Experimental and modeling studies of ultrasound-assisted release of phenolics from oak chips into model wine.

PubMed

Tao, Yang; Zhang, Zhihang; Sun, Da-Wen

2014-09-01

The enhancement of release of oak-related compounds from oak chips during wine aging with oak chips may interest the winemaking industry. In this study, the 25-kHz ultrasound waves were used to intensify the mass transfer of phenolics from oak chips into a model wine. The influences of acoustic energy density (6.3-25.8 W/L) and temperature (15-25 °C) on the release kinetics of total phenolics were investigated systematically. The results exhibited that the total phenolic yield released was not affected by acoustic energy density significantly whereas it increased with the increase of temperature during sonication. Furthermore, to describe the mechanism of mass transfer of phenolics in model wine under ultrasonic field, the release kinetics of total phenolics was simulated by both a second-order kinetic model and a diffusion model. The modeling results revealed that the equilibrium concentration of total phenolics in model wine, the initial release rate and effective diffusivity of total phenolics generally increased with acoustic energy density and temperature. In addition, temperature had a negative effect on the second-order release rate constant whereas acoustic energy density had an opposite effect. Copyright © 2014 Elsevier B.V. All rights reserved.

Kinetic Modeling of Slow Energy Release in Non-Ideal Carbon Rich Explosives

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

Vitello, P; Fried, L; Glaesemann, K

2006-06-20

We present here the first self-consistent kinetic based model for long time-scale energy release in detonation waves in the non-ideal explosive LX-17. Non-ideal, insensitive carbon rich explosives, such as those based on TATB, are believed to have significant late-time slow release in energy. One proposed source of this energy is diffusion-limited growth of carbon clusters. In this paper we consider the late-time energy release problem in detonation waves using the thermochemical code CHEETAH linked to a multidimensional ALE hydrodynamics model. The linked CHEETAH-ALE model dimensional treats slowly reacting chemical species using kinetic rate laws, with chemical equilibrium assumed for speciesmore » coupled via fast time-scale reactions. In the model presented here we include separate rate equations for the transformation of the un-reacted explosive to product gases and for the growth of a small particulate form of condensed graphite to a large particulate form. The small particulate graphite is assumed to be in chemical equilibrium with the gaseous species allowing for coupling between the instantaneous thermodynamic state and the production of graphite clusters. For the explosive burn rate a pressure dependent rate law was used. Low pressure freezing of the gas species mass fractions was also included to account for regions where the kinetic coupling rates become longer than the hydrodynamic time-scales. The model rate parameters were calibrated using cylinder and rate-stick experimental data. Excellent long time agreement and size effect results were achieved.« less

Behaviour of oceanic 137Cs following the Fukushima Daiichi Nuclear Power Plant accident for four years simulated numerically by a regional ocean model

NASA Astrophysics Data System (ADS)

Tsumune, D.; Tsubono, T.; Aoyama, M.; Misumi, K.; Tateda, Y.

2015-12-01

A series of accidents at the Fukushima Dai-ichi Nuclear Power Plant (1F NPP) following the earthquake and tsunami of 11 March 2011 resulted in the release of radioactive materials to the ocean by two major pathways, direct release from the accident site and atmospheric deposition.We reconstructed spatiotemporal variability of 137Cs activity in the regional ocean for four years by numerical model, such as a regional scale and the North Pacific scale oceanic dispersion models, an atmospheric transport model, a sediment transport model, a dynamic biological compartment model for marine biota and river runoff model. Direct release rate of 137Cs were estimated for four years after the accident by comparing simulated results and observed activities very close to the site. The estimated total amounts of directly release was 3.6±0.7 PBq. Directly release rate of 137Cs decreased exponentially with time by the end of December 2012 and then, was almost constant. Decrease rate were quite small after 2013. The daily release rate of 137Cs was estimated to be the order of magnitude of 1010 Bq/day by the end of March 2015. The activity of directly released 137Cs was detectable only in the coastal zone after December 2012. Simulated 137Cs activities attributable to direct release were in good agreement with observed activities, a result that implies the estimated direct release rate was reasonable. There is no observed data of 137Cs activity in the ocean from 11 to 21 March 2011. Observed data of marine biota should reflect the history of 137Cs activity in this early period. We reconstructed the history of 137Cs activity in this early period by considering atmospheric deposition, river input, rain water runoff from the 1F NPP site. The comparisons between simulated 137Cs activity of marine biota by a dynamic biological compartment and observed data also suggest that simulated 137Cs activity attributable to atmospheric deposition was underestimated in this early period. The simulated river flux of 137Cs to the ocean did not effect on 137Cs activity in the ocean even if the parameters in this simulation have uncertainties because of the lack of observed data in rivers in the earlier period.

Behaviour of oceanic 137Cs following the Fukushima Daiichi Nuclear Power Plant accident for four years simulated numerically by a regional ocean model

NASA Astrophysics Data System (ADS)

Torn, M. S.; Koven, C. D.; Riley, W. J.; Zhu, B.; Hicks Pries, C.; Phillips, C. L.

2014-12-01

A series of accidents at the Fukushima Dai-ichi Nuclear Power Plant (1F NPP) following the earthquake and tsunami of 11 March 2011 resulted in the release of radioactive materials to the ocean by two major pathways, direct release from the accident site and atmospheric deposition.We reconstructed spatiotemporal variability of 137Cs activity in the regional ocean for four years by numerical model, such as a regional scale and the North Pacific scale oceanic dispersion models, an atmospheric transport model, a sediment transport model, a dynamic biological compartment model for marine biota and river runoff model. Direct release rate of 137Cs were estimated for four years after the accident by comparing simulated results and observed activities very close to the site. The estimated total amounts of directly release was 3.6±0.7 PBq. Directly release rate of 137Cs decreased exponentially with time by the end of December 2012 and then, was almost constant. Decrease rate were quite small after 2013. The daily release rate of 137Cs was estimated to be the order of magnitude of 1010 Bq/day by the end of March 2015. The activity of directly released 137Cs was detectable only in the coastal zone after December 2012. Simulated 137Cs activities attributable to direct release were in good agreement with observed activities, a result that implies the estimated direct release rate was reasonable. There is no observed data of 137Cs activity in the ocean from 11 to 21 March 2011. Observed data of marine biota should reflect the history of 137Cs activity in this early period. We reconstructed the history of 137Cs activity in this early period by considering atmospheric deposition, river input, rain water runoff from the 1F NPP site. The comparisons between simulated 137Cs activity of marine biota by a dynamic biological compartment and observed data also suggest that simulated 137Cs activity attributable to atmospheric deposition was underestimated in this early period. The simulated river flux of 137Cs to the ocean did not effect on 137Cs activity in the ocean even if the parameters in this simulation have uncertainties because of the lack of observed data in rivers in the earlier period.

Hydrodynamic Impacts on Dissolution, Transport and Absorption from Thousands of Drug Particles Moving within the Intestines

NASA Astrophysics Data System (ADS)

Behafarid, Farhad; Brasseur, James G.

2017-11-01

Following tablet disintegration, clouds of drug particles 5-200 μm in diameter pass through the intestines where drug molecules are absorbed into the blood. Release rate depends on particle size, drug solubility, local drug concentration and the hydrodynamic environment driven by patterned gut contractions. To analyze the dynamics underlying drug release and absorption, we use a 3D lattice Boltzmann model of the velocity and concentration fields driven by peristaltic contractions in vivo, combined with a mathematical model of dissolution-rate from each drug particle transported through the grid. The model is empirically extended for hydrodynamic enhancements to release rate by local convection and shear-rate, and incorporates heterogeneity in bulk concentration. Drug dosage and solubility are systematically varied along with peristaltic wave speed and volume. We predict large hydrodynamic enhancements (35-65%) from local shear-rate with minimal enhancement from convection. With high permeability boundary conditions, a quasi-equilibrium balance between release and absorption is established with volume and wave-speed dependent transport time scale, after an initial transient and before a final period of dissolution/absorption. Supported by FDA.

Comparative quantification of oxygen release by wetland plants: electrode technique and oxygen consumption model.

PubMed

Wu, Haiming; Liu, Jufeng; Zhang, Jian; Li, Cong; Fan, Jinlin; Xu, Xiaoli

2014-01-01

Understanding oxygen release by plants is important to the design of constructed wetlands for wastewater treatment. Lab-scale systems planted with Phragmites australis were studied to evaluate the amount of oxygen release by plants using electrode techniques and oxygen consumption model. Oxygen release rate (0.14 g O2/m(2)/day) measured using electrode techniques was much lower than that (3.94-25.20 gO2/m(2)/day) calculated using the oxygen consumption model. The results revealed that oxygen release by plants was significantly influenced by the oxygen demand for the degradation of pollutants, and the oxygen release rate increased with the rising of the concentration of degradable materials in the solution. The summary of the methods in qualifying oxygen release by wetland plants demonstrated that variations existed among different measuring methods and even in the same measuring approach. The results would be helpful for understanding the contribution of plants in constructed wetlands toward actual wastewater treatment.

Tailoring drug release rates in hydrogel-based therapeutic delivery applications using graphene oxide

PubMed Central

Zhi, Z. L.; Craster, R. V.

2018-01-01

Graphene oxide (GO) is increasingly used for controlling mass diffusion in hydrogel-based drug delivery applications. On the macro-scale, the density of GO in the hydrogel is a critical parameter for modulating drug release. Here, we investigate the diffusion of a peptide drug through a network of GO membranes and GO-embedded hydrogels, modelled as porous matrices resembling both laminated and ‘house of cards’ structures. Our experiments use a therapeutic peptide and show a tunable nonlinear dependence of the peptide concentration upon time. We establish models using numerical simulations with a diffusion equation accounting for the photo-thermal degradation of fluorophores and an effective percolation model to simulate the experimental data. The modelling yields an interpretation of the control of drug diffusion through GO membranes, which is extended to the diffusion of the peptide in GO-embedded agarose hydrogels. Varying the density of micron-sized GO flakes allows for fine control of the drug diffusion. We further show that both GO density and size influence the drug release rate. The ability to tune the density of hydrogel-like GO membranes to control drug release rates has exciting implications to offer guidelines for tailoring drug release rates in hydrogel-based therapeutic delivery applications. PMID:29445040

Release of Water Soluble Drugs from Dynamically Swelling POLY(2-HYDROXYETHYL Methacrylate - CO - Methacrylic Acid) Hydrogels.

NASA Astrophysics Data System (ADS)

Kou, Jim Hwai-Cher

In this study, ionizable copolymers of HEMA and methacrylic acid (MA) are investigated for their potential use in developing pH dependent oral delivery systems. Because of the MA units, these gels swell extensively at high pH. Since solute diffusion in the hydrophilic polymers depends highly on the water content of the matrix, it is anticipated that the release rate will be modulated by this pH induced swelling. From a practical point of view, the advantage of the present system is that one can minimize drug loss in the stomach and achieve a programmed release in intestine. This approach is expected to improve delivery of acid labile drugs or drugs that cause severe gastrointestinal side effects. This work mainly focuses on the basic understanding of the mechanism involved in drug release from the poly(HEMA -co- MA) gels, especially under dynamic swelling conditions. Equilibrium swelling is first characterized since water content is the major determinant of transport properties in these gels. Phenylpropanolamine (PPA) is chosen as the model drug for the release study and its diffusion characteristics in the gel matrix determined. The data obtained show that the PPA diffusivity follows the free volume theory of Yasuda, which explains the accelerating effect of swelling on drug release. A mathematical model based on a diffusion mechanism has been developed to describe PPA release from the swelling gels. Based on this model, several significant conclusions can be drawn. First, the release rate can be modulated by the aspect ratio of the cylindrical geometry, and this has a practical implication in dosage form design. Second, the release rate can be lowered quite considerably if the dimensional increase due to swelling is significant. Consequently, it is the balance between the drug diffusivity increase and the gel dimensional growth that determines the release rate from the swelling matrix. Third, quasi-steady release kinetics, which are characteristic of swelling release systems, can also be predicted by this model. PPA release from initially dry poly(HEMA -co- MA) gels has also been studied. The data show that the release rate is mainly controlled by the PPA loading level and quite insensitive to the methacrylic acid composition of the gels. These phenomena can be adequately explained by analyzing the transport resistances in the gels. The overall time scale of release from these gels were shown to be in the range which was suitable for oral controlled release applications. (Abstract shortened with permission of author.).

Analysis of Composite Skin-Stiffener Debond Specimens Using Volume Elements and a Shell/3D Modeling Technique

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Minguet, Pierre J.; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

The debonding of a skin/stringer specimen subjected to tension was studied using three-dimensional volume element modeling and computational fracture mechanics. Mixed mode strain energy release rates were calculated from finite element results using the virtual crack closure technique. The simulations revealed an increase in total energy release rate in the immediate vicinity of the free edges of the specimen. Correlation of the computed mixed-mode strain energy release rates along the delamination front contour with a two-dimensional mixed-mode interlaminar fracture criterion suggested that in spite of peak total energy release rates at the free edge the delamination would not advance at the edges first. The qualitative prediction of the shape of the delamination front was confirmed by X-ray photographs of a specimen taken during testing. The good correlation between prediction based on analysis and experiment demonstrated the efficiency of a mixed-mode failure analysis for the investigation of skin/stiffener separation due to delamination in the adherents. The application of a shell/3D modeling technique for the simulation of skin/stringer debond in a specimen subjected to three-point bending is also demonstrated. The global structure was modeled with shell elements. A local three-dimensional model, extending to about three specimen thicknesses on either side of the delamination front was used to capture the details of the damaged section. Computed total strain energy release rates and mixed-mode ratios obtained from shell/3D simulations were in good agreement with results obtained from full solid models. The good correlations of the results demonstrated the effectiveness of the shell/3D modeling technique for the investigation of skin/stiffener separation due to delamination in the adherents.

Development of gastro intestinal sustained release tablet formulation containing acryl-EZE and pH-dependent swelling HPMC K 15 M.

PubMed

Lamoudi, Lynda; Chaumeil, Jean Claude; Daoud, Kamel

2012-05-01

The aim of this study was to evaluate physical properties and release from matrix tablets containing different ratios of HPMC 15 M and Acryl-EZE. A further aim is to assess their suitability for pH dependent controlled release. Matrix tablets containing HPMC 15 M and Acryl-EZE were manufactured using a fluidized bed. The release from this matrix using Sodium Diclofenac (SD) as model drug is studied in two dissolution media (0.1 N HCl or pH = 6.8 phosphate buffer solution); the release rate, mechanism, and pH dependence were characterized by fitting four kinetic models and by using a similarity factor analysis. The obtained results revealed that the presence of Acryl-EZE in the matrix tablets is effective in protecting the dosage forms from release in acid environments such as gastric fluid. In pH = 6.8 phosphate buffer, the drug release rate and mechanism of release from all matrices is mainly controlled by HPMC 15 M. The model of Korsmeyer-Peppas was found to fit experimental dissolution results.

Evaluating release alternatives for a long-lived bird species under uncertainty about long-term demographic rates

USGS Publications Warehouse

Moore, Clinton T.; Converse, Sarah J.; Folk, Martin J.; Runge, Michael C.; Nesbitt, Stephen A.

2012-01-01

The release of animals to reestablish an extirpated population is a decision problem that is often attended by considerable uncertainty about the probability of success. Annual releases of captive-reared juvenile Whooping Cranes (Grus americana) were begun in 1993 in central Florida, USA, to establish a breeding, non-migratory population. Over a 12-year period, 286 birds were released, but by 2004, the introduced flock had produced only four wild-fledged birds. Consequently, releases were halted over managers' concerns about the performance of the released flock and uncertainty about the efficacy of further releases. We used data on marked, released birds to develop predictive models for addressing whether releases should be resumed, and if so, under what schedule. To examine the outcome of different release scenarios, we simulated the survival and productivity of individual female birds under a baseline model that recognized age and breeding-class structure and which incorporated empirically estimated stochastic elements. As data on wild-fledged birds from captive-reared parents were sparse, a key uncertainty that confronts release decision-making is whether captive-reared birds and their offspring share the same vital rates. Therefore, we used data on the only population of wild Whooping Cranes in existence to construct two alternatives to the baseline model. The probability of population persistence was highly sensitive to the choice of these three models. Under the baseline model, extirpation of the population was nearly certain under any scenario of resumed releases. In contrast, the model based on estimates from wild birds projected a high probability of persistence under any release scenario, including cessation of releases. Therefore, belief in either of these models suggests that further releases are an ineffective use of resources. In the third model, which simulated a population Allee effect, population persistence was sensitive to the release decision: high persistence probability was achieved only through the release of more birds, whereas extirpation was highly probable with cessation of releases. Despite substantial investment of time and effort in the release program, evidence collected to date does not favor one model over another; therefore, any decision about further releases must be made under considerable biological uncertainty. However, given an assignment of credibility weight to each model, a best, informed decision about releases can be made under uncertainty. Furthermore, if managers can periodically revisit the release decision and collect monitoring data to further inform the models, then managers have a basis for confronting uncertainty and adaptively managing releases through time.

Evaluation of Matrix Tablets Based on Eudragit®E100/Carbopol®971P Combinations for Controlled Release and Improved Compaction Properties of Water Soluble Model Drug Paracetamol.

PubMed

Obeidat, Wasfy M; Nokhodchi, Ali; Alkhatib, Hatim

2015-10-01

The purpose of this work was to investigate the influence of Eudragit®E100 polymer in modifying the release rates and compaction properties of water soluble model drug paracetamol from Carbopol®971P NF polymer matrix tablets prepared by direct compression. The effects of the ratio of the two polymers, the total polymeric content, and the tablets mechanical strength on paracetamol release rates were investigated. Dissolution studies were conducted using USP XX Π rotating paddle apparatus at 50 rpm and 37°C at three different stages (pH 1.2, 4.8, and 6.8). Results showed that the polymers combination improved significantly the compaction properties of paracetamol tablets as evident by the higher crushing strengths (8.3 ± 0.4 Kp) compared to polymer-free tablets (3.4 ± 0.2 Kp) at intermediate compression pressure of 490 MPa. When combined with Carbopol®971P NF, Eudragit®E100 was found to be capable of extending paracetamol release for more than 12 h compared to 1 h for polymers-free tablets. The combined polymers were able to control paracetamol release in a pH independent pattern. The f2 (similarity factor) analysis showed that the ratio between the polymers and the total polymer concentration exhibited significant impact on drug release rates. In conclusion, Eudragit®E100 when combined with Carbopol®971P NF was capable of improving the compaction and sustained release properties of paracetamol. Korsmeyer-Peppas model was found to be the most suitable for fitting drug release data. The polymer combinations can potentially be used to control the release rates of highly water soluble drugs.

Calsequestrin mediates changes in spontaneous calcium release profiles.

PubMed

Tania, Nessy; Keener, James P

2010-08-07

Calsequestrin (CSQ) is the primary calcium buffer within the sarcoplasmic reticulum (SR) of cardiac cells. It has also been identified as a regulator of Ryanodine receptor (RyR) calcium release channels by serving as a SR luminal sensor. When calsequestrin is free and unbound to calcium, it can bind to RyR and desensitize the channel from cytoplasmic calcium activation. In this paper, we study the role of CSQ as a buffer and RyR luminal sensor using a mechanistic model of RyR-CSQ interaction. By using various asymptotic approximations and mean first exit time calculation, we derive a minimal model of a calcium release unit which includes CSQ dependence. Using this model, we then analyze the effect of changing CSQ expression on the calcium release profile and the rate of spontaneous calcium release. We show that because of its buffering capability, increasing CSQ increases the spark duration and size. However, because of luminal sensing effects, increasing CSQ depresses the basal spark rate and increases the critical SR level for calcium release termination. Finally, we show that with increased bulk cytoplasmic calcium concentration, the CRU model exhibits deterministic oscillations.

Delamination modeling of laminate plate made of sublaminates

NASA Astrophysics Data System (ADS)

Kormaníková, Eva; Kotrasová, Kamila

2017-07-01

The paper presents the mixed-mode delamination of plates made of sublaminates. To this purpose an opening load mode of delamination is proposed as failure model. The failure model is implemented in ANSYS code to calculate the mixed-mode delamination response as energy release rate. The analysis is based on interface techniques. Within the interface finite element modeling there are calculated the individual components of damage parameters as spring reaction forces, relative displacements and energy release rates along the lamination front.

Self-assembling N-(9-Fluorenylmethoxycarbonyl)-l-Phenylalanine hydrogel as novel drug carrier.

PubMed

Snigdha, Kirti; Singh, Brijesh K; Mehta, Abijeet Singh; Tewari, R P; Dutta, P K

2016-12-01

Supramolecular hydrogel as a novel drug carrier was prepared from N-(9-Fluorenylmethoxycarbonyl) (Fmoc) modified l-phenylalanine. Its different properties like stability at different pH, temperature and rheology were evaluated in reference to salicylic acid (SA) as a model drug, entrapped in the supramolecular hydrogel network. The release behaviour of SA drug in supramolecular hydrogel was investigated by UV-vis spectroscopy. The influence of hydrogelator, pH values of the accepting media, temperature and concentration of SA drug on the release behaviour was investigated under static conditions. The results indicated that the release rate of SA in the supramolecular hydrogels was slightly retarded with an increase of the hydrogelator concentration. Also, the release rates of SA increased with an increase of temperature and its concentration. Furthermore, the release behaviour of SA was found to be different at various pH values in buffers. The study of the release kinetics indicated that the release behaviour of SA from the carrier was in accord with the Peppas model and the diffusion controlled mechanism involved in the Fickian model. Copyright © 2016 Elsevier B.V. All rights reserved.

A Method for Calculating Strain Energy Release Rates in Preliminary Design of Composite Skin/Stringer Debonding Under Multi-Axial Loading

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Minguet, Pierre J.; OBrien, T. Kevin

1999-01-01

Three simple procedures were developed to determine strain energy release rates, G, in composite skin/stringer specimens for various combinations of unaxial and biaxial (in-plane/out-of-plane) loading conditions. These procedures may be used for parametric design studies in such a way that only a few finite element computations will be necessary for a study of many load combinations. The results were compared with mixed mode strain energy release rates calculated directly from nonlinear two-dimensional plane-strain finite element analyses using the virtual crack closure technique. The first procedure involved solving three unknown parameters needed to determine the energy release rates. Good agreement was obtained when the external loads were used in the expression derived. This superposition technique was only applicable if the structure exhibits a linear load/deflection behavior. Consequently, a second technique was derived which was applicable in the case of nonlinear load/deformation behavior. The technique involved calculating six unknown parameters from a set of six simultaneous linear equations with data from six nonlinear analyses to determine the energy release rates. This procedure was not time efficient, and hence, less appealing. A third procedure was developed to calculate mixed mode energy release rates as a function of delamination lengths. This procedure required only one nonlinear finite element analysis of the specimen with a single delamination length to obtain a reference solution for the energy release rates and the scale factors. The delamination was extended in three separate linear models of the local area in the vicinity of the delamination subjected to unit loads to obtain the distribution of G with delamination lengths. This set of sub-problems was Although additional modeling effort is required to create the sub- models, this local technique is efficient for parametric studies.

A quantitative model for oxygen uptake and release in a family of hemeproteins.

PubMed

Bustamante, Juan P; Szretter, María E; Sued, Mariela; Martí, Marcelo A; Estrin, Darío A; Boechi, Leonardo

2016-06-15

Hemeproteins have many diverse functions that largely depend on the rate at which they uptake or release small ligands, like oxygen. These proteins have been extensively studied using either simulations or experiments, albeit only qualitatively and one or two proteins at a time. We present a physical-chemical model, which uses data obtained exclusively from computer simulations, to describe the uptake and release of oxygen in a family of hemeproteins, called truncated hemoglobins (trHbs). Through a rigorous statistical analysis we demonstrate that our model successfully recaptures all the reported experimental oxygen association and dissociation kinetic rate constants, thus allowing us to establish the key factors that determine the rates at which these hemeproteins uptake and release oxygen. We found that internal tunnels as well as the distal site water molecules control ligand uptake, whereas oxygen stabilization by distal site residues controls ligand release. Because these rates largely determine the functions of these hemeproteins, these approaches will also be important tools in characterizing the trHbs members with unknown functions. lboechi@ic.fcen.uba.ar Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

An empirical model for dissolution profile and its application to floating dosage forms.

PubMed

Weiss, Michael; Kriangkrai, Worawut; Sungthongjeen, Srisagul

2014-06-02

A sum of two inverse Gaussian functions is proposed as a highly flexible empirical model for fitting of in vitro dissolution profiles. The model was applied to quantitatively describe theophylline release from effervescent multi-layer coated floating tablets containing different amounts of the anti-tacking agents talc or glyceryl monostearate. Model parameters were estimated by nonlinear regression (mixed-effects modeling). The estimated parameters were used to determine the mean dissolution time, as well as to reconstruct the time course of release rate for each formulation, whereby the fractional release rate can serve as a diagnostic tool for classification of dissolution processes. The approach allows quantification of dissolution behavior and could provide additional insights into the underlying processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Toward a consistent model for strain accrual and release for the New Madrid Seismic Zone, central United States

USGS Publications Warehouse

Hough, S.E.; Page, M.

2011-01-01

At the heart of the conundrum of seismogenesis in the New Madrid Seismic Zone is the apparently substantial discrepancy between low strain rate and high recent seismic moment release. In this study we revisit the magnitudes of the four principal 1811–1812 earthquakes using intensity values determined from individual assessments from four experts. Using these values and the grid search method of Bakun and Wentworth (1997), we estimate magnitudes around 7.0 for all four events, values that are significantly lower than previously published magnitude estimates based on macroseismic intensities. We further show that the strain rate predicted from postglacial rebound is sufficient to produce a sequence with the moment release of one Mmax6.8 every 500 years, a rate that is much lower than previous estimates of late Holocene moment release. However, Mw6.8 is at the low end of the uncertainty range inferred from analysis of intensities for the largest 1811–1812 event. We show that Mw6.8 is also a reasonable value for the largest main shock given a plausible rupture scenario. One can also construct a range of consistent models that permit a somewhat higher Mmax, with a longer average recurrence rate. It is thus possible to reconcile predicted strain and seismic moment release rates with alternative models: one in which 1811–1812 sequences occur every 500 years, with the largest events being Mmax∼6.8, or one in which sequences occur, on average, less frequently, with Mmax of ∼7.0. Both models predict that the late Holocene rate of activity will continue for the next few to 10 thousand years.

Automatic Generation of Just-in-Time Online Assessments from Software Design Models

ERIC Educational Resources Information Center

Zualkernan, Imran A.; El-Naaj, Salim Abou; Papadopoulos, Maria; Al-Amoudi, Budoor K.; Matthews, Charles E.

2009-01-01

Computer software is pervasive in today's society. The rate at which new versions of computer software products are released is phenomenal when compared to the release rate of new products in traditional industries such as aircraft building. This rapid rate of change can partially explain why most certifications in the software industry are…

Building an Efficient Model for Afterburn Energy Release

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

Alves, S; Kuhl, A; Najjar, F

2012-02-03

Many explosives will release additional energy after detonation as the detonation products mix with the ambient environment. This additional energy release, referred to as afterburn, is due to combustion of undetonated fuel with ambient oxygen. While the detonation energy release occurs on a time scale of microseconds, the afterburn energy release occurs on a time scale of milliseconds with a potentially varying energy release rate depending upon the local temperature and pressure. This afterburn energy release is not accounted for in typical equations of state, such as the Jones-Wilkins-Lee (JWL) model, used for modeling the detonation of explosives. Here wemore » construct a straightforward and efficient approach, based on experiments and theory, to account for this additional energy release in a way that is tractable for large finite element fluid-structure problems. Barometric calorimeter experiments have been executed in both nitrogen and air environments to investigate the characteristics of afterburn for C-4 and other materials. These tests, which provide pressure time histories, along with theoretical and analytical solutions provide an engineering basis for modeling afterburn with numerical hydrocodes. It is toward this end that we have constructed a modified JWL equation of state to account for afterburn effects on the response of structures to blast. The modified equation of state includes a two phase afterburn energy release to represent variations in the energy release rate and an afterburn energy cutoff to account for partial reaction of the undetonated fuel.« less

Analyses for Debonding of Stitched Composite Sandwich Structures Using Improved Constitutive Models

NASA Technical Reports Server (NTRS)

Glaessgen, E. H.; Sleight, D. W.; Krishnamurthy, T.; Raju, I. S.

2001-01-01

A fracture mechanics analysis based on strain energy release rates is used to study the effect of stitching in bonded sandwich beam configurations. Finite elements are used to model the configurations. The stitches were modeled as discrete nonlinear spring elements with a compliance determined by experiment. The constitutive models were developed using the results of flatwise tension tests from sandwich material rather than monolithic material. The analyses show that increasing stitch stiffness, stitch density and debond length decrease strain energy release rates for a fixed applied load.

Cellular automata model for drug release from binary matrix and reservoir polymeric devices.

PubMed

Johannes Laaksonen, Timo; Mikael Laaksonen, Hannu; Tapio Hirvonen, Jouni; Murtomäki, Lasse

2009-04-01

Kinetics of drug release from polymeric tablets, inserts and implants is an important and widely studied area. Here we present a new and widely applicable cellular automata model for diffusion and erosion processes occurring during drug release from polymeric drug release devices. The model divides a 2D representation of the release device into an array of cells. Each cell contains information about the material, drug, polymer or solvent that the domain contains. Cells are then allowed to rearrange according to statistical rules designed to match realistic drug release. Diffusion is modeled by a random walk of mobile cells and kinetics of chemical or physical processes by probabilities of conversion from one state to another. This is according to the basis of diffusion coefficients and kinetic rate constants, which are on fundamental level just probabilities for certain occurrences. The model is applied to three kinds of devices with different release mechanisms: erodable matrices, diffusion through channels or pores and membrane controlled release. The dissolution curves obtained are compared to analytical models from literature and the validity of the model is considered. The model is shown to be compatible with all three release devices, highlighting easy adaptability of the model to virtually any release system and geometry. Further extension and applications of the model are envisioned.

LARC-1: a Los Alamos release calculation program for fission product transport in HTGRs during the LOFC accident

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

Carruthers, L.M.; Lee, C.E.

1976-10-01

The theoretical and numerical data base development of the LARC-1 code is described. Four analytical models of fission product release from an HTGR core during the loss of forced circulation accident are developed. Effects of diffusion, adsorption and evaporation of the metallics and precursors are neglected in this first LARC model. Comparison of the analytic models indicates that the constant release-renormalized model is adequate to describe the processes involved. The numerical data base for release constants, temperature modeling, fission product release rates, coated fuel particle failure fraction and aged coated fuel particle failure fractions is discussed. Analytic fits and graphicmore » displays for these data are given for the Ft. St. Vrain and GASSAR models.« less

A Phenomenological Synapse Model for Asynchronous Neurotransmitter Release

PubMed Central

Wang, Tao; Yin, Luping; Zou, Xiaolong; Shu, Yousheng; Rasch, Malte J.; Wu, Si

2016-01-01

Neurons communicate with each other via synapses. Action potentials cause release of neurotransmitters at the axon terminal. Typically, this neurotransmitter release is tightly time-locked to the arrival of an action potential and is thus called synchronous release. However, neurotransmitter release is stochastic and the rate of release of small quanta of neurotransmitters can be considerably elevated even long after the ceasing of spiking activity, leading to asynchronous release of neurotransmitters. Such asynchronous release varies for tissue and neuron types and has been shown recently to be pronounced in fast-spiking neurons. Notably, it was found that asynchronous release is enhanced in human epileptic tissue implicating a possibly important role in generating abnormal neural activity. Current neural network models for simulating and studying neural activity virtually only consider synchronous release and ignore asynchronous transmitter release. Here, we develop a phenomenological model for asynchronous neurotransmitter release, which, on one hand, captures the fundamental features of the asynchronous release process, and, on the other hand, is simple enough to be incorporated in large-size network simulations. Our proposed model is based on the well-known equations for short-term dynamical synaptic interactions and includes an additional stochastic term for modeling asynchronous release. We use experimental data obtained from inhibitory fast-spiking synapses of human epileptic tissue to fit the model parameters, and demonstrate that our model reproduces the characteristics of realistic asynchronous transmitter release. PMID:26834617

Mechanics of wafer bonding: Effect of clamping

NASA Astrophysics Data System (ADS)

Turner, K. T.; Thouless, M. D.; Spearing, S. M.

2004-01-01

A mechanics-based model is developed to examine the effects of clamping during wafer bonding processes. The model provides closed-form expressions that relate the initial geometry and elastic properties of the wafers to the final shape of the bonded pair and the strain energy release rate at the interface for two different clamping configurations. The results demonstrate that the curvature of bonded pairs may be controlled through the use of specific clamping arrangements during the bonding process. Furthermore, it is demonstrated that the strain energy release rate depends on the clamping configuration and that using applied loads usually leads to an undesirable increase in the strain energy release rate. The results are discussed in detail and implications for process development and bonding tool design are highlighted.

Modeling of Fission Gas Release in UO2

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

MH Krohn

2006-01-23

A two-stage gas release model was examined to determine if it could provide a physically realistic and accurate model for fission gas release under Prometheus conditions. The single-stage Booth model [1], which is often used to calculate fission gas release, is considered to be oversimplified and not representative of the mechanisms that occur during fission gas release. Two-stage gas release models require saturation at the grain boundaries before gas is release, leading to a time delay in release of gases generated in the fuel. Two versions of a two-stage model developed by Forsberg and Massih [2] were implemented using Mathcadmore » [3]. The original Forsbers and Massih model [2] and a modified version of the Forsberg and Massih model that is used in a commercially available fuel performance code (FRAPCON-3) [4] were examined. After an examination of these models, it is apparent that without further development and validation neither of these models should be used to calculate fission gas release under Prometheus-type conditions. There is too much uncertainty in the input parameters used in the models. In addition. the data used to tune the modified Forsberg and Massih model (FRAPCON-3) was collected under commercial reactor conditions, which will have higher fission rates relative to Prometheus conditions [4].« less

Fraction of organic carbon predicts labile desorption rates of chlorinated organic pollutants in laboratory-spiked geosorbents.

PubMed

Ginsbach, Jake W; Killops, Kato L; Olsen, Robert M; Peterson, Brittney; Dunnivant, Frank M

2010-05-01

The resuspension of large volumes of sediments that are contaminated with chlorinated pollutants continues to threaten environmental quality and human health. Whereas kinetic models are more accurate for estimating the environmental impact of these events, their widespread use is substantially hampered by the need for costly, time-consuming, site-specific kinetics experiments. The present study investigated the development of a predictive model for desorption rates from easily measurable sorbent and pollutant properties by examining the relationship between the fraction of organic carbon (fOC) and labile release rates. Duplicate desorption measurements were performed on 46 unique combinations of pollutants and sorbents with fOC values ranging from 0.001 to 0.150. Labile desorption rate constants indicate that release rates predominantly depend upon the fOC in the geosorbent. Previous theoretical models, such as the macro-mesopore and organic matter (MOM) diffusion model, have predicted such a relationship but could not accurately predict the experimental rate constants collected in the present study. An empirical model was successfully developed to correlate the labile desorption rate constant (krap) to the fraction of organic material where log(krap)=0.291-0.785 . log(fOC). These results provide the first experimental evidence that kinetic pollution releases during resuspension events are governed by the fOC content in natural geosorbents. Copyright (c) 2010 SETAC.

A mathematical model for interpreting in vitro rhGH release from laminar implants.

PubMed

Santoveña, A; García, J T; Oliva, A; Llabrés, M; Fariña, J B

2006-02-17

Recombinant human growth hormone (rhGH), used mainly for the treatment of growth hormone deficiency in children, requires daily subcutaneous injections. The use of controlled release formulations with appropriate rhGH release kinetics reduces the frequency of medication, improving patient compliance and quality of life. Biodegradable implants are a valid alternative, offering the feasibility of a regular release rate after administering a single dose, though it exists the slight disadvantage of a very minor surgical operation. Three laminar implant formulations (F(1), F(2) and F(3)) were produced by different manufacture procedures using solvent-casting techniques with the same copoly(D,L-lactic) glycolic acid (PLGA) polymer (Mw=48 kDa). A correlation in vitro between polymer matrix degradation and drug release rate from these formulations was found and a mathematical model was developed to interpret this. This model was applied to each formulation. The obtained results where explained in terms of manufacture parameters with the aim of elucidate whether drug release only occurs by diffusion or erosion, or by a combination of both mechanisms. Controlling the manufacture method and the resultant changes in polymer structure facilitates a suitable rhGH release profile for different rhGH deficiency treatments.

A prison mental health in-reach model informed by assertive community treatment principles: evaluation of its impact on planning during the pre-release period, community mental health service engagement and reoffending.

PubMed

McKenna, Brian; Skipworth, Jeremy; Tapsell, Rees; Madell, Dominic; Pillai, Krishna; Simpson, Alexander; Cavney, James; Rouse, Paul

2015-12-01

It is well recognised that prisoners with serious mental illness (SMI) are at high risk of poor outcomes on return to the community. Early engagement with mental health services and other community agencies could provide the substrate for reducing risk. To evaluate the impact of implementing an assertive community treatment informed prison in-reach model of care (PMOC) on post-release engagement with community mental health services and on reoffending rates. One hundred and eighty prisoners with SMI released from four prisons in the year before implementation of the PMOC were compared with 170 such prisoners released the year after its implementation. The assertive prison model of care was associated with more pre-release contacts with community mental health services and contacts with some social care agencies in some prisons. There were significantly more post-release community mental health service engagements after implementation of this model (Z = -2.388, p = 0.02). There was a trend towards reduction in reoffending rates after release from some of the prisons (Z =1.82, p = 0.07). Assertive community treatment applied to prisoners with mental health problems was superior to 'treatment as usual', but more work is needed to ensure that agencies will engage prisoners in pre-release care. The fact that the model showed some benefits in the absence of any increase in resources suggests that it may be the model per se that is effective. Copyright © 2014 John Wiley & Sons, Ltd.

Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers.

PubMed

Gobburu, J V; Agersø, H; Jusko, W J; Ynddal, L

1999-09-01

To examine the pharmacokinetics (PK) and pharmacodynamics (PD) of ipamorelin, a growth hormone (GH) releasing peptide, in healthy volunteers. A trial was conducted with a dose escalation design comprising 5 different infusion rates (4.21, 14.02, 42.13, 84.27 and 140.45 nmol/kg over 15 minutes) with eight healthy male subjects at each dose level. Concentrations of ipamorelin and growth hormone were measured. The PK parameters showed dose-proportionality, with a short terminal half-life of 2 hours, a clearance of 0.078 L/h/kg and a volume of distribution at steady-state of 0.22 L/kg. The time course of GH stimulation by ipamorelin showed a single episode of GH release with a peak at 0.67 hours and an exponential decline to negligible GH concentration at all doses. The ipamorelin-GH concentration relationship was characterized using an indirect response model and population fitting. The model employed a zero-order GH release rate over a finite duration of time to describe the episodic release of GH. Ipamorelin induces the release of GH at all dose levels with the concentration (SC50) required for half-maximal GH stimulation of 214 nmol/L and a maximal GH production rate of 694 mIU/L/h. The inter-individual variability of the PD parameters was larger than that of the PK parameters. The proposed PK/PD model provides a useful characterization of ipamorelin disposition and GH responses across a range of doses.

Dynamic Model for the Stocks and Release Flows of Engineered Nanomaterials.

PubMed

Song, Runsheng; Qin, Yuwei; Suh, Sangwon; Keller, Arturo A

2017-11-07

Most existing life-cycle release models for engineered nanomaterials (ENM) are static, ignoring the dynamics of stock and flows of ENMs. Our model, nanoRelease, estimates the annual releases of ENMs from manufacturing, use, and disposal of a product explicitly taking stock and flow dynamics into account. Given the variabilities in key parameters (e.g., service life of products and annual release rate during use) nanoRelease is designed as a stochastic model. We apply nanoRelease to three ENMs (TiO 2 , SiO 2 and FeO x ) used in paints and coatings through seven product applications, including construction and building, household and furniture, and automotive for the period from 2000 to 2020 using production volume and market projection information. We also consider model uncertainties using Monte Carlo simulation. Compared with 2016, the total annual releases of ENMs in 2020 will increase by 34-40%, and the stock will increase by 28-34%. The fraction of the end-of-life release among total release flows will increase from 11% in 2002 to 43% in 2020. As compared to static models, our dynamic model predicts about an order of magnitude lower values for the amount of ENM released from this sector in the near-term while stock continues to build up in the system.

Equilibrium and kinetic models for colloid release under transient solution chemistry conditions.

PubMed

Bradford, Scott A; Torkzaban, Saeed; Leij, Feike; Simunek, Jiri

2015-10-01

We present continuum models to describe colloid release in the subsurface during transient physicochemical conditions. Our modeling approach relates the amount of colloid release to changes in the fraction of the solid surface area that contributes to retention. Equilibrium, kinetic, equilibrium and kinetic, and two-site kinetic models were developed to describe various rates of colloid release. These models were subsequently applied to experimental colloid release datasets to investigate the influence of variations in ionic strength (IS), pH, cation exchange, colloid size, and water velocity on release. Various combinations of equilibrium and/or kinetic release models were needed to describe the experimental data depending on the transient conditions and colloid type. Release of Escherichia coli D21g was promoted by a decrease in solution IS and an increase in pH, similar to expected trends for a reduction in the secondary minimum and nanoscale chemical heterogeneity. The retention and release of 20nm carboxyl modified latex nanoparticles (NPs) were demonstrated to be more sensitive to the presence of Ca(2+) than D21g. Specifically, retention of NPs was greater than D21g in the presence of 2mM CaCl2 solution, and release of NPs only occurred after exchange of Ca(2+) by Na(+) and then a reduction in the solution IS. These findings highlight the limitations of conventional interaction energy calculations to describe colloid retention and release, and point to the need to consider other interactions (e.g., Born, steric, and/or hydration forces) and/or nanoscale heterogeneity. Temporal changes in the water velocity did not have a large influence on the release of D21g for the examined conditions. This insensitivity was likely due to factors that reduce the applied hydrodynamic torque and/or increase the resisting adhesive torque; e.g., macroscopic roughness and grain-grain contacts. Our analysis and models improve our understanding and ability to describe the amounts and rates of colloid release and indicate that episodic colloid transport is expected under transient physicochemical conditions. Published by Elsevier B.V.

Diffusion Performance of Fertilizer Nutrient through Polymer Latex Film.

PubMed

An, Di; Yang, Ling; Liu, Boyang; Wang, Ting-Jie; Kan, Chengyou

2017-12-20

Matching the nutrient release rate of coated fertilizer with the nutrient uptake rate of the crop is the best way to increase the utilization efficiency of nutrients and reduce environmental pollution from the fertilizer. The diffusion property and mechanism of nutrients through the film are the theoretical basis for the product pattern design of coated fertilizers. For the coated fertilizer with a single-component nutrient, an extended solution-diffusion model was used to describe the difference of nutrient release rate, and the release rate is proportional to the permeation coefficient and the solubility of the nutrient. For the double- and triple-component fertilizer of N-K, N-P, and N-P-K, because of the interaction among nutrient molecules and ions, the release rates of different nutrients were significantly affected by the components in the composite fertilizer. Coating the single-component fertilizer (i.e., nitrogen fertilizer, phosphate fertilizer, and potash fertilizer) first and subsequently bulk blending is expected to be a promising way to adjust flexibly the nutrient release rate to meet the nutrient uptake rate of the crop.

Statistical atmospheric inversion of local gas emissions by coupling the tracer release technique and local-scale transport modelling: a test case with controlled methane emissions

NASA Astrophysics Data System (ADS)

Ars, Sébastien; Broquet, Grégoire; Yver Kwok, Camille; Roustan, Yelva; Wu, Lin; Arzoumanian, Emmanuel; Bousquet, Philippe

2017-12-01

This study presents a new concept for estimating the pollutant emission rates of a site and its main facilities using a series of atmospheric measurements across the pollutant plumes. This concept combines the tracer release method, local-scale atmospheric transport modelling and a statistical atmospheric inversion approach. The conversion between the controlled emission and the measured atmospheric concentrations of the released tracer across the plume places valuable constraints on the atmospheric transport. This is used to optimise the configuration of the transport model parameters and the model uncertainty statistics in the inversion system. The emission rates of all sources are then inverted to optimise the match between the concentrations simulated with the transport model and the pollutants' measured atmospheric concentrations, accounting for the transport model uncertainty. In principle, by using atmospheric transport modelling, this concept does not strongly rely on the good colocation between the tracer and pollutant sources and can be used to monitor multiple sources within a single site, unlike the classical tracer release technique. The statistical inversion framework and the use of the tracer data for the configuration of the transport and inversion modelling systems should ensure that the transport modelling errors are correctly handled in the source estimation. The potential of this new concept is evaluated with a relatively simple practical implementation based on a Gaussian plume model and a series of inversions of controlled methane point sources using acetylene as a tracer gas. The experimental conditions are chosen so that they are suitable for the use of a Gaussian plume model to simulate the atmospheric transport. In these experiments, different configurations of methane and acetylene point source locations are tested to assess the efficiency of the method in comparison to the classic tracer release technique in coping with the distances between the different methane and acetylene sources. The results from these controlled experiments demonstrate that, when the targeted and tracer gases are not well collocated, this new approach provides a better estimate of the emission rates than the tracer release technique. As an example, the relative error between the estimated and actual emission rates is reduced from 32 % with the tracer release technique to 16 % with the combined approach in the case of a tracer located 60 m upwind of a single methane source. Further studies and more complex implementations with more advanced transport models and more advanced optimisations of their configuration will be required to generalise the applicability of the approach and strengthen its robustness.

A fission gas release correlation for uranium nitride fuel pins

NASA Technical Reports Server (NTRS)

Weinstein, M. B.; Davison, H. W.

1973-01-01

A model was developed to predict fission gas releases from UN fuel pins clad with various materials. The model was correlated with total release data obtained by different experimentors, over a range of fuel temperatures primarily between 1250 and 1660 K, and fuel burnups up to 4.6 percent. In the model, fission gas is transported by diffusion mechanisms to the grain boundaries where the volume grows and eventually interconnects with the outside surface of the fuel. The within grain diffusion coefficients are found from fission gas release rate data obtained using a sweep gas facility.

Controlled release of tetracycline-HCl from halloysite-polymer composite films.

PubMed

Ward, Christopher J; Song, Shang; Davis, Edward W

2010-10-01

The first direct comparison between two common methods for loading halloysite with a small molecule for controlled release is presented. While the methods differ in the degree of simplicity, they provide essentially the same level of loading and release kinetics. A tentative explanation of the "burst" effect often seen in the release of low molecular weight molecules from halloysite is provided. The ability of halloysite to mediate the release rate of a water soluble drug, tetracycline, from solution cast polyvinyl alcohol and polymethyl methacrylate films was evaluated. In some films, montmorillonite was also incorporated. The addition of montmorillonite to solutions used to cast tetracycline containing films significantly reduced the release rate from the dried films. The same overall effect was seen when the drug was loaded into halloysite prior to preparation of the films. In both cases, the release was best fit with the simple Higuchi model. However, when montmorillonite was added to solutions of polyvinyl alcohol and drug loaded halloysite the release profiles were better fit by the Ritgar-Peppas model for anomalous transport. Release from polymethyl methacrylate was reduced by a factor of three by incorporating the drug in halloysite prior to producing the films.

Effect of Nisin's Controlled Release on Microbial Growth as Modeled for Micrococcus luteus.

PubMed

Balasubramanian, Aishwarya; Lee, Dong Sun; Chikindas, Michael L; Yam, Kit L

2011-06-01

The need for safe food products has motivated food scientists and industry to find novel technologies for antimicrobial delivery for improving food safety and quality. Controlled release packaging is a novel technology that uses the package to deliver antimicrobials in a controlled manner and sustain antimicrobial stress on the targeted microorganism over the required shelf life. This work studied the effect of controlled release of nisin to inhibit growth of Micrococcus luteus (a model microorganism) using a computerized syringe pump system to mimic the release of nisin from packaging films which was characterized by an initially fast rate and a slower rate as time progressed. The results show that controlled release of nisin was strikingly more effective than instantly added ("formulated") nisin. While instant addition experiments achieved microbial inhibition only at the beginning, controlled release experiments achieved complete microbial inhibition for a longer time, even when as little as 15% of the amount of nisin was used as compared to instant addition.

Effects of formulation variables and post-compression curing on drug release from a new sustained-release matrix material: polyvinylacetate-povidone.

PubMed

Shao, Z J; Farooqi, M I; Diaz, S; Krishna, A K; Muhammad, N A

2001-01-01

A new commercially available sustained-release matrix material, Kollidon SR, composed of polyvinylacetate and povidone, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound, diphenhydramine HCl. Kollidon SR was found to provide a sustained-release effect for the model compound, with certain formulation and processing variables playing an important role in controlling its release kinetics. Formulation variables affecting the release include the level of the polymeric material in the matrix, excipient level, as well as the nature of the excipients (water soluble vs. water insoluble). Increasing the ratio of a water-insoluble excipient, Emcompress, to Kollidon SR enhanced drug release. The incorporation of a water-soluble excipient, lactose, accelerated its release rate in a more pronounced manner. Stability studies conducted at 40 degrees C/75% RH revealed a slow-down in dissolution rate for the drug-Kollidon SR formulation, as a result of polyvinylacetate relaxation. Further studies demonstrated that a post-compression curing step effectively stabilized the release pattern of formulations containing > or = 47% Kollidon SR. The release mechanism of Kollidon-drug and drug-Kollidon-Emcompress formulations appears to be diffusion controlled, while that of the drug-Kollidon-lactose formulation appears to be controlled predominantly by diffusion along with erosion.

Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism.

PubMed

Tomic, I; Vidis-Millward, A; Mueller-Zsigmondy, M; Cardot, J-M

2016-05-30

The objective of this study was development of accelerated in vitro release method for peptide loaded PLGA microspheres using flow-through apparatus and assessment of the effect of dissolution parameters (pH, temperature, medium composition) on drug release rate and mechanism. Accelerated release conditions were set as pH 2 and 45°C, in phosphate buffer saline (PBS) 0.02M. When the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were not affected, while release rate during erosion phase decreased two-fold due to slower ester bonds hydrolyses. Decreasing temperature from 45°C to 40°C, release rate showed three-fold deceleration without significant change in release mechanism. Effect of medium composition on drug release was tested in PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer concentration significantly affected drug release rate and mechanism due to the change in osmotic pressure, while ionic strength did not have any effect on peptide release. Furthermore, dialysis sac and sample-and-separate techniques were used, in order to evaluate significance of dissolution technique choice on the release process. After fitting obtained data to different mathematical models, flow-through method was confirmed as the most appropriate for accelerated in vitro dissolution testing for a given formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanistic modelling of drug release from a polymer matrix using magnetic resonance microimaging.

PubMed

Kaunisto, Erik; Tajarobi, Farhad; Abrahmsen-Alami, Susanna; Larsson, Anette; Nilsson, Bernt; Axelsson, Anders

2013-03-12

In this paper a new model describing drug release from a polymer matrix tablet is presented. The utilization of the model is described as a two step process where, initially, polymer parameters are obtained from a previously published pure polymer dissolution model. The results are then combined with drug parameters obtained from literature data in the new model to predict solvent and drug concentration profiles and polymer and drug release profiles. The modelling approach was applied to the case of a HPMC matrix highly loaded with mannitol (model drug). The results showed that the drug release rate can be successfully predicted, using the suggested modelling approach. However, the model was not able to accurately predict the polymer release profile, possibly due to the sparse amount of usable pure polymer dissolution data. In addition to the case study, a sensitivity analysis of model parameters relevant to drug release was performed. The analysis revealed important information that can be useful in the drug formulation process. Copyright © 2013 Elsevier B.V. All rights reserved.

Poly (lactic-co-glycolic acid) controlled release systems: experimental and modeling insights

PubMed Central

Hines, Daniel J.; Kaplan, David L.

2013-01-01

Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in drug release device formulation. Mathematical modeling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. The advantages and limitations of poly (lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled release technology that utilize PLGA. Mathematical modeling applied towards controlled release rates from PLGA-based devices will also be discussed to provide a complete picture of state of the art understanding of the control achievable with this polymeric system, as well as the limitations. PMID:23614648

Comparative drug release measurements in limited amounts of liquid: a suppository formulation study.

PubMed

Welch, Ken; Ek, Ragnar; Strømme, Maria

2006-07-01

A novel method for the investigation of drug formulations in limited liquid volumes is presented. The experimental setup consists of a measurement cell containing an absorbent sponge cloth placed between two parallel electrodes. Conductivity measurements are used to monitor the drug release from the dosage form. By varying the amount of water contained in the absorbent cloth surrounding the dosage form, it is possible to measure the drug release performance of the dosage form in very limited amounts of water. The method was employed to test four different tablet formulations consisting of the model drug NaCl incorporated in excipient matrices of hard fat, polyethylene glycol, microcrystalline cellulose and a mixture of microcrystalline cellulose and croscarmellose sodium (Ac-Di-Sol). The drug release rates of the different formulations in limited water volumes differed markedly from the release rates in an excess of water. Whereas the release rates from all tablet types in an excess of water showed only minor differences among the tablet types, the release rates from the tablets formulated with disintegrating excipients were clearly superior in limited water volumes. The developed method for drug release in limited volumes of liquid should be suitable for evaluation of rectal dosage forms.

Kinetics of piroxicam release from low-methylated pectin/zein hydrogel microspheres

USDA-ARS?s Scientific Manuscript database

The kinetics of a model drug (piroxicam) release from pectin/zein hydrogel microspheres was studied under conditions simulating the gastrointestinal tract. It is established that the rate-limiting step in the release mechanism is drug diffusion out of the microspheres rather than its dissolution. ...

Characteristics and degradation of chitosan/cellulose acetate microspheres with different model drugs

NASA Astrophysics Data System (ADS)

Zhou, Hui-yun; Chen, Xi-guang

2008-12-01

In this study, chitosan/cellulose acetate microspheres (CCAM) were prepared by W/O/W emulsification and solvent evaporation as a drug delivery system. The microspheres were spherical, free-flowing and non-aggregated. The CCAM had good flow and suspension ability. The loading efficiency of different model drugs increased with the increasing hydrophobicity of the drug. The loading efficiency of 6-mercaptopurine (6-MP) was more than 30% whereas that of ranitidine hydrochloride (RT) or acetaminophen (ACP) was only 10%. The pH values of solution affected the swelling ability of CCAM and the relative humidity had little effect on the characteristics of CCAM when it was not more than 75%. The CCAM system had a good effect on the controlled release of different model drugs. However, the release rate became slower with the increase of the hydrophobicity of drugs. The release rate of CCAM loaded with hydrophilic RT was almost 60% during 48 h and the release rate of CCAM loaded with hydrophobic drug of 6-MP was not more than 30%. In the meantime, the CCAM system was degradable in vitro and the degradation rate was faster in lysozyme solution than that in the medium of PBS. So the CCAM system was a degradable promising drug delivery system especially for hydrophobic drugs.

Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine.

PubMed

Tanaka, Nobuyuki; Imai, Keiji; Okimoto, Kazuto; Ueda, Satoshi; Tokunaga, Yuji; Ohike, Atsuo; Ibuki, Rinta; Higaki, Kazutaka; Kimura, Toshikiro

2005-11-28

The goal of this study is to develop a novel sustained-release (SR) system for poorly water-soluble drugs by applying solid dispersion (SD) technique for improving the solubility. The developed SR system, disintegration-controlled matrix tablet (DCMT), consists of hydrogenated soybean oil (HSO) as wax and SD granules containing low-substituted hydroxypropylcellulose (L-HPC) as a disintegrant. In this study, nilvadipine (NiD) was chosen as a model compound. Sustained-release profiles of NiD from DCMT were identically controlled in several dissolution mediums in spite of varying pH and agitation speed. The release of NiD from DCMT was sustained more effectively by increasing the amount of wax or by decreasing the amount of disintegrant, and supersaturation of NiD was achieved without any re-crystallization in dissolution medium. The release rate of NiD from DCMT was controlled by the disintegration rate of tablet. The release profile of NiD was described by the Hixson-Crowell's model better than zero-order kinetics, first-order kinetics and Higuchi's model, which supports that the release of NiD from DCMT is regulated by the disintegration of the tablet. From this study, it was clarified that DCMT was one of the promising SR systems applying SD for the poorly water-soluble drugs.

Fracture mechanics modeling of popping event during daughter cell separation.

PubMed

Jiang, Yuxuan; Liang, Xudong; Guo, Ming; Cao, Yanping; Cai, Shengqiang

2018-05-10

Most bacteria cells divide by binary fission which is part of a bacteria cell cycle and requires tight regulations and precise coordination. Fast separation of Staphylococcus Aureus (S. Aureus) daughter cells, named as popping event, has been observed in recent experiments. The popping event was proposed to be driven by mechanical crack propagation in the peripheral ring which connected two daughter cells before their separation. It has also been shown that after the fast separation, a small portion of the peripheral ring was left as a hinge. In the article, we develop a fracture mechanics model for the crack growth in the peripheral ring during S. Aureus daughter cell separation. In particular, using finite element analysis, we calculate the energy release rate associated with the crack growth in the peripheral ring, when daughter cells are inflated by a uniform turgor pressure inside. Our results show that with a fixed inflation of daughter cells, the energy release rate depends on the crack length non-monotonically. The energy release rate reaches a maximum value for a crack of an intermediate length. The non-monotonic relationship between the energy release rate and crack length clearly indicates that the crack propagation in the peripheral ring can be unstable. The computed energy release rate as a function of crack length can also be used to explain the existence of a small portion of peripheral ring remained as hinge after the popping event.

Optimization of Adhesive Pastes for Dental Caries Prevention.

PubMed

Sodata, Patteera; Juntavee, Apa; Juntavee, Niwut; Peerapattana, Jomjai

2017-11-01

Dental caries prevention products available on the market contain only remineralizing agents or antibacterial agents. This study aimed to develop adhesive pastes containing calcium phosphate and α-mangostin for dental caries prevention using the optimization technique. Calcium phosphate was used as a remineralizing agent, and extracted α-mangostin was used as an antibacterial agent. The effect of the independent variables, which were fumed silica, Eudragit ® EPO, polyethylene glycol, and ethyl alcohol, on the responses was investigated. The drying time, erosion rate, calcium release rate, and α-mangostin release rate were established as the measured responses. An equation and a model of the relationship were constructed. An optimal formulation was obtained, and its effect on dental caries prevention was investigated using the pH-cycling model. The quadratic equation revealed that the drying time, calcium release rate, and α-mangostin release rate tended to decrease when increasing the fumed silica and decreasing other factors. The erosion rate tended to increase when decreasing Eudragit ® EPO and increasing other factors. The observed responses of the optimal adhesive pastes were not significantly different from the predicted responses. This result demonstrated that optimization is an efficient technique in the formulation development of the adhesive pastes. In addition, the optimal adhesive pastes could enhance acid resistance activity to the tooth enamel.

Evaluation of Water Year 2011 Glen Canyon Dam Flow Release Scenarios on Downstream Sand Storage along the Colorado River in Arizona

USGS Publications Warehouse

Wright, Scott A.; Grams, Paul E.

2010-01-01

This report describes numerical modeling simulations of sand transport and sand budgets for reaches of the Colorado River below Glen Canyon Dam. Two hypothetical Water Year 2011 annual release volumes were each evaluated with six hypothetical operational scenarios. The six operational scenarios include the current operation, scenarios with modifications to the monthly distribution of releases, and scenarios with modifications to daily flow fluctuations. Uncertainties in model predictions were evaluated by conducting simulations with error estimates for tributary inputs and mainstem transport rates. The modeling results illustrate the dependence of sand transport rates and sand budgets on the annual release volumes as well as the within year operating rules. The six operational scenarios were ranked with respect to the predicted annual sand budgets for Marble Canyon and eastern Grand Canyon reaches. While the actual WY 2011 annual release volume and levels of tributary inputs are unknown, the hypothetical conditions simulated and reported herein provide reasonable comparisons between the operational scenarios, in a relative sense, that may be used by decision makers within the Glen Canyon Dam Adaptive Management Program.

Influence of drug property and product design on in vitro-in vivo correlation of complex modified-release dosage forms.

PubMed

Qiu, Yihong; Li, Xia; Duan, John Z

2014-02-01

The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release. Three analgesic drugs were used as model compounds, and simulations of in vivo pharmacokinetic profiles were conducted using different release rates of the ER component and various IR percentages. Plasma concentration-time profiles exhibiting a wide range of tmax and maximum observed plasma concentration (Cmax) were obtained from superposition of the simulated IR and ER profiles based on a linear IVIVC. It was found that depending on the drug and dosage form design, direct use of the superposed IR and ER data for IVIVC modeling and prediction may (1) be acceptable within errors, (2) become unreliable and less meaningful because of the confounding effect from the non-negligible IR contribution to Cmax, or (3) be meaningless because of the insensitivity of Cmax to release rate change of the ER component. Therefore, understanding the drug, design and drug release characteristics of the product is essential for assessing the validity, accuracy, and reliability of IVIVC of complex MR products obtained via directly modeling of in vivo data. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Radioactive release during nuclear accidents in Chernobyl and Fukushima

NASA Astrophysics Data System (ADS)

Nur Ain Sulaiman, Siti; Mohamed, Faizal; Rahim, Ahmad Nabil Ab

2018-01-01

Nuclear accidents that occurred in Chernobyl and Fukushima have initiated many research interests to understand the cause and mechanism of radioactive release within reactor compound and to the environment. Common types of radionuclide release are the fission products from the irradiated fuel rod itself. In case of nuclear accident, the focus of monitoring will be mostly on the release of noble gases, I-131 and Cs-137. As these are the only accidents have been rated within International Nuclear Events Scale (INES) Level 7, the radioactive release to the environment was one of the critical insights to be monitored. It was estimated that the release of radioactive material to the atmosphere due to Fukushima accident was approximately 10% of the Chernobyl accident. By referring to the previous reports using computational code systems to model the release rate, the release activity of I-131 and Cs-137 in Chernobyl was significantly higher compare to Fukushima. The simulation code also showed that Chernobyl had higher release rate of both radionuclides on the day of accident. Other factors affecting the radioactive release for Fukushima and Chernobyl accidents such as the current reactor technology and safety measures are also compared for discussion.

Comparison of 2D Finite Element Modeling Assumptions with Results From 3D Analysis for Composite Skin-Stiffener Debonding

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Paris, Isbelle L.; OBrien, T. Kevin; Minguet, Pierre J.

2004-01-01

The influence of two-dimensional finite element modeling assumptions on the debonding prediction for skin-stiffener specimens was investigated. Geometrically nonlinear finite element analyses using two-dimensional plane-stress and plane-strain elements as well as three different generalized plane strain type approaches were performed. The computed skin and flange strains, transverse tensile stresses and energy release rates were compared to results obtained from three-dimensional simulations. The study showed that for strains and energy release rate computations the generalized plane strain assumptions yielded results closest to the full three-dimensional analysis. For computed transverse tensile stresses the plane stress assumption gave the best agreement. Based on this study it is recommended that results from plane stress and plane strain models be used as upper and lower bounds. The results from generalized plane strain models fall between the results obtained from plane stress and plane strain models. Two-dimensional models may also be used to qualitatively evaluate the stress distribution in a ply and the variation of energy release rates and mixed mode ratios with delamination length. For more accurate predictions, however, a three-dimensional analysis is required.

Influence of 2D Finite Element Modeling Assumptions on Debonding Prediction for Composite Skin-stiffener Specimens Subjected to Tension and Bending

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Minguet, Pierre J.; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

The influence of two-dimensional finite element modeling assumptions on the debonding prediction for skin-stiffener specimens was investigated. Geometrically nonlinear finite element analyses using two-dimensional plane-stress and plane strain elements as well as three different generalized plane strain type approaches were performed. The computed deflections, skin and flange strains, transverse tensile stresses and energy release rates were compared to results obtained from three-dimensional simulations. The study showed that for strains and energy release rate computations the generalized plane strain assumptions yielded results closest to the full three-dimensional analysis. For computed transverse tensile stresses the plane stress assumption gave the best agreement. Based on this study it is recommended that results from plane stress and plane strain models be used as upper and lower bounds. The results from generalized plane strain models fall between the results obtained from plane stress and plane strain models. Two-dimensional models may also be used to qualitatively evaluate the stress distribution in a ply and the variation of energy release rates and mixed mode ratios with lamination length. For more accurate predictions, however, a three-dimensional analysis is required.

A smoothed stochastic earthquake rate model considering seismicity and fault moment release for Europe

NASA Astrophysics Data System (ADS)

Hiemer, S.; Woessner, J.; Basili, R.; Danciu, L.; Giardini, D.; Wiemer, S.

2014-08-01

We present a time-independent gridded earthquake rate forecast for the European region including Turkey. The spatial component of our model is based on kernel density estimation techniques, which we applied to both past earthquake locations and fault moment release on mapped crustal faults and subduction zone interfaces with assigned slip rates. Our forecast relies on the assumption that the locations of past seismicity is a good guide to future seismicity, and that future large-magnitude events occur more likely in the vicinity of known faults. We show that the optimal weighted sum of the corresponding two spatial densities depends on the magnitude range considered. The kernel bandwidths and density weighting function are optimized using retrospective likelihood-based forecast experiments. We computed earthquake activity rates (a- and b-value) of the truncated Gutenberg-Richter distribution separately for crustal and subduction seismicity based on a maximum likelihood approach that considers the spatial and temporal completeness history of the catalogue. The final annual rate of our forecast is purely driven by the maximum likelihood fit of activity rates to the catalogue data, whereas its spatial component incorporates contributions from both earthquake and fault moment-rate densities. Our model constitutes one branch of the earthquake source model logic tree of the 2013 European seismic hazard model released by the EU-FP7 project `Seismic HAzard haRmonization in Europe' (SHARE) and contributes to the assessment of epistemic uncertainties in earthquake activity rates. We performed retrospective and pseudo-prospective likelihood consistency tests to underline the reliability of our model and SHARE's area source model (ASM) using the testing algorithms applied in the collaboratory for the study of earthquake predictability (CSEP). We comparatively tested our model's forecasting skill against the ASM and find a statistically significant better performance for testing periods of 10-20 yr. The testing results suggest that our model is a viable candidate model to serve for long-term forecasting on timescales of years to decades for the European region.

In silico study on the effects of matrix structure in controlled drug release

NASA Astrophysics Data System (ADS)

Villalobos, Rafael; Cordero, Salomón; Maria Vidales, Ana; Domínguez, Armando

2006-07-01

Purpose: To study the effects of drug concentration and spatial distribution of the medicament, in porous solid dosage forms, on the kinetics and total yield of drug release. Methods: Cubic networks are used as models of drug release systems. They were constructed by means of the dual site-bond model framework, which allows a substrate to have adequate geometrical and topological distribution of its pore elements. Drug particles can move inside the networks by following a random walk model with excluded volume interactions between the particles. The drug release time evolution for different drug concentration and different initial drug spatial distribution has been monitored. Results: The numerical results show that in all the studied cases, drug release presents an anomalous behavior, and the consequences of the matrix structural properties, i.e., drug spatial distribution and drug concentration, on the drug release profile have been quantified. Conclusions: The Weibull function provides a simple connection between the model parameters and the microstructure of the drug release device. A critical modeling of drug release from matrix-type delivery systems is important in order to understand the transport mechanisms that are implicated, and to predict the effect of the device design parameters on the release rate.

Computational Studies of Drug Release, Transport and Absorption in the Human Intestines

NASA Astrophysics Data System (ADS)

Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.

2016-11-01

Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.

Simulation of the hydrodynamic conditions of the eye to better reproduce the drug release from hydrogel contact lenses: experiments and modeling.

PubMed

Pimenta, A F R; Valente, A; Pereira, J M C; Pereira, J C F; Filipe, H P; Mata, J L G; Colaço, R; Saramago, B; Serro, A P

2016-12-01

Currently, most in vitro drug release studies for ophthalmic applications are carried out in static sink conditions. Although this procedure is simple and useful to make comparative studies, it does not describe adequately the drug release kinetics in the eye, considering the small tear volume and flow rates found in vivo. In this work, a microfluidic cell was designed and used to mimic the continuous, volumetric flow rate of tear fluid and its low volume. The suitable operation of the cell, in terms of uniformity and symmetry of flux, was proved using a numerical model based in the Navier-Stokes and continuity equations. The release profile of a model system (a hydroxyethyl methacrylate-based hydrogel (HEMA/PVP) for soft contact lenses (SCLs) loaded with diclofenac) obtained with the microfluidic cell was compared with that obtained in static conditions, showing that the kinetics of release in dynamic conditions is slower. The application of the numerical model demonstrated that the designed cell can be used to simulate the drug release in the whole range of the human eye tear film volume and allowed to estimate the drug concentration in the volume of liquid in direct contact with the hydrogel. The knowledge of this concentration, which is significantly different from that measured in the experimental tests during the first hours of release, is critical to predict the toxicity of the drug release system and its in vivo efficacy. In conclusion, the use of the microfluidic cell in conjunction with the numerical model shall be a valuable tool to design and optimize new therapeutic drug-loaded SCLs.

Phase Composition Control of Calcium Phosphate Nanoparticles for Tunable Drug Delivery Kinetics and Treatment of Osteomyelitis. Part 1: Preparation and Drug Release

PubMed Central

Uskoković, Vuk; Desai, Tejal A.

2012-01-01

Developed in this study is a multifunctional material for simultaneous osseoinduction and drug delivery, potentially applicable in the treatment of osteomyelitis. It is composed of agglomerates of nanoparticles of calcium phosphate (CAP) with different monophasic contents. The drug loading capacity and the release kinetics were investigated on two model drug compounds with different chemical structures, sizes and adsorption propensities: bovine serum albumin and fluorescein. Loading of CAP powders with small molecule drugs was achieved by physisorption and desiccation-induced agglomeration of nanoparticulate subunits into microscopic blocks. The material dissolution rate and the drug release rate depended on the nature of the CAP phase, decreasing from monocalcium phosphate to monetite to amorphous CAP and calcium pyrophosphate to hydroxyapatite. The sustained release of the two model drugs was shown to be directly relatable to the degradation rate of CAP carriers. It was demonstrated that the degradation rate of the carrier and the drug release kinetics could be made tunable within the time scale of 1–2 h for the most soluble CAP phase, monocalcium phosphate, to 1–2 years for the least soluble one, hydroxyapatite. From the standpoint of antibiotic therapy for osteomyelitis, typically lasting for six weeks, the most prospective CAP powder was amorphous CAP with its release time scale for a small organic molecule, the same category to which antibiotics belong, of 1 – 2 months under the conditions applied in our experiments. By combining these different CAP phases in various proportions, drug release profiles could be tailored to the therapeutic occasion. PMID:23115118

A mathematical model for the release of noble gas and Cs from porous nuclear fuel based on VEGA 1&2 experiments

NASA Astrophysics Data System (ADS)

Simones, M. P.; Reinig, M. L.; Loyalka, S. K.

2014-05-01

Release of fission products from nuclear fuel in accidents is an issue of major concern in nuclear reactor safety, and there is considerable room for development of improved models, supported by experiments, as one needs to understand and elucidate role of various phenomena and parameters. The VEGA (Verification Experiments of radionuclides Gas/Aerosol release) program on several irradiated nuclear fuels investigated the release rates of radionuclides and results demonstrated that the release rates of radionuclides from all nuclear fuels tested decreased with increasing external gas pressure surrounding the fuel. Hidaka et al. (2004-2011) accounted for this pressure effect by developing a 2-stage diffusion model describing the transport of radionuclides in porous nuclear fuel. We have extended this 2-stage diffusion model to account for mutual binary gas diffusion in the open pores as well as to introduce the appropriate parameters to cover the slip flow regime (0.01 ⩽ Kn ⩽ 0.1). While we have directed our numerical efforts toward the simulation of the VEGA experiments and assessments of differences from the results of Hidaka et al., the model and the techniques reported here are of larger interest as these would aid in modeling of diffusion in general (e.g. in graphite and other nuclear materials of interest).

Radon Release and Its Simulated Effect on Radiation Doses.

PubMed

Orabi, Momen

2017-03-01

One of the main factors that affect the uncertainty in calculating the gamma-radiation absorbed dose rate inside a room is the variation in the degree of secular equilibrium of the considered radioactive series. A component of this factor, considered in this paper, is the release of radon (Rn) from building materials to the living space of the room. This release takes place through different steps. These steps are represented and mathematically formulated. The diffusion of radon inside the material is described by Fick's second law. Some of the factors affecting the radon release rate (e.g. covering walls, moisture, structure of the building materials, etc.) are discussed. This scheme is used to study the impact of radon release on the gamma-radiation absorbed dose rate inside a room. The investigation is carried out by exploiting the MCNP simulation software. Different building materials are considered with different radon release rates. Special care is given to Rn due to its relatively higher half-life and higher indoor concentration than the other radon isotopes. The results of the presented model show that the radon release is of a significant impact in some building materials.

