MWCNTs was illustrated by XRD. Polydispersive index and zeta potential were found to be 0.261 and −15.0 mV, respectively. Dexamethasone release increased by 55%, 65% and 95% in pH of 7.4, 6.5 and 5.5 respectively as evaluated by UV-VIS. The functionalized VA-MWCNTs were demonstrated to be less toxic in PC-12 cells in the concentration range from 20 to 20,000 µg/mL. These findings have demonstrated the potential of VA-MWCNTs in the enhancement of fast and prolonged release of dexamethasone which could lead to the effective treatment of ischemic stroke. More work is under way for targeting ischemic sites using atrial natriuretic peptide antibody in stroke rats.

Biophysical characterization of hydrogel-core, lipid-shell nanoparticles (nanolipogels) for HIV chemoprophylaxis

NASA Astrophysics Data System (ADS)

Mahadevan, Reena

Nanoparticles are emerging as versatile vehicles for drug delivery, providing targeting, protection, and controlled-release capabilities to encapsulated cargo. Polymeric nanoparticles made from poly(lactide-co-glycolide) (PLGA) are biodegradable, exhibit tunable drug release, and have encapsulated a wide variety of biological agents. However, PLGA nanoparticles are relatively inefficient at encapsulating small-molecule hydrophilic drugs. Liposomes encapsulate greater amounts of hydrophilic agents and demonstrate good cellular affinity; however, they lack controlled-release functionality. Hydrogel-core lipid-shell nanoparticles, or nanolipogels, combine the controlled-release capability of polymeric nanocarriers with the hydrophilic and cellular affinity of liposomes into a single drug delivery vehicle. This study establishes a facile, reproducible synthetic protocol for nanolipogels and evaluates hydrogel swelling as a mechanism for release of the small hydrophilic antiretroviral azidothymidine from nanolipogels.

Wearable Large-Scale Perovskite Solar-Power Source via Nanocellular Scaffold.

PubMed

Hu, Xiaotian; Huang, Zengqi; Zhou, Xue; Li, Pengwei; Wang, Yang; Huang, Zhandong; Su, Meng; Ren, Wanjie; Li, Fengyu; Li, Mingzhu; Chen, Yiwang; Song, Yanlin

2017-11-01

Dramatic advances in perovskite solar cells (PSCs) and the blossoming of wearable electronics have triggered tremendous demands for flexible solar-power sources. However, the fracturing of functional crystalline films and transmittance wastage from flexible substrates are critical challenges to approaching the high-performance PSCs with flexural endurance. In this work, a nanocellular scaffold is introduced to architect a mechanics buffer layer and optics resonant cavity. The nanocellular scaffold releases mechanical stresses during flexural experiences and significantly improves the crystalline quality of the perovskite films. The nanocellular optics resonant cavity optimizes light harvesting and charge transportation of devices. More importantly, these flexible PSCs, which demonstrate excellent performance and mechanical stability, are practically fabricated in modules as a wearable solar-power source. A power conversion efficiency of 12.32% for a flexible large-scale device (polyethylene terephthalate substrate, indium tin oxide-free, 1.01 cm 2 ) is achieved. This ingenious flexible structure will enable a new approach for development of wearable electronics. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A global design of high power Nd 3+-Yb 3+ co-doped fiber lasers

NASA Astrophysics Data System (ADS)

Fan, Zhang; Chuncan, Wang; Tigang, Ning

2008-09-01

A global optimization method - niche hybrid genetic algorithm (NHGA) based on fitness sharing and elite replacement is applied to optimize Nd3+-Yb3+ co-doped fiber lasers (NYDFLs) for obtaining maximum signal output power. With a objective function and different pumping powers, five critical parameters (the fiber length, L; the proportion of pump power for pumping Nd3+, η; Nd3+ and Yb3+ concentrations, NNd and NYb and output mirror reflectivity, Rout) of the given NYDFLs are optimized by solving the rate and power propagation equations. Results show that dividing equally the input pump power among 808 nm (Nd3+) and 940 nm (Yb3+) is not an optimal choice and the pump power of Nd3+ ions should be kept around 10-13.78% of the total pump power. Three optimal schemes are obtained by NHGA and the highest slope efficiency of the laser is able to reach 80.1%.

Preparation of bimetallic Cu-Co nanocatalysts on poly (diallyldimethylammonium chloride) functionalized halloysite nanotubes for hydrolytic dehydrogenation of ammonia borane

NASA Astrophysics Data System (ADS)

Liu, Yang; Zhang, Jun; Guan, Huijuan; Zhao, Yafei; Yang, Jing-He; Zhang, Bing

2018-01-01

In present work, we prepared the bimetallic Cu-Co nanocatalysts on poly (diallyldimethylammonium chloride) functionalized halloysite nanotubes (Cu-Co/PDDA-HNTs) by a deposition-reduction technique at room temperature. The analysis of XRD, SEM, TEM, HAADF-STEM and XPS were employed to systematically investigate the morphology, particle size, structure and surface properties of the nanocomposite. The results reveal that the PDDA coating with thickness of ∼15 nm could be formed on the surface of HNTs, and the existence of PDDA is beneficial to deposit Cu and Co nanoparticles (NPs) with high dispersibility on the surface. While the cost-effective nanocomposite was used for the hydrolytic dehydrogenation of ammonia-borane (NH3BH3), the nanocatalyst showed extraordinary catalytic properties with high total turnover frequency of 30.8 molH2/(molmetal min), low activation energy of 35.15 kJ mol-1 and high recycling stability (>90% conversion at 10th reuse). These results indicate that the bimetallic Cu-Co nanocatalysts on PDDA functionalized HNTs have particular potential for application in release hydrogen process.

Insulating Ferromagnetic LaCoO3-δ Films: A Phase Induced by Ordering of Oxygen Vacancies

NASA Astrophysics Data System (ADS)

Biškup, Neven; Salafranca, Juan; Mehta, Virat; Oxley, Mark P.; Suzuki, Yuri; Pennycook, Stephen J.; Pantelides, Sokrates T.; Varela, Maria

2014-02-01

The origin of ferromagnetism in strained epitaxial LaCoO3 films has been a long-standing mystery. Here, we combine atomically resolved Z-contrast imaging, electron-energy-loss spectroscopy, and density-functional calculations to demonstrate that, in epitaxial LaCoO3 films, oxygen-vacancy superstructures release strain, control the film's electronic properties, and produce the observed ferromagnetism via the excess electrons in the Co d states. Although oxygen vacancies typically dope a material n-type, we find that ordered vacancies induce Peierls-like minigaps which, combined with strain relaxation, trigger a nonlinear rupture of the energy bands, resulting in insulating behavior.

Development of novel cationic chitosan-and anionic alginate–coated poly(d,l-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol

PubMed Central

Sanna, Vanna; Roggio, Anna Maria; Siliani, Silvia; Piccinini, Massimo; Marceddu, Salvatore; Mariani, Alberto; Sechi, Mario

2012-01-01

Background Resveratrol, like other natural polyphenols, is an extremely photosensitive compound with low chemical stability, which limits the therapeutic application of its beneficial effects. The development of innovative formulation strategies, able to overcome physicochemical and pharmacokinetic limitations of this compound, may be achieved via suitable carriers able to associate controlled release and protection. In this context, nanotechnology is proving to be a powerful strategy. In this study, we developed novel cationic chitosan (CS)- and anionic alginate (Alg)-coated poly(d,l-lactide-co-glycolide) nanoparticles (NPs) loaded with the bioactive polyphenolic trans-(E)-resveratrol (RSV) for biomedical applications. Methods NPs were prepared by the nanoprecipitation method and characterized in terms of morphology, size and zeta potential, encapsulation efficiency, Raman spectroscopy, swelling properties, differential scanning calorimetry, and in vitro release studies. The protective effect of the nanosystems under the light-stressed RSV and long-term stability were investigated. Results NPs turned out to be spherical in shape, with size ranging from 135 to about 580 nm, depending on the composition and the amount of polyelectrolytes, while the encapsulation efficiencies increased from 8% of uncoated poly(d,l-lactide-co-glycolide) (PLGA) to 23% and 32% of Alg- and CS-coated PLGA NPs, respectively. All nanocarriers are characterized by a biphasic release pattern, and more effective controlled release rates are obtained for NPs formulated with higher polyelectrolyte concentrations. Stability studies revealed that encapsulation provides significant protection against light-exposure degradation, by reducing the trans–cis photoisomerization reaction. Moreover, the nanosystems are able to prevent the degradation of trans isoform and the leakage of RSV from the carrier for a period of 6 months. Conclusion Our findings indicated that the newly developed CS- and Alg-coated PLGA NPs are suitable to be used for the delivery of bioactive RSV. The encapsulation of RSV into optimized polymeric NPs provides improved drug loading, effective controlled release, and protection against light-exposure degradation, thus opening new perspectives for the delivery of bioactive related phytochemicals to be used for (nano)chemoprevention/chemotherapy. PMID:23093904

Peptide-directed self-assembly of functionalized polymeric nanoparticles. Part II: effects of nanoparticle composition on assembly behavior and multiple drug loading ability.

PubMed

Xiang, Xu; Ding, Xiaochu; Moser, Trevor; Gao, Qi; Shokuhfar, Tolou; Heiden, Patricia A

2015-04-01

Peptide-functionalized polymeric nanoparticles were designed and self-assembled into continuous nanoparticle fibers and three-dimensional scaffolds via ionic complementary peptide interaction. Different nanoparticle compositions can be designed to be appropriate for each desired drug, so that the release of each drug is individually controlled and the simultaneous sustainable release of multiple drugs is achieved in a single scaffold. A self-assembled scaffold membrane was incubated with NIH3T3 fibroblast cells in a culture dish that demonstrated non-toxicity and non-inhibition on cell proliferation. This type of nanoparticle scaffold combines the advantages of peptide self-assembly and the versatility of polymeric nanoparticle controlled release systems for tissue engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Co-culture of clonal beta cells with GLP-1 and glucagon-secreting cell line impacts on beta cell insulin secretion, proliferation and susceptibility to cytotoxins.

PubMed

Green, Alastair D; Vasu, Srividya; Moffett, R Charlotte; Flatt, Peter R

2016-06-01

We investigated the direct effects on insulin releasing MIN6 cells of chronic exposure to GLP-1, glucagon or a combination of both peptides secreted from GLUTag L-cell and αTC1.9 alpha-cell lines in co-culture. MIN6, GLUTag and αTC1.9 cell lines exhibited high cellular hormone content and release of insulin, GLP-1 and glucagon, respectively. Co-culture of MIN6 cells with GLUTag cells significantly increased cellular insulin content, beta-cell proliferation, insulin secretory responses to a range of established secretogogues and afforded protection against exposure cytotoxic concentrations of glucose, lipid, streptozotocin or cytokines. Benefits of co-culture of MIN6 cells with αTC1.9 alphacells were limited to enhanced beta-cell proliferation with marginal positive actions on both insulin secretion and cellular protection. In contrast, co-culture of MIN6 with GLUTag cells plus αTC1.9 cells, markedly enhanced both insulin secretory responses and protection against beta-cell toxins compared with co-culture with GLUTag cells alone. These data indicate important long-term effects of conjoint GLP-1 and glucagon exposure on beta-cell function. This illustrates the possible functional significance of alpha-cell GLP-1 production as well as direct beneficial effects of dual agonism at beta-cell GLP-1 and glucagon receptors. Copyright © 2016 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

Field demonstration of CO2 leakage detection in potable aquifers with a pulselike CO2-release test.

PubMed

Yang, Changbing; Hovorka, Susan D; Delgado-Alonso, Jesus; Mickler, Patrick J; Treviño, Ramón H; Phillips, Straun

2014-12-02

This study presents two field pulselike CO2-release tests to demonstrate CO2 leakage detection in a shallow aquifer by monitoring groundwater pH, alkalinity, and dissolved inorganic carbon (DIC) using the periodic groundwater sampling method and a fiber-optic CO2 sensor for real-time in situ monitoring of dissolved CO2 in groundwater. Measurements of groundwater pH, alkalinity, DIC, and dissolved CO2 clearly deviated from their background values, showing responses to CO2 leakage. Dissolved CO2 observed in the tests was highly sensitive in comparison to groundwater pH, DIC, and alkalinity. Comparison of the pulselike CO2-release tests to other field tests suggests that pulselike CO2-release tests can provide reliable assessment of geochemical parameters indicative of CO2 leakage. Measurements by the fiber-optic CO2 sensor, showing obvious leakage signals, demonstrated the potential of real-time in situ monitoring of dissolved CO2 for leakage detection at a geologic carbon sequestration (GCS) site. Results of a two-dimensional reactive transport model reproduced the geochemical measurements and confirmed that the decrease in groundwater pH and the increases in DIC and dissolved CO2 observed in the pulselike CO2-release tests were caused by dissolution of CO2 whereas alkalinity was likely affected by carbonate dissolution.

In-vitro release and permeation studies of ketoconazole from optimized dermatological vehicles using powder, nanoparticles and solid dispersion forms of drug

NASA Astrophysics Data System (ADS)

Mohammed, Irfan A.

To optimize the clinical efficacy of Ketoconazole from an externally applied product, this project was undertaken to evaluate the drug release/permeation profile from various dermatological vehicles using regular powder, nanoparticles and solid dispersion forms with reduced level of drug. Nanoparticles of drug were prepared by wet media milling method using Polyvinylpyrrolidone (PVP-10K) as a stabilizer. The nanoparticles were in the size range of 250-300nm. Solid dispersion was prepared by solvent evaporation method using drug to PVP-10K at a weight ratio of (1:2). Formulations containing 1% w/w drug were developed using HPMC gel, Carbomer gel and a cationic cream as the vehicles. Penetration enhancers including propylene glycol (PG), dimethylsulfoxide (DMSO) and polyethylene glycol 400 (PEG-400) at various levels were evaluated. A commercial 2% w/w ketoconazole product was included as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for two and six hour studies. Among the formulations evaluated, the general rank order of the drug release through the cellulose membrane was observed to be: HPMC gel base > Anionic gel base > Cationic gel base > Commercial product. The addition of penetration enhancers showed variable effects in all samples evaluated. However, the HPMC gel-based vehicle showed significant effect in enhancing the drug release in the presence of DMSO. The formulation containing 1% w/w ketoconazole and 20% w/w DMSO gave a maximum drug release of 20.21% when compared to only 1.60% from the commercial product. This represents a twelve fold increase in the release of ketoconazole from the formulation. Furthermore, when the optimum gel-based formulation containing 1% w/w ketoconazole was studied over an extended period of 6 hours, it gave 36.01% drug release from the sample formulation compared to only 2.00% from the commercial product. Finally, this formulation was selected to study for its drug release/permeation profile using the human cadaver skin as the diffusion barrier. Here, as expected, the drug release from both the formulations tested was significantly reduced due to the resistance posed by the skin. After 6 hours, the drug release form the commercial product was 0.17% when compared to 2.80% from the optimum formulation. Once again, this indicated that the experimental formulation exhibits superior drug release dynamics. The selected formulations were further evaluated for their in-vitro anti-fungal activities using yeast microorganisms. The results correlated to the in-vitro drug release profile, where HPMC based formulations exhibited a greater area of zone of inhibition for the growth of microorganisms when compared to diminutive area of zone of inhibition for the commercial product. The release data from all the samples were treated to calculate various physical parameters including: diffusion co-efficient, partition co-efficient, steady state flux and lag period etc. Interestingly, the values for the steady state flux and diffusion coefficient were found to be the highest from the optimum formulation and the values for the lag time and partition coefficient were observed to be the lowest. This supports the evidence that the drug from this formulation is readily diffusible to the skin at a steady rate after its application at the site. In-vitro drug diffusion studies and in-vitro anti-fungal studies proved useful in screening various dermatological formulations of ketoconazole compared to the commercial product containing 2% w/w drug. The HPMC based optimum formulation with reduced level of drug represents 15 folds increase through human cadaver skin and also exhibited augmented anti-fungal activity. This supports that by using an appropriate vehicle and proper incorporation of drug, one can optimize the drug release from topical formulation for maximum therapeutic effect.

Design and elaboration of freeze-dried PLGA nanoparticles for the transcorneal permeation of carprofen: Ocular anti-inflammatory applications.

PubMed

Parra, Alexander; Mallandrich, Mireia; Clares, Beatriz; Egea, María A; Espina, Marta; García, María L; Calpena, Ana C

2015-12-01

This work aimed the design and development of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) for the ocular delivery of Carprofen (CP) by a central rotatable composite design 2(3)+ star. NPs showed adequate size for ocular administration (189.50 ± 1.67 nm), low polydispersity (0.01 ± 0.01), negative charge surface (-22.80 ± 0.66 mV) and optimal entrapment efficiency (74.70 ± 0.95%). Physicochemical analysis confirmed that CP was dispersed inside the NPs. The drug release followed a first order kinetic model providing greater sustained CP release after lyophilization. Ex vivo permeation analysis through isolated rabbit cornea revealed that a sufficient amount of CP was retained in the tissue avoiding excessive permeation and thus, potential systemic levels. Ex vivo ocular tolerance results showed no signs of ocular irritancy, which was also confirmed by in vivo Draize test. In vivo ocular anti-inflammatory efficacy test confirmed an optimal efficacy of NPs and its potential application in eye surgery. Copyright © 2015 Elsevier B.V. All rights reserved.

Computational studies of metal-metal and metal-ligand interactions

NASA Technical Reports Server (NTRS)

Barnes, Leslie A.

1992-01-01

The geometric structure of Cr(CO)6 is optimized at the modified coupled-pair functional (MCPF), single and double excitation coupled-cluster (CCSD) and CCSD(T) levels of theory (including a perturbational estimate for connected triple excitations), and the force constants for the totally symmetric representation are determined. The geometry of Cr(CO)5 is partially optimized at the MCPF, CCSD and CCSD(T) levels of theory. Comparison with experimental data shows that the CCSD(T) method gives the best results for the structures and force constants, and that remaining errors are probably due to deficiencies in the one-particle basis sets used for CO. A detailed comparison of the properties of free CO is therefore given, at both the MCPF and CCSD/CCSD(T) levels of treatment, using a variety of basis sets. With very large one-particle basis sets, the SSCD(T) method gives excellent results for the bond distance, dipole moment and harmonic frequency of free CO. The total binding energies of Cr(CO)6 and Cr(CO)5 are also determined at the MCPF, CCSD and CCSD(T) levels of theory. The CCSD(T) method gives a much larger total binding energy than either the MCPF or CCSD methods. An analysis of the basis set superposition error (BSSE) at the MCPF level of treatment points out limitations in the one-particle basis used here and in a previous study. Calculations using larger basis sets reduced the BSSE, but the total binding energy of Cr(CO)6 is still significantly smaller than the experimental value, although the first CO bond dissociation energy of Cr(CO)6 is well described. An investigation of 3s3p correlation reveals only a small effect. The remaining discrepancy between the experimental and theoretical total binding energy of Cr(CO)6 is probably due to limitations in the one-particle basis, rather than limitations in the correlation treatment. In particular an additional d function and an f function on each C and O are needed to obtain quantitative results. This is underscored by the fact that even using a very large primitive se (1042 primitive functions contracted to 300 basis functions), the superposition error for the total binding energy of Cr(CO)6 is 22 kcal/mol at the MCPF level of treatment.

Sustained-release of naproxen sodium from electrospun-aligned PLLA-PCL scaffolds.

PubMed

Lui, Yuan Siang; Lewis, Mark P; Loo, Say Chye Joachim

2017-04-01

Spontaneous tendon healing may result in reduced tissue functionality. In view of this, tissue engineering (TE) emerges as a promising approach in promoting proper tendon regeneration. However, unfavourable post-surgical adhesion formations restrict adequate tendon healing through the TE approach. Naproxen sodium (NPS), a non-steroidal anti-inflammatory drug (NSAID), has been demonstrated to prevent adhesions by inhibiting the inflammatory response. Therefore, in this study, various factors, such as polymer composition, i.e. different poly-l-lactic acid (PLLA):polycaprolactone (PCL) ratios, and percentage of water:hexafluoroisopropanol (HFIP; as co-solvent) ratios, were investigated to understand how these can influence the release of NPS from electrospun scaffolds. By adjusting the amount of water as the co-solvent, NPS could be released sustainably for as long as 2 weeks. Scaffold breaking strength was also enhanced with the addition of water as the co-solvent. This NPS-loaded scaffold showed no significant cytotoxicity, and L929 murine fibroblasts cultured on the scaffolds were able to proliferate and align along the fibre orientation. These scaffolds with desirable tendon TE characteristics would be promising candidates in achieving better tendon regeneration in vivo. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

A water management decision support system contributing to sustainability

NASA Astrophysics Data System (ADS)

Horváth, Klaudia; van Esch, Bart; Baayen, Jorn; Pothof, Ivo; Talsma, Jan; van Heeringen, Klaas-Jan

2017-04-01

Deltares and Eindhoven University of Technology are developing a new decision support system (DSS) for regional water authorities. In order to maintain water levels in the Dutch polder system, water should be drained and pumped out from the polders to the sea. The time and amount of pumping depends on the current sea level, the water level in the polder, the weather forecast and the electricity price forecast and possibly local renewable power production. This is a multivariable optimisation problem, where the goal is to keep the water level in the polder within certain bounds. By optimizing the operation of the pumps the energy usage and costs can be reduced, hence the operation of the regional water authorities can be more sustainable, while also anticipating on increasing share of renewables in the energy mix in a cost-effective way. The decision support system, based on Delft-FEWS as operational data-integration platform, is running an optimization model built in RTC-Tools 2, which is performing real-time optimization in order to calculate the pumping strategy. It is taking into account the present and future circumstances. As being the core of the real time decision support system, RTC-Tools 2 fulfils the key requirements to a DSS: it is fast, robust and always finds the optimal solution. These properties are associated with convex optimization. In such problems the global optimum can always be found. The challenge in the development is to maintain the convex formulation of all the non-linear components in the system, i.e. open channels, hydraulic structures, and pumps. The system is introduced through 4 pilot projects, one of which is a pilot of the Dutch Water Authority Rivierenland. This is a typical Dutch polder system: several polders are drained to the main water system, the Linge. The water from the Linge can be released to the main rivers that are subject to tidal fluctuations. In case of low tide, water can be released via the gates. In case of high tide, water should be pumped. The goal of the pilot is to make the operation of the regional water authority more sustainable and cost-efficient. Sustainability can be achieved by minimizing the CO2 production trough minimizing the energy used for pumping. This work is showing the functionalities of the new decision support system, using RTC-Tools 2, through the example of a pilot project.

Release of a wound-healing agent from PLGA microspheres in a thermosensitive gel.

PubMed

Machado, H A; Abercrombie, J J; You, T; Deluca, P P; Leung, K P

2013-01-01

The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4-7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 μm. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant consideration and testing in animal wound models for treating combat-related injuries.

Impact of Elevated CO2 on Trace Element Release from Aquifer Sediments of the San Joaquin Valley, CA

NASA Astrophysics Data System (ADS)

Fox, P. M.; Nico, P. S.; Davis, J. A.; Spycher, N.

2014-12-01

Carbon capture and storage (CCS) is a promising technique for mitigating climate change by storing large volumes of carbon dioxide in deep saline aquifers. In California, the thick marine sediments of the Central and Salinas Valleys have been identified as prime targets for future CO2 storage. However, the potential impacts on water quality of overlying drinking-water aquifers must be studied before CCS can be implemented. In this study, we compare trace element release from San Joaquin Valley aquifer sediments with a wide range of textural and redox properties. Kinetic batch experiments were performed with artificial groundwater continuously equilibrated under CO2-saturated (at 1 atm) and background CO2 (0.002-0.006 atm) conditions, resulting in a shift of nearly 3 pH units. In addition, the reversibility of trace element release was studied by sequentially lowering the CO2 from 1.0 atm to 0.5 atm to background concentrations (0.002-0.006 atm) for CO2-saturated systems in order to mimic the dissipation of a CO2 plume in the aquifer. During exposure to high CO2, a number of elements displayed enhanced release compared to background CO2 experiments (Ca, Mg, Li, Si, B, As, Sr, Ni, Fe, Mn, V, Ti, and Co) with concentrations of As, Fe, and Mn exceeding EPA maximum contaminant levels in some cases. On the other hand, Mo and U showed suppressed release. Most intriguing, many of the elements showing enhanced release displayed at least some degree of irreversibility when CO2 concentrations were decreased to background levels. In fact, in some cases (i.e., for V), an element showed further release when CO2 concentrations were decreased. These results suggest that there may be longer-term effects on groundwater quality that persist even after the CO2 plume has dissipated. Several different mechanisms of trace element release including ion exchange, desorption, and carbonate mineral dissolution are explored. Preliminary modeling results suggest that carbonate mineral dissolution can play a key role in driving trace element release even in sediments where carbonates are in low abundance.

Sugarcane vinasse CO2 gasification and release of ash-forming matters in CO2 and N2 atmospheres.

PubMed

Dirbeba, Meheretu Jaleta; Brink, Anders; DeMartini, Nikolai; Lindberg, Daniel; Hupa, Mikko

2016-10-01

Gasification of sugarcane vinasse in CO2 and the release of ash-forming matters in CO2 and N2 atmospheres were investigated using a differential scanning calorimetry and thermogravimetric analyzer (DSC-TGA) at temperatures between 600 and 800°C. The results showed that pyrolysis is the main mechanism for the release of the organics from vinasse. Release of ash-forming matters in the vinasse is the main cause for vinasse char weight losses in the TGA above 700°C. The losses are higher in N2 than in CO2, and increase considerably with temperature. CO2 gasification also consumes the carbon in the vinasse chars while suppressing alkali release. Alkali release was also significant due to volatilization of KCl and reduction of alkali sulfate and carbonate by carbon. The DSC measured thermal events during heating up in N2 atmosphere that correspond to predicted melting temperatures of alkali salts in the char. Copyright © 2016 Elsevier Ltd. All rights reserved.

A critical review on the interaction of substrate nutrient balance and microbial community structure and function in anaerobic co-digestion.

PubMed

Xu, Rong; Zhang, Kai; Liu, Pu; Khan, Aman; Xiong, Jian; Tian, Fake; Li, Xiangkai

2018-01-01

Anaerobic co-digestion generally results in a higher yield of biogas than mono-digestion, hence co-digestion has become a topic of general interest in recent studies of anaerobic digestion. Compared with mono-digestion, co-digestion utilizes multiple substrates. The balance of substrate nutrient in co-digestion comprises better adjustments of C/N ratio, pH, moisture, trace elements, and dilution of toxic substances. All of these changes could result in positive shifts in microbial community structure and function in the digestion processes and consequent augmentation of biogas production. Nevertheless, there have been few reviews on the interaction of nutrient and microbial community in co-digestions. The objective of this review is to investigate recent achievements and perspectives on the interaction of substrate nutrient balance and microbial community structure and function. This may provide valuable information on the optimization of combinations of substrates and prediction of bioreactor performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study on O2-supplying characteristics of Azolla in Controlled Ecological Life Support System

NASA Astrophysics Data System (ADS)

Chen, Min; Deng, Sufang; Yang, Youquang; Huang, Yibing; Liu, Zhongzhu

Azolla has high growth and propagation rate, strong photosynthetic O2-releasing ability and rich nutrient value. It is able to be used as salad-type vegetable, and can also be cultured on wet bed in multi-layer condition. Hence, it possesses a potential functioning as providing O2, fresh vegetable and absorbing CO2 for Controlled Ecological Life Support System in space. In this study, we try to make clear the O2-providing characteristics of Azolla in controlled close chamber under manned condition in order to lay a foundation for Azolla as a biological component in the next ground simulated experiment and space application. A closed test cham-ber of Controlled Ecological Life Support System and Azolla wet-culturing devices were built to measure the changes of atmospheric O2-CO2 concentration inside chamber under "Azolla-fish -men" coexisting condition. The results showed that, the amount of O2 consumption is 80.49 83.07 ml/h per kilogram fish, the amount of CO2 emissions is 70.49 73.56 ml/(kg • h); O2 consumption of trial volunteers is 19.71 L/h, the volume of respiration release CO2 18.90 L/h .Artificial light intensity of Azolla wet culture under 70009000 Lx, people respiration and Azolla photosynthesis complemented each other, the atmospheric O2-CO2 concentration inside chamber maintained equilibration. Elevated atmospheric CO2 concentrations in close chamber have obvious effects on enhancing Azolla net photosynthesis efficiency. This shows that Azolla has strong photosynthetic O2-releasing ability, which equilibrates the O2-CO2 concentration inside chamber in favor of human survival, and then verifies the prospect of Azolla in space application.

Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics

PubMed Central

Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

2012-01-01

The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet. PMID:23960836

Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics.

PubMed

Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

2013-04-01

The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

A novel method to harvest Chlorella sp. by co-flocculation/air flotation.

PubMed

Zhang, Haiyang; Lin, Zhe; Tan, Daoyong; Liu, Chunhua; Kuang, Yali; Li, Zhu

2017-01-01

To develop a more effective dissolved air flotation process for harvesting microalgae biomass, a co-flocculation/air flotation (CAF) system was developed that uses an ejector followed by a helix tube flocculation reactor (HTFR) as a co-flocculation device to harvest Chlorella sp. 64.01. The optimal size distribution of micro-bubbles and an air release efficiency of 96 % were obtained when the flow ratio of inlet fluid (raw water) to motive fluid (saturated water) of the ejector was 0.14. With a reaction time of 24 s in the HTFR, microalgae cells and micro-bubbles were well flocculated, and these aerated flocs caused a fast rising velocity (96 m/h) and high harvesting efficiency (94 %). In a CAF process, micro-bubbles can be encapsulated into microalgae flocs, which makes aerated flocs more stable. CAF is an effective approach to harvesting microalgae.

Optimization of a novel wax matrix system using aminoalkyl methacrylate copolymer E and ethylcellulose to suppress the bitter taste of acetaminophen.

PubMed

Shiino, Kai; Iwao, Yasunori; Miyagishima, Atsuo; Itai, Shigeru

2010-08-16

The purpose of the present study was to design and evaluate a novel wax matrix system containing various ratios of aminoalkyl methacrylate copolymer E (AMCE) and ethylcellulose (EC) as functional polymers in order to achieve the optimal acetaminophen (APAP) release rate for taste masking. A two factor, three level (3(2)) full factorial study design was used to optimize the ratios of AMCE and EC, and the release of APAP from the wax matrix was evaluated using a stationary disk in accordance with the paddle method. The disk was prepared by congealing glyceryl monostearate (GM), a wax with a low melting point, with various ratios of polymers and APAP. The criteria for release rate of APAP from the disk at pH 4.0 and pH 6.5 were calculated to be more than 0.5017 microg/(mlxmin) and less than 0.1414 microg/(mlxmin), respectively, under the assumption that the particle size of spherical matrix should be 100 microm. In multiple regression analysis, the release of APAP at pH 4.0 was found to increase markedly as the concentration of AMCE increased, whereas the release of APAP at pH 6.5 decreased as the EC concentration increased, even when a high level of AMCE was incorporated. Using principle component analysis, it was found that the viscosity of the matrix affects the pH-dependent release of APAP at pH 4.0 and pH 6.5. Furthermore, using multiple regression analysis, the optimum ratio of APAP:AMCE:EC:GM was found to be 30:7:10:53, and the release pattern of APAP from the optimum wax formulation nearly complied with the desired criteria. Therefore, the present study demonstrated that the incorporation of AMCE and EC into a wax matrix system enabled the appropriate release of APAP as a means of taste masking. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Development of low methoxy amidated pectin-based mucoadhesive patches for buccal delivery of triclosan: effect of cyclodextrin complexation.

PubMed

Jug, Mario; Kosalec, Ivan; Maestrelli, Francesca; Mura, Paola

2012-11-06

A novel mucoadhesive buccal patch formulation of triclosan (TR), a broad spectrum antibacterial agent, was developed using low methoxy amidated pectin (AMP). The integrity of AMP matrix was improved by addition of 20% (w/w) Carbopol (CAR). The efficiency of β-cyclodextrin-epichlorohydrin polymer (EPIβCD) and anionic carboxymethylated β-cyclodextrin-epichlorohydrin polymer (CMEPIβCD) in optimization of TR solubility and release from such a matrix was investigated and confronted to that of parent β-cyclodextrin (βCD). Loading of TR/βCD co-ground complex into AMP/CAR matrix resulted in a biphasic release profile which was sensitive upon the hydration degree of the matrix, due to lower solubilizing efficiency of βCD, while the drug release from patches loaded with TR/EPIβCD complex was significantly faster with a constant release rate. Microbiological studies evidenced faster onset and more pronounced antibacterial action of TR/EPIβCD loaded patches, clearly demonstrating their good therapeutic potential in eradication of Streptococcus mutans, a cariogenic bacteria, from the oral cavity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Co-Optimization of Fuels and Engines | Transportation Research | NREL

Science.gov Websites

Co-Optimization of Fuels and Engines Co-Optimization of Fuels and Engines Photo of silver sedan in ), eight other national laboratories, and industry on the Co-Optimization of Fuels & Engines (Co-Optima research activities and accomplishments of the Co-Optima initiative in the Co-Optimization of Fuels &

Development of a calcium phosphate co-precipitate/poly(lactide-co-glycolide) DNA delivery system: release kinetics and cellular transfection studies.

PubMed

Kofron, Michelle D; Laurencin, Cato T

2004-06-01

One of the most common non-viral methods for the introduction of foreign deoxyribonucleic acid (DNA) into cultured cells is calcium phosphate co-precipitate transfection. This technique involves the encapsulation of DNA within a calcium phosphate co-precipitate, particulate addition to in vitro cell culture, endocytosis of the co-precipitate, and exogenous DNA expression by the transfected cell. In this study, we fabricated a novel non-viral gene transfer system by adsorbing DNA, encapsulated in calcium phosphate (DNA/Ca-P) co-precipitates, to biodegradable two- and three-dimensional poly(lactide-co-glycolide) matrices (2D-DNA/Ca-P/PLAGA, 3D-DNA/Ca-P/PLAGA). Co-precipitate release studies demonstrated an initial burst release over the first 48 h. By day 7, approximately 96% of the initially adsorbed DNA/Ca-P co-precipitate had been released. This was followed by low levels of co-precipitate release for 42 days. Polymerase chain reaction was used to demonstrate the ability of the released DNA containing co-precipitates to transfect SaOS-2 cells cultured in vitro on the 3D-DNA/Ca-P/PLAGA matrix and maintenance of the structural integrity of the exogenous DNA. In summary, a promising system for the incorporation and controlled delivery of exogenous genes encapsulated within a calcium phosphate co-precipitate from biodegradable polymeric matrices has been developed and may have applicability to the delivery of therapeutic genes and the transfection of other cell types.

Characterization and evaluation of self-nanoemulsifying sustained-release pellet formulation of ziprasidone with enhanced bioavailability and no food effect.

PubMed

Miao, Yanfei; Chen, Guoguang; Ren, Lili; Pingkai, Ouyang

2016-09-01

The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential. In vitro drug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10 h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.

Detection of Evolved Carbon Dioxide in the Rocknest Eolian Bedform by the Sample Analysis at Mars(SAM) Instrument at the Mars Curiosity Landing Site

NASA Technical Reports Server (NTRS)

Sutter, B.; Archer, D.; McAdam, A.; Franz, H.; Ming, D. W.; Eigenbrode, J. L.; Glavin, D. P.; Mahaffy, P.; Stern, J.; Navarro-Gonzalez, R.

2013-01-01

The Sample Analysis at Mars (SAM) instrument detected four releases of carbon dioxide (CO2) that ranged from 100 to 700 C from the Rocknest eolian bedform material (Fig. 1). Candidate sources of CO2 include adsorbed CO2, carbonate(s), combusted organics that are either derived from terrestrial contamination and/or of martian origin, occluded or trapped CO2, and other sources that have yet to be determined. The Phoenix Lander s Thermal Evolved Gas Analyzer (TEGA) detected two CO2 releases (400-600, 700-840 C) [1,2]. The low temperature release was attributed to Fe- and/or Mg carbonates [1,2], per-chlorate interactions with carbonates [3], nanophase carbonates [4] and/or combusted organics [1]. The high temperature CO2 release was attributed to a calcium bearing carbonate [1,2]. No evidence of a high temperature CO2 release similar to the Phoenix material was detected in the Rocknest materials by SAM. The objectives of this work are to evaluate the temperature and total contribution of each Rocknest CO2 release and their possible sources. Four CO2 releases from the Rocknest material were detected by SAM. Potential sources of CO2 are adsorbed CO2, (peak 1) and Fe/Mg carbonates (peak 4). Only a fraction of peaks 2 and 3 (0.01 C wt.%) may be partially attributed to combustion of organic contamination. Meteoritic organics mixed in the Rocknest bedform could be present, but the peak 2 and 3 C concentration (approx.0.21 C wt. %) is likely too high to be attributed solely to meteoritic organic C. Other inorganic sources of C such as interactions of perchlorates and carbonates and sources yet to be identified will be evaluated to account for CO2 released from the thermal decomposition of Rocknest material.

Optimal insecticide-treated bed-net coverage and malaria treatment in a malaria-HIV co-infection model.

PubMed

Mohammed-Awel, Jemal; Numfor, Eric

2017-03-01

We propose and study a mathematical model for malaria-HIV co-infection transmission and control, in which malaria treatment and insecticide-treated nets are incorporated. The existence of a backward bifurcation is established analytically, and the occurrence of such backward bifurcation is influenced by disease-induced mortality, insecticide-treated bed-net coverage and malaria treatment parameters. To further assess the impact of malaria treatment and insecticide-treated bed-net coverage, we formulate an optimal control problem with malaria treatment and insecticide-treated nets as control functions. Using reasonable parameter values, numerical simulations of the optimal control suggest the possibility of eliminating malaria and reducing HIV prevalence significantly, within a short time horizon.

Synthesis of arbitrary pulse waveforms in QCL-seeded ns-pulse CO₂ laser for optimization of an LPP EUV source.

PubMed

Nowak, Krzysztof M; Kurosawa, Yoshiaki; Suganuma, Takashi; Kawasuji, Yasufumi; Nakarai, Hiroaki; Saito, Takashi; Fujimoto, Junichi; Mizoguchi, Hakaru

2016-07-01

One of the unique features of the quantum-cascade-laser-seeded, nanosecond-pulse CO₂ laser, invented for the purpose of generation of extreme UV by laser-produced-plasma, is a robust synthesis of arbitrary pulse waveforms. In the present Letter we report on experimental results that are, to our best knowledge, the first demonstration of such functionality obtainable from nanosecond-pulse CO₂ laser technology. An online pulse duration adjustment within 10-40 ns was demonstrated, and a few exemplary pulse waveforms were synthesized, such as "tophat," "tailspike," and "leadspike" shapes. Such output characteristics may be useful to optimize the performance of LPP EUV source.

Theoretical studies of ground and excited electronic States in a series of rhenium(i) bipyridine complexes containing diarylethynyl-based structure.

