Evaluation of pheromone release from commercial mating disruption dispensers.

PubMed

Tomaszewska, Elizabeth; Hebert, Vincent R; Brunner, Jay F; Jones, Vincent P; Doerr, Mike; Hilton, Richard

2005-04-06

Pome fruit growers and crop consultants have expressed concerns about the seasonal release performance of commercial codling moth mating disruption dispenser products. Because of these concerns, we developed a laboratory flow-through volatile collection system (VCS) for measuring the volatile release of the codling moth sex pheromone, codlemone, from commercially available hand-applied dispensers. Under controlled air-flow and temperature conditions, the released vapor was trapped onto a polyurethane foam adsorbent followed by solvent extraction, solvent reduction, and GC/MS determination. Method recovery and breakthrough validations were performed to demonstrate system reliability before determining codlemone release from commercial dispensers field-aged over 140 days. The volatile collection was carried out in a consistent manner among five dispenser types most commonly used by growers, so that direct comparison of performance could be made. The comparison showed differences in the amount of pheromone released and in the patterns of release throughout the season between dispenser types. The variation in release performance demonstrates the need for routine evaluation of commercially marketed mating disruption dispensers. We believe that the simple and cost-effective volatile collection system can assist pheromone dispenser manufacturers in determining seasonal dispenser performance before new products are introduced into the commercial market and in rapidly verifying dispenser release when field-aged dispenser efficacy is in question.

The Blocking Flap for Ulnar Nerve Instability After In Situ Release: Technique and a Grading System of Ulnar Nerve Instability to Guide Treatment.

PubMed

Tang, Peter

2017-12-01

In situ ulnar nerve release has been gaining popularity as a simple, effective, and low-morbidity procedure for the treatment of cubital tunnel syndrome. One concern with the technique is how to manage the unstable ulnar nerve after release. It is unclear how much nerve subluxation will lead to problems and surprisingly there is no grading system to assess ulnar nerve instability. I propose such a grading system, as well as a new technique to stabilize the unstable ulnar nerve. The blocking flap technique consists of raising a rectangular flap off the flexor/pronator fascia and attaching it to the posterior subcutaneous flap so that it blocks the nerve from subluxation/dislocation.

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.

Controlled release of cyclosporine A self-nanoemulsifying systems from osmotic pump tablets: near zero-order release and pharmacokinetics in dogs.

PubMed

Zhang, Xi; Yi, Yueneng; Qi, Jianping; Lu, Yi; Tian, Zhiqiang; Xie, Yunchang; Yuan, Hailong; Wu, Wei

2013-08-16

It is very important to enhance the absorption simultaneously while designing controlled release delivery systems for poorly water-soluble and poorly permeable drugs (BCS IV). In this study, controlled release of cyclosporine (CyA) was achieved by the osmotic release strategy taking advantage of the absorption-enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDSs). The liquid SNEDDS consisting of Labrafil M 1944CS, Transcutol P and Cremophor EL was absorbed by the osmotic tablet core excipients (sucrose, lactose monohydrate, polyethylene oxide, and partly pregelatinized starch) and then transformed into osmotic tablets. Near zero-order release could be achieved for CyA-loaded nanoemulsions reconstituted from the SNEDDS. In general, the influencing factor study indicated that the release rate increased with increase of inner osmotic pressure, ratio of osmotic agent to suspending agent, content of pore-forming agent, and size of release orifice, whereas the thickness of the membrane impeded the release of CyA nanoemulsion. Pharmacokinetic study showed steady blood CyA profiles with prolonged Tmax and MRT, and significantly reduced Cmax for self-nanoemulsifying osmotic pump tablet (SNEOPT) in comparison with highly fluctuating profiles of the core tablet and Sandimmune Neoral(®). However, similar oral bioavailability was observed for either controlled release or non-controlled release formulations. It was concluded that simultaneous controlling on CyA release and absorption-enhancing had been achieved by a combination of osmotic tablet and SNEDDS. Copyright © 2013 Elsevier B.V. All rights reserved.

Enzymatic Filter for Improved Separation of Output Signals in Enzyme Logic Systems towards 'Sense and Treat' Medicine

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

Mailloux, Shay; Zavalov, Oleksandr; Guz, Nataliia

2014-01-01

The major challenge for application of autonomous medical sensing systems is the noise produced by non-zero physiological concentrations of the sensed target. If the level of noise is high, then a real signal indicating abnormal changes in the physiological levels of the analytes might be hindered. Inevitably, this could lead to wrong diagnostics and treatment, and would have a negative impact on human health. Here, we report the realization of a filter system implemented to improve both the fidelity of sensing and accuracy of consequent drug release. A new filtering method was tested in the sensing system for the diagnosismore » of liver injury. This sensing system used the enzymes alanine transaminase (ALT) and aspartate transaminase (AST) as the inputs. Furthermore, the output of the sensing system was designed to trigger drug release, and therefore, the role of the filter in drug release was also investigated. The drug release system consists of beads with an iron - cross-linked alginate core coated with different numbers of layers of poly-L-lysine. Dissolution of the beads by the output signals of the sensing system in the presence and absence of the filter was monitored by release of encapsulated in the beads rhodamine - 6G dye mimicking release of a real drug. The obtained results offer a new view on the problem of noise reduction for systems intended to be part of sense and treat medical devices.« less

Common Badging and Access Control System (CBACS)

NASA Technical Reports Server (NTRS)

Baldridge, Tim

2005-01-01

The goals of the project are: Achieve high business value through a common badging and access control system that integrates with smart cards. Provide physical (versus logical) deployment of smart cards initially. Provides a common consistent and reliable environment into which to release the smart card. Gives opportunity to develop agency-wide consistent processes, practices and policies. Enables enterprise data capture and management. Promotes data validation prior to SC issuance.

Quantification of effect of sequential posteromedial release on flexion and extension gaps: a computer-assisted study in cadaveric knees.

PubMed

Mullaji, Arun; Sharma, Amit; Marawar, Satyajit; Kanna, Raj

2009-08-01

A novel sequence of posteromedial release consistent with surgical technique of total knee arthroplasty was performed in 15 cadaveric knees. Medial and lateral flexion and extension gaps were measured after each step of the release using a computed tomography-free computer navigation system. A spring-loaded distractor and a manual distractor were used to distract the joint. Posterior cruciate ligament release increased flexion more than extension gap; deep medial collateral ligament release had a negligible effect; semimembranosus release increased the flexion gap medially; reduction osteotomy increased medial flexion and extension gaps; superficial medial collateral ligament release increased medial joint gap more in flexion and caused severe instability. This sequence of release led to incremental and differential effects on flexion-extension gaps and has implications in correcting varus deformity.

Mass spectra of neutral particles released during electrical breakdown of thin polymer films

NASA Technical Reports Server (NTRS)

Kendall, B. R. F.

1985-01-01

A special type of time-of-flight mass spectrometer triggered from the breakdown event was developed to study the composition of the neutral particle flux released during the electrical breakdown of polymer films problem. Charge is fed onto a metal-backed polymer surface by a movable smooth platinum contact. A slowly increasing potential from a high-impedance source is applied to the contact until breakdown occurs. The breakdown characteristics is made similar to those produced by an electron beam charging system operating at similar potentials. The apparatus showed that intense instantaneous fluxes of neutral particles are released from the sites of breakdown events. For Teflon FEP films of 50 and 75 microns thickness the material released consists almost entirely of fluorocarbon fragments, some of them having masses greater than 350 atomic mass units amu, while the material released from a 50 micron Kapton film consists mainly of light hydrocarbons with masses at or below 44 amu, with additional carbon monoxide and carbon dioxide. The apparatus is modified to allow electron beam charging of the samples.

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.

Time and pH dependent colon specific, pulsatile delivery of theophylline for nocturnal asthma.

PubMed

Mastiholimath, V S; Dandagi, P M; Jain, S Samata; Gadad, A P; Kulkarni, A R

2007-01-02

In this study, investigation of an oral colon specific, pulsatile device to achieve time and/or site specific release of theophylline, based on chronopharmaceutical consideration. The basic design consists of an insoluble hard gelatin capsule body, filled with eudragit microcapsules of theophylline and sealed with a hydrogel plug. The entire device was enteric coated, so that the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. The theophylline microcapsules were prepared in four batches, with Eudragit L-100 and S-100 (1:2) by varying drug to polymer ratio and evaluated for the particle size, drug content and in vitro release profile and from the obtained results; one better formulation was selected for further fabrication of pulsatile capsule. Different hydrogel polymers were used as plugs, to maintain a suitable lag period and it was found that the drug release was controlled by the proportion of polymers used. In vitro release studies of pulsatile device revealed that, increasing the hydrophilic polymer content resulted in delayed release of theophylline from microcapsules. The gamma scintigraphic study pointed out the capability of the system to release drug in lower parts of GIT after a programmed lag time for nocturnal asthma. Programmable pulsatile, colon-specific release has been achieved from a capsule device over a 2-24h period, consistent with the demands of chronotherapeutic drug delivery.

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.

Strategies to overcome pH-dependent solubility of weakly basic drugs by using different types of alginates.

PubMed

Gutsche, S; Krause, M; Kranz, H

2008-12-01

Weakly basic drugs demonstrate higher solubility at lower pH, thus often leading to faster drug release at lower pH. The objective of this study was to achieve pH-independent release of weakly basic drugs from extended release formulations based on the naturally occurring polymer sodium alginate. Three approaches to overcome the pH-dependent solubility of the weakly basic model drug verapamil hydrochloride were investigated. First, matrix tablets were prepared by direct compression of drug substance with different types of sodium alginate only. Second, pH-modifiers were added to the drug/alginate matrix systems. Third, press-coated tablets consisting of an inner pH-modifier tablet core and an outer drug/sodium alginate coat were prepared. pH-Independent drug release was achieved from matrix tablets consisting of selected alginates and drug substance only. Alginates are better soluble at higher pH. Therefore, they are able to compensate the poor solubility of weakly basic drugs at higher pH as the matrix of the tablets dissolves faster. This approach was successful when using alginates that demonstrated fast hydration and erosion at higher pH. The approach failed for alginates with less-pronounced erosion at higher pH. The addition of fumaric acid to drug/alginate-based matrix systems decreased the microenvironmental pH within the tablets thus increasing the solubility of the weakly basic drug at higher pH. Therefore, pH-independent drug release was achieved irrespective of the type of alginate used. Drug release from press-coated tablets did not provide any further advantages as compound release remained pH-dependent.

Fabrication of core-shell micro/nanoparticles for programmable dual drug release by emulsion electrospraying

NASA Astrophysics Data System (ADS)

Wang, Yazhou; Zhang, Yiqiong; Wang, Bochu; Cao, Yang; Yu, Qingsong; Yin, Tieying

2013-06-01

The study aimed at constructing a novel drug delivery system for programmable multiple drug release controlled with core-shell structure. The core-shell structure consisted of chitosan nanoparticles as core and polyvinylpyrrolidone micro/nanocoating as shell to form core-shell micro/nanoparticles, which was fabricated by ionic gelation and emulsion electrospray methods. As model drug agents, Naproxen and rhodamine B were encapsulated in the core and shell regions, respectively. The core-shell micro/nanoparticles thus fabricated were characterized and confirmed by scanning electron microscope, transmission electron microscope, and fluorescence optical microscope. The core-shell micro/nanoparticles showed good release controllability through drug release experiment in vitro. It was noted that a programmable release pattern for dual drug agents was also achieved by adjusting their loading regions in the core-shell structures. The results indicate that emulsion electrospraying technology is a promising approach in fabrication of core-shell micro/nanoparticles for programmable dual drug release. Such a novel multi-drug delivery system has a potential application for the clinical treatment of cancer, tuberculosis, and tissue engineering.

The consistency approach for quality control of vaccines - a strategy to improve quality control and implement 3Rs.

PubMed

De Mattia, Fabrizio; Chapsal, Jean-Michel; Descamps, Johan; Halder, Marlies; Jarrett, Nicholas; Kross, Imke; Mortiaux, Frederic; Ponsar, Cecile; Redhead, Keith; McKelvie, Jo; Hendriksen, Coenraad

2011-01-01

Current batch release testing of established vaccines emphasizes quality control of the final product and is often characterized by extensive use of animals. This report summarises the discussions of a joint ECVAM/EPAA workshop on the applicability of the consistency approach for routine release of human and veterinary vaccines and its potential to reduce animal use. The consistency approach is based upon thorough characterization of the vaccine during development and the principle that the quality of subsequent batches is the consequence of the strict application of a quality system and of a consistent production of batches. The concept of consistency of production is state-of-the-art for new-generation vaccines, where batch release is mainly based on non-animal methods. There is now the opportunity to introduce the approach into established vaccine production, where it has the potential to replace in vivo tests with non-animal tests designed to demonstrate batch quality while maintaining the highest quality standards. The report indicates how this approach may be further developed for application to established human and veterinary vaccines and emphasizes the continuing need for co-ordination and harmonization. It also gives recommendations for work to be undertaken in order to encourage acceptance and implementation of the consistency approach. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.

MODELS-3 (CMAQ). NARSTO NEWS (VOL. 3, NO. 2, SUMMER/FALL 1999)

EPA Science Inventory

A revised version of the U.S. EPA's Models-3/CMAQ system was released on June 30, 1999. Models-3 consists of a sophisticated computational framework for environmental models allowing for much flexibility in the communications between component parts of the system, in updating or ...

Evaluation of quality of life and sexual functioning of women using levonorgestrel-releasing intrauterine contraceptive system--Mirena.

PubMed

Skrzypulec, Violetta; Drosdzol, Agnieszka

2008-12-01

The advantages ensuing from the high contraceptive efficacy, positive effect on the parameters of the menstrual cycle as well as other values of the levonorgestrel-releasing intrauterine system may play an important role in women's sexual life. The aim of the study was to evaluate the effect of the levonorgestrel-releasing intrauterine system on the quality of life and sexual functioning of women. The research encompassed 200 women aged between 30 and 45. 52 women using the levonorgestrel-releasing intrauterine system were qualified to the study as the research group (Mirena Group). The control groups consisted of 48 women using a different type of intrauterine device (Control Group I--Other IUD) and 50 women using no contraception (Control Group II). A specific questionnaire with a general part concerning socio-demographic conditions, a part dealing with contraception and Polish version of self-evaluation inventories: Short Form-36 Health Survey, Female Sexual Function Index and Mell-Krat Scale was used as a research tool. Quality of life parameters for women using the Mirena system were higher than for the control groups, especially in the aspect of general health, energy/fatigue and emotional well-being. A significant beneficial effect of the levonorgestrel-releasing intrauterine system on sexual functioning (sexual desire and arousal) was also revealed in the study. Sexual dysfunctions were diagnosed in 20.8% of Other IUD, 34.7% of Control Group II and 9.6% of Mirena Group. Levonorgestrel-releasing intrauterine system increases female quality of life and sexual functioning parameters.

Polymeric nanotheranostics for real-time non-invasive optical imaging of breast cancer progression and drug release.

PubMed

Ferber, Shiran; Baabur-Cohen, Hemda; Blau, Rachel; Epshtein, Yana; Kisin-Finfer, Einat; Redy, Orit; Shabat, Doron; Satchi-Fainaro, Ronit

2014-09-28

Polymeric nanocarriers conjugated with low molecular weight drugs are designed in order to improve their efficacy and toxicity profile. This approach is particularly beneficial for anticancer drugs, where the polymer-drug conjugates selectively accumulate at the tumor site, due to the enhanced permeability and retention (EPR) effect. The conjugated drug is typically inactive, and upon its pH- or enzymatically-triggered release from the carrier, it regains its therapeutic activity. These settings lack information regarding drug-release time, kinetics and location. Thereby, real-time non-invasive intravital monitoring of drug release is required for theranostics (therapy and diagnostics). We present here the design, synthesis and characterization of a theranostic nanomedicine, based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer, owing its fluorescence-based monitoring of site-specific drug release to a self-quenched near-infrared fluorescence (NIRF) probe. We designed two HPMA copolymer-based systems that complement to a theranostic nanomedicine. The diagnostic system consists of self-quenched Cy5 (SQ-Cy5) as a reporter probe and the therapeutic system is based on the anticancer agent paclitaxel (PTX). HPMA copolymer-PTX/SQ-Cy5 systems enable site-specific release upon enzymatic degradation in cathepsin B-overexpressing breast cancer cells. The release of the drug occurs concomitantly with the activation of the fluorophore to its Turn-ON state. HPMA copolymer-SQ-Cy5 exhibits preferable body distribution and drug release compared with the free drug and probe when administered to cathepsin B-overexpressing 4T1 murine mammary adenocarcinoma-bearing mice. This approach of co-delivery of two complementary systems serves as a proof-of-concept for real-time deep tissue intravital orthotopic monitoring and may have the potential use in clinical utility as a theranostic nanomedicine. Copyright © 2014. Published by Elsevier Ireland Ltd.

Recent advances in oral pulsatile drug delivery.

PubMed

Kalantzi, Lida E; Karavas, Evangelos; Koutris, Efthimios X; Bikiaris, Dimitrios N

2009-01-01

Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.

Corticostriatal dysfunction underlies diminished striatal ascorbate release in the R6/2 mouse model of Huntington’s disease

PubMed Central

Dorner, Jenelle L.; Miller, Benjamin R.; Klein, Emma L.; Murphy-Nakhnikian, Alexander; Andrews, Rachel L.; Barton, Scott J.; Rebec, George V.

2009-01-01

A behavior-related deficit in the release of ascorbate (AA), an antioxidant vitamin, occurs in the striatum of R6/2 mice expressing the human mutation for Huntington’s disease (HD), a dominantly inherited condition characterized by striatal dysfunction. To determine the role of corticostriatal fibers in AA release, we combined slow-scan voltammetry with electrical stimulation of cortical afferents to measure evoked fluctuations in extracellular AA in wild-type (WT) and R6/2 striatum. Although cortical stimulation evoked a rapid increase in AA release in both groups, the R6/2 response had a significantly shorter duration and smaller magnitude than WT. To determine if corticostriatal dysfunction also underlies the behavior-related AA deficit in R6/2s, we measured striatal AA release in separate groups of mice treated with d-amphetamine (5 mg/kg), a psychomotor stimulant known to release AA from corticostriatal terminals independently of dopamine. Relative to WT, both AA release and behavioral activation were diminished in R6/2 mice. Collectively, our results show that the corticostriatal pathway is directly involved in AA release and that this system is dysfunctional in HD. Moreover, because AA release requires glutamate uptake, a failure of striatal AA release in HD is consistent with an overactive glutamate system and diminished glutamate transport, both of which are thought to be central to HD pathogenesis. PMID:19616518

High-amylose sodium carboxymethyl starch matrices for oral, sustained drug-release: formulation aspects and in vitro drug-release evaluation.

PubMed

Brouillet, F; Bataille, B; Cartilier, L

2008-05-22

High-amylose sodium carboxymethyl starch (HASCA), produced by spray-drying (SD), was previously shown to have interesting properties as a promising pharmaceutical sustained drug-release tablet excipient for direct compression, including ease of manufacture and high crushing strength. This study describes the effects of some important formulation parameters, such as compression force (CF), tablet weight (TW), drug-loading and electrolyte particle size, on acetaminophen-release performances from sustained drug-release matrix tablets based on HASCA. An interesting linear relationship between TW and release time was observed for a typical formulation of the system consisting of 40% (w/w) acetaminophen as model drug and 27.5% NaCl as model electrolyte dry-mixed with HASCA. Application of the Peppas and Sahlin model gave a better understanding of the mechanisms involved in drug-release from the HASCA matrix system, which is mainly controlled by surface gel layer formation. Indeed, augmenting TW increased the contribution of the diffusion mechanism. CFs ranging from 1 to 2.5 tonnes/cm(2) had no significant influence on the release properties of tablets weighing 400 or 600 mg. NaCl particle size did not affect the acetaminophen-release profile. Finally, these results prove that the new SD process developed for HASCA manufacture is suitable for obtaining similar-quality HASCA in terms of release and compression performances.

Programming of Multicomponent Temporal Release Profiles in 3D Printed Polypills via Core-Shell, Multilayer, and Gradient Concentration Profiles.

PubMed

Haring, Alexander P; Tong, Yuxin; Halper, Justin; Johnson, Blake N

2018-06-10

Additive manufacturing (AM) appears poised to provide novel pharmaceutical technology and controlled release systems, yet understanding the effects of processing and post-processing operations on pill design, quality, and performance remains a significant barrier. This paper reports a study of the relationship between programmed concentration profile and resultant temporal release profile using a 3D printed polypill system consisting of a Food and Drug Administration (FDA) approved excipient (Pluronic F-127) and therapeutically relevant dosages of three commonly used oral agents for treatment of type 2 diabetes (300-500 mg per pill). A dual-extrusion hydrogel microextrusion process enables the programming of three unique concentration profiles, including core-shell, multilayer, and gradient structures. Experimental and computational studies of diffusive mass transfer processes reveal that programmed concentration profiles are dynamic throughout both pill 3D printing and solidification. Spectrophotometric assays show that the temporal release profiles could be selectively programmed to exhibit delayed, pulsed, or constant profiles over a 5 h release period by utilizing the core-shell, multilayer, and gradient distributions, respectively. Ultimately, this work provides new insights into the mass transfer processes that affect design, quality, and performance of spatially graded controlled release systems, as well as demonstrating the potential to create disease-specific polypill technology with programmable temporal release profiles. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chronomodulated drug delivery system of urapidil for the treatment of hypertension

PubMed Central

Chaudhary, Sona S.; Patel, Hetal K.; Parejiya, Punit B.; Shelat, Pragna K.

2015-01-01

Introduction: Hypertension is a disease which shows circadian rhythm in the pattern of two peaks, one in the evening at about 7pm and other in the early morning between 4 am to 8 am. Conventional therapies are incapable to target those time points when actually the symptoms get worsened. To achieve drug release at two time points, chronomodulated delivery system may offer greater benefits. Materials and methods: The chronomodulated system comprised of dual approach; immediate release granules (IRG) and pulsatile release mini-tablets (PRM) filled in the hard gelatin capsule. The mini-tablets were coated using Eudragit S-100 which provided the lag time. To achieve the desired release, various parameters like coating duration and coat thickness were studied. The immediate release granules were evaluated for micromeritical properties and drug release, while mini-tablets were evaluated for various parameters such as hardness, thickness, friability, weight variation, drug content, and disintegration time and in-vitro drug release. Compatibility of drug-excipient was checked by fourier transform infrared spectroscopy and Differential scanning calorimetry studies and pellets morphology was done by Scanning electron microscopy studies. Results: The in-vitro release profile suggested that immediate release granules gives drug release within 20 min at the time of evening attack while the programmed pulsatile release was achieved from coated mini-tablets after a lag time of 9hrs, which was consistent with the demand of drug during early morning hour attack. Pellets found to be spherical in shape with smooth surface. Moreover compatibility studies illustrated no deleterious reaction between drug and polymers used in the study. Conclusions: The dual approach of developed chronomodulated formulation found to be satisfactory in the treatment of hypertension. PMID:25838996

In Vivo Imaging of the Stability and Sustained Cargo Release of an Injectable Amphipathic Peptide-Based Hydrogel.

PubMed

Oyen, Edith; Martin, Charlotte; Caveliers, Vicky; Madder, Annemieke; Van Mele, Bruno; Hoogenboom, Richard; Hernot, Sophie; Ballet, Steven

2017-03-13

Hydrogels are promising materials for biomedical applications such as tissue engineering and controlled drug release. In the past two decades, the peptide hydrogel subclass has attracted an increasing level of interest from the scientific community because of its numerous advantages, such as biocompatibility, biodegradability, and, most importantly, injectability. Here, we report on a hydrogel consisting of the amphipathic hexapeptide H-FEFQFK-NH 2 , which has previously shown promising in vivo properties in terms of releasing morphine. In this study, the release of a small molecule, a peptide, and a protein cargo as representatives of the three major drug classes is directly visualized by in vivo fluorescence and nuclear imaging. In addition, the in vivo stability of the peptide hydrogel system is investigated through the use of a radiolabeled hydrogelator sequence. Although it is shown that the hydrogel remains present for several days, the largest decrease in volume takes place within the first 12 h of subcutaneous injection, which is also the time frame wherein the cargos are released. Compared to the situation in which the cargos are injected in solution, a prolonged release profile is observed up to 12 h, showing the potential of our hydrogel system as a scaffold for controlled drug delivery. Importantly, this study elucidates the release mechanism of the peptide hydrogel system that seems to be based on erosion of the hydrogel providing a generally applicable controlled release platform for small molecule, peptide, and protein drugs.

Nonclinical evaluation of the potential for mast cell activation by an erythropoietin analog

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

Weaver, James L., E-mail: James.Weaver@fda.hhs.gov; Boyne, Michael, E-mail: mboyne@biotechlogic.com; Pang, Eric, E-mail: Eric.Pang@fda.hhs.gov

The erythropoietin analog peginesatide was withdrawn from marketing due to unexpected severe anaphylactic reactions associated with administration of the multi-use formulation. The adverse events occurred rapidly following the first ever administration of the drug with most affected patients becoming symptomatic in less than 30 min. This is most consistent with an anaphylactoid reaction due to direct activation of mast cells. Laboratory evaluation was undertaken using rat peritoneal mast cells as the model system. Initial studies showed that high concentrations of the formulated drug as well as formulated vehicle alone could cause mast cell degranulation as measured by histamine release. Themore » purified active drug was not able to cause histamine release whereas the vehicle filtrate and lab created drug vehicle were equally potent at causing histamine release. Individual formulations of vehicle leaving one component out showed that histamine release was due to phenol. Dose response studies with phenol showed a very sharp dose response curve that was similar in three buffer systems. Cellular analysis by flow cytometry showed that the histamine release was not due to cell death, and that changes in light scatter parameters consistent with degranulation were rapidly observed. Limited testing with primary human mast cells showed a similar dose response of histamine release with exposure to phenol. To provide in vivo confirmation, rats were injected with vehicle formulated with various concentrations of phenol via a jugular vein cannula. Significant release of histamine was detected in blood samples taken 2 min after dosing at the highest concentrations tested. - Highlights: • Peginesatide caused severe anaphylactoid reactions in 0.2% of patients. • Both formulated drug and vehicle cause degranulation of rat mast cells. • Phenol was identified as the vehicle component causing degranulation. • Human mast cells show similar dose response to phenol as rat mast cells. • Histamine release could be caused in vivo in rats by rapid phenol injection.« less

Large Scale Software Building with CMake in ATLAS

NASA Astrophysics Data System (ADS)

Elmsheuser, J.; Krasznahorkay, A.; Obreshkov, E.; Undrus, A.; ATLAS Collaboration

2017-10-01

The offline software of the ATLAS experiment at the Large Hadron Collider (LHC) serves as the platform for detector data reconstruction, simulation and analysis. It is also used in the detector’s trigger system to select LHC collision events during data taking. The ATLAS offline software consists of several million lines of C++ and Python code organized in a modular design of more than 2000 specialized packages. Because of different workflows, many stable numbered releases are in parallel production use. To accommodate specific workflow requests, software patches with modified libraries are distributed on top of existing software releases on a daily basis. The different ATLAS software applications also require a flexible build system that strongly supports unit and integration tests. Within the last year this build system was migrated to CMake. A CMake configuration has been developed that allows one to easily set up and build the above mentioned software packages. This also makes it possible to develop and test new and modified packages on top of existing releases. The system also allows one to detect and execute partial rebuilds of the release based on single package changes. The build system makes use of CPack for building RPM packages out of the software releases, and CTest for running unit and integration tests. We report on the migration and integration of the ATLAS software to CMake and show working examples of this large scale project in production.

76 FR 16653 - Petition for Exemption; Summary of Petition Received

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

.... (FWIA) is requesting relief from the requirement to provide minimum fuel supply on flight release forms in pounds or gallons. The exemption will enable FWIA to state the minimum fuel supply in the unit of measurement that is consistent with the aircraft fuel system and the company's weight and balance system. [FR...

A controlled antibiotic release system to prevent orthopedic-implant associated infections: An in vitro study

PubMed Central

Gimeno, Marina; Pinczowski, Pedro; Pérez, Marta; Giorello, Antonella; Martínez, Miguel Ángel; Santamaría, Jesús; Arruebo, Manuel; Luján, Lluís

2015-01-01

A new device for local delivery of antibiotics is presented, with potential use as a drug-eluting fixation pin for orthopedic applications. The implant consists of a stainless steel hollow tubular reservoir packed with the desired antibiotic. Release takes place through several orifices previously drilled in the reservoir wall, a process that does not compromise the mechanical properties required for the implant. Depending on the antibiotic chosen and the number of orifices, the release profile can be tailored from a rapid release of the load (ca. 20 h) to a combination of rapid initial release and slower, sustained release for a longer period of time (ca. 200 h). An excellent bactericidal action is obtained, with 4-log reductions achieved in as little as 2 h, and total bacterial eradication in 8 h using 6-pinholed implants filled with cefazolin. PMID:26297104

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.

A novel osmotic pump-based controlled delivery system consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen: in vitro and in vivo evaluation.

PubMed

Li, Shujuan; Wang, Xiaoyu; Wang, Yingying; Zhao, Qianqian; Zhang, Lina; Yang, Xinggang; Liu, Dandan; Pan, Weisan

2015-01-01

In this study, a novel controlled release osmotic pump capsule consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen (FP) was developed to improve the solubility and oral bioavailability of FP and to minimize the fluctuation of plasma concentration. The pH-modulated solid dispersion containing FP, Kollidon® 12 PF and Na2CO3 at a weight ratio of 1/4.5/0.02 was prepared using the solvent evaporation method. The osmotic pump capsule was assembled by semi-permeable capsule shell of cellulose acetate (CA) prepared by the perfusion method. Then, the solid dispersion, penetration enhancer, and suspending agents were tableted and filled into the capsule. Central composite design-response surface methodology was used to evaluate the influence of factors on the responses. A second-order polynomial model and a multiple linear model were fitted to correlation coefficient of drug release profile and ultimate cumulative release in 12 h, respectively. The actual response values were in good accordance with the predicted ones. The optimized formulation showed a complete drug delivery and zero-order release rate. Beagle dogs were used to be conducted in the pharmacokinetic study. The in vivo study indicated that the relative bioavailability of the novel osmotic pump system was 133.99% compared with the commercial preparation. The novel controlled delivery system with combination of pH-modulated solid dispersion and osmotic pump system is not only a promising strategy to improve the solubility and oral bioavailability of poorly soluble ionizable drugs but also an effective way to reduce dosing frequency and minimize the plasma fluctuation.

pH responsive controlled release of anti-cancer hydrophobic drugs from sodium alginate and hydroxyapatite bi-coated iron oxide nanoparticles.

PubMed

Manatunga, Danushika C; de Silva, Rohini M; de Silva, K M Nalin; de Silva, Nuwan; Bhandari, Shiva; Yap, Yoke Khin; Costha, N Pabakara

2017-08-01

Developing a drug carrier system which could perform targeted and controlled release over a period of time is utmost concern in the pharmaceutical industry. This is more relevant when designing drug carriers for poorly water soluble drug molecules such as curcumin and 6-gingerol. Development of a drug carrier system which could overcome these limitations and perform controlled and targeted drug delivery is beneficial. This study describes a promising approach for the design of novel pH sensitive sodium alginate, hydroxyapatite bilayer coated iron oxide nanoparticle composite (IONP/HAp-NaAlg) via the co-precipitation approach. This system consists of a magnetic core for targeting and a NaAlg/HAp coating on the surface to accommodate the drug molecules. The nanocomposite was characterized using FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. The loading efficiency and loading capacity of curcumin and 6-gingerol were examined. In vitro drug releasing behavior of curcumin and 6-gingerol was studied at pH 7.4 and pH 5.3 over a period of seven days at 37°C. The mechanism of drug release from the nanocomposite of each situation was studied using kinetic models and the results implied that, the release is typically via diffusion and a higher release was observed at pH 5.3. This bilayer coated system can be recognized as a potential drug delivery system for the purpose of curcumin and 6-gingerol release in targeted and controlled manner to treat diseases such as cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled porosity osmotic pump-based controlled release systems of pseudoephedrine. I. Cellulose acetate as a semipermeable membrane.

PubMed

Makhija, Sapna N; Vavia, Pradeep R

2003-04-14

A controlled porosity osmotic pump-based drug delivery system has been described in this study. Unlike the elementary osmotic pump (EOP) which consists of an osmotic core with the drug surrounded by a semipermeable membrane drilled with a delivery orifice, controlled porosity of the membrane is accomplished by the use of different channeling agents in the coating. The usual dose of pseudoephedrine is 60 mg to be taken three or four times daily. It has a short plasma half life of 5-8 h. Hence, pseudoephedrine was chosen as a model drug with an aim to develop a controlled release system for a period of 12 h. Sodium bicarbonate was used as the osmogent. The effect of different ratios of drug:osmogent on the in-vitro release was studied. Cellulose acetate (CA) was used as the semipermeable membrane. Different channeling agents tried were diethylphthalate (DEP), dibutylphthalate (DBP), dibutylsebacate (DBS) and polyethyleneglycol 400 (PEG 400). The effect of polymer loading on in-vitro drug release was studied. It was found that drug release rate increased with the amount of osmogent due to the increased water uptake, and hence increased driving force for drug release. This could be retarded by the proper choice of channeling agent in order to achieve the desired zero order release profile. Also the lag time seen with tablets coated using diethylphthalate as channeling agent was reduced by using a hydrophilic plasticizer like polyethyleneglycol 400 in combination with diethylphthalate. This system was found to deliver pseudoephedrine at a zero order rate for 12 h. The effect of pH on drug release was also studied. The optimized formulations were subjected to stability studies as per ICH guidelines at different temperature and humidity conditions.

Biocompatibility and antifibrotic effect of UV-cross-linked hyaluronate as a release-system for tranilast after trabeculectomy in a rabbit model--a pilot study.

PubMed

Spitzer, Martin S; Sat, Macarena; Schramm, Charlotte; Schnichels, Sven; Schultheiss, Maximilian; Yoeruek, Efdal; Dzhelebov, Dimitar; Szurman, Peter

2012-06-01

To analyze the release kinetics and the clinical and histological effects of UV-cross-linked hyaluronic acid as a release-system for the transforming growth factor β-2 antagonist tranilast with anti-phlogistic properties on intraocular pressure after trabeculectomy in an aggressive scarring animal model. Hyaluronate acid was UV-cross linked and loaded with tranilast. The release of tranilast into a buffered salt solution was assessed spectrophotometrically. Glaucoma filtration surgery, similar to that performed in clinical practice, was performed on chinchilla rabbits. The rabbits were divided in 3 groups. (Group A: trabeculectomy alone, group B: trabeculectomy with a cross-linked hyaluronic acid gel preparation and group C: trabeculectomy with cross-linked hyaluronic gel preparation mixed with tranilast). Antifibrotic efficacy was established by clinical response and histologic examination. The cross-linked gels released tranilast for up to 26 h. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. Both the gel preparation alone and the gel preparation mixed with tranilast were well tolerated in vivo. No adverse effects such as inflammation, corneal toxicity or blurring of the optical media were observed. The intraocular pressure reached preoperative levels within 9 days after surgery in control animals and group B, but remained significantly reduced (p = 0.00016) in the group with tranilast until day 22. The data of this pilot study suggest that the intraoperative application of UV-crossed linked hyaluronic acid used as a slow release system for tranilast may improve the surgical outcome of glaucoma filtration surgery.

FTIR Analyses of Hypervelocity Impact Deposits: DebriSat Tests

DTIC Science & Technology

2015-03-27

Aerospace Concept Design Center advised on selection of materials for various subsystems. • Test chamber lined with “soft catch” foam panels to trap...C-0001 Authorized by: Space Systems Group Distribution Statement A: Approved for public release; distribution unlimited Report...Pre Preshot target was a multi-shock shield supplied by NASA designed to catch the projectile. It consisted of seven bumper panels consisting of

Formulation, development, and evaluation of floating pulsatile drug delivery system of atenolol.

PubMed

Jagdale, Swati C; Sali, Monali S; Barhate, Ajay L; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The objective of this work was to develop and evaluate a floating-pulsatile drug delivery of atenolol. The floating-pulsatile concept was applied to increase the gastric residence of the dosage form by having lag phase followed by a burst release. The system was generated which consisted of three different parts: a core tablet, containing the active ingredient; an erodible outer shell; and a top cover buoyant layer. The dry, coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with hydroxypropyl methylcellulose (HPMC) K100 M, citric acid, and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their physical properties in vitro release as well as in vivo behavior. The results showed that K3 (180 mg of HPMC K4 M) and K6 (290 mg of HPMC E15 LV) with a buoyant layer were the best formulation, with lag times of 5.2 ± 0.1 h and 4.1 ± 0.2 h, respectively. Floating time was controlled by the quantity and composition of the buoyant layer. In-vitro results point out the capability of the system with its prolonged residence of the tablets in the stomach and release of drug after a programmed lag time. This was confirmed by in vivo x-ray technique. The objective of the present work was to develop a floating-pulsatile oral drug delivery system of atenolol with addition of hydroxylpropyl methylcellulose (HPMC) K100 M, HPMC K4 M, and HPMC E15 LV in different ratios with citric acid and sodium bicarbonate as gas-forming agents. The system consist of three different parts: a core tablet, containing the active ingredient; a bottom layer that erodes; and a top cover floating layer. Atenolol, a β-blocker, is prescribed widely in diverse cardiovascular diseases, for example, hypertension, angina pectoris, arrhythmias, and myocardial infarction. Developed formulations were evaluated for their physical properties and vitro release as well as in vivo behavior. The results showed that K3 (180 mg HPMC K4 M) and K6 (290 mg of HPMC E15 LV) with a buoyant layer were the best formulations with the lag times of 5.2 ± 0.1 h and 4.1 ± 0.2 h, respectively, and were found to be the best choice for manufacturing tablets.

Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.

PubMed

Yi, Tao; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

2008-08-07

The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.

A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

PubMed

Wu, Daocheng; Wan, Mingxi

2008-01-01

Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

Handling System for Iridium-192 Seeds

NASA Technical Reports Server (NTRS)

Carpenter, W.; Wodicka, D.

1973-01-01

A complete system is proposed for safe handling of iridium-192 seeds used to internally irradiate malignant growths. A vibratory hopper feeds the seeds onto a transport system for deposit in a magazine or storage area. A circular magazine consisting of segmented plastic tubing with holes in the walls to accommodate the seeds seems feasible. The magazine is indexed to stop and release a seed for calibration and deposition.

The Development of a Test System for the Evaluation of Reverse Osmosis Water Purification Membranes

DTIC Science & Technology

1984-06-01

processes consist of high rate filtration followed by the reverse osmosis system. Under the present concept there will be two units: one will produce 600...of the National Toxicology Program, National Institute of Health. No official data has. been released on the teratogenicity of D.MMP. Healh ýz

In-situ characterization of wildland fire behavior

Treesearch

Bret Butler; D. Jimenez; J. Forthofer; Paul Sopko; K. Shannon; Jim Reardon

2010-01-01

A system consisting of two enclosures has been developed to characterize wildand fire behavior: The first enclosure is a sensor/data logger combination that measures and records convective/radiant energy released by the fire. The second is a digital video camera housed in a fire proof enclosure that records visual images of fire behavior. Together this system provides...

Design and In Vitro Evaluation of Compression-coated Pulsatile Release Tablets of Losartan Potassium

PubMed Central

Bajpai, M.; Singh, D. C. P.; Bhattacharya, A.; Singh, A.

2012-01-01

In majority of individuals blood pressure rises in the early morning hours, which lead to serious cardiovascular complications. Formulation of pulsatile system makes it possible to deliver drug at definite period of time when symptoms of the disease condition are most critical. The purpose of the present work was to develop pulsatile release tablet of losartan potassium for chronotherapy in hypertension. The prepared system consisted of a core tablet coated with versatile and safe hydrophilic cellulosic ethers such as, hydroxypropyl methylcellulose, hydroxypropyl cellulose and sodium carboxy methylcellulose to produce burst release after predetermined lag time. Various formulation factors were studied through series of test and in vitro dissolution study. It was found that core tablets containing superdisintegrant failed to produce burst drug release pattern while effervescent agent was able to do so. Results also reveal that coating composition and coating level affects lag time. Formulation containing effervescent agent in core and coated with 200 mg hydroxypropyl cellulose provide lag time of 4.5 h with 73% drug release in 6 h that followed a sigmoidal release pattern. These values were close to the desired objective of producing lag time of 5-6 h followed by fast drug release. This approach can thus provide a useful means for timed release of losartan and is helpful for patients with morning surge. PMID:23325989

Photo-Redox Activated Drug Delivery Systems Operating Under Two Photon Excitation in the Near-IR

PubMed Central

Guardado-Alvarez, Tania M.; Devi, Lekshmi Sudha; Vabre, Jean-Marie; Pecorelli, Travis; Schwartz, Benjamin J.; Durand, Jean-Olivier; Mongin, Olivier; Blanchard-Desce, Mireille; Zink, Jeffrey I.

2014-01-01

We report the design and synthesis of a nano-container consisting of mesoporous silica nanoparticles with the pore openings covered by “snap-top” caps that are opened by near-IR light. A photo transducer molecule that is a reducing agent in an excited electronic state is covalently attached to the system. Near IR two-photon excitation causes inter-molecular electron transfer that reduces a disulfide bond holding the cap in place, thus allowing the cargo molecules to escape. We describe the operation of the “snap-top” release mechanism by both one- and two-photon activation. This system presents a proof of concept of a near-IR photoredox-induced nanoparticle delivery system that may lead to a new type of photodynamic drug release therapy. PMID:24647752

Photo-redox activated drug delivery systems operating under two photon excitation in the near-IR.

PubMed

Guardado-Alvarez, Tania M; Devi, Lekshmi Sudha; Vabre, Jean-Marie; Pecorelli, Travis A; Schwartz, Benjamin J; Durand, Jean-Olivier; Mongin, Olivier; Blanchard-Desce, Mireille; Zink, Jeffrey I

2014-05-07

We report the design and synthesis of a nano-container consisting of mesoporous silica nanoparticles with the pore openings covered by "snap-top" caps that are opened by near-IR light. A photo transducer molecule that is a reducing agent in an excited electronic state is covalently attached to the system. Near IR two-photon excitation causes inter-molecular electron transfer that reduces a disulfide bond holding the cap in place, thus allowing the cargo molecules to escape. We describe the operation of the "snap-top" release mechanism by both one- and two-photon activation. This system presents a proof of concept of a near-IR photoredox-induced nanoparticle delivery system that may lead to a new type of photodynamic drug release therapy.

Evaluation of matrix type mucoadhesive tablets containing indomethacin for buccal application.

PubMed

Ikeuchi-Takahashi, Yuri; Sasatsu, Masanaho; Onishi, Hiraku

2013-09-10

Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered for pain relief from oral mucositis. However, the systemic administration of NSAIDs is limited due to systemic side effects. To avoid these side effects and treat local lesions effectively, a matrix type mucoadhesive tablet was developed. A mixture of hard fat, ethylcellulose (EC) and polyethylene glycol (PEG) was used as a matrix base, and indomethacin (IMC) was used as the principal agent. In tablets consisting of hard fat, EC and IMC, the drug release was sustained. In tablets consisting of hard fat, EC, considerable amounts of PEG and IMC, the drug release was relatively increased and IMC existed as the molecular phase or in an amorphous state. The in vitro adhesive force of the tablets consisting of hard fat, EC, considerable amounts of PEG and IMC was significantly increased as compared with the tablets consisting of hard fat and IMC. A significantly high tissue concentration and significantly low plasma concentration were observed after buccal administration of this matrix type mucoadhesive tablet as compared with that after oral administration of IMC. Thus, the matrix type mucoadhesive tablet has good potential as a preparation for the treatment of pain due to oral aphtha. Copyright © 2013 Elsevier B.V. All rights reserved.

Experimental investigation of thermal processes in the multi-ring Couette system with counter rotation of cylinders

NASA Astrophysics Data System (ADS)

Mamonov, V. N.; Nazarov, A. D.; Serov, A. F.; Terekhov, V. I.

2016-01-01

The effect of parameters of the multi-ring Couette system with counter rotating coaxial cylinders on the process of thermal energy release in a viscous liquid filling this system is considered with regard to the problem of determining the possibility of creating the high-performance wind heat generator. The multi-cylinder rotor design allows directly conversion of the mechanical power of a device consisting of two "rotor" wind turbines with a common axis normal to the air flow into the thermal energy in a wide range of rotational speed of the cylinders. Experimental results on the measurement of thermal power released in the pilot heat generator at different relative angular speeds of cylinder rotation are presented.

Boeing's Dart and Starliner Parachute System Test

NASA Image and Video Library

2018-02-22

Boeing conducted the first in a series of reliability tests of its CST-100 Starliner flight drogue and main parachute system by releasing a long, dart-shaped test vehicle from a C-17 aircraft over Yuma, Arizona. Two more tests are planned using the dart module, as well as three similar reliability tests using a high fidelity capsule simulator designed to simulate the CST-100 Starliner capsule’s exact shape and mass. In both the dart and capsule simulator tests, the test spacecraft are released at various altitudes to test the parachute system at different deployment speeds, aerodynamic loads, and or weight demands. Data collected from each test is fed into computer models to more accurately predict parachute performance and to verify consistency from test to test.

75 FR 22565 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... collect, assemble, interpret, analyze, report and publish surveys; research, study, statistical and... commercial entities, for surveys or research, where such releases are consistent with the mission of the...): To collect, assemble, interpret, analyze, report and publish surveys; research, study, statistical...

Regional Differential Effects of the Novel Histamine H3 Receptor Antagonist 6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) on Histamine Release in the Central Nervous System of Freely Moving Rats

PubMed Central

Giannoni, Patrizia; Medhurst, Andrew D.; Passani, Maria Beatrice; Giovannini, Maria Grazia; Ballini, Chiara; Corte, Laura Della

2010-01-01

After oral administration, the nonimidazole histamine H3 receptor antagonist, 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), increased histamine release from the tuberomammillary nucleus, where all histaminergic somata are localized, and from where their axons project to the entire brain. To further understand functional histaminergic circuitry in the brain, dual-probe microdialysis was used to pharmacologically block H3 receptors in the tuberomammillary nucleus, and monitor histamine release in projection areas. Perfusion of the tuberomammillary nucleus with GSK189254 increased histamine release from the tuberomammillary nucleus, nucleus basalis magnocellularis, and cortex, but not from the striatum or nucleus accumbens. Cortical acetylcholine (ACh) release was also increased, but striatal dopamine release was not affected. When administered locally, GSK189254 increased histamine release from the nucleus basalis magnocellularis, but not from the striatum. Thus, defined by their sensitivity to GSK189254, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner. Consistent with its effects on cortical ACh release, systemic administration of GSK189254 antagonized the amnesic effects of scopolamine in the rat object recognition test, a cognition paradigm with important cortical components. PMID:19815811

Controlled Release System for Localized and Sustained Drug Delivery Applications

NASA Astrophysics Data System (ADS)

Rodriguez, Lidia Betsabe

Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is possible to prepare biodegradable microparticles with a uniform size distribution and high drug loading efficiency. However, this could only be achieved with a hybrid system consisting of chitosan matrix interior and then exterior coating of PLGA or PLA. A two layer coating of PLGA 50:50 was shown to be optimal with sustainable controlled drug release for almost 5 days and with 91% of degradation (weight loss) in 8 weeks.

Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

PubMed Central

Kim, Min Soo; Yeom, Dong Woo; Kim, Sung Rae; Yoon, Ho Yub; Kim, Chang Hyun; Son, Ho Yong; Kim, Jin Han; Lee, Sangkil; Choi, Young Wook

2017-01-01

A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD. PMID:28053506

[Analysis of antibiotic diffusion from agarose gel by spectrophotometry and laser interferometry methods].

PubMed

Arabski, Michał; Wasik, Sławomir; Piskulak, Patrycja; Góźdź, Natalia; Slezak, Andrzej; Kaca, Wiesław

2011-01-01

The aim of this study was to analysis of antibiotics (ampicilin, streptomycin, ciprofloxacin or colistin) release from agarose gel by spectrophotmetry and laser interferometry methods. The interferometric system consisted of a Mach-Zehnder interferometer with a He-Ne laser, TV-CCD camera, computerised data acquisition system and a gel system. The gel system under study consists of two cuvettes. We filled the lower cuvette with an aqueous 1% agarose solution with the antibiotics at initial concentration of antibiotics in the range of 0.12-2 mg/ml for spectrophotmetry analysis or 0.05-0.5 mg/ml for laser interferometry methods, while in the upper cuvette there was pure water. The diffusion was analysed from 120 to 2400 s with a time interval of deltat = 120 s by both methods. We observed that 0.25-1 mg/ml and 0,05 mg/ml are minimal initial concentrations detected by spectrophotometric and laser interferometry methods, respectively. Additionally, we observed differences in kinetic of antibiotic diffusion from gel measured by both methods. In conclusion, the laser interferometric method is a useful tool for studies of antibiotic release from agarose gel, especially for substances are not fully soluble in water, for example: colistin.

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.

Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system.

PubMed

Giray, Seda; Bal, Tuğba; Kartal, Ayse M; Kızılel, Seda; Erkey, Can

2012-05-01

A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. Copyright © 2012 Wiley Periodicals, Inc.

Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol.

PubMed

Jagdale, Swati C; Bari, Nilesh A; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 3² full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol

PubMed Central

Jagdale, Swati C.; Bari, Nilesh A.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form. PMID:24367788

pH- and thermo-responsive microcontainers as potential drug delivery systems: Morphological characteristic, release and cytotoxicity studies.

PubMed

Efthimiadou, Eleni K; Tapeinos, Christos; Tziveleka, Leto-Aikaterini; Boukos, Nikos; Kordas, George

2014-04-01

Polymeric pH- and thermo-sensitive microcontainers (MCs) were developed as a potential drug delivery system for cancer therapy. It is well known that cancer cells exhibit notable characteristics such as acidic pH due to glycolytic cycle and higher temperature due to their higher proliferation rate. Based on these characteristics, we constructed a dual pH- and thermo-sensitive material for specific drug release on the pathological tissue. The MC's fabrication is based on a two-step procedure, in which, the first step involves the core synthesis and the second one is related to the shell formation. The core consists of poly(methyl methacrylate (PMMA), while the shell consists of PMMA, poly(isopropylacrylamide), poly(acrylic acid) and poly(divinylbenzene). Three different types of MCs were synthesized based on the seed polymerization method. The synthesized MCs were characterized structurally by Fourier transform infrared and morphologically by scanning electron microscopy. Dynamic light scattering was also used to study their behavior in aqueous solution under different pH and temperature conditions. For the loading and release study, the anthracycline drug daunorubicin (DNR) was used as a model drug, and its release properties were evaluated under different pH and thermo-conditions. Cytotoxicity studies were also carried out against MCF-7 breast cancer and 3T3 mouse embryonic fibroblast cells. According to our results, the synthesized microcontainers present desired pH and thermo behavior and can be applied in drug delivery systems. It is worth mentioning that the synthesized microcontainers which incorporated the drug DNR exhibit higher toxicity than the free drug. Copyright © 2014 Elsevier B.V. All rights reserved.

The stress response and immune system share, borrow, and reconfigure their physiological network elements: Evidence from the insects.

PubMed

Adamo, Shelley A

2017-02-01

The classic biomedical view is that stress hormone effects on the immune system are largely pathological, especially if the stress is chronic. However, more recent interpretations have focused on the potential adaptive function of these effects. This paper examines stress response-immune system interactions from a physiological network perspective, using insects because of their simpler physiology. For example, stress hormones can reduce disease resistance, yet activating an immune response results in the release of stress hormones in both vertebrates and invertebrates. From a network perspective, this phenomenon is consistent with the 'sharing' of the energy-releasing ability of stress hormones by both the stress response and the immune system. Stress-induced immunosuppression is consistent with the stress response 'borrowing' molecular components from the immune system to increase the capacity of stress-relevant physiological processes (i.e. a trade off). The insect stress hormones octopamine and adipokinetic hormone can also 'reconfigure' the immune system to help compensate for the loss of some of the immune system's molecular resources (e.g. apolipophorin III). This view helps explain seemingly maladaptive interactions between the stress response and immune system. The adaptiveness of stress hormone effects on individual immune components may be apparent only from the perspective of the whole organism. These broad principles will apply to both vertebrates and invertebrates. Copyright © 2016 Elsevier Inc. All rights reserved.

Building a polysaccharide hydrogel capsule delivery system for control release of ibuprofen.

PubMed

Chen, Zhi; Wang, Ting; Yan, Qing

2018-02-01

Development of a delivery system which can effectively carry hydrophobic drugs and have pH response is becoming necessary. Here we demonstrate that through preparation of β-cyclodextrin polymer (β-CDP), a hydrophobic drug molecule of ibuprofen (IBU) was incorporated into our prepared β-CDP inner cavities, aiming to improve the poor water solubility of IBU. A core-shell capsule structure has been designed for achieving the drug pH targeted and sustained release. This delivery system was built with polysaccharide polymer of Sodium alginate (SA), sodium carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC) by physical cross-linking. The drug pH-response control release is this hydrogel system's chief merit, which has potential value for synthesizing enteric capsule. Besides, due to our simple preparing strategy, optimal conditions can be readily determined and the synthesis process can be accurately controlled, leading to consistent and reproducible hydrogel capsules. In addition, phase-solubility method was used to investigate the solubilization effect of IBU by β-CDP. SEM was used to prove the forming of core and shell structure. FT-IR and 1 H-NMR were also used to perform structural characteristics. By the technique of UV determination, the pH targeted and sustained release study were also performed. The results have proved that our prepared polysaccharide hydrogel capsule delivery system has potential applications as oral drugs delivery in the field of biomedical materials.

Release of metal ions from fixed orthodontic appliance: an in vitro study in continuous flow system.

PubMed

Mikulewicz, Marcin; Chojnacka, Katarzyna; Wołowiec, Paulina

2014-01-01

To evaluate the release of metal ions from fixed orthodontic appliances. A new system for in vitro testing of dental materials was constructed and consisted of a thermostatic glass reactor that enabled immersion of the studied material. Experimental conditions reflected the human oral cavity, with a temperature of 37°C and a saliva flow rate of 0.5mL/min. The simulated fixed orthodontic appliance made of stainless steel was evaluated. Sampling was performed at several time points during the 28-day study, and the metal ion concentration was determined by inductively coupled plasma optical emission spectrometry. The total mass of released metal ions from the appliance during 4 weeks of the experiment was as follows nickel 18.7 μg, chromium 5.47 μg, copper 31.3 μg. The estimated doses of nickel, chromium, and copper determined by extrapolation of experimental data released during the treatment period were far below the toxic dose to humans. This shows that orthodontic treatment might not be a significant source of exposure to these metal ions.

CO2 bubbling-based 'Nanobomb' System for Targetedly Suppressing Panc-1 Pancreatic Tumor via Low Intensity Ultrasound-activated Inertial Cavitation.

PubMed

Zhang, Kun; Xu, Huixiong; Chen, Hangrong; Jia, Xiaoqing; Zheng, Shuguang; Cai, Xiaojun; Wang, Ronghui; Mou, Juan; Zheng, Yuanyi; Shi, Jianlin

2015-01-01

Noninvasive and targeted physical treatment is still desirable especially for those cancerous patients. Herein, we develop a new physical treatment protocol by employing CO2 bubbling-based 'nanobomb' system consisting of low-intensity ultrasound (1.0 W/cm(2)) and a well-constructed pH/temperature dual-responsive CO2 release system. Depending on the temperature elevation caused by exogenous low-intensity therapeutic ultrasound irradiation and the low pH caused by the endogenous acidic-environment around/within tumor, dual-responsive CO2 release system can quickly release CO2 bubbles, and afterwards, the generated CO2 bubbles waves will timely explode before dissolution due to triggering by therapeutic ultrasound waves. Related bio-effects (e.g., cavitation, mechanical, shock waves, etc) caused by CO2 bubbles' explosion effectively induce instant necrosis of panc-1 cells and blood vessel destruction within panc-1 tumor, and consequently inhibit the growth of panc-1 solid tumor, simultaneously minimizing the side effects to normal organs. This new physiotherapy employing CO2 bubbling-based 'nanobomb' system promises significant potentials in targetedly suppressing tumors, especially for those highly deadly cancers.

CO2 bubbling-based 'Nanobomb' System for Targetedly Suppressing Panc-1 Pancreatic Tumor via Low Intensity Ultrasound-activated Inertial Cavitation

PubMed Central

Zhang, Kun; Xu, Huixiong; Chen, Hangrong; Jia, Xiaoqing; Zheng, Shuguang; Cai, Xiaojun; Wang, Ronghui; Mou, Juan; Zheng, Yuanyi; Shi, Jianlin

2015-01-01

Noninvasive and targeted physical treatment is still desirable especially for those cancerous patients. Herein, we develop a new physical treatment protocol by employing CO2 bubbling-based 'nanobomb' system consisting of low-intensity ultrasound (1.0 W/cm2) and a well-constructed pH/temperature dual-responsive CO2 release system. Depending on the temperature elevation caused by exogenous low-intensity therapeutic ultrasound irradiation and the low pH caused by the endogenous acidic-environment around/within tumor, dual-responsive CO2 release system can quickly release CO2 bubbles, and afterwards, the generated CO2 bubbles waves will timely explode before dissolution due to triggering by therapeutic ultrasound waves. Related bio-effects (e.g., cavitation, mechanical, shock waves, etc) caused by CO2 bubbles' explosion effectively induce instant necrosis of panc-1 cells and blood vessel destruction within panc-1 tumor, and consequently inhibit the growth of panc-1 solid tumor, simultaneously minimizing the side effects to normal organs. This new physiotherapy employing CO2 bubbling-based 'nanobomb' system promises significant potentials in targetedly suppressing tumors, especially for those highly deadly cancers. PMID:26379793

Seat Interfaces for Aircrew Performance and Safety

DTIC Science & Technology

2010-01-01

Quantum -II Desktop System consists of a keyboard and hardware accessories (electrodes, cables, etc.), and interfaces with a desktop computer via software...segment. Resistance and reactance data was collected to estimate blood volume changes. The Quantum -II Desktop system collected continuous data of...Approved for public release; distribution unlimited. 88 ABW Cleared 03/13/2015; 88ABW-2015-1053. mockup also included a laptop computer , a

40 CFR 63.1361 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... pressure relief device. This release can be one release or a series of releases over a short time period... reduces the mass of HAP emitted to the air. The equipment may consist of an individual device or a series... do not occur simultaneously in a batch operation. A batch process consists of a series of batch...

Vehicle Tracking System using Nanotechnology Satellites and Tags

NASA Technical Reports Server (NTRS)

Lorenzini, Dino A.; Tubis, Chris

1995-01-01

This paper describes a joint project to design, develop, and deploy a satellite based tracking system incorporating micro-nanotechnology components. The system consists of a constellation of 'nanosats', a satellite command station and data collection sites, and a large number of low-cost electronic 'tags'. Both government and commercial applications are envisioned for the satellite based tracking system. The projected low price for the tracking service is made possible by the lightweight nanosats and inexpensive electronic tags which use high production volume single chip transceivers and microprocessor devices. The nanosat consists of a five inch aluminum cube with body mounted solar panels (GaAs solar cells) on all six faces. A UHF turnstile antenna and a simple, spring release mechanism complete the external configuration of the spacecraft.

Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold

PubMed Central

Koutsopoulos, Sotirios; Unsworth, Larry D.; Nagai, Yusuke; Zhang, Shuguang

2009-01-01

The release kinetics for a variety of proteins of a wide range of molecular mass, hydrodynamic radii, and isoelectric points through a nanofiber hydrogel scaffold consisting of designer self-assembling peptides were studied by using single-molecule fluorescence correlation spectroscopy (FCS). In contrast to classical diffusion experiments, the single-molecule approach allowed for the direct determination of diffusion coefficients for lysozyme, trypsin inhibitor, BSA, and IgG both inside the hydrogel and after being released into the solution. The results of the FCS analyses and the calculated pristine in-gel diffusion coefficients were compared with the values obtained from the Stokes–Einstein equation, Fickian diffusion models, and the literature. The release kinetics suggested that protein diffusion through nanofiber hydrogels depended primarily on the size of the protein. Protein diffusivities decreased, with increasing hydrogel nanofiber density providing a means of controlling the release kinetics. Secondary and tertiary structure analyses and biological assays of the released proteins showed that encapsulation and release did not affect the protein conformation and functionality. Our results show that this biocompatible and injectable designer self-assembling peptide hydrogel system may be useful as a carrier for therapeutic proteins for sustained release applications. PMID:19273853

AVETMISS: The Standard for VET Financial Data. Release 1.7. Updated

ERIC Educational Resources Information Center

National Centre for Vocational Education Research (NCVER), 2009

2009-01-01

The Standard for Vocational Education and Training (VET) financial data offers a nationally consistent standard for the collection, reporting and analysis of the public vocational education and training system information throughout Australia. It forms part of the Australian Vocational Education and Training Management Information Statistical…

C.U.B.E. Program Administration Materials.

ERIC Educational Resources Information Center

Vincennes Univ., IN.

This manual consists of forms and guidelines for use in administering the adult basic education teaching/learning management system called CUBE (Continuity and Unity in Basic Education). Provided in the manual are a variety of orientation forms, including daily attendance records, enrollment forms, publication release forms, and fact sheets on the…

MULTI-VIEWPOINT OBSERVATIONS OF A WIDELY DISTRIBUTED SOLAR ENERGETIC PARTICLE EVENT: THE ROLE OF EUV WAVES AND WHITE-LIGHT SHOCK SIGNATURES

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

Kouloumvakos, A.; Patsourakos, S.; Nindos, A.

2016-04-10

On 2012 March 7, two large eruptive events occurred in the same active region within 1 hr from each other. Each consisted of an X-class flare, a coronal mass ejection (CME), an extreme-ultraviolet (EUV) wave, and a shock wave. The eruptions gave rise to a major solar energetic particle (SEP) event observed at widely separated (∼120°) points in the heliosphere. From multi-viewpoint energetic proton recordings we determine the proton release times at STEREO B and A (STB, STA) and the first Lagrange point (L1) of the Sun–Earth system. Using EUV and white-light data, we determine the evolution of the EUVmore » waves in the low corona and reconstruct the global structure and kinematics of the first CME’s shock, respectively. We compare the energetic proton release time at each spacecraft with the EUV waves’ arrival times at the magnetically connected regions and the timing and location of the CME shock. We find that the first flare/CME is responsible for the SEP event at all three locations. The proton release at STB is consistent with arrival of the EUV wave and CME shock at the STB footpoint. The proton release time at L1 was significantly delayed compared to STB. Three-dimensional modeling of the CME shock shows that the particle release at L1 is consistent with the timing and location of the shock’s western flank. This indicates that at L1 the proton release did not occur in low corona but farther away from the Sun. However, the extent of the CME shock fails to explain the SEP event observed at STA. A transport process or a significantly distorted interplanetary magnetic field may be responsible.« less

Colon targeted delivery systems of metronidazole based on osmotic technology: development and evaluation.

PubMed

Kumar, Pramod; Singh, Sanjay; Mishra, Brahmeshwar

2008-09-01

Colon targeted delivery systems of metronidazole (MTZ) based on osmotic technology were developed. The developed systems consisted of osmotic core (drug, osmotic agent and wicking agent), coated with semipermeable membrane (SPM) containing guar gum as pore former, coated core were then further coated with enteric coating to protect the system from acidic environment of stomach. The effect of various formulation variables namely the level of wicking agent (sodium lauryl sulphate), osmotic agent in the osmotic core, the level of pore former (guar gum) in SPM, and the thickness of SPM, were studied on physical parameters and drug release characteristics of developed formulations. MTZ release was inversely proportional to SPM thickness, but directly related to the level of pore former, wicking agent and osmotic agent. On the other hand burst strength of the exhausted shells was decreased with the increase in level of pore former in the membrane but increased with the increase in the thickness of SPM. The drug release from the developed formulations was independent of pH, and agitation intensity, but dependent on the osmotic pressure of the release media. The thickness of enteric coating could prevent formation of delivery pores before contact with simulated colonic fluid, but had no effect on drug release. Result of SEM studies showed the formation of in-situ delivery pores in the membrane from where the drug release occurred, and the number of pores formed were directly related to the initial level of pore former (guar gum) in SPM. The manufacturing procedure was found to be reproducible and formulations were found to be stable during 3 months of accelerated stability studies.

IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (Etbe) ...

EPA Pesticide Factsheets

In September 2016, the U.S. Environmental Protection Agency's (USEPA) released the draft Integrated Risk Information System (IRIS) Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE). Consistent with the 2013 IRIS Enhancements, draft IRIS assessments are released prior to external peer review for a 60-day public comment period and discussed at an upcoming public science meeting. Accordingly, the toxicological review, supplementary information, and other materials pertaining to this draft assessment are posted on this site. This material is being released for public viewing and comment prior to a public meeting, providing an opportunity for the IRIS Program to engage in early discussions with stakeholders and the public on data that may be used to identify adverse health effects and characterize exposure-response relationships.

Contribution of Impulsivity and Serotonin Receptor Neuroadaptations to the Development of an MDMA ('Ecstasy') Substance Use Disorder.

PubMed

Schenk, Susan; Aronsen, Dane

As is the case with other drugs of abuse, a proportion of ecstasy users develop symptoms consistent with a substance use disorder (SUD). In this paper, we propose that the pharmacology of MDMA, the primary psychoactive component of ecstasy tablets, changes markedly with repeated exposure and that neuroadaptations in dopamine and serotonin brain systems underlie the shift from MDMA use to MDMA misuse in susceptible subjects. Data from both the human and laboratory animal literature are synthesized to support the idea that (1) MDMA becomes a less efficacious serotonin releaser and a more efficacious dopamine releaser with the development of behaviour consistent with an SUD and (2) that upregulated serotonin receptor mechanisms contribute to the development of the MDMA SUD via dysregulated inhibitory control associated with the trait of impulsivity.

Chandra X-ray Center Science Data Systems Regression Testing of CIAO

NASA Astrophysics Data System (ADS)

Lee, N. P.; Karovska, M.; Galle, E. C.; Bonaventura, N. R.