Estimations of direct release rate of 137Cs and 90Sr to the ocean from the Fukushima Dai-ichi Nuclear Power Plant for five-and-a-half years

NASA Astrophysics Data System (ADS)

Tsumune, Daisuke; Aoyama, Michio; Tsubono, Takaki; Misumi, Kazuhiro; Tateda, Yutaka

2017-04-01

A series of accidents at the Fukushima Dai-ichi Nuclear Power Plant (1F NPP) following the earthquake and tsunami of 11 March 2011 resulted in the release of radioactive materials to the ocean by two major pathways, direct release from the accident site and atmospheric deposition. Additional release pathways by river input and runoff from 1F NPP site with precipitation and were also effective for coastal zone in the specific periods before starting direct release on March 26 2011. Direct release from 1F NPP site is dominant one year after the accident. We estimated the direct release rate of 137Cs and 90Sr for more than five-and-a-half years after the accident by the Regional Ocean Model System (ROMS). Direct release rate of 137Cs were estimated for five-and-a-half years after the accident by comparing simulated results and measured activities adjacent to the 1F NPP site(at 5,6 discharge and south discharge). Directly release rate of 137Cs was estimated to be the order of magnitude of 1014 Bq/day and decreased exponentially with time to be the order of magnitude of 109 Bq/day by the end of September 2016. Estimated direct release rate have exponentially reduced with constant rate since November 2011. Apparent half-life of direct release rate was estimated to be 346 days. The estimated total amounts of directly released 137Cs was 3.7±0.7 PBq for five and a half years. Simulated 137Cs activities attributable to direct release were in good agreement with observed activities, a result that implies the estimated direct release rate was reasonable. Simulated 137Cs activity affected off coast in the Fukushima prefecture. We used the measured 137Cs activities by the Tokyo Electric Power Company (TEPCO) for the estimation of direct release. The sea water samples were corrected from the coast. The averaged 137Cs activities from November 2013 to June 2016 were 391 and 383 Bq/m3 at 5,6 discharge and south discharge, respectively. The averaged 137Cs activities measured by the Nuclear Regulation Agency (NRA) is about five times smaller than the one by the TEPCO because the NRA corrected seawater samples at 300-500m offshore by ship. Horizontal resolution of the model was 1km x 1km, therefore it is important to consider the difference of activities in the sub-grid scale for the detailed estimations of direct release. 90Sr/137Cs activity ratio measured adjacent to the 1F NPP is variable with time. The 90Sr/137Cs activity ratio was 0.62 due to the global fallout before the accident. The 90Sr/137Cs activity ratio decreased to 0.01 after the accident before April 2011. And the ratio increased to 1 by September 2013. And then the ratio decreased to 0.1-1. After October 2015, the ratio decreased to 0.1-0.2. Directly release rate of 90Sr was estimated to be the order of magnitude of 1012 Bq/day and decreased to the order of magnitude of 108 Bq/day by the end of September 2016. The estimated total amounts of directly released 90Sr was 35 ± 7 TBq.

Toward a reaction rate model of condensed-phase RDX decomposition under high temperatures

NASA Astrophysics Data System (ADS)

Schweigert, Igor

2014-03-01

Shock ignition of energetic molecular solids is driven by microstructural heterogeneities, at which even moderate stresses can result in sufficiently high temperatures to initiate material decomposition and the release of the chemical energy. Mesoscale modeling of these ``hot spots'' requires a chemical reaction rate model that describes the energy release with a sub-microsecond resolution and under a wide range of temperatures. No such model is available even for well-studied energetic materials such as RDX. In this presentation, I will describe an ongoing effort to develop a reaction rate model of condensed-phase RDX decomposition under high temperatures using first-principles molecular dynamics, transition-state theory, and reaction network analysis. This work was supported by the Naval Research Laboratory, by the Office of Naval Research, and by the DOD High Performance Computing Modernization Program Software Application Institute for Multiscale Reactive Modeling of Insensitive Munitions.

Toward a reaction rate model of condensed-phase RDX decomposition under high temperatures

NASA Astrophysics Data System (ADS)

Schweigert, Igor

2015-06-01

Shock ignition of energetic molecular solids is driven by microstructural heterogeneities, at which even moderate stresses can result in sufficiently high temperatures to initiate material decomposition and chemical energy release. Mesoscale modeling of these ``hot spots'' requires a reaction rate model that describes the energy release with a sub-microsecond resolution and under a wide range of temperatures. No such model is available even for well-studied energetic materials such as RDX. In this presentation, I will describe an ongoing effort to develop a reaction rate model of condensed-phase RDX decomposition under high temperatures using first-principles molecular dynamics, transition-state theory, and reaction network analysis. This work was supported by the Naval Research Laboratory, by the Office of Naval Research, and by the DoD High Performance Computing Modernization Program Software Application Institute for Multiscale Reactive Modeling of Insensitive Munitions.

Predicting red wolf release success in the southeastern United States

USGS Publications Warehouse

van Manen, Frank T.; Crawford, Barron A.; Clark, Joseph D.

2000-01-01

Although the red wolf (Canis rufus) was once found throughout the southeastern United States, indiscriminate killing and habitat destruction reduced its range to a small section of coastal Texas and Louisiana. Wolves trapped from 1973 to 1980 were taken to establish a captive breeding program that was used to repatriate 2 mainland and 3 island red wolf populations. We collected data from 320 red wolf releases in these areas and classified each as a success or failure based on survival and reproductive criteria, and whether recaptures were necessary to resolve conflicts with humans. We evaluated the relations between release success and conditions at the release sites, characteristics of released wolves, and release procedures. Although <44% of the variation in release success was explained, model performance based on jackknife tests indicated a 72-80% correct prediction rate for the 4 operational models we developed. The models indicated that success was associated with human influences on the landscape and the level of wolf habituation to humans prior to release. We applied the models to 31 prospective areas for wolf repatriation and calculated an index of release success for each area. Decision-makers can use these models to objectively rank prospective release areas and compare strengths and weaknesses of each.

Properties of hot-melt extruded theophylline tablets containing poly(vinyl acetate).

PubMed

Zhang, F; McGinity, J W

2000-09-01

The objectives of this study were to investigate the properties of poly(vinyl acetate) (PVAc) as a retardant polymer and to study the drug release mechanism of theophylline from matrix tablets prepared by hot-melt extrusion. A physical mixture of drug, polymer, and drug release modifiers was fed into the equipment and heated inside the barrel of the extruder. The cylindrical extrudates were either cut into tablets or ground into granules and compressed with other excipients into tablets. Due to the low glass transition temperature of the PVAc, the melt extrusion process was conducted at approximately 70 degrees C. Theophylline was used as the model drug in this study. Theophylline was present in the extrudate in its crystalline form and was released from the tablets by diffusion. The Higuchi diffusion model and percolation theories were applied to the dissolution data to explain the drug release properties of the matrix systems. The release rate was shown to be dependent on the granule size, drug particle size, and drug loading in the tablets. Water-soluble polymers were demonstrated to be efficient release rate modifiers for this system.

Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs

NASA Astrophysics Data System (ADS)

Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

2006-05-01

Mats of PVA nanofibres were successfully prepared by the electrospinning process and were developed as carriers of drugs for a transdermal drug delivery system. Four types of non-steroidal anti-inflammatory drug with varying water solubility property, i.e. sodium salicylate (freely soluble in water), diclofenac sodium (sparingly soluble in water), naproxen (NAP), and indomethacin (IND) (both insoluble in water), were selected as model drugs. The morphological appearance of the drug-loaded electrospun PVA mats depended on the nature of the model drugs. The 1H-nuclear magnetic resonance results confirmed that the electrospinning process did not affect the chemical integrity of the drugs. Thermal properties of the drug-loaded electrospun PVA mats were analysed by differential scanning calorimetry and thermogravimetric analysis. The molecular weight of the model drugs played a major role on both the rate and the total amount of drugs released from the as-prepared drug-loaded electrospun PVA mats, with the rate and the total amount of the drugs released decreasing with increasing molecular weight of the drugs. Lastly, the drug-loaded electrospun PVA mats exhibited much better release characteristics of the model drugs than drug-loaded as-cast films.

SP industry calorimeter for rate of heat release measurements up to 10MW

NASA Astrophysics Data System (ADS)

Dahlberg, Martin

The Swedish National Testing and Research Institute (SP) has installed a 10 MW fire calorimeter for rate of heat release measurements, similar to the one at Factory Mutual Research Corporation (FMRC). It can be used to classify commodities with respect to their fire hazard, to evaluate the efficiency of sprinkler systems, for chemical analysis of the combustion gases from hazardous fires, to produce input data for the fire modelling, etc. A large hood collects the fire gases and leads them into a duct where gas velocity, gas temperature, smoke density, and contents of oxygen, carbon dioxide, and carbon monoxide are measured. On the basis of these measurements, mass flow and rate of heat release are calculated. The rate of heat release is calculated according to the oxygen consumption principle. The upper limit for measurements is approximately 10 MW and the lower is 0.1 MW.

Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.

PubMed

Hiremath, Praveen S; Saha, Ranendra N

2008-01-01

The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer-Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f (2) metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

A personalized medicine approach to the design of dry powder inhalers: Selecting the optimal amount of bypass.

PubMed

Kopsch, Thomas; Murnane, Darragh; Symons, Digby

2017-08-30

In dry powder inhalers (DPIs) the patient's inhalation manoeuvre strongly influences the release of drug. Drug release from a DPI may also be influenced by the size of any air bypass incorporated in the device. If the amount of bypass is high less air flows through the entrainment geometry and the release rate is lower. In this study we propose to reduce the intra- and inter-patient variations of drug release by controlling the amount of air bypass in a DPI. A fast computational method is proposed that can predict how much bypass is needed for a specified drug delivery rate for a particular patient. This method uses a meta-model which was constructed using multiphase computational fluid dynamic (CFD) simulations. The meta-model is applied in an optimization framework to predict the required amount of bypass needed for drug delivery that is similar to a desired target release behaviour. The meta-model was successfully validated by comparing its predictions to results from additional CFD simulations. The optimization framework has been applied to identify the optimal amount of bypass needed for fictitious sample inhalation manoeuvres in order to deliver a target powder release profile for two patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Rainfall-Induced Release of Fecal Coliforms and Other Manure Constituents: Comparison and Modeling▿

PubMed Central

Guber, A. K.; Shelton, D. R.; Pachepsky, Y. A.; Sadeghi, A. M.; Sikora, L. J.

2006-01-01

Modeling release of fecal coliforms is an important component of fate and transport simulations related to environmental water quality. Manure constituents other than fecal coliforms may serve as natural tracers of fecal contamination provided that their release from manure to runoff is similar to the fecal coliform release. The objectives of this work were to compare release of fecal coliforms (FC), chloride (Cl−), organic carbon (OC), and water-soluble phosphorus (P) from dissolving manure and to assess the performance of three models in describing the observed release. Bovine manure was applied on 0.5- by 0.3-m bare and vegetated subplots with 20% slope on sandy loam and clay loam soils. Concentrations of Cl−, FC, OC, and P were measured in runoff collected from troughs at the edges of the subplots at 5-min intervals during 1-h rainfall simulations. The one-parametric exponential model and two-parametric Vadas-Kleinman-Sharpley model and Bradford-Schijven model were fitted to the data. The Bradford-Schijven model had uncorrelated parameters, one of which was linearly related to the irrigation rate, and another parameter reflected the presence or the absence of vegetation. Kinetics of the FC release from manure was similar to the release kinetics of P and OC. The Bradford-Schijven model is recommended to simulate the release of manure constituents. PMID:17028232

Preparation and pharmaceutical evaluation of new sustained-release capsule including starch-sponge matrix (SSM).

PubMed

Shibata, Nobuhito; Nishumura, Asako; Naruhashi, Kazumasa; Nakao, Yurie; Miura, Rieko

2010-05-01

The focus of current study was to demonstrate a new sustained-release capsule including starch-sponge matrix (SSM) and to investigate how the pharmaceutical properties of SSM affect the drug release or its pharmacokinetic properties. Three representative drugs (uranine [UN], indomethacin [IMC] and nifedipine [NFP]) with different physicochemical properties (LogP(ow): 0.10, 1.18 and 3.23, respectively) were selected as model drugs. Model drug was dispersioned in pastelike cornstarch (starch glue) after heating 2.0-3.0% cornstarch suspension with electromagnetic wave at 2450 MHz (700 W) for l min. Then the drug mixture was encapsulated into a gratin capsule by a syringe, and the SSM including drug was prepared by means of a freeze-dried method. Essentially, drug-free SSM has a porous and netlike structure, and the distribution aspect of model drugs in the SSM depends on physicochemical properties between cornstarch glue and drugs. UN with much lower lipophilicity exists in continues phase of SSM, and IMC or NFP with a moderate or a higher lipophilicity exist in continues phase or porous space of the SSM. In the in vitro dissolution study, the release rate of drug from the SSM was mainly dependent on the lipophilicities of drugs, showing a rank order of the release rate of UN>IMC>NFP. In addition, the in vitro release rate for each drug was well regulated by changing the initial concentration of cornstarch suspension. In vivo absorption studies after intraduodenal administration of SSM capsule including model drug revealed that the sustained-release effects also could be regulated by the initial concentration of starch suspension. Moreover, the sustained-release effect of SSM capsule was enhanced with an increase in the lipophilicity of drug, and local-residential and mucoadhesive properties of SSM in the intestine provided stable supply of drugs from the SSM. The SSM capsule we developed here shows promising results as an oral drug delivery system for sustained-release regulation or target specificity. 2009 Elsevier Masson SAS. All rights reserved.

Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: establishment of level A IVIVC.

PubMed

Sankalia, Jolly M; Sankalia, Mayur G; Mashru, Rajashree C

2008-07-02

The purpose of this study was to examine a level A in vitro-in vivo correlation (IVIVC) for glipizide hydrophilic sustained-release matrices, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. The effect of polymeric blends of ethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, xanthan gum, guar gum, Starch 1500, and lactose on in vitro release profiles was studied and fitted to various release kinetics models. Water uptake kinetics with scanning electron microscopy (SEM) was carried out to support the drug release mechanism. An IVIVC was established by comparing the pharmacokinetic parameters of optimized (M-24) and marketed (Glytop-2.5 SR) formulations after single oral dose studies on white albino rabbits. The matrix M-19 (xanthan:MCC PH301 at 70:40) and M-24 (xanthan:HPMC K4M:Starch 1500 at 70:25:15) showed the glipizide release within the predetermined constraints at all time points with Korsmeyer-Peppas' and zero-order release mechanism, respectively. Kopcha model revealed that the xanthan gum is the major excipient responsible for the diffusional release profile and was further supported by SEM and swelling studies. A significant level A IVIVC with acceptable limits of prediction errors (below 15%) enables the prediction of in vivo performance from their in vitro release profile. It was concluded that proper selection of rate-controlling polymers with release rate modifier excipients will determine overall release profile, duration and mechanism from directly compressed matrices.

A Cohesive Zone Approach for Fatigue-Driven Delamination Analysis in Composite Materials

NASA Astrophysics Data System (ADS)

Amiri-Rad, Ahmad; Mashayekhi, Mohammad

2017-08-01

A new model for prediction of fatigue-driven delamination in laminated composites is proposed using cohesive interface elements. The presented model provides a link between cohesive elements damage evolution rate and crack growth rate of Paris law. This is beneficial since no additional material parameters are required and the well-known Paris law constants are used. The link between the cohesive zone method and fracture mechanics is achieved without use of effective length which has led to more accurate results. The problem of unknown failure path in calculation of the energy release rate is solved by imposing a condition on the damage model which leads to completely vertical failure path. A global measure of energy release rate is used for the whole cohesive zone which is computationally more efficient compared to previous similar models. The performance of the proposed model is investigated by simulation of well-known delamination tests and comparison against experimental data of the literature.

On the identification of cohesive parameters for printed metal-polymer interfaces

NASA Astrophysics Data System (ADS)

Heinrich, Felix; Langner, Hauke H.; Lammering, Rolf

2017-05-01

The mechanical behavior of printed electronics on fiber reinforced composites is investigated. A methodology based on cohesive zone models is employed, considering interfacial strengths, stiffnesses and critical strain energy release rates. A double cantilever beam test and an end notched flexure test are carried out to experimentally determine critical strain energy release rates under fracture modes I and II. Numerical simulations are performed in Abaqus 6.13 to model both tests. Applying the simulations, an inverse parameter identification is run to determine the full set of cohesive parameters.

Dose assessment for various coals in the coal-fired power plant

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

Antic, D.; Sokcic-Kostic, M.

1993-01-01

The radiation exposure of the public in the vicinity of a coal-fired power plant has been studied. The experimental data on uranium, thorium, and potassium content in selected coals from Serbia and Bosnia have been used to calculate the release rates of natural radionuclides from the power plant. A generalized model for analysis of radiological impact of an energy source that includes the two-dimensional version of the cloud model simulates the transport of radionuclides released to the atmosphere. The inhalation dose rates are assessed for various meteorological conditions.

Electrosprayed nanoparticle delivery system for controlled release.

PubMed

Eltayeb, Megdi; Stride, Eleanor; Edirisinghe, Mohan; Harker, Anthony

2016-09-01

This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70nm at the rate of 1.37×10(9) nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈21% and the encapsulation efficiency ≈70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. Copyright © 2016 Elsevier B.V. All rights reserved.

Modeling the purging of dense fluid from a street canyon driven by an interfacial mixing flow and skimming flow

NASA Astrophysics Data System (ADS)

Baratian-Ghorghi, Z.; Kaye, N. B.

2013-07-01

An experimental study is presented to investigate the mechanism of flushing a trapped dense contaminant from a canyon by turbulent boundary layer flow. The results of a series of steady-state experiments are used to parameterize the flushing mechanisms. The steady-state experimental results for a canyon with aspect ratio one indicate that dense fluid is removed from the canyon by two different processes, skimming of dense fluid from the top of the dense layer; and by an interfacial mixing flow that mixes fresh fluid down into the dense lower layer (entrainment) while mixing dense fluid into the flow above the canyon (detrainment). A model is developed for the time varying buoyancy profile within the canyon as a function of the Richardson number which parameterizes both the interfacial mixing and skimming processes observed. The continuous release steady-state experiments allowed for the direct measurement of the skimming and interfacial mixing flow rates for any layer depth and Richardson number. Both the skimming rate and the interfacial mixing rate were found to be power-law functions of the Richardson number of the layer. The model results were compared to the results of previously published finite release experiments [Z. Baratian-Ghorghi and N. B. Kaye, Atmos. Environ. 60, 392-402 (2012)], 10.1016/j.atmosenv.2012.06.077. A high degree of consistency was found between the finite release data and the continuous release data. This agreement acts as an excellent check on the measurement techniques used, as the finite release data was based on curve fitting through buoyancy versus time data, while the continuous release data was calculated directly by measuring the rate of addition of volume and buoyancy once a steady-state was established. Finally, a system of ordinary differential equations is presented to model the removal of dense fluid from the canyon based on empirical correlations of the skimming and interfacial mixing taken form the steady-state experiments. The ODE model predicts well the time taken for a finite volume of dense fluid to be flushed from a canyon.

Intravascular Drug Release Kinetics Dictate Arterial Drug Deposition, Retention, and Distribution

PubMed Central

Balakrishnan, Brinda; Dooley, John F.; Kopia, Gregory; Edelman, Elazer R.

2007-01-01

Millions of patients worldwide have received drug-eluting stents to reduce their risk for in-stent restenosis. The efficacy and toxicity of these local therapeutics depend upon arterial drug deposition, distribution, and retention. To examine how administered dose and drug release kinetics control arterial drug uptake, a model was created using principles of computational fluid dynamics and transient drug diffusion-convection. The modeling predictions for drug elution were validated using empiric data from stented porcine coronary arteries. Inefficient, minimal arterial drug deposition was predicted when a bolus of drug was released and depleted within seconds. Month-long stent-based drug release efficiently delivered nearly continuous drug levels, but the slow rate of drug presentation limited arterial drug uptake. Uptake was only maximized when the rates of drug release and absorption matched, which occurred for hour-long drug release. Of the two possibly means for increasing the amount of drug on the stent, modulation of drug concentration potently impacts the magnitude of arterial drug deposition, while changes in coating drug mass affect duration of release. We demonstrate the importance of drug release kinetics and administered drug dose in governing arterial drug uptake and suggest novel drug delivery strategies for controlling spatio-temporal arterial drug distribution. PMID:17868948

Pest persistence and eradication conditions in a deterministic model for sterile insect release.

PubMed

Gordillo, Luis F

2015-01-01

The release of sterile insects is an environment friendly pest control method used in integrated pest management programmes. Difference or differential equations based on Knipling's model often provide satisfactory qualitative descriptions of pest populations subject to sterile release at relatively high densities with large mating encounter rates, but fail otherwise. In this paper, I derive and explore numerically deterministic population models that include sterile release together with scarce mating encounters in the particular case of species with long lifespan and multiple matings. The differential equations account separately the effects of mating failure due to sterile male release and the frequency of mating encounters. When insects spatial spread is incorporated through diffusion terms, computations reveal the possibility of steady pest persistence in finite size patches. In the presence of density dependence regulation, it is observed that sterile release might contribute to induce sudden suppression of the pest population.

Modeling the suppression of sea lamprey populations by the release of sterile males or sterile females

USGS Publications Warehouse

Klassen, Waldemar; Adams, Jean V.; Twohey, Michael B.

2004-01-01

The suppressive effects of trapping adult sea lampreys, Petromyzon marinus Linnaeus, and releasing sterile males (SMRT) or females (SFRT) into a closed system were expressed in deterministic models. Suppression was modeled as a function of the proportion of the population removed by trapping, the number of sterile animals released, the reproductive rate and sex ratio of the population, and (for the SFRT) the rate of polygyny. Releasing sterile males reduced populations more quickly than did the release of sterile females. For a population in which 30% are trapped, sterile animals are initially released at ratio of 10 sterile to 1 fertile animal, 5 adult progeny are produced per fertile mating, 60% are male, and males mate with an average of 1.65 females, the initial population is reduced 87% by SMRT and 68% by SFRT in one generation. The extent of suppression achieved is most sensitive to changes in the initial sterile release ratio. Given the current status of sea lamprey populations and trapping operations in the Great Lakes, the sterile-male-release technique has the best chance for success on a lake-wide basis if implemented in Lake Michigan. The effectiveness of the sterile-female-release technique should be investigated in a controlled study. Advancing trapping technology should be a high priority in the near term, and artificial rearing of sea lampreys to the adult stage should be a high priority in the long term. The diligent pursuit of sea lamprey suppression over a period of several decades can be expected to yield great benefits.

Comparison of DSMC Reaction Models with QCT Reaction Rates for Nitrogen

DTIC Science & Technology

2016-07-17

The U.S. Government is joint author of the work and has the right to use, modify, reproduce, release, perform, display, or disclose the work. 13...Distribution A: Approved for Public Release, Distribution Unlimited PA #16299 Introduction • Comparison with measurements is final goal • Validation...model verification and parameter adjustment • Four chemistry models: total collision energy (TCE), quantum kinetic (QK), vibration-dissociation favoring

[Numerical simulation of the effect of virtual stent release pose on the expansion results].

PubMed

Li, Jing; Peng, Kun; Cui, Xinyang; Fu, Wenyu; Qiao, Aike

2018-04-01

The current finite element analysis of vascular stent expansion does not take into account the effect of the stent release pose on the expansion results. In this study, stent and vessel model were established by Pro/E. Five kinds of finite element assembly models were constructed by ABAQUS, including 0 degree without eccentricity model, 3 degree without eccentricity model, 5 degree without eccentricity model, 0 degree axial eccentricity model and 0 degree radial eccentricity model. These models were divided into two groups of experiments for numerical simulation with respect to angle and eccentricity. The mechanical parameters such as foreshortening rate, radial recoil rate and dog boning rate were calculated. The influence of angle and eccentricity on the numerical simulation was obtained by comparative analysis. Calculation results showed that the residual stenosis rates were 38.3%, 38.4%, 38.4%, 35.7% and 38.2% respectively for the 5 models. The results indicate that the pose has less effect on the numerical simulation results so that it can be neglected when the accuracy of the result is not highly required, and the basic model as 0 degree without eccentricity model is feasible for numerical simulation.

Combined application of mixture experimental design and artificial neural networks in the solid dispersion development.

PubMed

Medarević, Djordje P; Kleinebudde, Peter; Djuriš, Jelena; Djurić, Zorica; Ibrić, Svetlana

2016-01-01

This study for the first time demonstrates combined application of mixture experimental design and artificial neural networks (ANNs) in the solid dispersions (SDs) development. Ternary carbamazepine-Soluplus®-poloxamer 188 SDs were prepared by solvent casting method to improve carbamazepine dissolution rate. The influence of the composition of prepared SDs on carbamazepine dissolution rate was evaluated using d-optimal mixture experimental design and multilayer perceptron ANNs. Physicochemical characterization proved the presence of the most stable carbamazepine polymorph III within the SD matrix. Ternary carbamazepine-Soluplus®-poloxamer 188 SDs significantly improved carbamazepine dissolution rate compared to pure drug. Models developed by ANNs and mixture experimental design well described the relationship between proportions of SD components and percentage of carbamazepine released after 10 (Q10) and 20 (Q20) min, wherein ANN model exhibit better predictability on test data set. Proportions of carbamazepine and poloxamer 188 exhibited the highest influence on carbamazepine release rate. The highest carbamazepine release rate was observed for SDs with the lowest proportions of carbamazepine and the highest proportions of poloxamer 188. ANNs and mixture experimental design can be used as powerful data modeling tools in the systematic development of SDs. Taking into account advantages and disadvantages of both techniques, their combined application should be encouraged.

Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release

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

Szegedi, A., E-mail: szegedi@chemres.h; Popova, M.; Goshev, I.

2011-05-15

MCM-41 and SBA-15 silica materials with spherical morphology and different particle sizes were synthesized and modified by post-synthesis method with 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, were carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, thermal analysis, elemental analysis and FT-IR spectroscopy. Surface modification with amino groups resulted in high degree of ibuprofen loading and slow rate of release for MCM-41, whereas it was the opposite for SBA-15. The adsorbed drug content and the delivery rate can be predetermined by the choicemore » of mesoporous material with the appropriate structural characteristics and surface functionality. -- Graphical Abstract: Ibuprofen delivery from the parent and amino-modified spherical MCM-41 materials with 100 nm (small) and 500 nm (large) particle sizes. Display Omitted Highlights: {yields} Spherical type MCM-41 and SBA-15 with different particle sizes were modified by APTES. {yields} Adsorption and release rate of ibuprofen were compared. {yields} High degree of ibuprofen loading, slow release rate for MCM-41, the opposite for SBA-15. {yields} MCM-41 with 100 nm particles was more stable and showed slower release rate« less

Impact of physicochemical properties of porous silica materials conjugated with dexamethasone via pH-responsive hydrazone bond on drug loading and release behavior

NASA Astrophysics Data System (ADS)

Numpilai, Thanapha; Witoon, Thongthai; Chareonpanich, Metta; Limtrakul, Jumras

2017-02-01

The conjugation of dexamethasone (DEX) onto modified-porous silica materials via a pH-responsive hydrazone bond has been reported to be highly efficient method to specifically deliver the DEX to diseased sites. However, the influence of physicochemical properties of porous silica materials has not yet been fully understood. In this paper, the impact of pore sizes, particle sizes and silanol contents on surface functionalization, drug loading and release behavior of porous silica materials conjugated with dexamethasone via pH-responsive hydrazone bond was investigated. The grafting density was found to relate to the number of silanol groups on the surface of porous silica materials. The particle size and macropores of the porous silica materials played an vital role on the drug loading and release behavior. Although the porous silica materials with larger particle sizes possessed a lower grafting density, a larger amount of drug loading could be achieved. Moreover, the porous silica materials with larger particle sizes showed a slower release rate of DEX due to a longer distance for cleaved DEX diffusion out of pores. DEX release rate exhibited pH-dependent, sustained release. At pH 4.5, the amount of DEX release within 10 days could be controlled in the range of 12.74-36.41%, depending on the host material. Meanwhile, less than 1.5% of DEX was released from each of type of the porous silica materials at pH 7.4. The results of silica dissolution suggested that the degradation of silica matrix did not significantly affect the release rate of DEX. In addition, the kinetic modeling studies revealed that the DEX releases followed Korsmeyer-Peppas model with a release exponent (n) ranged from 0.3 to 0.47, indicating a diffusion-controlled release mechanism.

Influence of Polymer Type on the Physical Properties and Release Profile of Papaverine Hydrochloride From Hard Gelatin Capsules.

PubMed

Polski, Andrzej; Iwaniak, Karol; Kasperek, Regina; Modrzewska, Joanna; Sobótka-Polska, Karolina; Sławińska, Karolina; Poleszak, Ewa

2015-01-01

The capsule is one of the most important solid dosage forms in the pharmaceutical industry. It is easier and faster to produce than a tablet, because it requires fewer excipients. Generally, capsules are easy to swallow and mask any unpleasant taste of the substances used while their release profiles can be easily modified. Papaverine hydrochloride was used as a model substance to show different release profiles using different excipients. The main aim of the study was to analyze the impact of using different polymers on the release profile of papaverine hydrochloride from hard gelatin capsules. Six series of hard gelatin capsules containing papaverine hydrochloride as a model drug and different excipients were made. Then, the angle of repose, flow rate, mass flow rate and volume flow rate of the powders used for capsule production were analyzed. The uniform weight and disintegration time of the capsules were studied. The dissolution study was performed in a basket apparatus, while the amount of papaverine hydrochloride released was determined spectrophotometrically at 251 nm. Only one formula of powder had satisfactory flow properties, while all formulas had good Hausner ratios. The best properties were from powder containing polyvinylpyrrolidone 10k. The disintegration time of capsules varied from 1:30 min to 2:00 min. As required by Polish Pharmacopoeia X, 80% of the active substance in all cases was released within 15 minutes. The capsules with polyvinylpyrrolidone 10k were characterized by the longest release. On the other hand, capsules containing microcrystalline cellulose had the fastest release profile. Using 10% of different polymers, without changing the other excipients, had a significant impact on the physical properties of the powders and papaverine hydrochloride release profile. The two most preferred capsule formulations contained either polyvinylpyrrolidone 10k or microcrystalline cellulose.

Experimental study and modelling of deuterium thermal release from Be-D co-deposited layers

NASA Astrophysics Data System (ADS)

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

2014-07-01

A study of the thermal desorption of deuterium from 1 µm thick co-deposited Be-(0.1)D layers formed at 330 K by a magnetron sputtering technique is reported. A range of thermal desorption rates 0 ⩽ β ⩽ 1.0 K s-1 are explored with a view to studying the effectiveness of the proposed ITER wall and divertor bake procedure (β = 0 K s-1) to be carried out at 513 and 623 K. Fixed temperature bake durations up to 24 h are examined. The experimental thermal release data are used to validate a model input into the Tritium Migration and Analysis Program (TMAP-7). Good agreement with experiment is observed for a TMAP-7 model incorporating trap populations of activation energies for D release of 0.80 and 0.98 eV, and a dynamically computed surface D atomic to molecular recombination rate.

Measuring the Acoustic Release of a Chemotherapeutic Agent from Folate-Targeted Polymeric Micelles.

PubMed

Abusara, Ayah; Abdel-Hafez, Mamoun; Husseini, Ghaleb

2018-08-01

In this paper, we compare the use of Bayesian filters for the estimation of release and re-encapsulation rates of a chemotherapeutic agent (namely Doxorubicin) from nanocarriers in an acoustically activated drug release system. The study is implemented using an advanced kinetic model that takes into account cavitation events causing the antineoplastic agent's release from polymeric micelles upon exposure to ultrasound. This model is an improvement over the previous representations of acoustic release that used simple zero-, first- and second-order release and re-encapsulation kinetics to study acoustically triggered drug release from polymeric micelles. The new model incorporates drug release and micellar reassembly events caused by cavitation allowing for the controlled release of chemotherapeutics specially and temporally. Different Bayesian estimators are tested for this purpose including Kalman filters (KF), Extended Kalman filters (EKF), Particle filters (PF), and multi-model KF and EKF. Simulated and experimental results are used to verify the performance of the above-mentioned estimators. The proposed methods demonstrate the utility and high-accuracy of using estimation methods in modeling this drug delivery technique. The results show that, in both cases (linear and non-linear dynamics), the modeling errors are expensive but can be minimized using a multi-model approach. In addition, particle filters are more flexible filters that perform reasonably well compared to the other two filters. The study improved the accuracy of the kinetic models used to capture acoustically activated drug release from polymeric micelles, which may in turn help in designing hardware and software capable of precisely controlling the delivered amount of chemotherapeutics to cancerous tissue.

Acid volatile sulfides oxidation and metals (Mn, Zn) release upon sediment resuspension: laboratory experiment and model development.

PubMed

Hong, Yong Seok; Kinney, Kerry A; Reible, Danny D

2011-03-01

Sediment from the Anacostia River (Washington, DC, USA) was suspended in aerobic artificial river water for 14 d to investigate the dynamics of dissolved metals release and related parameters including pH, acid volatile sulfides (AVS), and dissolved/solid phase Fe(2+). To better understand and predict the underlying processes, a mathematical model is developed considering oxidation of reduced species, dissolution of minerals, pH changes, and pH-dependent metals' sorption to sediment. Oxidation rate constants of elemental sulfur and zinc sulfide, and a dissolution rate constant of carbonate minerals, were adjusted to fit observations. The proposed model and parameters were then applied, without further calibration, to literature-reported experimental observations of resuspension in an acid sulfate soil collected in a coastal flood plain. The model provided a good description of the dynamics of AVS, Fe(2+), S(0)((s)), pH, dissolved carbonates concentrations, and the release of Ca((aq)), Mg((aq)), and Zn((aq)) in both sediments. Accurate predictions of Mn((aq)) release required adjustment of sorption partitioning coefficient, presumably due to the presence of Mn scavenging by phases not accounted for in the model. The oxidation of AVS (and the resulting release of sulfide-bound metals) was consistent with a two-step process, a relatively rapid AVS oxidation to elemental sulfur (S(0)((s))) and a slow oxidation of S(0)((s)) to SO(4)(2-)((aq)), with an associated decrease in pH from neutral to acidic conditions. This acidification was the dominant factor for the release of metals into the aqueous phase. Copyright © 2010 SETAC.

The dispersion releaser technology is an effective method for testing drug release from nanosized drug carriers.

PubMed

Janas, Christine; Mast, Marc-Phillip; Kirsamer, Li; Angioni, Carlo; Gao, Fiona; Mäntele, Werner; Dressman, Jennifer; Wacker, Matthias G

2017-06-01

The dispersion releaser (DR) is a dialysis-based setup for the analysis of the drug release from nanosized drug carriers. It is mounted into dissolution apparatus2 of the United States Pharmacopoeia. The present study evaluated the DR technique investigating the drug release of the model compound flurbiprofen from drug solution and from nanoformulations composed of the drug and the polymer materials poly (lactic acid), poly (lactic-co-glycolic acid) or Eudragit®RSPO. The drug loaded nanocarriers ranged in size between 185.9 and 273.6nm and were characterized by a monomodal size distribution (PDI<0.1). The membrane permeability constants of flurbiprofen were calculated and mathematical modeling was applied to obtain the normalized drug release profiles. For comparing the sensitivities of the DR and the dialysis bag technique, the differences in the membrane permeation rates were calculated. Finally, different formulation designs of flurbiprofen were sensitively discriminated using the DR technology. The mechanism of drug release from the nanosized carriers was analyzed by applying two mathematical models described previously, the reciprocal powered time model and the three parameter model. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-random dispersal in the butterfly Maniola jurtina: implications for metapopulation models.

PubMed Central

Conradt, L; Bodsworth, E J; Roper, T J; Thomas, C D

2000-01-01

The dispersal patterns of animals are important in metapopulation ecology because they affect the dynamics and survival of populations. Theoretical models assume random dispersal but little is known in practice about the dispersal behaviour of individual animals or the strategy by which dispersers locate distant habitat patches. In the present study, we released individual meadow brown butterflies (Maniola jurtina) in a non-habitat and investigated their ability to return to a suitable habitat. The results provided three reasons for supposing that meadow brown butterflies do not seek habitat by means of random flight. First, when released within the range of their normal dispersal distances, the butterflies orientated towards suitable habitat at a higher rate than expected at random. Second, when released at larger distances from their habitat, they used a non-random, systematic, search strategy in which they flew in loops around the release point and returned periodically to it. Third, butterflies returned to a familiar habitat patch rather than a non-familiar one when given a choice. If dispersers actively orientate towards or search systematically for distant habitat, this may be problematic for existing metapopulation models, including models of the evolution of dispersal rates in metapopulations. PMID:11007325

Study of the ionization rate of the released deuterium in vacuum arc discharges with metal deuteride cathodes

NASA Astrophysics Data System (ADS)

Liu, Fei-Xiang; Long, Ji-Dong; Zheng, Le; Dong, Pan; Li, Chen; Chen, Wei

2018-02-01

The ionization rate of the released deuterium from a metal deuteride cathode in vacuum arc discharges is investigated by both experiments and modeling analysis. Experimental results show that the deuterium ionization rate increases from 2% to 30% with the increasing arc current in the range of 2-100 A. Thus the full ionization assumption, as is widely used in arc plasma simulations, is not satisfied for the released deuterium at low discharge current. According to the modeling results, the neutral-to-ion conversion efficiency for the deuterium traveling across the cathodic spot region can be significantly less than one, due to the fast plasma expansion and rarefaction in the vacuum. In addition, the model also reveals that, unlike the metal atoms which are mainly ionized in the sheath region and flow back to the cathode, the deuterium ionization primarily occurs in the quasi-neutral region and moves towards the anode. Consequently, the cathodic sheath layer acts like a filter that increases the deuterium fraction beyond the sheath region.

Simulation and parametric study of a film-coated controlled-release pharmaceutical.

PubMed

Borgquist, Per; Zackrisson, Gunnar; Nilsson, Bernt; Axelsson, Anders

2002-04-23

Pharmaceutical formulations can be designed as Multiple Unit Systems, such as Roxiam CR, studied in this work. The dose is administrated as a capsule, which contains about 100 individual pellets, which in turn contain the active drug remoxipride. Experimental data for a large number of single pellets can be obtained by studying the release using microtitre plates. This makes it possible to study the release of the individual subunits making up the total dose. A mathematical model for simulating the release of remoxipride from single film-coated pellets is presented including internal and external mass transfer hindrance apart from the most important film resistance. The model can successfully simulate the release of remoxipride from single film-coated pellets if the lag phase of the experimental data is ignored. This was shown to have a minor influence on the release rate. The use of the present model is demonstrated by a parametric study showing that the release process is film-controlled, i.e. is limited by the mass transport through the polymer coating. The model was used to fit the film thickness and the drug loading to the experimental release data. The variation in the fitted values was similar to that obtained in the experiments.

Formation of mannitol core microparticles for sustained release with lipid coating in a mini fluid bed system.

PubMed

Wang, Bifeng; Friess, Wolfgang

2017-11-01

The goal of this study was to prepare sustained release microparticles for methyl blue and aspartame as sparingly and freely water-soluble model drugs by lipid film coating in a Mini-Glatt fluid bed, and to assess the effect of coating load of two of lipids, hard fat and glyceryl stearate, on the release rates. 30g drug-loaded mannitol carrier microparticles with average diameter of 500 or 300μm were coated with 5g, 10g, 20g and 30g lipids, respectively. The model drugs were completely released in vitro through pores which mainly resulted from dissolution of the polyol core beads. The release of methyl blue from microparticles based on 500μm carrier beads extended up to 25days, while aspartame release from microparticles formed from 300μm carrier beads was extended to 7days. Although glyceryl stearate exhibits higher wettability, burst and release rates were similar for the two lipid materials. Polymorphic transformation of the hart fat was observed upon release. The lipid-coated microparticles produced with 500μm carrier beads showed slightly lower burst release compared to the microparticles produced with 300μm carrier beads as they carried relatively thicker lipid layer based on an equivalent lipid to mannitol ratio. Aspartame microparticles showed a much faster release than methyl blue due to the higher water-solubility of aspartame. Copyright © 2017 Elsevier B.V. All rights reserved.

Kinetic models for the release of the anticancer drug doxorubicin from biodegradable polylactide/metal oxide-based hybrids.

PubMed

Mhlanga, Nikiwe; Ray, Suprakas Sinha

2015-01-01

For decades, studies on drug-release kinetics have been an important topic in the field of drug delivery because they provide important insights into the mechanism of drug release from carriers. In this work, polylactide (PLA), doxorubicin (DOX), and metal oxide (MO) (titanium dioxide, magnetic iron oxide, and zinc oxide) spheres were synthesised using the solvent-evaporation technique and were tested for sustained drug release. The efficacy of a dosage system is determined by its ability to deliver the drug at a sustained rate, afford an increased plasma half-life, a minimum exposure of toxic drugs to healthy cells and a high drug pay load. Mathematical models were used to elucidate the release mechanism of the drug from the spheres. The release fitted a zero-order model with a correlation coefficient in the range of 0.9878-0.9891 and the release mechanism followed an anomalous release, meaning drug release was afforded through both diffusion and the dissolution of PLA. Therefore, PLA/DOX/MO released the same amount of drug per unit time. Consequently, the potential for PLA use as a carrier was ascertained. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of the Heat Release Rate from the Mass Loss Calorimeter to the Cone Calorimeter for Wood-based Materials

Treesearch

Laura E. Hasburgh; Robert H. White; Mark A. Dietenberger; Charles R. Boardman

2015-01-01

There is a growing demand for material properties to be used as inputs in fi re behavior models designed to address building fire safety. This comparative study evaluates using the mass loss calorimeter as an alternative to the cone calorimeter for obtaining heat release rates of wood-based materials. For this study, a modified mass loss calorimeter utilized an...

Optimum timing for integrated pest management: modelling rates of pesticide application and natural enemy releases.

PubMed

Tang, Sanyi; Tang, Guangyao; Cheke, Robert A

2010-05-21

Many factors including pest natural enemy ratios, starting densities, timings of natural enemy releases, dosages and timings of insecticide applications and instantaneous killing rates of pesticides on both pests and natural enemies can affect the success of IPM control programmes. To address how such factors influence successful pest control, hybrid impulsive pest-natural enemy models with different frequencies of pesticide sprays and natural enemy releases were proposed and analyzed. With releasing both more or less frequent than the sprays, a stability threshold condition for a pest eradication periodic solution is provided. Moreover, the effects of times of spraying pesticides (or releasing natural enemies) and control tactics on the threshold condition were investigated with regard to the extent of depression or resurgence resulting from pulses of pesticide applications. Multiple attractors from which the pest population oscillates with different amplitudes can coexist for a wide range of parameters and the switch-like transitions among these attractors showed that varying dosages and frequencies of insecticide applications and the numbers of natural enemies released are crucial. To see how the pesticide applications could be reduced, we developed a model involving periodic releases of natural enemies with chemical control applied only when the densities of the pest reached the given Economic Threshold. The results indicate that the pest outbreak period or frequency largely depends on the initial densities and the control tactics. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Decoding nitric oxide release rates of amine-based diazeniumdiolates.

PubMed

Wang, Yan-Ni; Collins, Jack; Holland, Ryan J; Keefer, Larry K; Ivanic, Joseph

2013-08-01

Amine-based diazeniumdiolates (NONOates) have garnered widespread use as nitric oxide (NO) donors, and their potential for nitroxyl (HNO) release has more recently been realized. While NO release rates can vary significantly with the type of amine, half-lives of seconds to days under physiological conditions, there is as yet no way to determine a priori the NO or HNO production rates of a given species, and no discernible trends have manifested other than that secondary amines produce only NO (i.e., no HNO). As a step to understanding these complex systems, here we describe a procedure for modeling amine-based NONOates in water solvent that provides an excellent correlation (R(2) = 0.94) between experimentally measured dissociation rates of seven secondary amine species and their computed NO release activation energies. The significant difference in behavior of NONOates in the gas and solvent phases is also rigorously demonstrated via explicit additions of quantum mechanical water molecules. The presented results suggest that the as-yet unsynthesized simplest amine-based NONOate, the diazeniumdiolated ammonia anion [H2N-N(O)═NO(-)], could serve as an unperturbed HNO donor. These results provide a step forward toward the accurate modeling of general NO and/or HNO donors as well as for the identification of tailored prodrug candidates.

Kinetic and theoretical studies of novel biodegradable thermo-sensitive xerogels based on PEG/PVP/silica for sustained release of enrofloxacin

NASA Astrophysics Data System (ADS)

Ebadi, Azra; Rafati, Amir Abbas; Bavafa, Sadeghali; Mohammadi, Masoumah

2017-12-01

This study involves the synthesis of a new silica-based colloidal hybrid system. In this new hybrid system, poly (ethylene glycol) (PEG) and thermo-sensitive amphiphilic biocompatible poly (vinyl pyrrolidone) (PVP) were used to create suitable storage for hydrophobic drugs. The possibility of using variable PVP/PEG molar ratios to modulate drug release rate from silica nanoparticles was a primary goal of the current research. In addition, an investigation of the drug release kinetic was conducted. To achieve this, silica nanoparticles were synthesized in poly (ethylene glycol) (PEG) and poly (vinyl pyrrolidone) (PVP) solution incorporated with enrofloxacin (EFX) (as a model hydrophobic drug), using a simple synthetic strategy of hybrid materials which avoided waste and multi-step processes. The impacts of PVP/PEG molar ratios, temperature, and pH of the release medium on release kinetic were investigated. The physicochemical properties of the drug-loaded composites were studied by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). In vitro drug release studies demonstrated that the drug release rate, which was evaluated by analyzing the experimental data with seven kinetic models in a primarily non-Fickian diffusion-controlled process, aligned well with both Ritger-Peppas and Sahlin-Peppas equations.

Modeling the pharmacokinetics of extended release pharmaceutical systems

NASA Astrophysics Data System (ADS)

di Muria, Michela; Lamberti, Gaetano; Titomanlio, Giuseppe

2009-03-01

The pharmacokinetic (PK) models predict the hematic concentration of drugs after the administration. In compartment modeling, the body is described by a set of interconnected “vessels” or “compartments”; the modeling consisting of transient mass balances. Usually the orally administered drugs were considered as immediately available: this cannot describe the administration of extended-release systems. In this work we added to the traditional compartment models the ability to account for a delay in administration, relating this delay to in vitro data. Firstly, the method was validated, applying the model to the dosage of nicotine by chewing-gum; the model was tuned by in vitro/in vivo data of drugs (divalproex-sodium and diltiazem) with medium-rate release kinetics, then it was applied in describing in vivo evolutions due to the assumption of fast- and slow-release systems. The model reveals itself predictive, the same of a Level A in vitro/in vivo correlation, but being physically based, it is preferable to a purely statistical method.

Assimilation of concentration measurements for retrieving multiple point releases in atmosphere: A least-squares approach to inverse modelling

NASA Astrophysics Data System (ADS)

Singh, Sarvesh Kumar; Rani, Raj

2015-10-01

The study addresses the identification of multiple point sources, emitting the same tracer, from their limited set of merged concentration measurements. The identification, here, refers to the estimation of locations and strengths of a known number of simultaneous point releases. The source-receptor relationship is described in the framework of adjoint modelling by using an analytical Gaussian dispersion model. A least-squares minimization framework, free from an initialization of the release parameters (locations and strengths), is presented to estimate the release parameters. This utilizes the distributed source information observable from the given monitoring design and number of measurements. The technique leads to an exact retrieval of the true release parameters when measurements are noise free and exactly described by the dispersion model. The inversion algorithm is evaluated using the real data from multiple (two, three and four) releases conducted during Fusion Field Trials in September 2007 at Dugway Proving Ground, Utah. The release locations are retrieved, on average, within 25-45 m of the true sources with the distance from retrieved to true source ranging from 0 to 130 m. The release strengths are also estimated within a factor of three to the true release rates. The average deviations in retrieval of source locations are observed relatively large in two release trials in comparison to three and four release trials.

Detailed source term estimation of the atmospheric release for the Fukushima Daiichi Nuclear Power Station accident by coupling simulations of an atmospheric dispersion model with an improved deposition scheme and oceanic dispersion model

NASA Astrophysics Data System (ADS)

Katata, G.; Chino, M.; Kobayashi, T.; Terada, H.; Ota, M.; Nagai, H.; Kajino, M.; Draxler, R.; Hort, M. C.; Malo, A.; Torii, T.; Sanada, Y.

2015-01-01

Temporal variations in the amount of radionuclides released into the atmosphere during the Fukushima Daiichi Nuclear Power Station (FNPS1) accident and their atmospheric and marine dispersion are essential to evaluate the environmental impacts and resultant radiological doses to the public. In this paper, we estimate the detailed atmospheric releases during the accident using a reverse estimation method which calculates the release rates of radionuclides by comparing measurements of air concentration of a radionuclide or its dose rate in the environment with the ones calculated by atmospheric and oceanic transport, dispersion and deposition models. The atmospheric and oceanic models used are WSPEEDI-II (Worldwide version of System for Prediction of Environmental Emergency Dose Information) and SEA-GEARN-FDM (Finite difference oceanic dispersion model), both developed by the authors. A sophisticated deposition scheme, which deals with dry and fog-water depositions, cloud condensation nuclei (CCN) activation, and subsequent wet scavenging due to mixed-phase cloud microphysics (in-cloud scavenging) for radioactive iodine gas (I2 and CH3I) and other particles (CsI, Cs, and Te), was incorporated into WSPEEDI-II to improve the surface deposition calculations. The results revealed that the major releases of radionuclides due to the FNPS1 accident occurred in the following periods during March 2011: the afternoon of 12 March due to the wet venting and hydrogen explosion at Unit 1, midnight of 14 March when the SRV (safety relief valve) was opened three times at Unit 2, the morning and night of 15 March, and the morning of 16 March. According to the simulation results, the highest radioactive contamination areas around FNPS1 were created from 15 to 16 March by complicated interactions among rainfall, plume movements, and the temporal variation of release rates. The simulation by WSPEEDI-II using the new source term reproduced the local and regional patterns of cumulative surface deposition of total 131I and 137Cs and air dose rate obtained by airborne surveys. The new source term was also tested using three atmospheric dispersion models (Modèle Lagrangien de Dispersion de Particules d'ordre zéro: MLDP0, Hybrid Single Particle Lagrangian Integrated Trajectory Model: HYSPLIT, and Met Office's Numerical Atmospheric-dispersion Modelling Environment: NAME) for regional and global calculations, and the calculated results showed good agreement with observed air concentration and surface deposition of 137Cs in eastern Japan.

Controlled release properties of zein-fatty acid blend films for multiple bioactive compounds.

PubMed

Arcan, Iskender; Yemenicioğlu, Ahmet

2014-08-13

To develop edible films having controlled release properties for multiple bioactive compounds, hydrophobicity and morphology of zein films were modified by blending zein with oleic (C18:1)Δ⁹, linoleic (C18:2)Δ(9,12), or lauric (C₁₂) acids in the presence of lecithin. The blend zein films showed 2-8.5- and 1.6-2.9-fold lower initial release rates for the model active compounds, lysozyme (LYS) and (+)-catechin (CAT), than the zein control films, respectively. The change of fatty acid chain length affected both CAT and LYS release rates while the change of fatty acid double bond number affected only the CAT release rate. The film morphologies suggested that the blend films owe their controlled release properties mainly to the microspheres formed within their matrix and encapsulation of active compounds. The blend films showed antilisterial activity and antioxidant activity up to 81 μmol Trolox/cm². The controlled release of multiple bioactive compounds from a single film showed the possibility of combining application of active and bioactive packaging technologies and improving not only safety and quality but also health benefits of packed food.

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.

Swelling kinetics of spray-dried chitosan acetate assessed by magnetic resonance imaging and their relation to drug release kinetics of chitosan matrix tablets.

PubMed

Huanbutta, Kampanart; Sriamornsak, Pornsak; Limmatvapirat, Sontaya; Luangtana-anan, Manee; Yoshihashi, Yasuo; Yonemochi, Etsuo; Terada, Katsuhide; Nunthanid, Jurairat

2011-02-01

Magnetic resonance imaging (MRI) was used to assess in situ swelling behaviors of spray-dried chitosan acetate (CSA) in 0.1N HCl, pH 6.8 and pH 5.0 Tris-HCl buffers. The in vitro drug releases from CSA matrix tablets containing the model drugs, diclofenac sodium and theophylline were investigated in all media using USP-4 apparatus. The effect of chitosan molecular weight, especially in pH 6.8 Tris-HCl, was also studied. In 0.1N HCl, the drug release from the matrix tablets was the lowest in relation to the highest swelling of CSA. The swelling kinetics in Tris-HCl buffers are Fickian diffusion according to their best fit to Higuchi's model as well as the drug release kinetics in all the media. The high swelling rate (k(s)(')) was found to delay the drug release rate (k'). The linear relationship between the swelling and fractions of drug release in Tris-HCl buffers was observed, indicating an important role of the swelling on controlling the drug release mechanism. Additionally, CSA of 200 and 800 kDa chitosan did not swell in pH 6.8 Tris-HCl but disintegrated into fractions, and the drug release from the matrix tablets was the highest. Copyright © 2010 Elsevier B.V. All rights reserved.

Experiments on the high-temperature behaviour of neutron-irradiated uranium dioxide and fission products, volume 8, number 1

NASA Astrophysics Data System (ADS)

Tanke, R. H. J.

The release rate of fission products from overheated UO2, the chemical form of these fission products, and the transport mechanism inside the nuclear fuel are determined. UO spheres of approximately 1 mm diameter, irradiated in a high-flux reactor were used for the experiments. The chemical forms of the particles released from the spheres during evaporation were determined by mass spectrometry and the release rate of the mission products was determined by gamma spectrometry. A gamma topographer was developed to determine the change with temperature in the three dimensional distribution of radioactive fission products in the spheres. No clear relationship between the stoichiometry of the spheres and uranium consumption were shown. A diffusion model was used to determine the activation energy for the diffusion of fission products. It is concluded that the microstructure of the nuclear fuel greatly affects the number of free oxygen atoms, the release rate and the chemical form of the fission products. The evaporation of the UO2 matrix is the main mechanism for the release of all fission products at temperatures above 2300 K. Barium can be as volatile as iodine. Niobium and lanthenum can be volatile. Molecular combinations of the fission products, iodine, cesium and tellurium, are highly unlikely to be present inside the fuel. Barium and nobium may form compounds with oxygen and are then released as simple oxides. Fission products are released from overheated UO2 or as oxides. A new model is proposed for describing the behavior of oxygen in irradiated nuclear fuel.

Development of near zero-order release dosage forms using three-dimensional printing (3-DP) technology.

PubMed

Wang, Chen-Chao; Tejwani Motwani, Monica R; Roach, Willie J; Kay, Jennifer L; Yoo, Jaedeok; Surprenant, Henry L; Monkhouse, Donald C; Pryor, Timothy J

2006-03-01

Three near zero-order controlled-release pseudoephedrine hydrochloride (PEH) formulations demonstrating proportional release rates were developed using 3-Dimensional Printing (3-DP) technology. Mixtures of Kollidon SR and hydroxypropylmethyl cellulose (HPMC) were used as drug carriers. The release rates were adjusted by varying the Kollidon SR-HPMC ratio while keeping fabrication parameters constant. The dosage forms were composed of an immediate release core and a release rate regulating shell, fabricated with an aqueous PEH and an ethanolic triethyl citrate (TEC) binder, respectively. The dosage form design called for the drug to be released via diffusional pathways formed by HPMC in the shell matrix. The release rate was shown to increase correspondingly with the fraction of HPMC contained in the polymer blend. The designed formulations resulted in dosage forms that were insensitive to changes in pH of the dissolution medium, paddle stirring rate, and the presence/absence of a sinker. The near zero-order release properties were unchanged regardless of the dissolution test being performed on either single cubes or on a group of eight cubes encased within a gelatin capsule shell. The chemical and dissolution properties of the three formulations remained unchanged following 1 month's exposure to 25 degrees C/60% RH or 40 degrees C/75% RH environment under open container condition. The in vivo performance of the three formulations was evaluated using a single-dose, randomized, open-label, four-way crossover clinical study composed of 10 fasted healthy volunteers. The pharmacokinetic parameters were analyzed using a noncompartmental model. Qualitative rank order linear correlations between in vivo absorption profiles and in vitro dissolution parameters (with slope and intercept close to unity and origin, respectively) were obtained for all three formulations, indicating good support for a Level A in vivo/in vitro correlation.

TRANSPORT, FATE AND RISK IMPLICATIONS OF ENVIRONMENTALLY ACCEPTABLE ENDPOINT DECISIONS

EPA Science Inventory

The second and third year project goals are the following: Continue to develop and finalize the expected source zone module incorporating slow release and finalize the contaminated soil screening model. Chemical rate of release data will be obtained and used with t...

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.

Exploring virus release as a bottleneck for the spread of influenza A virus infection in vitro and the implications for antiviral therapy with neuraminidase inhibitors

PubMed Central

Kowal, Szymon; Cardenas, Daniel A.; Beauchemin, Catherine A. A.

2017-01-01

Mathematical models (MMs) have been used to study the kinetics of influenza A virus infections under antiviral therapy, and to characterize the efficacy of antivirals such as neuraminidase inhibitors (NAIs). NAIs prevent viral neuraminidase from cleaving sialic acid receptors that bind virus progeny to the surface of infected cells, thereby inhibiting their release, suppressing infection spread. When used to study treatment with NAIs, MMs represent viral release implicitly as part of viral replication. Consequently, NAIs in such MMs do not act specifically and exclusively on virus release. We compared a MM with an explicit representation of viral release (i.e., distinct from virus production) to a simple MM without explicit release, and investigated whether parameter estimation and the estimation of NAI efficacy were affected by the use of a simple MM. Since the release rate of influenza A virus is not well-known, a broad range of release rates were considered. If the virus release rate is greater than ∼0.1 h−1, the simple MM provides accurate estimates of infection parameters, but underestimates NAI efficacy, which could lead to underdosing and the emergence of NAI resistance. In contrast, when release is slower than ∼0.1 h−1, the simple MM accurately estimates NAI efficacy, but it can significantly overestimate the infectious lifespan (i.e., the time a cell remains infectious and producing free virus), and it will significantly underestimate the total virus yield and thus the likelihood of resistance emergence. We discuss the properties of, and a possible lower bound for, the influenza A virus release rate. PMID:28837615

Debond Analyses for Stitched Composite Structures

NASA Technical Reports Server (NTRS)

Glaessgen, E. H.; Raju, I. S.; Poe, C. C., Jr.

1998-01-01

The effect of stitching on mode I and mode II strain energy release rates for debond configurations is studied using an analysis based on plate finite elements and the virtual crack closure technique. The stitches were modeled as discrete nonlinear fastener elements with a compliance determined by experiment. The axial and shear behavior of the stitches was considered with both the compliances and failure loads assumed to be independent. The mode I strain energy release rate, G(sub I), was shown to decrease once the debond had grown beyond the first row of stitches and was reduced to zero for long debonds, however, the mode II strain energy release rate, G(sub II), continued to be of significant magnitude over the range of debond lengths considered.

Photoimages and the release characteristics of lipophilic matrix tablets containing highly water-soluble potassium citrate with high drug loadings.

PubMed

Cao, Qing-Ri; Kim, Tae-Wan; Lee, Beom-Jin

2007-07-18

Two types of the carnauba wax-based lipophilic matrix tablet using spray-dried granules (SDT) or directly compressible powdered mixtures (DCT) were prepared for sustained release. The model drug was a highly water-soluble potassium citrate and loaded about 74% of the total tablet weight. The SDT slowly eroded and disintegrated during the release study without showing sustained release when the hydrophilic excipients were added. In contrast, the DCT was more efficient for sustained release. The release rate decreased with increasing carnauba wax concentration. In particular, the sustained release rate was markedly pronounced when the lipophilic stearyl alcohol and stearic acid were combined with the carnauba wax. The surface of the intact DCT appeared to be smooth and rusty. The DCT rose to the surface from the bottom of the vessel during the release test, and numerous pores and cracks with no signs of disintegration were also observed after the release test. The release profile was dependent on the formulation composition and preparation method of the matrix tablet. Diffusion-controlled leaching through the channels of the pores and cracks of the lipophilic matrix tablet (DCT) is a key to the sustained release.

Modeling and measurement of vesicle pools at the cone ribbon synapse: changes in release probability are solely responsible for voltage-dependent changes in release

PubMed Central

Thoreson, Wallace B.; Van Hook, Matthew J.; Parmelee, Caitlyn; Curto, Carina

2015-01-01

Post-synaptic responses are a product of quantal amplitude (Q), size of the releasable vesicle pool (N), and release probability (P). Voltage-dependent changes in presynaptic Ca2+ entry alter post-synaptic responses primarily by changing P but have also been shown to influence N. With simultaneous whole cell recordings from cone photoreceptors and horizontal cells in tiger salamander retinal slices, we measured N and P at cone ribbon synapses by using a train of depolarizing pulses to stimulate release and deplete the pool. We developed an analytical model that calculates the total pool size contributing to release under different stimulus conditions by taking into account the prior history of release and empirically-determined properties of replenishment. The model provided a formula that calculates vesicle pool size from measurements of the initial post-synaptic response and limiting rate of release evoked by a train of pulses, the fraction of release sites available for replenishment, and the time constant for replenishment. Results of the model showed that weak and strong depolarizing stimuli evoked release with differing probabilities but the same size vesicle pool. Enhancing intraterminal Ca2+ spread by lowering Ca2+ buffering or applying BayK8644 did not increase PSCs evoked with strong test steps showing there is a fixed upper limit to pool size. Together, these results suggest that light-evoked changes in cone membrane potential alter synaptic release solely by changing release probability. PMID:26541100

Modeling and experimental methods to predict oxygen distribution in bone defects following cell transplantation.

PubMed

Heylman, Christopher M; Santoso, Sharon; Krebs, Melissa D; Saidel, Gerald M; Alsberg, Eben; Muschler, George F

2014-04-01

We have developed a mathematical model that allows simulation of oxygen distribution in a bone defect as a tool to explore the likely effects of local changes in cell concentration, defect size or geometry, local oxygen delivery with oxygen-generating biomaterials (OGBs), and changes in the rate of oxygen consumption by cells within a defect. Experimental data for the oxygen release rate from an OGB and the oxygen consumption rate of a transplanted cell population are incorporated into the model. With these data, model simulations allow prediction of spatiotemporal oxygen concentration within a given defect and the sensitivity of oxygen tension to changes in critical variables. This information may help to minimize the number of experiments in animal models that determine the optimal combinations of cells, scaffolds, and OGBs in the design of current and future bone regeneration strategies. Bone marrow-derived nucleated cell data suggest that oxygen consumption is dependent on oxygen concentration. OGB oxygen release is shown to be a time-dependent function that must be measured for accurate simulation. Simulations quantify the dependency of oxygen gradients in an avascular defect on cell concentration, cell oxygen consumption rate, OGB oxygen generation rate, and OGB geometry.

A sequential vesicle pool model with a single release sensor and a Ca(2+)-dependent priming catalyst effectively explains Ca(2+)-dependent properties of neurosecretion.

PubMed

Walter, Alexander M; Pinheiro, Paulo S; Verhage, Matthijs; Sørensen, Jakob B

2013-01-01

Neurotransmitter release depends on the fusion of secretory vesicles with the plasma membrane and the release of their contents. The final fusion step displays higher-order Ca(2+) dependence, but also upstream steps depend on Ca(2+). After deletion of the Ca(2+) sensor for fast release - synaptotagmin-1 - slower Ca(2+)-dependent release components persist. These findings have provoked working models involving parallel releasable vesicle pools (Parallel Pool Models, PPM) driven by alternative Ca(2+) sensors for release, but no slow release sensor acting on a parallel vesicle pool has been identified. We here propose a Sequential Pool Model (SPM), assuming a novel Ca(2+)-dependent action: a Ca(2+)-dependent catalyst that accelerates both forward and reverse priming reactions. While both models account for fast fusion from the Readily-Releasable Pool (RRP) under control of synaptotagmin-1, the origins of slow release differ. In the SPM the slow release component is attributed to the Ca(2+)-dependent refilling of the RRP from a Non-Releasable upstream Pool (NRP), whereas the PPM attributes slow release to a separate slowly-releasable vesicle pool. Using numerical integration we compared model predictions to data from mouse chromaffin cells. Like the PPM, the SPM explains biphasic release, Ca(2+)-dependence and pool sizes in mouse chromaffin cells. In addition, the SPM accounts for the rapid recovery of the fast component after strong stimulation, where the PPM fails. The SPM also predicts the simultaneous changes in release rate and amplitude seen when mutating the SNARE-complex. Finally, it can account for the loss of fast- and the persistence of slow release in the synaptotagmin-1 knockout by assuming that the RRP is depleted, leading to slow and Ca(2+)-dependent fusion from the NRP. We conclude that the elusive 'alternative Ca(2+) sensor' for slow release might be the upstream priming catalyst, and that a sequential model effectively explains Ca(2+)-dependent properties of secretion without assuming parallel pools or sensors.

A Sequential Vesicle Pool Model with a Single Release Sensor and a Ca2+-Dependent Priming Catalyst Effectively Explains Ca2+-Dependent Properties of Neurosecretion

PubMed Central

Walter, Alexander M.; Pinheiro, Paulo S.; Verhage, Matthijs; Sørensen, Jakob B.

2013-01-01

Neurotransmitter release depends on the fusion of secretory vesicles with the plasma membrane and the release of their contents. The final fusion step displays higher-order Ca2+ dependence, but also upstream steps depend on Ca2+. After deletion of the Ca2+ sensor for fast release – synaptotagmin-1 – slower Ca2+-dependent release components persist. These findings have provoked working models involving parallel releasable vesicle pools (Parallel Pool Models, PPM) driven by alternative Ca2+ sensors for release, but no slow release sensor acting on a parallel vesicle pool has been identified. We here propose a Sequential Pool Model (SPM), assuming a novel Ca2+-dependent action: a Ca2+-dependent catalyst that accelerates both forward and reverse priming reactions. While both models account for fast fusion from the Readily-Releasable Pool (RRP) under control of synaptotagmin-1, the origins of slow release differ. In the SPM the slow release component is attributed to the Ca2+-dependent refilling of the RRP from a Non-Releasable upstream Pool (NRP), whereas the PPM attributes slow release to a separate slowly-releasable vesicle pool. Using numerical integration we compared model predictions to data from mouse chromaffin cells. Like the PPM, the SPM explains biphasic release, Ca2+-dependence and pool sizes in mouse chromaffin cells. In addition, the SPM accounts for the rapid recovery of the fast component after strong stimulation, where the PPM fails. The SPM also predicts the simultaneous changes in release rate and amplitude seen when mutating the SNARE-complex. Finally, it can account for the loss of fast- and the persistence of slow release in the synaptotagmin-1 knockout by assuming that the RRP is depleted, leading to slow and Ca2+-dependent fusion from the NRP. We conclude that the elusive ‘alternative Ca2+ sensor’ for slow release might be the upstream priming catalyst, and that a sequential model effectively explains Ca2+-dependent properties of secretion without assuming parallel pools or sensors. PMID:24339761

Synthesis and Characterization of Chlorpyrifos/Copper(II) Schiff Base Mesoporous Silica with pH Sensitivity for Pesticide Sustained Release.

PubMed

Chen, Huayao; Lin, Yueshun; Zhou, Hongjun; Zhou, Xinhua; Gong, Sheng; Xu, Hua

2016-11-02

The salicylaldehyde-modified mesoporous silica (SA-MCM-41) was prepared through a co-condensation method. Through the bridge effect from the copper ion, which also acts as the nutrition of the plant, the model drug chlorpyrifos (CH) was supported on the copper(II) Schiff base mesoporous silica (Cu-MCM-41) to form a highly efficient sustained-release system (CH-Cu-MCM-41) for pesticide delivery. The experimental results showed that the larger the concentration of the copper ion, the more adsorption capacity (AC) of Cu-MCM-41 for chlorpyrifos and the smaller its release rate. The results confirmed the existence of a coordination bond between SA-MCM-41 and copper ions as well as a coordination bond between Cu-MCM-41 and chlorpyrifos. The AC of SA-MCM-41 is 106 mg/g, while that of Cu-MCM-41 is 295 mg/g. The as-synthesized system showed significant pH sensitivity. Under the condition of pH ≤ 7, the release rate of chlorpyrifos decreased with increasing pH, whereas its release rate in weak base conditions was slightly larger than that in weak acid conditions. Meanwhile, the drug release rate of the as-synthesized system was also affected by the temperature. Their sustained-release curves can be described by the Korsmeyer-Peppas equation.

A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis

PubMed Central

Schlesinger, Erica; Johengen, Daniel; Luecke, Ellen; Rothrock, Ginger; McGowan, Ian; van der Straten, Ariane; Desai, Tejal

2016-01-01

Purpose The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by long acting drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP. Methods A thin-film polycaprolactone (PCL) membrane controls drug release from a reservoir. To achieve membrane controlled release, TAF requires a formulation excipient such as PEG300 to increase the dissolution rate and reservoir solubility. Short-term In vitro release studies are used to develop an empirical design model, which is applied to the production of in vitro prototype devices demonstrating up to 90-days of linear release and TAF chemical stability. Results The size and shape of the TFPD are tunable, achieving release rates ranging from 0.5–4.4 mg/day in devices no larger than a contraceptive implant. Based on published data for oral TAF, subcutaneous constant-rate release for HIV PrEP is estimated at < 2.8mg/day. Prototype devices demonstrated linear release at 1.2mg/day for up to 90 days and at 2.2mg/day for up to 60 days. Conclusions We present a biodegradable TFPD for subcutaneous delivery of TAF for HIV PrEP. The size, shape and release rate of the device are tunable over a > 8-fold range. PMID:26975357

Release modeling and comparison of nanoarchaeosomal, nanoliposomal and pegylated nanoliposomal carriers for paclitaxel.

PubMed

Movahedi, Fatemeh; Ebrahimi Shahmabadi, Hasan; Alavi, Seyed Ebrahim; Koohi Moftakhari Esfahani, Maedeh

2014-09-01

Breast cancer is the most prevalent cancer among women. Recently, delivering by nanocarriers has resulted in a remarkable evolution in treatment of numerous cancers. Lipid nanocarriers are important ones while liposomes and archaeosomes are common lipid nanocarriers. In this work, paclitaxel was used and characterized in nanoliposomal and nanoarchaeosomal form to improve efficiency. To increase stability, efficiency and solubility, polyethylene glycol 2000 (PEG 2000) was added to some samples. MTT assay confirmed effectiveness of nanocarriers on MCF-7 cell line and size measuring validated nano-scale of particles. Nanoarchaeosomal carriers demonstrated highest encapsulation efficiency and lowest release rate. On the other hand, pegylated nanoliposomal carrier showed higher loading efficiency and less release compared with nanoliposomal carrier which verifies effect of PEG on improvement of stability and efficiency. Additionally, release pattern was modeled using artificial neural network (ANN) and genetic algorithm (GA). Using ANN modeling for release prediction, resulted in R values of 0.976, 0.989 and 0.999 for nanoliposomal, pegylated nanoliposomal and nanoarchaeosomal paclitaxel and GA modeling led to values of 0.954, 0.951 and 0.976, respectively. ANN modeling was more successful in predicting release compared with the GA strategy.

Formulation and in-vitro evaluation of directly compressed controlled release matrices of Losartan Potassium using Ethocel Grade 100 as rate retarding agent.

PubMed

Khan, Kamran Ahmad; Khan, Gul Majid; Zeeshan Danish, Muhammad; Akhlaq; Khan, Haroon; Rehman, Fazal; Mehsud, Saifullah

2015-12-30

Current study was aimed to develop 200mg controlled release matrix tablets of Losartan Potassium using Ethocel 100 Premium and Ethocel 100 FP Premium as rate controlling polymer. In-vitro studies were performed according to USP Method-I in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature of the dissolution medium was kept constant at 37±0.5°C at 100rpm. Flow properties, physical quality control tests, effect of polymer size and drug-to-polymers ratios were studied using different kinetics models such as 1st-order, zero-order, Hixon Crowell model, Highuchi model and Power law. Difference factor f1 and similarity factor f2 were applied for dissolution profiles against Cardaktin® tablets used as a reference formulation. The matrices with polymer ethocel 100 FP Premiums have prolonged the drug release rate as compared to polymer ethocel 100 Premiums. The n values matrices with polymer ethocel grade 100 ranged from 0.603 to 0.857 indicating that the drug release occurred by anomalous non fickian diffusion kinetics while then value of reference Cardaktin® tablet was measured as 0.125 indicating that these tablets do not follow power law. The dissolution profiles of test formulations were different than that of reference Cardaktin®. This suggests the polymer Ethocel grade 100 can be proficiently incorporated in fabrication and development of once a day controlled release matrix tablets. Copyright © 2015. Published by Elsevier B.V.

Solid dispersion of acetaminophen and poly(ethylene oxide) prepared by hot-melt mixing.

PubMed

Yang, Min; Wang, Peng; Huang, Chien-Yueh; Ku, M Sherry; Liu, Huiju; Gogos, Costas

2010-08-16

In this study, a model drug, acetaminophen (APAP), was melt mixed with poly(ethylene oxide) (PEO) using a Brabender mixer. APAP was found to recrystallize upon cooling to room temperature for all the drug loadings investigated. Higher drug loading leads to faster recrystallization rate. However, the morphology of the recrystallized drug crystals is identical in samples with different drug loadings and does not change with the storage time. To adjust the drug's dissolution rate, nanoclay Cloisite 15A and 30B were added into the binary mixture. The presence of either of the nanoclay dramatically accelerates the drug's recrystallization rate and slows down the drug's releasing rate. The drop of the releasing rate is mainly due to the decrease of wettability, as supported by the contact angle data. Data analysis of the dissolution results suggests that the addition of nanoclays changes the drug's release mechanism from erosion dominant to diffusion dominant. This study suggests that nanoclays may be utilized to tailor the drug's releasing rate and to improve the dosage form's stability by dramatically shortening the lengthy recrystallization process. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Humoral regulation of heart rate during digestion in pythons (Python molurus and Python regius).

PubMed

Enok, Sanne; Simonsen, Lasse Stærdal; Pedersen, Signe Vesterskov; Wang, Tobias; Skovgaard, Nini

2012-05-15

Pythons exhibit a doubling of heart rate when metabolism increases several times during digestion. Pythons, therefore, represent a promising model organism to study autonomic cardiovascular regulation during the postprandial state, and previous studies show that the postprandial tachycardia is governed by a release of vagal tone as well as a pronounced stimulation from nonadrenergic, noncholinergic (NANC) factors. Here we show that infusion of plasma from digesting donor pythons elicit a marked tachycardia in fasting snakes, demonstrating that the NANC factor resides in the blood. Injections of the gastrin and cholecystokinin receptor antagonist proglumide had no effect on double-blocked heart rate or blood pressure. Histamine has been recognized as a NANC factor in the early postprandial period in pythons, but the mechanism of its release has not been identified. Mast cells represent the largest repository of histamine in vertebrates, and it has been speculated that mast cells release histamine during digestion. Treatment with the mast cell stabilizer cromolyn significantly reduced postprandial heart rate in pythons compared with an untreated group but did not affect double-blocked heart rate. While this study indicates that histamine induces postprandial tachycardia in pythons, its release during digestion is not stimulated by gastrin or cholecystokinin nor is its release from mast cells a stimulant of postprandial tachycardia.