PubMed

Yang, Li; Ren, Ai-Min; Feng, Ji-Kang; Liu, Xiao-Dong; Ma, Yu-Guang; Zhang, Hong-Xing

2004-09-20

The photophysical properties, which vary as X is varied, of Re(I)-halide complexes (X2-bpy)ReICl(CO)3 (where X=ph, DAE, DNE, and DPE; ph = phenyl (1); DAE = di(amineoethynylbenzene) (2); DPE = di(phenylethynylbenzene) (3); DNE = di(nitroethynylbenzene) (4); bpy=2,2'bipyridine), are investigated using density functional theory (DFT). The electronic properties of the neutral molecules, in addition to the positive and negative ions, are studied using B3LYP functional. Excited singlet and triplet states are examined using time-dependent density functional theory (TDDFT). The low-lying excited-state geometries are optimized at the ab initio configuration interaction singlets level. As shown, the diarylethynyl-based structure is an integral component of the bpy pi-conjugated network, which results in a good planar structure. The occupied orbitals involved in the transitions have a significant mixture of metal Re and group Cl, and the lowest unoccupied orbital is a pi orbital, which extends from ligand bpy to diarylethynyl-based substituents. The luminescence for each complex originates from the lowest triplet excited states and is assigned to the mixing of MLCT and LLCT characters. Significant insights on the effects of these diarylethynyl conjugated structure and ending substituents (NH2, ph, and NO2) on absorption and emission spectra are observed by analysis of the results of the TDDFT method. The diarylethynyl-based pi-conjugated network makes both the absorption and emission spectra red-shifted compared with simple complex (bpy)ReICl(CO)3. Furthermore, an electron-releasing group (NH2) makes absorption and emission spectra blue-shift and an electron-withdrawing group (NO2) makes them red-shift. Copyright 2004 American Chemical Society

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

PubMed Central

Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

2014-01-01

Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

High-capacity thermo-responsive magnetic molecularly imprinted polymers for selective extraction of curcuminoids.

PubMed

You, Qingping; Zhang, Yuping; Zhang, Qingwen; Guo, Junfang; Huang, Weihua; Shi, Shuyun; Chen, Xiaoqin

2014-08-08

Thermo-responsive magnetic molecularly imprinted polymers (TMMIPs) for selective recognition of curcuminoids with high capacity and selectivity have firstly been developed. The resulting TMMIPs were characterized by TEM, FT-IR, TGA, VSM and UV, which indicated that TMMIPs showed thermo-responsiveness [lower critical solution temperature (LCST) at 33.71°C] and rapid magnetic separation (5s). The polymerization, adsorption and release conditions were optimized in detail to obtain the highest binding capacity, selectivity and release ratio. We found that the adopted thermo-responsive monomer [N-isopropylacrylamide (NIPAm)] could be considered not only as inert polymer backbone for thermo-responsiveness but also as functional co-monomers combination with basic monomer (4-VP) for more specific binding sites when ethanol was added in binding solution. The maximum adsorption capacity with highest selectivity of curcumin was 440.3μg/g (1.93 times that on MMIPs with no thermosensitivity) at 45°C (above LCST) in 20% (v/v) ethanol solution on shrunk TMMIPs, and the maximum release proportion was about 98% at 20°C (below LCST) in methanol-acetic acid (9/1, v/v) solution on swelled TMMIPs. The adsorption process between curcumin and TMMIPs followed Langumuir adsorption isotherm and pseudo-first-order reaction kinetics. The prepared TMMIPs also showed high reproducibility (RSD<6% for batch-to-batch evaluation) and stability (only 7% decrease after five cycles). Subsequently, the TMMIPs were successfully applied for selective extraction of curcuminoids from complex natural product, Curcuma longa. Copyright © 2014 Elsevier B.V. All rights reserved.

Formulation, optimization and characterization of cationic polymeric nanoparticles of mast cell stabilizing agent using the Box-Behnken experimental design.

PubMed

Gajra, Balaram; Patel, Ravi R; Dalwadi, Chintan

2016-01-01

The present research work was intended to develop and optimize sustained release of biodegradable chitosan nanoparticles (CSNPs) as delivery vehicle for sodium cromoglicate (SCG) using the circumscribed Box-Behnken experimental design (BBD) and evaluate its potential for oral permeability enhancement. The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on particle size and entrapment efficiency (%EE) of SCG-CSNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized SCG-CSNPs were evaluated for physicochemical, morphological, in-vitro characterizations and permeability enhancement potential by ex-vivo and uptake study using CLSM. SCG-CSNPs exhibited particle size of 200.4 ± 4.06 nm and %EE of 62.68 ± 2.4% with unimodal size distribution having cationic, spherical, smooth surface. Physicochemical and in-vitro characterization revealed existence of SCG in amorphous form inside CSNPs without interaction and showed sustained release profile. Ex-vivo and uptake study showed the permeability enhancement potential of CSNPs. The developed SCG-CSNPs can be considered as promising delivery strategy with respect to improved permeability and sustained drug release, proving importance of CSNPs as potential oral delivery system for treatment of allergic rhinitis. Hence, further studies should be performed for establishing the pharmacokinetic potential of the CSNPs.

Facile synthesis of functionalized ionic surfactant templated mesoporous silica for incorporation of poorly water-soluble drug.

PubMed

Li, Jing; Xu, Lu; Yang, Baixue; Wang, Hongyu; Bao, Zhihong; Pan, Weisan; Li, Sanming

2015-08-15

The present paper reported amino group functionalized anionic surfactant templated mesoporous silica (Amino-AMS) for loading and release of poorly water-soluble drug indomethacin (IMC) and carboxyl group functionalized cationic surfactant templated mesoporous silica (Carboxyl-CMS) for loading and release of poorly water-soluble drug famotidine (FMT). Herein, Amino-AMS and Carboxyl-CMS were facilely synthesized using co-condensation method through two types of silane coupling agent. Amino-AMS was spherical nanoparticles, and Carboxyl-CMS was well-formed spherical nanosphere with a thin layer presented at the edge. Drug loading capacity was obviously enhanced when using Amino-AMS and Carboxyl-CMS as drug carriers due to the stronger hydrogen bonding force formed between surface modified carrier and drug. Amino-AMS and Carboxyl-CMS had the ability to transform crystalline state of loaded drug from crystalline phase to amorphous phase. Therefore, IMC loaded Amino-AMS presented obviously faster release than IMC because amorphous phase of IMC favored its dissolution. The application of asymmetric membrane capsule delayed FMT release significantly, and Carboxyl-CMS favored sustained release of FMT due to its long mesoporous channels and strong interaction formed between its carboxyl group and amino group of FMT. Copyright © 2015 Elsevier B.V. All rights reserved.

Quality by Design (QbD) Approach for Development of Co-Processed Excipient Pellets (MOMLETS) By Extrusion-Spheronization Technique.

PubMed

Patel, Hetal; Patel, Kishan; Tiwari, Sanjay; Pandey, Sonia; Shah, Shailesh; Gohel, Mukesh

2016-01-01

Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets. Co-processed excipient prepared by spray drying (US4744987; US5686107; WO2003051338) and coprecipitation technique (WO9517831) are patented. The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD). Co-processed excipient core pellets (MOMLETS) were developed by extrusion spheronization technique using Quality by Design (QbD) approach. BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor. Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot was constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (Extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The control space was identified in which desired quality of the pellets can be obtained. Co-processed excipient core pellets (MOMLETS) were successfully developed by QbD approach. Versatility, Industrial scalability and simplicity are the main features of the proposed research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

NASA Astrophysics Data System (ADS)

Kan, Xianwen; Geng, Zhirong; Zhao, Yao; Wang, Zhilin; Zhu, Jun-Jie

2009-04-01

Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe3O4 nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

Controlled release from thermo-sensitive PNVCL-co-MAA electrospun nanofibers: The effects of hydrophilicity/hydrophobicity of a drug.

PubMed

Liu, Lin; Bai, Shaoqing; Yang, Huiqin; Li, Shubai; Quan, Jing; Zhu, Limin; Nie, Huali

2016-10-01

The thermo-sensitive copolymer poly(N-vinylcaprolactam-co-methacrylic acid) (PNVCL-co-MAA) was synthesized by free radical polymerization and the resulting nanofibers were fabricated using an electrospinning process. The molecular weight of the copolymer was adjusted by varying the content of methacrylic acid (MAA) while keeping that of N-vinylcaprolactam (NVCL) constant. Hydrophilic captopril and hydrophobic ketoprofen were used as model drugs, and PNVCL-co-MAA nanofibers were used as the drug carrier to investigate the effects of drug on its release properties from nanofibers at different temperatures. The results showed that slow release over several hours was observed at 40°C (above the lower critical solution temperature (LCST) of PNVCL-co-MAA), while the drugs exhibited a burst release of several seconds at 20°C (below the LCST). Drug release slowed with increasing content of the hydrophobic monomer NVCL. The hydrophilic captopril was released at a higher rate than the hydrophobic ketoprofen. The drug release characteristics were dependent on the temperature, the portion of hydrophilic groups and hydrophobic groups in the copolymer and hydrophilicity/hydrophobicity of drug. Study on the mechanism of release showed that Korsmeyer-Peppas model as a major drug release mechanism. Given these results, the PNVCL-co-MAA copolymers are proposed to have useful applications in intellectual drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Real-time CO2 sensor for the optimal control of electronic EGR system

NASA Astrophysics Data System (ADS)

Kim, Gwang-jung; Choi, Byungchul; Choi, Inchul

2013-12-01

In modern diesel engines, EGR (Exhaust Gas Recirculation) is an important technique used in nitrogen oxide (NOx) emission reduction. This paper describes the development and experimental results of a fiber-optical sensor using a 2.7 μm wavelength absorption to quantify the simultaneous CO2 concentration which is the primary variable of EGR rate (CO2 in the exhaust gas versus CO2 in the intake gas, %). A real-time laser absorption method was developed using a DFB (distributed feedback) diode laser and waveguide to make optimal design and control of electronic EGR system required for `Euro-6' and `Tier 4 Final' NOx emission regulations. While EGR is effective to reduce NOx significantly, the amount of HC and CO is increased in the exhaust gas if EGR rate is not controlled based on driving conditions. Therefore, it is important to recirculate an appropriate amount of exhaust gas in the operation condition generating high volume of NOx. In this study, we evaluated basic characteristics and functions of our optical sensor and studied basically in order to find out optimal design condition. We demonstrated CO2 measurement speed, accuracy and linearity as making a condition similar to real engine through the bench-scale experiment.

Optimizing Binding Energies of Key Intermediates for CO 2 Hydrogenation to Methanol over Oxide-Supported Copper

DOE PAGES

None, None

2016-08-29

Rational optimization of catalytic performance has been one of the major challenges in catalysis. We report a bottom-up study on the ability of TiO 2 and ZrO 2 to optimize the CO 2 conversion to methanol on Cu, using combined density functional theory (DFT) calculations, kinetic Monte Carlo (KMC) simulations, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) measurements, and steady-state flow reactor tests. Furthermore, the theoretical results from DFT and KMC agree with in situ DRIFTS measurements, showing that both TiO 2 and ZrO 2 help to promote methanol synthesis on Cu via carboxyl intermediates and the reversemore » water–gas-shift (RWGS) pathway; the formate intermediates, on the other hand, likely act as a spectator eventually. The origin of the superior promoting effect of ZrO 2 is associated with the fine-tuning capability of reduced Zr 3+ at the interface, being able to bind the key reaction intermediates, e.g. *CO 2, *CO, *HCO, and *H 2CO, moderately to facilitate methanol formation. Our study demonstrates the importance of synergy between theory and experiments to elucidate the complex reaction mechanisms of CO 2 hydrogenation for the realization of a better catalyst by design.« less

Joint optimization of green vehicle scheduling and routing problem with time-varying speeds

PubMed Central

Zhang, Dezhi; Wang, Xin; Ni, Nan; Zhang, Zhuo

2018-01-01

Based on an analysis of the congestion effect and changes in the speed of vehicle flow during morning and evening peaks in a large- or medium-sized city, the piecewise function is used to capture the rules of the time-varying speed of vehicles, which are very important in modelling their fuel consumption and CO2 emission. A joint optimization model of the green vehicle scheduling and routing problem with time-varying speeds is presented in this study. Extra wages during nonworking periods and soft time-window constraints are considered. A heuristic algorithm based on the adaptive large neighborhood search algorithm is also presented. Finally, a numerical simulation example is provided to illustrate the optimization model and its algorithm. Results show that, (1) the shortest route is not necessarily the route that consumes the least energy, (2) the departure time influences the vehicle fuel consumption and CO2 emissions and the optimal departure time saves on fuel consumption and reduces CO2 emissions by up to 5.4%, and (3) extra driver wages have significant effects on routing and departure time slot decisions. PMID:29466370

Joint optimization of green vehicle scheduling and routing problem with time-varying speeds.

PubMed

Zhang, Dezhi; Wang, Xin; Li, Shuangyan; Ni, Nan; Zhang, Zhuo

2018-01-01

Based on an analysis of the congestion effect and changes in the speed of vehicle flow during morning and evening peaks in a large- or medium-sized city, the piecewise function is used to capture the rules of the time-varying speed of vehicles, which are very important in modelling their fuel consumption and CO2 emission. A joint optimization model of the green vehicle scheduling and routing problem with time-varying speeds is presented in this study. Extra wages during nonworking periods and soft time-window constraints are considered. A heuristic algorithm based on the adaptive large neighborhood search algorithm is also presented. Finally, a numerical simulation example is provided to illustrate the optimization model and its algorithm. Results show that, (1) the shortest route is not necessarily the route that consumes the least energy, (2) the departure time influences the vehicle fuel consumption and CO2 emissions and the optimal departure time saves on fuel consumption and reduces CO2 emissions by up to 5.4%, and (3) extra driver wages have significant effects on routing and departure time slot decisions.

Drug delivery from hydrophobic-modified mesoporous silicas: Control via modification level and site-selective modification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang Qunli, E-mail: tangqunli@hnu.c; State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001; Chen Yuxi

2010-01-15

Dimethylsilyl (DMS) modified mesoporous silicas were successfully prepared via co-condensation and post-grafting modification methods. The post-grafting modification was carried out by the reaction of the as-synthesized MCM-41 material (before CTAB removal) with diethoxydimethylsinale (DEDMS). N{sub 2} adsorption-desorption and {sup 29}Si MAS NMR characterization demonstrated that different amount of DMS groups were successfully incorporated into the co-condensation modified samples, and the functional DMS groups were placed selectively on the pore openings and external pore surfaces in the post-grafting modified samples. Subsequently, the controlled drug delivery properties from the resulting DMS-modified mesoporous silicas were investigated in detail. The drug adsorption experiments showedmore » that the adsorption capacities were mainly depended on the content of silanol group (CSG) in the corresponding carriers. The in vitro tests exhibited that the incorporation of DMS groups greatly retarded the ibuprofen release rate. Moreover, the ibuprofen release profiles could be well modulated by varying DMS modification levels and site-selective distribution of functional groups in mesoporous carriers. - The distribution of DMS groups on the pore surfaces of the mesostructures strongly affects the drug release rate. The P-M41-1 and the P-M41-2 possess the close DMS modification levels as the C-M41-10, but the ibuprofen release rates from the P-M41-1 and P-M41-2 are much slower than that from the C-M41-10.« less

Introducing a decomposition rate modifier in the Rothamsted Carbon Model to predict soil organic carbon stocks in saline soils.

PubMed

Setia, Raj; Smith, Pete; Marschner, Petra; Baldock, Jeff; Chittleborough, David; Smith, Jo

2011-08-01

Soil organic carbon (SOC) models such as the Rothamsted Carbon Model (RothC) have been used to estimate SOC dynamics in soils over different time scales but, until recently, their ability to accurately predict SOC stocks/carbon dioxide (CO(2)) emissions from salt-affected soils has not been assessed. Given the large extent of salt-affected soils (19% of the 20.8 billion ha of arable land on Earth), this may lead to miss-estimation of CO(2) release. Using soils from two salt-affected regions (one in Punjab, India and one in South Australia), an incubation study was carried out measuring CO(2) release over 120 days. The soils varied both in salinity (measured as electrical conductivity (EC) and calculated as osmotic potential using EC and water content) and sodicity (measured as sodium adsorption ratio, SAR). For soils from both regions, the osmotic potential had a significant positive relationship with CO(2)-C release, but no significant relationship was found between SAR and CO(2)-C release. The monthly cumulative CO(2)-C was simulated using RothC. RothC was modified to take into account reductions in plant inputs due to salinity. A subset of non-salt-affected soils was used to derive an equation for a "lab-effect" modifier to account for changes in decomposition under lab conditions and this modifier was significantly related with pH. Using a subset of salt-affected soils, a decomposition rate modifier (as a function of osmotic potential) was developed to match measured and modelled CO(2)-C release after correcting for the lab effect. Using this decomposition rate modifier, we found an agreement (R(2) = 0.92) between modelled and independently measured data for a set of soils from the incubation experiment. RothC, modified by including reduced plant inputs due to salinity and the salinity decomposition rate modifier, was used to predict SOC stocks of soils in a field in South Australia. The predictions clearly showed that SOC stocks are reduced in saline soils. Therefore both the decomposition rate modifier and plant input modifier should be taken into account when accounting for SOC turnover in saline soils. Since modeling has previously not accounted for the impact of salinity, our results suggest that previous predictions may have overestimated SOC stocks.

Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles.

PubMed

Dhar, Shanta; Gu, Frank X; Langer, Robert; Farokhzad, Omid C; Lippard, Stephen J

2008-11-11

Cisplatin is used to treat a variety of tumors, but dose limiting toxicities or intrinsic and acquired resistance limit its application in many types of cancer including prostate. We report a unique strategy to deliver cisplatin to prostate cancer cells by constructing Pt(IV)-encapsulated prostate-specific membrane antigen (PSMA) targeted nanoparticles (NPs) of poly(D,L-lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-functionalized controlled release polymers. By using PLGA-b-PEG nanoparticles with PSMA targeting aptamers (Apt) on the surface as a vehicle for the platinum(IV) compound c,t,c-[Pt(NH(3))(2)(O(2)CCH(2)CH(2)CH(2)CH(2)CH(3))(2)Cl(2)] (1), a lethal dose of cisplatin was delivered specifically to prostate cancer cells. PSMA aptamer targeted delivery of Pt(IV) cargos to PSMA(+) LNCaP prostate cancer cells by endocytosis of the nanoparticle vehicles was demonstrated using fluorescence microscopy by colocalization of green fluorescent labeled cholesterol-encapsulated NPs and early endosome marker EEA-1. The choice of linear hexyl chains in 1 was the result of a systematic study to optimize encapsulation and controlled release from the polymer without compromising either feature. Release of cisplatin from the polymeric nanoparticles after reduction of 1 and formation of cisplatin 1,2-intrastrand d(GpG) cross-links on nuclear DNA was confirmed by using a monoclonal antibody for the adduct. A comparison between the cytotoxic activities of Pt(IV)-encapsulated PLGA-b-PEG NPs with the PSMA aptamer on the surface (Pt-NP-Apt), cisplatin, and the nontargeted Pt(IV)-encapsulated NPs (Pt-NP) against human prostate PSMA-overexpressing LNCaP and PSMA(-) PC3 cancer cells revealed significant differences. The effectiveness of PSMA targeted Pt-NP-Apt nanoparticles against the PSMA(+) LNCaP cells is approximately an order of magnitude greater than that of free cisplatin.

Application of mixture experimental design in the formulation and optimization of matrix tablets containing carbomer and hydroxy-propylmethylcellulose.

PubMed

Petrovic, Aleksandra; Cvetkovic, Nebojsa; Ibric, Svetlana; Trajkovic, Svetlana; Djuric, Zorica; Popadic, Dragica; Popovic, Radmila

2009-12-01

Using mixture experimental design, the effect of carbomer (Carbopol((R)) 971P NF) and hydroxypropylmethylcellulose (Methocel((R)) K100M or Methocel((R)) K4M) combination on the release profile and on the mechanism of drug liberation from matrix tablet was investigated. The numerical optimization procedure was also applied to establish and obtain formulation with desired drug release. The amount of TP released, release rate and mechanism varied with carbomer ratio in total matrix and HPMC viscosity. Increasing carbomer fractions led to a decrease in drug release. Anomalous diffusion was found in all matrices containing carbomer, while Case - II transport was predominant for tablet based on HPMC only. The predicted and obtained profiles for optimized formulations showed similarity. Those results indicate that Simplex Lattice Mixture experimental design and numerical optimization procedure can be applied during development to obtain sustained release matrix formulation with desired release profile.

Magnetically triggered dual functional nanoparticles for resistance-free apoptotic hyperthermia.

PubMed

Yoo, Dongwon; Jeong, Heeyeong; Noh, Seung-Hyun; Lee, Jae-Hyun; Cheon, Jinwoo

2013-12-02

Overcoming resistance: Heat-treated cancer cells possess a protective mechanism for resistance and survival. Resistance-free apoptosis-inducing magnetic nanoparticles (RAINs) successfully promote hyperthermic apoptosis, obstructing cell survival by triggering two functional units of heat generation and the release of geldanamycin (GM) for heat shock protein (Hsp) inhibition under an alternating magnetic field (AMF). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Shock-induced CO2 loss from CaCO3: Implications for early planetary atmospheres

NASA Technical Reports Server (NTRS)

Lange, M. A.; Ahrens, T. J.

1984-01-01

Recovered samples from shock recovery experiments on single crystal calcite were subjected to thermogravimetric analysis to determine the amount of post-shock CO2, the decarbonization interval and the activation energy, for the removal of remaining CO2 in shock-loaded calcite. Comparison of post-shock CO2 with that initially present determines shock-induced CO2 loss as a function of shock pressure. Incipient to complete CO2 loss occurs over a pressure range of approximately 10 to approximately 70 GPa. Optical and scanning electron microscopy reveal structural changes, which are related to the shock-loading. The occurrence of dark, diffuse areas, which can be resolved as highly vesicular areas as observed with a scanning electron microscope are interpreted as representing quenched partial melts, into which shock-released CO2 was injected. The experimental results are used to constrain models of shock-produced, primary CO2 atmospheres on the accreting terrestrial planets.

Intensification of marrubiin concentration by optimization of microwave-assisted (low CO2 yielding) extraction process for Marrubium vulgare using central composite design and antioxidant evaluation.

PubMed

Mittal, Vineet; Nanda, Arun

2017-12-01

Marrubium vulgare Linn (Lamiaceae) was generally extracted by conventional methods with low yield of marrubiin; these processes were not considered environment friendly. This study extracts the whole plant of M. vulgare by microwave assisted extraction (MAE) and optimizes the effect of various extraction parameters on the marrubiin yield by using Central Composite Design (CCD). The selected medicinal plant was extracted using ethanol: water (1:1) as solvent by MAE. The plant material was also extracted using a Soxhlet and the various extracts were analyzed by HPTLC to quantify the marrubiin concentration. The optimized conditions for the microwave-assisted extraction of selected medicinal plant was microwave power of 539 W, irradiation time of 373 s and solvent to drug ratio, 32 mL per g of the drug. The marrubiin concentration in MAE almost doubled relative to the traditional method (0.69 ± 0.08 to 1.35 ± 0.04%). The IC 50 for DPPH was reduced to 66.28 ± 0.6 μg/mL as compared to conventional extract (84.14 ± 0.7 μg/mL). The scanning electron micrographs of the treated and untreated drug samples further support the results. The CCD can be successfully applied to optimize the extraction parameters (MAE) for M. vulgare. Moreover, in terms of environmental impact, the MAE technique could be assumed as a 'Green approach' because the MAE approach for extraction of plant released only 92.3 g of CO 2 as compared to 3207.6 g CO 2 using the Soxhlet method of extraction.

Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages

PubMed Central

Sawle, Philip; Foresti, Roberta; Mann, Brian E; Johnson, Tony R; Green, Colin J; Motterlini, Roberto

2005-01-01

The enzyme heme oxygenase-1 (HO-1) is a cytoprotective and anti-inflammatory protein that degrades heme to produce biliverdin/bilirubin, ferrous iron and carbon monoxide (CO). The anti-inflammatory properties of HO-1 are related to inhibition of adhesion molecule expression and reduction of oxidative stress, while exogenous CO gas treatment decreases the production of inflammatory mediators such as cytokines and nitric oxide (NO). CO-releasing molecules (CO-RMs) are a novel group of substances identified by our group that are capable of modulating physiological functions via the liberation of CO. We aimed in this study to examine the potential anti-inflammatory characteristics of CORM-2 and CORM-3 in an in vitro model of lipopolysaccharide (LPS)-stimulated murine macrophages. Stimulation of RAW264.7 macrophages with LPS resulted in increased expression of inducible NO synthase (iNOS) and production of nitrite. CORM-2 or CORM-3 (10–100 μM) reduced nitrite generation in a concentration-dependent manner but did not affect the protein levels of iNOS. CORM-3 also decreased nitrite levels when added 3 or 6 h after LPS exposure. CORM-2 or CORM-3 did not cause any evident cytotoxicity and produced an increase in HO-1 expression and heme oxygenase activity; this effect was completely prevented by the thiol donor N-acetylcysteine. CORM-3 also considerably reduced the levels of tumor necrosis factor-α, another mediator of the inflammatory response. The inhibitory effects of CORM-2 and CORM-3 were not observed when the inactive compounds, which do not release CO, were coincubated with LPS. These results indicate that CO liberated by CORM-2 and CORM-3 significantly suppresses the inflammatory response elicited by LPS in cultured macrophages and suggest that CO carriers can be used as an effective strategy to modulate inflammation. PMID:15880142

Antibacterial and Odontogenesis Efficacy of Mineral Trioxide Aggregate Combined with CO2 Laser Treatment.

PubMed

Hsu, Tuan-Ti; Yeh, Chia-Hung; Kao, Chia-Tze; Chen, Yi-Wen; Huang, Tsui-Hsien; Yang, Jaw-Ji; Shie, Ming-You

2015-07-01

Mineral trioxide aggregate (MTA) has been successfully used in clinical applications in endodontics. Studies show that the antibacterial effects of CO2 laser irradiation are highly efficient when bacteria are embedded in biofilm because of a photothermal mechanism. The aim of this study was to confirm the effects of CO2 laser irradiation on MTA with regard to both material characterization and cell viability. MTA was irradiated with a dental CO2 laser using directly mounted fiber optics in the wound healing mode with a spot area of 0.25 cm(2) and then stored in an incubator at 100% relative humidity and 37°C for 1 day to set. The human dental pulp cells cultured on MTA were analyzed along with their proliferation and odontogenic differentiation behaviors. The results indicate that the setting time of MTA after irradiation by the CO2 laser was significantly reduced to 118 minutes rather than the usual 143 minutes. The maximum diametral tensile strength and x-ray diffraction patterns were similar to those obtained without CO2 laser irradiation. However, the CO2 laser irradiation increased the amount of Ca and Si ions released from the MTA and regulated cell behavior. CO2 laser-irradiated MTA promoted odontogenic differentiation of hDPCs, with the increased formation of mineralized nodules on the substrate's surface. It also up-regulated the protein expression of multiple markers of odontogenic and the expression of dentin sialophosphoprotein protein. The current study provides new and important data about the effects of CO2 laser irradiation on MTA with regard to the decreased setting time and increased ion release. Taking cell functions into account, the Si concentration released from MTA with laser irradiation may be lower than a critical value, and this information could lead to the development of new regenerative therapies for dentin and periodontal tissue. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Halloysite clay nanotubes for resveratrol delivery to cancer cells.

PubMed

Vergaro, Viviana; Lvov, Yuri M; Leporatti, Stefano

2012-09-01

Halloysite is natural aluminosilicate clay with hollow tubular structure which allows loading with low soluble drugs using their saturated solutions in organic solvents. Resveratrol, a polyphenol known for having antioxidant and antineoplastic properties, is loaded inside these clay nanotubes lumens. Release time of 48 h is demonstrated. Spectroscopic and ζ-potential measurements are used to study the drug loading/release and for monitoring the nanotube layer-by-layer (LbL) coating with polyelectrolytes for further release control. Resveratrol-loaded clay nanotubes are added to breast cell cultures for toxicity tests. Halloysite functionalization with LbL polyelectrolyte multilayers remarkably decrease nanotube self-toxicity. MTT measurements performed with a neoplastic cell lines model system (MCF-7) as function of the resveratrol-loaded nanotubes concentration and incubation time indicate that drug-loaded halloysite strongly increase of cytotoxicity leading to cell apoptosis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional microorganisms for functional food quality.

PubMed

Gobbetti, M; Cagno, R Di; De Angelis, M

2010-09-01

Functional microorganisms and health benefits represent a binomial with great potential for fermented functional foods. The health benefits of fermented functional foods are expressed either directly through the interactions of ingested live microorganisms with the host (probiotic effect) or indirectly as the result of the ingestion of microbial metabolites synthesized during fermentation (biogenic effect). Since the importance of high viability for probiotic effect, two major options are currently pursued for improving it--to enhance bacterial stress response and to use alternative products for incorporating probiotics (e.g., ice cream, cheeses, cereals, fruit juices, vegetables, and soy beans). Further, it seems that quorum sensing signal molecules released by probiotics may interact with human epithelial cells from intestine thus modulating several physiological functions. Under optimal processing conditions, functional microorganisms contribute to food functionality through their enzyme portfolio and the release of metabolites. Overproduction of free amino acids and vitamins are two classical examples. Besides, bioactive compounds (e.g., peptides, γ-amino butyric acid, and conjugated linoleic acid) may be released during food processing above the physiological threshold and they may exert various in vivo health benefits. Functional microorganisms are even more used in novel strategies for decreasing phenomenon of food intolerance (e.g., gluten intolerance) and allergy. By a critical approach, this review will aim at showing the potential of functional microorganisms for the quality of functional foods.

Design of a composite drug delivery system to prolong functionality of cell-based scaffolds.

PubMed

Murua, Ainhoa; Herran, Enara; Orive, Gorka; Igartua, Manoli; Blanco, Francisco Javier; Pedraz, José Luis; Hernández, Rosa M

2011-04-04

Cell encapsulation technology raises hopes in medicine and biotechnology. However, despite important advances in the field in the past three decades, several challenges associated with the biocompatibility are still remaining. In the present study, the effect of a temporary release of an anti-inflammatory agent on co-administered encapsulated allogeneic cells was investigated. The aim was to determine the biocompatibility and efficacy of the approach to prevent the inflammatory response. A composite delivery system comprised of alginate-poly-l-lysine-alginate (APA)-microencapsulated Epo-secreting myoblasts and dexamethasone (DXM)-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres was implanted in the subcutaneous space of Balb/c mice for 45 days. The use of independently co-implanted DXM-loaded PLGA microspheres resulted in an improved functionality of the cell-based graft, evidenced by significantly higher hematocrit levels found in the cell-implanted groups by day 45, which was found to be more pronounced when higher cell-doses (100 μL) were employed. Moreover, no major host reaction was observed upon implantation of the systems, showing good biocompatibility and capability to partially avoid the inflammatory response, probably due to the immunosuppressive effects related to DXM. The findings of this study imply that DXM-loaded PLGA microspheres show promise as release systems to enhance biocompatibility and offer advantage in the development of long-lasting and effective implantable microencapsulated cells by generating a potential immunopriviledged local environment and an effective method to limit the structural ensheathing layer caused by inflammation. Copyright © 2010 Elsevier B.V. All rights reserved.

Effects of sulfate on heavy metal release from iron corrosion scales in drinking water distribution system.

PubMed

Sun, Huifang; Shi, Baoyou; Yang, Fan; Wang, Dongsheng

2017-05-01

Trace heavy metals accumulated in iron corrosion scales within a drinking water distribution system (DWDS) could potentially be released to bulk water and consequently deteriorate the tap water quality. The objective of this study was to identify and evaluate the release of trace heavy metals in DWDS under changing source water conditions. Experimental pipe loops with different iron corrosion scales were set up to simulate the actual DWDS. The effects of sulfate levels on heavy metal release were systemically investigated. Heavy metal releases of Mn, Ni, Cu, Pb, Cr and As could be rapidly triggered by sulfate addition but the releases slowly decreased over time. Heavy metal release was more severe in pipes transporting groundwater (GW) than in pipes transporting surface water (SW). There were strong positive correlations (R 2  > 0.8) between the releases of Fe and Mn, Fe and Ni, Fe and Cu, and Fe and Pb. When switching to higher sulfate water, iron corrosion scales in all pipe loops tended to be more stable (especially in pipes transporting GW), with a larger proportion of stable constituents (mainly Fe 3 O 4 ) and fewer unstable compounds (β-FeOOH, γ-FeOOH, FeCO 3 and amorphous iron oxides). The main functional iron reducing bacteria (IRB) communities were favorable for the formation of Fe 3 O 4 . The transformation of corrosion scales and the growth of sulfate reducing bacteria (SRB) accounted for the gradually reduced heavy metal release with time. The higher metal release in pipes transporting GW could be due to increased Fe 6 (OH) 12 CO 3 content under higher sulfate concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Smoke and fire characteristics for cerrado and deforestation burns in Brazil - BASE-B experiment

NASA Technical Reports Server (NTRS)

Ward, D. E.; Susott, R. A.; Kauffman, J. B.; Babbitt, R. E.; Cummings, D. L.; Dias, B.; Holben, B. N.; Kaufman, Y. J.; Rasmussen, R. A.; Setzer, A. W.

1992-01-01

Five test fires were performed during August and September 1990 in the cerrado (savannalike region) in central Brazil (three fires) and tropical moist forest (two fires) in the eastern Amazon. This paper details the gases released, the ratios of the gases to each other and to particulate matter, fuel loads, and the fraction consumed (combustion factors), and the fire behavior associated with biomass consumption. Models are presented for evaluating emission factors for CH4, CO2, CO, H2, and particles less than 2.5 micron diam (PM2.5) as a function of combustion efficiency. The ratio of carbon released as CO2 (combustion efficiency) for the cerrado fires averaged 0.94 and for the deforestation fires it decreased from 0.88 for the flaming phase to less than 0.80 during the smoldering phase of combustion. For tropical ecosystems, emissions of most products of incomplete combustion are projected to be lower than previous estimates for savanna ecosystems and somewhat higher for fires used for deforestation purposes.

Factors affecting symptoms and functionality of patients with carpal tunnel syndrome: a retrospective study

PubMed Central

Yucel, Hulya

2015-01-01

[Purpose] The aim of this retrospective study was to determine the associations between clinical, physical, and neurophysiological outcomes and self-reported symptoms and functions of patients after surgical carpal tunnel release. [Subjects and Methods] Among 261 patients who had undergone open surgical carpal tunnel release within the last three years, 83 (mean age 50.27 ± 11.13 years) participated in this study. Their socio-demographics and comorbidities were recorded. The intensity of pain, paresthesia, and fatigue symptoms in the hand were assessed by means of a Visual Analogue Scale, the Semmes-Weinstein Monofilaments test of light touch pressure sensation, and Jamar dynamometry for measurement of grip and pinch strengths. The Boston Carpal Tunnel Questionnaire evaluated the severity of symptoms and hand functional status, and the variables were analyzed by multivariate linear regression. [Results] The severity of the symptoms and functional status of release surgery patients was associated with diabetes mellitus, migraine, night pain, paresthesia and fatigue symptoms, impaired light touch pressure, and lack of medical treatment. [Conclusion] Appropriate post-surgery treatment programs for these factors should be taken into consideration to help patients obtain optimal functionality and health in their daily lives. PMID:25995565

Metal release and speciation of released chromium from a biomedical CoCrMo alloy into simulated physiologically relevant solutions.

PubMed

Hedberg, Yolanda; Odnevall Wallinder, Inger

2014-05-01

The objective of this study was to investigate the extent of released Co, Cr(III), Cr(VI), and Mo from a biomedical high-carbon CoCrMo alloy exposed in phosphate-buffered saline (PBS), without and with the addition of 10 µM H2 O2 (PBS + H2 O2 ), and 10 g L(-1) bovine serum albumin (PBS + BSA) for time periods up to 28 days. Comparative studies were made on AISI 316L for the longest time period. No Cr(VI) release was observed for any of the alloys in either PBS or PBS + H2 O2 at open-circuit potential (no applied potential). However, at applied potentials (0.7 V vs. Ag/AgCl), Cr was primarily released as Cr(VI). Co was preferentially released from the CoCrMo alloy at no applied potential. As a consequence, Cr was enriched in the utmost surface oxide reducing the extent of metal release over time. This passivation effect was accelerated in PBS + H2 O2 . As previously reported for 316L, BSA may also enhance metal release from CoCrMo. However, this was not possible to verify due to the precipitation of metal-protein complexes with reduced metal concentrations in solution as a consequence. This was particularly important for Co-BSA complexes after sufficient time and resulted in an underestimation of metals in solution. Copyright © 2013 Wiley Periodicals, Inc.

Differences in the catalytic mechanisms of mesophilic and thermophilic indole-3-glycerol phosphate synthase enzymes at their adaptive temperatures.

PubMed

Zaccardi, Margot J; Mannweiler, Olga; Boehr, David D

2012-02-10

Thermophilic enzymes tend to be less catalytically-active at lower temperatures relative to their mesophilic counterparts, despite having very similar crystal structures. An often cited hypothesis for this general observation is that thermostable enzymes have evolved a more rigid tertiary structure in order to cope with their more extreme, natural environment, but they are also less flexible at lower temperatures, leading to their lower catalytic activity under mesophilic conditions. An alternative hypothesis, however, is that complementary thermophilic-mesophilic enzyme pairs simply operate through different evolutionary-optimized catalytic mechanisms. In this communication, we present evidence that while the steps of the catalytic mechanisms for mesophilic and thermophilic indole-3-glycerol phosphate synthase (IGPS) enzymes are fundamentally similar, the identity of the rate-determining step changes as a function of temperature. Our findings indicate that while product release is rate-determining at 25°C for thermophilic IGPS, near its adaptive temperature (75°C), a proton transfer event, involving a general acid, becomes rate-determining. The rate-determining steps for thermophilic and mesophilic IGPS enzymes are also different at their respective, adaptive temperatures with the mesophilic IGPS-catalyzed reaction being rate-limited before irreversible CO2 release, and the thermophilic IGPS-catalyzed reaction being rate limited afterwards. Copyright © 2012 Elsevier Inc. All rights reserved.

NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy.

PubMed

Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2015-09-24

Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL 'opens' to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism.

PubMed

Wang, Lexi; Wang, Aiping; Zhao, Xiaolei; Liu, Ximing; Wang, Dan; Sun, Fengying; Li, Youxin

2012-05-10

Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics, risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide-co-glycolide)(PLGA) as carrier, were investigated. Significant difference was observed in the solution-gel transition mechanism of the two systems: homogeneous system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was dispersed. Fast solvent extractions were found in both systems, but in comparison with the high drug release rate from homogeneous system of drug/polymer/NMP, a fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was not accompanied by a high drug release rate but a rapid solidification of the implant, which resulted in a high drug retention, well-controlled initial burst and slow release of the drug. In vivo study on beagle dogs showed a more than 3-week sustained release with limited initial burst. Pharmacologic evaluation on optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day to 38 day on the MK-801 induced schizophrenic behavior mice model. A long sustained-release antipsychotic ISFI of 50% drug loading and controlled burst release was achieved, which indicated a good potential in clinic application. Copyright © 2012 Elsevier B.V. All rights reserved.

Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

NASA Astrophysics Data System (ADS)

Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

2016-03-01

Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

NASA Astrophysics Data System (ADS)

Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2015-09-01

Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

Delamination Analysis of a Multilayered Two-Dimensional Functionally Graded Cantilever Beam

NASA Astrophysics Data System (ADS)

Rizov, V.

2017-11-01

Delamination fracture behaviour of a multilayered two-dimensional functionally graded cantilever beam is analyzed in terms of the strain energy release rate. The beam is made of an arbitrary number of layers. Perfect adhesion is assumed between layers. Each layer has individual thickness and material properties. Besides, the material is two-dimensional functionally graded in the cross-section of each layer. There is a delamination crack located arbitrary between layers. The beam is loaded by a bending moment applied at the free end of the lower crack arm. The upper crack arm is free of stresses. The solution to strain energy release rate derived is applied to investigate the influence of the crack location and the material gradient on the delamination fracture. The results obtained can be used to optimize the multilayered two-dimensional functionally graded beam structure with respect to the delamination fracture behaviour.

Improvement of Oral Bioavailability of Lopinavir Without Co-administration of Ritonavir Using Microspheres of Thiolated Xyloglucan.