2011-07-01

The Chandra Interactive Analysis of Observations (CIAO) is a software system developed for the analysis of Chandra X-ray Observatory observations. An important component of a successful CIAO release is the repeated testing of the tools across various platforms to ensure consistent and scientifically valid results. We describe the procedures of the scientific regression testing of CIAO and the enhancements made to the testing system to increase the efficiency of run time and result validation.

Design, testing, fabrication and launch support of a liquid chemical barium release payload (utilizing the liquid fluorine-barium salt/hydrazine system)

NASA Technical Reports Server (NTRS)

Stokes, C. S.; Smith, E. W.; Murphy, W. J.

1972-01-01

A payload was designed which included a cryogenic oxidizer tank, a fuel tank, and burner section. Release of 30 lb of chemicals was planned to occur in 2 seconds at the optimum oxidizer to fuel ratio. The chemicals consisted of 17 lb of liquid fluorine oxidizer and 13 lb of hydrazine-barium salt fuel mixture. The fuel mixture was 17% barium chloride, 16% barium nitrate, and 67% hydrazine, and contained 2.6 lb of available barium. Two significant problem areas were resolved during the program: explosive valve development and burner operation. The release payload was flight tested, from Wallops Island, Virginia. The release took place at an altitude of approximately 260 km. The release produced a luminous cloud which expanded very rapidly, disappearing to the human eye in about 20 seconds. Barium ion concentration slowly increased over a wide area of sky until measurements were discontinued at sunrise (about 30 minutes).

PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins.

PubMed

Minardi, Silvia; Pandolfi, Laura; Taraballi, Francesca; De Rosa, Enrica; Yazdi, Iman K; Liu, Xeuwu; Ferrari, Mauro; Tasciotti, Ennio

2015-08-05

In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based on a core consisting of the nanostructured silicon multistage vector (MSV) and a poly(dl-lactide-co-glycolide) acid (PLGA) outer shell. Both of the two components of the resulting composite microspheres (PLGA-MSV) can be independently tailored to achieve multiple release kinetics contributing to the control of the release profile of a reporter protein in vitro. The influence of MSV shape (hemispherical or discoidal) and size (1, 3, or 7 μm) on PLGA-MSV's morphology and size distribution was investigated. Second, the copolymer ratio of the PLGA used to fabricate the outer shell of PLGA-MSV was varied. The composites were fully characterized by optical microscopy, scanning electron microscopy, ζ potential, Fourier transform infrared spectroscopy, and thermogravimetric analysis-differential scanning calorimetry, and their release kinetics over 30 days. PLGA-MSV's biocompatibility was assessed in vitro with J774 macrophages. Finally, the formulation of PLGA-MSV was selected, which concurrently provided the most consistent microsphere size and allowed for a zero-order release kinetic. The selected PLGA-MSVs were injected in a subcutaneous model in mice, and the in vivo release of the reporter protein was followed over 2 weeks by intravital microscopy, to assess if the zero-order release was preserved. PLGA-MSV was able to retain the payload over 2 weeks, avoiding the initial burst release typical of most drug delivery systems. Finally, histological evaluation assessed the biocompatibility of the platform in vivo.

The release profiles of intact and enzymatically digested hyaluronic acid from semisolid formulations using multi-layer membrane system.

PubMed

Alkrad, Jamal Alyoussef; Mrestani, Yahya; Neubert, Reinhard H H

2003-07-01

A multi-layer membrane system was used to measure in vitro release of hydrophilic macromolecules such as hyaluronic acid (HA) from semisolid formulations. One enzymatically digested HA-derivative with molecular mass of 22 kDa (HA-D) and 1200 kDa intact HA (HA) were incorporated into three semisolid formulations: water-containing hydrophilic ointment (WHO), amphiphilic cream (AC) and water-containing wool wax alcohol ointment (WWO). Because of the high hydrophilic properties of HA-D and HA, the artificial model membranes consisted of collodion as the matrix and glycerol as the hydrophilic acceptor phase. The area under the concentration-time curve and the mean dissolution time were used as a quantitative parameter to characterise the rate and extent of release in vitro. This study showed that the HA-D and HA release as hydrophilic substances from WHO was higher than both from AC and WWO. It was observed that 83% of HA-D1 was released from WHO after 2 h; in contrast, only 10% was released from 2% HA from the same vehicle during the same time. In conclusion, the in vitro availability of enzymatically digested HA-D was higher for WHO than for the other formulations, AC and WWO. Similarly, the availability of HA-D was higher than that of HA from the same formulations.

Molecularly Imprinted Microrods via Mesophase Polymerization.

PubMed

Parisi, Ortensia Ilaria; Scrivano, Luca; Candamano, Sebastiano; Ruffo, Mariarosa; Vattimo, Anna Francesca; Spanedda, Maria Vittoria; Puoci, Francesco

2017-12-28

The aim of the present research work was the synthesis of molecularly imprinted polymers (MIPs) with a rod-like geometry via "mesophase polymerization". The ternary lyotropic system consisting of sodium dodecyl sulfate (SDS), water, and decanol was chosen to prepare a hexagonal mesophase to direct the morphology of the synthesized imprinted polymers using theophylline, methacrylic acid, and ethylene glycol dimethacrylate as a drug model template, a functional monomer, and a crosslinker, respectively. The obtained molecularly imprinted microrods (MIMs) were assessed by performing binding experiments and in vitro release studies, and the obtained results highlighted good selective recognition abilities and sustained release properties. In conclusion, the adopted synthetic strategy involving a lyotropic mesophase system allows for the preparation of effective MIPs characterized by a rod-like morphology.

Release of Self-Healing Agents in a Material: What Happens Next?

PubMed

Lee, Min Wook; Yoon, Sam S; Yarin, Alexander L

2017-05-24

A microfluidic chip-like setup consisting of a vascular system of microchannels alternatingly filled with either a resin monomer or a curing agent is used to study the intrinsic physical healing mechanism in self-healing materials. It is observed that, as a prenotched crack propagates across the chip, the resin and curing agent are released from the damaged channels. Subsequently, both the resin and the curing agent wet the surrounding polydimethylsiloxane (PDMS) matrix and spread over the crack banks until the two blobs come in contact, mix, and polymerize through an organometallic cross-linking reaction. Moreover, the polymerized domains form a system of pillars, which span the crack banks on the opposite side. This "stitching" phenomenon prevents further propagation of the crack.

TSPA 1991: An initial total-system performance assessment for Yucca Mountain; Yucca Mountain Site Characterization Project

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

Barnard, R.W.; Wilson, M.L.; Dockery, H.A.

1992-07-01

This report describes an assessment of the long-term performance of a repository system that contains deeply buried highly radioactive waste; the system is assumed to be located at the potential site at Yucca Mountain, Nevada. The study includes an identification of features, events, and processes that might affect the potential repository, a construction of scenarios based on this identification, a selection of models describing these scenarios (including abstraction of appropriate models from detailed models), a selection of probability distributions for the parameters in the models, a stochastic calculation of radionuclide releases for the scenarios, and a derivation of complementary cumulativemore » distribution functions (CCDFs) for the releases. Releases and CCDFs are calculated for four categories of scenarios: aqueous flow (modeling primarily the existing conditions at the site, with allowances for climate change), gaseous flow, basaltic igneous activity, and human intrusion. The study shows that models of complex processes can be abstracted into more simplified representations that preserve the understanding of the processes and produce results consistent with those of more complex models.« less

To bind or not to bind? Different temporal binding effects from voluntary pressing and releasing actions.

PubMed

Zhao, Ke; Chen, Yu-Hsin; Yan, Wen-Jing; Fu, Xiaolan

2013-01-01

Binding effect refers to the perceptual attraction between an action and an outcome leading to a subjective compression of time. Most studies investigating binding effects exclusively employ the "pressing" action without exploring other types of actions. The present study addresses this issue by introducing another action, releasing action or the voluntary lifting of the finger/wrist, to investigate the differences between voluntary pressing and releasing actions. Results reveal that releasing actions led to robust yet short-lived temporal binding effects, whereas pressing condition had steady temporal binding effects up to super-seconds. The two actions also differ in sensitivity to changes in temporal contiguity and contingency, which could be attributed to the difference in awareness of action. Extending upon current models of "willed action," our results provide insights from a temporal point of view and support the concept of a dual system consisting of predictive motor control and top-down mechanisms.

Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

NASA Astrophysics Data System (ADS)

Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

2016-09-01

Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

Natural and Diverted Low-Flow Duration Discharges for Streams Affected by the Waiahole Ditch System, Windward O`ahu, Hawai`i

USGS Publications Warehouse

Yeung, Chiu W.; Fontaine, Richard A.

2007-01-01

For nearly a century, the Waiahole Ditch System has diverted an average of approximately 27 million gallons per day of water from the wet, northeastern part of windward O`ahu, Hawai`i, to the dry, central part of the island to meet irrigation needs. The system intercepts large amounts of dike-impounded ground water at high altitudes (above approximately 700 to 800 ft) that previously discharged to Waiahole (and its tributaries Waianu and Uwao), Waikane, and Kahana Streams through seeps and springs. Diversion of this ground water has significantly diminished low flows in these streams. Estimates of natural and diverted flows are needed by water managers for (1) setting permanent instream flow standards to protect, enhance, and reestablish beneficial instream uses of water in the diverted streams and (2) allocating the diverted water for instream and offstream uses. Data collected before construction of the Waiahole Ditch System reflect natural (undiverted) flow conditions. Natural low-flow duration discharges for percentiles ranging from 50 to 99 percent were estimated for four sites at altitudes of 75 to 320 feet in Waiahole Stream (and its tributaries Waianu and Uwao Streams), for six sites at altitudes of 10 to 220 feet in Waikane Stream, and for three sites at altitudes of 30 to 80 feet in Kahana Stream. Among the available low-flow estimates along each affected stream, the highest natural Q50 (median) flows on Waiahole (altitude 250 ft), Waianu (altitude 75 ft), Waikane (altitude 75 ft), and Kahana Streams (altitude 30 ft) are 13, 7.0, 5.5, and 22 million gallons per day, respectively. Q50 (median) is just one of five duration percentiles presented in this report to quantify low-flow discharges. All flow-duration estimates were adjusted to a common period of 1960-2004 (called the base period). Natural flow-duration estimates compared favorably with limited pre-ditch streamflow data available for Waiahole and Kahana Streams. Data collected since construction of the ditch system reflect diverted flow conditions, which can be further divided into pre-release and post-release periods - several flow releases to Waiahole, Waianu, and Waikane Streams were initiated between December 1994 and October 2002. Comparison of pre-release to natural flows indicate that the effects of the Waiahole Ditch System diversion are consistently greater at lower low-flow conditions (Q99 to Q90) than at higher low-flow conditions (Q75 to Q50). Results also indicate that the effects of the diversion become less significant as the streams gain additional ground water at lower altitudes. For Waiahole Stream, pre-release flows range from 25 to 28 percent of natural flows at an altitude of 250 feet and from 19 to 20 percent at an altitude of 320 feet. For Waikane Stream, pre-release flows range from 30 to 46 percent of natural flows at an altitude of 10 feet and from 7 to 19 percent at an altitude of 220 feet. For Kahana Stream, pre-release flows range from 65 to 72 percent of natural flows at an altitude of 30 feet and from 58 to 71 percent at an altitude of 80 feet. Estimates of post-release flows were compared with estimates of natural flows to assess how closely current streamflows are to natural conditions. For Waianu Stream, post-release flows at an altitude of 75 feet are 41 to 46 percent lower than corresponding natural flows. For Waikane Stream, post-release flows at an altitude of 75 feet are within 12 percent of the corresponding natural flows. Comparisons of pre-release and post-release flows for Waikane Stream at altitudes of 10 to 220 feet were used to assess downstream changes in flow along the stream reach where flow releases were made. For a particular stream altitude, proportions of pre-release to post-release flows associated with median flows are consistently greater than proportions associated with lower low flows because the relative effect of the flow release is smaller at higher low flows. Similarly, for a particular f

The Role of the Central Noradrenergic System in Behavioral Inhibition

PubMed Central

Stone, Eric A.; Lin, Yan; Sarfraz, Yasmeen; Quartermain, David

2011-01-01

Although the central noradrenergic system has been shown to be involved in a number of behavioral and neurophysiological processes, the relation of these to its role in depressive illness has been difficult to define. The present review discusses the hypothesis that one of its chief functions that may be related to affective illness is the inhibition of behavioral activation, a prominent symptom of the disorder. This hypothesis is found to be consistent with most previous neuropsychopharmacological and immunohistochemical experiments on active behavior in rodents in a variety of experimental conditions using manipulation of neurotransmission at both locus coeruleus and forebrain adrenergic receptors. The findings support a mechanism in which high rates of noradrenergic neural activity suppress the neural activity of principal neurons in forebrain regions mediating active behavior. The suppression may be mediated through postsynaptic galaninergic and adrenergic receptors, and via the release of corticotrophin-releasing hormone. The hypothesis is consistent with clinical evidence for central noradrenergic system hyperactivity in depressives and with the view that this hyperactivity is a contributing etiological factor in the disorder. A similar mechanism may underlie the ability of the noradrenergic system to suppress seizure activity suggesting that inhibition of the spread of neural activation may be a unifying function. PMID:21315760

Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release.

PubMed

Streubel, A; Siepmann, J; Bodmeier, R

2003-01-01

The aim of this study was to develop and physicochemically characterize single unit, floating controlled drug delivery systems consisting of (i). polypropylene foam powder, (ii). matrix-forming polymer(s), (iii). drug, and (iv). filler (optional). The highly porous foam powder provided low density and, thus, excellent in vitro floating behavior of the tablets. All foam powder-containing tablets remained floating for at least 8 h in 0.1 N HCl at 37 degrees C. Different types of matrix-forming polymers were studied: hydroxypropyl methylcellulose (HPMC), polyacrylates, sodium alginate, corn starch, carrageenan, gum guar and gum arabic. The tablets eroded upon contact with the release medium, and the relative importance of drug diffusion, polymer swelling and tablet erosion for the resulting release patterns varied significantly with the type of matrix former. The release rate could effectively be modified by varying the "matrix-forming polymer/foam powder" ratio, the initial drug loading, the tablet geometry (radius and height), the type of matrix-forming polymer, the use of polymer blends and the addition of water-soluble or water-insoluble fillers (such as lactose or microcrystalline cellulose). The floating behavior of the low density drug delivery systems could successfully be combined with accurate control of the drug release patterns.

Increased glutamate-stimulated norepinephrine release from prefrontal cortex slices of spontaneously hypertensive rats.

PubMed

Russell, V A; Wiggins, T M

2000-12-01

Spontaneously hypertensive rats (SHR) have behavioral characteristics (hyperactivity, impulsiveness, poorly sustained attention) similar to the behavioral disturbances of children with attention-deficit hyperactivity disorder (ADHD). We have previously shown that dopaminergic and noradrenergic systems are disturbed in the prefrontal cortex of SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. It was of interest to determine whether the underlying neural circuits that use glutamate as a neurotransmitter function normally in the prefrontal cortex of SHR. An in vitro superfusion technique was used to demonstrate that glutamate caused a concentration-dependent stimulation of [3H]norepinephrine release from rat prefrontal cortex slices. Glutamate (100 microM and 1 mM) caused significantly greater release of norepinephrine from prefrontal cortex slices of SHR than from control slices. The effect of glutamate was not mediated by NMDA receptors, since NMDA (10 and 100 microM) did not exert any effect on norepinephrine release and MK-801 (10 microM) did not antagonize the effect of 100 microM glutamate. These results demonstrate that glutamate stimulates norepinephrine release from rat prefrontal cortex slices and that this increase is enhanced in SHR. The results are consistent with the suggestion that the noradrenergic system is overactive in prefrontal cortex of SHR, the animal model for ADHD.

Project W-211, initial tank retrieval systems, retrieval control system software configuration management plan

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

RIECK, C.A.

1999-02-23

This Software Configuration Management Plan (SCMP) provides the instructions for change control of the W-211 Project, Retrieval Control System (RCS) software after initial approval/release but prior to the transfer of custody to the waste tank operations contractor. This plan applies to the W-211 system software developed by the project, consisting of the computer human-machine interface (HMI) and programmable logic controller (PLC) software source and executable code, for production use by the waste tank operations contractor. The plan encompasses that portion of the W-211 RCS software represented on project-specific AUTOCAD drawings that are released as part of the C1 definitive designmore » package (these drawings are identified on the drawing list associated with each C-1 package), and the associated software code. Implementation of the plan is required for formal acceptance testing and production release. The software configuration management plan does not apply to reports and data generated by the software except where specifically identified. Control of information produced by the software once it has been transferred for operation is the responsibility of the receiving organization.« less

Improving Parolees' Participation in Drug Treatment and Other Services through Strengths Case Management.

PubMed

Prendergast, Michael; Cartier, Jerome J

2008-01-01

In an effort to increase participation in community aftercare treatment for substance-abusing parolees, an intervention based on a transitional case management (TCM) model that focuses mainly on offenders' strengths has been developed and is under testing. This model consists of completion, by the inmate, of a self-assessment of strengths that informs the development of the continuing care plan, a case conference call shortly before release, and strengths case management for three months post-release to promote retention in substance abuse treatment and support the participant's access to designated services in the community. The post-release component consists of a minimum of one weekly client/case manager meeting (in person or by telephone) for 12 weeks. The intervention is intended to improve the transition process from prison to community at both the individual and systems level. Specifically, the intervention is designed to improve outcomes in parolee admission to, and retention in, community-based substance-abuse treatment, parolee access to other needed services, and recidivism rates during the first year of parole. On the systems level, the intervention is intended to improve the communication and collaboration between criminal justice agencies, community-based treatment organizations, and other social and governmental service providers. The TCM model is being tested in a multisite study through the Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) research cooperative funded by the National Institute of Drug Abuse.

A novel experimental design method to optimize hydrophilic matrix formulations with drug release profiles and mechanical properties.

PubMed

Choi, Du Hyung; Lim, Jun Yeul; Shin, Sangmun; Choi, Won Jun; Jeong, Seong Hoon; Lee, Sangkil

2014-10-01

To investigate the effects of hydrophilic polymers on the matrix system, an experimental design method was developed to integrate response surface methodology and the time series modeling. Moreover, the relationships among polymers on the matrix system were studied with the evaluation of physical properties including water uptake, mass loss, diffusion, and gelling index. A mixture simplex lattice design was proposed while considering eight input control factors: Polyethylene glycol 6000 (x1 ), polyethylene oxide (PEO) N-10 (x2 ), PEO 301 (x3 ), PEO coagulant (x4 ), PEO 303 (x5 ), hydroxypropyl methylcellulose (HPMC) 100SR (x6 ), HPMC 4000SR (x7 ), and HPMC 10(5) SR (x8 ). With the modeling, optimal formulations were obtained depending on the four types of targets. The optimal formulations showed the four significant factors (x1 , x2 , x3 , and x8 ) and other four input factors (x4 , x5 , x6 , and x7 ) were not significant based on drug release profiles. Moreover, the optimization results were analyzed with estimated values, targets values, absolute biases, and relative biases based on observed times for the drug release rates with four different targets. The result showed that optimal solutions and target values had consistent patterns with small biases. On the basis of the physical properties of the optimal solutions, the type and ratio of the hydrophilic polymer and the relationships between polymers significantly influenced the physical properties of the system and drug release. This experimental design method is very useful in formulating a matrix system with optimal drug release. Moreover, it can distinctly confirm the relationships between excipients and the effects on the system with extensive and intensive evaluations. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Characteristics of taurine release in slices from adult and developing mouse brain stem.

PubMed

Saransaari, P; Oja, S S

2006-07-01

Taurine has been thought to function as a regulator of neuronal activity, neuromodulator and osmoregulator. Moreover, it is essential for the development and survival of neural cells and protects them under cell-damaging conditions. Taurine is also involved in many vital functions regulated by the brain stem, including cardiovascular control and arterial blood pressure. The release of taurine has been studied both in vivo and in vitro in higher brain areas, whereas the mechanisms of release have not been systematically characterized in the brain stem. The properties of release of preloaded [(3)H]taurine were now characterized in slices prepared from the mouse brain stem from developing (7-day-old) and young adult (3-month-old) mice, using a superfusion system. In general, taurine release was found to be similar to that in other brain areas, consisting of both Ca(2+)-dependent and Ca(2+)-independent components. Moreover, the release was mediated by Na(+)-, Cl(-)-dependent transporters operating outwards, as both Na(+)-free and Cl(-) -free conditions greatly enhanced it. Cl(-) channel antagonists and a Cl(-) transport inhibitor reduced the release at both ages, indicating that a part of the release occurs through ion channels. Protein kinases appeared not to be involved in taurine release in the brain stem, since substances affecting the activity of protein kinase C or tyrosine kinase had no significant effects. The release was modulated by cAMP second messenger systems and phospholipases at both ages. Furthermore, the metabotropic glutamate receptor agonists likewise suppressed the K(+)-stimulated release at both ages. In the immature brain stem, the ionotropic glutamate receptor agonists N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) potentiated taurine release in a receptor-mediated manner. This could constitute an important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions.

Cholesterol Alters the Dynamics of Release in Protein Independent Cell Models for Exocytosis

NASA Astrophysics Data System (ADS)

Najafinobar, Neda; Mellander, Lisa J.; Kurczy, Michael E.; Dunevall, Johan; Angerer, Tina B.; Fletcher, John S.; Cans, Ann-Sofie

2016-09-01

Neurons communicate via an essential process called exocytosis. Cholesterol, an abundant lipid in both secretory vesicles and cell plasma membrane can affect this process. In this study, amperometric recordings of vesicular dopamine release from two different artificial cell models created from a giant unilamellar liposome and a bleb cell plasma membrane, show that with higher membrane cholesterol the kinetics for vesicular release are decelerated in a concentration dependent manner. This reduction in exocytotic speed was consistent for two observed modes of exocytosis, full and partial release. Partial release events, which only occurred in the bleb cell model due to the higher tension in the system, exhibited amperometric spikes with three distinct shapes. In addition to the classic transient, some spikes displayed a current ramp or plateau following the maximum peak current. These post spike features represent neurotransmitter release from a dilated pore before constriction and show that enhancing membrane rigidity via cholesterol adds resistance to a dilated pore to re-close. This implies that the cholesterol dependent biophysical properties of the membrane directly affect the exocytosis kinetics and that membrane tension along with membrane rigidity can influence the fusion pore dynamics and stabilization which is central to regulation of neurochemical release.

Characterizing use-phase chemical releases, fate, and disposal for modeling longitudinal human exposures to consumer products

EPA Science Inventory

The US EPA’s Human Exposure Model (HEM) is an integrated modeling system to estimate human exposure to chemicals in household consumer products. HEM consists of multiple modules, which may be run either together, or independently. The Source-to-Dose (S2D) module in HEM use...

78 FR 3479 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68535; File No. SR-OCC-2012-24] Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Make Its By-Laws and Rules Consistent With Recent System Changes to the Stock Loan/Hedge...

Analysis of volatiles induced by oviposition of elm leaf beetle Xanthogaleruca luteola on Ulmus minor.

PubMed

Wegener, R; Schulz, S; Meiners, T; Hadwich, K; Hilker, M

2001-03-01

Egg deposition of the elm leaf beetle Xanthogaleruca luteola causes the emission of volatiles from its food plant, Ulmus minor. These volatiles are exploited by the egg parasitoid, Oomyzus gallerucae, to locate its host. In contrast to other tritrophic systems, the release of volatiles is not induced by feeding but by egg deposition. Previous investigations showed that the release is systemic and can be triggered by jasmonic acid. Comparison of headspace analysis revealed similarities in the blend of volatiles emitted following egg deposition and feeding. The mixture consists of more than 40 compounds; most of the substances are terpenoids. Leaves next to those carrying eggs emit fewer compounds. When treated with jasmonic acid, leaves emit a blend that consists almost exclusively of terpenoids. Dichloromethane extracts of leaves treated with jasmonic acid were also investigated. After separation of extracts of jasmonate induced elm leaves on silica, we obtained a fraction of terpenoid hydrocarbons that was attractive to the parasitoids. This indicates that jasmonic acid stimulates the production of terpenoid hydrocarbons that convey information of egg deposition to the parasitoid.

Formulation development of allopurinol suppositories and injectables.

PubMed

Lee, D K; Wang, D P

1999-11-01

Allopurinol was formulated into injectable and suppository dosage forms. The injectable formulation was prepared by dissolving allopurinol in a cosolvent system consisting of dimethyl sulfoxide (DMSO) and propylene glycol (v/v = 50/50). The stability of allopurinol in the cosolvent system was studied under accelerated storage conditions, and results indicate first-order degradation kinetics with an activation energy of 24.3 kcal/mol. The development of suppository dosage forms was performed by formulating allopurinol with polyethylene glycol (PEG) mixtures of different molecular weights. In vitro release profiles of suppositories formulated with different polyethylene bases were obtained in the pH 7.4 buffer solution using the USP 23 paddle method at 100 rpm. Results indicate that the release rate of the suppository formulations containing PEG 1500/PEG 4000 at the ratio (w/w) of 2.5/10 to 10/2.5 appeared to be similar. However, the addition of sodium lauryl sulfate in the suppository decreased the release rate of allopurinol significantly. A future study to establish in vitro/in vivo correlation (iv/ivc) is suggested.

MAIL LOG, program theory, volume 1. [Scout project automatic data system

NASA Technical Reports Server (NTRS)

Harris, D. K.

1979-01-01

The program theory used to obtain the software package, MAIL LOG, developed for the Scout Project Automatic Data System, SPADS, is described. The program is written in FORTRAN for the PRIME 300 computer system. The MAIL LOG data base consists of three main subfiles: (1) incoming and outgoing mail correspondence; (2) design information releases and reports; and (3) drawings and engineering orders. All subroutine descriptions, flowcharts, and MAIL LOG outputs are given and the data base design is described.

Controlled extended octenidine release from a bacterial nanocellulose/Poloxamer hybrid system.

PubMed

Alkhatib, Y; Dewaldt, M; Moritz, S; Nitzsche, R; Kralisch, D; Fischer, D

2017-03-01

Although bacterial nanocellulose (BNC) has been widely investigated in the last 10years as drug delivery system, up to now no long-term controlled release of drugs could be realized. Therefore, the aim of the present work was the development of a BNC-based drug delivery system that provides prolonged retention time for the antiseptic octenidine up to one week with improved mechanical and antimicrobial properties as well as a high biocompatibility. BNC was modified by incorporation of differently concentrated Poloxamers 338 and 407 as micelles and gels that were extensively investigated regarding size, surface charge, and dynamic viscosity. Depending on type and concentration of the Poloxamer, a retarded octenidine release up to one week could be accomplished. Additionally, superior material properties such as high compression stability and water binding could be achieved. The antimicrobial activity of octenidine against Staphylococcus aureus and Pseudomonas aeruginosa was not changed by the use of Poloxamers. Excellent biocompatibility of the Poloxamer loaded BNC could be demonstrated after local administration in a shell-less hen's egg model. In conclusion, a long-term delivery system consisting of BNC and Poloxamer could be developed for octenidine as a ready-to-use system e.g. for long-term dermal wound treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Design and Implementation of a Wireless Sensor Network-Based Remote Water-Level Monitoring System

PubMed Central

Li, Xiuhong; Cheng, Xiao; Gong, Peng; Yan, Ke

2011-01-01

The proposed remote water-level monitoring system (RWMS) consists of a field sensor module, a base station module, adata center module and aWEB releasing module. It has advantages in real time and synchronized remote control, expandability, and anti-jamming capabilities. The RWMS can realize real-time remote monitoring, providing early warning of events and protection of the safety of monitoring personnel under certain dangerous circumstances. This system has been successfully applied in Poyanghu Lake. The cost of the whole system is approximately 1,500 yuan (RMB). PMID:22319377

Design and implementation of a wireless sensor network-based remote water-level monitoring system.

PubMed

Li, Xiuhong; Cheng, Xiao; Gong, Peng; Yan, Ke

2011-01-01

The proposed remote water-level monitoring system (RWMS) consists of a field sensor module, a base station module, a data center module and a WEB releasing module. It has advantages in real time and synchronized remote control, expandability, and anti-jamming capabilities. The RWMS can realize real-time remote monitoring, providing early warning of events and protection of the safety of monitoring personnel under certain dangerous circumstances. This system has been successfully applied in Poyanghu Lake. The cost of the whole system is approximately 1,500 yuan (RMB).

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.

Mail LOG: Program operating instructions

NASA Technical Reports Server (NTRS)

Harris, D. K.

1979-01-01

The operating instructions for the software package, MAIL LOG, developed for the Scout Project Automatic Data System, SPADS, are provided. The program is written in FORTRAN for the PRIME 300 computer system. The MAIL LOG program has the following four modes of operation: (1) INPUT - putting new records into the data base (2) REVISE - changing or modifying existing records in the data base (3) SEARCH - finding special records existing in the data base (4) ARCHIVE - store or put away existing records in the data base. The output includes special printouts of records in the data base and results from the INPUT and SEARCH modes. The MAIL LOG data base consists of three main subfiles: Incoming and outgoing mail correspondence; Design Information Releases and Releases and Reports; and Drawings and Engineering orders.

Enhanced bioremediation of BTEX using immobilized nutrients: Field demonstration and monitoring

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

Borden, R.C.; Goin, R.T.; Kao, C.M.

1996-12-01

A permeable barrier system was developed for controlling the migration of dissolved contaminant plumes in ground water. The barrier system consisted of a line of closely spaced wells installed perpendicular to the contaminant plume. Each well contained concrete briquets that released oxygen and nitrate at a controlled rate, enhancing the aerobic biodegradation of dissolved hydrocarbons in the downgradient aquifer. A full scale permeable barrier system was constructed at a gasoline-spill site near Leland, NC. Initially, increased dissolved oxygen and decreased benzene, toluene, ethylbenzene, and xylene isomer (BTEX) concentrations in the downgradient aquifer indicated that oxygen released from the remediation wellsmore » was enhancing biodegradation. Field tracer tests and soil analyses performed at the conclusion of the project indicated that the aquifer in the vicinity of the remediation wells was being clogged by precipitation from iron minerals.« less

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.

Elution characteristics of teicoplanin-loaded biodegradable borate glass/chitosan composite.

PubMed

Jia, Wei-Tao; Zhang, Xin; Zhang, Chang-Qing; Liu, Xin; Huang, Wen-Hai; Rahaman, Mohamed N; Day, Delbert E

2010-03-15

Local antibiotic delivery system has an advantage over systemic antibiotic for osteomyelitis treatment due to the delivery of high local antibiotic concentration while avoiding potential systemic toxicity. Composite biomaterials with multifunctional roles, consisting of a controlled antibiotic release, a mechanical (load-bearing) function, and the ability to promote bone regeneration, gradually become the most active area of investigation and development of local antibiotic delivery vehicles. In the present study, a composite of borate glass and chitosan (designated BG/C) was developed as teicoplanin delivery vehicle. The in vitro elution kinetics and antibacterial activity of teicoplanin released from BG/C composite as a function of immersion time were determined. Moreover, the pH changes of eluents and the bioactivity of the composite were characterized using scanning electron microscopy coupled with energy-dispersive spectroscopy and X-ray diffraction analysis. 2009 Elsevier B.V. All rights reserved.

Polymer-coated albumin microspheres as carriers for intravascular tumour targeting of cisplatin.

PubMed

Verrijk, R; Smolders, I J; McVie, J G; Begg, A C

1991-01-01

We used a poly-lactide-co-glycolide polymer (PLAGA 50:50) to formulate cisplatin (cDDP) into microspheres designed for intravascular administration. Two systems were developed. PLAGA-coated albumin microspheres and microspheres consisting of PLAGA only. PLAGA-coated microspheres displayed a mean diameter of 31.8 +/- 0.9 microns and a payload of 7.5% cDDP (w/w). Solid PLAGA microspheres exhibited a mean diameter of 19.4 +/- 0.6 microns and a payload of 20% cDDP. Release characteristics and in vitro effects on L1210 leukemia and B16 melanoma cell lines were investigated. Both types of microsphere overcame the initial rapid release of cDDP (burst effect), and PLAGA-coated albumin microspheres also showed a lag phase of approximately 30 min before cDDP release began. PLAGA-coated albumin microspheres released most of their payload through diffusion, and the coating eventually cracked after 7 days' incubation in saline supplemented with 0.1% Tween at 37 degrees C, enabling the release of any cDDP remaining. Effects of platinum, pre-released from PLAGA-coated albumin microspheres on the in vitro growth of L1210 cells were comparable with those of standard formulations (dissolved) of cDDP. Material released from non-drug-loaded PLAGA microspheres had no effect on L1210 cell growth, suggesting the absence of cytotoxic compounds in the matrix. The colony-forming ability of B16 cells was also equally inhibited by standard cDDP and pre-released drug. These studies show that formulation of cDDP in PLAGA-based microspheres prevents the rapid burst effect of cDDP seen in previous preparations and offers an improved system of administration for hepatic artery infusion or adjuvant therapy, enabling better clinical handling and the promise of a higher ratio of tumour tissue to normal tissue.

Development and agronomical validation of new fertilizer compositions of high bioavailability and reduced potential nutrient losses.

PubMed

Erro, Javier; Urrutia, Oscar; San Francisco, Sara; Garcia-Mina, Jose M

2007-09-19

To optimize the economical cost of each unit of fertilizer applied and to reduce the environmental contamination caused by nutrient losses, the development of highly efficient granulated fertilizers is of great importance. This study proposes a strategy that consists of developing specific fertilizers having nutrient release patterns that are dependent on plant activity in the rhizosphere. This type of fertilizer is named "rhizosphere-controlled fertilizer" (RCF fertilizer). This fertilizer is based on the introduction of an organomineral matrix composed of metal [Mg (Ca is also possible), Zn (Fe and other metals are also possible)]-humic phosphates. The presence of this matrix modifies the nutrient release pattern of the fertilizer. In this way there are two main nutrient fractions: (i) a water-soluble fraction or "starter" fraction and (ii) a "rhizosphere-controlled" fraction insoluble in water but soluble by the action of the rhizospheric acids released by plants and microorganisms. This study shows the chemical and structural characterization of the organomineral matrix, as well as its efficiency in slowing the nutrient release rate of the RCF fertilizer, principally with respect to P and N. It is demonstrated how these properties of the matrix were also reflected in the significant reduction in both ammonia volatilization and N leaching in a pot system consisting of wheat plants cultivated in a calcareous soil and fertilized with a RCF fertilizer.

Hydrophobic interaction mediated coating of Pluronics on mesoporous silica nanoparticle with stimuli responsiveness for cancer therapy.

PubMed

Sha, Luping; Wang, Da; Mao, Yuling; Shi, Wei; Gao, Tianbin; Zhao, Qinfu; Wang, Si-Ling

2018-05-22

In this research, a novel method was used to successfully make Pluronic P123 stably coated on mesoporous silica nanoparticles (MSN). That P123 and MSN co-constructed a drug delivery system (DDS) had not been reported. In this DDS, the coating of P123 was realized through hydrophobic interaction with octadecyl chain modified MSN. Experiments found only Pluronic with an appropriate ratio of hydrophilic and lipophilic segment could keep the nanoassemblies stable. For comparison, nanoassemblies consisted of P123 and octadecyl chain modified MSN with or without disulfide bond were prepared, which were denoted as PSMSN and PMSN respectively. Disulfide bond was expected to endow the system with redox-responsiveness to enhance the therapeutic effect meanwhile decrease toxicity. A series of experiments including characterization of the nanoparticles, in vitro drug release, cell uptake and cellular drug release, in vitro cytotoxicity, cell migration and biodistribution of the nanoparticles were carried out. Compared with PMSN, PSMSN displayed redox-responsive drug release property not only in in vitro release text, but also on the cellular level. In addition, cell migration experiments proved that the coating of P123 endowed the system with the ability of anti-metastasis. The accumulation of P123 in tumor was enhanced after coating on MSN by virtue of the "EPR" effect of nanoparticles compared with the solution form. . © 2018 IOP Publishing Ltd.

Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters.

PubMed

Kanani, Kunal; Gatoulis, Sergio C; Voelker, Michael

2015-08-03

Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer's clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA) is rapidly converted into its main active metabolite, salicylic acid (SA). Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters.

Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters

PubMed Central

Kanani, Kunal; Gatoulis, Sergio C.; Voelker, Michael

2015-01-01

Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA) is rapidly converted into its main active metabolite, salicylic acid (SA). Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters. PMID:26247959

Synthesis, characterization and drug release properties of 3D chitosan/clinoptilolite biocomposite cryogels.

PubMed

Dinu, Maria Valentina; Cocarta, Ana Irina; Dragan, Ecaterina Stela

2016-11-20

Three-dimensional (3D) biocomposites based on chitosan (CS) and clinoptilolite (CPL) were prepared by cryogelation and their potential application as drug carriers was investigated. Variation of CPL content from 0 to 33wt.% allowed the formation of biocomposites with heterogeneous morphologies consisting of randomly distributed pores. The further increase of CPL content led to ordered porous architectures where parallel pore channels were observed. The CPL content had a strong influence on water uptake, as well as on the cumulative release of diclofenac sodium (DS) and indomethacin (IDM). It was demonstrated that the drug delivery preferentially takes place in phosphate buffer saline (pH 7.4) in comparison to simulated gastric fluid (pH 1.2), where only a reduced drug release was observed. The drug release mechanism dominating these systems is described as a pseudo-Fickian diffusion, but it changes to non-Fickian release when 33wt.% of CPL was entrapped into the CS matrix or when IDM was loaded into biocomposites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oral controlled release optimization of pellets prepared by extrusion-spheronization processing.

PubMed

Bianchini, R; Vecchio, C

1989-06-01

Controlled release high dosage forms of a typical drug such as Indobufen were prepared as multiple-unit doses by employing extrusion-spheronization processing and subsequently film coating operations. The effects of drug particle size, drug/binder ratio, extruder screen size and preparation reproducibility on the physical properties of the spherical granules were evaluated. Controlled release optimization was obtained on the same granules by coating with polymeric membranes of different thickness consisting of water-soluble and insoluble substances. Film coating was applied from an organic solution using pan coating technique. The drug diffusion is allowed by dissolution of part of the membrane leaving small channels of the polymer coat. Further preparations were conducted to evaluate coatings applied from aqueous dispersion (pseudolatex) using air suspension coating technique. In this system the drug diffusion is governed by the intrinsic pore network of the membrane. The most promising preparations having the desired in vitro release, were metered into hard capsules to obtain the drug unit dosage. Accelerated stability tests were carried out to assess the influence of time and the other storage parameters on the drug release profile.

A ROS-Assisted Calcium Wave Dependent on the AtRBOHD NADPH Oxidase and TPC1 Cation Channel Propagates the Systemic Response to Salt Stress.

PubMed

Evans, Matthew J; Choi, Won-Gyu; Gilroy, Simon; Morris, Richard J

2016-07-01

Plants exhibit rapid, systemic signaling systems that allow them to coordinate physiological and developmental responses throughout the plant body, even to highly localized and quickly changing environmental stresses. The propagation of these signals is thought to include processes ranging from electrical and hydraulic networks to waves of reactive oxygen species (ROS) and cytoplasmic Ca(2+) traveling throughout the plant. For the Ca(2+) wave system, the involvement of the vacuolar ion channel TWO PORE CHANNEL1 (TPC1) has been reported. However, the precise role of this channel and the mechanism of cell-to-cell propagation of the wave have remained largely undefined. Here, we use the fire-diffuse-fire model to analyze the behavior of a Ca(2+) wave originating from Ca(2+) release involving the TPC1 channel in Arabidopsis (Arabidopsis thaliana). We conclude that a Ca(2+) diffusion-dominated calcium-induced calcium-release mechanism is insufficient to explain the observed wave transmission speeds. The addition of a ROS-triggered element, however, is able to quantitatively reproduce the observed transmission characteristics. The treatment of roots with the ROS scavenger ascorbate and the NADPH oxidase inhibitor diphenyliodonium and analysis of Ca(2+) wave propagation in the Arabidopsis respiratory burst oxidase homolog D (AtrbohD) knockout background all led to reductions in Ca(2+) wave transmission speeds consistent with this model. Furthermore, imaging of extracellular ROS production revealed a systemic spread of ROS release that is dependent on both AtRBOHD and TPC1 These results suggest that, in the root, plant systemic signaling is supported by a ROS-assisted calcium-induced calcium-release mechanism intimately involving ROS production by AtRBOHD and Ca(2+) release dependent on the vacuolar channel TPC1. © 2016 American Society of Plant Biologists. All Rights Reserved.

An airborne perfluorocarbon tracer system and its first application for a Lagrangian experiment

NASA Astrophysics Data System (ADS)

Ren, Y.; Baumann, R.; Schlager, H.

2015-01-01

A perfluorocarbon tracer system (PERTRAS), specifically designed for Lagrangian aircraft experiments, has been developed by the Deutsches Zentrum für Luft- und Raumfahrt (German Aerospace Center, DLR). It consists of three main parts: a tracer release unit (RU), an adsorption tube sampler (ATS), and a tracer analytical system. The RU was designed for airborne tracer release experiments; meanwhile, it can be used on various platforms for different experimental purposes (here research vessel). PERTRAS was for the first time applied in the field campaign Stratospheric ozone: Halogen Impacts in a Varying Atmosphere (SHIVA) in November 2011. An amount of 8.8 kg perfluoromethylcyclopentane (PMCP) was released aboard the research vessel Sonne (RV Sonne) near the operational site of this campaign, Miri, Malaysia, on 21 November. The tracer samples collected using the ATS onboard the DLR research aircraft Falcon were analyzed in the laboratory using a thermal desorber-gas chromatography-mass spectrometry (TD-GC-MS) system. Guided by forecasts calculated with the Lagrangian model Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT), 64 tracer samples were collected onboard the Falcon approximately 5 and 25 h after the release, mostly with a time resolution of 1 min. Enhanced PMCP concentrations relative to ambient PMCP background values (mean: 6.62 fmol mol-1) were detected during three intersects of the fresh tracer plume (age 5 h), with a maximum value of 301.33 fmol mol-1. This indicates that the fresh tracer plume was successfully intercepted at the forecast position. During the second flight, 25 h after the release, the center of tracer plume was not detected by the sampling system due to a faster advection of the plume than forecast. The newly developed PERTRAS system has been successfully deployed for the first time. The instrumental setup and comparisons between the measurements and HYSPLIT simulations are presented in this study.

An airborne perfluorocarbon tracer system and its first application for a Lagrangian experiment

NASA Astrophysics Data System (ADS)

Ren, Y.; Baumann, R.; Schlager, H.

2014-07-01

A perfluorocarbon tracer system (PERTRAS), specifically designed for Lagrangian aircraft experiments, has been developed by the Deutsches Zentrum für Luft- und Raumfahrt (German Aerospace Center, DLR). It consists of three main parts: a tracer release unit (RU), an adsorption tube sampler (ATS) and a tracer analytical system. The RU was designed for airborne tracer release experiments; meanwhile, it can be used on various platforms for different experimental purpose (here research vessel). PERTRAS was for the first time applied in the field campaign Stratospheric ozone: halogen Impacts in a Varying Atmosphere (SHIVA) in November 2011. An amount of 8.8 kg perfluoromethylcyclopentane (PMCP) was released aboard the research vessel Sonne (RV Sonne) near the operational site of this campaign, Miri, Malaysia, on 21 November. The tracer samples collected using the ATS on board the DLR research aircraft Falcon were analyzed in the laboratory using a thermal desorber/gas chromatography/mass spectrometry (TD/GC/MS) system. Guided by forecasts calculated with the Lagrangian model, Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT), 64 tracer samples were collected onboard the Falcon approximately 5 and 25 h after the release, respectively, mostly with a time resolution of 1 min. Enhanced PMCP concentrations relative to ambient PMCP background values (mean: 6.62 fmol mol-1) were detected during three intersects of the fresh tracer plume (age 5 h), with a maximum value of 301.33 fmol mol-1. This indicates that the fresh tracer plume was successfully intercepted at the forecasted position. During the second flight, 25 h after the release, the center of tracer plume was not detected by the sampling system due to a faster advection of the plume than forecasted. The newly developed PERTRAS system has been successfully deployed for the first time. The instrumental set-up and comparisons between the measurements and HYSPLIT simulations are presented in this study.

A novel liposomal drug delivery system for PMMA bone cements

PubMed Central

Birchall, James C.; Evans, Samuel L.; Denyer, Stephen P.

2015-01-01

Abstract The population in developed countries is ageing and the number of people experiencing joint‐related conditions, such as osteoarthritis, is expected to increase. Joint replacements are currently the most effective treatment for severe joint conditions and although many of these procedures are successful, infection developing after the procedure is still an issue, requiring complex and expensive revisions. Whilst incorporating a powdered antibiotic within the bone cement can reduce infection rates, the powder frequently agglomerates, resulting in poor antibiotic release characteristics and compromised mechanical performance of the cement. To overcome these issues, a novel delivery system consisting of antibiotic‐loaded nano‐sized liposomes was developed for inclusion into polymethyl methacrylate (PMMA) bone cement. This system was tested in a commercial cement (Palacos R) and consistently delivered a higher percentage (22%) of the incorporated antibiotic when compared to the powdered antibiotic cement (9%), meaning less antibiotic needs to be incorporated than with conventional cement. The novel system resulted in a controlled and gradual release of antibiotic over a longer, 30‐day period and enhanced the toughness, bending strength and Vickers hardness of the cement, without altering its polymerization or molecular structure. This new material has the potential to significantly reduce infections in cemented joint replacements leading to enhanced patient quality of life and reduced healthcare costs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1510–1524, 2016. PMID:26256271

Controlled release for crop and wood protection: Recent progress toward sustainable and safe nanostructured biocidal systems.

PubMed

Mattos, Bruno D; Tardy, Blaise L; Magalhães, Washington L E; Rojas, Orlando J

2017-09-28

We review biocide delivery systems (BDS), which are designed to deter or control harmful organisms that damage agricultural crops, forests and forest products. This is a timely topic, given the growing socio-economical concerns that have motivated major developments in sustainable BDS. Associated designs aim at improving or replacing traditional systems, which often consist of biocides with extreme behavior as far as their solubility in water. This includes those that compromise or pollute soil and water (highly soluble or volatile biocides) or those that present low bioavailability (poorly soluble biocides). Major breakthroughs are sought to mitigate or eliminate consequential environmental and health impacts in agriculture and silviculture. Here, we consider the most important BDS vehicles or carriers, their synthesis, the environmental impact of their constituents and interactions with the active components together with the factors that affect their rates of release such as environmental factors and interaction of BDS with the crops or forest products. We put in perspective the state-of-the-art nanostructured carriers for controlled release, which need to address many of the challenges that exist in the application of BDS. Copyright © 2017 Elsevier B.V. All rights reserved.

3D printed multi-compartment capsular devices for two-pulse oral drug delivery.

PubMed

Maroni, A; Melocchi, A; Parietti, F; Foppoli, A; Zema, L; Gazzaniga, A

2017-12-28

In the drug delivery area, versatile therapeutic systems intended to yield customized combinations of drugs, drug doses and release kinetics have drawn increasing attention, especially because of the advantages that personalized pharmaceutical treatments would offer. In this respect, a previously proposed capsular device able to control the release performance based on its design and composition, which could extemporaneously be filled, was improved to include multiple separate compartments so that differing active ingredients or formulations may be conveyed. The compartments, which may differ in thickness and composition, resulted from assembly of two hollow halves through a joint also acting as a partition. The systems were manufactured by fused deposition modeling (FDM) 3D printing, which holds special potential for product personalization, and injection molding (IM) that would enable production on a larger scale. Through combination of compartments having wall thickness of 600 or 1200μm, composed of promptly soluble, swellable/erodible or enteric soluble polymers, devices showing two-pulse release patterns, consistent with the nature of the starting materials, were obtained. Systems fabricated using the two techniques exhibited comparable performance, thus proving the prototyping ability of FDM versus IM. Copyright © 2017 Elsevier B.V. All rights reserved.

Scalable Integrated Multi-Mission Support System (SIMSS) Simulator Release 2.0 for GMSEC

NASA Technical Reports Server (NTRS)

Kim, John; Velamuri, Sarma; Casey, Taylor; Bemann, Travis

2012-01-01

Scalable Integrated Multi-Mission Support System (SIMSS) Simulator Release 2.0 software is designed to perform a variety of test activities related to spacecraft simulations and ground segment checks. This innovation uses the existing SIMSS framework, which interfaces with the GMSEC (Goddard Mission Services Evolution Center) Application Programming Interface (API) Version 3.0 message middleware, and allows SIMSS to accept GMSEC standard messages via the GMSEC message bus service. SIMSS is a distributed, component-based, plug-and-play client-server system that is useful for performing real-time monitoring and communications testing. SIMSS runs on one or more workstations, and is designed to be user-configurable, or to use predefined configurations for routine operations. SIMSS consists of more than 100 modules that can be configured to create, receive, process, and/or transmit data. The SIMSS/GMSEC innovation is intended to provide missions with a low-cost solution for implementing their ground systems, as well as to significantly reduce a mission s integration time and risk.

The effect of methylcellulose on metronidazole release from polyacrylic acid hydrogels.

PubMed

Musial, Witold

2007-08-01

Topical treatment of acne rosacea, a chronic condition characterized by recurrent course for many years, is primarily based on metronidazole preparations. The aim of this study was to evaluate the effect of various acrylic acid polymers, in composition with methylcellulose on metronidazole release rate from hydrogels proposed for the treatment of acne rosacea. Viscosity and release studies using "Paddle over Disk" system with semipermeable membrane of MWCO 3500 were performed. Compositions of Carbopol 971P and methylcellulose revealed an increase in viscosity with increasing concentration of methylcellulose in the range of 17200-26166 mPa.s. In all the examined formulations, the release process was characterized by a two-stage course. Among bipolymeric formulations, the highest first-stage release rate of 9.18 x 10(-3) min(-1) was determined for the gel consisting of 2.00% Carbopol 980NF with 1.00% methylcellulose. The second-stage release rates ranged between 2.88 x 10(-3) and 8.00 x 10(-3) min(-1). Two-stage release course can thus be attributed to metronidazole distribution into two compartments of hydrogel matrix. Proposed gels, with similar rheological properties, may be used for ex vivo and in vivo studies to obtain a suitable drug activity of metronidazole in the treatment of acne rosacea.

Controls on Fe(II)-Activated Trace Element Release from Goethite and Hematite

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

Frierdich, Andrew J.; Catalano, Jeffrey G.

2012-03-26

Electron transfer and atom exchange (ETAE) between aqueous Fe(II) and Fe(III) oxides induces surface growth and dissolution that affects trace element fate and transport. We have recently demonstrated Ni(II) cycling through goethite and hematite (adsorbed Ni incorporates into the mineral structure and preincorporated Ni releases to solution) during Fe(II)-Fe(III) ETAE. However, the chemical parameters affecting net trace element release remain unknown. Here, we examine the chemical controls on Ni(II) and Zn(II) release from Ni- and Zn-substituted goethite and hematite during reaction with Fe(II). Release follows a rate law consistent with surface reaction limited mineral dissolution and suggests that release occursmore » near sites of Fe(III) reductive dissolution during Fe(II)-Fe(III) ETAE. Metal substituent type affects reactivity; Zn release is more pronounced from hematite than goethite, whereas the opposite trend occurs for Ni. Buildup of Ni or Zn in solution inhibits further release but this resumes upon fluid exchange, suggesting that sustained release is possible under flow conditions. Mineral and aqueous Fe(II) concentrations as well as pH strongly affect sorbed Fe(II) concentrations, which directly control the reaction rates and final metal concentrations. Our results demonstrate that structurally incorporated trace elements are mobilized from iron oxides into fluids without abiotic or microbial net iron reduction. Such release may affect micronutrient availability, contaminant transport, and the distribution of redox-inactive trace elements in natural and engineered systems.« less

Preparation and evaluation of Vinpocetine self-emulsifying pH gradient release pellets.

PubMed

Liu, Mengqi; Zhang, Shiming; Cui, Shuxia; Chen, Fen; Jia, Lianqun; Wang, Shu; Gai, Xiumei; Li, Pingfei; Yang, Feifei; Pan, Weisan; Yang, Xinggang

2017-11-01

The main objective of this study was to develop a pH gradient release pellet with self-emulsifying drug delivery system (SEDDS), which could not only improve the oral bioavailability of Vinpocetine (VIN), a poor soluble drug, but reduce the fluctuation of plasma concentration. First, the liquid VIN SEDDS formulation was prepared. Then the self-emulsifying pH gradient release pellets were prepared by extrusion spheronization technique, and formulation consisted by the liquid SEDDS, absorbent (colloidal silicon dioxide), penetration enhancer (sodium chloride), microcrystalline cellulose, ethyl alcohol, and three coating materials (HPMC, Eudragit L30D55, Eudragit FS30D) were eventually selected. Three kinds of coated pellets were mixed in capsules with the mass ratio of 1:1:1. The release curves of capsules were investigated in vitro under the simulated gastrointestinal conditions. In addition, the oral bioavailability and pharmacokinetics of VIN self-emulsifying pH gradient release pellets, commercial tablets and liquid VIN SEDDS were evaluated in Beagle dogs. The oral bioavailability of self-emulsifying pH gradient release pellets was about 149.8% of commercial VIN tablets, and it was about 86% of liquid VIN SEDDS, but there were no significant difference between liquid SEDDS and self-emulsifying pH gradient release pellets. In conclusion, the self-emulsifying pH gradient release pellets could significantly enhance the absorption of VIN and effectively achieve a pH gradient release. And the self-emulsifying pH gradient release pellet was a promising method to improve bioavailability of insoluble drugs.

Photolabile ruthenium complexes to cage and release a highly cytotoxic anticancer agent.

PubMed

Wei, Jianhua; Renfrew, Anna K

2018-02-01

CHS-828 (N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N″-4-pyridyl guanidine) is an anticancer agent with low bioavailability and high systemic toxicity. Here we present an approach to improve the therapeutic profile of the drug using photolabile ruthenium complexes to generate light-activated prodrugs of CHS-828. Both prodrug complexes are stable in the dark but release CHS-828 when irradiated with visible light. The complexes are water-soluble and accumulate in tumour cells in very high concentrations, predominantly in the mitochondria. Both prodrug complexes are significantly less cyototoxic than free CHS-828 in the dark but their toxicity increases up to 10-fold in combination with visible light. The cellular responses to light treatment are consistent with release of the cytotoxic CHS-828 ligand. Copyright © 2017 Elsevier Inc. All rights reserved.

A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways

NASA Astrophysics Data System (ADS)

Spring, Bryan Q.; Bryan Sears, R.; Zheng, Lei Zak; Mai, Zhiming; Watanabe, Reika; Sherwood, Margaret E.; Schoenfeld, David A.; Pogue, Brian W.; Pereira, Stephen P.; Villa, Elizabeth; Hasan, Tayyaba

2016-04-01

Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)—a multikinase inhibitor—encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release while reducing systemic drug exposure and associated toxicities.

Development of a new delivery system consisting in 'drug-in cyclodextrin-in PLGA nanoparticles'.

PubMed

Mura, Paola; Maestrelli, Francesca; Cecchi, Matteo; Bragagni, Marco; Almeida, Antonio

2010-01-01

A combined approach based on drug cyclodextrin (CD) complexation and loading into PLGA nanoparticles (NP) has been developed to improve oxaprozin therapeutic efficiency. This strategy exploits the solubilizing and stabilizing properties of CDs and the prolonged-release and targeting properties of PLGA NPs. Drug-loaded NPs, prepared by double-emulsion, were examined for dimensions, zeta-potential and entrapment efficiency. Solid-state studies demonstrated the absence of drug-polymer interactions and assessed the amorphous state of the drug-CD complex loaded into NPs. Drug release rate from NPs was strongly influenced by the presence and kind of CD used. The percentage released at 24 h varied from 16% (plain drug-loaded NPs) to 50% (drug-betaCD-loaded NPs) up to 100% (drug-methylbetaCD-loaded NPs). This result suggests the possibility of using CD complexation not only to promote, but also to regulate drug release rate from NPs, by selecting the proper type of CD or CD combination.

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.

Under stressful conditions activation of the ionotropic P2X7 receptor differentially regulates GABA and glutamate release from nerve terminals of the rat cerebral cortex.

PubMed

Barros-Barbosa, Aurora R; Oliveira, Ângela; Lobo, M Graça; Cordeiro, J Miguel; Correia-de-Sá, Paulo

2018-01-01

γ-Aminobutyric acid (GABA) and glutamate (Glu) are the main inhibitory and excitatory neurotransmitters in the central nervous system (CNS), respectively. Fine tuning regulation of extracellular levels of these amino acids is essential for normal brain activity. Recently, we showed that neocortical nerve terminals from patients with epilepsy express higher amounts of the non-desensitizing ionotropic P2X7 receptor. Once activated by ATP released from neuronal cells, the P2X7 receptor unbalances GABAergic vs. glutamatergic neurotransmission by differentially interfering with GABA and Glu uptake. Here, we investigated if activation of the P2X7 receptor also affects [ 3 H]GABA and [ 14 C]Glu release measured synchronously from isolated nerve terminals (synaptosomes) of the rat cerebral cortex. Data show that activation of the P2X7 receptor consistently increases [ 14 C]Glu over [ 3 H]GABA release from cortical nerve terminals, but the GABA/Glu ratio depends on extracellular Ca 2+ concentrations. While the P2X7-induced [ 3 H]GABA release is operated by a Ca 2+ -dependent pathway when external Ca 2+ is available, this mechanism shifts towards the reversal of the GAT1 transporter in low Ca 2+ conditions. A different scenario is verified regarding [ 14 C]Glu outflow triggered by the P2X7 receptor, since the amino acid seems to be consistently released through the recruitment of connexin-containing hemichannels upon P2X7 activation, both in the absence and in the presence of external Ca 2+ . Data from this study add valuable information suggesting that ATP, via P2X7 activation, not only interferes with the high-affinity uptake of GABA and Glu but actually favors the release of these amino acids through distinct molecular mechanisms amenable to differential therapeutic control. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

A computer-based servo system for controlling isotonic contractions of muscle.

PubMed

Smith, J P; Barsotti, R J

1993-11-01

We have developed a computer-based servo system for controlling isotonic releases in muscle. This system is a composite of commercially available devices: an IBM personal computer, an analog-to-digital (A/D) board, an Akers AE801 force transducer, and a Cambridge Technology motor. The servo loop controlling the force clamp is generated by computer via the A/D board, using a program written in QuickBASIC 4.5. Results are shown that illustrate the ability of the system to clamp the force generated by either skinned cardiac trabeculae or single rabbit psoas fibers down to the resolution of the force transducer within 4 ms. This rate is independent of the level of activation of the tissue and the size of the load imposed during the release. The key to the effectiveness of the system consists of two algorithms that are described in detail. The first is used to calculate the error signal to hold force to the desired level. The second algorithm is used to calculate the appropriate gain of the servo for a particular fiber and the size of the desired load to be imposed. The results show that the described computer-based method for controlling isotonic releases in muscle represents a good compromise between simplicity and performance and is an alternative to the custom-built digital/analog servo devices currently being used in studies of muscle mechanics.

The conductivity measurements applied for the evaluation of controlled release of chlorhexidine from thermosensitive N-isopropylacrylamide derivative microgels.

PubMed

Musiał, Witold; Kokol, Vanja; Voncina, Bojana

2009-01-01

The aim of the work was the evaluation of the conductivity changes in aqueous environment, consisting of chlorhexidine, and N-isopropylacrylamide derivative microgel, during increasing the temperature between 25 degrees C and 42 degrees C, as a prerequisite to develop the this microgel for controlled release of chlorhexidine, when alterations in temperature are involved. Conductivity of studied systems underwent specific alterations, when temperature increased. For the system with polymer PNM I the values of conductivity were in the range 104,47 microS/cm - 134,70 microS/ cm, for temperature range 25 degrees C and 42 degrees C. In the case of PNM II - CX system, respective values reached 91,75 microS/cm - 135,95 microS/cm. The lowest conductivity values were observed when PNM III - CX mixture was studied: 96,90 microS/cm and 117,37 microS/cm. When a complex of derivatives of N-isopropylacrylamide with chlorhexidine undergoes thermal alteration, there is a potential to obtain controlled release of chlorhexidine from the polymeric bead in the range between 25 degrees C and 42 degrees C. The affinity of chlorhexidine to the polymer may be assessed in this systems applying the conductivity measurements. The solubility of chlorhexidine in the polymeric systems should be in future evaluated, to determine role of this factor in the conductivity alterations.

Rhodamine/Nanodiamond as a System Model for Drug Carrier.

PubMed

Reina, G; Orlanducci, S; Cairone, C; Tamburri, E; Lenti, S; Cianchetta, I; Rossi, M; Terranova, M L

2015-02-01

In this paper we present some strategies that are being developed in our labs towards enabling nanodiamond-based applications for drug delivery. Rhodamine B (RhB) has been choosen as model molecule to study the loading of nanodiamonds with active moieties and the conditions for their controlled release. In order to test the chemical/physical interactions between functionalized detonation nanodiamond (DND) and complex molecules, we prepared and tested different RhB@DND systems, with RhB adsorbed or linked by ionic bonding to the DND surface. The chemical state of the DND surfaces before conjugation with the RhB molecules, and the chemical features of the DND-RhB interactions have been deeply analysed by coupling DND with Au nanoparticles and taking advantage of surface enhanced Raman spectroscopy SERS. The effects due to temperature and pH variations on the process of RhB release from the DND carrier have been also investigated. The amounts of released molecules are consistent with those required for effective drug action in conventional therapeutic applications, and this makes the DND promising nanostructured cargos for drug delivery applications.

Ion release from dental casting alloys as assessed by a continuous flow system: Nutritional and toxicological implications.

PubMed

López-Alías, José F; Martinez-Gomis, Jordi; Anglada, Josep M; Peraire, Maria

2006-09-01

The aims of this study were to quantify the metallic ions released by various dental alloys subjected to a continuous flow of saliva and to estimate the nutritional and toxicological implications of such a release. Four pieces of three nickel-based, one noble, one high-noble and two copper-aluminum alloys were cast and then immersed in a continuous flow of artificial saliva for 15 days. To simulate three meals a day, casts were subjected to thrice-daily episodes, lasting 30 min each and consisting of pH decreases and salinity increases. After 15 days, the metallic ions in the artificial saliva were analyzed. Data were expressed as averaged release rate: microg/cm2/day of ion released for each alloy. The highest value of 95% Cl of each ion was adapted to a hypothetical worst scenario of a subject with 100 cm2 of exposed metal surface. The results were compared with the tolerable upper daily intake level of each ion. The copper-aluminum alloys released copper, aluminum, nickel, manganese and iron. The nickel-based alloys essentially released nickel and chromium, while the beryllium-containing alloy released beryllium and significantly more nickel. The noble and high-noble alloys were very resistant to corrosion. The amount of ions released remained far below the upper tolerable intake level, with the exception of nickel, released by beryllium-containing nickel-based alloy, whose levels approach 50% of this threshold. The daily amount of ions released seems to be far below the tolerable upper intake levels for each ion.

A Model Action Pla to Reduce the Use and Release of CFCs in Air- Conditioning and Refrigeration Systems

DTIC Science & Technology

1992-09-01

ccmpounds discussed in the research. Chiorofluorocarbon nolecules consist entirely of chlorine, fluorine, and carbon atoms. When a hydrogen atm is bonded...of carbon, hydrogen, and fluorine atoms contained in the compound. Chlorine atms miake up the remaining available bond sites. For exanple, CFC-l1...HCFC-22 has been successfully tested as a substitute for CFC-12 and CFC-502 in retrofitted supermarket refrigeration systems. There is same loss of

Development and Overview of CPAS Sasquatch Airdrop Landing Location Predictor Software

NASA Technical Reports Server (NTRS)

Bledsoe, Kristin J.; Bernatovich, Michael A.

2015-01-01

The Capsule Parachute Assembly System (CPAS) is the parachute system for NASA's Orion spacecraft. CPAS is currently in the Engineering Development Unit (EDU) phase of testing. The test program consists of numerous drop tests, wherein a test article rigged with parachutes is extracted from an aircraft. During such tests, range safety is paramount, as is the recoverability of the parachutes and test article. It is crucial to establish a release point from the aircraft that will ensure that the article and all items released from it during flight will land in a designated safe area. The Sasquatch footprint tool was developed to determine this safe release point and to predict the probable landing locations (footprints) of the payload and all released objects. In 2012, a new version of Sasquatch, called Sasquatch Polygons, was developed that significantly upgraded the capabilities of the footprint tool. Key improvements were an increase in the accuracy of the predictions, and the addition of an interface with the Debris Tool (DT), an in-flight debris avoidance tool for use on the test observation helicopter. Additional enhancements include improved data presentation for communication with test personnel and a streamlined code structure. This paper discusses the development, validation, and performance of Sasquatch Polygons, as well as its differences from the original Sasquatch footprint tool.

The spontaneous and evoked release of spermine from rat brain in vitro.

PubMed Central

Harman, R. J.; Shaw, G. G.