Rates of zinc and trace metal release from dissolving sphalerite at pH 2.0-4.0

USGS Publications Warehouse

Stanton, M.R.; Gemery-Hill, P. A.; Shanks, Wayne C.; Taylor, C.D.

2008-01-01

High-Fe and low-Fe sphalerite samples were reacted under controlled pH conditions to determine nonoxidative rates of release of Zn and trace metals from the solid-phase. The release (solubilization) of trace metals from dissolving sphalerite to the aqueous phase can be characterized by a kinetic distribution coefficient, (Dtr), which is defined as [(Rtr/X(tr)Sph)/(RZn/X(Zn) Sph)], where R is the trace metal or Zn release rate, and X is the mole fraction of the trace metal or Zn in sphalerite. This coefficient describes the relationship of the sphalerite dissolution rate to the trace metal mole fraction in the solid and its aqueous concentration. The distribution was used to determine some controls on metal release during the dissolution of sphalerite. Departures from the ideal Dtr of 1.0 suggest that some trace metals may be released via different pathways or that other processes (e.g., adsorption, solubility of trace minerals such as galena) affect the observed concentration of metals. Nonoxidative sphalerite dissolution (mediated by H+) is characterized by a "fast" stage in the first 24-30 h, followed by a "slow" stage for the remainder of the reaction. Over the pH range 2.0-4.0, and for similar extent of reaction (reaction time), sphalerite composition, and surface area, the rates of release of Zn, Fe, Cd, Cu, Mn and Pb from sphalerite generally increase with lower pH. Zinc and Fe exhibit the fastest rates of release, Mn and Pb have intermediate rates of release, and Cd and Cu show the slowest rates of release. The largest variations in metal release rates occur at pH 2.0. At pH 3.0 and 4.0, release rates show less variation and appear less dependent on the metal abundance in the solid. For the same extent of reaction (100 h), rates of Zn release range from 1.53 ?? 10-11 to 5.72 ?? 10-10 mol/m2/s; for Fe, the range is from 4.59 ?? 10-13 to 1.99 ?? 10-10 mol/m2/s. Trace metal release rates are generally 1-5 orders of magnitude slower than the Zn or Fe rates. Results indicate that the distributions of Fe and Cd are directly related to the rate of sphalerite dissolution throughout the reaction at pH 3.0 and 4.0 because these two elements substitute readily into sphalerite. These two metals are likely to be more amenable to usage in predictive acid dissolution models because of this behavior. The Pb distribution shows no strong relation to sphalerite dissolution and appears to be controlled by pH-dependent solubility, most likely related to trace amounts of galena. The distribution of Cu is similar to that of Fe but is the most-dependent of all metals on its mole fraction ratio (Zn:Cu) in sphalerite. The Mn distributions suggest an increase in the rate of Mn release relative to sphalerite dissolution occurs in low Mn samples as pH increases. The Mn distribution in high Mn samples is nearly independent of pH and sphalerite dissolution at pH 2.0 but shows a dependence on these two parameters at higher pH (3.0-4.0).

The role of a detailed aqueous phase source release model in the LANL area G performance assessment

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

Vold, E.L.; Shuman, R.; Hollis, D.K.

1995-12-31

A preliminary draft of the Performance Assessment for the Los Alamos National Laboratory (LANL) low-level radioactive waste disposal facility at Area G is currently being completed as required by Department of Energy orders. A detailed review of the inventory data base records and the existing models for source release led to the development of a new modeling capability to describe the liquid phase transport from the waste package volumes. Nuclide quantities are sorted down to four waste package release categories for modeling: rapid release, soil, concrete/sludge, and corrosion. Geochemistry for the waste packages was evaluated in terms of the equilibriummore » coefficients, Kds, and elemental solubility limits, Csl, interpolated from the literature. Percolation calculations for the base case closure cover show a highly skewed distribution with an average of 4 mm/yr percolation from the disposal unit bottom. The waste release model is based on a compartment representation of the package efflux, and depends on package size, percolation rate or Darcy flux, retardation coefficient, and moisture content.« less

A vacuum microgripping tool with integrated vibration releasing capability

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

Rong, Weibin; Fan, Zenghua, E-mail: zenghua-fan@163.com; Wang, Lefeng

2014-08-01

Pick-and-place of micro-objects is a basic task in various micromanipulation demands. Reliable releasing of micro-objects is usually disturbed due to strong scale effects. This paper focuses on a vacuum micro-gripper with vibration releasing functionality, which was designed and assembled for reliable micromanipulation tasks. Accordingly, a vibration releasing strategy of implementing a piezoelectric actuator on the vacuum microgripping tool is presented to address the releasing problem. The releasing mechanism was illustrated using a dynamic micro contact model. This model was developed via theoretical analysis, simulations and pull-off force measurement using atomic force microscopy. Micromanipulation experiments were conducted to verify the performancemore » of the vacuum micro-gripper. The results show that, with the assistance of the vibration releasing, the vacuum microgripping tool can achieve reliable release of micro-objects. A releasing location accuracy of 4.5±0.5 μm and a successful releasing rate of around 100% (which is based on 110 trials) were achieved for manipulating polystyrene microspheres with radius of 35–100 μm.« less

Investigating the role of ion-pair strategy in regulating nicotine release from patch: Mechanistic insights based on intermolecular interaction and mobility of pressure sensitive adhesive.

PubMed

Li, Qiaoyun; Wan, Xiaocao; Liu, Chao; Fang, Liang

2018-07-01

The aim of this study was to prepare a drug-in-adhesive patch of nicotine (NIC) and use ion-pair strategy to regulate drug delivery rate. Moreover, the mechanism of how ion-pair strategy regulated drug release was elucidated at molecular level. Formulation factors including pressure sensitive adhesives (PSAs), drug loading and counter ions (C 4 , C 6 , C 8 , C 10 , and C 12 ) were screened. In vitro release experiment and in vitro transdermal experiment were conducted to determine the rate-limiting step in drug delivery process. FT-IR and molecular modeling were used to characterize the interaction between drug and PSA. Thermal analysis and rheology study were conducted to investigate the mobility variation of PSA. The optimized patch prepared with NIC-C 8 had the transdermal profile fairly close to that of the commercial product (p > 0.05). The release rate constants (k) of NIC, NIC-C 4 and NIC-C 10 were 21.1, 14.4 and 32.4, respectively. Different release rates of NIC ion-pair complexes were attributed to the dual effect of ion-pair strategy on drug release. On one hand, ion-pair strategy enhanced the interaction between drug and PSA, which inhibited drug release. On the other hand, using ion-pair strategy improved the mobility of PSA, which facilitated drug release. Drug release behavior was determined by combined effect of two aspects above. These conclusions provided a new idea for us to regulate drug release behavior from patch. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of drug particle size in ultrasound compacted tablets. Continuum percolation model approach.

PubMed

Millán, Mónica; Caraballo, Isidoro

2006-03-09

The main objective of this work is to study the influence of the drug particle size on the pharmaceutical availability of ultrasound compacted tablets. Inert matrix systems containing different drug particle sizes were prepared using both, an ultrasound-assisted press and a traditional eccentric machine. Potassium chloride was used as drug model and Eudragit RS-PM as matrix forming excipient. The excipient particle size was kept constant. The cross-sectional microphotographs of ultrasound tablets show the existence of a quasi-continuum medium. Keeping constant the drug load, US-tablets showed very similar release rates, whereas for traditional tablets, an increase in the particle size resulted in a clear decrease in the release rate. In these tablets, the excipient forms an almost continuum medium. In an infinite theoretical system of these characteristics, the size of the drug particles will not modify the percolation threshold. The percolation of the excipient in this system can be assimilated to a continuum percolation model. In accordance with the proposed model, a lower influence of the drug particle size on the drug release rate was obtained for the US-tablets in comparison with traditional tablets. This fact can be indicative of the similarity of the drug percolation thresholds in these systems.

The Use of a Mesoscale Climate Model to Validate the Nocturnal Carbon Flux over a Forested Site

NASA Astrophysics Data System (ADS)

Werth, D.; Parker, M.; Kurzeja, R.; Leclerc, M.; Watson, T.

2007-12-01

The Savannah River National Laboratory is initiating a comprehensive carbon dioxide monitoring and modeling program in collaboration with the University of Georgia and the Brookhaven National Laboratory. One of the primary goals is to study the dynamics of carbon dioxide in the stable nocturnal boundary layer (NBL) over a forested area of the Savannah River Site in southwest South Carolina. In the nocturnal boundary layer (NBL), eddy flux correlation is less effective in determining the release of CO2 due to respiration. Theoretically, however, the flux can be inferred by measuring the build up of CO2 in the stable layer throughout the night. This method of monitoring the flux will be validated and studied in more detail with both observations and the results of a high-resolution regional climate model. The experiment will involve two phases. First, an artificial tracer will be released into the forest boundary layer and observed through an array of sensors and at a flux tower. The event will be simulated with the RAMS climate model run at very high resolution. Ideally, the tracer will remain trapped within the stable layer and accumulate at rates which will allow us to infer the release rate, and this should compare well to the actual release rate. If an unknown mechanism allows the tracer to escape, the model simulation would be used to reveal it. In the second phase, carbon fluxes will be measured overnight through accumulation in the overlying layer. The RAMS model will be coupled with the SiB carbon model to simulate the nocturnal cycle of carbon dynamics, and this will be compared to the data collected during the night. As with the tracer study, the NBL method of flux measurement will be validated against the model. The RAMS-SiB coupled model has been run over the SRS at high-resolution to simulate the NBL, and results from simulations of both phases of the project will be presented.

Quantification of methane fluxes from industrial sites using a combination of a tracer release method and a Gaussian model

NASA Astrophysics Data System (ADS)

Ars, S.; Broquet, G.; Yver-Kwok, C.; Wu, L.; Bousquet, P.; Roustan, Y.

2015-12-01

Greenhouse gas (GHG) concentrations keep on increasing in the atmosphere since industrial revolution. Methane (CH4) is the second most important anthropogenic GHG after carbon dioxide (CO2). Its sources and sinks are nowadays well identified however their relative contributions remain uncertain. The industries and the waste treatment emit an important part of the anthropogenic methane that is difficult to quantify because the sources are fugitive and discontinuous. A better estimation of methane emissions could help industries to adapt their mitigation's politic and encourage them to install methane recovery systems in order to reduce their emissions while saving money. Different methods exist to quantify methane emissions. Among them is the tracer release method consisting in releasing a tracer gas near the methane source at a well-known rate and measuring both their concentrations in the emission plume. The methane rate is calculated using the ratio of methane and tracer concentrations and the emission rate of the tracer. A good estimation of the methane emissions requires a good differentiation between the methane actually emitted by the site and the methane from the background concentration level, but also a good knowledge of the sources distribution over the site. For this purpose, a Gaussian plume model is used in addition to the tracer release method to assess the emission rates calculated. In a first step, the data obtained for the tracer during a field campaign are used to tune the model. Different model's parameterizations have been tested to find the best representation of the atmospheric dispersion conditions. Once these parameters are set, methane emissions are estimated thanks to the methane concentrations measured and a Bayesian inversion. This enables to adjust the position and the emission rate of the different methane sources of the site and remove the methane background concentration.

A novel approach to multihazard modeling and simulation.

PubMed

Smith, Silas W; Portelli, Ian; Narzisi, Giuseppe; Nelson, Lewis S; Menges, Fabian; Rekow, E Dianne; Mincer, Joshua S; Mishra, Bhubaneswar; Goldfrank, Lewis R

2009-06-01

To develop and apply a novel modeling approach to support medical and public health disaster planning and response using a sarin release scenario in a metropolitan environment. An agent-based disaster simulation model was developed incorporating the principles of dose response, surge response, and psychosocial characteristics superimposed on topographically accurate geographic information system architecture. The modeling scenarios involved passive and active releases of sarin in multiple transportation hubs in a metropolitan city. Parameters evaluated included emergency medical services, hospital surge capacity (including implementation of disaster plan), and behavioral and psychosocial characteristics of the victims. In passive sarin release scenarios of 5 to 15 L, mortality increased nonlinearly from 0.13% to 8.69%, reaching 55.4% with active dispersion, reflecting higher initial doses. Cumulative mortality rates from releases in 1 to 3 major transportation hubs similarly increased nonlinearly as a function of dose and systemic stress. The increase in mortality rate was most pronounced in the 80% to 100% emergency department occupancy range, analogous to the previously observed queuing phenomenon. Effective implementation of hospital disaster plans decreased mortality and injury severity. Decreasing ambulance response time and increasing available responding units reduced mortality among potentially salvageable patients. Adverse psychosocial characteristics (excess worry and low compliance) increased demands on health care resources. Transfer to alternative urban sites was possible. An agent-based modeling approach provides a mechanism to assess complex individual and systemwide effects in rare events.

Electrospun Polymer Blend Nanofibers for Tunable Drug Delivery: The Role of Transformative Phase Separation on Controlling the Release Rate.

PubMed

Tipduangta, Pratchaya; Belton, Peter; Fábián, László; Wang, Li Ying; Tang, Huiru; Eddleston, Mark; Qi, Sheng

2016-01-04

Electrospun fibrous materials have a wide range of biomedical applications, many of them involving the use of polymers as matrices for incorporation of therapeutic agents. The use of polymer blends improves the tuneability of the physicochemical and mechanical properties of the drug loaded fibers. This also benefits the development of controlled drug release formulations, for which the release rate can be modified by altering the ratio of the polymers in the blend. However, to realize these benefits, a clear understanding of the phase behavior of the processed polymer blend is essential. This study reports an in depth investigation of the impact of the electrospinning process on the phase separation of a model partially miscible polymer blend, PVP K90 and HPMCAS, in comparison to other conventional solvent evaporation based processes including film casting and spin coating. The nanoscale stretching and ultrafast solvent removal of electrospinning lead to an enhanced apparent miscibility between the polymers, with the same blends showing micronscale phase separation when processed using film casting and spin coating. Nanoscale phase separation in electrospun blend fibers was confirmed in the dry state. Rapid, layered, macroscale phase separation of the two polymers occurred during the wetting of the fibers. This led to a biphasic drug release profile from the fibers, with a burst release from PVP-rich phases and a slower, more continuous release from HPMCAS-rich phases. It was noted that the model drug, paracetamol, had more favorable partitioning into the PVP-rich phase, which is likely to be a result of greater hydrogen bonding between PVP and paracetamol. This led to higher drug contents in the PVP-rich phases than the HPMCAS-rich phases. By alternating the proportions of the PVP and HPMCAS, the drug release rate can be modulated.

A method to quantify at late imaging a release rate of 18F-FDG in tissues.

PubMed

Laffon, Eric; Allard, Michèle; Marthan, Roger; Ducassou, Dominique

2005-08-01

This theoretical work shows that the rate constant for the (18)F-FDG release in tissues can be assessed without needing any arterial blood sampling. The method requires that the clearance of (18)F-FDG from plasma has occurred, whereas (18)F-FDG is still present in the tissue. This condition can be met dating from 3 h after (18)F-FDG injection, when hydration and/or phlorizin injection are applied after the routine static acquisition. The release rate constant can be obtained from a graphical analysis performed at the later decreasing phase of the tissue tracer activity. A two-compartment and a three-compartment model are developed, both in accordance with one another. To cite this article: E. Laffon et al., C. R. Biologies 328 (2005).

Conductive polymer nanotube patch for fast and controlled ex vivo transdermal drug delivery.

PubMed

Nguyen, Thao M; Lee, Sebin; Lee, Sang Bok

2014-10-01

To uptake and release hydrophilic model drugs and insulin in a novel conductive polymer (CP) nanotube transdermal patch. The externally controlled transdermal delivery of model drugs and insulin were tested ex vivo and results were compared with CP films. The unique intrinsic properties of CPs provide electrostatic interaction between the model drugs and polymer backbone. When a pulsed potential was applied, the drug delivery release profile mimics that of injection delivery. With a constant potential applied, the release rate constants of the patch system were up to three-times faster than the control (0 V) and released approximately 80% more drug molecules over 24 h. The CP nanotube transdermal patch represents a new and promising drug method, specifically for hydrophilic molecules, which have been a large obstacle for conventional transdermal drug delivery systems.

Models to describe the thermal development rates of Cycloneda sanguinea L. (Coleoptera: Coccinelidae).

PubMed

Pachú, Jéssica Ks; Malaquias, José B; Godoy, Wesley Ac; de S Ramalho, Francisco; Almeida, Bruna R; Rossi, Fabrício

2018-04-01

Precise estimates of the lower (T min ) and higher (T max ) thermal thresholds as well as the temperature range that provides optimum performance (T opt ) enable to obtain the desired number of individuals in conservation systems, rearing and release of natural enemies. In this study, the relationship between the development rates of Cycloneda sanguinea L. (Coleoptera: Coccinelidae) and temperature was described using non-linear models developed by Analytis, Brière, Lactin, Lamb, Logan and Sharpe & DeMichele. There were differences between the models, considering the estimates of the parameters T min , T max , and T opt . All of the tested models were able to describe non-linear responses involving the development rates of C. sanguinea at constant temperatures. Lactin and Lamb gave the highest z weight for egg, while Analytis, Sharpe & DeMichele and Brière gave the highest values for larvae and pupae. The more realistic T opt estimated by the models varied from 29° to 31°C for egg, 27-28 °C for larvae and 28-29 °C for pupae. The Logan, Lactin and Analytis models estimated the T max for egg, larvae and pupae to be approximately 34 °C, while the T min estimated by the Analytis model was 16 °C for larvae and pupae. The information generated by our research will contribute towards improving the rearing and release of C. sanguinea in biological control programs, accurately controlling the rate of development in laboratory conditions or even scheduling the most favourable this species' release. Copyright © 2018 Elsevier Ltd. All rights reserved.

Atmospheric modeling of Mars CH4 subsurface clathrates releases mimicking SAM and 2003 Earth-based detections

NASA Astrophysics Data System (ADS)

Pla-García, J.; Rafkin, S. C.

2017-12-01

The aim of this work is to establish the amount of mixing during all martian seasons to test whether CH4 releases inside or outside of Gale crater are consistent with MSL-SAM observations. Several modeling scenarios were configured, including instantaneous and steady releases, both inside and outside the crater. A simulation to mimic the 2003 Earth-based detections (Mumma et al. 2009 or M09) was also performed. In the instantaneous release inside Gale experiments, Ls270 was shown to be the faster mixing season when air within and outside the crater was well mixed: all tracer mass inside the crater is diluted after just 8 hours. The mixing of near surface crater air with the external environment in the rest of the year is potentially rapid but slower than Ls270.In the instantaneous release outside Gale (NW) experiment, in just 12 hours the CH4 that makes it to the MSL landing location is diluted by six orders of magnitude. The timescale of mixing in MRAMS experiments is on the order of 1 sol regardless of season. The duration of the CH4 peak observed by SAM is 100 sols. Therefore there is a steady release inside the crater, or there is a very large magnitude steady release outside the crater. In the steady release Gale experiments, CH4 flux rate from ground is 1.8 kg m-2 s-1 (derived from Gloesener et al. 2017 clathrates fluxes) and it is not predictive. In these experiments, 200 times lower CH4 values detected by SAM are modeled around MSL location. There are CH4 concentration variations of orders of magnitude depending on the hour, so timing of SAM measurements is important. With a larger (but further away) outside crater release area compared to inside, similar CH4 values around MSL are modeled, so distance to source is important. In the steady experiments mimicking M09 detection release area, only 12 times lower CH4 values detected by SAM are modeled around MSL. The highest value in the M09 modeled scenario (0.6 ppbv) is reached in Ls270. This value is the highest of all modeled experiments. With our initial conditions (flux rates, release area size and distance to MSL), SAM should not be able (or very difficult) to detect CH4, but if we multiply flux by 12, increase the release area or move it closer to MSL (or all of above), it may be possible to get CH4 values that SAM could detect regardless where it comes from: inside, outside (close to) or far away from Gale.

Kinetic Release of Alkalinity from Particle-Containing Oil-in-Water Emulsions

NASA Astrophysics Data System (ADS)

Muller, K.; Chapra, S. C.; Ramsburg, A.

2014-12-01

Oil-in-water emulsions are typically employed during remediation to promote biotic reduction of contaminants. Emulsions, however, hold promise for encapsulated delivery of many types of active ingredients required for successful site remediation or long-term site stewardship. Our research is currently focused on using alkalinity-containing particles held within oil-in-water emulsions to sustain control of subsurface pH. Here we describe results from laboratory experiments and mathematical modeling conducted to quantify the kinetics associated with the emulsion delivery and alkalinity release process. Kinetically stable oil-in-water emulsions containing (~60 nmCaCO3 or ~100 nm MgO particles) were previously developed using soybean oil and Gum Arabic as a stabilizing agent. Batch and column experiments were employed to assess the accessibility and release of the alkalinity from the emulsion. Successive additions of HCl were used in batch systems to produce several pH responses (pH rebounds) that were subsequently modeled to elucidate release mechanisms and rates for varying emulsion compositions and particle types. Initial results suggest that a linear-driving-force model is generally able to capture the release behavior in the batch system when the temporally-constant, lumped mass-transfer coefficient is scaled by the fraction of particle mass remaining within the droplets. This result suggests that the rate limiting step in the release process may be the interphase transfer of reactive species at the oil-water interface. 1-d column experiments were also completed in order to quantify the extent and rate of alkalinity release from emulsion droplets retained in a sandy medium. Alkalinity release from the retained droplets treated a pH 4 influent water for 25-60 pore volumes (the duration depended on particle type and mass loading), and the cessation in treatment corresponded to exhaustion of the particle mass held within the oil. Column experiments were simulated using a transport code containing the linear-driving-force expression evaluated in the batch experiments. In these simulations the lumped mass transfer coefficient was fit and compared with values predicted using existing correlations for liquid-liquid and solid-liquid interfaces in porous media.

Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

PubMed Central

Hafeman, Andrea E.; Li, Bing; Yoshii, Toshitaka; Zienkiewicz, Katarzyna; Davidson, Jeffrey M.; Guelcher, Scott A.

2013-01-01

Purpose The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering. Methods Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured. Results Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter. Conclusions Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering. PMID:18516665

Testing and Life Prediction for Composite Rotor Hub Flexbeams

NASA Technical Reports Server (NTRS)

Murri, Gretchen B.

2004-01-01

A summary of several studies of delamination in tapered composite laminates with internal ply-drops is presented. Initial studies used 2D FE models to calculate interlaminar stresses at the ply-ending locations in linear tapered laminates under tension loading. Strain energy release rates for delamination in these laminates indicated that delamination would likely start at the juncture of the tapered and thin regions and grow unstably in both directions. Tests of glass/epoxy and graphite/epoxy linear tapered laminates under axial tension delaminated as predicted. Nonlinear tapered specimens were cut from a full-size helicopter rotor hub and were tested under combined constant axial tension and cyclic transverse bending loading to simulate the loading experienced by a rotorhub flexbeam in flight. For all the tested specimens, delamination began at the tip of the outermost dropped ply group and grew first toward the tapered region. A 2D FE model was created that duplicated the test flexbeam layup, geometry, and loading. Surface strains calculated by the model agreed very closely with the measured surface strains in the specimens. The delamination patterns observed in the tests were simulated in the model by releasing pairs of MPCs along those interfaces. Strain energy release rates associated with the delamination growth were calculated for several configurations and using two different FE analysis codes. Calculations from the codes agreed very closely. The strain energy release rate results were used with material characterization data to predict fatigue delamination onset lives for nonlinear tapered flexbeams with two different ply-dropping schemes. The predicted curves agreed well with the test data for each case studied.

Development of theophylline sustained release dosage form based on Kollidon SR.

PubMed

Reza, Md Selim; Quadir, Mohiuddin Abdul; Haider, Syed Shabbir

2002-01-01

Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Four matrix tablet formulations were prepared by dry blending and direct compression of Kollidon SR and HPMC-15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage of theophylline. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release with an initial burst effect. Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug with subsequent minimization of burst effect as confirmed by mean dissolution time, T50 and Higuchi release rate data. Among the batches containing HPMC-15 cps, a direct relationship was obtained between release rate and the percentage of HPMC used. A suitable controlled release profile was obtained with the matrix tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed close resemblance to commercial products and compliance with USP specification. The results were explored and explained by the difference of physico-chemical property and hydration characteristics of the polymers. In addition to this result, the exponential model was applied to characterize the drug release behaviour from polymeric systems. It was found that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an important role in the release of drug from HPMC containing tablets with a trend towards zero-order or case II release. In vitro release profile of two commercial brands were also undertaken for comparison and modulation of the experimental batches.

Intestinal Targeting of Ganciclovir Release Employing a Novel HEC-PAA Blended Lyomatrix.

PubMed

Mabrouk, Mostafa; Mulla, Jameel A S; Kumar, Pradeep; Chejara, Dharmesh R; Badhe, Ravindra V; Choonara, Yahya E; du Toit, Lisa C; Pillay, Viness

2016-10-01

A hydroxyethylcellulose-poly(acrylic acid) (HEC-PAA) lyomatrix was developed for ganciclovir (GCV) intestine targeting to overcome its undesirable degradation in the stomach. GCV was encapsulated within the HEC-PAA lyomatrix prepared by lyophilization. Conventional tablets were also prepared with identical GCV concentrations in order to compare the GCV release behavior from the lyomatrix and tablets. GCV incorporation (75.12%) was confirmed using FTIR, DSC, and TGA. The effect of GCV loading on the microstructure properties of the lyomatrix was evaluated by SEM, AFM, and BET surface area measurements. The in vitro drug release study showed steady and rapid release profiles from the GCV-loaded lyomatrix compared with the tablet formulation at identical pH values. Minimum GCV release was observed at acidic pH (≤40%) and maximum release occurred at intestinal pH values (≥90%) proving the intestinal targeting ability of the lyomatrix. Kinetic modeling revealed that the GCV-loaded lyomatrix exhibited zero-order release kinetics (n = 1), while the tablets were best described via the Peppas model. Textural analysis highlighted enhanced matrix resilience and rigidity gradient (12.5%, 20 Pa) for the GCV-loaded lyomatrix compared to the pure (7%, 9.5 Pa) HEC-PAA lyomatrix. Bench-top MRI imaging was used to confirm the mechanism of GCV release behavior by monitoring the swelling and erosion rates. The swelling and erosion rate of the tablets was not sufficient to achieve rapid zero-order GCV release as with the lyomatrix. These combined results suggest that the HEC-PAA lyomatrix may be suitable for GCV intestinal targeting after oral administration.

Implications of nonrandom seed abscission and global stilling for migration of wind-dispersed plant species.

PubMed

Thompson, Sally E; Katul, Gabriel G

2013-06-01

Migration of plant populations is a potential survival response to climate change that depends critically on seed dispersal. Biological and physical factors determine dispersal and migration of wind-dispersed species. Recent field and wind tunnel studies demonstrate biological adaptations that bias seed release toward conditions of higher wind velocity, promoting longer dispersal distances and faster migration. However, another suite of international studies also recently highlighted a global decrease in near-surface wind speeds, or 'global stilling'. This study assessed the implications of both factors on potential plant population migration rates, using a mechanistic modeling framework. Nonrandom abscission was investigated using models of three seed release mechanisms: (i) a simple drag model; (ii) a seed deflection model; and (iii) a 'wear and tear' model. The models generated a single functional relationship between the frequency of seed release and statistics of the near-surface wind environment, independent of the abscission mechanism. An Inertial-Particle, Coupled Eulerian-Lagrangian Closure model (IP-CELC) was used to investigate abscission effects on seed dispersal kernels and plant population migration rates under contemporary and potential future wind conditions (based on reported global stilling trends). The results confirm that nonrandom seed abscission increased dispersal distances, particularly for light seeds. The increases were mitigated by two physical feedbacks: (i) although nonrandom abscission increased the initial acceleration of seeds from rest, the sensitivity of the seed dispersal to this initial condition declined as the wind speed increased; and (ii) while nonrandom abscission increased the mean dispersal length, it reduced the kurtosis of seasonal dispersal kernels, and thus the chance of long-distance dispersal. Wind stilling greatly reduced the modeled migration rates under biased seed release conditions. Thus, species that require high wind velocities for seed abscission could experience threshold-like reductions in dispersal and migration potential if near-surface wind speeds continue to decline. © 2013 Blackwell Publishing Ltd.

Inverse modelling of radionuclide release rates using gamma dose rate observations

NASA Astrophysics Data System (ADS)

Hamburger, Thomas; Stohl, Andreas; von Haustein, Christoph; Thummerer, Severin; Wallner, Christian

2014-05-01

Severe accidents in nuclear power plants such as the historical accident in Chernobyl 1986 or the more recent disaster in the Fukushima Dai-ichi nuclear power plant in 2011 have drastic impacts on the population and environment. The hazardous consequences reach out on a national and continental scale. Environmental measurements and methods to model the transport and dispersion of the released radionuclides serve as a platform to assess the regional impact of nuclear accidents - both, for research purposes and, more important, to determine the immediate threat to the population. However, the assessments of the regional radionuclide activity concentrations and the individual exposure to radiation dose underlie several uncertainties. For example, the accurate model representation of wet and dry deposition. One of the most significant uncertainty, however, results from the estimation of the source term. That is, the time dependent quantification of the released spectrum of radionuclides during the course of the nuclear accident. The quantification of the source terms of severe nuclear accidents may either remain uncertain (e.g. Chernobyl, Devell et al., 1995) or rely on rather rough estimates of released key radionuclides given by the operators. Precise measurements are mostly missing due to practical limitations during the accident. Inverse modelling can be used to realise a feasible estimation of the source term (Davoine and Bocquet, 2007). Existing point measurements of radionuclide activity concentrations are therefore combined with atmospheric transport models. The release rates of radionuclides at the accident site are then obtained by improving the agreement between the modelled and observed concentrations (Stohl et al., 2012). The accuracy of the method and hence of the resulting source term depends amongst others on the availability, reliability and the resolution in time and space of the observations. Radionuclide activity concentrations are observed on a relatively sparse grid and the temporal resolution of available data may be low within the order of hours or a day. Gamma dose rates on the other hand are observed routinely on a much denser grid and higher temporal resolution. Gamma dose rate measurements contain no explicit information on the observed spectrum of radionuclides and have to be interpreted carefully. Nevertheless, they provide valuable information for the inverse evaluation of the source term due to their availability (Saunier et al., 2013). We present a new inversion approach combining an atmospheric dispersion model and observations of radionuclide activity concentrations and gamma dose rates to obtain the source term of radionuclides. We use the Lagrangian particle dispersion model FLEXPART (Stohl et al., 1998; Stohl et al., 2005) to model the atmospheric transport of the released radionuclides. The gamma dose rates are calculated from the modelled activity concentrations. The inversion method uses a Bayesian formulation considering uncertainties for the a priori source term and the observations (Eckhardt et al., 2008). The a priori information on the source term is a first guess. The gamma dose rate observations will be used with inverse modelling to improve this first guess and to retrieve a reliable source term. The details of this method will be presented at the conference. This work is funded by the Bundesamt für Strahlenschutz BfS, Forschungsvorhaben 3612S60026. References Davoine, X. and Bocquet, M., Atmos. Chem. Phys., 7, 1549-1564, 2007. Devell, L., et al., OCDE/GD(96)12, 1995. Eckhardt, S., et al., Atmos. Chem. Phys., 8, 3881-3897, 2008. Saunier, O., et al., Atmos. Chem. Phys., 13, 11403-11421, 2013. Stohl, A., et al., Atmos. Environ., 32, 4245-4264, 1998. Stohl, A., et al., Atmos. Chem. Phys., 5, 2461-2474, 2005. Stohl, A., et al., Atmos. Chem. Phys., 12, 2313-2343, 2012.

Extended release dosage form of glipizide: development and validation of a level A in vitro-in vivo correlation.

PubMed

Ghosh, Animesh; Bhaumik, Uttam Kumar; Bose, Anirbandeep; Mandal, Uttam; Gowda, Veeran; Chatterjee, Bappaditya; Chakrabarty, Uday Sankar; Pal, Tapan Kumar

2008-10-01

Defining a quantitative and reliable relationship between in vitro drug release and in vivo absorption is highly desired for rational development, optimization, and evaluation of controlled-release dosage forms and manufacturing process. During the development of once daily extended-release (ER) tablet of glipizide, a predictive in vitro drug release method was designed and statistically evaluated using three formulations with varying release rates. In order to establish internally and externally validated level A in vitro-in vivo correlation (IVIVC), a total of three different ER formulations of glipizide were used to evaluate a linear IVIVC model based on the in vitro test method. For internal validation, a single-dose four-way cross over study (n=6) was performed using fast-, moderate-, and slow-releasing ER formulations and an immediate-release (IR) of glipizide as reference. In vitro release rate data were obtained for each formulation using the United States Pharmacopeia (USP) apparatus II, paddle stirrer at 50 and 100 rev. min(-1) in 0.1 M hydrochloric acid (HCl) and pH 6.8 phosphate buffer. The f(2) metric (similarity factor) was used to analyze the dissolution data. The formulations were compared using area under the plasma concentration-time curve, AUC(0-infinity), time to reach peak plasma concentration, T(max), and peak plasma concentration, C(max), while correlation was determined between in vitro release and in vivo absorption. A linear correlation model was developed using percent absorbed data versus percent dissolved from the three formulations. Predicted glipizide concentrations were obtained by convolution of the in vivo absorption rates. Prediction errors were estimated for C(max) and AUC(0-infinity) to determine the validity of the correlation. Apparatus II, pH 6.8 at 100 rev. min(-1) was found to be the most discriminating dissolution method. Linear regression analysis of the mean percentage of dose absorbed versus the mean percentage of in vitro release resulted in a significant correlation (r(2)>or=0.9) for the three formulations.

Pore structures in an implantable sol gel titania ceramic device used in controlled drug release applications: A modeling study

NASA Astrophysics Data System (ADS)

Peterson, Aaron; Lopez, Tessy; Islas, Emma Ortiz; Gonzalez, Richard D.

2007-04-01

Several process variables, which may be helpful in optimizing the rate at which drugs are released from implantable, sol-gel titania devices have been identified in this study. The controlled rate of drug release is compared for two different anticonvulsant drugs, valproic acid and sodic phenytoin. Contrary to what one might expect, when the concentration is increased in the titania reservoir the rate of initial drug delivery decreases. This is a desirable result, because it may reduce the danger of a high initial discharge, which may harm the epileptic rat. The structure of the porous structure within the titania network has been studied using a generalized form of the BET equation which considers only n layers. In general, following an initial discharge, the rate at which the drug is released will increase with the increasing concentration. Pore mouth blocking can present a problem. However, this problem tends to disappear following the initial discharge. The extent of drug loading is a useful variable parameter, which can be adjusted in order to deliver the amount of drug required in a given application.

Convergence of strain energy release rate components for edge-delaminated composite laminates

NASA Technical Reports Server (NTRS)

Raju, I. S.; Crews, J. H., Jr.; Aminpour, M. A.

1987-01-01

Strain energy release rates for edge delaminated composite laminates were obtained using quasi 3 dimensional finite element analysis. The problem of edge delamination at the -35/90 interfaces of an 8-ply composite laminate subjected to uniform axial strain was studied. The individual components of the strain energy release rates did not show convergence as the delamination tip elements were made smaller. In contrast, the total strain energy release rate converged and remained unchanged as the delamination tip elements were made smaller and agreed with that calculated using a classical laminated plate theory. The studies of the near field solutions for a delamination at an interface between two dissimilar isotropic or orthotropic plates showed that the imaginary part of the singularity is the cause of the nonconvergent behavior of the individual components. To evaluate the accuracy of the results, an 8-ply laminate with the delamination modeled in a thin resin layer, that exists between the -35 and 90 plies, was analyzed. Because the delamination exists in a homogeneous isotropic material, the oscillatory component of the singularity vanishes.

Enclosure fire hazard analysis using relative energy release criteria. [burning rate and combustion control

NASA Technical Reports Server (NTRS)

Coulbert, C. D.

1978-01-01

A method for predicting the probable course of fire development in an enclosure is presented. This fire modeling approach uses a graphic plot of five fire development constraints, the relative energy release criteria (RERC), to bound the heat release rates in an enclosure as a function of time. The five RERC are flame spread rate, fuel surface area, ventilation, enclosure volume, and total fuel load. They may be calculated versus time based on the specified or empirical conditions describing the specific enclosure, the fuel type and load, and the ventilation. The calculation of these five criteria, using the common basis of energy release rates versus time, provides a unifying framework for the utilization of available experimental data from all phases of fire development. The plot of these criteria reveals the probable fire development envelope and indicates which fire constraint will be controlling during a criteria time period. Examples of RERC application to fire characterization and control and to hazard analysis are presented along with recommendations for the further development of the concept.

[The release of biologically active compounds from peat peloids].

PubMed

Babaskin, D V

2011-01-01

This work had the objective to study kinetics of the release of flavonoides from peat peloid compositions containing extracts of medicinal herbs in model systems.The key parameters of the process are defined. The rate of liberation of flavonoides is shown to depend on their initial concentration in the compositions being used. The influence of the flavonoide composition of the tested extracts and dimethylsulfoxide on the release of biologically active compounds contained in the starting material in the model environment is estimated. The possibility of the layer-by-layer deposition of the compositions and peat peloids in order to increase the efficacy of flavonoide release from the starting composition and to ensure more rational utilization of the extracts of medicinal plants is demonstrated.

Kinetics of killing Listeria monocytogenes by macrophages: correlation of /sup 3/H-DNA release from labeled bacteria and changes in numbers of viable organisms by mathematical model

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

Davies, W.A.

1982-12-01

Conventional methods of assessing antibacterial activities of macrophages by viable counting are limited by the precision of the statistics and are difficult to interpret quantitatively because of unrestrained extracellular growth of bacteria. An alternative technique based on the release of radioactive DNA from labeled bacteria has been offered as overcoming these drawbacks. To assess it for use with macrophages I have made a correlation with the conventional viable counting method using a mathematical model. Opsonized Listeria monocytogenes labeled with /sup 3/H-thymidine were exposed to rat macrophages for periods up to 4 hr. Numbers of viable bacteria determined after sonication increasedmore » exponentially in the absence of live cells and this growth rate was progressively inhibited by increasing numbers of macrophages. After a lag period of 30-60 min soluble /sup 3/H appeared in the supernatant, the amount increasing with time and numbers of macrophages. To correlate these data I developed a mathematical model that considered that changes in numbers of viable organisms were due to the difference between rates of 1) growth of extracellular bacteria and 2) killing within the macrophage. On the basis of this model curves of best fit to the viable counts data were used to predict the release of radioactivity, assuming that death of a bacterium led to the total release of its label. These predictions and the experimental data agreed well, the lag period of 30-60 min between death of the bacterium and release of radioactivity being consistent with intracellular digestion. Release of soluble radioactivity appears to be an accurate reflection of the number of bacteria killed within the macrophage.« less

Development of a level A in vitro-in vivo correlation for extended release dosage forms of quetiapine fumarate.

PubMed

Gonçalves de Lima, L; Rossi de Campos, D

2016-05-01

Quetiapine is an atypical antipsychotic recommended as first-line treatment for acute bipolar depression. The extended-release quetiapine formulation is intended to be administered as an once-daily dosing. The development of an in vitro-in vivo correlation (IVIVC) and the use of in vitro data to predict in vivo bioavailability parameters has been of great interest for the rational development and evaluation process for extended release dosage forms. The aim of this study was to develop an IVIVC for quetiapine extended release formulation. In vitro dissolution rate data were obtained using USP apparatus 2 at 50 rpm, in 3 bio-relevant dissolution media with different pH values (1.2, 4.5 and 6.8). The drug release profiles of the 2 extended release dosage forms were compared using the similarity factor (f 2). The relative bioavailability of quetiapine was evaluated by a single-dose, randomized-sequence, open-label, 2 period cross over study with 16 healthy volunteers. A linear level A IVIVC model was established using percentage of absorbed and dissolved data obtained at pH 1.2. The developed IVIVC model was employed to predict quetiapine concentration-time profiles, as well as the bioequivalence parameters for test formulation. Percent prediction errors were estimated for Cmax and AUC to evaluate the validity of the correlation. The values did not exceed 15%, proving the predictability of the correlation model. In conclusion, the established level A IVIVC model proved to be an excellent tool for predicting the rate and extent of quetiapine absorption as characterized by Cmax and AUC for test formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Modulating drug release from gastric-floating microcapsules through spray-coating layers.

PubMed

Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

2014-01-01

Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

Costs and benefits of trap-neuter-release and euthanasia for removal of urban cats in Oahu, Hawaii.

PubMed

Lohr, Cheryl A; Cox, Linda J; Lepczyk, Christopher A

2013-02-01

Our goal was to determine whether it is more cost-effective to control feral cat abundance with trap-neuter-release programs or trap and euthanize programs. Using STELLA 7, systems modeling software, we modeled changes over 30 years in abundance of cats in a feral colony in response to each management method and the costs and benefits associated with each method . We included costs associated with providing food, veterinary care, and microchips to the colony cats and the cost of euthanasia, wages, and trapping equipment in the model. Due to a lack of data on predation rates and disease transmission by feral cats the only benefits incorporated into the analyses were reduced predation on Wedge-tailed Shearwaters (Puffinus pacificus). When no additional domestic cats were abandoned by owners and the trap and euthanize program removed 30,000 cats in the first year, the colony was extirpated in at least 75% of model simulations within the second year. It took 30 years for trap-neuter-release to extirpate the colony. When the cat population was supplemented with 10% of the initial population size per year, the colony returned to carrying capacity within 6 years and the trap and euthanize program had to be repeated, whereas trap-neuter-release never reduced the number of cats to near zero within the 30-year time frame of the model. The abandonment of domestic cats reduced the cost effectiveness of both trap-neuter-release and trap and euthanize. Trap-neuter-release was approximately twice as expensive to implement as a trap and euthanize program. Results of sensitivity analyses suggested trap-neuter-release programs that employ volunteers are still less cost-effective than trap and euthanize programs that employ paid professionals and that trap-neuter-release was only effective when the total number of colony cats in an area was below 1000. Reducing the rate of abandonment of domestic cats appears to be a more effective solution for reducing the abundance of feral cats. ©2012 Society for Conservation Biology.

Investigating the Release of a Hydrophobic Peptide from Matrices of Biodegradable Polymers: An Integrated Method Approach

PubMed Central

Gubskaya, Anna V.; Khan, I. John; Valenzuela, Loreto M.; Lisnyak, Yuriy V.; Kohn, Joachim

2013-01-01

The objectives of this work were: (1) to select suitable compositions of tyrosine-derived polycarbonates for controlled delivery of voclosporin, a potent drug candidate to treat ocular diseases, (2) to establish a structure-function relationship between key molecular characteristics of biodegradable polymer matrices and drug release kinetics, and (3) to identify factors contributing in the rate of drug release. For the first time, the experimental study of polymeric drug release was accompanied by a hierarchical sequence of three computational methods. First, suitable polymer compositions used in subsequent neural network modeling were determined by means of response surface methodology (RSM). Second, accurate artificial neural network (ANN) models were built to predict drug release profiles for fifteen polymers located outside the initial design space. Finally, thermodynamic properties and hydrogen-bonding patterns of model drug-polymer complexes were studied using molecular dynamics (MD) technique to elucidate a role of specific interactions in drug release mechanism. This research presents further development of methodological approaches to meet challenges in the design of polymeric drug delivery systems. PMID:24039300

CFD modelling wall heat transfer inside a combustion chamber using ANSYS forte

NASA Astrophysics Data System (ADS)

Plengsa-ard, C.; Kaewbumrung, M.

2018-01-01

A computational model has been performed to analyze a wall heat transfer in a single cylinder, direct injection and four-stroke diesel engine. A direct integration using detailed chemistry CHEMKIN is employed in a combustion model and the Reynolds Averaged Navier Stokes (RANS) turbulence model is used to simulate the flow in the cylinder. To obtain heat flux results, a modified classical variable-density wall heat transfer model is also performed. The model is validated using experimental data from a CUMMINs engine operated with a conventional diesel combustion. One operating engine condition is simulated. Comparisons of simulated in-cylinder pressure and heat release rates with experimental data shows that the model predicts the cylinder pressure and heat release rates reasonably well. The contour plot of instantaneous temperature are presented. Also, the contours of predicted heat flux results are shown. The magnitude of peak heat fluxes as predicted by the wall heat transfer model is in the range of the typical measure values in diesel combustion.

Delamination micromechanics analysis

NASA Technical Reports Server (NTRS)

Adams, D. F.; Mahishi, J. M.

1985-01-01

A three-dimensional finite element analysis was developed which includes elastoplastic, orthotropic material response, and fracture initiation and propagation. Energy absorption due to physical failure processes characteristic of the heterogeneous and anisotropic nature of composite materials is modeled. A local energy release rate in the presence of plasticity was defined and used as a criterion to predict the onset and growth of cracks in both micromechanics and macromechanics analyses. This crack growth simulation technique is based upon a virtual crack extension method. A three-dimensional finite element micromechanics model is used to study the effects of broken fibers, cracked matrix and fiber-matrix debond on the fracture toughness of the unidirectional composite. The energy release rates at the onset of unstable crack growth in the micromechanics analyses are used as critical energy release rates in the macromechanics analysis. This integrated micromechanical and macromechanical fracture criterion is shown to be very effective in predicting the onset and growth of cracks in general multilayered composite laminates by applying the criterion to a single-edge notched graphite/epoxy laminate subjected to implane tension normal to the notch.

Release kinetics of volatile organic compounds from roasted and ground coffee: online measurements by PTR-MS and mathematical modeling.

PubMed

Mateus, Maria-L; Lindinger, Christian; Gumy, Jean-C; Liardon, Remy

2007-12-12

The present work shows the possibilities and limitations in modeling release kinetics of volatile organic compounds (VOCs) from roasted and ground coffee by applying physical and empirical models such as the diffusion and Weibull models. The release kinetics of VOCs were measured online by proton transfer reaction-mass spectrometry (PTR-MS). Compounds were identified by GC-MS, and the contribution of the individual compounds to different mass fragments was elucidated by GC/PTR-MS. Coffee samples roasted to different roasting degrees and ground to different particle sizes were studied under dry and wet stripping conditions. To investigate the accuracy of modeling the VOC release kinetics recorded using PTR-MS, online kinetics were compared with kinetics reconstituted from purge and trap samplings. Results showed that uncertainties in ion intensities due to the presence of isobaric species may prevent the development of a robust mathematical model. Of the 20 identified compounds, 5 were affected to a lower extent as their contribution to specific m/z intensity varied by <15% over the stripping time. The kinetics of these compounds were fitted using physical and statistical models, respectively, the diffusion and Weibull models, which helped to identify the underlying release mechanisms. For dry stripping, the diffusion model allowed a good representation of the release kinetics, whereas for wet stripping conditions, release patterns were very complex and almost specific for each compound analyzed. In the case of prewetted coffee, varying particle size (approximately 400-1200 microm) had no significant effect on the VOC release rate, whereas for dry coffee, the release was faster for smaller particles. The absence of particle size effect in wet coffee was attributed to the increase of opened porosity and compound diffusivity by solubilization and matrix relaxation. To conclude, the accurate modeling of VOC release kinetics from coffee allowed small variations in compound release to be discriminated. Furthermore, it evidenced the different aroma compositions that may be obtained depending on the time when VOCs are recovered.

Sill intrusion driven fluid flow and vent formation in volcanic basins: Modeling rates of volatile release and paleoclimate effects

NASA Astrophysics Data System (ADS)

Iyer, Karthik; Schmid, Daniel

2016-04-01

Evidence of mass extinction events in conjunction with climate change occur throughout the geological record and may be accompanied by pronounced negative carbon isotope excursions. The processes that trigger such globally destructive changes are still under considerable debate. These include mechanisms such as poisoning from trace metals released during large volcanic eruptions (Vogt, 1972), CO2 released from lava degassing during the formation of Large Igneous Provinces (LIPs) (Courtillot and Renne, 2003) and CH4 release during the destabilization of sub-seafloor methane (Dickens et al., 1995), to name a few. Thermogenic methane derived from contact metamorphism associated with magma emplacement and cooling in sedimentary basins has been recently gaining considerable attention as a potential mechanism that may have triggered global climate events in the past (e.g. Svensen and Jamtveit, 2010). The discovery of hydrothermal vent complexes that are spatially associated with such basins also supports the discharge of greenhouse gases into the atmosphere (e.g. Jamtveit et al., 2004; Planke et al., 2005; Svensen et al., 2006). A previous study that investigated this process using a fluid flow model (Iyer et al., 2013) suggested that although hydrothermal plume formation resulting from sill emplacement may indeed release large quantities of methane at the surface, the rate at which this methane is released into the atmosphere is too slow to trigger, by itself, some of the negative δ13C excursions observed in the fossil record over short time scales observed in the fossil record. Here, we reinvestigate the rates of gas release during sill emplacement in a case study from the Harstad Basin off-shore Norway with a special emphasis on vent formation. The presented study is based on a seismic line that crosses multiple sill structures emplaced around 55 Ma within the Lower Cretaceous sediments. A single well-defined vent complex is interpreted above the termination of the main sill in the region. We use a 2D, hybrid FEM/FVM model that solves for fully compressible fluid flow to quantify the thermogenic release and transport of methane and to evaluate flow patterns within these systems. Additionally, vent formation in the model is implemented by simple fracture criteria that modify the permeability structure when the fluid pressure exceeds a threshold determined by the lithostatic pressure. The model with fracture formation is able to reproduce a single vent complex at the observed location above the main sill tip. This is very different from hydrothermal plume formation elsewhere in the region and occurs over short time scales (hundreds of years) and results in fluid focusing in that region. The rate of degassing and the resulting negative δ13C excursion from the vent model is then compared to models where only hydrothermal plume formation results in gas transportation. Lastly, variations in the amount of gas liberated in the system are investigated based on kerogen type and other mineral reactions such as limestone decarbonation and halite breakdown in the affected source rock.

Establishing and applying of a coupled individual based model of edible jellyfish(Rhopilema esculentum Kishinouye) releasing in the Liaodong Bay

NASA Astrophysics Data System (ADS)

Yin, Liping; Qiao, Fangli

2017-04-01

A three-dimensional circulation-surface wave coupled hydrodynamic model coupled with an individual-based jellyfish model was established to investigate the influence of physical process on edible jellyfish releasing stock enhancement in Liaodong Bay. Sensitivity experiments show that the wind intensity and direction have both direct and indirect impacts on the distribution of the jellyfish. When the wind is strong, the surface current in Liaodong Bay has the same direction of the wind. Under the co-effect of the ocean current transport and the surface wind transport, the jellyfish inhabits in the northeast of Liaodong bay, which is consistent with the observation. In the circumstance of weak wind, the circulation is clockwise and the jellyfish will spread around the 5m isobaths following the circulation. Research of the jellyfish distribution shows that the releasing jellyfish will stay in Liaodong bay in its whole life history, hence Liaodong Bay is a quite suitable area for enhancement releasing. The influence of the temperature on releasing region and date is also investigated. The threshold date during 2008 to 2016 is calculated, which is the date when the temperature of water within 10m isobaths in Liaodong Bay rises up to 15oC. In 2010, the threshold date came about one week later while the medusa releasing date remains the same in 2009. As a result, higher fatality rate of medusa caused by the cold water resulted in lower recapture rate in 2010. Therefore, the releasing date and location should be varied according to environmental conditions. The threshold date tends to appear earlier during 2008 to 2016, which suggests an earlier releasing date. In summer, due to the cold water mass intrusion from the south, the releasing date in the north area should be earlier than in the south.

Pathways of proton release in the bacteriorhodopsin photocycle

NASA Technical Reports Server (NTRS)

Zimanyi, L.; Varo, G.; Chang, M.; Ni, B.; Needleman, R.; Lanyi, J. K.

1992-01-01

The pH dependencies of the rate constants in the photocycles of recombinant D96N and D115N/D96N bacteriorhodopsins were determined from time-resolved difference spectra between 70 ns and 420 ms after photoexcitation. The results were consistent with the model suggested earlier for proteins containing D96N substitution: BR hv----K----L----M1----M2----BR. Only the M2----M1 back-reaction was pH-dependent: its rate increased with increasing [H+] between pH 5 and 8. We conclude from quantitative analysis of this pH dependency that its reverse, the M1----M2 reaction, is linked to the release of a proton from a group with a pKa = 5.8. This suggests a model for wild-type bacteriorhodopsin in which at pH greater than 5.8 the transported proton is released on the extracellular side from this as yet unknown group and on the 100-microseconds time scale, but at pH less than 5.8, the proton release occurs from another residue and later in the photocycle most likely directly from D85 during the O----BR reaction. We postulate, on the other hand, that proton uptake on the cytoplasmic side will be by D96 and during the N----O reaction regardless of pH. The proton kinetics as measured with indicator dyes confirmed the unique prediction of this model: at pH greater than 6, proton release preceded proton uptake, but at pH less than 6, the release was delayed until after the uptake. The results indicated further that the overall M1----M2 reaction includes a second kinetic step in addition to proton release; this is probably the earlier postulated extracellular-to-cytoplasmic reorientation switch in the proton pump.

STEADY STATE FLAMMABLE GAS RELEASE RATE CALCULATION AND LOWER FLAMMABILITY LEVEL EVALUATION FOR HANFORD TANK WASTE

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

HU TA

2009-10-26

Assess the steady-state flammability level at normal and off-normal ventilation conditions. The hydrogen generation rate was calculated for 177 tanks using the rate equation model. Flammability calculations based on hydrogen, ammonia, and methane were performed for 177 tanks for various scenarios.

Scaling behavior of microbubbles rising in water-saturated porous media

NASA Astrophysics Data System (ADS)

Kong, X.; Ma, Y.; Scheuermann, A.; Bringemeier, D.; Galindo-Torres, S. A.; Saar, M. O.; Li, L.

2015-12-01

Gas transport in the form of discrete microbubbles in saturated porous media is of importance in a number of processes relevant to many geo-environmental and engineering systems such as bubbling of greenhouse gases in river and sea beds, hydrocarbon gas migration in coal cleats and rock fractures, and air sparging for remediation of soil contaminated with volatile organic compounds. Under the assumption of no or minor volume expansion during gravity-driven migration, the transport of a single microbubble can be well described using various drag force models. However, not enough attention has been paid to the collective behavior of microbubbles during their ascend as a plume through the saturated porous medium, involving dynamic interactions between individual bubbles, bubbles and the ambient fluid, as well as bubbles and the solid matrix. With our quasi-2D, lab-scale microbubble migration experiments, where bubbles are continuously released from a diffuser at the bottom of a porous bed of hydrated gel beads, we establish a scaling relationship between the gas (bubble) release rate and various characteristic parameters of the bubble plume, such as plume tip velocity, plume width, and breakthrough time of the plume front. We find that the characteristic width of the bubble plume varies as a power of both the gas release rate and the bed thickness, with exponents of 0.2 and 0.4, respectively. Moreover, the characteristic breakthrough time also scales with both the gas release rate and the bed thickness with power-law exponents of -0.4 and 1.2, respectively. The mean pore-water velocity of the circulating ambient water also follows a power-law relationship with the gas release rate being an exponent of 0.6 of the gas release rate. This can be quantitatively proven using a simplified momentum exchange model together with the above power-law exponents for the bubble plume. These analyses on the experimental results are carried out on the basis of non-dimensional parameters and variables in order to explore the bubble transport mechanism in a way that is independent of the actual scale of the physical model. Our findings thus have implications for engineering processes and for fundamental research on bubble transport phenomena in porous media in general.

Assessing the release of copper from nanocopper-treated and conventional copper-treated lumber into marine waters I: Concentrations and rates.

PubMed

Parks, Ashley N; Cantwell, Mark G; Katz, David R; Cashman, Michaela A; Luxton, Todd P; Ho, Kay T; Burgess, Robert M

2018-03-25

Little is known about the release of metal engineered nanomaterials (ENMs) from consumer goods, including lumber treated with micronized copper. Micronized copper is a recent form of antifouling wood preservative containing nanosized copper particles for use in pressure-treated lumber. The present study investigated the concentrations released and the release rate of total copper over the course of 133 d under freshwater, estuarine, and marine salinity conditions (0, 1, 10, and 30‰) for several commercially available pressure-treated lumbers: micronized copper azole (MCA) at 0.96 and 2.4 kg/m 3 , alkaline copper quaternary (ACQ) at 0.30 and 9.6 kg/m 3 , and chromated copper arsenate (CCA) at 40 kg/m 3 . Lumber was tested as blocks and as sawdust. Overall, copper was released from all treated lumber samples. Under leaching conditions, total release ranged from 2 to 55% of the measured copper originally in the lumber, with release rate constants from the blocks of 0.03 to 2.71 (units per day). Generally, measured release and modeled equilibrium concentrations were significantly higher in the estuarine conditions compared with freshwater or marine salinities, whereas rate constants showed very limited differences between salinities. Furthermore, organic carbon was released during the leaching and demonstrated a significant relationship with released copper concentrations as a function of salinity. The results indicate that copper is released into estuarine/marine waters from multiple wood treatments including lumber amended with nanoparticle-sized copper. Environ Toxicol Chem 2018;9999:1-13. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Inverse modelling of radionuclide release rates using gamma dose rate observations

NASA Astrophysics Data System (ADS)

Hamburger, Thomas; Evangeliou, Nikolaos; Stohl, Andreas; von Haustein, Christoph; Thummerer, Severin; Wallner, Christian

2015-04-01

Severe accidents in nuclear power plants such as the historical accident in Chernobyl 1986 or the more recent disaster in the Fukushima Dai-ichi nuclear power plant in 2011 have drastic impacts on the population and environment. Observations and dispersion modelling of the released radionuclides help to assess the regional impact of such nuclear accidents. Modelling the increase of regional radionuclide activity concentrations, which results from nuclear accidents, underlies a multiplicity of uncertainties. One of the most significant uncertainties is the estimation of the source term. That is, the time dependent quantification of the released spectrum of radionuclides during the course of the nuclear accident. The quantification of the source term may either remain uncertain (e.g. Chernobyl, Devell et al., 1995) or rely on estimates given by the operators of the nuclear power plant. Precise measurements are mostly missing due to practical limitations during the accident. The release rates of radionuclides at the accident site can be estimated using inverse modelling (Davoine and Bocquet, 2007). The accuracy of the method depends amongst others on the availability, reliability and the resolution in time and space of the used observations. Radionuclide activity concentrations are observed on a relatively sparse grid and the temporal resolution of available data may be low within the order of hours or a day. Gamma dose rates, on the other hand, are observed routinely on a much denser grid and higher temporal resolution and provide therefore a wider basis for inverse modelling (Saunier et al., 2013). We present a new inversion approach, which combines an atmospheric dispersion model and observations of radionuclide activity concentrations and gamma dose rates to obtain the source term of radionuclides. We use the Lagrangian particle dispersion model FLEXPART (Stohl et al., 1998; Stohl et al., 2005) to model the atmospheric transport of the released radionuclides. The inversion method uses a Bayesian formulation considering uncertainties for the a priori source term and the observations (Eckhardt et al., 2008, Stohl et al., 2012). The a priori information on the source term is a first guess. The gamma dose rate observations are used to improve the first guess and to retrieve a reliable source term. The details of this method will be presented at the conference. This work is funded by the Bundesamt für Strahlenschutz BfS, Forschungsvorhaben 3612S60026. References Davoine, X. and Bocquet, M., Atmos. Chem. Phys., 7, 1549-1564, 2007. Devell, L., et al., OCDE/GD(96)12, 1995. Eckhardt, S., et al., Atmos. Chem. Phys., 8, 3881-3897, 2008. Saunier, O., et al., Atmos. Chem. Phys., 13, 11403-11421, 2013. Stohl, A., et al., Atmos. Environ., 32, 4245-4264, 1998. Stohl, A., et al., Atmos. Chem. Phys., 5, 2461-2474, 2005. Stohl, A., et al., Atmos. Chem. Phys., 12, 2313-2343, 2012.

Separation of crack extension modes in orthotropic delamination models

NASA Technical Reports Server (NTRS)

Beuth, Jack L.

1995-01-01

In the analysis of an interface crack between dissimilar elastic materials, the mode of crack extension is typically not unique, due to oscillatory behavior of near-tip stresses and displacements. This behavior currently limits the applicability of interfacial fracture mechanics as a means to predict composite delamination. The Virtual Crack Closure Technique (VCCT) is a method used to extract mode 1 and mode 2 energy release rates from numerical fracture solutions. The mode of crack extension extracted from an oscillatory solution using the VCCT is not unique due to the dependence of mode on the virtual crack extension length, Delta. In this work, a method is presented for using the VCCT to extract Delta-independent crack extension modes for the case of an interface crack between two in-plane orthotropic materials. The method does not involve altering the analysis to eliminate its oscillatory behavior. Instead, it is argued that physically reasonable, Delta-independent modes of crack extension can be extracted from oscillatory solutions. Knowledge of near-tip fields is used to determine the explicit Delta dependence of energy release rate parameters. Energy release rates are then defined that are separated from the oscillatory dependence on Delta. A modified VCCT using these energy release rate definitions is applied to results from finite element analyses, showing that Delta-independent modes of crack extension result. The modified technique has potential as a consistent method for extracting crack extension modes from numerical solutions. The Delta-independent modes extracted using this technique can also serve as guides for testing the convergence of finite element models. Direct applications of this work include the analysis of planar composite delamination problems, where plies or debonded laminates are modeled as in-plane orthotropic materials.

Multiple emulsions as effective platforms for controlled anti-cancer drug delivery.

PubMed

Dluska, Ewa; Markowska-Radomska, Agnieszka; Metera, Agata; Tudek, Barbara; Kosicki, Konrad

2017-09-01

Developing pH-responsive multiple emulsion platforms for effective glioblastoma multiforme therapy with reduced toxicity, a drug release study and modeling. Cancer cell line: U87 MG, multiple emulsions with pH-responsive biopolymer and encapsulated doxorubicin (DOX); preparation of multiple emulsions in a Couette-Taylor flow biocontactor, in vitro release study of DOX (fluorescence intensity analysis), in vitro cytotoxicity study (alamarBlue cell viability assay) and numerical simulation of DOX release rates. The multiple emulsions offered a high DOX encapsulation efficiency (97.4 ± 1%) and pH modulated release rates of a drug. Multiple emulsions with a low concentration of DOX (0.02 μM) exhibited broadly advanced cell (U87 MG) cytotoxicity than free DOX solution used at the same concentration. Emulsion platforms could be explored for potential delivery of chemotherapeutics in glioblastoma multiforme therapy.

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

Jablonská, Jana, E-mail: jana.jablonska@vsb.cz; Kozubková, Milada, E-mail: milada.kozubkova@vsb.cz

Cavitation today is a very important problem that is solved by means of experimental and mathematical methods. The article deals with the generation of cavitation in convergent divergent nozzle of rectangular cross section. Measurement of pressure, flow rate, temperature, amount of dissolved air in the liquid and visualization of cavitation area using high-speed camera was performed for different flow rates. The measurement results were generalized by dimensionless analysis, which allows easy detection of cavitation in the nozzle. For numerical simulation the multiphase mathematical model of cavitation consisting of water and vapor was created. During verification the disagreement with the measurementsmore » for higher flow rates was proved, therefore the model was extended to multiphase mathematical model (water, vapor and air), due to release of dissolved air. For the mathematical modeling the multiphase turbulence RNG k-ε model for low Reynolds number flow with vapor and air cavitation was used. Subsequently the sizes of the cavitation area were verified. In article the inlet pressure and loss coefficient depending on the amount of air added to the mathematical model are evaluated. On the basis of the approach it may be create a methodology to estimate the amount of released air added at the inlet to the modeled area.« less

Biocontrol in an impulsive predator-prey model.

PubMed

Terry, Alan J

2014-10-01

We study a model for biological pest control (or "biocontrol") in which a pest population is controlled by a program of periodic releases of a fixed yield of predators that prey on the pest. Releases are represented as impulsive increases in the predator population. Between releases, predator-pest dynamics evolve according to a predator-prey model with some fairly general properties: the pest population grows logistically in the absence of predation; the predator functional response is either of Beddington-DeAngelis type or Holling type II; the predator per capita birth rate is bounded above by a constant multiple of the predator functional response; and the predator per capita death rate is allowed to be decreasing in the predator functional response and increasing in the predator population, though the special case in which it is constant is permitted too. We prove that, when the predator functional response is of Beddington-DeAngelis type and the predators are not sufficiently voracious, then the biocontrol program will fail to reduce the pest population below a particular economic threshold, regardless of the frequency or yield of the releases. We prove also that our model possesses a pest-eradication solution, which is both locally and globally stable provided that predators are sufficiently voracious and that releases occur sufficiently often. We establish, curiously, that the pest-eradication solution can be locally stable whilst not being globally stable, the upshot of which is that, if we delay a biocontrol response to a new pest invasion, then this can change the outcome of the response from pest eradication to pest persistence. Finally, we state a number of specific examples for our model, and, for one of these examples, we corroborate parts of our analysis by numerical simulations. Copyright © 2014 Elsevier Inc. All rights reserved.

FY2017 ILAW Glass Corrosion Testing with the Single-Pass Flow-Through Method

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

Neeway, James J.; Asmussen, Robert M.; Cordova, Elsa

The inventory of immobilized low-activity waste (ILAW) produced at the Hanford Tank Waste Treatment and Immobilization Plant (WTP) will be disposed of at the near-surface, on-site Integrated Disposal Facility (IDF). When groundwater comes into contact with the waste form, the glass will corrode and radionuclides will be released into the near-field environment. Because the release of the radionuclides is dependent on the dissolution rate of the glass, it is important that the performance assessment (PA) model accounts for the dissolution rate of the glass as a function of various conditions. To accomplish this, an IDF PA glass dissolution model basedmore » on Transition State Theory (TST) can be employed. The model is able to account for changes in temperature, exposed surface area, and pH of the contacting solution as well as the effect of silicon solution concentrations, specifically the activity of orthosilicic acid (H4SiO4), whose concentration is directly linked to the glass dissolution rate. In addition, the IDF PA model accounts for the ion exchange process. The effect of temperature, pH, H4SiO4 activity, and the rate of ion exchange can be parameterized and implemented directly into the PA rate model. The rate model parameters are derived from laboratory tests with the single-pass flow-through (SPFT) method. The provided data can be used by glass researchers to further the understanding of ILAW glass behavior, by IDF PA modelers to use the rate model parameters in PA modeling efforts, and by Department of Energy (DOE) contractors and decision makers as they assess the IDF PA program.« less

The stability analysis of the nutrition restricted dynamic model of the microalgae biomass growth

NASA Astrophysics Data System (ADS)

Ratianingsih, R.; Fitriani, Nacong, N.; Resnawati, Mardlijah, Widodo, B.

2018-03-01

The biomass production is very essential in microalgae farming such that its growth rate is very important to be determined. This paper proposes the dynamics model of it that restricted by its nutrition. The model is developed by considers some related processes that are photosynthesis, respiration, nutrition absorption, stabilization, lipid synthesis and CO2 mobilization. The stability of the dynamical system that represents the processes is analyzed using the Jacobian matrix of the linearized system in the neighborhood of its critical point. There is a lipid formation threshold needed to require its existence. In such case, the absorption rate of respiration process has to be inversely proportional to the absorption rate of CO2 due to photosynthesis process. The Pontryagin minimal principal also shows that there are some requirements needed to have a stable critical point, such as the rate of CO2 released rate, due to the stabilization process that is restricted by 50%, and the threshold of its shifted critical point. In case of the rate of CO2 released rate due to the photosynthesis process is restricted in such interval; the stability of the model at the critical point could not be satisfied anymore. The simulation shows that the external nutrition plays a role in glucose formation such that sufficient for the biomass growth and the lipid production.

Fluoride release and recharge behavior of a nano-filled resin-modified glass ionomer compared with that of other fluoride releasing materials.

PubMed

Mitra, Sumita B; Oxman, Joe D; Falsafi, Afshin; Ton, Tiffany T

2011-12-01

To compare the long-term fluoride release kinetics of a novel nano-filled two-paste resin-modified glass-ionomer (RMGI), Ketac Nano (KN) with that of two powder-liquid resin-modified glass-ionomers, Fuji II LC (FLC) and Vitremer (VT) and one conventional glass-ionomer, Fuji IX (FIX). Fluoride release was measured in vitro using ion-selective electrodes. Kinetic analysis was done using regression analysis and compared with existing models for GIs and compomers. In a separate experiment the samples of KN and two conventional glass-ionomers, FIX and Ketac Molar (KM) were subjected to a treatment with external fluoride source (Oral-B Neutra-Foam) after 3 months of fluoride release and the recharge behavior studied for an additional 7-day period. The cumulative amount of fluoride released from KN, VT and FLC and the release profiles were statistically similar but greater than that for FIX at P < 0.05. All four materials, including KN, showed a burst of fluoride ions at shorter times (t) and an overall rate dependence on t1/2 typical for glass-ionomers. The coating of KN with its primer and of DY with its adhesive did not significantly alter the fluoride release behavior of the respective materials. The overall rate for KN was significantly higher than for the compomer DY. DY showed a linear rate of release vs. t and no burst effect as expected for compomers. The nanoionomer KN showed fluoride recharge behavior similar to the conventional glass ionomers FIX and KM. Thus, it was concluded that the new RMGI KN exhibits fluoride ion release behavior similar to typical conventional and RMGIs and that the primer does not impede the release of fluoride.

Studies on a novel doughnut-shaped minitablet for intraocular drug delivery.

PubMed

Choonara, Yahya E; Pillay, Viness; Carmichael, Trevor; Danckwerts, Michael P

2007-12-28

The objective of this study was to evaluate the effect of 2 independent formulation variables on the drug release from a novel doughnut-shaped minitablet (DSMT) in order to optimize formulations for intraocular drug delivery. Formulations were based on a 3(2) full-factorial design. The 2 independent variables were the concentration of Resomer (% wt/wt) and the type of Resomer grade (RG502, RG503, and RG504), respectively. The evaluated response was the drug release rate constant computed from a referenced marketed product and in vitro drug release data obtained at pH 7.4 in simulated vitreous humor. DSMT devices were prepared containing either of 2 model drugs, ganciclovir or foscarnet, using a Manesty F3 tableting press fitted with a novel central-rod, punch, and die setup. Dissolution data revealed biphasic drug release behavior with 55% to 60% drug released over 120 days. The inherent viscosity of the various Resomer grades and the concentration were significant to achieve optimum release rate constants. Using the resultant statistical relationships with the release rate constant as a response, the optimum formulation predicted for devices formulated with foscarnet was 70% wt/wt of Resomer RG504, while 92% wt/wt of Resomer RG503 was ideal for devices formulated with ganciclovir. The results of this study revealed that the full-factorial design was a suitable tool to predict an optimized formulation for prolonged intraocular drug delivery.

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.

Oxygen consumption by oak chips in a model wine solution; Influence of the botanical origin, toast level and ellagitannin content.

PubMed

Navarro, María; Kontoudakis, Nikolaos; Giordanengo, Thomas; Gómez-Alonso, Sergio; García-Romero, Esteban; Fort, Francesca; Canals, Joan Miquel; Hermosín-Gutíerrez, Isidro; Zamora, Fernando

2016-05-15

The botanical origin, toast level and ellagitannin content of oak chips in a model wine solution have been studied in terms of their influence on oxygen consumption. French oak chips released significantly higher amounts of ellagitannins than American oak chips at any toast level. The release of ellagitannins by oak chips decreased as the toast level increased in the French oak but this trend was not so clear in American oak. Oxygen consumption rate was clearly related to the level of released ellagitannins. Therefore, oak chips should be chosen for their potential to release ellagitannins release should be considered, not only because they can have a direct impact on the flavor and body of the wine, but also because they can protect against oxidation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of food characteristics, storage conditions, and electron beam irradiation on active agent release from polyamide-coated LDPE films.

PubMed

Han, J; Castell-Perez, M E; Moreira, R G

2008-03-01

We investigated the effect of electron beam irradiation, storage conditions, and model food pH on the release characteristics of trans-cinnamaldehyde incorporated into polyamide-coated low-density polyethylene (LDPE) films. Active agent release rate on irradiated films (up to 20.0 kGy) decreased by 69% compared with the nonirradiated controls, from 0.252 to 0.086 microg/mL/h. Storage temperature (4, 21, and 35 degrees C) and pH (4, 7, and 10) of the food simulant solutions (10% aqueous ethanol) affected the release rate of trans-cinnamaldehyde. As expected, antimicrobial release rate decreased to 0.013 microg/mL/h at the refrigerated temperature (4 degrees C) compared to the higher temperatures (0.029 and 0.035 microg/mL/h at 21 and 35 degrees C). The fastest release rate occurred when exposed to the acidic food simulant solution (pH 4). In aqueous solution, trans-cinnamaldehyde was highly unstable to ionizing radiation, with loss in concentration from 24.50 to 1.36 microg/mL after exposure to 2.0 kGy. Fourier transform infrared (FTIR) analysis revealed that exposure to ionizing radiation up to 10.0 kGy did not affect the structural conformation of LDPE/polyamide films and the trans-cinnamaldehyde in the films, though it induced changes in the functional group of trans-cinnamaldehyde when dose increased up to 20.0 kGy. Studies with a radiation-stable compound (naphthalene) showed that ionizing radiation induced the crosslinking in polymer networks of LDPE/polyamide film and caused slow and gradual release of the compound. This study demonstrated that irradiation serves as a controlling factor for release of active compounds, with potential applications in the development of antimicrobial packaging systems.

How to adjust desired drug release patterns from ethylcellulose-coated dosage forms.

