Enteric protection of naproxen in a fixed-dose combination product produced by hot-melt co-extrusion.

PubMed

Vynckier, A-K; De Beer, M; Monteyne, T; Voorspoels, J; De Beer, T; Remon, J P; Vervaet, C

2015-08-01

In this study hot-melt co-extrusion is used as processing technique to manufacture a fixed-dose combination product providing enteric protection to naproxen incorporated in the core and immediate release to esomeprazole magnesium embedded in the coat. The plasticizing effect of naproxen and triethyl citrate (TEC) was tested on the enteric polymers investigated (Eudragit(®) L100-55, HPMC-AS-LF and HPMCP-HP-50). Core matrix formulations containing HPMC-AS-LF, TEC and a naproxen load of 15, 30 and 50% were processed and characterized. The in vitro naproxen release in 0.1N HCl was prevented for 2h for all formulations. The physicochemical state of the drug in the extrudates was determined and a stability study was performed. Intermolecular interactions between naproxen and polymer were identified using attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopy. When esomeprazole magnesium was formulated in a polyethylene oxide 100K:polyethylene glycol 4K (1:1) matrix, separated from the naproxen-containing layer, the formulation could be easily processed and complete in vitro drug release was observed after 45 min. When co-extruding the core/coat dosage form it was observed that a third layer of polymer, separating the naproxen loaded enteric formulation in the core from the coat, is required to prevent degradation of the acid-labile esomeprazole magnesium at the core/coat interface. Copyright © 2015 Elsevier B.V. All rights reserved.

Mutagenic activity of south Indian food items.

PubMed

Sivaswamy, S N; Balachandran, B; Balanehru, S; Sivaramakrishnan, V M

1991-08-01

Dietary components and food dishes commonly consumed in South India were screened for their mutagenic activity. Kesari powder, calamus oil, palm drink, toddy and Kewra essence were found to be strongly mutagenic; garlic, palm oil, arrack, onion and pyrolysed portions of bread toast, chicory powder were weakly mutagenic, while tamarind and turmeric were not. Certain salted, sundried and oil fried food items were also mutagenic. Cissus quadrangularis was mutagenic, while 'decoctions' of cumin seeds, aniseeds and ginger were not. Several perfumes, essential oils and colouring agents, which are commonly used were also screened and many of them exhibited their mutagenic potential by inducing the 'reverse mutation' in Salmonella typhimurium tester strains.

Adjustment of Jacobs' formulation to the case of Mercury

NASA Astrophysics Data System (ADS)

Chiappini, M.; de Santis, A.

1991-04-01

Magnetic investigations play an important role in studies on the constitution of planetary interiors. One of these techniques (the so-called Jacobs' formulation), appropriately modified, has been applied to the case of Mercury. According to the results found, the planet, supposed to be divided internally as the earth (crust-mantle-core), would have a core/planet volume ratio of 28 percent, much greater than the earth's core percentage (16 percent). This result is in agreement with previous work which used other independent methods.

Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation.

PubMed

Kulhari, Hitesh; Pooja, Deep; Singh, Mayank K; Chauhan, Abhay S

2015-02-01

Abstract Cisplatin is mainly used in the treatment of ovarian, head and neck and testicular cancer. Poor solubility and non-specific interactions causes hurdles in the development of successful cisplatin formulation. There were few reports on poly(amidoamine) (PAMAM) dendrimer-cisplatin complexes for anticancer treatment. But the earlier research was mainly focused on therapeutic effect of PAMAM dendrimer-cisplatin complex, with less attention paid on the formulation development of these complexes. Objective of the present study is to optimize and validate the carboxylate-terminated, EDA core PAMAM dendrimer-based cisplatin formulation with respect to various variables such as dendrimer core, generation, drug entrapment, purification, yield, reproducibility, stability, storage and in-vitro release. Dendrimer-cisplatin complex was prepared by an efficient method which significantly increases the % platinum (Pt) content along with the product yield. Dendrimers showed reproducible (∼27%) platinum loading by weight. Variation in core and generations does not produce significant change in the % Pt content. Percentage Pt content of dendrimeric formulation increases with increase in drug/dendrimer mole ratio. Formulation with low drug/dendrimer mole ratio showed delayed release compared to the higher drug/dendrimer mole ratio; these dendrimer formulations are stable in room temperature. In vitro release profiles of the stored dendrimer-cisplatin samples showed comparatively slow release of cisplatin, which may be due to formation of strong bond between cisplatin and dendrimer. This study will contribute to create a fine print for the formulation development of PAMAM dendrimer-cisplatin complexes.

Bradford's law: identification of the core journals for neurosurgery and its subspecialties.

PubMed

Venable, Garrett T; Shepherd, Brandon A; Loftis, Christopher M; McClatchy, S Gray; Roberts, Mallory L; Fillinger, Meghan E; Tansey, James B; Klimo, Paul

2016-02-01

Bradford's law describes the scatter of citations for a given subject or field. It can be used to identify the most highly cited journals for a field or subject. The objective of this study was to use currently accepted formulations of Bradford's law to identify core journals of neurosurgery and neurosurgical subspecialties. All original research publications from 2009 to 2013 were analyzed for the top 25 North American academic neurosurgeons from each subspecialty. The top 25 were chosen from a ranked career h-index list identified from previous studies. Egghe's formulation and the verbal formulation of Bradford's law were applied to create specific citation density zones and identify the core journals for each subspecialty. The databases were then combined to identify the core journals for all of academic neurosurgery. Using Bradford's verbal law with 4 zone models, the authors were able to identify the core journals of neurosurgery and its subspecialties. The journals found in the most highly cited first zone are presented here as the core journals. For neurosurgery as a whole, the core included the following journals: Journal of Neurosurgery, Neurosurgery, Spine, Stroke, Neurology, American Journal of Neuroradiology, International Journal of Radiation Oncology Biology Physics, and New England Journal of Medicine. The core journals for each subspecialty are presented in the manuscript. Bradford's law can be used to identify the core journals of neurosurgery and its subspecialties. The core journals vary for each neurosurgical subspecialty, but Journal of Neurosurgery and Neurosurgery are among the core journals for each neurosurgical subspecialty.

Combinatorial optimization games

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

Deng, X.; Ibaraki, Toshihide; Nagamochi, Hiroshi

1997-06-01

We introduce a general integer programming formulation for a class of combinatorial optimization games, which immediately allows us to improve the algorithmic result for finding amputations in the core (an important solution concept in cooperative game theory) of the network flow game on simple networks by Kalai and Zemel. An interesting result is a general theorem that the core for this class of games is nonempty if and only if a related linear program has an integer optimal solution. We study the properties for this mathematical condition to hold for several interesting problems, and apply them to resolve algorithmic andmore » complexity issues for their cores along the line as put forward in: decide whether the core is empty; if the core is empty, find an imputation in the core; given an imputation x, test whether x is in the core. We also explore the properties of totally balanced games in this succinct formulation of cooperative games.« less

Developing core outcome measurement sets for clinical trials: OMERACT filter 2.0.

PubMed

Boers, Maarten; Kirwan, John R; Wells, George; Beaton, Dorcas; Gossec, Laure; d'Agostino, Maria-Antonietta; Conaghan, Philip G; Bingham, Clifton O; Brooks, Peter; Landewé, Robert; March, Lyn; Simon, Lee S; Singh, Jasvinder A; Strand, Vibeke; Tugwell, Peter

2014-07-01

Lack of standardization of outcome measures limits the usefulness of clinical trial evidence to inform health care decisions. This can be addressed by agreeing on a minimum core set of outcome measures per health condition, containing measures relevant to patients and decision makers. Since 1992, the Outcome Measures in Rheumatology (OMERACT) consensus initiative has successfully developed core sets for many rheumatologic conditions, actively involving patients since 2002. Its expanding scope required an explicit formulation of its underlying conceptual framework and process. Literature searches and iterative consensus process (surveys and group meetings) of stakeholders including patients, health professionals, and methodologists within and outside rheumatology. To comprehensively sample patient-centered and intervention-specific outcomes, a framework emerged that comprises three core "Areas," namely Death, Life Impact, and Pathophysiological Manifestations; and one strongly recommended Resource Use. Through literature review and consensus process, core set development for any specific health condition starts by identifying at least one core "Domain" within each of the Areas to formulate the "Core Domain Set." Next, at least one applicable measurement instrument for each core Domain is identified to formulate a "Core Outcome Measurement Set." Each instrument must prove to be truthful (valid), discriminative, and feasible. In 2012, 96% of the voting participants (n=125) at the OMERACT 11 consensus conference endorsed this model and process. The OMERACT Filter 2.0 explicitly describes a comprehensive conceptual framework and a recommended process to develop core outcome measurement sets for rheumatology likely to be useful as a template in other areas of health care. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical and Colloidal Stability of Carboxylated Core-Shell Magnetite Nanoparticles Designed for Biomedical Applications

PubMed Central

Szekeres, Márta; Tóth, Ildikó Y.; Illés, Erzsébet; Hajdú, Angéla; Zupkó, István; Farkas, Katalin; Oszlánczi, Gábor; Tiszlavicz, László; Tombácz, Etelka

2013-01-01

Despite the large efforts to prepare super paramagnetic iron oxide nanoparticles (MNPs) for biomedical applications, the number of FDA or EMA approved formulations is few. It is not known commonly that the approved formulations in many instances have already been withdrawn or discontinued by the producers; at present, hardly any approved formulations are produced and marketed. Literature survey reveals that there is a lack for a commonly accepted physicochemical practice in designing and qualifying formulations before they enter in vitro and in vivo biological testing. Such a standard procedure would exclude inadequate formulations from clinical trials thus improving their outcome. Here we present a straightforward route to assess eligibility of carboxylated MNPs for biomedical tests applied for a series of our core-shell products, i.e., citric acid, gallic acid, poly(acrylic acid) and poly(acrylic acid-co-maleic acid) coated MNPs. The discussion is based on physicochemical studies (carboxylate adsorption/desorption, FTIR-ATR, iron dissolution, zeta potential, particle size, coagulation kinetics and magnetization measurements) and involves in vitro and in vivo tests. Our procedure can serve as an example to construct adequate physico-chemical selection strategies for preparation of other types of core-shell nanoparticles as well. PMID:23857054

Synthesis, Characterization, and In Vivo Efficacy of Shell Cross-Linked Nanoparticle Formulations Carrying Silver Antimicrobials as Aerosolized Therapeutics

PubMed Central

2014-01-01

The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195

[Studies on preparation of sustained-release Shuxiong formulation, a traditional Chinese medicine compound recipe, using time-controlled release techniques].

PubMed

Song, Hong-Tao; Zhang, Qian; Jiang, Peng; Guo, Tao; Chen, Da-Wei; He, Zhong-Gui

2006-09-01

To prepare a sustained-release formulation of traditional Chinese medicine compound recipe by adopting time-controlled release techniques. Shuxiong tablets were chosen as model drug. The prescription and technique of core tablets were formulated with selecting disintegrating time and swelling volume of core tablets in water as index. The time-controlled release tablets were prepared by adopting press-coated techniques, using PEG6000, HCO and EVA as coating materials. The influences of compositions, preparation process and dissolution conditions in vitro on the lag time (T(lag)) of drug release were investigated. The composition of core tablets was as follow: 30% of drug, 50% MCC and 20% CMS-Na. The T(lag) of time-controlled release tablets was altered remarkably by PEG6000 content of the outer layer, the amount of outer layer and hardness of tablet. The viscosity of dissolution media and basket rotation had less influence on the T(lag) but more on rate of drug release. The core tablets pressed with the optimized composition had preferable swelling and disintegrating properties. The shuxiong sustained-release formulations which contained core tablet and two kinds of time-controlled release tablets with 3 h and 6 h of T(lag) could release drug successively at 0 h, 3 h and 6 h in vitro. The technique made it possible that various components with extremely different physicochemical properties in these preparations could release synchronously.

Food bodies in Cissus verticillata (Vitaceae): ontogenesis, structure and functional aspects

PubMed Central

Paiva, Elder Antônio Sousa; Buono, Rafael Andrade; Lombardi, Julio Antonio

2009-01-01

Background and Aims The distinction between pearl bodies (or pearl glands) and food bodies (FBs) is not clear; neither is our understanding of what these structures really represent. The present work examined the ontogenesis, structure, ultrastructure and histochemical aspects of the protuberances in Cissus verticillata, which have been described since the beginning of the 19th century as pearl glands or pearl bodies, in order to establish a relationship between their structure and function. Methods Segments of stems and leaves in different stages of development were collected and fixed for study under light microscopy as well as electron transmission and scanning microscopy. Samples of FBs were subjected to chemical analysis using thin-layer chromatography. Key Results The FBs in C. verticillata are globose and attached to the plant by a short peduncle. These structures are present along the entire stem during primary growth, and on the inflorescence axis and the abaxial face of the leaves. The FBs were observed to be of mixed origin, with the participation of both the epidermis and the underlying parenchymatic cells. The epidermis is uniseriate with a thin cuticle, and the cells have dense cytoplasm and a large nucleus. The internal parenchymatic cells have thin walls; in the young structures these cells have dense cytoplasm with a predominance of mitochondria and plastids. In the mature FBs, the parenchymatic cells accumulate oils and soluble sugars; dictyosomes and rough endoplasmic reticulum predominate in the cytoplasm; the vacuoles are ample. Removal of the FBs appears to stimulate the formation of new ones, at the same place. Conclusions The vegetative vigour of the plant seems to influence the number of FBs produced, with more vigorous branches having greater densities of FBs. The results allow the conclusion that the structures traditionally designated pearl glands or pearl bodies in C. verticillata constitute FBs that can recruit large numbers of ants. PMID:19049986

IN VITRO EFFICACY OF EXTRACTS FROM PLANTS USED BY SMALL-HOLDER FARMERS IN THE TREATMENT OF DERMATOPHILOSIS IN CATTLE.