1981-01-01

1 The efflux of previously accumulated [3H]-spermine from brain slices was measured using a continuous perfusion system. The spontaneous efflux was biphasic, consisting of an initial rapid efflux followed by a much slower release. 2 The slices were depolarized by the addition to the medium of high potassium concentrations, ouabain or veratrine. 3 At concentrations greater than 30 mM, potassium evoked a striking increase in the release of [3H]-spermine. Following uptake in the presence of 5.7 x 10(-9)M [3H]-spermine, K+-evoked release was dependent on the presence of calcium ions. Release of spermine after uptake at 5.6 x 10(-8)M or 5.0 x 10(-7)M was not calcium-dependent. 4 The calcium-dependent, K+-stimulated release of spermine was inhibited in the presence of diphenylhydantoin (5 x 10(-5)M) or ruthenium red (10(-5)M). 5 Following uptake of 5.7 x 10(-9)M [3H]-spermine in a sodium-free medium, the calcium-dependent, K+-stimulated release was significantly inhibited. 5 Ouabain (10(-4)M) caused a large but calcium-independent increase in the efflux of [3H]-spermine. 7 Veratrine-induced release was less substantial but was increased in a calcium-free medium. Release evoked by veratrine was abolished in the absence of sodium. 8 These results are discussed with respect to a possible 'neurotransmitter' or 'neuromodulator' role for spermine. PMID:6169383

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

PubMed

Pfister, Lukas A; Alther, Eva; Papaloïzos, Michaël; Merkle, Hans P; Gander, Bruno

2008-06-01

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

Risperidone mucoadhesive buccal tablets: formulation design, optimization and evaluation

PubMed Central

Çelik, Burak

2017-01-01

The aim of this study was to design and optimize risperidone (RIS) mucoadhesive buccal tablets for systemic delivery as an alternative route. Direct compression method was used for the preparation of buccal tablets, and screening studies were conducted with different polymers to determine their effects on tablet characteristics. Carbopol® (CP) and sodium alginate (SA) were selected as two polymer types for further optimization studies by applying response surface methodology. Tablet hardness (TH), ex vivo residence time (RT), and peak detachment force (DF) from buccal mucosa were selected as three important responses. Physicochemical compatibility of formulation excipients and RIS was evaluated by using Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) analysis. In vitro drug release profiles and release kinetics were investigated; swelling index and matrix erosion studies were conducted. Optimum formulation consisted of 16.4% CP and 20.3% SA, which provided 7.67±0.29 hour ex vivo RT, 45.52±4.85 N TH, and 2.12±0.17 N DF. FT-IR spectroscopy and DSC analysis revealed that there was no chemical interaction present between tablet ingredients. Cumulative RIS release of >90% was achieved after 8 hours of in vitro dissolution studies, which was supported by swelling and matrix erosion analysis. Mechanism of RIS release was fitted best to zero-order model, while release exponent (n) value of 0.77 demonstrated an anomalous (non-Fickian) release, indicating combined erosion and swelling mechanism. The results suggested that optimized buccal tablets of RIS would be a promising and alternative delivery system for the treatment of schizophrenia. PMID:29225461

The vaccines consistency approach project: an EPAA initiative.

PubMed

De Mattia, F; Hendriksen, C; Buchheit, K H; Chapsal, J M; Halder, M; Lambrigts, D; Redhead, K; Rommel, E; Scharton-Kersten, T; Sesardic, T; Viviani, L; Ragan, I

2015-01-01

The consistency approach for release testing of established vaccines promotes the use of in vitro, analytical, non-animal based systems allowing the monitoring of quality parameters during the whole production process. By using highly sensitive non-animal methods, the consistency approach has the potential to improve the quality of testing and to foster the 3Rs (replacement, refinement and reduction of animal use) for quality control of established vaccines. This concept offers an alternative to the current quality control strategy which often requires large numbers of laboratory animals. In order to facilitate the introduction of the consistency approach for established human and veterinary vaccine quality control, the European Partnership for Alternatives to Animal Testing (EPAA) initiated a project, the "Vaccines Consistency Approach Project", aiming at developing and validating the consistency approach with stakeholders from academia, regulators, OMCLs, EDQM, European Commission and industry. This report summarises progress since the project's inception.

RMP Guidance for Warehouses - Chapter 4: Offsite Consequence Analysis

EPA Pesticide Factsheets

Offsite consequence analysis (OCA) informs government and the public about potential consequences of an accidental toxic or flammable chemical release at your facility, and consists of a worst-case release scenario and alternative release scenarios.

Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume

PubMed Central

Ivannikov, Maxim V.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

2012-01-01

Synaptic plasticity in many regions of the central nervous system leads to the continuous adjustment of synaptic strength, which is essential for learning and memory. In this study, we show by visualizing synaptic vesicle release in mouse hippocampal synaptosomes that presynaptic mitochondria and specifically, their capacities for ATP production are essential determinants of synaptic vesicle exocytosis and its magnitude. Total internal reflection microscopy of FM1-43 loaded hippocampal synaptosomes showed that inhibition of mitochondrial oxidative phosphorylation reduces evoked synaptic release. This reduction was accompanied by a substantial drop in synaptosomal ATP levels. However, cytosolic calcium influx was not affected. Structural characterization of stimulated hippocampal synaptosomes revealed that higher total presynaptic mitochondrial volumes were consistently associated with higher levels of exocytosis. Thus, synaptic vesicle release is linked to the presynaptic ability to regenerate ATP, which itself is a utility of mitochondrial density and activity. PMID:22772899

Role of iron and aluminum coagulant metal residuals and lead release from drinking water pipe materials.

PubMed

Knowles, Alisha D; Nguyen, Caroline K; Edwards, Marc A; Stoddart, Amina; McIlwain, Brad; Gagnon, Graham A

2015-01-01

Bench-scale experiments investigated the role of iron and aluminum residuals in lead release in a low alkalinity and high (> 0.5) chloride-to-sulfate mass ratio (CSMR) in water. Lead leaching was examined for two lead-bearing plumbing materials, including harvested lead pipe and new lead: tin solder, after exposure to water with simulated aluminum sulfate, polyaluminum chloride and ferric sulfate coagulation treatments with 1-25-μM levels of iron or aluminum residuals in the water. The release of lead from systems with harvested lead pipe was highly correlated with levels of residual aluminum or iron present in samples (R(2) = 0.66-0.88), consistent with sorption of lead onto the aluminum and iron hydroxides during stagnation. The results indicate that aluminum and iron coagulant residuals, at levels complying with recommended guidelines, can sometimes play a significant role in lead mobilization from premise plumbing.

A Review of Disintegration Mechanisms and Measurement Techniques.

PubMed

Markl, Daniel; Zeitler, J Axel

2017-05-01

Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the processability or to affect the drug release behaviour in the body. These complex porous systems undergo different mechanisms when they come in contact with physiological fluids. The performance of a drug is primarily influenced by the disintegration and dissolution behaviour of the powder compact. The disintegration process is specifically critical for immediate-release dosage forms. Its mechanisms and the factors impacting disintegration are discussed and methods used to study the disintegration in-situ are presented. This review further summarises mathematical models used to simulate disintegration phenomena and to predict drug release kinetics.

In-situ measurement of temperature during rapid thermite deflagrations

NASA Astrophysics Data System (ADS)

Densmore, John; Sullivan, Kyle

Thermites are composite materials that consist of a fuel (metal) and oxidizer (metal oxide), that upon reaction can release a large amount of energy (20.8 kJ/cc for Al:CuO). The time scale for a thermite to release energy (ms) is much longer than a typical detonation (us). In-situ temperature and/or thermal flux measurements can provide fundamental insight into the reaction mechanisms. This information can inform the design and optimization of energy transport during a deflagration, to optimize the energy release rate. To measure the temperature we use a burn tube apparatus and various pyrometry techniques to measure the spatial temperature field as a reaction proceeds towards completion. We show that system properties can be adjusted to achieve custom thermal properties. Lawrence Livermore National Laboratory is operated by Lawrence Livermore National Security, LLC, for the U.S. Department of Energy, National Nuclear Security Administration under Contract DE-AC52-07NA27344.

40 CFR 63.1361 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... can be one release or a series of releases over a short time period due to a malfunction in the... reduces the mass of HAP emitted to the air. The equipment may consist of an individual device or a series... do not occur simultaneously in a batch operation. A batch process consists of a series of batch...

Magnetically guided release of ciprofloxacin from superparamagnetic polymer nanocomposites.

PubMed

Gupta, Rashmi; Bajpai, A K

2011-01-01

Tailored with superparamagnetic properties the magnetic nanocomposites have been thoroughly investigated in recent past because of their potential applications in the fields of biomedicine and bioengineering such as protein detection, magnetic targeted drug carriers, bioseparation, magnetic resonance imaging contrast agents and hyperthermia. Magnetic drug targeting has come up as a safe and effective drug-delivery technology, i.e., with the least amount of magnetic particles a maximum of drug may be easily administered and transported to the site of choice. In the present work novel magnetic drug-targeting carriers consisting of magnetic nanoparticles encapsulated within a smart polymer matrix with potential of controlled drug release is described. To make such magnetic polymeric drug-delivery systems, both the magnetic nanoparticles and antibiotic drug (ciprofloxacin) were incorporated into the hydrogel. The controlled release process and release profiles were investigated as a function of experimental protocols such as percent loading of drug, chemical composition of the nanocomposite, pH of release media and strength of magnetic field on the release profiles. The structure, morphology and compositions of magnetic hydrogel nanocomposites were characterized by FT-IR, TEM, XRD and VSM techniques. It was found that magnetic nanocomposites were biocompatible and superparamagnetic in nature and could be used as a smart drug carrier for controlled and targeted drug delivery.

Thermogenic methane release as a cause for the long duration of the PETM

PubMed Central

Frieling, Joost; Svensen, Henrik H.; Planke, Sverre; Cramwinckel, Margot J.; Selnes, Haavard; Sluijs, Appy

2016-01-01

The Paleocene–Eocene Thermal Maximum (PETM) (∼56 Ma) was a ∼170,000-y (∼170-kyr) period of global warming associated with rapid and massive injections of 13C-depleted carbon into the ocean–atmosphere system, reflected in sedimentary components as a negative carbon isotope excursion (CIE). Carbon cycle modeling has indicated that the shape and magnitude of this CIE are generally explained by a large and rapid initial pulse, followed by ∼50 kyr of 13C-depleted carbon injection. Suggested sources include submarine methane hydrates, terrigenous organic matter, and thermogenic methane and CO2 from hydrothermal vent complexes. Here, we test for the contribution of carbon release associated with volcanic intrusions in the North Atlantic Igneous Province. We use dinoflagellate cyst and stable carbon isotope stratigraphy to date the active phase of a hydrothermal vent system and find it to postdate massive carbon release at the onset of the PETM. Crucially, however, it correlates to the period within the PETM of longer-term 13C-depleted carbon release. This finding represents actual proof of PETM carbon release from a particular reservoir. Based on carbon cycle box model [i.e., Long-Term Ocean–Atmosphere–Sediment Carbon Cycle Reservoir (LOSCAR) model] experiments, we show that 4–12 pulses of carbon input from vent systems over 60 kyr with a total mass of 1,500 Pg of C, consistent with the vent literature, match the shape of the CIE and pattern of deep ocean carbonate dissolution as recorded in sediment records. We therefore conclude that CH4 from the Norwegian Sea vent complexes was likely the main source of carbon during the PETM, following its dramatic onset. PMID:27790990

Glutamatergic transmission in the central nucleus of the amygdala is selectively altered in Marchigian Sardinian alcohol-preferring rats: alcohol and CRF effects

PubMed Central

Herman, Melissa A.; Varodayan, Florence P.; Oleata, Christopher S.; Luu, George; Kirson, Dean; Heilig, Markus; Ciccocioppo, Roberto; Roberto, Marisa

2015-01-01

The CRF system of the central nucleus of the amygdala (CeA) is important for the processing of anxiety, stress, and effects of acute and chronic ethanol. We previously reported that ethanol decreases evoked glutamate transmission in the CeA of Sprague Dawley rats and that ethanol dependence alters glutamate release in the CeA. Here, we examined the effects of ethanol, CRF and a CRF1 receptor antagonist on spontaneous and evoked glutamatergic transmission in CeA neurons from Wistar and Marchigian Sardinian Preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and characterized by heightened activity of the CRF1 system. Basal spontaneous and evoked glutamate transmission in CeA neurons from msP rats was increased compared to Wistar rats. Ethanol had divergent effects, either increasing or decreasing spontaneous glutamate release in the CeA of Wistar rats. This bidirectional effect was retained in msP rats, but the magnitude of the ethanol-induced increase in glutamate release was significantly smaller. The inhibitory effect of ethanol on evoked glutamatergic transmission was similar in both strains. CRF also either increased or decreased spontaneous glutamate release in CeA neurons of Wistar rats, however, in msP rats CRF only increased glutamate release. The inhibitory effect of CRF on evoked glutamatergic transmission was also lost in neurons from msP rats. A CRF1 antagonist produced only minor effects on spontaneous glutamate transmission, which were consistent across strains, and no effects on evoked glutamate transmission. These results demonstrate that the genetically altered CRF system of msP rats results in alterations in spontaneous and stimulated glutamate signaling in the CeA that may contribute to both the anxiety and drinking behavioral phenotypes. PMID:26519902

Mixed-Mode Slip Behavior of the Altotiberina Low-Angle Normal Fault System (Northern Apennines, Italy) through High-Resolution Earthquake Locations and Repeating Events

NASA Astrophysics Data System (ADS)

Valoroso, Luisa; Chiaraluce, Lauro; Di Stefano, Raffaele; Monachesi, Giancarlo

2017-12-01

We generated a 4.5-year-long (2010-2014) high-resolution earthquake catalogue, composed of 37,000 events with ML < 3.9 and MC = 0.5 completeness magnitude, to report on the seismic activity of the Altotiberina (ATF) low-angle normal fault system and to shed light on the mechanical behavior and seismic potential of this fault, which is capable of generating a M7 event. Seismicity defines the geometry of the fault system composed of the low-angle (15°-20°) ATF, extending for 50 km along strike and between 4 and 16 km at depth showing an 1.5 km thick fault zone made of multiple subparallel slipping planes, and a complex network of synthetic/antithetic higher-angle segments located in the ATF hanging wall (HW) that can be traced along strike for up to 35 km. Ninety percent of the recorded seismicity occurs along the high-angle HW faults during a series of minor, sometimes long-lasting (months) seismic sequences with multiple MW3+ mainshocks. Remaining earthquakes (ML < 2.4) are released instead along the low-angle ATF at a constant rate of 2.2 events per day. Within the ATF-related seismicity, we found 97 clusters of repeating earthquakes (RE), mostly consisting of doublets occurring during short interevent time (hours). RE are located within the geodetically recognized creeping portions of the ATF, around the main locked asperity. The rate of occurrence of RE seems quite synchronous with the ATF-HW seismic release, suggesting that creeping may guide the strain partitioning in the ATF system. The seismic moment released by the ATF seismicity accounts for 30% of the geodetic one, implying aseismic deformation. The ATF-seismicity pattern is thus consistent with a mixed-mode (seismic and aseismic) slip behavior.

Nanostructured DPA-MPC-DPA triblock copolymer gel for controlled drug release of ketoprofen and spironolactone.

PubMed

Azmy, Bahaa; Standen, Guy; Kristova, Petra; Flint, Andrew; Lewis, Andrew L; Salvage, Jonathan P

2017-08-01

Uncontrolled rapid release of drugs can reduce their therapeutic efficacy and cause undesirable toxicity; however, controlled release from reservoir materials helps overcome this issue. The aims of this study were to determine the release profiles of ketoprofen and spironolactone from a pH-responsive self-assembling DPA-MPC-DPA triblock copolymer gel and elucidate underlying physiochemical properties. Drug release profiles from DPA 50 -MPC 250 -DPA 50 gel (pH 7.5), over 32 h (37 °C), were determined using UV-Vis spectroscopy. Nanoparticle size was measured by dynamic light scattering (DLS) and critical micelle concentration (CMC) by pyrene fluorescence. Polymer gel viscosity was examined via rheology, nanoparticle morphology investigated using scanning transmission electron microscopy (STEM) and the gel matrix observed using cryo-scanning electron microscopy (Cryo-SEM). DPA 50 -MPC 250 -DPA 50 copolymer (15% w/v) formed a free-standing gel (pH 7.5) that controlled drug release relative to free drugs. The copolymer possessed a low CMC, nanoparticle size increased with copolymer concentration, and DLS data were consistent with STEM. The gel displayed thermostable viscosity at physiological temperatures, and the gel matrix was a nanostructured aggregation of smaller nanoparticles. The DPA 50 -MPC 250 -DPA 50 copolymer gel could be used as a drug delivery system to provide the controlled drug release of ketoprofen and spironolactone. © 2017 Royal Pharmaceutical Society.

Release of EPA and DHA from salmon oil - a comparison of in vitro digestion with human and porcine gastrointestinal enzymes.

PubMed

Aarak, K E; Kirkhus, B; Holm, H; Vogt, G; Jacobsen, M; Vegarud, G E

2013-10-01

In the present study, we hypothesised whether in vitro digestion of salmon oil would release different amounts of PUFA depending on the origin of the lipolytic enzymes used. For this purpose, in vitro digestion of salmon oil (SO) was performed using human duodenal juice (HDJ) or a commercial enzyme preparation consisting of porcine pancreatin and bile (PB). The lipolytic effect was determined by measuring the release of fatty acids (FA) using solid-phase extraction and GC-flame ionisation detection, withdrawing samples every 20 min during digestion. The amount of FA released indicated that a plateau was reached after 80 min with approximately similar amounts of FA detected using both HDJ and PB (379 (sd 18) and 352 (sd 23) mg/g SO, respectively). However, the release of 18 : 2, EPA (20 : 5) and DHA (22 : 6) was significantly different during in vitro digestion. At 80 min, HDJ and PB released 43 and 33% of 18 : 2, 14 and 9% of EPA and 11 and 9% of DHA, respectively. Both enzyme preparations released approximately the same amounts of the other FA analysed. The effect of the addition of bile salts (BS) was significantly different in the two enzyme systems, where porcine pancreatin highly responded to the increase in BS concentration, in contrast to HDJ.

Potential risks of TiO2 and ZnO nanoparticles released from sunscreens into outdoor swimming pools.

PubMed

Jeon, Soo-Kyung; Kim, Eun-Ju; Lee, Jaesang; Lee, Seunghak

2016-11-05

The potential risks of nanoparticles (NPs) in sunscreens being released into swimming water were evaluated by a series of laboratory experiments simulating the fate and transport of NPs in outdoor swimming pools. NPs released from sunscreen-applied skin were estimated using pig skins covered with five different commercial sunscreens containing TiO2, ZnO, or both at various concentrations. Assuming that the swimming water treatment processes consisted of filtration, UV irradiation, heating, and chlorination, possible removal of the released NPs by each process was estimated. Generation of hydrogen peroxide (H2O2) by the NPs under sunlight and after UV photochemical treatment were measured, and the H2O2 concentration possibly present in the swimming pool was calculated based on some specific scenarios of operating an outdoor swimming pool. It was found that a significant amount of the NPs in sunscreens could be released into the swimming water, and accumulate during circulation through the treatment system. However, the concentration of H2O2 possibly present in the swimming pool should be below the level at which an adverse effect to bathers is concerned. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of salinity and temperature shock on Kappaphycus alvarezii seaweed spores release

NASA Astrophysics Data System (ADS)

Harwinda, F. K.; Satyantini, W. H.; Masithah, E. W.

2018-04-01

One of the reproductive aspects of development step that is considered as the solution of this issue is seaweed sporulation technique through which is induced through salinity and temperature shock. This study aims to determine the effect of combination and interaction of salinity and temperature shock on the release of K. alvarezii spores in order to produce superior seeds. This research was conducted using Complete Randomized Design Factorial which consists of nine combinations of treatments and three replications. The used treatment in this study is the combination of different environmental factors such as salinity shock and temperature shock. The data were analyzed using ANOVA (Analysis of Variance) followed by Duncan Multiple Range Test. The results showed that salinity (31 ppt, 33 ppt, and 35 ppt) and temperature (30°C, 32°C, and 34°C). shock affected the osmoregulation system and the release of K. alvarezii spores. The salinity shock and temperature shock had interaction with K. alvarezii spore release on the sixth and seventh day with the best treatment at 32°C temperature and 31 ppt salinity and released 5413 cells/ml spores on the seventh day.

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.

Photocatalytic dehydrogenation of formic acid on CdS nanorods through Ni and Co redox mediation under mild conditions.

PubMed

Khan, Muhammad Abdullah; Rehman, Zia-Ur-; Nasir, Jamal Abdul; Hafeez, Muhammad; Arshad, Muhammad; Ali, Naveed Zafar; Teixieira, Ivo F; McPherson, Ian

2018-05-30

Selective release of hydrogen from formic acid (FA) is deemed feasible to solve issues associated with the release and storage of hydrogen. Here, we present a new efficient photocatalytic system consisting of CdS nanorods (NR), Ni, and Co to liberate hydrogen from formic acid. The optimised noble metal free catalytic system employs Ni/Co as a redox mediator to relay electrons and holes from CdS-NR to the Ni and Co respectively, which also deters the oxidation of CdS-NR. As a result, a high hydrogen production activity of 32.6 mmolh-1g-1 from the decomposition of FA was noted. Furthermore, the photocatalytic system exhibit sustained H2 production rate for 12 hours with sequential turnover numbers surpassing 4×103, 3×103 and 2×103 for Co-Ni/CdS-NR, Ni-CdS-NR and CoCl2/CdS-NR respectively. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carboxymethyl starch and lecithin complex as matrix for targeted drug delivery: I. Monolithic mesalamine forms for colon delivery.

PubMed

Mihaela Friciu, Maria; Canh Le, Tien; Ispas-Szabo, Pompilia; Mateescu, Mircea Alexandru

2013-11-01

For drugs expected to act locally in the colon, and for successful treatment, a delivery device is necessary, in order to limit the systemic absorption which decreases effectiveness and causes important side effects. Various delayed release systems are currently commercialized; most of them based on pH-dependent release which is sensitive to gastrointestinal pH variation. This study proposes a novel excipient for colon delivery. This new preparation consists in the complexation between carboxymethyl starch (CMS) and Lecithin (L). As opposed to existing excipients, the new complex is pH-independent, inexpensive, and easy to manufacture and allows a high drug loading. FTIR, X-ray, and SEM structural analysis all support the hypothesis of the formation of a complex. By minor variation of the excipient content within the tablet, it is possible to modulate the release time and delivery at specific sites of the gastrointestinal tract. This study opens the door to a new pH-independent delivery system for mesalamine targeted administration. Our novel formulation fits well with the posology of mesalamine, used in the treatment of Inflammatory Bowel Disease (IBD), which requires repeated administrations (1g orally four times a day) to maintain a good quality of life. Copyright © 2013 Elsevier B.V. All rights reserved.

Development and Testing of a Drogue Parachute System for X-37 ALTV/B-52H Separation

NASA Technical Reports Server (NTRS)

Whitmore, Stephen A.; Cobleigh, Brent R.; Jacobson, Steven R.; Jensen, Steven C.; Hennings, Elsa J.

2004-01-01

Multiple scenarios were identified in which the X-37 approach and landing test vehicle (ALTV) catastrophically recontacts the B-52H carrier aircraft after separation. The most cost-effective recontact risk mitigation is the prelaunch deployment of a drogue parachute that is released after the X-37 ALTV has safely cleared the B-52H. After release, a fully-inflated drogue parachute takes 30 min to reach ground and results in a large footprint that excessively restricts the days available for flight. To reduce the footprint, a passive collapse mechanism consisting of an elastic reefing line attached to the parachute skirt was developed. At flight loads the elastic is stretched, allowing full parachute inflation. After release, drag loads drop dramatically and the elastic line contracts, reducing the frontal drag area. A 50-percent drag reduction results in an approximately 75-percent ground footprint reduction. Eleven individual parachute designs were evaluated at flight load dynamic pressures in the High Velocity Airflow System (HIVAS) at the Naval Air Warfare Center (NAWC), China Lake, California. Various options for the elastic reefing system were also evaluated at HIVAS. Two best parachute designs were selected from HIVAS to be carried forward to flight test. Detailed HIVAS test results are presented in this report.

Development and Testing of a Drogue Parachute System for X-37 ALTV/B-52H Separation

NASA Technical Reports Server (NTRS)

Whitmore, Stephen A.; Cobleigh, Brent R.; Jacobson, Steven R.; Jensen, Steven C.; Hennings, Elsa J.

2004-01-01

Multiple scenarios were identified in which the X-37 approach and landing test vehicle (ALTV) catastrophically recontacts the B-52H carrier aircraft after separation. The most cost-effective recontact risk mitigation is the prelaunch deployment of a drogue parachute that is released after the X-37 ALTV has safely cleared the B-52H. After release, a fully-inflated drogue parachute takes 30 min to reach ground and results in a large footprint that excessively restricts the days available for flight. To reduce the footprint, a passive collapse mechanism consisting of an elastic reefing line attached to the parachute skirt was developed. At flight loads the elastic is stretched, allowing full parachute inflation. After release, drag loads drop dramatically and the elastic line contracts, reducing the frontal drag area. A 50 percent drag reduction results in an approximately 75 percent ground footprint reduction. Eleven individual parachute designs were evaluated at flight load dynamic pressures in the High Velocity Airflow System (HIVAS) at the Naval Air Warfare Center (NAWC), China Lake, California. Various options for the elastic reefing system were also evaluated at HIVAS. Two best parachute designs were selected from HIVAS to be carried forward to flight test. Detailed HIVAS test results are presented in this report.

Microencapsulation of hydrophilic drug substances using biodegradable polyesters. Part II: Implants allowing controlled drug release--a feasibility study using bisphosphonates.

PubMed

Weidenauer, U; Bodmer, D; Kissel, T

2004-03-01

The prolonged delivery of hydrophilic drug salts from hydrophobic polymer carriers at high drug loading is an ambitious goal. Pamidronate disodium salt (APD) containing implants prepared from spray-dried microparticles were investigated using a laboratory ram extruder. An APD-containing polymer matrix consisting of an APD-chitosan implant embedded in the biodegradable polymer D,L-poly(lactide-co-glycolide acid-glucose) (PLG-GLU) was compared with a matrix system with the micronized drug distributed in the PLG-GLU. The APD-chitosan matrix system showed a triphasic release behaviour at loading levels of 6.86 and 15.54% (w/w) over 36 days under in-vitro conditions. At higher loading (31.92%), a drug burst was observed within 6 days due to the formation of pores and channels in the polymeric matrix. In contrast, implants containing the micronized drug showed a more continuous release profile over 48 days up to a loading of 31.78% (w/w). At a drug loading of 46.17% (w/w), a drug burst was observed. Using micronized drug salts and reducing the surface area available for diffusion, parenteral delivery systems for highly water-soluble drug candidates were shown to be technically feasible at high drug loadings.

Adaptation of a 15-ft-dia ribbon parachute and a 73-ft cross main recovery parachute for cargo delivery from high altitude

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

Pepper, W.B.; Lucero, H.; Klimas, P.C.

1984-01-01

An existing parachute system has been adapted for delivery of a resupply container at high altitudes from aircraft. The parachute system consists of a 15-ft diameter ribbon parachute reefed for 10 seconds and a 73-ft diameter cross parachute reefed for 10 seconds. A solid state recorder in the 2341 1b drop test vehicle was used to obtain deceleration history with time. Two drop tests using the Navy A7 aircraft were conducted at Stallion Site, White Sands Missile Range, New Mexico. Drop release conditions were 250 KCAS at 20,000 ft above sea level from the first test and 230 KCAS atmore » 22,000 ft msl for the second. A new load transfer bridle was designed and tested to release the first stage parachute and replace a costly mechanical load plate.« less

Development of a novel tablet-in-capsule formulation of mesalamine for inflammatory bowel disease.

PubMed

Patel, Mayur M; Amin, Avani F

2013-01-01

The objective of the present work was to develop a tablet-in-capsule type of multiunit system, which releases the drug in a controlled manner at pre-programmed time intervals. The system consists of an enteric-coated hydroxypropyl methylcellulose capsule filled with four units of mesalamine minitablets, each of which was further coated with different ratios of Eudragit(®) E100 and Eudragit(®) RS100. In vitro evaluation of tablets coated with Eudragit(®) E100 and Eudragit(®) RS100 at different pH conditions revealed that at lower pH levels (2.0, 3.6 and 5.5 pH), the drug release is mainly governed by the dissolution of Eudragit(®) E100 from the Eudragit(®) E100 and Eudragit(®) RS100 coat. In vitro evaluation of capsules enteric coated with Eudragit(®) L100 and Eudragit(®) S100 revealed that a maximum lag time of 3 h and 4 h was obtained, respectively. In vivo roentgenographic evaluation in rabbits revealed that the developed system remained intact until it reaches the targeted region of the gastrointestinal tract, i.e. ileum and colon, where the tablets were released after the dissolution of the enteric coat Eudragit(®) L100 and Eudragit(®) S100, respectively. The developed system exhibited a promising targeting behavior and hence may be used for the treatment of inflammatory bowel disease.

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

Hematoma-inspired alginate/platelet releasate/CaPO4 composite: initiation of the inflammatory-mediated response associated with fracture repair in vitro and ex vivo injection delivery.

PubMed

McCanless, Jonathan D; Jennings, Lisa K; Bumgardner, Joel D; Cole, Judith A; Haggard, Warren O

2012-08-01

A clinical need continues for consistent bone remodeling within problematic sites such as those of fracture nonunion, avascular necrosis, or irregular bone formations. In attempt to address such needs, a biomaterial system is proposed to induce early inflammatory responses after implantation and to provide later osteoconductive scaffolding for bone regeneration. Biomaterial-induced inflammation would parallel the early stage of hematoma-induced fracture repair and allow scaffold-promoted remodeling of osseous tissue to a healthy state. Initiation of the wound healing cascade by two human concentrated platelet releasate-containing alginate/β-tricalcium phosphate biocomposites has been studied in vitro using the TIB-71™ RAW264.7 mouse monocyte cell line. Inflammatory responses inherent to the base material were found and could be modulated through incorporation of platelet releasate. Differences in hydrogel wt% (2 vs. 8 %) and/or calcium phosphate granule vol.% (20 vs. 10 %) allowed for tuning the response associated with platelet releasate-associated growth factor elution. Tunability from completely suppressing the inflammatory response to augmenting the response was observed through varied elution profiles of both releasate-derived bioagents and impurities inherent to alginate. A 2.5-fold upregulation of inducible-nitric oxide synthase gene expression followed by a tenfold increase in nitrite media levels was induced by inclusion of releasate within the 8 wt%/10 vol.% formulation and was comparable to an endotoxin positive control. Whereas, near complete elimination of inflammation was seen when releasate was included within the 2 wt%/20 vol.% formulation. These in vitro results suggested tunable interactions between the multiple platelet releasate-derived bioagents and the biocomposites for enhancing hematoma-like fracture repair. Additionally, minimally invasive delivery for in situ curing of the implant system via injection was demonstrated in rat tail vertebrae using microcomputed tomography.

Sasquatch Footprint Tool

NASA Technical Reports Server (NTRS)

Bledsoe, Kristin

2013-01-01

The Crew Exploration Vehicle Parachute Assembly System (CPAS) is the parachute system for NASA s Orion spacecraft. The test program consists of numerous drop tests, wherein a test article rigged with parachutes is extracted or released from an aircraft. During such tests, range safety is paramount, as is the recoverability of the parachutes and test article. It is crucial to establish an aircraft release point that will ensure that the article and all items released from it will land in safe locations. A new footprint predictor tool, called Sasquatch, was created in MATLAB. This tool takes in a simulated trajectory for the test article, information about all released objects, and atmospheric wind data (simulated or actual) to calculate the trajectories of the released objects. Dispersions are applied to the landing locations of those objects, taking into account the variability of winds, aircraft release point, and object descent rate. Sasquatch establishes a payload release point (e.g., where the payload will be extracted from the carrier aircraft) that will ensure that the payload and all objects released from it will land in a specified cleared area. The landing locations (the final points in the trajectories) are plotted on a map of the test range. Sasquatch was originally designed for CPAS drop tests and includes extensive information about both the CPAS hardware and the primary test range used for CPAS testing. However, it can easily be adapted for more complex CPAS drop tests, other NASA projects, and commercial partners. CPAS has developed the Sasquatch footprint tool to ensure range safety during parachute drop tests. Sasquatch is well correlated to test data and continues to ensure the safety of test personnel as well as the safe recovery of all equipment. The tool will continue to be modified based on new test data, improving predictions and providing added capability to meet the requirements of more complex testing.

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

Pirhonen, P.

Life-cycle assessment is usually based on regular discharges that occur at a more or less constant rate. Nevertheless, the more factors that are taken into account in the LCA the better picture it gives on the environmental aspects of a product. In this study an approach to incorporate accidental releases into a products` life-cycle assessment was developed. In this approach accidental releases are divided into two categories. The first category consists of those unplanned releases which occur with a predicted level and frequency. Due to the high frequency and small release size at a time, these accidental releases can bemore » compared to continuous emissions. Their global impacts are studied in this approach. Accidental releases of the second category are sudden, unplanned releases caused by exceptional situations, e.g. technical failure, action error or disturbances in process conditions. These releases have a singular character and local impacts are typical of them. As far as the accidental releases of the second category are concerned, the approach introduced in this study results in a risk value for every stage of a life-cycle, the sum of which is a risk value for the whole life-cycle. Risk value is based on occurrence frequencies of incidents and potential environmental damage caused by releases. Risk value illustrates the level of potential damage caused by accidental releases related to the system under study and is meant to be used for comparison of these levels of two different products. It can also be used to compare the risk levels of different stages of the life-cycle. An approach was illustrated using petrol as an example product. The whole life-cycle of petrol from crude oil production to the consumption of petrol was studied.« less

Releasable Asbestos Field Sampler (RAFS) Operation Manual

EPA Science Inventory

The Releasable Asbestos Field Sampler (RAFS) is a field instrument that provides an in-situ measurement of asbestos releasability from consistent and reproducible mechanical agitation of the source material such as soil. The RAFS was designed to measure concentration (asbestos st...

A gastro-resistant ovalbumin bi-layered mini-tablet-in-tablet system for the delivery of Lactobacillus acidophilus probiotic to simulated human intestinal and colon conditions.

PubMed

Govender, Mershen; Choonara, Yahya Essop; van Vuuren, Sandy; Kumar, Pradeep; du Toit, Lisa Claire; Pillay, Viness

2015-07-01

The viability of probiotic bacteria during formulation processes and delivery is vital to ensure health benefits. This study focuses on the use of gastro-resistant denatured ovalbumin for the targeted delivery of probiotic Lactobacillus acidophilus to simulated human intestinal and colon conditions through a bi-layered mini-tablet-in-tablet system (BMTTS). The BMTTS consists of two gastro-resistant ovalbumin mini-tablets containing L. acidophilus suspended in lactose and eudragit S100 for targeted intestinal and colonic delivery respectively. Luminescence has been utilized to ensure probiotic viability during formulation processes in addition to determining all probiotic release profiles. The mechanism of probiotic release from the ovalbumin matrix was ascertained using mathematical modelling and molecular docking studies. Magnetic resonance imaging and differential scanning calorimetry are also included as part of the in-vitro characterization of the ovalbumin system. The BMTTS was effective in the delivery of L. acidophilus to simulated human intestinal and colon conditions. Formulation processes were furthermore determined to maintain probiotic viability. Statistical analysis of the release data noted a significant effect of pH denaturation on the release properties of ovalbumin. Magnetic resonance imaging results have indicated a decrease in ovalbumin matrix size upon exposure to simulated intestinal fluid. Molecular docking studies carried out depicted the interaction and binding positions inherent to the ovalbumin-pancreatic trypsin interaction complex indicating the possible enzymatic degradation of ovalbumin leading to the release of the probiotic from the protein matrix. The BMTTS has been determined to be effective in the protection and delivery of probiotic L. acidophilus to simulated human intestinal and colonic conditions. Molecular docking analysis has noted that pancreatin exerts a significant effect on probiotic release from the gastro-resistant ovalbumin matrix. © 2015 Royal Pharmaceutical Society.

Bioburden release of Ariane 5 Fairing Acoustic Protection Panels

NASA Astrophysics Data System (ADS)

Stieglmeier, Michaela; Rohr, Thomas; Schmeitzky, Olivier; Rumler, Peter; Kminek, Gerhard

The ESA-NASA ExoMars mission will be subject to strict Planetary Protection constrictions. The original ExoMars mission concept was based on an Ariane 5 launch system. Like all launch systems, the Ariane 5 fairing is lined with acoustic protection panels. These panels consist of an outer polyester/cotton fabric and an inner open celled foam. During launch the panels will be exposed to vibrations and a decrease in pressure. A release of possible external and/ or embedded microbes would cause a contamination of the satellite. Planetary Protection requirements for ExoMars imply the determination of the bioburden release from the Ariane 5 Fairing Acoustic Protection Panels (FAP-panels). Thus a study at ESTEC was performed comparing the bioburden release of a sterilized and non-sterilized panel by simulating a launch environment. Panels were mounted in test jigs above a sterile ground plate. Sterile stainless steel witness plates for the determination of bioburden release were mounted on the latter. The launch environment was simulated in two different tests. In a vacuum chamber the panels were exposed to a depressurization event. For the simulation of the vibrations the jigs were mounted in the Large European Acoustic Facility (LEAF) at ESTEC. After each test witness plates were demounted under sterile conditions and analyzed for microbial growth by incubating them in agar. Furthermore pieces of the outer fabric as well as the inner foam were taken and examined for embedded microbes. In total the amount of embedded microbes was very low and there was no significant difference between the sterilized and non-sterilized panel concerning the released bioburden. Thus sterilization of the Ariane 5 FAP-panels seems not necessary to comply with Planetary Protection constraints. Although the ExoMars project will use a different launch system in the new mission concept, the data acquired during these tests can be used for future scientific satellites launched with Ariane 5.

Source Term Estimates of Radioxenon Released from the BaTek Medical Isotope Production Facility Using External Measured Air Concentrations

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

Eslinger, Paul W.; Cameron, Ian M.; Dumais, Johannes R.

2015-10-01

Abstract Batan Teknologi (BaTek) operates an isotope production facility in Serpong, Indonesia that supplies 99mTc for use in medical procedures. Atmospheric releases of Xe-133 in the production process at BaTek are known to influence the measurements taken at the closest stations of the International Monitoring System (IMS). The purpose of the IMS is to detect evidence of nuclear explosions, including atmospheric releases of radionuclides. The xenon isotopes released from BaTek are the same as those produced in a nuclear explosion, but the isotopic ratios are different. Knowledge of the magnitude of releases from the isotope production facility helps inform analystsmore » trying to decide whether a specific measurement result came from a nuclear explosion. A stack monitor deployed at BaTek in 2013 measured releases to the atmosphere for several isotopes. The facility operates on a weekly cycle, and the stack data for June 15-21, 2013 show a release of 1.84E13 Bq of Xe-133. Concentrations of Xe-133 in the air are available at the same time from a xenon sampler located 14 km from BaTek. An optimization process using atmospheric transport modeling and the sampler air concentrations produced a release estimate of 1.88E13 Bq. The same optimization process yielded a release estimate of 1.70E13 Bq for a different week in 2012. The stack release value and the two optimized estimates are all within 10 percent of each other. Weekly release estimates of 1.8E13 Bq and a 40 percent facility operation rate yields a rough annual release estimate of 3.7E13 Bq of Xe-133. This value is consistent with previously published estimates of annual releases for this facility, which are based on measurements at three IMS stations. These multiple lines of evidence cross-validate the stack release estimates and the release estimates from atmospheric samplers.« less

An enhanced chemiluminescence resonance energy transfer system based on target recycling G-guadruplexes/hemin DNAzyme catalysis and its application in ultrasensitive detection of DNA.

PubMed

Chen, Jia; Huang, Yong; Vdovenko, Marina; Sakharov, Ivan Yu; Su, Guifa; Zhao, Shulin

2015-06-01

An enhanced chemiluminescence resonance energy transfer (CRET) system based on target recycling G-guadruplexes/hemin DNAzyme catalysis was developed for ultrasensitive detection of DNA. CRET system consists of luminol as chemiluminescent donor, and fluorescein isothiocyanate (FITC) as acceptor. The sensitive detection was achieved by using the system consisted of G-riched DNA, blocker DNA, and the Nb.BbvCI biocatalyst. Upon addition of target DNA to the system, target DNA hybridizes with the quasi-circular DNA structure, and forms a DNA duplex. The formation of DNA duplex triggers selective enzymatic cleavage of quasi-circular DNA by Nb.BbvCI, resulting in the release of target DNA and two G-riched DNAzyme segments. Released target DNA then hybridizes with another quasi-circular DNA structure to initiate the cleavage of the quasi-circular DNA structure. Eventually, each target DNA can go through many cycles, resulting in the digestion of many quasi-circular DNA structures, generating many G-riched DNAzyme segments. G-riched DNAzyme segment products assemble with hemin to form stable hemin/G-quadruplexes that exhibit peroxidase-like activity which can catalyze the oxidation of luminol by H2O2 to produce CL signals. In the presence of FITC, CL of luminol can excite FITC molecules, and thus produced CRET between the luminol and FITC. This unique analysis strategy gives a detection limit down to 80 fM, which is at least four orders of magnitude lower than that of unamplified DNA detection methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Solid-phase arsenic speciation in aquifer sediments: A micro-X-ray absorption spectroscopy approach for quantifying trace-level speciation

DOE PAGES

Nicholas, Sarah L.; Erickson, Melinda L.; Woodruff, Laurel G.; ...

2017-05-19

Arsenic (As) is a geogenic contaminant affecting groundwater in geologically diverse systems globally. Arsenic release from aquifer sediments to groundwater is favored when biogeochemical conditions, especially oxidation-reduction (redox) potential, in aquifers fluctuate. The specific objective of this research is to identify the solid-phase sources and geochemical mechanisms of release of As in aquifers of the Des Moines Lobe glacial advance. The overarching concept is that conditions present at the aquifer-aquitard interfaces promote a suite of geochemical reactions leading to mineral alteration and release of As to groundwater. A microprobe X-ray absorption spectroscopy (μXAS) approach is developed and applied to rotosonicmore » drill core samples to identify the solid-phase speciation of As in aquifer, aquitard, and aquifer-aquitard interface sediments. This approach addresses the low solid-phase As concentrations, as well as the fine-scale physical and chemical heterogeneity of the sediments. The spectroscopy data are analyzed using novel cosine-distance and correlation-distance hierarchical clustering for Fe 1s and As 1s μXAS datasets. The solid-phase Fe and As speciation is then interpreted using sediment and well-water chemical data to propose solid-phase As reservoirs and release mechanisms. The results confirm that in two of the three locations studied, the glacial sediment forming the aquitard is the source of As to the aquifer sediments. The results are consistent with three different As release mechanisms: (1) desorption from Fe (oxyhydr)oxides, (2) reductive dissolution of Fe (oxyhydr)oxides, and (3) oxidative dissolution of Fe sulfides. The findings confirm that glacial sediments at the interface between aquifer and aquitard are geochemically active zones for As. The diversity of As release mechanisms is consistent with the geographic heterogeneity seen in the distribution of elevated-As wells.« less

Solid-phase arsenic speciation in aquifer sediments: A micro-X-ray absorption spectroscopy approach for quantifying trace-level speciation

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

Nicholas, Sarah L.; Erickson, Melinda L.; Woodruff, Laurel G.

Arsenic (As) is a geogenic contaminant affecting groundwater in geologically diverse systems globally. Arsenic release from aquifer sediments to groundwater is favored when biogeochemical conditions, especially oxidation-reduction (redox) potential, in aquifers fluctuate. The specific objective of this research is to identify the solid-phase sources and geochemical mechanisms of release of As in aquifers of the Des Moines Lobe glacial advance. The overarching concept is that conditions present at the aquifer-aquitard interfaces promote a suite of geochemical reactions leading to mineral alteration and release of As to groundwater. A microprobe X-ray absorption spectroscopy (μXAS) approach is developed and applied to rotosonicmore » drill core samples to identify the solid-phase speciation of As in aquifer, aquitard, and aquifer-aquitard interface sediments. This approach addresses the low solid-phase As concentrations, as well as the fine-scale physical and chemical heterogeneity of the sediments. The spectroscopy data are analyzed using novel cosine-distance and correlation-distance hierarchical clustering for Fe 1s and As 1s μXAS datasets. The solid-phase Fe and As speciation is then interpreted using sediment and well-water chemical data to propose solid-phase As reservoirs and release mechanisms. The results confirm that in two of the three locations studied, the glacial sediment forming the aquitard is the source of As to the aquifer sediments. The results are consistent with three different As release mechanisms: (1) desorption from Fe (oxyhydr)oxides, (2) reductive dissolution of Fe (oxyhydr)oxides, and (3) oxidative dissolution of Fe sulfides. The findings confirm that glacial sediments at the interface between aquifer and aquitard are geochemically active zones for As. The diversity of As release mechanisms is consistent with the geographic heterogeneity seen in the distribution of elevated-As wells.« less

Supply and demand for endocannabinoids

PubMed Central

Alger, Bradley E.; Kim, Jimok

2011-01-01

The endocannabinoid system consists of G-protein coupled cannabinoid receptors that can be activated by cannabis-derived drugs and small lipids called endocannabinoids, plus associated biochemical machinery (precursors, synthetic and degradative enzymes, transporters). The endocannabinoid system in the brain primarily influences neuronal synaptic communication, and affects biological – functions including eating, anxiety, learning and memory, growth and development – via an array of actions throughout the nervous system. While many aspects of synaptic regulation by endocannabinoids are becoming clear, details of the subcellular organization and regulation of the endocannabinoid system are less well understood. This review focuses on recent investigations that illuminate fundamental issues of endocannabinoid storage, release, and functional roles. PMID:21507493

Composite material consisting of microporous β-TCP ceramic and alginate for delayed release of antibiotics.

PubMed

Seidenstuecker, Michael; Ruehe, Juergen; Suedkamp, Norbert P; Serr, Annerose; Wittmer, Annette; Bohner, Marc; Bernstein, Anke; Mayr, Hermann O

2017-03-15

The aim of this study was to produce a novel composite of microporous β-TCP filled with alginate and Vancomycin (VAN) to prolong the release behavior of the antibiotic for up to 28days. Using the flow chamber developed by the group, porous ceramics in a directional flow were filled with alginates of different composition containing 50mg/mL of antibiotics. After cross-linking the alginate with calcium ions, incubation took place in 10mL double-distilled water for 4weeks at 37°C. At defined times (1, 2, 3, 6, 9, 14, 20 and 28days), the liquid was completely exchanged and analyzed by capillary zone electrophoresis and microtiter trials. For statistical purposes, the mean and standard deviation were calculated and analyzed by ANOVA. The release of VAN from alginate was carried out via an external calcium source over the entire period with concentrations above the minimal inhibitory concentration (MIC). The burst release measured 35.2±1.5%. The release of VAN from alginate with an internal calcium source could only be observed over 14days. The burst release here was 61.9±4.3%. The native alginate's burst release was 54.1±7.8%; that of the sterile alginate 40.5±6.4%. The microtiter experiments revealed efficacy over the entire study period for VAN. The MIC value was determined in the release experiments as well in a range of 0.5-2.0μg/mL against Staphylococcus aureus. Drug release systems based on β-TCP and hydrogels are well documented in literature. However, in all described systems the ceramic, as granule or powder, is inserted into a hydrogel. In our work, we do the opposite, a hydrogel which acts as reservoir for antibiotics is placed into a porous biodegradable ceramic. Eventually, this system should be applied as treatment of bone infections. Contrary to the "granule in hydrogel" composites it has the advantage of mechanical stability. Thus, it can take over functions of the bone during the healing process. For a quicker translation from our scientific research into clinical use, only FDA approved materials were used in this work. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Linked-List-Based Multibody Dynamics (MBDyn) Engine

NASA Technical Reports Server (NTRS)

MacLean, John; Brain, Thomas; Wuiocho, Leslie; Huynh, An; Ghosh, Tushar

2012-01-01

This new release of MBDyn is a software engine that calculates the dynamics states of kinematic, rigid, or flexible multibody systems. An MBDyn multibody system may consist of multiple groups of articulated chains, trees, or closed-loop topologies. Transient topologies are handled through conservation of energy and momentum. The solution for rigid-body systems is exact, and several configurable levels of nonlinear term fidelity are available for flexible dynamics systems. The algorithms have been optimized for efficiency and can be used for both non-real-time (NRT) and real-time (RT) simulations. Interfaces are currently compatible with NASA's Trick Simulation Environment. This new release represents a significant advance in capability and ease of use. The two most significant new additions are an application programming interface (API) that clarifies and simplifies use of MBDyn, and a link-list infrastructure that allows a single MBDyn instance to propagate an arbitrary number of interacting groups of multibody top ologies. MBDyn calculates state and state derivative vectors for integration using an external integration routine. A Trickcompatible interface is provided for initialization, data logging, integration, and input/output.

Clouds and the Earth's Radiant Energy System (CERES) algorithm theoretical basis document. Volume 1; Overviews (subsystem 0)

NASA Technical Reports Server (NTRS)

Wielicki, Bruce A. (Principal Investigator); Barkstrom, Bruce R. (Principal Investigator); Baum, Bryan A.; Cess, Robert D.; Charlock, Thomas P.; Coakley, James A.; Green, Richard N.; Lee, Robert B., III; Minnis, Patrick; Smith, G. Louis

1995-01-01

The theoretical bases for the Release 1 algorithms that will be used to process satellite data for investigation of the Clouds and the Earth's Radiant Energy System (CERES) are described. The architecture for software implementation of the methodologies is outlined. Volume 1 provides both summarized and detailed overviews of the CERES Release 1 data analysis system. CERES will produce global top-of-the-atmosphere shortwave and longwave radiative fluxes at the top of the atmosphere, at the surface, and within the atmosphere by using the combination of a large variety of measurements and models. The CERES processing system includes radiance observations from CERES scanning radiometers, cloud properties derived from coincident satellite imaging radiometers, temperature and humidity fields from meteorological analysis models, and high-temporal-resolution geostationary satellite radiances to account for unobserved times. CERES will provide a continuation of the ERBE record and the lowest error climatology of consistent cloud properties and radiation fields. CERES will also substantially improve our knowledge of the Earth's surface radiation budget.

System-based approach for an advanced drug delivery platform

NASA Astrophysics Data System (ADS)

Kulinsky, Lawrence; Xu, Han; Tsai, Han-Kuan A.; Madou, Marc

2006-03-01

Present study is looking at the problem of integrating drug delivery microcapsule, a bio-sensor, and a control mechanism into a biomedical drug delivery system. A wide range of medical practices from cancer therapy to gastroenterological treatments can benefit from such novel bio-system. Drug release in our drug delivery system is achieved by electrochemically actuating an array of polymeric valves on a set of drug reservoirs. The valves are bi-layer structures, made in the shape of a flap hinged on one side to a valve seat, and consisting of thin films of evaporated gold and electrochemically deposited polypyrrole (PPy). These thin PPy(DBS) bi-layer flaps cover access holes of underlying chambers micromachined in a silicon substrate. Chromium and polyimide layers are applied to implement "differential adhesion" to obtain a voltage induced deflection of the bilayer away from the drug reservoir. The Cr is an adhesion-promoting layer, which is used to strongly bind the gold layer down to the substrate, whereas the gold adheres weakly to polyimide. Drug actives (dry or wet) were pre-stored in the chambers and their release is achieved upon the application of a small bias (~ 1V). Negative voltage causes cation adsorption and volume change in PPy film. This translates into the bending of the PPy/Au bi-layer actuator and release of the drug from reservoirs. This design of the drug delivery module is miniaturized to the dimensions of 200μm valve diameter. Galvanostatic and potentiostatic PPy deposition methods were compared, and potentiostatic deposition method yields film of more uniform thickness. PPy deposition experiments with various pyrrole and NaDBS concentrations were also performed. Glucose biosensor based on glucose oxidase (GOx) embedded in the PPy matrix during elechtrochemical deposition was manufactured and successfully tested. Multiple-drug pulsatile release and continuous linear release patterns can be implemented by controlling the operation of an array of valves. Varying amounts of drugs, together with more complex controlling strategies would allow creation of more complex drug delivery patterns.

The ALICE Software Release Validation cluster

NASA Astrophysics Data System (ADS)

Berzano, D.; Krzewicki, M.

2015-12-01

One of the most important steps of software lifecycle is Quality Assurance: this process comprehends both automatic tests and manual reviews, and all of them must pass successfully before the software is approved for production. Some tests, such as source code static analysis, are executed on a single dedicated service: in High Energy Physics, a full simulation and reconstruction chain on a distributed computing environment, backed with a sample “golden” dataset, is also necessary for the quality sign off. The ALICE experiment uses dedicated and virtualized computing infrastructures for the Release Validation in order not to taint the production environment (i.e. CVMFS and the Grid) with non-validated software and validation jobs: the ALICE Release Validation cluster is a disposable virtual cluster appliance based on CernVM and the Virtual Analysis Facility, capable of deploying on demand, and with a single command, a dedicated virtual HTCondor cluster with an automatically scalable number of virtual workers on any cloud supporting the standard EC2 interface. Input and output data are externally stored on EOS, and a dedicated CVMFS service is used to provide the software to be validated. We will show how the Release Validation Cluster deployment and disposal are completely transparent for the Release Manager, who simply triggers the validation from the ALICE build system's web interface. CernVM 3, based entirely on CVMFS, permits to boot any snapshot of the operating system in time: we will show how this allows us to certify each ALICE software release for an exact CernVM snapshot, addressing the problem of Long Term Data Preservation by ensuring a consistent environment for software execution and data reprocessing in the future.

Tailoring the mucoadhesive and sustained release characteristics of mesalamine loaded formulations for local treatment of distal forms of ulcerative colitis.

PubMed

Ali, Hany S M; Hanafy, Ahmed F; El Achy, Samar N

2016-10-10

Direct delivery of sustained therapeutic levels of mesalamine (MS) via rectal systems to manage distal forms of ulcerative colitis was studied. The High molecular weight hydroxypropyl methylcellulose (HPMC K4M) polymer was combined with hydrophilic surfactants to control polymer hydration process allowing optimization of the mucoadhesive and controlled drug release properties for the rectal systems. Physical mixtures and granules of MS and HPMC K4M were prepared and in vitro characterized using scanning electron microscope, differential scanning calorimetry and X-ray diffraction techniques. Rectal formulations were prepared utilizing MS-HPMC K4M mixtures in different polyethylene glycol (PEG) combination bases. The developed rectal formulations were investigated for physical, mucoadhesion, in-vitro drug release and swelling characteristics. Results revealed acceptable physical characteristics of the prepared formulations with good content uniformity and minimum weight variation. Sustained release patterns of MS form HPMC K4M based formulations were observed. Formulations prepared using high proportions of the polymer or PEG 400 showed higher extent of mucoadhesion, swelling and greatly extended drug release time. Efficacy of an optimized formulation was assessed using the acetic acid induced colitis model in rats and compared to a reference polymer-free formulation of the drug. Clinical evaluation included bleeding from rectum, consistency of animal stool and colon/body weight ratio. Furthermore, histopathological analysis was carried out to evaluate the degree of inflammation and mucosal damage. Overall results showed a significant enhancement in the clinical pictures and colon histopathology of animals treated by the sustained release mucoadhesive formulation compared to the reference polymer free formulation and the non-treated colitis group. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of Cotton-Wool-Like Poly(lactic acid)-Based Composites Consisting of Core-Shell-Type Fibers

PubMed Central

Wang, Jian; Zhou, Pin; Obata, Akiko; Jones, Julian R.; Kasuga, Toshihiro

2015-01-01

In previous works, we reported the fabrication of cotton-wool-like composites consisting of siloxane-doped vaterite and poly(l-lactic acid) (SiVPCs). Various irregularly shaped bone voids can be filled with the composite, which effectively supplies calcium and silicate ions, enhancing the bone formation by stimulating the cells. The composites, however, were brittle and showed an initial burst release of ions. In the present work, to improve the mechanical flexibility and ion release, the composite fiber was coated with a soft, thin layer consisting of poly(d,l-lactic-co-glycolic acid) (PLGA). A coaxial electrospinning technique was used to prepare a cotton-wool-like material comprising “core-shell”-type fibers with a diameter of ~12 µm. The fibers, which consisted of SiVPC coated with a ~2-µm-thick PLGA layer, were mechanically flexible; even under a uniaxial compressive load of 1.5 kPa, the cotton-wool-like material did not exhibit fracture of the fibers and, after removing the load, showed a ~60% recovery. In Tris buffer solution, the initial burst release of calcium and silicate ions from the “core-shell”-type fibers was effectively controlled, and the ions were slowly released after one day. Thus, the mechanical flexibility and ion-release behavior of the composites were drastically improved by the thin PLGA coating. PMID:28793691

Trajectories of psychological distress after prison release: implications for mental health service need in ex-prisoners.

PubMed

Thomas, E G; Spittal, M J; Heffernan, E B; Taxman, F S; Alati, R; Kinner, S A

2016-02-01

Understanding individual-level changes in mental health status after prison release is crucial to providing targeted and effective mental health care to ex-prisoners. We aimed to describe trajectories of psychological distress following prison discharge and compare these trajectories with mental health service use in the community. The Kessler Psychological Distress Scale (K10) was administered to 1216 sentenced adult prisoners in Queensland, Australia, before prison release and approximately 1, 3 and 6 months after release. We used group-based trajectory modeling to identify K10 trajectories after release. Contact with community mental health services in the year following release was assessed via data linkage. We identified five trajectory groups, representing consistently low (51.1% of the cohort), consistently moderate (29.8%), high increasing (11.6%), high declining (5.5%) and consistently very high (1.9%) psychological distress. Mood disorder, anxiety disorder, history of self-harm and risky drug use were risk factors for the high increasing, very high and high declining trajectory groups. Women were over-represented in the high increasing and high declining groups, but men were at higher risk of very high psychological distress. Within the high increasing and very high groups, 25% of participants accessed community mental health services in the first year post-release, for a median of 4.4 contact hours. For the majority of prisoners with high to very high psychological distress, distress persists after release. However, contact with mental health services in the community appears low. Further research is required to understand barriers to mental health service access among ex-prisoners.

TEAMBLOCKS: HYBRID ABSTRACTIONS FOR PROVABLE MULTI-AGENT AUTONOMY

DTIC Science & Technology

2017-07-28

Raspberry Pi 23 can easily satisfy control loop periods on the order of 10−3s. Thus, we assume that the time to execute a piece of control code, ∆t...Release; Distribution Unlimited. 23 State Space The state space of the aircraft is X = R3 × SO(3) × R3 × R3; states consist of • pI ∈ R3, the...the tbdemo_ghaexecution script uses this operation to make feedback system out of the product of the linear system and PI controller. tbread

Comparisons of seismic and geodetic strain across the East African rift: Implications for magmatism during rifting

NASA Astrophysics Data System (ADS)

Lindsey, N.; Ebinger, C. J.; Pritchard, M. E.; Cote, D. M.

2010-12-01

Knowledge of how the continental lithosphere accommodates strain in an active rift setting is essential to both earthquake and volcanic hazard analyses. Far-field and impinging mantle plumes drive extension within the fault-bounded rift systems of East Africa. Our study aims to evaluate models of distributed strain and localized strain between multiple rigid plates using earthquake catalogs and existing constraints, including high resolution DEMs that reveal the spatial distribution of young faults across the broad uplifts of eastern and southern Africa. We determine cumulative seismic moment release within 0.5 degree bins across the Afro-Arabian rift system using the entire NEIC earthquake catalog (1973-present), and compare these results to geodetic estimates of strain and extensional velocity. The small bin size permits comparison of strain with geological factors, including geological terrain, border fault distribution, and the presence or absence of volcanism. Our results highlight the significance of magmatism in strain accommodation across the rift system, and suggest that some strain and magmatism occur within ‘rigid blocks’, such as the Tanzania craton. Throughout the Afro-Arabian rift system, seismic moment release lags geodetic moment release by a factor of 2, consistent with aseismic creep deformation. However, our comparisons indicate that aseismic deformation accounts for a much higher percent of geodetic moment release: approximately 90% in the Main Ethiopian and Eastern rifts, and >97% in the Afar rift zone where incipient seafloor spreading occurs. The time-averaged strain distributions match the estimates from intense seismo-volcanic rifting episodes in Afar, indicating the data base is representative of longer-term patterns in Afar. We see no systematic variation in interbasinal accommodation zones or rift segment offsets, arguing against the development of transform-like structures prior to plate rupture.

In situ detection of the Zn(2+) release process of ZnO NPs in tumour cells by confocal laser scanning fluorescence microscopy.

PubMed

Song, Wenshuang; Tang, Xiaoling; Li, Yong; Sun, Yang; Kong, Jilie; Qingguang, Ren

2016-08-01

The use of zinc oxide (ZnO) nanoparticles (NPs) for cancer is not yet clear for human clinical applications, which is primarily due to the lack of a better understanding of the action mechanisms and cellular consequences of the direct exposure of cells to these NPs. In this work, the authors have selected zinquin ethyl ester, a Zn(2+)-specific fluorescent molecular probe, to efficiently differentiate ZnO NPs and Zn(2+), and combined with confocal laser scanning microscopy (CLSM) to in situ study the Zn(2+) release process of ZnO NPs in cancer cell system through detecting the change of Zn(2+) level over time. During the experiments, the authors have designed the test group ZnO-2 in addition to assess the influence of a long-term storage on the characteristics of ZnO NPs in aqueous solution, and the Zn(2+) release process of ZnO NPs in cancer cell system. After three-month storage at room temperature, the release process became earlier and faster, which was consistent with previous results of transmission electron microscope, UV-Vis and PL spectra. It is a good detection method that combination of Zn(2+)-specific fluorescent molecular probe and CLSM, which will be helpful for ZnO NPs using in clinical research.

Polymeric micellar pH-sensitive drug delivery system for doxorubicin.

PubMed

Hrubý, Martin; Konák, Cestmír; Ulbrich, Karel

2005-03-02

A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (Mw/Mn ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with Rh(a)=104 nm in phosphate-buffered saline. After incubation in buffers at 37 degrees C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached.

Monoterpenes released from fruit, plant, and vegetable systems.

PubMed

Iqbal, Mohammad Asif; Kim, Ki-Hyun; Ahn, Jeong Hyeon

2014-09-29

To quantify the emission rate of monoterpenes (MTs) from diverse natural sources, the sorbent tube (ST)-thermal desorption (TD) method was employed to conduct the collection and subsequent detection of MTs by gas chromatography. The calibration of MTs, when made by both mass spectrometric (MS) and flame ionization detector (FID), consistently exhibited high coefficient of determination values (R2 > 0.99). This approach was employed to measure their emission rate from different fruit/plant/vegetable (F/P/V) samples with the aid of an impinger-based dynamic headspace sampling system. The results obtained from 10 samples (consisting of carrot, pine needle (P. sylvestris), tangerine, tangerine peel, strawberry, sepals of strawberry, plum, apple, apple peel, and orange juice) marked α-pinene, β-pinene, myrcene, α-terpinene, R-limonene, γ-terpinene, and p-cymene as the most common MTs. R-limonene was the major species emitted from citrus fruits and beverages with its abundance exceeding 90%. In contrast, α-pinene was the most abundant MT (37%) for carrot, while it was myrcene (31%) for pine needle. The overall results for F/P/V samples confirmed α-pinene, β-pinene, myrcene, α-terpinene, and γ-terpinene as common MTs. Nonetheless, the types and magnitude of MTs released from fruits were distinguished from those of vegetables and plants.

19 CFR 4.38 - Release of cargo.

Code of Federal Regulations, 2011 CFR

2011-04-01

... for release without submission of paper documents after reviewing the entry data submitted... imported. (1) Where the cargo arrives by vessel, the report shall consist of the following data elements... following data elements: (i) Air waybill number; (ii) Quantity released; (iii) Entry number (including filer...

19 CFR 4.38 - Release of cargo.

Code of Federal Regulations, 2013 CFR

2013-04-01

... for release without submission of paper documents after reviewing the entry data submitted... imported. (1) Where the cargo arrives by vessel, the report shall consist of the following data elements... following data elements: (i) Air waybill number; (ii) Quantity released; (iii) Entry number (including filer...

19 CFR 4.38 - Release of cargo.

Code of Federal Regulations, 2012 CFR

2012-04-01

... for release without submission of paper documents after reviewing the entry data submitted... imported. (1) Where the cargo arrives by vessel, the report shall consist of the following data elements... following data elements: (i) Air waybill number; (ii) Quantity released; (iii) Entry number (including filer...

19 CFR 4.38 - Release of cargo.

Code of Federal Regulations, 2014 CFR

2014-04-01

... for release without submission of paper documents after reviewing the entry data submitted... imported. (1) Where the cargo arrives by vessel, the report shall consist of the following data elements... following data elements: (i) Air waybill number; (ii) Quantity released; (iii) Entry number (including filer...

19 CFR 4.38 - Release of cargo.

Code of Federal Regulations, 2010 CFR

2010-04-01

... for release without submission of paper documents after reviewing the entry data submitted... imported. (1) Where the cargo arrives by vessel, the report shall consist of the following data elements... following data elements: (i) Air waybill number; (ii) Quantity released; (iii) Entry number (including filer...

Effect of gas release in hot molding on flexural strength of composite friction brake

NASA Astrophysics Data System (ADS)

Rusdja, Andy Permana; Surojo, Eko; Muhayat, Nurul; Raharjo, Wijang Wisnu

2018-02-01

Composite friction brake is a vital part of braking system which serves to reduce the speed of vehicle. To fulfill the requirement of brake performance, composite friction brake must have friction and mechanical characteristic as required. The characteristics of composite friction brake are affected by brake material formulation and manufacturing parameter. In the beginning of hot molding, intermittent hot pressing was carried out to release the gases that consist of ammonia gas and water vapor. In composite friction brake, phenolic resin containing hexamethylenetetramine (HMTA) is often used as a binder. During hot molding, the reaction of phenolic resin and HMTA forms ammonia gas. Hot molding also generates water vapor because raw materials absorb moisture from environment when they are placed in storage. The gas release in hot molding is supposed affecting mechanical properties because it avoid entrapped gas in composite, so that this research investigated effect of gas release on flexural strength. Manufacturing of composite specimen was carried out as follow: mixing of raw materials, cold molding, and hot molding. In this research, duration of intermittent hot pressing and number of gas release were varied. The flexural strength of specimen was measured using three point bending test. The results showed that flexural strength specimens that were manufactured without gas release, using 4 times gas release with intermittent hot pressing for 5 and 10 seconds were not remarkably different. Conversely, hot molding using 4 times gas release with intermittent hot pressing for 15 seconds decreased flexural strength of composite. Hot molding using 2, 4, and 8 times gas release with intermittent hot pressing for 10 seconds also had no effect on increasing flexural strength. Increasing of flexural strength of composite was obtained only by using 6 times gas release with intermittent hot pressing for 10 seconds.