PubMed

Madgulkar, Ashwini R; Bhalekar, Mangesh R; Kadam, Ashwini A

2018-01-01

Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T 80 , surface morphology, and mucoadhesion employing in vitro wash off test. The microspheres were optimized by 3 2 factorial design. The optimized thiomeric microsphere formulation revealed 93.12% entrapment efficiency, time for 80% drug release (T 80 ) of 358.1 min, and 88% mucoadhesion after 1 h. The permeation of lopinavir from microspheres was enhanced 3.15 times as determined by ex vivo study using everted chick intestine and increased relative bioavailability over 3.22-fold over combination of lopinavir and ritonavir as determined by in vivo study in rat model.

Optimization of Preparation Techniques for Poly(Lactic Acid-Co-Glycolic Acid) Nanoparticles

NASA Astrophysics Data System (ADS)

Birnbaum, Duane T.; Kosmala, Jacqueline D.; Brannon-Peppas, Lisa

2000-06-01

Microparticles and nanoparticles of poly(lactic acid-co-glycolic acid) (PLAGA) are excellent candidates for the controlled release of many pharmaceutical compounds because of their biodegradable nature. The preparation of submicron PLAGA particles poses serious challenges that are not necessarily present when preparing microparticles. We have evaluated several combinations of organic solvents and surfactants used in the formulation of PLAGA nanoparticles. Critical factors such as the ability to separate the nanoparticles from the surfactant, the ability to re-suspend the nanoparticles after freeze-drying, formulation yield and nanoparticle size were studied. The smallest particles were obtained using the surfactant/solvent combination of sodium dodecyl sulfate and ethyl acetate (65 nm) and the largest particles were obtained using poly(vinyl alcohol) and dichloromethane (466 nm). However, the optimal nanoparticles were produced using either acetone or ethyl acetate as the organic solvent and poly(vinyl alcohol) or human serum albumin as the surfactant. This is because the most critical measure of performance of these nanoparticles proved to be their ability to re-suspend after freeze-drying.

GABAA receptor: a unique modulator of excitability, Ca2+ signaling, and catecholamine release of rat chromaffin cells.

PubMed

Alejandre-García, Tzitzitlini; Peña-Del Castillo, Johanna G; Hernández-Cruz, Arturo

2018-01-01

The role of gamma-aminobutyric acid (GABA) in adrenal medulla chromaffin cell (CC) function is just beginning to unfold. GABA is stored in catecholamine (CA)-containing dense core granules and is presumably released together with CA, ATP, and opioids in response to physiological stimuli, playing an autocrine-paracrine role on CCs. The reported paradoxical "dual action" of GABA A -R activation (enhancement of CA secretion and inhibition of synaptically evoked CA release) is only one aspect of GABA's multifaceted actions. In this review, we discuss recent physiological experiments on rat CCs in situ which suggest that GABA regulation of CC function may depend on the physiological context: During non-stressful conditions, GABA A -R activation by endogenous GABA tonically inhibits acetylcholine release from splanchnic nerve terminals and decreases spontaneous Ca 2+ fluctuations in CCs, preventing unwanted CA secretion. During intense stress, splanchnic nerve terminals release acetylcholine, which depolarizes CCs and allows the Ca 2+ influx that triggers the release of CA and GABA. With time, CA secretion declines, due to voltage-independent inhibition of Ca 2+ channels and desensitization of cholinergic nicotinic receptors. Nonetheless, acute activation of GABA A -R is depolarizing in about 50% of CCs, and thus GABA, acting as an autocrine/paracrine mediator, could help to maintain CA exocytosis under stress. GABA A -R activation is not excitatory in about half of CCs' population because it hyperpolarizes them or elicits no response. This percentage possibly varies, depending on functional demands, since GABA A -R-mediated actions are determined by the intracellular chloride concentration ([Cl - ] i ) and therefore on the activity of cation-chloride co transporters, which is functionally regulated. These findings underscore a potential importance of a novel and complex GABA-mediated regulation of CC function and of CA secretion.

A Computationally Inexpensive Optimal Guidance via Radial-Basis-Function Neural Network for Autonomous Soft Landing on Asteroids

PubMed Central

Zhang, Peng; Liu, Keping; Zhao, Bo; Li, Yuanchun

2015-01-01

Optimal guidance is essential for the soft landing task. However, due to its high computational complexities, it is hardly applied to the autonomous guidance. In this paper, a computationally inexpensive optimal guidance algorithm based on the radial basis function neural network (RBFNN) is proposed. The optimization problem of the trajectory for soft landing on asteroids is formulated and transformed into a two-point boundary value problem (TPBVP). Combining the database of initial states with the relative initial co-states, an RBFNN is trained offline. The optimal trajectory of the soft landing is determined rapidly by applying the trained network in the online guidance. The Monte Carlo simulations of soft landing on the Eros433 are performed to demonstrate the effectiveness of the proposed guidance algorithm. PMID:26367382

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases.

PubMed

Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

2015-01-01

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits.

A multiple functional connector for high-resolution optical satellites

NASA Astrophysics Data System (ADS)

She, Fengke; Zheng, Gangtie

2017-11-01

For earth observation satellites, perturbations from actuators, such as CMGs and momentum wheels, and thermal loadings from support structures often have significant impact on the image quality of an optical. Therefore, vibration isolators and thermal deformation releasing devices nowadays often become important parts of an image satellite. However, all these devices will weak the connection stiffness between the optical instrument and the satellite bus structure. This will cause concern of the attitude control system design for worrying about possible negative effect on the attitude control. Therefore, a connection design satisfying all three requirements is a challenge of advanced image satellites. Chinese scientists have proposed a large aperture high-resolution satellite for earth observation. To meet all these requirements and ensure image quality, specified multiple function connectors are designed to meet these challenging requirements, which are: isolating vibration, releasing thermal deformation and ensuring whole satellite dynamic properties [1]. In this paper, a parallel spring guide flexure is developed for both vibration isolation and thermal deformation releasing. The stiffness of the flexure is designed to meet the vibration isolation requirement. To attenuate vibration, and more importantly to satisfy the stability requirement of the attitude control system, metal damping, which has many merits for space applications, are applied in this connecter to provide a high damping ratio and nonlinear stiffness. The capability of the connecter for vibration isolation and attenuation is validated through numerical simulation and experiments. Connecter parameter optimization is also conducted to meet both requirements of thermal deformation releasing and attitude control. Analysis results show that the in-orbit attitude control requirement is satisfied while the thermal releasing performance is optimized. The design methods and analysis results are also provided in the present paper.

Effects of pore CaCO3 form agencies on dissolution mechanisms of amoxicillin drugs encapsulated in hydrogels full-IPN chitosan N-vinyl caprolactam

NASA Astrophysics Data System (ADS)

Budianto, Emil; Fauzia, Maghfira

2018-04-01

The administration of amoxicillin trihydrate in Helicobacter pylori infection is not effective enough because the conventional preparations used have a short retention time in the stomach. To overcome this problem, amoxicillin trihydrate was encapsulated into the floating drug delivery matrix-matrix. In this study, the full-ipn acetaldehyde crosslinked hydrogel (N-vinyl caprolactam) was synthesized with a 10% CaCO3 pore forming agent and then encapsulated on amoxicillin trihydrate and studied the mechanism of drug dissolution with its kinetic kinetics approach. The K-PNVCL Hydrogel produces optimal properties which are then loaded with amoxicillin trihydrate in situ and post loading. In this research, we have got the percentage of swelling, floating time, the efficiency of in situ and post loading 873%; 3.15 minutes; 99.8% and 99.4%. The dissolution test was performed on amoxicillin trihydrate which had been encapsulated K-PNVCL hydrogel in vitro at pH 1.2 resulting in 94.5% for in situ loading and 98.5% for post loading. Results of the kinetics of drug release for post loading and in situ loading methods tend to follow the Higuchi model kinetics. The drug release mechanism occurs by Fickian diffusion. Proof of drug release mechanism from K-PNVCL hydrogel matrix is further done by Scanning Electron Microscope (SEM) instrument.

Neuroprotective, neurotherapeutic, and neurometabolic effects of carbon monoxide.

PubMed

Mahan, Vicki L

2012-12-27

Studies in animal models show that the primary mechanism by which heme-oxygenases impart beneficial effects is due to the gaseous molecule carbon monoxide (CO). Produced in humans mainly by the catabolism of heme by heme-oxygenase, CO is a neurotransmitter important for multiple neurologic functions and affects several intracellular pathways as a regulatory molecule. Exogenous administration of inhaled CO or carbon monoxide releasing molecules (CORM's) impart similar neurophysiological responses as the endogenous gas. Its' involvement in important neuronal functions suggests that regulation of CO synthesis and biochemical properties may be clinically relevant to neuroprotection and the key may be a change in metabolic substrate from glucose to lactate. Currently, the drug is under development as a therapeutic agent and safety studies in humans evaluating the safety and tolerability of inhaled doses of CO show no clinically important abnormalities, effects, or changes over time in laboratory safety variables. As an important therapeutic option, inhaled CO has entered clinical trials and its clinical role as a neuroprotective and neurotherapeutic agent has been suggested. In this article, we review the neuroprotective effects of endogenous CO and discuss exogenous CO as a neuroprotective and neurotherapeutic agent.

MO-FG-BRA-05: Next Generation Radiotherapy Biomaterials Loaded With Gold Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cifter, G; Ngwa, W; Univ Massachusetts Lowell, Lowell, MA

2015-06-15

Purpose: It has been proposed that routinely used inert radiotherapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smarter ones by coating/loading them with radiosensitizing gold nanoparticles (GNPs), for sustained in-situ release after implantation to enhance RT. In this work, we developed prototypes of such RT biomaterials and investigated the sustained release of GNPs from the biomaterials as a function of design parameters. Methods: Prototype smart biomaterials were produced by incorporating the GNPs in poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production. For comparison, commercially available spacers were also coated with a polymer film loaded with fluorescentmore » GNP. Optical/spectroscopy methods were used to monitor in vitro release of GNPs over time as a function of different design parameters: polymer weighting, type, and initial (loading) GNP concentrations. Inductively coupled plasma mass spectrometry was employed to verify GNP release. Results: Results showed that gold nanoparticles could be successfully loaded in the new RT biomaterial prototypes. Burst release of GNPs could be achieved within 1 to 25 days depending on the preparation approach. Burst release was followed by sustained release profile over time. The amount of released GNP increased with increasing loading concentration as expected. The release profiles could also be customized as a function of polymer weighting, or preparation approaches. Conclusion: Considered together, our results highlight potential for the development of next generation RT biomaterials loaded with GNPs customizable to different RT schedules. Such biomaterials could be employed as needed instead of currently used inert spacers/fiducials at no additional inconvenience to patients, to enhance RT.« less

Targeted drug delivery and enhanced intracellular release using functionalized liposomes

NASA Astrophysics Data System (ADS)

Garg, Ashish

The ability to target cancer cells using an appropriate drug delivery system can significantly reduce the associated side effects from cancer therapies and can help in improving the overall quality of life, post cancer survival. Integrin alpha5beta1 is expressed on several types of cancer cells, including colon cancer and plays an important role in tumor growth and metastasis. Thus, the ability to target the integrin alpha 5beta1 using an appropriate drug delivery nano-vector can significantly help in inhibiting tumor growth and reducing tumor metastasis. The work in this thesis focuses on designing and optimizing, functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that specifically target the integrin alpha5beta1. The PEG provides a steric barrier allowing the liposomes to circulate in the blood for longer duration and the functionalizing moiety, PR_b peptide specifically recognizes and binds to integrin alpha5beta1 expressing cells. The work demonstrates that by optimizing the amount of PEG and PR_b on the liposomal interface, nano-vectors can be engineered that bind to CT26.WT colon cancer cells in a specific manner and internalize through alpha 5beta1-mediated endocytosis. To further improve the efficacy of the system, PR_b functionalized pH-sensitive stealth liposomes that exhibit triggered release under mild acidic conditions present in endocytotic vesicles were designed. The study showed that PR_b functionalized pH-sensitive stealth liposomes, undergo destabilization under mildly acidic conditions and incorporation of the PR_b peptide does not significantly affect the pH-sensitivity of the liposomes. PR_b functionalized pH-sensitive stealth liposomes bind to CT26.WT colon carcinoma cells that express integrin alpha5beta 1, undergo cellular internalization, and release their load intracellularly in a short period of time as compared to other formulations. PR_b-targeted pH-sensitive stealth liposomes encapsulating 5-fluorouracil (5-FU) show significantly higher cytotoxicity than the PR_b-targeted inert stealth liposomes and the non-targeted stealth liposomes (both pH-sensitive and inert). The studies demonstrated that optimized PR_b functionalized pH sensitive liposomes have the potential to deliver a payload, such as chemotherapeutic agents, directly to colon cancer cells in an efficient and specific manner.

Carbon Flux Signal Detection for the ASCENDS mission

NASA Astrophysics Data System (ADS)

Hammerling, D.; Michalak, A. M.; Kawa, S. R.; Doney, S. C.; Schaefer, K. M.

2012-12-01

Emerging satellite observations of carbon dioxide (CO2) offer novel and distinctive opportunities for quantifying the carbon cycle, which is an important scientific and societal challenge with anthropogenic CO2 emissions and accumulation rates in the atmosphere still on the rise. One mission in the planning stage is the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission, which is a laser CO2 sensing mission with an anticipated launch date around 2022. Notable features of this mission include the ability to sample at night and at high latitudes, which passive missions cannot do because of their reliance on reflected sunlight. In this work we present findings from signal detection studies, i.e. experiments that investigate if perturbations in carbon fluxes can be detected in the ASCENDS observations of atmospheric CO2 concentrations. The experiments employ a realistic synthetic-data setup using the PCTM/GEOS-5/CASA GFED CO2 flux and transport model in combination with CALIPSO and MODIS measurements. The signal detection approach applied uses a geostatistical mapping methodology that can leverage the information content of nearby observations, thereby potentially facilitating enhanced signal detection. The specific perturbation scenarios investigated are: carbon release from the melting of permafrost in the high Northern latitudes, the shifting of fossil fuel emissions from Europe to P.R. China, and natural variability in the CO2 fluxes in the Southern Ocean. Results indicate that the permafrost carbon release is comparatively easy to detect, while the Southern Ocean change is more challenging. The ability to detect a shift in fossil fuel emissions strongly depends on its magnitude: a 50% decrease in Europe is easily detectible, while a 20% decrease is only marginally so. A key conclusion is that the optimal signal detection strategy is intrinsically linked to how the carbon flux perturbations translate into atmospheric CO2 concentrations, which varies significantly among the investigated scenarios.

Stabilizing Alginate Confinement and Polymer Coating of CO-Releasing Molecules Supported on Iron Oxide Nanoparticles To Trigger the CO Release by Magnetic Heating.

PubMed

Meyer, Hajo; Winkler, Felix; Kunz, Peter; Schmidt, Annette M; Hamacher, Alexandra; Kassack, Matthias U; Janiak, Christoph

2015-12-07

Maghemite (Fe2O3) iron oxide nanoparticles (IONPs) were synthesized, modified with covalent surface-bound CO-releasing molecules of a tri(carbonyl)-chlorido-phenylalaninato-ruthenium(II) complex (CORM), and coated with a dextran polymer. The time- and temperature-dependent CO release from this CORM-3 analogue was followed by a myoglobin assay. A new measurement method for the myoglobin assay was developed, based on confining "water-soluble" polymer-coated Dextran500k@CORM@IONP particles in hollow spheres of nontoxic and easily prepared calcium alginate. Dropping a mixture of Dextran500k@CORM@IONP and sodium alginate into a CaCl2 solution leads to stable hollow spheres of Ca(2+) cross-linked alginate which contain the Dextran500k@CORM@IONP particles. This "alginate-method" (i) protects CORM-3 analogues from rapid CO-displacement reactions with a protein, (ii) enables a spatial separation of the CORM from its surrounding myoglobin assay with the alginate acting as a CO-permeable membrane, and (iii) allows the use of substances with high absorptivity (such as iron oxide nanoparticles) in the myoglobin assay without interference in the optical path of the UV cell. Embedding the CORM@IONP nanoparticles in the alginate vessel represents a compartmentation of the reactive component and allows for close contact with, yet facile separation from, the surrounding myoglobin assay. The half-life of the CO release from Dextran500k@CORM@IONP particles surrounded by alginate was determined to be 890 ± 70 min at 20 °C. An acceleration of the CO release occurs at higher temperature with a half-life of 172 ± 27 min at 37 °C and 45 ± 7 min at 50 °C. The CO release can be triggered in an alternating current magnetic field (31.7 kA m(-1), 247 kHz, 39.9 mT) through local magnetic heating of the susceptible iron oxide nanoparticles. With magnetic heating at 20 °C in the bulk solution, the half-life of CO release from Dextran500k@CORM@IONP particles decreased to 155 ± 18 min without a noticeable temperature increase in the dispersion. At 37 and 50 °C, the half-life for the CO release triggered by local magnetic heating was 65 ± 5 min and 30 ± 3 min, respectively. Thus, at a physiological temperature of 37 °C, magnetic heating accelerates the CO release of the IONP-bound CORM by a factor of ∼ 2.6. The activation energy for CO release from a CORM-3 analogue was determined to be EA = 78 kJ/mol.

Prolonged release matrix tablet of pyridostigmine bromide: formulation and optimization using statistical methods.

PubMed

Bolourchian, Noushin; Rangchian, Maryam; Foroutan, Seyed Mohsen

2012-07-01

The aim of this study was to design and optimize a prolonged release matrix formulation of pyridostigmine bromide, an effective drug in myasthenia gravis and poisoning with nerve gas, using hydrophilic - hydrophobic polymers via D-optimal experimental design. HPMC and carnauba wax as retarding agents as well as tricalcium phosphate were used in matrix formulation and considered as independent variables. Tablets were prepared by wet granulation technique and the percentage of drug released at 1 (Y(1)), 4 (Y(2)) and 8 (Y(3)) hours were considered as dependent variables (responses) in this investigation. These experimental responses were best fitted for the cubic, cubic and linear models, respectively. The optimal formulation obtained in this study, consisted of 12.8 % HPMC, 24.4 % carnauba wax and 26.7 % tricalcium phosphate, had a suitable prolonged release behavior followed by Higuchi model in which observed and predicted values were very close. The study revealed that D-optimal design could facilitate the optimization of prolonged release matrix tablet containing pyridostigmine bromide. Accelerated stability studies confirmed that the optimized formulation remains unchanged after exposing in stability conditions for six months.

Constraint programming based biomarker optimization.

PubMed

Zhou, Manli; Luo, Youxi; Sun, Guoquan; Mai, Guoqin; Zhou, Fengfeng

2015-01-01

Efficient and intuitive characterization of biological big data is becoming a major challenge for modern bio-OMIC based scientists. Interactive visualization and exploration of big data is proven to be one of the successful solutions. Most of the existing feature selection algorithms do not allow the interactive inputs from users in the optimizing process of feature selection. This study investigates this question as fixing a few user-input features in the finally selected feature subset and formulates these user-input features as constraints for a programming model. The proposed algorithm, fsCoP (feature selection based on constrained programming), performs well similar to or much better than the existing feature selection algorithms, even with the constraints from both literature and the existing algorithms. An fsCoP biomarker may be intriguing for further wet lab validation, since it satisfies both the classification optimization function and the biomedical knowledge. fsCoP may also be used for the interactive exploration of bio-OMIC big data by interactively adding user-defined constraints for modeling.

Thermal and Evolved Gas Analysis of "Nanophase" Carbonates: Implications for Thermal and Evolved Gas Analysis on Mars Missions

NASA Technical Reports Server (NTRS)

Lauer, Howard V., Jr.; Archer, P. D., Jr.; Sutter, B.; Niles, P. B.; Ming, Douglas W.

2012-01-01

Data collected by the Mars Phoenix Lander's Thermal and Evolved Gas Analyzer (TEGA) suggested the presence of calcium-rich carbonates as indicated by a high temperature CO2 release while a low temperature (approx.400-680 C) CO2 release suggested possible Mg- and/or Fe-carbonates [1,2]. Interpretations of the data collected by Mars remote instruments is done by comparing the mission data to a database on the thermal properties of well-characterized Martian analog materials collected under reduced and Earth ambient pressures [3,4]. We are proposing that "nano-phase" carbonates may also be contributing to the low temperature CO2 release. The objectives of this paper is to (1) characterize the thermal and evolved gas proper-ties of carbonates of varying particle size, (2) evaluate the CO2 releases from CO2 treated CaO samples and (3) examine the secondary CO2 release from reheated calcite of varying particle size.

PAPR reduction in CO-OFDM systems using IPTS and modified clipping and filtering

NASA Astrophysics Data System (ADS)

Tong, Zheng-rong; Hu, Ya-nong; Zhang, Wei-hua

2018-05-01

Aiming at the problem of the peak to average power ratio ( PAPR) in coherent optical orthogonal frequency division multiplexing (CO-OFDM), a hybrid PAPR reduction technique of the CO-OFDM system by combining iterative partial transmit sequence (IPTS) scheme with modified clipping and filtering (MCF) is proposed. The simulation results show that at the complementary cumulative distribution function ( CCDF) of 10-4, the PAPR of proposed scheme is optimized by 1.86 dB and 2.13 dB compared with those of IPTS and CF schemes, respectively. Meanwhile, when the bit error rate ( BER) is 10-3, the optical signal to noise ratio ( OSNR) are optimized by 1.57 dB and 0.66 dB compared with those of CF and IPTS-CF schemes, respectively.

Neuron cells uptake of polymeric microcapsules and subsequent intracellular release.

PubMed

Pavlov, Anton M; Sapelkin, Andrei V; Huang, Xinyue; P'ng, Ken M Y; Bushby, Andy J; Sukhorukov, Gleb B; Skirtach, André G

2011-06-14

Neuron cells uptake of biodegradable and synthetic polymeric microcapsules functionalized with aggregates of gold nanoparticles incorporated into their shells is demonstrated in situ. In addition to traditionally used optical microscopy, electron microscopy is used both for higher-resolution imaging and for confirming the uptake by focused ion beam cross-sectioning of specific cells in situ. Subsequently, physical methods of release are compared to chemical methods wherein laser-induced intracellular release of dextran molecules into the cytosol of hippocampal neuron cells is studied in comparison to biodegradation. Implications of this work for neuroscience, bio-medicine and single cell studies are discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Regolith Volatile Characterization (RVC) in RESOLVE

NASA Technical Reports Server (NTRS)

Captain, Janine; Lueck, Dale; Gibson, Tracy; Levine, Lanfang

2010-01-01

Resource investigation in the lunar poles is of importance to the potential impact of in-situ resource utilization (ISRU). The RESOLVE project developed a payload to investigate the permanently shadowed areas of the lunar poles and demonstrate ISRU technology. As a part of the RESOLVE project, the regolith volatile characterization (RVC) subsystem was designed to examine the release of volatiles from sample cores. The test sample was heated in the reactor to release the volatiles where they were analyzed with gas chromatography. Subsequently, the volatile sample was introduced into the lunar water resource demonstration (LWRD) subsystem where the released hydrogen and water were selectively captured. The objective of the Regolith Volatile Characterization (RVC) subsystem was to heat the crushed core sample and determine the desorption of volatile species of interest. The RVC subsystem encompasses the reactor and the system for volatile analysis. The system was designed to analyze H2, He, CO, CO2, N2, 02, CH4, H2S and H2O. The GC chosen for this work is a Siemens MicroSAM process GC with 3 columns and 8 TCD detectors. Neon was chosen as the carrier gas to enhance the analysis of hydrogen and helium.The limit of detection for the gases is approx.1000ppm for H2, CO. CO2 , N2, O2 and H2 S. The limit of detection for CH4 is approx.4000ppm and the water limit of detection is -10000 ppm with a sample analysis time of 2-3 minutes. These values (with the exception of water and H2S) were determined by dilution of a six gas mixture from Scott Gas (5% CO2, CO, O2, N2, 4% CH4 and H2) using mass flow controllers (MFC5). Water was calibrated at low levels using an in house relative humidity (RH) generator. H 2S and high concentrations of H2 were calibrated by diluting a pure stream of gas with MFCs. Higher concentrations of N2 and 02 were calibrated using Air again diluting with MFCs. There were three modification goals for the GC in EBU2 that would allow this process GC to be used in the field demo for RESOLVE. The first modification was to decrease the weight associated with the GC, this included eliminating the explosion proof case (Figure 1) and replacing it with a lightweight case as well as using an on board COPV tank for the neon carrier gas. The next goal was to add a second oven for the molecular sieve column to allow for dual temperature control during GC operation; the separation of hydrogen and helium is optimum at lower temperatures while the water analysis required higher temperatures creating a competing design requirement. The second oven also allows a lower limit of detection for water quantification and avoids the possibility of water condensing in the GC which could ruin the column characteristics. The final goal was to modify the column arrangement to optimize the system for our specific application. Figure 2 shows the internal details of the module optimized optimized for our field application. The modifications and performance of the gas analysis system will be discussed in detail.

Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress

NASA Astrophysics Data System (ADS)

Pangeni, Rudra; Sharma, Shrestha; Mustafa, Gulam; Ali, Javed; Baboota, Sanjula

2014-12-01

Resveratrol, a potent natural antioxidant, possesses a wide range of pharmacological activities, but its oral bioavailability is very low due to its extensive hepatic and presystemic metabolism. The aim of the present study was to formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant for the better management of Parkinson’s disease. The nanoemulsion was prepared by a spontaneous emulsification method, followed by high-pressure homogenization. Ternary phase diagrams were constructed to locate the area of nanoemulsion. The prepared formulations were studied for globule size, zeta potential, refractive index, viscosity, surface morphology and in vitro and ex vivo release. The homogenized formulation, which contained 150 mg ml-1 of resveratrol, showed spherical globules with an average globule diameter of 102 ± 1.46 nm, a least poly dispersity index of 0.158 ± 0.02 and optimal zeta potential values of -35 ± 0.02. The cumulative percentage drug release for the pre-homogenized resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized nanoemulsion were 24.18 ± 2.30%, 54.32 ± 0.95% and 88.57 ± 1.92%, respectively, after 24 h. The ex vivo release also showed the cumulative percentage drug release of 85.48 ± 1.34% at 24 h. The antioxidant activity determined by using a DPPH assay showed high scavenging efficiency for the optimized formulation. Pharmacokinetic studies showed the higher concentration of the drug in the brain (brain/blood ratio: 2.86 ± 0.70) following intranasal administration of the optimized nanoemulsion. Histopathological studies showed decreased degenerative changes in the resveratrol nanoemulsion administered groups. The levels of GSH and SOD were significantly higher, and the level of MDA was significantly lower in the resveratrol nanoemulsion treated group.

Development and optimization of doxorubicin loaded poly(lactic-co-glycolic acid) nanobubbles for drug delivery into HeLa cells.

PubMed

Deng, Liwei; Li, Li; Yang, Hong; Li, Li; Zhao, Fenglong; Wu, Chunhui; Liu, Yiyao

2014-04-01

Microbubbles (MBs, usually 2-8 microm) as ultrasound contrast agent and drug carrier are promising for ultrasonic imaging and drug delivery. However, MBs posed some limitations due to their large diameters. In the current study, we developed a nanoscale bubbles (nanobubbles, NBs) by encapsulating the doxorubicin (DOX) into poly(lactic-co-glycolic acid) (PLGA) shells (denoted as DOX-PLGA NBs) for drug delivery into cancer cells. The size, morphology, particle stability, drug encapsulation efficiency, and drug payload were determined. The results showed that the DOX-PLGA NBs were uniform (270 +/- 3 nm) and spherical with a smooth surface, and were well dispersed and stable in water. The encapsulation efficiency and payload of DOX increased with its initial loading concentrations. The release behavior of DOX from the DOX-PLGA NBs exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release at both pH 7.4 and pH 4.4, and also presented in a pH-triggered releasing profile. The qualitative analysis of cellular internalization into HeLa cells by inverted fluorescence microscope showed that the cellular uptake of DOX-PLGA NBs was both concentration- and time-dependent. Moreover, the cell viability was also investigated using CCK-8 assay. It was found that DOX-PLGA NBs showed greater HeLa cell growth inhibition effect in vitro compared with free DOX. It was concluded that the DOX-PLGA NBs were biocompatible and appropriate for anti-cancer drug delivery, and were potentially promising as a new therapeutic system for cancer treatment.

Engineering few-layer MoTe2 devices by Co/hBN tunnel contacts

NASA Astrophysics Data System (ADS)

Zhu, Mengjian; Luo, Wei; Wu, Nannan; Zhang, Xue-ao; Qin, Shiqiao

2018-04-01

2H phase Molybdenum ditelluride (MoTe2) is a layered two-dimensional (2D) semiconductor that has recently gained extensive attention for its intriguing properties, demonstrating great potential for nanoelectronics and optoelectronics. Optimizing the electric contacts to MoTe2 is a critical step for realizing high performance devices. Here, we demonstrate Co/hBN tunnel contacts to few-layer MoTe2. In sharp contrast to the p-type conduction of Co contacted MoTe2, Co/hBN tunnel contacted MoTe2 devices show clear n-type transport properties. Our first principles calculation reveals that the inserted few-layer hBN strongly interacts with Co and significantly reduces its work-function by ˜1.2 eV, while MoTe2 itself has a much weaker influence on the work-function of Co. This allows us to build MoTe2 diodes using the mixed Co/hBN and Co contact architecture, which can be switched from p-n type to n-p type by changing the gate-voltage, paving the way for engineering multi-functional devices based on atomically thin 2D semiconductors.

Patch test reactivity to a cobalt-chromium-molybdenum alloy and stainless steel in metal-allergic patients in correlation to the metal ion release.

PubMed

Summer, Burkhard; Fink, Ulrich; Zeller, Richard; Rueff, Franziska; Maier, Sonja; Roider, Gabriele; Thomas, Peter

2007-07-01

Nickel, chromium, and cobalt released from stainless steel and CoCrMo alloys have been postulated to trigger hypersensitivity reactions. The objective of this study was to assess the ion release from a CoCrMo alloy and stainless steel in vitro and the cutaneous reactivity to it by patch test. 52 metal-allergic patients and 48 non-allergic controls were patch tested to stainless steel and CoCrMo discs. In addition, using atomic absorption spectrometry, the release of nickel, cobalt, and chromium from both materials was assessed upon 2-day exposure to distilled water, artificial sweat (AS), and cell culture medium. There was low nickel ion release from stainless steel (0.3-0.46 microg/cm(2)/2 days) and CoCrMo discs (up to 0.33 microg/cm(2)/2 days) into the different elution media. Chromium release from the 2 materials was also very low (0.06-0.38 microg/cm(2)/2 days from stainless steel and 0.52-1.36 microg/cm(2)/2 days from CoCrMo alloy). In contrast, AS led to abundant cobalt release (maximally 18.94 microg/cm(2)/2 days) from the CoCrMo discs, with concomitant eczematous reaction upon patch testing: 0 of the 52 metal-allergic patients reacted to stainless steel discs and 5 of the 52 patients to CoCrMo discs (all 5 patients were cobalt allergic and 3 also nickel and chromium allergic). None of the controls reacted to the discs. Apart from nickel being a focus of allergological research, our results point to the possibly underestimated association of cobalt release and potential hyperreactivity to CoCrMo alloy.

Further Studies on Oxalic Acid Biosynthesis in Oxalate-accumulating Plants 1

PubMed Central

Nuss, Richard F.; Loewus, Frank A.

1978-01-01

l-Ascorbic acid functions as a precursor of oxalic acid in several oxalate-accumulating plants. The present study extends this observation to include Rumex crispus L. (curly dock), Amaranthus retroflexus L. (red root pigweed), Chenopodium album L. (lamb's-quarters), Beta vulgaris L. (sugar beet), Halogeton glomeratus M. Bieb. (halogeton), and Rheum rhabarbarum L. (rhubarb). Several species with low oxalate content are also examined. When l-[1-14C]ascorbic acid is supplied to young seedlings of R. crispus or H. glomeratus, a major portion of the 14C is released over a 24-hour period as 14CO2 and only a small portion is recovered as [14C]oxalate, unlike cuttings from 2- or 4-month-old plants which retain a large part of the 14C as [14C]oxalic acid and release very little 14CO2. Support for an intermediate role of oxalate in the release of 14CO2 from l-[1-14C]ascorbic acid is seen in the rapid release of 14CO2 by R. crispus and H. glomeratus seedlings labeled with [14C]oxalic acid. The common origin of oxalic acid carbon in the C1 and C2 fragment from l-ascorbic acid is demonstrated by comparison of 14C content of oxalic acid in several oxalate-accumulators after cuttings or seedlings are supplied equal amounts of l-[1-14C]- or l-[UL-14C]ascorbic acid. Theoretically, l-[1-14C]ascorbic acid will produce labeled oxalic acid containing three times as much 14C as l-[UL-14C]ascorbic acid when equal amounts of label are provided. Experimentally, a ratio of 2.7 ± 0.5 is obtained in duplicate experiments with six different species. PMID:16660342

Measuring Infiltration Rates in Homes as a Basis for Understanding Indoor Air Quality

NASA Astrophysics Data System (ADS)

Jerz, G. G.; Lamb, B. K.; Pressley, S. N.; O'Keeffe, P.; Fuchs, M.; Kirk, M.

2015-12-01

Infiltration rates, or the rate of air exchange, of houses are important to understand because ventilation can be a dominate factor in determining indoor air quality. There are chemicals that are emitted from surfaces or point sources inside the home which are harmful to humans; these chemicals come from various objects including furniture, cleaning supplies, building materials, gas stoves, and the surrounding environment. The use of proper ventilation to cycle cleaner outdoor air into the house can be crucial for maintaining healthy living conditions in the home. At the same time, there can also be outdoor pollutants which infiltrate the house and contribute to poor indoor air quality. In either case, it is important to determine infiltration rates as a function of outdoor weather conditions, the house structure properties and indoor heating and cooling systems. In this work, the objective is to measure ventilation rates using periodic releases of a tracer gas and measuring how quickly the tracer concentration decays. CO2 will be used as the tracer gas because it is inert and harmless at low levels. An Arduino timer is connected to a release valve which controls the release of 9.00 SLPM of CO2 into the uptake vent within the test home. CO2 will be released until there is at least a 200 to 300 ppm increase above ambient indoor levels. Computers with CO2 sensors and temperature/pressure sensors attached will be used to record data from different locations within the home which will continuously record data up to a week. The results from these periodic ventilation measurements will be analyzed with respect to outdoor wind and temperature conditions and house structure properties. The data will be used to evaluate an established indoor air quality model.

Nickel(0)-Catalyzed Inert C-O Bond Functionalization: Organo Rare-Earth Metal Complex as the Coupling Partner.

PubMed

Yan, Xiangqian; Yang, Fanzhi; Cai, Guilong; Meng, Qingwei; Li, Xiaofang

2018-02-02

An organo rare-earth metal complex has been employed as a highly efficient nucleophile in Ni(0)-catalyzed C-O bond functionalization. The optimized catalytic system which consists of Ni(cod) 2 , PCy 3 , and t-BuONa could smoothly convert 1 equiv of naphthyl ethers to alkylated naphthalene analogues with 0.4 equiv of Ln(CH 2 SiMe 3 ) 3 (THF) 2 , delivering good to excellent yields. The reaction system could also activate the ArCH 2 -O bond with mild base.

Optimally designed collagen/polycaprolactone biocomposites supplemented with controlled release of HA/TCP/rhBMP-2 and HA/TCP/PRP for hard tissue regeneration.

PubMed

Kim, WonJin; Jang, Chul Ho; Kim, GeunHyung

2017-09-01

Collagen has been widely used as a very promising material to regenerate various tissues. It is a chief component of the extracellular matrix, and encourages various biological effects conducive to tissue regeneration. However, poor mechanical stability, low processability, and high level of water absorption can lead to impaired control of growth factor release and have impeded the use of collagen as a functional biomedical scaffold. Here, to overcome the shortcomings of collagen scaffolds, we have additively manufactured collagen/polycaprolactone (PCL) biocomposites supplemented with a bioceramic (hydroxyapatite (HA)/β-tricalcium-phosphate (TCP)) and two growth factors (recombinant human bone morphogenetic protein-2 [rhBMP-2] and platelet-rich plasma [PRP]). Various weight fractions of PCL in the collagen/PCL composites were manipulated to select optimal growth factor release and highly active cellular responses. After the optimal concentration of PCL in the collagen/PCL scaffold was determined, biocomposites supplemented with bioceramic/growth-factors were fabricated. Continuously released growth factors were assumed to increase the in vitro cellular activities of the osteoblast-like cells (MG63) cultured on the biocomposites. In vitro cellular responses, including osteogenic activities, were examined, and results showed that compared to the HA/TCP/rhBMP-2 supplemented scaffold the HA/TCP/PRP biocomposites provide significantly high cellular activities (cell proliferation: >1.3-fold) and mineralization (calcium deposition: >1.4-fold, osteocalcin: >2.6-fold) sufficient for regenerating bone tissue. Copyright © 2017. Published by Elsevier B.V.

Biodegradable fibre scaffolds incorporating water-soluble drugs and proteins.

PubMed

Ma, J; Meng, J; Simonet, M; Stingelin, N; Peijs, T; Sukhorukov, G B

2015-07-01

A new type of biodegradable drug-loaded fibre scaffold has been successfully produced for the benefit of water-soluble drugs and proteins. Model drug loaded calcium carbonate (CaCO3) microparticles incorporated into poly(lactic acid-co-glycolic acid) (PLGA) fibres were manufactured by co-precipitation of CaCO3 and the drug molecules, followed by electrospinning of a suspension of such drug-loaded microparticles in a PLGA solution. Rhodamine 6G and bovine serum albumin were used as model drugs for our release study, representing small bioactive molecules and protein, respectively. A bead and string structure of fibres was achieved. The drug release was investigated with different drug loadings and in different pH release mediums. Results showed that a slow and sustained drug release was achieved in 40 days and the CaCO3 microparticles used as the second barrier restrained the initial burst release.

Source term identification in atmospheric modelling via sparse optimization

NASA Astrophysics Data System (ADS)

Adam, Lukas; Branda, Martin; Hamburger, Thomas

2015-04-01

Inverse modelling plays an important role in identifying the amount of harmful substances released into atmosphere during major incidents such as power plant accidents or volcano eruptions. Another possible application of inverse modelling lies in the monitoring the CO2 emission limits where only observations at certain places are available and the task is to estimate the total releases at given locations. This gives rise to minimizing the discrepancy between the observations and the model predictions. There are two standard ways of solving such problems. In the first one, this discrepancy is regularized by adding additional terms. Such terms may include Tikhonov regularization, distance from a priori information or a smoothing term. The resulting, usually quadratic, problem is then solved via standard optimization solvers. The second approach assumes that the error term has a (normal) distribution and makes use of Bayesian modelling to identify the source term. Instead of following the above-mentioned approaches, we utilize techniques from the field of compressive sensing. Such techniques look for a sparsest solution (solution with the smallest number of nonzeros) of a linear system, where a maximal allowed error term may be added to this system. Even though this field is a developed one with many possible solution techniques, most of them do not consider even the simplest constraints which are naturally present in atmospheric modelling. One of such examples is the nonnegativity of release amounts. We believe that the concept of a sparse solution is natural in both problems of identification of the source location and of the time process of the source release. In the first case, it is usually assumed that there are only few release points and the task is to find them. In the second case, the time window is usually much longer than the duration of the actual release. In both cases, the optimal solution should contain a large amount of zeros, giving rise to the concept of sparsity. In the paper, we summarize several optimization techniques which are used for finding sparse solutions and propose their modifications to handle selected constraints such as nonnegativity constraints and simple linear constraints, for example the minimal or maximal amount of total release. These techniques range from successive convex approximations to solution of one nonconvex problem. On simple examples, we explain these techniques and compare them from the point of implementation simplicity, approximation capability and convergence properties. Finally, these methods will be applied on the European Tracer Experiment (ETEX) data and the results will be compared with the current state of arts techniques such as regularized least squares or Bayesian approach. The obtained results show the surprisingly good results of these techniques. This research is supported by EEA/Norwegian Financial Mechanism under project 7F14287 STRADI.