PubMed

Ndhlovu, Daud N; Masika, Patrick J

2017-01-01

Bovine dermatophilosis, an important skin disease of cattle caused by Dermatophilus congolensis , negatively impacts the livelihoods of small-holder farmers in Zimbabwe. This impact is through, morbidity, loss of draught animal power, costs incurred to manage the disease, losses associated with devalued damaged hides and the resultant culling of some of the affected cattle. Due to the inaccessibility of conventional drugs to manage bovine dermatophilosis, farmers have been reported to use local medicinal plants to manage the disease. The aim of the study was to evaluate the in vitro antimicrobial activities of three plants that small-holder farmers in Zimbabwe used to manage bovine dermatophilosis. Dried plant materials were ground into powder and extracted individually using, water, 80 % acetone and 80 % methanol. The antimicrobial properties of the plants were evaluated against two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and one Gram-positive (Staphylococcus aureus) reference bacterial strains. They were further evaluated against a field isolate of Dermatophilus congolensis . The assays used were the disc diffusion, minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Acetone and methanol extracts had superior inhibitory activities than did those of water. Pterocarpus angolensis DC extracts had better inhibitory properties with absolute MIC values of 0.156 - 5 mg/ml, Cissus Quadrangularis L had MIC values in the range 0.156 - 5 mg/ml while that of Catunaregam spinosa Thunb, Terveng was 0.156 - 10 mg/ml. Dermatophilus congolensis was more sensitive to Pterocarpus angolensis DC average MIC = 0.63 mg/ml than to Cissus quadrangularis L average MIC = 1.25 mg/ml and Catunaregam. spinosa Thunb, Terveng average MIC = 2.08 mg/ml. These results suggest the potential antibacterial activities of extracts of the three plants and hence farmers are, in a way, justified in using the plants. Better results (lower MIC) could be obtained by extracting and evaluating pure active compounds of the plants.

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

PubMed

Liu, Longxiao; Wang, Jinchao; Zhu, Suyan

2007-04-01

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

Preparation of acetaminophen capsules containing beads prepared by hot-melt direct blend coating.

PubMed

Pham, Loan; Christensen, John M

2014-02-01

Twelve hydrophobic coating agents were assessed for their effects on drug release after coating sugar cores by a flexible hot-melt coating method using direct blending. Drug-containing pellets were also produced and used as cores. The cores were coated with single or double wax layers containing acetaminophen (APAP). The harder the wax, the slower the resultant drug releases from single-coated beads. Wax coating can be deposited on cores up to 28% of the beads final weight and reaching 58% with wax and drug. Carnauba-coated beads dissolved in approximately 6 h releasing 80% of the loaded drug. Applying another wax layer extended drug release over 20 h, while still delivering 80% of the loaded drug. When drug-containing pellets (33-58% drug loading) were used as cores, double wax-coated pellets exhibited a near zero-order drug release for 16 h, releasing 80% of the loaded drug delivering 18 mg/h. The simple process of hot-melt coating by direct blending of pellet-containing drug-coated formulations provides excellent options for immediate and sustained release formulations when higher lipid coating or drug loading is warranted. Predicted plasma drug concentration time profiles using convolution and in vitro drug release properties of the beads were performed for optimal formulations.

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.

Cationic niosomes an effective gene carrier composed of novel spermine-derivative cationic lipids: effect of central core structures.

PubMed

Opanasopit, Praneet; Leksantikul, Lalita; Niyomtham, Nattisa; Rojanarata, Theerasak; Ngawhirunpat, Tanasait; Yingyongnarongkul, Boon-Ek

2017-05-01

Cationic niosomes formulated from Span 20, cholesterol (Chol) and novel spermine-based cationic lipids of multiple central core structures (di(oxyethyl)amino, di(oxyethyl)amino carboxy, 3-amino-1,2-dioxypropyl and 2-amino-1,3-dioxypropyl) were successfully prepared for improving transfection efficiency in vitro. The niosomes composed of spermine cationic lipid with central core structure of di(oxyethyl)amino revealed the highest gene transfection efficiency. To investigate the factors affecting gene transfection and cell viability including differences in the central core structures of cationic lipids, the composition of vesicles, molar ratio of cationic lipids in formulations and the weight ratio of niosomes to DNA. Cationic niosomes composed of nonionic surfactants (Span20), cholesterol and spermine-based cationic lipids of multiple central core structures were formulated. Gene transfection and cell viability were evaluated on a human cervical carcinoma cell line (HeLa cells) using pDNA encoding green fluorescent protein (pEGFP-C2). The morphology, size and charge were also characterized. High transfection efficiency was obtained from cationic niosomes composed of Span20:Chol:cationic lipid at the molar ratio of 2.5:2.5:0.5 mM. Cationic lipids with di(oxyethyl)amino as a central core structure exhibited highest transfection efficiency. In addition, there was also no serum effect on transfection efficiency. These novel cationic niosomes may constitute a good alternative carrier for gene transfection.

Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation.

PubMed

Zhao, Peiqi; Wang, Hanjie; Yu, Man; Liao, Zhenyu; Wang, Xianhuo; Zhang, Fei; Ji, Wei; Wu, Bing; Han, Jinghua; Zhang, Haichang; Wang, Huaqing; Chang, Jin; Niu, Ruifang

2012-06-01

A functional drug carrier comprised of folic acid modified lipid-shell and polymer-core nanoparticles (FLPNPs) including poly(D,L-lactide-co-glycolide) (PLGA) core, PEGylated octadecyl-quaternized lysine modified chitosan (PEG-OQLCS) as lipid-shell, folic acid as targeting ligand and cholesterol was prepared and evaluated for targeted delivery of paclitaxel (PTX). Confocal microscopy analysis confirmed the coating of the lipid-shell on the polymer-core. Physicochemical characterizations of FLPNPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. The internalization efficiency and targeting ability of FLPNPs were demonstrated by flow cytometry and confocal microscopy. PTX loaded FLPNPs showed a significantly higher cytotoxicity than the commercial PTX formulation (Taxol®). The intravenous administration of PTX encapsulated FLPNPs led to tumor regression and improvement of animal survival in a murine model, compared with that observed with Taxol® and biodistribution study showed that PTX concentration in tumor for PTX encapsulated FLPNPs was higher than other PTX formulations. Our data indicate that PTX loaded FLPNPs are a promising nano-sized drug formulation for cancer therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Preparation of microcapsules with self-microemulsifying core by a vibrating nozzle method.

PubMed

Homar, Miha; Suligoj, Dasa; Gasperlin, Mirjana

2007-02-01

Incorporation of drugs in self-microemulsifying systems (SMES) offers several advantages for their delivery, the main one being faster drug dissolution and absorption. Formulation of SMES in solid dosage forms can be difficult and, to date, most SMES are applied in liquid dosage form or soft gelatin capsules. This study has explored the incorporation of SMES in microcapsules, which could then be used for formulation of solid dosage forms. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to produce alginate microcapsules with a self-microemulsifying core. Retention of the core phase was improved by optimization of encapsulator parameters and modification of the shell forming phase and hardening solution. The mean encapsulation efficiency of final batches was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that production of microcapsules with a self-microemulsifying core is possible and that the process is stable and reproducible.

Teaching Cultural Competence to Psychiatry Residents: Seven Core Concepts and Their Implications for Therapeutic Technique.

PubMed

Pena, Jose M; Manguno-Mire, Gina; Kinzie, Erik; Johnson, Janet E

2016-04-01

The authors describe the Tulane Model for teaching cultural competence to psychiatry residents in order to outline an innovative approach to curricula development in academic psychiatry. The authors focus on the didactic experience that takes place during the first and second postgraduate years and present seven core concepts that should inform the emerging clinician's thinking in the formulation of every clinical case. The authors discuss the correspondence between each core concept and the Outline for Cultural Formulation, introduced in Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV and updated in DSM-5. The authors illustrate how each of the core concepts is utilized as a guideline for teaching residents a process for eliciting culturally relevant information from their patients and their personal histories and how to apply that knowledge in the assessment and treatment of patients in clinical settings.

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

Williamson, David L.; Olson, Jerry G.; Hannay, Cécile

An error in the energy formulation in the Community Atmosphere Model (CAM) is identified and corrected. Ten year AMIP simulations are compared using the correct and incorrect energy formulations. Statistics of selected primary variables all indicate physically insignificant differences between the simulations, comparable to differences with simulations initialized with rounding sized perturbations. The two simulations are so similar mainly because of an inconsistency in the application of the incorrect energy formulation in the original CAM. CAM used the erroneous energy form to determine the states passed between the parameterizations, but used a form related to the correct formulation for themore » state passed from the parameterizations to the dynamical core. If the incorrect form is also used to determine the state passed to the dynamical core the simulations are significantly different. In addition, CAM uses the incorrect form for the global energy fixer, but that seems to be less important. The difference of the magnitude of the fixers using the correct and incorrect energy definitions is very small.« less

Energy considerations in the Community Atmosphere Model (CAM)

DOE PAGES

Williamson, David L.; Olson, Jerry G.; Hannay, Cécile; ...

2015-06-30

An error in the energy formulation in the Community Atmosphere Model (CAM) is identified and corrected. Ten year AMIP simulations are compared using the correct and incorrect energy formulations. Statistics of selected primary variables all indicate physically insignificant differences between the simulations, comparable to differences with simulations initialized with rounding sized perturbations. The two simulations are so similar mainly because of an inconsistency in the application of the incorrect energy formulation in the original CAM. CAM used the erroneous energy form to determine the states passed between the parameterizations, but used a form related to the correct formulation for themore » state passed from the parameterizations to the dynamical core. If the incorrect form is also used to determine the state passed to the dynamical core the simulations are significantly different. In addition, CAM uses the incorrect form for the global energy fixer, but that seems to be less important. The difference of the magnitude of the fixers using the correct and incorrect energy definitions is very small.« less

Elongated Microcapsules and Their Formation

NASA Technical Reports Server (NTRS)

Calle, Luz M. (Inventor); Li, Wenyan N. (Inventor); Buhrow, Jerry W. (Inventor); Perusich, Stephen A. (Inventor); Jolley, Scott T. (Inventor); Gibson, Tracy L. (Inventor); Williams, Martha K. (Inventor)

2015-01-01

Elongated microcapsules, such as elongated hydrophobic-core and hydrophilic-core microcapsules, may be formed by pulse stirring an emulsion or shearing an emulsion between two surfaces moving at different velocities. The elongated microcapsules may be dispersed in a coating formulation, such as paint.

WETTABILITY AND PREDICTION OF OIL RECOVERY FROM RESERVOIRS DEVELOPED WITH MODERN DRILLING AND COMPLETION FLUIDS

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

Jill S. Buckley; Norman R. Morrow

2006-01-01

The objectives of this project are: (1) to improve understanding of the wettability alteration of mixed-wet rocks that results from contact with the components of synthetic oil-based drilling and completion fluids formulated to meet the needs of arctic drilling; (2) to investigate cleaning methods to reverse the wettability alteration of mixed-wet cores caused by contact with these SBM components; and (3) to develop new approaches to restoration of wetting that will permit the use of cores drilled with SBM formulations for valid studies of reservoir properties.

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

PubMed

Liu, Longxiao; Che, Binjie

2006-10-01

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

Irradiation effect of low-energy ion on polyurethane nanocoating containing metal oxide nanoparticles

NASA Astrophysics Data System (ADS)

Verma, Jaya; Nigam, Subhasha; Sinha, Surbhi; Sikarwar, B. S.; Bhattacharya, Arpita

2017-12-01

Irradiation effect of low-energy ion beam has been investigated on nanocoating developed with silica, titania and silica-titania core-shell nanoparticles embedded in an organic binder for nanopaint application. In this work, we have taken polyurethane as a model organic binder. Silica nanoparticles have been prepared through sol-gel synthesis with a particle size of 85 nm. Titania and core-shell nanoparticles have been prepared through both sol-gel and peptization process. Particle sizes obtained were 107 nm for titania and 240 nm for core-shell nanoparticles prepared through sol-gel process and 75 nm for TiO2 and 144 nm for core-shell nanoparticles prepared through peptization process. The coating formulations were developed with the above nanoparticles individually and nanoparticle concentration was varied from 1 to 6 wt% and the best performance in terms of hydrophobicity was obtained with 4 wt % of the nanoparticles in polyurethane coating formulation. All the coating formulations prepared were applied on a glass substrate and dried at 100°C. The dry film thickness obtained was around 100 µm in each case. These films dried on glass substrate were irradiated by nitrogen and argon ion beam with energy of 26 keV at fluences of 1014 to 1016 ions/cm2. The anti-algal property of the irradiated samples was improved and hydrophobicity was reduced.

Transformable liquid-metal nanomedicine

NASA Astrophysics Data System (ADS)

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-12-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core-shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity.

Ion Structure Near a Core-Shell Dielectric Nanoparticle

NASA Astrophysics Data System (ADS)

Ma, Manman; Gan, Zecheng; Xu, Zhenli

2017-02-01

A generalized image charge formulation is proposed for the Green's function of a core-shell dielectric nanoparticle for which theoretical and simulation investigations are rarely reported due to the difficulty of resolving the dielectric heterogeneity. Based on the formulation, an efficient and accurate algorithm is developed for calculating electrostatic polarization charges of mobile ions, allowing us to study related physical systems using the Monte Carlo algorithm. The computer simulations show that a fine-tuning of the shell thickness or the ion-interface correlation strength can greatly alter electric double-layer structures and capacitances, owing to the complicated interplay between dielectric boundary effects and ion-interface correlations.

Controlled release liquid dosage formulation

DOEpatents

Benton, Ben F.; Gardner, David L.