Modulation of a pulsatile release drug delivery system using different swellable/rupturable materials.

PubMed

El-Maradny, Hoda A

2007-11-01

Diclofenac sodium tablets consisting of core coated with two layers of swelling and rupturable coatings were prepared and evaluated as a pulsatile drug delivery system. Cores containing the drug were prepared by direct compression using microcrystalline cellulose and Ludipress as hydrophilic excipients with the ratio of 1:1. Cores were then coated sequentially with an inner swelling layer of different swellable materials; either Explotab, Croscarmellose sodium, or Starch RX 1500, and an outer rupturable layer of different levels of ethylcellulose. The effect of the nature of the swelling layer and the level of the rupturable coating on the lag time and the water uptake were investigated. Drug release rate studies were performed using USP paddle method. Results showed the dependence of the lag time and water uptake prior to tablet rupture on the nature of the swelling layer and the coating levels. Explotab showed a significant decrease in the lag time, followed by Croscarmellose sodium and finally by Starch RX 1500. Increasing the level of ethylcellulose coating retarded the diffusion of the release medium to the swelling layer and the rupture of the coat, thus prolonging the lag time.

In vivo investigation of twin-screw extruded lipid implants for vaccine delivery.

PubMed

Even, Marie-Paule; Young, Katie; Winter, Gerhard; Hook, Sarah; Engert, Julia

2014-07-01

Sustained release systems have become the focus of attention in vaccine delivery as they may reduce or prevent the need for repeated dosing. In this work, lipid implants were prepared by twin-screw extrusion and investigated as vaccine delivery systems in vivo. The lipid implants consisted of cholesterol, soybean lecithin, and Dynasan 114. Ovalbumin (OVA) was employed as a model antigen and Quil-A (QA) as an adjuvant. In addition, OVA and QA loaded liposomes were prepared by the lipid-film hydration method, freeze-dried and then added to the lipid matrix prior to extrusion. Implants were administered subcutaneously and the kinetics of antigen release as well as the overall immune response stimulated were analysed by measuring CD4(+) and CD8(+) T cell proliferation, OVA-specific IgG production as well as cytokine (IFN-γ and IL4) secretion. Vaccine release from the implants was completed by 14 days. Inclusion of adjuvant into the implants was required for the generation of cellular and humoral immune responses. Inclusion of liposomes into the implant did not enhance the resulting immune responses generated. Copyright © 2014 Elsevier B.V. All rights reserved.

Requirement for Coenzyme Q in Plasma Membrane Electron Transport

NASA Astrophysics Data System (ADS)

Sun, I. L.; Sun, E. E.; Crane, F. L.; Morre, D. J.; Lindgren, A.; Low, H.

1992-12-01

Coenzyme Q is required in the electron transport system of rat hepatocyte and human erythrocyte plasma membranes. Extraction of coenzyme Q from the membrane decreases NADH dehydrogenase and NADH:oxygen oxidoreductase activity. Addition of coenzyme Q to the extracted membrane restores the activity. Partial restoration of activity is also found with α-tocopherylquinone, but not with vitamin K_1. Analogs of coenzyme Q inhibit NADH dehydrogenase and oxidase activity and the inhibition is reversed by added coenzyme Q. Ferricyanide reduction by transmembrane electron transport from HeLa cells is inhibited by coenzyme Q analogs and restored with added coenzyme Q10. Reduction of external ferricyanide and diferric transferrin by HeLa cells is accompanied by proton release from the cells. Inhibition of the reduction by coenzyme Q analogs also inhibits the proton release, and coenzyme Q10 restores the proton release activity. Trans-plasma membrane electron transport stimulates growth of serum-deficient cells, and added coenzyme Q10 increases growth of HeLa (human adenocarcinoma) and BALB/3T3 (mouse fibroblast) cells. The evidence is consistent with a function for coenzyme Q in a trans-plasma membrane electron transport system which influences cell growth.

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation.

PubMed

Collins, Anne L; Aitken, Tara J; Greenfield, Venuz Y; Ostlund, Sean B; Wassum, Kate M

2016-11-01

Environmental reward-predictive cues can motivate reward-seeking behaviors. Although this influence is normally adaptive, it can become maladaptive in disordered states, such as addiction. Dopamine release in the nucleus accumbens core (NAc) is known to mediate the motivational impact of reward-predictive cues, but little is known about how other neuromodulatory systems contribute to cue-motivated behavior. Here, we examined the role of the NAc cholinergic receptor system in cue-motivated behavior using a Pavlovian-to-instrumental transfer task designed to assess the motivating influence of a reward-predictive cue over an independently-trained instrumental action. Disruption of NAc muscarinic acetylcholine receptor activity attenuated, whereas blockade of nicotinic receptors augmented cue-induced invigoration of reward seeking. We next examined a potential dopaminergic mechanism for this behavioral effect by combining fast-scan cyclic voltammetry with local pharmacological acetylcholine receptor manipulation. The data show evidence of opposing modulation of cue-evoked dopamine release, with muscarinic and nicotinic receptor antagonists causing suppression and augmentation, respectively, consistent with the behavioral effects of these manipulations. In addition to demonstrating cholinergic modulation of naturally-evoked and behaviorally-relevant dopamine signaling, these data suggest that NAc cholinergic receptors may gate the expression of cue-motivated behavior through modulation of phasic dopamine release.

Controlled release chamber for dispensing aromatic substances.

PubMed

Cilek, J E; Hallmon, C F

2008-12-01

A novel device for the containment and precise release of aromatic substances is described. The device consists of a threaded-tubular polyvinyl chloride chamber (and screw-top cap) with ports for introduction and release of gaseous compounds. This chamber is inexpensive, easy to assemble, and useful for evaluating the combined release of carbon dioxide and aromatic hygroscopic substances as mosquito attractants in field studies.

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.

Melanoma-targeted delivery system (part 1): design, synthesis and evaluation of releasable disulfide drug by glutathione.

PubMed

El Aissi, Radhia; Chezal, Jean-Michel; Tarrit, Sébastien; Chavignon, Olivier; Moreau, Emmanuel

2015-08-28

Here we describe the design and synthesis of a prodrug developed for pigmented melanoma therapy, consisting of a Melanin-Targeting Probe (MTP) conjugated to 5-iodo-2'-deoxyuridine (IUdR) with a reduction-sensitive pre-determined breaking point. Compared with the non-cleavable conjugate (17b), prodrug (17a) bearing a self-immolative disulfide linker achieved complete release of IUdR within 20 min in the presence of reducing agents such as DTT or glutathione. Analytical results also showed that prodrug (17a) was more sensitive than parent non-cleavable conjugate (17b) for a concentration range of glutathione similar to that found in the intracellular compartment of tumours. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Period of an Interrupted Pendulum

NASA Astrophysics Data System (ADS)

Miller, Bradley E.

2002-11-01

While demonstrating a classic conservation-of-energy problem to my AP Physics students, I became curious about the periodic motion that ensued for certain initial conditions. The original problem consists of releasing a mass at the end of a string from an initial position horizontal to the plane of a table. The string comes in contact with a peg some distance below the point where the string is attached at the top. One is asked to find what minimum fraction of the string's length should the peg be placed to have the mass complete a circle about the peg. However, when the mass is released from much lower heights, the system undergoes periodic motion that can be thought of as an interrupted pendulum.

Computer Controlled Portable Greenhouse Climate Control System for Enhanced Energy Efficiency

NASA Astrophysics Data System (ADS)

Datsenko, Anthony; Myer, Steve; Petties, Albert; Hustek, Ryan; Thompson, Mark

2010-04-01

This paper discusses a student project at Kettering University focusing on the design and construction of an energy efficient greenhouse climate control system. In order to maintain acceptable temperatures and stabilize temperature fluctuations in a portable plastic greenhouse economically, a computer controlled climate control system was developed to capture and store thermal energy incident on the structure during daylight periods and release the stored thermal energy during dark periods. The thermal storage mass for the greenhouse system consisted of a water filled base unit. The heat exchanger consisted of a system of PVC tubing. The control system used a programmable LabView computer interface to meet functional specifications that minimized temperature fluctuations and recorded data during operation. The greenhouse was a portable sized unit with a 5' x 5' footprint. Control input sensors were temperature, water level, and humidity sensors and output control devices were fan actuating relays and water fill solenoid valves. A Graphical User Interface was developed to monitor the system, set control parameters, and to provide programmable data recording times and intervals.

Sardine (Sardina pilchardus) larval dispersal in the Iberian upwelling system, using coupled biophysical techniques

NASA Astrophysics Data System (ADS)

Santos, A. M. P.; Nieblas, A.-E.; Verley, P.; Teles-Machado, A.; Bonhommeau, S.; Lett, C.; Garrido, S.; Peliz, A.

2018-03-01

The European sardine (Sardina pilchardus) is the most important small pelagic fishery of the Western Iberia Upwelling Ecosystem (WIUE). Recently, recruitment of this species has declined due to changing environmental conditions. Furthermore, controversies exist regarding its population structure with barriers thought to exist between the Atlantic-Iberian Peninsula, Northern Africa, and the Mediterranean. Few studies have investigated the transport and dispersal of sardine eggs and larvae off Iberia and the subsequent impact on larval recruitment variability. Here, we examine these issues using a Regional Ocean Modeling System climatology (1989-2008) coupled to the Lagrangian transport model, Ichthyop. Using biological parameters from the literature, we conduct simulations that investigate the effects of spawning patchiness, diel vertical migration behaviors, and egg buoyancy on the transport and recruitment of virtual sardine ichthyoplankton on the continental shelf. We find that release area, release depth, and month of release all significantly affect recruitment. Patchiness has no effect and diel vertical migration causes slightly lower recruitment. Egg buoyancy effects are significant and act similarly to depth of release. As with other studies, we find that recruitment peaks vary by latitude, explained here by the seasonal variability of offshore transport. We find weak, continuous alongshore transport between release areas, though a large proportion of simulated ichthyoplankton transport north to the Cantabrian coast (up to 27%). We also show low level transport into Morocco (up to 1%) and the Mediterranean (up to 8%). The high proportion of local retention and low but consistent alongshore transport supports the idea of a series of metapopulations along this coast.

Impacts of water quality on the corrosion of cast iron pipes for water distribution and proposed source water switch strategy.

PubMed

Hu, Jun; Dong, Huiyu; Xu, Qiang; Ling, Wencui; Qu, Jiuhui; Qiang, Zhimin

2018-02-01

Switch of source water may induce "red water" episodes. This study investigated the impacts of water quality on iron release, dissolved oxygen consumption (ΔDO), corrosion scale evolution and bacterial community succession in cast iron pipes used for drinking water distribution at pilot scale, and proposed a source water switch strategy accordingly. Three sets of old cast iron pipe section (named BP, SP and GP) were excavated on site and assembled in a test base, which had historically transported blended water, surface water and groundwater, respectively. Results indicate that an increasing Cl - or SO 4 2- concentration accelerated iron release, but alkalinity and calcium hardness exhibited an opposite tendency. Disinfectant shift from free chlorine to monochloramine slightly inhibited iron release, while the impact of peroxymonosulfate depended on the source water historically transported in the test pipes. The ΔDO was highly consistent with iron release in all three pipe systems. The mass ratio of magnetite to goethite in the corrosion scales of SP was higher than those of BP and GP and kept almost unchanged over the whole operation period. Siderite and calcite formation confirmed that an increasing alkalinity and hardness inhibited iron release. Iron-reducing bacteria decreased in the BP but increased in the SP and GP; meanwhile, sulfur-oxidizing, sulfate-reducing and iron oxidizing bacteria increased in all three pipe systems. To avoid the occurrence of "red water", a source water switch strategy was proposed based on the difference between local and foreign water qualities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Model for Microcapsule Drug Release with Ultrasound-Activated Enhancement.

PubMed

Tsao, Nadia H; Hall, Elizabeth A H

2017-11-14

Microbubbles and microcapsules of silane-polycaprolactone (SiPCL) have been filled with a fluorescent acridium salt (lucigenin) as a model for a drug-loaded delivery vehicle. The uptake and delivery were studied and compared with similar microbubbles and microcapsules of silica/mercaptosilica (S/M/S). Positively charged lucigenin was encapsulated through an electrostatic mechanism, following a Type I Langmuir isotherm as expected, but with an additional multilayer uptake that leads to a much higher loading for the SiPCL system (∼280 μg/2.4 × 10 9 microcapsules compared with ∼135 μg/2.4 × 10 9 microcapsules for S/M/S). Whereas the lucigenin release from the S/M/S bubbles and capsules loaded below the solubility limit is consistent with diffusion from a monolithic structure, the SiPCL structures show distinct release patterns; the Weibull function predicts a general trend for diffusion from normal Euclidean space at short times tending toward diffusion out of fractal spaces with increasing time. As a slow release system, the dissolution time (T d ) increases from 1 to 2 days for the S/M/S and for the low concentration, loaded SiPCl vehicles to ∼10 days for the high loaded microcapsules. However, T d can be reduced on insonation to 2 days, indicating the potential to gain control over the local enhanced release with ultrasound. This was tested for a docetaxel model and its effect on C4-2B prostate cancer cells, showing improved cell toxicity for concentrations below the normal EC 50 in solution.

Mental Health Services Use Trends in Canadian Veterans: A Population-Based Retrospective Cohort Study in Ontario.

PubMed

Mahar, Alyson L; Aiken, Alice B; Cramm, Heidi; Whitehead, Marlo; Groome, Patti; Kurdyak, Paul

2017-01-01

A substantial evidence base in the peer-reviewed literature exists investigating mental illness in the military, but relatively less is documented about mental illness in veterans. This study uses provincial, administrative data to study the use of mental health services by Canadian veterans in Ontario. This was a retrospective cohort study of Canadian Armed Forces and Royal Canadian Mounted Police veterans who were released between 1990 and 2013 and resided in Ontario. Mental health-related primary care physician, psychiatrist, emergency department (ED) visits, and psychiatric hospitalisations were counted. Repeated measures were presented in 5-year intervals, stratified by age at release. The cohort included 23,818 veterans. In the first 5 years following entry into the health care system, 28.9% of veterans had ≥1 mental health-related primary care physician visit, 5.8% visited a psychiatrist at least once, and 2.4% received acute mental health services at an ED. The use of mental health services was consistent over time. Almost 8% of veterans aged 30 to 39 years saw a psychiatrist in the first 5 years after release, compared to 3.5% of veterans aged ≥50 years at release. The youngest veterans at release (<30 years) were the most frequent users of ED services for a mental health-related reason (5.1% had at least 1 ED visit). Understanding how veterans use the health care system for mental health problems is an important step to ensuring needs are met during the transition to civilian life.

Bioaccumulation factors and the steady state assumption for cesium isotopes in aquatic foodwebs near nuclear facilities.

PubMed

Rowan, D J

2013-07-01

Steady state approaches, such as transfer coefficients or bioaccumulation factors, are commonly used to model the bioaccumulation of (137)Cs in aquatic foodwebs from routine operations and releases from nuclear generating stations and other nuclear facilities. Routine releases from nuclear generating stations and facilities, however, often consist of pulses as liquid waste is stored, analyzed to ensure regulatory compliance and then released. The effect of repeated pulse releases on the steady state assumption inherent in the bioaccumulation factor approach has not been evaluated. In this study, I examine the steady state assumption for aquatic biota by analyzing data for two cesium isotopes in the same biota, one isotope in steady state (stable (133)Cs) from geologic sources and the other released in pulses ((137)Cs) from reactor operations. I also compare (137)Cs bioaccumulation factors for similar upstream populations from the same system exposed solely to weapon test (137)Cs, and assumed to be in steady state. The steady state assumption appears to be valid for small organisms at lower trophic levels (zooplankton, rainbow smelt and 0+ yellow perch) but not for older and larger fish at higher trophic levels (walleye). Attempts to account for previous exposure and retention through a biokinetics approach had a similar effect on steady state, upstream and non-steady state, downstream populations of walleye, but were ineffective in explaining the more or less constant deviation between fish with steady state exposures and non-steady state exposures of about 2-fold for all age classes of walleye. These results suggest that for large, piscivorous fish, repeated exposure to short duration, pulse releases leads to much higher (137)Cs BAFs than expected from (133)Cs BAFs for the same fish or (137)Cs BAFs for similar populations in the same system not impacted by reactor releases. These results suggest that the steady state approach should be used with caution in any situation where reactor releases are episodic or pulse in nature, even if the magnitude of these releases is small. Copyright © 2012. Published by Elsevier Ltd.

Striatal dopamine release codes uncertainty in pathological gambling.

PubMed

Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka; Møller, Arne; Doudet, Doris Jeanne; Gjedde, Albert

2012-10-30

Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand, dopamine release coded uncertainty, we would find an inversely U-shaped function. The data supported an inverse U-shaped relation between striatal dopamine release and IGT performance if the pathological gambling group, but not in the healthy control group. These results are consistent with the hypothesis of dopaminergic sensitivity toward uncertainty, and suggest that dopaminergic sensitivity to uncertainty is pronounced in pathological gambling, but not among non-gambling healthy controls. The findings have implications for understanding dopamine dysfunctions in pathological gambling and addictive behaviors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Thermo-responsive mesoporous silica/lipid bilayer hybrid nanoparticles for doxorubicin on-demand delivery and reduced premature release.

PubMed

Zhang, Qing; Chen, Xuanxuan; Shi, Huihui; Dong, Gaoqiu; Zhou, Meiling; Wang, Tianji; Xin, Hongliang

2017-12-01

Hybrid nanocarriers based on mesoporous silica nanoparticles (MSNs) and supported lipid bilayer (SLB) have been studied as drug delivery system. It still remains challenges to develop these nanocarriers (SLB-MSNs) with on-demand drug release profile for chemotherapy. Here, we reported the biocompatible SLB-MSNs with high drug loading, which could release doxorubicin (DOX) in response to hyperthermia and reduce premature release. After synthesis of MSNs via a sol-gel procedure, the thermo-responsive SLB was deposited on the MSNs by sonication to completely seal the mesopores. The obtained SLB-MSNs consisted of 50 nm-sized MSN cores and 6.3 nm-thick SLB shells. Due to the big surface and pore volume of MSNs, the high drug loading content (7.30±0.02%) and encapsulation efficiency (91.16±0.28%) were achieved. The SLB blocking the mesopores reduced 50% of premature release and achieved on-demand release in a thermo-responsive manner. Moreover, SLB-MSNs showed good hemocompatibility at any tested concentration (25-700μg/mL), while bare MSNs caused 100% of hemolysis at concentration larger than 325μg/mL. In addition, in vitro U251 cell uptake experiment demonstrated that compared with uncapped MSNs, SLB-MSNs could prevent untargeted cellular uptake of DOX owing to reduced premature release and steric hindrance of PEG, which would be beneficial to minimize toxicity for healthy tissues. These results indicated that SLB-MSNs with thermo-responsive release capacity possessed great potential in future synergistic thermo-chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

A unified multicomponent stress-diffusion model of drug release from non-biodegradable polymeric matrix tablets.

PubMed

Salehi, Ali; Zhao, Jin; Cabelka, Tim D; Larson, Ronald G

2016-02-28

We propose a new transport model of drug release from hydrophilic polymeric matrices, based on Stefan-Maxwell flux laws for multicomponent transport. Polymer stress is incorporated in the total mixing free energy, which contributes directly to the diffusion driving force while leading to time-dependent boundary conditions at the tablet interface. Given that hydrated matrix tablets are dense multicomponent systems, extended Stefan-Maxwell (ESM) flux laws are adopted to ensure consistency with the Onsager reciprocity principle and the Gibbs-Duhem thermodynamic constraint. The ESM flux law for any given component takes into account the friction exerted by all other species and is invariant with respect to reference velocity, thus satisfying Galilean translational invariance. Our model demonstrates that penetrant-induced plasticization of polymer chains partially or even entirely offsets the steady decline of chemical potential gradients at the tablet-medium interface that drive drug release. Utilizing a Flory-Huggins thermodynamic model, a modified form of the upper convected Maxwell constitutive equation for polymer stress and a Fujita-type dependence of mutual diffusivities on composition, depending on parameters, Fickian, anomalous or case II drug transport arises naturally from the model, which are characterized by quasi-power-law release profiles with exponents ranging from 0.5 to 1, respectively. A necessary requirement for non-Fickian release in our model is that the matrix stress relaxation time is comparable to the time scale for water diffusion. Mutual diffusivities and their composition dependence are the most decisive factors in controlling drug release characteristics in our model. Regression of the experimental polymer dissolution and drug release profiles in a system of Theophylline/cellulose (K15M) demonstrate that API-water mutual diffusivity in the presence of excipient cannot generally be taken as a constant. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

On the Relation of Setting and Early-Age Strength Development to Porosity and Hydration in Cement-Based Materials

PubMed Central

Lootens, Didier; Bentz, Dale P.

2016-01-01

Previous research has demonstrated a linear relationship between compressive strength (mortar cubes and concrete cylinders) and cumulative heat release normalized per unit volume of (mixing) water for a wide variety of cement-based mixtures at ages of 1 d and beyond. This paper utilizes concurrent ultrasonic reflection and calorimetry measurements to further explore this relationship from the time of specimen casting to 3 d. The ultrasonic measurements permit a continuous evaluation of thickening, setting, and strength development during this time period for comparison with the ongoing chemical reactions, as characterized by isothermal calorimetry measurements. Initially, the ultrasonic strength-heat release relation depends strongly on water-to-cement ratio, as well as admixture additions, with no universal behavior. Still, each individual strength-heat release curve is consistent with a percolation-based view of the cement setting process. However, beyond about 8 h for the systems investigated in the present study, the various strength-heat release curves merge towards a single relationship that broadly characterizes the development of strength as a function of heat released (fractional space filled), demonstrating that mortar and/or concrete strength at early ages can be effectively monitored using either ultrasonic or calorimetry measurements on small paste or mortar specimens. PMID:27046956

Analgesic and anti-inflammatory controlled-released injectable microemulsion: Pseudo-ternary phase diagrams, in vitro, ex vivo and in vivo evaluation.

PubMed

Pineros, Isabel; Slowing, Karla; Serrano, Dolores R; de Pablo, Esther; Ballesteros, Maria Paloma

2017-04-01

Development of analgesic and anti-inflammatory controlled-released injectable microemulsions utilising lysine clonixinate (LC) as model drug and generally regarded as safe (GRAS) excipients. Different microemulsions were optimised through pseudo-ternary phase diagrams and characterised measuring droplet size, viscosity, ex vivo haemolytic activity and in vitro drug release. The anti-inflammatory and analgesic activity was tested in mice (Hot plate test) and rats (Carrageenan-induced paw edema test) respectively and their activity was compared to an aqueous solution of LC salt. The aqueous solution showed a faster and shorter response whereas the optimised microemulsion increased significantly (p<0.01) the potency and duration of the analgesic and anti-inflammatory activity after deep intramuscular injection. The droplet size and the viscosity were key factors to control the drug release from the systems and enhance the effect of the formulations. The microemulsion consisting of Labrafil®/Lauroglycol®/Polysorbate 80/water with LC (56.25/18.75/15/10, w/w) could be a promising formulation after buccal surgery due to its ability to control the drug release and significantly achieve greater analgesic and anti-inflammatory effect over 24h. Copyright © 2016. Published by Elsevier B.V.

On the Relation of Setting and Early-Age Strength Development to Porosity and Hydration in Cement-Based Materials.

PubMed

Lootens, Didier; Bentz, Dale P

2016-04-01

Previous research has demonstrated a linear relationship between compressive strength (mortar cubes and concrete cylinders) and cumulative heat release normalized per unit volume of (mixing) water for a wide variety of cement-based mixtures at ages of 1 d and beyond. This paper utilizes concurrent ultrasonic reflection and calorimetry measurements to further explore this relationship from the time of specimen casting to 3 d. The ultrasonic measurements permit a continuous evaluation of thickening, setting, and strength development during this time period for comparison with the ongoing chemical reactions, as characterized by isothermal calorimetry measurements. Initially, the ultrasonic strength-heat release relation depends strongly on water-to-cement ratio, as well as admixture additions, with no universal behavior. Still, each individual strength-heat release curve is consistent with a percolation-based view of the cement setting process. However, beyond about 8 h for the systems investigated in the present study, the various strength-heat release curves merge towards a single relationship that broadly characterizes the development of strength as a function of heat released (fractional space filled), demonstrating that mortar and/or concrete strength at early ages can be effectively monitored using either ultrasonic or calorimetry measurements on small paste or mortar specimens.

Understanding controlled drug release from mesoporous silicates: theory and experiment.

PubMed

Ukmar, T; Maver, U; Planinšek, O; Kaučič, V; Gaberšček, M; Godec, A

2011-11-07

Based on the results of carefully designed experiments upgraded with appropriate theoretical modeling, we present clear evidence that the release curves from mesoporous materials are significantly affected by drug-matrix interactions. In experimental curves, these interactions are manifested as a non-convergence at long times and an inverse dependence of release kinetics on pore size. Neither of these phenomena is expected in non-interacting systems. Although both phenomena have, rather sporadically, been observed in previous research, they have not been explained in terms of a general and consistent theoretical model. The concept is demonstrated on a model drug indomethacin embedded into SBA-15 and MCM-41 porous silicates. The experimental release curves agree exceptionally well with theoretical predictions in the case of significant drug-wall attractions. The latter are described using a 2D Fokker-Planck equation. One could say that the interactions affect the relative cross-section of pores where the local flux has a non-vanishing axial component and in turn control the effective transfer of drug into bulk solution. Finally, we identify the critical parameters determining the pore size dependence of release kinetics and construct a dynamic phase diagram of the various resulting transport regimes. Copyright © 2011 Elsevier B.V. All rights reserved.

Subcutaneous Administration of Otelixizumab is Limited by Injection Site Reactions: Results of an Exploratory Study in Type 1 Diabetes Mellitus Patients.

PubMed

MacDonald, A; Ambery, P; Donaldson, J; Hicks, K; Keymeulen, B; Parkin, J

2016-05-01

Targeting CD3 antigens on human T lymphocytes with monoclonal antibodies has been shown to reduce the rate of decline of C-peptides in recent-onset type 1 diabetes mellitus patients. However, effective doses are associated with infusion reactions typical of "cytokine release syndrome" and appear to be dose-limiting when administered as short-duration infusions. A possible alternative approach, which may reduce the rate of T cell activation and consequent systemic cytokine release, is to inject subcutaneously. We investigated single- and repeat-dose subcutaneous administration of the anti-CD3 monoclonal antibody otelixizumab in small cohorts of patients with type 1 diabetes. Transient reductions in free or unbound CD3 antigen on CD4+ and CD8+ cells and absolute lymphocyte count were observed in the blood of these patients during treatment, consistent with the known mechanism of action of otelixizumab and other anti-CD3 monoclonal antibodies. This was despite the very low systemic exposure of antibodies measured during the same time period. With the exception of sporadic headaches, other symptoms associated with cytokine release syndrome, such as fever, nausea, vomiting, myalgia, and arthralgia, were absent in treated patients. However, treatment-related injection site reactions were consistently observed. The reactions were erythematous and their sizes were dose-dependent; in some cases, reactions persisted for up to 2 weeks following the start of treatment. While patients responded well to topical corticosteroid treatment and prophylaxis reduced the intensity of injection site reactions, the reactions were considered dose-limiting and higher doses were not investigated. © Georg Thieme Verlag KG Stuttgart · New York.

Diblock Terpolymers Are Tunable and pH Responsive Vehicles To Increase Hydrophobic Drug Solubility for Oral Administration.

PubMed

Tale, Swapnil; Purchel, Anatolii A; Dalsin, Molly C; Reineke, Theresa M

2017-11-06

Synthetic polymers offer tunable platforms to create new oral drug delivery vehicles (excipients) to increase solubility, supersaturation maintenance, and bioavailability of poorly aqueous soluble pharmaceutical candidates. Five well-defined diblock terpolymers were synthesized via reversible addition-fragmentation chain transfer polymerization (RAFT) and consist of a first block of either poly(ethylene-alt-propylene) (PEP), poly(N-isopropylacrylamide) (PNIPAm), or poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) and a second hydrophilic block consisting of a gradient copolymer of N,N-dimethylacrylamide (DMA) and 2-methacrylamidotrehalose (MAT). This family of diblock terpolymers offers hydrophobic, hydrophilic, or H-bonding functionalities to serve as noncovalent sites of drug binding. Drug-polymer spray dried dispersions (SDDs) were created with a model drug, probucol, and characterized by differential scanning calorimetry (DSC). These studies revealed that probucol crystallinity decreased with increasing H-bonding sites available in the polymer. The PNIPAm-b-P(DMA-grad-MAT) systems revealed the best performance at pH 6.5, where immediate probucol release and effective maintenance of 100% supersaturation was found, which is important for facilitating drug solubility in more neutral conditions (intestinal environment). However, the PDEAEMA-b-P(DMA-grad-MAT) system revealed poor probucol dissolution at pH 6.5 and 5.1. Alternatively, at an acidic pH of 3.1, a rapid and high dissolution profile and effective supersaturation maintenance of up to 90% of the drug was found, which could be useful for triggering drug release in acidic environments (stomach). The PEP-b-P(DMA-grad-MAT) system showed poor performance (only ∼20% of drug solubility at pH 6.5), which was attributed to the low solubility of the polymers in the dissolution media. This work demonstrates the utility of diblock terpolymers as a potential new excipient platform to optimize design parameters for triggered release and solubilizing hydrophobic drug candidates for oral delivery.

In Vivo Formation of Cubic Phase in Situ after Oral Administration of Cubic Phase Precursor Formulation Provides Long Duration Gastric Retention and Absorption for Poorly Water-Soluble Drugs.

PubMed

Pham, Anna C; Hong, Linda; Montagnat, Oliver; Nowell, Cameron J; Nguyen, Tri-Hung; Boyd, Ben J

2016-01-04

Lipid-based liquid crystalline systems based on the combination of digestible and nondigestible lipids have been proposed as potential sustained release delivery systems for oral delivery of poorly water-soluble drugs. The potential for cubic phase liquid crystal formation to induce dramatically extended gastric retention in vivo has been shown previously to strongly influence the resulting pharmacokinetics of incorporated drug. In vitro studies showing the in situ formation of cubic phase from a disordered precursor comprising a mixture of digestible and nondigestible lipids under enzymatic digestion have also recently been reported. Combining both concepts, here we show the potential for such systems to form in vivo, increasing gastric retention, and providing a sustained release effect for a model poorly water-soluble drug cinnarizine. A mixture of phytantriol and tributyrin at an 85:15 mass ratio, shown previously to form cubic phase under the influence of digestion, induced a similar pharmacokinetic profile to that in the absence of tributyrin, but completely different from tributyrin alone. The gastric retention of the formulation, assessed using micro-X-ray CT imaging, was also consistent with the pharmacokinetic behavior, where phytantriol alone and with 15% tributyrin was greater than that of tributyrin in the absence of phytantriol. Thus, the concept of precursor lipid systems that form cubic phase in situ during digestion in vivo has been demonstrated and opens new opportunities for sustained release of poorly water-soluble drugs.

Detonation Characteristics of Mixtures of HMX and Emulsion Explosives

DTIC Science & Technology

1989-04-01

and an aqueous emulsion explo- sive have been determined. The emulsion explosive consisted of amonium - nitrate , sodium- nitrate and water in the...1989 D Cb ID A Final Report C14 Approved for public release; distribution unlimited. AIR FORCE WEAPONS LABORATORY Air Force Systems Command Kirtland...TERMS (ContInue on nvwn Nf ocosury and idsŘ by block number) FIELD GROUP SUB-GROUP Explosives; Ammonium Nitrate ;- 19 01Emulsion Explosives; ( 07 04

Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I.

PubMed

Mehta, R; Teckoe, J; Schoener, C; Workentine, S; Ferrizzi, D; Rajabi-Siahboomi, A

2016-12-01

Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms. For multiparticulate extended release dosage forms, the drug release is typically governed by the properties of the barrier membrane coating. The ICH Pharmaceutical Development Guideline (ICH Q8) requires an understanding of the influence of critical material attributes and critical process parameters on the drug release of a pharmaceutical product. Using this understanding, it is possible to develop robust formulations with consistent drug release characteristics. Critical material attributes for ethylcellulose were evaluated, and polymer molecular weight variation (viscosity) was considered to be the most critical attribute that can impact drug release. To investigate the effect of viscosity variation within the manufacturer's specifications of ethylcellulose, extended release multiparticulate formulations of two model drugs, metoprolol tartrate and acetaminophen, were developed using ETHOCEL™ as the rate controlling polymer. Quality by Design (QbD) samples of ETHOCEL Std. 10, 20, and 100 Premium grades representing the low, medium, and high molecular weight (viscosity) material were organically coated onto drug layered multiparticulates to a 15% weight gain (WG). The drug release was found to be similar (f 2  > 50) for both metoprolol tartrate and acetaminophen multiparticulates at different coating weight gains of ethylcellulose, highlighting consistent and robust drug release performance. The use of ETHOCEL QbD samples also serves as a means to develop multiparticulate dosage formulations according to regulatory guidelines.

Development of advanced lightweight containment systems

NASA Technical Reports Server (NTRS)

Stotler, C.

1981-01-01

Parametric type data were obtained on advanced lightweight containment systems. These data were used to generate design methods and procedures necessary for the successful development of such systems. The methods were then demonstrated through the design of a lightweight containment system for a CF6 size engine. The containment concept evaluated consisted basically of a lightweight structural sandwich shell wrapped with dry Kevlar cloth. The initial testing was directed towards the determination of the amount of Kevlar required to result in threshold containment for a specific set of test conditions. A relationship was then developed between the thickness required and the energy of the released blade so that the data could be used to design for conditions other than those tested.

Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery

PubMed Central

Nath, Bipul; Nath, Lila Kanta

2013-01-01

The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms. PMID:26555985

U.S. EPA response to the Fukushima Daiichi Nuclear Power Plant accident.

PubMed

Tupin, Edward A; Boyd, Michael A; Mosser, Jennifer E; Wieder, Jessica S

2012-05-01

During the spring of 2011, the U.S. Environmental Protection Agency (EPA) used its national radiation monitoring and sampling system, RadNet, to detect, identify, and inform the public about radioactive material in the United States resulting from Japan's Fukushima Daiichi Nuclear Power Plant release. The RadNet system monitors ambient air, drinking water, precipitation, and pasteurized milk for radionuclides. To supplement its existing stationary (fixed) continuous air monitoring system, EPA deployed additional air monitors to Saipan, Guam, and locations in the western United States. The Agency also accelerated the regular quarterly sampling of milk and drinking water and collected an additional round of samples. For two months, staff located at EPA's Headquarters Emergency Operations Center, west coast regional offices, and National Air and Radiation Environmental Lab worked seven days a week to handle the increased radiochemical sample analysis from air filters, precipitation, drinking water, and milk; provide interagency scientific input; and answer press and public inquiries. EPA's data was consistent with what was expected from the Fukushima Daiichi Nuclear Power Plant release. The levels of radioactivity were so low that the readings from the near-real-time RadNet air monitors stayed within normal background ranges. Detailed sample analyses were needed to identify the radionuclides associated with the release. Starting at the end of April and continuing through May 2011, levels of radioactive material decreased as expected.

Finite-element three-dimensional ground-water (FE3DGW) flow model - formulation, program listings and users' manual

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

Gupta, S.K.; Cole, C.R.; Bond, F.W.

1979-12-01

The Assessment of Effectiveness of Geologic Isolation Systems (AEGIS) Program is developing and applying the methodology for assessing the far-field, long-term post-closure safety of deep geologic nuclear waste repositories. AEGIS is being performed by Pacific Northwest Laboratory (PNL) under contract with the Office of Nuclear Waste Isolation (OWNI) for the Department of Energy (DOE). One task within AEGIS is the development of methodology for analysis of the consequences (water pathway) from loss of repository containment as defined by various release scenarios. Analysis of the long-term, far-field consequences of release scenarios requires the application of numerical codes which simulate the hydrologicmore » systems, model the transport of released radionuclides through the hydrologic systems to the biosphere, and, where applicable, assess the radiological dose to humans. Hydrologic and transport models are available at several levels of complexity or sophistication. Model selection and use are determined by the quantity and quality of input data. Model development under AEGIS and related programs provides three levels of hydrologic models, two levels of transport models, and one level of dose models (with several separate models). This document consists of the description of the FE3DGW (Finite Element, Three-Dimensional Groundwater) Hydrologic model third level (high complexity) three-dimensional, finite element approach (Galerkin formulation) for saturated groundwater flow.« less

Model‐Informed Development and Registration of a Once‐Daily Regimen of Extended‐Release Tofacitinib

PubMed Central

Lamba, M; Hutmacher, MM; Furst, DE; Dikranian, A; Dowty, ME; Conrado, D; Stock, T; Nduaka, C; Cook, J

2017-01-01

Extended‐release (XR) formulations enable less frequent dosing vs. conventional (e.g., immediate release (IR)) formulations. Regulatory registration of such formulations typically requires pharmacokinetic (PK) and clinical efficacy data. Here we illustrate a model‐informed, exposure–response (E‐R) approach to translate controlled trial data from one formulation to another without a phase III trial, using a tofacitinib case study. Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). E‐R analyses were conducted using validated clinical endpoints from phase II dose–response and nonclinical dose fractionation studies of the IR formulation. Consistent with the delay in clinical response dynamics relative to PK, average concentration was established as the relevant PK parameter for tofacitinib efficacy and supported pharmacodynamic similarity. These evaluations, alongside demonstrated equivalence in total systemic exposure between IR and XR formulations, provided the basis for the regulatory approval of tofacitinib XR once daily by the US Food and Drug Administration. PMID:27859030

Elevated moisture stimulates carbon loss from mineral soils by releasing protected organic matter.

PubMed

Huang, Wenjuan; Hall, Steven J

2017-11-24

Moisture response functions for soil microbial carbon (C) mineralization remain a critical uncertainty for predicting ecosystem-climate feedbacks. Theory and models posit that C mineralization declines under elevated moisture and associated anaerobic conditions, leading to soil C accumulation. Yet, iron (Fe) reduction potentially releases protected C, providing an under-appreciated mechanism for C destabilization under elevated moisture. Here we incubate Mollisols from ecosystems under C 3 /C 4 plant rotations at moisture levels at and above field capacity over 5 months. Increased moisture and anaerobiosis initially suppress soil C mineralization, consistent with theory. However, after 25 days, elevated moisture stimulates cumulative gaseous C-loss as CO 2 and CH 4 to >150% of the control. Stable C isotopes show that mineralization of older C 3 -derived C released following Fe reduction dominates C losses. Counter to theory, elevated moisture may significantly accelerate C losses from mineral soils over weeks to months-a critical mechanistic deficiency of current Earth system models.

Dibutyryl cyclic AMP stimulates expression of ependymin mRNA and the synthesis and release of the protein into the culture medium by neuroblastoma cells (NB2a/d1).

PubMed

Shashoua, V E; Nolan, P M; Shea, T B; Milinazzo, B

1992-06-01

Northern blot, immunoprecipitation, and gel electrophoretic data demonstrate that the mouse neuroblastoma NB2a/d1 cells express ependymin mRNA and synthesize and release into the culture medium a protein with immunoreactivity and electrophoretic mobility properties identical to ependymin. This is a brain extracellular glycoprotein that has been implicated in the consolidation process of memory formation and neuronal regeneration. In labeling experiments with 35S-methionine, dibutyrylcyclic3',5'-adenosine-monophosphate (dbcAMP) was found to stimulate the expression of ependymin mRNA and the enhanced synthesis and release of ependymin into the culture medium at the same time that dbcAMP stimulation of neurite outgrowth takes place. These results are consistent with the proposed role of the protein in the mechanism of neuronal regeneration and synaptogenesis. The data indicate that the NB2a/d1 cell line is a good model system for studies of the functional properties of ependymin.

Spacelab data processing facility (SLDPF) quality assurance (QA)/data accounting (DA) expert systems - Transition from prototypes to operational systems

NASA Technical Reports Server (NTRS)

Basile, Lisa

1988-01-01

The SLDPF is responsible for the capture, quality monitoring processing, accounting, and shipment of Spacelab and/or Attached Shuttle Payloads (ASP) telemetry data to various user facilities. Expert systems will aid in the performance of the quality assurance and data accounting functions of the two SLDPF functional elements: the Spacelab Input Processing System (SIPS) and the Spacelab Output Processing System (SOPS). Prototypes were developed for each as independent efforts. The SIPS Knowledge System Prototype (KSP) used the commercial shell OPS5+ on an IBM PC/AT; the SOPS Expert System Prototype used the expert system shell CLIPS implemented on a Macintosh personal computer. Both prototypes emulate the duties of the respective QA/DA analysts based upon analyst input and predetermined mission criteria parameters, and recommended instructions and decisions governing the reprocessing, release, or holding for further analysis of data. These prototypes demonstrated feasibility and high potential for operational systems. Increase in productivity, decrease of tedium, consistency, concise historical records, and a training tool for new analyses were the principal advantages. An operational configuration, taking advantage of the SLDPF network capabilities, is under development with the expert systems being installed on SUN workstations. This new configuration in conjunction with the potential of the expert systems will enhance the efficiency, in both time and quality, of the SLDPF's release of Spacelab/AST data products.

Spacelab data processing facility (SLDPF) Quality Assurance (QA)/Data Accounting (DA) expert systems: Transition from prototypes to operational systems

NASA Technical Reports Server (NTRS)

Basile, Lisa

1988-01-01

The SLDPF is responsible for the capture, quality monitoring processing, accounting, and shipment of Spacelab and/or Attached Shuttle Payloads (ASP) telemetry data to various user facilities. Expert systems will aid in the performance of the quality assurance and data accounting functions of the two SLDPF functional elements: the Spacelab Input Processing System (SIPS) and the Spacelab Output Processing System (SOPS). Prototypes were developed for each as independent efforts. The SIPS Knowledge System Prototype (KSP) used the commercial shell OPS5+ on an IBM PC/AT; the SOPS Expert System Prototype used the expert system shell CLIPS implemented on a Macintosh personal computer. Both prototypes emulate the duties of the respective QA/DA analysts based upon analyst input and predetermined mission criteria parameters, and recommended instructions and decisions governing the reprocessing, release, or holding for further analysis of data. These prototypes demonstrated feasibility and high potential for operational systems. Increase in productivity, decrease of tedium, consistency, concise historial records, and a training tool for new analyses were the principal advantages. An operational configuration, taking advantage of the SLDPF network capabilities, is under development with the expert systems being installed on SUN workstations. This new configuration in conjunction with the potential of the expert systems will enhance the efficiency, in both time and quality, of the SLDPF's release of Spacelab/AST data products.

Cu/Mn bimetallic catalysis enables carbonylative Suzuki-Miyaura coupling with unactivated alkyl electrophiles.

PubMed

Pye, Dominic R; Cheng, Li-Jie; Mankad, Neal P

2017-07-01

A bimetallic system consisting of Cu-carbene and Mn-carbonyl co-catalysts was employed for carbonylative C-C coupling of arylboronic esters with alkyl halides, allowing for the convergent synthesis of ketones. The system operates under mild conditions and exhibits complementary reactivity to Pd catalysis. The method is compatible with a wide range of arylboronic ester nucleophiles and proceeds smoothly for both primary and secondary alkyl iodide electrophiles. Preliminary mechanistic experiments corroborate a hypothetical catalytic mechanism consisting of co-dependent cycles wherein the Cu-carbene co-catalyst engages in transmetallation to generate an organocopper nucleophile, while the Mn-carbonyl co-catalyst activates the alkyl halide electrophile by single-electron transfer and then undergoes reversible carbonylation to generate an acylmanganese electrophile. The two cycles then intersect with a heterobimetallic, product-releasing C-C coupling step.

Nanotechnological advances for cutaneous release of tretinoin: an approach to minimize side effects and improve therapeutic efficacy.

PubMed

Raminelli, Ana Claudia Pompeu; Romero, Valeria; Semreen, Mohammad H; Leonardi, Gislaine Ricci

2018-03-12

The clinical efficacy of the topical tretinoin is widely studied and has been well established for many therapeutic interventions, among some, photoaging, acne, and melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling, remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery profile is essential to understand the therapeutic action of the drug. Herein we highlight further advances and an update on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrins, nanostructured polymers and other technological systems that reduce its side effects and improve the permeation profile to potentiate efficacy and drug safety on the skin. Pharmaceutical preparations were developed and evaluated for permeability in in vitro models using pig ear, snake, mouse and human skin, and potential for irritation was also verified using release systems for tretinoin and compared to available commercial formulations. Overall results indicated the composition, charge and size of the system influences the tretinoin delivery, modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous drug delivery. As evident from the literature, the tretinoin technological delivery systems consist an innovative and potential management for increasing the patient compliance presenting safety and efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

New polyvinyl chloride (PVC) nanocomposite consisting of aromatic polyamide and chitosan modified ZnO nanoparticles with enhanced thermal stability, low heat release rate and improved mechanical properties

NASA Astrophysics Data System (ADS)

Hajibeygi, Mohsen; Maleki, Mahdiye; Shabanian, Meisam; Ducos, Franck; Vahabi, Henri

2018-05-01

New ternary nanocomposite systems containing polylvinyl chloride (PVC), chitosan modified ZnO (CMZN) nanoparticles and new synthesized polyamide (PA) were designed and prepared by solution casting method. As a potential reinforcement, CMZN was used in PVC system combined with and without PA. Morphology, mechanical, thermal and combustion properties of the all PVC systems were studied. In the presence of the CMZN, PA showed a synergistic effect on improvement of the all investigated properties of PVC. The 5 mass% loss temperature (T5) was increased from 195 °C to 243 °C in PVC/CMZN-PA nanocomposite containing 1 mass% of each PA and CMZN (PZP 2). The peak of heat release rate was decreased from 131 W/g for PVC to 104 W/g for PVC/CMZN-PA nanocomposite containing 3 mass% of each PA and CMZN (PZP 6). According to the tensile tests, compared to the neat PVC, the tensile strength was increased from 35.4 to 53.4 MPa for PZP 6.

Design of hydrogen vent line for the cryogenic hydrogen system in J-PARC

NASA Astrophysics Data System (ADS)

Tatsumoto, Hideki; Aso, Tomokazu; Kato, Takashi; Ohtsu, Kiichi; Hasegawa, Shoichi; Maekawa, Fujio; Futakawa, Masatoshi

2009-02-01

As one of the main experimental facilities in J-PARC, an intense spallation neutron source (JSNS) driven by a 1-MW proton beam selected supercritical hydrogen at a temperature of 20 K and a pressure of 1.5 MPa as a moderator material. Moderators are controlled by a cryogenic hydrogen system that has a hydrogen relief system, which consists of high and low pressure stage of manifolds, a hydrogen vent line and a stack, in order to release hydrogen to the outside safely. The design of the hydrogen vent line should be considered to prevent purge nitrogen gas in the vent line from freezing when releasing the cryogenic hydrogen, to prevent moisture in the stack placed in an outdoor location from freezing, and to inhibit large piping temperature reduction at a building wall penetration. In this work, temperature change behaviors in the hydrogen vent line were analyzed by using a CFD code, STAR-CD. We determined required sizes of the vent line based on the analytical results and its layout in the building.

Development and characterization of a new oral dapsone nanoemulsion system: permeability and in silico bioavailability studies

PubMed Central

Monteiro, Lidiane M; Lione, Viviane F; do Carmo, Flavia A; do Amaral, Lilian H; da Silva, Julianna H; Nasciutti, Luiz E; Rodrigues, Carlos R; Castro, Helena C; de Sousa, Valeria P; Cabral, Lucio M

2012-01-01

Background Dapsone is described as being active against Mycobacterium leprae, hence its role in the treatment of leprosy and related pathologies. Despite its therapeutic potential, the low solubility of dapsone in water results in low bioavailability and high microbial resistance. Nanoemulsions are pharmaceutical delivery systems derived from micellar solutions with a good capacity for improving absorption. The aim of this work was to develop and compare the permeability of a series of dapsone nanoemulsions in Caco-2 cell culture against that of effective permeability in the human body simulated using Gastroplus™ software. Methods and results The release profiles of the dapsone nanoemulsions using different combinations of surfactants and cosolvent showed a higher dissolution rate in simulated gastric and enteric fluid than did the dispersed dapsone powder. The drug release kinetics were consistent with a Higuchi model. Conclusion This comparison of dapsone permeability in Caco-2 cells with effective permeability in the human body simulated by Gastroplus showed a good correlation and indicates potential improvement in the biodisponibility of dapsone using this new system. PMID:23055729

Development and characterization of a new oral dapsone nanoemulsion system: permeability and in silico bioavailability studies.

PubMed

Monteiro, Lidiane M; Lione, Viviane F; do Carmo, Flavia A; do Amaral, Lilian H; da Silva, Julianna H; Nasciutti, Luiz E; Rodrigues, Carlos R; Castro, Helena C; de Sousa, Valeria P; Cabral, Lucio M

2012-01-01

Dapsone is described as being active against Mycobacterium leprae, hence its role in the treatment of leprosy and related pathologies. Despite its therapeutic potential, the low solubility of dapsone in water results in low bioavailability and high microbial resistance. Nanoemulsions are pharmaceutical delivery systems derived from micellar solutions with a good capacity for improving absorption. The aim of this work was to develop and compare the permeability of a series of dapsone nanoemulsions in Caco-2 cell culture against that of effective permeability in the human body simulated using Gastroplus™ software. The release profiles of the dapsone nanoemulsions using different combinations of surfactants and cosolvent showed a higher dissolution rate in simulated gastric and enteric fluid than did the dispersed dapsone powder. The drug release kinetics were consistent with a Higuchi model. This comparison of dapsone permeability in Caco-2 cells with effective permeability in the human body simulated by Gastroplus showed a good correlation and indicates potential improvement in the biodisponibility of dapsone using this new system.

Variation in Nutrient Release of Polymer-Coated Fertilizers

Treesearch

Douglass F. Jacobs

2005-01-01

Polymer-coated fertilizers (PCF) are used primarily in horticultural plant production. However, interest in using these fertilizers in forest tree nurseries has increased over the last decade. Compared to immediately-available forms of fertilizer and other controlled-release fertilizer types, PCF tend to release nutrients in a relatively consistent flow over time. This...

76 FR 22164 - Notice of Intent To Rule on Request To Release Airport Property at Houma Terrebonne Airport...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-20

... To Release Airport Property at Houma Terrebonne Airport, Houma, LA AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of request to release airport property. SUMMARY: The FAA proposes to..., Louisiana. The property consists of two small parcels of land, together with all the improvements situated...

76 FR 25402 - Notice of Intent To Rule on Request To Release Airport Property at Hammond Northshore Regional...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... To Release Airport Property at Hammond Northshore Regional Airport, Hammond, LA AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of request to release airport property. SUMMARY: The FAA... Airport, Hammond, Louisiana. The property consists of vacant land located on the corner of Industrial Park...

Hydrogen Bearing Material in the Lunar Exosphere

NASA Astrophysics Data System (ADS)

Hurley, D.; Benna, M.; Colaprete, A.; Retherford, K. D.; Cook, J. C.; Elphic, R. C.; Farrell, W. M.; Killen, R. M.; Sarantos, M.

2015-12-01

We report on observations of water and its daughters in the lunar exosphere. Data from LADEE NMS, LADEE UVS, and LRO LAMP indicating the presence of H, H2, OH, and H2O are presented in terms of their relationship to external drivers. These observations point to the roles of solar wind and micrometeoroids in the source and release of hydrogen-bearing atoms and molecules in the exosphere. In particular, the implantation of H via solar wind is found to be the largest contributor to H2 in the moon's exosphere. However, the spatial distribution is more consistent with a release mechanism centered on the morning hemisphere. Thus the data are consistent with H2 created through a 2-step process involving the implantation of solar wind and subsequent release by micrometeoroids. This accounts for >12% of the solar wind H budget, leaving < 50% of the solar wind proton budget unobserved. LADEE data are consistent with water mainly being released by micrometeoroids. We present an overall picture of the present-day water cycle occurring on the Moon.

User's manual for the Composite HTGR Analysis Program (CHAP-1)

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

Gilbert, J.S.; Secker, P.A. Jr.; Vigil, J.C.

1977-03-01

CHAP-1 is the first release version of an HTGR overall plant simulation program with both steady-state and transient solution capabilities. It consists of a model-independent systems analysis program and a collection of linked modules, each representing one or more components of the HTGR plant. Detailed instructions on the operation of the code and detailed descriptions of the HTGR model are provided. Information is also provided to allow the user to easily incorporate additional component modules, to modify or replace existing modules, or to incorporate a completely new simulation model into the CHAP systems analysis framework.

The Effect of Birthrate Granularity on the Release- to- Birth Ratio for the AGR-1 In-core Experiment

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

Dawn Scates; John Walter

The AGR-1 Advanced Gas Reactor (AGR) tristructural-isotropic-particle fuel experiment underwent 13 irradiation intervals from December 2006 until November 2009 within the Idaho National Laboratory Advanced Test Reactor in support of the Next Generation Nuclear Power Plant program. During this multi-year experiment, release-to-birth rate ratios were computed at the end of each operating interval to provide information about fuel performance. Fission products released during irradiation were tracked daily by the Fission Product Monitoring System using 8-hour measurements. Birth rates calculated by MCNP with ORIGEN for as-run conditions were computed at the end of each irradiation interval. Each time step in MCNPmore » provided neutron flux, reaction rates and AGR-1 compact composition, which were used to determine birth rates using ORIGEN. The initial birth-rate data, consisting of four values for each irradiation interval at the beginning, end, and two intermediate times, were interpolated to obtain values for each 8-hour activity. The problem with this method is that any daily changes in heat rates or perturbations, such as shim control movement or core/lobe power fluctuations, would not be reflected in the interpolated data and a true picture of the system would not be presented. At the conclusion of the AGR-1 experiment, great efforts were put forth to compute daily birthrates, which were reprocessed with the 8-hour release activity. The results of this study are presented in this paper.« less

The effect of birthrate granularity on the release-to-birth ratio for the AGR-1 in-core experiment

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

D. M. Scates; J. B. Walter; J. T. Maki

The AGR-1 Advanced Gas Reactor (AGR) tristructural-isotropic-particle fuel experiment underwent 13 irradiation intervals from December 2006 until November 2009 within the Idaho National Laboratory Advanced Test Reactor in support of the Next Generation Nuclear Power Plant program. During this multi-year experiment, release-to-birth rate ratios were computed at the end of each operating interval to provide information about fuel performance. Fission products released during irradiation were tracked daily by the Fission Product Monitoring System using 8-h measurements. Birth rate calculated by MCNP with ORIGEN for as-run conditions were computed at the end of each irradiation interval. Each time step in MCNPmore » provided neutron flux, reaction rates and AGR-1 compact composition, which were used to determine birth rate using ORIGEN. The initial birth-rate data, consisting of four values for each irradiation interval at the beginning, end, and two intermediate times, were interpolated to obtain values for each 8-h activity. The problem with this method is that any daily changes in heat rates or perturbations, such as shim control movement or core/lobe power fluctuations, would not be reflected in the interpolated data and a true picture of the system would not be presented. At the conclusion of the AGR-1 experiment, great efforts were put forth to compute daily birthrates, which were reprocessed with the 8-h release activity. The results of this study are presented in this paper.« less

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

PubMed

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

[Modern polymers in matrix tablets technology].

PubMed

Zimmer, Łukasz; Kasperek, Regina; Poleszak, Ewa

2014-01-01

Matrix tablets are the most popular method of oral drug administration, and polymeric materials have been used broadly in matrix formulations to modify and modulate drug release rate. The main goal of the system is to extend drug release profiles to maintain a constant in vivo plasma drug concentration and a consistent pharmacological effect. Polymeric matrix tablets offer a great potential as oral controlled drug delivery systems. Cellulose derivatives, like hydroxypropyl methylcellulose (HPMC) are often used as matrix formers. However, also other types of polymers can be used for this purpose including: Kollidon SR, acrylic acid polymers such as Eudragits and Carbopols. Nevertheless, polymers of natural origin like: carragens, chitosan and alginates widely used in the food and cosmetics industry are now coming to the fore of pharmaceutical research and are used in matrix tablets technology. Modern polymers allow to obtain matrix tablets by 3D printing, which enables to develop new formulation types. In this paper, the polymers used in matrix tablets technology and examples of their applications were described.

Techniques for the measurements of the line of sight velocity of high altitude Barium clouds

NASA Technical Reports Server (NTRS)

Mende, S. B.

1981-01-01

It is demonstrated that for maximizing the scientific output of future ion cloud release experiments a new type of instrument is required which will measure the line of sight velocity of the ion cloud by the Doppler Technique. A simple instrument was constructed using a 5 cm diameter solid Fabry-Perot etalon coupled to a low light level integrating television camera. It was demonstrated that the system has both the sensitivity and spectral resolution for the detection of ion clouds and the measurement of their line of sight Doppler velocity. The tests consisted of (1) a field experiment using a rocket barium cloud release to check the sensitivity, (2) laboratory experiments to show the spectral resolving capabilities of the system. The instrument was found to be operational if the source was brighter than about 1 kilorayleigh and it had a wavelength resolution much better than .2A which corresponds to about 12 km/sec or an acceleration potential of 100 volts.

Data Acquisition Backbone Core DABC release v1.0

NASA Astrophysics Data System (ADS)

Adamczewski-Musch, J.; Essel, H. G.; Kurz, N.; Linev, S.

2010-04-01

The Data Acquisition Backbone Core (DABC) is a general purpose software framework designed for the implementation of a wide-range of data acquisition systems - from various small detector test beds to high performance systems. DABC consists of a compact data-flow kernel and a number of plug-ins for various functional components like data inputs, device drivers, user functional modules and applications. DABC provides configurable components for implementing event building over fast networks like InfiniBand or Gigabit Ethernet. A generic Java GUI provides the dynamic control and visualization of control parameters and commands, provided by DIM servers. A first set of application plug-ins has been implemented to use DABC as event builder for the front-end components of the GSI standard DAQ system MBS (Multi Branch System). Another application covers the connection to DAQ readout chains from detector front-end boards (N-XYTER) linked to read-out controller boards (ROC) over UDP into DABC for event building, archiving and data serving. This was applied for data taking in the September 2008 test beamtime for the CBM experiment at GSI. DABC version 1.0 is released and available from the website.

In-vitro and in-vivo characterization of a buprenorphine delivery system.

PubMed

Kleppner, Sofie R; Patel, Raj; McDonough, Joseph; Costantini, Lauren C

2006-03-01

Buprenorphine is a mu-opioid receptor partial agonist with enhanced safety and comparable efficacy to methadone for treatment of opioid dependence. The sublingual formulation of buprenorphine, approved for treatment of opioid dependence, produces variable buprenorphine blood levels and requires frequent dosing that limits patient compliance. To achieve stable buprenorphine levels that may improve patient outcome, an implantable sustained buprenorphine delivery system was developed. Each implant consists of ethylene vinyl acetate copolymer and 90 mg buprenorphine HCl, and measures 26 mm in length and 2.4 mm in diameter. Steady-state release in-vitro was 0.5 mg/implant/day. In-vivo pharmacokinetics and safety were examined for up to 52 weeks in beagle dogs receiving 8, 16 or 24 subcutaneous implants. Plasma buprenorphine concentrations correlated with the number of implants administered. Peak buprenorphine concentrations were generally reached within 24 h after implantation. Steady-state plasma levels were attained between 3 and 8 weeks, and were maintained for study duration, with a calculated mean release rate of 0.14+/-0.04 mg/implant/day. There were no test-article-related adverse effects. This delivery system can provide long-term stable systemic buprenorphine levels, and may increase patient compliance, thereby improving outcome for opioid-dependent patients.

Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers.

PubMed

Grabovac, Vjera; Föger, Florian; Bernkop-Schnürch, Andreas

2008-02-04

The aim of this study was to develop and evaluate a novel three-layered oral delivery system for insulin in vivo. The patch system consisted of a mucoadhesive layer, a water insoluble backing layer made of ethylcellulose and an enteric coating made of Eudragit. Drug release studies were performed in media mimicking stomach and intestinal fluids. For in vivo studies patch systems were administered orally to conscious non-diabetic rats. Orally administered insulin in aqueous solution was used as control. After the oral administration of the patch systems a decrease of glucose and increase of insulin blood levels were measured. The mucoadhesive layer, exhibiting a diameter of 2.5mm and a weight of 5mg, comprised polycarbophil-cysteine conjugate (49%), bovine insulin (26%), gluthatione (5%) and mannitol (20%). 74.8+/-4.8% of insulin was released from the delivery system over 6h. Six hours after administration of the patch system mean maximum decrease of blood glucose level of 31.6% of the initial value could be observed. Maximum insulin concentration in blood was 11.3+/-6.2ng/ml and was reached 6h after administration. The relative bioavailability of orally administered patch system versus subcutaneous injection was 2.2%. The results indicate that the patch system provides enhancement of intestinal absorption and thereby offers a promising strategy for peroral peptide delivery.

Sustained-release microsphere formulation containing an agrochemical by polyurethane polymerization during an agitation granulation process.

PubMed

Terada, Takatoshi; Tagami, Manabu; Ohtsubo, Toshiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2016-07-25

In this report, a new solventless microencapsulation method by synthesizing polyurethane (PU) from polyol and isocyanate during an agglomeration process in a high-speed mixing apparatus was developed. Clothianidin (CTD), which is a neonicotinoid insecticide and highly effective against a wide variety of insect pests, was used as the model compound. The microencapsulated samples covered with PU (CTD microspheres) had a median diameter of <75μm and sustained-release properties. The CTD microspheres were analyzed by synchrotron X-ray computed tomography measurements. Multiple cores of CTD and other solid excipient were dispersed in PU. Although voids appeared in the CTD microspheres after CTD release, the spherical shape of the microspheres remained stable and no change in its framework was observed. The experimental release data were highly consistent with the Baker-Lonsdale model derived from drug release of spherical monolithic dispersions and consistent with the computed tomography measurements. Copyright © 2016 Elsevier B.V. All rights reserved.

Heterogeneity of transverse-axial tubule system in mouse atria: Remodeling in atrial-specific Na+-Ca2+ exchanger knockout mice.

PubMed

Yue, Xin; Zhang, Rui; Kim, Brian; Ma, Aiqun; Philipson, Kenneth D; Goldhaber, Joshua I

2017-07-01

Transverse-axial tubules (TATs) are commonly assumed to be sparse or absent in atrial myocytes from small animals. Atrial myocytes from rats, cats and rabbits lack TATs, which results in a characteristic "V"-shaped Ca release pattern in confocal line-scan recordings due to the delayed rise of Ca in the center of the cell. To examine TAT expression in isolated mouse atrial myocytes, we loaded them with the membrane dye Di-4-ANEPPS to label TATs. We found that >80% of atrial myocytes had identifiable TATs. Atria from male mice had a higher TAT density than female mice, and TAT density correlated with cell width. Using the fluorescent Ca indicator Fluo-4-AM and confocal imaging, we found that wild type (WT) mouse atrial myocytes generate near-synchronous Ca transients, in contrast to the "V"-shaped pattern typically reported in other small animals such as rat. In atrial-specific Na-Ca exchanger (NCX) knockout (KO) mice, which develop sinus node dysfunction and atrial hypertrophy with dilation, we found a substantial loss of atrial TATs in isolated atrial myocytes. There was a greater loss of transverse tubules compared to axial tubules, resulting in a dominance of axial tubules. Consistent with the overall loss of TATs, NCX KO atrial myocytes displayed a "V"-shaped Ca transient with slower and reduced central (CT) Ca release and uptake in comparison to subsarcolemmal (SS) Ca release. We compared chemically detubulated (DT) WT cells to KO, and found similar slowing of CT Ca release and uptake. However, SS Ca transients in the WT DT cells had faster uptake kinetics than KO cells, consistent with the presence of NCX and normal sarcolemmal Ca efflux in the WT DT cells. We conclude that the remodeling of NCX KO atrial myocytes is accompanied by a loss of TATs leading to abnormal Ca release and uptake that could impact atrial contractility and rhythm. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacokinetic variability of long-acting stimulants in the treatment of children and adults with attention-deficit hyperactivity disorder.

PubMed

Ermer, James C; Adeyi, Ben A; Pucci, Michael L

2010-12-01

Methylphenidate- and amfetamine-based stimulants are first-line pharmacotherapies for attention-deficit hyperactivity disorder, a common neurobehavioural disorder in children and adults. A number of long-acting stimulant formulations have been developed with the aim of providing once-daily dosing, employing various means to extend duration of action, including a transdermal delivery system, an osmotic-release oral system, capsules with a mixture of immediate- and delayed-release beads, and prodrug technology. Coefficients of variance of pharmacokinetic measures can estimate the levels of pharmacokinetic variability based on the measurable variance between different individuals receiving the same dose of stimulant (interindividual variability) and within the same individual over multiple administrations (intraindividual variability). Differences in formulation clearly impact pharmacokinetic profiles. Many medications exhibit wide interindividual variability in clinical response. Stimulants with low levels of inter- and intraindividual variability may be better suited to provide consistent levels of medication to patients. The pharmacokinetic profile of stimulants using pH-dependent bead technology can vary depending on food consumption or concomitant administration of medications that alter gastric pH. While delivery of methylphenidate with the transdermal delivery system would be unaffected by gastrointestinal factors, intersubject variability is nonetheless substantial. Unlike the beaded formulations and, to some extent (when considering total exposure) the osmotic-release formulation, systemic exposure to amfetamine with the prodrug stimulant lisdexamfetamine dimesylate appears largely unaffected by such factors, likely owing to its dependence on systemic enzymatic cleavage of the precursor molecule, which occurs primarily in the blood involving red blood cells. The high capacity but as yet unidentified enzymatic system for conversion of lisdexamfetamine dimesylate may contribute to its consistent pharmacokinetic profile. The reasons underlying observed differential responses to stimulants are likely to be multifactorial, including pharmacodynamic factors. While the use of stimulants with low inter- and intrapatient pharmacokinetic variability does not obviate the need to titrate stimulant doses, stimulants with low intraindividual variation in pharmacokinetic parameters may reduce the likelihood of patients falling into subtherapeutic drug concentrations or reaching drug concentrations at which the risk of adverse events increases. As such, clinicians are urged both to adjust stimulant doses based on therapeutic response and the risk for adverse events and to monitor patients for potential causes of pharmacokinetic variability.