PubMed

Siepmann, F; Hoffmann, A; Leclercq, B; Carlin, B; Siepmann, J

2007-06-04

The aim of this study was to provide an easy and efficient tool to adjust desired drug release kinetics from (aqueous) ethylcellulose-coated solid dosage forms and to better understand the underlying mass transport mechanisms. Pure ethylcellulose films are poorly permeable for many substances and can result in very low release rates for certain drugs from coated dosage forms, if the film coatings are completely formed and remain intact upon exposure to the release media. To increase the permeability of the polymeric membranes, different amounts of a water-soluble poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer (PVA-PEG graft copolymer) were added to an aqueous ethylcellulose dispersion (Aquacoat ECD). Importantly, the presence of only a low percentage of this hydrophilic copolymer significantly increased the resulting water uptake rate and extent, dry weight loss and drug permeability of the films. In contrast to hydroxypropyl methylcellulose (HPMC), the PVA-PEG graft copolymer does not cause flocculation of the colloidal coating dispersion (leading to potentially variable release rates). Interestingly, the transport of water as well as of the model drug theophylline through the polymeric networks was primarily controlled by pure diffusion. The penetration kinetics could be quantitatively described by Fick's law of diffusion, irrespective of the type of release medium and PVA-PEG graft copolymer content. Most important from a practical point of view, a broad spectrum of pH-independent drug release rates can easily be obtained from drug-loaded pellets by simply varying the PVA-PEG graft copolymer content. An appropriate curing step after coating is required, but interestingly the investigated curing conditions (differing in time and relative humidity) resulted in very similar drug release patterns, indicating that stable film structures are likely to be achieved.

Formulation of bi-layer matrix tablets of tramadol hydrochloride: Comparison of rate retarding ability of the incorporated hydrophilic polymers.

PubMed

Arif, Hasanul; Al-Masum, Abdullah; Sharmin, Florida; Reza, Selim; Sm Islam, Sm Ashraful

2015-05-01

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique. Each tablet contains an instant release layer with a sustained release layer. The instant release layer was found to release the initial dose immediately within minutes. The instant release layer was combined with sustained release matrix made of varying quantity of Methocel K4M, Methocel K15MCR and Carbomer 974P. Bi-layer tablets were evaluated for various physical tests including weight variation, thickness and diameter, hardness and percent friability. Drug release from bi-layer tablet was studied in acidic medium and buffer medium for two and six hours respectively. Sustained release of tramadol hydrochloride was observed with a controlled fashion that was characteristic to the type and extent of polymer used. % Drug release from eight-hour dissolution study was fitted with several kinetic models. Mean dissolution time (MDT) and fractional dissolution values (T25%, T50% and T80%) were also calculated as well, to compare the retarding ability of the polymers. Methocel K15MCR was found to be the most effective in rate retardation of freely water-soluble tramadol hydrochloride compared to Methocel K4M and Capbomer 974P, when incorporated at equal ratio in the formulation.

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Torres, Gonzalo E; Wagner, Amy K

2015-03-02

Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology. Copyright © 2015 Elsevier B.V. All rights reserved.

Estimating accidental pollutant releases in the built environment from turbulent concentration signals

NASA Astrophysics Data System (ADS)

Ben Salem, N.; Salizzoni, P.; Soulhac, L.

2017-01-01

We present an inverse atmospheric model to estimate the mass flow rate of an impulsive source of pollutant, whose position is known, from concentration signals registered at receptors placed downwind of the source. The originality of this study is twofold. Firstly, the inversion is performed using high-frequency fluctuating, i.e. turbulent, concentration signals. Secondly, the inverse algorithm is applied to a dispersion process within a dense urban canopy, at the district scale, and a street network model, SIRANERISK, is adopted. The model, which is tested against wind tunnel experiments, simulates the dispersion of short-duration releases of pollutant in different typologies of idealised urban geometries. Results allow us to discuss the reliability of the inverse model as an operational tool for crisis management and the risk assessments related to the accidental release of toxic and flammable substances.

Drug release from and hydrolytic degradation of a poly(ethylene glycol) grafted poly(3-hydroxyoctanoate).

PubMed

Kim, Hyung Woo; Chung, Chung Wook; Hwang, Sung Joo; Rhee, Young Ha

2005-07-01

Monoacrylate-poly(ethylene glycol)-grafted poly(3-hydroxyoctanoate) (PEGMA-g-PHO) copolymers were synthesized to develop a swelling-controlled release delivery system for ibuprofen as a model drug. The in vitro hydrolytic degradation of and the drug release from a film made of the PEGMA-g-PHO copolymer were carried out in a phosphate buffer saline (pH 7.4) medium. The hydrolytic degradation of the copolymer was strongly dependent on the degree of grafting (DG) of the PEGMA group. The degradation rate of the copolymer films in vitro increased with increasing DG of the PEGMA group on the PHO chain. The copolymer films showed a controlled delivery of ibuprofen to the medium in periods of time that depend on the composition, hydrophilic/hydrophobic characteristics, initial drug loading amount and film thickness of the graft copolymer support. The drug release rate from the grafted copolymer films was faster than the rate of weight loss of the films themselves. In particular, a combination of the low DG of the PEGMA group in the PHO chains with the low ibuprofen solubility in water led to long-term constant release from these matrices in vitro.

Lubiprostone stimulates small intestinal mucin release

PubMed Central

2012-01-01

Background Lubiprostone is a synthetic bicyclic fatty acid derivative of prostaglandin E1 (PGE1) used for chronic constipation. The best known action of lubiprostone is simulation of Cl- dependent fluid secretion. In a mouse model of the genetic disease cystic fibrosis, we previously showed that in vivo administration of lubiprostone resulted in greater mucus accumulation in the small intestine. The aim of this study was to directly test whether lubiprostone stimulates intestinal mucin release. Methods Mucin release was measured by mounting segments (4-5 cm) of mouse proximal-mid small intestine in an organ bath, allowing access to the perfusate (luminal) and the bath (serosal) solutions. Nifedipine (10-6 M) and indomethacin (10-5 M) were included in all solutions to inhibit smooth muscle activity and endogenous prostaglandin production, respectively. The tissue was equilibrated under flow for 30 min, using the perfusate collected during the final 10 min of the equilibration period to measure unstimulated release rate. Stimulus was then added to either the perfusate or the bath and the perfusate was collected for another 30 min to measure the stimulated mucin release rate. Mucin in perfusates was quantified by periodic acid-Schiff's base dot-blot assay, using purified pig gastric mucin as a standard. Results When applied luminally at 1 μM lubiprostone was ineffective at stimulating mucin release. When added to the serosal solution, 1 μM lubiprostone stimulated mucin release to ~300% of the unstimulated rate. As a positive control, serosal 1 μM prostaglandin E2 increased mucin release to ~400% of the unstimulated rate. Conclusions These results support the idea that lubiprostone has prostaglandin-like actions on the intestine, which includes stimulation of mucin release. Stimulation of mucin release by lubiprostone may be protective in gastrointestinal conditions where loss of mucus is believed to contribute to pathogenesis. Thus, in addition to chronic constipation, there is greater potential for the therapeutic applications of lubiprostone. PMID:23130661

Lubiprostone stimulates small intestinal mucin release.

PubMed

De Lisle, Robert C

2012-11-06

Lubiprostone is a synthetic bicyclic fatty acid derivative of prostaglandin E1 (PGE1) used for chronic constipation. The best known action of lubiprostone is simulation of Cl- dependent fluid secretion. In a mouse model of the genetic disease cystic fibrosis, we previously showed that in vivo administration of lubiprostone resulted in greater mucus accumulation in the small intestine. The aim of this study was to directly test whether lubiprostone stimulates intestinal mucin release. Mucin release was measured by mounting segments (4-5 cm) of mouse proximal-mid small intestine in an organ bath, allowing access to the perfusate (luminal) and the bath (serosal) solutions. Nifedipine (10-6 M) and indomethacin (10-5 M) were included in all solutions to inhibit smooth muscle activity and endogenous prostaglandin production, respectively. The tissue was equilibrated under flow for 30 min, using the perfusate collected during the final 10 min of the equilibration period to measure unstimulated release rate. Stimulus was then added to either the perfusate or the bath and the perfusate was collected for another 30 min to measure the stimulated mucin release rate. Mucin in perfusates was quantified by periodic acid-Schiff's base dot-blot assay, using purified pig gastric mucin as a standard. When applied luminally at 1 μM lubiprostone was ineffective at stimulating mucin release. When added to the serosal solution, 1 μM lubiprostone stimulated mucin release to ~300% of the unstimulated rate. As a positive control, serosal 1 μM prostaglandin E2 increased mucin release to ~400% of the unstimulated rate. These results support the idea that lubiprostone has prostaglandin-like actions on the intestine, which includes stimulation of mucin release. Stimulation of mucin release by lubiprostone may be protective in gastrointestinal conditions where loss of mucus is believed to contribute to pathogenesis. Thus, in addition to chronic constipation, there is greater potential for the therapeutic applications of lubiprostone.

Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®.

PubMed

Caccavo, D; Barba, A A; d'Amore, M; De Piano, R; Lamberti, G; Rossi, A; Colombo, P

2017-12-01

The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used asa fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel Pharmacokinetic-Pharmacodynamic Model for Prediction of Outcomes with an Extended-Release Formulation of Ciprofloxacin

PubMed Central

Meagher, Alison K.; Forrest, Alan; Dalhoff, Axel; Stass, Heino; Schentag, Jerome J.

2004-01-01

The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers. The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approximately 50% greater with the IR formulation. The geometric mean plasma ciprofloxacin concentrations were applied to an in vitro pharmacokinetic-pharmacodynamic model exposing three different clinical strains of Escherichia coli (MICs, 0.03, 0.5, and 2.0 mg/liter) to 24 h of simulated concentrations in plasma. A novel mathematical model was derived to describe the time course of bacterial CFU, including capacity-limited replication and first-order rate of bacterial clearance, and to model the effects of ciprofloxacin concentrations on these processes. A “mixture model” was employed which allowed as many as three bacterial subpopulations to describe the total bacterial load at any moment. Comparing the two formulations at equivalent daily doses, the rates and extents of bacterial killing were similar with the IR and XR formulations at MICs of 0.03 and 2.0 mg/liter. At an MIC of 0.5 mg/liter, however, the 1,000-mg/day XR formulation showed a moderate advantage in antibacterial effect: the area under the CFU-time curve was 45% higher for the IR regimen; the nadir log CFU and 24-h log CFU values for the IR regimen were 3.75 and 2.49, respectively; and those for XR were 4.54 and 3.13, respectively. The mathematical model explained the differences in bacterial killing rate for two regimens with identical AUC/MIC ratios. PMID:15155200

Cadmium biosorption rate in protonated Sargassum biomass

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

Yang, J.; Volesky, B.

1999-03-01

Biosorption of the heavy metal ion Cd{sup 2+} by protonated nonliving brown alga Sargassum fluitans biomass was accompanied by the release of hydrogen protons from the biomass. The uptake of cadmium and the release of proton matched each other throughout the biosorption process. The end-point titration methodology was used to maintain the constant pH 4.0 for developing the dynamic sorption rate. The sorption isotherm could be well represented by the Langmuir sorption model. A mass transfer model assuming the intraparticle diffusion in a one-dimensional thin plate as a controlling step was developed to describe the overall biosorption rate of cadmiummore » ions in flat seaweed biomass particles. The overall biosorption mathematical model equations were solved numerically yielding the effective diffusion coefficient D{sub e} about 3.5 {times} 10{sup {minus}6} cm{sup 2}/s. This value matches that obtained for the desorption process and is approximately half of that of the molecular diffusion coefficient for cadmium ions in aqueous solution.« less

Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

PubMed

Ijaz, Hira; Qureshi, Junaid; Danish, Zeeshan; Zaman, Muhammad; Abdel-Daim, Mohamed; Hanif, Muhammad; Waheed, Imran; Mohammad, Imran Shair

2015-11-01

The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully.

Theory for rates, equilibrium constants, and Brønsted slopes in F1-ATPase single molecule imaging experiments

PubMed Central

Volkán-Kacsó, Sándor; Marcus, Rudolph A.

2015-01-01

A theoretical model of elastically coupled reactions is proposed for single molecule imaging and rotor manipulation experiments on F1-ATPase. Stalling experiments are considered in which rates of individual ligand binding, ligand release, and chemical reaction steps have an exponential dependence on rotor angle. These data are treated in terms of the effect of thermodynamic driving forces on reaction rates, and lead to equations relating rate constants and free energies to the stalling angle. These relations, in turn, are modeled using a formalism originally developed to treat electron and other transfer reactions. During stalling the free energy profile of the enzymatic steps is altered by a work term due to elastic structural twisting. Using biochemical and single molecule data, the dependence of the rate constant and equilibrium constant on the stall angle, as well as the Børnsted slope are predicted and compared with experiment. Reasonable agreement is found with stalling experiments for ATP and GTP binding. The model can be applied to other torque-generating steps of reversible ligand binding, such as ADP and Pi release, when sufficient data become available. PMID:26483483

A theoretical approach to evaluate the release rate of acetaminophen from erosive wax matrix dosage forms.

PubMed

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

2011-07-29

To predict drug dissolution and understand the mechanisms of drug release from wax matrix dosage forms containing glyceryl monostearate (GM; a wax base), aminoalkyl methacrylate copolymer E (AMCE; a pH-dependent functional polymer), and acetaminophen (APAP; a model drug), we tried to derive a novel mathematical model with respect to erosion and diffusion theory. Our model exhibited good agreement with the whole set of experimentally obtained values pertaining to APAP release at pH 4.0 and pH 6.5. In addition, this model revealed that the eroding speed of wax matrices was strongly influenced by the loading content of AMCE, but not that of APAP, and that the diffusion coefficient increased as APAP loading decreased and AMCE loading increased, thus directly defining the physicochemical properties of erosion and diffusion. Therefore, this model might prove a useful equation for the precise prediction of dissolution and for understanding the mechanisms of drug release from wax matrix dosage forms. Copyright © 2011 Elsevier B.V. All rights reserved.

Nambe Pueblo Water Budget and Forecasting model.

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

Brainard, James Robert

2009-10-01

This report documents The Nambe Pueblo Water Budget and Water Forecasting model. The model has been constructed using Powersim Studio (PS), a software package designed to investigate complex systems where flows and accumulations are central to the system. Here PS has been used as a platform for modeling various aspects of Nambe Pueblo's current and future water use. The model contains three major components, the Water Forecast Component, Irrigation Scheduling Component, and the Reservoir Model Component. In each of the components, the user can change variables to investigate the impacts of water management scenarios on future water use. The Watermore » Forecast Component includes forecasting for industrial, commercial, and livestock use. Domestic demand is also forecasted based on user specified current population, population growth rates, and per capita water consumption. Irrigation efficiencies are quantified in the Irrigated Agriculture component using critical information concerning diversion rates, acreages, ditch dimensions and seepage rates. Results from this section are used in the Water Demand Forecast, Irrigation Scheduling, and the Reservoir Model components. The Reservoir Component contains two sections, (1) Storage and Inflow Accumulations by Categories and (2) Release, Diversion and Shortages. Results from both sections are derived from the calibrated Nambe Reservoir model where historic, pre-dam or above dam USGS stream flow data is fed into the model and releases are calculated.« less

Novel kinetic model of the removal of divalent heavy metal ions from aqueous solutions by natural clinoptilolite.

PubMed

Jovanovic, Mina; Rajic, Nevenka; Obradovic, Bojana

2012-09-30

Removal of heavy metal ions from aqueous solutions using zeolites is widely described by pseudo-second order kinetics although this model may not be valid under all conditions. In this work, we have extended approaches used for derivation of this model in order to develop a novel kinetic model that is related to the ion exchange mechanism underlying sorption of metal ions in zeolites. The novel model assumed two reversible steps, i.e. release of sodium ions from the zeolite lattice followed by bonding of the metal ion. The model was applied to experimental results of Cu(II) sorption by natural clinoptilolite-rich zeolitic tuff at different initial concentrations and temperatures and then validated by predictions of ion exchange kinetics of other divalent heavy metal ions (i.e. Mn(II), Zn(II) and Pb(II)). Model predictions were in excellent agreements with experimental data for all investigated systems. In regard to the proposed mechanism, modeling results implied that the sodium ion release rate was constant for all investigated metals while the overall rate was mainly determined by the rate of heavy metal ion bonding to the lattice. In addition, prediction capabilities of the novel model were demonstrated requiring one experimentally determined parameter, only. Copyright © 2012 Elsevier B.V. All rights reserved.

Simulated Carbon Cycling in a Model Microbial Mat.

NASA Astrophysics Data System (ADS)

Decker, K. L.; Potter, C. S.

2006-12-01

We present here the novel addition of detailed organic carbon cycling to our model of a hypersaline microbial mat ecosystem. This ecosystem model, MBGC (Microbial BioGeoChemistry), simulates carbon fixation through oxygenic and anoxygenic photosynthesis, and the release of C and electrons for microbial heterotrophs via cyanobacterial exudates and also via a pool of dead cells. Previously in MBGC, the organic portion of the carbon cycle was simplified into a black-box rate of accumulation of simple and complex organic compounds based on photosynthesis and mortality rates. We will discuss the novel inclusion of fermentation as a source of carbon and electrons for use in methanogenesis and sulfate reduction, and the influence of photorespiration on labile carbon exudation rates in cyanobacteria. We will also discuss the modeling of decomposition of dead cells and the ultimate release of inorganic carbon. The detailed modeling of organic carbon cycling is important to the accurate representation of inorganic carbon flux through the mat, as well as to accurate representation of growth models of the heterotrophs under different environmental conditions. Because the model ecosystem is an analog of ancient microbial mats that had huge impacts on the atmosphere of early earth, this MBGC can be useful as a biological component to either early earth models or models of other planets that potentially harbor life.

Toxic industrial chemical (TIC) source emissions modeling for pressurized liquefied gases

NASA Astrophysics Data System (ADS)

Britter, Rex; Weil, Jeffrey; Leung, Joseph; Hanna, Steven

2011-01-01

The objective of this article is to report current toxic industrial chemical (TIC) source emissions formulas appropriate for use in atmospheric comprehensive risk assessment models so as to represent state-of-the-art knowledge. The focus is on high-priority scenarios, including two-phase releases of pressurized liquefied gases such as chlorine from rail cars. The total mass released and the release duration are major parameters, as well as the velocity, thermodynamic state, and amount and droplet sizes of imbedded aerosols of the material at the exit of the rupture, which are required as inputs to the subsequent jet and dispersion modeling. Because of the many possible release scenarios that could develop, a suite of model equations has been described. These allow for gas, two-phase or liquid storage and release through ruptures of various types including sharp-edged and "pipe-like" ruptures. Model equations for jet depressurization and phase change due to flashing are available. Consideration of the importance of vessel response to a rupture is introduced. The breakup of the jet into fine droplets and their subsequent suspension and evaporation, or rainout is still a significant uncertainty in the overall modeling process. The recommended models are evaluated with data from various TIC field experiments, in particular recent experiments with pressurized liquefied gases. It is found that there is typically a factor of two error in models compared with research-grade observations of mass flow rates. However, biases are present in models' estimates of the droplet size distributions resulting from flashing releases.

Numerical investigation of the effect of delaminations on fracture characteristics of glare

NASA Astrophysics Data System (ADS)

Bhat, Sunil; Narayanan, S.

2013-10-01

A finite element examination of the effect of delaminations on fracture characteristics of fibre metal laminate (Glare), by comparing energy release rates of normal cracks in laminates with and without delaminations, is presented in the paper. Glare comprising thin cracked 2024-T3 aerospace aluminum alloy layers alternately bonded with E-glass fibre based composite prepregs is considered for the analysis. Delaminations are modeled with interface cohesive elements. Energy release rates of normal cracks in laminates with delaminations are found to be higher than those in the laminates without delaminations.

The effect of charge on the release kinetics from polysaccharide-nanoclay composites

NASA Astrophysics Data System (ADS)

Del Buffa, Stefano; Grifoni, Emanuele; Ridi, Francesca; Baglioni, Piero

2015-03-01

The objective of this study was to integrate inorganic halloysite nanotubes (HNT) with chitosan and hyaluronic acid to obtain hybrid nanocomposites with opposing charges and to investigate their potential in the controlled release of drug model probes. Two oppositely charged polysaccharides, chitosan and hyaluronic acid, were selected for their biocompatibility and their importance in biomedical applications. The high surface area and the hollow nanometric-sized lumen of HNT allowed for the efficient loading of rhodamine 110 and carboxyfluorescein, used as models for oppositely charged drugs. In the case of chitosan, the preparation of the nanocomposite was carried out exploiting the electrostatic interaction between the polymer and HNT in water, while with hyaluronic acid, a covalent functionalization strategy was employed to couple the polymer with the clay. Nanocomposites were characterized with thermal, microscopic, and spectroscopic techniques, and the release kinetics of the model compounds was assessed by fluorescence measurements. The release curves were fitted with a model able to account for the desorption process from the external and the internal halloysite surfaces. The results show that both polymeric coatings alter the release of the probes, indicating a key role of both charge and coating composition on the initial and final amount of released dye, as well as on the rate of the desorption process.

Development of a Model for the Heat Release Rate of Wood. A Status Report.

DTIC Science & Technology

1985-05-01

K) *contraction factor L effective heat of gasification (kJ/kg) (positive) Lv latent heat of vaporization of water (kJ/kg) (positive) m mass (kg) M...designates the slice bounded by the rear surface 0 ambient or original *0 oxygen R radiation rel release S front surface of specimen Vol volatiles ix w water ...calorimeter. Along the other pathway, char is formed with the release of water and other volatiles having low heats of combustion. The effective heat of

Modeling Patterns of Total Dissolved Solids Release from Central Appalachia, USA, Mine Spoils.

PubMed

Clark, Elyse V; Zipper, Carl E; Daniels, W Lee; Orndorff, Zenah W; Keefe, Matthew J

2017-01-01

Surface mining in the central Appalachian coalfields (USA) influences water quality because the interaction of infiltrated waters and O with freshly exposed mine spoils releases elevated levels of total dissolved solids (TDS) to streams. Modeling and predicting the short- and long-term TDS release potentials of mine spoils can aid in the management of current and future mining-influenced watersheds and landscapes. In this study, the specific conductance (SC, a proxy variable for TDS) patterns of 39 mine spoils during a sequence of 40 leaching events were modeled using a five-parameter nonlinear regression. Estimated parameter values were compared to six rapid spoil assessment techniques (RSATs) to assess predictive relationships between model parameters and RSATs. Spoil leachates reached maximum values, 1108 ± 161 μS cm on average, within the first three leaching events, then declined exponentially to a breakpoint at the 16th leaching event on average. After the breakpoint, SC release remained linear, with most spoil samples exhibiting declines in SC release with successive leaching events. The SC asymptote averaged 276 ± 25 μS cm. Only three samples had SCs >500 μS cm at the end of the 40 leaching events. Model parameters varied with mine spoil rock and weathering type, and RSATs were predictive of four model parameters. Unweathered samples released higher SCs throughout the leaching period relative to weathered samples, and rock type influenced the rate of SC release. The RSATs for SC, total S, and neutralization potential may best predict certain phases of mine spoil TDS release. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

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.

Accelerated dissolution testing for controlled release microspheres using the flow-through dissolution apparatus.

PubMed

Collier, Jarrod W; Thakare, Mohan; Garner, Solomon T; Israel, Bridg'ette; Ahmed, Hisham; Granade, Saundra; Strong, Deborah L; Price, James C; Capomacchia, A C

2009-01-01

Theophylline controlled release capsules (THEO-24 CR) were used as a model system to evaluate accelerated dissolution tests for process and quality control and formulation development of controlled release formulations. Dissolution test acceleration was provided by increasing temperature, pH, flow rate, or adding surfactant. Electron microscope studies on the theophylline microspheres subsequent to each experiment showed that at pH values of 6.6 and 7.6 the microspheres remained intact, but at pH 8.6 they showed deterioration. As temperature was increased from 37-57 degrees C, no change in microsphere integrity was noted. Increased flow rate also showed no detrimental effect on integrity. The effect of increased temperature was determined to be the statistically significant variable.

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

Li, Dongdong, E-mail: lidongchem@sina.cn; Zhu, Yuntao; Liang, Zhiqiang

Highlights: ► The synthesized mesoporous hydroxyapatite has nanostructure and bioactivity. ► The materials have high surface area and amino group. ► The materials show higher drug loading and slower release rate than pure HAP. - Abstract: Mesoporous nanosized hydroxyapatite (HAP) functionalized by alendronate (ALN) was synthesized using cationic surfactant CTAB as template. The structural, morphological and textural properties were fully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and N{sub 2} adsorption/desorption. Then the obtained materials were performed as drug delivery carriers using ibuprofen (IBU) as a model drug to investigate their drug storage/releasemore » properties in simulated body fluid (SBF). The materials showed relatively slower release rate compared with HAP due to the ionic interaction between -NH{sub 3}{sup +} on the matrix and -COO{sup −}belongs to IBU. The system provides a new concept for improving the drug loading or slowing down the release rate.« less

Delivery of prazosin hydrochloride from osmotic pump system prepared by coating the core tablet with an indentation.

PubMed

Liu, Longxiao; Wang, Jinchao; Zhu, Suyan

2007-04-01

The preparation of an osmotic pump tablet was simplified by elimination of laser drilling using prazosin hydrochloride as the model drug. The osmotic pump system was obtained by coating the indented core tablet compressed by the punch with a needle. A multiple regression equation was achieved with the experimental data of core tablet formulations, and then the formulation was optimized. The influences of the indentation size of the core tablet, environmental media, and agitation rate on drug release profile were investigated. The optimal osmotic pump tablet was found to deliver prazosin hydrochloride at an approximately constant rate up to 24 hr, and independent on both release media and agitation rate. Indentation size of core tablet hardly affected drug release in the range of 0.80-1.15 mm. The method that is simplified by elimination of laser drilling may be promising for preparation of an osmotic pump tablet.

[Effect of the interaction of microorganisms and iron oxides on arsenic releasing into groundwater in Chinese Loess].

PubMed

Xie, Yun-Yun; Chen, Tian-Hu; Zhou, Yue-Fei; Xie, Qiao-Qin

2013-10-01

A large part of groundwater in the Chinese Loess Plateau area is characterized by high arsenic concentration. Anaerobic bacteria have been considered to play key roles in promoting arsenic releasing from loess to groundwater. However, this hypothesis remains unconfirmed. Based on modeling experiments, this study investigated the speciation of arsenic in loess, and then determined the release rates and quantities of arsenic with the mediation of anaerobic bacteria. The results showed that arsenic contents in loess were between 23 mg.kg-1 and 30 mg.kg-1. No obvious arsenic content difference among loess samples was observed. The ratios for specific adsorbed, iron oxides co-precipitated and silicate co-precipitated arsenic were 37.76% , 36. 15% and 25. 69% , respectively. Indigenous microorganisms, dissimilatory iron reducing bacteria (DIRB) and sulfate reducing bacteria (SRB) could all promote the release of arsenic from loess. Organic matters highly affected the release rates. More than 100 mg.L-1 sodium lactate was required for all bacterial experiments to facilitate obvious arsenic release. Considering the redox condition in loess, the contribution of SRB to arsenic release in loess area was less feasible than that of DIRB and indigenous microorganisms.

Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: An assessment on mechanism of drug release.

PubMed

Al-Hanbali, Othman A; Hamed, Rania; Arafat, Mosab; Bakkour, Youssef; Al-Matubsi, Hisham; Mansour, Randa; Al-Bataineh, Yazan; Aldhoun, Mohammad; Sarfraz, Muhammad; Dardas, Abdel Khaleq Yousef

2018-01-01

In this study, hydrophilic hydroxypropyl methylcellulose matrices with various concentrations of Poloxamer 188 were used in the development of oral controlled release tablets containing diclofenac sodium. Four formulations of hydrophilic matrix tablets containing 16.7% w/w HPMC and 0, 6.7, 16.7 and 25.0% w/w Poloxamer 188, respectively, were developed. Tablets were prepared by direct compression and characterized for diameter, hardness, thickness, weight and uniformity of content. The influence of various blends of hydroxypropyl methylcellulose and Poloxamer 188 on the in vitro dissolution profile and mechanism of drug release of was investigated. In the four formulations, the rate of drug release decreased with increasing the concentration of Poloxamer 188 at the initial dissolution stages due to the increase in the apparent viscosity of the gel diffusion layer. However, in the late dissolution stages, the rate of drug release increased with increasing Poloxamer 188 concentration due to the increase in wettability and dissolution of the matrix. The kinetic of drug release from the tablets followed non-Fickian mechanism, as predicted by Korsmeyer-Peppas model, which involves diffusion through the gel layer and erosion of the matrix system.

On numerical model of time-dependent processes in three-dimensional porous heat-releasing objects

NASA Astrophysics Data System (ADS)

Lutsenko, Nickolay A.

2016-10-01

The gas flows in the gravity field through porous objects with heat-releasing sources are investigated when the self-regulation of the flow rate of the gas passing through the porous object takes place. Such objects can appear after various natural or man-made disasters (like the exploded unit of the Chernobyl NPP). The mathematical model and the original numerical method, based on a combination of explicit and implicit finite difference schemes, are developed for investigating the time-dependent processes in 3D porous energy-releasing objects. The advantage of the numerical model is its ability to describe unsteady processes under both natural convection and forced filtration. The gas cooling of 3D porous objects with different distribution of heat sources is studied using computational experiment.

Rapid rates of aerobic methane oxidation at the feather edge of gas hydrate stability in the waters of Hudson Canyon, US Atlantic Margin

NASA Astrophysics Data System (ADS)

Leonte, Mihai; Kessler, John D.; Kellermann, Matthias Y.; Arrington, Eleanor C.; Valentine, David L.; Sylva, Sean P.

2017-05-01

Aerobic oxidation is an important methane sink in seawater overlying gas seeps. Recent surveys have identified active methane seeps in the waters of Hudson Canyon, US Atlantic Margin near the updip limit of methane clathrate hydrate stability. The close proximity of these seeps to the upper stability limit of methane hydrates suggests that changing bottom water temperatures may influence the release rate of methane into the overlying water column. In order to assess the significance of aerobic methane oxidation in limiting the atmospheric expression of methane released from Hudson Canyon, the total extent of methane oxidized along with integrated oxidation rates were quantified. These calculations were performed by combining the measurements of the natural levels of methane concentrations, stable carbon isotopes, and water current velocities into kinetic isotope models yielding rates ranging from 22.8 ± 17 to 116 ± 76 nM/day with an average of 62.7 ± 37 nM/day. Furthermore, an average of 63% of methane released into the water column from an average depth of 515 m was oxidized before leaving this relatively small study area (6.5 km2). Results from the kinetic isotope model were compared to previously-published but concurrently-sampled ex situ measurements of oxidation potential performed using 13C-labeled methane. Ex situ rates were substantially lower, ranging from 0.1 to 22.5 nM/day with an average of 5.6 ± 2.3 nM/day, the discrepancy likely due to the inherent differences between these two techniques. Collectively, the results reveal exceptionally-rapid methane oxidation, with turnover times for methane as low as 0.3-3.7 days, indicating that methane released to the water column is removed quantitatively within the greater extent of Hudson Canyon. The red line represents the original Rayleigh model output, Eq. (1), detailed in the text. The red line represents the original Rayleigh model output, Eq. (1), detailed in the text.

A method for simulating the release of natural gas from the rupture of high-pressure pipelines in any terrain.

PubMed

Deng, Yajun; Hu, Hongbing; Yu, Bo; Sun, Dongliang; Hou, Lei; Liang, Yongtu

2018-01-15

The rupture of a high-pressure natural gas pipeline can pose a serious threat to human life and environment. In this research, a method has been proposed to simulate the release of natural gas from the rupture of high-pressure pipelines in any terrain. The process of gas releases from the rupture of a high-pressure pipeline is divided into three stages, namely the discharge, jet, and dispersion stages. Firstly, a discharge model is established to calculate the release rate of the orifice. Secondly, an improved jet model is proposed to obtain the parameters of the pseudo source. Thirdly, a fast-modeling method applicable to any terrain is introduced. Finally, based upon these three steps, a dispersion model, which can take any terrain into account, is established. Then, the dispersion scenarios of released gas in four different terrains are studied. Moreover, the effects of pipeline pressure, pipeline diameter, wind speed and concentration of hydrogen sulfide on the dispersion scenario in real terrain are systematically analyzed. The results provide significant guidance for risk assessment and contingency planning of a ruptured natural gas pipeline. Copyright © 2017. Published by Elsevier B.V.

Effects of Sulfate, Chloride, and Bicarbonate on Iron Stability in a PVC-U Drinking Pipe

PubMed Central

Wang, Jiaying; Tao, Tao; Yan, Hexiang

2017-01-01

In order to describe iron stability in plastic pipes and to ensure the drinking water security, the influence factors and rules for iron adsorption and release were studied, dependent on the Unplasticized poly (vinyl chloride) (PVC-U) drinking pipes employed in this research. In this paper, sulfate, chloride, and bicarbonate, as well as synthesized models, were chosen to investigate the iron stability on the inner wall of PVC-U drinking pipes. The existence of the three kinds of anions could significantly affect the process of iron adsorption, and a positive association was found between the level of anion concentration and the adsorption rate. However, the scaling formed on the inner surface of the pipes would be released into the water under certain conditions. The Larson Index (LI), used for a synthetic consideration of anion effects on iron stability, was selected to investigate the iron release under multi-factor conditions. Moreover, a well fitted linear model was established to gain a better understanding of iron release under multi-factor conditions. The simulation results demonstrated that the linear model was better fitted than the LI model for the prediction of iron release. PMID:28629192

The association of the original OSHA chemical hazard communication standard with reductions in acute work injuries/illnesses in private industry and the industrial releases of chemical carcinogens.

PubMed

Oleinick, Arthur

2014-02-01

OSHA predicted the original chemical Hazard Communication Standard (HCS) would cumulatively reduce the lost workday acute injury/illness rate for exposure events by 20% over 20 years and reduce exposure to chemical carcinogens. JoinPoint trend software identified changes in the rate of change of BLS rates for days away from work for acute injuries/illnesses during 1992-2009 for manufacturing and nonmanufacturing industries for both chemical, noxious or allergenic injury exposure events and All other exposure events. The annual percent change in the rates was used to adjust observed numbers of cases to estimate their association with the standard. A case-control study of EPA's Toxic Release Inventory 1988-2009 data compared carcinogen and non-carcinogens' releases. The study estimates that the HCS was associated with a reduction in the number of acute injuries/illnesses due to chemical injury exposure events over the background rate in the range 107,569-459,395 (Hudson method/modified BIC model) depending on whether the HCS is treated as a marginal or sole factor in the decrease. Carcinogen releases have declined at a substantially faster rate than control non-carcinogens. The previous HCS standard was associated with significant reductions in chemical event acute injuries/illnesses and chemical carcinogen exposures. © 2013 Wiley Periodicals, Inc.

Modeling of the Modulation by Buffers of Ca2+ Release through Clusters of IP3 Receptors

PubMed Central

Zeller, S.; Rüdiger, S.; Engel, H.; Sneyd, J.; Warnecke, G.; Parker, I.; Falcke, M.

2009-01-01

Abstract Intracellular Ca2+ release is a versatile second messenger system. It is modeled here by reaction-diffusion equations for the free Ca2+ and Ca2+ buffers, with spatially discrete clusters of stochastic IP3 receptor channels (IP3Rs) controlling the release of Ca2+ from the endoplasmic reticulum. IP3Rs are activated by a small rise of the cytosolic Ca2+ concentration and inhibited by large concentrations. Buffering of cytosolic Ca2+ shapes global Ca2+ transients. Here we use a model to investigate the effect of buffers with slow and fast reaction rates on single release spikes. We find that, depending on their diffusion coefficient, fast buffers can either decouple clusters or delay inhibition. Slow buffers have little effect on Ca2+ release, but affect the time course of the signals from the fluorescent Ca2+ indicator mainly by competing for Ca2+. At low [IP3], fast buffers suppress fluorescence signals, slow buffers increase the contrast between bulk signals and signals at open clusters, and large concentrations of buffers, either fast or slow, decouple clusters. PMID:19686646

Yardang evolution from maturity to demise

NASA Astrophysics Data System (ADS)

Barchyn, Thomas E.; Hugenholtz, Chris H.

2015-07-01

Yardangs are enigmatic wind-parallel ridges sculpted by aeolian processes that are found extensively in arid environments on Earth and Mars. No general theory exists to explain the long-term evolution of yardangs, curtailing modeling of landscape evolution and dynamics of suspended sediment release. We present a hypothesis of yardang evolution using relative rates of sediment flux, interyardang corridor downcutting, yardang denudation, substrate erodibility, and substrate clast content. To develop and sustain yardangs, corridor downcutting must exceed yardang vertical denudation and deflation. However, erosion of substrate yields considerable quantities of sediment that shelters corridors, slowing downcutting. We model the evolution of yardangs through various combinations of rates and substrate compositions, demonstrating the life span, suspended sediment release, and resulting landscape evolution. We find that yardangs have a distinct and predictable evolution, with inevitable demise and unexpectedly dynamic and autogenic erosion rates driven by subtle differences in substrate clast composition.

The Influence of Polyethylene Glycol Solution on the Dissolution Rate of Sustained Release Morphine.

PubMed

Hodgman, Michael; Holland, Michael G; Englich, Ulrich; Wojcik, Susan M; Grant, William D; Leitner, Erich

2016-12-01

Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350 g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations. An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations. In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG. The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.

Assessing the impacts of sustainable agricultural practices for water quality improvements in the Vouga catchment (Portugal) using the SWAT model.

PubMed

Rocha, João; Roebeling, Peter; Rial-Rivas, María Ermitas

2015-12-01

The extensive use of fertilizers has become one of the most challenging environmental issues in agricultural catchment areas. In order to reduce the negative impacts from agricultural activities and to accomplish the objectives of the European Water Framework Directive we must consider the implementation of sustainable agricultural practices. In this study, we assess sustainable agricultural practices based on reductions in N-fertilizer application rates (from 100% to 0%) and N-application methods (single, split and slow-release) across key agricultural land use classes in the Vouga catchment, Portugal. The SWAT model was used to relate sustainable agricultural practices, agricultural yields and N-NO3 water pollution deliveries. Results show that crop yields as well as N-NO3 exportation rates decrease with reductions in N-application rates and single N-application methods lead to lower crop yields and higher N-NO3 exportation rates as compared to split and slow-release N-application methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Mineralization dynamics in soil fertilized with seaweed-fish waste compost.

PubMed

Illera-Vives, Marta; López-Fabal, Adolfo; López-Mosquera, M Elvira; Ribeiro, Henrique M

2015-12-01

Seaweed and fish waste can be composted together to obtain fertilizer with high organic matter and nutrient contents. The nutrients, however, are mostly in organic form and must be mineralized to make them available to plants. The objective of this work was to establish a usage guideline for the compost by studying its mineralization dynamics. Also, the release of inorganic N and C from soil fertilized with the compost was monitored and modelled. C and N were released throughout the assay, to an extent significantly dependent on fertilizer rate. Mineralization of both elements fitted a first-order exponential model, and each fertilizer rate required using a specific fitting model. An increased rate favoured mineralization (especially of carbon). After 90 days, 2.3% of C and 7.7% of N were mineralized (and 23.3% of total nitrogen made plant available) with the higher rate. C mineralization was slow because organic matter in the compost was very stable. On the other hand, the relatively high initial content in mineral N of the compost increased gradually by the effect of mineralization. The amount of N available would suffice to meet the requirements of moderately demanding crops at the lower fertilizer rate, and even those of more demanding crops at the higher rate. © 2015 Society of Chemical Industry.

Chitosan nanoparticles for the linear release of model cationic Peptide.

PubMed

Piras, Anna Maria; Sandreschi, Stefania; Maisetta, Giuseppantonio; Esin, Semih; Batoni, Giovanna; Chiellini, Federica

2015-07-01

The present study is focused on the development of a model drug delivery system (DDS) based on Chitosan (CS) nanoparticles using Renin substrate I (RSI) as model agent. RSI shares the main chemical-physical features of several biologically active antimicrobial peptides (AMPs). AMPs have a great therapeutic potential that is hampered by their lability in the biological fluids and as such they are perfect candidates for DDS. The development studies of quality DDS loaded with AMPs would require highly sensitive and specific quantification assays. The use of RSI allowed for the fine-tuning and optimization of the formulation parameters to promote the hydrophobic interactions between CS and the cationic peptide, favour the loading of the active ingredient and enhance the release properties of the carrier. RSI was encapsulated in chitosan NPs by mean of ionic gelation and a chromogenic enzymatic essay was carried out for the release kinetics evaluation. The developed formulations displayed almost 100% of encapsulation efficacy, low burst percentages, and a linear release of the model peptide. A release model was created showing a direct dependence on both the amount of RSI and NPs radius. Although CS has always been formulated with negatively charged active agents (e.g. oligonucleotides or anionic proteins), the use of ionotropic gelation in presence of a small cationic active agent promoted the formation of "core-shell" NPs. The described model, with tuneable linear release rates, appears eligible for further exploitation such as the loading of therapeutically active AMPs.

The rate of polymerase release upon filling the gap between Okazaki fragments is inadequate to support cycling during lagging strand synthesis.

PubMed

Dohrmann, Paul R; Manhart, Carol M; Downey, Christopher D; McHenry, Charles S

2011-11-18

Upon completion of synthesis of an Okazaki fragment, the lagging strand replicase must recycle to the next primer at the replication fork in under 0.1 s to sustain the physiological rate of DNA synthesis. We tested the collision model that posits that cycling is triggered by the polymerase encountering the 5'-end of the preceding Okazaki fragment. Probing with surface plasmon resonance, DNA polymerase III holoenzyme initiation complexes were formed on an immobilized gapped template. Initiation complexes exhibit a half-life of dissociation of approximately 15 min. Reduction in gap size to 1 nt increased the rate of dissociation 2.5-fold, and complete filling of the gap increased the off-rate an additional 3-fold (t(1/2)~2 min). An exogenous primed template and ATP accelerated dissociation an additional 4-fold in a reaction that required complete filling of the gap. Neither a 5'-triphosphate nor a 5'-RNA terminated oligonucleotide downstream of the polymerase accelerated dissociation further. Thus, the rate of polymerase release upon gap completion and collision with a downstream Okazaki fragment is 1000-fold too slow to support an adequate rate of cycling and likely provides a backup mechanism to enable polymerase release when the other cycling signals are absent. Kinetic measurements indicate that addition of the last nucleotide to fill the gap is not the rate-limiting step for polymerase release and cycling. Modest (approximately 7 nt) strand displacement is observed after the gap between model Okazaki fragments is filled. To determine the identity of the protein that senses gap filling to modulate affinity of the replicase for the template, we performed photo-cross-linking experiments with highly reactive and non-chemoselective diazirines. Only the α subunit cross-linked, indicating that it serves as the sensor. Copyright © 2011 Elsevier Ltd. All rights reserved.

Modeling topographic influences on fuel moisture and fire danger in complex terrain to improve wildland fire management decision support

Treesearch

Zachary A. Holden; W. Matt Jolly

2011-01-01

Fire danger rating systems commonly ignore fine scale, topographically-induced weather variations. These variations will likely create heterogeneous, landscape-scale fire danger conditions that have never been examined in detail. We modeled the evolution of fuel moistures and the Energy Release Component (ERC) from the US National Fire Danger Rating System across the...

Surface displacements and energy release rates for constant stress drop slip zones in joined elastic quarter spaces

NASA Astrophysics Data System (ADS)

Rodgers, Michael J.; Wen, Shengmin; Keer, Leon M.

2000-08-01

A three-dimensional quasi-static model of faulting in an elastic half-space with a horizontal change of material properties (i.e., joined elastic quarter spaces) is considered. A boundary element method is used with a stress drop slip zone approach so that the fault surface relative displacements as well as the free surface displacements are approximated in elements over their respective domains. Stress intensity factors and free surface displacements are calculated for a variety of cases to show the phenomenological behavior of faulting in such a medium. These calculations showed that the behavior could be distinguished from a uniform half-space. Slip in a stiffer material increases, while slip in a softer material decreases the energy release rate and the free surface displacements. Also, the 1989 Kalapana earthquake was located on the basis of a series of forward searches using this method and leveling data. The located depth is 8 km, which is the closer to the seismically inferred depth than that determined from other models. Finally, the energy release rate, which can be used as a fracture criterion for fracture at this depth, is calculated to be 11.1×106 J m-2.

Does Don Fisher's high-pressure manifold model account for phloem transport and resource partitioning?

PubMed Central

Patrick, John W.

2013-01-01

The pressure flow model of phloem transport envisaged by Münch (1930) has gained wide acceptance. Recently, however, the model has been questioned on structural and physiological grounds. For instance, sub-structures of sieve elements may reduce their hydraulic conductances to levels that impede flow rates of phloem sap and observed magnitudes of pressure gradients to drive flow along sieve tubes could be inadequate in tall trees. A variant of the Münch pressure flow model, the high-pressure manifold model of phloem transport introduced by Donald Fisher may serve to reconcile at least some of these questions. To this end, key predicted features of the high-pressure manifold model of phloem transport are evaluated against current knowledge of the physiology of phloem transport. These features include: (1) An absence of significant gradients in axial hydrostatic pressure in sieve elements from collection to release phloem accompanied by transport properties of sieve elements that underpin this outcome; (2) Symplasmic pathways of phloem unloading into sink organs impose a major constraint over bulk flow rates of resources translocated through the source-path-sink system; (3) Hydraulic conductances of plasmodesmata, linking sieve elements with surrounding phloem parenchyma cells, are sufficient to support and also regulate bulk flow rates exiting from sieve elements of release phloem. The review identifies strong circumstantial evidence that resource transport through the source-path-sink system is consistent with the high-pressure manifold model of phloem transport. The analysis then moves to exploring mechanisms that may link demand for resources, by cells of meristematic and expansion/storage sinks, with plasmodesmal conductances of release phloem. The review concludes with a brief discussion of how these mechanisms may offer novel opportunities to enhance crop biomass yields. PMID:23802003

Panel Stiffener Debonding Analysis using a Shell/3D Modeling Technique

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Ratcliffe, James G.; Minguet, Pierre J.

2008-01-01

A shear loaded, stringer reinforced composite panel is analyzed to evaluate the fidelity of computational fracture mechanics analyses of complex structures. Shear loading causes the panel to buckle. The resulting out -of-plane deformations initiate skin/stringer separation at the location of an embedded defect. The panel and surrounding load fixture were modeled with shell elements. A small section of the stringer foot, web and noodle as well as the panel skin near the delamination front were modeled with a local 3D solid model. Across the width of the stringer fo to, the mixed-mode strain energy release rates were calculated using the virtual crack closure technique. A failure index was calculated by correlating the results with a mixed-mode failure criterion of the graphite/epoxy material. The objective was to study the effect of the fidelity of the local 3D finite element model on the computed mixed-mode strain energy release rates and the failure index.

Panel-Stiffener Debonding and Analysis Using a Shell/3D Modeling Technique

NASA Technical Reports Server (NTRS)

Krueger, Ronald; Ratcliffe, James G.; Minguet, Pierre J.

2007-01-01

A shear loaded, stringer reinforced composite panel is analyzed to evaluate the fidelity of computational fracture mechanics analyses of complex structures. Shear loading causes the panel to buckle. The resulting out-of-plane deformations initiate skin/stringer separation at the location of an embedded defect. The panel and surrounding load fixture were modeled with shell elements. A small section of the stringer foot, web and noodle as well as the panel skin near the delamination front were modeled with a local 3D solid model. Across the width of the stringer foot, the mixed-mode strain energy release rates were calculated using the virtual crack closure technique. A failure index was calculated by correlating the results with a mixed-mode failure criterion of the graphite/epoxy material. The objective was to study the effect of the fidelity of the local 3D finite element model on the computed mixed-mode strain energy release rates and the failure index.

Simple model for the reconstruction of radionuclide concentrations and radiation exposures along the Techa River

NASA Technical Reports Server (NTRS)

Vorobiova, M. I.; Degteva, M. O.; Neta, M. O. (Principal Investigator)

1999-01-01

The Techa River (Southern Urals, Russia) was contaminated in 1949-1956 by liquid radioactive wastes from the Mayak complex, the first Russian facility for the production of plutonium. The measurements of environmental contamination were started in 1951. A simple model describing radionuclide transport along the free-flowing river and the accumulation of radionuclides by bottom sediments is presented. This model successfully correlates the rates of radionuclide releases as reconstructed by the Mayak experts, hydrological data, and available environmental monitoring data for the early period of contamination (1949-1951). The model was developed to reconstruct doses for people who lived in the riverside communities during the period of the releases and who were chronically exposed to external and internal irradiation. The model fills the data gaps and permits reconstruction of external gamma-exposure rates in air on the river bank and radionuclide concentrations in river water used for drinking and other household needs in 1949-1951.

Rapid dissolution of propofol emulsions under sink conditions.

PubMed

Damitz, Robert; Chauhan, Anuj

2015-03-15

Pain accompanying intravenous injections of propofol is a major problem in anesthesia. Pain is ascribed to the interaction of propofol with the local vasculature and could be impacted by rapid dissolution of the emulsion formulation to release the drug. In this paper, we measure the dissolution of propofol emulsions including the commercial formulation Diprivan(®). We image the turbidity of blood protein sink solutions after emulsions are injected. The images are digitized, and the drug release times are estimated from the pixel intensity data for a range of starting emulsion droplet size. Drug release times are compared to a mechanistic model. After injection, pixel intensity or turbidity decreases due to reductions in emulsion droplet size. Drug release times can still be measured even if the emulsion does not completely dissolve such as with Diprivan(®). Both pure propofol emulsions and Diprivan(®) release drug very rapidly (under five seconds). Reducing emulsion droplet size significantly increases the drug release rate. Drug release times observed are slightly longer than the model prediction likely due to imperfect mixing. Drug release from emulsions occurs very rapidly after injection. This could be a contributing factor to pain on injection of propofol emulsions. Copyright © 2015. Published by Elsevier B.V.

Impact of Release Rates on the Effectiveness of Augmentative Biological Control Agents

PubMed Central

Crowder, David W.

2007-01-01

To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoidsor predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism. PMID:20307240

Predicting the size-dependent tissue accumulation of agents released from vascular targeted nanoconstructs

NASA Astrophysics Data System (ADS)

de Tullio, Marco D.; Singh, Jaykrishna; Pascazio, Giuseppe; Decuzzi, Paolo

2014-03-01

Vascular targeted nanoparticles have been developed for the delivery of therapeutic and imaging agents in cancer and cardiovascular diseases. However, at authors' knowledge, a comprehensive systematic analysis on their delivery efficiency is still missing. Here, a computational model is developed to predict the vessel wall accumulation of agents released from vascular targeted nanoconstructs. The transport problem for the released agent is solved using a finite volume scheme in terms of three governing parameters: the local wall shear rate , ranging from to ; the wall filtration velocity , varying from to ; and the agent diffusion coefficient , ranging from to . It is shown that the percentage of released agent adsorbing on the vessel walls in the vicinity of the vascular targeted nanoconstructs reduces with an increase in shear rate , and with a decrease in filtration velocity and agent diffusivity . In particular, in tumor microvessels, characterized by lower shear rates () and higher filtration velocities (), an agent with a diffusivity (i.e. a 50 nm particle) is predicted to deposit on the vessel wall up to of the total released dose. Differently, drug molecules, exhibiting a smaller size and much higher diffusion coefficient (), are predicted to accumulate up to . In healthy vessels, characterized by higher and lower , the largest majority of the released agent is redistributed directly in the circulation. These data suggest that drug molecules and small nanoparticles only can be efficiently released from vascular targeted nanoconstructs towards the diseased vessel walls and tissue.

Numerical prediction of mechanical properties of Pb-Sn solder alloys containing antimony, bismuth and or silver ternary trace elements

NASA Astrophysics Data System (ADS)

Gadag, Shiva P.; Patra, Susant

2000-12-01

Solder joint interconnects are mechanical means of structural support for bridging the various electronic components and providing electrical contacts and a thermal path for heat dissipation. The functionality of the electronic device often relies on the structural integrity of the solder. The dimensional stability of solder joints is numerically predicted based on their mechanical properties. Algorithms to model the kinetics of dissolution and subsequent growth of intermetallic from the complete knowledge of a single history of time-temperature-reflow profile, by considering equivalent isothermal time intervals, have been developed. The information for dissolution is derived during the heating cycle of reflow and for the growth process from cooling curve of reflow profile. A simple and quick analysis tool to derive tensile stress-strain maps as a function of the reflow temperature of solder and strain rate has been developed by numerical program. The tensile properties are used in modeling thermal strain, thermal fatigue and to predict the overall fatigue life of solder joints. The numerical analysis of the tensile properties as affected by their composition and rate of testing, has been compiled in this paper. A numerical model using constitutive equation has been developed to evaluate the interfacial fatigue crack growth rate. The model can assess the effect of cooling rate, which depends on the level of strain energy release rate. Increasing cooling rate from normalizing to water-quenching, enhanced the fatigue resistance to interfacial crack growth by up to 50% at low strain energy release rate. The increased cooling rates enhanced the fatigue crack growth resistance by surface roughening at the interface of solder joint. This paper highlights salient features of process modeling. Interfacial intermetallic microstructure is affected by cooling rate and thereby affects the mechanical properties.

Epidemiology of Infectious Disease–Related Death After Release from Prison, Washington State, United States, and Queensland, Australia: A Cohort Study

PubMed Central

Blatchford, Patrick J.; Forsyth, Simon J.; Stern, Marc F.; Kinner, Stuart A.

2016-01-01

Objectives People in prison may be at high risk for infectious diseases and have an elevated risk of death immediately after release compared with later; their risk of death is elevated for at least a decade after release. We compared rates, characteristics, and prison-related risk factors for infectious disease–related mortality among people released from prisons in Queensland, Australia, and Washington State, United States, regions with analogous available data. Methods We analyzed data from retrospective cohort studies of people released from prison in Queensland (1997–2007, n=37,180) and Washington State (1999–2009, n=76,208) and linked identifiers from each cohort to its respective national death index. We estimated infectious disease–related mortality rates (deaths per person-years in community) and examined associations using Cox proportional hazard models. Results The most frequent infectious disease–related underlying cause of death after release from prison was pneumonia (43%, 23/54 deaths) in the Australian cohort and viral hepatitis (40%, 69/171 deaths) in the U.S. cohort. The infectious disease–related mortality rate was significantly higher in the U.S. cohort than in the Australian cohort (51.2 vs. 26.5 deaths per 100,000 person-years; incidence rate ratio = 1.93, 95% confidence interval 1.42, 2.62). In both cohorts, increasing age was strongly associated with mortality from infectious diseases. Conclusion Differences in the epidemiology of infectious disease–related mortality among people released from prison may reflect differences in patterns of community health service delivery in each region. These findings highlight the importance of preventing and treating hepatitis C and other infectious diseases during the transition from prison to the community. PMID:27453602

Epidemiology of Infectious Disease-Related Death After Release from Prison, Washington State, United States, and Queensland, Australia: A Cohort Study.

PubMed

Binswanger, Ingrid A; Blatchford, Patrick J; Forsyth, Simon J; Stern, Marc F; Kinner, Stuart A

2016-01-01

People in prison may be at high risk for infectious diseases and have an elevated risk of death immediately after release compared with later; their risk of death is elevated for at least a decade after release. We compared rates, characteristics, and prison-related risk factors for infectious disease-related mortality among people released from prisons in Queensland, Australia, and Washington State, United States, regions with analogous available data. We analyzed data from retrospective cohort studies of people released from prison in Queensland (1997-2007, n=37,180) and Washington State (1999-2009, n=76,208) and linked identifiers from each cohort to its respective national death index. We estimated infectious disease-related mortality rates (deaths per person-years in community) and examined associations using Cox proportional hazard models. The most frequent infectious disease-related underlying cause of death after release from prison was pneumonia (43%, 23/54 deaths) in the Australian cohort and viral hepatitis (40%, 69/171 deaths) in the U.S. cohort. The infectious disease-related mortality rate was significantly higher in the U.S. cohort than in the Australian cohort (51.2 vs. 26.5 deaths per 100,000 person-years; incidence rate ratio = 1.93, 95% confidence interval 1.42, 2.62). In both cohorts, increasing age was strongly associated with mortality from infectious diseases. Differences in the epidemiology of infectious disease-related mortality among people released from prison may reflect differences in patterns of community health service delivery in each region. These findings highlight the importance of preventing and treating hepatitis C and other infectious diseases during the transition from prison to the community.

Preparation and Characterization of Amylose Inclusion Complexes for Drug Delivery Applications.

PubMed

Carbinatto, Fernanda M; Ribeiro, Tatiana S; Colnago, Luiz Alberto; Evangelista, Raul Cesar; Cury, Beatriz S F

2016-01-01

Amylose complexes with nimesulide (NMS) and praziquantel (PZQ) were prepared by a simple and low cost method, so that high yield (>57%) and drug content (up to 68.16%) were achieved. The influence of drug:polymer ratio, temperature, and presence of palmitic acid on the complexes properties was evaluated. Differential scanning calorimetry, X-ray diffraction, and nuclear magnetic resonance data evidenced the drug-polymer interaction and the formation of inclusion complexes with semi-crystalline structures related to type II complexes. The drug release rates from complexes were lowered in acid media (pH 1.2) and phosphate buffer (pH 6.9). The presence of pancreatin promoted a significant acceleration of the release rates of both drugs, evidencing the enzymatic degradability of these complexes. The highest enzymatic resistance of PZQ1:30PA60°C complex makes the release time longer and the full release of PZQ in phosphate buffer with pancreatin occurred at 240 min, whereas the complexes with NMS and PZQ1:5PA90°C did it in 60 min. According to the Weibull model, the drug release process in media without enzyme occurred by complex mechanisms involving diffusion, swelling, and erosion. In media containing pancreatin, generally, the better correlation was with the first order, evidencing the acceleration of the release rates of drugs in the early stages of the test, due to enzymatic degradation.

Antifouling composites with self-adaptive controlled release based on an active compound intercalated into layered double hydroxides

NASA Astrophysics Data System (ADS)

Yang, Miaosen; Gu, Lianghua; Yang, Bin; Wang, Li; Sun, Zhiyong; Zheng, Jiyong; Zhang, Jinwei; Hou, Jian; Lin, Cunguo

2017-12-01

This paper reports a novel method to prepare the antifouling composites with properties of self-adaptive controlled release (defined as control the release rate autonomously and adaptively according to the change of environmental conditions) by intercalation of sodium paeonolsilate (PAS) into MgAl and ZnAl layered double hydroxide (LDH) with the molar ratio (M2+/M3+) of 2:1 and 3:1, respectively. The powder X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) confirm the intercalation of PAS into the galleries of LDH. The controlled release behavior triggered by temperature for the PAS-LDH composites has been investigated, and the results show that the release rate of all PAS-LDH composites increases as the increase of temperature. However, the MgAl-PAS-LDH composites (Mg2Al-PAS-LDH and Mg3Al-PAS-LDH) exhibit the increased release rate of 0.21 ppm/°C from 15 to 30 °C in 3.5% NaCl solution, more than three times of the ZnAl-PAS-LDH composites (0.06 ppm/°C), owing to the confined microenvironment influenced by metal types in LDH layers. In addition, a possible diffusion-controlled process with surface diffusion, bulk diffusion and heterogeneous flat surface diffusion has been revealed via fitting four kinetic equations. Moreover, to verify the practical application of the PAS-LDH composites, a model coating denoted as Mg2Al-PAS-LDH coating was fabricated. The release result displays that the release rate increases or decreases as temperature altered at 15 and 25 °C alternately, indicating its self-adaptive controlled release behavior with temperature. Moreover, the superior resistance to the settlement of Ulva spores at 15 and 25 °C was observed for the Mg2Al-PAS-LDH coating, as a result of the controllable release of antifoulant. Therefore, this work provides a facile and effective method for the fabrication of antifouling composites with self-adaptive controlled release behavior in response to temperature, which can be used to prolong the lifetime of antifouling coatings.

Fibrous dosage forms by wet 3D-micro-patterning: process design, manufacture, and drug release rate.

PubMed

Blaesi, Aron H; Saka, Nannaji

2018-06-19

Recently, we have introduced fibrous dosage forms prepared by 3D-micro-patterning of drug-laden viscous melts. Such dosage forms enable predictable microstructures and increased drug release rates, and they can be manufactured continuously. However, melt processing is not applicable if the melting temperature of the formulation is greater than the degradation temperature of the drug or of the excipient. In this work, therefore, a continuous wet micro-patterning process that operates at ambient temperature is presented. The excipient is plasticized by a solvent and the patterned dosage form is solidified by air drying. Process models show that the micro-patterning time is the ratio of the fiber length in the dosage form and the velocity of the fiber stream. It was 1.3 minutes in the experiments, but can be reduced further. The drying time is limited by the diffusive flux of solvent through the fibers: it was about 3 minutes for the experimental conditions. Furthermore, models are developed to illustrate the effects of fiber radius, inter-fiber spacing, viscosity of the drug-excipient-solvent mixture, and drying conditions on the microstructure of the dosage form. Models and experimental results show that for a viscosity of the wet fibers of the order 10 3 Pa·s, both the patterned microstructure is well preserved and the crossed fibers are well bonded. Finally, the drug release rate by the dosage forms is experimentally determined and theoretically modeled. The results of the experiments validate the models fairly. Copyright © 2018. Published by Elsevier B.V.

Organically bound tritium (OBT) for various plants in the vicinity of a continuous atmospheric tritium release.

PubMed

Vichot, L; Boyer, C; Boissieux, T; Losset, Y; Pierrat, D

2008-10-01

In order to quantify tritium impact on the environmental, we studied vegetation continuously exposed to a tritiated atmosphere. We chose lichens as bio-indicators, trees for determination of past tritium releases of the Valduc Centre, and lettuce as edible vegetables for dose calculation regarding neighbourhood. The Pasquill and Doury models from the literature were tested to estimate tritium concentration in the air around vegetable for distance from the release point less than 500 m. The results in tree rings show that organically bound tritium (OBT) concentration was strongly correlated with tritium releases. Using the GASCON model, the modelled variation of OBT concentration with distance was correlated with the measurements. Although lichens are recognized as bio-indicators, our experiments show that they were not convenient for environmental surveys because their age is not definitive. Thus, tritium integration time cannot be precisely determined. Furthermore, their biological metabolism is not well known and tritium concentration appears to be largely dependent on species. An average conversion rate of HTO to OBT was determined for lettuce of about 0.20-0.24% h(-1). Nevertheless, even if it is equivalent to values already published in the literature for other vegetation, we have shown that this conversion rate, established by weekly samples, varies by a factor of 10 during the different stages of lettuce development, and that its variation is linked to the biomass derivative.

Two release rates from monolithic carboxymethyl starch tablets: formulation, characterization, and in vitro/in vivo evaluation.

PubMed

Le, Tien Canh; Mateescu, Mircea Alexandru

2017-08-01

Most of non-steroidal anti-inflammatory drugs (NSAIDs) including ibuprofen at more than 1200 mg/day may generate gastrointestinal and cardiovascular side effects. Bilayer or multiparticulate devices have been developed for controlled release in order to prevent undesired side effects. A new "two release rate (2RR) monolithic tablets" approach is now proposed for controlled release of poorly soluble drugs, particularly NSAIDs. Ibuprofen was used as model drug. This concept is based on a calcium carboxymethyl-starch (CaCMS) complex as a novel, low-cost excipient for monolithic dosage forms easy to manufacture by direct compaction. The in vitro dissolution from CaCMS formulations (tablets containing 400 or 600 mg active principle) showed two distinct release rates: (i) an initial fast release (for 30 min in simulated gastric fluid) of about 200 mg ibuprofen, an amount similar to the dosage of conventional immediate-release form (Motrin® 200 mg), and (ii) a slow release of remaining about 200 or 400 mg for a period of 12 h. A preliminary in vivo study (beagle dogs) showed pharmacokinetic parameters of one single controlled-release dosage of ibuprofen (400 mg) formulated with CaCMS, near equivalence with multiple doses (three tablets of 200 mg ibuprofen) of conventional Motrin®. A marked reduction (with 33%) of administered dose (400 instead 600 mg) was achieved by the new formulation with equivalent therapeutic effects. This dose reduction may be beneficial and is expected to minimize side damage risks. Although the present study was limited to NSAIDs, the 2RR concept can be applied for other drugs, particularly for subjects unable to follow frequent administrations.

Dynamic leaching studies of 48 MWd/kgU UO2 commercial spent nuclear fuel under oxic conditions

NASA Astrophysics Data System (ADS)

Serrano-Purroy, D.; Casas, I.; González-Robles, E.; Glatz, J. P.; Wegen, D. H.; Clarens, F.; Giménez, J.; de Pablo, J.; Martínez-Esparza, A.

2013-03-01

The leaching of a high-burn-up spent nuclear fuel (48 MWd/KgU) has been studied in a carbonate-containing solution and under oxic conditions using a Continuously Stirred Tank Flow-Through Reactor (CSTR). Two samples of the fuel, one prepared from the centre of the pellet (labelled CORE) and another one from the fuel pellet periphery, enriched with the so-called High Burn-Up Structure (HBS, labelled OUT) have been used.For uranium and actinides, the results showed that U, Np, Am and Cm gave very similar normalized dissolution rates, while Pu showed slower dissolution rates for both samples. In addition, dissolution rates were consistently two to four times lower for OUT sample compared to CORE sample.Considering the fission products release the main results are that Y, Tc, La and Nd dissolved very similar to uranium; while Cs, Sr, Mo and Rb have up to 10 times higher dissolution rates. Rh, Ru and Zr seemed to have lower dissolution rates than uranium. The lowest dissolution rates were found for OUT sample.Three different contributions were detected on uranium release, modelled and attributed to oxidation layer, fines and matrix release.

Marine structure derived calcium phosphate-polymer biocomposites for local antibiotic delivery.

PubMed

Macha, Innocent J; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L; Milthorpe, Bruce

2015-01-20

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery.

Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery

PubMed Central

Macha, Innocent J.; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L.; Milthorpe, Bruce

2015-01-01

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery. PMID:25608725

Crack Development in Cross-Ply Laminates Under Uniaxial Tension

NASA Technical Reports Server (NTRS)

Gyekenyesi, Andrew L.

1996-01-01

This study addresses matrix-dominated failures in carbon fiber/polymer matrix composite laminates in a cross-ply lay-up. The events of interest are interlaminar fracture in the form of transverse cracks in the 90' plies and longitudinal splitting in the 0 deg plies and interlaminar fracture in the form of 0/90 delamination. These events were observed using various nondestructive evaluation (NDE) techniques during static tensile tests. Acoustic emission (AE) x radiography, and edge view microscopy were the principal ones utilized in a real-time environment. A comparison of the NDE results with an analytical model based on the classical linear fracture mechanics concept of strain energy release rate as a criterion for crack growth was performed. The virtual crack closure theory was incorporated with a finite element model to generate strain energy release rate curves for the analytical case. Celion carbon fiber/polyimide matrix (G30-500/PMR-15) was the material tested with cross-ply lay-ups of (0(2)/90(6))s and (0(4)/90(4))s. The test specimens contained thermally induced cracks caused by the high-temperature processing. The analytical model was updated to compensate for the initial damage and to study further accumulation by taking into account the crack interactions. By correlating the experimental and analytical data, the critical energy release rates were found for the observable events of interest.

Fatigue damage mechanics of notched graphite-epoxy laminates

NASA Astrophysics Data System (ADS)

Spearing, Mark; Beaumont, Peter W. R.; Ashby, Michael F.

A modeling approach is presented that recognizes that the residual properties of composite laminates after any form of loading depend on the damage state. Therefore, in the case of cyclic loading, it is necessary to first derive a damage growth law and then relate the residual properties to the accumulated damage. The propagation of fatigue damage in notched laminates is investigated. A power law relationship between damage growth and the strain energy release rate is developed. The material constants used in the model have been determined in independent experiments and are invariant for all the layups investigated. The strain energy release rates are calculated using a simple finite element representation of the damaged specimen. The model is used to predict the effect of tension-tension cyclic loading on laminates of the T300/914C carbon-fiber epoxy system. The extent of damage propagation is successfully predicted in a number of cross-ply laminates.

Elastic interactions between single microcrack and single osteon microstructure of human femur cortical bone

NASA Astrophysics Data System (ADS)

Mansor, N. N.; Daud, R.; Basaruddin, K. S.; Mat, F.; Bajuri, Y.; Ariffin, A. K.

2017-09-01

Inmultiscale Haversian system of cortical bone fracture, a homogenous bone modeling consideration is limited to only one Young modulus was significant for each cortex without having any constituents in that bone. A two dimension model of human femur cortical bone is presented by considering the anatomical positions of four cortices, e.g anterior, posterior, medial and lateral. The Haversian system is modeled under tensile loading by considering the interstitial matrix, osteon and cement line mechanical properties. The interaction between single microcrack and single osteon is evaluated using linear elastic fracture mechanics theory, and was determined using of stress intensity factor, strain energy release rate, and the critical stress intensity factor and critical strain energy release rate parameter. The results indicate that the medial cortex has the highest SIFs while the lowest was posterior cortex. The Young modulus of material was greatly influence the fracture parameters. More stiff the material, the SIF was reduced.

Sequential delivery of TAT-HSP27 and VEGF using microsphere/hydrogel hybrid systems for therapeutic angiogenesis.

PubMed

Shin, Seung-Hwa; Lee, Jangwook; Lim, Kwang Suk; Rhim, Taiyoun; Lee, Sang Kyung; Kim, Yong-Hee; Lee, Kuen Yong

2013-02-28

Ischemic disease is associated with high mortality and morbidity rates, and therapeutic angiogenesis via systemic or local delivery of protein drugs is one potential approach to treat the disease. In this study, we hypothesized that combined delivery of TAT-HSP27 (HSP27 fused with transcriptional activator) and VEGF could enhance the therapeutic efficacy in an ischemic mouse model, and that sequential release could be critical in therapeutic angiogenesis. Alginate hydrogels containing TAT-HSP27 as an anti-apoptotic agent were prepared, and porous PLGA microspheres loaded with VEGF as an angiogenic agent were incorporated into the hydrogels to prepare microsphere/hydrogel hybrid delivery systems. Sequential in vitro release of TAT-HSP27 and VEGF was achieved by the hybrid systems. TAT-HSP27 was depleted from alginate gels in 7 days, while VEGF was continually released for 28 days. The release rate of VEGF was attenuated by varying the porous structures of PLGA microspheres. Sequential delivery of TAT-HSP27 and VEGF was critical to protect against muscle degeneration and fibrosis, as well as to promote new blood vessel formation in the ischemic site of a mouse model. This approach to controlling the sequential release behaviors of multiple drugs could be useful in the design of novel drug delivery systems for therapeutic angiogenesis. Copyright © 2012 Elsevier B.V. All rights reserved.

An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing.

PubMed

Alhijjaj, Muqdad; Belton, Peter; Qi, Sheng

2016-11-01

FDM 3D printing has been recently attracted increasing research efforts towards the production of personalized solid oral formulations. However, commercially available FDM printers are extremely limited with regards to the materials that can be processed to few types of thermoplastic polymers, which often may not be pharmaceutically approved materials nor ideal for optimizing dosage form performance of poor soluble compounds. This study explored the use of polymer blends as a formulation strategy to overcome this processability issue and to provide adjustable drug release rates from the printed dispersions. Solid dispersions of felodipine, the model drug, were successfully fabricated using FDM 3D printing with polymer blends of PEG, PEO and Tween 80 with either Eudragit E PO or Soluplus. As PVA is one of most widely used polymers in FDM 3D printing, a PVA based solid dispersion was used as a benchmark to compare the polymer blend systems to in terms of processability. The polymer blends exhibited excellent printability and were suitable for processing using a commercially available FDM 3D printer. With 10% drug loading, all characterization data indicated that the model drug was molecularly dispersed in the matrices. During in vitro dissolution testing, it was clear that the disintegration behavior of the formulations significantly influenced the rates of drug release. Eudragit EPO based blend dispersions showed bulk disintegration; whereas the Soluplus based blends showed the 'peeling' style disintegration of strip-by-strip. The results indicated that interplay of the miscibility between excipients in the blends, the solubility of the materials in the dissolution media and the degree of fusion between the printed strips during FDM process can be used to manipulate the drug release rate of the dispersions. This brings new insight into the design principles of controlled release formulations using FDM 3D printing. Copyright © 2016 Elsevier B.V. All rights reserved.

Design and evaluation of liposomal formulation of pilocarpine nitrate.

PubMed

Rathod, S; Deshpande, S G

2010-03-01

Prolonged release drug delivery system of pilocarpine nitrate was made by optimizing thin layer film hydration method. Egg phosphatidylcholine and cholesterol were used to make multilamellar vesicles. Effects of charges over the vesicles were studied by incorporating dicetylphosphate and stearylamine. Various factors, which may affect the size, shape, encapsulation efficiency and release rate, were studied. Liposomes in the size range 0.2 to 1 µm were obtained by optimizing the process. Encapsulation efficiency of neutral, positive and negatively charged liposomes were found to be 32.5, 35.4 and 34.2 percent, respectively. In vitro drug release rate was studied on specially designed model. Biological response in terms of reduction in intraocular pressure was observed on rabbit eyes. Pilocarpine nitrate liposomes were lyophilized and stability studies were conducted.

The evaluation of physical properties of injection molded systems based on poly(ethylene oxide) (PEO).

PubMed

Pajander, Jari; Rensonnet, Alexia; Hietala, Sami; Rantanen, Jukka; Baldursdottir, Stefania

2017-02-25

The effect of product design parameters on the formation and properties of an injection molded solid dosage form consisting of poly(ethylene oxide)s (PEO) and two different active pharmaceutical ingredients (APIs) was studied. The product design parameters explored were melting temperature and the duration of melting, API loading degree and the molecular weight (M w ) of PEO. The solid form composition of the model APIs, theophylline and carbamazepine, was of specific interest, and its possible impact on the in vitro drug release behavior. M w of PEO had the greatest impact on the release rate of both APIs. High M w resulted in slower API release rate. Process temperature had two-fold effect with PEO 300,000g/mol. Firstly, higher process temperature transformed the crystalline part of the polymer into metastable folded form (more folded crystalline regions) and less into the more stable extended form (more extended crystalline regions), which lead to enhanced theophylline release rate. Secondly, the higher process temperature seemed to induce carbamazepine polymorphic transformation from p-monoclinic form III (carbamazepine (M)) into trigonal form II (carbamazepine (T)). The results indicated that the actual content of carbamazepine (T) affected drug release behavior more than the magnitude of transformation. Copyright © 2016 Elsevier B.V. All rights reserved.