1989-01-01

A liquid dual coated dosage formulation sustained release pharmaceutic having substantial shelf life prior to ingestion is disclosed. A dual coating is applied over controlled release cores to form dosage forms and the coatings comprise fats melting at less than approximately 101.degree. F. overcoated with cellulose acetate phthalate or zein. The dual coated dosage forms are dispersed in a sugar based acidic liquid carrier such as high fructose corn syrup and display a shelf life of up to approximately at least 45 days while still retaining their release profiles following ingestion. Cellulose acetate phthalate coated dosage form cores can in addition be dispersed in aqueous liquids of pH <5.

Study of controlled-release floating tablets of dipyridamole using the dry-coated method.

PubMed

Chen, Kai; Wen, Haoyang; Yang, Feifei; Yu, Yibin; Gai, Xiumei; Wang, Haiying; Li, Pingfei; Pan, Weisan; Yang, Xinggang

2018-01-01

Dipyridamole (DIP), having a short biological half-life, has a narrow absorption window and is primarily absorbed in the stomach. So, the purpose of this study was to prepare controlled-release floating (CRF) tablets of dipyridamole by the dry-coated method. The influence of agents with different viscosity, hydroxypropylmethylcellulose (HPMC) and polyvinylpyrollidon K30 (PVP K30) in the core tablet and low-viscosity HPMC and PVP K30 in the coating layer on drug release, were investigated. Then, a study with a three-factor, three-level orthogonal experimental design was used to optimize the formulation of the CRF tablets. After data processing, the optimized formulation was found to be: 80 mg HPMC K4M in the core tablet, 80 mg HPMC E15 in core tablet and 40 mg PVP K30 in the coating layer. Moreover, an in vitro buoyancy study showed that the optimized formulation had an excellent floating ability and could immediately float without a lag time and this lasted more than 12 h. Furthermore, an in vivo gamma scintigraphic study showed that the gastric residence time of the CRF tablet was about 8 h.

A three-dimensional nonlinear Timoshenko beam based on the core-congruential formulation

NASA Technical Reports Server (NTRS)

Crivelli, Luis A.; Felippa, Carlos A.

1992-01-01

A three-dimensional, geometrically nonlinear two-node Timoshenkoo beam element based on the total Larangrian description is derived. The element behavior is assumed to be linear elastic, but no restrictions are placed on magnitude of finite rotations. The resulting element has twelve degrees of freedom: six translational components and six rotational-vector components. The formulation uses the Green-Lagrange strains and second Piola-Kirchhoff stresses as energy-conjugate variables and accounts for the bending-stretching and bending-torsional coupling effects without special provisions. The core-congruential formulation (CCF) is used to derived the discrete equations in a staged manner. Core equations involving the internal force vector and tangent stiffness matrix are developed at the particle level. A sequence of matrix transformations carries these equations to beam cross-sections and finally to the element nodal degrees of freedom. The choice of finite rotation measure is made in the next-to-last transformation stage, and the choice of over-the-element interpolation in the last one. The tangent stiffness matrix is found to retain symmetry if the rotational vector is chosen to measure finite rotations. An extensive set of numerical examples is presented to test and validate the present element.

Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology.

PubMed

Tian, Zhiqiang; Yu, Qin; Xie, Yunchang; Li, Fengqian; Lu, Yi; Dong, Xiaochun; Zhao, Weili; Qi, Jianping; Wu, Wei

2016-08-01

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles. NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references. NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation. Controlled release of integral NLCs is achieved by the osmotic pump strategy.

Physical Compatibility of Calcium Acetate and Potassium Phosphates in Parenteral Nutrition Solutions Containing Aminosyn II.

PubMed

Zhang, Y; Xu, Q; Trissel, L A; Baker, M B

1999-01-01

Numerous factors have been identified that influence the amount of calcium and phosphates that can remain in solution or will precipitate from parenteral nutrition solutions. Two of the most important such factors are the specific formulation of the amino acid source and the salt form of the calcium source. The purpose of this study was to evaluate the physical compatibility of calcium (as acetate) and potassium phophates in Aminosyn II-based parenteral nutrition solutions. Five representative core parenteral nutrition formulations containing Aminosyn II 2% to 5% were evaluated. Varying amounts of calcium acetate and potassium phosphates were added to samples of the core formulations to identify the concentrations at which precipitation just began to occur. A total of five series of concentrations was tested wiht maxima of calcium 40 mEq/L and phosphates 40 mM/L. The samples were evaluated by visual observation with the unaided eye and by use of a Tyndall beam to accentuate the visibility of small particles and low-level turbidity. For samples not exhibiting visible particles or haze, the turbidity and particle content were measured electronically. Evaluations were performed initially during the first 15 minutes after mixing and after 48 hours of storage at 23 deg and 37 deg C. The precipitation potential of calcium and phosphates in the five representative parenteral nutrition solutions containing Aminosyn II at a a variety of concentrations has been evaluated over a broad range of concentrations has been evaluated over a broad rage of concentrations. The results are presented in tabular form and were used to determine the boundary between compatibility and incompatibility in each of the five core parenteral nutrtion formulations. The boundary lines or compatibility curves were constructed for each of the formulations and are presented graphically.

Development of sustained and dual drug release co-extrusion formulations for individual dosing.

PubMed

Laukamp, Eva Julia; Vynckier, An-Katrien; Voorspoels, Jody; Thommes, Markus; Breitkreutz, Joerg

2015-01-01

In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation of bilayer-core osmotic pump tablet by coating the indented core tablet.

PubMed

Liu, Longxiao; Xu, Xiangning

2008-03-20

In this paper, a bilayer-core osmotic pump tablet (OPT) which does not require laser drilling to form the drug delivery orifice is described. The bilayer-core consisted of two layers: (a) push layer and (b) drug layer, and was made with a modified upper tablet punch, which produced an indentation at the center of the drug layer surface. The indented tablets were coated by using a conventional pan-coating process. Although the bottom of the indentation could be coated, the side face of the indentation was scarcely sprayed by the coating solution and this part of the tablet remained at least partly uncoated leaving an aperture from which drug release could occur. Nifedipine was selected as the model drug. Sodium chloride was used as osmotic agent, polyvinylpyrrolidone as suspending agent and croscarmellose sodium as expanding agent. The indented core tablet was coated by ethyl cellulose as semipermeable membrane containing polyethylene glycol 400 for controlling the membrane permeability. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f(2)). It was found that the optimal OPT was able to deliver nifedipine at an approximate zero-order up to 24 h, independent on both release media and agitation rates. The preparation of bilayer-core OPT was simplified by coating the indented core tablet, by which sophisticated technology of the drug layer identification and laser drilling could be eliminated. It might be promising in the field of preparation of bilayer-core OPT.

Medico-botanical study of Yercaud hills in the eastern Ghats of Tamil Nadu, India.

PubMed

Parthipan, M; Aravindhan, V; Rajendran, A

2011-04-01

The study reports medicinal plant survey was conceded in Yercaud hills ranges of Eastern Ghats, Tamil Nadu, India. The study primarily based on field surveys conducted throughout the hills, where dwellers provided information on plant species used as medicine, plant parts used to prepare the remedies and ailments to which the remedies were prescribed. The study resulted about 48- plant species belonging to 45- genera and 29- families of medicinal plants related to folk medicine used by the local people. Among them the most common plants viz., Asparagus racemosus Willd., Cissus quadrangularis L., Gymnema sylvestre R. Br., Hemidesmus indicus (L.) R. Br., Justisia adhatoda L., Ocimum sanctum L., Phyllanthes amarus Schum. & Thonn., Piper nigrum L., Solanum nigrum L., Tinospora cordifolia (Thunb.) Miers, Tridax procumbens L. and Zingiber officinale Roscoe which are used in their daily life to cure various ailments.

Balancing Risks and Resources: Financial Strategies for Colleges and Universities.

ERIC Educational Resources Information Center

Dickmeyer, Nathan

1982-01-01

Financial strategies, plans to increase return--and risk--up to the point (but not beyond) where the protection of core activities may begin to break down, are addressed. The stages for developing a financial strategy are: (1) formulate and examine academic program, research, and marketing strategies; (2) define core activities necessary to…

Reducing numerical costs for core wide nuclear reactor CFD simulations by the Coarse-Grid-CFD

NASA Astrophysics Data System (ADS)

Viellieber, Mathias; Class, Andreas G.

2013-11-01

Traditionally complete nuclear reactor core simulations are performed with subchannel analysis codes, that rely on experimental and empirical input. The Coarse-Grid-CFD (CGCFD) intends to replace the experimental or empirical input with CFD data. The reactor core consists of repetitive flow patterns, allowing the general approach of creating a parametrized model for one segment and composing many of those to obtain the entire reactor simulation. The method is based on a detailed and well-resolved CFD simulation of one representative segment. From this simulation we extract so-called parametrized volumetric forces which close, an otherwise strongly under resolved, coarsely-meshed model of a complete reactor setup. While the formulation so far accounts for forces created internally in the fluid others e.g. obstruction and flow deviation through spacers and wire wraps, still need to be accounted for if the geometric details are not represented in the coarse mesh. These are modelled with an Anisotropic Porosity Formulation (APF). This work focuses on the application of the CGCFD to a complete reactor core setup and the accomplishment of the parametrization of the volumetric forces.

Immunization of Mice by BCG Formulated HCV Core Protein Elicited Higher Th1-Oriented Responses Compared to Pluronic-F127 Copolymer

PubMed Central

Yazdanian, Maryam; Memarnejadian, Arash; Mahdavi, Mehdi; Sadat, Seyed Mehdi; Motevali, Fatemeh; Vahabpour, Rouhollah; Khanahmad, Hossein; Siadat, Seyed Davar; Aghasadeghi, Mohammad Reza; Roohvand, Farzin

2013-01-01

Background A supreme vaccine for Hepatitis C virus (HCV) infection should elicit strong Th1-oriented cellular responses. In the absence of a Th1-specific adjuvant, immunizations by protein antigens generally induce Th2-type and weak cellular responses. Objectives To evaluate the adjuvant effect of BCG in comparison with nonionic copolymer-Pluronic F127 (F127) as a classic adjuvant in the formulation of HCV core protein (HCVcp) as a candidate vaccine for induction of Th1 immune responses. Materials and Methods Expression of N-terminally His-Tagged HCVcp (1-122) by pIVEX2.4a-core vector harboring the corresponding gene under the control of arabinose-inducible (araBAD) promoter was achieved in BL21-AI strain of E.coli and purified through application of nitrilotriacetic acid (Ni-NTA) chromatography. Mice were immunized subcutaneously (s.c.) in base of the tail with 100 μl of immunogen (F127+HCVcp or BCG+HCVcp; 5 μgHCVcp/mouse/dose) or control formulations (PBS, BCG, F127) at weeks 0, 3, 6. Total and subtypes of IgG, as well as cellular immune responses (Proliferation, In vivo CTL and IFN-γ/IL-4 ELISpot assays against a strong and dominant H2-d restricted, CD8+-epitopic peptide, core 39-48; RRGPRLGVRA of HCVcp) were compared in each group of immunized animals. Results Expression and purification of core protein around the expected size (21 kDa) was confirmed by Western blotting. The HCVcp + BCG vaccinated mice showed significantly higher lymphocyte proliferation and IFN-γ production but lower levels of cell lysis (45% versus 62% in CTL assay) than the HCVcp+F127 immunized animals. “Besides, total anti-core IgG and IgG1 levels were significantly higher in HCVcp + F127 immunized mice as compared to HCVcp + BCG vaccinated animals, indicating relatively higher efficacy of F127 for the stimulation of humoral and Th2-oriented immune responses”. Conclusions Results showed that HCVcp + BCG induced a moderate CTL and mixed Th1/Th2 immune responses with higher levels of cell proliferation and IFN-γ secretion, indicating that BCG may have a better outcome when formulated in HCVcp-based subunit vaccines. PMID:24348641

Multiphysics Analysis of a Solid-Core Nuclear Thermal Engine Thrust Chamber

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Canabal, Francisco; Cheng, Gary; Chen, Yen-Sen

2006-01-01

The objective of this effort is to develop an efficient and accurate thermo-fluid computational methodology to predict environments for a hypothetical solid-core, nuclear thermal engine thrust chamber. The computational methodology is based on an unstructured-grid, pressure-based computational fluid dynamics methodology. Formulations for heat transfer in solids and porous media were implemented and anchored. A two-pronged approach was employed in this effort: A detailed thermo-fluid analysis on a multi-channel flow element for mid-section corrosion investigation; and a global modeling of the thrust chamber to understand the effect of hydrogen dissociation and recombination on heat transfer and thrust performance. The formulations and preliminary results on both aspects are presented.

The development of a stable, coated pellet formulation of a water-sensitive drug, a case study: development of a stable core formulation.

PubMed

Fitzpatrick, Shaun; Taylor, Scott; Booth, Steven W; Newton, Michael J

2006-01-01

A development program has been carried out to provide a stable extrusion/spheronisation pellet formulation for a highly water-soluble drug, sitagliptin, which undergoes a change in physical form on processing and is subject to hydrolytic decomposition. A conventional extrusion/spheronization formulation resulted in significant degradation of the drug. The inclusion of glyceryl monostearate into the formulation was found to reduce the water levels required to such a level that there was no significant degradation of the drug during processing to form pellets. The use of a ram extruder to screen formulations with small quantities minimizes the need for the drug in the formulation-screening process, and the results from this method of extrusion were found to be translatable to the use of a screen extruder, which allowed scale-up of the process.

Invalidating childhood environments and core beliefs in women with eating disorders.