A novel coating concept for ileo-colonic drug targeting: proof of concept in humans using scintigraphy.

PubMed

Varum, F J O; Hatton, G B; Freire, A C; Basit, A W

2013-08-01

The in vivo proof of concept of a novel double-coating system, based on enteric polymers, which accelerated drug release in the ileo-colonic region, was investigated in humans. Prednisolone tablets were coated with a double-coating formulation by applying an inner layer composed of EUDRAGIT S neutralised to pH 8.0 and a buffer salt (10% KH₂PO₄), which was overcoated with layer of standard EUDRAGIT S organic solution. For comparison, a single coating system was produced by applying the same amount of EUDRAGIT S organic solution on the tablet cores. Dissolution tests on the tablets were carried out using USP II apparatus in 0.1N HCl for 2 h and subsequently in pH 7.4 Krebs bicarbonate buffer. For comparison, tablets were also tested under the USP method established for modified release mesalamine formulations. Ten fasted volunteers received the double-coated and single-coated tablets in a two-way crossover study. The formulations were radiolabelled and followed by gamma scintigraphy; the disintegration times and positions were recorded. There was no drug release from the single-coated or double-coated tablets in 0.1N HCl for 2h. The single-coated tablets showed slow release in subsequent Krebs bicarbonate buffer with a lag time of 120 min, while in contrast drug release from the double-coated tablets was initiated at 60 min. In contrast, using the USP dissolution method, normally employed for modified release mesalamine products, no discrimination was attained. The in vivo disintegration of the single-coated EUDRAGIT S tablets in the large intestine was erratic. Furthermore, in 2 volunteers, the single-coated tablet was voided intact. Double-coated tablets disintegrated in a more consistent way, mainly in the ileo-caecal junction or terminal ileum. The accelerated in vivo disintegration of the double-coating EUDRAGIT S system can overcome the limitations of conventional enteric coatings targeting the colon and avoid the pass-through of intact tablets. Moreover, Krebs bicarbonate buffer has the ability to discriminate between formulations designed to target the ileo-colonic region. Copyright © 2013 Elsevier B.V. All rights reserved.

Influence of ciprofloxacin-based additives on the hydrolysis of nanofiber polyurethane membranes.

PubMed

Wright, Meghan E E; Wong, Andrew T; Levitt, Daniel; Parrag, Ian C; Yang, Meilin; Santerre, J Paul

2018-05-01

A degradable polycarbonate urethane (PCNU) and an antimicrobial oligomer (AO) were used to generate anti-infective nanofiber scaffolds through blend electrospinning. The AO consists of two molecules of ciprofloxacin (CF) bound through hydrolysable linkages to triethylene glycol. The membranes were conceived for use as tissue engineering scaffolds for the regeneration of soft tissues for the periodontium, where there would be a need for a local dose of antibiotic to the periodontal space as the scaffold degrades in order to prevent biomaterial-associated infection. Scaffolds were made using AO at 7 and 15% w/w equivalent CF, and compared to scaffolds with 15% w/w CF (with HCl counterion). AO was hydrolyzed and released CF continuously over 28 days, while the 15% w/w CF HCl scaffolds showed a burst release within hours, with no subsequent release in the subsequent 28 day period. Released CF from both the AO and CF HCl scaffolds had a similar minimum inhibitory concentration to that of off-the-shelf CF. Interestingly, the introduction of drug in either form (AO or CF HCl) was found to increase the hydrolytic stability of the electrospun degradable PCNU scaffold matrix itself. The alteration of hydrolysis kinetics was attributed to changes in the hydrogen bonding character and microstructure within the scaffolds, introduced by the presence of CF. This study has revealed that in generating in situ drug release systems, the secondary effects of the added drug on the degradation properties of the polymeric carriers must be considered, particularly for systems that act dually as tissue engineering scaffolds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1211-1222, 2018. © 2018 Wiley Periodicals, Inc.

Rail Shear and Short Beam Shear Properties of Various 3-Dimensional (3-D) Woven Composites

DTIC Science & Technology

2016-01-01

the preforms. It is a low- viscosity 2-phased toughened epoxy resin system consisting of part A (resin mixture of diglycidylether epoxy toughener...Delamination resistant laminates by Z-fiber pinning. Composites: Part A. 2005;36:55–64. 6. Clay S, Pommer A. Z-pin stubble technology advanced research...characterization of montmorillonite clay -filled SC-15 epoxy. Materials Letters. 2006;60:869–873. Approved for public release; distribution is

The monocarboxylate carrier from rat liver mitochondria. Purification and kinetic characterization in a reconstituted system.

PubMed

Capuano, F; Di Paola, M; Azzi, A; Papa, S

1990-02-12

The monocarboxylate (pyruvate) carrier was extracted from rat liver mitochondria with Triton X-100 in the presence of asolectin and partially purified by chromatography on HTP. The HTP eluate reconstituted in liposomes was shown to catalyze active pyruvatein/acetoacetateout and acetoacetatein/pyruvateout counter-exchange. Kinetic characterization of the reconstituted pyruvate carrier was achieved by an original spectrophotometric method consisting of determination of substrate release from proteoliposomes with a coupled enzymatic assay.

GEOS axial booms

NASA Technical Reports Server (NTRS)

Schmidt, G. K.

1979-01-01

A booms and mechanisms subsystem was designed, developed, and qualified for the geostationary scientific satellite GEOS. Part of this subsystem consist of four axial booms consisting of one pair of 1 m booms and one pair of 2.5 m booms. Each of these booms is carrying one bird cage electric field sensor. Alignment accuracy requirements led to a telescopic type solution. Deployment is performed by pressurized nitrogen. At deployment in orbit two of these booms showed some anomalies and one of these two deployed only about 80%. Following this malfunction a detailed failure investigation was performed resulting in a design modification of some critical components as release mechanism, guide sleeves of the telescopic elements, and pressure system.

Cyclodextrin based nanosponges for pharmaceutical use: a review.

PubMed

Tejashri, Gursalkar; Amrita, Bajaj; Darshana, Jain

2013-09-01

Nanosponges are a novel class of hyper-crosslinked polymer based colloidal structures consisting of solid nanoparticles with colloidal sizes and nanosized cavities. These nano-sized colloidal carriers have been recently developed and proposed for drug delivery, since their use can solubilize poorly water-soluble drugs and provide prolonged release as well as improve a drug's bioavailability by modifying the pharmacokinetic parameters of actives. Development of nanosponges as drug delivery systems, with special reference to cyclodextrin based nanosponges, is presented in this article. In the current review, attempts have been made to illustrate the features of cyclodextrin based nanosponges and their applications in pharmaceutical formulations. Special emphasis has been placed on discussing the methods of preparation, characterization techniques and applications of these novel drug delivery carriers for therapeutic purposes. Nanosponges can be referred to as solid porous particles having a capacity to load drugs and other actives into their nanocavity; they can be formulated as oral, parenteral, topical or inhalation dosage forms. Nanosponges offer high drug loading compared to other nanocarriers and are thus suitable for solving issues related to stability, solubility and delayed release of actives. Controlled release of the loaded actives and solubility enhancement of poorly water-soluble drugs are major advantages of nanosponge drug delivery systems.

Spokane Tribal Hatchery, 2003 Annual Report.

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

Peone, Tim L.

2004-05-01

Due to the construction and operation of Grand Coulee Dam (1939), anadromous salmon have been eradicated and resident fish populations permanently altered in the upper Columbia River region. Federal and private hydropower dam operations throughout the Columbia River system severely limits indigenous fish populations in the upper Columbia. Artificial production has been determined appropriate for supporting a harvestable fishery for kokanee salmon (Oncorhynchus nerka) and rainbow trout (Oncorhynchus mykiss) in Lake Roosevelt and Banks Lake (Grand Coulee Dam impoundments). A collaborative multi-agency artificial production program for the Lake Roosevelt and Banks Lake fisheries exists consisting of the Spokane Tribal Hatchery,more » Sherman Creek Hatchery, Ford Trout Hatchery and the Lake Roosevelt Kokanee and Rainbow Trout Net Pen Rearing Projects. These projects operate complementary of one another to target an annual release of 1 million yearling kokanee and 500,000 yearling rainbow trout for Lake Roosevelt and 1.4 million kokanee fry/fingerlings for Banks Lake. Combined fish stocking by the hatcheries and net pen rearing projects in 2003 included: 899,168 kokanee yearlings released into Lake Roosevelt; 1,087,331 kokanee fry/fingerlings released into Banks Lake, 44,000 rainbow trout fingerlings and; 580,880 rainbow trout yearlings released into Lake Roosevelt. Stock composition of 2003 releases consisted of Lake Whatcom kokanee, 50:50 diploid-triploid Spokane Trout Hatchery (McCloud River) rainbow trout and Phalon Lake red-band rainbow trout. All kokanee were marked with either thermal, oxytetracyline or fin clips prior to release. Preliminary 2003 Lake Roosevelt fisheries investigations indicate hatchery/net pen stocking significantly contributed to harvestable rainbow trout and kokanee salmon fisheries. An increase in kokanee harvest was primarily owing to new release strategies. Walleye predation, early maturity and entrainment through Grand Coulee Dam continues to have a negative impact on adult kokanee returns and limits the success of hatchery/net pen stocking on the number of harvestable fish. Preliminary results of gonad necropsies indicate a reduced incidence of precocious kokanee produced at the Spokane Tribal Hatchery in 2003. This was a probable attribute of change in hatchery rearing practices employed on 2002 brood year kokanee produced in 2003, primarily thermal manipulation and feed protein source. Kokanee and rainbow trout fingerlings transferred to Lake Roosevelt and Banks Lake net pen rearing operations in the fall of 2003 for subsequent release as yearlings in 2004 consisted of 645,234 rainbow trout and 627,037 kokanee salmon. A total of 590,000 Lake Whatcom kokanee fingerlings were carried over at the Spokane Tribal Hatchery for stocking as yearlings in 2004. Recommendations for future hatchery/net pen operations include use of stocks compatible or native to the upper Columbia River, continue hatchery-rearing practices to reduce precocity rates of kokanee and continue new kokanee stocking strategies associated with increased kokanee harvest rates.« less

Chemical synapses without synaptic vesicles: Purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex.

PubMed

Romanov, Roman A; Lasher, Robert S; High, Brigit; Savidge, Logan E; Lawson, Adam; Rogachevskaja, Olga A; Zhao, Haitian; Rogachevsky, Vadim V; Bystrova, Marina F; Churbanov, Gleb D; Adameyko, Igor; Harkany, Tibor; Yang, Ruibiao; Kidd, Grahame J; Marambaud, Philippe; Kinnamon, John C; Kolesnikov, Stanislav S; Finger, Thomas E

2018-05-08

Conventional chemical synapses in the nervous system involve a presynaptic accumulation of neurotransmitter-containing vesicles, which fuse with the plasma membrane to release neurotransmitters that activate postsynaptic receptors. In taste buds, type II receptor cells do not have conventional synaptic features but nonetheless show regulated release of their afferent neurotransmitter, ATP, through a large-pore, voltage-gated channel, CALHM1. Immunohistochemistry revealed that CALHM1 was localized to points of contact between the receptor cells and sensory nerve fibers. Ultrastructural and super-resolution light microscopy showed that the CALHM1 channels were consistently associated with distinctive, large (1- to 2-μm) mitochondria spaced 20 to 40 nm from the presynaptic membrane. Pharmacological disruption of the mitochondrial respiratory chain limited the ability of taste cells to release ATP, suggesting that the immediate source of released ATP was the mitochondrion rather than a cytoplasmic pool of ATP. These large mitochondria may serve as both a reservoir of releasable ATP and the site of synthesis. The juxtaposition of the large mitochondria to areas of membrane displaying CALHM1 also defines a restricted compartment that limits the influx of Ca 2+ upon opening of the nonselective CALHM1 channels. These findings reveal a distinctive organelle signature and functional organization for regulated, focal release of purinergic signals in the absence of synaptic vesicles. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Changes in the Genetic Structure of Aedes aegypti (Diptera: Culicidae) Populations in Queensland, Australia, Across Two Seasons: Implications for Potential Mosquito Releases

PubMed Central

ENDERSBY, N. M.; HOFFMANN, A. A.; WHITE, V. L.; RITCHIE, S. A.; JOHNSON, P. H.; WEEKS, A. R.

2012-01-01

Diseases transmitted by mosquitoes could be controlled if vector populations were replaced with strains that have reduced vector competency. Such a strategy is being developed for control of dengue virus which is transmitted by Aedes aegypti (L.) (Diptera: Culicidae). Mosquitoes artificially infected with the bacterium, Wolbachia pipientis Hertig, are being assessed as candidates for release at the adult stage with the aim of replacement of the wild population. Wolbachia can reduce the capacity of Ae. aegypti to transmit dengue virus and has potential to be driven through the natural population via a system of cytoplasmic incompatibility. Deployment of benign mosquito strains will be influenced by population size and structure of wild-type Ae. aegypti in proposed release areas, as well as rates of gene flow among populations in the wet and dry tropical seasons. Mosquitoes from northern Queensland were screened with genetic markers to find an optimal locality for release of a benign strain of Ae. aegypti. The inland towns of Chillagoe and Charters Towers and the coastal town of Ingham had mosquito populations that were partly genetically isolated from mosquitoes in other areas across both seasons. These locations may be suitable release sites if it is important for the released strain to be restricted during initial phases of implementation. Smaller genetic differences were also evident among other regions and were consistent over two seasons (wet and dry). PMID:21936318

Synchronized and sustained release of multiple components in silymarin from erodible glyceryl monostearate matrix system.

PubMed

Lu, Cheng; Lu, Yi; Chen, Jian; Zhang, Wentong; Wu, Wei

2007-05-01

Development of sustained delivery systems for herbal medicines was very difficult because of their complexity in composition. The concept of synchronized release from sustained release systems, which is characterized by release of multiple components in their original ratio that defines a herbal medicine, served as the basis for keeping the original pharmacological activity. In this study, erodible matrix systems based on glyceryl monostearate and polyethylene glycol 6000 or poloxamer 188 were prepared to perform strict control on synchronized release of the five active components of silymarin, i.e. taxifolin, silychrystin, silydianin, isosilybin and silybin. The matrix system was prepared by a melt fusion method. Synchronized release was achieved with high similarity factor f(2) values between each two of the five components. Erosion profiles of the matrix were in good correlation with release profiles of the five components, showing erosion-controlled release mechanisms. Through tuning some of the formulation variables, the system can be adjusted for synchronized and sustained release of silymarin for oral administration. In vitro hemolysis study indicated that the synchronized release samples showed a much better stabilizing effect on erythrocyte membrane.

RMP Guidance for Offsite Consequence Analysis

EPA Pesticide Factsheets

Offsite consequence analysis (OCA) consists of a worst-case release scenario and alternative release scenarios. OCA is required from facilities with chemicals above threshold quantities. RMP*Comp software can be used to perform calculations described here.

Mesoporous silica nanoparticles as smart and safe devices for regulating blood biomolecule levels

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

Zhao, Yan

2011-01-01

Stimuli-responsive end-capped MSN materials are promising drug carriers that securely deliver a large payload of drug molecules without degradation or premature release. A general review of the recent progress in this field is presented, including a summary of a series of hard and soft caps for drug encapsulation and a variety of internal and external stimuli for controlled release of different therapeutics, a discussion of the biocompatibility of MSN both in vitro and in vivo, and a description of the sophisticated stimuli-responsive systems with novel capping agents and controlled release mechanism. The unique internal and external surfaces of MSN weremore » utilized for the development of a glucose-responsive double delivery system end-capped with insulin. This unique system consists of functionalized MSNs capable of releasing insulin when the concentration of sugar in blood exceeds healthy levels. The insulin-free nanoparticles are then up taken by pancreatic cells, and release inside of them another biomolecule that stimulates the production of more insulin. The in vivo application of this system for the treatment of diabetes requires further understanding on the biological behaviors of these nanoparticles in blood vessels. The research presented in this dissertation demonstrated the size and surface effects on the interaction of MSNs with red blood cell membranes, and discovered how the surface of the nanoparticles can be modified to improve their compatibility with red blood cells and avoid their dangerous side effects. In order to optimize the properties of MSN for applying them as efficient intracellular drug carriers it is necessary to understand the factors that can regulate their internalization into and exocytosis out of the cells. The correlation between the particle morphology and aggregation of MSNs to the effectiveness of cellular uptake is discussed and compared with different cell lines. The differences in the degree of exocytosis of MSNs between healthy and cancer cells is reported and found to be responsible for the asymmetric transfer of the particles between both cell types. The fundamental studies on the hemocompatibility, endo- and exocytosis of MSN along with its ability to sequentially release multiple therapeutics in response to different stimuli, allow us to propose MSN as an intravascular vehicle with a great potential for various biomedical applications.« less

Asynchronous Processing of a Constellation of Geostationary and Polar-Orbiting Satellites for Fire Detection and Smoke Estimation

NASA Astrophysics Data System (ADS)

Hyer, E. J.; Peterson, D. A.; Curtis, C. A.; Schmidt, C. C.; Hoffman, J.; Prins, E. M.

2014-12-01

The Fire Locating and Monitoring of Burning Emissions (FLAMBE) system converts satellite observations of thermally anomalous pixels into spatially and temporally continuous estimates of smoke release from open biomass burning. This system currently processes data from a constellation of 5 geostationary and 2 polar-orbiting sensors. Additional sensors, including NPP VIIRS and the imager on the Korea COMS-1 geostationary satellite, will soon be added. This constellation experiences schedule changes and outages of various durations, making the set of available scenes for fire detection highly variable on an hourly and daily basis. Adding to the complexity, the latency of the satellite data is variable between and within sensors. FLAMBE shares with many fire detection systems the goal of detecting as many fires as possible as early as possible, but the FLAMBE system must also produce a consistent estimate of smoke production with minimal artifacts from the changing constellation. To achieve this, NRL has developed a system of asynchronous processing and cross-calibration that permits satellite data to be used as it arrives, while preserving the consistency of the smoke emission estimates. This talk describes the asynchronous data ingest methodology, including latency statistics for the constellation. We also provide an overview and show results from the system we have developed to normalize multi-sensor fire detection for consistency.

Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30% ethanolic dried extract derived from local Phyllanthus urinaria for skin antiaging.

PubMed

Mahdi, Elrashid Saleh; Noor, Azmin Mohd; Sakeena, Mohamed Hameem; Abdullah, Ghassan Z; Abdulkarim, Muthanna F; Sattar, Munavvar Abdul

2011-01-01

Recently there has been a remarkable surge of interest about natural products and their applications in the cosmetic industry. Topical delivery of antioxidants from natural sources is one of the approaches used to reverse signs of skin aging. The aim of this research was to develop a nanoemulsion cream for topical delivery of 30% ethanolic extract derived from local Phyllanthus urinaria (P. urinaria) for skin antiaging. Palm kernel oil esters (PKOEs)-based nanoemulsions were loaded with P. urinaria extract using a spontaneous method and characterized with respect to particle size, zeta potential, and rheological properties. The release profile of the extract was evaluated using in vitro Franz diffusion cells from an artificial membrane and the antioxidant activity of the extract released was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method. Formulation F12 consisted of wt/wt, 0.05% P. urinaria extract, 1% cetyl alcohol, 0.5% glyceryl monostearate, 12% PKOEs, and 27% Tween 80/Span 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and a 59.5% phosphate buffer system at pH 7.4. Formulation F36 was comprised of 0.05% P. urinaria extract, 1% cetyl alcohol, 1% glyceryl monostearate, 14% PKOEs, 28% Tween 80/Span 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and 56% phosphate buffer system at pH 7.4 with shear thinning and thixotropy. The droplet size of F12 and F36 was 30.74 nm and 35.71 nm, respectively, and their nanosizes were confirmed by transmission electron microscopy images. Thereafter, 51.30% and 51.02% of the loaded extract was released from F12 and F36 through an artificial cellulose membrane, scavenging 29.89% and 30.05% of DPPH radical activity, respectively. The P. urinaria extract was successfully incorporated into a PKOEs-based nanoemulsion delivery system. In vitro release of the extract from the formulations showed DPPH radical scavenging activity. These formulations can neutralize reactive oxygen species and counteract oxidative injury induced by ultraviolet radiation and thereby ameliorate skin aging.

Alpha 2 LASSO Data Bundles

DOE Data Explorer

Gustafson, William Jr; Vogelmann, Andrew; Endo, Satoshi; Toto, Tami; Xiao, Heng; Li, Zhijin; Cheng, Xiaoping; Kim, Jinwon; Krishna, Bhargavi

2015-08-31

The Alpha 2 release is the second release from the LASSO Pilot Phase that builds upon the Alpha 1 release. Alpha 2 contains additional diagnostics in the data bundles and focuses on cases from spring-summer 2016. A data bundle is a unified package consisting of LASSO LES input and output, observations, evaluation diagnostics, and model skill scores. LES input include model configuration information and forcing data. LES output includes profile statistics and full domain fields of cloud and environmental variables. Model evaluation data consists of LES output and ARM observations co-registered on the same grid and sampling frequency. Model performance is quantified by skill scores and diagnostics in terms of cloud and environmental variables.

Adding dynamic rules to self-organizing fuzzy systems

NASA Technical Reports Server (NTRS)

Buhusi, Catalin V.

1992-01-01

This paper develops a Dynamic Self-Organizing Fuzzy System (DSOFS) capable of adding, removing, and/or adapting the fuzzy rules and the fuzzy reference sets. The DSOFS background consists of a self-organizing neural structure with neuron relocation features which will develop a map of the input-output behavior. The relocation algorithm extends the topological ordering concept. Fuzzy rules (neurons) are dynamically added or released while the neural structure learns the pattern. The DSOFS advantages are the automatic synthesis and the possibility of parallel implementation. A high adaptation speed and a reduced number of neurons is needed in order to keep errors under some limits. The computer simulation results are presented in a nonlinear systems modelling application.

Scalable Integrated Multi-Mission Support System Simulator Release 3.0

NASA Technical Reports Server (NTRS)

Kim, John; Velamuri, Sarma; Casey, Taylor; Bemann, Travis

2012-01-01

The Scalable Integrated Multi-mission Support System (SIMSS) is a tool that performs a variety of test activities related to spacecraft simulations and ground segment checks. SIMSS is a distributed, component-based, plug-and-play client-server system useful for performing real-time monitoring and communications testing. SIMSS runs on one or more workstations and is designed to be user-configurable or to use predefined configurations for routine operations. SIMSS consists of more than 100 modules that can be configured to create, receive, process, and/or transmit data. The SIMSS/GMSEC innovation is intended to provide missions with a low-cost solution for implementing their ground systems, as well as significantly reducing a mission s integration time and risk.

The magnitude and relevance of the February 2014 radiation release from the Waste Isolation Pilot Plant repository in New Mexico, USA.

PubMed

Thakur, P; Lemons, B G; White, C R

2016-09-15

After almost fifteen years of successful waste disposal operations, the first unambiguous airborne radiation release from the Waste Isolation Pilot Plant (WIPP) was detected beyond the site boundary on February 14, 2014. It was the first accident of its kind in the 15-year operating history of the WIPP. The accident released moderate levels of radioactivity into the underground air. A small but measurable amount of radioactivity also escaped to the surface through the ventilation system and was detected above ground. The dominant radionuclides released were americium and plutonium, in a ratio consistent with the known content of a breached drum. The radiation release was caused by a runaway chemical reaction inside a transuranic (TRU) waste drum which experienced a seal and lid failure, spewing radioactive materials into the repository. According to source-term estimation, approximately 2 to 10Ci of radioactivity was released from the breached drum into the underground, and an undetermined fraction of that source term became airborne, setting off an alarm and triggering the closure of seals designed to force exhausting air through a system of filters including high-efficiency-particulate-air (HEPA) filters. Air monitoring across the WIPP site intensified following the first reports of radiation detection underground to determine the extent of impact to WIPP personnel, the public, and the environment, if any. This article attempts to compile and interpret analytical data collected by an independent monitoring program conducted by the Carlsbad Environmental Monitoring & Research Center (CEMRC) and by a compliance-monitoring program conducted by the WIPP's management and operating contractor, the Nuclear Waste Partnership (NWP), LLC., in response to the accident. Both the independent and the WIPP monitoring efforts concluded that the levels detected were very low and localized, and no radiation-related health effects among local workers or the public would be expected. Published by Elsevier B.V.

Dynamic in vivo imaging of dual-triggered microspheres for sustained release applications: synthesis, characterization and cytotoxicity study.

PubMed

Efthimiadou, Eleni K; Tapeinos, Christos; Chatzipavlidis, Alexandros; Boukos, Nikos; Fragogeorgi, Eirini; Palamaris, Lazaros; Loudos, George; Kordas, George

2014-01-30

This paper deals with the synthesis, characterization and property evaluation of drug-loaded magnetic microspheres with pH-responsive cross-linked polymer shell. The synthetic procedure consists of 3 steps, of which the first two comprise the synthesis of a poly methyl methacrylate (PMMA) template and the synthesis of a shell by using acrylic acid (AA) and methyl methacrylate (MMA) as monomers, and divinyl benzene (DVB) as cross-linker. The third step of the procedure refers to the formation of magnetic nanoparticles on the microsphere's surface. AA that attaches pH-sensitivity in the microspheres and magnetic nanoparticles in the inner and the outer surface of the microspheres, enhance the efficacy of this intelligent drug delivery system (DDS), which constitutes a promising approach toward cancer therapy. A number of experimental techniques were used to characterize the resulting microspheres. In order to investigate the in vitro controlled release behavior of the synthesized microspheres, we studied the Dox release percentage under different pH conditions and under external magnetic field. Hyperthermia caused by an alternating magnetic field (AFM) is used in order to study the doxorubicin (Dox) release behavior from microspheres with pH functionality. The in vivo fate of these hybrid-microspheres was tracked by labeling them with the γ-emitting radioisotope (99m)Tc after being intravenously injected in normal mice. According to our results, microsphere present a pH depending and a magnetic heating, release behavior. As expected, labeled microspheres were mainly found in the mononuclear phagocyte system (MPS). The highlights of the current research are: (i) to illustrate the advantages of controlled release by combining hyperthermia and pH-sensitivity and (ii) to provide noninvasive, in vivo information on the spatiotemporal biodistribution of these microsphere by dynamic γ-imaging. Copyright © 2013 Elsevier B.V. All rights reserved.

Perfluoroalkyl and polyfluoroalkyl substances removal in a full-scale tropical constructed wetland system treating landfill leachate.

PubMed

Yin, Tingru; Chen, Huiting; Reinhard, Martin; Yi, Xinzhu; He, Yiliang; Gin, Karina Yew-Hoong

2017-11-15

Landfill leachate is often an important source of emerging organic contaminants including perfluoroalkyl and polyfluoroalkyl substances (PFASs) requiring proper treatment to protect surface water and groundwater resources. This study investigated the occurrence of PFASs in the leachate of a capped landfill site in Singapore and the efficacy of PFASs removal during flow through a constructed wetland (CW) treatment system. The CW treatment system consists of equalization tank, aeration lagoons, sedimentation tank, reed beds and polishing ponds. Target compounds included 11 perfluoroalkyl acids (PFAAs) (7 perfluoroalkyl carboxylic acids (PFCAs) and 4 perfluoroalkane sulfonates (PFSAs)) and 7 PFAA precursors. Although total PFASs concentrations in the leachate varied widely (1269 to 7661 ng/L) over the one-year sampling period, the PFASs composition remained relatively stable with PFCAs consistently being predominant (64.0 ± 3.8%). Perfluorobutane sulfonate (PFBS) concentrations were highly correlated with total PFASs concentrations and could be an indicator for the release of PFASs from this landfill. The release of short-chain PFAAs strongly depended on precipitation whereas concentrations of the other PFASs appeared to be controlled by partitioning. Overall, the CW treatment system removed 61% of total PFASs and 50-96% of individual PFASs. PFAAs were removed most efficiently in the reed bed (42-49%), likely due to the combination of sorption to soils and sediments and plant uptake, whereas most of the PFAA precursors (i.e. 5:3 fluorotelomer carboxylate (5:3 acid), N-substituted perfluorooctane sulfonamides (N-MeFOSAA and N-EtFOSAA)) were removed in the aeration lagoon (>55%) by biodegradation. The sedimentation tank and polishing ponds were relatively inefficient, with only 7% PFASs removal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Compatibility Studies of Hydrogen Peroxide and a New Hypergolic Fuel Blend

NASA Technical Reports Server (NTRS)

Baldridge, Jennifer; Villegas, Yvonne

2002-01-01

Several preliminary materials compatibility studies have been conducted to determine the practicality of a new hypergolic fuel system. Hypergolic fuel ignites spontaneously as the oxidizer decomposes and releases energy in the presence of the fuel. The bipropellant system tested consists of high-test hydrogen peroxide (HTP) and a liquid fuel blend consisting of a hydrocarbon fuel, an ignition enhancer and a transition metal catalyst. In order for further testing of the new fuel blend to take place, some basic materials compatibility and HTP decomposition studies must be accomplished. The thermal decomposition rate of HTP was tested using gas evolution and isothermal microcalorimetry (IMC). Materials were analyzed for compatibility with hydrogen peroxide including a study of the affect welding has on stainless steel elemental composition and its relation to HTP decomposition. Compatibility studies of valve materials in the fuel blend were performed to determine the corrosion resistance of the materials.

Biodegradable injectable in situ implants and microparticles for sustained release of montelukast: in vitro release, pharmacokinetics, and stability.

PubMed

Ahmed, Tarek A; Ibrahim, Hany M; Samy, Ahmed M; Kaseem, Alaa; Nutan, Mohammad T H; Hussain, Muhammad Delwar

2014-06-01

The objective of this study was to investigate the sustained release of a hydrophilic drug, montelukast (MK), from two biodegradable polymeric drug delivery systems, in situ implant (ISI) and in situ microparticles (ISM). N-Methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), triacetin, and ethyl acetate were selected as solvents. The release of 10% (w/v) MK from both systems containing poly-lactic-co-glycolic acid (PLGA) as the biodegradable polymer was compared. Upon contact with the aqueous medium, the PLGA in ISI and ISM systems solidified resulting in implants and microparticles, respectively. The in vitro drug release from the ISI system showed marked difference from miscible solvents (NMP and DMSO) than the partially miscible ones (triacetin and ethyl acetate), and the drug release decreased with increased PLGA concentration. In the ISM system, the initial in vitro drug release decreased with decreased ratio of polymer phase to external oil phase. In vivo studies in rats showed that ISM had slower drug release than the drug release from ISI. Also, the ISM system when compared to ISI system had significantly reduced initial burst effect. In vitro as well as the in vivo studies for both ISI and ISM systems showed sustained release of MK. The ISM system is suitable for sustained release of MK over 4-week period with a lower initial burst compared to the ISI system. Stability studies of the ISI and ISM formulations showed that MK is stable in the formulations stored at 4°C for more than 2 years.

Release of picloram from leafy spurge (Euphorbia esula L. ) roots

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

Hickman, M.V.

1988-01-01

Picloram (4-amino-3,5,6-trichloro-2-pyridinecarboxylic acid) exudation from leafy spurge (Euphorbia esula L.) roots following foliar application was determined with field trials examining the effects of plant growth stage, picloram rate, and time interval after treatment and with laboratory studies examining the effects of picloram rate, picloram plus 2,4-D, and root temperature. Release of /sup 14/C from leafy spurge roots in the laboratory was not affected by picloram rates from <0.005 to 0.28 kg/ha or by combining picloram at 0.14 kg/ha plus 2,4-D up to 1.12 kg/ha. No consistent effect was detected for increasing root temperatures from 14 to 32 C. The temperaturemore » coefficient (Q/sub 10/) for picloram release was 1.3 +/- 0.8. Most /sup 14/C exudates from leafy spurge roots co-chromatographed with /sup 14/C-picloram suggesting that picloram is exuded as the parent acid or a rapidly hydrolyzed metabolite. Most picloram release occurred from the upper 5 cm of the root system. /sup 14/C distribution in leafy spurge suggests symplastic movement. Only about 28% of the applied picloram was absorbed, 75% remained in the leaves and stems of the plants. Over 60% of the /sup 14/C that entered the plant roots was released to the nutrient solution.« less

Thermosensitive gemcitabine-magnetoliposomes for combined hyperthermia and chemotherapy

NASA Astrophysics Data System (ADS)

Ferreira, Roberta V.; da Mata Martins, Thaís Maria; Goes, Alfredo Miranda; Fabris, José D.; Cavalcante, Luis Carlos D.; Eugenio Fernandez Outon, Luis; Domingues, Rosana Z.

2016-02-01

The combination of magnetic hyperthermia therapy with the controlled release of chemotherapeutic agents in tumors may be an efficient therapeutic with few side effects because the bioavailability, tolerance and amount of the drug can be optimized. Here, we prepared magnetoliposomes consisting of magnetite nanoparticle cores and the anticancer drug gemcitabine encapsulated by a phospholipid bilayer. The potential of these magnetoliposomes for controlled drug release and cancer treatment via hyperthermic behavior was investigated. The magnetic nanoparticle encapsulation efficiency was dependent on the initial amount of magnetite nanoparticles present at the encapsulation stage; the best formulation was 66%. We chose this formulation to characterize the physicochemical properties of the magnetoliposomes and to encapsulate gemcitabine. The mean particle size and distribution were determined by dynamic light scattering (DLS), and the zeta potential was measured. The magnetoliposome formulations all had acceptable characteristics for systemic administration, with a mean size of approximately 150 nm and a polydispersity index <0.2. The magnetoliposomes were stable in aqueous suspension for at least one week, as determined by DLS. Temperature increases due to the dissipation energy of magnetoliposome suspensions subjected to an applied alternating magnetic field (AMF) were measured at different magnetic field intensities, and the values were appropriated for cancer treatments. The drug release profile at 37 °C showed that 17% of the gemcitabine was released after 72 h. Drug release from magnetoliposomes exposed to an AMF for 5 min reached 70%.

50 CFR 600.425 - Release of statistics.

Code of Federal Regulations, 2012 CFR

2012-10-01

... will be processed consistent with the NOAA FOIA regulations (15 CFR part 903), NAO 205-14, Department of Commerce Administrative Orders 205-12 and 205-14 and 15 CFR part 4. (c) NOAA does not release or...

50 CFR 600.425 - Release of statistics.

Code of Federal Regulations, 2013 CFR

2013-10-01

... will be processed consistent with the NOAA FOIA regulations (15 CFR part 903), NAO 205-14, Department of Commerce Administrative Orders 205-12 and 205-14 and 15 CFR part 4. (c) NOAA does not release or...

50 CFR 600.425 - Release of statistics.

Code of Federal Regulations, 2014 CFR

2014-10-01

... will be processed consistent with the NOAA FOIA regulations (15 CFR part 903), NAO 205-14, Department of Commerce Administrative Orders 205-12 and 205-14 and 15 CFR part 4. (c) NOAA does not release or...

Characterizations of Plasticized Polymeric Film Coatings for Preparing Multiple-Unit Floating Drug Delivery Systems (muFDDSs) with Controlled-Release Characteristics

PubMed Central

Chen, Ying-Chen; Wang, Yu-Chun; Ho, Hsiu-O; Sheu, Ming-Thau

2014-01-01

Effervescent multiple-unit floating drug delivery systems (muFDDSs) consisting of drug (lorsartan)- and effervescent (sodium bicarbonate)-containing pellets were characterized in this study. The mechanical properties (stress and strain at rupture, Young’s modulus, and toughness) of these plasticized polymeric films of acrylic (Eudragit RS, RL, and NE) and cellulosic materials (ethyl cellulose (EC), and Surelease) were examined by a dynamic mechanical analyzer. Results demonstrated that polymeric films prepared from Surelease and EC were brittle with less elongation compared to acrylic films. Eudragit NE films were very flexible in both the dry and wet states. Because plasticizer leached from polymeric films during exposure to the aqueous medium, plasticization of wet Eudragit RS and RL films with 15% triethyl citrate (TEC) or diethyl phthalate (DEP) resulted in less elongation. DEP might be the plasticizer of choice among the plasticizers examined in this study for Eudragit RL to provide muFDDSs with a short time for all pellets to float (TPF) and a longer period of floating. Eudragit RL and RS at a 1∶1 ratio plasticized with 15% DEP were optimally selected as the coating membrane for the floating system. Although the release of losartan from the pellets was still too fast as a result of losartan being freely soluble in water, muFDDSs coated with Eudragit RL and RS at a 1∶1 ratio might have potential use for the sustained release of water-insoluble or the un-ionized form of drugs from gastroretentive drug delivery systems. PMID:24967594

Multifunctional Thin Film Biomatrice Biosensor in a Degradable Scaffold Containing Bone Morphogenetic Protein-2 (BMP-2) for Controlled Release in Skeletal Tissue Engineering

NASA Astrophysics Data System (ADS)

McDaniel, Harvey; Lomax, Linda

2001-03-01

Bone morphonogenetic proteins (BMP-2) have been under investigation for three decades. Deminerialized bone and extracts of deminerialized bone are o steoinductive with a temporal sequence of bone induction. Native and recombi nant BMP's have shown the ability, thru growth and differentiative factors t o induce de novo bone formation both invitro and invivo. Their principle fun ction is to induce transformation of undifferentiated mesenchymal cells into osteoblasts. Native and recombinant BMP's, when purified and used without carrier disp erse after implantation and exert no effect on bone induction. The delivery system provides the missing component to successsfully applying osteogenic p roteins for clinical need. Biological and physio-chemical properties are str ictly adhered tofor a successful delivery system. The BMP delivery system ca rrier for osteo inductive payload provided; 1)non tumorgenic genecity, 2) no n immunogenecity, 3) water insoluble, 4) biosorbability with predictable enz ymatic degradation, and 5) an optimized surface for compatibility, cell migr ation and attachment with a negative surface change that encouraged target c ell attachment. Being a controlled Release System, it binded the proteins wi th predictible BMP released kinetics. Porosity with interconnecting voids pr otected the BMP from noon specific proteolysis and promoted rapid vascular a nd mesenchymal invasion. Far wide ranging clinical applications of mechanica l and biofunctional requirements were met with the BMP delivery system. Cohe sion and malleability were reqiured forcontour augmentation, and reconstruct ion of the discontinuity defects, prevented dislocation and retained the sha pe and bone replaced the system. Biological systems have elastic activity associated with them. The activi ty was current associated with a time dependant biological/biochemical react ion (enzymic activity). Bioelectric phoenomena associated with charged molec ules in a biologic structure caused changes in distribution resulting from s pecific processes altering the local anatomy. Electron conductivity mechanisms in the body involved ions as charge carr iers. Bioelectric signal detection involved interacting ionic charge carrier s and transducing ionic current into electric current required by wires (fib eroptic electrolets impregnated on a thin filmed-collagen biomatrix and elec tronic instrumentation(invitro test setup)). The transducing function of the invitro testing was carried out by the electrodes consisting of electrical conduction (thin film biomatrix) in contact with the aqueous solution of the bone. Performance parameters of the system were given special consideration because of the interaction between electrons in the electrodes and ions in the body. The surgical protocol consisted of minimally invasive surgical pro tocol with an out patient procedure.

Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti

PubMed Central

Schmidt, Tom L.; Barton, Nicholas H.; Rašić, Gordana; Turley, Andrew P.; Montgomery, Brian L.; Iturbe-Ormaetxe, Inaki; Cook, Peter E.; Ryan, Peter A.; Ritchie, Scott A.; Hoffmann, Ary A.; O’Neill, Scott L.

2017-01-01

Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100–200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation. PMID:28557993

Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti.

PubMed

Schmidt, Tom L; Barton, Nicholas H; Rašić, Gordana; Turley, Andrew P; Montgomery, Brian L; Iturbe-Ormaetxe, Inaki; Cook, Peter E; Ryan, Peter A; Ritchie, Scott A; Hoffmann, Ary A; O'Neill, Scott L; Turelli, Michael

2017-05-01

Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100-200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation.

Development of novel small molecules for imaging and drug release

NASA Astrophysics Data System (ADS)

Cao, Yanting

Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the last part, a new photo-initiated fluorescent anticancer prodrug for DNA alkylating agent mechlorethamine releasing and monitoring has been developed. The theranostic prodrug consists a photolabile NPE group, an inactive form of mechlorethamine and a nonfluorescent coumarin in one small molecule. It is demonstrated that the prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, while the original parent drug mechlorethamine can be photocontrol-released and induces effective DNA cross-linking activity. Importantly, the drug release progress can be conveniently monitored by the 'off-on' fluorescence enhancement in cells. Moreover, the selective prodrug is not only cell permeable but also nuclear permeable. Therefore, the prodrug serves as a promising drug delivery system for spatiotemporal control release and monitoring of an anticancer drug to obtain the optimal treatment efficacy.

The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-) : cystine supplier and beyond.

PubMed

Conrad, Marcus; Sato, Hideyo

2012-01-01

The oxidative stress-inducible cystine/glutamate exchange system, system x (c) (-) , transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x (c) (-) has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x (c) (-) may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x (c) (-) research up to now.

Radioxenon spiked air

DOE PAGES

Watrous, Matthew G.; Delmore, James E.; Hague, Robert K.; ...

2015-08-27

Four of the radioactive xenon isotopes ( 131mXe, 133mXe, 133Xe and 135Xe) with half-lives ranging from 9 h to 12 days are produced from nuclear fission and can be detected from days to weeks following their production and release. Being inert gases, they are readily transported through the atmosphere. Sources for release of radioactive xenon isotopes include operating nuclear reactors via leaks in fuel rods, medical isotope production facilities, and nuclear weapons' detonations. They are not normally released from fuel reprocessing due to the short half-lives. The Comprehensive Nuclear-Test-Ban Treaty has led to creation of the International Monitoring System. Themore » International Monitoring System, when fully implemented, will consist of one component with 40 stations monitoring radioactive xenon around the globe. Monitoring these radioactive xenon isotopes is important to the Comprehensive Nuclear-Test-Ban Treaty in determining whether a seismically detected event is or is not a nuclear detonation. A variety of radioactive xenon quality control check standards, quantitatively spiked into various gas matrices, could be used to demonstrate that these stations are operating on the same basis in order to bolster defensibility of data across the International Monitoring System. This study focuses on Idaho National Laboratory's capability to produce three of the xenon isotopes in pure form and the use of the four xenon isotopes in various combinations to produce radioactive xenon spiked air samples that could be subsequently distributed to participating facilities.« less

NIR and MR imaging supported hydrogel based delivery system for anti-TNF alpha probiotic therapy of IBD

NASA Astrophysics Data System (ADS)

Janjic, Jelena M.; Berlec, Ales; Bagia, Christina; Liu, Lu S.; Jeric, Irenej; Gach, Michael; Janjic, Bratislav M.; Strukelj, Borut

2016-03-01

Current treatment of inflammatory bowel disease (IBD) is largely symptomatic and consists of anti-inflammatory agents, immune-suppressives or antibiotics, whereby local luminal action is preferred to minimize systemic side-effects. Recently, anti-TNFα therapy has shown considerable success and is now being routinely used. Here we present a novel approach of using perfluorocarbon (PFC) nanoemulsion containing hydrogels (nanoemulgels) as imaging supported delivery systems for anti-TNF alpha probiotic delivery in IBD. To further facilitate image-guided therapy a food-grade lactic acid bacterium Lactococcus lactis capable of TNFα-binding was engineered to incorporate infrared fluorescent protein (IRFP). This modified bacteria was then incorporated into novel PFC nanoemulgels. The nanoemulgels presented here are designed to deliver locally anti-TNFα probiotic in the lower colon and rectum and provide dual imaging signature of gel delivery (MRI) across the rectum and lower colon and bacteria release (NIR). NIR imaging data in vitro demonstrates high IRFP expressing and TNFα-binding bacteria loading in the hydrogel and complete release in 3 hours. Stability tests indicate that gels remain stable for at least 14 days showing no significant change in droplet size, zeta potential and pH. Flow cytometry analyses demonstrate the NIRF expressing bacteria L. lactis binds TNFα in vitro upon release from the gels. Magnetic resonance and near-infrared imaging in vitro demonstrates homogeneity of hydrogels and the imaging capacity of the overall formulation.

Radioxenon spiked air

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

Watrous, Matthew G.; Delmore, James E.; Hague, Robert K.

Four of the radioactive xenon isotopes ( 131mXe, 133mXe, 133Xe and 135Xe) with half-lives ranging from 9 h to 12 days are produced from nuclear fission and can be detected from days to weeks following their production and release. Being inert gases, they are readily transported through the atmosphere. Sources for release of radioactive xenon isotopes include operating nuclear reactors via leaks in fuel rods, medical isotope production facilities, and nuclear weapons' detonations. They are not normally released from fuel reprocessing due to the short half-lives. The Comprehensive Nuclear-Test-Ban Treaty has led to creation of the International Monitoring System. Themore » International Monitoring System, when fully implemented, will consist of one component with 40 stations monitoring radioactive xenon around the globe. Monitoring these radioactive xenon isotopes is important to the Comprehensive Nuclear-Test-Ban Treaty in determining whether a seismically detected event is or is not a nuclear detonation. A variety of radioactive xenon quality control check standards, quantitatively spiked into various gas matrices, could be used to demonstrate that these stations are operating on the same basis in order to bolster defensibility of data across the International Monitoring System. This study focuses on Idaho National Laboratory's capability to produce three of the xenon isotopes in pure form and the use of the four xenon isotopes in various combinations to produce radioactive xenon spiked air samples that could be subsequently distributed to participating facilities.« less

Depot formulation of vasoactive intestinal peptide by protamine-based biodegradable nanoparticles.

PubMed

Wernig, Karin; Griesbacher, Martin; Andreae, Fritz; Hajos, Franz; Wagner, Julian; Mosgoeller, Wilhelm; Zimmer, Andreas

2008-09-10

Drug delivery of protein and peptide-based drugs, which represent a growing and important therapeutic class, is hampered by these drugs' very short half-lives. High susceptibility towards enzymatic degradation necessitates frequent drug administration followed by poor adherence to therapy. Among these drugs is vasoactive intestinal peptide (VIP), a potent systemic and pulmonary vasodilator, which is a promising drug for the treatment of idiopathic pulmonary arterial hypertension (IPAH). Encapsulation of VIP into the nanoparticle matrix of biodegradable protamine-oligonucleotide nanoparticles (proticles) protects the peptide against rapid enzymatic degradation. Additionally, the nanoparticle matrix will be able to sustain drug release. Proticles consist of 18mer non-sense oligonucleotides and protamine, a polycationic arginine-rich peptide. VIP encapsulation occurs during self-assembly of the components. Within the present study, we evaluate nanoparticle size (hydrodynamic diameter) and zeta potential of VIP-loaded proticles as well as encapsulation efficiency and VIP release. Further, the pharmacological VIP response of "encapsulated VIP" is investigated using an ex vivo lung arterial model system. We found satisfying encapsulation efficiency (up to 80%), VIP release (77-87%), and an appropriate nanoparticle size (177-251 nm). Investigations on rat pulmonary arteries showed a modified VIP response of proticle-associated VIP. We noted differences in the profile of artery relaxation where VIP proticles lead to a 20-30% lower relaxation maximum than aqueous VIP solutions followed by prolonged vasodilatation. Our data indicate that proticles could be a feasible drug delivery system for a pulmonary VIP depot formulation.

Model of care transformation: a health care system CNE's journey.

PubMed

Swick, Maureen; Doulaveris, Phyllis; Christensen, Patricia

2012-01-01

In 2001, the Institute of Medicine released the report "Crossing the Quality Chasm: A New Health System for the 21st Century." The report criticizes our health care system and argues that we are failing to provide Americans with the high-quality and affordable health care they deserve and need. While incremental progress has been made, we continue to strive for improved care quality, and our rising costs are potentially catastrophic. Consistent with the Institute of Medicine report, and its reputation for innovation, Inova Health System identified care model transformation as a system priority. Given that the organization is replacing its electronic health record and introducing advanced analytic capabilities, the opportunity to transform the model of care in tandem with core clinical platform enhancement was a compelling reason to move forward.

Simulation methods supporting homologation of Electronic Stability Control in vehicle variants

NASA Astrophysics Data System (ADS)

Lutz, Albert; Schick, Bernhard; Holzmann, Henning; Kochem, Michael; Meyer-Tuve, Harald; Lange, Olav; Mao, Yiqin; Tosolin, Guido

2017-10-01

Vehicle simulation has a long tradition in the automotive industry as a powerful supplement to physical vehicle testing. In the field of Electronic Stability Control (ESC) system, the simulation process has been well established to support the ESC development and application by suppliers and Original Equipment Manufacturers (OEMs). The latest regulation of the United Nations Economic Commission for Europe UN/ECE-R 13 allows also for simulation-based homologation. This extends the usage of simulation from ESC development to homologation. This paper gives an overview of simulation methods, as well as processes and tools used for the homologation of ESC in vehicle variants. The paper first describes the generic homologation process according to the European Regulation (UN/ECE-R 13H, UN/ECE-R 13/11) and U.S. Federal Motor Vehicle Safety Standard (FMVSS 126). Subsequently the ESC system is explained as well as the generic application and release process at the supplier and OEM side. Coming up with the simulation methods, the ESC development and application process needs to be adapted for the virtual vehicles. The simulation environment, consisting of vehicle model, ESC model and simulation platform, is explained in detail with some exemplary use-cases. In the final section, examples of simulation-based ESC homologation in vehicle variants are shown for passenger cars, light trucks, heavy trucks and trailers. This paper is targeted to give a state-of-the-art account of the simulation methods supporting the homologation of ESC systems in vehicle variants. However, the described approach and the lessons learned can be used as reference in future for an extended usage of simulation-supported releases of the ESC system up to the development and release of driver assistance systems.

The regulation of ATP release from the urothelium by adenosine and transepithelial potential.

PubMed

Dunning-Davies, Bryony M; Fry, Christopher H; Mansour, Dina; Ferguson, Douglas R

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Stretch of the urothelium, as occurs during bladder filling, is associated with a release of ATP that is postulated to act as a sensory neurotransmitter. The regulation of ATP release is poorly understood and in particular if there is a feedback mechanism provided by ATP itself. Adenosine, a breakdown product of ATP, is a potent inhibitor of stretch-induced ATP release, acting through and A1 receptor; endogenous levels are about 0.6μM. Data are consistent with ATP release relying on the rise of intracellular Ca2+. Transepithelial potential also controls ATP release, also acting via an A1 receptor-dependent pathway. To test the hypothesis that distension-induced ATP release from the bladder urothelium is regulated by adenosine as well as changes to transurothelial potential (TEP). To examine the role of changes to intracellular [Ca(2+) ] in ATP release. Rabbit urothelium/suburothelium membranes were used in an Ussing chamber system. Distension was induced by fluid removal from the chamber bathing the serosal (basolateral) membrane face. The TEP and short-circuit current were measured. ATP was measured in samples aspirated from the serosal chamber by a luciferin-luciferase assay. Intracellular [Ca(2+) ] was measured in isolated urothelial cells using the fluorochrome Fura-2. All experiments were performed at 37°C. Distension-induced ATP release was decreased by adenosine (1-10 μm) and enhanced by adenosine deaminase and A1- (but not A2-) receptor antagonists. Distension-induced ATP release was reduced by 2-APB, nifedipine and capsazepine; capsaicin induced ATP release in the absence of distension. ATP and capsaicin, but not adenosine, generated intracellular Ca(2+) transients; adenosine did not affect the ATP-generated Ca(2+) transient. ATP release was dependent on a finite transepithelial potential. Changes to TEP, in the absence of distension, generated ATP release that was in turn reduced by adenosine. Adenosine exerts a powerful negative feedback control of ATP release from the urothelium via A1 receptor activation. Distension-induced ATP release may be mediated by a rise of the intracellular [Ca(2+) ]. Modulation of distension-induced ATP release by adenosine and TEP may have a common pathway. © 2012 BJU International.

Liquid crystalline systems for transdermal delivery of celecoxib: in vitro drug release and skin permeation studies.

PubMed

Estracanholli, Eder André; Praça, Fabíola Silva Garcia; Cintra, Ana Beatriz; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

2014-12-01

Liquid crystalline systems of monoolein/water could be a promising approach for the delivery of celecoxib (CXB) to the skin because these systems can sustain drug release, improve drug penetration into the skin layers and minimize side effects. This study evaluated the potential of these systems for the delivery of CXB into the skin based on in vitro drug release and skin permeation studies. The amount of CXB that permeated into and/or was retained in the skin was assayed using an HPLC method. Polarizing light microscopy studies showed that liquid crystalline systems of monoolein/water were formed in the presence of CXB, without any changes in the mesophases. The liquid crystalline systems decreased drug release when compared to control solution. Drug release was independent of the initial water content of the systems and CXB was released from cubic phase systems, irrespective of the initial water content. The systems released the CXB following zero-order release kinetics. In vitro drug permeation studies showed that cubic phase systems allowed drug permeation and retention in the skin layers. Cubic phase systems of monoolein/water may be promising vehicles for the delivery of CXB in/through the skin because it improved CXB skin permeation compared with the control solution.

Hindered disulfide bonds to regulate release rate of model drug from mesoporous silica.

PubMed

Nadrah, Peter; Maver, Uroš; Jemec, Anita; Tišler, Tatjana; Bele, Marjan; Dražić, Goran; Benčina, Mojca; Pintar, Albin; Planinšek, Odon; Gaberšček, Miran

2013-05-01

With the advancement of drug delivery systems based on mesoporous silica nanoparticles (MSNs), a simple and efficient method regulating the drug release kinetics is needed. We developed redox-responsive release systems with three levels of hindrance around the disulfide bond. A model drug (rhodamine B dye) was loaded into MSNs' mesoporous voids. The pore opening was capped with β-cyclodextrin in order to prevent leakage of drug. Indeed, in absence of a reducing agent the systems exhibited little leakage, while the addition of dithiothreitol cleaved the disulfide bonds and enabled the release of cargo. The release rate and the amount of released dye were tuned by the level of hindrance around disulfide bonds, with the increased hindrance causing a decrease in the release rate as well as in the amount of released drug. Thus, we demonstrated the ability of the present mesoporous systems to intrinsically control the release rate and the amount of the released cargo by only minor structural variations. Furthermore, an in vivo experiment on zebrafish confirmed that the present model delivery system is nonteratogenic.

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

PubMed

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

2017-05-19

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

Infectious diseases: Surveillance, genetic modification and simulation

USGS Publications Warehouse

Koh, H. L.; Teh, S.Y.; De Angelis, D. L.; Jiang, J.

2011-01-01

Infectious diseases such as influenza and dengue have the potential of becoming a worldwide pandemic that may exert immense pressures on existing medical infrastructures. Careful surveillance of these diseases, supported by consistent model simulations, provides a means for tracking the disease evolution. The integrated surveillance and simulation program is essential in devising effective early warning systems and in implementing efficient emergency preparedness and control measures. This paper presents a summary of simulation analysis on influenza A (H1N1) 2009 in Malaysia. This simulation analysis provides insightful lessons regarding how disease surveillance and simulation should be performed in the future. This paper briefly discusses the controversy over the experimental field release of genetically modified (GM) Aedes aegypti mosquito in Malaysia. Model simulations indicate that the proposed release of GM mosquitoes is neither a viable nor a sustainable control strategy. ?? 2011 WIT Press.

Effect of marbling on volatile generation, oral breakdown and in mouth flavor release of grilled beef.

PubMed

Frank, Damian; Kaczmarska, Kornelia; Paterson, Janet; Piyasiri, Udayasika; Warner, Robyn

2017-11-01

While the positive effect of intramuscular fat (IMF) on beef tenderness is well-established, its role in flavor generation and flavor release is less defined. To increase understanding, real-time volatile generation was monitored during grilling of beefsteaks (grass and grain-fed Angus and grass-fed Wagyu) with different amounts of IMF by proton transfer reaction mass spectrometry. Volatile concentration increased significantly (p<0.001) when the IMF was >~10%, but did not differ (p>0.05) at lower IMF levels (5.2-10.2%). In vivo release of volatiles during consumption of grilled steaks was also measured using human subjects. Pre- and postswallow volatile release profiles varied according to marbling level and volatile fat solubility. In-mouth release of key hydrophilic volatiles was significantly greater (p<0.05) in high IMF grilled beef, consistent with more intense sensory flavor. Faster oral breakdown and higher peak saliva concentrations of non-volatile flavor compounds in high IMF grilled beef were consistent with higher tenderness and more intense flavor perception. Copyright © 2017. Published by Elsevier Ltd.

Features of the solar array drive mechanism for the space telescope

NASA Technical Reports Server (NTRS)

Hostenkamp, R. G.

1985-01-01

The solar array drive mechanism for the Space Telescope embodies several features not customarily found on solar array drives. Power and signal transfer is achieved by means of a flexible wire harness for which the chosen solution, consisting of 168 standard wires, is described. The torque performance data of the harness over its temperature range are presented. The off load system which protects the bearings from the launch loads is released by a trigger made from Nitinol, the memory alloy. The benefits of memory alloy and the caveats for the design are briefly discussed. The design of the off load system is described and test experience is reported.

Design study of 10 kW direct fission target for RISP project

NASA Astrophysics Data System (ADS)

Tshoo, K.; Jang, D. Y.; Woo, H. J.; Kang, B. H.; Kim, G. D.; Hwang, W.; Kim, Y. K.

2014-03-01

We are developing Isotope Separation On-Line (ISOL) target system, which consists of 1.3 mm-thick uranium-carbide multi-disks and cylindrical tantalum heater, to be installed in new facility for Rare Isotope Science Project in Korea. The intense neutron-rich nuclei are produced via the fission process using the uranium carbide targets with a 70 MeV proton beam. The fission rate was estimated to be ˜1.5 × 1013/sec for 10 kW proton beam. The target system has been designed to be operated at a temperature of ˜2000 °C so as to improve the release effciency.

A Concept and Implementation of Optimized Operations of Airport Surface Traffic

NASA Technical Reports Server (NTRS)

Jung, Yoon C.; Hoang, Ty; Montoya, Justin; Gupta, Gautam; Malik, Waqar; Tobias, Leonard

2010-01-01

This paper presents a new concept of optimized surface operations at busy airports to improve the efficiency of taxi operations, as well as reduce environmental impacts. The suggested system architecture consists of the integration of two decoupled optimization algorithms. The Spot Release Planner provides sequence and timing advisories to tower controllers for releasing departure aircraft into the movement area to reduce taxi delay while achieving maximum throughput. The Runway Scheduler provides take-off sequence and arrival runway crossing sequence to the controllers to maximize the runway usage. The description of a prototype implementation of this integrated decision support tool for the airport control tower controllers is also provided. The prototype decision support tool was evaluated through a human-in-the-loop experiment, where both the Spot Release Planner and Runway Scheduler provided advisories to the Ground and Local Controllers. Initial results indicate the average number of stops made by each departure aircraft in the departure runway queue was reduced by more than half when the controllers were using the advisories, which resulted in reduced taxi times in the departure queue.

A pure magnetite hydrogel: synthesis, properties and possible applications.

PubMed

Anastasova, Elizaveta I; Ivanovski, Vladimir; Fakhardo, Anna F; Lepeshkin, Artem I; Omar, Suheir; Drozdov, Andrey S; Vinogradov, Vladimir V

2017-11-22

A magnetite-only hydrogel was prepared for the first time by weak base mediated gelation of stable magnetite hydrosols at room temperature. The hydrogel consists of 10 nm magnetite nanoparticles linked by interparticle Fe-O-Fe bonds and has the appearance of a dark-brown viscous thixotropic material. The water content in the hydrogel could be up to 93.6% by mass while volume fraction reaches 99%. The material shows excellent biocompatibility and minor cytotoxic effects at concentrations up to 207 μg mL -1 . The gel shows excellent sorption capacity for heavy metal adsorption such as chrome and lead ions, which is 225% more than the adsorption capacity of magnetite nanoparticles. Due to thixotropic nature, the gel demonstrates mechanical stimuli-responsive release behavior with up to 98% release triggered by ultrasound irradiation. The material shows superparamagnetic behavior with a coercivity of 65 emu g -1 at 6000 Oe. The magnetite gels prepared could be used for the production of magnetite aerogels, magnetic drug delivery systems with controlled release and highly efficient sorbents for hydrometallurgy.

'Skidding' of the CRRES G-9 barium release

NASA Technical Reports Server (NTRS)

Huba, J. D.; Mitchell, H. G.; Fedder, J. A.; Bernhardt, P. A.

1992-01-01

A simulation study and experimental data of the CRRES G-9 ionospheric barium release are presented. The simulation study is based on a 2D electrostatic code that incorporates time-dependent coupling to the background plasma. It is shown that the densest portion of the barium ion cloud 'skids' about 15 km within the first three seconds following the release, consistent with the optical data analyses.

A Methodology for the Integration of a Mechanistic Source Term Analysis in a Probabilistic Framework for Advanced Reactors

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

Grabaskas, Dave; Brunett, Acacia J.; Bucknor, Matthew

GE Hitachi Nuclear Energy (GEH) and Argonne National Laboratory are currently engaged in a joint effort to modernize and develop probabilistic risk assessment (PRA) techniques for advanced non-light water reactors. At a high level, the primary outcome of this project will be the development of next-generation PRA methodologies that will enable risk-informed prioritization of safety- and reliability-focused research and development, while also identifying gaps that may be resolved through additional research. A subset of this effort is the development of PRA methodologies to conduct a mechanistic source term (MST) analysis for event sequences that could result in the release ofmore » radionuclides. The MST analysis seeks to realistically model and assess the transport, retention, and release of radionuclides from the reactor to the environment. The MST methods developed during this project seek to satisfy the requirements of the Mechanistic Source Term element of the ASME/ANS Non-LWR PRA standard. The MST methodology consists of separate analysis approaches for risk-significant and non-risk significant event sequences that may result in the release of radionuclides from the reactor. For risk-significant event sequences, the methodology focuses on a detailed assessment, using mechanistic models, of radionuclide release from the fuel, transport through and release from the primary system, transport in the containment, and finally release to the environment. The analysis approach for non-risk significant event sequences examines the possibility of large radionuclide releases due to events such as re-criticality or the complete loss of radionuclide barriers. This paper provides details on the MST methodology, including the interface between the MST analysis and other elements of the PRA, and provides a simplified example MST calculation for a sodium fast reactor.« less

Film coatings for oral pulsatile release.

PubMed

Maroni, Alessandra; Zema, Lucia; Loreti, Giulia; Palugan, Luca; Gazzaniga, Andrea

2013-12-05

Pulsatile delivery is generally intended as a release of the active ingredient that is delayed for a programmable period of time to meet particular chronotherapeutic needs and, in the case of oral administration, also target distal intestinal regions, such as the colon. Most oral pulsatile delivery platforms consist in coated formulations wherein the applied polymer serves as the release-controlling agent. When exposed to aqueous media, the coating initially performs as a protective barrier and, subsequently, undergoes a timely failure based on diverse mechanisms depending on its physico-chemical and formulation characteristics. Indeed, it may be ruptured because of the gradual expansion of the core, swell and/or erode due to the glassy-rubbery polymer transition or become permeable thus allowing the drug molecules to diffuse outwards. Otherwise, when the coating is a semipermeable membrane provided with one or more orifices, the drug is released through the latter as a result of an osmotic water influx. The vast majority of pulsatile delivery systems described so far have been prepared by spray-coating, which offers important versatility and feasibility advantages over other techniques such as press- and dip-coating. In the present article, the design, manufacturing and performance of spray-coated pulsatile delivery platforms is thus reviewed. Copyright © 2013 Elsevier B.V. All rights reserved.

Hydrazone linked doxorubicin-PLA prodrug nanoparticles with high drug loading

NASA Astrophysics Data System (ADS)

Gatti, Simone; Agostini, Azzurra; Capasso Palmiero, Umberto; Colombo, Claudio; Peviani, Marco; Biffi, Alessandra; Moscatelli, Davide

2018-07-01

An optimal drug delivery system should be characterized by biocompatibility, biodegradability, high drug loading and favorable drug release profile. To achieve this goal a hydrazone linked doxorubicin-poly(lactic acid) prodrug (PLA-DOX) was synthesized by the functionalization of a short polymer chain produced by ring opening polymerization. The hydrophobic prodrug generated in this way was nanoprecipitated using a block copolymer to form polymeric nanoparticles (NPs) with a quantitative loading efficiency and a high and tunable drug loading. The effects of the concentration of the PLA-DOX prodrug and surfactant were studied by dynamic light scattering showing a range of NP size between 50 and 90 nm and monodispersed size distributions with polydispersity indexes lower then 0.27 up to a maximum DOX concentration of 27% w/w. The release profile of DOX from these NPs, tested at different pH conditions, showed a higher release rate in acidic conditions, consistent with the nature of the hydrazone bond which was used to conjugate the drug to the polymer. In vitro cytotoxicity studies performed on BV2 microglia-like cell line highlighted a specific cytotoxic effect of these NPs suggesting the maintenance of the drug efficacy and a modified release profile upon encapsulation of DOX in the NPs.

Montmorillonite nanodevices for the colon metronidazole delivery.

PubMed

Calabrese, Ilaria; Cavallaro, Gennara; Scialabba, Cinzia; Licciardi, Mariano; Merli, Marcello; Sciascia, Luciana; Turco Liveri, Maria Liria

2013-11-30

The adsorption profiles of the antibiotic metronidazole (MNE) into the K10-montmorillonite (MMT-K10) clay and the subsequent release have been investigated as a function of pH and MNE/MMT-K10 ratio, in order to evaluate the potential of the MNE/MMT-K10 hybrids as controlled drug delivery system. The adsorption mechanism has been first elucidated by performing complementary equilibrium and kinetic studies and through the X-ray diffractometry (XRD) characterization of the obtained composite materials. The gathered results allowed us to propose a mechanism consisting of a multi-step pathway involving the neutral and the cationic form of the drug, which interact with different sites of the clay surfaces, i.e. the interlayer region and the faces of the lamella. In a second step the drug release kinetics has been studied under physiological pH mimicking conditions simulating the oral drug administration and delivery. For the sake of comparison the commercial formulation has also been employed for the release studies. The investigation of the release profiles and the comparison with the commercial formulation of the drug reveal that the new-tailor made formulation could be fruitful exploited for successfully prolonged the action of drug in the desired site. Copyright © 2013 Elsevier B.V. All rights reserved.