Modified ensemble Kalman filter for nuclear accident atmospheric dispersion: prediction improved and source estimated.

PubMed

Zhang, X L; Su, G F; Yuan, H Y; Chen, J G; Huang, Q Y

2014-09-15

Atmospheric dispersion models play an important role in nuclear power plant accident management. A reliable estimation of radioactive material distribution in short range (about 50 km) is in urgent need for population sheltering and evacuation planning. However, the meteorological data and the source term which greatly influence the accuracy of the atmospheric dispersion models are usually poorly known at the early phase of the emergency. In this study, a modified ensemble Kalman filter data assimilation method in conjunction with a Lagrangian puff-model is proposed to simultaneously improve the model prediction and reconstruct the source terms for short range atmospheric dispersion using the off-site environmental monitoring data. Four main uncertainty parameters are considered: source release rate, plume rise height, wind speed and wind direction. Twin experiments show that the method effectively improves the predicted concentration distribution, and the temporal profiles of source release rate and plume rise height are also successfully reconstructed. Moreover, the time lag in the response of ensemble Kalman filter is shortened. The method proposed here can be a useful tool not only in the nuclear power plant accident emergency management but also in other similar situation where hazardous material is released into the atmosphere. Copyright © 2014 Elsevier B.V. All rights reserved.

Predicting seed dispersal using a Lagrangian Stochastic Model

NASA Astrophysics Data System (ADS)

Hsieh, C. I.; Chen, C. W.; Su, M. D.

2017-12-01

Migration and expansion of a plant species are determined by longdistance dispersion (LDD). A more sophisticated mechanical dispersion model is needed for mimicking LDD of wind-driven seeds. This study simulated seed dispersion trajectories in canopy turbulence by using the Lagrangian stochastic dispersion model under varying atmospheric stabilities in conjunction with the effects of turbulent kinetic energy dissipation rate intermittency. The effects of friction velocity, seed release height, and seed terminal velocity were also studied. The results showed that both the unstable atmosphere and the inclusion of the dissipation rate intermittency in the model could increase seeds' LDD. The number of seeds that escape the canopy volume by dissipation intermittency is increased under unstable atmospheric conditions. As a result, more seeds can be transported a further distance. When dissipation intermittency is included under astrong unstable atmosphere, the peak location of dispersal kernel tends to be closer to the source. Contrasting this, under both neutral and stable conditions when LDD of both are similar, the peak location will be further away from the source. However higher friction velocity, higher seed release height, and lower seed terminal velocity will all increase the LDD of seeds irregardless of atmospheric conditions. The change of LDD due to change in friction velocity, seed release height, or the seed terminal velocity, would be heightened under unstable conditions

Force and number of myosin motors during muscle shortening and the coupling with the release of the ATP hydrolysis products

PubMed Central

Caremani, Marco; Melli, Luca; Dolfi, Mario; Lombardi, Vincenzo; Linari, Marco

2015-01-01

The chemo-mechanical cycle of the myosin II–actin reaction in situ has been investigated in Ca2+-activated skinned fibres from rabbit psoas, by determining the number and strain (s) of myosin motors interacting during steady shortening at different velocities (V) and the effect of raising inorganic phosphate (Pi) concentration. It was found that in control conditions (no added Pi), shortening at V ≤ 350 nm s–1 per half-sarcomere, corresponding to force (T) greater than half the isometric force (T0), decreases the number of myosin motors in proportion to the reduction of T, so that s remains practically constant and similar to the T0 value independent of V. At higher V the number of motors decreases less than in proportion to T, so that s progressively decreases. Raising Pi concentration by 10 mm, which reduces T0 and the number of motors by 40–50%, does not influence the dependence on V of number and strain. A model simulation of the myosin–actin reaction in which the structural transitions responsible for the myosin working stroke and the release of the hydrolysis products are orthogonal explains the results assuming that Pi and then ADP are released with rates that increase as the motor progresses through the working stroke. The rate of ADP release from the conformation at the end of the working stroke is also strain-sensitive, further increasing by one order of magnitude within a few nanometres of negative strain. These results provide the molecular explanation of the relation between the rate of energy liberation and the load during muscle contraction. Key points Muscle contraction is due to cyclical ATP-driven working strokes in the myosin motors while attached to the actin filament. Each working stroke is accompanied by the release of the hydrolysis products, orthophosphate and ADP. The rate of myosin–actin interactions increases with the increase in shortening velocity. We used fast half-sarcomere mechanics on skinned muscle fibres to determine the relation between shortening velocity and the number and strain of myosin motors and the effect of orthophosphate concentration. A model simulation of the myosin–actin reaction explains the results assuming that orthophosphate and then ADP are released with rates that increase as the motor progresses through the working stroke. The ADP release rate further increases by one order of magnitude with the rise of negative strain in the final motor conformation. These results provide the molecular explanation of the relation between the rate of energy liberation and shortening velocity during muscle contraction. PMID:26041599

FY2016 ILAW Glass Corrosion Testing with the Single-Pass Flow-Through Method

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

Neeway, James J.; Asmussen, Robert M.; Parruzot, Benjamin PG

The inventory of immobilized low-activity waste (ILAW) produced at the Hanford Tank Waste Treatment and Immobilization Plant (WTP) will be disposed of at the near-surface, on-site Integrated Disposal Facility (IDF). When groundwater comes into contact with the waste form, the glass will corrode and radionuclides will be released into the near-field environment. Because the release of the radionuclides is dependent on the dissolution rate of the glass, it is important that the performance assessment (PA) model accounts for the dissolution rate of the glass as a function of various chemical conditions. To accomplish this, an IDF PA model based onmore » Transition State Theory (TST) can be employed. The model is able to account for changes in temperature, exposed surface area, and pH of the contacting solution as well as the effect of silicon concentrations in solution, specifically the activity of orthosilicic acid (H4SiO4), whose concentration is directly linked to the glass dissolution rate. In addition, the IDF PA model accounts for the alkali-ion exchange process as sodium is leached from the glass and into solution. The effect of temperature, pH, H4SiO4 activity, and the rate of ion-exchange can be parameterized and implemented directly into the PA rate law model. The rate law parameters are derived from laboratory tests with the single-pass flow-through (SPFT) method. To date, rate law parameters have been determined for seven ILAW glass compositions, thus additional rate law parameters on a wider range of compositions will supplement the existing body of data for PA maintenance activities. The data provided in this report can be used by ILAW glass scientists to further the understanding of ILAW glass behavior, by IDF PA modelers to use the rate law parameters in PA modeling efforts, and by Department of Energy (DOE) contractors and decision makers as they assess the IDF PA program.« less

Cyclodextrin modified hydrogels of PVP/PEG for sustained drug release.

PubMed

Nielsen, Anne Louise; Madsen, Flemming; Larsen, Kim Lambertsen

2009-02-01

Hydrogels are water swollen networks of polymers and especially hydrogels consisting of poly vinylpyrrolidone/poly ethyleneglycol-dimethacrylate (PVP/PEG-DMA) blends show promising wound care properties. Enhanced functionality of the hydrogels can be achieved by incorporating drugs and other substances that may assist wound healing into the gel matrix. Controlling the release of active compounds from the hydrogels may be possible by carefully modifying the polymer matrix. For this purpose, cyclodextrins (CD) were grafted to the polymer matrix in 4-5 w/w% in an attempt to retard the release of water-soluble drugs. Ibuprofenate (IBU) was chosen as model drug and loaded in IBU/CD ratios of 0.6, 1.2, and 2.5. Vinyl derivatives of alpha-, beta- and gamma-CD were produced, added to the prepolymer blend and cured by UV-light. During this curing process the CD derivatives were covalently incorporated into the hydrogel matrix. The modified hydrogels were loaded with ibuprofenate by swelling. The release of the model drug from CD modified hydrogels show that especially covalently bonded beta-cyclodextrin can change both the release rate and the release profile of ibuprofen.

Demographics of an experimentally released population of elk in Great Smoky Mountains National Park

USGS Publications Warehouse

Murrow, Jennifer L.; Clark, Joseph D.; Delozier, E. Kim

2009-01-01

We assessed the potential for reestablishing elk (Cervus elaphus) in Great Smoky Mountains National Park (GSMNP), USA, by estimating vital rates of experimentally released animals from 2001 to 2006. Annual survival rates for calves ranged from 0.333 to 1.0 and averaged 0.592. Annual survival for subadult and adult elk (i.e., ≥1 yr of age) ranged from 0.690 to 0.933, depending on age and sex. We used those and other vital rates to model projected population growth and viability using a stochastic individual-based model. The annual growth rate (λ) of the modeled population over a 25-year period averaged 0.996 and declined from 1.059 the first year to 0.990 at year 25. The modeled population failed to attain a positive 25-year mean growth rate in 46.0% of the projections. Poor calf recruitment was an important determinant of low population growth. Predation by black bears (Ursus americanus) was the dominant calf mortality factor. Most of the variance of growth projections was due to demographic variation resulting from the small population size (n  =  61). Management actions such as predator control may help increase calf recruitment, but our projections suggest that the GSMNP elk population may be at risk for some time because of high demographic variation.

Comparison of three nonlinear models to describe long-term tag shedding by lake trout

USGS Publications Warehouse

Fabrizio, Mary C.; Swanson, Bruce L.; Schram, Stephen T.; Hoff, Michael H.

1996-01-01

We estimated long-term tag-shedding rates for lake trout Salvelinus namaycush using two existing models and a model we developed to account for the observed permanence of some tags. Because tag design changed over the course of the study, we examined tag-shedding rates for three types of numbered anchor tags (Floy tags FD-67, FD-67C, and FD-68BC) and an unprinted anchor tag (FD-67F). Lake trout from the Gull Island Shoal region, Lake Superior, were double-tagged, and subsequent recaptures were monitored in annual surveys conducted from 1974 to 1992. We modeled tag-shedding rates, using time at liberty and probabilities of tag shedding estimated from fish released in 1974 and 1978–1983 and later recaptured. Long-term shedding of numbered anchor tags in lake trout was best described by a nonlinear model with two parameters: an instantaneous tag-shedding rate and a constant representing the proportion of tags that were never shed. Although our estimates of annual shedding rates varied with tag type (0.300 for FD-67, 0.441 for FD-67C, and 0.656 for FD-68BC), differences were not significant. About 36% of tags remained permanently affixed to the fish. Of the numbered tags that were shed (about 64%), two mechanisms contributed to tag loss: disintegration and dislodgment. Tags from about 11% of recaptured fish had disintegrated, but most tags were dislodged. Unprinted tags were shed at a significant but low rate immediately after release, but the long-term, annual shedding rate of these tags was only 0.013. Compared with unprinted tags, numbered tags dislodged at higher annual rates; we hypothesized that this was due to the greater frictional drag associated with the larger cross-sectional area of numbered tags.

Particulate Matter Emissions for Fires in the Palmetto-Gallberry Fuel Type

Treesearch

Darold E. Ward

1983-01-01

Fire management specialists in the southeastern United States needing guides for predicting or assessing particulate matter emission factors, emission rates, and heat release rate can use the models presented in this paper for making these predictions as a function of flame length in the palmetto-gallberry fuel type.

LIGHT NONAQUEOUS-PHASE LIQUID HYDROCARBON WEATHERING AT SOME JP-4 FUEL RELEASE SITES

EPA Science Inventory

A fuel weathering study was conducted for database entries to estimate natural light, nonaqueousphase
liquid weathering and source-term reduction rates for use in natural attenuation models. A range of BTEX
weathering rates from mobile LNAPL plumes at eight field sites with...

Exploring the correlation between the sequence composition of the nucleotide binding G5 loop of the FeoB GTPase domain (NFeoB) and intrinsic rate of GDP release.

PubMed

Guilfoyle, Amy P; Deshpande, Chandrika N; Schenk, Gerhard; Maher, Megan J; Jormakka, Mika

2014-12-12

GDP release from GTPases is usually extremely slow and is in general assisted by external factors, such as association with guanine exchange factors or membrane-embedded GPCRs (G protein-coupled receptors), which accelerate the release of GDP by several orders of magnitude. Intrinsic factors can also play a significant role; a single amino acid substitution in one of the guanine nucleotide recognition motifs, G5, results in a drastically altered GDP release rate, indicating that the sequence composition of this motif plays an important role in spontaneous GDP release. In the present study, we used the GTPase domain from EcNFeoB (Escherichia coli FeoB) as a model and applied biochemical and structural approaches to evaluate the role of all the individual residues in the G5 loop. Our study confirms that several of the residues in the G5 motif have an important role in the intrinsic affinity and release of GDP. In particular, a T151A mutant (third residue of the G5 loop) leads to a reduced nucleotide affinity and provokes a drastically accelerated dissociation of GDP.

Models for integrated pest control and their biological implications.

PubMed

Tang, Sanyi; Cheke, Robert A

2008-09-01

Successful integrated pest management (IPM) control programmes depend on many factors which include host-parasitoid ratios, starting densities, timings of parasitoid releases, dosages and timings of insecticide applications and levels of host-feeding and parasitism. Mathematical models can help us to clarify and predict the effects of such factors on the stability of host-parasitoid systems, which we illustrate here by extending the classical continuous and discrete host-parasitoid models to include an IPM control programme. The results indicate that one of three control methods can maintain the host level below the economic threshold (ET) in relation to different ET levels, initial densities of host and parasitoid populations and host-parasitoid ratios. The effects of host intrinsic growth rate and parasitoid searching efficiency on host mean outbreak period can be calculated numerically from the models presented. The instantaneous pest killing rate of an insecticide application is also estimated from the models. The results imply that the modelling methods described can help in the design of appropriate control strategies and assist management decision-making. The results also indicate that a high initial density of parasitoids (such as in inundative releases) and high parasitoid inter-generational survival rates will lead to more frequent host outbreaks and, therefore, greater economic damage. The biological implications of this counter intuitive result are discussed.

Mathematical Description of Complex Chemical Kinetics and Application to CFD Modeling Codes

NASA Technical Reports Server (NTRS)

Bittker, D. A.

1993-01-01

A major effort in combustion research at the present time is devoted to the theoretical modeling of practical combustion systems. These include turbojet and ramjet air-breathing engines as well as ground-based gas-turbine power generating systems. The ability to use computational modeling extensively in designing these products not only saves time and money, but also helps designers meet the quite rigorous environmental standards that have been imposed on all combustion devices. The goal is to combine the very complex solution of the Navier-Stokes flow equations with realistic turbulence and heat-release models into a single computer code. Such a computational fluid-dynamic (CFD) code simulates the coupling of fluid mechanics with the chemistry of combustion to describe the practical devices. This paper will focus on the task of developing a simplified chemical model which can predict realistic heat-release rates as well as species composition profiles, and is also computationally rapid. We first discuss the mathematical techniques used to describe a complex, multistep fuel oxidation chemical reaction and develop a detailed mechanism for the process. We then show how this mechanism may be reduced and simplified to give an approximate model which adequately predicts heat release rates and a limited number of species composition profiles, but is computationally much faster than the original one. Only such a model can be incorporated into a CFD code without adding significantly to long computation times. Finally, we present some of the recent advances in the development of these simplified chemical mechanisms.

Mathematical description of complex chemical kinetics and application to CFD modeling codes

NASA Technical Reports Server (NTRS)

Bittker, D. A.

1993-01-01

A major effort in combustion research at the present time is devoted to the theoretical modeling of practical combustion systems. These include turbojet and ramjet air-breathing engines as well as ground-based gas-turbine power generating systems. The ability to use computational modeling extensively in designing these products not only saves time and money, but also helps designers meet the quite rigorous environmental standards that have been imposed on all combustion devices. The goal is to combine the very complex solution of the Navier-Stokes flow equations with realistic turbulence and heat-release models into a single computer code. Such a computational fluid-dynamic (CFD) code simulates the coupling of fluid mechanics with the chemistry of combustion to describe the practical devices. This paper will focus on the task of developing a simplified chemical model which can predict realistic heat-release rates as well as species composition profiles, and is also computationally rapid. We first discuss the mathematical techniques used to describe a complex, multistep fuel oxidation chemical reaction and develop a detailed mechanism for the process. We then show how this mechanism may be reduced and simplified to give an approximate model which adequately predicts heat release rates and a limited number of species composition profiles, but is computationally much faster than the original one. Only such a model can be incorporated into a CFD code without adding significantly to long computation times. Finally, we present some of the recent advances in the development of these simplified chemical mechanisms.

Simulating future water temperatures in the North Santiam River, Oregon

NASA Astrophysics Data System (ADS)

Buccola, Norman L.; Risley, John C.; Rounds, Stewart A.

2016-04-01

A previously calibrated two-dimensional hydrodynamic and water-quality model (CE-QUAL-W2) of Detroit Lake in western Oregon was used in conjunction with inflows derived from Precipitation-Runoff Modeling System (PRMS) hydrologic models to examine in-lake and downstream water temperature effects under future climate conditions. Current and hypothetical operations and structures at Detroit Dam were imposed on boundary conditions derived from downscaled General Circulation Models in base (1990-1999) and future (2059-2068) periods. Compared with the base period, future air temperatures were about 2 °C warmer year-round. Higher air temperature and lower precipitation under the future period resulted in a 23% reduction in mean annual PRMS-simulated discharge and a 1 °C increase in mean annual estimated stream temperatures flowing into the lake compared to the base period. Simulations incorporating current operational rules and minimum release rates at Detroit Dam to support downstream habitat, irrigation, and water supply during key times of year resulted in lower future lake levels. That scenario results in a lake level that is above the dam's spillway crest only about half as many days in the future compared to historical frequencies. Managing temperature downstream of Detroit Dam depends on the ability to blend warmer water from the lake's surface with cooler water from deep in the lake, and the spillway is an important release point near the lake's surface. Annual average in-lake and release temperatures from Detroit Lake warmed 1.1 °C and 1.5 °C from base to future periods under present-day dam operational rules and fill schedules. Simulated dam operations such as beginning refill of the lake 30 days earlier or reducing minimum release rates (to keep more water in the lake to retain the use of the spillway) mitigated future warming to 0.4 and 0.9 °C below existing operational scenarios during the critical autumn spawning period for endangered salmonids. A hypothetical floating surface withdrawal at Detroit Dam improved temperature control in summer and autumn (0.6 °C warmer in summer, 0.6 °C cooler in autumn compared to existing structures) without altering release rates or lake level management rules.

Transient heat and mass transfer analysis in a porous ceria structure of a novel solar redox reactor

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

Chandran, RB; Bader, R; Lipinski, W

2015-06-01

Thermal transport processes are numerically analyzed for a porous ceria structure undergoing reduction in a novel redox reactor for solar thermochemical fuel production. The cylindrical reactor cavity is formed by an array of annular reactive elements comprising the porous ceria monolith integrated with gas inlet and outlet channels. Two configurations are considered, with the reactor cavity consisting of 10 and 20 reactive elements, respectively. Temperature dependent boundary heat fluxes are obtained on the irradiated cavity wall by solving for the surface radiative exchange using the net radiation method coupled to the heat and mass transfer model of the reactive element.more » Predicted oxygen production rates are in the range 40-60 mu mol s(-1) for the geometries considered. After an initial rise, the average temperature of the reactive element levels off at 1660 and 1680 K for the two geometries, respectively. For the chosen reduction reaction rate model, oxygen release continues after the temperature has leveled off which indicates that the oxygen release reaction is limited by chemical kinetics and/or mass transfer rather than by the heating rate. For a fixed total mass of ceria, the peak oxygen release rate is doubled for the cavity with 20 reactive elements due to lower local oxygen partial pressure. (C) 2015 Elsevier Masson SAS. All rights reserved.« less

Controls on Nitrous Oxide Emissions from the Hyporheic Zones of Streams.

PubMed

Quick, Annika M; Reeder, W Jeffery; Farrell, Tiffany B; Tonina, Daniele; Feris, Kevin P; Benner, Shawn G

2016-11-01

The magnitude and mechanisms of nitrous oxide (N 2 O) release from rivers and streams are actively debated. The complex interactions of hydrodynamic and biogeochemical controls on emissions of this important greenhouse gas preclude prediction of when and where N 2 O emissions will be significant. We present observations from column and large-scale flume experiments supporting an integrative model of N 2 O emissions from stream sediments. Our results show a distinct, replicable, pattern of nitrous oxide generation and consumption dictated by subsurface (hyporheic) residence times and biological nitrogen reduction rates. Within this model, N 2 O emission from stream sediments requires subsurface residence times (and microbially mediated reduction rates) be sufficiently long (and fast reacting) to produce N 2 O by nitrate reduction but also sufficiently short (or slow reacting) to limit N 2 O conversion to dinitrogen gas. Most subsurface exchange will not result in N 2 O emissions; only specific, intermediate, residence times (reaction rates) will both produce and release N 2 O to the stream. We also confirm previous observations that elevated nitrate and declining organic carbon reactivity increase N 2 O production, highlighting the importance of associated reaction rates in controlling N 2 O accumulation. Combined, these observations help constrain when N 2 O release will occur, providing a predictive link between stream geomorphology, hydrodynamics, and N 2 O emissions.

Impact of sodium caseinate concentration and location on magnesium release from multiple W/O/W emulsions.

PubMed

Bonnet, Marie; Cansell, Maud; Placin, Frédéric; Anton, Marc; Leal-Calderon, Fernando

2010-06-15

Water-in-oil-in-water (W/O/W) double emulsions were prepared and the rate of release of magnesium ions from the internal to the external aqueous phase was followed. Sodium caseinate was used not only as a hydrophilic surface-active species but also as a chelating agent able to bind magnesium ions. The release occurred without film rupturing (no coalescence). The kinetics of the release process depended on the location (in only one or in both aqueous compartments) and on the concentration of sodium caseinate. The rate of release increased with the concentration of sodium caseinate in the external phase and decreased when sodium caseinate was present in the inner droplets. The experiments were interpreted within the frame of a mean-field model based on diffusion, integrating the effect of ion binding. The data could be adequately fitted by considering a time-dependent permeation coefficient of the magnesium ions across the oil phase. Our results suggested that ion permeability was influenced by the state of the protein interfacial layers which itself depended on the extent of magnesium binding.

Pseudo Random Stimulus Response of Combustion Systems.

DTIC Science & Technology

1980-01-01

is also 7 applicable to the coalescence/dispersion (C/D) micromixing model In the C/D model, micromixing is simulated by considering the reacting...the turbulent fluctuations on the local heat release rate. Thus the micromixing ’noise’ measurements will not be valid, however, deductions

Towards Optimal Design of Cancer Nanomedicines: Multi-stage Nanoparticles for the Treatment of Solid Tumors.

PubMed

Stylianopoulos, Triantafyllos; Economides, Eva-Athena; Baish, James W; Fukumura, Dai; Jain, Rakesh K

2015-09-01

Conventional drug delivery systems for solid tumors are composed of a nano-carrier that releases its therapeutic load. These two-stage nanoparticles utilize the enhanced permeability and retention (EPR) effect to enable preferential delivery to tumor tissue. However, the size-dependency of the EPR, the limited penetration of nanoparticles into the tumor as well as the rapid binding of the particles or the released cytotoxic agents to cancer cells and stromal components inhibit the uniform distribution of the drug and the efficacy of the treatment. Here, we employ mathematical modeling to study the effect of particle size, drug release rate and binding affinity on the distribution and efficacy of nanoparticles to derive optimal design rules. Furthermore, we introduce a new multi-stage delivery system. The system consists of a 20-nm primary nanoparticle, which releases 5-nm secondary particles, which in turn release the chemotherapeutic drug. We found that tuning the drug release kinetics and binding affinities leads to improved delivery of the drug. Our results also indicate that multi-stage nanoparticles are superior over two-stage nano-carriers provided they have a faster drug release rate and for high binding affinity drugs. Furthermore, our results suggest that smaller nanoparticles achieve better treatment outcome.

Oleic acid stimulates glucagon-like peptide-1 release from enteroendocrine cells by modulating cell respiration and glycolysis.

PubMed

Clara, Rosmarie; Langhans, Wolfgang; Mansouri, Abdelhak

2016-03-01

Glucagon-like peptide-1 (GLP-1) is a potent satiating and incretin hormone released by enteroendocrine L-cells in response to eating. Dietary fat, in particular monounsaturated fatty acids, such as oleic acid (OA), potently stimulates GLP-1 secretion from L-cells. It is, however, unclear whether the intracellular metabolic handling of OA is involved in this effect. First we determined the optimal medium for the bioenergetics measurements. Then we examined the effect of OA on the metabolism of the immortalized enteroendocrine GLUTag cell model and assessed GLP-1 release in parallel. We measured oxygen consumption rate and extracellular acidification rate in response to OA and to different metabolic inhibitors with the Seahorse extracellular flux analyzer. OA increased cellular respiration and potently stimulated GLP-1 release. The fatty acid oxidation inhibitor etomoxir did neither reduce OA-induced respiration nor affect the OA-induced GLP-1 release. In contrast, inhibition of the respiratory chain or of downstream steps of aerobic glycolysis reduced the OA-induced GLP-1 release, and an inhibition of the first step of glycolysis by addition of 2-deoxy-d-glucose even abolished it. These findings indicate that an indirect stimulation of glycolysis is crucial for the OA-induced release of GLP-1. Copyright © 2015 Elsevier Inc. All rights reserved.

DEMONSTRATION OF LEACHXS/ORCHESTRA CAPABILITIES BY SIMULATING CONSTITUENT RELEASE FROM A CEMENTITIOUS WASTE FORM IN A REINFORCED CONCRETE VAULT

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

Langton, C.; Meeussen, J.; Sloot, H.

2010-03-31

The objective of the work described in this report is to demonstrate the capabilities of the current version of LeachXS{trademark}/ORCHESTRA for simulating chemical behavior and constituent release processes in a range of applications that are relevant to the CBP. This report illustrates the use of LeachXS{trademark}/ORCHESTRA for the following applications: (1) Comparing model and experimental results for leaching tests for a range of cementitious materials including cement mortars, grout, stabilized waste, and concrete. The leaching test data includes liquid-solid partitioning as a function of pH and release rates based on laboratory column, monolith, and field testing. (2) Modeling chemical speciationmore » of constituents in cementitious materials, including liquid-solid partitioning and release rates. (3) Evaluating uncertainty in model predictions based on uncertainty in underlying composition, thermodynamic, and transport characteristics. (4) Generating predominance diagrams to evaluate predicted chemical changes as a result of material aging using the example of exposure to atmospheric conditions. (5) Modeling coupled geochemical speciation and diffusion in a three layer system consisting of a layer of Saltstone, a concrete barrier, and a layer of soil in contact with air. The simulations show developing concentration fronts over a time period of 1000 years. (6) Modeling sulfate attack and cracking due to ettringite formation. A detailed example for this case is provided in a separate article by the authors (Sarkar et al. 2010). Finally, based on the computed results, the sensitive input parameters for this type of modeling are identified and discussed. The chemical speciation behavior of substances is calculated for a batch system and also in combination with transport and within a three layer system. This includes release from a barrier to the surrounding soil as a function of time. As input for the simulations, the physical and chemical properties of the materials are used. The test cases used in this demonstration are taken from Reference Cases for Use in the Cementitious Barriers Partnership (Langton et al. 2009). Before it is possible to model the release of substances from stabilized waste or radioactive grout through a cement barrier into the engineered soil barrier or natural soil, the relevant characteristics of such materials must be known. Additional chemical characteristics are needed for mechanistic modeling to be undertaken, not just the physical properties relevant for modeling of transport. The minimum required properties for modeling are given in Section 5.0, 'Modeling the chemical speciation of a material'.« less

Controlled release of tocopherols from polymer blend films

NASA Astrophysics Data System (ADS)

Obinata, Noe

Controlled release packaging has great potential to increase storage stability of foods by releasing active compounds into foods continuously over time. However, a major limitation in development of this technology is the inability to control the release and provide rates useful for long term storage of foods. Better understanding of the factors affecting active compound release is needed to overcome this limitation. The objective of this research was to investigate the relationship between polymer composition, polymer processing method, polymer morphology, and release properties of active compounds, and to provide proof of principle that compound release is controlled by film morphology. A natural antioxidant, tocopherol was used as a model active compound because it is natural, effective, heat stable, and soluble in most packaging polymers. Polymer blend films were produced from combination of linear low density polyethylene (LLDPE) and high density polyethylene (HDPE), polypropylene (PP), or polystyrene (PS) with 3000 ppm mixed tocopherols using conventional blending method and innovative blending method, smart blending with a novel mixer using chaotic advection. Film morphologies were visualized with scanning electron microscopy (SEM). Release of tocopherols into 95% ethanol as a food simulant was measured by UV/Visible spectrophotometry or HPLC, and diffusivity of tocopherols in the polymers was estimated from this data. Polymer composition (blend proportions) and processing methods have major effects on film morphology. Four different types of morphologies, dispersed, co-continuous, fiber, and multilayer structures were developed by either conventional extrusion or smart blending. With smart blending of fixed polymer compositions, different morphologies were progressively developed with fixed polymer composition as the number of rod rotations increased, providing a way to separate effects of polymer composition and morphology. The different morphologies obtained using conventional and smart blending greatly affected tocopherol release. Strong correlation was observed between morphology and release rate: multilayer, slow release; co-continuous and fiber, moderate; disperse: fast release. Results indicate that morphology can be manipulated by polymer composition and processing method, and release rates of tocopherols are varied with polymer morphology. Manipulating polymer compositions and film morphologies may provide a means to control the release of tocopherols from food contact films.

Effect of drug lipophilicity on in vitro release rate from oil vehicles using nicotinic acid esters as model prodrug derivatives.

PubMed

Weng Larsen, S; Engelbrecht Thomsen, A E; Rinvar, E; Friis, G J; Larsen, C

2001-03-23

The rate constants for transfer of a homologous series of nicotinic acid esters from oil vehicles to aqueous buffer phases were determined using a rotating dialysis cell. The chemical stability of butyl nicotinate has been investigated at 60 degrees C over pH range 0.5--10. Maximum stability occurs at pH 4--5 and an inflection point was seen around the pK(a). For the nicotinic acid esters, a linear correlation was established between the first-order rate constant related to attainment of equilibrium, k(obs) and the apparent partition coefficient, P(app): log k(obs)=-0.83log P(app)+0.26 (k(obs) in h(-1), n=9). For hexyl nicotinate with a true partition coefficient of 4 it was possible to determine k(obs) by decreasing pH in the aqueous release medium to 2.05. Thus, under the latter experimental conditions estimation of the relative release rates for the esters were performed. The ratio between the specific rate constant k(ow), related to the transport from oil vehicle to aqueous phase, for ethyl and hexyl nicotinate was 139. The hydrophobic substituent constant for a methylene group, pi(CH(2)), was determined for nicotinic acid esters in different oil/buffer partitioning systems to 0.54--0.58. Addition of hydroxypropyl-beta-cyclodextrin to the aqueous release medium did not enhance the transport rate of the esters from the oil phase.

An LNG release, transport, and fate model system for marine spills.

PubMed

Spaulding, Malcolm L; Swanson, J Craig; Jayko, Kathy; Whittier, Nicole

2007-02-20

LNGMAP, a fully integrated, geographic information based modular system, has been developed to predict the fate and transport of marine spills of LNG. The model is organized as a discrete set of linked algorithms that represent the processes (time dependent release rate, spreading, transport on the water surface, evaporation from the water surface, transport and dispersion in the atmosphere, and, if ignited, burning and associated radiated heat fields) affecting LNG once it is released into the environment. A particle-based approach is employed in which discrete masses of LNG released from the source are modeled as individual masses of LNG or spillets. The model is designed to predict the gas mass balance as a function of time and to display the spatial and temporal evolution of the gas (and radiated energy field). LNGMAP has been validated by comparisons to predictions of models developed by ABS Consulting and Sandia for time dependent point releases from a draining tank, with and without burning. Simulations were in excellent agreement with those performed by ABS Consulting and consistent with Sandia's steady state results. To illustrate the model predictive capability for realistic emergency scenarios, simulations were performed for a tanker entering Block Island Sound. Three hypothetical cases were studied: the first assumes the vessel continues on course after the spill starts, the second that the vessel stops as soon as practical after the release begins (3 min), and the third that the vessel grounds at the closest site practical. The model shows that the areas of the surface pool and the incident thermal radiation field (with burning) are minimized and dispersed vapor cloud area (without burning) maximized if the vessel continues on course. For this case the surface pool area, with burning, is substantially smaller than for the without burning case because of the higher mass loss rate from the surface pool due to burning. Since the vessel speed substantially exceeds the spill spreading rate, both the thermal radiation fields and surface pool trail the vessel. The relative directions and speeds of the wind and vessel movement govern the orientation of the dispersed plume. If the vessel stops, the areas of the surface pool and incident radiation field (with burning) are maximized and the dispersed cloud area (without burning) minimized. The longer the delay in stopping the vessel, the smaller the peak values are for the pool area and the size of the thermal radiation field. Once the vessel stops, the spill pool is adjacent to the vessel and moving down current. The thermal radiation field is oriented similarly. These results may be particularly useful in contingency planning for underway vessels.

Open circuit voltage durability study and model of catalyst coated membranes at different humidification levels

NASA Astrophysics Data System (ADS)

Kundu, Sumit; Fowler, Michael W.; Simon, Leonardo C.; Abouatallah, Rami; Beydokhti, Natasha

Fuel cell material durability is an area of extensive research today. Chemical degradation of the ionomer membrane is one important degradation mechanism leading to overall failure of fuel cells. This study examined the effects of relative humidity on the chemical degradation of the membrane during open circuit voltage testing. Five Gore™ PRIMEA ® series 5510 catalyst coated membranes were degraded at 100%, 75%, 50%, and 20% RH. Open circuit potential and cumulative fluoride release were monitored over time. Additionally scanning electron microscopy images were taken at end of the test. The results showed that with decreasing RH fluoride release rate increased as did performance degradation. This was attributed to an increase in gas crossover with a decrease in RH. Further, it is also shown that interruptions in testing may heavily influence cumulative fluoride release measurements where frequent stoppages in testing will cause fluoride release to be underestimated. SEM analysis shows that degradation occurred in the ionomer layer close to the cathode catalyst. A chemical degradation model of the ionomer membrane was used to model the results. The model was able to predict fluoride release trends, including the effects of interruptions, showing that changes in gas crossover with RH could explain the experimental results.

Detailed source term estimation of atmospheric release during the Fukushima Dai-ichi nuclear power plant accident by coupling atmospheric and oceanic dispersion models

NASA Astrophysics Data System (ADS)

Katata, Genki; Chino, Masamichi; Terada, Hiroaki; Kobayashi, Takuya; Ota, Masakazu; Nagai, Haruyasu; Kajino, Mizuo

2014-05-01

Temporal variations of release amounts of radionuclides during the Fukushima Dai-ichi Nuclear Power Plant (FNPP1) accident and their dispersion process are essential to evaluate the environmental impacts and resultant radiological doses to the public. Here, we estimated a detailed time trend of atmospheric releases during the accident by combining environmental monitoring data and coupling atmospheric and oceanic dispersion simulations by WSPEEDI-II (Worldwide version of System for Prediction of Environmental Emergency Dose Information) and SEA-GEARN developed by the authors. New schemes for wet, dry, and fog depositions of radioactive iodine gas (I2 and CH3I) and other particles (I-131, Te-132, Cs-137, and Cs-134) were incorporated into WSPEEDI-II. The deposition calculated by WSPEEDI-II was used as input data of ocean dispersion calculations by SEA-GEARN. The reverse estimation method based on the simulation by both models assuming unit release rate (1 Bq h-1) was adopted to estimate the source term at the FNPP1 using air dose rate, and air sea surface concentrations. The results suggested that the major release of radionuclides from the FNPP1 occurred in the following periods during March 2011: afternoon on the 12th when the venting and hydrogen explosion occurred at Unit 1, morning on the 13th after the venting event at Unit 3, midnight on the 14th when several openings of SRV (steam relief valve) were conducted at Unit 2, morning and night on the 15th, and morning on the 16th. The modified WSPEEDI-II using the newly estimated source term well reproduced local and regional patterns of air dose rate and surface deposition of I-131 and Cs-137 obtained by airborne observations. Our dispersion simulations also revealed that the highest radioactive contamination areas around FNPP1 were created from 15th to 16th March by complicated interactions among rainfall (wet deposition), plume movements, and phase properties (gas or particle) of I-131 and release rates associated with reactor pressure variations in Units 2 and 3.

Final report on the Controlled Cold Helium Spill Test in the LHC tunnel at CERN

NASA Astrophysics Data System (ADS)

Dufay-Chanat, L.; Bremer, J.; Casas-Cubillos, J.; Chorowski, M.; Grabowski, M.; Jedrusyna, A.; Lindell, G.; Nonis, M.; Koettig, T.; Vauthier, N.; van Weelderen, R.; Winkler, T.

2015-12-01

The 27 km circumference LHC underground tunnel is a space in which the helium cooled LHC magnets are installed. The vacuum enclosures of the superconducting magnets are protected by over-pressure safety relief devices that open whenever cold helium escapes either from the magnet cold enclosure or from the helium supply headers, into this vacuum enclosure. A 3-m long no stay zone around these devices is defined based on scale model studies, protecting the personnel against cold burns or asphyxia caused by such a helium release event. Recently, several simulation studies have been carried out modelling the propagation of the helium/air mixture, resulting from the opening of such a safety device, along the tunnel. The released helium flows vary in the range between 1 kg/s and 0.1 kg/s. To validate these different simulation studies, real life mock-up tests have been performed inside the LHC tunnel, releasing helium flow rates of 1 kg/s, 0.3 kg/s and 0.1 kg/s. For each test, up to 1000 liters of liquid helium were released under standard operational tunnel conditions. The data recorded include oxygen concentration, temperature and flow speed measurements, and video footage used to assess qualitatively the visibility. These measurements have been made in the up- and downstream directions, with respect to the air ventilation flow, of the spill point. This paper presents the experimental set-up under which these release tests were made, the effects of these releases on the atmospheric tunnel condition as a function of the release flow rate. We discuss the modification to the personnel access conditions to the LHC tunnel that are presently implemented as a result of these tests.

Quick Release of Internal Water Storage in a Glacier Leads to Underestimation of the Hazard Potential of Glacial Lake Outburst Floods From Lake Merzbacher in Central Tian Shan Mountains

NASA Astrophysics Data System (ADS)

Shangguan, Donghui; Ding, Yongjian; Liu, Shiyin; Xie, Zunyi; Pieczonka, Tino; Xu, Junli; Moldobekov, Bolot

2017-10-01

Glacial meltwater and ice calving contribute to the flood volume of glacial lakes such as Lake Merzbacher in the Tian Shan Mountains of central Asia. In this study, we simulated the lake's volume by constructing an empirical relationship between the area of Lake Merzbacher, determined from satellite images, and the lake's water storage, derived from digital elevation models. Results showed that the lake water supply rate before Glacial Lake Outburst Floods (GLOFs) generally agreed well with those during the GLOFs from 2009 to 2012 but not in 2008 and 2015. Furthermore, we found that the combination of glacial meltwater and ice calving is not enough to fully explain the supply rate during GLOFs in 1996 and 1999, suggesting other factors affect the supply rate during GLOFs as well. To examine this further, we compared the water supply rate before and during GLOF events in 1999 and 2008. We inferred that quickly released short-term and intermediate-term water storage by glaciers have likely contributed to both flood events in those years. This study highlights the need to improve our understanding of the supply component of outburst floods, such as irregularly released stored water may lead to GLOF events with generally three different types: case I (singular event-triggered englacial water release), case II (glacier melt due to temperature changes), and case III (englacial water release mixed with glacier melt).

In vivo release of levonorgestrel from Sino-implant (II) — an innovative comparison of explant data.

PubMed

Callahan, Rebecca L; Taylor, Douglas; Jenkins, David W; Owen, Derek H; Cheng, Linan; Cancel, Aida M; Dorflinger, Laneta J; Steiner, Markus J

2015-10-01

Measuring the amount of progestin remaining in contraceptive implants used for different lengths of time provides useful information on in vivo release kinetics including change over time. We compared estimated in vivo levonorgestrel (LNG) release rates derived from Sino-implant (II) explants with similar data from removed Jadelle. We measured LNG remaining in 44 sets of Sino-implant (II) used for up to 7 years and removed in four Chinese clinics. Results were compared with published data for Jadelle explants used for up to 36 months. We estimated and compared monthly and daily LNG release rates for the two products using prediction models for drug release. We also estimated the dissolution profile similarity factor, f2, for LNG release. Both Sino-implant (II) and Jadelle release approximately 30% of total LNG load after 3 years. Results of fitting the data to a biologically plausible modified Higuchi prediction model indicate comparable release through 3 years. An estimated similarity factor of 80.6 (90% confidence interval: 70.8-85.7) indicates similarity in the dissolution profiles of the two implants. LNG release in vivo measured through explant analysis suggest that Sino-implant (II) and Jadelle may perform similarly through 3 years of use and could remain highly effective beyond this time point. These results align with published data for Jadelle and Sino-implant (II) showing high effectiveness for 5 years. Ongoing clinical studies comparing the products over 5 years present an opportunity to verify this supportive measure of clinical effectiveness. This innovative approach provides evidence that Sino-implant (II) may perform clinically similarly to Jadelle over 3 years and remain a highly effective contraceptive beyond this time point. Data from explant analyses show promise for investigating the equivalence of elusion profiles of contraceptive implants. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Channelled tablets: An innovative approach to accelerating drug release from 3D printed tablets.

PubMed

Sadia, Muzna; Arafat, Basel; Ahmed, Waqar; Forbes, Robert T; Alhnan, Mohamed A

2018-01-10

Conventional immediate release dosage forms involve compressing the powder with a disintegrating agent that enables rapid disintegration and dissolution upon oral ingestion. Among 3D printing technologies, the fused deposition modelling (FDM) 3D printing technique has a considerable potential for patient-specific dosage forms. However, the use of FDM 3D printing in tablet manufacturing requires a large portion of polymer, which slows down drug release through erosion and diffusion mechanisms. In this study, we demonstrate for the first time the use of a novel design approach of caplets with perforated channels to accelerate drug release from 3D printed tablets. This strategy has been implemented using a caplet design with perforating channels of increasing width (0.2, 0.4, 0.6, 0.8 or 1.0mm) and variable length, and alignment (parallel or at right angle to tablet long axis). Hydrochlorothiazide (BCS class IV drug) was chosen as the model drug as enhanced dissolution rate is vital to guarantee oral bioavailability. The inclusion of channels exhibited an increase in the surface area/volume ratio, however, the release pattern was also influenced by the width and the length of the channel. A channel width was ≥0.6mm deemed critical to meet the USP criteria of immediate release products. Shorter multiple channels (8.6mm) were more efficient at accelerating drug release than longer channels (18.2mm) despite having comparable surface area/mass ratio. This behaviour may be linked to the reduced flow resistance within the channels and the faster fragmentation during dissolution of these tablets. In conclusion, the width and length of the channel should be carefully considered in addition to surface area/mass when optimizing drug release from 3D printed designs. The incorporation of short channels can be adopted in the designs of dosage forms, implants or stents to enhance the release rate of eluting drug from polymer-rich structures. Copyright © 2017 Elsevier B.V. All rights reserved.

Release of chemical permeation enhancers from drug-in-adhesive transdermal patches.

PubMed

Qvist, Michael H; Hoeck, Ulla; Kreilgaard, Bo; Madsen, Flemming; Frokjaer, Sven

2002-01-14

There is only limited knowledge of how chemical permeation enhancers release from transdermal drug delivery systems of the drug-in-adhesive type. In this study, the release of eight commonly known enhancers from eight types of polymer adhesives was evaluated using Franz diffusion cells. It was shown that all the enhancers released completely from the adhesives and followed a square root of time kinetic (Higuchi law). Using a statistical analysis it was shown that the release rate was more dependent on the type of enhancer than on the type of polymers. The mean release rates were in the range from 2.2 to 11.1%/ radical t for the slowest and fastest releasing enhancers, which correspond to a 50% release within 500 and 20 min, respectively. Furthermore, the release rates were inversely proportional to the cube root of the molal volumes of the enhancers and to their logarithmic partition coefficients between the polymer adhesive and the receptor fluid. It was found that the observed release rates were probably due to a high diffusion coefficient of the enhancers rather than due to an inhomogeneous embedment of the enhancers in the adhesives. The type of adhesive showed minor influence on the release rate, especially among the acrylic polymers no difference was seen. However, compared to the acrylic adhesives, the polyisobutylene adhesive showed slower release rates, while the silicone adhesive showed slightly faster release rates.

Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT)

NASA Astrophysics Data System (ADS)

Nagesha, D. K.; Tada, D. B.; Stambaugh, C. K. K.; Gultepe, E.; Jost, E.; Levy, C. O.; Cormack, R.; Makrigiorgos, G. M.; Sridhar, S.

2010-10-01

Image-guided radiation treatments (IGRT) routinely utilize radio-opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. The therapeutic efficiency of IGRT can be further enhanced by biological in situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs). In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer poly(methyl methacrylate) (PMMA) coating and (ii) poly(d,l-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. In the first case of free Dox release, an initial release within the first few hours was followed by a sustained release over the course of the next 3 months. In the second platform, release of NPs and the free drug was controlled by the degradation rate of the chitosan matrix and PLGA. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.

Effects of solubilizing surfactants and loading of antiviral, antimicrobial, and antifungal drugs on their release rates from ethylene vinyl acetate copolymer

PubMed Central

Tallury, Padmavathy; Randall, Marcus K; Thaw, Khin L; Preisser, John S.; Kalachandra, Sid

2013-01-01

Objectives This study investigates the effects of surfactants and drug loading on the drug release rate from ethylene vinyl acetate (EVA) copolymer. The release rate of nystatin from EVA was studied with addition of non-ionic surfactants Tween 60 and Cremophor RH 40. In addition, the effect of increasing drug load on the release rates of nystatin, chlorhexidine diacetate and acyclovir is also presented. Method Polymer casting solutions were prepared by stirring EVA copolymer and nystatin (2.5 wt %) in dichloromethane. Nystatin and surfactants were added in ratios of (1:1), (1:2) and (1:3). Drug loading was studied with 2.5, 5.0, 7.5, and 10.0% wt. proportions of nystatin, chlorhexidine diacetate and acyclovir incorporated into a separate polymer. Three drug loaded polymer square films (3cm × 3cm × 0.08 cm) were cut from dry films to follow the kinetics of drug release at 37°C. 10 ml of either distilled water or PBS was used as the extracting medium that was replaced daily. PBS was used for nystatin release with addition of surfactants and water was used for the study on drug loading and surfactant release. The rate of drug release was measured by UV-spectrophotometer. The amount of surfactant released was determined by HPLC. Results The release of nystatin was low in PBS and its release rate increased with the addition of surfactants. Also, increasing surfactant concentrations resulted in increased drug release rates. The release rates of chlorhexidine diacetate (p<0.0001), acyclovir (p<0.0003) and nystatin (p<0.0017) linearly increased with increasing drug loads. The amount of surfactants released was above the CMC. Significance This study demonstrates that the three therapeutic agents show a sustained rate of drug release from EVA copolymer over extended periods of time. Nystatin release in PBS is low owing to its poor solubility. Its release rate is enhanced by addition of surfactants and increasing the drug load as well. PMID:17049593

Dissolution kinetics of a lunar glass simulant at 25 degrees C: the effect of pH and organic acids

NASA Technical Reports Server (NTRS)

Eick, M. J.; Grossl, P. R.; Golden, D. C.; Sparks, D. L.; Ming, D. W.

1996-01-01

The dissolution kinetics of a simulated lunar glass were examined at pH 3, 5, and 7. Additionally, the pH 7 experiments were conducted in the presence of citric and oxalic acid at concentrations of 2 and 20 mM. The organic acids were buffered at pH 7 to examine the effect of each molecule in their dissociated form. At pH 3, 5, and 7, the dissolution of the synthetic lunar glass was observed to proceed via a two-stage process. The first stage involved the parabolic release of Ca, Mg, Al, and Fe, and the linear release of Si. Dissolution was incongruent, creating a leached layer rich in Si and Ti which was verified by transmission electron microscopy (TEM). During the second stage the release of Ca, Mg, Al, and Fe was linear. A coupled diffusion/surface dissolution model was proposed for dissolution of the simulated lunar glass at pH 3, 5, and 7. During the first stage the initial release of mobile cations (i.e., Ca, Mg, Al, Fe) was limited by diffusion through the surface leached layer of the glass (parabolic release), while Si release was controlled by the hydrolysis of the Si-O-Al bonds at the glass surface (linear release). As dissolution continued, the mobile cations diffused from greater depths within the glass surface. A steady-state was then reached where the diffusion rate across the increased path lengths equalled the Si release rate from the surface. In the presence of the organic acids, the dissolution of the synthetic lunar glass proceeded by a one stage process. The release of Ca, Mg, Al, and Fe followed a parabolic relationship, while the release of Si was linear. The relative reactivity of the organic acids used in the experiments was citrate > oxalate. A thinner leached layer rich in Si/Ti, as compared to the pH experiments, was observed using TEM. Rate data suggest that the chemisorption of the organic anion to the surface silanol groups was responsible for enhanced dissolution in the presence of the organic acids. It is proposed that the increased rate of Si release is responsible for the one stage parabolic release of mobile cations and the relatively thin leached layer compared to experiments at pH 3 and 5.

Modeling Dynamic Helium Release as a Tracer of Rock Deformation

DOE PAGES

Gardner, W. Payton; Bauer, Stephen J.; Kuhlman, Kristopher L.; ...

2017-11-03

Here, we use helium released during mechanical deformation of shales as a signal to explore the effects of deformation and failure on material transport properties. A dynamic dual-permeability model with evolving pore and fracture networks is used to simulate gases released from shale during deformation and failure. Changes in material properties required to reproduce experimentally observed gas signals are explored. We model two different experiments of 4He flow rate measured from shale undergoing mechanical deformation, a core parallel to bedding and a core perpendicular to bedding. We also found that the helium signal is sensitive to fracture development and evolutionmore » as well as changes in the matrix transport properties. We constrain the timing and effective fracture aperture, as well as the increase in matrix porosity and permeability. Increases in matrix permeability are required to explain gas flow prior to macroscopic failure, and the short-term gas flow postfailure. Increased matrix porosity is required to match the long-term, postfailure gas flow. This model provides the first quantitative interpretation of helium release as a result of mechanical deformation. The sensitivity of this model to changes in the fracture network, as well as to matrix properties during deformation, indicates that helium release can be used as a quantitative tool to evaluate the state of stress and strain in earth materials.« less

Modeling Dynamic Helium Release as a Tracer of Rock Deformation

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

Gardner, W. Payton; Bauer, Stephen J.; Kuhlman, Kristopher L.

Here, we use helium released during mechanical deformation of shales as a signal to explore the effects of deformation and failure on material transport properties. A dynamic dual-permeability model with evolving pore and fracture networks is used to simulate gases released from shale during deformation and failure. Changes in material properties required to reproduce experimentally observed gas signals are explored. We model two different experiments of 4He flow rate measured from shale undergoing mechanical deformation, a core parallel to bedding and a core perpendicular to bedding. We also found that the helium signal is sensitive to fracture development and evolutionmore » as well as changes in the matrix transport properties. We constrain the timing and effective fracture aperture, as well as the increase in matrix porosity and permeability. Increases in matrix permeability are required to explain gas flow prior to macroscopic failure, and the short-term gas flow postfailure. Increased matrix porosity is required to match the long-term, postfailure gas flow. This model provides the first quantitative interpretation of helium release as a result of mechanical deformation. The sensitivity of this model to changes in the fracture network, as well as to matrix properties during deformation, indicates that helium release can be used as a quantitative tool to evaluate the state of stress and strain in earth materials.« less

Constraints on the frequency-magnitude relation and maximum magnitudes in the UK from observed seismicity and glacio-isostatic recovery rates

NASA Astrophysics Data System (ADS)

Main, Ian; Irving, Duncan; Musson, Roger; Reading, Anya

1999-05-01

Earthquake populations have recently been shown to have many similarities with critical-point phenomena, with fractal scaling of source sizes (energy or seismic moment) corresponding to the observed Gutenberg-Richter (G-R) frequency-magnitude law holding at low magnitudes. At high magnitudes, the form of the distribution depends on the seismic moment release rate Msolar and the maximum magnitude m_max . The G-R law requires a sharp truncation at an absolute maximum magnitude for finite Msolar. In contrast, the gamma distribution has an exponential tail which allows a soft or `credible' maximum to be determined by negligible contribution to the total seismic moment release. Here we apply both distributions to seismic hazard in the mainland UK and its immediate continental shelf, constrained by a mixture of instrumental, historical and neotectonic data. Tectonic moment release rates for the seismogenic part of the lithosphere are calculated from a flexural-plate model for glacio-isostatic recovery, constrained by vertical deformation rates from tide-gauge and geomorphological data. Earthquake focal mechanisms in the UK show near-vertical strike-slip faulting, with implied directions of maximum compressive stress approximately in the NNW-SSE direction, consistent with the tectonic model. Maximum magnitudes are found to be in the range 6.3-7.5 for the G-R law, or 7.0-8.2 m_L for the gamma distribution, which compare with a maximum observed in the time period of interest of 6.1 m_L . The upper bounds are conservative estimates, based on 100 per cent seismic release of the observed vertical neotectonic deformation. Glacio-isostatic recovery is predominantly an elastic rather than a seismic process, so the true value of m_max is likely to be nearer the lower end of the quoted range.

Effect of ingested lipids on drug dissolution and release with concurrent digestion: a modeling approach

PubMed Central

Buyukozturk, Fulden; Di Maio, Selena; Budil, David E.; Carrier, Rebecca L.

2014-01-01

Purpose To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen. Methods Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in a model SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model. Results Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion were observed and predicted by the developed model. 90 minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion. Conclusion A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs. PMID:24234918

Modification of drug release from acetaminophen granules by melt granulation technique - consideration of release kinetics.

PubMed

Uhumwangho, M U; Okor, R S

2006-01-01

Acetaminophen granules have been formed by a melt granulation process with the objective of retarding drug release for prolonged action formulations. The waxes used were goat wax, carnuba wax and glyceryl monostearate. In the melt granulation procedure, acetaminophen powder was triturated with the melted waxes and passed through a sieve of mesh 10 (aperture size 710 microm). The content of wax in resulting granules ranged from 10 to 40%w/w. Acetaminophen granules were also formed by the convectional method of wet granulation with starch mucilage (20%w/w). The granules were subjected to in-vitro drug release tests. The release data were subjected to analysis by three different well-established mathematical models (release kinetics) namely, - zero order flux, first order, and the Higuchi square root of time relationship. The convectional granules exhibited an initial zero order flux (first 55%) followed by a first order release profile (the remaining 45%). The pattern of drug release from the melt granulations was consistent with the first order kinetic and the Higuchi square root of time relationship, indicating a diffusion-controlled release mechanism. The first order release rate constant of the convectional granules was 1.95 +/- 0.02 h(-1). After melt granulation (wax content, 20%w/w) the rate constants dropped drastically to 0.130+/-0.001 h(-1) (goat wax), 0.120+/-0.003 h(-1) (carnuba wax), and 0.130+/-0.002 h(-1) (glyceryl monosterate) indicating that all three waxes were equivalent in retarding drug release from the melt granulations.

Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

PubMed Central

Vijayakumar, Vediappan; Subramanian, Kaliappagounder

2013-01-01

Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

Bioactive Nano-Fibrous Scaffolds for Bone and Cartilage Tissue Engineering

NASA Astrophysics Data System (ADS)

Feng, Kai

Scaffolds that can mimic the structural features of natural extracellular matrix and can deliver biomolecules in a controlled fashion may provide cells with a favorable microenvironment to facilitate tissue regeneration. Biodegradable nanofibrous scaffolds with interconnected pore network have previously been developed in our laboratory to mimic collagen matrix and advantageously support both bone and cartilage regeneration. This dissertation project aims to expand both the structural complexity and the biomolecule delivery capacity of such biomimetic scaffolds for tissue engineering. We first developed a nanofibrous scaffold that can release an antibiotic (doxycycline) with a tunable release rate and a tunable dosage, which was demonstrated to be able to inhibit bacterial growth over a prolonged time period. We then developed a nanofibrous tissue-engineciing scaffold that can release basic fibroblast growth factor (bFGF) in a spatially and temporally controlled fashion. In a mouse subcutaneous implantation model, the bFGF-releasing scaffold was shown to enhance cell penetration, tissue ingrowth and angiogenesis. It was also found that both the dose and the release rate of bFGF play roles in the biologic function of the scaffold. After that, we developed a nanofibrous PLLA scaffold that can release both bone morphogenetic protein 7 (BMP-7) and platelet-derived growth factor (PDGF) with distinct dosages and release kinetics. It was demonstrated that BMP-7 and PDGF could synergistically enhance bone regeneration using a mouse ectopic bone formation model and a rat periodontal fenestration defect regeneration model. The regeneration outcome was dependent on the dosage, the ratio and the release kinetics of the two growth factors. Last, we developed an anisotropic composite scaffold with an upper layer mimicking the superficial zone of cartilage and a lower layer mimicking the middle zone of cartilage. The thin superficial layer was fabricated using an electrospinning technique to support a more parallel ECM orientation to the cartilage surface. The lower layer was fabricated using a phase-separation technique to support a more isotropic ECM distribution. Human bone marrow-derived mesenchymal stem cells (hMSCs) were seeded on this complex scaffold and cultured under chondrogenic conditions. The results showed that the composite scaffold was indeed able to support anisotropic cartilage tissue structure formation.

Preparation of monolithic osmotic pump system by coating the indented core tablet.

PubMed

Liu, Longxiao; Che, Binjie

2006-10-01

A method for the preparation of monolithic osmotic pump tablet was obtained by coating the indented core tablet compressed by the punch with a needle. Atenolol was used as the model drug, sodium chloride as osmotic agent and polyethylene oxide as suspending agent. Ethyl cellulose was employed as semipermeable membrane containing polyethylene glycol 400 as plasticizer for controlling membrane permeability. The formulation of atenolol osmotic pump tablet was optimized by orthogonal design and evaluated by similarity factor (f2). The optimal formulation was evaluated in various release media and agitation rates. Indentation size of core tablet hardly affected drug release in the range of (1.00-1.14) mm. The optimal osmotic tablet was found to be able to deliver atenolol at an approximately constant rate up to 24h, independent of both release media and agitation rate. The method that is simplified by coating the indented core tablet with the elimination of laser drilling may be promising in the field of the preparation of osmotic pump tablet.

In situ release rates of Cu and Zn from commercial antifouling paints at different salinities.

PubMed

Lagerström, Maria; Lindgren, J Fredrik; Holmqvist, Albin; Dahlström, Mia; Ytreberg, Erik

2018-02-01

Antifouling paints are environmentally risk assessed based on their biocidal release rates to the water phase. In situ release rates of copper (Cu) and zinc (Zn) were derived for five commercial paints in two recreational marinas with different salinities (5 and 14 PSU) using an X-Ray Fluorescence spectrometer (XRF). Salinity was found to significantly affect the Cu release, with twice the amount of Cu released at the higher salinity, while its influence on the Zn release was paint-specific. Site-specific release rates for water bodies with salinity gradients, e.g. the Baltic Sea, are therefore necessary for more realistic risk assessments of antifouling paints. Furthermore, the in situ release rates were up to 8 times higher than those generated using standardized laboratory or calculation methods. The environmental risk assessment repeated with the field release rates concludes that it is questionable whether the studied products should be allowed on the Swedish market. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Swelling, erosion and drug release characteristics of salbutamol sulfate from hydroxypropyl methylcellulose-based matrix tablets.

PubMed

Chaibva, Faith A; Khamanga, Sandile M M; Walker, Roderick B

2010-12-01

Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.

A squeeze-type osmotic tablet for controlled delivery of nifedipine.

PubMed

Park, Jung Soo; Shin, Jun Hyun; Lee, Dong Hun; Kim, Moon Suk; Rhee, John M; Lee, Hai Bang; Khang, Gilson

2008-01-01

Osmotic delivery systems are based on osmotic driving force. Nifedipine tablets, available under the trade names Procardia XL (Pfizer) and Adalat (Bayer), are commercialized drug-delivery systems of an elemental osmotic pump that the push-pull osmotic tablet operates successfully in delivering water-insoluble drugs. For the improvement of the release pattern and the solubility of the drug, we developed a squeeze-type osmotic tablet (SQT) for nifedipine as a model drug. The SQT was composed of one or more ring type of squeeze-push layer (squeeze-disc) and a centered drug core. Squeeze-discs were stacked up with different physicochemical properties with gradient such as viscosity, swelling ratio and water absorption ratio using the osmotic agents from a disc of bottom to top. The present work investigated the effect of different preparation factors, such as hydrophilic polymers, the molecular weight of polymers, coating process, orifice size and types of excipient on release performance of nifedipine. With the purpose of delivering water-insoluble nifedipine at an approximate zero-order rate and step-function rate for 24 h, SQT has been successfully prepared, and significantly improved in the release rate and patterns in comparison with the Adalat push-pull system in vitro release features.

Ni and Cr addition to alloy waste forms to reduce radionuclide environmental releases

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

Olson, L.

2016-10-11

Reference alloy waste forms (RAW) were fabricated and underwent hybrid corrosion/immersion testing to parameterize the ANL analytical oxidative-dissolution model to enable the calculation of fractional release rates and to determine the effectiveness of Ni and Cr trim additions in reducing release rates of radionuclide surrogates. Figure 1 shows the prototypical multiphase microstructure of the alloys with each phase type contributing about equally to the exposed surface area. The waste forms tested at SRNL were variations of the RAW-6 formulation that uses HT9 as the main alloy component, and are meant to enable evaluation of the impact of Ni and Crmore » trim additions on the release rates of actinides and Tc-99. The test solutions were deaerated alkaline and acidic brines, ranging in pH 3 to pH 10, representing potential repositories with those conditions. The testing approach consisted of 4 major steps; 1) bare surface corrosion measurements at pH values of 3, 5, 8, and 10, 2) hybrid potentiostatic hold/exposure measurements at pH 3, 3) measurement of radionuclide concentrations and relations to anodic current from potentiostatic holds, and 4) identification of corroding phases using SEM/EDS of electrodes.« less

Adhesive-Bonded Composite Joint Analysis with Delaminated Surface Ply Using Strain-Energy Release Rate

NASA Technical Reports Server (NTRS)

Chadegani, Alireza; Yang, Chihdar; Smeltzer, Stanley S. III

2012-01-01

This paper presents an analytical model to determine the strain energy release rate due to an interlaminar crack of the surface ply in adhesively bonded composite joints subjected to axial tension. Single-lap shear-joint standard test specimen geometry with thick bondline is followed for model development. The field equations are formulated by using the first-order shear-deformation theory in laminated plates together with kinematics relations and force equilibrium conditions. The stress distributions for the adherends and adhesive are determined after the appropriate boundary and loading conditions are applied and the equations for the field displacements are solved. The system of second-order differential equations is solved to using the symbolic computation tool Maple 9.52 to provide displacements fields. The equivalent forces at the tip of the prescribed interlaminar crack are obtained based on interlaminar stress distributions. The strain energy release rate of the crack is then determined by using the crack closure method. Finite element analyses using the J integral as well as the crack closure method are performed to verify the developed analytical model. It has been shown that the results using the analytical method correlate well with the results from the finite element analyses. An attempt is made to predict the failure loads of the joints based on limited test data from the literature. The effectiveness of the inclusion of bondline thickness is justified when compared with the results obtained from the previous model in which a thin bondline and uniform adhesive stresses through the bondline thickness are assumed.

Uranium Release from Acidic Weathered Hanford Sediments: Single-Pass Flow-Through and Column Experiments

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

Wang, Guohui; Um, Wooyong; Wang, Zheming

The reaction of acidic radioactive waste with sediments can induce mineral transformation reactions that, in turn, control contaminant fate. Here, sediment weathering by synthetic uranium-containing acid solutions was investigated using bench-scale experiments to simulate waste disposal conditions at Hanford’s cribs, USA. During acid weathering, the presence of phosphate exerted a strong influence over uranium mineralogy and a rapidly precipitated, crystalline uranium phosphate phase (meta-ankoleite [K(UO2)(PO4)·3H2O]) was identified using spectroscopic and diffraction-based techniques. In phosphate-free system, uranium oxyhydroxide minerals such as K-compreignacite [K2(UO2)6O4(OH)6·7H2O] were formed. Single-pass flow-through (SPFT) and column leaching experiments using synthetic Hanford pore water showed that uranium precipitatedmore » as meta-ankoleite during acid weathering was strongly retained in the sediments, with an average release rate of 2.67E-12 mol g-1 s-1. In the absence of phosphate, uranium release was controlled by dissolution of uranium oxyhydroxide (compreignacite-type) mineral with a release rate of 1.05-2.42E-10 mol g-1 s-1. The uranium mineralogy and release rates determined for both systems in this study support the development of accurate U-release models for prediction of contaminant transport. These results suggest that phosphate minerals may be a good candidate for uranium remediation approaches at contaminated sites.« less

Uranium Release from Acidic Weathered Hanford Sediments: Single-Pass Flow-Through and Column Experiments.

PubMed

Wang, Guohui; Um, Wooyong; Wang, Zheming; Reinoso-Maset, Estela; Washton, Nancy M; Mueller, Karl T; Perdrial, Nicolas; O'Day, Peggy A; Chorover, Jon

2017-10-03

The reaction of acidic radioactive waste with sediments can induce mineral transformation reactions that, in turn, control contaminant fate. Here, sediment weathering by synthetic uranium-containing acid solutions was investigated using bench-scale experiments to simulate waste disposal conditions at Hanford's cribs (Hanford, WA). During acid weathering, the presence of phosphate exerted a strong influence over uranium mineralogy and a rapidly precipitated, crystalline uranium phosphate phase (meta-ankoleite [K(UO 2 )(PO 4 )·3H 2 O]) was identified using spectroscopic and diffraction-based techniques. In phosphate-free system, uranium oxyhydroxide minerals such as K-compreignacite [K 2 (UO 2 ) 6 O 4 (OH) 6 ·7H 2 O] were formed. Single-pass flow-through (SPFT) and column leaching experiments using synthetic Hanford pore water showed that uranium precipitated as meta-ankoleite during acid weathering was strongly retained in the sediments, with an average release rate of 2.67 × 10 -12 mol g -1 s -1 . In the absence of phosphate, uranium release was controlled by dissolution of uranium oxyhydroxide (compreignacite-type) mineral with a release rate of 1.05-2.42 × 10 -10 mol g -1 s -1 . The uranium mineralogy and release rates determined for both systems in this study support the development of accurate U-release models for the prediction of contaminant transport. These results suggest that phosphate minerals may be a good candidate for uranium remediation approaches at contaminated sites.

Radiogenic helium in shallow groundwater within a clay till, southwestern Ontario

USGS Publications Warehouse

Sheldon, Amy L.; Solomon, D. Kip; Poreda, Robert J.; Hunt, Andrew

2003-01-01

Profiles of 4He in pore water were measured in clay aquitards in SW Ontario. The 4He distributions are consistent with groundwater velocities that are <6 mm yr−1, and thus diffusion is the dominant transport mechanism for 4He. Modeling indicates that the effective diffusion coefficient for 4He is 6.3 ± 1.6 × 10−6 cm2 s−1. Furthermore, the profiles are consistent with the internal release of 4He from aquitard sediments at a rate of 0.03–0.13 μcc(STP) kg−1 yr−1. These rates are also consistent with laboratory release experiments and, on average, are 600 times greater than the production of 4He from U/Th decay. Modeling and the ratio of 21Ne to 4He within the sediments indicate that although the aquitards were deposited about 13 kA BP, the sediments released >70% of initial 4He for 50 to 60 kA prior to incorporation into the till.

Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model.

PubMed

Zhao, Chunxia; Gunawardana, Manjula; Villinger, Francois; Baum, Marc M; Remedios-Chan, Mariana; Moench, Thomas R; Zeitlin, Larry; Whaley, Kevin J; Bohorov, Ognian; Smith, Thomas J; Anderson, Deborah J; Moss, John A

2017-07-01

The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known human immunodeficiency virus type 1 (HIV-1) isolates in vitro , is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other underdeveloped regions may be limited by the high cost of conventionally produced antibodies and the limited capacity to manufacture such antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana -manufactured VRC01 (VRC01-N) over a range of release rates have been developed. The pharmacokinetics and preliminary safety of VRC01-N pod-IVRs were evaluated in a rhesus macaque model. The devices sustained VRC01-N release for up to 21 days at controlled rates, with mean steady-state VRC01-N levels in vaginal fluids in the range of 10 2 to 10 3 μg g -1 being correlated with in vitro release rates. No adverse safety indications were observed. These findings indicate that pod-IVRs are promising devices for the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection and merit further preclinical evaluation. Copyright © 2017 American Society for Microbiology.

Predicting dredging-associated effects to coral reefs in Apra Harbor, Guam - Part 1: Sediment exposure modeling.

PubMed

Gailani, Joseph Z; Lackey, Tahirih C; King, David B; Bryant, Duncan; Kim, Sung-Chan; Shafer, Deborah J

2016-03-01

Model studies were conducted to investigate the potential coral reef sediment exposure from dredging associated with proposed development of a deepwater wharf in Apra Harbor, Guam. The Particle Tracking Model (PTM) was applied to quantify the exposure of coral reefs to material suspended by the dredging operations at two alternative sites. Key PTM features include the flexible capability of continuous multiple releases of sediment parcels, control of parcel/substrate interaction, and the ability to efficiently track vast numbers of parcels. This flexibility has facilitated simulating the combined effects of sediment released from clamshell dredging and chiseling within Apra Harbor. Because the rate of material released into the water column by some of the processes is not well understood or known a priori, the modeling approach was to bracket parameters within reasonable ranges to produce a suite of potential results from multiple model runs. Sensitivity analysis to model parameters is used to select the appropriate parameter values for bracketing. Data analysis results include mapping the time series and the maximum values of sedimentation, suspended sediment concentration, and deposition rate. Data were used to quantify various exposure processes that affect coral species in Apra Harbor. The goal of this research is to develop a robust methodology for quantifying and bracketing exposure mechanisms to coral (or other receptors) from dredging operations. These exposure values were utilized in an ecological assessment to predict effects (coral reef impacts) from various dredging scenarios. Copyright © 2015. Published by Elsevier Ltd.

Evaluation of hydrophobic materials as matrices for controlled-release drug delivery.

PubMed

Quadir, Mohiuddin Abdul; Rahman, M Sharifur; Karim, M Ziaul; Akter, Sanjida; Awkat, M Talat Bin; Reza, Md Selim

2003-07-01

The present study was undertaken to evaluate the effect of different insoluble and erodable wax-lipid based materials and their content level on the release profile of drug from matrix systems. Matrix tablets of theophylline were prepared using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol and glyceryl monostearate as rate-retarding agents by direct compression process. The release of theophylline from these hydrophobic matrices was studied over 8-hours in buffer media of pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The release kinetics was found to be governed by the type and content of hydrophobic materials in the matrix. At lower level of wax matrices (25%), a potential burst release was observed with all the materials being studied. Bees wax could not exert any sustaining action while an extensive burst release was found with carnauba wax at this hydrophobic load. Increasing the concentration of fat-wax materials significantly decreased the burst effect of drug from the matrix. At higher hydrophobic level (50% of the matrix), the rate and extent of drug release was significantly reduced due to increased tortuosity and reduced porosity of the matrix. Cetostearyl alcohol imparted the strongest retardation of drug release irrespective of fat-wax level. Numerical fits indicate that the Higuchi square root of time model was the most appropriate one for describing the release profile of theophylline from hydrophobic matrices. The release mechanism was also explored and explained with biexponential equation. Application of this model indicates that Fickian or case I kinetics is the predominant mechanism of drug release from these wax-lipid matrices. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be attributed to some level of swelling and erosion within this matrix at lower fat-wax level which is also supported by release exponent values and Fickian fraction release against time profile of this agent. The results generated in this study showed that proper selection of these hydrophobic materials based on their physico-chemical properties is important in designing wax matrix tablets with desired dissolution profile.

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology.

PubMed

Mohammed, Noorullah Naqvi; Majumdar, Soumyajit; Singh, Abhilasha; Deng, Weibin; Murthy, Narasimha S; Pinto, Elanor; Tewari, Divya; Durig, Thomas; Repka, Michael A

2012-12-01

The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

Potential Application of Silica Mineral from Dieng Mountain in Agriculture Sector to Control the Release Rate of Fertilizer Elements

NASA Astrophysics Data System (ADS)

Solihin; Mursito, Anggoro Tri; Dida, Eki N.; Erlangga, Bagus D.; Widodo

2017-07-01

Silica mineral, which comes along with geothermal fluid in Dieng, is a product of erosion, decomposition and dissolution of silicon oxide based mineral, which is followed by precipitation to form silica mineral. This silica cell structure is non crystalline, and it contains 85,60 % silicon oxide, 6.49 volatile elements, and also other oxide elements. Among the direct potential application of this silica is as raw material in slow release fertilizer. Silica in compacted slow release fertilizer is able control the release rate of fertilizer elements. Two type of slow release fertilizer has been made by using silica as the matrix in these slow release fertilizer. The first type is the mixing of ordinary solid fertilizer with Dieng silica, whereas the second one is the mixing of disposal leach water with Dieng silica. The release test shows that both of these modified fertilizers have slow release fertilizer characteristic. The release rate of fertilizer elements (magnesium, potassium, ammonium, and phosphate) can be significantly reduced. The addition of kaolin in the first type of slow release fertilizer makes the release rate of fertilizer elements can be more slowed down. Meanwhile in the second type of slow release fertilizer, the release rate is determined by ratio of silica/hydrogel. The lowest release rate is achieved by sample that has highest ratio of silica/hydrogel.