PubMed

Ford, Gillian; Waller, Glenn; Mountford, Victoria

2011-01-01

It can be hypothesised that invalidating environments in childhood influence the negative core beliefs that are found in the eating disorders. This study of eating-disordered women aimed to test the relationships between perceived childhood invalidating environments and negative core beliefs. Forty-one eating-disordered females completed the measures of childhood invalidating experiences and core beliefs. Such core beliefs were most closely related to the individuals' perceptions of having grown up in a 'chaotic' family environment. Future clinical practice should continue to target core beliefs in formulating cases of eating disorders. Explaining those core beliefs may depend on understanding the individual's experiences of invalidation in early years. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association.

Single Additive Enables 3D Printing of Highly Loaded Iron Oxide Suspensions.

PubMed

Hodaei, Amin; Akhlaghi, Omid; Khani, Navid; Aytas, Tunahan; Sezer, Dilek; Tatli, Buse; Menceloglu, Yusuf Z; Koc, Bahattin; Akbulut, Ozge

2018-03-21

A single additive, a grafted copolymer, is designed to ensure the stability of suspensions of highly loaded iron oxide nanoparticles (IOPs) and to facilitate three-dimensional (3D) printing of these suspensions in the filament form. This poly (ethylene glycol)-grafted copolymer of N-[3(dimethylamino)propyl]methacrylamide and acrylic acid harnesses both electrostatic and steric repulsion to realize an optimum formulation for 3D printing. When used at 1.15 wt % (by the weight of IOPs), the suspension attains ∼81 wt % solid loading-96% of the theoretical limit as calculated by the Krieger-Dougherty equation. Rectangular, thick-walled toroidal, and thin-walled toroidal magnetic cores and a porous lattice structure are fabricated to demonstrate the utilization of this suspension as an ink for 3D printing. The electrical and magnetic properties of the magnetic cores are characterized through impedance spectroscopy (IS) and vibrating sample magnetometry (VSM), respectively. The IS indicates the possibility of utilizing wire-wound 3D printed cores as the inductive coils. The VSM verifies that the magnetic properties of IOPs before and after the ink formulation are kept almost unchanged because of the low dosage of the additive. This particle-targeted approach for the formulation of 3D printing inks allows embodiment of a fully aqueous system with utmost target material content.

Constitutive Modeling of the Facesheet to Core Interface in Honeycomb Sandwich Panels Subject to Mode I Delamination

NASA Technical Reports Server (NTRS)

Hoewer, Daniel; Lerch, Bradley A.; Bednarcyk, Brett A.; Pineda, Evan Jorge; Reese, Stefanie; Simon, Jaan-Willem

2017-01-01

A new cohesive zone traction-separation law, which includes the effects of fiber bridging, has been developed, implemented with a finite element (FE) model, and applied to simulate the delamination between the facesheet and core of a composite honeycomb sandwich panel. The proposed traction-separation law includes a standard initial cohesive component, which accounts for the initial interfacial stiffness and energy release rate, along with a new component to account for the fiber bridging contribution to the delamination process. Single cantilever beam tests on aluminum honeycomb sandwich panels with carbon fiber reinforced polymer facesheets were used to characterize and evaluate the new formulation and its finite element implementation. These tests, designed to evaluate the mode I toughness of the facesheet to core interface, exhibited significant fiber bridging and large crack process zones, giving rise to a concave downward concave upward pre-peak shape in the load-displacement curve. Unlike standard cohesive formulations, the proposed formulation captures this observed shape, and its results have been shown to be in excellent quantitative agreement with experimental load-displacement and apparent critical energy release rate results, representative of a payload fairing structure, as well as local strain fields measured with digital image correlation.

Free-edge effects in a cylindrical sandwich panel with a flexible core and laminated composite face sheets

NASA Astrophysics Data System (ADS)

Afshin, M.; Sadighi, M.; Shakeri, M.

2010-12-01

In the present study, the static response of cylindrical sandwich panels with a flexible core is investigated. The face sheets are considered as composite laminates with a cross-ply lay-up and the core as a flexible elastic medium. The flexibility of the low-strength core leads to high stress concentrations in terms of peeling stresses between the face sheets and the core at edges of the sandwich panel. To take into account the compressibility of the core and to determine the free-edge stresses of sandwich structures accurately, the Reddy layerwise theory (LWT) is used in this paper. The paper outlines the mathematical formulation, along with a numerical study, of a cylindrical sandwich panel with two simply supported and two free edges under a transverse load. The formulation includes the derivation of field equations along with boundary conditions. A Levy-type solution procedure is performed to determine the distributions of stresses and strains. In the numerical study, first a comparison is made with results from the commercial finite-element software ANSYS to verify the LWT results. Finally, a parametric study is conducted, and the effect caused by varying different parameters, such as the radii of curvature and the core to face sheet thickness ratio, on the results are investigated. The results obtained demonstrate a good agreement between LWT and FEM solutions and show increasing interlaminar stresses in the free edge of the sandwich panel

A resin composite material containing an eugenol derivative for intracanal post cementation and core build-up restoration.

PubMed

Almaroof, A; Rojo, L; Mannocci, F; Deb, S

2016-02-01

To formulate and evaluate new dual cured resin composite based on the inclusion of eugenyl methacrylate monomer (EgMA) with Bis-GMA/TEGDMA resin systems for intracanal post cementation and core build-up restoration of endodontically treated teeth. EgMA was synthesized and incorporated at 5% (BTEg5) or 10% (BTEg10) into dual-cure formulations. Curing properties, viscosity, Tg, radiopacity, static and dynamic mechanical properties of the composites were determined and compared with Clearfil™DC Core-Plus, a commercial dual-cure, two-component composite. Statistical analysis of the data was performed with ANOVA and the Tukey's post-hoc test. The experimental composites were successfully prepared, which exhibited excellent curing depths of 4.9, 4.7 and 4.2 mm for BTEg0, BTEg5 and BTEg10 respectively, which were significantly higher than Clearfil™DC. However, the inclusion of EgMA initially led to a lower degree of cure, which increased when measured at 24 h with values comparable to formulations without EgMA, indicating post-curing. The inclusion of EgMA also lowered the polymerization exotherm thereby reducing the potential of thermal damage to host tissue. Both thermal and viscoelastic analyses confirmed the ability of the monomer to reduce the stiffness of the composites by forming a branched network. The compressive strength of BTEg5 was significantly higher than the control whilst flexural strength increased significantly from 95.9 to 114.8 MPa (BTEg5) and 121.9 MPa (BTEg10). Radiopacity of the composites was equivalent to ∼3 mm Al allowing efficient diagnosis. The incorporation of EgMA within polymerizable formulations provides a novel approach to prepare reinforced resin composite material for intracanal post cementation and core build-up and the potential to impart antibacterial properties of eugenol to endodontic restorations. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Oakland and San Francisco Create Course Pathways through Common Core Mathematics. White Paper

ERIC Educational Resources Information Center

Daro, Phil

2014-01-01

The Common Core State Standards for Mathematics (CCSS-M) set rigorous standards for each of grades 6, 7 and 8. Strategic Education Research Partnership (SERP) has been working with two school districts, Oakland Unified School District and San Francisco Unified School District, to evaluate extant policies and practices and formulate new policies…

Formulation of an aloe-based product according to Iranian traditional medicine and development of its analysis method.

PubMed

Moein, Elham; Hajimehdipoor, Homa; Toliyat, Tayebeh; Choopani, Rasool; Hamzeloo-Moghadam, Maryam

2017-08-29

Currently, people are more interested to traditional medicine. The traditional formulations should be converted to modern drug delivery systems to be more acceptable for the patients. In the present investigation, a poly herbal medicine "Ayarij-e-Faiqra" (AF) based on Iranian traditional medicine (ITM) has been formulated and its quality control parameters have been developed. The main ingredients of AF including barks of Cinnamomum zeylanicum Blume and Cinnamomum cassia J. Presl, the rhizomes of Nardostachys jatamansi DC., the fruits of Piper cubeba L.f., the flowers of Rosa damascena Herrm., the oleo gum resin of Pistacia terebinthus L. and Aloe spp. dried juice were powdered and used for preparing seven tablet formulations of the herbal mixture. Flowability of the different formulated powders was examined and the best formulations were selected (F6&F7). The tablets were prepared from the selected formulations compared according to the physical characteristics and finally, F7 was selected and coated. Physicochemical characters of core and coated AF tablets were determined and the HPLC method for quantitation of aloin as a marker of tablets was selected and verified according to selectivity, linearity, precision, recovery, LOD and LOQ. The results showed that core and coated AF tablets were in agreement with USP requirements for herbal drugs. They had acceptable appearance, disintegration time, friability, hardness, dissolution behavior, weight variation and content uniformity. The amount of aloin in tablets was found 123.1 mg/tab. The HPLC method for aloin determination in AF tablets was verified according to selectivity, linearity (5-500 μg/ml, r 2 :0.9999), precision (RSD: 1.62%), recovery (108.0%), LOD & LOQ (0.0053 & 0.0161 μg/ml). The formulated tablets could be a good substitute for powder and capsules of AF in ITM clinics with a feasible and precise method for its quality control. Ayarij-e-Faiqra formulation.

Resilient Urban Infrastructures - Basics of Smart Sustainable Cities

NASA Astrophysics Data System (ADS)

Timashev, S. A.

2017-11-01

In this paper the notion of urban infrastructure resilience is formulated being expressed verbally and strictly in conditional probability terms. It is further used to formulate several most important features of a smart city. This multidisciplinary and multifaceted approach is used to explain the concept of quantitative resilience in urban design, operation, managing urban risk and mitigating of the consequences of a natural or industrial disaster. The extremely urgent problem is formulated on how to connect the physical and spatial (core) resiliencies with the functional, organizational, economic and social resiliencies.

Development of modified-release tablets of zolpidem tartrate by biphasic quick/slow delivery system.

PubMed

Mahapatra, Anjan Kumar; Sameeraja, N H; Murthy, P N

2015-06-01

Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium starch glycolate acts as a superdisintegrant in immediate-release part and hydroxypropyl methyl cellulose as a release retarding agent in extended-release core. Tablets were prepared by direct compression. Both the core and the coat contained the drug. The pre-compression blends were evaluated for angle of repose, bulk density, and compressibility index. The tablets were evaluated for thickness, hardness, weight variation test, friability, and in vitro release studies. No interaction was observed between zolpidem tartrate and excipients from the Fourier transform infrared spectroscopy and differential scanning calorimetry analysis. The results of all the formulations prepared were compared with reference product Stilnoct®. Optimized formulations showed release patterns that match the United States Pharmacopeia (USP) guidelines for zolpidem tartrate extended-release tablets. The mechanism of drug release was studied using different mathematical models, and the optimized formulation has shown Fickian diffusion. Accelerated stability studies were performed on the optimized formulation.

Bermuda 2.0: reflections from Santa Cruz

PubMed Central

Reardon, Jenny; Ankeny, Rachel A.; Bangham, Jenny; W. Darling, Katherine; Hilgartner, Stephen; Jones, Kathryn Maxson; Shapiro, Beth; Stevens, Hallam

2016-01-01

Abstract In February 1996, the genome community met in Bermuda to formulate principles for circulating genomic data. Although it is now 20 years since the Bermuda Principles were formulated, they continue to play a central role in shaping genomic and data-sharing practices. However, since 1996, “openness” has become an increasingly complex issue. This commentary seeks to articulate three core challenges data-sharing faces today. PMID:28369360

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

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.

Simultaneous Optimization of Multiple Response Variables for the Gelatin-chitosan Microcapsules Containing Angelica Essential Oil.

PubMed

Li, Qiang; Sun, Li-Jian; Gong, Xian-Feng; Wang, Yang; Zhao, Xue-Ling

2017-01-01

Angelica essential oil (AO), a major pharmacologically active component of Angelica sinensis (Oliv.) Diels, possesses hemogenesis, analgesic activities, and sedative effect. The application of AO in pharmaceutical systems had been limited because of its low oxidative stability. The AO-loaded gelatin-chitosan microcapsules with prevention from oxidation were developed and optimized using response surface methodology. The effects of formulation variables (pH at complex coacervation, gelatin concentration, and core/wall ratio) on multiple response variables (yield, encapsulation efficiency, antioxidation rate, percent of drug released in 1 h, and time to 85% drug release) were systemically investigated. A desirability function that combined these five response variables was constructed. All response variables investigated were found to be highly dependent on the formulation variables, with strong interactions observed between the formulation variables. It was found that optimum overall desirability of AO microcapsules could be obtained at pH 6.20, gelatin concentration 25.00%, and core/wall ratio 40.40%. The experimental values of the response variables highly agreed with the predicted values. The antioxidation rate of optimum formulation was approximately 8 times higher than that of AO. The in-vitro drug release from microcapsules was followed Higuchi model with super case-II transport mechanism.

Formulation of long-wavelength indocyanine green nanocarriers.

PubMed

Pansare, Vikram J; Faenza, William J; Lu, Hoang; Adamson, Douglas H; Prud'homme, Robert K

2017-09-01

Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved fluorophore with excitation and emission wavelengths inside the "optical imaging window," has been incorporated into nanocarriers (NCs) to achieve enhanced circulation time, targeting, and real-time tracking in vivo. While previous studies transferred ICG exogenously into NCs, here, a one-step rapid precipitation process [flash nanoprecipitation (FNP)] creates ICG-loaded NCs with tunable, narrow size distributions from 30 to 180 nm. A hydrophobic ion pair of ICG-tetraoctylammonium or tetradodecylammonium chloride is formed either in situ during FNP or preformed then introduced into the FNP feed stream. The NCs are formulated with cores comprising either vitamin E (VE) or polystyrene (PS). ICG core loadings of 30 wt. % for VE and 10 wt. % for PS are achieved. However, due to a combination of molecular aggregation and Förster quenching, maximum fluorescence (FL) occurs at 10 wt. % core loading. The FL-per-particle scales with core diameter to the third power, showing that FNP enables uniform volume encapsulation. By varying the ICG counter-ion ratio, encapsulation efficiencies above 80% are achieved even in the absence of ion pairing, which rises to 100% with 1∶1 ion pairing. Finally, while ICG ion pairs are shown to be stable in buffer, they partition out of NC cores in under 30 min in the presence of physiological albumin concentrations. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Formulation of long-wavelength indocyanine green nanocarriers

NASA Astrophysics Data System (ADS)

Pansare, Vikram J.; Faenza, William J.; Lu, Hoang; Adamson, Douglas H.; Prud'homme, Robert K.