Coenzyme Q10 inhibits the release of glutamate in rat cerebrocortical nerve terminals by suppression of voltage-dependent calcium influx and mitogen-activated protein kinase signaling pathway.

PubMed

Chang, Yi; Huang, Shu-Kuei; Wang, Su-Jane

2012-12-05

This study investigates the effects and possible mechanism of coenzyme Q10 (CoQ10) on endogenous glutamate release in the cerebral cortex nerve terminals of rats. CoQ10 inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP). CoQ10 reduced the depolarization-induced increase in cytosolic [Ca2+]c but did not alter the 4-AP-mediated depolarization. The effect of CoQ10 on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels and mitogen-activated protein kinase kinase (MEK). In addition, CoQ10 decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK. Moreover, the inhibition of glutamate release by CoQ10 was strongly attenuated in mice without synapsin I. These results suggest that CoQ10 inhibits glutamate release from cortical synaptosomes in rats through the suppression of the presynaptic voltage-dependent Ca2+ entry and ERK/synapsin I signaling pathway.

Design and development of bio-inspired framework for reservoir operation optimization

NASA Astrophysics Data System (ADS)

Asvini, M. Sakthi; Amudha, T.

2017-12-01

Frameworks for optimal reservoir operation play an important role in the management of water resources and delivery of economic benefits. Effective utilization and conservation of water from reservoirs helps to manage water deficit periods. The main challenge in reservoir optimization is to design operating rules that can be used to inform real-time decisions on reservoir release. We develop a bio-inspired framework for the optimization of reservoir release to satisfy the diverse needs of various stakeholders. In this work, single-objective optimization and multiobjective optimization problems are formulated using an algorithm known as "strawberry optimization" and tested with actual reservoir data. Results indicate that well planned reservoir operations lead to efficient deployment of the reservoir water with the help of optimal release patterns.

Formulation, in vitro evaluation and study of variables on tri-layered gastro-retentive delivery system of diltiazem HCl.

PubMed

Raut Desai, Shilpa; Rohera, Bhagwan D

2014-03-01

Tri-layered floating tablets using only one grade of polyethylene oxide (PEO) would enable easy manufacturing, reproducibility and controlled release for highly soluble drugs. To evaluate the potential of PEO as a sole polymer for the controlled release and to study the effect of formulation variables on release and gastric retention of highly soluble Diltiazem hydrochloride (DTZ). Tablets were compressed with middle layer consisting of drug and polymer while outer layers consisted of polymer with sodium bicarbonate. Design of formulation to obtain 12 h, zero-order release and rapid floatation was done by varying the grades, quantity of PEO and sodium bicarbonate. Dissolution data were fitted in drug release models and swelling/erosion studies were undertaken to verify the drug release mechanism. Effect of formulation variables and tablet surface morphology using scanning electron microscopy were studied. The optimized formula passed the criteria of USP dissolution test I and exhibited floating lag-time of 3-4 min. Drug release was faster from low molecular weight (MW) PEO as compared to high MW. With an increase in the amount of sodium bicarbonate, faster buoyancy was achieved due to the increased CO2 gas formation. Drug release followed zero-order and gave a good fit to the Korsmeyer-Peppas model, which suggested that drug release was due to diffusion through polymer swelling. Zero-order, controlled release profile with the desired buoyancy can be achieved by using optimum formula quantities of sodium bicarbonate and polymer. The tri-layered system shows promising delivery of DTZ, and possibly other water-soluble drugs.

Biodegradable FeMnSi Sputter-Coated Macroporous Polypropylene Membranes for the Sustained Release of Drugs

PubMed Central

Fornell, Jordina; Soriano, Jorge; Guerrero, Miguel; Sirvent, Juan de Dios; Ferran-Marqués, Marta; Ibáñez, Elena; Barrios, Leonardo; Baró, Maria Dolors; Suriñach, Santiago; Nogués, Carme; Sort, Jordi; Pellicer, Eva

2017-01-01

Pure Fe and FeMnSi thin films were sputtered on macroporous polypropylene (PP) membranes with the aim to obtain biocompatible, biodegradable and, eventually, magnetically-steerable platforms. Room-temperature ferromagnetic response was observed in both Fe- and FeMnSi-coated membranes. Good cell viability was observed in both cases by means of cytotoxicity studies, though the FeMnSi-coated membranes showed higher biodegradability than the Fe-coated ones. Various strategies to functionalize the porous platforms with transferrin-Alexa Fluor 488 (Tf-AF488) molecules were tested to determine an optimal balance between the functionalization yield and the cargo release. The distribution of Tf-AF488 within the FeMnSi-coated PP membranes, as well as its release and uptake by cells, was studied by confocal laser scanning microscopy. A homogeneous distribution of the drug within the membrane skeleton and its sustained release was achieved after three consecutive impregnations followed by the addition of a layer made of gelatin and maltodextrin, which prevented exceedingly fast release. The here-prepared organic-inorganic macroporous membranes could find applications as fixed or magnetically-steerable drug delivery platforms. PMID:28672792

pH sensitive silica nanotubes as rationally designed vehicles for NSAIDs delivery.

PubMed

Sousa, Célia T; Nunes, Cláudia; Proença, Mariana P; Leitão, Diana C; Lima, José L F C; Reis, Salette; Araújo, João P; Lúcio, Marlene

2012-06-01

A novel pH-sensitive drug delivery system based on functionalized silica nanotubes was developed for the incorporation of non-steroidal anti-inflammatory drugs (NSAIDs), aimed at a tailored drug release in acidic conditions characteristic of inflamed tissues. Silica nanotubes (SNTs) were synthesized by a nanoporous alumina template assisted sol-gel method. Inner surfaces were physically and chemically modified to improve both the functionalization and subsequent incorporation of the drug. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and transmission electron microscopy (TEM) were used to characterize the designed nanocarriers and their functionalization. To achieve the highest degree of functionalization, three types of aminosilanes were tested and calcination conditions were optimized. APTES was shown to be the most effective aminosilane regarding the functionalization of the SNTs' inner surface and an adequate calcination temperature (220°C) was found to attain mechanical stability without compromising functionalization efficiency. Finally, the incorporation of naproxen into the nanotubes was accessed by fluorescence measurements and drug release studies were performed, revealing that the electrostatic linkage ensures effective release of the drug in the acidic pH typical of inflamed cells, while maintaining the SNT-drug conjugates stable at the typical bloodstream pH. Copyright © 2012 Elsevier B.V. All rights reserved.

L-Carnitine suppresses oleic acid-induced membrane permeability transition of mitochondria.

PubMed

Oyanagi, Eri; Yano, Hiromi; Kato, Yasuko; Fujita, Hirofumi; Utsumi, Kozo; Sasaki, Junzo

2008-10-01

Membrane permeability transition (MPT) of mitochondria has an important role in apoptosis of various cells. The classic type of MPT is characterized by increased Ca(2+) transport, membrane depolarization, swelling, and sensitivity to cyclosporin A. In this study, we investigated whether L-carnitine suppresses oleic acid-induced MPT using isolated mitochondria from rat liver. Oleic acid-induced MPT in isolated mitochondria, inhibited endogenous respiration, caused membrane depolarization, and increased large amplitude swelling, and cytochrome c (Cyt. c) release from mitochondria. L-Carnitine was indispensable to beta-oxidation of oleic acid in the mitochondria, and this reaction required ATP and coenzyme A (CoA). In the presence of ATP and CoA, L-carnitine stimulated oleic acid oxidation and suppressed the oleic acid-induced depolarization, swelling, and Cyt. c release. L-Carnitine also contributed to maintaining mitochondrial function, which was decreased by the generation of free fatty acids with the passage of time after isolation. These results suggest that L-carnitine acts to maintain mitochondrial function and suppresses oleic acid-mediated MPT through acceleration of beta-oxidation. Copyright (c) 2008 John Wiley & Sons, Ltd.

Electrospun nanofibers-mediated on-demand drug release.

PubMed

Chen, Menglin; Li, Yan-Fang; Besenbacher, Flemming

2014-11-01

A living system has a complex and accurate regulation system with intelligent sensor-processor-effector components to enable the release of vital bioactive substances on demand at a specific site and time. Stimuli-responsive polymers mimic biological systems in a crude way where an external stimulus results in a change in conformation, solubility, or alternation of the hydrophilic/hydrophobic balance, and consequently release of a bioactive substance. Electrospinning is a straightforward and robust method to produce nanofibers with the potential to incorporate drugs in a simple, rapid, and reproducible process. This feature article emphasizes an emerging area using an electrospinning technique to generate biomimetic nanofibers as drug delivery devices that are responsive to different stimuli, such as temperature, pH, light, and electric/magnetic field for controlled release of therapeutic substances. Although at its infancy, the mimicry of these stimuli-responsive nanofibers to the function of the living systems includes both the fibrous structural feature and bio-regulation function as an on demand drug release depot. The electrospun nanofibers with extracellular matrix morphology intrinsically guide cellular drug uptake, which will be highly desired to translate the promise of drug delivery for the clinical success. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization, in vitro release and bioavailability of gamma-oryzanol-loaded calcium pectinate microparticles reinforced with chitosan.

PubMed

Kim, Jong Soo; Lee, Ji-Soo; Chang, Pahn-Shick; Lee, Hyeon Gyu

2010-09-30

Response surface methodology was used to optimize coating conditions, including chitosan concentration (X(1)) and coating time (X(2)), for sustained release of chitosan-coated Ca-pectinate (CP) microparticles containing oryzanol (OZ). The optimized values of X(1) and X(2) were found to be 1.48% and 69.92 min, respectively. These optimized values agreed favorably with the predicted results, indicating the utility of predictive models for the release of OZ in simulated intestinal fluid. In vitro release studies revealed that the chitosan-coated CP microparticles were quite stable under acidic conditions, but swell and disintegrate under alkaline conditions. In vivo release study of OZ, physically entrapped within chitosan-coated CP microcapsules, demonstrated the sustained release of OZ and could be used to improve the bioavailability of OZ following oral administration. Copyright 2010 Elsevier B.V. All rights reserved.

Image guided drug release from pH-sensitive Ion channel-functionalized stealth liposomes into an in vivo glioblastoma model.

PubMed

Pacheco-Torres, Jesus; Mukherjee, Nobina; Walko, Martin; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdan, Sebastian; Kocer, Armagan

2015-08-01

Liposomal drug delivery vehicles are promising nanomedicine tools for bringing cytotoxic drugs to cancerous tissues selectively. However, the triggered cargo release from liposomes in response to a target-specific stimulus has remained elusive. We report on functionalizing stealth-liposomes with an engineered ion channel and using these liposomes in vivo for releasing an imaging agent into a cerebral glioma rodent model. If the ambient pH drops below a threshold value, the channel generates temporary pores on the liposomes, thus allowing leakage of the intraluminal medicines. By using magnetic resonance spectroscopy and imaging, we show that engineered liposomes can detect the mildly acidic pH of the tumor microenvironment with 0.2 pH unit precision and they release their content into C6 glioma tumors selectively, in vivo. A drug delivery system with this level of sensitivity and selectivity to environmental stimuli may well serve as an optimal tool for environmentally-triggered and image-guided drug release. Cancer remains a leading cause of mortality worldwide. With advances in science, delivery systems of anti-cancer drugs have also become sophisticated. In this article, the authors designed and characterized functionalized liposomal vehicles, which would release the drug payload in a highly sensitive manner in response to a change in pH environment in an animal glioma model. The novel data would enable better future designs of drug delivery systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Insulating ferromagnetic oxide films: the controlling role of oxygen vacancy ordering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salafranca Laforga, Juan I; Salafranca, Juan; Biskup, Nevenko

2014-01-01

The origin of ferromagnetism in strained epitaxial LaCoO3 films has been a long-standing mystery. Here, we combine atomically resolved Z-contrast imaging, electron-energy-loss spectroscopy, and density-functional calculations to demonstrate that, in epitaxial LaCoO3 films, oxygen-vacancy superstructures release strain, control the film s electronic properties, and produce the observed ferromagnetism via the excess electrons in the Co d states. Although oxygen vacancies typically dope a material n-type, we find that ordered vacancies induce Peierls-like minigaps which, combined with strain relaxation, trigger a nonlinear rupture of the energy bands, resulting in insulating behavior.

Nanoemulsion: for improved oral delivery of repaglinide.

PubMed

Akhtar, Juber; Siddiqui, Hefazat Hussain; Fareed, Sheeba; Badruddeen; Khalid, Mohammad; Aqil, Mohammed

2016-07-01

Repaglinide (RPG) is a fast-acting prandial glucose regulator. It acts by stimulating insulin release from pancreatic β-cells. Recurrent dosing of RPG before each meal is burdensome remedy. Hence the plan of the present study was to evaluate nanoemulsion as a hopeful carrier for RPG for persistent hypoglycemic effect. The drug was incorporated into oil phase of nanoemulsion to give improved biopharmaceutical properties as compared to the lipid-based systems. Pseudo ternary phase diagrams were prepared by aqueous titration method. Formulations were selected at a difference of 5% w/w of oil from the o/w nanoemulsion region of phase diagrams. The optimized nanoemulsion formulation constituted sefsol-218 (5% v/v) as an oil phase, 30% v/v of Tween-80 and transcutol as a surfactant and co-surfactant to restrain nanodroplet size and low viscosity and distilled water (65%). In vitro dissolution studies showed higher drug release (98.22%), finest droplet size (76.23 nm), slightest polydispersity value (0.183), least viscosity (21.45 cps) and immeasurable dilution capability from the nanoemulsion as compared with existing oral tablet formulation. The optimized RPG nanoemulsion formulation showed better hypoglycemic effect in comparison to tablet formulation in experimental diabetic rats. No significant variations were also observed in the optimized formulation when subjected to accelerated stability study at different temperature and relative humidity over a period of 3 months.

Co-Optimization of Electricity Transmission and Generation Resources for Planning and Policy Analysis: Review of Concepts and Modeling Approaches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, Venkat; Ho, Jonathan; Hobbs, Benjamin F.

2016-05-01

The recognition of transmission's interaction with other resources has motivated the development of co-optimization methods to optimize transmission investment while simultaneously considering tradeoffs with investments in electricity supply, demand, and storage resources. For a given set of constraints, co-optimized planning models provide solutions that have lower costs than solutions obtained from decoupled optimization (transmission-only, generation-only, or iterations between them). This paper describes co-optimization and provides an overview of approaches to co-optimizing transmission options, supply-side resources, demand-side resources, and natural gas pipelines. In particular, the paper provides an up-to-date assessment of the present and potential capabilities of existing co-optimization tools, andmore » it discusses needs and challenges for developing advanced co-optimization models.« less

Co-precipitation of tobramycin into biomimetically coated orthopedic fixation pins employing submicron-thin seed layers of hydroxyapatite.

PubMed

Sörensen, Jan H; Lilja, Mirjam; Åstrand, Maria; Sörensen, Torben C; Procter, Philip; Strømme, Maria; Steckel, Hartwig

2014-01-01

The migration, loosening and cut-out of implants and nosocomial infections are current problems associated with implant surgery. New innovative strategies to overcome these issues are emphasized in today's research. The current work presents a novel strategy involving co-precipitation of tobramycin with biomimetic hydroxyapatite (HA) formation to produce implant coatings that control local drug delivery to prevent early bacterial colonization of the implant. A submicron- thin HA layer served as seed layer for the co-precipitation process and allowed for incorporation of tobramycin in the coating from a stock solution of antibiotic concentrations as high as 20 mg/ml. Concentrations from 0.5 to 20 mg/ml tobramycin and process temperatures of 37 °C and 60 °C were tested to assess the optimal parameters for a thin tobramycin- delivering HA coating on discs and orthopedic fixation pins. The morphology and thickness of the coating and the drug-release profile were evaluated via scanning electron microscopy and high performance liquid chromatography. The coatings delivered pharmaceutically relevant amounts of tobramycin over a period of 12 days. To the best of our knowledge, this is the longest release period ever observed for a fast-loaded biomimetic implant coating. The presented approach could form the foundation for development of combination device/antibiotic delivery vehicles tailored to meet well-defined clinical needs while combating infections and ensuring fast implant in-growth.

Rigorous ILT optimization for advanced patterning and design-process co-optimization

NASA Astrophysics Data System (ADS)

Selinidis, Kosta; Kuechler, Bernd; Cai, Howard; Braam, Kyle; Hoppe, Wolfgang; Domnenko, Vitaly; Poonawala, Amyn; Xiao, Guangming

2018-03-01

Despite the large difficulties involved in extending 193i multiple patterning and the slow ramp of EUV lithography to full manufacturing readiness, the pace of development for new technology node variations has been accelerating. Multiple new variations of new and existing technology nodes have been introduced for a range of device applications; each variation with at least a few new process integration methods, layout constructs and/or design rules. This had led to a strong increase in the demand for predictive technology tools which can be used to quickly guide important patterning and design co-optimization decisions. In this paper, we introduce a novel hybrid predictive patterning method combining two patterning technologies which have each individually been widely used for process tuning, mask correction and process-design cooptimization. These technologies are rigorous lithography simulation and inverse lithography technology (ILT). Rigorous lithography simulation has been extensively used for process development/tuning, lithography tool user setup, photoresist hot-spot detection, photoresist-etch interaction analysis, lithography-TCAD interactions/sensitivities, source optimization and basic lithography design rule exploration. ILT has been extensively used in a range of lithographic areas including logic hot-spot fixing, memory layout correction, dense memory cell optimization, assist feature (AF) optimization, source optimization, complex patterning design rules and design-technology co-optimization (DTCO). The combined optimization capability of these two technologies will therefore have a wide range of useful applications. We investigate the benefits of the new functionality for a few of these advanced applications including correction for photoresist top loss and resist scumming hotspots.

Carbon dioxide instantly sensitizes female yellow fever mosquitoes to human skin odours.

PubMed

Dekker, Teun; Geier, Martin; Cardé, Ring T

2005-08-01

Female mosquitoes are noted for their ability to use odours to locate a host for a blood meal. Two sensory organs contribute to their sense of smell: the maxillary palps, which measure the level of CO2, and the antennae, which detect other host-released odours. To establish the relative importance and interactions of CO2 and other body emissions in freely flying mosquitoes, we presented female yellow fever mosquitoes Aedes aegypti L. with broad plumes of human skin odour and CO2 at natural concentrations and dilutions thereof in a wind tunnel. 3-D video-recorded flight tracks were reconstructed. Activation, flight velocity, upwind turning and source finding waned quickly as skin odours were diluted, whereas in the presence of CO2 these parameters remained unchanged over more than a 100-fold dilution from exhaled concentrations. Although mosquitoes were behaviourally less sensitive to skin odours than to CO2, their sensitivity to skin odours increased transiently by at least fivefold immediately following a brief encounter with a filament of CO2. This sensitization was reflected in flight velocity, track angle, turning rate upon entering and exiting the broad odour plume and, ultimately, in the source-finding rate. In Ae. aegypti, CO2 thus functions as a ;releaser' for a higher sensitivity and responsiveness to skin odours. The initially low responsiveness of mosquitoes to skin odours, their high sensitivity to CO2, and the sensitization of the olfactory circuitry by CO2 are ecologically relevant, because rapidly fluctuating CO2 levels reliably signal a potential host. Possible mechanisms of the instantaneous sensitization are considered.

Preparation of psoralen polymer-lipid hybrid nanoparticles and their reversal of multidrug resistance in MCF-7/ADR cells.

PubMed

Huang, Qingqing; Cai, Tiange; Li, Qianwen; Huang, Yinghong; Liu, Qian; Wang, Bingyue; Xia, Xi; Wang, Qi; Whitney, John C C; Cole, Susan P C; Cai, Yu

2018-11-01

Multidrug resistance (MDR) is the leading cause of failure for breast cancer in the clinic. Thus far, polymer-lipid hybrid nanoparticles (PLN) loaded chemotherapeutic agents has been used to overcome MDR in breast cancer. In this study, we prepared psoralen polymer-lipid hybrid nanoparticles (PSO-PLN) to reverse drug resistant MCF-7/ADR cells in vitro and in vivo. PSO-PLN was prepared by the emulsification evaporation-low temperature solidification method. The formulation, water solubility and bioavailability, particle size, zeta potential and entrapment efficiency, and in vitro release experiments were optimized in order to improve the activity of PSO to reverse MDR. Optimal formulation: soybean phospholipids 50 mg, poly(lactic-co-glycolic) acid (PLGA) 15 mg, PSO 3 mg, and Tween-80 1%. The PSO-PLN possessed a round appearance, uniform size, exhibited no adhesion. The average particle size was 93.59 ± 2.87 nm, the dispersion co-efficient was 0.249 ± 0.06, the zeta potential was 25.47 ± 2.84 mV. In vitro analyses revealed that PSO resistance index was 3.2, and PSO-PLN resistance index was 5.6, indicating that PSO-PLN versus MCF-7/ADR reversal effect was significant. Moreover, PSO-PLN is somewhat targeted to the liver, and has an antitumor effect in the xenograft model of drug-resistant MCF-7/ADR cells. In conclusion, PSO-PLN not only reverses MDR but also improves therapeutic efficiency by enhancing sustained release of PSO.

Development of Microemulsion Based Nabumetone Transdermal Delivery For Treatment of Arthritis.

PubMed

Jagdale, Swati; Deore, Gokul; Chabukswar, Anuruddha

2018-02-26

Background Nabumetone is biopharmaceutics classification system (BCS) class II drug, widely used in the treatment of osteoarthritis and rheumatoid arthritis. The most frequently reported adverse reactions for the drug involve disturbance in gastrointestinal tract , diarrhea, dyspepsia and abdominal pain. Microemulgel has advantages of microemulsion for improving solubility for hydrophobic drug. Patent literature had shown that the work for drug has been carried on spray chilling, enteric coated tablet, and topical formulation which gave idea for present research work for development of transdermal delivery. Objective Objective of the present research work was to optimize transdermal microemulgel delivery for Nabumetone for treatment of arthritis. Method Oil, surfactant and co-surfactant were selected based on solubility study for the drug. Gelling agents used were Carbopol 934 and HPMC K100M. Optimization was carried out using 32 factorial design. Characterization and evaluation were carried out for microemulsion and microemulsion based gel. Results Field emission-scanning electron microscopy (FE-SEM) study of the microemulsion revealed globules of 50-200 nm size . Zeta potential -9.50 mV indicated good stability of microemulsion. Globule size measured by dynamic light scattering (zetasizer) was 160 nm. Design expert gave optimized batch as F7 which contain 0.2% w/w drug, 4.3% w/w liquid paraffin, 0.71% w/w tween 80, 0.35% w/w propylene glycol, 0.124% w/w Carbopol 934, 0.187% w/w HPMC K100M and 11.68% w/w water. In-vitro diffusion study for F7 batch showed 99.16±2.10 % drug release through egg membrane and 99.15±2.73% drug release in ex-vivo study. Conclusion Nabumetone microemulgel exhibiting good in-vitro and ex-vivo controlled drug release was optimized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

a Study of Using Hydrogen Gas for Steam Boiler in CHOLOR- Alkali Manufacturing

NASA Astrophysics Data System (ADS)

Peantong, Sasitorn; Tangjitsitcharoen, Somkiat

2017-06-01

Main products of manufacturing of Cholor - Alkali, which commonly known as industrial chemical, are chlorine gas (Cl2), Sodium Hydroxide (NaOH) and hydrogen gas (H2). Chorine gas and sodium hydroxide are two main products for commercial profit; where hydrogen gas is by product. Most industries release hydrogen gas to atmosphere as it is non-profitable and less commercial scale. This study aims to make the most use of hydrogen as a substitute energy of natural gas for steam boiler to save energy cost. The second target of this study is to reduce level of CO2 release to air as a consequence of boiler combustion. This study suggests to install boiler that bases on hydrogen as main power with a high turndown ratio of at least 1:6. However, this case study uses boiler with two mode such as natural gas (NG) mode and mixed mode as they need to be flexible for production. Never the less, the best boiler selection is to use single mode energy of hydrogen. The most concerned issue about hydrogen gas is explosion during combustion stage. Stabilization measures at emergency stop is introduced to control H2 pressure to protect the explosion. This study varies ratio of natural gas to hydrogen gas to find the optimal level of two energy sources for boiler and measure total consumption through costing model; where CO2 level is measured at the boiler stack. The result of this study shows that hydrogen gas can be a substitute energy with natural gas and can reduce cost. Natural gas cost saving is 248,846 baht per month and reduce level of NOx is 80 ppm 7% O2 and 2 % of CO2 release to air as a consequence of boiler combustion.

Uniaxial pressure effect on the magnetic ordered moment and transition temperatures in BaFe2 -xTxAs2 (T =Co,Ni )

NASA Astrophysics Data System (ADS)

Tam, David W.; Song, Yu; Man, Haoran; Cheung, Sky C.; Yin, Zhiping; Lu, Xingye; Wang, Weiyi; Frandsen, Benjamin A.; Liu, Lian; Gong, Zizhou; Ito, Takashi U.; Cai, Yipeng; Wilson, Murray N.; Guo, Shengli; Koshiishi, Keisuke; Tian, Wei; Hitti, Bassam; Ivanov, Alexandre; Zhao, Yang; Lynn, Jeffrey W.; Luke, Graeme M.; Berlijn, Tom; Maier, Thomas A.; Uemura, Yasutomo J.; Dai, Pengcheng

2017-02-01

We use neutron diffraction and muon spin relaxation to study the effect of in-plane uniaxial pressure on the antiferromagnetic (AF) orthorhombic phase in BaFe2As2 and its Co- and Ni-substituted members near optimal superconductivity. In the low-temperature AF ordered state, uniaxial pressure necessary to detwin the orthorhombic crystals also increases the magnetic ordered moment, reaching an 11% increase under 40 MPa for BaFe1.9Co0.1As2 , and a 15% increase for BaFe1.915Ni0.085As2 . We also observe an increase of the AF ordering temperature (TN) of about 0.25 K/MPa in all compounds, consistent with density functional theory calculations that reveal better Fermi surface nesting for itinerant electrons under uniaxial pressure. The doping dependence of the magnetic ordered moment is captured by combining dynamical mean field theory with density functional theory, suggesting that the pressure-induced moment increase near optimal superconductivity is closely related to quantum fluctuations and the nearby electronic nematic phase.

Simultaneous quantification of vitamin E, γ-oryzanols and xanthophylls from rice bran essences extracted by supercritical CO2.

PubMed

Sookwong, Phumon; Suttiarporn, Panawan; Boontakham, Pittayaporn; Seekhow, Pattawat; Wangtueai, Sutee; Mahatheeranont, Sugunya

2016-11-15

Since the nutrition value of rice is diminished during rice processing, technology that can preserve and sustain functional compounds is necessary. In this study, supercritical carbon dioxide (SC-CO2) extraction was optimized for operational conditions (time, temperature, pressure and modifier) to extract vitamin E, γ-oryzanols and xanthophylls from rice bran. The simultaneous quantification of the compounds was developed using high-performance liquid chromatography with diode array and fluorescence detectors. Central composite design and respond surface methodology were applied to achieve optimum extraction conditions. The optimized conditions were 60min, 43°C, 5420psi with 10% ethanol as a modifier. Pigmented rice bran extracts contained greater amounts of functional phytochemicals than non-pigmented rice bran extracts (0.68, 1410, and non-detectable μg/g compared with 16.65, 2480, and 0.10μg/g of vitamin E, γ-oryzanols and xanthophylls in pigmented and non-pigmented ones, respectively). SC-CO2 extraction with modifier would be promising for preparation of phytochemical essences for therapeutic purpose. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stochastic injection-strategy optimization for the preliminary assessment of candidate geological storage sites

NASA Astrophysics Data System (ADS)

Cody, Brent M.; Baù, Domenico; González-Nicolás, Ana

2015-09-01

Geological carbon sequestration (GCS) has been identified as having the potential to reduce increasing atmospheric concentrations of carbon dioxide (CO2). However, a global impact will only be achieved if GCS is cost-effectively and safely implemented on a massive scale. This work presents a computationally efficient methodology for identifying optimal injection strategies at candidate GCS sites having uncertainty associated with caprock permeability, effective compressibility, and aquifer permeability. A multi-objective evolutionary optimization algorithm is used to heuristically determine non-dominated solutions between the following two competing objectives: (1) maximize mass of CO2 sequestered and (2) minimize project cost. A semi-analytical algorithm is used to estimate CO2 leakage mass rather than a numerical model, enabling the study of GCS sites having vastly different domain characteristics. The stochastic optimization framework presented herein is applied to a feasibility study of GCS in a brine aquifer in the Michigan Basin (MB), USA. Eight optimization test cases are performed to investigate the impact of decision-maker (DM) preferences on Pareto-optimal objective-function values and carbon-injection strategies. This analysis shows that the feasibility of GCS at the MB test site is highly dependent upon the DM's risk-adversity preference and degree of uncertainty associated with caprock integrity. Finally, large gains in computational efficiency achieved using parallel processing and archiving are discussed.

New Class of Hybrid Materials for Detection, Capture, and "On-Demand" Release of Carbon Monoxide.

PubMed

Pitto-Barry, Anaïs; Lupan, Alexandru; Ellingford, Christopher; Attia, Amr A A; Barry, Nicolas P E

2018-04-25

Carbon monoxide (CO) is both a substance hazardous to health and a side product of a number of industrial processes, such as methanol steam reforming and large-scale oxidation reactions. The separation of CO from nitrogen (N 2 ) in industrial processes is considered to be difficult because of the similarities of their electronic structures, sizes, and physicochemical properties (e.g., boiling points). Carbon monoxide is also a major poison in fuel cells because of its adsorption onto the active sites of the catalysts. It is therefore of the utmost economic importance to discover new materials that enable effective CO capture and release under mild conditions. However, methods to specifically absorb and easily release CO in the presence of contaminants, such as water, nitrogen, carbon dioxide, and oxygen, at ambient temperature are not available. Here, we report the simple and versatile fabrication of a new class of hybrid materials that allows capture and release of carbon monoxide under mild conditions. We found that carborane-containing metal complexes encapsulated in networks made of poly(dimethylsiloxane) react with CO, even when immersed in water, leading to dramatic color and infrared signature changes. Furthermore, we found that the CO can be easily released from the materials by simply dipping the networks into an organic solvent for less than 1 min, at ambient temperature and pressure, which not only offers a straightforward recycling method, but also a new method for the "on-demand" release of carbon monoxide. We illustrated the utilization of the on-demand release of CO from the networks by carrying out a carbonylation reaction on an electron-deficient metal complex that led to the formation of the CO-adduct, with concomitant recycling of the gel. We anticipate that our sponge-like materials and scalable methodology will open up new avenues for the storage, transport, and controlled release of CO, the silent killer and a major industrial poison.

Can gamma irradiation during radiotherapy influence the metal release process for biomedical CoCrMo and 316L alloys?

PubMed

Wei, Zheng; Edin, Jonathan; Karlsson, Anna Emelie; Petrovic, Katarina; Soroka, Inna L; Odnevall Wallinder, Inger; Hedberg, Yolanda

2018-02-09

The extent of metal release from implant materials that are irradiated during radiotherapy may be influenced by irradiation-formed radicals. The influence of gamma irradiation, with a total dose of relevance for radiotherapy (e.g., for cancer treatments) on the extent of metal release from biomedical stainless steel AISI 316L and a cobalt-chromium alloy (CoCrMo) was investigated in physiological relevant solutions (phosphate buffered saline with and without 10 g/L bovine serum albumin) at pH 7.3. Directly after irradiation, the released amounts of metals were significantly higher for irradiated CoCrMo as compared to nonirradiated CoCrMo, resulting in an increased surface passivation (enhanced passive conditions) that hindered further release. A similar effect was observed for 316L showing lower nickel release after 1 h of initially irradiated samples as compared to nonirradiated samples. However, the effect of irradiation (total dose of 16.5 Gy) on metal release and surface oxide composition and thickness was generally small. Most metals were released initially (within seconds) upon immersion from CoCrMo but not from 316L. Albumin induced an increased amount of released metals from AISI 316L but not from CoCrMo. Albumin was not found to aggregate to any greater extent either upon gamma irradiation or in the presence of trace metal ions, as determined using different light scattering techniques. Further studies should elucidate the effect of repeated friction and fractionated low irradiation doses on the short- and long term metal release process of biomedical materials. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc.

Antishear Stress Bionic Carbon Nanotube Mesh Coating with Intracellular Controlled Drug Delivery Constructing Small-Diameter Tissue-Engineered Vascular Grafts.

PubMed

Ding, Ning; Dou, Ce; Wang, Yuxin; Liu, Feila; Guan, Ge; Huo, Da; Li, Yanzhao; Yang, Jingyuan; Wei, Keyu; Yang, Mingcan; Tan, Ju; Zeng, Wen; Zhu, Chuhong

2018-06-01

Small-diameter (<6 mm) tissue-engineered blood vessels (TEBVs) have a low patency rate due to chronic inflammation mediated intimal hyperplasia. Functional coating with drug release is a promising solution, but preventing the released drug from being rushed away by blood flow remains a great challenge. A single-walled carboxylic acid functionalized carbon nanotube (C-SWCNT) is used to build an irregular mesh for TEBV coating. However, an interaction between the released drug and the cells is still insufficient due to the blood flow. Thus, an intracellular drug delivery system mediated by macrophage cellular uptake is designed. Resveratrol (RSV) modified CNT is used for macrophage uptake. M1 macrophage uptakes CNT-RSV and then converts to the M2 phenotype upon intracellular RSV release. Prohealing M2 macrophage inhibits the chronic inflammation thus maintains the contractile phenotype of the vascular smooth muscle cell (VSMC), which reduces intimal hyperplasia. Additionally, RSV released from the mesh coating also directly protects the contractile VSMCs from being converted to a secretory phenotype. Through antishear stress coating and macrophage-based intracellular drug delivery, CNT-RSV TEBVs exhibit a long-term anti-intimal hyperplasia function. Animal transplantation studies show that the patency rate remains high until day 90 after grafting in rat carotid arteries. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual-Functionalization Device for Therapy through Dopamine Release and Monitoring.

PubMed

Fabregat, Georgina; Giménez, Alessia; Díaz, Angélica; Puiggalí, Jordi; Alemán, Carlos

2018-05-01

A dual-functional device is fabricated to release progressively dopamine (DA) from a biohydrogel under real-time monitoring via electrochemical detection. For this purpose, a poly-γ-glutamic acid biohydrogel is assembled with a poly(3,4-ethylenedioxythiophene) (PEDOT) layer, previously deposited onto a screen printed electrode. The biohydrogel is formulated to achieve dimensional stability and maximum DA-loading capacity. Conditions for DA-loading are influenced by the oxidation of the neurotransmitter in acid environments and the poor resistance of PEDOT to the lyophilization. The performance of the device is proved in a medium with the physiological pH of blood and the cerebrospinal fluid. The progressive release of DA is successfully monitored by the device, the limit of detection and sensitivity of the integrated sensor being 450 × 10 -9 m and 8 × 10 -5 mA µm -1 , respectively. The effect of electrochemical stimulation in the kinetics of the DA release is also investigated applying potential ramps in cyclic phase to alter the biohydrogel morphology. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Co-delivery of doxorubicin and arsenite with reduction and pH dual-sensitive vesicle for synergistic cancer therapy

NASA Astrophysics Data System (ADS)

Zhang, Lu; Xiao, Hong; Li, Jingguo; Cheng, Du; Shuai, Xintao

2016-06-01

Drug resistance is the underlying cause for therapeutic failure in clinical cancer chemotherapy. A prodrug copolymer mPEG-PAsp(DIP-co-BZA-co-DOX) (PDBD) was synthesized and assembled into a nanoscale vesicle comprising a PEG corona, a reduction and pH dual-sensitive hydrophobic membrane and an aqueous lumen encapsulating doxorubicin hydrochloride (DOX.HCl) and arsenite (As). The dual stimulation-sensitive design of the vesicle gave rise to rapid release of the physically entrapped DOX.HCl and arsenite inside acidic lysosomes, and chemically conjugated DOX inside the cytosol with high glutathione (GSH) concentration. In the optimized concentration range, arsenite previously recognized as a promising anticancer agent from traditional Chinese medicine can down-regulate the expressions of anti-apoptotic and multidrug resistance proteins to sensitize cancer cells to chemotherapy. Consequently, the DOX-As-co-loaded vesicle demonstrated potent anticancer activity. Compared to the only DOX-loaded vesicle, the DOX-As-co-loaded one induced more than twice the apoptotic ratio of MCF-7/ADR breast cancer cells at a low As concentration (0.5 μM), due to the synergistic effects of DOX and As. The drug loading strategy integrating chemical conjugation and physical encapsulation in stimulation-sensitive carriers enabled efficient drug loading in the formulation.Drug resistance is the underlying cause for therapeutic failure in clinical cancer chemotherapy. A prodrug copolymer mPEG-PAsp(DIP-co-BZA-co-DOX) (PDBD) was synthesized and assembled into a nanoscale vesicle comprising a PEG corona, a reduction and pH dual-sensitive hydrophobic membrane and an aqueous lumen encapsulating doxorubicin hydrochloride (DOX.HCl) and arsenite (As). The dual stimulation-sensitive design of the vesicle gave rise to rapid release of the physically entrapped DOX.HCl and arsenite inside acidic lysosomes, and chemically conjugated DOX inside the cytosol with high glutathione (GSH) concentration. In the optimized concentration range, arsenite previously recognized as a promising anticancer agent from traditional Chinese medicine can down-regulate the expressions of anti-apoptotic and multidrug resistance proteins to sensitize cancer cells to chemotherapy. Consequently, the DOX-As-co-loaded vesicle demonstrated potent anticancer activity. Compared to the only DOX-loaded vesicle, the DOX-As-co-loaded one induced more than twice the apoptotic ratio of MCF-7/ADR breast cancer cells at a low As concentration (0.5 μM), due to the synergistic effects of DOX and As. The drug loading strategy integrating chemical conjugation and physical encapsulation in stimulation-sensitive carriers enabled efficient drug loading in the formulation. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07868g

PEGylated Biodegradable Polyesters for PGSS Microparticles Formulation: Processability, Physical and Release Properties.

PubMed

Perinelli, D R; Cespi, M; Bonacucina, G; Naylor, A; Whitaker, M; Lam, J K W; Howdle, S M; Casettari, L; Palmieri, G F

2016-01-01

Particles from Gas Saturated Solution (PGSS) is an emergent method that employs supercritical carbon dioxide (scCO2) to produce microparticles. It is suitable for encapsulating biologically active compounds including therapeutic peptides and proteins. Poly(lactide acid) (PLA) and/or poly(lactic-coglycolic acid) (PLGA) are the most commonly used materials in PGSS, due to their good processability in scCO2. Previous studies demonstrated that the properties of the microparticles can be modulated by adding polyethylene glycol (PEG) or tri-block PEGylated copolymers. In the present work, the effect of the addition of biodegradable PEGylated di-block copolymers on the physical properties and drug release performance of microparticles prepared by PGSS technique was evaluated. mPEG5kDa-P(L)LA and mPEG5kDa-P(L)LGA with similar molecular weights were synthesized and their behaviour, when exposed to supercritical CO2, was investigated. Different microparticle formulations, composed of a high (81%) or low (9%) percentage of the synthesized copolymers were prepared and compared in terms of particle size distribution, morphology, yield and protein release. Drug release studies were performed using bovine serum albumin (BSA) as a model protein. PEGylated copolymers showed good processability in PGSS without significant changes to the physical properties of the microparticles. However, the addition of PEG exerted a modulating effect on the microparticle drug dissolution behaviour, increasing the rate of BSA release as a function of its content in the formulation. This study demonstrated the feasibility of producing microparticles by using PEGylated di-block copolymers through a PGSS technique at mild operating conditions (low operating pressure and temperature).