Continuous manufacturing of extended release tablets via powder mixing and direct compression.

PubMed

Ervasti, Tuomas; Simonaho, Simo-Pekka; Ketolainen, Jarkko; Forsberg, Peter; Fransson, Magnus; Wikström, Håkan; Folestad, Staffan; Lakio, Satu; Tajarobi, Pirjo; Abrahmsén-Alami, Susanna

2015-11-10

The aim of the current work was to explore continuous dry powder mixing and direct compression for manufacturing of extended release (ER) matrix tablets. The study was span out with a challenging formulation design comprising ibuprofen compositions with varying particle size and a relatively low amount of the matrix former hydroxypropyl methylcellulose (HPMC). Standard grade HPMC (CR) was compared to a recently developed direct compressible grade (DC2). The work demonstrate that ER tablets with desired quality attributes could be manufactured via integrated continuous mixing and direct compression. The most robust tablet quality (weight, assay, tensile strength) was obtained using high mixer speed and large particle size ibuprofen and HPMC DC2 due to good powder flow. At low mixer speed it was more difficult to achieve high quality low dose tablets. Notably, with HPMC DC2 the processing conditions had a significant effect on drug release. Longer processing time and/or faster mixer speed was needed to achieve robust release with compositions containing DC2 compared with those containing CR. This work confirms the importance of balancing process parameters and material properties to find consistent product quality. Also, adaptive control is proven a pivotal means for control of continuous manufacturing systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimization of gatifloxacin liposomal hydrogel for enhanced transcorneal permeation.

PubMed

Hosny, Khaled Mohamed

2010-03-01

The aim of this study was to prepare and characterize a topically effective prolonged-release ophthalmic gatifloxacin liposomal hydrogel formulation. Reverse-phase evaporation was used for the preparation of liposomes consisting of phosphatidylcholine (PC) and cholesterol (CH). The effect of PC:CH molar ratio on the percentage of drug encapsulated was investigated. The effect of additives, such as stearylamine (SA) or dicetyl phosphate (DP), as positive and negative charge inducers, respectively, was studied. Morphology, mean size, encapsulation efficiency, and in vitro release of gatifloxacin from liposomes were evaluated. For hydrogel preparation, carbopol 940 was applied. In vitro transcorneal permeation through excised albino rabbit cornea was also determined. Optimal encapsulation efficiency was found at the 5:3 PC:CH molar ratio; by increasing CH content above this limit, the encapsulation efficiency decreased. Positively charged liposomes showed superior entrapment efficiency over other liposomes. Hydrogel-containing liposomes with lipid content PC, CH, and SA in a molar ratio of 5:3:1, respectively, showed best release and transcorneal permeation. These results suggest that the encapsulation of gatifloxacin into liposomes prolonged the in vitro release, depending on composition of the vesicles. In addition, the polymer hydrogel used in the preparation ensured steady, prolonged transcorneal permeation. In conclusion, gatifloxacin liposomal hydrogel is a suitable delivery system for the improvement of the ocular bioavailability of gatifloxacin.

Hydrodynamic Capture and Release of Passively Driven Particles by Active Particles Under Hele-Shaw Flows

NASA Astrophysics Data System (ADS)

Mishler, Grant; Tsang, Alan Cheng Hou; Pak, On Shun

2018-03-01

The transport of active and passive particles plays central roles in diverse biological phenomena and engineering applications. In this paper, we present a theoretical investigation of a system consisting of an active particle and a passive particle in a confined micro-fluidic flow. The introduction of an external flow is found to induce the capture of the passive particle by the active particle via long-range hydrodynamic interactions among the particles. This hydrodynamic capture mechanism relies on an attracting stable equilibrium configuration formed by the particles, which occurs when the external flow intensity exceeds a certain threshold. We evaluate this threshold by studying the stability of the equilibrium configurations analytically and numerically. Furthermore, we study the dynamics of typical capture and non-capture events and characterize the basins of attraction of the equilibrium configurations. Our findings reveal a critical dependence of the hydrodynamic capture mechanism on the external flow intensity. Through adjusting the external flow intensity across the stability threshold, we demonstrate that the active particle can capture and release the passive particle in a controllable manner. Such a capture-and-release mechanism is desirable for biomedical applications such as the capture and release of therapeutic payloads by synthetic micro-swimmers in targeted drug delivery.

Can lipid nanoparticles improve intestinal absorption?

PubMed

Mendes, M; Soares, H T; Arnaut, L G; Sousa, J J; Pais, A A C C; Vitorino, C

2016-12-30

Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs. Copyright © 2016 Elsevier B.V. All rights reserved.

Application of clotrimazole via a novel controlled release device provides potent retinal protection.

PubMed

Nezhad, Zhaleh Kashkouli; Nagai, Nobuhiro; Yamamoto, Kotaro; Kaji, Hirokazu; Nishizawa, Matsuhiko; Saya, Hideyuki; Nakazawa, Toru; Abe, Toshiaki

2015-09-01

Age-related macular degeneration is the leading cause of legal blindness among older individuals. Therefore, the development of new therapeutic agents and optimum drug delivery systems for its treatment are crucial. In this study, we investigate whether clotrimazole (CLT) is capable of protecting retinal cells against oxidative-induced injury and the possible inhibitory effect of a sustained CLT-release device against light-induced retinal damage in rats. In vitro results indicated pretreatment of immortalized retinal pigment epithelium cells (RPE-J cells) with 10-50 µM CLT before exposure to oxygen/glucose deprivation conditions for 48 h decreased the extent of cell death, attenuated the percentage of reactive oxygen species-positive cells, and decreased the levels of cleaved caspase-3. The device consists of a separately fabricated reservoir, a CLT formulation, and a controlled release cover, which are made of poly(ethyleneglycol) dimethacrylate (PEGDM) and tri(ethyleneglycol) dimethacrylate (TEGDM). The release rate of CLT was successfully tuned by changing the ratio of PEGDM/TEGDM in the cover. In vivo results showed that use of a CLT-loaded device lessened the reduction of electroretinographic amplitudes after light exposure. These findings indicate that the application of a polymeric CLT-loaded device may be a promising method for the treatment of some retinal disorders.

The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 3: Pig islet product manufacturing and release testing.

PubMed

Korbutt, Gregory S

2009-01-01

This chapter provides recommendations on pig islet product manufacturing and release testing to scientific and corporate programs interested in future clinical studies using xenogeneic porcine pancreatic islet cell products for the treatment of type 1 diabetes.To facilitate control of manufacturing as well as reproducibility and consistency of product lots, the manufacturing process, and the manufacturing facility must be in compliance with current Good Manufacturing Practices regulations. Data must be provided to demonstrate that islet products can be consistently prepared that would meet basic lot release requirements. To facilitate product safety: (i) materials used in the manufacturing process, including the pig pancreas, must be free of adventitious agents; (ii) islets must be manufactured using aseptic processing; and (iii) final product must undergo tests for sterility, mycoplasma (if cultured) and endotoxin. Safety specifications for pig islet product release include a negative Gram stain and an endotoxin content of <5.0 EU/kg recipient body weight. Product post-release assessments must include sterility cultures on the final product. Because results for sterility are available only retrospectively, a plan of action must be in place for patient notification and treatment in case the sterility culture results are positive for contamination. Product characterization information must address important aspects of lot release testing such as identity/purity (cell composition), quantity [islet equivalents (IE), cell number] and potency (insulin secretory capacity, oxygen consumption rate corrected for DNA or transplant bioassay in immunoincompetent diabetic mice). This information is also critical to demonstrate manufacturing control and product consistency across multiple islet preparations (lots). Providing islet products containing an islet mass sufficient to restore euglycemia in trial participants (>or=10 000 IE/kg) requires pooling of islets from multiple donor pancreata (two to four from adult donors and seven to 10 from neonatal donors). Demonstration of product consistency across products from individual pancreata would warrant release testing to be performed on a sample of the pooled product. As product development and clinical trials advance, the increasingly more detailed specifications of potency assays on adult porcine islet products are expected to be predictive of post-transplant glycemic control. The immaturity of fetal and neonatal porcine islet tissue precludes the use of in vitro insulin secretion as a potency test as part of lot release testing; another measure of potency appropriate to fetal and neonatal cells will need to be developed for product release testing and evaluation of aliquots of these products in mouse transplant bioassays should be performed to provide meaningful post-release information.

Real-time measurements to characterize dynamics of emulsion interface during simulated intestinal digestion.

PubMed

Pan, Yuanjie; Nitin, N

2016-05-01

Efficient delivery of bioactives remains a critical challenge due to their limited bioavailability and solubility. While many encapsulation systems are designed to modulate the digestion and release of bioactives within the human gastrointestinal tract, there is limited understanding of how engineered structures influence the delivery of bioactives. The objective of this study was to develop a real-time quantitative method to measure structural changes in emulsion interface during simulated intestinal digestion and to correlate these changes with the release of free fatty acids (FFAs). Fluorescence resonant energy transfer (FRET) was used for rapid in-situ measurement of the structural changes in emulsion interface during simulated intestinal digestion. By using FRET, changes in the intermolecular spacing between the two different fluorescent probes labeled emulsifier were characterized. Changes in FRET measurements were compared with the release of FFAs. The results showed that bile salts and pancreatic lipase interacted immediately with the emulsion droplets and disrupted the emulsion interface as evidenced by reduction in FRET efficacy compared to the control. Similarly, a significant amount of FFAs was released during digestion. Moreover, addition of a second layer of polymers at emulsion interface decreased the extent of interface disruption by bile salts and pancreatic lipase and impacted the amount or rate of FFA release during digestion. These results were consistent with the lower donor/acceptor ratio of the labeled probes from the FRET result. Overall, this study provides a novel approach to analyze the dynamics of emulsion interface during digestion and their relationship with the release of FFAs. Copyright © 2016 Elsevier B.V. All rights reserved.

Turbulence-induced resonance vibrations cause pollen release in wind-pollinated Plantago lanceolata L. (Plantaginaceae).

PubMed

Timerman, David; Greene, David F; Urzay, Javier; Ackerman, Josef D

2014-12-06

In wind pollination, the release of pollen from anthers into airflows determines the quantity and timing of pollen available for pollination. Despite the ecological and evolutionary importance of pollen release, wind-stamen interactions are poorly understood, as are the specific forces that deliver pollen grains into airflows. We present empirical evidence that atmospheric turbulence acts directly on stamens in the cosmopolitan, wind-pollinated weed, Plantago lanceolata, causing resonant vibrations that release episodic bursts of pollen grains. In laboratory experiments, we show that stamens have mechanical properties corresponding to theoretically predicted ranges for turbulence-driven resonant vibrations. The mechanical excitation of stamens at their characteristic resonance frequency caused them to resonate, shedding pollen vigorously. The characteristic natural frequency of the stamens increased over time with each shedding episode due to the reduction in anther mass, which increased the mechanical energy required to trigger subsequent episodes. Field observations of a natural population under turbulent wind conditions were consistent with these laboratory results and demonstrated that pollen is released from resonating stamens excited by small eddies whose turnover periods are similar to the characteristic resonance frequency measured in the laboratory. Turbulence-driven vibration of stamens at resonance may be a primary mechanism for pollen shedding in wind-pollinated angiosperms. The capacity to release pollen in wind can be viewed as a primary factor distinguishing animal- from wind-pollinated plants, and selection on traits such as the damping ratio and flexural rigidity may be of consequence in evolutionary transitions between pollination systems. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Turbulence-induced resonance vibrations cause pollen release in wind-pollinated Plantago lanceolata L. (Plantaginaceae)

PubMed Central

Timerman, David; Greene, David F.; Urzay, Javier; Ackerman, Josef D.

2014-01-01

In wind pollination, the release of pollen from anthers into airflows determines the quantity and timing of pollen available for pollination. Despite the ecological and evolutionary importance of pollen release, wind–stamen interactions are poorly understood, as are the specific forces that deliver pollen grains into airflows. We present empirical evidence that atmospheric turbulence acts directly on stamens in the cosmopolitan, wind-pollinated weed, Plantago lanceolata, causing resonant vibrations that release episodic bursts of pollen grains. In laboratory experiments, we show that stamens have mechanical properties corresponding to theoretically predicted ranges for turbulence-driven resonant vibrations. The mechanical excitation of stamens at their characteristic resonance frequency caused them to resonate, shedding pollen vigorously. The characteristic natural frequency of the stamens increased over time with each shedding episode due to the reduction in anther mass, which increased the mechanical energy required to trigger subsequent episodes. Field observations of a natural population under turbulent wind conditions were consistent with these laboratory results and demonstrated that pollen is released from resonating stamens excited by small eddies whose turnover periods are similar to the characteristic resonance frequency measured in the laboratory. Turbulence-driven vibration of stamens at resonance may be a primary mechanism for pollen shedding in wind-pollinated angiosperms. The capacity to release pollen in wind can be viewed as a primary factor distinguishing animal- from wind-pollinated plants, and selection on traits such as the damping ratio and flexural rigidity may be of consequence in evolutionary transitions between pollination systems. PMID:25297315

The influence of spray-drying parameters on phase behavior, drug distribution, and in vitro release of injectable microspheres for sustained release.

PubMed

Meeus, Joke; Lenaerts, Maité; Scurr, David J; Amssoms, Katie; Davies, Martyn C; Roberts, Clive J; Van Den Mooter, Guy

2015-04-01

For ternary solid dispersions, it is indispensable to characterize their structure, phase behavior, and the spatial distribution of the dispersed drug as this might influence the release profile and/or stability of these formulations. This study shows how formulation (feed concentration) and process (feed rate, inlet air temperature, and atomizing air pressure) parameters can influence the characteristics of ternary spray-dried solid dispersions. The microspheres considered here consist of a poly(lactic-co-glycolic acid) (PLGA) surface layer and an underlying polyvinylpyrrolidone (PVP) phase. A poorly soluble active pharmaceutical ingredient (API) was molecularly dispersed in this matrix. Differences were observed in component miscibility, phase heterogeneity, particle size, morphology, as well as API surface coverage for selected spray-drying parameters. Observed differences are likely because of changes in the droplet generation, evaporation, and thus particle formation processes. However, varying particle characteristics did not influence the drug release of the formulations studied, indicating the robustness of this approach to produce particles of consistent drug release characteristics. This is likely because of the fact that the release is dominated by diffusion from the PVP layer through pores in the PLGA surface layer and that observed differences in the latter have no influence on the release. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Landfills as critical infrastructures: analysis of observational datasets after 12 years of non-invasive monitoring

NASA Astrophysics Data System (ADS)

Scozzari, Andrea; Raco, Brunella; Battaglini, Raffaele

2016-04-01

This work presents the results of more than ten years of observations, performed on a regular basis, on a municipal solid waste disposal located in Italy. Observational data are generated by the combination of non-invasive techniques, involving the direct measurement of biogas release to the atmosphere and thermal infrared imaging. In fact, part of the generated biogas tends to escape from the landfill surface even when collecting systems are installed and properly working. Thus, methodologies for estimating the behaviour of a landfill system by means of direct and/or indirect measurement systems have been developed in the last decades. It is nowadays known that these infrastructures produce more than 20% of the total anthropogenic methane released to the atmosphere, justifying the need for a systematic and efficient monitoring of such infrastructures. During the last 12 years, observational data regarding a solid waste disposal site located in Tuscany (Italy) have been collected on a regular basis. The collected datasets consist in direct measurements of gas flux with the accumulation chamber method, combined with the detection of thermal anomalies by infrared radiometry. This work discusses the evolution of the estimated performance of the landfill system, its trends, the benefits and the critical aspects of such relatively long-term monitoring activity.

Multilayered materials based on biopolymers as drug delivery systems.

PubMed

Vilela, Carla; Figueiredo, Ana R P; Silvestre, Armando J D; Freire, Carmen S R

2017-02-01

The design of efficient therapeutic delivery devices has become a tremendously active area of research with a strong contribution from the layer-by-layer (LbL) technology. The application of this simple yet firmly established technique for the design of drug reservoirs originates a multitude of multilayered systems of tailored architecture and with a high level of control of drug administration. Areas covered: This review will focus on the most recent and original research on LbL assemblies based on biopolymers including polysaccharides, polypeptides and proteins, with potential use in drug delivery. Herein, drug reservoirs consisting of multilayered planar films and capsules will be examined with emphasis on the ones benefiting from the non-cytotoxic and biocompatible nature of biopolymers, which are suitable to load, protect and release a high payload of toxic and fragile drugs. Expert opinion: The combination of biopolymers with LbL technology has undergone extensive research, still, there is a multitude of R&D opportunities for the design of smart drug delivery systems with distinct multilayered morphologies, low immunological response, non-invasive drug release devices, as well as the design of theranostic systems combining diagnostics and therapeutic features. Further developments in terms of scaling towards mass production in the pharmaceutical industry are expected in the long-term.

Biocompatible and biodegradable dual-drug release system based on silk hydrogel containing silk nanoparticles.

PubMed

Numata, Keiji; Yamazaki, Shoya; Naga, Naofumi

2012-05-14

We developed a facile and quick ethanol-based method for preparing silk nanoparticles and then fabricated a biodegradable and biocompatible dual-drug release system based on silk nanoparticles and the molecular networks of silk hydrogels. Model drugs incorporated in the silk nanoparticles and silk hydrogels showed fast and constant release, respectively, indicating successful dual-drug release from silk hydrogel containing silk nanoparticles. The release behaviors achieved by this dual-drug release system suggest to be regulated by physical properties (e.g., β-sheet contents and size of the silk nanoparticles and network size of the silk hydrogels), which is an important advantage for biomedical applications. The present silk-based system for dual-drug release also demonstrated no significant cytotoxicity against human mesenchymal stem cells (hMSCs), and thus, this silk-based dual-drug release system has potential as a versatile and useful new platform of polymeric materials for various types of dual delivery of bioactive molecules.

Abundance and Isotopic Composition of Xenon in the Ungrouped Achondrite NWA 7325

NASA Astrophysics Data System (ADS)

Crowther, S. A.; Jastrzebski, N. D.; Weber, I.; Hiesinger, H.; Gilmour, J. D.

2014-09-01

Xe releases from mid-temperature heating steps have a consistent 129Xe/132Xe ratio suggesting a trapped component with a signature inherited from a reservoir affected by 129I decay. Higher temperature releases indicate an in situ component.

Designed drug-release systems having various breathable polyurethane film-backed hydrocolloid acrylated adhesive layers for moisture healing.

PubMed

Chang, Ching-Hsien; Liu, Hsia-Wei; Huang, Ching-Cheng

2014-01-01

A series of designed drug-release systems were prepared and established for clear moisture healing. These systems were designed to have an interpenetrating polymer network (IPN) structure, which contained a breathable polyurethane film, hydrocolloidlayer, and polyacrylate adhesive layer. Breathable polyurethane film (2000 g/m(2)/24 hr) with high moisture permeability was employed as a base for new drug-release systems or wound dressings. All drug-release systems having a polyurethane film-backed hydrocolloid acrylated adhesive layer showed an increase of water uptakes with increasing time. After 114 hours, high water uptakes of drug-release systems with 20% hydrocolloid components were observed in the values of 160, 1100, and 1870% for different additional hydrocolloid components of carboxymethylcellulose, sodium alginate, and carbomer U10, respectively. New drug-release systems of polyurethane film-backed hydrocolloid/adhesive layers could be designed and established for wound care managements.

Drug delivery systems with modified release for systemic and biophase bioavailability.

PubMed

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology.

PubMed

Altman, Roy; Bosch, Bill; Brune, Kay; Patrignani, Paola; Young, Clarence

2015-05-01

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects. Since its introduction in 1973, a number of different diclofenac-containing drug products have been developed with the goal of improving efficacy, tolerability, and patient convenience. Delayed- and extended-release forms of diclofenac sodium were initially developed with the goal of improving the safety profile of diclofenac and providing convenient, once-daily dosing for the treatment of patients with chronic pain. New drug products consisting of diclofenac potassium salt were associated with faster absorption and rapid onset of pain relief. These include diclofenac potassium immediate-release tablets, diclofenac potassium liquid-filled soft gel capsules, and diclofenac potassium powder for oral solution. The advent of topical formulations of diclofenac enabled local treatment of pain and inflammation while minimizing systemic absorption of diclofenac. SoluMatrix diclofenac, consisting of submicron particles of diclofenac free acid and a proprietary combination of excipients, was developed to provide analgesic efficacy at reduced doses associated with lower systemic absorption. This review illustrates how pharmaceutical technology has been used to modify the pharmacokinetic properties of diclofenac, leading to the creation of novel drug products with improved clinical utility.

Analysis of LNG peakshaving-facility release-prevention systems

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

Pelto, P.J.; Baker, E.G.; Powers, T.B.

1982-05-01

The purpose of this study is to provide an analysis of release prevention systems for a reference LNG peakshaving facility. An overview assessment of the reference peakshaving facility, which preceeded this effort, identified 14 release scenarios which are typical of the potential hazards involved in the operation of LNG peakshaving facilities. These scenarios formed the basis for this more detailed study. Failure modes and effects analysis and fault tree analysis were used to estimate the expected frequency of each release scenario for the reference peakshaving facility. In addition, the effectiveness of release prevention, release detection, and release control systems weremore » evaluated.« less

Shock loading and release behavior of silicon nitride

NASA Astrophysics Data System (ADS)

Kawai, N.; Tsuru, T.; Hidaka, N.; Liu, X.; Mashimo, T.

2017-01-01

Shock-reshock and shock-release experiments were performed on silicon nitride ceramics above and below its phase transition pressure. Experimental results clearly show the occurrence of elastic-plastic transition and phase transition during initial shock loading. The HEL and phase transition stress are determined as 11.6 and 34.5 GPa, respectively. Below the phase transition stress, the reshock profile consists of the single shock with short rise time, while the release profile shows the gradual release followed by rapid one. Above phase transition stress, reshock and release behavior varies with the initial shock stress. In the case of reshock and release from about 40 GPa, the reshock structure is considerably dispersed, while the release structure shows rapid release. In the reshock profile from about 50 GPa, the formation of the shock wave with the small ramped precursor is observed. And, the release response from same shocked condition shows initial gradual release and subsequent quite rapid one. These results would provide the information about how phase transformation kinetics effects on the reshock and release behavior.

A pH-responsive carboxymethyl dextran-based conjugate as a carrier of docetaxel for cancer therapy.

PubMed

Han, Hwa Seung; Lee, Minchang; An, Jae Yoon; Son, Soyoung; Ko, Hyewon; Lee, Hansang; Chae, Yee Soo; Kang, Young Mo; Park, Jae Hyung

2016-05-01

Although docetaxel is available for the treatment of various cancers, its clinical applications are limited by its poor water solubility and toxicity to normal cells, resulting in severe adverse effects. In this study, we synthesized a polymeric conjugate with an acid-labile ester linkage, consisting of carboxymethyl dextran (CMD) and docetaxel (DTX), as a potential anticancer drug delivery system. The conjugate exhibited sustained release of DTX in physiological buffer (pH 7.4), whereas its release rate increased remarkably under mildly acidic conditions (pH < 6.5), mimicking the intracellular environment. Cytotoxicity tests conducted in vitro demonstrated that the conjugate exhibited much higher toxicity to cancer cells under mildly acidic conditions than at physiological buffer (pH 7.4). These results implied that the ester linkage in the conjugate allowed for selective release of biologically active DTX under mildly acidic conditions. The in vivo biodistribution of a Cy5.5-labeled conjugate was observed using the noninvasive optical imaging technique after its systemic administration into tumor-bearing mice. The conjugate was effectively accumulated into the tumor site, which may have been because of an enhanced permeability and retention effect. In addition, in vivo antitumor efficacy of the conjugate was significantly higher than that of free DTX. Overall, the CMD-based conjugate might have promising potential as a carrier of DTX for cancer therapy. © 2015 Wiley Periodicals, Inc.

Mount St. Helens Ecosystem Restoration General Reevaluation Study Reconnaissance Report

DTIC Science & Technology

2007-07-01

consist of several smaller channels ( braided ). 1 Hoffstadt Creek Currently maintaining stable connection to North Fork Toutle. Second confluence forms...during high runoff conditions, good holding pools at or just below several of the release sites are limited, and the release hoses need improvements to...Adult coho and steelhead release just above the SRS into the braided sections of the North Fork Toutle River passed upstream into tributaries, with

Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome.

PubMed

Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

2016-01-01

Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a novel avenue to modulate and protect the vaginal microbiota.

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

Brownlow, D.T.; Escude, S.; Johanneson, O.H.

The 1500 Area at Kelly Air Force Base (AFB) was the site of a subsurface release of approximately 1,000 gallons of JP-4 jet fuel. Preliminary studies found evidence of hydrocarbon contamination extending from 10 feet below ground surface (bgs) down to the shallow water table, at 20 to 25 feet bgs. In June of 1993, Kelly AFB authorized the installation and evaluation of a bioventing system at this site to aid in the cleanup of the hydrocarbon contaminated soils. The purpose of the bioventing system is to aerate subsurface soils within and immediately surrounding the release area, in order tomore » stimulate in-situ biological activity and enhance the natural bioremediation capacity of the soil. Augmenting oxygen to the indigenous soil microorganisms promotes the aerobic metabolism of fuel hydrocarbons in the soil. In vadose zone soils exhibiting relatively good permeability, bioventing has proven to be a highly cost effective remediation technology for treating fuel contaminated soils. In November, 1993, a Start-Up Test program consisting of an In-Situ Respiration Test (ISRT) and an Air Permeability Test was performed at the 1500 Area Spill Site.« less

Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

PubMed

Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

1999-05-01

Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

Regulation Effects by Programmed Molecules for Transcription-Based Diagnostic Automata towards Therapeutic Use

NASA Astrophysics Data System (ADS)

Hirabayashi, Miki; Ohashi, Hirotada; Kubo, Tai

We have presented experimental analysis on the controllability of our transcription-based diagnostic biomolecular automata by programmed molecules. Focusing on the noninvasive transcriptome diagnosis by salivary mRNAs, we already proposed the novel concept of diagnostic device using DNA computation. This system consists of the main computational element which has a stem shaped promoter region and a pseudo-loop shaped read-only memory region for transcription regulation through the conformation change caused by the recognition of disease-related biomarkers. We utilize the transcription of malachite green aptamer sequence triggered by the target recognition for observation of detection. This algorithm makes it possible to release RNA-aptamer drugs multiply, different from the digestion-based systems by the restriction enzyme which was proposed previously, for the in-vivo use, however, the controllability of aptamer release is not enough at the previous stage. In this paper, we verified the regulation effect on aptamer transcription by programmed molecules in basic conditions towards the developm! ent of therapeutic automata. These results would bring us one step closer to the realization of new intelligent diagnostic and therapeutic automata based on molecular circuits.

Maximum reasonable radioxenon releases from medical isotope production facilities and their effect on monitoring nuclear explosions.

PubMed

Bowyer, Theodore W; Kephart, Rosara; Eslinger, Paul W; Friese, Judah I; Miley, Harry S; Saey, Paul R J

2013-01-01

Fission gases such as (133)Xe are used extensively for monitoring the world for signs of nuclear testing in systems such as the International Monitoring System (IMS). These gases are also produced by nuclear reactors and by fission production of (99)Mo for medical use. Recently, medical isotope production facilities have been identified as the major contributor to the background of radioactive xenon isotopes (radioxenon) in the atmosphere (Stocki et al., 2005; Saey, 2009). These releases pose a potential future problem for monitoring nuclear explosions if not addressed. As a starting point, a maximum acceptable daily xenon emission rate was calculated, that is both scientifically defendable as not adversely affecting the IMS, but also consistent with what is possible to achieve in an operational environment. This study concludes that an emission of 5 × 10(9) Bq/day from a medical isotope production facility would be both an acceptable upper limit from the perspective of minimal impact to monitoring stations, but also appears to be an achievable limit for large isotope producers. Copyright © 2012 Elsevier Ltd. All rights reserved.

Electronic equipment vulnerability to fire released carbon fibers

NASA Technical Reports Server (NTRS)

Pride, R. A.; Mchatton, A. D.; Musselman, K. A.

1980-01-01

The vulnerability of electronic equipment to damage by carbon fibers released from burning aircraft type structural composite materials was investigated. Tests were conducted on commercially available stereo power amplifiers which showed that the equipment was damaged by fire released carbon fibers but not by the composite resin residue, soot and products of combustion of the fuel associated with burning the carbon fiber composites. Results indicate that the failure rates of the equipment exposed to the fire released fiber were consistent with predictions based on tests using virgin fibers.

Increased in vivo release of neuropeptide S in the amygdala of freely moving rats after local depolarisation and emotional stress.

PubMed

Ebner, Karl; Rjabokon, Alesja; Pape, Hans-Christian; Singewald, Nicolas

2011-10-01

Intracerebral microdialysis in conjunction with a highly sensitive radioimmunoassay was used to study the in vivo release of neuropeptide S (NPS) within the amygdala of freely moving rats. NPS was consistently detected in basolateral amygdala dialysates and the release considerably enhanced in response to local depolarisation as well as exposure to forced swim stress. Thus, our data demonstrate for the first time emotional stress-induced release of NPS in the amygdala supporting a functional role of endogenous NPS in stress/anxiety-related phenomena.

CRRES Prelaunch Mission Operation Report

NASA Technical Reports Server (NTRS)

1990-01-01

The overall NASA Combined Release and Radiation Effects Satellite (CRRES) program consists of a series of chemical releases from the PEGSAT spacecraft, the CRRES spacecraft and sounding rockets. The first chemical releases were made from the PEGSAT spacecraft in April, 1990 over northern Canada. In addition to the releases planned from the CRRES spacecraft there are releases from sounding rockets planned from the Kwajalein rocket range in July and August, 1990 and from Puerto Rico in June and July, 1991. It shows the major milestones in the overall CRRES program. This Mission Operations Report only describes the NASA mission objectives of the CRRES/Geosynchronous Transfer Orbit (GTO) mission.

The General Mission Analysis Tool (GMAT) System Test Plan

NASA Technical Reports Server (NTRS)

Conway, Darrel J.; Hughes, Steven P.

2007-01-01

This document serves as the System Test Approach for the GMAT Project. Preparation for system testing consists of three major stages: 1) The Test Approach sets the scope of system testing, the overall strategy to be adopted, the activities to be completed, the general resources required and the methods and processes to be used to test the release. It also details the activities, dependencies and effort required to conduct the System Test. 2) Test Planning details the activities, dependencies and effort required to conduct the System Test. 3) Test Cases documents the tests to be applied, the data to be processed, the automated testing coverage and the expected results. This document covers the first two of these items, and established the framework used for the GMAT test case development. The test cases themselves exist as separate components, and are managed outside of and concurrently with this System Test Plan.

Temperature Jump Pyrolysis Studies of RP 2 Fuel

DTIC Science & Technology

2017-01-09

Release; Distribution Unlimited. The U.S. Government is joint author of the work and has the right to use, modify , reproduce, release, perform...Mixture RP-2 is a real fuel consisting of hundreds of different compounds; comprised primarily of kerosene There is little sulfur containing

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

The Hazard Notification System (HANS)

NASA Astrophysics Data System (ADS)

Snedigar, S. F.; Venezky, D. Y.

2009-12-01

The Volcano Hazards Program (VHP) has developed a Hazard Notification System (HANS) for distributing volcanic activity information collected by scientists to airlines, emergency services, and the general public. In the past year, data from HANS have been used by airlines to make decisions about diverting or canceling flights during the eruption of Mount Redoubt. HANS was developed to provide a single system that each of the five U.S. volcano observatories could use for communicating and storing volcanic information about the 160+ potentially active U.S. volcanoes. The data that cover ten tables and nearly 100 fields are now stored in similar formats, and the information can be released in styles requested by our agency partners, such as the International Civil Aviation Organization (ICAO). Currently, HANS has about 4500 reports stored; on average, two - three reports are added daily. HANS (at its most basic form) consists of a user interface for entering data into one of many release types (Daily Status Reports, Weekly Updates, Volcano Activity Notifications, etc.); a database holding previous releases as well as observatory information such as email address lists and volcano boilerplates; and a transmission system for formatting releases and sending them out by email or other web related system. The user interface to HANS is completely web based, providing access to our observatory scientists from any online PC. The underlying database stores the observatory information and drives the observatory and program websites' dynamic updates and archived information releases. HANS also runs scripts for generating several different feeds including the program home page Volcano Status Map. Each observatory has the capability of running an instance of HANS. There are currently three instances of HANS and each instance is synchronized to all other instances using a master-slave environment. Information can be entered on any node; slave nodes transmit data to the master node, and the master retransmits that data to all slave nodes. All data transfer between instances uses the Simple Object Access Protocol (SOAP) as the envelope in which data are transmitted between nodes. The HANS data synchronization not only works as a backup feature, but also acts as a simple fault-tolerant system. Information from any observatory can be entered on any instance, and still be transmitted to the specified observatory's distribution list, which provides added flexibility if there is a disruption in access from an area that needs to send an update. Additionally, having the same information available on our multiple websites is necessary for communicating our scientists' most up-to-date information.

Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy.

PubMed

Jeyamohan, Prashanti; Hasumura, Takashi; Nagaoka, Yutaka; Yoshida, Yasuhiko; Maekawa, Toru; Kumar, D Sakthi

2013-01-01

The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light-heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy.

Detailed analysis of the male reproductive system in a potential bio-indicator species – The marine invertebrate Galeolaria caespitosa (Polychaeta: Serpulidae)

PubMed Central

Lu, Yonggang; Aitken, Robert John; Lin, Minjie

2017-01-01

For the first time, this study has systemically investigated the male reproductive system in a sessile broadcast-spawning marine invertebrate, Galeolaria caespitosa (Polychaeta: Serpulidae), which has significant potential as a bio-indicator species of coastal marine pollution. The abdomen of G. caespitosa was divided by intersegmental septa into over 80 trunk segments. Each segment served as a germinal chamber with a C-shaped gonadal arrangement consisting of several distinct compartments: a seminiferous epithelium (SE) compartment located in the centre of the chamber, with each of its two ends connecting to a nurse cell (NC) compartment and then an efferent duct (ED) compartment. The SE compartment contained a multilayered seminiferous epithelium where spermatogenesis was initiated. Spermatids were released in pairs into the lumen of the SE compartment and then transported to the NC compartment where they underwent spermiogenesis with the support of secretory vesicles released by the nurse cells. Spermatozoa were stored in the ED compartment and subsequently released into the seawater through the vas deferens. Unlike vertebrates where germ cells differentiated in close proximity to the nurse cell population (i.e. Sertoli cells), the spermatogenic cells of G. caespitosa exhibited no direct contact with supporting cells at any spermatogenic stage. This finding suggested that the spermatogenesis in G. caespitosa was more dependent on intrinsic developmental programming than most species. Notwithstanding such differences, there were clear parallels between the male reproductive system of G. caespitosa and mammals, in terms of the structure and function. The independence of spermatogenic cells from supporting cells in G. caespitosa raised the possibility of inducing spermiogenesis in vitro, which would provide a useful tool to dissect the mechanisms underlying this complex cell differentiation process in invertebrates and other higher order animals. PMID:28369153

MAPLE deposited polymeric blends coatings for controlled drug delivery

NASA Astrophysics Data System (ADS)

Paun, Irina Alexandra; Ion, Valentin; Moldovan, Antoniu; Dinescu, Maria

2012-07-01

We report on the use of Matrix Assisted Pulsed Laser Evaporation (MAPLE) for producing coatings of polymer blends for controlled drug delivery. The coatings consisting of blends of polyethylene glycol: poly(lactide-co-glycolide) (PEG: PLGA blends) are compared with those consisting of individual polymers (PEG, PLGA) in terms of chemical composition, morphology, hydrophilicity and optical constants. The release kinetics of an anti-inflammatory drug (indomethacin) through the polymeric coatings is monitored and possible mechanisms of the drug release are discussed. Furthermore, the compatibility of the polymeric coatings with blood constituents is investigated. Finally, the perspectives for employing MAPLE for producing coatings of polymer blends to be used in implants that deliver drugs in a controlled manner, along with the routes to be followed for elucidating the mechanism of drug release, are revealed.

Dual-controlled release system of drugs for bone regeneration.

PubMed

Kim, Yang-Hee; Tabata, Yasuhiko

2015-11-01

Controlled release systems have been noted to allow drugs to enhance their ability for bone regeneration. To this end, various biomaterials have been used as the release carriers of drugs, such as low-molecular-weight drugs, growth factors, and others. The drugs are released from the release carriers in a controlled fashion to maintain their actions for a long time period. Most research has been focused on the controlled release of single drugs to demonstrate the therapeutic feasibility. Controlled release of two combined drugs, so-called dual release systems, are promising and important for tissue regeneration. This is because the tissue regeneration process of bone formation is generally achieved by multiple bioactive molecules, which are produced from cells by other molecules. If two types of bioactive molecules, (i.e., drugs), are supplied in an appropriate fashion, the regeneration process of living bodies will be efficiently promoted. This review focuses on the bone regeneration induced by dual-controlled release of drugs. In this paper, various dual-controlled release systems of drugs aiming at bone regeneration are overviewed explaining the type of drugs and their release materials. Copyright © 2015 Elsevier B.V. All rights reserved.

Monitoring diffuse volcanic degassing during volcanic unrests: the case of Campi Flegrei (Italy)

NASA Astrophysics Data System (ADS)

Cardellini, Carlo; Chiodini, Giovanni; Avino, Rosario; Bagnato, Emanuela; Caliro, Stefano; Frondini, Francesco; Lelli, Matteo; Rosiello, Angelo

2017-04-01

Hydrothermal activity at Solfatara of Pozzuoli (Campi Flegrei caldera, Italy) results on a large area of hot soils, diffuse CO2 degassing and numerous fumaroles, releasing at the surface large amounts of gasses and thermal energy. Solfatara is one of the first sites of the world where the techniques for measuring and interpreting soil CO2 diffuse degassing were developed during 1990's and, more recently, it has become a sort of natural laboratory for testing new types of measurements of the CO2 fluxes from hydrothermal sites. The results of 30 diffuse CO2 flux surveys performed at Solfatara from 1998 to 2016 are presented and discussed. CO2 soil fluxes were measured over an area of about 1.2  1.2 km including the Solfatara crater and the hydrothermal site of Pisciarelli using the accumulation chamber technique. Each survey consisted in a number of CO2 flux measurements varying from 372 to 583 resulting in a total of 13158 measurements. This data set is one of the largest dataset ever made in the world on a single degassing volcanic-hydrothermal system. It is particularly relevant in the frame of volcanological sciences because it was acquired during a long period of unrest at Campi Flegrei caldera and because Solfatara release an amount of CO2 comparable to that released by medium-large volcanic plumes. Statistical and geostatistical elaborations of CO2 flux data allowed to characterise the sources of soil diffuse degassing, to define the extent of the area interested by the release of hydrothermal CO2 (Solfatara DDS) and to quantify the total amount of released CO2. During the last eighteen years relevant variations affected Solfatara degassing, and in particular the "background" CO2 emission , the extent of DDS and the total CO2 output, that may reflect variations in the subterraneous gas plume feeding the Solfatara and Pisciarelli emissions. In fact, the most relevant variations in Solfatara diffuse degassing well correlates with steam condensation and temperature increase affecting the Solfatara system resulting from repeated inputs of magmatic fluids into the hydrothermal systems as suggested by Chiodini et al., (2015; 2016; 2017) and show a long-term increase on the amount of released CO2 that accompanies the ongoing unrest of Campi Flegrei caldera.

Application of a biphasic test for characterization of in vitro drug release of immediate release formulations of celecoxib and its relevance to in vivo absorption.

PubMed

Shi, Yi; Gao, Ping; Gong, Yuchuan; Ping, Haili

2010-10-04

A biphasic in vitro test method was used to examine release profiles of a poorly soluble model drug, celecoxib (CEB), from its immediate release formulations. Three formulations of CEB were investigated in this study, including a commercial Celebrex capsule, a solution formulation (containing cosolvent and surfactant) and a supersaturatable self-emulsifying drug delivery system (S-SEDDS). The biphasic test system consisted of an aqueous buffer and a water-immiscible organic solvent (e.g., octanol) with the use of both USP II and IV apparatuses. The aqueous phase provided a nonsink dissolution medium for CEB, while the octanol phase acted as a sink for CEB partitioning. For comparison, CEB concentration-time profiles of these formulations in the aqueous medium under either a sink condition or a nonsink condition were also explored. CEB release profiles of these formulations observed in the aqueous medium from either the sink condition test, the nonsink condition test, or the biphasic test have little relevance to the pharmacokinetic observations (e.g., AUC, C(max)) in human subjects. In contrast, a rank order correlation among the three CEB formulations is obtained between the in vitro AUC values of CEB from the octanol phase up to t = 2 h and the in vivo mean AUC (or C(max)) values. As the biphasic test permits a rapid removal of drug from the aqueous phase by partitioning into the organic phase, the amount of drug in the organic phase represents the amount of drug accumulated in systemic circulation in vivo. This hypothesis provides the scientific rationale for the rank order relationship among these CEB formulations between their CEB concentrations in the organic phase and the relative AUC or C(max). In addition, the biphasic test method permits differentiation and discrimination of key attributes among the three different CEB formulations. This work demonstrates that the biphasic in vitro test method appears to be useful as a tool in evaluating performance of formulations of poorly water-soluble drugs and to provide potential for establishing an in vitro-in vivo relationship.

Use of personal digital assistants in diagnostic radiology resident education.

PubMed

Nishino, Mizuki; Busch, James M; Wei, Jesse; Barbaras, Larry; Yam, Chun-Shan; Hatabu, Hiroto

2004-10-01

Personal digital assistants (PDAs) are gaining widespread use in the medical community. We introduced a PDA-based mobile system that provides departmental and educational information with a seamless connection to the intranet. The objective of this study is to determine the impact a PDA has on educational resources (learning or data reference) brought to work and used at home by a radiology resident based on user surveys. Survey was performed on 32 radiology residents in our department before and 6 months after the release of the PDA-based system. We assessed the changes in (1) sources of learning at home and at work, and in (2) data reference. The second survey also evaluated the usefulness of each component of the system. After the release of the PDA-based mobile system, the use of "digital books and references" as data references and educational resources that were brought to work every day significantly increased (P = .016, P < .0001, respectively). "Traditional books and references" remained the "most useful source in learning radiology"; however, "digital books and references" increased as the residents' first choice from 0% to 16% within 6 months of introducing the package (P = .125). The introduction of a PDA-based system consisting of educational and departmental information had a statistically significant impact in increasing the use of digitized information in radiology resident education.

Alternative barging strategies to improve survival of salmonids transported from Lower Granite Dam: Final report from the 2006-2008 spring/summer Chinook salmon and Steelhead juvenile migrations

USGS Publications Warehouse

Marsh, Tiffani M.; Muir, William D.; Sandford, Benjamin P.; Smith, Steven G.; Elliott, Diane G.

2012-01-01

We found no evidence of a consistent difference in SARs for fish released at the two barge-release locations. Data were not sufficient to evaluate the effects of fish pathogens on avian predation. There was clear evidence that fish of both species released at Astoria were less vulnerable to avian predators than those released at the customary site at Skamania Landing. Unfortunately, this survival benefit did not translate to higher SARs, as it was offset by higher rates of straying by fish released from Astoria. This was likely a result of greater impairment to homing ability for fish released at Astoria.

Insights into the Earth System mass variability from CSR-RL05 GRACE gravity fields

NASA Astrophysics Data System (ADS)

Bettadpur, S.

2012-04-01

The next-generation Release-05 GRACE gravity field data products are the result of extensive effort applied to the improvements to the GRACE Level-1 (tracking) data products, and to improvements in the background gravity models and processing methodology. As a result, the squared-error upper-bound in RL05 fields is half or less than the squared-error upper-bound in RL04 fields. The CSR-RL05 field release consists of unconstrained gravity fields as well as a regularized gravity field time-series that can be used for several applications without any post-processing error reduction. This paper will describe the background and the nature of these improvements in the data products, and provide an error characterization. We will describe the insights these new series offer in measuring the mass flux due to diverse Hydrologic, Oceanographic and Cryospheric processes.

IRIS Toxicological Review of Benzo[a]pyrene (Interagency ...

EPA Pesticide Factsheets

On August 21, 2013, the draft Toxicological Review of Benzo[a]pyrene and the draft charge to external peer reviewers were released for public review and comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science consultation materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Benzo[a]pyrene and the charge to external peer reviewers, are posted on this site. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.

Solar Thermal Energy Storage in a Photochromic Macrocycle.

PubMed

Vlasceanu, Alexandru; Broman, Søren L; Hansen, Anne S; Skov, Anders B; Cacciarini, Martina; Kadziola, Anders; Kjaergaard, Henrik G; Mikkelsen, Kurt V; Nielsen, Mogens Brøndsted

2016-07-25

The conversion and efficient storage of solar energy is recognized to hold significant potential with regard to future energy solutions. Molecular solar thermal batteries based on photochromic systems exemplify one possible technology able to harness and apply this potential. Herein is described the synthesis of a macrocycle based on a dimer of the dihydroazulene/vinylheptafulvene (DHA/VHF) photo/thermal couple. By taking advantage of conformational strain, this DHA-DHA macrocycle presents an improved ability to absorb and store incident light energy in chemical bonds (VHF-VHF). A stepwise energy release over two sequential ring-closing reactions (VHF→DHA) combines the advantages of an initially fast discharge, hypothetically addressing immediate energy consumption needs, followed by a slow process for consistent, long-term use. This exemplifies another step forward in the molecular engineering and design of functional organic materials towards solar thermal energy storage and release. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanostructured nanoparticles of self-assembled lipid pro-drugs as a route to improved chemotherapeutic agents.

PubMed

Sagnella, Sharon M; Gong, Xiaojuan; Moghaddam, Minoo J; Conn, Charlotte E; Kimpton, Kathleen; Waddington, Lynne J; Krodkiewska, Irena; Drummond, Calum J

2011-03-01

We demonstrate that oral delivery of self-assembled nanostructured nanoparticles consisting of 5-fluorouracil (5-FU) lipid prodrugs results in a highly effective, target-activated, chemotherapeutic agent, and offers significantly enhanced efficacy over a commercially available alternative that does not self-assemble. The lipid prodrug nanoparticles have been found to significantly slow the growth of a highly aggressive mouse 4T1 breast tumour, and essentially halt the growth of a human MDA-MB-231 breast tumour in mouse xenografts. Systemic toxicity is avoided as prodrug activation requires a three-step, enzymatic conversion to 5-FU, with the third step occurring preferentially at the tumour site. Additionally, differences in the lipid prodrug chemical structure and internal nanostructure of the nanoparticle dictate the enzymatic conversion rate and can be used to control sustained release profiles. Thus, we have developed novel oral nanomedicines that combine sustained release properties with target-selective activation.

Thick thermal barrier coatings for diesel components

NASA Technical Reports Server (NTRS)

Yonushonis, T. M.

1991-01-01

An engineered thick thermal barrier coating consisting of multiple layers of zirconia and CoCrAlY with a zirconia top layer and having a system thermal conductance less than 410 w/m(exp 2)K exceeded the 100 hour engine durability goals set forth in this program. The thermal barrier coatings were intact at the test conclusion. Back to back single cylinder research engine tests were conducted with watercooled, metal hardware and oil-cooled, thermal barrier coating insulated hardware to determine apparent heat release and fuel economy. Apparent heat release data revealed that the insulated engine had a shorter ignition delay and a longer combustion duration than the metal engine. The insulated engine fuel economy was approximately two percent worse on average for this series of tests. There was no attempt to optimize engine efficiency of the insulated engine by modifying the engine timing, coating, or other techniques.

Spokane Tribal Hatchery, 2004 Annual Report.

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

Peone, Tim L.

2005-03-01

Due to the construction and operation of Grand Coulee Dam (1939), anadromous salmon have been eradicated and resident fish populations permanently altered in the upper Columbia River region. Federal and private hydropower dam operations throughout the Columbia River system severely limits indigenous fish populations in the upper Columbia. Artificial production has been determined appropriate for supporting a harvestable fishery for kokanee salmon (Oncorhynchus nerka) and rainbow trout (Oncorhynchus mykiss) in Lake Roosevelt and Banks Lake (Grand Coulee Dam impoundments). A collaborative multi-agency artificial production program for the Lake Roosevelt and Banks Lake fisheries exists consisting of the Spokane Tribal Hatchery,more » Sherman Creek Hatchery, Ford Trout Hatchery and the Lake Roosevelt Kokanee and Rainbow Trout Net Pen Rearing Projects. These projects operate complementary of one another to target an annual release of 1 million yearling kokanee and 500,000 yearling rainbow trout for Lake Roosevelt and 1.4 million kokanee fry/fingerlings for Banks Lake. Fish produced by this project in 2004 to meet collective fish production and release goals included: 1,655,722 kokanee fingerlings, 537,783 rainbow trout fingerlings and 507,660 kokanee yearlings. Kokanee yearlings were adipose fin clipped before release. Stock composition consisted of Lake Whatcom kokanee, 50:50 diploid-triploid Spokane Trout Hatchery (McCloud River) rainbow trout and Phalon Lake red-band rainbow trout. All kokanee were marked with either thermal, oxytetracyline or fin clips prior to release. Preliminary 2004 Lake Roosevelt fisheries investigations indicate hatchery/net pen stocking significantly contributed to harvestable rainbow trout and kokanee salmon fisheries. An increase in kokanee harvest was primarily owing to new release strategies. Walleye predation, early maturity and entrainment through Grand Coulee Dam continues to have a negative impact on adult kokanee returns and limits the success of hatchery/net pen stocking on the number of harvestable fish. Recommendations for future hatchery/net pen operations include use of stocks compatible or native to the upper Columbia River, continue hatchery-rearing practices to reduce precocity rates of kokanee and continue new kokanee stocking strategies associated with increased kokanee harvest rates.« less

40 CFR 63.1361 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... can be one release or a series of releases over a short time period due to a malfunction in the... or a series of devices. Examples include incinerators, carbon adsorption units, condensers, flares... do not occur simultaneously in a batch operation. A batch process consists of a series of batch...

49 CFR 229.135 - Event recorders.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Locomotive position in consist (lead or trail); (xxiii) Tractive effort; (xxiv) Cruise control on/off, if so...; (xviii) Brakes apply summary train line; (xix) Brakes released summary train line; (xx) Cruise control on... determining, that a brake application or release resulted from manipulation of brake controls at the position...

49 CFR 229.135 - Event recorders.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Locomotive position in consist (lead or trail); (xxiii) Tractive effort; (xxiv) Cruise control on/off, if so...; (xviii) Brakes apply summary train line; (xix) Brakes released summary train line; (xx) Cruise control on... determining, that a brake application or release resulted from manipulation of brake controls at the position...

49 CFR 229.135 - Event recorders.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Locomotive position in consist (lead or trail); (xxiii) Tractive effort; (xxiv) Cruise control on/off, if so...; (xviii) Brakes apply summary train line; (xix) Brakes released summary train line; (xx) Cruise control on... determining, that a brake application or release resulted from manipulation of brake controls at the position...

49 CFR 229.135 - Event recorders.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Locomotive position in consist (lead or trail); (xxiii) Tractive effort; (xxiv) Cruise control on/off, if so...; (xviii) Brakes apply summary train line; (xix) Brakes released summary train line; (xx) Cruise control on... determining, that a brake application or release resulted from manipulation of brake controls at the position...

IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE) (Interagency Science Consultation Draft)

EPA Science Inventory

In September 2016, EPA released the draft IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE) for public comment and discussion. The draft assessment was reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent ...

Characteristics of inositol trisphosphate-mediated Ca/sup 2 +/ release from permeabilized hepatocytes

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

Joseph, S.K.; Williamson, J.R.

1986-11-05

Ca/sup 2 +/ release triggered by inositol trisphosphate (Ins(1,4,5)P/sub 3/) has been measured in saponin-permeabilized hepatocytes with /sup 45/Ca/sup 2 +/ or Quin 2. The initial rate of Ca/sup 2 +/ release was not greatly affected by the incubation temperature. The amount of Ca/sup 2 +/ released by Ins(1,4,5)P/sub 3/ was not affected by pH (6.5-8.0). La/sup 3 +/ (100 ..mu..M) markedly inhibited the effect of 1 ..mu..M Ins(1,4,5)P/sub 3/. The possibility that La/sup 3 +/ chelates Ins(1,4,5)P/sub 3/ cannot be excluded since the effect of La/sup 3 +/ could be overcome by increasing the Ins(1,4,5)P/sub 3/ concentration. Ins(1,4,5)P/sub 3/-mediatedmore » Ca/sup 2 +/ release showed a requirement for permeant cations in the incubation medium. Optimal release was observed with potassium gluconate. Other monovalent cations, with the exception of Li/sup +/, can substitute for K/sup +/. Permeant anions, at concentrations above 40 mM, inhibited Ca/sup 2 +/ release produced by Ins(1,4,5)P/sub 3/. Cl/sup -/, Br/sup -/, I/sup -/, and SO/sup 2 -//sub 4/ were equally effective as inhibitors. Ins(1,4,5)P/sub 3/ also caused the release of /sup 54/Mn/sup 2 +/ and /sup 85/Sr/sup 2 +/ accumulated by the permeabilized hepatocytes. The results are consistent with Ins(1,4,5)P/sub 3/ promoting the membrane translocation of divalent cations through an ion channel rather than an ion carrier. The translocation of positive charge through this channel is balanced by ancillary movements of monovalent cations and anions across the reticular membranes. The transport systems responsible for these compensatory ion movements may represent a potential site for the regulation of the hormone-mediated Ca/sup 2 +/ signal.« less

Designing an extended release waxy matrix tablet containing nicardipine–hydroxy propyl β cyclodextrin complex

PubMed Central

Al-Zein, Hind; Sakeer, Khalil; Alanazi, Fars K.

2011-01-01

Aim The current study aimed to prepare a sustained release tablet for a drug which has poor solubility in alkaline medium using complexation with cyclodextrin. Nicardipine hydrochloride (NC) a weak basic drug was chosen as a model drug for this study. Method Firstly the most suitable binary system NC-HPβCD was selected in order to improve drug solubility in the intestinal media and then embedding the complexed drug into a plastic matrix, by fusion method, consists of glycerol monostearate (GMS) as an inert waxy substance and polyethylene glycol 4000 (PEG4000) as a channeling agent, after that the final solid dispersion [(NC:HPβCD):GMS:PEG4000] which was prepared at different ratios was mixed with other excipients, avicel PH101, lactose, and talc, to get a tablet owning dissolution profile complying with the FDA and USP requirements for the extended release solid dosage forms. Results Infrared spectroscopy (IR), differential scanning colorimetry (DSC), polarized microscopy and X-ray diffractometry proved that the coevaporation technique was effective in preparing amorphous cyclodextrin complexes with NC and trapping of NC within the HPβCD cavity by dissolving both in ethanol and evaporate the solvent using a rotavapor at 65 °C. Dissolution profile of NC enhanced significantly in pH 6.8 from NC:HPβCD inclusion complex prepared by the rotavapor (t-test Student p < 0.05). The release of NC from tablet containing [(NC:HPβCD):GMS:PEG4000] [(1):0.75:0.5] (w/w/w) solid dispersion (F8) was complying with the FDA dissolution requirements for extended release dosage forms, and studying the kinetics of the release showed that the diffusional contribution is the major factor controlling the drug release from that formula. Conclusion The prepared waxy matrix tablet containing NC complexes with CD shows promising results as extended release tablets. PMID:23960765

alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex.

PubMed

Livingstone, Phil D; Srinivasan, Jayaraman; Kew, James N C; Dawson, Lee A; Gotti, Cecilia; Moretti, Milena; Shoaib, Mohammed; Wonnacott, Susan

2009-02-01

Nicotine enhances attentional and working memory aspects of executive function in the prefrontal cortex (PFC) where dopamine plays a major role. Here, we have determined the nicotinic acetylcholine receptor (nAChR) subtypes that can modulate dopamine release in rat PFC using subtype-selective drugs. Nicotine and 5-Iodo-A-85380 (beta2* selective) elicited [(3)H]dopamine release from both PFC and striatal prisms in vitro and dopamine overflow from medial PFC in vivo. Blockade by dihydro-beta-erythroidine supports the participation of beta2* nAChRs. However, insensitivity of nicotine-evoked [(3)H]dopamine release to alpha-conotoxin-MII in PFC prisms suggests no involvement of alpha6beta2* nAChRs, in contrast to the striatum, and this distinction is supported by immunoprecipitation of nAChR subunits from these tissues. The alpha7 nAChR-selective agonists choline and Compound A also promoted dopamine release from PFC in vitro and in vivo, and their effects were enhanced by the alpha7 nAChR-selective allosteric potentiator PNU-120596 and blocked by specific antagonists. DNQX and MK801 inhibited [(3)H]dopamine release evoked by choline and PNU-120596, suggesting crosstalk between alpha7 nAChRs, glutamate and dopamine in the PFC. In vivo, systemic (but not local) administration of PNU-120596, in the absence of agonist, facilitated dopamine overflow in the medial PFC, consistent with the activation of extracortical alpha7 nAChRs by endogenous acetylcholine or choline. These data establish that both beta2* and alpha7 nAChRs can modulate dopamine release in the PFC in vitro and in vivo. Through their distinct actions on dopamine release, these nAChR subtypes could contribute to executive function, making them specific therapeutic targets for conditions such as schizophrenia and attention deficit hyperactivity disorder.

Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30% ethanolic dried extract derived from local Phyllanthus urinaria for skin antiaging

PubMed Central

Mahdi, Elrashid Saleh; Noor, Azmin Mohd; Sakeena, Mohamed Hameem; Abdullah, Ghassan Z; Abdulkarim, Muthanna F; Sattar, Munavvar Abdul

2011-01-01

Background Recently there has been a remarkable surge of interest about natural products and their applications in the cosmetic industry. Topical delivery of antioxidants from natural sources is one of the approaches used to reverse signs of skin aging. The aim of this research was to develop a nanoemulsion cream for topical delivery of 30% ethanolic extract derived from local Phyllanthus urinaria (P. urinaria) for skin antiaging. Methods Palm kernel oil esters (PKOEs)-based nanoemulsions were loaded with P. urinaria extract using a spontaneous method and characterized with respect to particle size, zeta potential, and rheological properties. The release profile of the extract was evaluated using in vitro Franz diffusion cells from an artificial membrane and the antioxidant activity of the extract released was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method. Results Formulation F12 consisted of wt/wt, 0.05% P. urinaria extract, 1% cetyl alcohol, 0.5% glyceryl monostearate, 12% PKOEs, and 27% Tween® 80/Span® 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and a 59.5% phosphate buffer system at pH 7.4. Formulation F36 was comprised of 0.05% P. urinaria extract, 1% cetyl alcohol, 1% glyceryl monostearate, 14% PKOEs, 28% Tween® 80/Span® 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and 56% phosphate buffer system at pH 7.4 with shear thinning and thixotropy. The droplet size of F12 and F36 was 30.74 nm and 35.71 nm, respectively, and their nanosizes were confirmed by transmission electron microscopy images. Thereafter, 51.30% and 51.02% of the loaded extract was released from F12 and F36 through an artificial cellulose membrane, scavenging 29.89% and 30.05% of DPPH radical activity, respectively. Conclusion The P. urinaria extract was successfully incorporated into a PKOEs-based nanoemulsion delivery system. In vitro release of the extract from the formulations showed DPPH radical scavenging activity. These formulations can neutralize reactive oxygen species and counteract oxidative injury induced by ultraviolet radiation and thereby ameliorate skin aging. PMID:22072884

The Role of Acoustic Cavitation in Ultrasound-triggered Drug Release from Echogenic Liposomes

NASA Astrophysics Data System (ADS)

Kopechek, Jonathan A.

Cardiovascular disease (CVD) is the leading cause of death in the United States and globally. CVD-related mortality, including coronary heart disease, heart failure, or stroke, generally occurs due to atherosclerosis, a condition in which plaques build up within arterial walls, potentially causing blockage or rupture. Targeted therapies are needed to achieve more effective treatments. Echogenic liposomes (ELIP), which consist of a lipid membrane surrounding an aqueous core, have been developed to encapsulate a therapeutic agent and/or gas bubbles for targeted delivery and ultrasound image enhancement. Under certain conditions ultrasound can cause nonlinear bubble growth and collapse, known as "cavitation." Cavitation activity has been associated with enhanced drug delivery across cellular membranes. However, the mechanisms of ultrasound-mediated drug release from ELIP have not been previously investigated. Thus, the objective of this dissertation is to elucidate the role of acoustic cavitation in ultrasound-mediated drug release from ELIP. To determine the acoustic and physical properties of ELIP, the frequency-dependent attenuation and backscatter coefficients were measured between 3 and 30 MHz. The results were compared to a theoretical model by measuring the ELIP size distribution in order to determine properties of the lipid membrane. It was found that ELIP have a broad size distribution and can provide enhanced ultrasound image contrast across a broad range of clinically-relevant frequencies. Calcein, a hydrophilic fluorescent dye, and papaverine, a lipophilic vasodilator, were separately encapsulated in ELIP and exposed to color Doppler ultrasound pulses from a clinical diagnostic ultrasound scanner in a flow system. Spectrophotometric techniques (fluorescence and absorbance measurements) were used to detect calcein or papaverine release. As a positive control, Triton X-100 (a non-ionic detergent) was added to ELIP samples not exposed to ultrasound in order to release encapsulated agents completely. Also, sham samples without Triton X-100 or ultrasound exposure were used as negative controls. Color Doppler ultrasound did not release encapsulated calcein or papaverine from ELIP even though there was a complete loss of echogenicity. In subsequent experiments, calcein and rosiglitazone, a hydrophobic anti-diabetic drug, were separately encapsulated in ELIP and exposed to pulsed Doppler ultrasound in a flow system while monitoring cavitation. Samples were exposed to ultrasound pressures above and below cavitation thresholds. In addition, Triton X-100 was used for positive control samples and sham samples were also tested without ultrasound exposure. Adding Triton X-100 resulted in complete release of encapsulated calcein or rosiglitzone. However, Doppler ultrasound exposure did not induce calcein or rosiglitazone release from ELIP in the flow system even when there was persistent cavitation activity and a loss of echogenicity. The results of this dissertation indicate that cavitation of encapsulated bubbles in ELIP solutions is not sufficient to induce drug release. It is possible that ultrasoundmediated thermal processes may have a stronger effect on ELIP permeability than cavitation activity. Perhaps ultrasound-triggered drug release will be possible by improving the ELIP formulation or encapsulating a different gas instead of air. However, cavitation is not a reliable indicator of ultrasound-mediated drug release with the ELIP formulations used in this dissertation.

Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

PubMed Central

Barnewall, Roy E.; Comer, Jason E.; Miller, Brian D.; Gutting, Bradford W.; Wolfe, Daniel N.; Director-Myska, Alison E.; Nichols, Tonya L.; Taft, Sarah C.

2012-01-01

Repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as B. anthracis spores, the causative agent of anthrax. Studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 106 colony forming units (CFU) of B. anthracis spores) and included a pilot feasibility characterization study, acute exposure study, and a multiple 15 day exposure study. This manuscript focuses on the state-of-the-science aerosol methodologies used to generate and aerosolize consistent daily low aerosol concentrations and resultant low inhalation doses to rabbits. The pilot feasibility characterization study determined that the aerosol system was consistent and capable of producing very low aerosol concentrations. In the acute, single day exposure experiment, targeted inhaled doses of 1 × 102, 1 × 103, 1 × 104, and 1 × 105 CFU were used. In the multiple daily exposure experiment, rabbits were exposed multiple days to targeted inhaled doses of 1 × 102, 1 × 103, and 1 × 104 CFU. In all studies, targeted inhaled doses remained consistent from rabbit-to-rabbit and day-to-day. The aerosol system produced aerosolized spores within the optimal mass median aerodynamic diameter particle size range to reach deep lung alveoli. Consistency of the inhaled dose was aided by monitoring and recording respiratory parameters during the exposure with real-time plethysmography. Overall, the presented results show that the animal aerosol system was stable and highly reproducible between different studies and over multiple exposure days. PMID:22919662

SPI/U3.2. Security Profile Inspector for UNIX Systems

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

Bartoletti, A.

1994-08-01

SPI/U3.2 consists of five tools used to assess and report the security posture of computers running the UNIX operating system. The tools are: Access Control Test: A rule-based system which identifies sequential dependencies in UNIX access controls. Binary Authentication Tool: Evaluates the release status of system binaries by comparing a crypto-checksum to provide table entries. Change Detection Tool: Maintains and applies a snapshot of critical system files and attributes for purposes of change detection. Configuration Query Language: Accepts CQL-based scripts (provided) to evaluate queries over the status of system files, configuration of services and many other elements of UNIX systemmore » security. Password Security Inspector: Tests for weak or aged passwords. The tools are packaged with a forms-based user interface providing on-line context-sensistive help, job scheduling, parameter management and output report management utilities. Tools may be run independent of the UI.« less

A hybrid power system for unmanned aerial vehicle electromagnetic launcher

NASA Astrophysics Data System (ADS)

Wang, Zhiren; Wu, Jun; Huang, Shengjun

2018-06-01

According to the UAV electromagnetic catapult with fixed timing, a hybrid energy storage system consist with battery and super capacitor is designed, in order to reduce the volume and weight of the energy storage system. The battery is regarded as the energy storage device and the super capacitor as power release device. Firstly, the battery charges the super capacitor, and then the super capacitor supplies power to electromagnetic catapult separately. The strategy is using the Buck circuit to charge the super capacitor with constant current and using the Boost circuit to make super capacitor provide a stable voltage circuit for electromagnetic catapult. The Simulink simulation results show that the designed hybrid energy storage system can meet the requirements of electromagnetic catapult. Compared with the system powered by the battery alone, the proposed scheme can reduce the number of batteries, and greatly reduce the volume and weight of the energy storage system.