2017-09-01

Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved fluorophore with excitation and emission wavelengths inside the "optical imaging window," has been incorporated into nanocarriers (NCs) to achieve enhanced circulation time, targeting, and real-time tracking in vivo. While previous studies transferred ICG exogenously into NCs, here, a one-step rapid precipitation process [flash nanoprecipitation (FNP)] creates ICG-loaded NCs with tunable, narrow size distributions from 30 to 180 nm. A hydrophobic ion pair of ICG-tetraoctylammonium or tetradodecylammonium chloride is formed either in situ during FNP or preformed then introduced into the FNP feed stream. The NCs are formulated with cores comprising either vitamin E (VE) or polystyrene (PS). ICG core loadings of 30 wt. % for VE and 10 wt. % for PS are achieved. However, due to a combination of molecular aggregation and Förster quenching, maximum fluorescence (FL) occurs at 10 wt. % core loading. The FL-per-particle scales with core diameter to the third power, showing that FNP enables uniform volume encapsulation. By varying the ICG counter-ion ratio, encapsulation efficiencies above 80% are achieved even in the absence of ion pairing, which rises to 100% with 1∶1 ion pairing. Finally, while ICG ion pairs are shown to be stable in buffer, they partition out of NC cores in under 30 min in the presence of physiological albumin concentrations.

Multiple core-hole formation by free-electron laser radiation in molecular nitrogen

NASA Astrophysics Data System (ADS)

Banks, H. I. B.; Little, D. A.; Emmanouilidou, A.

2018-05-01

We investigate the formation of multiple-core-hole states of molecular nitrogen interacting with a free-electron laser pulse. In previous work, we obtained bound and continuum molecular orbitals in the single-center expansion scheme and used these orbitals to calculate photo-ionization and auger decay rates. We extend our formulation to track the proportion of the population that accesses single-site versus two-site double-core-hole (TSDCH) states, before the formation of the final atomic ions. We investigate the pulse parameters that favor the formation of the single-site and TSDCH as well as triple-core-hole states for 525 and 1100 eV photons.

Personal and Social Values and Skills: A Study Completed for the Saskatchewan Department of Education Core Curriculum Investigation Project.

ERIC Educational Resources Information Center

Malikail, Joseph S.; Stewart, J. Douglas

As an agency of socialization, one of the main purposes of the school is to prepare children for responsible membership in society and to encourage appropriate social/moral attitudes and behavior necessary for good citizenship. This study of personal and social skills and values was conducted to help formulate the Canadian core curriculum.…

Multi-Group Formulation of the Temperature-Dependent Resonance Scattering Model and its Impact on Reactor Core Parameters

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

Ghrayeb, Shadi Z.; Ougouag, Abderrafi M.; Ouisloumen, Mohamed

2014-01-01

A multi-group formulation for the exact neutron elastic scattering kernel is developed. It incorporates the neutron up-scattering effects, stemming from lattice atoms thermal motion and accounts for it within the resulting effective nuclear cross-section data. The effects pertain essentially to resonant scattering off of heavy nuclei. The formulation, implemented into a standalone code, produces effective nuclear scattering data that are then supplied directly into the DRAGON lattice physics code where the effects on Doppler Reactivity and neutron flux are demonstrated. The correct accounting for the crystal lattice effects influences the estimated values for the probability of neutron absorption and scattering,more » which in turn affect the estimation of core reactivity and burnup characteristics. The results show an increase in values of Doppler temperature feedback coefficients up to -10% for UOX and MOX LWR fuels compared to the corresponding values derived using the traditional asymptotic elastic scattering kernel. This paper also summarizes the results done on this topic to date.« less

Finite element formulation of viscoelastic sandwich beams using fractional derivative operators

NASA Astrophysics Data System (ADS)

Galucio, A. C.; Deü, J.-F.; Ohayon, R.

This paper presents a finite element formulation for transient dynamic analysis of sandwich beams with embedded viscoelastic material using fractional derivative constitutive equations. The sandwich configuration is composed of a viscoelastic core (based on Timoshenko theory) sandwiched between elastic faces (based on Euler-Bernoulli assumptions). The viscoelastic model used to describe the behavior of the core is a four-parameter fractional derivative model. Concerning the parameter identification, a strategy to estimate the fractional order of the time derivative and the relaxation time is outlined. Curve-fitting aspects are focused, showing a good agreement with experimental data. In order to implement the viscoelastic model into the finite element formulation, the Grünwald definition of the fractional operator is employed. To solve the equation of motion, a direct time integration method based on the implicit Newmark scheme is used. One of the particularities of the proposed algorithm lies in the storage of displacement history only, reducing considerably the numerical efforts related to the non-locality of fractional operators. After validations, numerical applications are presented in order to analyze truncation effects (fading memory phenomena) and solution convergence aspects.

Bermuda 2.0: reflections from Santa Cruz.

PubMed

Reardon, Jenny; Ankeny, Rachel A; Bangham, Jenny; W Darling, Katherine; Hilgartner, Stephen; Jones, Kathryn Maxson; Shapiro, Beth; Stevens, Hallam

2016-12-01

In February 1996, the genome community met in Bermuda to formulate principles for circulating genomic data. Although it is now 20 years since the Bermuda Principles were formulated, they continue to play a central role in shaping genomic and data-sharing practices. However, since 1996, "openness" has become an increasingly complex issue. This commentary seeks to articulate three core challenges data-sharing faces today. © The Authors 2016. Published by Oxford University Press.

Heat transfer evaluation in a plasma core reactor

NASA Technical Reports Server (NTRS)

Smith, D. E.; Smith, T. M.; Stoenescu, M. L.

1976-01-01

Numerical evaluations of heat transfer in a fissioning uranium plasma core reactor cavity, operating with seeded hydrogen propellant, was performed. A two-dimensional analysis is based on an assumed flow pattern and cavity wall heat exchange rate. Various iterative schemes were required by the nature of the radiative field and by the solid seed vaporization. Approximate formulations of the radiative heat flux are generally used, due to the complexity of the solution of a rigorously formulated problem. The present work analyzes the sensitivity of the results with respect to approximations of the radiative field, geometry, seed vaporization coefficients and flow pattern. The results present temperature, heat flux, density and optical depth distributions in the reactor cavity, acceptable simplifying assumptions, and iterative schemes. The present calculations, performed in cartesian and spherical coordinates, are applicable to any most general heat transfer problem.

An investigation into moisture barrier film coating efficacy and its relevance to drug stability in solid dosage forms.

PubMed

Mwesigwa, Enosh; Basit, Abdul W

2016-01-30

Barrier coatings are frequently employed on solid oral dosage forms under the assumption that they prevent moisture sorption into tablet cores thereby averting premature degradation of moisture-sensitive active ingredients. However, the efficacy of moisture barrier coatings remains unproven and they may actually accelerate degradation. This study aimed to investigate the barrier performance of four coating systems following application onto a low hygroscopic tablet formulation containing aspirin as a model moisture sensitive drug. Tablets were prepared by direct compaction and coated with aqueous dispersions of Eudragit(®) L30 D-55, Eudragit(®) EPO, Opadry(®) AMB and Sepifilm(®) LP at the vendors' recommended weight gains. Moisture uptake was studied by dynamic vapor sorption at 0 and 75% RH (25°C). Accelerated stability studies were undertaken at 75% RH/25°C for 90 days and HPLC assay was used to determine aspirin content. Uncoated tablet cores equilibrated rapidly and took up very little water (0.09%). The mean water uptake for coated cores was higher than for the uncoated formulation and varied as follows: 0.19% (Eudragit(®) L30 D-55), 0.35% (Opadry(®) AMB), 0.49% (Sepifilm(®) LP) and 0.76% (Eudragit(®) EPO). The level of aspirin decreased in all the samples such that by the time the study was terminated, the mean aspirin recovered was as follows: uncoated cores 80.0%; Eudragit® L30 D-55 coated cores 78.8%; Opadry(®) AMB coated cores 76.2%, Sepifilm(®) LP coated cores 76.0% and Eudragit(®) EPO coated samples 66.5%. From these results, it is concluded that the efficacy of moisture barrier polymer coatings on low hygroscopic cores is limited, and application of these coatings can, instead, enhance drug degradation in solid dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

What Do Core Obligations under the Right to Health Bring to Universal Health Coverage?

PubMed

Forman, Lisa; Beiersmann, Claudia; Brolan, Claire E; Mckee, Martin; Hammonds, Rachel; Ooms, Gorik

2016-12-01

Can the right to health, and particularly the core obligations of states specified under this right, assist in formulating and implementing universal health coverage (UHC), now included in the post-2015 Sustainable Development Goals? In this paper, we examine how core obligations under the right to health could lead to a version of UHC that is likely to advance equity and rights. We first address the affinity between the right to health and UHC as evinced through changing definitions of UHC and the health domains that UHC explicitly covers. We then engage with relevant interpretations of the right to health, including core obligations. We turn to analyze what core obligations might bring to UHC, particularly in defining what and who is covered. Finally, we acknowledge some of the risks associated with both UHC and core obligations and consider potential avenues for mitigating these risks.

Multigroup computation of the temperature-dependent Resonance Scattering Model (RSM) and its implementation

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

Ghrayeb, S. Z.; Ouisloumen, M.; Ougouag, A. M.

2012-07-01

A multi-group formulation for the exact neutron elastic scattering kernel is developed. This formulation is intended for implementation into a lattice physics code. The correct accounting for the crystal lattice effects influences the estimated values for the probability of neutron absorption and scattering, which in turn affect the estimation of core reactivity and burnup characteristics. A computer program has been written to test the formulation for various nuclides. Results of the multi-group code have been verified against the correct analytic scattering kernel. In both cases neutrons were started at various energies and temperatures and the corresponding scattering kernels were tallied.more » (authors)« less

Antigenic potential of a highly conserved Neisseria meningitidis lipopolysaccharide inner core structure defined by chemical synthesis.

PubMed

Reinhardt, Anika; Yang, You; Claus, Heike; Pereira, Claney L; Cox, Andrew D; Vogel, Ulrich; Anish, Chakkumkal; Seeberger, Peter H

2015-01-22

Neisseria meningitidis is a leading cause of bacterial meningitis worldwide. We studied the potential of synthetic lipopolysaccharide (LPS) inner core structures as broadly protective antigens against N. meningitidis. Based on the specific reactivity of human serum antibodies to synthetic LPS cores, we selected a highly conserved LPS core tetrasaccharide as a promising antigen. This LPS inner core tetrasaccharide induced a robust IgG response in mice when formulated as an immunogenic glycoconjugate. Binding of raised mouse serum to a broad collection of N. meningitidis strains demonstrated the accessibility of the LPS core on viable bacteria. The distal trisaccharide was identified as the crucial epitope, whereas the proximal Kdo moiety was immunodominant and induced mainly nonprotective antibodies that are responsible for lack of functional protection in polyclonal serum. Our results identified key antigenic determinants of LPS core glycan and, hence, may aid the design of a broadly protective immunization against N. meningitidis. Copyright © 2015 Elsevier Ltd. All rights reserved.

The development of a multidisciplinary, evidence-based guideline for "HIV and employment".

PubMed

Wagener, Marlies N; Roelofs, Pepijin; Miedema, Harold S; Brandjes, Dees P M; Dahmen, Rutger; van Gorp, Eric C M

2015-01-01

The objective of this study was to develop a multidisciplinary guideline that supports the care and vocational rehabilitation of HIV-infected people with employment-related problems. The guideline was developed according to the "evidence-based guideline development" method developed by the Dutch Institute for Health Care Improvement. This method consists of the following steps: forming a multidisciplinary core group and an expert panel, formulating key questions, searching and appraising the available literature, formulating considerations and recommendations, peer reviewing the draft guideline, and authorizing the final guideline. All relevant professional associations were represented in the core group that was assembled to develop the guideline, i.e., HIV doctors, HIV nurses, general practitioners, occupational health physicians, psychologists, social workers, occupational health nurses, vocational experts, and insurance physicians. Five key questions for the guideline were formulated with the following themes: determinants of employment, disclosure and stigma, self-management, interventions, and the organization of care. In the literature review on these topics, 45 studies met the inclusion criteria. The methodological quality of the included articles was poor. Factors such as patient preferences and medical/ethical issues were considered. The recommendations in the guideline are a weighting of the scientific evidence and the considerations of the core group. The guideline, as well as its summary for daily practice, clarifies the most important barriers and facilitators to people with HIV either staying at work or returning to work, and it constitutes a clinical, easy-to-use guideline for health-care providers and how they can support people with HIV who want to work.

Surface integral analogy approaches for predicting noise from 3D high-lift low-noise wings

NASA Astrophysics Data System (ADS)

Yao, Hua-Dong; Davidson, Lars; Eriksson, Lars-Erik; Peng, Shia-Hui; Grundestam, Olof; Eliasson, Peter E.