Incorporation of iodine in polymeric microparticles and emulsions

NASA Astrophysics Data System (ADS)

Kolontaeva, Olga A.; Khokhlova, Anastasia R.; Markina, Natalia E.; Markin, Alexey V.; Burmistrova, Natalia A.

2016-04-01

Application of different methods for formation of microcontainers containing iodine is proposed in this paper. Two types of microcontainers: microemulsions and microparticles have been investigated, conditions and methods for obtaining microcontainers were optimized. Microparticles were formed by layer-by-layer method with cores of calcium carbonate (CaCO3) as templates. Incorporation of complexes of iodine with polymers (chitosan, starch, polyvinyl alcohol) into core, shell and hollow capsules was investigated and loadings of microparticles with iodine were estimated. It was found that the complex of iodine with chitosan adsorbed at CaCO3 core is the most stable under physiological conditions and its value of loading can be 450 μg of I2 per 1 g of CaCO3. Moreover, chitosan was chosen as a ligand because of its biocompatibility and biodegradability as well as very low toxicity while its complex with iodine is very stable. A small amount of microparticles containing a iodine-chitosan complex can be used for prolonged release of iodine in the human body since iodine daily intake for adults is around 100 μg. "Oil-in-water" emulsions were prepared by ultrasonication of iodinated oils (sunflower and linseed) with sodium laurilsulfate (SLS) as surfactant solution. At optimal conditions, the homogenous emulsions remained stable for weeks, with total content of iodine in such emulsion being up to 1% (w/w). The oil:SLS ratio was equal to 1:10 (w/w), optimal duration and power of ultrasound exposure were 1.5 min and 7 W, correspondingly. Favorable application of iodized linseed oil for emulsion preparation with suitable oil microdroplets size was proved.

Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

NASA Astrophysics Data System (ADS)

Geng, Hongquan; Song, Hua; Qi, Jun; Cui, Daxiang

2011-12-01

We fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic- co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

Chemical release from single-PMMA microparticles monitored by CARS microscopy

NASA Astrophysics Data System (ADS)

Enejder, Annika; Svedberg, Fredrik; Nordstierna, Lars; Nydén, Magnus

2011-03-01

Microparticles loaded with antigens, proteins, DNA, fungicides, and other functional agents emerge as ideal vehicles for vaccine, drug delivery, genetic therapy, surface- and crop protection. The microscopic size of the particles and their collective large specific surface area enables highly active and localized release of the functional substance. In order to develop designs with release profiles optimized for the specific application, it is desirable to map the distribution of the active substance within the particle and how parameters such as size, material and morphology affect release rates at single particle level. Current imaging techniques are limited in resolution, sensitivity, image acquisition time, or sample treatment, excluding dynamic studies of active agents in microparticles. Here, we demonstrate that the combination of CARS and THG microscopy can successfully be used, by mapping the spatial distribution and release rates of the fungicide and food preservative IPBC from different designs of PMMA microparticles at single-particle level. By fitting a radial diffusion model to the experimental data, single particle diffusion coefficients can be determined. We show that release rates are highly dependent on the size and morphology of the particles. Hence, CARS and THG microscopy provides adequate sensitivity and spatial resolution for quantitative studies on how singleparticle properties affect the diffusion of active agents at microscopic level. This will aid the design of innovative microencapsulating systems for controlled release.

Optimization of tetracycline hydrochloride adsorption on amino modified SBA-15 using response surface methodology.

PubMed

Hashemikia, Samaneh; Hemmatinejad, Nahid; Ahmadi, Ebrahim; Montazer, Majid

2015-04-01

Several researchers are focused on preparation of mesoporous silica as drug carriers with high loading efficiency to control or sustain the drug release. Carriers with highly loaded drug are utilized to minimize the time of drug intake. In this study, amino modified SBA-15 was synthesized through grafting with amino propyl triethoxy silane and then loaded with tetracycline hydrochloride. The drug loading was optimized by using the response surface method considering various factors including drug to silica ratio, operation time, and temperature. The drug to silica ratio indicated as the most influential factor on the drug loading yield. Further, a quadratic polynomial equation was developed to predict the loading percentage. The experimental results indicated reasonable agreement with the predicted values. The modified and drug loaded mesoporous particles were characterized by FT-IR, SEM, TEM, X-ray diffraction (XRD), elemental analysis and N2 adsorption-desorption. The release profiles of tetracycline-loaded particles were studied in different pH. Also, Higuchi equation was used to analyze the release profile of the drug and to evaluate the kinetic of drug release. The drug release rate followed the conventional Higuchi model that could be controlled by amino-functionalized SBA-15. Further, the drug delivery system based on amino modified SBA-15 exhibits novel features with an appropriate usage as an anti-bacterial drug delivery system with effective management of drug adsorption and release. Copyright © 2014 Elsevier Inc. All rights reserved.

Organic nanoparticle systems for spatiotemporal control of multimodal chemotherapy

PubMed Central

Meng, Fanfei; Han, Ning; Yeo, Yoon

2017-01-01

Introduction Chemotherapeutic drugs are used in combination to target multiple mechanisms involved in cancer cell survival and proliferation. Carriers are developed to deliver drug combinations to common target tissues in optimal ratios and desirable sequences. Nanoparticles (NP) have been a popular choice for this purpose due to their ability to increase the circulation half-life and tumor accumulation of a drug. Areas covered We review organic NP carriers based on polymers, proteins, peptides, and lipids for simultaneous delivery of multiple anticancer drugs, drug/sensitizer combinations, drug/photodynamic- or photothermal therapy combinations, and drug/gene therapeutics with examples in the past three years. Sequential delivery of drug combinations, based on either sequential administration or built-in release control, is introduced with an emphasis on the mechanistic understanding of such control. Expert opinion Recent studies demonstrate how a drug carrier can contribute to co-localizing drug combinations in optimal ratios and dosing sequences to maximize the synergistic effects. We identify several areas for improvement in future research, including the choice of drug combinations, circulation stability of carriers, spatiotemporal control of drug release, and the evaluation and clinical translation of combination delivery. PMID:27476442

Caracterisation experimentale et numerique de la flamme de carburants synthetiques gazeux

NASA Astrophysics Data System (ADS)

Ouimette, Pascale

The goal of this research is to characterize experimentally and numerically laminar flames of syngas fuels made of hydrogen (H2), carbon monoxide (CO), and carbon dioxide (CO2). More specifically, the secondary objectives are: 1) to understand the effects of CO2 concentration and H2/CO ratio on NOx emissions, flame temperature, visible flame height, and flame appearance; 2) to analyze the influence of H2/CO ratio on the lame structure, and; 3) to compare and validate different H2/CO kinetic mechanisms used in a CFD (computational fluid dynamics) model over different H2/CO ratios. Thus, the present thesis is divided in three chapters, each one corresponding to a secondary objective. For the first part, experimentations enabled to conclude that adding CO2 diminishes flame temperature and EINOx for all equivalence ratios while increasing the H2/CO ratio has no influence on flame temperature but increases EINOx for equivalence ratios lower than 2. Concerning flame appearance, a low CO2 concentration in the fuel or a high H2/CO ratio gives the flame an orange color, which is explained by a high level of CO in the combustion by-products. The observed constant flame temperature with the addition of CO, which has a higher adiabatic flame temperature, is mainly due to the increased heat loss through radiation by CO2. Because NOx emissions of H2/CO/CO 2 flames are mainly a function of flame temperature, which is a function of the H2/CO ratio, the rest of the thesis concentrates on measuring and predicting species in the flame as a good prediction of species and heat release will enable to predict NOx emissions. Thus, for the second part, different H2/CO fuels are tested and major species are measured by Raman spectroscopy. Concerning major species, the maximal measured H 2O concentration decreases with addition of CO to the fuel, while the central CO2 concentration increases, as expected. However, at 20% of the visible flame height and for all fuels tested herein, the measured CO2 concentration is lower than its stoechiometric value while the measured H2O already reached its stoechiometric concentration. The slow chemical reactions necessary to produce CO2 compared to the ones forming H2O could explain this difference. For the third part, a numerical model is created for a partially premixed flame of 50% H 2 / 50% CO. This model compares different combustion mechanisms and shows that a reduced kinetic mechanism reduces simulation times while conserving the results quality of more complex kinetic schemes. This numerical model, which includes radiation heat losses, is also validated for a large range of fuels going from 100% H2 to 5% H2 / 95% CO. The most important recommendation of this work is to include a NOx mechanism to the numerical model in order to eventually determine an optimal fuel. It would also be necessary to validate the model over a wide range for different parameters such as equivalence ratio, initial temperature and initial pressure.

Folic acid-functionalized magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell composite particles: synthesis and application in drug release.

PubMed

Yang, Dandan; Wei, Kaiwei; Liu, Qi; Yang, Yong; Guo, Xue; Rong, Hongren; Cheng, Mei-Ling; Wang, Guoxiu

2013-07-01

A drug delivery system was designed by deliberately combining the useful functions into one entity, which was composed of magnetic ZnFe2O4 hollow microsphere as the core, and mesoporous silica with folic acid molecules as the outer shell. Amine groups coated magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell (MZHM-MSS-NH2) composite particles were first synthesized by a one-pot direct co-condensation method. Subsequently a novel kind of folic acid-functionalized magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell (MZHM-MSS-NHFA) composite particles were synthesized by conjugating folic acid as targeted molecule to MZHM-MSS-NH2. Ibuprofen, a well-known antiphlogistic drug, was used as a model drug to assess the loading and releasing behavior of the composite microspheres. The results show that the MZHM-MSS-NHFA system has the higher capacity of drug storage and good sustained drug-release property. Copyright © 2013 Elsevier B.V. All rights reserved.

Photoregulation of fructose and glucose respiration in the intact chloroplasts of Chlamydomonas reinhardtii F-60 and spinach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, K.K.; Changguo Chen; Gibbs, M.

1993-04-01

The photoregulation of chloroplastic respiration was studied by monitoring in darkness and in light the release of [sup 14]CO[sub 2] from whole chloroplasts of Chlamydomonas reinhardtii F-60 and spinach (Spinacia oleracea L.) supplied externally with [[sup 14]C]glucose and [[sup 14]C]fructose, respectively. CO[sub 2] release was inhibited more than 90% in both chloroplasts by a light intensity of 4 W m[sup [minus]2]. Oxidants, oxaloacetate in Chlamydomonas, nitrite in spinach, and phenazine methosulfate in both chloroplasts, reversed the inhibition. The onset of the photoinhibitory effect on CO[sub 2] release was relatively rapid compared to the restoration of CO[sub 2] release following illumination.more » In both darkened chloroplasts, dithiothreitol inhibited release. Of the four enzymes (fructokinase, phosphoglucose isomerase, glucose-6-P dehydrogenase, and gluconate-6-P dehydrogenase) in the pathway catalyzing the release of CO[sub 2] from fructose, only glucose-6-P dehydrogenase was deactivated by light and by dithiothreitol. 33 refs., 3 figs., 4 tabs.« less

Organic Combustion in the Presence of Ca-Carbonate and Mg-Perchlorate: A Possible Source for the Low Temperature CO2 Release Seen in Mars Phoenix Thermal and Evolved Gas Analyzer Data

NASA Technical Reports Server (NTRS)

Archer, Douglas; Ming, D.; Niles, P.; Sutter, B.; Lauer, H.

2012-01-01

Two of the most important discoveries of the Phoenix Lander were the detection of approx.0.6% perchlorate [1] and 3-5% carbonate [2] in landing site soils. The Thermal and Evolved Gas Analyzer (TEGA) instrument on the Phoenix lander could heat samples up to approx.1000 C and monitor evolved gases with a mass spectrometer. TEGA detected a low (approx.350 C) and high (approx.750 C) temperature CO2 release. The high temp release was attributed to the thermal decomposition of Ca-carbonate (calcite). The low temperature CO2 release could be due to desorption of CO2, decomposition of a different carbonate mineral, or the combustion of organic material. A new hypothesis has also been proposed that the low temperature CO2 release could be due to the early breakdown of calcite in the presence of the decomposition products of certain perchlorate salts [3]. We have investigated whether or not this new hypothesis is also compatible with organic combustion. Magnesium perchlorate is stable as Mg(ClO4)2-6H2O on the martian surface [4]. During thermal decomposition, this perchlorate salt releases H2O, Cl2, and O2 gases. The Cl2 can react with water to form HCl which then reacts with calcite, releasing CO2 below the standard thermal decomposition temperature of calcite. However, when using concentrations of perchlorate and calcite similar to what was detected by Phoenix, the ratio of high:low temperature CO2 evolved is much larger in the lab, indicating that although this process might contribute to the low temp CO2 release, it cannot account for all of it. While H2O and Cl2 cause calcite decomposition, the O2 evolved during perchlorate decomposition can lead to the combustion of any reduced carbon present in the sample [5]. We investigate the possible contribution of organic molecules to the low temperature CO2 release seen on Mars.

Fe Isolated Single Atoms on S, N Codoped Carbon by Copolymer Pyrolysis Strategy for Highly Efficient Oxygen Reduction Reaction.

PubMed

Li, Qiheng; Chen, Wenxing; Xiao, Hai; Gong, Yue; Li, Zhi; Zheng, Lirong; Zheng, Xusheng; Yan, Wensheng; Cheong, Weng-Chon; Shen, Rongan; Fu, Ninghua; Gu, Lin; Zhuang, Zhongbin; Chen, Chen; Wang, Dingsheng; Peng, Qing; Li, Jun; Li, Yadong

2018-06-01

Heteroatom-doped Fe-NC catalyst has emerged as one of the most promising candidates to replace noble metal-based catalysts for highly efficient oxygen reduction reaction (ORR). However, delicate controls over their structure parameters to optimize the catalytic efficiency and molecular-level understandings of the catalytic mechanism are still challenging. Herein, a novel pyrrole-thiophene copolymer pyrolysis strategy to synthesize Fe-isolated single atoms on sulfur and nitrogen-codoped carbon (Fe-ISA/SNC) with controllable S, N doping is rationally designed. The catalytic efficiency of Fe-ISA/SNC shows a volcano-type curve with the increase of sulfur doping. The optimized Fe-ISA/SNC exhibits a half-wave potential of 0.896 V (vs reversible hydrogen electrode (RHE)), which is more positive than those of Fe-isolated single atoms on nitrogen codoped carbon (Fe-ISA/NC, 0.839 V), commercial Pt/C (0.841 V), and most reported nonprecious metal catalysts. Fe-ISA/SNC is methanol tolerable and shows negligible activity decay in alkaline condition during 15 000 voltage cycles. X-ray absorption fine structure analysis and density functional theory calculations reveal that the incorporated sulfur engineers the charges on N atoms surrounding the Fe reactive center. The enriched charge facilitates the rate-limiting reductive release of OH* and therefore improved the overall ORR efficiency. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microscopically based energy density functionals for nuclei using the density matrix expansion: Implementation and pre-optimization

NASA Astrophysics Data System (ADS)

Stoitsov, M.; Kortelainen, M.; Bogner, S. K.; Duguet, T.; Furnstahl, R. J.; Gebremariam, B.; Schunck, N.

2010-11-01

In a recent series of articles, Gebremariam, Bogner, and Duguet derived a microscopically based nuclear energy density functional by applying the density matrix expansion (DME) to the Hartree-Fock energy obtained from chiral effective field theory two- and three-nucleon interactions. Owing to the structure of the chiral interactions, each coupling in the DME functional is given as the sum of a coupling constant arising from zero-range contact interactions and a coupling function of the density arising from the finite-range pion exchanges. Because the contact contributions have essentially the same structure as those entering empirical Skyrme functionals, a microscopically guided Skyrme phenomenology has been suggested in which the contact terms in the DME functional are released for optimization to finite-density observables to capture short-range correlation energy contributions from beyond Hartree-Fock. The present article is the first attempt to assess the ability of the newly suggested DME functional, which has a much richer set of density dependencies than traditional Skyrme functionals, to generate sensible and stable results for nuclear applications. The results of the first proof-of-principle calculations are given, and numerous practical issues related to the implementation of the new functional in existing Skyrme codes are discussed. Using a restricted singular value decomposition optimization procedure, it is found that the new DME functional gives numerically stable results and exhibits a small but systematic reduction of our test χ2 function compared to standard Skyrme functionals, thus justifying its suitability for future global optimizations and large-scale calculations.

Fate of peat-derived carbon and associated CO2 and CO emissions from two Southeast Asian estuaries

NASA Astrophysics Data System (ADS)

Müller, D.; Warneke, T.; Rixen, T.; Müller, M.; Mujahid, A.; Bange, H. W.; Notholt, J.

2015-06-01

Coastal peatlands in Southeast Asia release large amounts of organic carbon to rivers, which transport it further to the adjacent estuaries. However, little is known about the fate of this terrestrial material in the coastal ocean. Although Southeast Asia is, by area, considered a hotspot of estuarine CO2 emissions, studies in this region are very scarce. We measured dissolved and particulate organic carbon, carbon dioxide (CO2) partial pressure and carbon monoxide (CO) concentrations in two tropical estuaries in Sarawak, Malaysia, whose coastal area is covered by peatlands. We surveyed the estuaries of the rivers Lupar and Saribas during the wet and dry season, respectively. The spatial distribution and the carbon-to-nitrogen ratios of dissolved organic matter (DOM) suggest that peat-draining rivers convey terrestrial organic carbon to the estuaries. We found evidence that a large fraction of this carbon is respired. The median pCO2 in the estuaries ranged between 618 and 5064 μatm with little seasonal variation. CO2 fluxes were determined with a floating chamber and estimated to amount to 14-272 mol m-2 yr-1, which is high compared to other studies from tropical and subtropical sites. In contrast, CO concentrations and fluxes were relatively moderate (0.3-1.4 nmol L-1 and 0.8-1.9 mmol m-2 yr-1) if compared to published data for oceanic or upwelling systems. We attributed this to the large amounts of suspended matter (4-5004 mg L-1), limiting the light penetration depth. However, the diurnal variation of CO suggests that it is photochemically produced, implying that photodegradation might play a role for the removal of DOM from the estuary as well. We concluded that unlike smaller peat-draining tributaries, which tend to transport most carbon downstream, estuaries in this region function as an efficient filter for organic carbon and release large amounts of CO2 to the atmosphere. The Lupar and Saribas mid-estuaries release 0.4 ± 0.2 Tg C yr-1, which corresponds to approximately 80% of the emissions from the aquatic systems in these two catchments.

Controlled Release from Recombinant Polymers

PubMed Central

Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

2014-01-01

Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

Single ocular injection of a sustained-release anti-VEGF delivers 6 months pharmacokinetics and efficacy in a primate laser CNV model

PubMed Central

Adamson, Peter; Wilde, Thomas; Dobrzynski, Eric; Sychterz, Caroline; Polsky, Rodd; Kurali, Edit; Haworth, Richard; Tang, Chi-Man; Korczynska, Justyna; Cook, Fiona; Papanicolaou, Irene; Tsikna, Lemy; Roberts, Chris; Hughes-Thomas, Zoe; Walford, James; Gibson, Daniel; Warrack, John; Smal, Jos; Verrijk, Ruud; Miller, Paul E.; Nork, T. Michael; Prusakiewicz, Jeffery; Streit, Timothy; Sorden, Steven; Struble, Craig; Christian, Brian; Catchpole, Ian R.

2017-01-01

A potent anti-vascular endothelial growth factor (VEGF) biologic and a compatible delivery system were co-evaluated for protection against wet age-related macular degeneration (AMD) over a 6month period following a single intravitreal (IVT) injection. The anti-VEGF molecule is dimeric, containing two different anti-VEGF domain antibodies (dAb) attached to a human IgG1 Fc region: a dual dAb. The delivery system is based on microparticles of PolyActive™ hydrogel co-polymer. The molecule was evaluated both in vitro for potency against VEGF and in ocular VEGF-driven efficacy modelsin vivo. The dual dAb is highly potent, showing a lower IC50 than aflibercept in VEGF receptor binding assays (RBAs) and retaining activity upon release from microparticles over 12 months in vitro. Microparticles released functional dual dAb in rabbit and primate eyes over 6 months at sufficient levels to protect Cynomolgus against laser-induced grade IV choroidal neovascularisation (CNV). This demonstrates proof of concept for delivery of an anti-VEGF molecule within a sustained-release system, showing protection in a pre-clinical primate model of wet AMD over 6 months. Polymer breakdown and movement of microparticles in the eye may limit development of particle-based approaches for sustained release after IVT injection. PMID:27810558

Polymer-Based Nanofibers Impregnated with Drug Infused Plant Virus Particles as a Responsive Fabric for Therapeutic Delivery

NASA Astrophysics Data System (ADS)

Honarbakhsh, Sara

A biodegradable and controlled drug delivery system has been developed herein composed of electrospun polymeric nanofibers impregnated with cargo loaded Red clover necrotic mosaic virus (RCNMV)---a robust plant virus---as the drug carrier nanoparticle. In this system, controlled drug release is achieved by altering the porosity of the biodegradable matrix as well as controlling the position and distribution of the cargo loaded nanocarriers in the matrix. Solution electrospinning as well as dipping method are used to create and to impregnate the matrix (the fibers of which possess uniformly distributed nano-size surface pores) with cargo loaded nanocarriers. Prior to the impregnation stage of cargo loaded nanocarriers into the matrix, compatibility of a group of candidate cargos (Ampicillin, Novanthrone, Doxorubicin and Ethidium Bromide) and RCNMV functionality with potential electrospinning solvents were investigated and a solvent with the least degradative effect was selected. In order to achieve both sustained and immediate drug release profiles, cargo loaded nanocarriers were embedded into the matrix---through co-spinning process---as well as on the surface of matrix fibers---through dipping method. SEM, TEM and Fluorescent Light Microscopy images of the medicated structures suggested that the nanocarriers were incorporated into/on the matrix. In vitro release assays were also carried out the results of which confirmed having obtained sustained release in the co-spun medicated structures where as dipped samples showed an immediate release profile.

Effect of Polymer Porosity on Aqueous Self-Healing Encapsulation of Proteins in PLGA Microspheres

PubMed Central

Reinhold, Samuel E.

2014-01-01

Self-healing (SH) poly(lactic-co-glycolic acid) (PLGA) microspheres are a unique class of functional biomaterials capable of microencapsulating process-sensitive proteins by simple mixing and heating the drug-free polymer in aqueous protein solution. Drug-free SH microspheres of PLGA 50/50 with percolating pore networks of varying porosity (ε = 0.49–73) encapsulate increasing lysozyme (~1–10% w/w) with increasing ε, with typically ~20–25% pores estimated assessible to entry by the enzyme from the external solution. Release kinetics of lysozyme under physiological conditions is continuous over > 2 weeks and most strongly influenced by ε and protein loading before reaching a lag phase until 28 days at the study completion. Recovered enzyme after release is typically predominantly monomeric and active. Formulations containing acid-neutralizing MgCO3 at >4.3% exhibit >97% monomeric and active protein after the release with full mass balance recovery. Hence, control of SH polymer ε is a key parameter to development of this new class of biomaterials. PMID:24285573

Hollow Carbon Nanobubbles: Synthesis, Chemical Functionalization, and Container-Type Behavior in Water.

PubMed

Hofer, Corinne J; Grass, Robert N; Zeltner, Martin; Mora, Carlos A; Krumeich, Frank; Stark, Wendelin J

2016-07-18

Thin-walled, hollow carbon nanospheres with a hydrophobic interior and good water dispersability can be synthesized in two steps: First, metal nanoparticles, coated with a few layers of graphene-like carbon, are selectively modified on the outside with a covalently attached hydrophilic polymer. Second, the metal core is removed at elevated temperature treatment with acid, leaving a well-defined carbon-based hydrophobic cavity. Loading experiments with the dye rhodamine B and doxorubicin confirmed the filling and release of a cargo and adjustment of a dynamic equilibrium (cargo-loaded versus release). Rhodamine B preferably accumulates in the interior of the bubbles. Filled nanobubbles allowed constant dye release into pure water. Studies of the concentration-dependent loading and release show an unusual hysteresis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Effective Way to Optimize the Functionality of Graphene-Based Nanocomposite: Use of the Colloidal Mixture of Graphene and Inorganic Nanosheets

NASA Astrophysics Data System (ADS)

Jin, Xiaoyan; Adpakpang, Kanyaporn; Young Kim, In; Mi Oh, Seung; Lee, Nam-Suk; Hwang, Seong-Ju

2015-06-01

The best electrode performance of metal oxide-graphene nanocomposite material for lithium secondary batteries can be achieved by using the colloidal mixture of layered CoO2 and graphene nanosheets as a precursor. The intervention of layered CoO2 nanosheets in-between graphene nanosheets is fairly effective in optimizing the pore and composite structures of the Co3O4-graphene nanocomposite and also in enhancing its electrochemical activity via the depression of interaction between graphene nanosheets. The resulting CoO2 nanosheet-incorporated nanocomposites show much greater discharge capacity of ~1750 mAhg-1 with better cyclability and rate characteristics than does CoO2-free Co3O4-graphene nanocomposite (~1100 mAhg-1). The huge discharge capacity of the present nanocomposite is the largest one among the reported data of cobalt oxide-graphene nanocomposite. Such a remarkable enhancement of electrode performance upon the addition of inorganic nanosheet is also observed for Mn3O4-graphene nanocomposite. The improvement of electrode performance upon the incorporation of inorganic nanosheet is attributable to an improved Li+ ion diffusion, an enhanced mixing between metal oxide and graphene, and the prevention of electrode agglomeration. The present experimental findings underscore an efficient and universal role of the colloidal mixture of graphene and redoxable metal oxide nanosheets as a precursor for improving the electrode functionality of graphene-based nanocomposites.

Super-optimal CO2 reduces seed yield but not vegetative growth in wheat

NASA Technical Reports Server (NTRS)

Grotenhuis, T. P.; Bugbee, B.

1997-01-01

Although terrestrial atmospheric CO2 levels will not reach 1000 micromoles mol-1 (0.1%) for decades, CO2 levels in growth chambers and greenhouses routinely exceed that concentration. CO2 levels in life support systems in space can exceed 10000 micromoles mol-1(1%). Numerous studies have examined CO2 effects up to 1000 micromoles mol-1, but biochemical measurements indicate that the beneficial effects of CO2 can continue beyond this concentration. We studied the effects of near-optimal (approximately 1200 micromoles mol-1) and super-optimal CO2 levels (2400 micromoles mol-1) on yield of two cultivars of hydroponically grown wheat (Triticum aestivum L.) in 12 trials in growth chambers. Increasing CO2 from sub-optimal to near-optimal (350-1200 micromoles mol-1) increased vegetative growth by 25% and seed yield by 15% in both cultivars. Yield increases were primarily the result of an increased number of heads per square meter. Further elevation of CO2 to 2500 micromoles mol-1 reduced seed yield by 22% (P < 0.001) in cv. Veery-10 and by 15% (P < 0.001) in cv. USU-Apogee. Super-optimal CO2 did not decrease the number of heads per square meter, but reduced seeds per head by 10% and mass per seed by 11%. The toxic effect of CO2 was similar over a range of light levels from half to full sunlight. Subsequent trials revealed that super-optimal CO2 during the interval between 2 wk before and after anthesis mimicked the effect of constant super-optimal CO2. Furthermore, near-optimal CO2 during the same interval mimicked the effect of constant near-optimal CO2. Nutrient concentration of leaves and heads was not affected by CO2. These results suggest that super-optimal CO2 inhibits some process that occurs near the time of seed set resulting in decreased seed set, seed mass, and yield.

Development of sustained and dual drug release co-extrusion formulations for individual dosing.

PubMed

Laukamp, Eva Julia; Vynckier, An-Katrien; Voorspoels, Jody; Thommes, Markus; Breitkreutz, Joerg

2015-01-01

In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential retention and release of CO 2 and CH 4 in kerogen nanopores: Implications for gas extraction and carbon sequestration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, Tuan Anh; Wang, Yifeng; Xiong, Yongliang

Methane (CH 4) and carbon dioxide (CO 2), the two major components generated from kerogen maturation, are stored dominantly in nanometer-sized pores in shale matrix as (1) a compressed gas, (2) an adsorbed surface species and/or (3) a species dissolved in pore water (H 2O). In addition, supercritical CO 2 has been proposed as a fracturing fluid for simultaneous enhanced oil/gas recovery (EOR) and carbon sequestration. A mechanistic understanding of CH 4-CO 2-H 2O interactions in shale nanopores is critical for designing effective operational processes. Using molecular simulations, we show that kerogen preferentially retains CO 2 over CH 4 andmore » that the majority of CO 2 either generated during kerogen maturation or injected in EOR will remain trapped in the kerogen matrix. The trapped CO 2 may be released only if the reservoir pressure drops below the supercritical CO 2 pressure. When water is present in the kerogen matrix, it may block CH 4 release. Furthermore, the addition of CO 2 may enhance CH 4 release because CO 2 can diffuse through water and exchange for adsorbed methane in the kerogen nanopores.« less

Differential retention and release of CO 2 and CH 4 in kerogen nanopores: Implications for gas extraction and carbon sequestration

DOE PAGES

Ho, Tuan Anh; Wang, Yifeng; Xiong, Yongliang; ...

2018-02-06

Methane (CH 4) and carbon dioxide (CO 2), the two major components generated from kerogen maturation, are stored dominantly in nanometer-sized pores in shale matrix as (1) a compressed gas, (2) an adsorbed surface species and/or (3) a species dissolved in pore water (H 2O). In addition, supercritical CO 2 has been proposed as a fracturing fluid for simultaneous enhanced oil/gas recovery (EOR) and carbon sequestration. A mechanistic understanding of CH 4-CO 2-H 2O interactions in shale nanopores is critical for designing effective operational processes. Using molecular simulations, we show that kerogen preferentially retains CO 2 over CH 4 andmore » that the majority of CO 2 either generated during kerogen maturation or injected in EOR will remain trapped in the kerogen matrix. The trapped CO 2 may be released only if the reservoir pressure drops below the supercritical CO 2 pressure. When water is present in the kerogen matrix, it may block CH 4 release. Furthermore, the addition of CO 2 may enhance CH 4 release because CO 2 can diffuse through water and exchange for adsorbed methane in the kerogen nanopores.« less

Reliable LC-MS quantitative glycomics using iGlycoMab stable isotope labeled glycans as internal standards.

PubMed

Zhou, Shiyue; Tello, Nadia; Harvey, Alex; Boyes, Barry; Orlando, Ron; Mechref, Yehia

2016-06-01

Glycans have numerous functions in various biological processes and participate in the progress of diseases. Reliable quantitative glycomic profiling techniques could contribute to the understanding of the biological functions of glycans, and lead to the discovery of potential glycan biomarkers for diseases. Although LC-MS is a powerful analytical tool for quantitative glycomics, the variation of ionization efficiency and MS intensity bias are influencing quantitation reliability. Internal standards can be utilized for glycomic quantitation by MS-based methods to reduce variability. In this study, we used stable isotope labeled IgG2b monoclonal antibody, iGlycoMab, as an internal standard to reduce potential for errors and to reduce variabililty due to sample digestion, derivatization, and fluctuation of nanoESI efficiency in the LC-MS analysis of permethylated N-glycans released from model glycoproteins, human blood serum, and breast cancer cell line. We observed an unanticipated degradation of isotope labeled glycans, tracked a source of such degradation, and optimized a sample preparation protocol to minimize degradation of the internal standard glycans. All results indicated the effectiveness of using iGlycoMab to minimize errors originating from sample handling and instruments. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Activation of platelet-rich plasma using thrombin receptor agonist peptide.

PubMed

Landesberg, Regina; Burke, Andrea; Pinsky, David; Katz, Ronald; Vo, Jennifer; Eisig, Sidney B; Lu, Helen H

2005-04-01

This study proposes an alternative preparation method of platelet-rich plasma (PRP). Specifically, we compare the use of thrombin receptor agonist peptide-6 (TRAP) and bovine thrombin as a clotting agent in the preparation of PRP. PRP was prepared by centrifugation and clotted with thrombin or TRAP. In vitro clotting times were monitored as a function of TRAP concentration, and clot retraction was determined by measuring clot diameter over time. Following the optimization of TRAP concentration, experiments were repeated with the addition of several commercially available bone substitutes. The release of PRP-relevant growth factors as a function of PRP preparation was also determined. The most rapid polymerization of PRP takes place with the addition of thrombin, followed by TRAP/Allogro (Ceramed, Lakewood, CO), TRAP/BioGlass (Mo-Sci, Rolla, MN), TRAP/BioOss (Osteohealth, Shirley, NY), and TRAP alone. Thrombin caused considerable clot retraction (43%), whereas TRAP alone resulted in only 15% retraction. TRAP/Allogro, TRAP/BioOss, and TRAP/BioGlass all exhibited minimal retraction (8%). The use of TRAP to activate clot formation in the preparation of PRP may be a safe alternative to bovine thrombin. It results in an excellent working time and significantly less clot retraction than the currently available methods of PRP production.

Highly Efficient Gating of Electrically Actuated Nanochannels for Pulsatile Drug Delivery Stemming from a Reversible Wettability Switch.

PubMed

Zhang, Qianqian; Kang, Jianxin; Xie, Zhiqiang; Diao, Xungang; Liu, Zhaoyue; Zhai, Jin

2018-01-01

Many ion channels in the cell membrane are believed to function as gates that control the water and ion flow through the transitions between an inherent hydrophobic state and a stimuli-induced hydration state. The construction of nanofluidic gating systems with high gating efficiency and reversibility is inspired by this hydrophobic gating behavior. A kind of electrically actuated nanochannel is developed by integrating a polypyrrole (PPy) micro/nanoporous film doped with perfluorooctanesulfonate ions onto an anodic aluminum oxide nanoporous membrane. Stemming from the reversible wettability switch of the doped PPy film in response to the applied redox potentials, the nanochannels exhibit highly efficient and reversible gating behaviors. The optimized gating ratio is over 10 5 , which is an ultrahigh value when compared with that of the existing reversibly gated nanochannels with comparable pore diameters. Furthermore, the gating behavior of the electrically actuated nanochannels shows excellent repeatability and stability. Based on this highly efficient and reversible gating function, the electrically actuated nanochannels are further applied for drug delivery, which achieves the pulsatile release of two water-soluble drug models. The electrically actuated nanochannels may find potential applications in accurate and on-demand drug therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Research Progress on the Interaction Effects and Its Neural Mechanisms between Physical Fatigue and Mental Fatigue].

PubMed

Zhang, Lixin; Zhang, Chuncui; He, Feng; Zhao, Xin; Qi, Hongzhi; Wan, Baikun; Ming, Dong

2015-10-01

Fatigue is an exhaustion state caused by prolonged physical work and mental work, which can reduce working efficiency and even cause industrial accidents. Fatigue is a complex concept involving both physiological and psychological factors. Fatigue can cause a decline of concentration and work performance and induce chronic diseases. Prolonged fatigue may endanger life safety. In most of the scenarios, physical and mental workloads co-lead operator into fatigue state. Thus, it is very important to study the interaction influence and its neural mechanisms between physical and mental fatigues. This paper introduces recent progresses on the interaction effects and discusses some research challenges and future development directions. It is believed that mutual influence between physical fatigue and mental fatigue may occur in the central nervous system. Revealing the basal ganglia function and dopamine release may be important to explore the neural mechanisms between physical fatigue and mental fatigue. Future effort is to optimize fatigue models, to evaluate parameters and to explore the neural mechanisms so as to provide scientific basis and theoretical guidance for complex task designs and fatigue monitoring.

Toxic effects of vanadium (V) on a combined autotrophic denitrification system using sulfur and hydrogen as electron donors.

PubMed

Chen, Dan; Xiao, Zhixing; Wang, Hongyu; Yang, Kai

2018-05-27

Vanadium (V) is a common heavy metal and often co-occurs with nitrate in effluents from mining and metal finishing industry. In the present study, the toxic effects of V(V) were examined in a sulfur and hydrogen based autotrophic denitrification system. This combined system achieved simultaneously microbial denitrification and V(V) reduction. High concentration of V(V) (60 and 100 mg/L) inhibited the denitrification activities, while 30 mg/L V(V) had a very slight effect. V(V) induced increases of lactate dehydrogenase release and reactive oxygen species production, which may inhibit nitrate and nitrite reductases activities and abundances of denitrifying functional genes. Moreover, the extracellular polymeric substance production was also suppressed under V(V) stress, thereby decreasing the amount of biofilm biomass. Microbial community analyses suggesting the genus Bacillus may have higher tolerance to V(V). These findings can provide scientific basis for the optimized design of treatment system to remove nitrate and V(V) simultaneously. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Optimization of calcium alginate floating microspheres loading aspirin by artificial neural networks and response surface methodology].

PubMed

Zhang, An-yang; Fan, Tian-yuan

2010-04-18

To investigate the preparation and optimization of calcium alginate floating microspheres loading aspirin. A model was used to predict the in vitro release of aspirin and optimize the formulation by artificial neural networks (ANNs) and response surface methodology (RSM). The amounts of the material in the formulation were used as inputs, while the release and floating rate of the microspheres were used as outputs. The performances of ANNs and RSM were compared. ANNs were more accurate in prediction. There was no significant difference between ANNs and RSM in optimization. Approximately 90% of the optimized microspheres could float on the artificial gastric juice over 4 hours. 42.12% of aspirin was released in 60 min, 60.97% in 120 min and 78.56% in 240 min. The release of the drug from the microspheres complied with Higuchi equation. The aspirin floating microspheres with satisfying in vitro release were prepared successfully by the methods of ANNs and RSM.

Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol.

PubMed

Jagdale, Swati C; Bari, Nilesh A; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 3² full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol

PubMed Central

Jagdale, Swati C.; Bari, Nilesh A.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form. PMID:24367788

A global analysis of adaptive evolution of operons in cyanobacteria.

PubMed

Memon, Danish; Singh, Abhay K; Pakrasi, Himadri B; Wangikar, Pramod P

2013-02-01

Operons are an important feature of prokaryotic genomes. Evolution of operons is hypothesized to be adaptive and has contributed significantly towards coordinated optimization of functions. Two conflicting theories, based on (i) in situ formation to achieve co-regulation and (ii) horizontal gene transfer of functionally linked gene clusters, are generally considered to explain why and how operons have evolved. Furthermore, effects of operon evolution on genomic traits such as intergenic spacing, operon size and co-regulation are relatively less explored. Based on the conservation level in a set of diverse prokaryotes, we categorize the operonic gene pair associations and in turn the operons as ancient and recently formed. This allowed us to perform a detailed analysis of operonic structure in cyanobacteria, a morphologically and physiologically diverse group of photoautotrophs. Clustering based on operon conservation showed significant similarity with the 16S rRNA-based phylogeny, which groups the cyanobacterial strains into three clades. Clade C, dominated by strains that are believed to have undergone genome reduction, shows a larger fraction of operonic genes that are tightly packed in larger sized operons. Ancient operons are in general larger, more tightly packed, better optimized for co-regulation and part of key cellular processes. A sub-clade within Clade B, which includes Synechocystis sp. PCC 6803, shows a reverse trend in intergenic spacing. Our results suggest that while in situ formation and vertical descent may be a dominant mechanism of operon evolution in cyanobacteria, optimization of intergenic spacing and co-regulation are part of an ongoing process in the life-cycle of operons.

Surface PEGylation of mesoporous silica materials via surface-initiated chain transfer free radical polymerization: Characterization and controlled drug release.