Advances in mechanistic understanding of release rate control mechanisms of extended-release hydrophilic matrix tablets.

PubMed

Timmins, Peter; Desai, Divyakant; Chen, Wei; Wray, Patrick; Brown, Jonathan; Hanley, Sarah

2016-08-01

Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are described, recent advances including the role of percolation thresholds, the application on magnetic resonance and other spectroscopic imaging techniques are considered. The influence of polymer and dosage form characteristics are reviewed. The utility of mathematical modeling is described. Finally, how all the information derived from applying the developed mechanistic understanding from all of these tools can be brought together to develop a robust and reliable hydrophilic matrix extended-release tablet formulation is proposed.

A Controlled Drug-Delivery Experiment Using Alginate Beads

ERIC Educational Resources Information Center

Farrell, Stephanie; Vernengo, Jennifer

2012-01-01

This paper describes a simple, cost-effective experiment which introduces students to drug delivery and modeling using alginate beads. Students produce calcium alginate beads loaded with drug and measure the rate of release from the beads for systems having different stir rates, geometries, extents of cross-linking, and drug molecular weight.…

Synaptic release and extracellular actions of Zn2+ limit propagation of spreading depression and related events in vitro and in vivo

PubMed Central

Aiba, Isamu; Carlson, Andrew P.; Sheline, Christian T.

2012-01-01

Cortical spreading depression (CSD) is a consequence of a slowly propagating wave of neuronal and glial depolarization (spreading depolarization; SD). Massive release of glutamate contributes to SD propagation, and it was recently shown that Zn2+ is also released from synaptic vesicles during SD. The present study examined consequences of extracellular Zn2+ accumulation on the propagation of SD. SD mechanisms were studied first in murine brain slices, using focal KCl applications as stimuli and making electrical and optical recordings in hippocampal area CA1. Elevating extracellular Zn2+ concentrations with exogenous ZnCl2 reduced SD propagation rates. Selective chelation of endogenous Zn2+ (using TPEN or CaEDTA) increased SD propagation rates, and these effects appeared due to chelation of Zn2+ derived from synaptic vesicles. Thus, in tissues where synaptic Zn2+ release was absent [knockout (KO) of vesicular Zn2+ transporter ZnT-3], SD propagation rates were increased, and no additional increase was observed following chelation of endogenous Zn2+ in these tissues. The role of synaptic Zn2+ was then examined on CSD in vivo. ZnT-3 KO animals had higher susceptibility to CSD than wild-type controls as evidenced by significantly higher propagation rates and frequencies. Studies of candidate mechanisms excluded changes in neuronal excitability, presynaptic release, and GABA receptors but left open a possible contribution of N-methyl-d-aspartate (NMDA) receptor inhibition. These results suggest the extracellular accumulation of synaptically released Zn2+ can serve as an intrinsic inhibitor to limit SD events. The inhibitory action of extracellular Zn2+ on SD may counteract to some extent the neurotoxic effects of intracellular Zn2+ accumulation in acute brain injury models. PMID:22131381

Synaptic release and extracellular actions of Zn2+ limit propagation of spreading depression and related events in vitro and in vivo.

PubMed

Aiba, Isamu; Carlson, Andrew P; Sheline, Christian T; Shuttleworth, C William

2012-02-01

Cortical spreading depression (CSD) is a consequence of a slowly propagating wave of neuronal and glial depolarization (spreading depolarization; SD). Massive release of glutamate contributes to SD propagation, and it was recently shown that Zn(2+) is also released from synaptic vesicles during SD. The present study examined consequences of extracellular Zn(2+) accumulation on the propagation of SD. SD mechanisms were studied first in murine brain slices, using focal KCl applications as stimuli and making electrical and optical recordings in hippocampal area CA1. Elevating extracellular Zn(2+) concentrations with exogenous ZnCl(2) reduced SD propagation rates. Selective chelation of endogenous Zn(2+) (using TPEN or CaEDTA) increased SD propagation rates, and these effects appeared due to chelation of Zn(2+) derived from synaptic vesicles. Thus, in tissues where synaptic Zn(2+) release was absent [knockout (KO) of vesicular Zn(2+) transporter ZnT-3], SD propagation rates were increased, and no additional increase was observed following chelation of endogenous Zn(2+) in these tissues. The role of synaptic Zn(2+) was then examined on CSD in vivo. ZnT-3 KO animals had higher susceptibility to CSD than wild-type controls as evidenced by significantly higher propagation rates and frequencies. Studies of candidate mechanisms excluded changes in neuronal excitability, presynaptic release, and GABA receptors but left open a possible contribution of N-methyl-d-aspartate (NMDA) receptor inhibition. These results suggest the extracellular accumulation of synaptically released Zn(2+) can serve as an intrinsic inhibitor to limit SD events. The inhibitory action of extracellular Zn(2+) on SD may counteract to some extent the neurotoxic effects of intracellular Zn(2+) accumulation in acute brain injury models.

Improved estimates of environmental copper release rates from antifouling products.

PubMed

Finnie, Alistair A

2006-01-01

The US Navy Dome method for measuring copper release rates from antifouling paint in-service on ships' hulls can be considered to be the most reliable indicator of environmental release rates. In this paper, the relationship between the apparent copper release rate and the environmental release rate is established for a number of antifouling coating types using data from a variety of available laboratory, field and calculation methods. Apart from a modified Dome method using panels, all laboratory, field and calculation methods significantly overestimate the environmental release rate of copper from antifouling coatings. The difference is greatest for self-polishing copolymer antifoulings (SPCs) and smallest for certain erodible/ablative antifoulings, where the ASTM/ISO standard and the CEPE calculation method are seen to typically overestimate environmental release rates by factors of about 10 and 4, respectively. Where ASTM/ISO or CEPE copper release rate data are used for environmental risk assessment or regulatory purposes, it is proposed that the release rate values should be divided by a correction factor to enable more reliable generic environmental risk assessments to be made. Using a conservative approach based on a realistic worst case and accounting for experimental uncertainty in the data that are currently available, proposed default correction factors for use with all paint types are 5.4 for the ASTM/ISO method and 2.9 for the CEPE calculation method. Further work is required to expand this data-set and refine the correction factors through correlation of laboratory measured and calculated copper release rates with the direct in situ environmental release rate for different antifouling paints under a range of environmental conditions.

Comminution of solids caused by kinetic energy of high shear strain rate, with implications for impact, shock, and shale fracturing.

PubMed

Bazant, Zdenek P; Caner, Ferhun C

2013-11-26

Although there exists a vast literature on the dynamic comminution or fragmentation of rocks, concrete, metals, and ceramics, none of the known models suffices for macroscopic dynamic finite element analysis. This paper outlines the basic idea of the macroscopic model. Unlike static fracture, in which the driving force is the release of strain energy, here the essential idea is that the driving force of comminution under high-rate compression is the release of the local kinetic energy of shear strain rate. The density of this energy at strain rates >1,000/s is found to exceed the maximum possible strain energy density by orders of magnitude, making the strain energy irrelevant. It is shown that particle size is proportional to the -2/3 power of the shear strain rate and the 2/3 power of the interface fracture energy or interface shear stress, and that the comminution process is macroscopically equivalent to an apparent shear viscosity that is proportional (at constant interface stress) to the -1/3 power of this rate. A dimensionless indicator of the comminution intensity is formulated. The theory was inspired by noting that the local kinetic energy of shear strain rate plays a role analogous to the local kinetic energy of eddies in turbulent flow.

Multi-regime transport model for leaching behavior of heterogeneous porous materials.

PubMed

Sanchez, F; Massry, I W; Eighmy, T; Kosson, D S

2003-01-01

Utilization of secondary materials in civil engineering applications (e.g. as substitutes for natural aggregates or binder constituents) requires assessment of the physical and environment properties of the product. Environmental assessment often necessitates evaluation of the potential for constituent release through leaching. Currently most leaching models used to estimate long-term field performance assume that the species of concern is uniformly dispersed in a homogeneous porous material. However, waste materials are often comprised of distinct components such as coarse or fine aggregates in a cement concrete or waste encapsulated in a stabilized matrix. The specific objectives of the research presented here were to (1) develop a one-dimensional, multi-regime transport model (i.e. MRT model) to describe the release of species from heterogeneous porous materials and, (2) evaluate simple limit cases using the model for species when release is not dependent on pH. Two different idealized model systems were considered: (1) a porous material contaminated with the species of interest and containing inert aggregates and, (2) a porous material containing the contaminant of interest only in the aggregates. The effect of three factors on constituent release were examined: (1) volume fraction of material occupied by the aggregates compared to a homogeneous porous material, (2) aggregate size and, (3) differences in mass transfer rates between the binder and the aggregates. Simulation results confirmed that assuming homogeneous materials to evaluate the release of contaminants from porous waste materials may result in erroneous long-term field performance assessment.

Harvest and reporting rates of game-farm ring-necked pheasants

USGS Publications Warehouse

Diefenbach, D.R.; Riegner, C.F.; Hardisky, T.S.

2000-01-01

Many state natural resource agencies release ring-necked pheasants (Phasianus colchicus) for hunting, but the effectiveness of these programs has never been evaluated on a statewide basis. We conducted a reward-band study to estimate harvest, reporting, and survival rates of pheasants raised and released by the Pennsylvania Game Commission (PGC) for the fall 1998 hunting season. We banded 6,770 of 199,613 released pheasants with leg bands worth $0-$400. Rewards >$75 produced 100% reporting rates. Hunters reported 71.0% of harvested pheasants banded with standard bands (no reward). Cocks had an estimated 62.3% harvest rate when released on public land and a 46.8% harvest rate on private land. Hens had an estimated 50.4% harvest rate when released on public land and a 31.1% harvest rate on private land. Estimated harvest rate for hen pheasants released in September in the either-sex zone was 15.5%. In the late season, pheasants released on public land had a 33.6% harvest rate and a 23.5% harvest rate on private land. We found that few pheasants (30 days and birds released on public land had reduced survival rates primarily because of greater harvest rates. In fiscal year 1998-99, the net cost to raise and release 199,613 pheasants was $2,813,138 ($14.09 per bird). The average cost per harvested pheasant was $29.10, but ranged from $22.63 to $90.74 depending on the date and location of release. We estimated that 49.9% (82,017 birds) of pheasants stocked immediately prior to and during the regular and late seasons (excluding September releases of hens) were harvested by hunters. Percentage of pheasants harvested by hunters could be increased by expanding the either-sex zone in Pennsylvania so that more hens could be legally killed by hunters and by allocating releases to seasons and locations with greater harvest rates. However, before such changes are implemented, we recommend a survey of Pennsylvania pheasant hunters to ascertain their opinions and desires regarding releases of game-farm pheasants.

Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability.

PubMed

Solanki, Nayan G; Tahsin, Md; Shah, Ankita V; Serajuddin, Abu T M

2018-01-01

The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling. Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10% and 20% w/w of haloperidol using Kollidon ® VA64, Kollicoat ® IR, Affinsiol ™ 15 cP, and HPMCAS either individually or as binary blends (Kollidon ® VA64 + Affinisol ™ 15 cP, 1:1; Kollidon ® VA64 + HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100% and 60% infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon ® VA64-Affinisol ™ 15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60% and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon ® VA64 and Affinisol ™ 15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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.

Spatially resolved heat release rate measurements in turbulent premixed flames

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

Ayoola, B.O.; Kaminski, C.F.; Balachandran, R.

Heat release rate is a fundamental property of great importance for the theoretical and experimental elucidation of unsteady flame behaviors such as combustion noise, combustion instabilities, and pulsed combustion. Investigations of such thermoacoustic interactions require a reliable indicator of heat release rate capable of resolving spatial structures in turbulent flames. Traditionally, heat release rate has been estimated via OH or CH radical chemiluminescence; however, chemiluminescence suffers from being a line-of-sight technique with limited capability for resolving small-scale structures. In this paper, we report spatially resolved two-dimensional measurements of a quantity closely related to heat release rate. The diagnostic technique usesmore » simultaneous OH and CH{sub 2}O planar laser-induced fluorescence (PLIF), and the pixel-by-pixel product of the OH and CH{sub 2}O PLIF signals has previously been shown to correlate well with local heat release rates. Results from this diagnostic technique, which we refer to as heat release rate imaging (HR imaging), are compared with traditional OH chemiluminescence measurements in several flames. Studies were performed in lean premixed ethylene flames stabilized between opposed jets and with a bluff body. Correlations between bulk strain rates and local heat release rates were obtained and the effects of curvature on heat release rate were investigated. The results show that the heat release rate tends to increase with increasing negative curvature for the flames investigated for which Lewis numbers are greater than unity. This correlation becomes more pronounced as the flame gets closer to global extinction.« less

Poly(2-ethyl-2-oxazoline) as matrix excipient for drug formulation by hot melt extrusion and injection molding.

PubMed

Claeys, Bart; Vervaeck, Anouk; Vervaet, Chris; Remon, Jean Paul; Hoogenboom, Richard; De Geest, Bruno G

2012-10-15

Here we evaluate poly(2-ethyl-2-oxazoline)s (PEtOx) as a matrix excipient for the production of oral solid dosage forms by hot melt extrusion (HME) followed by injection molding (IM). Using metoprolol tartrate as a good water-soluble model drug we demonstrate that drug release can be delayed by HME/IM, with the release rate controlled by the molecular weight of the PEtOx. Using fenofibrate as a lipophilic model drug we demonstrate that relative to the pure drug the dissolution rate is strongly enhanced by formulation in HME/IM tablets. For both drug molecules we find that solid solutions, i.e. molecularly dissolved drug in a polymeric matrix, are obtained by HME/IM. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sodium and sulfur release and recapture during black liquor burning

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

Frederick, W.J.; Iisa, K.; Wag, K.

1995-08-01

The objective of this study was to provide data on sulfur and sodium volatilization during black liquor burning, and on SO2 capture by solid sodium carbonate and sodium chloride. This data was interpreted and modeled into rate equations suitable for use in computational models for recovery boilers.

Toroidal-spiral particles for codelivery of anti-VEGFR-2 antibody and irinotecan: a potential implant to hinder recurrence of glioblastoma multiforme.

PubMed

Sharma, Vishal; Köllmer, Melanie; Szymusiak, Magdalena; Nitsche, Ludwig C; Gemeinhart, Richard A; Liu, Ying

2014-03-10

Heterogeneous toroidal-spiral particles (TSPs) were generated by polymer droplet sedimentation, interaction, and cross-linking. TSPs provide a platform for encapsulation and release of multiple compounds of different sizes and physicochemical properties. As a model system, we demonstrate the encapsulation and independently controlled release of an anti-VEGFR-2 antibody and irinotecan for the treatment of glioblastoma multiforme. The anti-VEGFR-2 antibody was released from the TS channels and its binding to HUVECs was confirmed by confocal microscopy and flow cytometry, suggesting active antibody encapsulation and release. Irinotecan, a small molecule drug, was released from the dense polymer matrix of poly(ethylene glycol) diacrylate (MW ~ 700 g/mol; PEGDA 700). Released irinotecan inhibited the proliferation of U251 malignant glioma cells. Since the therapeutic compounds are released through different pathways, specifically diffusion through the polymer matrix versus TS channels, the release rate can be controlled independently through the design of the structure and material of particle components.

Fission-gas release from uranium nitride at high fission rate density

NASA Technical Reports Server (NTRS)

Weinstein, M. B.; Kirchgessner, T. A.; Tambling, T. N.

1973-01-01

A sweep gas facility has been used to measure the release rates of radioactive fission gases from small UN specimens irradiated to 8-percent burnup at high fission-rate densities. The measured release rates have been correlated with an equation whose terms correspond to direct recoil release, fission-enhanced diffusion, and atomic diffusion (a function of temperature). Release rates were found to increase linearly with burnups between 1.5 and 8 percent. Pore migration was observed after operation at 1550 K to over 6 percent burnup.

The Fukushima releases: an inverse modelling approach to assess the source term by using gamma dose rate observations

NASA Astrophysics Data System (ADS)

Saunier, Olivier; Mathieu, Anne; Didier, Damien; Tombette, Marilyne; Quélo, Denis; Winiarek, Victor; Bocquet, Marc

2013-04-01

The Chernobyl nuclear accident and more recently the Fukushima accident highlighted that the largest source of error on consequences assessment is the source term estimation including the time evolution of the release rate and its distribution between radioisotopes. Inverse modelling methods have proved to be efficient to assess the source term due to accidental situation (Gudiksen, 1989, Krysta and Bocquet, 2007, Stohl et al 2011, Winiarek et al 2012). These methods combine environmental measurements and atmospheric dispersion models. They have been recently applied to the Fukushima accident. Most existing approaches are designed to use air sampling measurements (Winiarek et al, 2012) and some of them use also deposition measurements (Stohl et al, 2012, Winiarek et al, 2013). During the Fukushima accident, such measurements are far less numerous and not as well distributed within Japan than the dose rate measurements. To efficiently document the evolution of the contamination, gamma dose rate measurements were numerous, well distributed within Japan and they offered a high temporal frequency. However, dose rate data are not as easy to use as air sampling measurements and until now they were not used in inverse modelling approach. Indeed, dose rate data results from all the gamma emitters present in the ground and in the atmosphere in the vicinity of the receptor. They do not allow one to determine the isotopic composition or to distinguish the plume contribution from wet deposition. The presented approach proposes a way to use dose rate measurement in inverse modeling approach without the need of a-priori information on emissions. The method proved to be efficient and reliable when applied on the Fukushima accident. The emissions for the 8 main isotopes Xe-133, Cs-134, Cs-136, Cs-137, Ba-137m, I-131, I-132 and Te-132 have been assessed. The Daiichi power plant events (such as ventings, explosions…) known to have caused atmospheric releases are well identified in the retrieved source term, except for unit 3 explosion where no measurement was available. The comparisons between the simulations of atmospheric dispersion and deposition of the retrieved source term show a good agreement with environmental observations. Moreover, an important outcome of this study is that the method proved to be perfectly suited to crisis management and should contribute to improve our response in case of a nuclear accident.

Process-based modeling of silicate mineral weathering responses to increasing atmospheric CO2 and climate change

NASA Astrophysics Data System (ADS)

Banwart, Steven A.; Berg, Astrid; Beerling, David J.

2009-12-01

A mathematical model describes silicate mineral weathering processes in modern soils located in the boreal coniferous region of northern Europe. The process model results demonstrate a stabilizing biological feedback mechanism between atmospheric CO2 levels and silicate weathering rates as is generally postulated for atmospheric evolution. The process model feedback response agrees within a factor of 2 of that calculated by a weathering feedback function of the type generally employed in global geochemical carbon cycle models of the Earth's Phanerozoic CO2 history. Sensitivity analysis of parameter values in the process model provides insight into the key mechanisms that influence the strength of the biological feedback to weathering. First, the process model accounts for the alkalinity released by weathering, whereby its acceleration stabilizes pH at values that are higher than expected. Although the process model yields faster weathering with increasing temperature, because of activation energy effects on mineral dissolution kinetics at warmer temperature, the mineral dissolution rate laws utilized in the process model also result in lower dissolution rates at higher pH values. Hence, as dissolution rates increase under warmer conditions, more alkalinity is released by the weathering reaction, helping maintain higher pH values thus stabilizing the weathering rate. Second, the process model yields a relatively low sensitivity of soil pH to increasing plant productivity. This is due to more rapid decomposition of dissolved organic carbon (DOC) under warmer conditions. Because DOC fluxes strongly influence the soil water proton balance and pH, this increased decomposition rate dampens the feedback between productivity and weathering. The process model is most sensitive to parameters reflecting soil structure; depth, porosity, and water content. This suggests that the role of biota to influence these characteristics of the weathering profile is as important, if not more important, than the role of biota to influence mineral dissolution rates through changes in soil water chemistry. This process-modeling approach to quantify the biological weathering feedback to atmospheric CO2 demonstrates the potential for a far more mechanistic description of weathering feedback in simulations of the global geochemical carbon cycle.

A reaction-diffusion model of the Darien Gap Sterile Insect Release Method

NASA Astrophysics Data System (ADS)

Alford, John G.

2015-05-01

The Sterile Insect Release Method (SIRM) is used as a biological control for invasive insect species. SIRM involves introducing large quantities of sterilized male insects into a wild population of invading insects. A fertile/sterile mating produces offspring that are not viable and the wild insect population will eventually be eradicated. A U.S. government program maintains a permanent sterile fly barrier zone in the Darien Gap between Panama and Columbia to control the screwworm fly (Cochliomyia Hominivorax), an insect that feeds off of living tissue in mammals and has devastating effects on livestock. This barrier zone is maintained by regular releases of massive quantities of sterilized male screwworm flies from aircraft. We analyze a reaction-diffusion model of the Darien Gap barrier zone. Simulations of the model equations yield two types of spatially inhomogeneous steady-state solutions representing a sterile fly barrier that does not prevent invasion and a barrier that does prevent invasion. We investigate steady-state solutions using both phase plane methods and monotone iteration methods and describe how barrier width and the sterile fly release rate affects steady-state behavior.

Model of adipose tissue cellularity dynamics during food restriction.

PubMed

Soula, H A; Géloën, A; Soulage, C O

2015-01-07

Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Modeling Vascularized Bone Regeneration Within a Porous Biodegradable CaP Scaffold Loaded with Growth Factors

PubMed Central

Sun, X; Kang, Y; Bao, J; Zhang, Y; Yang, Y; Zhou, X

2013-01-01

Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors. PMID:23566802

Release kinetics of vanadium from vanadium titano-magnetite: The effects of pH, dissolved oxygen, temperature and foreign ions.

PubMed

Hu, Xingyun; Yue, Yuyan; Peng, Xianjia

2018-02-01

As part of a broader study of the environmental geochemistry behavior of vanadium (V), the release kinetics of V from the dissolution of natural vanadium titano-magnetite under environmentally relevant conditions was investigated. In both the acidic and basic domains, the V release rate was found to be proportional to fractional powers of hydrogen ion and dissolved oxygen activities. The dependence of the rate on dissolved oxygen can also be described in terms of the Langmuir adsorption model. The empirical rate equation is given by: r [Formula: see text] where, α=0.099-0.265, k'=3.2×10 -6 -1.7×10 -5 , K=2.7×10 4 -3.9×10 4 mol/L in acid solution (pH4.1), and α=-0.494-(-0.527), k'=2.0×10 4 -2.5×10 -11 , and K=4.1×10 3 -6.5×10 3 mol/L in basic solution (pH8.8) at 20°C. Based on the effect of temperature on the release rate of V, the activation energies of minerals at pH8.8 were determined to be 148-235kJ/mol, suggesting that the dissolution of vanadium titano-magnetite is a surface-controlled process. The presence of Na + , Ca 2+ , Mg 2+ , K + , NO 3 - , Cl - , SO 4 2- and CO 3 2- was found to accelerate the V release rates. This study improves the understanding of both the V pollution risk in some mine areas and the fate of V in the environment. Copyright © 2017. Published by Elsevier B.V.

CrossWater - Modelling micropollutant loads from different sources in the Rhine basin

NASA Astrophysics Data System (ADS)

Moser, Andreas; Bader, Hans-Peter; Fenicia, Fabrizio; Scheidegger, Ruth; Stamm, Christian

2015-04-01

The contamination of fresh surface waters with micropollutants originating from various sources is a growing environmental issue. The challenges for an effective political regulation are numerous, particularly for international water basins. One prerequisite for effective management is the knowledge of water quality across different parts of a basin. In this study within the Rhine basin, the spatial patterns of micropollutant loads and concentrations from different use classes are investigated with a mass flow analysis and compared to the established territorial jurisdictions on micropollutants and water quality. The source area of micropollutants depends on the specific use of a compound. The focus of this study is on i) herbicides from agricultural landuse, ii) biocides from material protection on buildings and iii) human pharmaceuticals from households. The total mass of micropollutants available for release to the stream network is estimated based on statistical application and consumption data. Based on GIS data of agricultural landuse, vector data of buildings, wastewater treatment plant (WWTP) locations, respectively, the available mass of micropollutants is spatially distributed to the catchment areas. The actual release of micropollutants to the stream network is calculated with empirical loss rates related to river discharge for agricultural herbicides and to precipitation for biocides. For the pharmaceuticals the release is coupled to the metabolism rates and elimination rates in WWTP. For a first approximation national sales are downscaled to the catchment level to specify the available mass for selected model compounds (agricultural herbicides: Isoproturon, biocides: Carbendazim, human pharmaceuticals: Carbamazepine and Diclofenac). The available mass of herbicides and biocides is multiplied with empirical loss rates independent from discharge or precipitation to calculate the loads. The release of the pharmaceuticals was calculated by multiplying average consumption numbers with the person equivalent of the WWTP and the elimination rates. The comparison of pollutant loads to 7-day composite samples of all compounds at 15 locations along the Rhine yield plausible results.

Release kinetics of papaverine hydrochloride from tablets with different excipients.

PubMed

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release.

Release Kinetics of Papaverine Hydrochloride from Tablets with Different Excipients

PubMed Central

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

Abstract The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release. PMID:25853076

Kinetics and Mechanisms of Chemical and Biological Agents Release from Biopolymeric Microcapsules.

PubMed

Vinceković, Marko; Jurić, Slaven; Đermić, Edyta; Topolovec-Pintarić, Snježana

2017-11-08

Kinetics and mechanisms of copper cations and Trichoderma viride spores release from uncoated and chitosan coated alginate microcapsules were investigated. The gelation of a fixed amount of sodium alginate at different concentrations of copper ion solutions resulted in distinct kinetics and release mechanisms. The increase in copper cation concentration promoted, but the presence of the chitosan layer on the microcapsule surface and the increase in microcapsule size reduced the rate of active agent release. Fitting to simple Korsmeyer-Peppas empirical model revealed that the underlying release mechanism (Fickian diffusion or a combination of the diffusion and erosion mechanisms) depends on the copper cation concentration and presence of T. viride spores. The investigation pointed out that the proper selection of formulation variables helps in designing microcapsules with the desirable release of copper ions and T. viride for plant protection and nutrition.

Atmospheric modeling of Mars CH4 subsurface clathrates releases mimicking SAM and 2003 Earth-based detections

NASA Astrophysics Data System (ADS)

Pla-Garcia, Jorge

2017-10-01

The aim of this work is to establish the amount of mixing during all martian seasons to test whether CH4 releases inside or outside of Gale crater are consistent with MSL-SAM observations. Several modeling scenarios were configured, including instantaneous and steady releases, both inside and outside the crater. A simulation to mimic the 2003 Earth-based detections (Mumma et al. 2009 or M09) was also performed. In the instantaneous release inside Gale experiments, Ls270 was shown to be the faster mixing season when air within and outside the crater was well mixed: all tracer mass inside the crater is diluted after just 8 hours. The mixing of near surface crater air with the external environment in the rest of the year is potentially rapid but slower than Ls270. In the instantaneous release outside Gale (NW) experiment, in just 12 hours the CH4 that makes it to the MSL landing location is diluted by six orders of magnitude. The timescale of mixing in the model is on the order of 1 sol regardless of season. The duration of the CH4 peak observed by SAM is 100 sols. Therefore there is a steady release inside the crater, or there is a large magnitude steady release outside the crater. In the steady release Gale experiments, CH4 flux rate from ground is 1.8 kg m-2 s-1 (Gloesener et al. 2017) and it is not predictive. In these experiments, ~200 times lower CH4 values detected by SAM are modeled around MSL location. There are CH4 concentration variations of orders of magnitude depending on the hour, so timing of SAM measurements is important. With a larger (but further away) outside crater release area compared to inside, similar CH4 values around MSL are modeled, so distance to source is important. In the steady experiments mimicking M09 detection release area, only 12 times lower CH4 values detected by SAM are modeled around MSL. The highest value in the M09 modeled scenario (0.6 ppbv) is reached in Ls270. This value is the highest of all modeled experiments. With our initial conditions, SAM should not be able to detect CH4, but if we multiply flux by 12, increase the release area or move it closer to MSL (or all of above), it may be possible to get CH4 values that SAM could detect regardless where it comes from.

Formulation and in vitro evaluation of sustained release matrix tablets using cross-linked natural gum.

PubMed

Jamil, Qurratul Ain; Masood, Muhammad Irfan; Jamil, Muhammad Nauman; Masood, Imran; Iqbal, Shahid Muhammad

2017-03-01

Polysaccharide gums because of their biocompatibility, biodegradability and non-immunogenic properties are considered as the best choice for preparing sustained release tablets as compared to their synthetic counterpart. The cross linking of natural gums in matrix tablets increase the sustained release property of matrix tablets. Isoniazid is a first line therapy of tuberculosis, belongs to BCS I with half-life of 3-4 hours. These characteristics make isoniazid a good candidate for sustained release dosage form. Karaya gum crossed linked with trisodium tri metaphosphate was used as release rate retardant for preparing isoniazid cross-linked matrix tablet. Total 8 sustained release formulations were prepared. Both granules and tablets were evaluated under in vitro condition against different parameters. Dissolution studies were performed with all eight formulations for 12 hours using USP apparatus I. Four formulations designated as F1, F2, F3, F4 have drug and karaya gum while other four formulations F5, F6, F7, F8 have drug and crossed linked polymer in ratios of 1:1, 1:2, 1:3 and 1:4 respectively. Dissolution data was analyzed by using different kinetic models. Best fit model for most efficient formulation was zero order while release mechanism was super case I. Formulation 8 showed sufficiently slow release kinetics and about 83% of drug was released in 10 hours, indicating that cross-linked karaya gum proved efficient in preparing sustained release tablets.

Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data

PubMed Central

Wojciechowski, Jessica; Mudge, Stuart; Upton, Richard N.; Foster, David J. R.

2017-01-01

ABSTRACT The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion (P < 0.01) and then backward deletion (P < 0.001) procedure. The final model was a two-compartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability (F), absorption lag (ALAG), and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 = 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the effect of female sex was a 14.4% increase in clearance. The manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens. PMID:28052851

Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data.

PubMed

Hopkins, Ashley M; Wojciechowski, Jessica; Abuhelwa, Ahmad Y; Mudge, Stuart; Upton, Richard N; Foster, David J R

2017-03-01

The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion ( P < 0.01) and then backward deletion ( P < 0.001) procedure. The final model was a two-compartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability ( F ), absorption lag (ALAG), and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 = 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the effect of female sex was a 14.4% increase in clearance. The manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens. Copyright © 2017 American Society for Microbiology.

The Role of Deposition in Limiting the Hazard Extent of Dense-Gas Plumes

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

Dillon, M B

2008-05-11

Accidents that involve large (multi-ton) releases of toxic industrial chemicals and form dense-gas clouds often yield far fewer fatalities, casualties and environmental effects than standard assessment and emergency response models predict. This modeling study, which considers both dense-gas turbulence suppression and deposition to environmental objects (e.g. buildings), demonstrates that dry deposition to environmental objects may play a significant role in reducing the distance at which adverse impacts occur - particularly under low-wind, stable atmospheric conditions which are often considered to be the worst-case scenario for these types of releases. The degree to which the released chemical sticks to (or reactsmore » with) environmental surfaces is likely a key parameter controlling hazard extents. In all modeled cases, the deposition to vertical surfaces of environmental objects (e.g. building walls) was more efficient in reducing atmospheric chemical concentrations than deposition to the earth's surface. This study suggests that (1) hazard extents may vary widely by release environment (e.g. grasslands vs. suburbia) and release conditions (e.g. sunlight or humidity may change the rate at which chemicals react with a surface) and (2) greenbelts (or similar structures) may dramatically reduce the impacts of large-scale releases. While these results are demonstrated to be qualitatively consistent with the downwind extent of vegetation damage in two chlorine releases, critical knowledge gaps exist and this study provides recommendations for additional experimental studies.« less

Microbial and sponge loops modify fish production in phase-shifting coral reefs.

PubMed

Silveira, Cynthia B; Silva-Lima, Arthur W; Francini-Filho, Ronaldo B; Marques, Jomar S M; Almeida, Marcelo G; Thompson, Cristiane C; Rezende, Carlos E; Paranhos, Rodolfo; Moura, Rodrigo L; Salomon, Paulo S; Thompson, Fabiano L

2015-10-01

Shifts from coral to algae dominance of corals reefs have been correlated to fish biomass loss and increased microbial metabolism. Here we investigated reef benthic and planktonic primary production, benthic dissolved organic carbon (DOC) release and bacterial growth efficiency in the Abrolhos Bank, South Atlantic. Benthic DOC release rates are higher while water column bacterial growth efficiency is lower at impacted reefs. A trophic model based on the benthic and planktonic primary production was able to predict the observed relative fish biomass in healthy reefs. In contrast, in impacted reefs, the observed omnivorous fish biomass is higher, while that of the herbivorous/coralivorous fish is lower than predicted by the primary production-based model. Incorporating recycling of benthic-derived carbon in the model through microbial and sponge loops explains the difference and predicts the relative fish biomass in both reef types. Increased benthic carbon release rates and bacterial carbon metabolism, but decreased bacterial growth efficiency could lead to carbon losses through respiration and account for the uncoupling of benthic and fish production in phase-shifting reefs. Carbon recycling by microbial and sponge loops seems to promote an increase of small-bodied fish productivity in phase-shifting coral reefs. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Recharge of the early atmosphere of Mars by impact-induced release of CO2

USGS Publications Warehouse

Carr, Michael H.

1989-01-01

Channels on the Martian surface suggest that Mars had an early, relatively thick atmosphere. If the atmosphere was thick enough for water to be stable at the surface, CO2 in the atmosphere would have been fixed as carbonates on a relatively short time scale, previously estimated to be 1 bar every 107 years. This loss must have been offset by some replenishment mechanism to account for the numerous valley networks in the oldest surviving terrains. Impacts could have released CO2 into the atmosphere by burial, by shock-induced release during impact events, and by addition of carbon to Mars from the impacting bolides. Depending on the relationship between the transient cavity diameter and the diameter of the resulting crater, burial rates as a result of impact gardening at the end of heavy bombardment are estimated to range from 20 to 45 m/106 years, on the assumption that cratering rates in Mars were similar to those of the Nectarian Period on the Moon. At these rates 0.1-0.2 bar of CO2 could have been released every 107 years as a result of burial to depths where dissociation temperatures of carbonates were reached. Modeling of large impacts suggests that an additional 0.01 to 0.02 bar of CO2 could have been released every 107 years during the actual impacts. In the unlikely event that all the impacting material was composed of carbonaceous chondrites, a further 0.3 bar of CO2 could have been added to the atmosphere every 107 years by oxidation of meteoritic carbon. Even when supplemented by the volcanically induced release of CO2, these release rates are barely sufficient to sustain an early atmosphere if water were continuously present at the surface. The results suggest that water may have been only intermittently present on the surface early in the planet's history.

Contributions of solar wind and micrometeoroids to molecular hydrogen in the lunar exosphere

NASA Astrophysics Data System (ADS)

Hurley, Dana M.; Cook, Jason C.; Retherford, Kurt D.; Greathouse, Thomas; Gladstone, G. Randall; Mandt, Kathleen; Grava, Cesare; Kaufmann, David; Hendrix, Amanda; Feldman, Paul D.; Pryor, Wayne; Stickle, Angela; Killen, Rosemary M.; Stern, S. Alan

2017-02-01

We investigate the density and spatial distribution of the H2 exosphere of the Moon assuming various source mechanisms. Owing to its low mass, escape is non-negligible for H2. For high-energy source mechanisms, a high percentage of the released molecules escape lunar gravity. Thus, the H2 spatial distribution for high-energy release processes reflects the spatial distribution of the source. For low energy release mechanisms, the escape rate decreases and the H2 redistributes itself predominantly to reflect a thermally accommodated exosphere. However, a small dependence on the spatial distribution of the source is superimposed on the thermally accommodated distribution in model simulations, where density is locally enhanced near regions of higher source rate. For an exosphere accommodated to the local surface temperature, a source rate of 2.2 g s-1 is required to produce a steady state density at high latitude of 1200 cm-3. Greater source rates are required to produce the same density for more energetic release mechanisms. Physical sputtering by solar wind and direct delivery of H2 through micrometeoroid bombardment can be ruled out as mechanisms for producing and liberating H2 into the lunar exosphere. Chemical sputtering by the solar wind is the most plausible as a source mechanism and would require 10-50% of the solar wind H+ inventory to be converted to H2 to account for the observations.

Contributions of Solar Wind and Micrometeoroids to Molecular Hydrogen in the Lunar Exosphere

NASA Technical Reports Server (NTRS)

Hurley, Dana M.; Cook, Jason C.; Retherford, Kurt D.; Greathouse, Thomas; Gladstone, G. Randall; Mandt, Kathleen; Grava, Cesare; Kaufmann, David; Hendrix, Amanda; Feldman, Paul D.;

Preparation of acetazolamide composite microparticles by supercritical anti-solvent techniques.

PubMed

Duarte, Ana Rita C; Roy, Christelle; Vega-González, Arlette; Duarte, Catarina M M; Subra-Paternault, Pascale

2007-03-06

The possibility of preparation of ophthalmic drug delivery systems using compressed anti-solvent technology was evaluated. Eudragit RS 100 and RL 100 were used as drug carriers, acetazolamide was the model drug processed. Compressed anti-solvent experiments were carried out as a semi-continuous or a batch operation from a liquid solution of polymer(s)+solute dissolved in acetone. Both techniques allowed the recovery of composite particles, but the semi-continuous operation yielded smaller and less aggregated populations than the batch operation. The release behaviour of acetazolamide from the prepared microparticles was studied and most products exhibited a slower release than the single drug. Moreover, the release could be controlled to some extent by varying the ratio of the two Eudragit used in the formulation and by selecting one or the other anti-solvent technique. Simple diffusion models satisfactorily described the release profiles. Composites specifically produced by semi-continuous technique have a drug release rate controlled by a diffusion mechanism, whereas for composites produced by the batch operation, the polymer swelling also contributes to the overall transport mechanism.

Enhanced biological phosphorus removal in a sequencing batch reactor using propionate as the sole carbon source.

PubMed

Pijuan, M; Saunders, A M; Guisasola, A; Baeza, J A; Casas, C; Blackall, L L

2004-01-05

An enhanced biological phosphorus removal (EBPR) system was developed in a sequencing batch reactor (SBR) using propionate as the sole carbon source. The microbial community was followed using fluorescence in situ hybridization (FISH) techniques and Candidatus 'Accumulibacter phosphatis' were quantified from the start up of the reactor until steady state. A series of SBR cycle studies was performed when 55% of the SBR biomass was Accumulibacter, a confirmed polyphosphate accumulating organism (PAO) and when Candidatus 'Competibacter phosphatis', a confirmed glycogen-accumulating organism (GAO), was essentially undetectable. These experiments evaluated two different carbon sources (propionate and acetate), and in every case, two different P-release rates were detected. The highest rate took place while there was volatile fatty acid (VFA) in the mixed liquor, and after the VFA was depleted a second P-release rate was observed. This second rate was very similar to the one detected in experiments performed without added VFA.A kinetic and stoichiometric model developed as a modification of Activated Sludge Model 2 (ASM2) including glycogen economy, was fitted to the experimental profiles. The validation and calibration of this model was carried out with the cycle study experiments performed using both VFAs. The effect of pH from 6.5 to 8.0 on anaerobic P-release and VFA-uptake and aerobic P-uptake was also studied using propionate. The optimal overall working pH was around 7.5. This is the first study of the microbial community involved in EBPR developed with propionate as a sole carbon source along with detailed process performance investigations of the propionate-utilizing PAOs. Copyright 2003 Wiley Periodicals, Inc.

Controlled-release Hydrogen Peroxide for On-site Treatment of Organic Pollutants in Urban Storm Runoff

NASA Astrophysics Data System (ADS)

Lee, E.; Sun, S.; Kim, Y.

2011-12-01

Nonpoint source (NPS) pollutants are the remaining cause of the environment problems, significantly impairing the hydrologic and biologic function of urban water systems and human health. Managing the NPS loads to urban aquatic systems remains a challenge because of ubiquitous contaminant sources and large pollutants loads in the first flush. Best management practices (BMPs) exist for reducing the NPS pollutants in urban storm waters, but the remedial efficiencies of these passive schemes are unpredictable. This study aims to develop a controlled-release system as part of an in situ chemical oxidation scheme designed for on-site treatment of organic pollutants in urban runoff. Controlled-release hydrogen peroxide (CR-HP) solids were manufactured by dispersing fine sodium percarbonate granules in paraffin wax matrices. Release kinetics and treatment efficiencies of CR-HP for BTEX and MTBE were investigated through a series of column tests. Release data indicated that the CR-HP could continually release hydrogen peroxide (H2O2) in flowing water at controlled rates over 276-1756 days, and the release rates could be adjusted by changing the mixing ratios of sodium percarbonate and wax matrices. Additional column tests and model calculations demonstrated that CR-HP/UV systems can provide low-cost, target-specific, and persistent source of oxidants for efficient treatment of organic compounds in urban storm runoff.

DNA release from lipoplexes by anionic lipids: correlation with lipid mesomorphism, interfacial curvature, and membrane fusion

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

Tarahovsky, Yury S.; Koynova, Rumiana; MacDonald, Robert C.

2010-01-18

DNA release from lipoplexes is an essential step during lipofection and is probably a result of charge neutralization by cellular anionic lipids. As a model system to test this possibility, fluorescence resonance energy transfer between DNA and lipid covalently labeled with Cy3 and BODIPY, respectively, was used to monitor the release of DNA from lipid surfaces induced by anionic liposomes. The separation of DNA from lipid measured this way was considerably slower and less complete than that estimated with noncovalently labeled DNA, and depends on the lipid composition of both lipoplexes and anionic liposomes. This result was confirmed by centrifugalmore » separation of released DNA and lipid. X-ray diffraction revealed a clear correlation of the DNA release capacity of the anionic lipids with the interfacial curvature of the mesomorphic structures developed when the anionic and cationic liposomes were mixed. DNA release also correlated with the rate of fusion of anionic liposomes with lipoplexes. It is concluded that the tendency to fuse and the phase preference of the mixed lipid membranes are key factors for the rate and extent of DNA release. The approach presented emphasizes the importance of the lipid composition of both lipoplexes and target membranes and suggests optimal transfection may be obtained by tailoring lipoplex composition to the lipid composition of target cells.« less

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.

Factors influencing release of phosphorus from sediments in a high productive polymictic lake system.

PubMed

Solim, S U; Wanganeo, A

2009-01-01

Phosphorus (P) release rates from bottom sediments are high (20.6 mg/m(2)/day) in Dal Lake (India), a polymictic hyper-eutrophic lake. These gross release rates occur over a period of 72 days during summer only. Likewise, a net internal load of 11.3 tons was obtained from mass balance estimates. Significant proportion i.e. approximately 80% of 287.3 tons/yr of nitrate nitrogen (NO(3)-N) load is either eliminated by denitrification or gets entrapped for a short period in high macrophyte biomass of 3.2 kg/m(2) f.w., which eventually get decomposed and nitrogen (N) is released back. These processes result in low lake water NO(3)-N concentrations which potentially influence sediment phosphorus (P) release. Especially, nitrate nitrogen (NO(3)-N) <500 microg/L in the lake waters were associated with high P concentrations. Phosphorus was also observed to increase significantly in relation to temperature and pH, and it seems likely that release of phosphorus and ammonical nitrogen (NH(4)-N) depend on decomposition of rich reserves of organic matter (893 tons d.w. in superficial 10-cm bottom sediment layer). Lake P concentrations were significantly predicted by a multivariate regression model developed for the lake. This study describes significance of various lake water variables in relation to P-release from bottom sediments.

Metal release from stainless steel particles in vitro-influence of particle size.

PubMed

Midander, K; Pan, J; Wallinder, I Odnevall; Leygraf, C

2007-01-01

Human inhalation of airborne metallic particles is important for health risk assessment. To study interactions between metallic particles and the human body, metal release measurements of stainless steel powder particles were performed in two synthetic biological media simulating lung-like environments. Particle size and media strongly influence the metal release process. The release rate of Fe is enhanced compared with Cr and Ni. In artificial lysosomal fluid (ALF, pH 4.5), the accumulated amounts of released metal per particle loading increase drastically with decreasing particle size. The release rate of Fe per unit surface area increases with decreasing particle size. Compared with massive sheet metal, fine powder particles (<4 microm) show similar release rates of Cr and Ni, but a higher release rate of Fe. Release rates in Gamble's solution (pH 7.4), for all powders investigated, are significantly lower compared to ALF. No clear trend is seen related to particle size in Gamble's solution.

Conductive polymer nanotube patch for fast and controlled in vivo transdermal drug delivery

NASA Astrophysics Data System (ADS)

Nguyen, Thao M.

Transdermal drug delivery has created new applications for existing therapies and offered an alternative to the traditional oral route where drugs can prematurely metabolize in the liver causing adverse side effects. Opening the transdermal delivery route to large hydrophilic drugs is one of the greatest challenges due to the hydrophobicity of the skin. However, the ability to deliver hydrophilic drugs using a transdermal patch would provide a solution to problems of other delivery methods for hydrophilic drugs. The switching of conductive polymers (CP) between redox states cause simultaneous changes in the polymer charge, conductivity, and volume—properties that can all be exploited in the biomedical field of controlled drug delivery. Using the template synthesis method, poly(3,4-ethylenedioxythiophene (PEDOT) nanotubes were synthesized electrochemically and a transdermal drug delivery patch was successfully designed and developed. In vitro and in vivo uptake and release of hydrophilic drugs were investigated. The relationship between the strength of the applied potential and rate of drug release were also investigated. Results revealed that the strength of the applied potential is proportional to the rate of drug release; therefore one can control the rate of drug release by controlling the applied potential. The in vitro studies focused on the kinetics of the drug delivery system. It was determined that the drug released mainly followed zero-order kinetics. In addition, it was determined that applying a releasing potential to the transdermal drug delivery system lead to a higher release rate constant (up to 7 times greater) over an extended period of time (˜24h). In addition, over 24 hours, an average of 80% more model drug molecules were released with an applied potential than without. The in vivo study showed that the drug delivery system was capable of delivering model hydrophilic drugs molecules through the dermis layer of the skin within 30 minutes, while the control showed no visible drugs at the same depth. Most importantly, it was determined that the delivery of drugs into the blood stream was stable within 20 minutes. The functionalization of CP was also studied in order to enhance the properties and drug loading capabilities of the polymers. The co-polymerization of poly(3,4-(2-methylene)propylenedioxythiophene) (PMProDot) with polystyrene (PS) and polyvinylcarbazole (PVK) through the highly reactive methylene group was achieved. The modified PMProDot nanotubes demonstrated response times that were two times faster than without modification. The modification of PEDOT nanotubes with polydopamine, a biocompatible polymer, was also investigated and achieved. In depth characterization of functionalized CP demonstrate the ability to fine tune the properties of the polymer in order to achieve the required therapeutic drug release profile.

Analysis of Composite Skin-Stiffener Debond Specimens Using a Shell/3D Modeling Technique and Submodeling

NASA Technical Reports Server (NTRS)

OBrien, T. Kevin (Technical Monitor); Krueger, Ronald; Minguet, Pierre J.

2004-01-01

The application of a shell/3D modeling technique for the simulation of skin/stringer debond in a specimen subjected to tension and three-point bending was studied. The global structure was modeled with shell elements. A local three-dimensional model, extending to about three specimen thicknesses on either side of the delamination front was used to model the details of the damaged section. Computed total strain energy release rates and mixed-mode ratios obtained from shell/3D simulations were in good agreement with results obtained from full solid models. The good correlation of the results demonstrated the effectiveness of the shell/3D modeling technique for the investigation of skin/stiffener separation due to delamination in the adherents. In addition, the application of the submodeling technique for the simulation of skin/stringer debond was also studied. Global models made of shell elements and solid elements were studied. Solid elements were used for local submodels, which extended between three and six specimen thicknesses on either side of the delamination front to model the details of the damaged section. Computed total strain energy release rates and mixed-mode ratios obtained from the simulations using the submodeling technique were not in agreement with results obtained from full solid models.

Novel sustained-release dosage forms of proteins using polyglycerol esters of fatty acids.

PubMed

Yamagata, Y; Iga, K; Ogawa, Y

2000-02-03

In order to develop a novel delivery system for proteins based on polyglycerol esters of fatty acids (PGEFs), we studied a model system using interferon-alpha (IFN-alpha) as the test protein. A cylindrical matrix was prepared by a heat extrusion technique using a lyophilized powder of the protein and 11 different types of synthetic PGEFs, which varied in degree of glycerol polymerization (di- and tetra-), chain length of fatty acids (myristate, palmitate and stearate) and degree of fatty acid esterification (mono-, di- and tri-). In an in-vitro release study using an enzyme-linked immunosorbent assay (ELISA) as a detection method, the matrices prepared from a monoglyceride (used for comparison) and from diglycerol esters exhibited a biphasic release pattern with a large initial burst followed by slow release. In contrast, the matrices prepared from tetraglycerol esters showed a steady rate of release without a large initial burst. In an in vivo release study, initial bursts of IFN-alpha release were, also, dramatically reduced when the matrices were prepared from the tetraglycerol esters of palmitate and stearate, and the mean residence time (MRT) of IFN-alpha was prolonged, whereas the matrices prepared from monoglyceride and from diglycerol esters showed large initial bursts of IFN-alpha release. Since the release rates from the matrices prepared from the tetraglycerol esters of palmitate and stearate were governed by Jander's equation modified for a cylindrical matrix, the release from those matrices was concluded to be a diffusion-controlled process. The bioavailability of IFN-alpha after implantation of the matrix formulation prepared using all types of PGEFs, except for tetraglycerol triesters, was almost equivalent to that after injection of IFN-alpha solution; consequently, IFN-alpha in these matrices appears to remain stable during the release period.

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

Mehl, M; Kukkadapu, G; Kumar, K

The use of gasoline in homogeneous charge compression ignition engines (HCCI) and in duel fuel diesel - gasoline engines, has increased the need to understand its compression ignition processes under engine-like conditions. These processes need to be studied under well-controlled conditions in order to quantify low temperature heat release and to provide fundamental validation data for chemical kinetic models. With this in mind, an experimental campaign has been undertaken in a rapid compression machine (RCM) to measure the ignition of gasoline mixtures over a wide range of compression temperatures and for different compression pressures. By measuring the pressure history duringmore » ignition, information on the first stage ignition (when observed) and second stage ignition are captured along with information on the phasing of the heat release. Heat release processes during ignition are important because gasoline is known to exhibit low temperature heat release, intermediate temperature heat release and high temperature heat release. In an HCCI engine, the occurrence of low-temperature and intermediate-temperature heat release can be exploited to obtain higher load operation and has become a topic of much interest for engine researchers. Consequently, it is important to understand these processes under well-controlled conditions. A four-component gasoline surrogate model (including n-heptane, iso-octane, toluene, and 2-pentene) has been developed to simulate real gasolines. An appropriate surrogate mixture of the four components has been developed to simulate the specific gasoline used in the RCM experiments. This chemical kinetic surrogate model was then used to simulate the RCM experimental results for real gasoline. The experimental and modeling results covered ultra-lean to stoichiometric mixtures, compressed temperatures of 640-950 K, and compression pressures of 20 and 40 bar. The agreement between the experiments and model is encouraging in terms of first-stage (when observed) and second-stage ignition delay times and of heat release rate. The experimental and computational results are used to gain insight into low and intermediate temperature processes during gasoline ignition.« less

Foraminiferal Stable Isotope Record at Millville, NJ: Implications for the onset of the PETM

NASA Astrophysics Data System (ADS)

Wright, J. D.; Miller, K. G.

2016-12-01

Traditional paleoceanographic tools (magneto-biostratigraphy, orbital cycles) are insufficient to assign rates to the initial release of carbon during the rapid onset of the PETM (<10 kyr). The ODP Leg 174AX Millville, NJ PETM section (70 m paleodepth) is >10 times more expanded relative to the thickest open ocean sites (e.g., Site 690). The onset interval at Millville is defined by a bulk carbonate δ13C of 3.5‰ across 25 cm interval. Two groups used the geochemical changes to constrain the timing for the initial pulse of carbon. Wright and Schaller (2013) focused on the differential responses in δ13C and %CaCO3 arguing that the release was fast (<1 year). Conversely, Zeebe et al. (2016) assumed the initial covariance in δ18O and δ13C represented equilibrium conditions, modeling a 4 kyr duration for the release. We generated planktonic and benthic foraminiferal stable isotope records across the onset of the PETM CIE at Millville. Most of the δ13C change recorded by foraminifera occurred over the 25 cm onset interval. However, foraminiferal δ18O values continue to decrease for another 1.5 m above the initial δ13C decrease contradicting Zeebe et al.'s assumption of equilibrium conditions. The foraminiferal stable isotope pattern is similar to the modeled response following a large, instantaneous release of light carbon to the atmosphere, that produces a rapid (decadal) scale warming in the surface air masses followed by continued warming but at a slower rate. Differential responses in δ13C, δ18O, and %CaCO3 at the onset of the PETM are consistent with an instantaneous initial release of carbon with centennial-scale warming that continued well after the initial carbon pulse similar to that predicted by climate models. Fitting the Millville isotope records to these models suggests that peak warmth followed the initial release by 100 to 200 years. The mid-shelf location of Millville a made it responsive to atmospheric changes unlike open ocean sites where thermal inertia dampens the larger atmosphere changes.

Techniques for rearing and releasing nonmigratory cranes: Lessons from the Mississippi Sandhill Crane program

USGS Publications Warehouse

Ellis, D.H.; Olsen, Glenn H.; Gee, G.F.; Nicolich, Jane M.; O'Malley, K.E.; Nagendran, Meenakshi; Hereford, Scott G.; Range, P.; Harper, W.T.; Ingram, R.P.; Smith, D.G.

1992-01-01

Captive-reared Mississippi sandhill cranes (Grus canadensis pulla) reared at the Patuxent Wildlife Research Center (Patuxent) have been released at the Mississippi Sandhill Crane National Wildlife Refuge (MSCNWR) since 1981. Of 131 birds released through December 1990, 103 were reared by foster parents. The remaining 28 were experimentally hand-reared in 1989 and 1990. After refining release procedures, parent-reared birds have integrated into the wild flock, many have survived, and some have bred. Releases of hand-reared cranes elsewhere in the 1970's were largely unsuccessful, at least in part due to the lack of a lengthy acclimation period. A new hand-rearing protocol holds promise in producing release-worthy birds. The technique employs some features first used in the 1960's (e.g., a costume for the human caretaker and model crane heads used to train chicks to feed). In the mid-1980's, the following features were added: (1) the costumed caretaker was given a visor and feathers, (2) a taxidermic crane head or a hand puppet was held or suspended from the ceiling for use in stimulating chicks to feed, (3) a taxidermic mount of a brooding crane supplied warmth, (4) a full-sized live crane was maintained in an adjacent pen and in visual contact with neonatal young to provide an imprinting model, and (5) a small group of adult (or subadult) cranes was penned adjacent to the outdoor chick pens to provide socialization models. Recent releases of Mississippi sandhill cranes hand-reared according to this protocol and released in Mississippi have had high first-year survival rates. The now-operational technique holds promise for producing large numbers of release-worthy birds.

Development of a multilayered association polymer system for sequential drug delivery

NASA Astrophysics Data System (ADS)

Chinnakavanam Sundararaj, Sharath kumar

As all the physiological processes in our body are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the primary objective of this research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. This particular device was designed aimed at the treatment of periodontitis, a highly prevalent oral inflammatory disease that affects 90% of the world population. This condition is caused by bacterial biofilm on the teeth, resulting in a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The polymers used for the fabrication of this multilayered device consists of cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion property of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. After the initial characterization of the CAPP system, the device was specifically modified to achieve sequential release of drugs aimed at the treatment of periodontitis. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. To obtain different erosion times and achieve appropriate release profiles specific to the disease condition, the device was modified by increasing the number of layers or by inclusion of a slower eroding polymer layer. In all the cases, the device was able to release the four different drugs in the designed temporal sequence. Analysis of antibiotic and antiinflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. Following extensive studies on the in vitro sequential drug release from these devices, the in vivo drug release profiles were investigated. The CAPP devices with different release rates and dosage formulations were implanted in a rat calvarial onlay model, and the in vivo drug release and erosion was compared with in vitro results. In vivo studies showed sequential release of drugs comparable to those measured in vitro, with some difference in drug release rates observed. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. KEYWORDS: Multiple drug delivery, Periodontitis, Cellulose acetate phthalate, Pluronic F-127, Sequential drug release, in vitro drug release, in vivo drug release.

Characterization of elemental release during microbe granite interactions at T = 28 °C

NASA Astrophysics Data System (ADS)

Wu, Lingling; Jacobson, Andrew D.; Hausner, Martina

2008-02-01

This study used batch reactors to characterize the mechanisms and rates of elemental release (Al, Ca, K, Mg, Na, F, Fe, P, Sr, and Si) during interaction of a single bacterial species ( Burkholderia fungorum) with granite at T = 28 °C for 35 days. The objective was to evaluate how actively metabolizing heterotrophic bacteria might influence granite weathering on the continents. We supplied glucose as a C source, either NH 4 or NO 3 as N sources, and either dissolved PO 4 or trace apatite in granite as P sources. Cell growth occurred under all experimental conditions. However, solution pH decreased from ˜7 to 4 in NH 4-bearing reactors, whereas pH remained near-neutral in NO 3-bearing reactors. Measurements of dissolved CO 2 and gluconate together with mass-balances for cell growth suggest that pH lowering in NH 4-bearing reactors resulted from gluconic acid release and H + extrusion during NH 4 uptake. In NO 3-bearing reactors, B. fungormum likely produced gluconic acid and consumed H + simultaneously during NO 3 utilization. Over the entire 35-day period, NH 4-bearing biotic reactors yielded the highest release rates for all elements considered. However, chemical analyses of biomass show that bacteria scavenged Na, P, and Sr during growth. Abiotic control reactors followed different reaction paths and experienced much lower elemental release rates compared to biotic reactors. Because release rates inversely correlate with pH, we conclude that proton-promoted dissolution was the dominant reaction mechanism. Solute speciation modeling indicates that formation of Al-F and Fe-F complexes in biotic reactors may have enhanced mineral solubilities and release rates by lowering Al and Fe activities. Mass-balances further reveal that Ca-bearing trace phases (calcite, fluorite, and fluorapatite) provided most of the dissolved Ca, whereas more abundant phases (plagioclase) contributed negligible amounts. Our findings imply that during the incipient stages of granite weathering, heterotrophic bacteria utilizing glucose and NH 4 only moderately elevate silicate weathering reactions that consume atmospheric CO 2. However, by enhancing the dissolution of non-silicate, Ca-bearing trace minerals, they could contribute to high Ca/Na ratios commonly observed in granitic watersheds.

Observed rate of ionization in shaped-charge releases of barium in the ionosphere

NASA Technical Reports Server (NTRS)

Hallinan, Thomas J.

1988-01-01

Data from 36 Ba shaped-charge releases carried out at an angle of less than 25 deg to the magnetic field, by the technique of Wescott et al. (1972) and Michel (1974), were examined for evidence of a sustained rate of ionization in excess of that attributable to sunlight. In four of the experiments, the time constant for the decay of the neutrals was measured using an ultrasensitive color TV camera and was found to have a value of about 30 sec, consistent with slow (solar) ionization. Although the qualitative appearance of most jets was found to be consistent with a slow process of ionization, some releases produced a thin confined jet that was suggestive of rapid ionization. Two of these jets were analyzed in detail, but no evidence of anomalous ionization was produced. The data obtained in this work agree with the geometrical predictions of the Swift model.

Lysine-based polycation:heparin coacervate for controlled protein delivery.

PubMed

Johnson, Noah Ray; Ambe, Trisha; Wang, Yadong

2014-01-01

Polycations have good potential as carriers of proteins and genetic material. However, poor control over the release rate and safety issues currently limit their use as delivery vehicles. Here we introduce a new lysine-based polycation, poly(ethylene lysinylaspartate diglyceride) (PELD), which exhibits high cytocompatibility. PELD self-assembles with the biological polyanion heparin into a coacervate that incorporates proteins with high loading efficiency. Coacervates of varying surface charge were obtained by simple alteration of the PELD:heparin ratio and resulted in diverse release profiles of the model protein bovine serum albumin. Therefore, coacervate charge represents a direct means of control over release rate and duration. The PELD coacervate also rapidly adsorbed onto a porous polymeric scaffold, demonstrating potential use in tissue engineering applications. This coacervate represents a safe and tunable protein delivery system for biomedical applications. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of smolt release timing and size on the survival of hatchery-origin coho salmon in the Strait of Georgia

NASA Astrophysics Data System (ADS)

Irvine, J. R.; O'Neill, M.; Godbout, L.; Schnute, J.

2013-08-01

Altering release sizes and timings of coho salmon smolts from hatcheries in the Strait of Georgia will not reverse the precipitous survival declines of the past three decades. We modeled the effects on survival of ocean entry year, mean smolt size (weight), and release day. Ocean entry year was by far the most important. During 1979-2006, smolt to adult survivals declined similarly for hatchery and wild coho salmon, although wild salmon consistently survived at higher rates. Best models differed among hatcheries, implying location-specific differences in the optimal size and timing of release. At four of five hatcheries, heavier smolts survived significantly better than lighter smolts. At one hatchery, a significant interaction between ocean entry year and smolt weight reflected an increased positive effect of weight later in the time series. At two Vancouver Island hatcheries, early release groups appeared to survive better than later releases in early years, while later release groups survived best in recent years. We recommend: (1) hatchery managers release coho salmon smolts throughout the outmigration period of higher surviving wild coho salmon smolts and (2) an experimental approach using hatcheries to evaluate density-dependent effects on coho salmon growth and survival.

Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

PubMed

Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

2008-01-01

The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

Levonorgestrel release rates over 5 years with the Liletta® 52-mg intrauterine system.

PubMed

Creinin, Mitchell D; Jansen, Rolf; Starr, Robert M; Gobburu, Joga; Gopalakrishnan, Mathangi; Olariu, Andrea

2016-10-01

To understand the potential duration of action for Liletta®, we conducted this study to estimate levonorgestrel (LNG) release rates over approximately 5½years of product use. Clinical sites in the U.S. Phase 3 study of Liletta collected the LNG intrauterine systems (IUSs) from women who discontinued the study. We randomly selected samples within 90-day intervals after discontinuation of IUS use through 900days (approximately 2.5years) and 180-day intervals for the remaining duration through 5.4years (1980days) to evaluate residual LNG content. We also performed an initial LNG content analysis using 10 randomly selected samples from a single lot. We calculated the average ex vivo release rate using the residual LNG content over the duration of the analysis. We analyzed 64 samples within 90-day intervals (range 6-10 samples per interval) through 900days and 36 samples within 180-day intervals (6 samples per interval) for the remaining duration. The initial content analysis averaged 52.0±1.8mg. We calculated an average initial release rate of 19.5mcg/day that decreased to 17.0, 14.8, 12.9, 11.3 and 9.8mcg/day after 1, 2, 3, 4 and 5years, respectively. The 5-year average release rate is 14.7mcg/day. The estimated initial LNG release rate and gradual decay of the estimated release rate are consistent with the target design and function of the product. The calculated LNG content and release rate curves support the continued evaluation of Liletta as a contraceptive for 5 or more years of use. Liletta LNG content and release rates are comparable to published data for another LNG 52-mg IUS. The release rate at 5years is more than double the published release rate at 3years with an LNG 13.5-mg IUS, suggesting continued efficacy of Liletta beyond 5years. Copyright © 2016 Elsevier Inc. All rights reserved.

Modeling E. coli Release And Transport In A Creek During Artificial High-Flow Events

NASA Astrophysics Data System (ADS)

Yakirevich, A.; Pachepsky, Y. A.; Gish, T. J.; Cho, K.; Shelton, D. R.; Kuznetsov, M. Y.

2012-12-01

In-stream fate and transport of E. coli, is a leading indicator of microbial contamination of natural waters, and so needs to be understood to eventually minimize surface water contamination by microbial organisms. The objective of this work was to simulate E. coli release and transport from soil sediment in a creek bed both during and after high water flow events. The artificial high-water flow events were created by releasing 60-80 m3 of city water on a tarp-covered stream bank at a rate of 60 L/s in four equal allotments in July of 2008, 2009 and 2010. The small first-order creek used in this study is part of the Beaver Dam Creek Tributary and is located at the USDA Optimizing Production inputs for Economic and Environmental Enhancement (OPE3) research site, in Beltsville, Maryland. In 2009 and 2010 a conservative tracer difluorobenzoic acid (DFBA) was added to the released water. Specifically, water flow rates, E. coli and DFBA concentrations as well as water turbidity were monitored with automated samplers at the ends of the three in-stream weirs reaching a total length of 630 m. Sediment particle size distributions and the streambed E. coli concentrations were measured along a creek before and after experiment. The observed DFBA breakthrough curves (BTCs) exhibited long tails after the water pulse and tracer peaks indicating that transient storage might be an important element of the in-stream transport process. Turbidity and E. coli BTCs also exhibited long tails indicative of transient storage and low rates of settling caused by re-entrainment. Typically, turbidity peaked prior to E. coli and returned to lower base-line levels more rapidly. A one-dimensional model was applied to simulate water flow, E. coli and DFBA transport during these experiments. The Saint-Venant equations were used to calculate water depth and discharge while a stream solute transport model accounted for advection-dispersion, lateral inflow/outflow, exchange with the transient storage, and resuspension of bacteria by shear stress from stream bottom sediments. Reach-specific model parameters were estimated by using observed time series of flow rates and concentrations at three weir stations. Transient storage and dispersion parameters were obtained with DFBA BTCs, then critical shear stress and resuspension rate were assessed by fitting computed E. coli BTCs to observations. To obtain a good model fit for E. coli, we generally had to make the transient storage for E. coli larger than for DFBA. Comparison of simulated and measured E. coli concentrations indicated that significant resuspension of E. coli continued when water flow returned to the base level after the water pulse passed and bottom shear stress was small. The hypothetical mechanism of this extended release could be the enhanced boundary layer (water-streambed) exchange due to changes in biofilm properties by erosion and sloughing detachment.

Development of an osmotic pump system for controlled delivery of diclofenac sodium.

PubMed

Emara, L H; Taha, N F; Badr, R M; Mursi, N M

2012-10-01

Based on an elementary osmotic pump, controlled release systems of diclofenac sodium (DS) were designed to deliver the drug in a zero-order release pattern. Osmotic pump tablets containing 100 mg DS were prepared and coated with either semipermeable (SPM) or microporous (PM) membranes. The tablet coats were composed of hydrophobic triacetin (TA) or hydrophilic polyethylene glycol 400 (PEG 400) incorporated in cellulose acetate (CA) solution, for SPM and PM, respectively. Variable tablet core compositions such as swelling polymers (PEO and HPMC) and osmotic agents (lactose, NaCl, and KCl) were studied. An optimized, sensitive and well controlled in vitro release design, based on the flow-through cell (FTC), was utilized to discriminate between preparations. The results revealed that the presence of PEG 400 in the coating membrane accelerated the drug release rate, while TA suppressed the release rate of DS. In the case of SPM, the amount of DS released was inversely proportional to the membrane thickness, where 5% (w/w) weight gain gave a higher DS release rate than 10% (w/w). Results of different tablet core compositions revealed that the release rate of DS decreased as PEO molecular weight increased. HPMC K15M showed the lowest DS release rate. The presence of lactose, KCl, or NaCl pronouncedly affected DS release rate depending on polymer type in the core. Scanning electron microscopy (SEM) confirmed formation of pores in the membrane that accounts for faster DS release rate. These results revealed that DS could be formulated as an osmotic pump system with a prolonged, zero-order release pattern.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: drug release and fronts movement kinetics.

PubMed

Marinich, J A; Ferrero, C; Jiménez-Castellanos, M R

2012-04-01

A previous paper deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure. Copyright © 2011 Elsevier B.V. All rights reserved.

Metal release rate from AISI 316L stainless steel and pure Fe, Cr and Ni into a synthetic biological medium--a comparison.

PubMed

Herting, G; Wallinder, I Odnevall; Leygraf, C

2008-09-01

Metal release rates from stainless steel grade 316L were investigated in artificial lysosomal fluid (ALF), simulating a human inflammatory cell response. The main focus was placed on release rates of main alloying elements using graphite furnace atomic absorption spectroscopy, and changes in surface oxide composition by means of X-ray photoelectron spectroscopy. To emphasise that alloys and pure metals possess totally different intrinsic properties, comparative studies were performed on the pure alloying constituents: iron, nickel and chromium. Significant differences in release rates were observed due to the presence of a passive surface film on stainless steel. Iron and nickel were released at rates more than 300 times lower from the 316L alloy compared with the pure metals whereas the release rate of chromium was similar. Iron was preferentially released compared with nickel and chromium. Immersion in ALF resulted in the gradual enrichment of chromium in the surface film, a small increase of nickel, and the reduction of oxidized iron with decreasing release rates of alloy constituents as a result. As expected, released metals from stainless steel grade 316L were neither in proportion to the bulk alloy composition nor to the surface film composition.

The Use of Lithium in the Treatment of Thyrotoxicosis

PubMed Central

Temple, R.; Berman, M.; Robbins, J.; Wolff, J.

1972-01-01

Since lithium has been shown to inhibit release of iodine from the thyroid, we have investigated its therapeutic potential in thyrotoxicosis. Eight detailed 131I kinetic studies were performed on seven thyrotoxic women and data was analyzed using a computer program. Lithium at serum levels of about 1 mEq liter decreased the loss of 131I from the thyroid, led to a fall in serum 131I levels and diminished urinary 131I excretion. Computer simulation of the lithium effect required, in every case, that lithium inhibit hormonal and nonhormonal thyroid iodine release. In five cases a second lithium effect was required for a satisfactory fit of the model soluton with observed data: namely, an inhibition of hormone disappearance from serum. Neither inhibition of release nor of hormone disappearance seemed to be affected by methimazole (release: 52% decrease without methimazole, 60% with methimazole; hormone disappearance: ∼60% decrease in both). When Li+ was discontinued, recovery of the iodine release rate and hormone disappearance rate over the observed time span was variable, ranging from no recovery to rates that exceeded pre-Li+ values. When Li+ is used alone its effect on serum hormone levels is diminished due to continued accumulation of iodide by the thyroid. Thus, serum thyroxine-iodine levels fell 21-30% in 6-8 days in patients who did not receive methimazole and 15-67% in the methimazole-treated subjects. For prolonged therapy, therefore, a thiocarbamide drug must be used in conjunction with Li+. The similarity of inhibition of iodine release from the thyroid produced by Li+ and iodides is discussed. PMID:4115707

Reformulation of Rothermel's wildland fire behaviour model for heterogeneous fuelbeds.

Treesearch

David V. Sandberg; Cynthia L. Riccardi; Mark D. Schaaf

2007-01-01

Abstract: The Fuel Characteristic Classification System (FCCS) includes equations that calculate energy release and one-dimensional spread rate in quasi-steady-state fires in heterogeneous but spatially uniform wildland fuelbeds, using a reformulation of the widely used Rothermel fire spread model. This reformulation provides an automated means to predict fire behavior...

RADSOURCE. Volume 1, Part 1, A scaling factor prediction computer program technical manual and code validation: Final report

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

Vance, J.N.; Holderness, J.H.; James, D.W.

1992-12-01

Waste stream scaling factors based on sampling programs are vulnerable to one or more of the following factors: sample representativeness, analytic accuracy, and measurement sensitivity. As an alternative to sample analyses or as a verification of the sampling results, this project proposes the use of the RADSOURCE code, which accounts for the release of fuel-source radionuclides. Once the release rates of these nuclides from fuel are known, the code develops scaling factors for waste streams based on easily measured Cobalt-60 (Co-60) and Cesium-137 (Cs-137). The project team developed mathematical models to account for the appearance rate of 10CFR61 radionuclides inmore » reactor coolant. They based these models on the chemistry and nuclear physics of the radionuclides involved. Next, they incorporated the models into a computer code that calculates plant waste stream scaling factors based on reactor coolant gamma- isotopic data. Finally, the team performed special sampling at 17 reactors to validate the models in the RADSOURCE code.« less

On the effect of irradiation-induced resolution in modelling fission gas release in UO2 LWR fuel

NASA Astrophysics Data System (ADS)

Lösönen, Pekka

2017-12-01

Irradiation resolution of gas atoms and vacancies from intra- and intergranular bubbles in sintered UO2 fuel was studied by comparing macroscopic models with a more mechanistic approach. The applied macroscopic models imply the resolution rate of gas atoms to be proportional to gas concentration in intragranular bubbles and at grain boundary (including intergranular bubbles). A relation was established between the macroscopic models and a single encounter of an energetic fission fragment with a bubble. The effect of bubble size on resolution was quantified. The number of resoluted gas atoms per encounter of a fission fragment per bubble was of the same order of magnitude for intra- and intergranular bubbles. However, the resulting macroscopic resolution rate of gas atoms was about two orders of magnitude larger from intragranular bubbles. The number of vacancies resoluted from a grain face bubble by a passing fission fragment was calculated. The obtained correlations for resolution of gas atoms from intragranular bubbles and grain boundaries and for resolution of vacancies from grain face bubbles were used to demonstrate the effect of irradiation resolution on fission gas release.

Hydroxyethyl Pachyman as a novel excipient for sustained-release matrix tablets.

PubMed

Zhou, Xiaoju; Wang, Pengyu; Wang, Jiong; Liu, Zhi; Hong, Xuechuan; Xiao, Yuling; Liu, Peng; Hu, Xianming

2016-12-10

This paper addressed the application of hydroxyethyl pachyman (HEP) as a novel matrix for sustained - release tablets, using diclofenac sodium (DS) as a model drug. The studies showed the HEP tablets prepared by wet granulation had much slower drug release as compared to those prepared by direct compression. Meanwhile, increasing the percentage of HEP in the formulations caused a decrease in drug release rates. Moreover, DS release from the HEP tablets was much higher at high pH (6.8) than that at low pH (1.2). Morphology studies proved the HEP tablet formed a continuous gel layer with porous inner structure in the dissolution media. Analysis of DS release profiles revealed that diffusion and matrix erosion occurred in simulated intestinal fluid(SIF, pH=6.8) for all the tablets. The experimental results predict HEP has a potential as a hydrophilic matrix in tablets to prolong drug release. Copyright © 2016 Elsevier Ltd. All rights reserved.