2014-06-01

Three surface integral approaches of the acoustic analogies are studied to predict the noise from three conceptual configurations of three-dimensional high-lift low-noise wings. The approaches refer to the Kirchhoff method, the Ffowcs Williams and Hawkings (FW-H) method of the permeable integral surface and the Curle method that is known as a special case of the FW-H method. The first two approaches are used to compute the noise generated by the core flow region where the energetic structures exist. The last approach is adopted to predict the noise specially from the pressure perturbation on the wall. A new way to construct the integral surface that encloses the core region is proposed for the first two methods. Considering the local properties of the flow around the complex object-the actual wing with high-lift devices-the integral surface based on the vorticity is constructed to follow the flow structures. The surface location is discussed for the Kirchhoff method and the FW-H method because a common surface is used for them. The noise from the core flow region is studied on the basis of the dependent integral quantities, which are indicated by the Kirchhoff formulation and by the FW-H formulation. The role of each wall component on noise contribution is analyzed using the Curle formulation. Effects of the volume integral terms of Lighthill's stress tensors on the noise prediction are then evaluated by comparing the results of the Curle method with the other two methods.

Oral delivery of insulin via polyethylene imine-based nanoparticles for colonic release allows glycemic control in diabetic rats.

PubMed

Salvioni, Lucia; Fiandra, Luisa; Del Curto, Maria Dorly; Mazzucchelli, Serena; Allevi, Raffaele; Truffi, Marta; Sorrentino, Luca; Santini, Benedetta; Cerea, Matteo; Palugan, Luca; Corsi, Fabio; Colombo, Miriam

2016-08-01

In this study, insulin-containing nanoparticles were loaded into pellet cores and orally administered to diabetic rats. Polyethylene imine-based nanoparticles, either placebo or loaded with insulin, were incorporated by extrusion and spheronization technology into cores that were subsequently coated with three overlapping layers and a gastroresistant film. The starting and coated systems were evaluated in vitro for their physico-technololgical characteristics, as well as disintegration and release performance. Nanoparticles-loaded cores showed homogeneous particle size distribution and shape. When a superdisintegrant and a soluble diluent were included in the composition enhanced disintegration and release performance were observed. The selected formulations, coated either with enteric or three-layer films, showed gastroresistant and release delayed behavior in vitro, respectively. The most promising formulations were finally tested for their hypoglycemic effect in diabetic rats. Only the nanoformulations loaded into the three-layer pellets were able to induce a significant hypoglycemic activity in diabetic rats. Our results suggest that this efficient activity could be attributed to a retarded release of insulin into the distal intestine, characterized by relatively low proteolytic activity and optimal absorption. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trials

PubMed Central

Othman, Ahmed A; Nothaft, Wolfram; Awni, Walid M; Dutta, Sandeep

2013-01-01

Aim To characterize quantitatively the relationship between ABT-102, a potent and selective TRPV1 antagonist, exposure and its effects on body temperature in humans using a population pharmacokinetic/pharmacodynamic modelling approach. Methods Serial pharmacokinetic and body temperature (oral or core) measurements from three double-blind, randomized, placebo-controlled studies [single dose (2, 6, 18, 30 and 40 mg, solution formulation), multiple dose (2, 4 and 8 mg twice daily for 7 days, solution formulation) and multiple-dose (1, 2 and 4 mg twice daily for 7 days, solid dispersion formulation)] were analyzed. nonmem was used for model development and the model building steps were guided by pre-specified diagnostic and statistical criteria. The final model was qualified using non-parametric bootstrap and visual predictive check. Results The developed body temperature model included additive components of baseline, circadian rhythm (cosine function of time) and ABT-102 effect (Emax function of plasma concentration) with tolerance development (decrease in ABT-102 Emax over time). Type of body temperature measurement (oral vs. core) was included as a fixed effect on baseline, amplitude of circadian rhythm and residual error. The model estimates (95% bootstrap confidence interval) were: baseline oral body temperature, 36.3 (36.3, 36.4)°C; baseline core body temperature, 37.0 (37.0, 37.1)°C; oral circadian amplitude, 0.25 (0.22, 0.28)°C; core circadian amplitude, 0.31 (0.28, 0.34)°C; circadian phase shift, 7.6 (7.3, 7.9) h; ABT-102 Emax, 2.2 (1.9, 2.7)°C; ABT-102 EC50, 20 (15, 28) ng ml−1; tolerance T50, 28 (20, 43) h. Conclusions At exposures predicted to exert analgesic activity in humans, the effect of ABT-102 on body temperature is estimated to be 0.6 to 0.8°C. This effect attenuates within 2 to 3 days of dosing. PMID:22966986

Technical report series on global modeling and data assimilation. Volume 5: Documentation of the AIRES/GEOS dynamical core, version 2

NASA Technical Reports Server (NTRS)

Suarez, Max J. (Editor); Takacs, Lawrence L.

1995-01-01

A detailed description of the numerical formulation of Version 2 of the ARIES/GEOS 'dynamical core' is presented. This code is a nearly 'plug-compatible' dynamics for use in atmospheric general circulation models (GCMs). It is a finite difference model on a staggered latitude-longitude C-grid. It uses second-order differences for all terms except the advection of vorticity by the rotation part of the flow, which is done at fourth-order accuracy. This dynamical core is currently being used in the climate (ARIES) and data assimilation (GEOS) GCMs at Goddard.

Can we decide which outcomes should be measured in every clinical trial? A scoping review of the existing conceptual frameworks and processes to develop core outcome sets.

PubMed

Idzerda, Leanne; Rader, Tamara; Tugwell, Peter; Boers, Maarten

2014-05-01

The usefulness of randomized control trials to advance clinical care depends upon the outcomes reported, but disagreement on the choice of outcome measures has resulted in inconsistency and the potential for reporting bias. One solution to this problem is the development of a core outcome set: a minimum set of outcome measures deemed critical for clinical decision making. Within rheumatology the Outcome Measures in Rheumatology (OMERACT) initiative has pioneered the development of core outcome sets since 1992. As the number of diseases addressed by OMERACT has increased and its experience in formulating core sets has grown, clarification and update of the conceptual framework and formulation of a more explicit process of area/domain core set development has become necessary. As part of the update process of the OMERACT Filter criteria to version 2, a literature review was undertaken to compare and contrast the OMERACT conceptual framework with others within and outside rheumatology. A scoping search was undertaken to examine the extent, range, and nature of conceptual frameworks for core set outcome selection in health. We searched the following resources: Cochrane Library Methods Group Register; Medline; Embase; PsycInfo; Environmental Studies and Policy Collection; and ABI/INFORM Global. We also conducted a targeted Google search. Five conceptual frameworks were identified: the WHO tripartite definition of health; the 5 Ds (discomfort, disability, drug toxicity, dollar cost, and death); the International Classification of Functioning (ICF); PROMIS (Patient-Reported Outcomes Measurement System); and the Outcomes Hierarchy. Of these, only the 5 Ds and ICF frameworks have been systematically applied in core set development. Outside the area of rheumatology, several core sets were identified; these had been developed through a limited range of consensus-based methods with varying degrees of methodological rigor. None applied a framework to ensure content validity of the end product. This scoping review reinforced the need for clear methods and standards for core set development. Based on these findings, OMERACT will make its own conceptual framework and working process more explicit. Proposals for how to achieve this were discussed at the OMERACT 11 conference.

Written case formulations in the treatment of anorexia nervosa: Evidence for therapeutic benefits.

PubMed

Allen, Karina L; O'Hara, Caitlin B; Bartholdy, Savani; Renwick, Beth; Keyes, Alexandra; Lose, Anna; Kenyon, Martha; DeJong, Hannah; Broadbent, Hannah; Loomes, Rachel; McClelland, Jessica; Serpell, Lucy; Richards, Lorna; Johnson-Sabine, Eric; Boughton, Nicky; Whitehead, Linette; Treasure, Janet; Wade, Tracey; Schmidt, Ulrike

2016-09-01

Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882). © 2016 Wiley Periodicals, Inc.

Extension to linear dynamics for hybrid stress finite element formulation based on additional displacements

NASA Astrophysics Data System (ADS)

Sumihara, K.

Based upon legitimate variational principles, one microscopic-macroscopic finite element formulation for linear dynamics is presented by Hybrid Stress Finite Element Method. The microscopic application of Geometric Perturbation introduced by Pian and the introduction of infinitesimal limit core element (Baby Element) have been consistently combined according to the flexible and inherent interpretation of the legitimate variational principles initially originated by Pian and Tong. The conceptual development based upon Hybrid Finite Element Method is extended to linear dynamics with the introduction of physically meaningful higher modes.

Phytochemical screening and antiviral activity of some medicinal plants from the island Soqotra.

PubMed

Mothana, Ramzi A A; Mentel, Renate; Reiss, Christiane; Lindequist, Ulrike

2006-04-01

Methanol and hot-aqueous extracts of 25 different plant species, used in Yemeni traditional medicine and growing, partly as endemic plants, on the island Soqotra have been investigated for their antiviral activity. In addition, the phytochemical identification of the main chemical constituents was performed. The extracts were assayed in two in vitro viral systems, which used influenza virus type A/MDCK cells and herpes simplex virus type 1/Vero cells, at non-cytotoxic concentrations. The herpes simplex virus type 1 showed more sensitivity than the influenza virus type A against the extracts investigated. The methanol extracts of Boswellia ameero, Boswellia elongata, Buxus hildebrandtii, Cissus hamaderohensis, Cleome socotrana, Dracaena cinnabari, Exacum affine, Jatropha unicostata and Kalanchoe farinacea showed anti-influenza virus type A activity with 50% inhibition (IC50) concentrations ranging from 0.7 to 12.5 microg/mL. In addition, 17 plants of the 25 investigated exhibited anti-HSV-1 activity. The antiviral activity of some active extracts was also observed on a molecular level. Copyright 2006 John Wiley & Sons, Ltd.

Preliminary screening of some traditional Zulu medicinal plants for antineoplastic activities versus the HepG2 cell line.

PubMed

Opoku, A R; Geheeb-Keller, M; Lin, J; Terblanche, S E; Hutchings, A; Chuturgoon, A; Pillay, D

2000-11-01

Aqueous and methanol extracts of nine traditional Zulu medicinal plants, Cissus quandrangularis L., Cyphostemma flaviflorum (Sprague) Descoings, Cyphostemma lanigerum (Harv.) Descoings ex Wild & Drum, Cyphostemma natalitium (Szyszyl.) J. v. d. Merwe, Cyphostemma sp., Rhoicissus digitata (L. F.) Gilg & Brandt, Rhoicissus rhomboidea (E. Mey. Ex harv.) Planch, Rhoicissus tomentosa (Lam.) Wild & Drum, R. tridentata (L. F.) Wild & Drum and Rhoicissus tridentata (L. F.) Wild & Drum subsp. cuneifolia (Eckl. & Zeyh.) N. R. Urton, all belonging to the Vitaceae family, were evaluated to determine their therapeutic potentials as antineoplastic agents. The antiproliferative activity in vitro against HepG2 cells was determined. Twenty-two of the twenty-seven crude plant extracts showed activities ranging from 25% to 97% inhibition of proliferation when compared with the control which showed no inhibitory activity. Higher degrees of growth inhibition were found in aqueous root extracts in comparison with the methanol extracts of the same plant parts. The results show potential antineoplastic activity, indicating some scientific validation for traditional usage. Copyright 2000 John Wiley & Sons, Ltd.

Influence of polymeric subcoats on the drug release properties of tablets powder-coated with pre-plasticized Eudragit L 100-55.

PubMed

Sauer, Dorothea; Watts, Alan B; Coots, Lonique B; Zheng, Weijia C; McGinity, James W

2009-02-09

The aim of the study was to investigate the properties of sodium valproate tablets that were dry powder-coated with pre-plasticized Eudragit L 100-55. Polyethylene glycol 3350 (PEG 3350) was used as primer to facilitate initial coating powder adhesion. Solubility parameters were employed to determine the wetting properties of the PEG 3350 primer. Additional PEG 3350 within the powder coating formulation was required to enable powder adhesion to the tablet cores. The application of a subcoat of either Eudragit E PO or Eudragit RL PO facilitated adhesion of the enteric polymer to the tablet cores and reduced the amount PEG 3350 required in the coating formulation. Since reduction of the PEG 3350 content produced less water-vapor permeable films, the enteric coating level necessary to control the drug release was decreased. PEG 3350 and Methocel K4M were incorporated in both Eudragit E PO and Eudragit RL PO subcoating formulations as pore forming agents. The influence of the pore forming excipients on physicochemical properties of free powder-cast films was investigated. The miscibility of the PEG 3350 and Methocel K4M in the film coating was correlated with their ability to function as pore forming agent.

40 CFR 63.7744 - How do I demonstrate continuous compliance with the work practice standards that apply to me?

Code of Federal Regulations, 2011 CFR

2011-07-01

... procedures used by the scrap supplier for either removing accessible mercury switches or for purchasing... chemical composition of all catalyst binder formulations applied in each furan warm box mold or core making...

40 CFR 63.7744 - How do I demonstrate continuous compliance with the work practice standards that apply to me?

Code of Federal Regulations, 2012 CFR

2012-07-01

... procedures used by the scrap supplier for either removing accessible mercury switches or for purchasing... chemical composition of all catalyst binder formulations applied in each furan warm box mold or core making...

40 CFR 63.7744 - How do I demonstrate continuous compliance with the work practice standards that apply to me?

Code of Federal Regulations, 2014 CFR

2014-07-01

... procedures used by the scrap supplier for either removing accessible mercury switches or for purchasing... chemical composition of all catalyst binder formulations applied in each furan warm box mold or core making...

40 CFR 63.7744 - How do I demonstrate continuous compliance with the work practice standards that apply to me?

Code of Federal Regulations, 2013 CFR

2013-07-01

... procedures used by the scrap supplier for either removing accessible mercury switches or for purchasing... chemical composition of all catalyst binder formulations applied in each furan warm box mold or core making...

Novel alginate hydrogel core-shell systems for combination delivery of ranitidine HCl and aceclofenac.