PubMed

Huang, Long; Liu, Meiying; Mao, Liucheng; Huang, Qiang; Huang, Hongye; Wan, Qing; Tian, Jianwen; Wen, Yuanqing; Zhang, Xiaoyong; Wei, Yen

2017-12-01

As a new type of mesoporous silica materials with large pore diameter (pore size between 2 and 50nm) and high specific surface areas, SBA-15 has been widely explored for different applications especially in the biomedical fields. The surface modification of SBA-15 with functional polymers has demonstrated to be an effective way for improving its properties and performance. In this work, we reported the preparation of PEGylated SBA-15 polymer composites through surface-initiated chain transfer free radical polymerization for the first time. The thiol group was first introduced on SBA-15 via co-condensation with γ-mercaptopropyltrimethoxysilane (MPTS), that were utilized to initiate the chain transfer free radical polymerization using poly(ethylene glycol) methyl ether methacrylate (PEGMA) and itaconic acid (IA) as the monomers. The successful modification of SBA-15 with poly(PEGMA-co-IA) copolymers was evidenced by a series of characterization techniques, including 1 H NMR, FT-IR, TGA and XPS. The final SBA-15-SH- poly(PEGMA-co-IA) composites display well water dispersity and high loading capability towards cisplatin (CDDP) owing to the introduction of hydrophilic PEGMA and carboxyl groups. Furthermore, the CDDP could be released from SBA-15-SH-poly(PEGMA-co-IA)-CDDP complexes in a pH dependent behavior, suggesting the potential controlled drug delivery of SBA-15-SH-poly(PEGMA-co-IA). More importantly, the strategy should be also useful for fabrication of many other functional materials for biomedical applications owing to the advantages of SBA-15 and well monomer adoptability of chain transfer free radical polymerization. Copyright © 2017 Elsevier B.V. All rights reserved.

Using NMR spectroscopy to elucidate the role of molecular motions in enzyme function

PubMed Central

Lisi, George P.; Loria, J. Patrick

2015-01-01

Conformational motions play an essential role in enzyme function, often facilitating the formation of enzyme-substrate complexes and/or product release. Although considerable debate remains regarding the role of molecular motions in the conversion of enzymatic substrates to products, numerous examples have found motions to be crucial for optimization of enzyme scaffolds, effective substrate binding, and product dissociation. Conformational fluctuations are often rate-limiting to enzyme catalysis, primarily through product release, with the chemical reaction occurring much more quickly. As a result, the direct involvement of motions at various stages along the enzyme reaction coordinate remains largely unknown and untested. In the following review, we describe the use of solution NMR techniques designed to probe various timescales of molecular motions and detail examples in which motions play a role in propagating catalytic effects from the active site and directly participate in essential aspects of enzyme function. PMID:26952190

Formation of nanoparticles of a hydrophilic drug using supercritical carbon dioxide and microencapsulation for sustained release.

PubMed

Thote, Amol J; Gupta, Ram B

2005-03-01

Our purpose was to produce nanoparticles of a hydrophilic drug with use of supercritical carbon dioxide (CO2), encapsulate the obtained nanoparticles into polymer microparticles with use of an anhydrous method and study their sustained in vitro drug release. The hydrophilic drug, dexamethasone phosphate, is dissolved in methanol and injected in supercritical CO2 with an ultrasonic field for enhanced molecular mixing (supercritical antisolvent technique with enhanced mass transfer [SAS-EM]). Supercritical CO2 rapidly extracts methanol leading to instantaneous precipitation of drug nanoparticles. The nanoparticles are then encapsulated in poly(lactide-co-glycolide) (PLGA) polymer by use of the anhydrous solid-oil-oil-oil technique. This results in a well-dispersed encapsulation of drug nanoparticles in polymer microspheres. In vitro drug release from these microparticles is studied. With supercritical CO2 used as an antisolvent, nanoparticles of dexamethasone phosphate were obtained in the range of 150 to 200 nm. On encapsulation in polylactide coglycolide, composite microspheres of approximately 70 microm were obtained. The in vitro drug release of these nanoparticles/microparticles composites shows sustained release of dexamethasone phosphate over a period of 700 hours with almost no initial burst release. Nanoparticles of dexamethasone phosphate can be produced with the SAS-EM technique. When microencapsulated, these particles can provide sustained drug release without initial burst release. Because the complete process is anhydrous, it can be easily extended to produce sustained release formulations of other hydrophilic drugs.

Ocean sequestration of carbon dioxide: modeling the deep ocean release of a dense emulsion of liquid Co2-in-water stabilized by pulverized limestone particles.

PubMed

Golomb, D; Pennell, S; Ryan, D; Barry, E; Swett, P

2007-07-01

The release into the deep ocean of an emulsion of liquid carbon dioxide-in-seawater stabilized by fine particles of pulverized limestone (CaCO3) is modeled. The emulsion is denser than seawater, hence, it will sink deeper from the injection point, increasing the sequestration period. Also, the presence of CaCO3 will partially buffer the carbonic acid that results when the emulsion eventually disintegrates. The distance that the plume sinks depends on the density stratification of the ocean, the amount of the released emulsion, and the entrainment factor. When released into the open ocean, a plume containing the CO2 output of a 1000 MW(el) coal-fired power plant will typically sink hundreds of meters below the injection point. When released from a pipe into a valley on the continental shelf, the plume will sink about twice as far because of the limited entrainment of ambient seawater when the plume flows along the valley. A practical system is described involving a static mixer for the in situ creation of the CO2/seawater/pulverized limestone emulsion. The creation of the emulsion requires significant amounts of pulverized limestone, on the order of 0.5 tons per ton of liquid CO2. That increases the cost of ocean sequestration by about $13/ ton of CO2 sequestered. However, the additional cost may be compensated by the savings in transportation costs to greater depth, and because the release of an emulsion will not acidify the seawater around the release point.

Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

PubMed

Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

2014-10-06

The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Orthogonal Clickable Iron Oxide Nanoparticle Platform for Targeting, Imaging, and On-Demand Release.

PubMed

Guldris, Noelia; Gallo, Juan; García-Hevia, Lorena; Rivas, José; Bañobre-López, Manuel; Salonen, Laura M

2018-04-12

A versatile iron oxide nanoparticle platform is reported that can be orthogonally functionalized to obtain highly derivatized nanomaterials required for a wide variety of applications, such as drug delivery, targeted therapy, or imaging. Facile functionalization of the nanoparticles with two ligands containing isocyanate moieties allows for high coverage of the surface with maleimide and alkyne groups. As a proof-of-principle, the nanoparticles were subsequently functionalized with a fluorophore as a drug model and with biotin as a targeting ligand towards tumor cells through Diels-Alder and azide-alkyne cycloaddition reactions, respectively. The thermoreversibility of the Diels-Alder product was exploited to induce the on-demand release of the loaded molecules by magnetic hyperthermia. Additionally, the nanoparticles were shown to target cancer cells through in vitro experiments, as analyzed by magnetic resonance imaging. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiple response optimization of processing and formulation parameters of Eudragit RL/RS-based matrix tablets for sustained delivery of diclofenac.

PubMed

Elzayat, Ehab M; Abdel-Rahman, Ali A; Ahmed, Sayed M; Alanazi, Fars K; Habib, Walid A; Sakr, Adel

2017-11-01

Multiple response optimization is an efficient technique to develop sustained release formulation while decreasing the number of experiments based on trial and error approach. Diclofenac matrix tablets were optimized to achieve a release profile conforming to USP monograph, matching Voltaren ® SR and withstand formulation variables. The percent of drug released at predetermined multiple time points were the response variables in the design. Statistical models were obtained with relative contour diagrams being overlaid to predict process and formulation parameters expected to produce the target release profile. Tablets were prepared by wet granulation using mixture of equivalent quantities of Eudragit RL/RS at overall polymer concentration of 10-30%w/w and compressed at 5-15KN. Drug release from the optimized formulation E4 (15%w/w, 15KN) was similar to Voltaren, conformed to USP monograph and found to be stable. Substituting lactose with mannitol, reversing the ratio between lactose and microcrystalline cellulose or increasing drug load showed no significant difference in drug release. Using dextromethorphan hydrobromide as a model soluble drug showed burst release due to higher solubility and formation of micro cavities. A numerical optimization technique was employed to develop a stable consistent promising formulation for sustained delivery of diclofenac.

Structures and Energetics of (MgCO 3 ) n Clusters ( n ≤ 16)

DOE PAGES

Chen, Mingyang; Jackson, Virgil E.; Felmy, Andrew R.; ...

2015-03-13

There is significant interest in the role of carbonate minerals for the storage of CO 2 and the role of prenucleation dusters in their formation. Global minima for (MgCO 3) n (n ≤ 16) structures were optimized using a tree growth-hybrid genetic algorithm in conjunction with MNDO/MNDO/d semiempirical molecular orbital calculations followed by density functional theory geometry optimizations with the B3LYP functional. The most stable isomers for (MgCO 3) n (n < 5) are approximately 2-dimensional. Mg can be bonded to one or two 0 atoms of a CO 3 2-, and the 1-O bonding scheme is more favored asmore » the cluster becomes larger. The average C-Mg coordination number increases as the cluster size increases, and at n = 16, the average C-Mg coordination number was calculated to be 5.2. The normalized dissociation energy to form monomers increases as n increases. At n = 16, the normalized dissociation energy is calculated to be 116.2 kcal/mol, as compared to the bulk value of 153.9 kcal/mol. The adiabatic reaction energies for the recombination reactions of (MgO) nclusters and CO 2 to form (MgCO 3) n were calculated. The exothermicity of the normalized recombination energy < RE >(CO 2) decreases as n increases and converged to the experimental bulk limit rapidly. The normalized recombination energy < RE >(CO 2) was calculated to be -52.2 kcal/mol for the monomer and -30.7 kcal/mol for n = 16, as compared to the experimental value of -27.9 kcal/mol for the solid phase reaction. Infrared spectra for the lowest energy isomers were calculated, and absorption bands in the previous experimental infrared studies were assigned with our density functional theory predictions. The 13C, 17O, and 25Mg NMR chemical shifts for the clusters were predicted. We found that the results provide insights into the structural and energetic transitions from nanoclusters of (MgCO 3) n to the bulk and the spectroscopic properties of clusters for their experimental identification.« less

Covalent modification of reduced graphene oxide by means of diazonium chemistry and use as a drug-delivery system.

PubMed

Wei, Guangcheng; Yan, Miaomiao; Dong, Renhao; Wang, Dong; Zhou, Xiangzhu; Chen, Jingfei; Hao, Jingcheng

2012-11-12

Under acidic conditions, reduced graphene oxide (rGO) was functionalized with p-aminobenzoic acid, which formed the diazonium ions through the diazotization with a wet-chemical method. Surfactants or stabilizers were not applied during the diazotization. After the functionalized rGO was treated through mild sonication in aqueous solution, these functionalized rGO sheets were less than two layers, which was determined by atomic force microscopy (AFM) imaging. The water solubility of functionalized rGO after the introduction of polyethyleneimine (PEI) was improved significantly; it was followed by covalent binding of folic acid (FA) molecules to the functionalized rGO to allow us to specifically target CBRH7919 cancer cells by using FA as a receptor. The loading and release behaviors of elsinochrome A (EA) and doxorubicin (DOX) on the functionalized rGO sheets were investigated. The EA loading ratio onto rGO-C(6)H(4)-CO-NH-PEI-NH-CO-FA (abbreviated rGO-PEI-FA, the weight ratio of drug loaded onto rGO-PEI-FA) was approximately 45.56 %, and that of DOX was approximately 28.62 %. It was interesting that the drug release from rGO-PEI-FA was pH- and salt-dependent. The results of cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM) assays, as well as cell morphology observations) clearly showed that the concentration of rGO-PEI-FA as the drug-delivery composite should be less than 12.5 mg L(-1). The conjugation of DOX and rGO-PEI-FA can enhance the cancer-cell apoptosis effectively and can also push the cancer cells to the vulnerable G2 phase of the cell cycle, which is most sensitive and susceptible to damage by drugs or radiation. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and properties of mecoprop-intercalated layered double hydroxide

NASA Astrophysics Data System (ADS)

Ahmed Khan, Modabber; Choi, Choong-Lyeal; Lee, Dong-Hoon; Park, Man; Lim, Bu-Kug; Lee, Jong-Yoon; Choi, Jyung

2007-08-01

This study carried out to elucidate the synthesis of MCPP LDH hybrid, release pattern of MCPP from MCPP LDH hybrid and their properties. MCPP LDH hybrid was synthesized from MCPP and Mg Al complex. Release pattern of MCPP from MCPP LDH hybrid was slower in distilled water and soil solution but it was slower in distilled water than soil solution. MCPP LDH hybrid has shown more stable condition than CO32- form of LDH in thermal and acidic condition. Therefore, MCPP LDH hybrid would lead as functional and benign pesticide to minimize the harmful effects on soil environment by bulk herbicides.

RIM-BPs Mediate Tight Coupling of Action Potentials to Ca(2+)-Triggered Neurotransmitter Release.

PubMed

Acuna, Claudio; Liu, Xinran; Gonzalez, Aneysis; Südhof, Thomas C

2015-09-23

Ultrafast neurotransmitter release requires tight colocalization of voltage-gated Ca(2+) channels with primed, release-ready synaptic vesicles at the presynaptic active zone. RIM-binding proteins (RIM-BPs) are multidomain active zone proteins that bind to RIMs and to Ca(2+) channels. In Drosophila, deletion of RIM-BPs dramatically reduces neurotransmitter release, but little is known about RIM-BP function in mammalian synapses. Here, we generated double conditional knockout mice for RIM-BP1 and RIM-BP2, and analyzed RIM-BP-deficient synapses in cultured hippocampal neurons and the calyx of Held. Surprisingly, we find that in murine synapses, RIM-BPs are not essential for neurotransmitter release as such, but are selectively required for high-fidelity coupling of action potential-induced Ca(2+) influx to Ca(2+)-stimulated synaptic vesicle exocytosis. Deletion of RIM-BPs decelerated action-potential-triggered neurotransmitter release and rendered it unreliable, thereby impairing the fidelity of synaptic transmission. Thus, RIM-BPs ensure optimal organization of the machinery for fast release in mammalian synapses without being a central component of the machinery itself. Copyright © 2015 Elsevier Inc. All rights reserved.

pH/NIR Light-Controlled Multidrug Release via a Mussel-Inspired Nanocomposite Hydrogel for Chemo-Photothermal Cancer Therapy

NASA Astrophysics Data System (ADS)

Ghavaminejad, Amin; Samarikhalaj, Melisa; Aguilar, Ludwig Erik; Park, Chan Hee; Kim, Cheol Sang

2016-09-01

This study reports on an intelligent composite hydrogel with both pH-dependent drug release in a cancer environment and heat generation based on NIR laser exposure, for the combined application of photothermal therapy (PTT) and multidrug chemotherapy. For the first time in the literature, Dopamine nanoparticle (DP) was incorporated as a highly effective photothermal agent as well as anticancer drug, bortezomib (BTZ) carrier inside a stimuli responsive pNIPAAm-co-pAAm hydrogel. When light is applied to the composite hydrogel, DP nanoparticle absorbs the light, which is dissipated locally as heat to impact cancer cells via hyperthermia. On the other hand, facile release of the anticancer drug BTZ from the surface of DP encapsulated hydrogel could be achieved due to the dissociation between catechol groups of DP and the boronic acid functionality of BTZ in typical acidic cancer environment. In order to increase the synergistic effect by dual drug delivery, Doxorubicin (DOXO) were also loaded to pNIPAAm-co-pAAm/DP-BTZ hydrogel and the effect of monotherapy as well as combined therapy were detailed by a complete characterization. Our results suggest that these mussel inspired nanocomposite with excellent heating property and controllable multidrug release can be considered as a potential material for cancer therapy.

Optimal design of microtube recuperators for an indirect supercritical carbon dioxide recompression closed Brayton cycle

DOE PAGES

Jiang, Yuan; Liese, Eric; Zitney, Stephen E.; ...

2018-02-25

This paper presents a baseline design and optimization approach developed in Aspen Custom Modeler (ACM) for microtube shell-and-tube exchangers (MSTEs) used for high- and low-temperature recuperation in a 10 MWe indirect supercritical carbon dioxide (sCO 2) recompression closed Brayton cycle (RCBC). The MSTE-type recuperators are designed using one-dimensional models with thermal-hydraulic correlations appropriate for sCO 2 and properties models that capture considerable nonlinear changes in CO 2 properties near the critical and pseudo-critical points. Using the successive quadratic programming (SQP) algorithm in ACM, optimal recuperator designs are obtained for either custom or industry-standard microtubes considering constraints based on current advancedmore » manufacturing techniques. The three decision variables are the number of tubes, tube pitch-to-diameter ratio, and tube diameter. Five different objective functions based on different key design measures are considered: minimization of total heat transfer area, heat exchanger volume, metal weight, thermal residence time, and maximization of compactness. Sensitivities studies indicate the constraint on the maximum number of tubes per shell does affect the number of parallel heat exchanger trains but not the tube selection, total number of tubes, tube length and other key design measures in the final optimal design when considering industry-standard tubes. In this study, the optimally designed high- and low-temperature recuperators have 47,000 3/32 inch tubes and 63,000 1/16 inch tubes, respectively. In addition, sensitivities to the design temperature approach and maximum allowable pressure drop are studied, since these specifications significantly impact the optimal design of the recuperators as well as the thermal efficiency and the economic performance of the entire sCO 2 Brayton cycle.« less

Optimal design of microtube recuperators for an indirect supercritical carbon dioxide recompression closed Brayton cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Yuan; Liese, Eric; Zitney, Stephen E.

This paper presents a baseline design and optimization approach developed in Aspen Custom Modeler (ACM) for microtube shell-and-tube exchangers (MSTEs) used for high- and low-temperature recuperation in a 10 MWe indirect supercritical carbon dioxide (sCO 2) recompression closed Brayton cycle (RCBC). The MSTE-type recuperators are designed using one-dimensional models with thermal-hydraulic correlations appropriate for sCO 2 and properties models that capture considerable nonlinear changes in CO 2 properties near the critical and pseudo-critical points. Using the successive quadratic programming (SQP) algorithm in ACM, optimal recuperator designs are obtained for either custom or industry-standard microtubes considering constraints based on current advancedmore » manufacturing techniques. The three decision variables are the number of tubes, tube pitch-to-diameter ratio, and tube diameter. Five different objective functions based on different key design measures are considered: minimization of total heat transfer area, heat exchanger volume, metal weight, thermal residence time, and maximization of compactness. Sensitivities studies indicate the constraint on the maximum number of tubes per shell does affect the number of parallel heat exchanger trains but not the tube selection, total number of tubes, tube length and other key design measures in the final optimal design when considering industry-standard tubes. In this study, the optimally designed high- and low-temperature recuperators have 47,000 3/32 inch tubes and 63,000 1/16 inch tubes, respectively. In addition, sensitivities to the design temperature approach and maximum allowable pressure drop are studied, since these specifications significantly impact the optimal design of the recuperators as well as the thermal efficiency and the economic performance of the entire sCO 2 Brayton cycle.« less

Study of Cs/NF3 adsorption on GaN (0 0 1) surface

NASA Astrophysics Data System (ADS)

Diao, Yu; Liu, Lei; Xia, Sihao; Kong, Yike

2017-03-01

To investigate the optoelectronics properties of Cs/NF3 adsorption on GaN (0 0 1) photocathode surface, different adsorption models of Cs-only, Cs/O, Cs/NF3 adsorption on GaN clean surface were established, respectively. Atomic structures, work function, adsorption energy, E-Mulliken charge distribution, density of states and optical properties of all these adsorption systems were calculated using first principles. Compared with Cs/O co-adsorption, Cs/NF3 co-adsorption show better stability and more decline of work function, which is more beneficial for photoemission efficiency. Besides, surface band structures of Cs/NF3 co-adsorption system exhibit metal properties, implying good conductivity. Meanwhile, near valence band minimum of Cs/NF3 co-adsorption system, more acceptor levels emerges to form a p-type emission surface, which is conductive to the escape of photoelectrons. In addition, imaginary part of dielectric function curve and absorption curve of Cs/NF3 co-adsorption system both move towards lower energy side. This work can direct the optimization of activation process of NEA GaN photocathode.

The Monitoring of Sallow CO2 Leakage From the CO2 Release Experiment in South Korea

NASA Astrophysics Data System (ADS)

Kim, H. J.; Han, S. H.; Kim, S.; Son, Y.

2017-12-01

This study was conducted to analyze the in-soil CO2 gas diffusion from the K-COSEM shallow CO2 release experiment. The study site consisting of five zones was built in Eumseong, South Korea, and approximately 1.8 t CO2 were injected from the perforated release well at Zones 1 to 4 from June 1 to 30, 2016. In-soil CO2 concentrations were measured once a day at 15 cm and 60 cm depths at 0 m, 2.5 m, 5.0 m, and 10.0 m away from the CO2 releasing well using a portable gas analyzer (GA5000) from May 11 to July 27, 2016. On June 4, CO2 leakage was simultaneously detected at 15 cm (8.8 %) and 60 cm (44.0 %) depths at 0 m from the well at Zone 3, and were increased up to about 30 % and 70 %, respectively. During the CO2 injection period, CO2 concentrations measured at 15 cm depth were significantly lower than those measured at 60 cm depth because of the atmospheric pressure effect. After stopping the CO2 injection, CO2 concentrations gradually decreased until July 27, but were still higher than the natural background concentration. This result suggested the possibility of long-term CO2 leakage. In addition, low levels of CO2 leakage were determined using CO2 regression analysis and CO2:O2 ratio. CO2 concentrations measured at 60 cm depth at 0 m from the well at Zones 1 to 4 consistently showed sigmoid increasing patterns with the injection time (R2=0.60-0.99). O2 concentrations at 15 cm and 60 cm depths from the CO2 release experiment were reached 0 % at about 76 % and 84 % of CO2 concentrations, respectively, whereas, those from biological reaction approached 0 % when CO2 increased to about 21 %. Therefore, deep underground monitoring would be able to detect CO2 leakage faster than near-surface monitoring, and CO2 regression and CO2:O2 ratio analyses seemed to be useful as clear indicators of CO2 leakage.

Thick thermal barrier coatings for diesel components

NASA Technical Reports Server (NTRS)

Yonushonis, T. M.

1991-01-01

An engineered thick thermal barrier coating consisting of multiple layers of zirconia and CoCrAlY with a zirconia top layer and having a system thermal conductance less than 410 w/m(exp 2)K exceeded the 100 hour engine durability goals set forth in this program. The thermal barrier coatings were intact at the test conclusion. Back to back single cylinder research engine tests were conducted with watercooled, metal hardware and oil-cooled, thermal barrier coating insulated hardware to determine apparent heat release and fuel economy. Apparent heat release data revealed that the insulated engine had a shorter ignition delay and a longer combustion duration than the metal engine. The insulated engine fuel economy was approximately two percent worse on average for this series of tests. There was no attempt to optimize engine efficiency of the insulated engine by modifying the engine timing, coating, or other techniques.

Optimal scheduling and its Lyapunov stability for advanced load-following energy plants with CO 2 capture

DOE PAGES

Bankole, Temitayo; Jones, Dustin; Bhattacharyya, Debangsu; ...

2017-11-03

In this study, a two-level control methodology consisting of an upper-level scheduler and a lower-level supervisory controller is proposed for an advanced load-following energy plant with CO 2 capture. With the use of an economic objective function that considers fluctuation in electricity demand and price at the upper level, optimal scheduling of energy plant electricity production and carbon capture with respect to several carbon tax scenarios is implemented. The optimal operational profiles are then passed down to corresponding lower-level supervisory controllers designed using a methodological approach that balances control complexity with performance. Finally, it is shown how optimal carbon capturemore » and electricity production rate profiles for an energy plant such as the integrated gasification combined cycle (IGCC) plant are affected by electricity demand and price fluctuations under different carbon tax scenarios. As a result, the paper also presents a Lyapunov stability analysis of the proposed scheme.« less

Optimal scheduling and its Lyapunov stability for advanced load-following energy plants with CO 2 capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bankole, Temitayo; Jones, Dustin; Bhattacharyya, Debangsu

In this study, a two-level control methodology consisting of an upper-level scheduler and a lower-level supervisory controller is proposed for an advanced load-following energy plant with CO 2 capture. With the use of an economic objective function that considers fluctuation in electricity demand and price at the upper level, optimal scheduling of energy plant electricity production and carbon capture with respect to several carbon tax scenarios is implemented. The optimal operational profiles are then passed down to corresponding lower-level supervisory controllers designed using a methodological approach that balances control complexity with performance. Finally, it is shown how optimal carbon capturemore » and electricity production rate profiles for an energy plant such as the integrated gasification combined cycle (IGCC) plant are affected by electricity demand and price fluctuations under different carbon tax scenarios. As a result, the paper also presents a Lyapunov stability analysis of the proposed scheme.« less

Regulation of C:N:P stoichiometry of microbes and soil organic matter by optimizing enzyme allocation: an omics-informed model study

NASA Astrophysics Data System (ADS)

Song, Y.; Yao, Q.; Wang, G.; Yang, X.; Mayes, M. A.

2017-12-01

Increasing evidences is indicating that soil organic matter (SOM) decomposition and stabilization process is a continuum process and controlled by both microbial functions and their interaction with minerals (known as the microbial efficiency-matrix stabilization theory (MEMS)). Our metagenomics analysis of soil samples from both P-deficit and P-fertilization sites in Panama has demonstrated that community-level enzyme functions could adapt to maximize the acquisition of limiting nutrients and minimize energy demand for foraging (known as the optimal foraging theory). This optimization scheme can mitigate the imbalance of C/P ratio between soil substrate and microbial community and relieve the P limitation on microbial carbon use efficiency over the time. Dynamic allocation of multiple enzyme groups and their interaction with microbial/substrate stoichiometry has rarely been considered in biogeochemical models due to the difficulties in identifying microbial functional groups and quantifying the change in enzyme expression in response to soil nutrient availability. This study aims to represent the omics-informed optimal foraging theory in the Continuum Microbial ENzyme Decomposition model (CoMEND), which was developed to represent the continuum SOM decomposition process following the MEMS theory. The SOM pools in the model are classified based on soil chemical composition (i.e. Carbohydrates, lignin, N-rich SOM and P-rich SOM) and the degree of SOM depolymerization. The enzyme functional groups for decomposition of each SOM pool and N/P mineralization are identified by the relative composition of gene copy numbers. The responses of microbial activities and SOM decomposition to nutrient availability are simulated by optimizing the allocation of enzyme functional groups following the optimal foraging theory. The modeled dynamic enzyme allocation in response to P availability is evaluated by the metagenomics data measured from P addition and P-deficit soil samples in Panama sites.The implementation of dynamic enzyme allocation in response to nutrient availability in the CoMEND model enables us to capture the varying microbial C/P ratio and soil carbon dynamics in response to shifting nutrient constraints over time in tropical soils.

Vasorelaxing effects and inhibition of nitric oxide in macrophages by new iron-containing carbon monoxide-releasing molecules (CO-RMs).

PubMed

Motterlini, Roberto; Sawle, Philip; Hammad, Jehad; Mann, Brian E; Johnson, Tony R; Green, Colin J; Foresti, Roberta

2013-02-01

Carbon monoxide-releasing molecules (CO-RMs) are a class of organometallo carbonyl complexes capable of delivering controlled quantities of CO gas to cells and tissues thus exerting a broad spectrum of pharmacological effects. Here we report on the chemical synthesis, CO releasing properties, cytotoxicity profile and pharmacological activities of four novel structurally related iron-allyl carbonyls. The major difference among the new CO-RMs tested was that three compounds (CORM-307, CORM-308 and CORM-314) were soluble in dimethylsulfoxide (DMSO), whereas a fourth one (CORM-319) was rendered water-soluble by reacting the iron-carbonyl with hydrogen tetrafluoroborate. We found that despite the fact all compounds liberated CO, CO-RMs soluble in DMSO caused a more pronounced toxic effect both in vascular and inflammatory cells as well as in isolated vessels. More specifically, iron carbonyls soluble in DMSO released CO with a fast kinetic and displayed a marked cytotoxic effect in smooth muscle cells and RAW 247.6 macrophages despite exerting a rapid and pronounced vasorelaxation ex vivo. In contrast, CORM-319 that is soluble in water and liberated CO with a slower rate, preserved smooth muscle cell viability, relaxed aortic tissue and exerted a significant anti-inflammatory effect in macrophages challenged with endotoxin. These data suggest that iron carbonyls can be used as scaffolds for the design and synthesis of pharmacologically active CO-RMs and indicate that increasing water solubility and controlling the rate of CO release are important parameters for limiting their potential toxic effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

Microencapsulated Dopamine (DA)-Induced Restitution of Function in 6-OHDA-Denervated Rat Striatum in vivo: Comparison Between Two Microsphere Excipients

PubMed Central

McRae, Amanda; Hjorth, Stephan; Mason, David W.; Dillon, Lynn; Tice, Thomas R.

1991-01-01

Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly [DL lactide-co-glycolide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microspheres encapsulated within two different polymer excipients into denervated- striatal tissue assures a prolonged release of the transmitter in vivo. Moreover, in this regard, the results show that there were clear cut temporal differences in the effect of the two DA microsphere formulations compared in this study, probably reflecting variations in the actual composition (i.e., lactide to glycolide ratio) of the two copolymer excipients examined. This technology has considerable potential for basic research with possible clinical application. PMID:1782252

Gentamicin Sulfate PEG-PLGA/PLGA-H Nanoparticles: Screening Design and Antimicrobial Effect Evaluation toward Clinic Bacterial Isolates

PubMed Central

Dorati, Rossella; DeTrizio, Antonella; Spalla, Melissa; Migliavacca, Roberta; Pagani, Laura; Pisani, Silvia; Chiesa, Enrica; Modena, Tiziana; Genta, Ida

2018-01-01

Nanotechnology is a promising approach both for restoring or enhancing activity of old and conventional antimicrobial agents and for treating intracellular infections by providing intracellular targeting and sustained release of drug inside infected cells. The present paper introduces a formulation study of gentamicin loaded biodegradable nanoparticles (Nps). Solid-oil-in water technique was studied for gentamicin sulfate nanoencapsulation using uncapped Polylactide-co-glycolide (PLGA-H) and Polylactide-co-glycolide-co-Polyethylenglycol (PLGA-PEG) blends. Screening design was applied to optimize: drug payload, Nps size and size distribution, stability and resuspendability after freeze-drying. PLGA-PEG concentration resulted most significant factor influencing particles size and drug content (DC): 8 w/w% DC and 200 nm Nps were obtained. Stirring rate resulted most influencing factor for size distribution (PDI): 700 rpm permitted to obtain homogeneous Nps dispersion (PDI = 1). Further experimental parameters investigated, by 23 screening design, were: polymer blend composition (PLGA-PEG and PLGA-H), Polyvinylalcohol (PVA) and methanol concentrations into aqueous phase. Drug content was increased to 10.5 w/w%. Nanoparticle lyophilization was studied adding cryoprotectants, polyvinypirrolidone K17 and K32, and sodiumcarboxymetylcellulose. Freeze-drying protocol was optimized by a mixture design. A freeze-dried Nps powder free resuspendable with stable Nps size and payload, was developed. The powder was tested on clinic bacterial isolates demonstrating that after encapsulation, gentamicin sulfate kept its activity. PMID:29329209

Zeolites for CO2-CO-O2 Separation to Obtain CO2-Neutral Fuels.

PubMed

Perez-Carbajo, Julio; Matito-Martos, Ismael; Balestra, Salvador R G; Tsampas, Mihalis N; van de Sanden, Mauritius C M; Delgado, José A; Águeda, V Ismael; Merkling, Patrick J; Calero, Sofia

2018-06-20

Carbon dioxide release has become an important global issue due to the significant and continuous rise in atmospheric CO 2 concentrations and the depletion of carbon-based energy resources. Plasmolysis is a very energy-efficient process for reintroducing CO 2 into energy and chemical cycles by converting CO 2 into CO and O 2 utilizing renewable electricity. The bottleneck of the process is that CO remains mixed with O 2 and residual CO 2 . Therefore, efficient gas separation and recuperation are essential for obtaining pure CO, which, via water gas shift and Fischer-Tropsch reactions, can lead to the production of CO 2 -neutral fuels. The idea behind this work is to provide a separation mechanism based on zeolites to optimize the separation of carbon dioxide, carbon monoxide, and oxygen under mild operational conditions. To achieve this goal, we performed a thorough screening of available zeolites based on topology and adsorptive properties using molecular simulation and ideal adsorption solution theory. FAU, BRE, and MTW are identified as suitable topologies for these separation processes. FAU can be used for the separation of carbon dioxide from carbon monoxide and oxygen and BRE or MTW for the separation of carbon monoxide from oxygen. These results are reinforced by pressure swing adsorption simulations at room temperature combining adsorption columns with pure silica FAU zeolite and zeolite BRE at a Si/Al ratio of 3. These zeolites have the added advantage of being commercially available.

Encapsulation of albumin in self-assembled layer-by-layer microcapsules: comparison of co-precipitation and adsorption techniques.

PubMed

Labala, Suman; Mandapalli, Praveen Kumar; Bhatnagar, Shubhmita; Venuganti, Venkata Vamsi Krishna

2015-01-01

The objective of this study is to prepare and characterize polymeric self-assembled layer-by-layer microcapsules (LbL-MC) to deliver a model protein, bovine serum albumin (BSA). The aim is to compare the BSA encapsulation in LbL-MC using co-precipitation and adsorption methods. In co-precipitation method, BSA was co-precipitated with growing calcium carbonate particles to form a core template. Later, poly(styrene sulfonate) and poly(allylamine hydrochloride) were sequentially adsorbed onto the CaCO3 templates. In adsorption method, preformed LbL-MC were incubated with BSA and encapsulation efficiency is optimized for pH and salt concentration. Free and BSA-encapsulated LbL-MC were characterized using Zetasizer, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy and differential scanning calorimeter. Later, in vitro release studies were performed using dialysis membrane method at pH 4, 7.4 and 9. Results from Zetasizer and SEM showed free LbL-MC with an average size and zeta-potential of 2.0 ± 0.6 μm and 8.1 ± 1.9 mV, respectively. Zeta-potential of BSA-loaded LbL-MC was (-)7.4 ± 0.7 mV and (-)5.7 ± 1.0 mV for co-precipitation and adsorption methods, respectively. In adsorption method, BSA encapsulation in LbL-MC was found to be greater at pH 6.0 and 0.2 M NaCl. Co-precipitation method provided four-fold greater encapsulation efficiency (%) of BSA in LbL-MC compared with adsorption method. At pH 4, the BSA release from LbL-MC was extended up to 120 h. Polyacrylamide gel electrophoresis showed that BSA encapsulated in LBL-MC through co-precipitation is stable toward trypsin treatment. In conclusion, co-precipitation method provided greater encapsulation of BSA in LbL-MC. Furthermore, LbL-MC can be developed as carriers for pH-controlled protein delivery.

Magnetic hyperthermia and pH-responsive effective drug delivery to the sub-cellular level of human breast cancer cells by modified CoFe2O4 nanoparticles.

PubMed

Oh, Yunok; Moorthy, Madhappan Santha; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Oh, Junghwan

2017-02-01

Magnetic iron oxide nanoparticles (MNPs) have been extensively utilized in a wide range of biomedical applications including magnetic hyperthermia agent. To improve the efficiency of the MNPs in therapeutic applications, in this study, we have synthesized CoFe 2 O 4 nanoparticles and its surface was further functionalized with meso-2,3-dimercaptosuccinic acid (DMSA). The anticancer agent, Doxorubucin (DOX) was conjugated with CoFe 2 O 4 @DMSA nanoparticle to evaluate the combined effects of thermotherapy and chemotherapy. The drug delivery efficiency of the DOX loaded CoFe 2 O 4 @DMSA nanoparticles were examined based on magnetically triggered delivery of DOX into the subcellular level of cancer cells by using MDA-MB-231 cell line. The amine part of the DOX molecules were effectively attached through an electrostatic interactions and/or hydrogen bonding interactions with the carboxylic acid groups of the DMSA functionalities present onto the surface of the CoFe 2 O 4 nanoparticles. The DOX loaded CoFe 2 O 4 @DMSA nanoparticles can effectively uptake with cancer cells via typical endocytosis process. After endocytosis, DOX release from CoFe 2 O 4 nanoparticles was triggered by intracellular endosomal/lysosomal acidic environments and the localized heat can be generated under an alternating magnetic field (AMF). In the presence of AMF, the released DOX molecules were accumulated with high concentrations into the subcellular level at a desired sites and exhibited a synergistic effect of an enhanced cell cytotoxicity by the combined effects of thermal-chemotherapy. Importantly, pH- and thermal-responsive Dox-loaded CoFe 2 O 4 nanoparticles induced significant cellular apoptosis more efficiently mediated by active mitochondrial membrane and ROS generation than the free Dox. Thus, the Dox-loaded CoFe 2 O 4 @DMSA nanoparticles can be used as a potential therapeutic agent in cancer therapy by combining the thermo-chemotherapy techniques. Copyright © 2016. Published by Elsevier B.V.

PUA/PSS multilayer coated CaCO3 microparticles as smart drug delivery vehicles.

PubMed

Du, Chao; Shi, Jun; Shi, Jin; Zhang, Li; Cao, Shaokui

2013-10-01

Hybrid CaCO3 microparticles coated by sodium poly(styrene sulfonate) (PSS) and aliphatic poly(urethane-amine) (PUA) were developed as thermal-/pH-responsive drug delivery vehicles via LbL self-assembly technique. The DOX release from the CaCO3 microparticles was higher than 60% within 36 h, whereas the value of PUA/PSS-coated microparticles was only 20%. The results demonstrated that the PUA/PSS multilayer coating could reduce the drug release rate and significantly assuage the initial burst release of DOX. In addition, the drug release of the hybrid microparticles was found to be thermal-/pH-dual responsive. More interestingly, more than 90% of DOX was released in 36 h at pH2.1 and 55 °C owing to the combined action of the dissolution of the CaCO3 core and the shrinkage of aliphatic PUA. Copyright © 2013 Elsevier B.V. All rights reserved.

Solvent Effects on the Photothermal Regeneration of CO 2 in Monoethanolamine Nanofluids

DOE PAGES

Nguyen, Du; Stolaroff, Joshuah; Esser-Kahn, Aaron

2015-11-02

We present that a potential approach to reduce energy costs associated with carbon capture is to use external and renewable energy sources. The photothermal release of CO 2 from monoethanolamine mediated by nanoparticles is a unique solution to this problem. When combined with light-absorbing nanoparticles, vapor bubbles form inside the capture solution and release the CO 2 without heating the bulk solvent. The mechanism by which CO 2 is released remained unclear, and understanding this process would improve the efficiency of photothermal CO 2 release. Here we report the use of different cosolvents to improve or reduce the photothermal regenerationmore » of CO 2 captured by monoethanolamine. We found that properties that reduce the residence time of the gas bubbles (viscosity, boiling point, and convection direction) can enhance the regeneration efficiencies. The reduction of bubble residence times minimizes the reabsorption of CO 2 back into the capture solvent where bulk temperatures remain lower than the localized area surrounding the nanoparticle. These properties shed light on the mechanism of release and indicated methods for improving the efficiency of the process. We used this knowledge to develop an improved photothermal CO 2 regeneration system in a continuously flowing setup. Finally, using techniques to reduce residence time in the continuously flowing setup, such as alternative cosolvents and smaller fluid volumes, resulted in regeneration efficiency enhancements of over 200%.« less

Solvent Effects on the Photothermal Regeneration of CO 2 in Monoethanolamine Nanofluids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Du; Stolaroff, Joshuah; Esser-Kahn, Aaron

We present that a potential approach to reduce energy costs associated with carbon capture is to use external and renewable energy sources. The photothermal release of CO 2 from monoethanolamine mediated by nanoparticles is a unique solution to this problem. When combined with light-absorbing nanoparticles, vapor bubbles form inside the capture solution and release the CO 2 without heating the bulk solvent. The mechanism by which CO 2 is released remained unclear, and understanding this process would improve the efficiency of photothermal CO 2 release. Here we report the use of different cosolvents to improve or reduce the photothermal regenerationmore » of CO 2 captured by monoethanolamine. We found that properties that reduce the residence time of the gas bubbles (viscosity, boiling point, and convection direction) can enhance the regeneration efficiencies. The reduction of bubble residence times minimizes the reabsorption of CO 2 back into the capture solvent where bulk temperatures remain lower than the localized area surrounding the nanoparticle. These properties shed light on the mechanism of release and indicated methods for improving the efficiency of the process. We used this knowledge to develop an improved photothermal CO 2 regeneration system in a continuously flowing setup. Finally, using techniques to reduce residence time in the continuously flowing setup, such as alternative cosolvents and smaller fluid volumes, resulted in regeneration efficiency enhancements of over 200%.« less

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases

PubMed Central

Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

2015-01-01

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits. PMID:25839217

Advances in Highly Constrained Multi-Phase Trajectory Generation using the General Pseudospectral Optimization Software (GPOPS)

DTIC Science & Technology

2013-08-01

release; distribution unlimited. PA Number 412-TW-PA-13395 f generic function g acceleration due to gravity h altitude L aerodynamic lift force L Lagrange...cost m vehicle mass M Mach number n number of coefficients in polynomial regression p highest order of polynomial regression Q dynamic pressure R...Method (RPM); the collocation points are defined by the roots of Legendre -Gauss- Radau (LGR) functions.9 GPOPS also automatically refines the “mesh” by

Unusual isotopic composition of C-CO2 from sterilized soil microcosms: a new way to separate intracellular from extracellular respiratory metabolisms.