An integrative theory of the phasic and tonic modes of dopamine modulation in the prefrontal cortex.

PubMed

Dreher, Jean-Claude; Burnod, Yves

2002-01-01

This paper presents a model of both tonic and phasic dopamine (DA) effects on maintenance of working memory representations in the prefrontal cortex (PFC). The central hypothesis is that DA modulates the efficacy of inputs to prefrontal pyramidal neurons to prevent interferences for active maintenance. Phasic DA release, due to DA neurons discharges, acts at a short time-scale (a few seconds), while the tonic mode of DA release, independent of DA neurons firing, acts at a long time-scale (a few minutes). The overall effect of DA modulation is modeled as a threshold restricting incoming inputs arriving on PFC neurons. Phasic DA release temporary increases this threshold while tonic DA release progressively increases the basal level of this threshold. Thus, unlike the previous gating theory of phasic DA release, proposing that it facilitates incoming inputs at the time of their arrival, the effect of phasic DA release is supposed to restrict incoming inputs during a period of time after DA neuron discharges. The model links the cellular and behavioral levels during performance of a working memory task. It allows us to understand why a critical range of DA D1 receptors stimulation is required for optimal working memory performance and how D1 receptor agonists (respectively antagonists) increase perseverations (respectively distractability). Finally, the model leads to several testable predictions, including that the PFC regulates DA neurons firing rate to adapt to the delay of the task and that increase in tonic DA release may either improve or decrease performance, depending on the level of DA receptors stimulation at the beginning of the task.

Nanostructured lipid carriers: effect of solid phase fraction and distribution on the release of encapsulated materials.

PubMed

Dan, Nily

2014-11-25

Emulsions, solid lipid nanoparticles (SLN), and nanostructured lipid carriers (NLC) containing a mix of liquid and solid domains are of interest as encapsulation vehicles for hydrophobic compounds. Studies of the release rate from these particles yield contradictory results: Some find that increasing the fraction of solid phase increases the rate of release and others the opposite. In this paper we study the release of encapsulated materials from lipid-based nanoparticles using Monte Carlo simulations. We find that, quite surprisingly, the release rate is largely insensitive to the size of solid domains or the fraction of solid phase. However, the distribution of the domains significantly affects the rate of release: Solid domains located at the interface with the surrounding solution inhibit transport, while nanoparticles where the solid domains are concentrated in the center enhance it. The latter can lead to release rates in NLCs that are faster than in the equivalent emulsions. We conclude that controlling the release rate from NLCs requires the ability to determine the location and distribution of the solid phase, which may be achieved through choice of the surfactants stabilizing the particles, incorporation of nucleation sites, and/or the cooling rates and temperatures.

The variation of magma discharge during basaltic eruptions

NASA Technical Reports Server (NTRS)

Wadge, G.

1981-01-01

The rate at which basaltic magma is discharged during many eruptions varies substantially. An individual eruption has an eruption rate, which is the volumetric rate of discharge averaged over the whole or a major part of an eruption, and an effusion rate, which is the volumetric flux rate at any given time. In many cases, the effusion rate soon reaches a maximum after a short period of waxing flow (partly because of magmatic expansion); it then falls more slowly in the later parts of the eruption. The release of elastic strain energy from stored magma and the subvolcanic reservoir during eruption can give a waning flow of this type an exponential form. A comparison of the eruption rates of eruptions of Mauna Loa, Kilauea and Etna shows that for each volcano there is a trend of decreasing effusion rate with increasing duration of eruption. It is noted that this relationship is not predicted by a simple elastic model of magma release. Two other processes are invoked to explain the eruptive histories of these volcanoes: modification of the eruptive conduits and the continued supply of magma from depth during eruption.

Effect of Substrate Compliance on Measuring Delamination Properties of Elastic Thin Foil

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

Liu, C.

Through the analysis of a model problem, a thin elastic plate bonded to an elastic foundation, we address several issues related to the miniature bulge test for measuring the energy-release rate associated with the interfacial fracture of a bimaterial system, where one of the constituents is a thin foil. These issues include the effect of the substrate compliance on the interpretation of the energy release rate, interfacial strength, and the identification of the boundary of the deforming bulge or the location of the interfacial crack front. The analysis done also suggests a way for measuring the so-called foundation modulus, whichmore » characterizes the property of the substrate. An experimental example, a stainless steel thin foil bonded to an aluminum substrate through hot-isostatic-pressing (HIP), is used to illustrate and highlight some of the conclusions of the model analysis.« less

Effect of Substrate Compliance on Measuring Delamination Properties of Elastic Thin Foil

DOE PAGES

Liu, C.

2018-03-20

Through the analysis of a model problem, a thin elastic plate bonded to an elastic foundation, we address several issues related to the miniature bulge test for measuring the energy-release rate associated with the interfacial fracture of a bimaterial system, where one of the constituents is a thin foil. These issues include the effect of the substrate compliance on the interpretation of the energy release rate, interfacial strength, and the identification of the boundary of the deforming bulge or the location of the interfacial crack front. The analysis done also suggests a way for measuring the so-called foundation modulus, whichmore » characterizes the property of the substrate. An experimental example, a stainless steel thin foil bonded to an aluminum substrate through hot-isostatic-pressing (HIP), is used to illustrate and highlight some of the conclusions of the model analysis.« less

Modeling potential responses to smallpox as a bioterrorist weapon.

PubMed

Meltzer, M I; Damon, I; LeDuc, J W; Millar, J D

2001-01-01

We constructed a mathematical model to describe the spread of smallpox after a deliberate release of the virus. Assuming 100 persons initially infected and 3 persons infected per infectious person, quarantine alone could stop disease transmission but would require a minimum daily removal rate of 50% of those with overt symptoms. Vaccination would stop the outbreak within 365 days after release only if disease transmission were reduced to <0.85 persons infected per infectious person. A combined vaccination and quarantine campaign could stop an outbreak if a daily quarantine rate of 25% were achieved and vaccination reduced smallpox transmission by > or = 33%. In such a scenario, approximately 4,200 cases would occur and 365 days would be needed to stop the outbreak. Historical data indicate that a median of 2,155 smallpox vaccine doses per case were given to stop outbreaks, implying that a stockpile of 40 million doses should be adequate.

The analytical solution for drug delivery system with nonhomogeneous moving boundary condition

NASA Astrophysics Data System (ADS)

Saudi, Muhamad Hakimi; Mahali, Shalela Mohd; Harun, Fatimah Noor

2017-08-01

This paper discusses the development and the analytical solution of a mathematical model based on drug release system from a swelling delivery device. The mathematical model is represented by a one-dimensional advection-diffusion equation with nonhomogeneous moving boundary condition. The solution procedures consist of three major steps. Firstly, the application of steady state solution method, which is used to transform the nonhomogeneous moving boundary condition to homogeneous boundary condition. Secondly, the application of the Landau transformation technique that gives a significant impact in removing the advection term in the system of equation and transforming the moving boundary condition to a fixed boundary condition. Thirdly, the used of separation of variables method to find the analytical solution for the resulted initial boundary value problem. The results show that the swelling rate of delivery device and drug release rate is influenced by value of growth factor r.

Mechanistic investigation of drug release from asymmetric membrane tablets: effect of media gradients (osmotic pressure and concentration), and potential coating failures on in vitro release.

PubMed

Am Ende, Mary Tanya; Miller, Lee A

2007-02-01

An asymmetric membrane (AM) tablet was developed for a soluble model compound to study the in vitro drug release mechanisms in challenge conditions, including osmotic gradients, concentration gradients, and under potential coating failure modes. Porous, semipermable membrane integrity may be compromised by a high fat meal or by the presence of a defect in the coating that could cause a safety concern about dose-dumping. The osmotic and diffusional release mechanisms of the AM tablet were independently shut down such that their individual contribution to the overall drug release was measured. Shut off of osmotic and diffusional release was accomplished by performing dissolution studies into receptor solutions with osmotic pressure above the internal core osmotic pressure and into receptor solutions saturated with drug, respectively. The effect of coating failure modes on in vitro drug release from the AM tablet was assessed through a simulated high-fat meal and by intentionally compromising the coating integrity. The predominant drug release mechanism for the AM tablet was osmotic and accounted for approximately 90-95% of the total release. Osmotic release was shutoff when the receptor media osmotic pressure exceeded 76 atm. Diffusional release of the soluble drug amounted to 5-10% of the total release mechanism. The observed negative in vitro food effect was attributed to the increased osmotic pressure from the high fat meal when compared to the predicted release rates in sucrose media with the same osmotic pressure. This suppression in drug release rate due to a high fat meal is not anticipated to affect in vivo performance of the dosage form, as the rise in pressure is short-lived. Drug release from the AM system studied was determined to be robust to varying and extreme challenge conditions. The conditions investigated included varying pH, agitation rate, media osmotic pressure, media saturated with drug to eliminate the concentration gradient, simulated high fat meal, and intentionally placed film coating defects. Osmotic and diffusional shut off experiments suggest that the mechanism governing drug release is a combination of osmotic and diffusional at approximately 90-95% and 5-10%, respectively. In addition, the coating failure mode studies revealed this formulation and design is not significantly affected by a high fat meal or by an intentionally placed defect in the film coating, and more specifically, did not result in a burst of drug release.

Meshless Local Petrov-Galerkin Method for Solving Contact, Impact and Penetration Problems

DTIC Science & Technology

2006-11-30

Crack Growth 3 point of view, this approach makes the full use of the ex- isting FE models to avoid any model regeneration , which is extremely high in...process, at point C, the pressure reduces to zero, but the volumet- ric strain does not go to zero due to the collapsed void volume. 2.2 Damage...lease rate to go beyond the critical strain energy release rate. Thus, the micro-cracks begin to growth inside these areas. At 10 micro-seconds, these

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

Simulating future water temperatures in the North Santiam River, Oregon

USGS Publications Warehouse

Buccola, Norman; Risley, John C.; Rounds, Stewart A.

2016-01-01

A previously calibrated two-dimensional hydrodynamic and water-quality model (CE-QUAL-W2) of Detroit Lake in western Oregon was used in conjunction with inflows derived from Precipitation-Runoff Modeling System (PRMS) hydrologic models to examine in-lake and downstream water temperature effects under future climate conditions. Current and hypothetical operations and structures at Detroit Dam were imposed on boundary conditions derived from downscaled General Circulation Models in base (1990–1999) and future (2059–2068) periods. Compared with the base period, future air temperatures were about 2 °C warmer year-round. Higher air temperature and lower precipitation under the future period resulted in a 23% reduction in mean annual PRMS-simulated discharge and a 1 °C increase in mean annual estimated stream temperatures flowing into the lake compared to the base period. Simulations incorporating current operational rules and minimum release rates at Detroit Dam to support downstream habitat, irrigation, and water supply during key times of year resulted in lower future lake levels. That scenario results in a lake level that is above the dam’s spillway crest only about half as many days in the future compared to historical frequencies. Managing temperature downstream of Detroit Dam depends on the ability to blend warmer water from the lake’s surface with cooler water from deep in the lake, and the spillway is an important release point near the lake’s surface. Annual average in-lake and release temperatures from Detroit Lake warmed 1.1 °C and 1.5 °C from base to future periods under present-day dam operational rules and fill schedules. Simulated dam operations such as beginning refill of the lake 30 days earlier or reducing minimum release rates (to keep more water in the lake to retain the use of the spillway) mitigated future warming to 0.4 and 0.9 °C below existing operational scenarios during the critical autumn spawning period for endangered salmonids. A hypothetical floating surface withdrawal at Detroit Dam improved temperature control in summer and autumn (0.6 °C warmer in summer, 0.6 °C cooler in autumn compared to existing structures) without altering release rates or lake level management rules.

Altering the rate of glucose release from starch-based foods by spray-drying with an extract from barley.

PubMed

Razzaq, Hussam A A; Sutton, Kevin H; Motoi, Lidia

2013-08-30

Health outcomes associated with sustained elevated blood glucose may be better managed by limiting glucose availability for uptake. Glucose release from consumed starch may be altered using various methods, but many are not suitable for high-carbohydrate foods. This study describes an approach to protect starch granules, while generally maintaining their physical characteristics, with an extract from barley using spray-drying. The use of the extract resulted in the coating of the starch granules with a film-like material composed of β-glucans and proteins. This coincided with a reduction in starch digestion and a significant increase in the indigestible (resistant) starch component. Substitution of the starch component in a model snack bar by the coated starch was also associated with lowering starch digestion in the bar. The barley extract provides a physical barrier that may limit the exposure of starch to the digestive enzymes and water, with a consequent reduction in starch digestion and the rate of glucose release. It is possible, therefore, to produce wheat starch with lower digestibility and glucose release rate that may be used as a healthier substitute in high-carbohydrate foods by coating the granules with polymers extracted from barley cereals through spray-drying. © 2013 Society of Chemical Industry.

Dissolution enhancement of a model poorly water-soluble drug, atorvastatin, with ordered mesoporous silica: comparison of MSF with SBA-15 as drug carriers.

PubMed

Maleki, Aziz; Hamidi, Mehrdad

2016-01-01

The purpose of this study was to develop mesoporous silica materials incorporated with poorly water-soluble drug atorvastatin calcium (AC) in order to improve drug dissolution, and intended to be orally administrated. A comparison between 2D-hexagonal silica nanostructured SBA-15 and mesocellular siliceous foam (MSF) with continuous 3D pore system on drug release rate was investigated. AC-loaded mesoporous silicas were characterized thorough N2 adsorption-desorption analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dynamic light scattering (DLS). Results demonstrated a successful incorporation of AC into the silica-based hosts. The results taken from the drug release tests were also analyzed using different parameters, namely similarity factor (f2), difference factor (f1), dissolution efficiency (DE%), mean dissolution rate (MDR) and dissolution time (tm%). It confirmed a significant enhancement in the release profile of atorvastatin calcium with SBA-15, and MSF as drug carrier. Moreover, in comparison with SBA-15, MSF showed faster release rate of AC in enzyme-free simulated gastric fluid (pH 1.2). We believed that our findings can help the use of mesoporous silica materials in improving bioavailability of poorly water-soluble drugs.

Islet oxygen consumption rate (OCR) dose predicts insulin independence for first clinical islet allotransplants

PubMed Central

Kitzmann, JP; O’Gorman, D; Kin, T; Gruessner, AC; Senior, P; Imes, S; Gruessner, RW; Shapiro, AMJ; Papas, KK

2014-01-01

Human islet allotransplant (ITx) for the treatment of type 1 diabetes is in phase III clinical registration trials in the US and standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose stimulated insulin release (GSIR), and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following one transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. In this paper we report on the assessment of clinical islet allograft preparations using islet oxygen consumption rate (OCR) dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. Results showed that OCR dose was most predictive of CTO. IE dose was also highly predictive, while GSIR and membrane integrity stains were not. In conclusion, OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical ITx. PMID:25131089

Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

PubMed

Korogiannaki, Myrto; Guidi, Giuliano; Jones, Lyndon; Sheardown, Heather

2015-09-01

This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile. © The Author(s) 2015.

Glucose-responsive microgels integrated with enzyme nanocapsules for closed-loop insulin delivery.

PubMed

Gu, Zhen; Dang, Tram T; Ma, Minglin; Tang, Benjamin C; Cheng, Hao; Jiang, Shan; Dong, Yizhou; Zhang, Yunlong; Anderson, Daniel G

2013-08-27

A glucose-responsive closed-loop insulin delivery system represents the ideal treatment of type 1 diabetes mellitus. In this study, we develop uniform injectable microgels for controlled glucose-responsive release of insulin. Monodisperse microgels (256 ± 18 μm), consisting of a pH-responsive chitosan matrix, enzyme nanocapsules, and recombinant human insulin, were fabricated through a one-step electrospray procedure. Glucose-specific enzymes were covalently encapsulated into the nanocapsules to improve enzymatic stability by protecting from denaturation and immunogenicity as well as to minimize loss due to diffusion from the matrix. The microgel system swelled when subjected to hyperglycemic conditions, as a result of the enzymatic conversion of glucose into gluconic acid and protonation of the chitosan network. Acting as a self-regulating valve system, microgels were adjusted to release insulin at basal release rates under normoglycemic conditions and at higher rates under hyperglycemic conditions. Finally, we demonstrated that these microgels with enzyme nanocapsules facilitate insulin release and result in a reduction of blood glucose levels in a mouse model of type 1 diabetes.

Variation of the energy release rate as a crack approaches and passes through an elastic inclusion

NASA Astrophysics Data System (ADS)

Li, Rongshun; Chudnovsky, A.

1993-02-01

The variation of the energy release rate (ERP) at the tip of a crack penetrating an elastic inclusion is analyzed using an approach involving modeling the random array of microcracks or other defects by an elastic inclusion with effective elastic properties. Computations are carried out using a finite element procedure. The eight-noded isoparametric serendipity element with the shift of the midpoint to the quarter-point is used to simulate the singularity at the crack tip, and the crack growth is accommodated by implementing a mesh regeneration technique. The ERP values were calculated for various crack tip positions which simulate the process of the crack approaching and penetrating the inclusion.

Variation of the energy release rate as a crack approaches and passes through an elastic inclusion

NASA Technical Reports Server (NTRS)

Li, Rongshun; Chudnovsky, A.

1993-01-01

The variation of the energy release rate (ERP) at the tip of a crack penetrating an elastic inclusion is analyzed using an approach involving modeling the random array of microcracks or other defects by an elastic inclusion with effective elastic properties. Computations are carried out using a finite element procedure. The eight-noded isoparametric serendipity element with the shift of the midpoint to the quarter-point is used to simulate the singularity at the crack tip, and the crack growth is accommodated by implementing a mesh regeneration technique. The ERP values were calculated for various crack tip positions which simulate the process of the crack approaching and penetrating the inclusion.

Barnacles resist removal by crack trapping

PubMed Central

Hui, Chung-Yuen; Long, Rong; Wahl, Kathryn J.; Everett, Richard K.

2011-01-01

We study the mechanics of pull-off of a barnacle adhering to a thin elastic layer which is bonded to a rigid substrate. We address the case of barnacles having acorn shell geometry and hard, calcarious base plates. Pull-off is initiated by the propagation of an interface edge crack between the base plate and the layer. We compute the energy release rate of this crack as it grows along the interface using a finite element method. We also develop an approximate analytical model to interpret our numerical results and to give a closed-form expression for the energy release rate. Our result shows that the resistance of barnacles to interfacial failure arises from a crack-trapping mechanism. PMID:21208968

Fire Detection Tradeoffs as a Function of Vehicle Parameters

NASA Technical Reports Server (NTRS)

Urban, David L.; Dietrich, Daniel L.; Brooker, John E.; Meyer, Marit E.; Ruff, Gary A.

2016-01-01

Fire survivability depends on the detection of and response to a fire before it has produced an unacceptable environment in the vehicle. This detection time is the result of interplay between the fire burning and growth rates; the vehicle size; the detection system design; the transport time to the detector (controlled by the level of mixing in the vehicle); and the rate at which the life support system filters the atmosphere, potentially removing the detected species or particles. Given the large differences in critical vehicle parameters (volume, mixing rate and filtration rate) the detection approach that works for a large vehicle (e.g. the ISS) may not be the best choice for a smaller crew capsule. This paper examines the impact of vehicle size and environmental control and life support system parameters on the detectability of fires in comparison to the hazard they present. A lumped element model was developed that considers smoke, heat, and toxic product release rates in comparison to mixing and filtration rates in the vehicle. Recent work has quantified the production rate of smoke and several hazardous species from overheated spacecraft polymers. These results are used as the input data set in the lumped element model in combination with the transport behavior of major toxic products released by overheating spacecraft materials to evaluate the necessary alarm thresholds to enable appropriate response to the fire hazard.

Comminution of solids caused by kinetic energy of high shear strain rate, with implications for impact, shock, and shale fracturing

PubMed Central

Bažant, Zdeněk P.; Caner, Ferhun C.

2013-01-01

Although there exists a vast literature on the dynamic comminution or fragmentation of rocks, concrete, metals, and ceramics, none of the known models suffices for macroscopic dynamic finite element analysis. This paper outlines the basic idea of the macroscopic model. Unlike static fracture, in which the driving force is the release of strain energy, here the essential idea is that the driving force of comminution under high-rate compression is the release of the local kinetic energy of shear strain rate. The density of this energy at strain rates >1,000/s is found to exceed the maximum possible strain energy density by orders of magnitude, making the strain energy irrelevant. It is shown that particle size is proportional to the −2/3 power of the shear strain rate and the 2/3 power of the interface fracture energy or interface shear stress, and that the comminution process is macroscopically equivalent to an apparent shear viscosity that is proportional (at constant interface stress) to the −1/3 power of this rate. A dimensionless indicator of the comminution intensity is formulated. The theory was inspired by noting that the local kinetic energy of shear strain rate plays a role analogous to the local kinetic energy of eddies in turbulent flow. PMID:24218624

Passive sampling of DDT, DDE and DDD in sediments: accounting for degradation processes with reaction-diffusion modeling.

PubMed

Tcaciuc, A Patricia; Borrelli, Raffaella; Zaninetta, Luciano M; Gschwend, Philip M

2018-01-24

Passive sampling is becoming a widely used tool for assessing freely dissolved concentrations of hydrophobic organic contaminants in environmental media. For certain media and target analytes, the time to reach equilibrium exceeds the deployment time, and in such cases, the loss of performance reference compounds (PRCs), loaded in the sampler before deployment, is one of the common ways used to assess the fractional equilibration of target analytes. The key assumption behind the use of PRCs is that their release is solely diffusion driven. But in this work, we show that PRC transformations in the sediment can have a measurable impact on the PRC releases and even allow estimation of that compound's transformation rate in the environment of interest. We found that in both field and lab incubations, the loss of the 13 C 2,4'-DDT PRC from a polyethylene (PE) passive sampler deployed at the sediment-water interface was accelerated compared to the loss of other PRCs ( 13 C-labeled PCBs, 13 C-labeled DDE and DDD). The DDT PRC loss was also accompanied by accumulation in the PE of its degradation product, 13 C 2,4'-DDD. Using a 1D reaction-diffusion model, we deduced the in situ degradation rates of DDT from the measured PRC loss. The in situ degradation rates increased with depth into the sediment bed (0.14 d -1 at 0-10 cm and 1.4 d -1 at 30-40 cm) and although they could not be independently validated, these rates compared favorably with literature values. This work shows that passive sampling users should be cautious when choosing PRCs, as degradation processes can affect some PRC's releases from the passive sampler. More importantly, this work opens up the opportunity for novel applications of passive samplers, particularly with regard to investigating in situ degradation rates, pathways, and products for both legacy and emerging contaminants. However, further work is needed to confirm that the rates deduced from model fitting of PRC loss are a true reflection of DDT transformation rates in sediments.

Letter: Modeling reactive shock waves in heterogeneous solids at the continuum level with stochastic differential equations

NASA Astrophysics Data System (ADS)

Kittell, D. E.; Yarrington, C. D.; Lechman, J. B.; Baer, M. R.

2018-05-01

A new paradigm is introduced for modeling reactive shock waves in heterogeneous solids at the continuum level. Inspired by the probability density function methods from turbulent reactive flows, it is hypothesized that the unreacted material microstructures lead to a distribution of heat release rates from chemical reaction. Fluctuations in heat release, rather than velocity, are coupled to the reactive Euler equations which are then solved via the Riemann problem. A numerically efficient, one-dimensional hydrocode is used to demonstrate this new approach, and simulation results of a representative impact calculation (inert flyer into explosive target) are discussed.

Modeling of outgassing and matrix decomposition in carbon-phenolic composites

NASA Technical Reports Server (NTRS)

Mcmanus, Hugh L.

1993-01-01

A new release rate equation to model the phase change of water to steam in composite materials was derived from the theory of molecular diffusion and equilibrium moisture concentration. The new model is dependent on internal pressure, the microstructure of the voids and channels in the composite materials, and the diffusion properties of the matrix material. Hence, it is more fundamental and accurate than the empirical Arrhenius rate equation currently in use. The model was mathematically formalized and integrated into the thermostructural analysis code CHAR. Parametric studies on variation of several parameters have been done. Comparisons to Arrhenius and straight-line models show that the new model produces physically realistic results under all conditions.

Finite element analysis of ion transport in solid state nuclear waste form materials

NASA Astrophysics Data System (ADS)

Rabbi, F.; Brinkman, K.; Amoroso, J.; Reifsnider, K.

2017-09-01

Release of nuclear species from spent fuel ceramic waste form storage depends on the individual constituent properties as well as their internal morphology, heterogeneity and boundary conditions. Predicting the release rate is essential for designing a ceramic waste form, which is capable of effectively storing the spent fuel without contaminating the surrounding environment for a longer period of time. To predict the release rate, in the present work a conformal finite element model is developed based on the Nernst Planck Equation. The equation describes charged species transport through different media by convection, diffusion, or migration. And the transport can be driven by chemical/electrical potentials or velocity fields. The model calculates species flux in the waste form with different diffusion coefficient for each species in each constituent phase. In the work reported, a 2D approach is taken to investigate the contributions of different basic parameters in a waste form design, i.e., volume fraction, phase dispersion, phase surface area variation, phase diffusion co-efficient, boundary concentration etc. The analytical approach with preliminary results is discussed. The method is postulated to be a foundation for conformal analysis based design of heterogeneous waste form materials.

Unleashing elastic energy: dynamics of energy release in rubber bands and impulsive biological systems

NASA Astrophysics Data System (ADS)

Ilton, Mark; Cox, Suzanne; Egelmeers, Thijs; Patek, S. N.; Crosby, Alfred J.

Impulsive biological systems - which include mantis shrimp, trap-jaw ants, and venus fly traps - can reach high speeds by using elastic elements to store and rapidly release energy. The material behavior and shape changes critical to achieving rapid energy release in these systems are largely unknown due to limitations of materials testing instruments operating at high speed and large displacement. In this work, we perform fundamental, proof-of-concept measurements on the tensile retraction of elastomers. Using high speed imaging, the kinematics of retraction are measured for elastomers with varying mechanical properties and geometry. Based on the kinematics, the rate of energy dissipation in the material is determined as a function of strain and strain-rate, along with a scaling relation which describes the dependence of maximum velocity on material properties. Understanding this scaling relation along with the material failure limits of the elastomer allows the prediction of material properties required for optimal performance. We demonstrate this concept experimentally by optimizing for maximum velocity in our synthetic model system, and achieve retraction velocities that exceed those in biological impulsive systems. This model system provides a foundation for future work connecting continuum performance to molecular architecture in impulsive systems.

Heat release rate of wood-plastic composites

Treesearch

N. M. Stark; R. H. White; C. M. Clemons

1997-01-01

Wood-plastic composites are becoming more important as a material that fulfills recycling needs. In this study, fire performance tests were conducted on several compositions of wood and plastic materials using the Ohio State University rate of heat release apparatus. Test results included five-minute average heat release rate in kW/m2 (HRR avg) and maximum heat release...

Recent MELCOR and VICTORIA Fission Product Research at the NRC

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

Bixler, N.E.; Cole, R.K.; Gauntt, R.O.

1999-01-21

The MELCOR and VICTORIA severe accident analysis codes, which were developed at Sandia National Laboratories for the U. S. Nuclear Regulatory Commission, are designed to estimate fission product releases during nuclear reactor accidents in light water reactors. MELCOR is an integrated plant-assessment code that models the key phenomena in adequate detail for risk-assessment purposes. VICTORIA is a more specialized fission- product code that provides detailed modeling of chemical reactions and aerosol processes under the high-temperature conditions encountered in the reactor coolant system during a severe reactor accident. This paper focuses on recent enhancements and assessments of the two codes inmore » the area of fission product chemistry modeling. Recently, a model for iodine chemistry in aqueous pools in the containment building was incorporated into the MELCOR code. The model calculates dissolution of iodine into the pool and releases of organic and inorganic iodine vapors from the pool into the containment atmosphere. The main purpose of this model is to evaluate the effect of long-term revolatilization of dissolved iodine. Inputs to the model include dose rate in the pool, the amount of chloride-containing polymer, such as Hypalon, and the amount of buffering agents in the containment. Model predictions are compared against the Radioiodine Test Facility (RTF) experiments conduced by Atomic Energy of Canada Limited (AECL), specifically International Standard Problem 41. Improvements to VICTORIA's chemical reactions models were implemented as a result of recommendations from a peer review of VICTORIA that was completed last year. Specifically, an option is now included to model aerosols and deposited fission products as three condensed phases in addition to the original option of a single condensed phase. The three-condensed-phase model results in somewhat higher predicted fission product volatilities than does the single-condensed-phase model. Modeling of U02 thermochemistry was also improved, and results in better prediction of vaporization of uranium from fuel, which can react with released fission products to affect their volatility. This model also improves the prediction of fission product release rates from fuel. Finally, recent comparisons of MELCOR and VICTORIA with International Standard Problem 40 (STORM) data are presented. These comparisons focus on predicted therrnophoretic deposition, which is the dominant deposition mechanism. Sensitivity studies were performed with the codes to examine experimental and modeling uncertainties.« less

A steady-state mechanism can account for the properties of inositol 2,4,5-trisphosphate-stimulated Ca2+ release from permeabilized L1210 cells.

PubMed Central

Loomis-Husselbee, J W; Dawson, A P

1993-01-01

We have investigated the effects of sub-maximal Ins(2,4,5)P3 concentrations on the Ca2+ permeability of the residual undischarged Ca2+ stores in electroporated or digitonin-permeabilized L1210 cells by measuring Ca(2+)-efflux rate after addition of the ATPase inhibitor thapsigargin. Low concentrations of Ins(2,4,5)P3, causing rapid discharge of a small proportion of the releasable Ca2+, result in a substantial stimulation of Ca2+ efflux after thapsigargin addition. This indicates firstly that in the absence of thapsigargin there must have been a substantial, counterbalancing, increase in rate of Ca2+ pumping, and secondly that the increased Ca2+ permeability is more consistent with a steady state than with a quantal model of Ca2+ release. Similar increases in passive Ca2+ permeability are produced by addition of concentrations of ionomycin which produce equivalent changes in Ca2+ loading to those produced by Ins(2,4,5)P3, although the time course and initial rate of Ca2+ release are very much slower. In the presence of a Ca(2+)-buffering system, the time course of Ca2+ release by Ins(2,4,5)P3 becomes superimposable on that of ionomycin, indicating that the initial rapid phase of Ins(2,4,5)P3-stimulated Ca2+ is at least partially due to positive feedback from extravesicular Ca2+. PMID:8382056

Refinement and evaluation of the Massachusetts firm-yield estimator model version 2.0

USGS Publications Warehouse

Levin, Sara B.; Archfield, Stacey A.; Massey, Andrew J.

2011-01-01

The firm yield is the maximum average daily withdrawal that can be extracted from a reservoir without risk of failure during an extended drought period. Previously developed procedures for determining the firm yield of a reservoir were refined and applied to 38 reservoir systems in Massachusetts, including 25 single- and multiple-reservoir systems that were examined during previous studies and 13 additional reservoir systems. Changes to the firm-yield model include refinements to the simulation methods and input data, as well as the addition of several scenario-testing capabilities. The simulation procedure was adapted to run at a daily time step over a 44-year simulation period, and daily streamflow and meteorological data were compiled for all the reservoirs for input to the model. Another change to the model-simulation methods is the adjustment of the scaling factor used in estimating groundwater contributions to the reservoir. The scaling factor is used to convert the daily groundwater-flow rate into a volume by multiplying the rate by the length of reservoir shoreline that is hydrologically connected to the aquifer. Previous firm-yield analyses used a constant scaling factor that was estimated from the reservoir surface area at full pool. The use of a constant scaling factor caused groundwater flows during periods when the reservoir stage was very low to be overestimated. The constant groundwater scaling factor used in previous analyses was replaced with a variable scaling factor that is based on daily reservoir stage. This change reduced instability in the groundwater-flow algorithms and produced more realistic groundwater-flow contributions during periods of low storage. Uncertainty in the firm-yield model arises from many sources, including errors in input data. The sensitivity of the model to uncertainty in streamflow input data and uncertainty in the stage-storage relation was examined. A series of Monte Carlo simulations were performed on 22 reservoirs to assess the sensitivity of firm-yield estimates to errors in daily-streamflow input data. Results of the Monte Carlo simulations indicate that underestimation in the lowest stream inflows can cause firm yields to be underestimated by an average of 1 to 10 percent. Errors in the stage-storage relation can arise when the point density of bathymetric survey measurements is too low. Existing bathymetric surfaces were resampled using hypothetical transects of varying patterns and point densities in order to quantify the uncertainty in stage-storage relations. Reservoir-volume calculations and resulting firm yields were accurate to within 5 percent when point densities were greater than 20 points per acre of reservoir surface. Methods for incorporating summer water-demand-reduction scenarios into the firm-yield model were developed as well as the ability to relax the no-fail reliability criterion. Although the original firm-yield model allowed monthly reservoir releases to be specified, there have been no previous studies examining the feasibility of controlled releases for downstream flows from Massachusetts reservoirs. Two controlled-release scenarios were tested—with and without a summer water-demand-reduction scenario—for a scenario with a no-fail criterion and a scenario that allows for a 1-percent failure rate over the entire simulation period. Based on these scenarios, about one-third of the reservoir systems were able to support the flow-release scenarios at their 2000–2004 usage rates. Reservoirs with higher storage ratios (reservoir storage capacity to mean annual streamflow) and lower demand ratios (mean annual water demand to annual firm yield) were capable of higher downstream release rates. For the purposes of this research, all reservoir systems were assumed to have structures which enable controlled releases, although this assumption may not be true for many of the reservoirs studied.

Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate.

PubMed

Schotten, Sebastiaan; Meijer, Marieke; Walter, Alexander Matthias; Huson, Vincent; Mamer, Lauren; Kalogreades, Lawrence; ter Veer, Mirelle; Ruiter, Marvin; Brose, Nils; Rosenmund, Christian; Sørensen, Jakob Balslev; Verhage, Matthijs; Cornelisse, Lennart Niels

2015-04-14

The energy required to fuse synaptic vesicles with the plasma membrane ('activation energy') is considered a major determinant in synaptic efficacy. From reaction rate theory, we predict that a class of modulations exists, which utilize linear modulation of the energy barrier for fusion to achieve supralinear effects on the fusion rate. To test this prediction experimentally, we developed a method to assess the number of releasable vesicles, rate constants for vesicle priming, unpriming, and fusion, and the activation energy for fusion by fitting a vesicle state model to synaptic responses induced by hypertonic solutions. We show that complexinI/II deficiency or phorbol ester stimulation indeed affects responses to hypertonic solution in a supralinear manner. An additive vs multiplicative relationship between activation energy and fusion rate provides a novel explanation for previously observed non-linear effects of genetic/pharmacological perturbations on synaptic transmission and a novel interpretation of the cooperative nature of Ca(2+)-dependent release.

Effects of membrane composition on release of model hydrophilic compound from osmotic delivery systems.

PubMed

Ozdemir, N; Ozalp, Y; Ozkan, Y

2000-01-01

In this study, the effects of surface-active agents in different types and concentrations, added into the coating solution, on release of model hydrophilic compound have been examined. For this purpose, the tablets, prepared with the use of methylene blue as a model substance, were coated by spray coating technique with cellulose acetate solution containing polyethylene glycol 400 as a plasticizer. In addition, cetylpyridinium chloride as cationic surface-active agent and sodium lauryl sulphate as anionic surface-active agent were added into coating solution in different concentrations. After creating a delivery orifice by a microdrill on the tablets, release of model hydrophilic compound was tested by the USP paddle method. The data obtained were evaluated according to the different kinetics and the mechanism of release from the preparations was examined. The surface properties of the coating material were investigated by scanning electron microscope taken before and after the contact with medium fluid, as well as the mechanical properties by tensile tests. In conclusion, it has been found that the cationic surface active agent, cetylpyridinium chloride reduced the lag time, observed during the release of model hydrophilic compound, as a result of its enhancing effect on wettability of tablets by reducing the contact angle between the medium fluid and the coating material. On the other hand, the anionic surface active agent, sodium lauryl sulphate has been inactivated possibly due to the interaction with model hydrophilic compound that has cationic properties and/or substances contained in membrane composition; thus, the lag time has not decreased and furthermore, a significant decrease in the delivery rate of model hydrophilic compound has been observed.

Comparison of the Kinetic Rate Law Parameters for the Dissolution of Natural and Synthetic Autunite in the Presence of Aqueous Bicarbonate Ions

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

Gudavalli, Ravi; Katsenovich, Yelena; Wellman, Dawn M.

2013-08-02

Bicarbonate is one of the most significant components within the uranium geochemical cycle. In aqueous solutions, bicarbonate forms strong complexes with uranium. As such, aqueous bicarbonate may significantly increase the rate of uranium release from uranium minerals. Quantifying the relationship of aqueous bicarbonate concentration to the rate of uranium release during dissolution is critical to understanding the long-term fate of uranium within the environment. Single-pass flow-through (SPTF) experiments were conducted to estimate the rate of uranium release from Na meta-autunite as a function of bicarbonate (0.0005-0.003 M) under the pH range of 6-11 and a temperature range of 5-60oC. Consistentmore » with the results of previous investigation, the rate of uranium release exhibited minimal dependency on temperature; but were strongly dependent on pH. Increasing aqueous bicarbonate concentrations afforded comparable increases in the rate of release of uranium. Most notably under low pH conditions the aqueous bicarbonate resulted in up to 370 fold increases in the rate of uranium release in relative to the rate of uranium release in the absence of bicarbonate. However, the effect of aqueous bicarbonate on the release of uranium was significantly less under higher pH conditions. It is postulated that at high pH values, surface sites are saturated with carbonate, thus the addition of more bicarbonate would have less effect on uranium release.« less

Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

PubMed

Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

2018-05-29

Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases. Copyright © 2018. Published by Elsevier B.V.

Many Vulnerable or a Few Resilient Specimens? Finding the Optimal for Reintroduction/Restocking Programs

PubMed Central

Gil, María del Mar; Palmer, Miquel; Grau, Amalia; Balle, Salvador

2015-01-01

Most reintroduction and restocking programs consist of releasing captive-raised juveniles. The usefulness of these programs has been questioned, and therefore, quality control is advisable. However, evaluating restocking effectiveness is challenging because mortality estimation is required. Most methods for estimating mortality are based on tag recovery. In the case of fish, juveniles are tagged before release, and fishermen typically recover tags when fish are captured. The statistical models currently available for analyzing these data assume either constant mortality rates, fixed tag non-reporting rates, or both. Here, instead, we proposed a method that considers the mortality rate variability as a function of age/size of the released juveniles. Furthermore, the proposed method can disentangle natural from fishing mortality, analyzing the temporal distribution of the captures reported by fishermen from multiple release events. This method is demonstrated with a restocking program of a top-predator marine fish, the meagre (Argyrosomus regius), in the Balearic Islands. The estimated natural mortality just after release was very high for young fish (m 0 = 0.126 day-1 for fish 180 days old), but it was close to zero for large/old fish. These large/old fish were more resilient to wild conditions, although a long time was needed to achieve a relevant reduction in natural mortality. Conversely, these large/old fish were more vulnerable to fishing, creating a trade-off in survival. The release age that maximizes the number of survivors after, for example, one year at liberty was estimated to be 1,173 days. However, the production cost of relatively old fish is high, and only a few fish can be produced and released within a realistic budget. Therefore, in the case of the meagre, increasing the number of released fish will have no or scarce effects on restocking success. Conversely, it is advisable implement measures to reduce the high natural mortality of young juveniles and/or the length of time needed to improve fish resilience. PMID:26394242

Analytical modeling of fire growth on fire-resistive wood-based materials with changing conditions

Treesearch

Mark A. Dietenberger

2006-01-01

Our analytical model of fire growth for the ASTM E 84 tunnel, which simultaneously predicts heat release rate, flame-over area, and pyrolysis area as functions of time for constant conditions, was documented in the 2001 BCC Symposium for different treated wood materials. The model was extended to predict ignition and fire growth on exterior fire-resistive structures...

Combustion Of Metals In Reduced Gravity And Extraterrestrial Environments

NASA Technical Reports Server (NTRS)

Abbud-Madrid, A.; Modak, A.; Branch, M. C.

2003-01-01

The recent focus of this research project has been to model the combustion of isolated metal droplets and, in particular, to couple the existing theories and formulations of phenomena such as condensation, reaction kinetics, radiation, and surface reactions to formulate a more complete combustion model. A fully transient, one-dimensional (spherical symmetry) numerical model that uses detailed chemical kinetics, multi-component molecular transport mechanisms, condensation kinetics, and gas phase radiation heat transfer was developed. A coagulation model was used to simulate the particulate formation of MgO. The model was used to simulate the combustion of an Mg droplet in pure O2 and CO2. Methanol droplet combustion is considered as a test case for the solution method for both quasi-steady and fully transient simulations. Although some important processes unique to methanol combustion, such as water absorption at the surface, are not included in the model, the results are in sufficient agreement with the published data. Since the major part of the heat released in combustion of Mg, and in combustion of metals in general, is due to the condensation of the metal oxide, it is very important to capture the condensation processes correctly. Using the modified nucleation theory, an Arrhenius type rate expression is derived to calculate the condensation rate of MgO. This expression can be easily included in the CHEMKIN reaction mechanism format. Although very little property data is available for MgO, the condensation rate expression derived using the existing data is able to capture the condensation of MgO. An appropriate choice of the reference temperature to calculate the rate coefficients allows the model to correctly predict the subsequent heat release and hence the flame temperature.

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.

Seafloor hydrothermal activity and spreading rates - The Eocene carbon dioxide greenhouse revisited

NASA Technical Reports Server (NTRS)

Kasting, J. F.; Richardson, S. M.

1985-01-01

A suggestion has been made that enhanced rates of hydrothermal activity during the Eocene could have caused a global warming by adding calcium to the ocean and pumping CO2 into the atmosphere (Owen and Rea, 1984). This phenomenon was purported to be consistent with the predictions of the CO2 geochemical cycle model of Berner, Lasaga and Garrels (1983) (henceforth BLAG). In fact, however, the BLAG model predicts only a weak connection between hydrothermal activity and atmospheric CO2 levels. By contrast, it predicts a strong correlation between seafloor spreading rates and pCO2, since the release rate of CO2 from carbonate metamorphism is assumed to be proportional to the mean spreading rate. The Eocene warming can be conveniently explained if the BLAG model is extended by assuming that the rate of carbonate metamorphism is also proportional to the total length of the midocean ridges from which the spreading originates.

Seafloor hydrothermal activity and spreading rates: the Eocene carbon dioxide greenhouse revisted

NASA Technical Reports Server (NTRS)

Kasting, J. F.; Richardson, S. M.

1985-01-01

A suggestion has been made that enhanced rates of hydrothermal activity during the Eocene could have caused a global warming by adding calcium to the ocean and pumping CO2 into the atmosphere (Owen and Rea, 1984). This phenomenon was purported to be consistent with the predictions of the CO2 geochemical cycle model of Berner, Lasaga and Garrels (1983) (henceforth BLAG). In fact, however, the BLAG model predicts only a weak connection between hydrothermal activity and atmospheric CO2 levels. By contrast, it predicts a strong correlation between seafloor spreading rates and pCO2, since the release rate of CO2 from carbonate metamorphism is assumed to be proportional to the mean spreading rate. The Ecocene warming can be conveniently explained if the BLAG model is extended by assuming that the rate of carbonate metamorphism is also proportional to the total length of the midocean ridges from which the spreading originates.

Combustion-acoustic stability analysis for premixed gas turbine combustors

NASA Technical Reports Server (NTRS)

Darling, Douglas; Radhakrishnan, Krishnan; Oyediran, Ayo; Cowan, Lizabeth

1995-01-01

Lean, prevaporized, premixed combustors are susceptible to combustion-acoustic instabilities. A model was developed to predict eigenvalues of axial modes for combustion-acoustic interactions in a premixed combustor. This work extends previous work by including variable area and detailed chemical kinetics mechanisms, using the code LSENS. Thus the acoustic equations could be integrated through the flame zone. Linear perturbations were made of the continuity, momentum, energy, chemical species, and state equations. The qualitative accuracy of our approach was checked by examining its predictions for various unsteady heat release rate models. Perturbations in fuel flow rate are currently being added to the model.

Radiation preparation of drug carriers based polyacrylic acid (PAAc) using poly(vinyl pyrrolidone) (PVP) as a template polymer

NASA Astrophysics Data System (ADS)

Abd El-Rehim, H. A.; Hegazy, E. A.; Khalil, F. H.; Hamed, N. A.

2007-01-01

The present study deals with the radiation synthesis of stimuli response hydrophilic polymers from polyacrylic acid (PAAc). To maintain the property of PAAc and control the water swellibility for its application as a drug delivery system, radiation polymerization of AAc in the presence of poly(vinyl pyrrolidone) (PVP) as a template polymer was carried out. Characterization of the prepared PAA/PVP inter-polymer complex was investigated by determining gel content, swelling property, hydrogel microstructure and the release rate of caffeine as a model drug. The release rate of caffeine from the PAA/PVP inter-polymer complexes showed pH-dependency, and seemed to be mainly controlled by the dissolution rate of the complex above a p Ka of PAAc. The prepared inter-polymer complex could be used for application as drug carriers.

Electrospray-assisted encapsulation of caffeine in alginate microhydrogels.

PubMed

Nikoo, Alireza Mehregan; Kadkhodaee, Rassoul; Ghorani, Behrouz; Razzaq, Hussam; Tucker, Nick

2018-05-02

One of the major challenges with microencapsulation and delivery of low molecular weight bioactive compounds is their diffusional loss during storage and process conditions as well as under gastric conditions. In an attempt to slow down the release rate of core material, electrospray fabricated calcium alginate microhydrogels were coated with low molecular weight and high molecular weight chitosans. Caffeine as a hydrophilic model compound was used due to its several advantages on human behavior especially increasing consciousness. Mathematical modeling of the caffeine release by fitting the data with Korsmeyer-Peppas model showed that Fick's diffusion law could be the prevalent mechanism of the release. Electrostatic interaction between alginate and chitosan (particularly in the presence of 1% low molecular weight chitosan) provided an effective barrier against caffeine release and significantly reduced swelling of particles compared to control samples. The results of this study demonstrated that calcium alginate microhydrogels coated by chitosan could be used for encapsulation of low molecular compounds. However, more complementary research must be done in this field. In addition, electrospray, by producing monodisperse particles, would be as an alternative method for fabrication of microparticles based on natural polymers. Copyright © 2018. Published by Elsevier B.V.

Fission-gas-release rates from irradiated uranium nitride specimens

NASA Technical Reports Server (NTRS)

Weinstein, M. B.; Kirchgessner, T. A.; Tambling, T. N.

1973-01-01

Fission-gas-release rates from two 93 percent dense UN specimens were measured using a sweep gas facility. Specimen burnup rates averaged .0045 and .0032 percent/hr, and the specimen temperatures ranged from 425 to 1323 K and from 552 to 1502 K, respectively. Burnups up to 7.8 percent were achieved. Fission-gas-release rates first decreased then increased with burnup. Extensive interconnected intergranular porosity formed in the specimen operated at over 1500 K. Release rate variation with both burnup and temperature agreed with previous irradiation test results.

Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

PubMed

Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

2016-06-01

Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment. © 2016 John Wiley & Sons A/S.

Development of In Vitro-In Vivo Correlation for Potassium Chloride Extended Release Tablet Formulation Using Urinary Pharmacokinetic Data.

PubMed

Mittapalli, Rajendar K; Marroum, Patrick; Qiu, Yihong; Apfelbaum, Kathleen; Xiong, Hao

2017-07-01

To develop and validate a Level A in vitro-in vivo correlation (IVIVC) for potassium chloride extended-release (ER) formulations. Three prototype ER formulations of potassium chloride with different in vitro release rates were developed and their urinary pharmacokinetic profiles were evaluated in healthy subjects. A mathematical model between in vitro dissolution and in vivo urinary excretion, a surrogate for measuring in vivo absorption, was developed using time-scale and time-shift parameters. The IVIVC model was then validated based on internal and external predictability. With the established IVIVC model, there was a good correlation between the observed fraction of dose excreted in urine and the time-scaled and time-shifted fraction of the drug dissolved, and between the in vitro dissolution time and the in vivo urinary excretion time for the ER formulations. The percent prediction error (%PE) on cumulative urinary excretion over the 24 h interval (A e0-24h ) and maximum urinary excretion rate (R max ) was less than 15% for the individual formulations and less than 10% for the average of the two formulations used to develop the model. Further, the %PE values using external predictability were below 10%. A novel Level A IVIVC was successfully developed and validated for the new potassium chloride ER formulations using urinary pharmacokinetic data. This successful IVIVC may facilitate future development or manufacturing changes to the potassium chloride ER formulation.

Pyrolysis kinetic and product analysis of different microalgal biomass by distributed activation energy model and pyrolysis-gas chromatography-mass spectrometry.

PubMed

Yang, Xuewei; Zhang, Rui; Fu, Juan; Geng, Shu; Cheng, Jay Jiayang; Sun, Yuan

2014-07-01

To assess the energy potential of different microalgae, Chlorella sorokiniana and Monoraphidium were selected for studying the pyrolytic behavior at different heating rates with the analytical method of thermogravimetric analysis (TG), distributed activation energy model (DAEM) and pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS). Results presented that Monoraphidium 3s35 showed superiority for pyrolysis at low heating rate. Calculated by DAEM, during the conversion rate range from 0.1 to 0.7, the activation energies of C. sorokiniana 21 were much lower than that of Monoraphidium 3s35. Both C. sorokiniana 21 and Monoraphidium 3s35 can produce certain amount (up to 20.50%) of alkane compounds, with 9-Octadecyne (C18H34) as the primary compound. Short-chain alkanes (C7-C13) with unsaturated carbon can be released in the pyrolysis at 500°C for both microalgal biomass. It was also observed that the pyrolysis of C. sorokiniana 21 released more alcohol compounds, while Monoraphidium 3s35 produced more saccharides. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reliability Analysis and Optimal Release Problem Considering Maintenance Time of Software Components for an Embedded OSS Porting Phase

NASA Astrophysics Data System (ADS)

Tamura, Yoshinobu; Yamada, Shigeru

OSS (open source software) systems which serve as key components of critical infrastructures in our social life are still ever-expanding now. Especially, embedded OSS systems have been gaining a lot of attention in the embedded system area, i.e., Android, BusyBox, TRON, etc. However, the poor handling of quality problem and customer support prohibit the progress of embedded OSS. Also, it is difficult for developers to assess the reliability and portability of embedded OSS on a single-board computer. In this paper, we propose a method of software reliability assessment based on flexible hazard rates for the embedded OSS. Also, we analyze actual data of software failure-occurrence time-intervals to show numerical examples of software reliability assessment for the embedded OSS. Moreover, we compare the proposed hazard rate model for the embedded OSS with the typical conventional hazard rate models by using the comparison criteria of goodness-of-fit. Furthermore, we discuss the optimal software release problem for the porting-phase based on the total expected software maintenance cost.

Influence of formulation technique on acrylate methacrylate copolymer modified paracetamol matrix tablets.

PubMed

Cash-Torunarigha, Omonyemen Edoise; Eichie, Florence Egbomonjiade; Arhewoh, Matthew Ikhuoria

2015-03-01

This work was designed to evaluate the influence of various methods such as dry granulation (DG), wet granulation (using the polymer in an ethanolic solution (WGO) or aqueous dispersion (WGA) and solid dispersion (SD) techniques, on properties of paracetamol matrix tablets prepared using varying concentrations of acrylate methacrylate copolymer. Tablet properties were investigated using official and unofficial standards. Drug dissolution profile assessed at pH 1.2 was studied spectrophotometrically at λ(max) of 245 nm. With the use of various kinetic models, the release mechanism of the drug was analyzed. The parameters, maximum amount of drug release (m(∞)) at time t(∞) were obtained, m(∞) was ≥ 91.36 %, while t(∞) was ≥ 4.5 h. The release rate constant (k) for DG tablets was 15.61 h(sup>-1(/sup>, while, WGO, WGA and SD tablets were 12.90, 11.03 and 10.75 h(-1) respectively. The matrix tablets, which exhibited marked retardation in drug release displayed a Higuchi square root of time model (R(2) > 0.98). The mechanism through which the drug was released was governed by Fickian diffusion release (n values < 0.5). The performance of the drug was affected by the formulation technique in the order of SD > WGO > WGA > DG.

Structural Evidence for a Sequential Release Mechanism for Activation of Heterotrimeric G Proteins

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

Kapoor, Neeraj; Menon, Santosh T.; Chauhan, Radha

2010-01-12

Heptahelical G-protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors couple to heterotrimeric G proteins to relay extracellular signals to intracellular signaling networks, but the molecular mechanism underlying guanosine 5'-diphosphate (GDP) release by the G protein {alpha}-subunit is not well understood. Amino acid substitutions in the conserved {alpha}5 helix of Gi, which extends from the C-terminal region to the nucleotide-binding pocket, cause dramatic increases in basal (receptor-independent) GDP release rates. For example, mutant G{alpha}{sub i1}-T329A shows an 18-fold increase in basal GDP release rate and, when expressed in culture, it causes a significant decrease in forskolin-stimulated cAMP accumulation. The crystal structure of G{alpha}{submore » i1}-T329A {center_dot} GDP shows substantial conformational rearrangement of the switch I region and additional striking alterations of side chains lining the catalytic pocket that disrupt the Mg{sup +2} coordination sphere and dislodge bound Mg{sup +2}. We propose a 'sequential release' mechanism whereby a transient conformational change in the {alpha}5 helix alters switch I to induce GDP release. Interestingly, this mechanistic model for heterotrimeric G protein activation is similar to that suggested for the activation of the plant small G protein Rop4 by RopGEF8.« less

Influence of eggs on the aroma composition of a sponge cake and on the aroma release in model studies on flavored sponge cakes.

PubMed

Pozo-Bayón, Maria Angeles; Ruíz-Rodríguez, Alejandro; Pernin, Karine; Cayot, Nathalie

2007-02-21

The use of solvent-assisted flavor evaporation extraction (SAFE) and purge and trap in Tenax allowed the identification of more than 100 volatile compounds in a sponge cake (SC-e). Gas chromatography-olfactometry (GC-O) of the SAFE extracts of crumb and crust were achieved in order to determine the most potent odorants of SC-e. The change in the traditional dough formulation of SC-e in which eggs were substituted by baking powder (SC-b) as the leavening agent produced important changes in some key aroma compounds. The release curves of some aroma compounds-some of them generated during baking and others added in the dough-were followed by cumulative headspace analysis. In the flavored SC-b, the aroma release curves showed a plateau after 15 min of purge, while the release increased proportionally with the purge time in the flavored SC-e. In general, except for some of the aroma compounds with the highest log P values, the rate of release of most of the added and generated aroma compounds was significantly influenced by the changes in the cake formulation. The higher rates of release found for the aroma compounds in SC-b could contribute to explain its rapid exhaustion of aroma compounds in the purge and trap experiments and might lead to poorer sensorial characteristics of this cake during storage.

Synthesis and evaluation of chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) as a drug carrier for controlled release of tramadol hydrochloride

PubMed Central

Subramanian, Kaliappa gounder; Vijayakumar, Vediappan

2011-01-01

Chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) has been synthesized for different feed ratios of 2-hydroxyethyl methacrylate and itaconic acid and characterized by FT-IR, thermogravimetry and swelling in simulated biological fluids (SBF) and evaluated as a drug carrier with model drug, tramadol hydrochloride (TRM). Grafting decreased the thermal stability of chitosan. FT-IR spectra of tablet did not reveal any molecular level (i.e. at <10 nm scale) drug–polymer interaction. But differential scanning calorimetric studies indicated a probable drug–polymer interaction at a scale >100 nm level. The observed Korsmeyer–Peppas’s power law exponents (0.19–1.21) for the in vitro release profiles of TRM in SBF and other drugs such as 5-fluorouracil (FU), paracetamol (PCM) and vanlafaxine hydrochloride (VNF) with the copolymer carriers revealed an anomalous drug release mechanism. The decreased release rates for the grafted chitosan and the enhanced release rate for the grafts with increasing itaconic acid content in the feed were more likely attributed to the enhanced drug–matrix interaction and polymer–SBF interactions, respectively. The different release profiles of FU, PCM, TRM and VNF with the copolymer matrix are attributed to the different chemical structures of drugs. The above features suggest the graft copolymer’s candidature for use as a promising oral drug delivery system. PMID:23960799

Bayesian estimation of a source term of radiation release with approximately known nuclide ratios

NASA Astrophysics Data System (ADS)

Tichý, Ondřej; Šmídl, Václav; Hofman, Radek

2016-04-01

We are concerned with estimation of a source term in case of an accidental release from a known location, e.g. a power plant. Usually, the source term of an accidental release of radiation comprises of a mixture of nuclide. The gamma dose rate measurements do not provide a direct information on the source term composition. However, physical properties of respective nuclide (deposition properties, decay half-life) can be used when uncertain information on nuclide ratios is available, e.g. from known reactor inventory. The proposed method is based on linear inverse model where the observation vector y arise as a linear combination y = Mx of a source-receptor-sensitivity (SRS) matrix M and the source term x. The task is to estimate the unknown source term x. The problem is ill-conditioned and further regularization is needed to obtain a reasonable solution. In this contribution, we assume that nuclide ratios of the release is known with some degree of uncertainty. This knowledge is used to form the prior covariance matrix of the source term x. Due to uncertainty in the ratios the diagonal elements of the covariance matrix are considered to be unknown. Positivity of the source term estimate is guaranteed by using multivariate truncated Gaussian distribution. Following Bayesian approach, we estimate all parameters of the model from the data so that y, M, and known ratios are the only inputs of the method. Since the inference of the model is intractable, we follow the Variational Bayes method yielding an iterative algorithm for estimation of all model parameters. Performance of the method is studied on simulated 6 hour power plant release where 3 nuclide are released and 2 nuclide ratios are approximately known. The comparison with method with unknown nuclide ratios will be given to prove the usefulness of the proposed approach. This research is supported by EEA/Norwegian Financial Mechanism under project MSMT-28477/2014 Source-Term Determination of Radionuclide Releases by Inverse Atmospheric Dispersion Modelling (STRADI).

Comprehensive study of the drug delivery properties of poly(l-lactide)-poly(ethylene glycol) nanoparticles in rats and tumor-bearing mice.

PubMed

Shalgunov, Vladimir; Zaytseva-Zotova, Daria; Zintchenko, Arkadi; Levada, Tatiana; Shilov, Yuri; Andreyev, Dmitry; Dzhumashev, Dzhangar; Metelkin, Evgeny; Urusova, Alexandra; Demin, Oleg; McDonnell, Kevin; Troiano, Greg; Zale, Stephen; Safarovа, Elmira

2017-09-10

Nanoparticles made of polylactide-poly(ethylene glycol) block-copolymer (PLA-PEG) are promising vehicles for drug delivery due to their biodegradability and controllable payload release. However, published data on the drug delivery properties of PLA-PEG nanoparticles are heterogeneous in terms of nanoparticle characteristics and mostly refer to low injected doses (a few mg nanoparticles per kg body weight). We have performed a comprehensive study of the biodistribution of nanoparticle formulations based on PLA-PEG nanoparticles of ~100nm size at injected doses of 30 to 140mg/kg body weight in healthy rats and nude tumor-bearing mice. Nanoparticle formulations differed by surface PEG coverage and by release kinetics of the encapsulated model active pharmaceutical ingredient (API). Increase in PEG coverage prolonged nanoparticle circulation half-life up to ~20h in rats and ~10h in mice and decreased retention in liver, spleen and lungs. Circulation half-life of the encapsulated API grew monotonously as the release rate slowed down. Plasma and tissue pharmacokinetics was dose-linear for inactive nanoparticles, but markedly dose-dependent for the model therapeutic formulation, presumably because of the toxic effects of released API. A mathematical model of API distribution calibrated on the data for inactive nanoparticles and conventional API form correctly predicted the distribution of the model therapeutic formulation at the lowest investigated dose, but for higher doses the toxic action of the released API had to be explicitly modelled. Our results provide a coherent illustration of the ability of controllable-release PLA-PEG nanoparticles to serve as an effective drug delivery platform to alter API biodistribution. They also underscore the importance of physiological effects of released drug in determining the biodistribution of therapeutic drug formulations at doses approaching tolerability limits. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Rate-programming of nano-particulate delivery systems for smart bioactive scaffolds in tissue engineering.

PubMed

Izadifar, Mohammad; Haddadi, Azita; Chen, Xiongbiao; Kelly, Michael E

2015-01-09

Development of smart bioactive scaffolds is of importance in tissue engineering, where cell proliferation, differentiation and migration within scaffolds can be regulated by the interactions between cells and scaffold through the use of growth factors (GFs) and extra cellular matrix peptides. One challenge in this area is to spatiotemporally control the dose, sequence and profile of release of GFs so as to regulate cellular fates during tissue regeneration. This challenge would be addressed by rate-programming of nano-particulate delivery systems, where the release of GFs via polymeric nanoparticles is controlled by means of the methods of, such as externally-controlled and physicochemically/architecturally-modulated so as to mimic the profile of physiological GFs. Identifying and understanding such factors as the desired release profiles, mechanisms of release, physicochemical characteristics of polymeric nanoparticles, and externally-triggering stimuli are essential for designing and optimizing such delivery systems. This review surveys the recent studies on the desired release profiles of GFs in various tissue engineering applications, elucidates the major release mechanisms and critical factors affecting release profiles, and overviews the role played by the mathematical models for optimizing nano-particulate delivery systems. Potentials of stimuli responsive nanoparticles for spatiotemporal control of GF release are also presented, along with the recent advances in strategies for spatiotemporal control of GF delivery within tissue engineered scaffolds. The recommendation for the future studies to overcome challenges for developing sophisticated particulate delivery systems in tissue engineering is discussed prior to the presentation of conclusions drawn from this paper.

Kinetics of scheelite dissolution in groundwater: defining the release rate of tungsten contamination from a natural source

NASA Astrophysics Data System (ADS)

Montgomery, S. D.; Mckibben, M. A.

2011-12-01

Tungsten, an emerging contaminant, has no EPA standard for its permissible levels in drinking water. At sites in California, Nevada, and Arizona there may be a correlation between elevated levels of tungsten in drinking water and clusters of childhood acute lymphocytic leukemia (ALL). Developing a better understanding of how tungsten is released from rocks into surface and groundwaters is therefore of growing environmental interest. Knowledge of tungstate ore mineral weathering processes, particularly the rates of dissolution of scheelite (CaWO4) in groundwater, could improve models of how tungsten is released and transported in natural waters. Our research is focusing on experimental determination of the rates and products of tungstate mineral dissolution in synthetic groundwater, as a function of temperature, pH and mineral surface area. The initial rate method is being used to develop rate laws. Batch reactor experiments are conducted within constant temperature circulation baths over a pH range of 2-9. Cleaned scheelite powder with grain diameters of 106-150um is placed between two screens in a sample platform and then placed inside a two liter Teflon vessel filled with synthetic groundwater. Ports on the vessel allow sample extraction, temperature and pH measurement, gas inflow, and water circulation. Aliquots of solution are taken periodically for product analysis by ICP -MS. Changes in mineral surface characteristics are monitored using SEM and EDS methods. Results so far reveal that the dissolution of scheelite is incongruent at both neutral and low pH. Solid tungstic acid forms on scheelite mineral surfaces under acidic conditions, implying that this phase controls the dissolution rate in acidic environments. The influence of dissolved CO2 and resultant calcium carbonate precipitation on the dissolution of scheelite at higher pH is also being investigated. The rate law being developed for scheelite dissolution will be useful in reactive-transport computer codes designed to model tungsten contamination in a variety of surface and groundwater settings.

Strain Rate Dependency of Fracture Toughness, Energy Release Rate and Geomechanical Attributes of Select Indian Shales

NASA Astrophysics Data System (ADS)

Mahanta, B.; Vishal, V.; Singh, T. N.; Ranjith, P.

2016-12-01

In addition to modern improved technology, it requires detailed understanding of rock fractures for the purpose of enhanced energy extraction through hydraulic fracturing of gas shales and geothermal energy systems. The understanding of rock fracture behavior, patterns and properties such as fracture toughness; energy release rate; strength and deformation attributes during fracturing hold significance. Environmental factors like temperature, pressure, humidity, water vapor and experimental condition such as strain rate influence the estimation of these properties. In this study, the effects of strain rates on fracture toughness, energy release rate as well as geomechanical properties like uniaxial compressive strength, Young's modulus, failure strain, tensile strength, and brittleness index of gas shales were investigated. In addition to the rock-mechanical parameters, the fracture toughness and the energy release rates were measured for three different modes viz. mode I, mixed mode (I-II) and mode II. Petrographic and X-ray diffraction (XRD) analyses were performed to identify the mineral composition of the shale samples. Scanning electron microscope (SEM) analyses were conducted to have an insight about the strain rate effects on micro-structure of the rock. The results suggest that the fracture toughness; the energy release rate as well as other geomechanical properties are a function of strain rates. At high strain rates, the strength and stiffness of shale increases which in turn increases the fracture toughness and the energy release rate of shale that may be due to stress redistribution during grain fracturing. The fracture toughness and the strain energy release rates for all the modes (I/I-II/II) are comparable at lower strain rates, but they vary considerably at higher strain rates. In all the cases, mode I and mode II fracturing requires minimum and maximum applied energy, respectively. Mode I energy release rate is maximum, compared to the other modes.

Temperature Treatment of Highly Porous Zirconium-Containing Metal-Organic Frameworks Extends Drug Delivery Release.

PubMed

Teplensky, Michelle H; Fantham, Marcus; Li, Peng; Wang, Timothy C; Mehta, Joshua P; Young, Laurence J; Moghadam, Peyman Z; Hupp, Joseph T; Farha, Omar K; Kaminski, Clemens F; Fairen-Jimenez, David

2017-06-07

Utilizing metal-organic frameworks (MOFs) as a biological carrier can lower the amount of the active pharmaceutical ingredient (API) required in cancer treatments to provide a more efficacious therapy. In this work, we have developed a temperature treatment process for delaying the release of a model drug compound from the pores of NU-1000 and NU-901, while taking care to utilize these MOFs' large pore volume and size to achieve exceptional model drug loading percentages over 35 wt %. Video-rate super-resolution microscopy reveals movement of MOF particles when located outside of the cell boundary, and their subsequent immobilization when taken up by the cell. Through the use of optical sectioning structured illumination microscopy (SIM), we have captured high-resolution 3D images showing MOF uptake by HeLa cells over a 24 h period. We found that addition of a model drug compound into the MOF and the subsequent temperature treatment process does not affect the rate of MOF uptake by the cell. Endocytosis analysis revealed that MOFs are internalized by active transport and that inhibiting the caveolae-mediated pathway significantly reduced cellular uptake of MOFs. Encapsulation of an anticancer therapeutic, alpha-cyano-4-hydroxycinnamic acid (α-CHC), and subsequent temperature treatment produced loadings of up to 81 wt % and demonstrated efficacy at killing cells beyond the burst release effect.

Factors affecting settling, survival, and viability of black bears reintroduced to Felsenthal National Wildlife Refuge, Arkansas

USGS Publications Warehouse

Wear, B.J.; Eastridge, R.; Clark, J.D.

2005-01-01

We used radiotelemetry and population modeling techniques to examine factors related to population establishment of black bears (Ursus americanus) reintroduced to Felsenthal National Wildlife Refuge (NWR), Arkansas. Our objectives were to determine whether settling (i.e., establishment of a home range at or near the release site), survival, recruitment, and population viability were related to age class of reintroduced bears, presence of cubs, time since release, or number of translocated animals. We removed 23 adult female black bears with 56 cubs from their winter dens at White River NWR and transported them 160 km to man-made den structures at Felsenthal NWR during spring 2000–2002. Total movement and average circuity of adult females decreased from 1 month, 6 months, and 1 year post-emergence (F2,14 =19.7, P < 0.001 and F2,14 =5.76, P=0.015, respectively). Mean first-year post-release survival of adult female bears was 0.624 (SE = 0.110, SEinterannual = 0.144), and the survival rate of their cubs was 0.750 (SE = 0.088, SEinterannual = 0.109). The homing rate (i.e., the proportion of bears that returned to White River NWR) was 13%. Annual survival for female bears that remained at the release site and survived >1-year post-release increased to 0.909 (SE = 0.097, SEinterannual=0.067; Z=3.5, P < 0.001). Based on stochastic population growth simulations, the average annual growth rate (λ) was 1.093 (SD = 0.053) and the probability of extinction with no additional stockings ranged from 0.56-1.30%. The bear population at Felsenthal NWR is at or above the number after which extinction risk declines dramatically, although additional releases of bears could significantly decrease time to population reestablishment. Poaching accounted for at least 3 of the 8 adult mortalities that we documented; illegal kills could be a significant impediment to population re-establishment at Felsenthal NWR should poaching rates escalate.

Transit losses and traveltimes of reservoir releases along the Arkansas River from Pueblo Reservoir to John Martin Reservoir, southeastern Colorado

USGS Publications Warehouse

Livingston, Russell K.

1978-01-01

The need for accurate information regarding the transit losses and traveltimes associated with releases from Pueblo Reservoir has been stimulated by construction of the U.S. Bureau of Reclamation's Fryingpan-Arkansas Project and a proposed winter-water storage program in Pueblo Reservoir. To meet this need, the U.S. Geological Survey, in cooperation with the Southeastern Colorado Water Conservancy District, studied the Arkansas River from Pueblo Reservoir to John Martin Reservoir, a distance of 142 river miles.The volumes of reservoir releases are decreased or delayed during tran-sit by bank storage, channel storage, and evaporation. Results from a com-puter model, calibrated by a controlled-test release from Pueblo Reservoir, indicate transit losses are greatest for small releases of short duration that are made during periods of low antecedent streamflow. For equivalent releases, transit losses during the winter are about 7 percent less than losses during the summer.Based on available streamflow records, the traveltime of reservoir releases in the study reach ranges from about 1.67 hours per mile at the downstream end of the study reach when antecedent streamflow is 10 cubic feet per second, to about 0.146 hour per mile at the upstream end of the study reach when antecedent streamflow is 3,000 cubic feet per second. Consequently, the traveltime of a release increases as antecedent streamflow diminishes.Management practices that may be used to benefit water users in the study area include selection of the optimum time, rate, and duration of a reservoir release to minimize the transit losses, determination of an accurate traveltime, and diversion at several incremental rates.

Roles of survival and dispersal in reintroduction success of Griffon vulture (Gyps fulvus).

PubMed

Le Gouar, Pascaline; Robert, Alexandre; Choisy, Jean-Pierre; Henriquet, Sylvain; Lecuyer, Philippe; Tessier, Christian; Sarrazin, François

2008-06-01

The success of reintroduction programs greatly depends on the amount of mortality and dispersal of the released individuals. Although local environmental pressures are likely to play an important role in these processes, they have rarely been investigated because of the lack of spatial replicates of reintroduction. In the present study, we analyzed a 25-year data set encompassing 272 individuals released in five reintroduction programs of Griffon Vultures (Gyps fulvus) in France to examine the respective roles of survival and dispersal in program successes and failures. We use recent developments in multi-strata capture-recapture models to take into account tag loss in survival estimates and to consider and estimate dispersal among release areas. We also examined the effects of sex, age, time, area, and release status on survival, and we tested whether dispersal patterns among release areas were consistent with habitat selection theories. Results indicated that the survival of released adults was reduced during the first year after release, with no difference between sexes. Taking into account local observations only, we found that early survival rates varied across sites. However when we distinguished dispersal from mortality, early survival rates became equal across release sites. It thus appears that among reintroduction programs difference in failure and success was due to differential dispersal among release sites. We revealed asymmetrical patterns of dispersal due to conspecific attraction: dispersers selected the closest and the largest population. We showed that mortality can be homogeneous from one program to another while, on the contrary, dispersal is highly dependent on the matrix of established populations. Dispersal behavior is thus of major interest for metapopulation restoration and should be taken into account in planning reintroduction designs.

Release from or through a wax matrix system. I. Basic release properties of the wax matrix system.

PubMed

Yonezawa, Y; Ishida, S; Sunada, H

2001-11-01

Release properties from a wax matrix tablet was examined. To obtain basic release properties, the wax matrix tablet was prepared from a physical mixture of drug and wax powder (hydrogenated caster oil) at a fixed mixing ratio. Properties of release from the single flat-faced surface or curved side surface of the wax matrix tablet were examined. The applicability of the square-root time law and of Higuchi equations was confirmed. The release rate constant obtained as g/min(1/2) changed with the release direction. However, the release rate constant obtained as g/cm2 x min(1/2) was almost the same. Hence it was suggested that the release property was almost the same and the wax matrix structure was uniform independent of release surface or direction at a fixed mixing ratio. However, these equations could not explain the entire release process. The applicability of a semilogarithmic equation was not as good compared with the square-root time law or Higuchi equation. However, it was revealed that the semilogarithmic equation was available to simulate the entire release process, even though the fit was somewhat poor. Hence it was suggested that the semilogarithmic equation was sufficient to describe the release process. The release rate constant was varied with release direction. However, these release rate constants were expressed by a function of the effective surface area and initial amount, independent of the release direction.

Release and diffusional modeling of metronidazole lipid matrices.