PubMed

Jana, Sougata; Samanta, Abhijit; Nayak, Amit Kumar; Sen, Kalyan Kumar; Jana, Subrata

2015-03-01

A novel hydrogel system was successfully developed based on core-shell approach for the delivery of ranitidine HCl and aceclofenac. Aceclofenac-loaded alginate microspheres coated with eudragit L-100 was used as core material and that of freeze-thaw cross-linked chitosan-PVA gels containing ranitidine HCl served as the shell-forming material. The alginate microspheres coated with eudragit L-100 showed drug encapsulation efficiency of 56.06±1.12 to 68.03±2.16% and had average particle sizes of 551.29±25.92 to 677.18±27.05 μm. The viscosity of chitosan-PVA gels ranged between 505.74±1.04 and 582.41±2.09 cps. The formulations were characterized by FTIR, SEM and polarized microscopy analyses. The release of ranitidine HCl was comparatively higher in acidic medium (pH 1.2) than in alkaline medium (pH 7.4). The release of aceclofenac became slower in alkaline medium (pH 7.4) and continued up to 3.5 h. Super case-II transport mechanism was assumed for the release of ranitidine HCl in both media; whereas non-Fickian (anomalous) diffusion mechanism predominated in the release of aceclofenc. Thus, hydrogel-based core-shell formulations were found suitable for simultaneous delivery of aceclofenac and ranitidine HCl which could minimize the chances of excessive gastric acid secretion through suitable ranitidine HCl release in gastric region. Copyright © 2014. Published by Elsevier B.V.

Optimization of Time Controlled 6-mercaptopurine Delivery for Site- Specific Targeting to Colon Diseases.

PubMed

Hude, Rahul U; Jagdale, Swati C

2016-01-01

6-MP has short elimination time (<2 h) and low bioavailability (~ 50%). Present study was aimed to develop time controlled and site targeted delivery of 6-Mercaptopurine (6-MP) for treatment of colon diseases. Compression coating technique was used. 32 full factorial design was designed for optimization of the outer coat for the core tablet. For outer coat amount of Eudragit RS 100 and hydroxypropyl methylcellulose (HPMC K100) were employed as independent variables each at three levels while responses evaluated were swelling index and bursting time. Direct compression method was used for tablets formulation. 80% w/w of microcrystalline cellulose and 20% w/w of croscarmellose sodium were found to be optimum concentration for the core tablet. The outer coat of optimized batch (ED) contains 21.05% w/w Eudragit RS 100 and 78.95% w/w HPMC K100 of total polymer weight. In-vitro dissolution study indicated that combination of polymer retards the drug release in gastric region and releases ≥95% of drug in colonic region after ≥7 h. Whereas in case of in-vivo placebo x-ray imaging study had shown that the tablet reaches colonic part after 5±0.5 h providing the proof of arrival in the colon. Stability study indicated that the optimized formulation were physically and chemically stable. Present research work concluded that compression coating by Eudragit RS 100 and HPMC K100 to 6-MP core provides potential colon targeted system with advantages of reduced gastric exposure and enhanced bioavailability. Formulation can be considered as potential and promising candidate for the treatment of colon diseases.

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.

Reducing the level of leaves damage of (Brassica rapa) caused by armyworm (Spodoptera litura F.) through liquid bioinsecticide formulation of bintaro (Cerbera odollam) leaves extract

NASA Astrophysics Data System (ADS)

Purwani, Kristanti Indah; Nurhatika, Sri; Ermavitalini, Dini; Saputro, Triono Bagus; Budiarti, Dwi Setia

2017-06-01

Bioinsecticide formulation conducted by adjuvant addition to improve its effecetiveness in the application. Its addition was only help to work whereas active compound and ingredient as a main core originated from plant simplicia. This research was utilized bintaro (Cerbera odollam) as simplicia. It already began to use it as bioinsecticide against armyworm (Spodoptera litura F) even formulation approachment was not conducted in mustard (Brassica rapa) in previous research. Mustard commodity commonly measured based on leaves performences, when its performance broke by pest such as armyworm might decline the commercial value. So this research aimed to determine the effectiveness of liquid biopesticide formulation of the active ingredient from bintaro (Cerbera odollam) leaf extract in pressing the attack larvae of S. litura F. Larvae deployed in mustard leaves (16 HST). Liquid bioinsecticide concentration formulated in 30%, 40%, 50%, 60%, and 70%. Spraying method used to against S. litura F. consisted on preventive (15 HST) and curative (17 HST). Leaves damage observation conducted at day - 35th (HST). The result showed the formulation suppressed larvae from 40% concentration in preventive way 15 HST and 60% concentration as curative way at 17 HST.

Assessment of planning abilities in individuals with mild cognitive impairment using an open-ended problem-solving task.

PubMed

Sanders, Chad; Low, Christina; Schmitter-Edgecombe, Maureen

2014-01-01

There is currently limited research evaluating planning abilities, a core subcomponent of executive functioning, in individuals with mild cognitive impairment (MCI). In the present study, we utilized the "Amap Task," an open-ended problem-solving task, to separately evaluate the formulation and execution components of planning ability in individuals with MCI. Thirty-seven cognitively healthy older adults and 37 individuals with MCI used a map layout of a university apartment to develop and write out a strategy (formulation stage) to successfully complete a list of tasks (e.g., retrieve and fill a water pitcher before placing it in the refrigerator). Subsequently, participants carried out the tasks in the apartment with the aid of their formulated plan (execution stage). MCI participants performed more poorly than older adult (OA) controls during both the formulation and execution stages on measures of task accuracy and task efficiency. However, both groups were able to adjust and improve task accuracy and efficiency from formulation to task execution. Finally, MCI participants took significantly longer to complete the task and adhered less to their formulated plans during task completion. Using an open-ended problem-solving task, the findings revealed that individuals with MCI experienced difficulties with both the formulation and execution components of planning. Like controls, participants with MCI were able to successfully modify their plan online, improving their performance from task formulation to task execution.

Experimenting with Mathematical Biology

ERIC Educational Resources Information Center

Sanft, Rebecca; Walter, Anne

2016-01-01

St. Olaf College recently added a Mathematical Biology concentration to its curriculum. The core course, Mathematics of Biology, was redesigned to include a wet laboratory. The lab classes required students to collect data and implement the essential modeling techniques of formulation, implementation, validation, and analysis. The four labs…

Application of ethyl cellulose, microcrystalline cellulose and octadecanol for wax based floating solid dispersion pellets.

PubMed

Yan, Hong-Xiang; Zhang, Shuang-Shuang; He, Jian-Hua; Liu, Jian-Ping

2016-09-05

The present study aimed to develop and optimize the wax based floating sustained-release dispersion pellets for a weakly acidic hydrophilic drug protocatechuic acid to achieve prolonged gastric residence time and improved bioavailability. This low-density drug delivery system consisted of octadecanol/microcrystalline cellulose mixture matrix pellet cores prepared by extrusion-spheronization technique, coated with drug/ethyl cellulose 100cp solid dispersion using single-step fluid-bed coating method. The formulation-optimized pellets could maintain excellent floating state without lag time and sustain the drug release efficiently for 12h based on non-Fickian transport mechanism. Observed by SEM, the optimized pellet was the dispersion-layered spherical structure containing a compact inner core. DSC, XRD and FTIR analysis revealed drug was uniformly dispersed in the amorphous molecule form and had no significant physicochemical interactions with the polymer dispersion carrier. The stability study of the resultant pellets further proved the rationality and integrity of the developed formulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of lycopene-loaded lipid-core nanocapsules: physicochemical characterization and stability study

NASA Astrophysics Data System (ADS)

dos Santos, Priscilla Pereira; Paese, Karina; Guterres, Silvia Stanisçuaski; Pohlmann, Adriana Raffin; Costa, Tania Hass; Jablonski, André; Flôres, Simone Hickmann; Rios, Alessandro de Oliveira

2015-02-01

The objective of this study was to develop lycopene-loaded lipid-core nanocapsules (Lyc-LNCs) by the interfacial deposition of preformed poly(ɛ-caprolactone) (PCL). Lyc extract (93.9 %) was obtained from tomatoes, and the organic phase was prepared with polymer (PCL), caprylic/capric triglycerides, sorbitan monostearate, and Lyc in a mixture of acetone and ethanol under magnetic stirring at 40 °C. The organic phase was injected into an aqueous phase containing polysorbate 80, and the suspension was concentrated under reduced pressure. The formulation with a Lyc concentration of 85 µg/mL was characterized in terms of size distribution, zeta potential, encapsulation efficiency, pH, viscosity, and color. The Lyc-LNC formulation presented stable values for the z-average (193 ± 4.7 nm) and zeta potential (-11.5 ± 0.40 mV). Despite the lower pH, Lyc content, and color change of the suspension, the nanocapsules showed satisfactory stability, presenting around 50 % Lyc content after 14 days of storage at room temperature (25 °C).

Pediatric drug formulation of sodium benzoate extended-release granules.

PubMed

Combescot, E; Morat, G; de Lonlay, P; Boudy, V

2016-01-01

Urea cycle disorders are a group of inherited orphan diseases leading to hyperammonemia. Current therapeutic strategy includes high doses of sodium benzoate leading to three or four oral intakes per day. As this drug is currently available in capsules or in solution, children are either unable to swallow the capsule or reluctant to take the drug due to its strong bitter taste. The objective of the present study was to develop solid, multiparticulate formulations of sodium benzoate, which are suitable for pediatric patients (i.e. flavor-masked, easy to swallow and with a dosing system). Drug layering and coating in a fluidized bed were applied for preparing sustained-release granules. Two types of inert cores (GalenIQ® and Suglets®) and three different polymers (Kollicoat®, Aquacoat® and Eudragit®) were tested in order to select the most appropriate polymer and starter core for our purpose. Physical characteristics and drug release profiles of the pellets were evaluated. A Suglets® core associated with a Kollicoat® coating seems to be the best combination for an extended release of sodium benzoate. A curing period of 8 h was necessary to complete film formation and the resulting drug release pattern was found to be dependent of the acidity of the release medium.

Preparation and characterization of dextran nanobubbles for oxygen delivery.

PubMed

Cavalli, R; Bisazza, A; Giustetto, P; Civra, A; Lembo, D; Trotta, G; Guiot, C; Trotta, M

2009-11-03

Dextran nanobubbles were prepared with a dextran shell and a perfluoropentan core in which oxygen was stored. To increase the stability polyvinylpirrolidone was also added to the formulation as stabilizing agent. Rhodamine B was used as fluorescent marker to obtain fluorescent nanobubbles. The nanobubble formulations showed sizes of about 500nm, a negative surface charge and a good capacity of loading oxygen, no hemolytic activity or toxic effect on cell lines. The fluorescent labelled nanobubbles could be internalized in Vero cells. Oxygen-filled nanobubbles were able to release oxygen in different hypoxic solutions at different time after their preparation in in vitro experiments. The oxygen release kinetics could be enhanced after nanobubble insonation with ultrasound at 2.5MHz. The oxygen-filled nanobubble formulations might be proposed for therapeutic applications in various diseases.

What could a strengthened right to health bring to the post-2015 health development agenda?: interrogating the role of the minimum core concept in advancing essential global health needs.

PubMed

Forman, Lisa; Ooms, Gorik; Chapman, Audrey; Friedman, Eric; Waris, Attiya; Lamprea, Everaldo; Mulumba, Moses

2013-12-01

Global health institutions increasingly recognize that the right to health should guide the formulation of replacement goals for the Millennium Development Goals, which expire in 2015. However, the right to health's contribution is undercut by the principle of progressive realization, which links provision of health services to available resources, permitting states to deny even basic levels of health coverage domestically and allowing international assistance for health to remain entirely discretionary. To prevent progressive realization from undermining both domestic and international responsibilities towards health, international human rights law institutions developed the idea of non-derogable "minimum core" obligations to provide essential health services. While minimum core obligations have enjoyed some uptake in human rights practice and scholarship, their definition in international law fails to specify which health services should fall within their scope, or to specify wealthy country obligations to assist poorer countries. These definitional gaps undercut the capacity of minimum core obligations to protect essential health needs against inaction, austerity and illegitimate trade-offs in both domestic and global action. If the right to health is to effectively advance essential global health needs in these contexts, weaknesses within the minimum core concept must be resolved through innovative research on social, political and legal conceptualizations of essential health needs. We believe that if the minimum core concept is strengthened in these ways, it will produce a more feasible and grounded conception of legally prioritized health needs that could assist in advancing health equity, including by providing a framework rooted in legal obligations to guide the formulation of new health development goals, providing a baseline of essential health services to be protected as a matter of right against governmental claims of scarcity and inadequate international assistance, and empowering civil society to claim fulfillment of their essential health needs from domestic and global decision-makers.

Mass spectrometric identification of Au68(SR)34 molecular gold nanoclusters with 34-electron shell closing.

PubMed

Dass, Amala

2009-08-26

The molecular formula Au(68)(SCH(2)CH(2)Ph)(34) has been assigned to the 14 kDa nanocluster using MALDI-TOF mass spectrometry. The 34-electron shell closing in a macroscopically obtained thiolated gold nanocluster is demonstrated. The Au(68) nanocluster is predicted to have a 49 atom Marks decahedral core with 19 inner core atoms and 30 outer atoms chelating with the staple motifs. The nanoclusters' predicted formulation is [Au](19+30) [Au(SR)(2)](11) [Au(2)(SR)(3)](4).

Development of autoclave moldable addition-type polyimides

NASA Technical Reports Server (NTRS)

Vaughan, R. W.; Jones, R. J.; Orell, M. K.; Zakrzewski, G. A.