NASA Astrophysics Data System (ADS)

Kéraval, Benoit; Alvarez, Gaël; Lehours, Anne Catherine; Amblard, Christian; Fontaine, Sebastien

2015-04-01

The mineralization of organic C requires two main steps. First, microorganisms secrete exoenzymes in soil in order to depolymerize plant and microbial cell walls and release soluble substrates for microbial assimilation. The second step of mineralization, during which C is released as CO2, implies the absorption and utilization of solubilized substrates by microbial cells with the aim to produce energy (ATP). In cells, soluble substrates are carried out by a cascade of respiratory enzymes, along which protons and electrons are transferred from a substrate to oxygen. Given the complexity of this oxidative metabolism and the typical fragility of respiratory enzymes, it is traditionally considered that respiration (second step of C mineralization process) is strictly an intracellular metabolism process. The recurrent observations of substantial CO2 emissions in soil microcosms where microbial cells have been reduced to extremely low levels challenges this paradigm. In a recent study where some respiratory enzymes have shown to function in an extracellular context in soils, Maire et al. (2013) suggested that an extracellular oxidative metabolism (EXOMET) substantially contributes to CO2 emission from soils. This idea is supported by the recent publication of Blankinship et al., 2014 who showed the presence of active enzymes involved in the Krebs cycle on soil particles. Many controversies subsist in the scientific community due to the presence of non-proliferating but morphologically intact cells after irradiation that could substantially contribute to those soil CO2 emissions. To test whether a purely extracellular oxidative metabolism contribute to soil CO2 emissions, we combined high doses of gamma irradiations to different time of soil autoclaving. The presence of active and non-active cells in soil was checked by DNA and RNA extraction and by electronic microscopy. None active cells (RNA-containing cells) were detectable after irradiation, but some morphological intact cells were observed by microscopy. These "ghost" cells were completely destroyed by the irradiation-autoclaving combination releasing large amount of soluble C. The soil respiration (O2 consumption and CO2 production) was reduced by irradiation and autoclaving but not stopped, suggesting the presence of an EXOMET. The delta 13C of CO2 released in the irradiated-autoclaved soil was strongly depleted (-70‰) indicating that this extracellular metabolism induced a substantial isotopic fractionation. Our findings suggest that two main oxidative metabolisms co-occur in soils: cell respiration and EXOMET. The isotopic fractionation induced by the EXOMET open perspectives for its quantification in non-sterilized living soils.

Oleic acid derivative of polyethylenimine-functionalized proliposomes for enhancing oral bioavailability of extract of Ginkgo biloba.

PubMed

Zheng, Bin; Yang, Shuang; Fan, Chunyu; Bi, Ye; Du, Lin; Zhao, Lingzhi; Lee, Robert J; Teng, Lesheng; Teng, Lirong; Xie, Jing

2016-05-01

The present systematic study focused to investigate the oleic acid derivative of branched polyethylenimine (bPEI-OA)-functionalized proliposomes for improving the oral delivery of extract of Ginkgo biloba (GbE). The GbE proliposomes were prepared by a spray drying method at varying ratios of egg yolk phosphatidylcholine and cholesterol, and the optimized formulation was tailored with bPEI-OA to obtain bPEI-OA-functionalized proliposomes. The formulations were characterized for particle size, zeta potential, and entrapment efficiency. The release of GbE from proliposomes exhibited a sustained release. And the release rate was regulated by changing the amount of bPEI-OA on the proliposomes. The physical state characterization studies showed some interactions between GbE and other materials, such as hydrogen bonds and van der Waals forces during the process of preparation of proliposomes. The in situ single-pass perfusion and oral bioavailability studies were performed in rats. The significant increase in absorption constant (Ka) and apparent permeability coefficient (Papp) from bPEI-OA-functionalized proliposomes indicated the importance of positive charge for effective uptake across the gastrointestinal tract. The oral bioavailability of bPEI-OA-functionalized proliposomes was remarkable enhanced in comparison with control and conventional proliposomes. The bPEI-OA-functionalized proliposomes showed great potential of improving oral absorption of GbE as a suitable carrier.

Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior.

PubMed

Patrick, Rhonda P; Ames, Bruce N

2015-06-01

Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory gating, and social behavior and that attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior all share in common defects in these functions. It has remained unclear why supplementation with omega-3 fatty acids and vitamin D improve cognitive function and behavior in these brain disorders. Here, we propose mechanisms by which serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D hormone. Inadequate levels of vitamin D (∼70% of the population) and omega-3 fatty acids are common, suggesting that brain serotonin synthesis is not optimal. We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. We propose a model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function and may be one underlying mechanism that contributes to neuropsychiatric disorders and depression. This model suggests that optimizing vitamin D and marine omega-3 fatty acid intake may help prevent and modulate the severity of brain dysfunction. © FASEB.

Nonsynaptic glycine release is involved in the early KCC2 expression.

PubMed

Allain, Anne-Emilie; Cazenave, William; Delpy, Alain; Exertier, Prisca; Barthe, Christophe; Meyrand, Pierre; Cattaert, Daniel; Branchereau, Pascal

2016-07-01

The cation-chloride co-transporters are important regulators of the cellular Cl(-) homeostasis. Among them the Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) is responsible for intracellular chloride accumulation in most immature brain structures, whereas the K(+) -Cl(-) co-transporter (KCC2) extrudes chloride from mature neurons, ensuring chloride-mediated inhibitory effects of GABA/glycine. We have shown that both KCC2 and NKCC1 are expressed at early embryonic stages (E11.5) in the ventral spinal cord (SC). The mechanisms by which KCC2 is prematurely expressed are unknown. In this study, we found that chronically blocking glycine receptors (GlyR) by strychnine led to a loss of KCC2 expression, without affecting NKCC1 level. This effect was not dependent on the firing of Na(+) action potentials but was mimicked by a Ca(2+) -dependent PKC blocker. Blocking the vesicular release of neurotransmitters did not impinge on strychnine effect whereas blocking volume-sensitive outwardly rectifying (VSOR) chloride channels reproduced the GlyR blockade, suggesting that KCC2 is controlled by a glycine release from progenitor radial cells in immature ventral spinal networks. Finally, we showed that the strychnine treatment prevented the maturation of rhythmic spontaneous activity. Thereby, the GlyR-activation is a necessary developmental process for the expression of functional spinal motor networks. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 764-779, 2016. © 2015 Wiley Periodicals, Inc.

Smoke and fire characteristics for cerrado and deforestation burns in Brazil: BASE-B experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, D.E.; Susott, R.A.; Babbitt, R.E.

1992-09-20

Fires of the tropical forests and savannas are a major source of particulate matter and trace gases affecting the atmosphere globally. A paucity of quantitative information exists for these ecosystems with respect to fuel biomass, smoke emissions, and fire behavior conditions affecting the release of emissions. Five test fires were performed during August and September 1990 in the cerrado (savannalike region) in central Brazil (three fires) and tropical moist forest (two fires) in the eastern Amazon. This paper details the gases released, the ratios of the gases to each other and to particulate matter, fuel loads and the fraction consumedmore » (combustion factors), and the fire behavior associated with biomass consumption. Models are presented for evaluating emission factors for CH{sub 4}, CO{sub 2}, CO, H{sub 2}, and particles less than 2.5 {mu}m diameter (PM2.5) as a function of combustion efficiency. The ratio of carbon released as CO{sub 2} (combustion efficiency) for the cerrado fires averaged 0.94 and for the deforestation fires it decreased from 0.88 for the flaming phase to <0.80 during the smoldering phase of combustion. For tropical ecosystems, emissions of most products of incomplete combustion are projected to be lower than previous estimates for savanna ecosystems and somewhat higher for fires used for deforestation purposes. 59 refs., 9 figs., 10 tabs.« less

First estimates of the contribution of CaCO3 precipitation to the release of CO2 to the atmosphere during young sea ice growth

NASA Astrophysics Data System (ADS)

Geilfus, N.-X.; Carnat, G.; Dieckmann, G. S.; Halden, N.; Nehrke, G.; Papakyriakou, T.; Tison, J.-L.; Delille, B.

2013-01-01

report measurements of pH, total alkalinity, air-ice CO2 fluxes (chamber method), and CaCO3 content of frost flowers (FF) and thin landfast sea ice. As the temperature decreases, concentration of solutes in the brine skim increases. Along this gradual concentration process, some salts reach their solubility threshold and start precipitating. The precipitation of ikaite (CaCO3.6H2O) was confirmed in the FF and throughout the ice by Raman spectroscopy and X-ray analysis. The amount of ikaite precipitated was estimated to be 25 µmol kg-1 melted FF, in the FF and is shown to decrease from 19 to 15 µmol kg-1 melted ice in the upper part and at the bottom of the ice, respectively. CO2 release due to precipitation of CaCO3 is estimated to be 50 µmol kg-1 melted samples. The dissolved inorganic carbon (DIC) normalized to a salinity of 10 exhibits significant depletion in the upper layer of the ice and in the FF. This DIC loss is estimated to be 2069 µmol kg-1 melted sample and corresponds to a CO2 release from the ice to the atmosphere ranging from 20 to 40 mmol m-2 d-1. This estimate is consistent with flux measurements of air-ice CO2 exchange. Our measurements confirm previous laboratory findings that growing young sea ice acts as a source of CO2 to the atmosphere. CaCO3 precipitation during early ice growth appears to promote the release of CO2 to the atmosphere; however, its contribution to the overall release by newly formed ice is most likely minor.

Interaction of the carbon monoxide-releasing molecule Ru(CO)3Cl(glycinate) (CORM-3) with Salmonella enterica serovar Typhimurium: in situ measurements of carbon monoxide binding by integrating cavity dual-beam spectrophotometry.

PubMed

Rana, Namrata; McLean, Samantha; Mann, Brian E; Poole, Robert K

2014-12-01

Carbon monoxide (CO) is a toxic gas that binds to haems, but also plays critical signalling and cytoprotective roles in mammalian systems; despite problems associated with systemic delivery by inhalation of the gas, it may be employed therapeutically. CO delivered to cells and tissues by CO-releasing molecules (CO-RMs) has beneficial and toxic effects not mimicked by CO gas; CO-RMs are also attractive candidates as novel antimicrobial agents. Salmonella enterica serovar Typhimurium is an enteropathogen causing gastroenteritis in humans. Recent studies have implicated haem oxygenase-1 (HO-1), the protein that catalyses the degradation of haem into biliverdin, free iron and CO, in the host immune response to Salmonella infection. In several studies, CO administration via CO-RMs elicited many of the protective roles of HO-1 induction and so we investigated the effects of a well-characterized water-soluble CO-RM, Ru(CO)3Cl(glycinate) (CORM-3), on Salmonella. CORM-3 exhibits toxic effects at concentrations significantly lower than those reported to cause toxicity to RAW 264.7 macrophages. We demonstrated here, through oxyhaemoglobin assays, that CORM-3 did not release CO spontaneously in phosphate buffer, buffered minimal medium or very rich medium. CORM-3 was, however, accumulated to high levels intracellularly (as shown by inductively coupled plasma MS) and released CO inside cells. Using growing Salmonella cultures without prior concentration, we showed for the first time that sensitive dual-beam integrating cavity absorption spectrophotometry can detect directly the CO released from CORM-3 binding in real-time to haems of the bacterial electron transport chain. The toxic effects of CO-RMs suggested potential applications as adjuvants to antibiotics in antimicrobial therapy. © 2014 The Authors.

Novel CO 2 Foam Concepts and Injection Schemes for Improving CO 2 Sweep Efficiency in Sandstone and Carbonate Hydrocarbon Formations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Quoc; Hirasaki, George; Johnston, Keith

2015-02-05

We explored cationic, nonionic and zwitterionic surfactants to identify candidates that have the potential to satisfy all the key requirements for CO 2 foams in EOR. We have examined the formation, texture, rheology and stability of CO 2 foams as a function of the surfactant structure and formulation variables including temperature, pressure, water/CO 2 ratio, surfactant concentration, salinity and concentration of oil. Furthermore, the partitioning of surfactants between oil and water as well as CO 2 and water was examined in conjunction with adsorption measurements on limestone by the Hirasaki lab to develop strategies to optimize the transport of surfactantsmore » in reservoirs.« less

Adsorption separation of carbon dioxide from flue gas by a molecularly imprinted adsorbent.

PubMed

Zhao, Yi; Shen, Yanmei; Ma, Guoyi; Hao, Rongjie

2014-01-01

CO2 separation by molecularly imprinted adsorbent from coal-fired flue gas after desulfurization system has been studied. The adsorbent was synthesized by molecular imprinted technique, using ethanedioic acid, acrylamide, and ethylene glycol dimethacrylate as the template, functional monomer, and cross-linker, respectively. According to the conditions of coal-fired flue gas, the influencing factors, including adsorption temperature, desorption temperature, gas flow rate, and concentrations of CO2, H2O, O2, SO2, and NO, were studied by fixed bed breakthrough experiments. The experimental conditions were optimized to gain the best adsorption performance and reduce unnecessary energy consumption in future practical use. The optimized adsorption temperature, desorption temperature, concentrations of CO2, and gas flow rate are 60 °C, 80 °C, 13%, and 170 mL/min, respectively, which correspond to conditions of practical flue gases to the most extent. The CO2 adsorption performance was nearly unaffected by H2O, O2, and NO in the flue gas, and was promoted by SO2 within the emission limit stipulated in the Chinese emission standards of air pollutants for a thermal power plant. The maximum CO2 adsorption capacity, 0.57 mmol/g, was obtained under the optimized experimental conditions, and the SO2 concentration was 150 mg/m(3). The influence mechanisms of H2O, O2, SO2, and NO on CO2 adsorption capacity were investigated by infrared spectroscopic analysis.

Targeted Intracellular Delivery of Antituberculosis Drugs to Mycobacterium tuberculosis-Infected Macrophages via Functionalized Mesoporous Silica Nanoparticles

PubMed Central

Lee, Bai-Yu; Xue, Min; Thomas, Courtney R.; Meng, Huan; Ferris, Daniel; Nel, Andre E.; Zink, Jeffrey I.

2012-01-01

Delivery of antituberculosis drugs by nanoparticles offers potential advantages over free drug, including the potential to target specifically the tissues and cells that are infected by Mycobacterium tuberculosis, thereby simultaneously increasing therapeutic efficacy and decreasing systemic toxicity, and the capacity for prolonged release of drug, thereby allowing less-frequent dosing. We have employed mesoporous silica nanoparticle (MSNP) drug delivery systems either equipped with a polyethyleneimine (PEI) coating to release rifampin or equipped with cyclodextrin-based pH-operated valves that open only at acidic pH to release isoniazid (INH) into M. tuberculosis-infected macrophages. The MSNP are internalized efficiently by human macrophages, traffic to acidified endosomes, and release high concentrations of antituberculosis drugs intracellularly. PEI-coated MSNP show much greater loading of rifampin than uncoated MSNP and much greater efficacy against M. tuberculosis-infected macrophages. MSNP were devoid of cytotoxicity at the particle doses employed for drug delivery. Similarly, we have demonstrated that the isoniazid delivered by MSNP equipped with pH-operated nanovalves kill M. tuberculosis within macrophages significantly more effectively than an equivalent amount of free drug. These data demonstrate that MSNP provide a versatile platform that can be functionalized to optimize the loading and intracellular release of specific drugs for the treatment of tuberculosis. PMID:22354311

TEGDMA and UDMA monomers released from composite dental material polymerized with diode and halogen lamps.

PubMed

Wacławczyk, Agnieszka; Postek-Stefańska, Lidia; Pietraszewska, Daria; Birkner, Ewa; Zalejska-Fiolka, Jolanta; Wysoczańska-Jankowicz, Iwona

2018-03-20

More than 35 substances released from composite fillings have been identified. Among these, basic monomers and the so-called co-monomers are most often reported. The substances released from polymer-based materials demonstrate allergenic, cytotoxic, genotoxic, mutagenic, embryotoxic, teratogenic, and estrogenic properties. The aim of this study was to measure the amounts of triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA) monomers released from composite dental fillings to citrate-phosphate buffer with the pH of 4, 6, 8 after 24 h and 6 months from the polymerization. Ten samples for each polymerization method had been made from the composite material (Filtek Supreme XT, 3M ESPE, St. Paul, USA), which underwent polymerization using the following lamps: halogen lamp (Translux CL, Heraeus Kulzer, Hanau, Germany) (sample H) and diode lamp (Elipar Freelight 2, 3M ESPE), with soft start function (group DS) and without that function (group DWS). It has been demonstrated that the type of light-curing units has a significant impact on the amount of TEGDMA and UDMA released. The amount of UDMA and TEGDMA monomers released from composite fillings differed significantly depending on the source of polymerization applied, as well as the pH of the solution and sample storage time. Elution of the monomers from composite material polymerized using halogen lamp was significantly greater as compared to curing with diode lamps.

Optimization of intermolecular potential parameters for the CO2/H2O mixture.

PubMed

Orozco, Gustavo A; Economou, Ioannis G; Panagiotopoulos, Athanassios Z

2014-10-02

Monte Carlo simulations in the Gibbs ensemble were used to obtain optimized intermolecular potential parameters to describe the phase behavior of the mixture CO2/H2O, over a range of temperatures and pressures relevant for carbon capture and sequestration processes. Commonly used fixed-point-charge force fields that include Lennard-Jones 12-6 (LJ) or exponential-6 (Exp-6) terms were used to describe CO2 and H2O intermolecular interactions. For force fields based on the LJ functional form, changes of the unlike interactions produced higher variations in the H2O-rich phase than in the CO2-rich phase. A major finding of the present study is that for these potentials, no combination of unlike interaction parameters is able to adequately represent properties of both phases. Changes to the partial charges of H2O were found to produce significant variations in both phases and are able to fit experimental data in both phases, at the cost of inaccuracies for the pure H2O properties. By contrast, for the Exp-6 case, optimization of a single parameter, the oxygen-oxygen unlike-pair interaction, was found sufficient to give accurate predictions of the solubilities in both phases while preserving accuracy in the pure component properties. These models are thus recommended for future molecular simulation studies of CO2/H2O mixtures.

Padé spectrum decompositions of quantum distribution functions and optimal hierarchical equations of motion construction for quantum open systems

NASA Astrophysics Data System (ADS)

Hu, Jie; Luo, Meng; Jiang, Feng; Xu, Rui-Xue; Yan, YiJing

2011-06-01

Padé spectrum decomposition is an optimal sum-over-poles expansion scheme of Fermi function and Bose function [J. Hu, R. X. Xu, and Y. J. Yan, J. Chem. Phys. 133, 101106 (2010)], 10.1063/1.3484491. In this work, we report two additional members to this family, from which the best among all sum-over-poles methods could be chosen for different cases of application. Methods are developed for determining these three Padé spectrum decomposition expansions at machine precision via simple algorithms. We exemplify the applications of present development with optimal construction of hierarchical equations-of-motion formulations for nonperturbative quantum dissipation and quantum transport dynamics. Numerical demonstrations are given for two systems. One is the transient transport current to an interacting quantum-dots system, together with the involved high-order co-tunneling dynamics. Another is the non-Markovian dynamics of a spin-boson system.

Intelligent Computation for Optimal Fabrication Condition of a Protein Chip with Ni-Co Alloy-Coated Surface.

PubMed

Chang, Yaw-Jen; Chang, Cheng-Hao

2016-06-01

Based on the principle of immobilized metal affinity chromatography (IMAC), it has been found that a Ni-Co alloy-coated protein chip is able to immobilize functional proteins with a His-tag attached. In this study, an intelligent computational approach was developed to promote the performance and repeatability of a Ni-Co alloy-coated protein chip. This approach was launched out of L18 experiments. Based on the experimental data, the fabrication process model of a Ni-Co protein chip was established by using an artificial neural network, and then an optimal fabrication condition was obtained using the Taguchi genetic algorithm. The result was validated experimentally and compared with a nitrocellulose chip. Consequentially, experimental outcomes revealed that the Ni-Co alloy-coated chip, fabricated using the proposed approach, had the best performance and repeatability compared with the Ni-Co chips of an L18 orthogonal array design and the nitrocellulose chip. Moreover, the low fluorescent background of the chip surface gives a more precise fluorescent detection. Based on a small quantity of experiments, this proposed intelligent computation approach can significantly reduce the experimental cost and improve the product's quality. © 2015 Society for Laboratory Automation and Screening.

Controlled release of ibuprofen by meso–macroporous silica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santamaría, E., E-mail: esthersantamaria@ub.edu; Maestro, A.; Porras, M.

2014-02-15

Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and releasemore » was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84{sub 5}0% (black triangles), P84{sub 7}5% (white diamonds), P84{sub 7}5% functionalized by grafting (black squares) and P84{sub 7}5% functionalized by co-condensation method (white triangles). Display Omitted - Highlights: • Ordered meso–macroporous material is used as a controlled delivery system for ibuprofen. • Incorporation of macropores in mesoporous silica improves ibuprofen adsorption. • Meso–macroporous structures provide a lower delivery than mesoporous silica. • APTES functionalization in meso–macroporous materials improves ibuprofen adsorption and delivery behaviour.« less

Thermodynamic model effects on the design and optimization of natural gas plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz, S.; Zabaloy, M.; Brignole, E.A.

1999-07-01

The design and optimization of natural gas plants is carried out on the basis of process simulators. The physical property package is generally based on cubic equations of state. By rigorous thermodynamics phase equilibrium conditions, thermodynamic functions, equilibrium phase separations, work and heat are computed. The aim of this work is to analyze the NGL turboexpansion process and identify possible process computations that are more sensitive to model predictions accuracy. Three equations of state, PR, SRK and Peneloux modification, are used to study the effect of property predictions on process calculations and plant optimization. It is shown that turboexpander plantsmore » have moderate sensitivity with respect to phase equilibrium computations, but higher accuracy is required for the prediction of enthalpy and turboexpansion work. The effect of modeling CO{sub 2} solubility is also critical in mixtures with high CO{sub 2} content in the feed.« less

Molecular Dynamics and Free Energy Simulations of Phenylacetate and CO2 Release from AMDase and Its G74C/C188S Mutant: A Possible Rationale for the Reduced Activity of the Latter.

PubMed

Karmakar, Tarak; Balasubramanian, Sundaram

2016-11-17

Arylmalonate decarboxylase (AMDase) catalyzes the decarboxylation of α-aryl-α-methyl malonates to produce optically pure α-arylpropionates of industrial and medicinal importance. Herein, atomistic molecular dynamics simulations have been carried out to delineate the mechanism of the release of product molecules phenylacetate (PAC) and carbon dioxide (CO 2 ), from the wild-type (WT) and its G74C/C188S mutant enzymes. Both of the product molecules follow a crystallographically characterized solvent-accessible channel to come out of the protein interior. A higher free energy barrier for the release of PAC from G74C/C188S compared to that in the WT is consistent with the experimentally observed compromised efficiency of the mutant. The release of CO 2 precedes that of PAC; free energy barriers for CO 2 and PAC release in the WT enzyme are calculated to be ∼1-2 and ∼23 kcal/mol, respectively. Postdecarboxylation, CO 2 moves toward a hydrophobic pocket formed by Pro 14, Leu 38, Leu 40, Leu 77, and the side chain of Tyr 48 which serves as its temporary "reservoir". CO 2 releases following a channel mainly decorated by apolar residues, unlike in the case of oxalate decarboxylase where polar residues mediate its transport.

Ultraefficient homogeneous catalyst for the CO2-to-CO electrochemical conversion.

PubMed

Costentin, Cyrille; Passard, Guillaume; Robert, Marc; Savéant, Jean-Michel

2014-10-21

A very efficient electrogenerated Fe(0) porphyrin catalyst was obtained by substituting in tetraphenylporphyrin two of the opposite phenyl rings by ortho-, ortho'-phenol groups while the other two are perfluorinated. It proves to be an excellent catalyst of the CO2-to-CO conversion as to selectivity (the CO faradaic yield is nearly quantitative), overpotential, and turnover frequency. Benchmarking with other catalysts, through catalytic Tafel plots, shows that it is the most efficient, to the best of our knowledge, homogeneous molecular catalyst of the CO2-to-CO conversion at present. Comparison with another Fe(0) tetraphenylporphyrin bearing eight ortho-, ortho'-phenol functionalities launches a general strategy where changes in substituents will be designed so as to optimize the operational combination of all catalyst elements of merit.

Intercalation and controlled release properties of vitamin C intercalated layered double hydroxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Xiaorui, E-mail: gxr_1320@sina.com; School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189; Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA

Two drug-inorganic composites involving vitamin C (VC) intercalated in Mg–Al and Mg–Fe layered double hydroxides (LDHs) have been synthesized by the calcination–rehydration (reconstruction) method. Powder X-ray diffraction (XRD), Fourier transform infrared (FTIR), and UV–vis absorption spectroscopy indicate a successful intercalation of VC into the interlayer galleries of the LDH host. Studies of VC release from the LDHs in deionised water and in aqueous CO{sub 3}{sup 2−} solutions imply that Mg{sub 3}Al–VC LDH is a better controlled release system than Mg{sub 3}Fe–VC LDH. Analysis of the release profiles using a number of kinetic models suggests a solution-dependent release mechanism, and amore » diffusion-controlled deintercalation mechanism in deionised water, but an ion exchange process in CO{sub 3}{sup 2−} solution. - Graphical abstract: Vitamin C anions have been intercalated in the interlayer space of layered double hydroxide and released in CO{sub 3}{sup 2−} solution and deionised water. - Highlights: • Vitamin C intercalated Mg–Al and Mg–Fe layered double hydroxides were prepared. • Release property of vitamin C in aqueous CO{sub 3}{sup 2−} solution is better. • Avrami-Erofe’ev and first-order models provide better fit for release results. • Diffusion-controlled and ion exchange processes occur in deionised water. • An ion exchange process occurs in CO{sub 3}{sup 2−} solution.« less

Controlled release of astaxanthin from nanoporous silicified-phospholipids assembled boron nitride complex for cosmetic applications

NASA Astrophysics Data System (ADS)

Lee, Hye Sun; Sung, Dae Kyung; Kim, Sung Hyun; Choi, Won Il; Hwang, Ee Tag; Choi, Doo Jin; Chang, Jeong Ho

2017-12-01

Nanoporous silicified-phospholipids assembled boron nitride (nSPLs@BN) powder was prepared and demonstrated for use in controlled release of anti-oxidant astaxanthin (AX) as a cosmetic application. The nanoporous silicified phospholipids (nSPLs) were obtained by the silicification with tetraethyl orthosilicate (TEOS) of the hydrophilic region of phospholipid bilayers. This process involved the co-assembly of chemically active phospholipid bilayers within the porous silica matrix. In addition, nSPLs@BN was characterized using several analytical techniques and tested to assess their efficiency as drug delivery systems. We calculated the maximum release amounts as a function of time and various pH. The release rate of AX from the nSPLs@BN for the initial 24 h was 10.7 μmol/(h mg) at pH 7.4. Furthermore, we determined the antioxidant activity (KD) for the released AX with DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical and the result was 34.6%.

Capybara Oil Improves Hepatic Mitochondrial Dysfunction, Steatosis, and Inflammation in a Murine Model of Nonalcoholic Fatty Liver Disease.

PubMed

Marinho, Polyana C; Vieira, Aline B; Pereira, Priscila G; Rabelo, Kíssila; Ciambarella, Bianca T; Nascimento, Ana L R; Cortez, Erika; Moura, Aníbal S; Guimarães, Fernanda V; Martins, Marco A; Barquero, Gonzalo; Ferreira, Rodrigo N; de Carvalho, Jorge J

2018-01-01

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of liver dysfunction worldwide and is commonly associated with obesity. Evidences suggest that NAFLD might be a mitochondrial disease, which contributes to the hepatic steatosis, oxidative stress, cytokine release, and cell death. Capybara oil (CO) is a rich source of polyunsaturated fatty acids (PUFA), which is known to improve inflammation and oxidative stress. In order to determine the effects of CO on NAFLD, C57Bl/6 mice were divided into 3 groups and fed a high-fat diet (HFD) (NAFLD group and NAFLD + CO group) or a control diet (CG group) during 16 weeks. The CO (1.5 g/kg/daily) was administered by gavage during the last 4 weeks of the diet protocol. We evaluated plasma liver enzymes, hepatic steatosis, and cytokine expression in liver as well as hepatocyte ultrastructural morphology and mitochondrial function. CO treatment suppressed hepatic steatosis, attenuated inflammatory response, and decreased plasma alanine aminotransferase (ALT) in mice with NAFLD. CO was also capable of restoring mitochondrial ultrastructure and function as well as balance superoxide dismutase and catalase levels. Our findings indicate that CO treatment has positive effects on NAFLD improving mitochondrial dysfunction, steatosis, acute inflammation, and oxidative stress.

Synthesis, characterization, and evaluation of paclitaxel loaded in six-arm star-shaped poly(lactic-co-glycolic acid)

PubMed Central

Chen, Yongxia; Yang, Ziying; Liu, Chao; Wang, Cuiwei; Zhao, Shunxin; Yang, Jing; Sun, Hongfan; Zhang, Zhengpu; Kong, Deling; Song, Cunxian

2013-01-01

Background Star-shaped polymers provide more terminal groups, and are promising for application in drug-delivery systems. Methods A new series of six-arm star-shaped poly(lactic-co-glycolic acid) (6-s-PLGA) was synthesized by ring-opening polymerization. The structure and properties of the 6-s-PLGA were characterized by carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry. Then, paclitaxel-loaded six-arm star-shaped poly(lactic-co-glycolic acid) nanoparticles (6-s-PLGA-PTX-NPs) were prepared under the conditions optimized by the orthogonal testing. High-performance liquid chromatography was used to analyze the nanoparticles’ encapsulation efficiency and drug-loading capacity, dynamic light scattering was used to determine their size and size distribution, and transmission electron microscopy was used to evaluate their morphology. The release performance of the 6-s-PLGA-PTX-NPs in vitro and the cytostatic effect of 6-s-PLGA-PTX-NPs were investigated in comparison with paclitaxel-loaded linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-PTX-NPs). Results The results of carbon-13 nuclear magnetic resonance spectroscopy and infrared spectroscopy suggest that the polymerization was successfully initiated by inositol and confirm the structure of 6-s-PLGA. The molecular weights of a series of 6-s-PLGAs had a ratio corresponding to the molar ratio of raw materials to initiator. Differential scanning calorimetry revealed that the 6-s-PLGA had a low glass transition temperature of 40°C–50°C. The 6-s-PLGA-PTX-NPs were monodispersed with an average diameter of 240.4±6.9 nm in water, which was further confirmed by transmission electron microscopy. The encapsulation efficiency of the 6-s-PLGA-PTX-NPs was higher than that of the L-PLGA-PTX-NPs. In terms of the in vitro release of nanoparticles, paclitaxel (PTX) was released more slowly and more steadily from 6-s-PLGA than from linear poly(lactic-co-glycolic acid). In the cytostatic study, the 6-s-PLGA-PTX-NPs and L-PLGA-PTX-NPs were found to have a similar antiproliferative effect, which indicates durable efficacy due to the slower release of the PTX when loaded in 6-s-PLGA. Conclusion The results suggest that 6-s-PLGA may be promising for application in PTX delivery to enhance sustained antiproliferative therapy. PMID:24235829

Goddard Institute for Space Studies (GISS) 3-Dimensional (3-D) Global Tracer Transport Model (DB1006)

DOE Data Explorer

Fung, I.

1993-01-01

This directory contains the input files used in simulations of atmospheric CO2 using the GISS 3-D global tracer transport model. The directory contains 16 files including a help file (CO2FUNG.HLP), 12 files containing monthly exchanges with vegetation and soils (CO2VEG.JAN - DEC), 1 file containing releases of CO2 from fossil fuel burning (CO2FOS.MRL), 1 file containing releases of CO2 from land transformations (CO2DEF.HOU), and 1 file containing the patterns of CO2 exchange with the oceans (CO2OCN.TAK).

Chemical and sewage sludge co-incineration in a full-scale MSW incinerator: toxic trace element mass balance.

PubMed

Biganzoli, Laura; Grosso, Mario; Giugliano, Michele; Campolunghi, Manuel

2012-10-01

Co-incineration of sludges with MSW is a quite common practice in Europe. This paper illustrates a case of co-incineration of both sewage sludges and chemical sludges, the latter obtained from drinking water production, in a waste-to-energy (WTE) plant located in northern Italy and equipped with a grate furnace, and compares the toxic trace elements mass balance with and without the co-incineration of sludges. The results show that co-incineration of sewage and chemical sludges does not result in an increase of toxic trace elements the total release in environment, with the exception of arsenic, whose total release increases from 1 mg t(fuel) (-1) during standard operation to 3 mg t(fuel) (-1) when sludges are co-incinerated. The increase of arsenic release is, however, attributable to the sole bottom ashes, where its concentration is five times higher during sludge co-incineration. No variation is observed for arsenic release at the stack. This fact is a further guarantee that the co-incineration of sludges, when performed in a state-of-the-art WTE plant, does not have negative effects on the atmospheric environment.

Development of a single-dose recombinant CAMP factor entrapping poly(lactide-co-glycolide) microspheres-based vaccine against Streptococcus agalactiae.

PubMed

Liu, Gang; Yin, Jinhua; Barkema, Herman W; Chen, Liben; Shahid, Muhammad; Szenci, Otto; De Buck, Jeroen; Kastelic, John P; Han, Bo

2017-03-01

Streptococcus agalactiae is an important contagious bovine mastitis pathogen. Although it is well controlled and even eradicated in most Northern European and North American dairy herds, the prevalence of this pathogen remains very high in China. However, research on development of a vaccine against S. agalactiae mastitis is scarce. The aims of the present study were to: (1) develop a single-dose vaccine against S. agalactiae based on poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) encapsulated CAMP factor, a conserved virulent protein encoded by S. agalactiae's cfb gene; and (2) evaluate its immunogenicity and protective efficacy in a mouse model. The cfb gene was cloned and expressed in a recombinant Escherichia coli strain Trans1-T1. The CAMP factor was tested to determine a safe dose range and then encapsulated in MS of PLGA (50:50) to assess its release pattern in vitro and immune reaction in vivo. Furthermore, a mouse model and a histopathological assay were developed to evaluate bacterial burden and vaccine efficacy. In the low dosage range (<100μg), CAMP factor had no obvious toxicity in mice. The release pattern in vitro was characterized by an initial burst release (44%), followed by a sustained and slower release over 7wk. In mice immunized with either pure CAMP factor protein or PLGA-CAMP, increased antibody titers were detected in the first 2wk, whereas only PLGA-CAMP immunization induced a sustained increase of antibody titers. In mice vaccinated with PLGA-CAMP, mortality and bacteria counts were lower (compared to a control group) after S. agalactiae challenge. Additionally, no pathological lesions were detected in the vaccinated group. Therefore, PLGA-CAMP conferred protective efficacy against S. agalactiae in our mouse model, indicating its potential as a vaccine against S. agalactiae mastitis. Furthermore, the slow-release kinetics of PLGA MS warranted optimism for development of a single-dose vaccine. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Bilayer tablets of Paliperidone for Extended release osmotic drug delivery

NASA Astrophysics Data System (ADS)

Chowdary, K. Sunil; Napoleon, A. A.

2017-11-01

The purpose of this study is to develop and optimize the formulation of paliperidone bilayer tablet core and coating which should meet in vitro performance of trilayered Innovator sample Invega. Optimization of core formulations prepared by different ratio of polyox grades and optimization of coating of (i) sub-coating build-up with hydroxy ethyl cellulose (HEC) and (ii).enteric coating build-up with cellulose acetate (CA). Some important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviours of Paliperidone. In vitro dissolution studies of Innovator sample (Invega) with formulations of different release rate which ever close release pattern during the whole 24 h test is finalized.

Cu(II)-catalyzed esterification reaction via aerobic oxidative cleavage of C(CO)-C(alkyl) bonds.

PubMed

Ma, Ran; He, Liang-Nian; Liu, An-Hua; Song, Qing-Wen

2016-02-04

A novel Cu(II)-catalyzed aerobic oxidative esterification of simple ketones for the synthesis of esters has been developed with wide functional group tolerance. This process is assumed to go through a tandem sequence consisting of α-oxygenation/esterification/nucleophilic addition/C-C bond cleavage and carbon dioxide is released as the only byproduct.

Mechanisms of Aromatase Inhibitor-induced Musculoskeletal Symptoms

DTIC Science & Technology

2012-07-01

through the TRPV1 cation channel, an important chemical and thermal nociceptive transducer (15). In addition to steroids supplied by circulation in...identify whether aromatase expression co-localizes with functional neuronal populations, such as TRPV1 or CGRP expressing sensory neurons...to augment neuropeptide release from cultured sensory neurons evoked by the inflammatory mediator bradykinin and TRPV1 -selective agonist capsaicin (17

Manganese phytate dotted polyaniline shell enwrapped carbon nanotube: Towards the reinforcements in fire safety and mechanical property of polymer.

PubMed

Wang, Junling; Zhan, Jing; Mu, Xiaowei; Jin, Xin; Chu, Fukai; Kan, Yongchun; Xing, Weiyi

2018-06-19

High fire hazard of epoxy resin (EP) has been an unavoidable obstruction on its wide application. Here, a manganese phytate dotted polyaniline shell enwrapped carbon nanotube (MPCNT) is facilely constructed and employed as flame retardant for EP. By adding 4.0 wt% MPCNT, the peak heat release rate, total heat release values, peak CO yields and total CO yields are decreased by 27.2, 12.3, 44.8, and 23.3%, respectively. The decreased absorbance intensity of toxic aromatic volatiles is also observed. Then, a tripartite cooperative flame retardant mechanism (a continuous barrier network, catalytic charring function of phytate, and catalytic activity of MnP/C system) is proposed. Furthermore, the storage modulus of EP composites with 2.0 and 4.0 wt% MPCNT are increased by 23.0 and 25.8% at 40 °C, respectively. Thus, the simultaneous reinforcements in fire safety and mechanical performance of EP are successfully achieved. This work may represent a significant step forward in the facile construction of functionalized carbon materials for achieving their whole potentials in polymer-matrix composite. Copyright © 2018. Published by Elsevier Inc.

Design, Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology

PubMed Central

Gunjal, P. T.; Shinde, M. B.; Gharge, V. S.; Pimple, S. V.; Gurjar, M. K.; Shah, M. N.

2015-01-01

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 32 full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D1 h,D6 h) and time required to 90% drug release (t90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet. PMID:26798171

Design, Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology.