Design of a nuclear isotope heat source assembly for a spaceborne mini-Brayton power module.

NASA Technical Reports Server (NTRS)

Wein, D.; Gorland, S. H.

1973-01-01

Results of a study to develop a feasible design definition of a heat source assembly (HSA) for use in nominal 500-, 1200-, or 2000-W(e) mini-Brayton spacecraft power systems. The HSA is a modular design which is used either as a single unit to provide thermal energy to the 500-W(e) mini-Brayton power module or in parallel with one or two additional HSAs for the 1200- or 2000-W(e) power module systems. Principal components consist of a multihundred watt RTG isotope heat source, a heat source heat exchanger which transfers the thermal energy from the heat source to the mini-Brayton power conversion system, an auxiliary cooling system which provides requisite cooling during nonoperation of the power conversion module and an emergency cooling system which precludes accidental release of isotope fuel in the event of system failure.

Consistent Transition of Salinity Retrievals From Aquarius to SMAP

NASA Astrophysics Data System (ADS)

Mears, C. A.; Meissner, T.; Wentz, F. J.; Manaster, A.

2017-12-01

The Aquarius Version 5.0 release in late 2017 has achieved an excellent level of accuracy and significantly mitigated most of the regional and seasonal biases that had been observed in prior releases. The SMAP NASA/RSS Version 2.0 release does not quite yet reach that level of accuracy. Our presentation discusses the necessary steps that need to be undertaken in the upcoming V 3.0 of the SMAP salinity retrieval algorithm to achieve a seamless transition between the salinity products from the two instruments. We also discuss where fundamental differences in the sensors make it difficult to reach complete consistency. In the Aquarius V 4.0 and earlier releases, comparison with ARGO floats have revealed small fresh biases at low latitudes and larger seasonally varying salty biases at high latitudes. These biases have been tracked back to inaccuracies in the models that are used for correcting the absorption by atmospheric oxygen and for correcting the wind induced roughness. The geophysical models have been changed in Aquarius V5.0, which resulted in a significant improvement of these biases. The upcoming SMAP V3 release will implement the same geophysical model. In deriving the changes of the geophysical model, monthly ARGO analyzed fields from Scripps are now being used consistently as reference salinity for both Aquarius V5.0 and the upcoming SMAP V3.0 releases. Earlier versions had used HYOCM as reference salinity field. The development of the Aquarius V 5.0 algorithm has already strongly benefited from the full 360o look capability of SMAP. This aided in deriving the correction of the reflected galaxy, which is a strong spurious signal for both sensors. Consistent corrections for the galactic signal are now used for both Aquarius and SMAP. It is also important to filter out rain when developing the GMF and when validating the satellite salinities versus in-situ measurements on order to avoid mismatches due to salinity stratification in the upper ocean layer. One major difference between Aquarius and SMAP is the emissive SMAP mesh antenna. In order to correct for it an accurate thermal model for the physical temperature of the SMAP antenna needs to be developed.

Assessing the In Vitro Drug Release from Lipid-Core Nanocapsules: a New Strategy Combining Dialysis Sac and a Continuous-Flow System.

PubMed

de Andrade, Diego Fontana; Zuglianello, Carine; Pohlmann, Adriana Raffin; Guterres, Silvia Stanisçuaski; Beck, Ruy Carlos Ruver

2015-12-01

The in vitro assessment of drug release from polymeric nanocapsules suspensions is one of the most studied parameters in the development of drug-loaded nanoparticles. Nevertheless, official methods for the evaluation of drug release from submicrometric carriers are not available. In this work, a new approach to assess the in vitro drug release profile from drug-loaded lipid-core nanocapsules (LNC) was proposed. A continuous-flow system (open system) was designed to evaluate the in vitro drug release profiles from different LNC formulations containing prednisolone or clobetasol propionate (LNC-CP) as drug model (LNC-PD) using a homemade apparatus. The release medium was constantly renewed throughout the experiment. A dialysis bag containing 5 mL of formulation (0.5 mg mL(-1)) was maintained inside the apparatus, under magnetic stirring and controlled temperature (37°C). In parallel, studies based on the conventional dialysis sac technique (closed system) were performed. It was possible to discriminate the in vitro drug release profile of different formulations using the open system. The proposed strategy improved the sink condition, by constantly renewing the release medium, thus maintaining the drug concentration farther from the saturated concentration in the release medium. Moreover, problems due to sampling errors can be easily overcome using this semi-automated system, since the collection is done automatically without interference from the analyst. The system proposed in this paper brings important methodological and analytical advantages, becoming a promising prototype semi-automated apparatus for performing in vitro drug release studies from drug-loaded lipid-core nanocapsules and other related nanoparticle drug delivery systems.

Thrombin stimulates increased plasminogen activator inhibitor-1 release from liver compared to lung endothelium.

PubMed

Huebner, Benjamin R; Moore, Ernest E; Moore, Hunter B; Gonzalez, Eduardo; Kelher, Marguerite R; Sauaia, Angela; Banerjee, Anirban; Silliman, Christopher C

2018-05-01

Plasminogen activator inhibitor-1 (PAI-1) is a major regulator of the fibrinolytic system, covalently binding to tissue plasminogen activator and blocking its activity. Fibrinolysis shutdown is evident in the majority of severely injured patients in the first 24 h and is thought to be due to PAI-1. The source of this PAI-1 is thought to be predominantly endothelial cells, but there are known organ-specific differences, with higher levels thought to be in the liver. Thrombin generation is also elevated in injured patients and is a potent stimulus for PAI-1 release in human umbilical endothelial cells. We hypothesize that thrombin induces liver endothelial cells to release increased amounts of PAI-1, versus pulmonary endothelium, consisting of both stored PAI-1 and a larger contribution from de novo PAI-1 synthesis. Human liver sinusoidal endothelial cells (LSECs) and human microvascular lung endothelial cells (HMVECs) were stimulated in vitro ± thrombin (1 and 5 IU/mL) for 15-240 min, the supernatants were collected, and PAI-1 was measured by enzyme-linked immunosorbent assays. To elucidate the PAI-1 contribution from storage versus de novo synthesis, cycloheximide (10 μg/mL) was added before thrombin in separate experiments. While both LSECs and HMVECs rapidly stimulated PAI-1 release, LSECs released more PAI-1 than HMVECs in response to high-dose thrombin, whereas low-dose thrombin did not provoke immediate release. LSECs continued to release PAI-1 over the ensuing 240 min, whereas HMVECs did not. Cycloheximide did not inhibit early PAI-1 release from LSECs but did at the later time points (30-240 min). Thrombin elicits increased amounts of PAI-1 release from liver endothelium compared with lung, with a small presynthesized stored contribution and a later, larger increase in PAI-1 release via de novo synthesis. This study suggests that the liver may be an important therapeutic target for inhibition of the hypercoagulable surgical patient and the associated complications that result. Copyright © 2017 Elsevier Inc. All rights reserved.

Iron and copper release in drinking-water distribution systems.

PubMed

Shi, Baoyou; Taylor, James S

2007-09-01

A large-scale pilot study was carried out to evaluate the impacts of changes in water source and treatment process on iron and copper release in water distribution systems. Finished surface waters, groundwaters, and desalinated waters were produced with seven different treatment systems and supplied to 18 pipe distribution systems (PDSs). The major water treatment processes included lime softening, ferric sulfate coagulation, reverse osmosis, nanofiltration, and integrated membrane systems. PDSs were constructed from PVC, lined cast iron, unlined cast iron, and galvanized pipes. Copper pipe loops were set up for corrosion monitoring. Results showed that surface water after ferric sulfate coagulation had low alkalinity and high sulfates, and consequently caused the highest iron release. Finished groundwater treated by conventional method produced the lowest iron release but the highest copper release. The iron release of desalinated water was relatively high because of the water's high chloride level and low alkalinity. Both iron and copper release behaviors were influenced by temperature.

Model studies on the release of aroma compounds from structured and nonstructured oil systems using proton-transfer reaction mass spectrometry.

PubMed

Landy, Pascale; Pollien, Philippe; Rytz, Andreas; Leser, Martin E; Sagalowicz, Laurent; Blank, Imre; Spadone, Jean-Claude

2007-03-07

Relative retention, volatility, and temporal release of volatile compounds taken from aldehyde, ester, and alcohol chemical classes were studied at 70 degrees C in model systems using equilibrium static headspace analysis and real time dynamic headspace analysis. These systems were medium-chain triglycerides (MCT), sunflower oil, and two structured systems, i.e., water-in-oil emulsion and L2 phase (water-in-oil microemulsion). Hydrophilic domains of the emulsion type media retained specifically the hydrophilic compounds and alcohols. Four kinetic parameters characterizing the concentration- and time-dependent releases were extracted from the aroma release curves. Most of the kinetic parameter values were higher in structured systems than in oils particularly when using MCT. The oil nature was found to better control the dynamic release profiles than the system structures. The release parameters were well-related (i) to the volatile hydrophobicity as a function of the oil used and (ii) to the retention data in the specific case of the L2 phase due to a specific release behavior of alcohols.

A Smart pH-responsive Nano-Carrier as a Drug Delivery System: A hybrid system comprised of mesoporous nanosilica MCM-41 (as a nano-container) & a pH-sensitive polymer (as smart reversible gatekeepers): Preparation, characterization and in vitro release studies of an anti-cancer drug.

PubMed

Abbaszad Rafi, Abdolrahim; Mahkam, Mehrdad; Davaran, Soodabeh; Hamishehkar, Hamed

2016-10-10

A smart pH-responsive drug nano-carrier for controlled release of anti-cancer therapeutics was developed through a facile route. The nano-carrier consisted of two main parts: first, the nano-container part (that mesoporous silica nanoparticles (MCM-41) were selected for this aim); and second, pH-sensitive gatekeepers (that a pH-sensitive polymer, Poly4-vinylpyridine, played this role). In the first step, MCM-41 was synthesized via template assisted sol-gel process. In the second step, polymerizable functional groups were attached onto pore entrances rather than inside walls. In the third step, polymeric gatekeepers were introduced onto pore entrances via precipitation polymerization of functionalized MCM-41 with monomers. Different methods and analysis, such as Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Powder Diffraction (XRD), Thermo-Gravimetric Analysis (TGA), Energy-Dispersive X-ray Spectroscopy (EDX), Zeta Potentials, Dynamic Light Scattering (DLS), Field Emission Scanning Electron Microscope (FE-SEM) and Transmission Electron Microscopy (TEM) were employed to approve the successful attachment of gatekeepers. Furthermore, the release studies of methotroxate (MTX), an anti-cancer drug, were performed in different media (pH4, 5.8 and 7.4) at 37±1°C. The release profiles and curves show that the release rates are completely pH-dependent and it proceeds with a decrease in pH. It is concluded that in the higher pH the gatekeepers are in their close state, but they switch to the open state as a consequence of repulsive forces between positively charged polymer chains appear in acidic media. The results suggest that this smart nano-carrier can be considered as an appropriate candidate to deliver therapeutics to cancerous tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a Transportation System in Iran

DTIC Science & Technology

1979-06-01

different capitals. A method of road building was developed I that consisted of paving the softer parts of the road and even of making artificial ruts...abstract entered in Block 20, If different from Report) 18. S U P P L E M E N T A R Y N O T E S Ap&lOVfcD FOR ljuBLIC RELEASE: IAW AFR 190-17 FREDRIC...roads into the provincial areas. * Generally the standards of pre-World War I road construction were different from those for modern road work

Oil Spill Cleanup

NASA Technical Reports Server (NTRS)

1994-01-01

Petroleum Remediation Product (PRP) is a new way of cleaning up oil spills. It consists of thousands of microcapsules, tiny balls of beeswax with hollow centers, containing live microorganisms and nutrients to sustain them. As oil flows through the microcapsule's shell, it is consumed and digested by the microorganisms. Pressure buildup causes the PRP to explode and the enzymes, carbon dioxide and water are released into the BioBoom used in conjunction with PRP, preventing contaminated water from spreading. The system incorporates technology originally developed at the Jet Propulsion Laboratory and Marshall Space Flight Center.

Off-surface infrared flow visualization

NASA Technical Reports Server (NTRS)

Manuel, Gregory S. (Inventor); Obara, Clifford J. (Inventor); Daryabeigi, Kamran (Inventor); Alderfer, David W. (Inventor)

1993-01-01

A method for visualizing off-surface flows is provided. The method consists of releasing a gas with infrared absorbing and emitting characteristics into a fluid flow and imaging the flow with an infrared imaging system. This method allows for visualization of off-surface fluid flow in-flight. The novelty of this method is found in providing an apparatus for flow visualization which is contained within the aircraft so as not to disrupt the airflow around the aircraft, is effective at various speeds and altitudes, and is longer-lasting than previous methods of flow visualization.

A Decision Support System for Mitigating Stream Temperature Impacts in the Sacramento River

NASA Astrophysics Data System (ADS)

Caldwell, R. J.; Zagona, E. A.; Rajagopalan, B.

2014-12-01

Increasing demands on the limited and variable water supply across the West can result in insufficient streamflow to sustain healthy fish habitat. We develop an integrated decision support system (DSS) for modeling and mitigating stream temperature impacts and demonstrate it on the Sacramento River system in California. Water management in the Sacramento River is a complex task with a diverse set of demands ranging from municipal supply to mitigation of fisheries impacts due to high water temperatures. Current operations utilize the temperature control device (TCD) structure at Shasta Dam to mitigate these high water temperatures downstream at designated compliance points. The TCD structure at Shasta Dam offers a rather unique opportunity to mitigate water temperature violations through adjustments to both release volume and temperature. In this study, we develop and evaluate a model-based DSS with four broad components that are coupled to produce the decision tool for stream temperature mitigation: (i) a suite of statistical models for modeling stream temperature attributes using hydrology and climate variables of critical importance to fish habitat; (ii) a reservoir thermal model for modeling the thermal structure and, consequently, the water release temperature, (iii) a stochastic weather generator to simulate weather sequences consistent with seasonal outlooks; and, (iv) a set of decision rules (i.e., 'rubric') for reservoir water releases in response to outputs from the above components. Multiple options for modifying releases at Shasta Dam were considered in the DSS, including mixing water from multiple elevations through the TCD and using different acceptable levels of risk. The DSS also incorporates forecast uncertainties and reservoir operating options to help mitigate stream temperature impacts for fish habitat, while efficiently using the reservoir water supply and cold pool storage. The use of these coupled tools in simulating impacts of future climate on stream temperature variability is also demonstrated. Results indicate that the DSS could substantially reduce the number of violations of thermal criteria, while ensuring maintenance of the cold pool storage throughout the summer.

Across North America tracer experiment (ANATEX): Sampling and analysis

NASA Astrophysics Data System (ADS)

Draxler, R. R.; Dietz, R.; Lagomarsino, R. J.; Start, G.

Between 5 January 1987 and 29 March 1987, there were 33 releases of different tracers from each of two sites: Glasgow, MT and St. Cloud, MN. The perfluorocarbon tracers were routinely released in a 3-h period every 2.5 days, alternating between daytime and night-time tracer releases. Ground-level air samples of 24-h duration were taken at 77 sites mostly located near rawinsonde stations east of 105°W and between 26°N and 55°N. Weekly air samples were taken at 12 remote sites between San Diego, CA and Pt. Barrow, AK and between Norway and the Canary Islands. Short-term 6-h samples were collected at ground level and 200 m AGL along an arc of five towers between Tulsa, OK and Green Bay, WI. Aircraft sampling within several hundred kilometers of both tracer release sites was used to establish the initial tracer path. Experimental design required improved sampler performance, new tracers with lower atmospheric backgrounds, and improvements in analytic precision. The advances to the perfluorocarbon tracer system are discussed in detail. Results from the tracer sampling showed that the average and peak concentrations measured over the daily ground-level sampling network were consistent with what would be calculated using mass conservative approaches. however, ground-level samples from individual tracer patterns showed considerable complexity due to vertical stability or the interaction of the tracer plumes with low pressure and frontal systems. These systems could pass right through the tracer plume without appreciable effect. Aircraft tracer measurements are used to confirm the initial tracer trajectory when the narrow plume may miss the coarser spaced ground-level sampling network. Tower tracer measurements showed a more complex temporal structure than evident from the longer duration ground-level sampling sites. Few above background plume measurements were evident in the more distant remote sampling network due to larger than expected uncertainties in the ambient background concentrations.

Loading, Release, Biodegradation, and Biocompatibility of a Nanovector Delivery System

NASA Technical Reports Server (NTRS)

Ferrai, Mauro; Tasciotti, Ennio

2012-01-01

A nanovector multistage system has been created to overcome or bypass sequential barriers within the human body, in order to deliver a therapeutic or imaging agent to a specific location. This innovation consists of a composition that includes two or more stages of particles, such that smaller, later-stage particles are contained in the larger, early-stage particles. An active agent, such as a therapeutic agent or imaging agent, is preferentially delivered and/or localized to a particular target site in the body of a subject. The multistage composition overcomes multiple biological barriers in the body. The multistage composition also allows for simultaneous delivery and localization at the same or different target sites of multiple active agents.

Kilauea's double eruption, 2008-2016: volatile budget and associated hazards

NASA Astrophysics Data System (ADS)

Sutton, A. J.; Elias, T.

2016-12-01

After 20 years of effusive behavior on Kilauea's East Rift Zone, a surge in magma supply brought about eruptive changes that significantly improved our understanding of volcanic processes and associated hazards. The volcano's summit deformation changes and increase in CO2 emissions signaled the supply surge beginning in 2003, and heralded the opening of the Overlook Vent in 2008. Along with the supply surge and vent opening came a dramatic spike in gas release. Summit SO2 emissions climbed from 0.2 kt/d to over 10 kt/d while East Rift discharge rose from 2 kt/d to about 6 kt/d before both summit and rift emissions began an overall decline in late 2008. In spite of the emissions decline, however, overall gas release from Kilauea remained well above the previous 20-year average through early 2014. Beginning in 2008, the annual gas budget released from the summit and rift combined, was more than 830 kt, 6.7 kt, and 3.7 kt of SO2, HCl, and HF, respectively. Effects of these elevated emissions sustained ongoing human health concerns and caused a multi-year agricultural disaster designation for the Island. The current activity of Kīlauea consists of a predominant summit gas eruption (where lava and ash discharge are trivial compared to gas release) and a more typical rift lava eruption with sufficient lava effusion to reach a community 20 km from the eruptive vent. An updated gas-based lava effusion estimate shows that Kilauea continued to erupt an average of 0.11 km^3 yr^-1 of dense rock equivalent lava between early 2012 and mid-2016. This value shows that despite the new regime of erupting most of its gas budget at the volcano's summit, the Kilauea system is still capable of pushing magma out of its rift at a rate consistent with the long term average.

Effects of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement.

PubMed

Takechi, M; Miyamoto, Y; Ishikawa, K; Nagayama, M; Kon, M; Asaoka, K; Suzuki, K

1998-02-01

The effect of added antibiotics on the basic properties of anti-washout-type fast-setting calcium phosphate cement (aw-FSCPC) was investigated in a preliminary evaluation of aw-FSCPC containing drugs. Flomoxef sodium was employed as the antibiotic and was incorporated into the powder-phase aw-FSCPC at up to 10%. The setting time, consistency, wet diametral tensile strength (DTS) value, and porosity were measured for aw-FSCPC containing various amounts of flomoxef sodium. X-ray diffraction (XRD) analysis was also conducted for the identification of products. To evaluate the drug-release profile, set aw-FSCPC was immersed in saline and the released flomoxef sodium was determined at regular intervals. The spread area of the cement paste as an index of consistency of the cement increased progressively with the addition of flomoxef sodium, and it doubled when the aw-FSCPC contained 8% flomoxef sodium. In contrast, the wet DTS value decreased with increase in flomoxef sodium content. Bulk density measurement and scanning electron microscopic observation revealed that the set mass was more porous with the amount of flomoxef sodium contained in the aw-FSCPC. The XRD analysis revealed that formation of hydroxyapatite (HAP) from aw-FSCPC was reduced even after 24 h, when the aw-FSCPC contained flomoxef sodium at > or = 6%. Therefore, the decrease of wet DTS value was thought to be partly the result of the increased porosity and inhibition of HAP formation in aw-FSCPC containing large amounts of flomoxef sodium. The flomoxef sodium release from aw-FSCPC showed the typical profile observed in a skeleton-type drug delivery system (DDS). The rate of drug release from aw-FSCPC can be controlled by changing the concentration of sodium alginate. Although flomoxef sodium addition has certain disadvantageous effects on the basic properties of aw-FSCPC, we conclude that aw-FSCPC is a good candidate for potential use as a DDS carrier that may be useful in surgical operations.

Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland.

PubMed

Soini, Tuuli; Hurskainen, Ritva; Grénman, Seija; Mäenpää, Johanna; Paavonen, Jorma; Pukkala, Eero

2014-08-01

To examine the association between premenopausal use of the levonorgestrel-releasing intrauterine system and cancer incidence in Finland with a special focus on endometrial adenocarcinoma. All Finnish women aged 30-49 years using a levonorgestrel-releasing intrauterine system for treatment of menorrhagia in 1994-2007 (n=93,843) were identified from the National Reimbursement Registry and linked to the Finnish Cancer Registry data. The incidence of cancers in levonorgestrel-releasing intrauterine system users was compared with that in the general population. A total of 2,781 cancer cases were detected in levonorgestrel-releasing intrauterine system users during the follow-up of 855,324 women-years. The standardized incidence ratio (observed-to-expected ratio) for endometrial adenocarcinoma was 0.50 (95% confidence interval [CI] 0.35-0.70; 34 observed compared with 68 expected cases) after the first levonorgestrel-releasing intrauterine system purchase and 0.25 (95% CI 0.05-0.73; three observed compared with 12 expected cases) after two purchases. The standardized incidence ratio for ovarian cancer was 0.60 (95% CI 0.45-0.76; 59 observed compared with 99 expected cases), for pancreatic cancer 0.50 (95% CI 0.28-0.81; 15 observed compared with 30 expected cases), and for lung cancer 0.68 (95% CI 0.49-0.91; 43 observed compared with 63 expected cases). The standardized incidence ratio for breast cancer among all levonorgestrel-releasing intrauterine system users was 1.19 (95% CI 1.13-1.25; 1,542 observed compared with 1,292 expected cases). The levonorgestrel-releasing intrauterine system may have a protective effect against endometrial malignant transformation. Using the levonorgestrel-releasing intrauterine system for treatment of menorrhagia during reproductive years was associated with a lower incidence of endometrial, ovarian, pancreatic, and lung cancers than expected. Levonorgestrel-releasing intrauterine system use was associated with a higher than expected incidence of breast cancer. II.

Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation.

PubMed

Pachis, K; Blazaki, S; Tzatzarakis, M; Klepetsanis, P; Naoumidi, E; Tsilimbaris, M; Antimisiaris, S G

2017-11-15

A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioactive peptides released during of digestion of processed milk

USDA-ARS?s Scientific Manuscript database

Most of the proteins contained in milk consist of alpha-s1-, alpha-s2-, beta- and kappa-casein, and some of the peptides contained in these caseins may impart health benefits. To determine if processing affected release of peptides, samples of raw (R), homogenized (H), homogenized and pasteurized (...

THE HYDROCARBON SPILL SCREENING MODEL (HSSM), VOLUME 2: THEORETICAL BACKGROUND AND SOURCE CODES

EPA Science Inventory

A screening model for subsurface release of a nonaqueous phase liquid which is less dense than water (LNAPL) is presented. The model conceptualizes the release as consisting of 1) vertical transport from near the surface to the capillary fringe, 2) radial spreading of an LNAPL l...

21 CFR 660.6 - Samples; protocols; official release.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Research, determines that the reliability and consistency of the finished product can be assured with a... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Samples; protocols; official release. 660.6 Section 660.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 660.6 - Samples; protocols; official release.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Research, determines that the reliability and consistency of the finished product can be assured with a... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Samples; protocols; official release. 660.6 Section 660.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

The kidney in the pathogenesis of hypertension: the role of renal nerves.

PubMed

DiBona, G F

1985-04-01

The intrinsic efferent innervation of the kidney consists of exclusively noradrenergic fibers that innervate the preglomerular and postgomerular vasculature, all elements of the juxtagomerular apparatus and virtually all segments of the nephron in both cortical and medullo-papillary regions. Increases in efferent renal sympathetic nerve activity produce renal vasoconstriction, release of renin, catecholamines, prostaglandins and other vasoactive substances, and increases in renal tubular sodium reabsorption; these responses are graded and differentiated. The intrinsic afferent innervation of the kidney consists of mechanoreceptors and chemoreceptors which participate in reno-renal and reno-systemic reflexes that modulate sympathetic neural outflow in an organ-specific differentiated pattern. Therefore, alterations in efferent and afferent renal nerve activity produce changes in several important renal functions known to contribute to the development and maintenance of hypertension.

Understanding and Controlling iron Release in Distribution Systems

EPA Science Inventory

Generation of red-water resulting from the release of iron from drinking water distribution system materials is a major consumer complaint of drinking water systems. The objective of this presentation is to provide a fundamental basis for iron release from drinking water distrib...

Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

PubMed

Shen, Jie; Burgess, Diane J

2012-07-01

This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Accelerated in vitro release testing methods for extended release parenteral dosage forms

PubMed Central

Shen, Jie; Burgess, Diane J.

2012-01-01

Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

Cu/Mn bimetallic catalysis enables carbonylative Suzuki–Miyaura coupling with unactivated alkyl electrophiles† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc01170a Click here for additional data file.

PubMed Central

Pye, Dominic R.; Cheng, Li-Jie

2017-01-01

A bimetallic system consisting of Cu-carbene and Mn-carbonyl co-catalysts was employed for carbonylative C–C coupling of arylboronic esters with alkyl halides, allowing for the convergent synthesis of ketones. The system operates under mild conditions and exhibits complementary reactivity to Pd catalysis. The method is compatible with a wide range of arylboronic ester nucleophiles and proceeds smoothly for both primary and secondary alkyl iodide electrophiles. Preliminary mechanistic experiments corroborate a hypothetical catalytic mechanism consisting of co-dependent cycles wherein the Cu-carbene co-catalyst engages in transmetallation to generate an organocopper nucleophile, while the Mn-carbonyl co-catalyst activates the alkyl halide electrophile by single-electron transfer and then undergoes reversible carbonylation to generate an acylmanganese electrophile. The two cycles then intersect with a heterobimetallic, product-releasing C–C coupling step. PMID:28966784

CD38 Mediates Angiotensin II–Induced Intracellular Ca2+ Release in Rat Pulmonary Arterial Smooth Muscle Cells

PubMed Central

Lee, Suengwon; Paudel, Omkar; Jiang, Yongliang; Yang, Xiao-Ru

2015-01-01

CD38 is a multifunctional enzyme that catalyzes the formation of the endogenous Ca2+-mobilizing messengers cyclic ADP-ribose (cADPR) and nicotinic acid adenosine dinucleotide phosphate (NAADP) for the activation of ryanodine receptors (RyRs) of sarcoplasmic reticulum and NAADP-sensitive Ca2+ release channels in endolysosomes, respectively. It plays important roles in systemic vascular functions, but there is little information on CD38 in pulmonary arterial smooth muscle cells (PASMCs). Earlier studies suggested a redox-sensing role of CD38 in hypoxic pulmonary vasoconstriction. This study sought to characterize its roles in angiotensin II (Ang II)–induced Ca2+ release (AICR) in PASMCs. Examination of CD38 expression in various rat arteries found high levels of CD38 mRNA and protein in pulmonary arteries. The Ang II–elicited Ca2+ response consisted of extracellular Ca2+ influx and intracellular Ca2+ release in PASMCs. AICR activated in the absence of extracellular Ca2+ was reduced by pharmacological or siRNA inhibition of CD38, by the cADPR antagonist 8-bromo-cADPR or ryanodine, and by the NAADP antagonist Ned-19 or disruption of endolysosomal Ca2+ stores with the vacuolar H+-ATPase inhibitor bafilomycin A1. Suppression of AICR by the inhibitions of cADPR- and NAADP-dependent pathways were nonadditive, indicating interdependence of RyR- and NAADP-gated Ca2+ release. Furthermore, AICR was inhibited by the protein kinase C inhibitor staurosporine, the nonspecific NADPH oxidase (NOX) inhibitors apocynin and diphenyleneiodonium, the NOX2-specific inhibitor gp91ds-tat, and the scavenger of reactive oxygen species (ROS) tempol. These results provide the first evidence that Ang II activates CD38-dependent Ca2+ release via the NOX2-ROS pathway in PASMCs. PMID:25078456

Mechanistic analysis of Zein nanoparticles/PLGA triblock in situ forming implants for glimepiride.

PubMed

Ahmed, Osama Abdelhakim Aly; Zidan, Ahmed Samir; Khayat, Maan

2016-01-01

The study aims at applying pharmaceutical nanotechnology and D-optimal fractional factorial design to screen and optimize the high-risk variables affecting the performance of a complex drug delivery system consisting of glimepiride-Zein nanoparticles and inclusion of the optimized formula with thermoresponsive triblock copolymers in in situ gel. Sixteen nanoparticle formulations were prepared by liquid-liquid phase separation method according to the D-optimal fractional factorial design encompassing five variables at two levels. The responses investigated were glimepiride entrapment capacity (EC), particle size and size distribution, zeta potential, and in vitro drug release from the prepared nanoparticles. Furthermore, the feasibility of embedding the optimized Zein-based glimepiride nanoparticles within thermoresponsive triblock copolymers poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) in in situ gel was evaluated for controlling glimepiride release rate. Through the systematic optimization phase, improvement of glimepiride EC of 33.6%, nanoparticle size of 120.9 nm with a skewness value of 0.2, zeta potential of 11.1 mV, and sustained release features of 3.3% and 17.3% drug released after 2 and 24 hours, respectively, were obtained. These desirability functions were obtained at Zein and glimepiride loadings of 50 and 75 mg, respectively, utilizing didodecyldimethylammonium bromide as a stabilizer at 0.1% and 90% ethanol as a common solvent. Moreover, incorporating this optimized formulation in triblock copolymers-based in situ gel demonstrated pseudoplastic behavior with reduction of drug release rate as the concentration of polymer increased. This approach to control the release of glimepiride using Zein nanoparticles/triblock copolymers-based in situ gel forming intramuscular implants could be useful for improving diabetes treatment effectiveness.

Controlled release of ibuprofen by meso-macroporous silica

NASA Astrophysics Data System (ADS)

Santamaría, E.; Maestro, A.; Porras, M.; Gutiérrez, J. M.; González, C.

2014-02-01

Structured meso-macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (EO19PO39EO19) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption-desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso-macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system.

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

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

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

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

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

DOE PAGES

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

2017-12-05

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

Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation.

PubMed

Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D

2016-01-01

Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy.

PubMed

Mou, Quanbing; Ma, Yuan; Zhu, Xinyuan; Yan, Deyue

2016-05-28

Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Higher levels of spontaneous breathing reduce lung injury in experimental moderate acute respiratory distress syndrome.

PubMed

Carvalho, Nadja C; Güldner, Andreas; Beda, Alessandro; Rentzsch, Ines; Uhlig, Christopher; Dittrich, Susanne; Spieth, Peter M; Wiedemann, Bärbel; Kasper, Michael; Koch, Thea; Richter, Torsten; Rocco, Patricia R; Pelosi, Paolo; de Abreu, Marcelo Gama

2014-11-01

To assess the effects of different levels of spontaneous breathing during biphasic positive airway pressure/airway pressure release ventilation on lung function and injury in an experimental model of moderate acute respiratory distress syndrome. Multiple-arm randomized experimental study. University hospital research facility. Thirty-six juvenile pigs. Pigs were anesthetized, intubated, and mechanically ventilated. Moderate acute respiratory distress syndrome was induced by repetitive saline lung lavage. Biphasic positive airway pressure/airway pressure release ventilation was conducted using the airway pressure release ventilation mode with an inspiratory/expiratory ratio of 1:1. Animals were randomly assigned to one of four levels of spontaneous breath in total minute ventilation (n = 9 per group, 6 hr each): 1) biphasic positive airway pressure/airway pressure release ventilation, 0%; 2) biphasic positive airway pressure/airway pressure release ventilation, > 0-30%; 3) biphasic positive airway pressure/airway pressure release ventilation, > 30-60%, and 4) biphasic positive airway pressure/airway pressure release ventilation, > 60%. The inspiratory effort measured by the esophageal pressure time product increased proportionally to the amount of spontaneous breath and was accompanied by improvements in oxygenation and respiratory system elastance. Compared with biphasic positive airway pressure/airway pressure release ventilation of 0%, biphasic positive airway pressure/airway pressure release ventilation more than 60% resulted in lowest venous admixture, as well as peak and mean airway and transpulmonary pressures, redistributed ventilation to dependent lung regions, reduced the cumulative diffuse alveolar damage score across lungs (median [interquartile range], 11 [3-40] vs 18 [2-69]; p < 0.05), and decreased the level of tumor necrosis factor-α in ventral lung tissue (median [interquartile range], 17.7 pg/mg [8.4-19.8] vs 34.5 pg/mg [29.9-42.7]; p < 0.05). Biphasic positive airway pressure/airway pressure release ventilation more than 0-30% and more than 30-60% showed a less consistent pattern of improvement in lung function, inflammation, and damage compared with biphasic positive airway pressure/airway pressure release ventilation more than 60%. In this model of moderate acute respiratory distress syndrome in pigs, biphasic positive airway pressure/airway pressure release ventilation with levels of spontaneous breath higher than usually seen in clinical practice, that is, more than 30% of total minute ventilation, reduced lung injury with improved respiratory function, as compared with protective controlled mechanical ventilation.

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.

Atmospheric Propagation Modeling Indicates Homing Pigeons use Loft-Specific Infrasonic 'Map' Cues

NASA Astrophysics Data System (ADS)

Hagstrum, J. T.; Baker, L. M.; Spritzer, J. M.; McKenna, M. H.

2011-12-01

Pigeons (Columba livia) released at distant sites commonly depart in directions significantly off the actual homeward bearing. Such site-dependent deviations, or biases, for birds from a given loft are generally stable over time, but can also change from hour to hour, day to day, and year to year. At some release sites, birds consistently vanish in random directions and have longer flight times and lower return rates. Release sites characterized by frequent disorientation are not uncommon for pigeon lofts in both Europe and the USA. One such site is the Jersey Hill fire tower in upstate New York located ~120 km W of the Cornell loft in Ithaca. Cornell birds released at Jersey Hill between 1968 and 1987 almost always vanished randomly, although birds from other lofts had little difficulty orienting there. The results for one day, however, stand out: on August 13, 1969, Cornell birds released at Jersey Hill vanished consistently to the NE (r = 0.921; n=7) and returned home after normal flight times. Cornell pigeons released the next day again showed 'normal' behavior for the site and departed randomly. If, in fact, the birds are using acoustic cues to navigate, the long-term acoustic 'dead' zone we propose for Jersey Hill, due to prevailing atmospheric conditions, indicates that the cues are coming from a single, relatively restricted area, most likely surrounding the home loft. We have modeled the transmission of infrasonic waves, presumably coupled to the atmosphere from ocean-generated microseisms (0.14 Hz), between the Cornell loft and a number of release sites using HARPA (Hamiltonian Acoustic Ray-tracing Program for the Atmosphere) and rawinsonde data collected near Albany and Buffalo, NY. The HARPA modeling shows that acoustic signals from the Cornell loft reached Jersey Hill only on a few release days with unusual atmospheric conditions, including August 13, and were launched at angles less than ~2° above horizontal, most likely from steep-sided terrain in the loft vicinity. Such low angles would require sound waves to be diffracted around intervening topography, and likely explains why birds released on August 13 vanished from Jersey Hill at a mean direction to the NE (33°) and not closer to the homeward bearing (85°). Cornell birds released at many sites have departure bearings consistent with such topographic effects. At the Dryden III release site just 13 km E of the Cornell loft, pigeons generally departed to the NW (321°, n=630), ~60° off the homeward bearing (258°). Apparently, infrasonic signals from the home loft area were being diffracted around higher terrain between the loft and release site.

Shock loading and release behavior of silicon nitride

NASA Astrophysics Data System (ADS)

Kawai, Nobuaki; Tsuru, Taiki; Hidaka, Naoto; Liu, Xun; Mashimo, Tsutomu

2015-06-01

Shock-reshock and shock-release experiments were performed on silicon nitride ceramics above and below its phase transition pressure. Experimental results clearly show the occurrence of elastic-plastic transition and phase transition during initial shock loading. The HEL and phase transition stress are determined as 11.6 GPa and 34.5 GPa, respectively. Below the phase transition point, the reshock profile consists of the single shock with short rise time, while the release profile shows the gradual release followed by more rapid one. Above the phase transition point, reshock and release behavior varies with the initial shock stress. In the case of reshock and release from about 40 GPa, the reshock structure is considerably dispersed, while the release structure shows rapid release. In the reshock profile from about 50 GPa, the formation of the shock wave with the small ramped precursor is observed. And, the release response from same condition shows initial gradual release and subsequent quite rapid one. These results would provide the information about how phase transformation kinetics effects on the reshock and release behavior.

Controlled Release of Antimicrobial ClO2 Gas from a Two-Layer Polymeric Film System.

PubMed

Bai, Zhifeng; Cristancho, Diego E; Rachford, Aaron A; Reder, Amy L; Williamson, Alexander; Grzesiak, Adam L

2016-11-16

We report a two-component label system comprising a chlorite-containing polymer film and an acid-containing polymer film that can release antimicrobial ClO 2 gas upon adhering the two films together to enable a reaction of the chlorite and acid under moisture exposure. The chlorite-containing film comprises a commercial acrylate-based pressure-sensitive adhesive polymer impregnated with sodium chlorite. The acid-containing film comprises a commercial poly(vinyl alcohol) polymer loaded with tartaric acid. Both of the films were prepared on low ClO 2 -absorbing substrate films from stable aqueous systems of the polymers with high reagent loading. Rapid and sustained releases of significant amounts of ClO 2 gas from the label system were observed in an in situ quantification system using UV-vis spectroscopy. It was found that the ClO 2 release is slower at a lower temperature and can be accelerated by moisture in the atmosphere and the films. Controlled release of ClO 2 gas from the label system was demonstrated by tailoring film composition and thickness. A model was developed to extract release kinetics and revealed good conversions of the label system. This two-component system can potentially be applied as a two-part label without premature release for applications in food packaging.

LARCRIM user's guide, version 1.0

NASA Technical Reports Server (NTRS)

Davis, John S.; Heaphy, William J.

1993-01-01

LARCRIM is a relational database management system (RDBMS) which performs the conventional duties of an RDBMS with the added feature that it can store attributes which consist of arrays or matrices. This makes it particularly valuable for scientific data management. It is accessible as a stand-alone system and through an application program interface. The stand-alone system may be executed in two modes: menu or command. The menu mode prompts the user for the input required to create, update, and/or query the database. The command mode requires the direct input of LARCRIM commands. Although LARCRIM is an update of an old database family, its performance on modern computers is quite satisfactory. LARCRIM is written in FORTRAN 77 and runs under the UNIX operating system. Versions have been released for the following computers: SUN (3 & 4), Convex, IRIS, Hewlett-Packard, CRAY 2 & Y-MP.

Preliminary Feasibility Study of a Hybrid Solar and Modular Pumped Storage Hydro System at Biosphere 2

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

Lansey, Kevin; Hortsman, Chris

2016-10-01

In this study, the preliminary feasibility of a hybrid solar and modular pumped storage system designed for high energy independence at Biosphere 2 is assessed. The system consists of an array of solar PV panels that generate electricity during the day to power both Biosphere 2 and a pump that sends water through a pipe to a tank at a high elevation. When solar power is not available, the water is released back down the pipe towards a tank at a lower elevation, where it passes through a hydraulic water turbine to generate hydroelectricity to power Biosphere 2. The hybridmore » system is sized to generate and store enough energy to enable Biosphere 2 to operate without a grid interconnection on an average day.« less

The Plumbing System Feeding the Lusi Eruption Revealed by Ambient Noise Tomography

NASA Astrophysics Data System (ADS)

Fallahi, Mohammad Javad; Obermann, Anne; Lupi, Matteo; Karyono, Karyono; Mazzini, Adriano

2017-10-01

Lusi is a sediment-hosted hydrothermal system featuring clastic-dominated geyser-like eruption behavior in East Java, Indonesia. We use 10 months of ambient seismic noise cross correlations from 30 temporary seismic stations to obtain a 3-D model of shear wave velocity anomalies beneath Lusi, the neighboring Arjuno-Welirang volcanic complex, and the Watukosek fault system connecting the two. Our work reveals a hydrothermal plume, rooted at a minimum 6 km depth that reaches the surface at the Lusi site. Furthermore, the inversion shows that this vertical anomaly is connected to the adjacent volcanic complex through a narrow ( 3 km wide) low velocity corridor slicing the survey area at a depth of 4-6 km. The NE-SW direction of this elongated zone matches the strike of the Watukosek fault system. Distinct magmatic chambers are also inferred below the active volcanoes. The large-scale tomography features an exceptional example of a subsurface connection between a volcanic complex and a solitary erupting hydrothermal system hosted in a hydrocarbon-rich back-arc sedimentary basin. These results are consistent with a scenario where deep-seated fluids (e.g., magmas and released hydrothermal fluids) flow along a region of enhanced transmissivity (i.e., the Watukosek fault system damage zone) from the volcanic arc toward the back arc basin where Lusi resides. The triggered metamorphic reactions occurring at depth in the organic-rich sediments generated significant overpressure and fluid upwelling that is today released at the spectacular Lusi eruption site.

Percutaneous carpal tunnel release compared with mini-open release using ultrasonographic guidance for both techniques.

PubMed

Nakamichi, Ken-ichi; Tachibana, Shintaro; Yamamoto, Seizo; Ida, Masayoshi

2010-03-01

To compare the outcomes of percutaneous carpal tunnel release (PCTR) and mini-open carpal tunnel release (mini-OCTR) using ultrasonographic guidance for both techniques. We included 74 hands of 65 women with idiopathic carpal tunnel syndrome (age, 52-71 y; mean, 58 y). Thirty-five hands of 29 women had the PCTR (release with a device consisting of an angled blade, guide, and holder, along a line midway between the median nerve and ulnar artery (safe line) under ultrasonography (incision, 4 mm), and 39 hands of 36 women had the mini-OCTR (release along the safe line, distally under direct vision (incision, 1-1.5 cm) and proximally under ultrasonography, using a device consisting of a basket punch and outer tube. Assessments at 3, 6, 13, 26, 52, and 104 weeks showed no significant differences in neurologic recovery between the groups (p > .05). The PCTR group had significantly less pain, greater grip and key-pinch strengths, and better satisfaction scores at 3 and 6 weeks (p < .05), and less scar sensitivity at 3, 6, and 13 weeks (p < .05). There were no complications. The PCTR provides the same neurologic recovery as does the mini-OCTR. The former leads to less postoperative morbidity and earlier functional return and achievement of satisfaction. Therapeutic III. Copyright 2010. Published by Elsevier Inc.

Efficacy and Safety of a Novel Three-Step Medial Release Technique in Varus Total Knee Arthroplasty.

PubMed

Kim, Min Woo; Koh, In Jun; Kim, Ju Hwan; Jung, Jae Jong; In, Yong

2015-09-01

We investigated the efficacy and safety of our novel three-step medial release technique in varus total knee arthroplasty (TKA) over time. Two hundred sixty seven consecutive varus TKAs were performed by applying the algorithmic release technique which consisted of sequential release of the deep medial collateral ligament (step 1), the semimembranosus (step 2), and multiple needle puncturing of the superficial medial collateral ligament (step 3). One hundred seventeen, 114, and 36 knees were balanced after step 1, 2, and 3 releases, respectively. There were no significant differences in changes of medial and lateral laxities between groups in over a year. Our novel stepwise medial release technique was efficacious and safe in balancing varus knees during TKA. Copyright © 2015 Elsevier Inc. All rights reserved.

Is antibiotic prophylaxis mandatory after the insertion of levonorgestrel-releasing intrauterine systemin order to decrease the risk of pelvic inflammatory disease?

PubMed

Munteanu, O; Radulescu, L; Bodean, O; Cirstoiu, C; Secara, D; Cirstoiu, M

2013-01-01

This study was undertaken in order to determine if antibiotic prophylaxis is mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. We prospectively evaluated 44 patients, admitted in the Bucharest Emergency Hospital between the 1ⁱ of February 2012 and the 1ⁱ of October 2012, in whom the levonorgestrel-releasing intrauterine system was inserted. The patients enrolled were divided into two groups. In group A, a number of 22 patients, received, after the insertion of levonorgestrel-releasing intrauterine system, 875mg Amoxicillin Trihydrate + 125 mg Potassium Clavulanate, a dose every 12 hours for 5 days. Group B was represented by the other 22 patients who did not receive antibiotic prophylaxis. All patients were reevaluated at 4 and 12 weeks after the insertion of levonorgestrel-releasing intrauterine system. During the first 4 weeks after the insertion of levonorgestrel-releasing intrauterine system only two patients, one from group A and one from group B were diagnosed with pelvic inflammatory disease. At a second follow up visit - 12 weeks after the insertion of levonorgestrel-releasing intrauterine system, no other patient was diagnosed with pelvic inflammatory disease. Antibiotic prophylaxis is not mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease.

48 CFR 1515.305-72 - Release of cost information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Release of cost information. 1515.305-72 Section 1515.305-72 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION... Release of cost information. (a) In accordance with FAR 15.305(a)(4), the contracting officer may release...

Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity

PubMed Central

Sacchi, Silvia; Novellis, Vito De; Paolone, Giovanna; Nuzzo, Tommaso; Iannotta, Monica; Belardo, Carmela; Squillace, Marta; Bolognesi, Paolo; Rosini, Elena; Motta, Zoraide; Frassineti, Martina; Bertolino, Alessandro; Pollegioni, Loredano; Morari, Michele; Maione, Sabatino; Errico, Francesco; Usiello, Alessandro

2017-01-01

D-aspartate levels in the brain are regulated by the catabolic enzyme D-aspartate oxidase (DDO). D-aspartate activates NMDA receptors, and influences brain connectivity and behaviors relevant to schizophrenia in animal models. In addition, recent evidence reported a significant reduction of D-aspartate levels in the post-mortem brain of schizophrenia-affected patients, associated to higher DDO activity. In the present work, microdialysis experiments in freely moving mice revealed that exogenously administered D-aspartate efficiently cross the blood brain barrier and stimulates L-glutamate efflux in the prefrontal cortex (PFC). Consistently, D-aspartate was able to evoke L-glutamate release in a preparation of cortical synaptosomes through presynaptic stimulation of NMDA, mGlu5 and AMPA/kainate receptors. In support of a potential therapeutic relevance of D-aspartate metabolism in schizophrenia, in vitro enzymatic assays revealed that the second-generation antipsychotic olanzapine, differently to clozapine, chlorpromazine, haloperidol, bupropion, fluoxetine and amitriptyline, inhibits the human DDO activity. In line with in vitro evidence, chronic systemic administration of olanzapine induces a significant extracellular release of D-aspartate and L-glutamate in the PFC of freely moving mice, which is suppressed in Ddo knockout animals. These results suggest that the second-generation antipsychotic olanzapine, through the inhibition of DDO activity, increases L-glutamate release in the PFC of treated mice. PMID:28393897

Synthesis of poly(N-isopropylacrylamide)-co-poly(phenylboronate ester) acrylate and study on their glucose-responsive behavior.

PubMed

Yao, Yuan; Shen, Heyun; Zhang, Guanghui; Yang, Jing; Jin, Xu

2014-10-01

We introduced thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) into the polymer structure of poly(ethylene glycol)-block-poly(phenylboronate ester) acrylate (MPEG-block-PPBDEMA) by block and random polymerization pathways in order to investigate the effect of polymer architecture on the glucose-responsiveness and enhance their insulin release controllability. By following the structure, the continuous PNIPAM shell of the triblock polymer MPEG-block-PNIPAM-block-PPBDEMA collapsing on the glucose-responsive PPBDEMA core formed the polymeric micelles with a core-shell-corona structure, and MPEG-block-(PNIPAM-rand-PPBDEMA) exhibited core-corona micelles in which the hydrophobic core consisted of PNIPAM and PPBDEMA segments when the environmental temperature was increased above low critical solution temperature (LCST) of PNIPAM. The micellar morphologies can be precisely controlled by temperature change between 15 and 37°C. As a result, the introduction of PNIPAM greatly enhanced the overall stability of insulin encapsulated in the polymeric micelles in the absence of glucose over incubation 80 h at 37°C. Comparing to MPEG-block-PNIPAM-block-PPBDEMA, the nanocarriers from MPEG-block-(PNIPAM-rand-PPBDEMA) showed great insulin release behavior which is zero insulin release without glucose, low release at normal blood glucose concentration (1.0 mg/mL). Therefore, these nanocarriers may be served as promising self-regulated insulin delivery system for diabetes treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Determinants of PDT-induced apoptosis

NASA Astrophysics Data System (ADS)

Kessel, David; Luo, Yu; Kim, Hyeong-Reh C.

2000-03-01

Photodynamic therapy can initiate cell death by apoptosis or necrosis. Using agents with known patterns of sub-cellular localization, we examined the correlation between sites of photodamage and the mode of cell death, using murine leukemia cells in vitro. Mitochondrial or mitochondrial/lysosomal photodamage caused the rapid release of cytochrome c. This effect was not temperature sensitive, and could be demonstrated immediately after irradiation of photosensitized cells at 10 degrees C. Subsequent warming to 37 degrees C led to a rapid apoptotic response, consistent with the known ability of cytochrome c to trigger the activation of caspase-3. In contrast, lysosomal or lysosomal/membrane photodamage resulted in the release of cathepsins and other proteolytic enzymes. A subsequent incubation at 37 degrees C resulted in mitochondrial degradation, leading to loss of cytochrome c within 30 min. The apoptotic response was both delayed and incomplete, with many dead cells not exhibiting an apoptotic morphology. The latter outcome was traced to photodamage to procaspase-3, an effect not observed with sensitizers that caused mainly mitochondrial photodamage. Studies in a cell-free system demonstrated that agents with lysosomal and/or membrane targets could bring about photoinactivation of caspase-3. These result are consistent with the proposal that photodynamic therapy can both activate and inactivate components of the apoptotic process.

Assessment of Complement Activation by Nanoparticles: Development of a SPR Based Method and Comparison with Current High Throughput Methods.

PubMed

Coty, Jean-Baptiste; Noiray, Magali; Vauthier, Christine

2018-04-26

A Surface Plasmon Resonance chip (SPR) was developed to study the activation of complement system triggered by nanomaterials in contact with human serum, which is an important concern today to warrant safety of nanomedicines. The developed chip was tested for its specificity in complex medium and its longevity of use. It was then employed to assess the release of complement fragments upon incubation of nanoparticles in serum. A comparison was made with other current methods assessing complement activation (μC-IE, ELISA). The SPR chip was found to give a consistent response for C3a release upon activation by nanoparticles. Results were similar to those obtained by μC-IE. However, ELISA detection of iC3b fragments showed an explained high non-specific background. The impact of sample preparation preceding the analysis was assessed with the newly develop SPR method. The removal of nanoparticles before analysis showed an important modification in the obtained response, possibly leading to false negative results. The SPR chip developed in this work allows for an automated assessment of complement activation triggered by nanoparticles with possibility of multiplexed analysis. The design of the chip proved to give consistent results of complement activation by nanoparticles.

Investigating the Eddy Diffusivity Concept in the Coastal Ocean

NASA Astrophysics Data System (ADS)

Rypina, I.; Kirincich, A.; Lentz, S. J.; Sundermeyer, M. A.

2016-12-01

We test the validity, utility, and limitations of the lateral eddy diffusivity concept in a coastal environment through analyzing data from coupled drifter and dye releases within the footprint of a high-resolution (800 m) high-frequency radar south of Martha's Vineyard, Massachusetts. Specifically, we investigate how well a combination of radar-based velocities and drifter-derived diffusivities can reproduce observed dye spreading over an 8-h time interval. A drifter-based estimate of an anisotropic diffusivity tensor is used to parameterize small-scale motions that are unresolved and under-resolved by the radar system. This leads to a significant improvement in the ability of the radar to reproduce the observed dye spreading. Our drifter-derived diffusivity estimates are O(10 m2/s), are consistent with the diffusivity inferred from aerial images of the dye taken using the quadcopter-mounted digital camera during the dye release, and are roughly an order of magnitude larger than diffusivity estimates of Okubo (O(1 m2/s)) for similar spatial scales ( 1 km). Despite the fact that the drifter-based diffusivity approach was successful in improving the ability of the radar to reproduce the observed dye spreading, the dispersion of drifters was, for the most part, not consistent with the diffusive spreading regime.

Scientific designs of pine seeds and pine cones for species conservation

NASA Astrophysics Data System (ADS)

Song, Kahye; Yeom, Eunseop; Kim, Hyejeong; Lee, Sang Joon

2015-11-01

Reproduction and propagation of species are the most important missions of every living organism. For effective species propagation, pine cones fold their scales under wet condition to prevent seeds from short-distance dispersal. They open and release their embedded seeds on dry and windy days. In this study, the micro-/macro-scale structural characteristics of pine cones and pine seeds are studied using various imaging modalities. Since the scales of pine cones consist of dead cells, the folding motion is deeply related to structural changes. The scales of pine cones consist of three layers. Among them, bract scales are only involved in collecting water. This makes pine cones reduce the amount of water and minimize the time spent on structural changes. These systems also involve in drying and recovery of pine cones. In addition, pine cones and pine seeds have advantageous structures for long-distance dispersal and response to natural disaster. Owing to these structural features, pine seeds can be released safely and efficiently, and these types of structural advantages could be mimicked for practical applications. This research was financially supported by the Creative Research Initiative of the Ministry of Science, ICT and Future Planning (MSIP) and the National Research Foundation (NRF) of Korea (Contract grant number: 2008-0061991).

Dopamine-assisted fixation of drug-loaded polymeric multilayers to osteoarticular implants for tuberculosis therapy.

PubMed

Li, Dan; Li, Litao; Ma, Yunlong; Zhuang, Yaping; Li, Dawei; Shen, Hong; Wang, Xing; Yang, Fei; Ma, Yuanzheng; Wu, Decheng

2017-03-28

Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment.

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

Bartoletti, T.

SPI/U3.1 consists of five tools used to assess and report the security posture of computers running the UNIX operating system. The tools are: Access Control Test: A rule-based system which identifies sequential dependencies in UNIX access controls. Binary Inspector Tool: Evaluates the release status of system binaries by comparing a crypto-checksum to provide table entries. Change Detection Tool: Maintains and applies a snapshot of critical system files and attributes for purposes of change detection. Configuration Query Language: Accepts CQL-based scripts (provided) to evaluate queries over the status of system files, configuration of services and many other elements of UNIX systemmore » security. Password Security Inspector: Tests for weak or aged passwords. The tools are packaged with a forms-based user interface providing on-line context-sensistive help, job scheduling, parameter management and output report management utilities. Tools may be run independent of the UI.« less

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

Bartoletti, Tony

SPI/U3.2 consists of five tools used to assess and report the security posture of computers running the UNIX operating system. The tools are: Access Control Test: A rule-based system which identifies sequential dependencies in UNIX access controls. Binary Authentication Tool: Evaluates the release status of system binaries by comparing a crypto-checksum to provide table entries. Change Detection Tool: Maintains and applies a snapshot of critical system files and attributes for purposes of change detection. Configuration Query Language: Accepts CQL-based scripts (provided) to evaluate queries over the status of system files, configuration of services and many other elements of UNIX systemmore » security. Password Security Inspector: Tests for weak or aged passwords. The tools are packaged with a forms-based user interface providing on-line context-sensistive help, job scheduling, parameter management and output report management utilities. Tools may be run independent of the UI.« less

The influence of air-conditioning on street temperatures in the city of Paris

NASA Astrophysics Data System (ADS)

de Munck, C. S.; Pigeon, G.; Masson, V.; Marchadier, C.; Meunier, F.; Tréméac, B.; Merchat, M.

2010-12-01

A consequence of urban heat islands in summer is the increased use of air-conditioning during extreme heat events : the use of air-conditioning systems, while cooling the inside of buildings releases waste heat (as latent and sensible heat) in the lower part of the urban atmosphere, hence potentially increasing air street temperatures where the heat is released. This may lead locally to a further increase in air street temperatures, therefore increasing the air cooling demand, while at the same time lowering the efficiency of air-conditioning units. A coupled model consisting of a meso-scale meteorological model (MESO-NH) and an urban energy balance model (TEB) has been implemented with an air-conditioning module and used in combination to real spatialised datasets to understand and quantify potential increases in temperature due to air-conditioning heat releases for the city of Paris . In a first instance, the current types of air-conditioning systems co-existing in the city were simulated (underground chilled water network, wet cooling towers and individual air-conditioning units) to study the effects of latent and sensible heat releases on street temperatures. In a third instance, 2 scenarios were tested to characterise the impacts of likely future trends in air-conditioning equipment in the city : a first scenario for which current heat releases were converted to sensible heat, and a second based on 2030s projections of air-conditioning equipment at the scale of the city. All the scenarios showed an increase in street temperature which, as expected, was greater at night time than day time. For the first two scenarios, this increase in street temperatures was localised at or near the sources of air-conditioner heat releases, while the 2030s air-conditioning scenario impacted wider zones in the city. The amplitude of the increase in temperature varied from 0,25°C to 1°C for the air-conditioning current state, between 0,25°C and 2°C for the sensible heat release only scenario, and finally from 0,25°C to 2 °C for the 2030s scenario, with impacts of up to 3°C locally. Overall, these results demonstrated to which extend the use air-conditioning could enhance street temperatures in the city of Paris and the importance of a spatialised approach.

Radiation signatures from a locally energized flaring loop

NASA Technical Reports Server (NTRS)

Emslie, A. G.; Vlahos, L.

1980-01-01

The radiation signatures from a locally energized solar flare loop based on the physical properties of the energy release mechanisms were consistent with hard X-ray, microwave, and EUV observations for plausible source parameters. It was found that a suprathermal tail of high energy electrons is produced by the primary energy release, and that the number of energetic charged particles ejected into the interplanetary medium in the model is consistent with observations. The radiation signature model predicts that the intrinsic polarization of the hard X-ray burst should increase over the photon energy range of 20 to 100 keV.

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

PubMed

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

2017-03-01

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

Environmental factors that influence cyanobacteria and geosmin occurrence in reservoirs

USGS Publications Warehouse

Journey, Celeste A.; Beaulieu, Karen M.; Bradley, Paul M.; Bradley, Paul M.

2013-01-01

Phytoplankton are small to microscopic, free-floating algae that inhabit the open water of freshwater, estuarine, and saltwater systems. In freshwater lake and reservoirs systems, which are the focus of this chapter, phytoplankton communities commonly consist of assemblages of the major taxonomic groups, including green algae, diatoms, dinoflagellates, and cyanobacteria. Cyanobacteria are a diverse group of single-celled organisms that can exist in a wide range of environments, not just open water, because of their adaptability. It is the adaptability of cyanobacteria that enables this group to dominate the phytoplankton community and even form nuisance or harmful blooms under certain environmental conditions. In fact, cyanobacteria are predicted to adapt favorably to future climate change in freshwater systems compared to other phytoplankton groups because of their tolerance to rising temperatures, enhanced vertical thermal stratification of aquatic ecosystems, and alterations in seasonal and interannual weather patterns. Understanding those environmental conditions that favor cyanobacterial dominance and bloom formation has been the focus of research throughout the world because of the concomitant production and release of nuisance and toxic cyanobacterial-derived compounds. However, the complex interaction among the physical, chemical, and biological processes within lakes, reservoirs, and large rivers often makes it difficult to identify primary environmental factors that cause the production and release of these cyanobacterial by-products.

New high-throughput measurement systems for radioactive wastes segregation and free release.

PubMed

Suran, J; Kovar, P; Smoldasova, J; Solc, J; Skala, L; Arnold, D; Jerome, S; de Felice, P; Pedersen, B; Bogucarska, T; Tzika, F; van Ammel, R

2017-12-01

This paper addresses the measurement facilities for pre-selection of waste materials prior to measurement for repository acceptance or possible free release (segregation measurement system); and free release (free release measurement system), based on a single standardized concept characterized by unique, patented lead-free shielding. The key objective is to improve the throughput, accuracy, reliability, modularity and mobility of segregation and free-release measurement. This will result in a more reliable decision-making with regard to the safe release and disposal of radioactive wastes into the environment and, resulting in positive economic outcomes. The research was carried out within "Metrology for Decommissioning Nuclear Facilities" (MetroDecom) project. Copyright © 2017 Elsevier Ltd. All rights reserved.

Readily releasable pool of synaptic vesicles measured at single synaptic contacts.

PubMed

Trigo, Federico F; Sakaba, Takeshi; Ogden, David; Marty, Alain

2012-10-30

To distinguish between different models of vesicular release in brain synapses, it is necessary to know the number of vesicles of transmitter that can be released immediately at individual synapses by a high-calcium stimulus, the readily releasable pool (RRP). We used direct stimulation by calcium uncaging at identified, single-site inhibitory synapses to investigate the statistics of vesicular release and the size of the RRP. Vesicular release, detected as quantal responses in the postsynaptic neuron, showed an unexpected stochastic variation in the number of quanta from stimulus to stimulus at high intracellular calcium, with a mean of 1.9 per stimulus and a maximum of three or four. The results provide direct measurement of the RRP at single synaptic sites. They are consistent with models in which release proceeds from a small number of vesicle docking sites with an average occupancy around 0.7.

SPALAX new generation: New process design for a more efficient xenon production system for the CTBT noble gas network.

PubMed

Topin, Sylvain; Greau, Claire; Deliere, Ludovic; Hovesepian, Alexandre; Taffary, Thomas; Le Petit, Gilbert; Douysset, Guilhem; Moulin, Christophe

2015-11-01

The SPALAX (Système de Prélèvement Automatique en Ligne avec l'Analyse du Xénon) is one of the systems used in the International Monitoring System of the Comprehensive Nuclear Test Ban Treaty (CTBT) to detect radioactive xenon releases following a nuclear explosion. Approximately 10 years after the industrialization of the first system, the CEA has developed the SPALAX New Generation, SPALAX-NG, with the aim of increasing the global sensitivity and reducing the overall size of the system. A major breakthrough has been obtained by improving the sampling stage and the purification/concentration stage. The sampling stage evolution consists of increasing the sampling capacity and improving the gas treatment efficiency across new permeation membranes, leading to an increase in the xenon production capacity by a factor of 2-3. The purification/concentration stage evolution consists of using a new adsorbent Ag@ZSM-5 (or Ag-PZ2-25) with a much larger xenon retention capacity than activated charcoal, enabling a significant reduction in the overall size of this stage. The energy consumption of the system is similar to that of the current SPALAX system. The SPALAX-NG process is able to produce samples of almost 7 cm(3) of xenon every 12 h, making it the most productive xenon process among the IMS systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Comparative Study on the Lot Release Systems for Vaccines as of 2016.

PubMed

Fujita, Kentaro; Naito, Seishiro; Ochiai, Masaki; Konda, Toshifumi; Kato, Atsushi

2017-09-25

Many countries have already established their own vaccine lot release system that is designed for each country's situation: while the World Health Organization promotes for the convergence of these regulatory systems so that vaccines of assured quality are provided globally. We conducted a questionnaire-based investigation of the lot release systems for vaccines in 7 countries and 2 regions. We found that a review of the summary protocol by the National Regulatory Authorities was commonly applied for the independent lot release of vaccines, however, we also noted some diversity between countries, especially in regard to the testing policy. Some countries and regions, including Japan, regularly tested every lot of vaccines, whereas the frequency of these tests was reduced in other countries and regions as determined based on the risk assessment of these products. Test items selected for the lot release varied among the countries or regions investigated, although there was a tendency to prioritize the potency tests. An understanding of the lot release policy may contribute to improving and harmonizing the lot release system globally in the future.

Assembled modules technology for site-specific prolonged delivery of norfloxacin.

PubMed

Oliveira, Paulo Renato; Bernardi, Larissa Sakis; Strusi, Orazio Luca; Mercuri, Salvatore; Segatto Silva, Marcos A; Colombo, Paolo; Sonvico, Fabio

2011-02-28

The aim of this research was to design and study norfloxacin (NFX) release in floating conditions from compressed hydrophilic matrices of hydroxypropylmethylcellulose (HPMC) or poly(ethylene oxide) (PEO). Module assembling technology for drug delivery system manufacturing was used. Two differently cylindrical base curved matrix/modules, identified as female and male, were assembled in void configuration by friction interlocking their concave bases obtaining a floating release system. Drug release and floatation behavior of this assembly was investigated. Due to the higher surface area exposed to the release medium, faster release was observed for individual modules compared to their assembled configuration, independently on the polymer used and concentration. The release curves analyzed using the Korsmeyer exponential equation and Peppas & Sahlin binomial equation showed that the drug release was controlled both by drug diffusion and polymer relaxation or erosion mechanisms. However, convective transport was predominant with PEO and at low content of polymers. NFX release from PEO polymeric matrix was more erosion dependent than HPMC. The assembled systems were able to float in vitro for up to 240min, indicating that this drug delivery system of norfloxacin could provide gastro-retentive site-specific release for increasing norfloxacin bioavailability. Copyright © 2010. Published by Elsevier B.V.

Spokane Tribal Hatchery, 2005 Annual Report.

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

Peone, Tim L.