PubMed

Ozyazici, Mine; Gökçe, Evren H; Ertan, Gökhan

2006-07-01

In this study, the first aim was to investigate the swelling and relaxation properties of lipid matrix on diffusional exponent (n). The second aim was to determine the desired release profile of metronidazole lipid matrix tablets. We prepared metronidazole lipid matrix granules using Carnauba wax, Beeswax, Stearic acid, Cutina HR, Precirol ATO 5, and Compritol ATO 888 by hot fusion method and pressed the tablets of these granules. In vitro release test was performed using a standard USP dissolution apparatus I (basket method) with a stirring rate of 100 rpm at 37 degrees C in 900 ml of 0.1 N hydrochloric acid, adjusted to pH 1.2, as medium for the formulations' screening. Hardness, diameter-height ratio, friability, and swelling ratio were determined. Target release profile of metronidazole was also drawn. Stearic acid showed the highest and Carnauba wax showed the lowest release rates in all formulations used. Swelling ratios were calculated after the dissolution of tablets as 9.24%, 6.03%, 1.74%, and 1.07% for Cutina HR, Beeswax, Precirol ATO 5, and Compritol ATO 888, respectively. There was erosion in Stearic acid, but neither erosion nor swelling in Carnauba wax, was detected. According to the power law analysis, the diffusion mechanism was expressed as pure Fickian for Stearic acid and Carnauba wax and the coupling of Fickian and relaxation contributions for other Cutina HR, Beeswax, Compritol ATO 888, and Precirol ATO 5 tablets. It was found that Beeswax (kd=2.13) has a very close drug release rate with the target profile (kt=1.95). Our results suggested that swelling and relaxation properties of lipid matrices should be examined together for a correct evaluation on drug diffusion mechanism of insoluble matrices.

Reconviction and revocation rates in Flanders after medium security treatment.

PubMed

Jeandarme, Inge; Habets, Petra; Oei, T I; Bogaerts, Stefan

2016-01-01

To examine the criminal outcome of Flemish forensic psychiatric patients ('internees') after medium security treatment. Also, the effect of conditional release on recidivism of two subgroups (internees under conditional release and internees who received unconditional release) was examined. Reconviction rates and revocation rates were collected for all participants. Kaplan-Meier survival analyses were used to investigate recidivism rates while controlling for time at risk. During the 10-year period, 502 offenders were discharged from medium security treatment. Over a follow-up period averaging 3.6years, 7.4% of discharged patients were reconvicted or received a new 'not guilty by reason of insanity' (NGRI) verdict for a violent offence. One-quarter of the population had their conditional release revoked. Part of the study population was granted unconditional release. Reconviction rates were higher after unconditional release in comparison to conditional release. The results of this study suggest that the court supervision of NGRI patients in Flanders is effective in protecting the community from further offending. Copyright © 2016 Elsevier Ltd. All rights reserved.

Engineering multi-stage nanovectors for controlled degradation and tunable release kinetics

PubMed Central

Martinez, Jonathan O.; Chiappini, Ciro; Ziemys, Arturas; Faust, Ari M.; Kojic, Milos; Liu, Xuewu; Ferrari, Mauro; Tasciotti, Ennio

2013-01-01

Nanovectors hold substantial promise in abating the off-target effects of therapeutics by providing a means to selectively accumulate payloads at the target lesion, resulting in an increase in the therapeutic index. A sophisticated understanding of the factors that govern the degradation and release dynamics of these nanovectors is imperative to achieve these ambitious goals. In this work, we elucidate the relationship that exists between variations in pore size and the impact on the degradation, loading, and release of multistage nanovectors. Larger pored vectors displayed faster degradation and higher loading of nanoparticles, while exhibiting the slowest release rate. The degradation of these particles was characterized to occur in a multi-step progression where they initially decreased in size leaving the porous core isolated, while the pores gradually increased in size. Empirical loading and release studies of nanoparticles along with diffusion modeling revealed that this prolonged release was modulated by the penetration within the porous core of the vectors regulated by their pore size. PMID:23911070

Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

PubMed

Shenderovich, Julia; Feldman, Mark; Kirmayer, David; Al-Quntar, Abed; Steinberg, Doron; Lavy, Eran; Friedman, Michael

2015-05-15

Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections. Copyright © 2015 Elsevier B.V. All rights reserved.

A shallow subsurface controlled release facility in Bozeman, Montana, USA, for testing near surface CO2 detection techniques and transport models

USGS Publications Warehouse

Spangler, L.H.; Dobeck, L.M.; Repasky, K.S.; Nehrir, A.R.; Humphries, S.D.; Keith, C.J.; Shaw, J.A.; Rouse, J.H.; Cunningham, A.B.; Benson, S.M.; Oldenburg, C.M.; Lewicki, J.L.; Wells, A.W.; Diehl, J.R.; Strazisar, B.R.; Fessenden, J.E.; Rahn, T.A.; Amonette, J.E.; Barr, J.L.; Pickles, W.L.; Jacobson, J.D.; Silver, E.A.; Male, E.J.; Rauch, H.W.; Gullickson, K.S.; Trautz, R.; Kharaka, Y.; Birkholzer, J.; Wielopolski, L.

2010-01-01

A controlled field pilot has been developed in Bozeman, Montana, USA, to study near surface CO2 transport and detection technologies. A slotted horizontal well divided into six zones was installed in the shallow subsurface. The scale and CO2 release rates were chosen to be relevant to developing monitoring strategies for geological carbon storage. The field site was characterized before injection, and CO2 transport and concentrations in saturated soil and the vadose zone were modeled. Controlled releases of CO2 from the horizontal well were performed in the summers of 2007 and 2008, and collaborators from six national labs, three universities, and the U.S. Geological Survey investigated movement of CO2 through the soil, water, plants, and air with a wide range of near surface detection techniques. An overview of these results will be presented. ?? 2009 The Author(s).

The Numerical Simulation of a Tracer-Release Field Project to Study Motion within the Nocturnal Boundary Layer

NASA Astrophysics Data System (ADS)

Werth, D. W.; Leclerc, M. Y.; Buckley, R.; Parker, M.; Kurzeja, R.; Duarte, H. F.; Zhang, G.; Durden, D.

2009-12-01

The Savannah River National Laboratory (SRNL), Brookhaven National Laboratory (BNL), the University of Georgia (UGA), and the National Oceanic and Atmospheric Administration (NOAA) conducted a regional tracer experiment to study the nocturnal behavior of CO2 in the vicinity of an instrumented tall tower during two nights on May 11th and 12th, 2009. The experiment consisted of a release of five perfluorocarbon tracer (PFTs) compounds in twelve unique locations in Aiken County, South Carolina. Intensive meteorological measurements including in-situ turbulence were made in conjunction with the release and sampling of the PFTs. A 300m tower was also used to collect data from higher levels, allowing us to determine the extent to which the tracer was mixed vertically. Lagrangian plume simulations performed during the experiment demonstrated transport over distances of >8 km, and correlated well with in situ sampling. The area was characterized by heavy vegetation cover, and carbon dioxide concentrations were also monitored in an effort to determine how respiration and advection affect CO2 levels in the stable layer. Tracer release locations were carefully selected via a fine-scale mesoscale modeling study of similar nights. The purpose of these experiments was to provide data that will be used to increase the understanding of the terrestrial carbon budget, especially with respect to nocturnal boundary layer (NBL) phenomena such as low level jets and breaking gravity waves. Using these data, a simulation of the motion of the tracer within the boundary layer was developed using the Regional Atmospheric Modeling System (RAMS) mesoscale model coupled to a tracer model. The RAMS model was also coupled to the Simple Biosphere (SiB) vegetation model, which allowed for the simulation of the release of carbon dioxide into the NBL. The simulation results are used to validate the NBL hypothesis of CO2 monitoring, by which the release of CO2 can be correlated with the accumulation of CO2 in the boundary layer beneath a stable ‘lid’, which impedes vertical mixing. This is done with both the tracer, in which the release rate is known and no advection occurs, and for CO2, in which the release rate is not known and for which advection of CO2 must be accounted. The high resolution of the simulation allows us to resolve the small-scale motions within the NBL, which are important to nocturnal transport. Flux data from the tall tower were studied to learn more about the eddy transport, and also to detect the occurrence of transport ‘events’ in which the CO2 and H2O values experience a sudden increase. A wavelet analysis is also applied, and reveals the existence of eddy activity dominated by eddies of diameter 90-240m.

Development of extended release dosage forms using non-uniform drug distribution techniques.

PubMed

Huang, Kuo-Kuang; Wang, Da-Peng; Meng, Chung-Ling

2002-05-01

Development of an extended release oral dosage form for nifedipine using the non-uniform drug distribution matrix method was conducted. The process conducted in a fluid bed processing unit was optimized by controlling the concentration gradient of nifedipine in the coating solution and the spray rate applied to the non-pareil beads. The concentration of nifedipine in the coating was controlled by instantaneous dilutions of coating solution with polymer dispersion transported from another reservoir into the coating solution at a controlled rate. The USP dissolution method equipped with paddles at 100 rpm in 0.1 N hydrochloric acid solution maintained at 37 degrees C was used for the evaluation of release rate characteristics. Results indicated that (1) an increase in the ethyl cellulose content in the coated beads decreased the nifedipine release rate, (2) incorporation of water-soluble sucrose into the formulation increased the release rate of nifedipine, and (3) adjustment of the spray coating solution and the transport rate of polymer dispersion could achieve a dosage form with a zero-order release rate. Since zero-order release rate and constant plasma concentration were achieved in this study using the non-uniform drug distribution technique, further studies to determine in vivo/in vitro correlation with various non-uniform drug distribution dosage forms will be conducted.

Analysis of dam-passage survival of yearling and subyearling Chinook salmon and juvenile steelhead at The Dalles Dam, Oregon, 2010

USGS Publications Warehouse

Beeman, John W.; Kock, Tobias J.; Perry, Russell W.; Smith, Steven G.

2011-01-01

We performed a series of analyses of mark-recapture data from a study at The Dalles Dam during 2010 to determine if model assumptions for estimation of juvenile salmonid dam-passage survival were met and if results were similar to those using the University of Washington's newly developed ATLAS software. The study was conducted by the Pacific Northwest National Laboratory and used acoustic telemetry of yearling Chinook salmon, juvenile steelhead, and subyearling Chinook salmon released at three sites according to the new virtual/paired-release statistical model. This was the first field application of the new model, and the results were used to measure compliance with minimum survival standards set forth in a recent Biological Opinion. Our analyses indicated that most model assumptions were met. The fish groups mixed in time and space, and no euthanized tagged fish were detected. Estimates of reach-specific survival were similar in fish tagged by each of the six taggers during the spring, but not in the summer. Tagger effort was unevenly allocated temporally during tagging of subyearling Chinook salmon in the summer; the difference in survival estimates among taggers was more likely a result of a temporal trend in actual survival than of tagger effects. The reach-specific survival of fish released at the three sites was not equal in the reaches they had in common for juvenile steelhead or subyearling Chinook salmon, violating one model assumption. This violation did not affect the estimate of dam-passage survival, because data from the common reaches were not used in its calculation. Contrary to expectation, precision of survival estimates was not improved by using the most parsimonious model of recapture probabilities instead of the fully parameterized model. Adjusting survival estimates for differences in fish travel times and tag lives increased the dam-passage survival estimate for yearling Chinook salmon by 0.0001 and for juvenile steelhead by 0.0004. The estimate was unchanged for subyearling Chinook salmon. The tag-life-adjusted dam-passage survival estimates from our analyses were 0.9641 (standard error [SE] 0.0096) for yearling Chinook salmon, 0.9534 (SE 0.0097) for juvenile steelhead, and 0.9404 (SE 0.0091) for subyearling Chinook salmon. These were within 0.0001 of estimates made by the University of Washington using the ATLAS software. Contrary to the intent of the virtual/paired-release model to adjust estimates of the paired-release model downward in order to account for differential handling mortality rates between release groups, random variation in survival estimates may result in an upward adjustment of survival relative to estimates from the paired-release model. Further investigation of this property of the virtual/paired-release model likely would prove beneficial. In addition, we suggest that differential selective pressures near release sites of the two control groups could bias estimates of dam-passage survival from the virtual/paired-release model.

Interaction between fed gastric media (Ensure Plus®) and different hypromellose based caffeine controlled release tablets: comparison and mechanistic study of caffeine release in fed and fasted media versus water using the USP dissolution apparatus 3.

PubMed

Franek, Frans; Holm, Per; Larsen, Frank; Steffansen, Bente

2014-01-30

The aim of the study was to investigate caffeine release in fed and fasted state media from three controlled release matrix tablets containing different HPMC viscosity grades. The biorelevant in vitro dissolution methods utilize the USP 3 dissolution apparatus and biorelevant media to simulate fed and fasted gastro-intestinal dissolution conditions. The effect of tablet reciprocation rate (dip speed) in dissolution media (10 and 15 dips per minute) and media (water, fed and fasted) on caffeine release rate from - and erosion rate of - 100, 4000 and 15,000 mPa s HPMC viscosity tablets was investigated using factorial designed experiments. Furthermore, the mechanism of release in Ensure Plus(®), a nutrition drink similar in composition to the FDA standard meal, was investigated by studying tablet swelling using texture analysis. Altering dip speed has negligible effect on release and erosion rates. Using fasted media instead of water slightly decreases caffeine release from 100 and 4000 mPa s HPMC viscosity tablets as well as erosion rates, while 15,000 mPa s tablets remain unaffected. Fed compared to fasted media decreases caffeine release rate, and the food effect is greater for the 100 mPa s viscosity tablets compared to the 4000 and 15,000 mPa s viscosity tablets. The investigation using texture analysis indicates that Ensure Plus(®) becomes rate-limiting for caffeine release from HPMC tablets by forming a hydrophobic barrier around the tablets. The barrier decreases tablet water permeation, which decreases erosion rate in 100 mPa s viscosity tablets, swelling in 15,000 mPa s viscosity tablets and caffeine release from both tablets. This observed interaction between Ensure Plus(®) and the HPMC tablets may translate into decreased drug release rate in the fed stomach, which may decrease the amount of drug available for absorption in the small intestine and thus reduce systemic drug exposure and maximum plasma concentration. Copyright © 2013 Elsevier B.V. All rights reserved.

Maximum earthquake magnitudes in the Aegean area constrained by tectonic moment release rates

NASA Astrophysics Data System (ADS)

Ch. Koravos, G.; Main, I. G.; Tsapanos, T. M.; Musson, R. M. W.

2003-01-01

Seismic moment release is usually dominated by the largest but rarest events, making the estimation of seismic hazard inherently uncertain. This uncertainty can be reduced by combining long-term tectonic deformation rates with short-term recurrence rates. Here we adopt this strategy to estimate recurrence rates and maximum magnitudes for tectonic zones in the Aegean area. We first form a merged catalogue for historical and instrumentally recorded earthquakes in the Aegean, based on a recently published catalogue for Greece and surrounding areas covering the time period 550BC-2000AD, at varying degrees of completeness. The historical data are recalibrated to allow for changes in damping in seismic instruments around 1911. We divide the area up into zones that correspond to recent determinations of deformation rate from satellite data. In all zones we find that the Gutenberg-Richter (GR) law holds at low magnitudes. We use Akaike's information criterion to determine the best-fitting distribution at high magnitudes, and classify the resulting frequency-magnitude distributions of the zones as critical (GR law), subcritical (gamma density distribution) or supercritical (`characteristic' earthquake model) where appropriate. We determine the ratio η of seismic to tectonic moment release rate. Low values of η (<0.5) corresponding to relatively aseismic deformation, are associated with higher b values (>1.0). The seismic and tectonic moment release rates are then combined to constrain recurrence rates and maximum credible magnitudes (in the range 6.7-7.6 mW where the results are well constrained) based on extrapolating the short-term seismic data. With current earthquake data, many of the tectonic zones show a characteristic distribution that leads to an elevated probability of magnitudes around 7, but a reduced probability of larger magnitudes above this value when compared with the GR trend. A modification of the generalized gamma distribution is suggested to account for this, based on a finite statistical second moment for the seismic moment distribution.

Effect of blood flow on near-the-wall mass transport of drugs and other bioactive agents: a simple formula to estimate boundary layer concentrations.

PubMed

Rugonyi, Sandra

2008-04-01

Transport of bioactive agents through the blood is essential for cardiovascular regulatory processes and drug delivery. Bioactive agents and other solutes infused into the blood through the wall of a blood vessel or released into the blood from an area in the vessel wall spread downstream of the infusion/release region and form a thin boundary layer in which solute concentration is higher than in the rest of the blood. Bioactive agents distributed along the vessel wall affect endothelial cells and regulate biological processes, such as thrombus formation, atherogenesis, and vascular remodeling. To calculate the concentration of solutes in the boundary layer, researchers have generally used numerical simulations. However, to investigate the effect of blood flow, infusion rate, and vessel geometry on the concentration of different solutes, many simulations are needed, leading to a time-consuming effort. In this paper, a relatively simple formula to quantify concentrations in a tube downstream of an infusion/release region is presented. Given known blood-flow rates, tube radius, solute diffusivity, and the length of the infusion region, this formula can be used to quickly estimate solute concentrations when infusion rates are known or to estimate infusion rates when solute concentrations at a point downstream of the infusion region are known. The developed formula is based on boundary layer theory and physical principles. The formula is an approximate solution of the advection-diffusion equations in the boundary layer region when solute concentration is small (dilute solution), infusion rate is modeled as a mass flux, and there is no transport of solute through the wall or chemical reactions downstream of the infusion region. Wall concentrations calculated using the formula developed in this paper were compared to the results from finite element models. Agreement between the results was within 10%. The developed formula could be used in experimental procedures to evaluate drug efficacy, in the design of drug-eluting stents, and to calculate rates of release of bioactive substances at active surfaces using downstream concentration measurements. In addition to being simple and fast to use, the formula gives accurate quantifications of concentrations and infusion rates under steady-state and oscillatory flow conditions, and therefore can be used to estimate boundary layer concentrations under physiological conditions.

Preparation and in vitro evaluation of a new fentanyl patch based on acrylic/silicone pressure-sensitive adhesive blends.

PubMed

Taghizadeh, Seyed Mojtaba; Soroushnia, Arezou; Mirzadeh, Hamid; Barikani, Mehdi

2009-04-01

In this study, the influence of the ratio of silicone (Si) to acrylic pressure-sensitive adhesive (PSA), polyvinyl pyrrolidone (PVP), and lauryl alcohol (LA) % (wt/wt) on the properties of a drug in adhesive patch containing 4% (wt/wt) fentanyl as model drug was evaluated. The dependent variables selected were drug solubility, in vitro drug release in the platforms as well as adhesion properties including peel strength and tack value. By using the central composite design of Design Expert software, it was found that the effect of each factor was different, yet all had influenced dependent variables significantly (p < .05). Quadratic model generated for various response variables using backward regression analysis was found to be statistically significant (p < .05). It was deduced that the presence of PVP and Si displayed similar trends on drug solubility and release. Each role played by Si with LA and PVP in release rate was separately investigated, and it was found that the presence of PVP and LA in lowering the amount of drug released was more dominant compared with that of Si. The release patterns at the early and later stages follow the Higuchi and semiempirical models, respectively. Effect of PVP as well as Si and LA were similar on tack value. The influence of LA compared to peeling characteristics of Si system was more pronounced.

Residual thermal and moisture influences on the strain energy release rate analysis of edge delamination

NASA Technical Reports Server (NTRS)

Obrien, T. K.; Raju, I. S.; Garber, D. P.

1985-01-01

A laminated plate theory analysis is developed to calculate the strain energy release rate associated with edge delamination growth in a composite laminate. The analysis includes the contribution of residual thermal and moisture stresses to the strain energy released. The strain energy release rate, G, increased when residual thermal effects were combined with applied mechanical strains, but then decreased when increasing moisture content was included. A quasi-three-dimensional finite element analysis indicated identical trends and demonstrated these same trends for the individual strain energy release rate components, G sub I and G sub II, associated with interlaminar tension and shear. An experimental study indicated that for T300/5208 graphite-epoxy composites, the inclusion of residual thermal and moisture stresses did not significantly alter the calculation of interlaminar fracture toughness from strain energy release rate analysis of edge delamination data taken at room temperature, ambient conditions.

Quantification of Energy Release in Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon

2003-01-01

Energy release rate is usually suggested as a quantifier for assessing structural damage tolerance. Computational prediction of energy release rate is based on composite mechanics with micro-stress level damage assessment, finite element structural analysis and damage progression tracking modules. This report examines several issues associated with energy release rates in composite structures as follows: Chapter I demonstrates computational simulation of an adhesively bonded composite joint and validates the computed energy release rates by comparison with acoustic emission signals in the overall sense. Chapter II investigates the effect of crack plane orientation with respect to fiber direction on the energy release rates. Chapter III quantifies the effects of contiguous constraint plies on the residual stiffness of a 90 ply subjected to transverse tensile fractures. Chapter IV compares ICAN and ICAN/JAVA solutions of composites. Chapter V examines the effects of composite structural geometry and boundary conditions on damage progression characteristics.

Quantification of Energy Release in Composite Structures

NASA Technical Reports Server (NTRS)

Minnetyan, Levon; Chamis, Christos C. (Technical Monitor)

2003-01-01

Energy release rate is usually suggested as a quantifier for assessing structural damage tolerance. Computational prediction of energy release rate is based on composite mechanics with micro-stress level damage assessment, finite element structural analysis and damage progression tracking modules. This report examines several issues associated with energy release rates in composite structures as follows: Chapter I demonstrates computational simulation of an adhesively bonded composite joint and validates the computed energy release rates by comparison with acoustic emission signals in the overall sense. Chapter II investigates the effect of crack plane orientation with respect to fiber direction on the energy release rates. Chapter III quantifies the effects of contiguous constraint plies on the residual stiffness of a 90 deg ply subjected to transverse tensile fractures. Chapter IV compares ICAN and ICAN/JAVA solutions of composites. Chapter V examines the effects of composite structural geometry and boundary conditions on damage progression characteristics.

Release behavior and kinetic evaluation of berberine hydrochloride from ethyl cellulose/chitosan microspheres

NASA Astrophysics Data System (ADS)

Zhou, Hui-Yun; Cao, Pei-Pei; Zhao, Jie; Wang, Zhi-Ying; Li, Jun-Bo; Zhang, Fa-Liang

2014-12-01

Novel ethyl cellulose/chitosan microspheres (ECCMs) were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 μm. The drug loading efficiency of berberine hydrochloride (BH) loaded in microspheres were affected by chitosan (CS) concentration, EC concentration and the volume ratio of V(CS)/ V(EC). ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid (dHCl) and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCl and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.

Distribution, origin and implications of seismic stress release in shallow and intermediate-depth subduction systems

NASA Astrophysics Data System (ADS)

Chen, Po-Fei

A characterization of focal mechanisms is developed for shallow and intermediate-depth earthquakes in the context of the local geometry of subduction systems. Its application to the Ryukyu-Taiwan-Luzon system is used to refine the spatial distribution of characteristic groups of earthquakes in the framework of local tectonic processes, such as flipping of the polarity of subduction and the nascent processes of arc-continent collision. The Harvard catalogue of Centroid Moment Tensor solutions is expanded to include intermediate-depth earthquakes from the WWSSN-HGLP era (1962--1975). Seventy-six new solutions are obtained, with the resulting dataset estimated to be complete for M0 ≥ 1026 dyn-cm. While source mechanisms from our new dataset are generally similar to those previously compiled in the Harvard catalogue, seismic moment release rates are found to be significantly smaller for the WWSSN era. The intermediate-depth seismicity of South America is compiled from the Harvard catalogue, using projection along local slab coordinates, to determine along-strike variations in the distribution of earthquakes and in the geometry of their stress release. Slab geometry is investigated in relation to slab stresses and the presence or absence of arc volcanism. Steeper-dipping slabs are found to exhibit consistent down-dip extension, a higher rate of seismic moment release and surface volcanism. Visualization using slab coordinate projections is extended systematically to a global survey of the geometry of stress release in intermediate-depth earthquakes. Various proposed models for all subduction zones are appraised, as contributors to stress regimes, based on global data compilations. Down-dip stresses, where prominent, are found to be consistent with the thermo-mechanical and petrological force models. Slab-normal conjugate stresses generally support the concept of earthquake reactivation of fossil faults. Patterns of lateral stresses support the predictions of the so-called "punctured-ping-pong-ball" model.

Monitoring and Predicting the Long Distance Transport of Fusarium graminearum, Causal Agent of Fusarium Head Blight in Wheat and Barley

NASA Astrophysics Data System (ADS)

Prussin, Aaron Justin, II

Fusarium head blight (FHB), caused by Fusarium graminearum , is a serious disease of wheat and barley that has caused several billion dollars in crop losses over the last decade in the United States. Spores of F. graminearum are released from corn and small grain residues left-over from the previous growing season and are transported long distances in the atmosphere before being deposited. Current risk assessment tools consider environmental conditions favorable for disease development, but do not include spore transport. Long distance transport models have been proposed for a number of plant pathogens, but many of these models have not been experimentally validated. In order to predict the atmospheric transport of F. graminearum, the potential source strength ( Qpot) of inoculum must be known. We conducted a series of laboratory and field experiments to estimate Qpot from a field-scale source of inoculum of F. graminearum. Perithecia were generated on artificial (carrot agar) and natural (corn stalk) substrates. Artificial substrate (carrot agar) produced 15+/-0.4 perithecia cm-2, and natural substrate (corn stalk) produced 44+/-2 perithecia cm-2. Individual perithecia were excised from both substrate types and allowed to release ascospores every 24 hours. Perithecia generated from artificial (carrot agar) and natural (corn stalk) substrates released a mean of 104+/-5 and 276+/-16 ascospores, respectively. A volumetric spore trap was placed inside a 3,716 m2 clonal source of inoculum in 2011 and 2012. Results indicated that ascospores were released under field conditions predominantly (>90%) during the night (1900 to 0700 hours). Estimates of Qpot for our field-scale sources of inoculum were approximately 4 billion ascospores per 3,716 m 2. Release-recapture studies were conducted from a clonal field-scale source of F. graminearum in 2011 and 2012. Microsatellites were used to identify the released clone of F. graminearum at distances up to 1 km from the source. Dispersal kernels for field observations were compared to results predicted by a Gaussian dispersal-based spore transport model. In 2011 and 2012, dispersal kernel shape coefficients were similar for both results observed in the field and predicted by the model, with both being dictated by a power law function, indicating that turbulence was the dominant transport factor on the scale we studied (˜ 1 km). Model predictions had a stronger correlation with the number of spores being released when using a time varying q0 emission rate (r= 0.92 in 2011 and r= 0.84 in 2012) than an identical daily pattern q0 emission rate (r= 0.35 in 2011 and r= 0.32 in 2012). The actual numbers of spores deposited were 3 and 2000 times lower than predicted if Qpot were equal to the actual number of spores released in 2011 and 2012, respectively. Future work should address estimating the actual number of spore released from an inoculated field during any given season, to improve prediction accuracy of the model. This work should assist in improving current risk assessment tools for FHB and contribute to the development of early warning systems for the spread of F. graminearum.

Controlling the Release of Indomethacin from Glass Solutions Layered with a Rate Controlling Membrane Using Fluid-Bed Processing. Part 2: The Influence of Formulation Parameters on Drug Release.

PubMed

Dereymaker, Aswin; Pelgrims, Jirka; Engelen, Frederik; Adriaensens, Peter; Van den Mooter, Guy

2017-04-03

This study aimed to investigate the pharmaceutical performance of an indomethacin-polyvinylpyrrolidone (PVP) glass solution applied using fluid bed processing as a layer on inert sucrose spheres and subsequently top-coated with a release rate controlling membrane consisting of either ethyl cellulose or Eudragit RL. The implications of the addition of a pore former (PVP) and the coating medium (ethanol or water) on the diffusion and release behavior were also considered. In addition, the role of a charge interaction between drug and controlled release polymer on the release was investigated. Diffusion experiments pointed to the influence of pore former concentration, rate controlling polymer type, and coating solvent on the permeability of the controlled release membranes. This can be translated to drug release tests, which show the potential of diffusion tests as a preliminary screening test and that diffusion is the main factor influencing release. Drug release tests also showed the effect of coating layer thickness. A charge interaction between INDO and ERL was demonstrated, but this had no negative effect on drug release. The higher diffusion and release observed in ERL-based rate controlling membranes was explained by a higher hydrophilicity, compared to EC.

Concomitant monitoring of implant formation and drug release of in situ forming poly (lactide-co-glycolide acid) implants in a hydrogel matrix mimicking the subcutis using UV-vis imaging.

PubMed

Sun, Yu; Jensen, Henrik; Petersen, Nickolaj J; Larsen, Susan W; Østergaard, Jesper

2018-02-20

For poly (lactide-co-glycolide acid) (PLGA)-based in situ forming implants, the rate of implant formation plays an important role in determining the overall drug release kinetics. Currently, in vitro techniques capable of characterizing the processes of drug release and implant formation at the same time are not available. A hydrogel-based in vitro experimental setup was recently developed requiring only microliter of formulation and forming a closed system potentially suitable for interfacing with various spectroscopic techniques. The aim of the present proof-of-concept study was to investigate the feasibility of concomitant UV imaging, Vis imaging and light microscopy for detailed characterization of the behavior of in situ forming PLGA implants in the hydrogel matrix mimicking the subcutis. The model compounds, piroxicam and α-lactalbumin were added to PLGA-1-methyl-2-pyrrolidinone and PLGA-triacetin solutions. Upon bringing the PLGA-solvent-compound pre-formulation in contact with the hydrogel, Vis imaging and light microscopy were applied to visualize the depot formation and UV imaging was used to quantify drug transport in the hydrogel. As compared to piroxicam, the α-lactalbumin invoked an acceleration of phase separation and an increase of implant size. α-Lactalbumin was released faster from the PLGA-1-methyl-2-pyrrolidinone system than the PLGA-triacetin system opposite to the piroxicam release pattern. A linear relationship between the rate of implant formation and initial compound release within the first 4h was established for the PLGA-NMP systems. This implies that phase separation may be one of the controlling factors in drug release. The rate of implant formation may be an important parameter for predicting and tailoring drug release. The approach combining UV imaging, Vis imaging and light microscopy may facilitate understanding of release processes and holds potential for becoming a useful tool in formulation development of in situ forming implants. Copyright © 2017 Elsevier B.V. All rights reserved.

Delamination properity of 2060 aluminium lithium alloy laminate

NASA Astrophysics Data System (ADS)

Guo, Xiang; Huang, Yi; Tong, Dihua; Ma, Shaojun

2018-03-01

Delamination is an significant property of aluminium lithium alloy laminate for damage tolerance design. Double Crack Lap Shear specimens of "2/1" structure are used for testing delamination properity. Experiments of 2 stress ratio conditions R=0.06, 0.5 are conducted, and 5 stress levels for each stress ratio. Delamination growth data b-N are obtained from 4 crack tips’ locations. The energy release rate, Gd, of the "2/1" structure laminate are calculated. Alderliesten modelis used for describing delamination growth db/dN and energy release rate Gd. Parameters Cd and nd in Alderliesten model are determined for R=0.06 and R=0.5 by linear fitting. An analysis is made by comparing the results of different stress ratio conditons.

Dynamics of Crust Dissolution and Gas Release in Tank 241-SY-101

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

Rassat, Scot D.; Stewart, Charles W.; Wells, Beric E.

2000-01-24

Due primarily to an increase in floating crust thickness, the waste level in Tank 241-SY-101 has grown appreciably and the flammable gas volume stored in the crust has become a potential hazard. To remediate gas retention in the crust and the potential for buoyant displacement gas releases from the nonconvective layer at the bottom of the tank, SY-101 will be diluted to dissolve a large fraction of the solids that allow the waste to retain gas. The plan is to transfer some waste out and back-dilute with water in several steps. In this work, mechanisms and rates of waste solidsmore » dissolution and gas releases are evaluated theoretically and experimentally. Particular emphasis is given to crust dissolution processes and associated gas releases, although dissolution and gas release from the mixed-slurry and nonconvective layers are also considered. The release of hydrogen gas to the tank domespace is modeled for a number of scenarios. Under the tank conditions expected at the time of back-dilution, no plausible continuous or sudden gas release scenarios resulting in flammable hydrogen concentrations were identified.« less

77 FR 47918 - Information Collection Activities (Released Rates)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-10

... decision in Released Rates of Motor Common Carriers of Household Goods, Docket No. RR 999 (Amendment No. 5... loss or damage that occurs during interstate household-good moves. See Safe, Accountable, Flexible... elects anything other than full-value protection. See Released Rates of Motor Common Carriers of...

Host-guest chemistry of dendrimer-drug complexes. 6. Fully acetylated dendrimers as biocompatible drug vehicles using dexamethasone 21-phosphate as a model drug.

PubMed

Yang, Kun; Weng, Liang; Cheng, Yiyun; Zhang, Hongfeng; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen

2011-03-17

Fully acetylated poly(amidoamine) (PAMAM) dendrimer was proposed as a biocompatible drug vehicle using dexamethasone 21-phosphate (Dp21) as a model drug. NMR techniques including (1)H NMR and 2D NOE NMR were used to characterize the host-guest chemistry of acetylated dendrimer/Dp21 and cationic dendrimer/Dp21 complexes. The pH-dependent micellization, complexation, and inclusion behaviors of Dp21 were observed in the presence of acetylated and cationic PAMAM dendrimers. Acetylated dendrimer only encapsulates Dp21 at acidic conditions, while cationic dendrimer can host Dp21 at both acidic and neutral conditions. The orientation of Dp21 molecules in the dendrimer cavities depends on the quaternization degree of tertiary amine groups of dendrimer and the protonation ratio of phosphate group of Dp21. A distinctive pH-dependent release behavior of Dp21 from the acetylated and nonacetylated dendritic matrix was observed: Dp21 exhibits a much slower release rate from acetylated dendrimer at lower pH conditions and a much faster release rate from nonacetylated dendrimer with decreasing pH values. Cytotoxicity studies further confirmed the biocompatibility of acetylated dendrimers, which are much safer in the delivery of therapeutics for the treatment of various diseases than nonacetylated dendrimers. The dendrimer-drug binding and release mechanisms provide a new insight for the design and optimization of biocompatible dendrimer-based drug delivery systems. © 2011 American Chemical Society

Water hyacinth: a possible alternative rate retarding natural polymer used in sustained release tablet design

PubMed Central

Khatun, Sabera; Sutradhar, Kumar B.

2014-01-01

In recent years natural polymers have been widely used because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5, 10, 15, 20, 25 and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr's Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM) studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37°C ± 0.5 temperature for 8 h. Though all the formulations comply with both BP and USP requirements, formulation F-1 (5% of Water hyacinth) was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell, and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations. PMID:24966835

Social Environment and Hospitalisation after Release from Prison: A Prospective Cohort Study

PubMed Central

2017-01-01

This study examined the association between remoteness and area disadvantage, and the rate of subsequent hospitalisation, in a cohort of adults released from prisons in Queensland. A baseline survey of 1267 adult prisoners within 6 weeks of expected release was prospectively linked with hospital, mortality and reincarceration records. Postcodes were used to assign remoteness and area disadvantage categories. Multivariate Andersen–Gill regression models were fitted to test for associations between remoteness, area disadvantage and hospitalisation after release from prison. Over a total of 3090.9 person-years of follow-up, the highest crude incidence rates were observed in areas characterised by remoteness and area disadvantage (crude incidence rate (IR) = 649; 95%CI: 526–791), followed by remoteness only (IR = 420; 95%CI: 349–501), severe area disadvantage only (IR = 403; 95%CI: 351–461), and neither of these factors (IR = 361; 95%CI: 336–388). Unadjusted analyses indicated that remoteness (hazard ratio (HR) = 1.32; 95%CI: 1.04–1.69; p = 0.024) was associated with increased risk of hospitalisation; however, this attenuated to the null after adjustment for covariate factors. The incidence of hospitalisation for those who live in remote or socio-economically disadvantaged areas is increased compared to their counterparts in more urban and less socio-economically disadvantaged areas. Experiencing both these factors together may compound the hospitalisation in the community. PMID:29149091

Sensitivity of the global submarine hydrate inventory to scenarios of future climate change

NASA Astrophysics Data System (ADS)

Hunter, S. J.; Goldobin, D. S.; Haywood, A. M.; Ridgwell, A.; Rees, J. G.

2013-04-01

The global submarine inventory of methane hydrate is thought to be considerable. The stability of marine hydrates is sensitive to changes in temperature and pressure and once destabilised, hydrates release methane into sediments and ocean and potentially into the atmosphere, creating a positive feedback with climate change. Here we present results from a multi-model study investigating how the methane hydrate inventory dynamically responds to different scenarios of future climate and sea level change. The results indicate that a warming-induced reduction is dominant even when assuming rather extreme rates of sea level rise (up to 20 mm yr-1) under moderate warming scenarios (RCP 4.5). Over the next century modelled hydrate dissociation is focussed in the top ˜100m of Arctic and Subarctic sediments beneath <500m water depth. Predicted dissociation rates are particularly sensitive to the modelled vertical hydrate distribution within sediments. Under the worst case business-as-usual scenario (RCP 8.5), upper estimates of resulting global sea-floor methane fluxes could exceed estimates of natural global fluxes by 2100 (>30-50TgCH4yr-1), although subsequent oxidation in the water column could reduce peak atmospheric release rates to 0.75-1.4 Tg CH4 yr-1.

Coupling of exothermic and endothermic hydrogen storage materials

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

Brooks, Kriston P.; Bowden, Mark E.; Karkamkar, Abhijeet J.

2016-08-01

Chemical hydrogen storage (CHS) materials are a high-storage-density alternative to the gaseous compressed hydrogen currently used to provide hydrogen for fuel cell vehicles. One of the challenges of CHS materials is addressing the thermodynamic and kinetic barriers required to break the chemical bonds and release the hydrogen. Coupling CHS reactions that are endothermic and exothermic during the dehydrogenation can improve the system on-board energy efficiency and thermal control, making such materials viable. Acceptable coupling between reactions requires both thermodynamic and kinetics considerations. Models were developed to predict the reaction enthalpy and rate required to achieve high conversions for both reactionsmore » based on experimental measurements. These modeling results show that the efficiency of coupling of an exothermic and endothermic reaction is more sensitive the magnitude of the ratio of the exothermic and endothermic enthalpies than the ratio of the rates of the two steps. The modeling shows further that a slower rate of the endothermic step is desirable to permit sufficient heating of the reactor by the exothermic step. We look at two examples of a sequential and parallel reaction scheme and provide some of the first insight into the required temperature range to maximize the H2 release from 1,2-BN cyclohexane and indoline.« less

Osmotic pressure driven protein release from viscous liquid, hydrophobic polymers based on 5-ethylene ketal ε-caprolactone: potential and mechanism.

PubMed

Babasola, Iyabo Oladunni; Zhang, Wei; Amsden, Brian G

2013-11-01

In this study, the potential of low molecular weight, viscous liquid polymers based on 5-ethylene ketal ε-caprolactone for localized delivery of proteins via an osmotic pressure release mechanism was investigated. Furthermore, the osmotic release mechanism from viscous liquid polymers was elucidated. 5-Ethylene ketal ε-caprolactone was homopolymerized or copolymerized with D,L-lactide (DLLA) by ring-opening polymerization. Polymer hydrophobicity was adjusted by choice of initiator; hydrophobic polymers were prepared by initiating with octan-1-ol, while more hydrophilic polymers were prepared by initiating with 350 g/mol methoxy poly(ethylene glycol) (PEG). Particles consisting of bovine serum albumin (BSA) as a model protein drug were co-lyophilized with trehalose at 50:50 and 10:90 (w/w) ratios and were mixed into the polymers at 1% and/or 5% (w/w) particle loading. The release and mechanism of release of BSA from the polymers were assessed in vitro. BSA was released in a sustained manner, with a near zero-order release profile and with minimal burst effect for 5-80 days depending on the polymer's hydrophilicity; the release was faster from the PEG initiated polymers than from the octan-1-ol initiated polymers. Increasing the particle loading from 1% to 5% (w/w) resulted in a more noticeable burst effect, but did not significantly increase the mass fraction release rate. This release behavior was determined to proceed as follows. Release from the polymer was triggered by the water activity gradient between the surrounding aqueous medium and the saturated solution, which forms when water is absorbed from the surrounding medium to dissolve a given particle. The generated pressure initiates swelling around the particle/polymer interface and creates a superhydrated polymer region through which the solute is transported by convection, at a rate determined by the osmotic pressure generated. Copyright © 2013 Elsevier B.V. All rights reserved.

In vitro biorelevant models for evaluating modified release mesalamine products to forecast the effect of formulation and meal intake on drug release.

PubMed

Andreas, Cord J; Chen, Ying-Chen; Markopoulos, Constantinos; Reppas, Christos; Dressman, Jennifer

2015-11-01

Postprandial administration of solid oral dosage forms greatly changes the dissolution environment compared to fasted state administration. The aims of this study were to investigate and forecast the effect of co-administration of a meal on drug release for delayed and/or extended release mesalamine formulations as well as design of in vitro tests to distinguish among formulations in a biorelevant way. Five different mesalamine formulations (Asacol® 400 mg, Mezavant® 1200 mg, Pentasa® 500 mg and Salofalk® in the 250 mg and 500 mg strengths) were investigated with biorelevant dissolution methods using the USP apparatus III and USP apparatus IV (open loop mode) under both fasted and fed state conditions, as well as with the dissolution methods described in pharmacopeia for delayed and extended release mesalamine products. Using the biorelevant experimental conditions proposed in this study, changes in release in the proximal gut due to meal intake are forecast to be minimal for Asacol®, Mezavant®, Pentasa® and Salofalk® 500 mg, while for Salofalk® 250 mg release was predicted to occur much earlier under fed state conditions. The USP apparatus III generally tended to result in faster dissolution rates and forecast more pronounced food effects for Salofalk® 250 mg than the USP apparatus IV. The biorelevant dissolution gradients were also able to reflect the in vivo behavior of the formulations. In vitro biorelevant models can be useful in the comparison of the release behavior from different delayed and extended release mesalamine formulations as well as forecasting effects of concomitant meal intake on drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of the Approximate Bayesian Computation methods in the stochastic estimation of atmospheric contamination parameters for mobile sources

NASA Astrophysics Data System (ADS)

Kopka, Piotr; Wawrzynczak, Anna; Borysiewicz, Mieczyslaw

2016-11-01

In this paper the Bayesian methodology, known as Approximate Bayesian Computation (ABC), is applied to the problem of the atmospheric contamination source identification. The algorithm input data are on-line arriving concentrations of the released substance registered by the distributed sensors network. This paper presents the Sequential ABC algorithm in detail and tests its efficiency in estimation of probabilistic distributions of atmospheric release parameters of a mobile contamination source. The developed algorithms are tested using the data from Over-Land Atmospheric Diffusion (OLAD) field tracer experiment. The paper demonstrates estimation of seven parameters characterizing the contamination source, i.e.: contamination source starting position (x,y), the direction of the motion of the source (d), its velocity (v), release rate (q), start time of release (ts) and its duration (td). The online-arriving new concentrations dynamically update the probability distributions of search parameters. The atmospheric dispersion Second-order Closure Integrated PUFF (SCIPUFF) Model is used as the forward model to predict the concentrations at the sensors locations.

Monte Carlo Model Insights into the Lunar Sodium Exosphere

NASA Technical Reports Server (NTRS)

Hurley, Dana M.; Killen, R. M.; Sarantos, M.

2012-01-01

Sodium in the lunar exosphere is released from the lunar regolith by several mechanisms. These mechanisms include photon stimulated desorption (PSD), impact vaporization, electron stimulated desorption, and ion sputtering. Usually, PSD dominates; however, transient events can temporarily enhance other release mechanisms so that they are dominant. Examples of transient events include meteor showers and coronal mass ejections. The interaction between sodium and the regolith is important in determining the density and spatial distribution of sodium in the lunar exosphere. The temperature at which sodium sticks to the surface is one factor. In addition, the amount of thermal accommodation during the encounter between the sodium atom and the surface affects the exospheric distribution. Finally, the fraction of particles that are stuck when the surface is cold that are rereleased when the surface warms up also affects the exospheric density. In [1], we showed the "ambient" sodium exosphere from Monte Carlo modeling with a fixed source rate and fixed surface interaction parameters. We compared the enhancement when a CME passes the Moon to the ambient conditions. Here, we compare model results to data in order to determine the source rates and surface interaction parameters that provide the best fit of the model to the data.

Supplemental water releases for fisheries restoration in a Brazilian floodplain River: A conceptual model

USGS Publications Warehouse

Godinho, Alexandre L.; Kynard, B.; Martinez, C.B.

2007-01-01

Highly productive floodplain rivers in Brazil and elsewhere provide livelihood and recreational fishing for millions of people around the world, but damming and controlled water discharge are a threat to these valuable ecosystems. Supplemental water releases (SWRs) at a dam are increasingly used for restoring fisheries productivity in many floodplain rivers. We proposed a conceptual model for a hypothetical water release to enhance fisheries using Tre??s Marias Reservoir (TMR) on the Sa??o Francisco River (SFR), Brazil. The information needed by the model follows: (i) Biologically, what is the best release date? (ii) How much water will be released? (iii) What is the pattern of impoundment and how much impounded water will be released? (iv) What is the lost revenue to the power plant associated with SWR? (v) What is the relationship between river discharge and the area of floodplain that is flooded? (vi) What is the relationship between SWR and fisheries value? Ichthyoplankton studies in the SFR showed a clear positive relationship between fish density and water level (WL). While the relationship between WL and floodplain area flooded and recruitment is not known, we concluded the best date for release is when there is a natural flood, which naturally triggers fish spawning and the SWR will add to the natural flood and cover a greater floodplain area. The released volume will range from 0.302km3 to 2.192 km3, depending on SWR duration. In most years from 1976 to 2003, TMR impounded enough water for SWR only in the second half of the fish-spawning season (January-March). Lost revenue at TMR depended on release volume and ranged from US$ 0.493 million to US$ 3.452 million for the actual power rate. However, SWR could increase commercial fisheries income an estimated US$ 4.468 million. We forecast that SWR can bring fisheries benefits that surpass the lost revenue.

Dual diagnosis of mental illness and substance use disorder and injury in adults recently released from prison: a prospective cohort study.

PubMed

Young, Jesse T; Heffernan, Ed; Borschmann, Rohan; Ogloff, James R P; Spittal, Matthew J; Kouyoumdjian, Fiona G; Preen, David B; Butler, Amanda; Brophy, Lisa; Crilly, Julia; Kinner, Stuart A

2018-05-01

People with mental illness and substance use disorder are over-represented in prisons. Injury-related mortality is elevated in people released from prison, and both mental illness and substance use disorder are risk factors for injury. Effective care coordination during the transition between criminal justice and community service providers improves health outcomes for people released from prison. However, the health outcomes and support needs of people with dual diagnosis (co-occurring mental illness and substance use disorder) released from prison are poorly understood. Here we aim to examine the association between dual diagnosis and non-fatal injury in adults released from prison. Pre-release interview data collected between Aug 1, 2008, and July 31, 2010, from a representative sample of sentenced adults (≥18 years) in Queensland, Australia, were linked, retrospectively and prospectively, to person-level, state-wide emergency department and hospital records. We identified dual diagnoses from inpatient, emergency department, and prison medical records. We modelled the association between mental health status and all injury resulting in hospital contact by fitting a multivariate Cox regression, adjusting for sociodemographic, health, and criminogenic covariates, and replacing missing covariate data by multiple imputation. In 1307 adults released from prison, there were 2056 person-years of follow-up (median 495 days, IQR 163-958). The crude injury rates were 996 (95% CI 893-1112) per 1000 person-years for the dual diagnosis group, 538 (441-657) per 1000 person-years for the mental illness only group, 413 (354-482) per 1000 person-years for the substance use disorder only group, and 275 (247-307) per 1000 person-years for the no mental disorder group. After adjusting for model covariates, the dual diagnosis (adjusted hazard rate ratio 3·27, 95% CI 2·30-4·64; p<0·0001) and mental illness only (1·87, 1·19-2·95; p=0·0071) groups were at increased risk of injury after release from prison compared with the group with no mental health disorders. People released from prison experience high rates of injury compared with the general population. Among people released from prison, dual diagnosis is associated with an increased risk of injury. Contact with the criminal justice system is a key opportunity to prevent subsequent injury morbidity in people with co-occurring mental health disorders. Engagement with integrated psychiatric and addiction treatment delivered without interruption during the transition from prison into the community might prevent the injury-related disparities experienced by this vulnerable group. The development of targeted injury prevention strategies for people with dual diagnosis released from prison is warranted. National Health and Medical Research Council. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

The mechanisms of drug release from solid dispersions in water-soluble polymers.

PubMed

Craig, Duncan Q M

2002-01-14

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. However, despite the publication of numerous original papers and reviews on the subject, the mechanisms underpinning the observed improvements in dissolution rate are not yet understood. In this review the current consensus with regard to the solid-state structure and dissolution properties of solid dispersions is critically assessed. In particular the theories of carrier- and drug-controlled dissolution are highlighted. A model is proposed whereby the release behaviour from the dispersions may be understood in terms of the dissolution or otherwise of the drug into the concentrated aqueous polymer layer adjacent to the solid surface, including a derivation of an expression to describe the release of intact particles from the dispersions. The implications of a deeper understanding of the dissolution mechanisms are discussed, with particular emphasis on optimising the choice of carrier and manufacturing method and the prediction of stability problems.

Effect of hydrophobic inclusions on polymer swelling kinetics studied by magnetic resonance imaging.

PubMed

Gajdošová, Michaela; Pěček, Daniel; Sarvašová, Nina; Grof, Zdeněk; Štěpánek, František

2016-03-16

The rate of drug release from polymer matrix-based sustained release formulations is often controlled by the thickness of a gel layer that forms upon contact with dissolution medium. The effect of formulation parameters on the kinetics of elementary rate processes that contribute to gel layer formation, such as water ingress, polymer swelling and erosion, is therefore of interest. In the present work, gel layer formation has been investigated by magnetic resonance imaging (MRI), which is a non-destructive method allowing direct visualization of effective water concentration inside the tablet and its surrounding. Using formulations with Levetiracetam as the active ingredient, HPMC as a hydrophilic matrix former and carnauba wax (CW) as a hydrophobic component in the matrix system, the effect of different ratios of these two ingredients on the kinetics of gel formation (MRI) and drug release (USP 4 like dissolution test) has been investigated and interpreted using a mathematical model. Copyright © 2016 Elsevier B.V. All rights reserved.

A Semi-Analytical Method for Determining the Energy Release Rate of Cracks in Adhesively-Bonded Single-Lap Composite Joints

NASA Technical Reports Server (NTRS)

Yang, Charles; Sun, Wenjun; Tomblin, John S.; Smeltzer, Stanley S., III

2007-01-01

A semi-analytical method for determining the strain energy release rate due to a prescribed interface crack in an adhesively-bonded, single-lap composite joint subjected to axial tension is presented. The field equations in terms of displacements within the joint are formulated by using first-order shear deformable, laminated plate theory together with kinematic relations and force equilibrium conditions. The stress distributions for the adherends and adhesive are determined after the appropriate boundary and loading conditions are applied and the equations for the field displacements are solved. Based on the adhesive stress distributions, the forces at the crack tip are obtained and the strain energy release rate of the crack is determined by using the virtual crack closure technique (VCCT). Additionally, the test specimen geometry from both the ASTM D3165 and D1002 test standards are utilized during the derivation of the field equations in order to correlate analytical models with future test results. The system of second-order differential field equations is solved to provide the adherend and adhesive stress response using the symbolic computation tool, Maple 9. Finite element analyses using J-integral as well as VCCT were performed to verify the developed analytical model. The finite element analyses were conducted using the commercial finite element analysis software ABAQUS. The results determined using the analytical method correlated well with the results from the finite element analyses.

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

Shlapakovski, A. S.; Beilin, L.; Krasik, Ya. E.

Nanosecond-scale evolution of plasma and RF electromagnetic fields during the release of energy from a microwave pulse compressor with a plasma interference switch was investigated numerically using the code MAGIC. The plasma was simulated in the scope of the gas conductivity model in MAGIC. The compressor embodied an S-band cavity and H-plane waveguide tee with a shorted side arm filled with pressurized gas. In a simplified approach, the gas discharge was initiated by setting an external ionization rate in a layer crossing the side arm waveguide in the location of the electric field antinode. It was found that with increasingmore » ionization rate, the microwave energy absorbed by the plasma in the first few nanoseconds increases, but the absorption for the whole duration of energy release, on the contrary, decreases. In a hybrid approach modeling laser ignition of the discharge, seed electrons were set around the electric field antinode. In this case, the plasma extends along the field forming a filament and the plasma density increases up to the level at which the electric field within the plasma decreases due to the skin effect. Then, the avalanche rate decreases but the density still rises until the microwave energy release begins and the electric field becomes insufficient to support the avalanche process. The extraction of the microwave pulse limits its own power by terminating the rise of the plasma density and filament length. For efficient extraction, a sufficiently long filament of dense plasma must have sufficient time to be formed.« less

Measurement of semiochemical release rates with a dedicated environmental control system

Treesearch

Heping Zhu; Harold W. Thistle; Christopher M. Ranger; Hongping Zhou; Brian L. Strom

2015-01-01

Insect semiochemical dispensers are commonly deployed under variable environmental conditions over a specified period. Predictions of their longevity are hampered by a lack of methods to accurately monitor and predict how primary variables affect semiochemical release rate. A system was constructed to precisely determine semiochemical release rates under...

40 CFR 302.8 - Continuous releases.

Code of Federal Regulations, 2010 CFR

2010-07-01

... that the release is continuous and stable in quantity and rate; (2) Change in the normal range. If... section, continuous and stable in quantity and rate. (b) Definitions. The following definitions apply to... conditions during the preceding year. Only releases that are both continuous and stable in quantity and rate...

SU-F-19A-08: Optimal Time Release Schedule of In-Situ Drug Release During Permanent Prostate Brachytherapy

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

Cormack, R; Ngwa, W; Makrigiorgos, G

Purpose: Permanent prostate brachytherapy spacers can be used to deliver sustained doses of radiosentitizing drug directly to the target, in order to enhance the radiation effect. Implantable nanoplatforms for chemo-radiation therapy (INCeRTs) have a maximum drug capacity and can be engineered to control the drug release schedule. The optimal schedule for sensitization during continuous low dose rate irradiation is unknown. This work studies the optimal release schedule of drug for both traditional sensitizers, and those that work by suppressing DNA repair processes. Methods: Six brachytherapy treatment plans were used to model the anatomy, implant geometry and calculate the spatial distributionmore » of radiation dose and drug concentrations for a range of drug diffusion parameters. Three state partial differential equations (cells healthy, damaged or dead) modeled the effect of continuous radiation (radiosensitivities α,β) and cellular repair (time tr) on a cell population. Radiosensitization was modeled as concentration dependent change in α,β or tr which with variable duration under the constraint of fixed total drug release. Average cell kill was used to measure effectiveness. Sensitization by means of both enhanced damage and reduced repair were studied. Results: Optimal release duration is dependent on the concentration of radiosensitizer compared to the saturation concentration (csat) above which additional sensitization does not occur. Long duration drug release when enhancing α or β maximizes cell death when drug concentrations are generally over csat. Short term release is optimal for concentrations below saturation. Sensitization by suppressing repair has a similar though less distinct trend that is more affected by the radiation dose distribution. Conclusion: Models of sustained local radiosensitization show potential to increase the effectiveness of radiation in permanent prostate brachytherapy. INCeRTs with high drug capacity produce the greatest benefit with drug release over weeks. If in-vivo drug concentrations are not able to approach saturation concentration, durations of days is optimal. DOD 1R21CA16977501; A. David Mazzone Awards Program 2012PD164.« less

Miniature bulge test and energy release rate in HIPed aluminum/aluminum interfacial fracture

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

Liu, C.; Lovato, M. L.; Clarke, K. D.

We summarize the development of a technique of using miniature bulge test combined with three-dimensional digital image correlation (3D-DIC) for measuring energy release rate or fracture toughness of bimaterial interface of thin metal foils. Furthermore, the energy release rate associated with the HIPed aluminum/aluminum interfacial delamination is determined experimentally using the proposed technique. Detailed discussions of the schemes of preparing and conducting the bulge test, and computing various quantities required for the determination of the energy release rate are presented.

Miniature bulge test and energy release rate in HIPed aluminum/aluminum interfacial fracture

DOE PAGES

Liu, C.; Lovato, M. L.; Clarke, K. D.; ...

2017-10-13

We summarize the development of a technique of using miniature bulge test combined with three-dimensional digital image correlation (3D-DIC) for measuring energy release rate or fracture toughness of bimaterial interface of thin metal foils. Furthermore, the energy release rate associated with the HIPed aluminum/aluminum interfacial delamination is determined experimentally using the proposed technique. Detailed discussions of the schemes of preparing and conducting the bulge test, and computing various quantities required for the determination of the energy release rate are presented.

Desorption kinetics of ciprofloxacin in municipal biosolids determined by diffusion gradient in thin films.

PubMed

D'Angelo, E; Starnes, D

2016-12-01

Ciprofloxacin (CIP) is a commonly-prescribed antibiotic that is largely excreted by the body, and is often found at elevated concentrations in treated sewage sludge (biosolids) at municipal wastewater treatment plants. When biosolids are applied to soils, they could release CIP to surface runoff, which could adversely affect growth of aquatic organisms that inhabit receiving water bodies. The hazard risk largely depends on the amount of antibiotic in the solid phase that can be released to solution (labile CIP), its diffusion coefficient, and sorption/desorption exchange rates in biosolids particles. In this study, these processes were evaluated in a Class A Exceptional Quality Biosolids using a diffusion gradient in thin films (DGT) sampler that continuously removed CIP from solution, which induced desorption and diffusion in biosolids. Mass accumulation of antibiotic in the sampler over time was fit by a diffusion transport and exchange model available in the software tool 2D-DIFS to derive the distribution coefficient of labile CIP (K dl ) and sorption/desorption rate constants in the biosolids. The K dl was 13 mL g -1 , which equated to 16% of total CIP in the labile pool. Although the proportion of labile CIP was considerable, release rates to solution were constrained by slow desorption kinetics (desorption rate constant = 4 × 10 -6 s -1 ) and diffusion rate (effective diffusion coefficient = 6 × 10 -9  cm 2  s -1 . Studies are needed to investigate how changes in temperature, water content, pH and other physical and chemical characteristics can influence antibiotic release kinetics and availability and mobility in biosolid-amended soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Stochastic Lanchester-type Combat Models I.

DTIC Science & Technology

1979-10-01

necessarily hold when the attrition rates become non- linear in b and/or r. 13 iL 4. OTHER COMBAT MODELS In this section we briefly describe how other...AD-A092 898 FLORIDA STATE UNIV TALLAHASSEE DEPT OF STATISTICS F/6 12/2 STOCHASTIC LANCHESTER-TYPE COMBAT MODELS I.(U) OCT 79 L BILLARD N62271-79-M...COMBAT MODELS I by L. BILLARD October 1979 Approved for public release; distribution unlimited. Prepared for: Naval Postgraduate School Monterey, CA 93940

A novel antiproliferative drug coating for glaucoma drainage devices.

PubMed

Ponnusamy, Thiruselvam; Yu, Haini; John, Vijay T; Ayyala, Ramesh S; Blake, Diane A

2014-01-01

The implantation of a glaucoma drainage device (GDD) is often necessary for intractable cases of glaucoma. Currently, the success rate of GDD implants is relatively low because fibrosis that develops during the wound-healing process ultimately blocks fluid drainage. We describe herein a novel porous coating for Ahmed glaucoma valves based on biodegradable poly(lactic-co-glycolic acid) (PLGA). Thin films of PLGA were fabricated using a spin-coating technique. The procedure led to an asymmetric pore structure that was exploited to control the rate of dissolution. Double-layered porous films were constructed to achieve continuous drug release. A cell culture system was used to test the efficacy of these coatings. Double-layered films were manufactured to provide a burst of mitomycin C (MMC) release followed by a slow release of 5-fluorouracil (5-FU), which together prevented fibrosis over the most active period of postoperative wound healing (0 to 28 d). Double-layered films containing 5-FU only in the bottom layer showed a 3- to 5-day delay in drug release, followed by a sharp increase that continued for ~28 days. MMC was stable only when surface-loaded, and this drug was therefore surface-loaded onto the top PLGA layer to provide a continuous release of antifibrotics over the wound-healing period. The combined use of both MMC and 5-FU in a biodegradable device inhibits cell proliferation in a tissue culture model and has the potential to reduce fibrosis and increase the success rate of GDD implants. The design is simple and can be scaled for commercial production.

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.

Characterization of drug-release kinetics in trabecular bone from titania nanotube implants

PubMed Central

Aw, Moom Sinn; Khalid, Kamarul A; Gulati, Karan; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

2012-01-01

Purpose The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery Methods Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm) and horizontal (0–10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days. Results Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT–Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone. Conclusion These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to optimize the delivery of specific therapies and to assist in the design of new drug delivery systems. This method has the potential to provide new knowledge to understand drug distribution in the bone environment and to considerably improve existing technologies for local administration in bone, including solving some critical problems in bone therapy and orthopedic implants. PMID:23028217

Characterization of drug-release kinetics in trabecular bone from titania nanotube implants.

PubMed

Aw, Moom Sinn; Khalid, Kamarul A; Gulati, Karan; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

2012-01-01

The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT-Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0-5 mm) and horizontal (0-10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days. Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT-Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT-Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone. These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to optimize the delivery of specific therapies and to assist in the design of new drug delivery systems. This method has the potential to provide new knowledge to understand drug distribution in the bone environment and to considerably improve existing technologies for local administration in bone, including solving some critical problems in bone therapy and orthopedic implants.

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

Diffusion of progestogens through Silastic rubber implants.

PubMed

Lifchez, A S; Scommegna, A

1970-05-01

Silastic rubber capsules in 2 thicknesses (.42 mm and .80 mm) and 3 lengths (9, 14, and 19 mm) were filled with progesterone, Provera, Norgestrel, or chlormadinone acetate and implanted under the skin of rats, and the amount of steroid released was measured after 1, 2, 4, and 8 weeks. The amount of steroid released was also measured from progesterone-filled capsules .42 mm thick and varying from 19-32 mm long inserted in the uterus of 16 women volunteers for 1-7 days. The rate of release of each steroid in the rats was found to be proportionate to the length of the capsule and related, but not proportional to the thickness of the capsule. The release rate of progesterone was 3-20 times greater than that of the other steroids, while Norgestrel diffused at the lowest rate. The influence of thickness of capsule was greater for the steroids with the highest diffusion rate, progesterone and chlormadinone acetate. The release rates of all except chlormadinone acetate were higher in the 1st week. The release rates of the synthetic progestins, unlike that of progesterone, were relatively constant after the 1st week. The release rate of progesterone tended to be related to the amount remaining in the capsule when the amount became small. The measured amount of progesterone released each day from each intrauterine capsule was also proportional to its length. It appears that Norgestrel, Provera, and chlormadinone acetate are all released slowly enough and have enough biologic activity at low concentrations to have a contraceptive effect for well over 1 year when administered in a 30 mm intrauterine capsule.

Statistics for laminar flamelet modeling

NASA Technical Reports Server (NTRS)

Cant, R. S.; Rutland, C. J.; Trouve, A.

1990-01-01

Statistical information required to support modeling of turbulent premixed combustion by laminar flamelet methods is extracted from a database of the results of Direct Numerical Simulation of turbulent flames. The simulations were carried out previously by Rutland (1989) using a pseudo-spectral code on a three dimensional mesh of 128 points in each direction. One-step Arrhenius chemistry was employed together with small heat release. A framework for the interpretation of the data is provided by the Bray-Moss-Libby model for the mean turbulent reaction rate. Probability density functions are obtained over surfaces of the constant reaction progress variable for the tangential strain rate and the principal curvature. New insights are gained which will greatly aid the development of modeling approaches.

Insights into accelerated liposomal release of topotecan in plasma monitored by a non-invasive fluorescence spectroscopic method

PubMed Central

Fugit, Kyle D.; Jyoti, Amar; Upreti, Meenakshi; Anderson, Bradley D.

2014-01-01

A non-invasive fluorescence method was developed to monitor liposomal release kinetics of the anticancer agent topotecan (TPT) in physiological fluids and subsequently used to explore the cause of accelerated release in plasma. Analyses of fluorescence excitation spectra confirmed that unencapsulated TPT exhibits a red shift in its spectrum as pH is increased. This property was used to monitor TPT release from actively loaded liposomal formulations having a low intravesicular pH. Mathematical release models were developed to extract reliable rate constants for TPT release in aqueous solutions monitored by fluorescence and release kinetics obtained by HPLC. Using the fluorescence method, accelerated TPT release was observed in plasma as previously reported in the literature. Simulations to estimate the intravesicular pH were conducted to demonstrate that accelerated release correlated with alterations in the low intravesicular pH. This was attributed to the presence of ammonia in plasma samples rather than proteins and other plasma components generally believed to alter release kinetics in physiological samples. These findings shed light on the critical role that ammonia may play in contributing to the preclinical/clinical variability and performance seen with actively-loaded liposomal formulations of TPT and other weakly-basic anticancer agents. PMID:25456833

Effects of absorption enhancers in chloroquine suppository formulations: I. In vitro release characteristics.

PubMed

Onyeji, C O; Adebayo, A S; Babalola, C P

1999-12-01

The need to develop chloroquine suppository formulations that yield optimal bioavailability of the drug has been emphasized. This study demonstrates the effects of incorporation of known absorption-enhancing agents (nonionic surfactants and sodium salicylate) on the in vitro release characteristics of chloroquine from polyethylene glycol (1000:4000, 75:25%, w/w) suppositories. The release rates were determined using a modification of the continuous flow bead-bed dissolution apparatus for suppositories. Results showed that the extent of drug release from suppositories containing any of three surfactants (Tween 20, Tween 80 and Brij 35) was 100%, whereas 88% release was obtained with control formulation (without enhancer) (P<0.05). However, Tween 20 was more effective than Brij 35 and Tween 80 in improving the drug release rate. There was a concentration-dependent effect with Tween 20, and 4% (w/w) of this surfactant was associated with the highest increase in the rate of drug release from the suppositories. Sodium salicylate at a concentration of 25% (w/w) also significantly enhanced the drug release rate, but a higher concentration of the adjuvant markedly reduced both the rate and extent of drug release. Combined incorporation of Tween 20 and sodium salicylate did not significantly modify (P0.05) the rate of drug release when compared to the effect of the more effective single agent. Due to their effects in improving the drug release profiles coupled with their intrinsic absorption-promoting properties, it is suggested that incorporation of 4% (w/w) Tween 20 and/or 25% (w/w) sodium salicylate in the composite polyethylene glycol chloroquine suppository formulations, may result in enhancement of rectal absorption of the drug. This necessitates an in vivo validation.

Ca2+-induced Ca2+ Release Phenomena in Mammalian Sympathetic Neurons Are Critically Dependent on the Rate of Rise of Trigger Ca2+

PubMed Central

Hernández-Cruz, Arturo; Escobar, Ariel L.; Jiménez, Nicolás

1997-01-01

The role of ryanodine-sensitive intracellular Ca2+ stores present in nonmuscular cells is not yet completely understood. Here we examine the physiological parameters determining the dynamics of caffeine-induced Ca2+ release in individual fura-2–loaded sympathetic neurons. Two ryanodine-sensitive release components were distinguished: an early, transient release (TR) and a delayed, persistent release (PR). The TR component shows refractoriness, depends on the filling status of the store, and requires caffeine concentrations ≥10 mM. Furthermore, it is selectively suppressed by tetracaine and intracellular BAPTA, which interfere with Ca2+-mediated feedback loops, suggesting that it constitutes a Ca2+-induced Ca2+-release phenomenon. The dynamics of release is markedly affected when Sr2+ substitutes for Ca2+, indicating that Sr2+ release may operate with lower feedback gain than Ca2+ release. Our data indicate that when the initial release occurs at an adequately fast rate, Ca2+ triggers further release, producing a regenerative response, which is interrupted by depletion of releasable Ca2+ and Ca2+-dependent inactivation. A compartmentalized linear diffusion model can reproduce caffeine responses: When the Ca2+ reservoir is full, the rapid initial Ca2+ rise determines a faster occupation of the ryanodine receptor Ca2+ activation site giving rise to a regenerative release. With the store only partially loaded, the slower initial Ca2+ rise allows the inactivating site of the release channel to become occupied nearly as quickly as the activating site, thereby suppressing the initial fast release. The PR component is less dependent on the store's Ca2+ content. This study suggests that transmembrane Ca2+ influx in rat sympathetic neurons does not evoke widespread amplification by CICR because of its inability to raise [Ca2+] near the Ca2+ release channels sufficiently fast to overcome their Ca2+-dependent inactivation. Conversely, caffeine-induced Ca2+ release can undergo considerable amplification especially when Ca2+ stores are full. We propose that the primary function of ryanodine-sensitive stores in neurons and perhaps in other nonmuscular cells, is to emphasize subcellular Ca2+ gradients resulting from agonist-induced intracellular release. The amplification gain is dependent both on the agonist concentration and on the filling status of intracellular Ca2+ stores. PMID:9041445

Polyamide nanocapsules and nano-emulsions containing Parsol® MCX and Parsol® 1789: in vitro release, ex vivo skin penetration and photo-stability studies.

PubMed

Hanno, Ibrahim; Anselmi, Cecilia; Bouchemal, Kawthar

2012-02-01

To prepare polyamide nanocapsules for skin photo-protection, encapsulating α-tocopherol, Parsol®MCX (ethylhexyl methoxycinnamate) and/or Parsol®1789 (butyl methoxydibenzoylmethane). Nanocapsules were obtained by combining spontaneous emulsification and interfacial polycondensation reaction between sebacoyl chloride and diethylenetriamine. Nano-emulsions used as control were obtained by the same process without monomers. The influence of carrier on release rate was studied in vitro with a membrane-free model. Epidermal penetration of encapsulated sunscreens was ex vivo evaluated using Franz diffusion cells. Ability of encapsulated sunscreens to improve photo-stability was verified by comparing percentage of degradation after UV radiation exposure. Sunscreen-containing nanocapsules (260-400 nm) were successfully prepared; yield of encapsulation was >98%. Parsol®MCX and Parsol®1789 encapsulation led to decreased release rate by up to 60% in comparison with nano-emulsion and allowed minimum penetration through pig ear epidermis. Presence of polyamide shell protected encapsulated sunscreen filters from photo-degradation without affecting their activity. Encapsulation of Parsol®MCX and Parsol®1789 into oil-core of polyamide nanocapsules allowed protection from photo-degradation, controlled release from nanocapsules, and limited penetration through pig ear epidermis.

Nature of, and the formaldehyde off-gassing characteristics of, urea-formaldehyde foam insulation (UFFI). Final report to the Canadian Department of Consumer and Corporate Affairs: Product Safety Branch

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

Gammage, R.B.

1981-07-30

This report is divisible into the following four sections that pertain to the nature, application, and performance of urea-formaldehyde (UF) resins and foams in regard to their formaldehyde outgassing characteristics: elements of basic chemistry that affect hydrolysis and stability; pertinent experimental findings of several studies on the release of formaldehyde from urea-formaldehyde foam insulation (UFFI); studies that model the diffusion of formaldehyde through drywall and correlate the rate of formaldehyde emission with the air exchange rate and the concentration of formaldehyde; and, viability of materials and equipment for the controlled production of UFFI. Results indicate that UFFI is a complexmore » and intrinsically unstable material that releases formaldehyde over long-time periods. Even the best foams available in the US, prepared from low formaldehyde resins according to eight different manufacturers' specifications, have abundant potential for long-term or chronic release of formaldehyde. At the present time it is not possible to state that UFFI is a material whose long-term formaldehyde release characteristics can be adequately controlled or predicted.« less

Magnetic high throughput screening system for the development of nano-sized molecularly imprinted polymers for controlled delivery of curcumin.

PubMed

Piletska, Elena V; Abd, Bashar H; Krakowiak, Agata S; Parmar, Anitha; Pink, Demi L; Wall, Katie S; Wharton, Luke; Moczko, Ewa; Whitcombe, Michael J; Karim, Kal; Piletsky, Sergey A

2015-05-07

Curcumin is a versatile anti-inflammatory and anti-cancer agent known for its low bioavailability, which could be improved by developing materials capable of binding and releasing drug in a controlled fashion. The present study describes the preparation of magnetic nano-sized Molecularly Imprinted Polymers (nanoMIPs) for the controlled delivery of curcumin and their high throughput characterisation using microtitre plates modified with magnetic inserts. NanoMIPs were synthesised using functional monomers chosen with the aid of molecular modelling. The rate of release of curcumin from five polymers was studied under aqueous conditions and was found to correlate well with the binding energies obtained computationally. The presence of specific monomers was shown to be significant in ensuring effective binding of curcumin and to the rate of release obtained. Characterisation of the polymer particles was carried out using dynamic light scattering (DLS) technique and scanning electron microscopy (SEM) in order to establish the relationship between irradiation time and particle size. The protocols optimised during this study could be used as a blueprint for the development of nanoMIPs capable of the controlled release of potentially any compound of interest.

Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing.

PubMed

Kurczewska, Joanna; Pecyna, Paulina; Ratajczak, Magdalena; Gajęcka, Marzena; Schroeder, Grzegorz

2017-09-01

The influence of an inorganic support - halloysite nanotubes - on the release rate and biological activity of the antibiotic encapsulated in alginate-based dressings was studied. The halloysite samples were loaded with approx. 10 wt.% of the antibiotic and then encapsulated in Alginate and Gelatin/Alginate gels. The material functionalized with aliphatic amine significantly extended the release of vancomycin from alginate-based gels as compared to that achieved when silica was used. After 24 h, the released amounts of the antibiotic immobilized at silica reached 70%, while for the drug immobilized at halloysite the released amount of vancomycin reached 44% for Alginate discs. The addition of gelatin resulted in even more prolonged sustained release of the drug. The antibiotic was released from the system with a double barrier with Higuchi kinetic model and Fickian diffusion mechanism. Only the immobilized drug encapsulated in Alginate gel demonstrated very good antimicrobial activity against various bacteria. The inhibition zones were greater than those of the standard discs for the staphylococci and enterococci bacteria tested. The addition of gelatin adversely affected the biological activity of the system. The inhibition zones were smaller than those of the reference samples. A reduction in the drug dose by half had no significant effect on changing the release rate and microbiological activity. The in vivo toxicity studies of the material with immobilized drug were carried out with Acutodesmus acuminatus and Daphnia magna . The material studied had no effect on the living organisms used in the bioassays. The proposed system with a double barrier demonstrated high storage stability.