PubMed

Gunjal, P T; Shinde, M B; Gharge, V S; Pimple, S V; Gurjar, M K; Shah, M N

2015-01-01

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 3(2) full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D1 h,D6 h) and time required to 90% drug release (t90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

Development and experimental design of a novel controlled-release matrix tablet formulation for indapamide hemihydrate.

PubMed

Antovska, Packa; Ugarkovic, Sonja; Petruševski, Gjorgji; Stefanova, Bosilka; Manchevska, Blagica; Petkovska, Rumenka; Makreski, Petre

2017-11-01

Development, experimental design and in vitro in vivo correlation (IVIVC) of controlled-release matrix formulation. Development of novel oral controlled delivery system for indapamide hemihydrate, optimization of the formulation by experimental design and evaluation regarding IVIVC on a pilot scale batch as a confirmation of a well-established formulation. In vitro dissolution profiles of controlled-release tablets of indapamide hemihydrate from four different matrices had been evaluated in comparison to the originator's product Natrilix (Servier) as a direction for further development and optimization of a hydroxyethylcellulose-based matrix controlled-release formulation. A central composite factorial design had been applied for the optimization of a chosen controlled-release tablet formulation. The controlled-release tablets with appropriate physical and technological properties had been obtained with a matrix: binder concentration variations in the range: 20-40w/w% for the matrix and 1-3w/w% for the binder. The experimental design had defined the design space for the formulation and was prerequisite for extraction of a particular formulation that would be a subject for transfer on pilot scale and IVIV correlation. The release model of the optimized formulation has shown best fit to the zero order kinetics depicted with the Hixson-Crowell erosion-dependent mechanism of release. Level A correlation was obtained.

Uniaxial pressure effect on the magnetic ordered moment and transition temperatures in BaFe 2 - x T x As 2 ( T = Co , Ni )

DOE PAGES

Tam, David W.; Song, Yu; Man, Haoran; ...

2017-02-17

In this paper, we use neutron diffraction and muon spin relaxation to study the effect of in-plane uniaxial pressure on the antiferromagnetic (AF) orthorhombic phase in BaFe 2As 2 and its Co- and Ni-substituted members near optimal superconductivity. In the low-temperature AF ordered state, uniaxial pressure necessary to detwin the orthorhombic crystals also increases the magnetic ordered moment, reaching an 11% increase under 40 MPa for BaFe 1.9Co 0.1As 2, and a 15% increase for BaFe 1.915Ni 0.085As 2. We also observe an increase of the AF ordering temperature (T N) of about 0.25 K/MPa in all compounds, consistent withmore » density functional theory calculations that reveal better Fermi surface nesting for itinerant electrons under uniaxial pressure. Finally, the doping dependence of the magnetic ordered moment is captured by combining dynamical mean field theory with density functional theory, suggesting that the pressure-induced moment increase near optimal superconductivity is closely related to quantum fluctuations and the nearby electronic nematic phase.« less

Co-culture with infrapatellar fat pad differentially stimulates proteoglycan synthesis and accumulation in cartilage and meniscus tissues.

PubMed

Nishimuta, James F; Bendernagel, Monica F; Levenston, Marc E

2017-09-01

Although osteoarthritis is widely viewed as a disease of the whole joint, relatively few studies have focused on interactions among joint tissues in joint homeostasis and degeneration. In particular, few studies have examined the effects of the infrapatellar fat pad (IFP) on cartilaginous tissues. The aim of this study was to test the hypothesis that co-culture with healthy IFP would induce degradation of cartilage and meniscus tissues. Bovine articular cartilage, meniscus, and IFP were cultured isolated or as cartilage-fat or meniscus-fat co-cultures for up to 14 days. Conditioned media were assayed for sulfated glycosaminoglycan (sGAG) content, nitrite content, and matrix metalloproteinase (MMP) activity, and explants were assayed for sGAG and DNA contents. Co-cultures exhibited increased cumulative sGAG release and sGAG release rates for both cartilage and meniscus, and the cartilage (but not meniscus) exhibited a substantial synergistic effect of co-culture (sGAG release in co-culture was significantly greater than the summed release from isolated cartilage and fat). Fat co-culture did not significantly alter the sGAG content of either cartilage or meniscus explants, indicating that IFP co-culture stimulated net sGAG production by cartilage. Nitrite release was increased relative to isolated tissue controls in co-cultured meniscus, but not the cartilage, with no synergistic effect of co-culture. Interestingly, MMP-2 production was decreased by co-culture for both cartilage and meniscus. This study demonstrates that healthy IFP may modulate joint homeostasis by stimulating sGAG production in cartilage. Counter to our hypothesis, healthy IFP did not promote degradation of either cartilage or meniscus tissues.

Carbon Monoxide-releasing Molecule-3 (CORM-3; Ru(CO)3Cl(Glycinate)) as a Tool to Study the Concerted Effects of Carbon Monoxide and Nitric Oxide on Bacterial Flavohemoglobin Hmp

PubMed Central

Tinajero-Trejo, Mariana; Denby, Katie J.; Sedelnikova, Svetlana E.; Hassoubah, Shahira A.; Mann, Brian E.; Poole, Robert K.

2014-01-01

CO and NO are small toxic gaseous molecules that play pivotal roles in biology as gasotransmitters. During bacterial infection, NO, produced by the host via the inducible NO synthase, exerts critical antibacterial effects while CO, generated by heme oxygenases, enhances phagocytosis of macrophages. In Escherichia coli, other bacteria and fungi, the flavohemoglobin Hmp is the most important detoxification mechanism converting NO and O2 to the ion nitrate (NO3−). The protoheme of Hmp binds not only O2 and NO, but also CO so that this ligand is expected to be an inhibitor of NO detoxification in vivo and in vitro. CORM-3 (Ru(CO)3Cl(glycinate)) is a metal carbonyl compound extensively used and recently shown to have potent antibacterial properties. In this study, attenuation of the NO resistance of E. coli by CORM-3 is demonstrated in vivo. However, polarographic measurements showed that CO gas, but not CORM-3, produced inhibition of the NO detoxification activity of Hmp in vitro. Nevertheless, CO release from CORM-3 in the presence of soluble cellular compounds is demonstrated by formation of carboxy-Hmp. We show that the inability of CORM-3 to inhibit the activity of purified Hmp is due to slow release of CO in protein solutions alone i.e. when sodium dithionite, widely used in previous studies of CO release from CORM-3, is excluded. Finally, we measure intracellular CO released from CORM-3 by following the formation of carboxy-Hmp in respiring cells. CORM-3 is a tool to explore the concerted effects of CO and NO in vivo. PMID:25193663

The Resolved Stellar Populations Early Release Science Program

NASA Astrophysics Data System (ADS)

Gilbert, Karoline; Weisz, Daniel; Resolved Stellar Populations ERS Program Team

2018-06-01

The Resolved Stellar Populations Early Release Science Program (PI D. Weisz) will observe Local Group targets covering a range of stellar density and star formation histories, including a globular cluster, and ultra-faint dwarf galaxy, and a star-forming dwarf galaxy. Using observations of these diverse targets we will explore a broad science program: we will measure star formation histories, the sub-solar stellar initial mass function, and proper motions, perform studies of evolved stars, and map extinction in the target fields. Our observations will be of high archival value for other science such as calibrating stellar evolution models, studying variable stars, and searching for metal-poor stars. We will determine optimal observational setups and develop data reduction techniques that will be common to JWST studies of resolved stellar populations. We will also design, test, and release point spread function (PSF) fitting software specific to NIRCam and NIRISS, required for the crowded stellar regime. Prior to the Cycle 2 Call for Proposals, we will release PSF fitting software, matched HST and JWST catalogs, and clear documentation and step-by-step tutorials (such as Jupyter notebooks) for reducing crowded stellar field data and producing resolved stellar photometry catalogs, as well as for specific resolved stellar photometry science applications.

Novel Membrane-Based Electrochemical Sensor for Real-Time Bio-Applications

PubMed Central

Alatraktchi, Fatima AlZahra'a; Bakmand, Tanya; Dimaki, Maria; Svendsen, Winnie E.

2014-01-01

This article presents a novel membrane-based sensor for real-time electrochemical investigations of cellular- or tissue cultures. The membrane sensor enables recording of electrical signals from a cell culture without any signal dilution, thus avoiding loss of sensitivity. Moreover, the porosity of the membrane provides optimal culturing conditions similar to existing culturing techniques allowing more efficient nutrient uptake and molecule release. The patterned sensor electrodes were fabricated on a porous membrane by electron-beam evaporation. The electrochemical performance of the membrane electrodes was characterized by cyclic voltammetry and chronoamperometry, and the detection of synthetic dopamine was demonstrated down to a concentration of 3.1 pM. Furthermore, to present the membrane-sensor functionality the dopamine release from cultured PC12 cells was successfully measured. The PC12 cells culturing experiments showed that the membrane-sensor was suitable as a cell culturing substrate for bio-applications. Real-time measurements of dopamine exocytosis in cell cultures were performed, where the transmitter release was recorded at the point of release. The developed membrane-sensor provides a new functionality to the standard culturing methods, enabling sensitive continuous in vitro monitoring and closely mimicking the in vivo conditions. PMID:25421738

Atmospheric carbon mineralization in an industrial-scale chrysotile mining waste pile.

PubMed

Nowamooz, Ali; Dupuis, J Christian; Beaudoin, Georges; Molson, John; Lemieux, Jean-Michel; Horswill, Micha; Fortier, Richard; Larachi, Faïçal; Maldague, Xavier; Constantin, Marc; Duchesne, Josee; Therrien, René

2018-06-12

Magnesium rich minerals that are abundant in ultramafic mining waste have the potential to be used as a safe and permanent sequestration solution for carbon dioxide (CO2). Our understanding of thermo-hydro-chemical regimes that govern this reaction at an industrial scale, however, has remained an important challenge to its widespread implementation. Through a year-long monitoring experiment performed at a 110Mt chrysotile waste pile, we have documented the existence of two distinct thermo-hydro-chemical regimes that control the ingress of CO2 and the subsequent mineral carbonation of the waste. The experimental results are supported by coupled free-air/porous media numerical flow and transport model that provides insights into optimization strategies to increase the efficiency of mineral sequestration at an industrial-scale. Although functioning passively under less than optimal conditions compared to lab-scale experiments, the 110Mt Thetford Mines pile is nevertheless estimated to be sequestering up to 100 tonnes of CO2 per year, with a potential total carbon capture capacity under optimal conditions of 3 Mt. Yearly, over 100 Mt of ultramafic mine waste suitable for mineral carbonation are generated by the global mining industry. Our results show that this waste material could become a safe and permanent carbon sink for diffuse sources of CO2.

Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS.

PubMed

Atkinson, L; Batten, T F C; Moores, T S; Varoqui, H; Erickson, J D; Deuchars, J

2004-01-01

Presynaptic P2X(7) receptors are thought to play a role in the modulation of transmitter release and have been localised to terminals with the location and morphology typical of excitatory boutons. To test the hypothesis that this receptor is preferentially associated with excitatory terminals we combined immunohistochemistry for the P2X(7) receptor subunit (P2X(7)R) with that for two vesicular glutamate transporters (VGLUT1 and VGLUT2) in the rat CNS. This confirmed that P2X(7)R immunoreactivity (IR) is present in glutamatergic terminals; however, whether it was co-localised with VGLUT1-IR or VGLUT2-IR depended on the CNS region examined. In the spinal cord, P2X(7)R-IR co-localised with VGLUT2-IR. In the brainstem, co-localisation of P2X(7)R-IR with VGLUT2-IR was widespread, but co-localisation with VGLUT1-IR was seen only in the external cuneate nucleus and spinocerebellar tract region of the ventral medulla. In the cerebellum, P2X(7)R-IR co-localised with both VGLUT1 and VGLUT2-IR in the granular layer. In the hippocampus it was co-localised only with VGLUT1-IR, including in the polymorphic layer of the dentate gyrus and the substantia radiatum of the CA3 region. In other forebrain areas, P2X(7)R-IR co-localised with VGLUT1-IR throughout the amygdala, caudate putamen, striatum, reticular thalamic nucleus and cortex and with VGLUT2-IR in the dorsal lateral geniculate nucleus, amygdala and hypothalamus. Dual labelling studies performed using markers for cholinergic, monoaminergic, GABAergic and glycinergic terminals indicated that in certain brainstem and spinal cord nuclei the P2X(7)R is also expressed by subpopulations of cholinergic and GABAergic/glycinergic terminals. These data support our previous hypothesis that the P2X(7)R may play a role in modulating glutamate release in functionally different systems throughout the CNS but further suggest a role in modulating release of inhibitory transmitters in some regions.

r.avaflow v1, an advanced open-source computational framework for the propagation and interaction of two-phase mass flows

NASA Astrophysics Data System (ADS)

Mergili, Martin; Fischer, Jan-Thomas; Krenn, Julia; Pudasaini, Shiva P.

2017-02-01

r.avaflow represents an innovative open-source computational tool for routing rapid mass flows, avalanches, or process chains from a defined release area down an arbitrary topography to a deposition area. In contrast to most existing computational tools, r.avaflow (i) employs a two-phase, interacting solid and fluid mixture model (Pudasaini, 2012); (ii) is suitable for modelling more or less complex process chains and interactions; (iii) explicitly considers both entrainment and stopping with deposition, i.e. the change of the basal topography; (iv) allows for the definition of multiple release masses, and/or hydrographs; and (v) serves with built-in functionalities for validation, parameter optimization, and sensitivity analysis. r.avaflow is freely available as a raster module of the GRASS GIS software, employing the programming languages Python and C along with the statistical software R. We exemplify the functionalities of r.avaflow by means of two sets of computational experiments: (1) generic process chains consisting in bulk mass and hydrograph release into a reservoir with entrainment of the dam and impact downstream; (2) the prehistoric Acheron rock avalanche, New Zealand. The simulation results are generally plausible for (1) and, after the optimization of two key parameters, reasonably in line with the corresponding observations for (2). However, we identify some potential to enhance the analytic and numerical concepts. Further, thorough parameter studies will be necessary in order to make r.avaflow fit for reliable forward simulations of possible future mass flow events.

Primary coenzyme Q10 (CoQ 10) deficiencies and related nephropathies.

PubMed

Ozaltin, Fatih

2014-06-01

Oxidative phosphorylation (OXPHOS) is a metabolic pathway that uses energy released by the oxidation of nutrients to generate adenosine triphosphate (ATP). Coenzyme Q10 (CoQ10), also known as ubiquinone, plays an essential role in the human body not only by generating ATP in the mitochondrial respiratory chain but also by providing protection from reactive oxygen species (ROS) and functioning in the activation of many mitochondrial dehydrogenases and enzymes required in pyrimidine nucleoside biosynthesis. The presentations of primary CoQ10 deficiencies caused by genetic mutations are very heterogeneous. The phenotypes related to energy depletion or ROS production may depend on the content of CoQ10 in the cell, which is determined by the severity of the mutation. Primary CoQ10 deficiency is unique among mitochondrial disorders because early supplementation with CoQ10 can prevent the onset of neurological and renal manifestations. In this review I summarize primary CoQ10 deficiencies caused by various genetic abnormalities, emphasizing its nephropathic form.

Development and Characterization of Novel Floating-Mucoadhesive Tablets Bearing Venlafaxine Hydrochloride.

PubMed

Misra, Raghvendra; Bhardwaj, Peeyush

2016-01-01

The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR) and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3) and citric acid were used as gas (CO2) generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72 ± 2.49 seconds and duration of floating 24.50 ± 0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF) at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr) and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr).

Optimized in vivo detection of dopamine release using 18F-fallypride PET.

PubMed

Ceccarini, Jenny; Vrieze, Elske; Koole, Michel; Muylle, Tom; Bormans, Guy; Claes, Stephan; Van Laere, Koen

2012-10-01

The high-affinity D(2/3) PET radioligand (18)F-fallypride offers the possibility of measuring both striatal and extrastriatal dopamine release during activation paradigms. When a single (18)F-fallypride scanning protocol is used, task timing is critical to the ability to explore both striatal and extrastriatal dopamine release simultaneously. We evaluated the sensitivity and optimal timing of task administration for a single (18)F-fallypride PET protocol and the linearized simplified reference region kinetic model in detecting both striatal and extrastriatal reward-induced dopamine release, using human and simulation studies. Ten healthy volunteers underwent a single-bolus (18)F-fallypride PET protocol. A reward responsiveness learning task was initiated at 100 min after injection. PET data were analyzed using the linearized simplified reference region model, which accounts for time-dependent changes in (18)F-fallypride displacement. Voxel-based statistical maps, reflecting task-induced D(2/3) ligand displacement, and volume-of-interest-based analysis were performed to localize areas with increased ligand displacement after task initiation, thought to be proportional to changes in endogenous dopamine release (γ parameter). Simulated time-activity curves for baseline and hypothetical dopamine release functions (different peak heights of dopamine and task timings) were generated using the enhanced receptor-binding kinetic model to investigate γ as a function of these parameters. The reward task induced increased ligand displacement in extrastriatal regions of the reward circuit, including the medial orbitofrontal cortex, ventromedial prefrontal cortex, and dorsal anterior cingulate cortex. For task timing of 100 min, ligand displacement was found for the striatum only when peak height of dopamine was greater than 240 nM, whereas for frontal regions, γ was always positive for all task timings and peak heights of dopamine. Simulation results for a peak height of dopamine of 200 nM showed that an effect of striatal ligand displacement could be detected only when task timing was greater than 120 min. The prefrontal and anterior cingulate cortices are involved in reward responsiveness that can be measured using (18)F-fallypride PET in a single scanning session. To measure both striatal and extrastriatal dopamine release, the height of dopamine released and task timing need to be considered in designing activation studies depending on regional D(2/3) density.

Development of a novel monoclonal antibody to human inducible co-stimulator ligand (ICOSL): Biological characteristics and application for enzyme-linked immunosorbent assay.

PubMed

Hu, Xiaohan; Wu, Jian; An, Jingnan; Hu, Yumin; Shen, Yu; Liu, Cuiping; Zhang, Xueguang

2016-07-01

ICOSL (B7-H2, CD275), a co-stimulatory molecule of the B7 superfamily, functions as a positive signal in immune response. To investigate whether ICOSL could be released into sera and the possible biological function of soluble ICOS (sICOSL), we generated and characterized a functional anti-human ICOSL monoclonal antibody (mAb), 20B10, and developed a novel enzyme-linked immunosorbent assay (ELISA) based on two anti-human ICOSL antibodies with different epitope specificities. Using the ELISA system, we found that sICOSL in the serum of healthy donors increases in an age-dependent manner and that the matrix metalloproteinase inhibitor (MMPI) could suppress sICOSL production. Together, these data demonstrate that the existence of circulating sICOSL in human serum might play an important role in immunoregulation. Copyright © 2016. Published by Elsevier B.V.

Hyperthermic overdrive: oxygen delivery does not limit thermal tolerance in Drosophila melanogaster.

PubMed

Mölich, Andreas B; Förster, Thomas D; Lighton, John R B

2012-01-01

The causes of thermal tolerance limits in animals are controversial. In many aquatic species, it is thought that the inability to deliver sufficient oxygen at high temperatures is more critical than impairment of molecular functions of the mitochondria. However, terrestrial insects utilize a tracheal system, and the concept of a mismatch between metabolic demand and circulatory performance might not apply to them. Using thermo-limit respirometry, it has been shown earlier in Drosophila melanogaster that CO(2) release rates at temperatures above the upper thermal limit (CT(max)) exceed the rate at CT(max). The nature of this post-CT(max), or "post-mortal" peak, is unknown. Either its source is increased aerobic mitochondrial respiration (hyperthermic overdrive), or an anaerobic process such as liberation of stored CO(2) from the hemolymph. The post-mortal peak of CO(2) release was found to be oxygen dependent. As the rate of CO(2) emission is a conservative indicator of rate of O(2) consumption, aerobic flux at the thermal limit is submaximal, which contradicts the theory that oxygen availability limits metabolic activity at high temperatures in insects. Consequently, the tracheal system should be capable of delivering sufficient oxygen for aerobic activity of the mitochondria at and above Ct(max).

Electroless plating Cu-Co-P polyalloy on UV/ozonolysis irradiated polyethylene terephthalate film and its corrosion resistance

NASA Astrophysics Data System (ADS)

Hou, Lei; Bi, Siyi; Zhao, Hang; Xu, Yumeng; Mu, Yuhang; Lu, Yinxiang

2017-05-01

High corrosion resistant Cu-Co-P coatings were firstly prepared on polyethylene terephthalate (PET) substrate by electroless plating in combination with UV/ozonolysis irradiation under optimized cobalt sulfate heptahydrate concentration, pH value, plating temperature and time. The copper polyalloy/PET composite can be obtained in three steps, namely: (i) the generation of oxygen-containing functionalities (carboxylic groups) onto PET surface through UV irradiation combined with ozone, (ii) Cu seeding catalysts were obtained after being immersed into cupric citrate and NaBH4 solutions subsequently, and (iii) Cu-Co-P polyalloy metallization using electroless plating bath. Attenuated total reflection fourier transformation infrared spectrometer (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), water contact angle measurement and energy dispersive X-ray analysis (EDAX) were utilized to track the surface changes during the whole process. The electroless plating conditions were optimized by an orthogonal experiment (L9(3)4) for Cu-Co-P coating as follows: CoSO4·7H2O addition of 0.08 M, pH value, plating temperature and time were set on 10.0, 35 °C and 25 min, respectively. Under the optimal conditions, copper polyalloy possessed high adhesive strength and the lowest surface resistance (8.06 Ω/sq), while maintaining reliability even after over 1000 times of bending and mechanical stress. The results of scanning electron microscope (SEM) and atomic force microscope (AFM) measurements showed that Cu-Co-P layer formed on PET surface was imparted with fine uniformity and high compactness. Electrochemical test revealed the optimized Cu-Co-P coatings exhibited high corrosion resistance in NaCl, NaOH and HCl solutions, respectively. The excellent electromagnetic interference shielding effectiveness (EMI SE >99.999% at frequency ranging from 30 MHz to 1000 MHz) of copper polyalloy/PET composites was confirmed by the spectrum analyzer. Therefore, this copper polyalloy will have potential applications in microelectronics packaging and coatings for anti-corrosion and electromagnetic interference shielding.

pH-Dependent, Thermosensitive Polymeric Nanocarriers for Drug Delivery to Solid Tumors

PubMed Central

Chen, Ching-Yi; Kim, Tae Hee; Wu, Wen-Chung; Huang, Chi-Ming; Wei, Hua; Mount, Christopher W.; Tian, Yanqing; Jang, Sei-Hum; Pun, Suzie H.; Jen, Alex K-Y

2013-01-01

Polymeric micelles are promising carriers for anticancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice. PMID:23498892

Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth

NASA Astrophysics Data System (ADS)

Lin, Keng-Min; Shea, Jill; Gale, Bruce K.; Sant, Himanshu; Larrabee, Patti; Agarwal, Jay

2016-04-01

Nerve injury can occur due to penetrating wounds, compression, traumatic stretch, and cold exposure. Despite prompt repair, outcomes are dismal. In an attempt to help resolve this challenge, in this work, a poly-lactic-co-glycolic acid (PLGA) nerve conduit with associated biodegradable drug reservoir was designed, fabricated, and tested. Unlike current nerve conduits, this device is capable of fitting various clinical scenarios by delivering different drugs without reengineering the whole system. To demonstrate the potential of this device for nerve repair, a series of experiments were performed using nerve growth factor (NGF). First, an NGF dosage curve was developed to determine the minimum NGF concentration for optimal axonal outgrowth on chick dorsal root ganglia (DRG) cells. Next, PLGA devices loaded with NGF were evaluated for sustained drug release and axon growth enhancement with the released drug. A 20 d in vitro release test was conducted and the nerve conduit showed the ability to meet and maintain the minimum NGF requirement determined previously. Bioactivity assays of the released NGF showed that drug released from the device between the 15th and 20th day could still promote axon growth (76.6-95.7 μm) in chick DRG cells, which is in the range of maximum growth. These novel drug delivery conduits show the ability to deliver NGF at a dosage that efficiently promotes ex vivo axon growth and have the potential for in vivo application to help bridge peripheral nerve gaps.

Polymer grafted-magnetic halloysite nanotube for controlled and sustained release of cationic drug.

PubMed

Fizir, Meriem; Dramou, Pierre; Zhang, Kai; Sun, Cheng; Pham-Huy, Chuong; He, Hua

2017-11-01

In this research, novel polymer grafted-magnetic halloysite nanotubes with norfloxacin loaded (NOR-MHNTs) and controlled-release, was achieved by surface-initiated precipitation polymerization. The magnetic halloysite nanotubes exhibited better adsorption of NOR (72.10mgg -1 ) compared with the pristine HNTs (30.80mgg -1 ). Various parameters influencing the drug adsorption of the MHNTs for NOR were studied. Polymer grafted NOR-MHNTs has been designed using flexible docking in computer simulation to choose optimal monomers. NOR-MHNTs/poly (methacrylic acid or acrylamide-co-ethylene glycol dimethacrylate) nanocomposite were synthesized using NOR-MHNTs, methacrylic acid (MAA) or acrylamide (AM), ethylene glycol dimethacrylate (EGDMA) and AIBN as nanotemplate, monomers, cross linker and initiator, respectively. The magnetic nanocomposites were characterized by FTIR, TEM, XRD and VSM. The magnetic nanocomposites show superparamagnetic property and fast magnetic response (12.09emug -1 ). The copolymerization of monomers and cross linker led to a better sustained release of norfloxacin (>60h) due to the strong interaction formed between monomers and this cationic drug. The cumulative release rate of NOR is closely related to the cross linker amount. In conclusion, combining the advantages of the high adsorption capacity and magnetic proprieties of this biocompatible clay nanotube and the advantages of polymer shell in the enhancement of controlled-sustained release of cationic drug, a novel formulation for the sustained-controlled release of bioactive agents is developed and may have considerable potential application in targeting drug delivery system. Copyright © 2017. Published by Elsevier Inc.

The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

PubMed Central

Jennings, Katie A.; Platt, Nicola J.; Cragg, Stephanie J.

2015-01-01

Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

Sustained release carrier for adenosine triphosphate as signaling molecule.

PubMed

Wischke, Christian; Weigel, Judith; Bulavina, Larisa; Lendlein, Andreas

2014-12-10

Adenosine triphosphate (ATP) is a molecule with a fascinating variety of intracellular and extracellular biological functions that go far beyond energy metabolism. Due to its limited passive diffusion through biological membranes, controlled release systems may allow to interact with ATP-mediated extracellular processes. In this study, two release systems were explored to evaluate the capacity for either long-term or short-term release: (i) Poly[(rac-lactide)-co-glycolide] (PLGA) implant rods were capable of ATP release over days to weeks, depending on the PLGA molecular weight and end-group capping, but were also associated with partial hydrolytic degradation of ATP to ADP and AMP, but not adenosine. (ii) Thermosensitive methylcellulose hydrogels with a gelation occurring at body temperature allowed combining adjustable loading levels and the capacity for injection, with injection forces less than 50N even for small 27G needles. Finally, a first in vitro study illustrated purinergic-triggered response of primary murine microglia to ATP released from hydrogels, demonstrating the potential relevance for biomedical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Islet graft survival and function: concomitant culture and transplantation with vascular endothelial cells in diabetic rats.

PubMed

Pan, Xiaoming; Xue, Wujun; Li, Yang; Feng, Xinshun; Tian, Xiaohui; Ding, Chenguang

2011-12-15

Human islet transplantation is a great potential therapy for type I diabetes. To investigate islet graft survival and function, we recently showed the improved effects after co-culture and co-transplantation with vascular endothelial cells (ECs) in diabetic rats. ECs were isolated, and the viability of isolated islets was assessed in two groups (standard culture group and co-culture group with ECs). Then streptozotocin-induced diabetic rats were divided into four groups before islet transplantation as follows: group A with infusion of islet grafts; group B with combined vascular ECs and islet grafts; groups C and D as controls with single ECs infusion and phosphate-buffered saline injection, respectively. Blood glucose and insulin concentrations were measured daily. Expression of vascular endothelial growth factor was investigated by immunohistochemical staining. The mean microvascular density was also calculated. More than 90% of acridine orange-propidium iodide staining positive islets demonstrated normal morphology while co-cultured with ECs for 7 days. Compared with standard control, insulin release assays showed a significantly higher simulation index in co-culture group except for the first day (P<0.05). After transplantation, there was a significant difference in concentrations of blood glucose and insulin among these groups after 3 days (P<0.05). The mean microvascular density in co-culture group was significantly higher than that in single islet group (P=0.04). Co-culture with ECs in vitro could improve the survival and function of isolated rat islet, and co-transplantation of islets with ECs could effectively prolong the islet graft survival in diabetic rats.

A generic analysis of energy use and solvent selection for CO2 separation from post-combustion flue gases

USGS Publications Warehouse

Lu, Y.; Chen, S.; Rostam-Abadi, M.

2008-01-01

A thermodynamic calculation was performed to determine the theoretical minimum energy used to separate CO2 from a coal combustion flue gas in a typical adsorption-desorption system. Under ideal conditions, the minimum energy required to separate CO2 from post-combustion flue gas and produce pure CO2 at 1 atmospheric pressure was only about 1183 kJ/kg CO2. This amount could double with the addition of the driving forces of mass and heat transfer and the adverse impacts of absorption heat release on adsorption capacity. Thermodynamic analyses were also performed for the aqueous amine-based absorption process. Two CO2 reaction mechanisms, the carbamate formation reaction with primary/secondary amines and the CO2 hydration reaction with tertiary amines, were included in the absorption reaction. The reaction heat, sensible heat, and stripping heat were all important to the total heat requirement. The heat use of an ideal tertiary amine amounted to 2786 kJ/kg, compared to 3211 kJ/kg for an ideal primary amine. The heat usage of an ideal amine was about 20% lower than that of commercially available amines. Optimizing the absorption process configuration could further reduce energy use. This is an abstract of a paper presented at the 2008 AIChE Spring National Meeting (New Orleans, LA 4/6-10/2008).

Greenhouse gas emissions from oilfield-produced water in Shengli Oilfield, Eastern China.

PubMed

Yang, Shuang; Yang, Wei; Chen, Guojun; Fang, Xuan; Lv, Chengfu; Zhong, Jiaai; Xue, Lianhua

2016-08-01

Greenhouse gas (GHG) emissions from oil and gas systems are an important component of the GHG emission inventory. To assess the carbon emissions from oilfield-produced water under atmospheric conditions correctly, in situ detection and simulation experiments were developed to study the natural release of GHG into the atmosphere in the Shengli Oilfield, the second largest oilfield in China. The results showed that methane (CH4) and carbon dioxide (CO2) were the primary gases released naturally from the oilfield-produced water. The atmospheric temperature and release time played important roles in determining the CH4 and CO2 emissions under atmospheric conditions. Higher temperatures enhanced the carbon emissions. The emissions of both CH4 and CO2 from oilfield-produced water were highest at 27°C and lowest at 3°C. The bulk of CH4 and CO2 was released from the oilfield-produced water during the first release period, 0-2hr, for each temperature, with a maximum average emission rate of 0.415gCH4/(m(3)·hr) and 3.934gCO2/(m(3)·hr), respectively. Then the carbon emissions at other time periods gradually decreased with the extension of time. The higher solubility of CO2 in water than CH4 results in a higher emission rate of CH4 than CO2 over the same release duration. The simulation proved that oilfield-produced water is one of the potential emission sources that should be given great attention in oil and gas systems. Copyright © 2016. Published by Elsevier B.V.

Characterization of temperature and pH-responsive poly-N-isopropylacrylamide-co-polymer nanoparticles for the release of antimicrobials

NASA Astrophysics Data System (ADS)

Hill, Laura E.; Gomes, Carmen L.

2014-09-01

Chitosan and alginate are both pH-responsive biopolymers extracted from crustacean exoskeletons and brown algae, respectively. Poly-N-isopropylacrylamide (PNIPAAM) is a hydrogel that becomes hydrophobic at a lower-critical solution temperature. This study sought to combine pH- and temperature-responsive polymers via crosslinking, in order to create a dual-stimuli responsive polymer for hydrophobic antimicrobial compounds delivery, improving their antimicrobial effects. Cinnamon bark extract (CBE) was used as a model for hydrophobic antimicrobial. Two co-polymers were synthesized to create two nanoparticles types: chitosan-co-PNIPAAM and alginate-co-PNIPAAM. Nanoparticles were formed from the resulting co-polymers using a self-assembly top-down process followed by glutaraldehyde or calcium chloride crosslinking. These nanoparticles were then used as controlled delivery vehicles for CBE, whose rapid release could be triggered by specific external stimuli. For the same pH and temperature conditions, the chitosan-co-PNIPAAM nanoparticles were significantly more potent bacterial inhibitors against both pathogens and also exhibited a faster CBE release over time as well as slightly higher entrapment efficiency. The alginate-co-PNIPAAM nanoparticles were significantly smaller and exhibited a slow, gradual release over a long time period. Although both nanoparticles were able to effectively inhibit pathogen growth at lower (P < 0.05) concentration than free CBE, the chitosan-co-PNIPAAM nanoparticles were more effective in delivering a natural antimicrobial with controlled release against foodborne pathogens.

Quantitative risk assessment of CO2 transport by pipelines--a review of uncertainties and their impacts.

PubMed

Koornneef, Joris; Spruijt, Mark; Molag, Menso; Ramírez, Andrea; Turkenburg, Wim; Faaij, André

2010-05-15

A systematic assessment, based on an extensive literature review, of the impact of gaps and uncertainties on the results of quantitative risk assessments (QRAs) for CO(2) pipelines is presented. Sources of uncertainties that have been assessed are: failure rates, pipeline pressure, temperature, section length, diameter, orifice size, type and direction of release, meteorological conditions, jet diameter, vapour mass fraction in the release and the dose-effect relationship for CO(2). A sensitivity analysis with these parameters is performed using release, dispersion and impact models. The results show that the knowledge gaps and uncertainties have a large effect on the accuracy of the assessed risks of CO(2) pipelines. In this study it is found that the individual risk contour can vary between 0 and 204 m from the pipeline depending on assumptions made. In existing studies this range is found to be between <1m and 7.2 km. Mitigating the relevant risks is part of current practice, making them controllable. It is concluded that QRA for CO(2) pipelines can be improved by validation of release and dispersion models for high-pressure CO(2) releases, definition and adoption of a universal dose-effect relationship and development of a good practice guide for QRAs for CO(2) pipelines. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Synthesis of calcium carbonate in alkali solution based on graphene oxide and reduced graphene oxide

NASA Astrophysics Data System (ADS)

Yaseen, Sarah Abduljabbar; Yiseen, Ghadah Abdaljabar; Li, Zongjin

2018-06-01

This paper reports a new approach of producing CaCO3 particles in alkali solution. CaCO3 particles with pure calcite structure were obtained from the reaction of water-dispersed graphene oxide (GO) or reduced graphene oxide (rGO) with either Ca(OH)2 or CaO. In Fourier Transform Infrared (FTIR) spectra, the pure calcite structure was demonstrated by fundamental bands at 1425 (ν3), 873 (ν2), and 712 cm-1 (ν4). The Raman spectra showed the characteristic peak of calcite structure at 1085 cm-1 (ν1). X-ray diffraction pattern (XRD) and X-ray photoelectron spectroscopy (XPS) analyses further confirmed that only the pure calcite phase of CaCO3 was formed in both synthesis approaches. Scanning electron microscopy (SEM), Energy dispersive X-ray analyzer (EDX), and High-resolution transmission electron microscopy (HRTEM) also confirmed that distorted cubic and rhombic calcite particles were obtained with GO, while the pine flower-like and flower-like particles were obtained with rGO, and the average crystallite sizes varied from 26 to 44 nm. The mechanism of the reaction was investigated and it was found that the decomposition of oxygen functional groups on the surface of GO or rGO in certain alkaline media to release CO, CO2, and water was a key process as the released CO2 further reacted with OH- and Ca2+ to form CaCO3. This demonstrated that both GO and rGO could be used as main reactants for the synthesis of calcite.

The synergistic effects of CO2 laser treatment with calcium silicate cement of antibacterial, osteogenesis and cementogenesis efficacy

NASA Astrophysics Data System (ADS)

Hsu, T.-T.; Kao, C.-T.; Chen, Y.-W.; Huang, T.-H.; Yang, J.-J.; Shie, M.-Y.

2015-05-01

Calcium silicate-based material (CS) has been successfully used in dental clinical applications. Some researches show that the antibacterial effects of CO2 laser irradiation are highly efficient when bacteria are embedded in biofilm, due to a photo-thermal mechanism. The purpose of this study was to confirm the effects of CO2 laser irradiation on CS, with regard to both material characterization and human periodontal ligament cell (hPDLs) viability. CS was irradiated with a dental CO2 laser using directly mounted fiber optics in wound healing mode with a spot area of 0.25 cm2, and then stored in an incubator at 100% relative humidity and 37 °C for 1 d to set. The hPDLs cultured on CS were analyzed, along with their proliferation and odontogenic differentiation behaviors. The results indicate that the CO2 laser irradiation increased the amount of Ca and Si ions released from the CS, and regulated cell behavior. CO2 laser-irradiated CS promoted cementogenic differentiation of hPDLs, with the increased formation of mineralized nodules on the substrate’s surface. It also up-regulated the protein expression of multiple markers of cementogenic and the expression of cementum attachment protein. The current study provides new and important data about the effects of CO2 laser irradiation on CS. Taking cell functions into account, the Si concentration released from CS with laser irradiated may be lower than a critical value, and this information could lead to the development of new regenerative therapies for dentin and periodontal tissue.

Particle-size distribution modified effective medium theory and validation by magneto-dielectric Co-Ti substituted BaM ferrite composites

NASA Astrophysics Data System (ADS)

Li, Qifan; Chen, Yajie; Harris, Vincent G.

2018-05-01

This letter reports an extended effective medium theory (EMT) including particle-size distribution functions to maximize the magnetic properties of magneto-dielectric composites. It is experimentally verified by Co-Ti substituted barium ferrite (BaCoxTixFe12-2xO19)/wax composites with specifically designed particle-size distributions. In the form of an integral equation, the extended EMT formula essentially takes the size-dependent parameters of magnetic particle fillers into account. It predicts the effective permeability of magneto-dielectric composites with various particle-size distributions, indicating an optimal distribution for a population of magnetic particles. The improvement of the optimized effective permeability is significant concerning magnetic particles whose properties are strongly size dependent.

Variations in respiratory excretion of carbon dioxide can be used to calculate pulmonary blood flow.

PubMed

Preiss, David A; Azami, Takafumi; Urman, Richard D

2015-02-01

A non-invasive means of measuring pulmonary blood flow (PBF) would have numerous benefits in medicine. Traditionally, respiratory-based methods require breathing maneuvers, partial rebreathing, or foreign gas mixing because exhaled CO2 volume on a per-breath basis does not accurately represent alveolar exchange of CO2. We hypothesized that if the dilutional effect of the functional residual capacity was accounted for, the relationship between the calculated volume of CO2 removed per breath and the alveolar partial pressure of CO2 would be reversely linear. A computer model was developed that uses variable tidal breathing to calculate CO2 removal per breath at the level of the alveoli. We iterated estimates for functional residual capacity to create the best linear fit of alveolar CO2 pressure and CO2 elimination for 10 minutes of breathing and incorporated the volume of CO2 elimination into the Fick equation to calculate PBF. The relationship between alveolar pressure of CO2 and CO2 elimination produced an R(2) = 0.83. The optimal functional residual capacity differed from the "actual" capacity by 0.25 L (8.3%). The repeatability coefficient leveled at 0.09 at 10 breaths and the difference between the PBF calculated by the model and the preset blood flow was 0.62 ± 0.53 L/minute. With variations in tidal breathing, a linear relationship exists between alveolar CO2 pressure and CO2 elimination. Existing technology may be used to calculate CO2 elimination during quiet breathing and might therefore be used to accurately calculate PBF in humans with healthy lungs.