2006-03-01

Due to the construction and operation of Grand Coulee Dam (1939), anadromous salmon have been eradicated and resident fish populations permanently altered in the upper Columbia River region. Federal and private hydropower dam operations throughout the Columbia River system severely limits indigenous fish populations in the upper Columbia. Artificial production has been determined appropriate for supporting harvestable fisheries for kokanee salmon (Oncorhynchus nerka) and rainbow trout (Oncorhynchus mykiss) in Lake Roosevelt and Banks Lake (Grand Coulee Dam impoundments). The Spokane Tribe, Washington Department of Fish and Wildlife, Colville Confederated Tribes and Lake Roosevelt Development Association/Lake Roosevelt Volunteer Net Pen Projectmore » are cooperating in a comprehensive artificial production program to produce kokanee salmon (Oncorhynchus nerka) and rainbow trout (Oncorhynchus mykiss) for annual releases into the project area. The program consists of the Spokane Tribal Hatchery, Sherman Creek Hatchery, Ford Trout Hatchery and Lake Roosevelt Rainbow Trout Net Pen Rearing Projects. The Lake Roosevelt and Banks Lake Fisheries Evaluation Program monitor and evaluates release strategies and production methods for the aforementioned projects. Between 1985 and 2005 the projects have collectively produced up to 800,000 rainbow trout and 4 million kokanee salmon for release into Lake Roosevelt and 1.4 million kokanee fry for Banks Lake annually. In 2005, the annual release goal included 3.3 million kokanee fry, 475,000 kokanee yearlings and 500,000 rainbow trout yearlings. Fish produced by this project in 2005 to meet collective fish production and release goals included: 3,446,438 kokanee fingerlings, 347,730 rainbow trout fingerlings and 525,721 kokanee yearlings. Kokanee yearlings were adipose fin clipped before release. Stock composition consisted of Meadow Creek and Lake Whatcom kokanee, diploid-triploid Spokane Trout Hatchery (McCloud River) rainbow trout and Phalon Lake red-band rainbow trout. All kokanee were marked with either thermal, oxytetracyline or fin clips prior to release. Preliminary 2004 Lake Roosevelt fisheries investigations indicate hatchery/net pen stocking significantly contributed to rainbow trout catch and harvest rates while the impact on the kokanee fishery was minimal. Success of the Lake Roosevelt kokanee artificial production program appears to be limited primarily owing to predation, precocity and high entrainment rates through Grand Coulee Dam. Recommendations for future hatchery/net pen operations include use of stocks compatible or native to the upper Columbia River, continue kokanee fry and post-smolt releases, 100% triploid hatchery stock rainbow trout used and adipose fin clip hatchery stock rainbow trout prior to release. The Spokane Tribal Hatchery is funded by the Bonneville Power Administration under directives by the Northwest Power Conservation Council Columbia River Basin Fish & Wildlife Program, Resident Fish Substitution Measures, 1987 to current (Subbasin Plan), as partial mitigation for anadromous and resident fish losses in the blocked areas above Chief Joseph and Grand Coulee Dams.« less

Lipid transfer in oil-in-water isasome emulsions: influence of arrested dynamics of the emulsion droplets entrapped in a hydrogel.

PubMed

Iglesias, Guillermo Ramón; Pirolt, Franz; Sadeghpour, Amin; Tomšič, Matija; Glatter, Otto

2013-12-17

The transfer kinetics of lipids between internally self-assembled droplets of O/W emulsions is studied. The droplets (isasomes) consist of various liquid-crystalline phases or W/O microemulsions stabilized by a polymeric stabilizer F127. The various internal phases were identified by the relative peak positions in the small-angle X-ray scattering (SAXS) curves. An arrested system composed of isasomes embedded in a gel matrix actually provides an additional possibility to control these systems in terms of the release of various host molecules. These experiments have been applied to examine the kinetics of the internal phase reorganization imposed by the lipids' release and uptake by the droplets embedded in a κ-carrageenan (KC) hydrogel network. Increasing the concentration of the gelling agent slows down the transfer from one droplet to the other through the aqueous phase. We examined the region where the free diffusion is stopped. i.e., the point where the system changes from the ergodic to the nonergodic state and the kinetics is essentially slowed down. This effect can be balanced by the addition of small amounts of free polymeric stabilizer, which speeds up the kinetics. This is even possible in the case of highly arrested dynamics of the emulsion droplets, as found for the highest KC hydrogel concentrations forming nonergodic systems.

Safinamide Differentially Modulates In Vivo Glutamate and GABA Release in the Rat Hippocampus and Basal Ganglia.

PubMed

Morari, Michele; Brugnoli, Alberto; Pisanò, Clarissa Anna; Novello, Salvatore; Caccia, Carla; Melloni, Elsa; Padoani, Gloria; Vailati, Silvia; Sardina, Marco

2018-02-01

Safinamide has been recently approved as an add-on to levodopa therapy for Parkinson disease. In addition to inhibiting monoamine oxidase type B, it blocks sodium channels and modulates glutamate (Glu) release in vitro. Since this property might contribute to the therapeutic action of the drug, we undertook the present study to investigate whether safinamide inhibits Glu release also in vivo and whether this effect is consistent across different brain areas and is selective for glutamatergic neurons. To this aim, in vivo microdialysis was used to monitor the spontaneous and veratridine-induced Glu and GABA release in the hippocampus and basal ganglia of naive, awake rats. Brain levels of safinamide were measured as well. To shed light on the mechanisms underlying the effect of safinamide, sodium currents were measured by patch-clamp recording in rat cortical neurons. Safinamide maximally inhibited the veratridine-induced Glu and GABA release in hippocampus at 15 mg/kg, which reached free brain concentrations of 1.89-1.37 µ M. This dose attenuated veratridine-stimulated Glu (but not GABA) release in subthalamic nucleus, globus pallidus, and substantia nigra reticulata, but not in striatum. Safinamide was ineffective on spontaneous neurotransmitter release. In vitro, safinamide inhibited sodium channels, showing a greater affinity at depolarized (IC 50 = 8 µ M) than at resting (IC 50 = 262 µ M) potentials. We conclude that safinamide inhibits in vivo Glu release from stimulated nerve terminals, likely via blockade of sodium channels at subpopulations of neurons with specific firing patterns. These data are consistent with the anticonvulsant and antiparkinsonian actions of safinamide and provide support for the nondopaminergic mechanism of its action. Copyright © 2018 The Author(s).

Tapioca starch graft copolymers and Dome Matrix® modules II. Effect of modules assemblage on riboflavin release kinetics.

PubMed

Casas, Marta; Strusi, Orazio Luca; Jiménez-Castellanos, M Rosa; Colombo, Paolo

2011-01-01

This paper studies the Riboflavin release from systems made of assembled modules of Dome Matrix® technology using tapioca starch-ethylmethacrylate (TSEMA) and tapioca hydroxypropylstarch-ethylmethacrylate (THSEMA) graft copolymers produced by two different drying methods. Two different shape modules were manufactured for this study, i.e., female and male modules, in order to facilitate their assemblage in "void configuration", a system with an internal void space. Drug release studies on void configurations based on THSEMA show faster releases than TSEMA; HPMC systems used as a comparative reference showed intermediate release. Moreover, using void configurations made with one module of TSEMA and the other of THSEMA is possible to average the drug release, without difference between the drying methods used for the polymers. With respect to the floatation characteristics, all the void configurations floated immediately and, due to the mass center of the system, the floatation position of the system was always axial with the female module up and the male down. The drug release studies performed with a sinker to force the immersion of the systems in the medium did not show differences with respect to the dissolution test without a sinker. The combination of floatation capability of the assembled modules and the prolonged drug release provided with the graft copolymers make these assembled modules candidates as controlled release gastro-retentive dosage forms. Copyright © 2010 Elsevier B.V. All rights reserved.

Constraining the Dynamics of Periodic Behavior at Mt. Semeru, Indonesia, Combining Numerical Modeling and Field Measurements of Gas emission

NASA Astrophysics Data System (ADS)

Smekens, J.; Clarke, A. B.; De'Michieli Vitturi, M.; Moore, G. M.

2012-12-01

Mt. Semeru is one of the most active explosive volcanoes on the island of Java in Indonesia. The current eruption style consists of small but frequent explosions and/or gas releases (several times a day) accompanied by continuous lava effusion that sporadically produces block-and-ash flows down the SE flank of the volcano. Semeru presents a unique opportunity to investigate the magma ascent conditions that produce this kind of persistent periodic behavior and the coexistence of explosive and effusive eruptions. In this work we use DOMEFLOW, a 1.5D transient isothermal numerical model, to investigate the dynamics of lava extrusion at Semeru. Petrologic observations from tephra and ballistic samples collected at the summit help us constrain the initial conditions of the system. Preliminary model runs produced periodic lava extrusion and pulses of gas release at the vent, with a cycle period on the order of hours, even though a steady magma supply rate was prescribed at the bottom of the conduit. Enhanced shallow permeability implemented in the model appears to create a dense plug in the shallow subsurface, which in turn plays a critical role in creating and controlling the observed periodic behavior. We measured SO2 fluxes just above the vent, using a custom UV imaging system. The device consists of two high-sensitivity CCD cameras with narrow UV filters centered at 310 and 330 nm, and a USB2000+ spectrometer for calibration and distance correction. The method produces high-frequency flux series with an accurate determination of the wind speed and plume geometry. The model results, when combined with gas measurements, and measurements of sulfur in both the groundmass and melt inclusions in eruptive products, could be used to create a volatile budget of the system. Furthermore, a well-calibrated model of the system will ultimately allow the characteristic periodicity and corresponding gas flux to be used as a proxy for magma supply rate.

Interface requirements to couple thermal-hydraulic codes to severe accident codes: ATHLET-CD

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

Trambauer, K.

1997-07-01

The system code ATHLET-CD is being developed by GRS in cooperation with IKE and IPSN. Its field of application comprises the whole spectrum of leaks and large breaks, as well as operational and abnormal transients for LWRs and VVERs. At present the analyses cover the in-vessel thermal-hydraulics, the early phases of core degradation, as well as fission products and aerosol release from the core and their transport in the Reactor Coolant System. The aim of the code development is to extend the simulation of core degradation up to failure of the reactor pressure vessel and to cover all physically reasonablemore » accident sequences for western and eastern LWRs including RMBKs. The ATHLET-CD structure is highly modular in order to include a manifold spectrum of models and to offer an optimum basis for further development. The code consists of four general modules to describe the reactor coolant system thermal-hydraulics, the core degradation, the fission product core release, and fission product and aerosol transport. Each general module consists of some basic modules which correspond to the process to be simulated or to its specific purpose. Besides the code structure based on the physical modelling, the code follows four strictly separated steps during the course of a calculation: (1) input of structure, geometrical data, initial and boundary condition, (2) initialization of derived quantities, (3) steady state calculation or input of restart data, and (4) transient calculation. In this paper, the transient solution method is briefly presented and the coupling methods are discussed. Three aspects have to be considered for the coupling of different modules in one code system. First is the conservation of masses and energy in the different subsystems as there are fluid, structures, and fission products and aerosols. Second is the convergence of the numerical solution and stability of the calculation. The third aspect is related to the code performance, and running time.« less

77 FR 52393 - Petition for Exemption From the Vehicle Theft Prevention Standard; BMW of North America, LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

... International Policy, Fuel Economy and Consumer Programs, National Highway Traffic Safety Administration, 1200... key, powered by a battery and consists of a transmitter/receiver which communicates with the EWS... and starter. The ignition and fuel supply are only released when a correct coded release signal has...

43 CFR 2.2 - What is DOI's policy regarding release of records under the FOIA?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false What is DOI's policy regarding release of... RECORDS AND TESTIMONY; FREEDOM OF INFORMATION ACT General Information § 2.2 What is DOI's policy regarding... public consistent with the spirit of the FOIA and the Privacy Act. ...

Missouri Assessment Program (MAP), Spring 2000: Elementary Health/Physical Education, Released Items, Grade 5.

ERIC Educational Resources Information Center

Missouri State Dept. of Elementary and Secondary Education, Jefferson City.

This document presents 10 released items from the Health/Physical Education Missouri Assessment Program (MAP) test given in the spring of 2000 to fifth graders. Items from the test sessions include: selected-response (multiple choice), constructed-response, and a performance event. The selected-response items consist of individual questions…

77 FR 2726 - General Services Administration Acquisition Regulation; Information Collection; Contract...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... Claims, regarding final payment under construction and building services contract. GSA Form 1142 was... (GSAR Part 532 and 552.232-72; GSA Form 1142 Release of Claims) AGENCY: Office of the Chief Acquisition... have used this form to achieve uniformity and consistency in the release of claims process. Public...

77 FR 38705 - Public Notice for Waiver of Aeronautical Land-Use Assurance; Chan Gurney Municipal Airport...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-28

... Aeronautical Land-Use Assurance; Chan Gurney Municipal Airport,Yankton, SD AGENCY: Federal Aviation... the Chan Gurney Municipal Airport, Yankton, South Dakota. The proposal consists of the trade of... airport property to be released at the Chan Gurney Municipal Airport. This property for release is for a...

Release of the ENDF/B-VII.1 Evaluated Nuclear Data File

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

Brown, David

2012-06-30

The Cross Section Evaluation Working Group (CSEWG) released the ENDF/B-VII.1 library on December 22, 2011. The ENDF/B-VII.1 library is CSEWG's latest recommended evaluated nuclear data file for use in nuclear science and technology applications, and incorporates advances made in the five years since the release of ENDF/B-VII.0, including: many new evaluation in the neutron sublibrary (423 in all and over 190 of these contain covariances), new fission product yields and a greatly improved decay data sublibrary. This summary barely touches on the five years worth of advances present in the ENDF/B-VII.1 library. We expect that these changes will lead tomore » improved integral performance in reactors and other applications. Furthermore, the expansion of covariance data in this release will allow for better uncertainty quantification, reducing design margins and costs. The ENDF library is an ongoing and evolving effort. Currently, the ENDF data community embarking on several parallel efforts to improve library management: (1) The adoption of a continuous integration system to provide evaluators 'instant' feedback on the quality of their evaluations and to provide data users with working 'beta' quality libraries in between major releases. (2) The transition to new hierarchical data format - the Generalized Nuclear Data (GND) format. We expect GND to enable new kinds of evaluated data which cannot be accommodated in the legacy ENDF format. (3) The development of data assimilation and uncertainty propagation techniques to enable the consistent use of integral experimental data in the evaluation process.« less

Microenvironmental pH is a key factor for exosome traffic in tumor cells.

PubMed

Parolini, Isabella; Federici, Cristina; Raggi, Carla; Lugini, Luana; Palleschi, Simonetta; De Milito, Angelo; Coscia, Carolina; Iessi, Elisabetta; Logozzi, Mariantonia; Molinari, Agnese; Colone, Marisa; Tatti, Massimo; Sargiacomo, Massimo; Fais, Stefano

2009-12-04

Exosomes secreted by normal and cancer cells carry and deliver a variety of molecules. To date, mechanisms referring to tumor exosome trafficking, including release and cell-cell transmission, have not been described. To gain insight into this, exosomes purified from metastatic melanoma cell medium were labeled with a lipid fluorescent probe, R18, and analyzed by spectrofluorometry and confocal microscopy. A low pH condition is a hallmark of tumor malignancy, potentially influencing exosome release and uptake by cancer cells. Using different pH conditions as a modifier of exosome traffic, we showed (i) an increased exosome release and uptake at low pH when compared with a buffered condition and (ii) exosome uptake by melanoma cells occurred by fusion. Membrane biophysical analysis, such as fluidity and lipid composition, indicated a high rigidity and sphingomyelin/ganglioside GM3 (N-acetylneuraminylgalactosylglucosylceramide) content in exosomes released at low pH. This was likely responsible for the increased fusion efficiency. Consistent with these results, pretreatment with proton pump inhibitors led to an inhibition of exosome uptake by melanoma cells. Fusion efficiency of tumor exosomes resulted in being higher in cells of metastatic origin than in those derived from primary tumors or normal cells. Furthermore, we found that caveolin-1, a protein involved in melanoma progression, is highly delivered through exosomes released in an acidic condition. The results of our study provide the evidence that exosomes may be used as a delivery system for paracrine diffusion of tumor malignancy, in turn supporting the importance of both exosomes and tumor pH as key targets for future anti-cancer strategies.

Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

PubMed Central

Song, Zhilin; Levin, Barry E.; Stevens, Wanida

2014-01-01

Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca2+]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P < 0.002). Oxytocin release was increased by glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating KATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P < 0.003; VP: P < 0.05). These results suggest that insulin activation of PI3K increases glucokinase-mediated ATP production inducing closure of KATP channels, opening of voltage-sensitive calcium channels, and stimulation of oxytocin and vasopressin release. The findings are consistent with SON oxytocin and vasopressin neurons functioning as glucose and “metabolic” sensors to participate in appetite regulation. PMID:24477542

Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors.

PubMed

Song, Zhilin; Levin, Barry E; Stevens, Wanida; Sladek, Celia D

2014-04-01

Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca(2+)]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P < 0.002). Oxytocin release was increased by glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating K ATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P < 0.003; VP: P < 0.05). These results suggest that insulin activation of PI3K increases glucokinase-mediated ATP production inducing closure of K ATP channels, opening of voltage-sensitive calcium channels, and stimulation of oxytocin and vasopressin release. The findings are consistent with SON oxytocin and vasopressin neurons functioning as glucose and "metabolic" sensors to participate in appetite regulation.

PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery.

PubMed

Chan, Juliana M; Zhang, Liangfang; Yuet, Kai P; Liao, Grace; Rhee, June-Wha; Langer, Robert; Farokhzad, Omid C

2009-03-01

Current approaches to encapsulate and deliver therapeutic compounds have focused on developing liposomal and biodegradable polymeric nanoparticles (NPs), resulting in clinically approved therapeutics such as Doxil/Caelyx and Genexol-PM, respectively. Our group recently reported the development of biodegradable core-shell NP systems that combined the beneficial properties of liposomal and polymeric NPs for controlled drug delivery. Herein we report the parameters that alter the biological and physicochemical characteristics, stability, drug release properties and cytotoxicity of these core-shell NPs. We further define scalable processes for the formulation of these NPs in a reproducible manner. These core-shell NPs consist of (i) a poly(D,L-lactide-co-glycolide) hydrophobic core, (ii) a soybean lecithin monolayer, and (iii) a poly(ethylene glycol) shell, and were synthesized by a modified nanoprecipitation method combined with self-assembly. Preparation of the NPs showed that various formulation parameters such as the lipid/polymer mass ratio and lipid/lipid-PEG molar ratio controlled NP physical stability and size. We encapsulated a model chemotherapy drug, docetaxel, in the NPs and showed that the amount of lipid coverage affected its drug release kinetics. Next, we demonstrated a potentially scalable process for the formulation, purification, and storage of NPs. Finally, we tested the cytotoxicity using MTT assays on two model human cell lines, HeLa and HepG2, and demonstrated the biocompatibility of these particles in vitro. Our data suggest that the PLGA-lecithin-PEG core-shell NPs may be a useful new controlled release drug delivery system.

Mechanistic modelling of drug release from polymer-coated and swelling and dissolving polymer matrix systems.

PubMed

Kaunisto, Erik; Marucci, Mariagrazia; Borgquist, Per; Axelsson, Anders

2011-10-10

The time required for the design of a new delivery device can be sensibly reduced if the release mechanism is understood and an appropriate mathematical model is used to characterize the system. Once all the model parameters are obtained, in silico experiments can be performed, to provide estimates of the release from devices with different geometries and compositions. In this review coated and matrix systems are considered. For coated formulations, models describing the diffusional drug release, the osmotic pumping drug release, and the lag phase of pellets undergoing cracking in the coating due to the build-up of a hydrostatic pressure are reviewed. For matrix systems, models describing pure polymer dissolution, diffusion in the polymer and drug release from swelling and eroding polymer matrix formulations are reviewed. Importantly, the experiments used to characterize the processes occurring during the release and to validate the models are presented and discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Production of bioinspired and rationally designed polymer hydrogels for controlled delivery of therapeutic proteins

NASA Astrophysics Data System (ADS)

Kim, Sung Hye

Hydrogel systems for controlled delivery therapeutic growth factors have been developed in a wide spectrum of strategies: these systems aim for the release of growth factors via a passive diffusion, electrostatic interaction, degradation of hydrogels, and responsiveness to external stimuli. Heparin, a highly sulfated glycosaminoglycan (GAG), was employed for a targeted delivery system of vascular endothelial growth factor (VEGF) to endothelial cells overexpressing a relevant receptor VEGFR-2. Addition of dimeric VEGF to 4-arm star-shaped poly(ethylene glycol) (PEG) immobilized with low-molecular weight heparin (LMWH) afforded a non-covalently assembled hydrogel via interaction between heparin and VEGF, with storage modulus 10 Pa. The release of VEGF and hydrogel erosion reached maximum 100 % at day 4 in the presence of VEGFR-2 overexpressing pocine aortic endothelial cell (PAE/KDR), while those of 80% were achieved via passive release at day 5 in the presence of PAE cell lacking VEGFR-2 or in the absence of cell, indicating that the release of VEGF was in targeted manner toward cell receptor. The proliferation of PAE/KDR in the presence of [PEG-LMWH/VEGF] hydrogel was greater by ca. 30% at day 4 compared to that of PAE, confirming that the release of VEGF was in response to the cellular demand. The phosphorylation fraction of VEGFR-2 on PAE/KDR was greater in the presence of [PEG-LMWH/VEGF] hydrogel, increasing from 0.568 at day 1 to 0.790 at day 4, whereas it was maintained at 0.230 at day 4 in the presence of [PEG-LMWH] hydrogel. This study has proven that this hydrogel, assembled via bio-inspired non-covalent interaction, liberating VEGFon celluar demand to target cell, eroding upon VEGF release, and triggering endothelial cell proliferation, could be used in multiple applications including targeted delivery and angiogenesis. Heparin has been widely exploited in growth factor delivery systems owing to its ability to bind many growth factors through the flexible patterns of functional groups. However, heterogeneity in the composition and in the polydispersity of heparin has been problematic in controlled delivery system and thus motivated the development of homogeneous heparin mimics. Peptides of appropriate sequence and chemical function have therefore recently emerged as potential replacements for heparin in select applications. Studied was the assessment of the binding affinities of multiple sulfated peptides (SPs) for a set of heparin-binding peptides (HBPs) and for VEGF; these binding partners have application in the selective immobilization of proteins and in hydrogel formation through non-covalent interactions. Sulfated peptides were produced via solid-phase methods, and their affinity for the HBPs and VEGF was assessed via affinity liquid chromatography (ALC), surface plasmon resonance (SPR), and in select cases, isothermal titration calorimetry (ITC). The shortest peptide, SPa, showed the highest affinity binding of HBPs and VEGF165 in both ALC and SPR measurements, with slight exceptions. Of the investigated HBPs, a peptide based on the heparin-binding domain of human platelet factor 4 showed greatest binding affinities toward all of the SPs, consistent with its stronger binding to heparin. The affinity between SPa and PF4ZIP was indicated via SPR ( KD = 5.27 muM) and confirmed via ITC (KD = 8.09 muM). The binding by SPa of both VEGF and HBPs suggests its use as a binding partner to multiple species, and the use of these interactions in assembly of materials. Given that the peptide sequences can be varied to control binding affinity and selectivity, opportunities are also suggested for the production of a wider array of matrices with selective binding and release properties useful for biomaterials applications. Hydrogel consisting of SPa was formed via a covalent Michael Addition reaction between maleimide- and thiol-terminated multi-arm PEGs and Cys-SPa. The mechanical property of hydrogel was tunable from ca. 186 to 1940 Pa. by varing the cross-linking density, suggesting its flexible applications depending on matrix needs. The non-anti-coagulative property of SPa, assessed via activated partial thromboplastin time (APTT) and HeptestRTM in comparison to LMWH, implied its usefulness in applications without excessive bleeding. The VEGF released from [PEG-SPa] hydrogel showed up to ca. 400% greater bioactivity on proliferation of human umbilical vein endothelical cell (HUVEC) compared to the VEGF incubated in solution for the same period: this was significantly higher than that of [PEG] hydrogel (ca. 280%), suggesting the SPa may protect the bioactivity of VEGF when bound. The release of dual growth factor, i.e. VEGF and fibroblast growth factor-2 (FGF-2), were investigated on [PEG-SPa] hydrogel: the release of bFGF was lower than that of VEGF due to weaker binding affinity to matrix-bound SPa. The HUVEC culture on dual growth factor loaded [PEG-SPa] showed that the synergistic effects of dual system in select concentrations, suggesting the opportunity of manipulating cell responses. Given that sulfated peptides for various binding targets with desired affinity can be identified, applications are suggested in multiple growth factors delivery where an integrated action of multiple growth factors is required, such as angiogenesis.

Identifying trout refuges in the Indian and Hudson Rivers in northern New York through airborne thermal infrared remote sensing

USGS Publications Warehouse

Ernst, Anne G.; Baldigo, Barry P.; Calef, Fred J.; Freehafer, Douglas A.; Kremens, Robert L.

2015-10-09

The locations and sizes of potential cold-water refuges for trout were examined in 2005 along a 27-kilometer segment of the Indian and Hudson Rivers in northern New York to evaluate the extent of refuges, the effects of routine flow releases from an impoundment, and how these refuges and releases might influence trout survival in reaches that otherwise would be thermally stressed. This river segment supports small populations of brook trout (Salvelinus fontinalis), brown trout (Salmo trutta), and rainbow trout (Oncorhynchus mykiss) and also receives regular releases of reservoir-surface waters to support rafting during the summer, when water temperatures in both the reservoir and the river frequently exceed thermal thresholds for trout survival. Airborne thermal infrared imaging was supplemented with continuous, in-stream temperature loggers to identify potential refuges that may be associated with tributary inflows or groundwater seeps and to define the extent to which the release flows decrease the size of existing refuges. In general, the release flows overwhelmed the refuge areas and greatly decreased the size and number of the areas. Mean water temperatures were unaffected by the releases, but small-scale heterogeneity was diminished. At a larger scale, water temperatures in the upper and lower segments of the reach were consistently warmer than in the middle segment, even during passage of release waters. The inability of remote thermal infrared images to consistently distinguish land from water (in shaded areas) and to detect groundwater seeps (away from the shallow edges of the stream) limited data analysis and the ability to identify potential thermal refuge areas.

[Controlled release of prednisolone from suppository prepared using powder of pulverized tablet].

PubMed

Tatsumi, Akitoshi; Oda, Shoko; Nakamoto, Tomoko; Muraoka, Reiko; Takahashi, Yoshiko; Tanaka, Kuniyoshi; Shikata, Toshiyuki; Tatsumi, Sumiyo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hamaguchi, Tsuneo; Kadobayashi, Muneo

2008-04-01

Prednisolone suppositories have been used successfully for the treatment of ulcerative colitis in hospital settings. However, the raw material of prednisolone suppository, JP prednisolone powder (JP Powder), was recently removed from the market. Therefore we studied the effects of raw material and suppository base on the release of prednisolone suppository for the purpose of designing a new suppository with similar effects to those of suppository prepared using JP powder (old suppository). New suppositories consisting of the powder of pulverized tablet as raw material and Witepsol H-15 and Witepsol E-75 as suppository base were prepared according to the fusion method. Suppository release test was performed by reciprocating dialysis tube method with tapping (RDT method) and dialysis tubing method (DT method). Both RDT method and DT method were performed using a suppository dissolution apparatus (modified JP disintegration apparatus) and a JP15 paddle apparatus, respectively. The test fluid was 50 mM phosphate buffer solution (pH 7.4) maintained at 37+/-0.5 degrees C. The results of release test by RDT method were similar to those of DT method. Release rate of prednisolone from the new suppository was much faster than that of old suppository. The addition of Witepsol E-75 to new suppository base markedly delayed the release of prednisolone from the new suppository. Release rate of prednisolone from the new suppository, consisting of pulverized tablet and Witepsol H-15 and Witepsol E-75 (76:24), corresponded well with that of the old suppository. It was suggested that this suppository could be used as incoming preparation of suppository prepared using JP powder.

Status of CSR RL06 GRACE reprocessing and preliminary results

NASA Astrophysics Data System (ADS)

Save, H.

2017-12-01

The GRACE project plans to re-processes the GRACE mission data in order to be consistent with the first gravity products released by the GRACE-FO project. The RL06 reprocessing will harmonize the GRACE time-series with the first release of GRACE-FO. This paper catalogues the changes in the upcoming RL06 release and discusses the quality improvements as compared to the current RL05 release. The processing and parameterization changes as compared to the current release are also discussed. This paper discusses the evolution of the quality of the GRACE solutions and characterize the errors over the past few years. The possible challenges associated with connecting the GRACE time series with that from GRACE-FO are also discussed.

Development of extended-release solid dispersion granules of tacrolimus: evaluation of release mechanism and human oral bioavailability.

PubMed

Tsunashima, Daisuke; Yamashita, Kazunari; Ogawara, Ken-Ichi; Sako, Kazuhiro; Hakomori, Tadashi; Higaki, Kazutaka

2017-12-01

We aimed to prepare a once-daily modified-release oral formulation of tacrolimus by utilizing an extended-release granules (ERG). Extended-release granules were prepared using ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC) and lactose via a solvent evaporation method with ethanol. Physicochemical and biopharmaceutical studies were performed to determine the formulation with optimum release profile of tacrolimus from ERG. Tacrolimus existed in an amorphous state in ERG. Tacrolimus release from ERG was attenuated by EC and facilitated by lactose, suggesting that drug release kinetics could adequately be regulated by these components. Those release profiles were consistent with Higuchi's equation, suggesting a diffusion-type release mechanism. Smooth surface of ERG changed to the structure with pores after the release test, likely derived from the dissolution of HPMC and lactose. But ERG structure formed by EC was still maintained after the release test, leading to the longer maintenance of diffusion-type release. Two ERG formulations selected by blood concentration simulation successfully provided long-term retention of tacrolimus in blood in a human absorption study. We successfully developed the formulation exhibiting a significant reduction in C max , the longer mean residence time and AUC close to that of an immediate-release tacrolimus formulation, being preferred from the viewpoint of safe and effective immunosuppressant pharmacotherapy. © 2017 Royal Pharmaceutical Society.

Is antibiotic prophylaxis mandatory after the insertion of levonorgestrel-releasing intrauterine systemin order to decrease the risk of pelvic inflammatory disease?

PubMed Central

Munteanu, O; Radulescu, L; Bodean, O; Cirstoiu, C; Secara, D; Cirstoiu, M

2013-01-01

Abstract Objective: This study was undertaken in order to determine if antibiotic prophylaxis is mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. Materials and methods: We prospectively evaluated 44 patients, admitted in the Bucharest Emergency Hospital between the 1ⁱ of February 2012 and the 1ⁱ of October 2012, in whom the levonorgestrel-releasing intrauterine system was inserted. The patients enrolled were divided into two groups. In group A, a number of 22 patients, received, after the insertion of levonorgestrel-releasing intrauterine system, 875mg Amoxicillin Trihydrate + 125 mg Potassium Clavulanate, a dose every 12 hours for 5 days. Group B was represented by the other 22 patients who did not receive antibiotic prophylaxis. All patients were reevaluated at 4 and 12 weeks after the insertion of levonorgestrel-releasing intrauterine system. Results: During the first 4 weeks after the insertion of levonorgestrel-releasing intrauterine system only two patients, one from group A and one from group B were diagnosed with pelvic inflammatory disease. At a second follow up visit – 12 weeks after the insertion of levonorgestrel-releasing intrauterine system, no other patient was diagnosed with pelvic inflammatory disease. Conclusion: Antibiotic prophylaxis is not mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. PMID:24868262

Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

PubMed

Chansanroj, Krisanin; Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele

2011-10-09

Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties. Copyright © 2011 Elsevier B.V. All rights reserved.

Enzyme-triggered compound release using functionalized antimicrobial peptide derivatives† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04435b Click here for additional data file.

PubMed Central

Kashibe, Masayoshi; Matsumoto, Kengo; Hori, Yuichiro

2017-01-01

Controlled release is one of the key technologies for medical innovation, and many stimulus-responsive nanocarriers have been developed to utilize this technology. Enzyme activity is one of the most useful stimuli, because many enzymes are specifically activated in diseased tissues. However, controlled release stimulated by enzyme activity has not been frequently reported. One of the reasons for this is the lack of versatility of carriers. Most of the reported stimulus-responsive systems involve a sophisticated design and a complicated process for the synthesis of stimulus-responsive nanocarrier components. The purpose of this study was to develop versatile controlled release systems triggered by various stimuli, including enzyme activity, without modifying the nanocarrier components. We developed two controlled release systems, both of which comprised a liposome as the nanocarrier and a membrane-damaging peptide, temporin L (TL), and its derivatives as the release-controllers. One system utilized branched peptides for proteases, and the other utilized phosphopeptides for phosphatases. In our systems, the target enzymes converted the non-membrane-damaging TL derivatives into membrane-damaging peptides and released the liposome inclusion. We demonstrated the use of our antimicrobial peptide-based controlled release systems for different enzymes and showed the promise of this technology as a novel theranostic tool. PMID:28451373

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

Proinflammatory effect in whole blood by free soluble bacterial components released from planktonic and biofilm cells.

PubMed

Oscarsson, Jan; Karched, Maribasappa; Thay, Bernard; Chen, Casey; Asikainen, Sirkka

2008-11-27

Aggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressive forms of periodontitis. Increasing evidence points to a link between periodontitis and cardiovascular diseases, however, the underlying mechanisms are poorly understood. This study investigated the pathogenic potential of free-soluble surface material, released from live planktonic and biofilm A. actinomycetemcomitans cells. By employing an ex vivo insert model (filter pore size 20 nm) we demonstrated that the A. actinomycetemcomitans strain D7S and its derivatives, in both planktonic and in biofilm life-form, released free-soluble surface material independent of outer membrane vesicles. This material clearly enhanced the production of several proinflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IL-8, MIP-1 beta) in human whole blood, as evidenced by using a cytokine antibody array and dissociation-enhanced-lanthanide-fluorescent-immunoassay. In agreement with this, quantitative real-time PCR indicated a concomitant increase in transcription of each of these cytokine genes. Experiments in which the LPS activity was blocked with polymyxin B showed that the stimulatory effect was only partly LPS-dependent, suggesting the involvement of additional free-soluble factors. Consistent with this, MALDI-TOF-MS and immunoblotting revealed release of GroEL-like protein in free-soluble form. Conversely, the immunomodulatory toxins, cytolethal distending toxin and leukotoxin, and peptidoglycan-associated lipoprotein, appeared to be less important, as evidenced by studying strain D7S cdt/ltx double, and pal single mutants. In addition to A. actinomycetemcomitans a non-oral species, Escherichia coli strain IHE3034, tested in the same ex vivo model also released free-soluble surface material with proinflammatory activity. A. actinomycetemcomitans, grown in biofilm and planktonic form, releases free-soluble surface material independent of outer membrane vesicles, which induces proinflammatory responses in human whole blood. Our findings therefore suggest that release of surface components from live bacterial cells could constitute a mechanism for systemic stimulation and be of particular importance in chronic localized infections, such as periodontitis.

Proinflammatory effect in whole blood by free soluble bacterial components released from planktonic and biofilm cells

PubMed Central

Oscarsson, Jan; Karched, Maribasappa; Thay, Bernard; Chen, Casey; Asikainen, Sirkka

2008-01-01

Background Aggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressive forms of periodontitis. Increasing evidence points to a link between periodontitis and cardiovascular diseases, however, the underlying mechanisms are poorly understood. This study investigated the pathogenic potential of free-soluble surface material, released from live planktonic and biofilm A. actinomycetemcomitans cells. Results By employing an ex vivo insert model (filter pore size 20 nm) we demonstrated that the A. actinomycetemcomitans strain D7S and its derivatives, in both planktonic and in biofilm life-form, released free-soluble surface material independent of outer membrane vesicles. This material clearly enhanced the production of several proinflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, MIP-1β) in human whole blood, as evidenced by using a cytokine antibody array and dissociation-enhanced-lanthanide-fluorescent-immunoassay. In agreement with this, quantitative real-time PCR indicated a concomitant increase in transcription of each of these cytokine genes. Experiments in which the LPS activity was blocked with polymyxin B showed that the stimulatory effect was only partly LPS-dependent, suggesting the involvement of additional free-soluble factors. Consistent with this, MALDI-TOF-MS and immunoblotting revealed release of GroEL-like protein in free-soluble form. Conversely, the immunomodulatory toxins, cytolethal distending toxin and leukotoxin, and peptidoglycan-associated lipoprotein, appeared to be less important, as evidenced by studying strain D7S cdt/ltx double, and pal single mutants. In addition to A. actinomycetemcomitans a non-oral species, Escherichia coli strain IHE3034, tested in the same ex vivo model also released free-soluble surface material with proinflammatory activity. Conclusion A. actinomycetemcomitans, grown in biofilm and planktonic form, releases free-soluble surface material independent of outer membrane vesicles, which induces proinflammatory responses in human whole blood. Our findings therefore suggest that release of surface components from live bacterial cells could constitute a mechanism for systemic stimulation and be of particular importance in chronic localized infections, such as periodontitis. PMID:19038023

Fabrication, Characterization, and Biological Activity of Avermectin Nano-delivery Systems with Different Particle Sizes

NASA Astrophysics Data System (ADS)

Wang, Anqi; Wang, Yan; Sun, Changjiao; Wang, Chunxin; Cui, Bo; Zhao, Xiang; Zeng, Zhanghua; Yao, Junwei; Yang, Dongsheng; Liu, Guoqiang; Cui, Haixin

2018-01-01

Nano-delivery systems for the active ingredients of pesticides can improve the utilization rates of pesticides and prolong their control effects. This is due to the nanocarrier envelope and controlled release function. However, particles containing active ingredients in controlled release pesticide formulations are generally large and have wide size distributions. There have been limited studies about the effect of particle size on the controlled release properties and biological activities of pesticide delivery systems. In the current study, avermectin (Av) nano-delivery systems were constructed with different particle sizes and their performances were evaluated. The Av release rate in the nano-delivery system could be effectively controlled by changing the particle size. The biological activity increased with decreasing particle size. These results suggest that Av nano-delivery systems can significantly improve the controllable release, photostability, and biological activity, which will improve efficiency and reduce pesticide residues.

Biotransformation of tributyltin to tin in freshwater river-bed sediments contaminated by an organotin release

USGS Publications Warehouse

Landmeyer, J.E.; Tanner, T.L.; Watt, B.E.

2004-01-01

The largest documented release of organotin compounds to a freshwater river system in the United States occurred in early 2000 in central South Carolina. The release consisted of an unknown volume of various organotin compounds such tetrabutyltin (TTBT), tributyltin (TBT), tetraoctyltin (TTOT), and trioctyl tin (TOT) and resulted in a massive fish kill and the permanent closures of a municipal wastewater treatment plant and a local city's only drinking-water intake. Initial sampling events in 2000 and 2001 indicated that concentrations of the ecologically toxic TTBT and TBT were each greater than 10 000 ??g/kg in surface-water bed sediments in depositional areas, such as lakes and beaver ponds downstream of the release. Bed-sediment samples collected between 2001 and 2003, however, revealed a substantial decrease in bed-sediment organotin concentrations and an increase in concentrations of degradation intermediate compounds. For example, in bed sediments of a representative beaver pond located about 1.6 km downstream of the release, total organotin concentrations [the sum of TTBT, TBT, and the TBT degradation intermediates dibutyltin (DBT) and monobutyltin (MBT)] decreased from 38 670 to 298 ??g/kg. In Crystal Lake, a large lake about 0.4 km downstream from the beaver pond, total organotin concentrations decreased from 28 300 to less than 5 ??g/kg during the same time period. Moreover, bed-sediment inorganic tin concentrations increased from pre-release levels of less than 800 to 32 700 ??g/kg during this time. These field data suggest that the released organotin compounds, such as TBT, are being transformed into inorganic tin by bed-sediment microbial processes. Microcosms were created in the laboratory that contained bed sediment from the two sites and were amended with tributyltin (as tributyltin chloride) under an ambient air headspace and sacrificially analyzed periodically for TBT, the biodegradation intermediates DBT and MBT, and tin. TBT concentrations decreased faster [half-life (t1/2) = 28 d] in the organic-rich sediments (21.5%) that characterized the beaver pond as compared to the slower (t1/2 = 78 d) degradation rate in the sandy, organic-poor, sediments (0.43%) of Crystal Lake. Moreover, the concentration of inorganic tin increased in microcosms containing bed sediments from both locations. These field and laboratory results suggest that biotransformation of the released organotins, in particular the ecologically detrimental TBT, does occur in this fresh surface-water system impacted with high concentrations of neat organotin compounds.

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.

Design and in vivo evaluation of a patch system based on thiolated polymers.

PubMed

Hoyer, Herbert; Greindl, Melanie; Bernkop-Schnürch, Andreas

2009-02-01

A new oral patch delivery system has been designed to increase the overall oral bioavailability of drugs within the gastrointestinal tract. The patch system consists of four layered films: a mucoadhesive matrix layer, a water insoluble backing layer, a middle layer and an enteric surface layer. The separation layer between the two matrix layers contained lactose, starch and confectioners' sugar. The matrix layer, exhibiting a diameter of 2.5 mm and a weight of 5 mg, comprised Polycarbophil-cysteine conjugate (49%), fluoresceine isothiocyanate-dextran (26%), glutathione (5%), and mannitol (20%). A standard tablet formulation consisting of the same matrix served as control. Entire fluoresceine isothiocyanate-dextran (FD(4)) was released from the delivery system within 2 h. For in vivo studies patch systems were administered orally to male Sprague-Dawley rats. Maximum FD(4) concentration in blood of the patch system was 46.1 +/- 8.9 ng/mL and was reached 3 h after administration. In contrast c(max) of control tablets displayed 50.5 +/- 14.9 ng/mL after 2 h and the absorption of FD(4) after administration in oral solution was negligible. The absolute bioavailability of orally administered patch systems and control tablets was 0.54% and 0.32% respectively. Results of this study indicate that a prolonged and higher oral bioavailability of FD(4) is obtained with patches than with tablets.

Noble gases released by vacuum crushing of EETA 79001 glass

NASA Technical Reports Server (NTRS)

Wiens, R. C.

1988-01-01

An EETA 79001 glass sample was crushed in a vacuum to observe the gases released. About 15 pct of the total gas concentrations were a mixture of a small amount of SPB-type gas with larger proportions of another air-like component. Less than 5 pct of the SPB gas was released by crushing, while 36-40 pct of the EETV (indigenous) gas was crush-released. The results are consistent with a siting of the EETV component in 10-100 micron vesicles seen in the glass. It is suggested that the SPB component is either in vesicles less than 6 microns in diameter or is primarily sited elsewhere.

Efficient Synthesis of a Maghemite/Gold Hybrid Nanoparticle System as a Magnetic Carrier for the Transport of Platinum-Based Metallotherapeutics

PubMed Central

Štarha, Pavel; Smola, David; Tuček, Jiří; Trávníček, Zdeněk

2015-01-01

The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH3)2Cl2], CDDP), are described. The final functionalized mag/Au–LA–CDDP* system consists of maghemite/gold nanoparticles (mag/Au) coated by lipoic acid (HLA; LA stands for deprotonated form of lipoic acid) and functionalized by activated cisplatin in the form of cis-[Pt(NH3)2(H2O)2]2+ (CDDP*). The relevant techniques (XPS, EDS, ICP-MS) proved the incorporation of the platinum-containing species on the surface of the studied hybrid system. HRTEM, TEM and SEM images showed the nanoparticles as spherical with an average size of 12 nm, while their superparamagnetic feature was proven by 57Fe Mössbauer spectroscopy. In the case of mag/Au, mag/Au–HLA and mag/Au–LA–CDDP*, weaker magnetic interactions among the Fe3+ centers of maghemite, as compared to maghemite nanoparticles (mag), were detected, which can be associated with the non-covalent coating of the maghemite surface by gold. The pH and time-dependent stability of the mag/Au–LA–CDDP* system in different media, represented by acetate (pH 5.0), phosphate (pH 7.0) and carbonate (pH 9.0) buffers and connected with the release of the platinum-containing species, showed the ability of CDDP* to be released from the functionalized nanosystem. PMID:25603182

TMBM: Tethered Micro-Balloons on Mars

NASA Technical Reports Server (NTRS)

Sims, M. H.; Greeley, R.; Cutts, J. A.; Yavrouian, A. H.; Murbach, M.

2000-01-01

The use of balloons/aerobots on Mars has been under consideration for many years. Concepts include deployment during entry into the atmosphere from a carrier spacecraft, deployment from a lander, use of super-pressurized systems for long duration flights, 'hot-air' systems, etc. Principal advantages include the ability to obtain high-resolution data of the surface because balloons provide a low-altitude platform which moves relatively slowly. Work conducted within the last few years has removed many of the technical difficulties encountered in deployment and operation of balloons/aerobots on Mars. The concept proposed here (a tethered balloon released from a lander) uses a relatively simple approach which would enable aspects of Martian balloons to be tested while providing useful and potentially unique science results. Tethered Micro-Balloons on Mars (TMBM) would be carried to Mars on board a future lander as a stand-alone experiment having a total mass of one to two kilograms. It would consist of a helium balloon of up to 50 cubic meters that is inflated after landing and initially tethered to the lander. Its primary instrumentation would be a camera that would be carried to an altitude of up to tens of meters above the surface. Imaging data would be transmitted to the lander for inclusion in the mission data stream. The tether would be released in stages allowing different resolutions and coverage. In addition during this staged release a lander camera system may observe the motion of the balloon at various heights above he lander. Under some scenarios upon completion of the primary phase of TMBM operations, the tether would be cut, allowing TMBM to drift away from the landing site, during which images would be taken along the ground.

Burridge-Knopoff Model as an Educational and Demonstrational Tool in Seismicity Prediction

NASA Astrophysics Data System (ADS)

Kato, M.

2007-12-01

While our effort is ongoing, the fact that predicting destructive earthquakes is not a straightforward business is hard to sell to the general public. Japan is prone to two types of destructive earthquakes; interplate events along Japan Trench and Nankai Trough, and intraplate events that often occur beneath megacities. Periodicity of interplate earthquakes is usually explained by the elastic rebound theory, but we are aware that the historical seismicity along Nankai Trough is not simply periodic. Inland intraplate events have geologically postulated recurrence intervals that are far longer than human lifetime, and we do not have ample knowledge to model their behavior that includes interaction among intraplate and interplate events. To demonstrate that accumulation and release of elastic energy is complex even in a simple system, we propose to utilize the Burridge-Knopoff (BK) model as a demonstrational tool. This original one-dimensional model is easy to construct and handle so that this is also an effective educational tool for classroom use. Our simulator is a simple realization of the original one dimensional BK, which consists of small blocks, springs and a motor. Accumulation and release of strain is visibly observable, and by guessing when the next large events occur we are able to intuitively learn that observation of strain accumulation is only one element in predicting large events. Quantitative analysis of the system is also possible by measuring the movement of blocks. While the long term average of strain energy is controlled by the loading rate, observed seismicity is neither time-predictable nor slip-predictable. Time between successive events is never a constant. Distribution of released energy obeys the power law, similar to Ishimoto- Iida and Gutenberg-Richter Law. This tool is also useful in demonstration of nonlinear behavior of complex system.

An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems.

PubMed

Jug, Mario; Hafner, Anita; Lovrić, Jasmina; Kregar, Maja Lusina; Pepić, Ivan; Vanić, Željka; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena

2018-01-05

In vitro dissolution/release tests are an important tool in the drug product development phase as well as in its quality control and the regulatory approval process. Mucosal drug delivery systems are aimed to provide both local and systemic drug action via mucosal surfaces of the body and exhibit significant differences in formulation design, as well as in their physicochemical and release characteristics. Therefore it is not possible to devise a single test system which would be suitable for release testing of such complex dosage forms. This article is aimed to provide a comprehensive review of both compendial and noncompendial methods used for in vitro dissolution/release testing of novel mucosal drug delivery systems aimed for ocular, nasal, oromucosal, vaginal and rectal administration. Copyright © 2017 Elsevier B.V. All rights reserved.

The development of a peak-time criterion for designing controlled-release devices.

PubMed

Simon, Laurent; Ospina, Juan

2016-08-25

This work consists of estimating dynamic characteristics for topically-applied drugs when the magnitude of the flux increases to a maximum value, called peak flux, before declining to zero. This situation is typical of controlled-released systems with a finite donor or vehicle volume. Laplace transforms were applied to the governing equations and resulted in an expression for the flux in terms of the physical characteristics of the system. After approximating this function by a second-order model, three parameters of this reduced structure captured the essential features of the original process. Closed-form relationships were then developed for the peak flux and time-to-peak based on the empirical representation. Three case studies that involve mechanisms, such as diffusion, partitioning, dissolution and elimination, were selected to illustrate the procedure. The technique performed successfully as shown by the ability of the second-order flux to match the prediction of the original transport equations. A main advantage of the proposed method is that it does not require a solution of the original partial differential equations. Less accurate results were noted for longer lag times. Copyright © 2016 Elsevier B.V. All rights reserved.

Monitoring diffuse volcanic degassing during volcanic unrests: the case of Campi Flegrei (Italy).

PubMed

Cardellini, C; Chiodini, G; Frondini, F; Avino, R; Bagnato, E; Caliro, S; Lelli, M; Rosiello, A

2017-07-28

In volcanoes with active hydrothermal systems, diffuse CO 2 degassing may constitute the primary mode of volcanic degassing. The monitoring of CO 2 emissions can provide important clues in understanding the evolution of volcanic activity especially at calderas where the interpretation of unrest signals is often complex. Here, we report eighteen years of CO 2 fluxes from the soil at Solfatara of Pozzuoli, located in the restless Campi Flegrei caldera. The entire dataset, one of the largest of diffuse CO 2 degassing ever produced, is made available for the scientific community. We show that, from 2003 to 2016, the area releasing deep-sourced CO 2 tripled its extent. This expansion was accompanied by an increase of the background CO 2 flux, over most of the surveyed area (1.4 km 2 ), with increased contributions from non-biogenic source. Concurrently, the amount of diffusively released CO 2 increased up to values typical of persistently degassing active volcanoes (up to 3000 t d -1 ). These variations are consistent with the increase in the flux of magmatic fluids injected into the hydrothermal system, which cause pressure increase and, in turn, condensation within the vapor plume feeding the Solfatara emission.

Systemic swings in end-Permian environments from Siberian Traps carbon and sulfur outgassing

NASA Astrophysics Data System (ADS)

Black, B. A.; Neely, R.; Lamarque, J. F.; Elkins-Tanton, L. T.; Kiehl, J. T.; Shields, C. A.; Mills, M. J.; Bardeen, C.

2017-12-01

U-Pb geochronology has revealed that Siberian Traps flood basalt magmatism coincided with the 252 Ma end-Permian mass extinction. Most environmental consequences of magmatism follow directly or indirectly from the release of sulfur and some combination of magmatic and metamorphic carbon to the atmosphere (exceptions include ozone depletion from halogen emissions, release of toxic metals, and enhanced weathering of fresh volcanic rocks). However, the critical combinations of forcing and stress that trigger global mass extinction remain unknown. In particular, the combined and competing effects of sulfur and carbon outgassing on Earth systems remain to be quantified. Here we present results from global climate model simulations of flood basalt outgassing that account for sulfur chemistry and aerosol microphysics. We consider the effects of sulfur and carbon in isolation and in tandem, and find that carbon and sulfur emissions combine to generate swings in climate, ocean circulation, and hydrology. Our simulations provide a self-consistent framework to quantitatively explain observed features of the end-Permian including surface warming, fluctuating ocean oxygenation, intense weathering, and carbon cycle perturbation, unifying observed changes in climate and geochemical cycles with feedbacks initiated by Siberian Traps magmatism.

Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan.

PubMed

El Maghraby, Gamal M; Elzayat, Ehab M; Alanazi, Fars K

2012-08-01

Alternative strategies are being employed to develop liquid oral sustained release formulation. These included ion exchange resin, sustained release suspensions and in situ gelling systems. The later mainly utilizes alginate solutions that form gels upon contact with calcium which may be administered separately or included in the alginate solution as citrate complex. This complex liberates calcium in the stomach with subsequent gellation. The formed gel can break after gastric emptying leading to dose dumping. Development of modified in situ gelling system which sustain dextromethorphan release in the stomach and intestine. Solutions containing alginate with calcium chloride and sodium citrate were initially prepared to select the formulation sustaining the release in the stomach. The best formulation was combined with chitosan. All formulations were characterized with respect to flow, gelling capacity, gelling strength and drug release. Increasing the concentration of alginate increased the gelling capacity and strength and reduced the rate of drug release in gastric conditions with 2% w/v alginate being the best formulation. However, these formulations failed to sustain the release in the intestinal conditions. Incorporation of chitosan with alginate increased the gelling capacity and strength and reduced the rate of drug release compared to alginate only system. The effect was optimum in formulation containing 1.5% w/v chitosan. The sustained release pattern was maintained both in the gastric and intestinal conditions and was comparable to that obtained from the marketed product. Alginate-chitosan based in situ gelling system is promising for developing liquid oral sustained release.

How Source Content Determines Intracellular Ca2+ Release Kinetics. Simultaneous Measurement of [Ca2+] Transients and [H+] Displacement in Skeletal Muscle

PubMed Central

Pizarro, Gonzalo; Ríos, Eduardo

2004-01-01

In skeletal muscle, the waveform of Ca2+ release under clamp depolarization exhibits an early peak. Its decay reflects an inactivation, which locally corresponds to the termination of Ca2+ sparks, and is crucial for rapid control. In cardiac muscle, both the frequency of spontaneous sparks (i.e., their activation) and their termination appear to be strongly dependent on the Ca2+ content in the sarcoplasmic reticulum (SR). In skeletal muscle, no such role is established. Seeking a robust measurement of Ca2+ release and a way to reliably modify the SR content, we combined in the same cells the “EGTA/phenol red” method (Pape et al., 1995) to evaluate Ca2+ release, with the “removal” method (Melzer et al., 1987) to evaluate release flux. The cytosol of voltage-clamped frog fibers was equilibrated with EGTA (36 mM), antipyrylazo III, and phenol red, and absorbance changes were monitored simultaneously at three wavelengths, affording largely independent evaluations of Δ[H+] and Δ[Ca2+] from which the amount of released Ca2+ and the release flux were independently derived. Both methods yielded mutually consistent evaluations of flux. While the removal method gave a better kinetic picture of the release waveform, EGTA/phenol red provided continuous reproducible measures of calcium in the SR (CaSR). Steady release permeability (P), reached at the end of a 120-ms pulse, increased as CaSR was progressively reduced by a prior conditioning pulse, reaching 2.34-fold at 25% of resting CaSR (four cells). Peak P, reached early during a pulse, increased proportionally much less with SR depletion, decreasing at very low CaSR. The increase in steady P upon depletion was associated with a slowing of the rate of decay of P after the peak (i.e., a slower inactivation of Ca2+ release). These results are consistent with a major inhibitory effect of cytosolic (rather than intra-SR) Ca2+ on the activity of Ca2+ release channels. PMID:15337820

Development of a Spring-Loaded Impact Device to Deliver Injurious Mechanical Impacts to the Articular Cartilage Surface

PubMed Central

Alexander, Peter G.; Song, Yingjie; Taboas, Juan M.; Chen, Faye H.; Melvin, Gary M.; Manner, Paul A.

2013-01-01

Objective: Traumatic impacts on the articular joint surface in vitro are known to lead to degeneration of the cartilage. The main objective of this study was to develop a spring-loaded impact device that can be used to deliver traumatic impacts of consistent magnitude and rate and to find whether impacts cause catabolic activities in articular cartilage consistent with other previously reported impact models and correlated with the development of osteoarthritic lesions. In developing the spring-loaded impactor, the operating hypothesis is that a single supraphysiologic impact to articular cartilage in vitro can affect cartilage integrity, cell viability, sulfated glycosaminoglycan and inflammatory mediator release in a dose-dependent manner. Design: Impacts of increasing force are delivered to adult bovine articular cartilage explants in confined compression. Impact parameters are correlated with tissue damage, cell viability, matrix and inflammatory mediator release, and gene expression 24 hours postimpact. Results: Nitric oxide release is first detected after 7.7 MPa impacts, whereas cell death, glycosaminoglycan release, and prostaglandin E2 release are first detected at 17 MPa. Catabolic markers increase linearly to maximal levels after ≥36 MPa impacts. Conclusions: A single supraphysiologic impact negatively affects cartilage integrity, cell viability, and GAG release in a dose-dependent manner. Our findings showed that 7 to 17 MPa impacts can induce cell death and catabolism without compromising the articular surface, whereas a 17 MPa impact is sufficient to induce increases in most common catabolic markers of osteoarthritic degeneration. PMID:26069650

Defined drug release from 3D-printed composite tablets consisting of drug-loaded polyvinylalcohol and a water-soluble or water-insoluble polymer filler.

PubMed

Tagami, Tatsuaki; Nagata, Noriko; Hayashi, Naomi; Ogawa, Emi; Fukushige, Kaori; Sakai, Norihito; Ozeki, Tetsuya

2018-05-30

3D-printed tablets are a promising new approach for personalized medicine. In this study, we fabricated composite tablets consisting of two components, a drug and a filler, by using a fused deposition modeling-type 3D printer. Polyvinylalcohol (PVA) polymer containing calcein (a model drug) was used as the drug component and PVA or polylactic acid (PLA) polymer without drug was used as the water-soluble or water-insoluble filler, respectively. Various kinds of drug-PVA/PVA and drug-PVA/PLA composite tablets were designed, and the 3D-printed tablets exhibited good formability. The surface area of the exposed drug component is highly correlated with the initial drug release rate. Composite tablets with an exposed top and a bottom covered with a PLA layer were fabricated. These tablets showed zero-order drug release by maintaining the surface area of the exposed drug component during drug dissolution. In contrast, the drug release profile varied for tablets whose exposed surface area changed. Composite tablets with different drug release lag times were prepared by changing the thickness of the PVA filler coating the drug component. These results which used PVA and PLA filler will provide useful information for preparing the tablets with multi-components and tailor-made tablets with defined drug release profiles using 3D printers. Copyright © 2018 Elsevier B.V. All rights reserved.

A Dynamical Analysis of a Piecewise Smooth Pest Control SI Model

NASA Astrophysics Data System (ADS)

Liu, Bing; Liu, Wanbo; Tao, Fennmei; Kang, Baolin; Cong, Jiguang

In this paper, we propose a piecewise smooth SI pest control system to model the process of spraying pesticides and releasing infectious pests. We assume that the pest population consists of susceptible pests and infectious pests, and that the disease spreads horizontally between pests. We take the susceptible pest as the control index on whether to implement chemical control and biological control strategies. Based on the theory of Filippov system, the sliding-mode domain and conditions for the existence of real equilibria, virtual equilibria, pseudo-equilibrium and boundary equilibria are given. Further, we show the global stability of real equilibria (or boundary equilibria) and pseudo-equilibrium. Our results can provide theoretical guidance for the problem of pest control.

Effects of carbon/graphite fiber contamination on high voltage electrical insulation

NASA Technical Reports Server (NTRS)

Garrity, T.; Eichler, C.

1980-01-01

The contamination mechanics and resulting failure modes of high voltage electrical insulation due to carbon/graphite fibers were examined. The high voltage insulation vulnerability to carbon/graphite fiber induced failure was evaluated using a contamination system which consisted of a fiber chopper, dispersal chamber, a contamination chamber, and air ducts and suction blower. Tests were conducted to evaluate the effects of fiber length, weathering, and wetness on the insulator's resistance to carbon/graphite fibers. The ability of nuclear, fossil, and hydro power generating stations to maintain normal power generation when the surrounding environment is contaminated by an accidental carbon fiber release was investigated. The vulnerability assessment included only the power plant generating equipment and its associated controls, instrumentation, and auxiliary and support systems.

Missouri Assessment Program (MAP), Spring 2000: High School Health/Physical Education, Released Items, Grade 9.

ERIC Educational Resources Information Center

Missouri State Dept. of Elementary and Secondary Education, Jefferson City.

This document presents 10 released items from the Health/Physical Education Missouri Assessment Program (MAP) test given in the spring of 2000 to ninth graders. Items from the test sessions include: selected-response (multiple choice), constructed-response, and a performance event. The selected-response items consist of individual questions…

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

Modeling transport kinetics in clinoptilolite-phosphate rock systems

NASA Technical Reports Server (NTRS)

Allen, E. R.; Ming, D. W.; Hossner, L. R.; Henninger, D. L.

1995-01-01

Nutrient release in clinoptilolite-phosphate rock (Cp-PR) systems occurs through dissolution and cation-exchange reactions. Investigating the kinetics of these reactions expands our understanding of nutrient release processes. Research was conducted to model transport kinetics of nutrient release in Cp-PR systems. The objectives were to identify empirical models that best describe NH4, K, and P release and define diffusion-controlling processes. Materials included a Texas clinoptilolite (Cp) and North Carolina phosphate rock (PR). A continuous-flow thin-disk technique was used. Models evaluated included zero order, first order, second order, parabolic diffusion, simplified Elovich, Elovich, and power function. The power-function, Elovich, and parabolic-diffusion models adequately described NH4, K, and P release. The power-function model was preferred because of its simplicity. Models indicated nutrient release was diffusion controlled. Primary transport processes controlling nutrient release for the time span observed were probably the result of a combination of several interacting transport mechanisms.

Construction of a novel pH-sensitive drug release system from mesoporous silica tablets coated with Eudragit

NASA Astrophysics Data System (ADS)

Xu, Yingpu; Qu, Fengyu; Wang, Yu; Lin, Huiming; Wu, Xiang; Jin, Yingxue

2011-03-01

A novel pH-sensitive drug release system has been established by coating Eudragit (Eud) on drug-loaded mesoporous silica (MS) tablets. The release rate of ibuprofen (IBU) from the MS was retarded by coating with Eudragit S-100, and the higher retardation was due to the increase of coating concentration and the coating layers. The target position of the release depended on the pH of the release medium, which was confirmed by the drug release from IBU/MS/Eud increasing rapidly with the change of medium pH from 1.2 to 7.4. This drug delivery system could prohibit irritant drug from leaking in the stomach and make it only release in the intestine. The loaded and unloaded drug samples were characterized by powder X-ray diffraction (XRD), Fourier transform infrared spectrometer (FTIR), N 2 adsorption/desorption, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet.

PubMed

Bhalekar, M R; Madgulkar, A R; Sheladiya, D D; Kshirsagar, S J; Wable, N D; Desale, S S

2008-01-01

The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 3(2) full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X(1)) and bees wax (X(2)) were selected as independent variables and release after 12 h and time required for 50% (t(50)) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t(50) but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings.

Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet

PubMed Central

Bhalekar, M. R.; Madgulkar, A. R.; Sheladiya, D. D.; Kshirsagar, S. J.; Wable, N. D.; Desale, S. S.

2008-01-01

The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 32 full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X1) and bees wax (X2) were selected as independent variables and release after 12 h and time required for 50% (t50) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t50 but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings. PMID:20046773

Defining System Boundaries of an Institution Nitrogen Footprint.

PubMed

de la Reguera, Elizabeth; Castner, Elizabeth A; Galloway, James N; Leach, Allison M; Leary, Neil; Tang, Jianwu

2017-04-01

A nitrogen (N) footprint quantifies the amount of reactive nitrogen released to the environment and can be measured at different scales. The N footprint of a university includes activities and consumption within its geographic boundaries as well as activities that support the institution. Determining system bounds of an N footprint depends on the institution's mission and provides a common baseline for comparison. A comparison of three scopes of the N footprint, which describe how emissions are directly related to an institution's activities, was conducted for seven institutions. Scopes follow the established definition for the carbon footprint. In this article, the authors propose a new system bounds definition (core campus versus adjunct). Two case studies were explored: how the N footprint of Dickinson College changed with air travel, and how the N footprint of the Marine Biological Laboratory changed with scientific research. Of the three scopes, scope 3 was consistently the largest proportion of the N footprint for all seven institutions. The core campus activities of Dickinson College made up 99 percent of its N footprint, with air travel making up the remaining 1 percent. The Marine Biological Laboratory's core campus activities made up 51 percent of its N footprint and the scientific research made up the remaining 49 percent. Institutions should define system bounds based on their mission and stay consistent with their boundaries following the baseline year. The core campus footprint could be used to compare institution footprints using consistent system bounds. How institutions define their boundaries will impact the recorded amount of nitrogen as well as how the institution will set reduction strategies.

Defining System Boundaries of an Institution Nitrogen Footprint

PubMed Central

Castner, Elizabeth A.; Galloway, James N.; Leach, Allison M.; Leary, Neil; Tang, Jianwu

2017-01-01

Abstract A nitrogen (N) footprint quantifies the amount of reactive nitrogen released to the environment and can be measured at different scales. The N footprint of a university includes activities and consumption within its geographic boundaries as well as activities that support the institution. Determining system bounds of an N footprint depends on the institution's mission and provides a common baseline for comparison. A comparison of three scopes of the N footprint, which describe how emissions are directly related to an institution's activities, was conducted for seven institutions. Scopes follow the established definition for the carbon footprint. In this article, the authors propose a new system bounds definition (core campus versus adjunct). Two case studies were explored: how the N footprint of Dickinson College changed with air travel, and how the N footprint of the Marine Biological Laboratory changed with scientific research. Of the three scopes, scope 3 was consistently the largest proportion of the N footprint for all seven institutions. The core campus activities of Dickinson College made up 99 percent of its N footprint, with air travel making up the remaining 1 percent. The Marine Biological Laboratory's core campus activities made up 51 percent of its N footprint and the scientific research made up the remaining 49 percent. Institutions should define system bounds based on their mission and stay consistent with their boundaries following the baseline year. The core campus footprint could be used to compare institution footprints using consistent system bounds. How institutions define their boundaries will impact the recorded amount of nitrogen as well as how the institution will set reduction strategies. PMID:29350212

Global classical solvability and stabilization in a two-dimensional chemotaxis-Navier-Stokes system modeling coral fertilization

NASA Astrophysics Data System (ADS)

Espejo, Elio; Winkler, Michael

2018-04-01

The interplay of chemotaxis, convection and reaction terms is studied in the particular framework of a refined model for coral broadcast spawning, consisting of three equations describing the population densities of unfertilized sperms and eggs and the concentration of a chemical released by the latter, coupled to the incompressible Navier-Stokes equations. Under mild assumptions on the initial data, global existence of classical solutions to an associated initial-boundary value problem in bounded planar domains is established. Moreover, all these solutions are shown to approach a spatially homogeneous equilibrium in the large time limit.