1976-01-01

Chemistry and processing modifications of the poly(Diels Alder) polyimide (PDA) resin were performed to obtain structural composites suitable for 589 K (600 F) service. This work demonstrated that the PDA resin formulation is suitable for service at 589 K (600 F) for up to 125 hours when used in combination with Hercules HTS graphite fiber. Sandwich panels were autoclave molded using PDA/HTS skins and polyimide/glass honeycomb core. Excellent adhesion between honeycomb core and the facing skins was demonstrated. Fabrication ease was demonstrated by autoclave molding three-quarter scale YF-12 wing panels.

Positive and Negative Aspects of Inclusion Services

ERIC Educational Resources Information Center

Hayes, Christye

2014-01-01

The purpose of this research paper was to investigate the conceptions and misconceptions of an inclusive education. Inclusion was formulated upon three core inclusionary principles, these being: setting diverse suitable learning challenges, responding to needs of pupils, and overcoming potential barriers to learning and assessment for individuals…

Fipronil mobility and transformation in undisturbed soil columns.

PubMed

Chatterjee, Niladri Sekhar; Gupta, Suman

2010-08-01

The downward movement of fipronil and its two toxic metabolites i.e. sulfone and desulfinyl were studied in undisturbed soil columns. Mobility behavior of two different formulations of fipronil viz granular and suspension concentrate were also studied. The undisturbed columns containing sandy loam soil were leached with water equivalent to 400 mm rainfall. Results revealed that although majority of the fipronil (approximately 80%) remained in top 0-5 cm layer, substantial amount (approximately 15%) moved to 5-10 cm depth. In case of metabolites sulfone and desulfinyl >90% of the residues remained in 0-5 cm core indicating low mobility of these metabolites in comparison to fipronil. Results of mobility behavior of fipronil in granular and SC formulations revealed low mobility in granular formulation. Sulfide was detected as the major degradation product in both the formulations and was found to be distributed throughout the column. A little amount of sulfone (0.1% of the total recovered) was also detected upto 10 cm depth.

Optimization of the injection molding process for development of high performance calcium oxide -based ceramic cores

NASA Astrophysics Data System (ADS)

Zhou, P. P.; Wu, G. Q.; Tao, Y.; Cheng, X.; Zhao, J. Q.; Nan, H.

2018-02-01

The binder composition used for ceramic injection molding plays a crucial role on the final properties of sintered ceramic and to avoid defects on green parts. In this study, the effects of binder compositions on the rheological, microstructures and the mechanical properties of CaO based ceramic cores were investigated. It was found that the optimized formulation for dispersant, solid loading was 1.5 wt% and 84 wt%, respectively. The microstructures, such as porosity, pore size distribution and grain boundary density were closely related to the plasticizer contents. The decrease of plasticizer contents can enhance the strength of the ceramic cores but with decreased shrinkage. Meanwhile, the creep resistance of ceramic cores was enhanced by decreasing of plasticizer contents. The flexural strength of the core was found to decrease with the increase of the porosity, the improvement of creep resistance is closely related to the decrease of porosity and grain boundary density.

Toward unified ice core chronologies with the DatIce tool

NASA Astrophysics Data System (ADS)

Toye Mahamadou Kele, H.; Lemieux-Dudon, B.; Blayo, E.

2012-04-01

Antarctic and Greenland ice cores provide a means to study the phase relationships of climate changes in both hemispheres. They also enable to study the timing between climate, and greenhouse gases or orbital forcings. One key step for such studies is to improve the absolute and relative precisions of ice core age scales (for ice and trapped gas), and beyond that, to try to reach the best consistency between chronologies of paleo records of any kind. The DatIce tool is designed to increase the consistency between pre-existing (also called background) core chronologies. It formulates a variational inverse problem which aims at correcting three key quantities that uniquely define the core age scales: the accumulation rate, the total thinning function, and the close-off depth. For that purpose, it integrates paleo data constraints of many types among which age markers (with for instance documented volcanoes eruptions), and stratigraphic links (with for instance abrupt changes in methane concentration). A cost function is built that enables to calculate new chronologies by making a trade-off between all the constraints (background chronologies and paleo data). The method presented in Lemieux-Dudon et al (2010) has already been applied simultaneously to EPICA EDML and EDC, Vostok and NGRIP. Currently, on going works are conducted at LSCE Saclay and LGGE Grenoble laboratories to construct unified Antarctic chronologies by applying the DatIce tool with new ice cores and new sets of paleo measurements. We here present the DatIce tool, the underlying methodology, and its potential applications. We further show some improvements that have been made recently. We especially adress the issue related to the calibration of the error of pre-existing core chronologies. They are inputs that may have a strong impact on the results. However these uncertainties are uneasy to analyze, since prior chronologies are most of the time assessed on the basis of glaciological models (firn densification and ice flow models) which still face large uncertainties (forcing fields, model parameters, mechanic and physic formulation). For that reason, we chose to calibrate errors by applying consistency diagnostics, a classical method in data assimilation (Desrozier et al, 2009).

Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo

PubMed Central

Klippstein, Rebecca; Wang, Julie Tzu-Wen; El-Gogary, Riham I; Bai, Jie; Mustafa, Falisa; Rubio, Noelia; Bansal, Sukhvinder; Al-Jamal, Wafa T; Al-Jamal, Khuloud T

2015-01-01

Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half-life and poor water solubility. Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic-co-glycolic acid) (PLGA)-based polymeric oil-cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico-chemical properties, and shelf-life stability. The results indicate that castor oil-cored PLGA-based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin-loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non-PEGylated NC, and accumulates in the subcutaneous CT26-tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer. PMID:26140363

Polymeric micelles with ionic cores containing biodegradable cross-links for delivery of chemotherapeutic agents.

PubMed

Kim, Jong Oh; Sahay, Gaurav; Kabanov, Alexander V; Bronich, Tatiana K

2010-04-12

Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca(2+)) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross-linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like nanospheres and demonstrated a time-dependent degradation in the conditions mimicking the intracellular reducing environment. The ionic character of the cores allowed to achieve a very high level of doxorubicin (DOX) loading (50% w/w) into the cross-linked micelles. DOX-loaded degradable cross-linked micelles exhibited more potent cytotoxicity against human A2780 ovarian carcinoma cells as compared to micellar formulations without disulfide linkages. These novel biodegradable cross-linked micelles are expected to be attractive candidates for delivery of anticancer drugs.

Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line.

PubMed

Charão, Mariele F; Baierle, Marília; Gauer, Bruna; Goethel, Gabriela; Fracasso, Rafael; Paese, Karina; Brucker, Natália; Moro, Angela M; Bubols, Guilherme B; Dias, Bruna B; Matte, Ursula S; Guterres, Silvia S; Pohlmann, Adriana R; Garcia, Solange C

2015-06-01

Many acute poisonings lack effective and specific antidotes. Due to both intentional and accidental exposures, paraquat (PQ) causes thousands of deaths annually, especially by pulmonary fibrosis. Melatonin (Mel), when incorporated into lipid-core nanocapsules (Mel-LNC), has enhanced antioxidant properties. The effects of such a formulation have not yet been studied with respect to mitigation of PQ- induced cytotoxicity and DNA damage. Here, we have tested whether Mel-LNC can ameliorate PQ-induced toxicity in the A549 alveolar epithelial cell line. Physicochemical characterization of the formulations was performed. Cellular uptake was measured using nanocapsules marked with rhodamine B. Cell viability was determined by the MTT assay and DNA damage was assessed by the comet assay. The enzyme-modified comet assay with endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) were used to investigate oxidative DNA damage. Incubation with culture medium for 24h did not alter the granulometric profile of Mel-LNC formulations. Following treatment (3 and 24h), red fluorescence was detected around the cell nucleus, indicating internalization of the formulation. Melatonin solution (Mel), Mel-LNC, and LNC did not have significant effects on cell viability or DNA damage. Pre-treatment with Mel-LNC enhanced cell viability and showed a remarkable reduction in % DNA in tail compared to the PQ group; this was not observed in cells pre-treated with Mel. PQ induces oxidative DNA damage detected with the enzyme-modified comet assay. Mel-LNC reduced this damage more effectively than did Mel. In summary, Mel-LNC is better than Mel at protecting A549 cells from the cytotoxic and genotoxic effects of PQ. Copyright © 2015 Elsevier B.V. All rights reserved.

The Coupling between Earth's Inertial and Rotational Eigenmodes

NASA Astrophysics Data System (ADS)

Triana, S. A.; Rekier, J.; Trinh, A.; Laguerre, R.; Zhu, P.; Dehant, V. M. A.

2017-12-01

Wave motions in the Earth's fluid core, supported by the restoring action of both buoyancy (within the stably stratified top layer) and the Coriolis force, lead to the existence of global oscillation modes, the so-called gravito-inertial modes. These fluid modes can couple with the rotational modes of the Earth by exerting torques on the mantle and the inner core. Viscous shear stresses at the fluid boundaries, along with pressure and gravitation, contribute to the overall torque balance. Previous research by Rogister & Valette (2009) suggests that indeed rotational and gravito-inertial modes are coupled, thus shifting the frequencies of the Chandler Wobble (CW), the Free Core Nutation (FCN) and the Free Inner Core Nutation (FICN). Here we present the first results from a numerical model of the Earth's fluid core and its interaction with the rotational eigenmodes. In this first step we consider a fluid core without a solid inner core and we restrict to ellipticities of the same order as the Ekman number. We formulate the problem as a generalised eigenvalue problem that solves simultaneously the Liouville equation for the rotational modes (the torque balance), and the Navier-Stokes equation for the inertial modes.

SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation, optimization and efficacy evaluation.

PubMed

Dimchevska, Simona; Geskovski, Nikola; Petruševski, Gjorgji; Chacorovska, Marina; Popeski-Dimovski, Riste; Ugarkovic, Sonja; Goracinova, Katerina

2017-03-01

One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol ® F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4 h.

Looking beyond the Boundaries: Time to Put Landmarks Back on the Cognitive Map?

ERIC Educational Resources Information Center

Lew, Adina R.

2011-01-01

Since the proposal of Tolman (1948) that mammals form maplike representations of familiar environments, cognitive map theory has been at the core of debates on the fundamental mechanisms of animal learning and memory. Traditional formulations of cognitive map theory emphasize relations between landmarks and between landmarks and goal locations as…

Low cost, formable, high T(sub c) superconducting wire

NASA Technical Reports Server (NTRS)

Smialek, James L. (Inventor)

1991-01-01

A ceramic superconductivity part such as a wire is produced through the partial oxidation of a specially formulated copper alloy in the core. The alloys contain low level quantities of rare earth and alkaline earth dopant elements. Upon oxidation at high temperature, superconducting oxide phases are formed as a thin film.

Developing Consensus on the CompHP Professional Standards for Health Promotion in Europe

ERIC Educational Resources Information Center

Speller, Viv; Parish, Richard; Davison, Heather; Zilnyk, Anna

2012-01-01

Building on the CompHP Core Competencies for health promotion the Professional Standards for Health Promotion have been developed and consulted on across Europe. The standards were formulated to fit within the complexity of professional, occupational and educational standards frameworks in Europe as learning outcome standards with performance…

Cognitive Aging and Computer-Based Instructional Design: Where Do We Go from Here?

ERIC Educational Resources Information Center

Van Gerven, Pascal W. M.; Paas, Fred; Tabbers, Huib K.

2006-01-01

In this article, the most relevant literature on cognitive aging and instructional design is merged to formulate recommendations for designing computer-based training material aimed at elderly learners. The core message is that researchers and instructional designers do not need to develop special computerized instruction for older adults. Rather,…

Conservation Education Improvement. Final Report.

ERIC Educational Resources Information Center

Diem, Kenneth L.; Hennebry, Howard M.

In an attempt to improve the teaching of conservation in elementary and junior high schools, a set of integrated sequential core units was formulated and tested in five Wyoming school districts during the fall and early winter of 1968. Based on a total sample of 840 elementary students (38% usable response) and 960 junior high students (49% usable…

Integration of Population Education in APPEAL. Volume One: Guidelines for Curriculum and Materials Development.

ERIC Educational Resources Information Center

United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

This research summary presents discussions from two regional workshops held in Indonesia and Pakistan in 1989 and 1991, respectively. The focus of the workshops was to formulate prototype instructional materials of population education core messages for primary education, literacy and continuing education programs in the Asia Pacific Programme of…

An Analysis of the Community College Concept in the Socialist Republic of Viet Nam

ERIC Educational Resources Information Center

Epperson, Cynthia K.

2010-01-01

The purpose of this study was to discover if core characteristics exist forming a Vietnamese community college model and to determine if the characteristics would explain the model. This study utilized three theoretical orientations while reviewing the existing literature, formulating the research questions, examining the data and drawing…

APPLYING THE PATUXENT LANDSCAPE UNIT MODEL TO HUMAN DOMINATED ECOSYSTEMS: THE CASE OF AGRICULTURE. (R827169)

EPA Science Inventory

Non-spatial dynamics are core to landscape simulations. Unit models simulate system interactions aggregated within one space unit of resolution used within a spatial model. For unit models to be applicable to spatial simulations they have to be formulated in a general enough w...

Vibrational effects in x-ray absorption and resonant inelastic x-ray scattering using a semiclassical scheme

NASA Astrophysics Data System (ADS)

Ljungberg, Mathias P.

2017-12-01

A method is presented for describing vibrational effects in x-ray absorption spectroscopy and resonant inelastic x-ray scattering (RIXS) using a combination of the classical Franck-Condon (FC) approximation and classical trajectories run on the core-excited state. The formulation of RIXS is an extension of the semiclassical Kramers-Heisenberg formalism of Ljungberg et al. [Phys. Rev. B 82, 245115 (2010), 10.1103/PhysRevB.82.245115] to the resonant case, retaining approximately the same computational cost. To overcome difficulties with connecting the absorption and emission processes in RIXS, the classical FC approximation is used for the absorption, which is seen to work well provided that a zero-point-energy correction is included. In the case of core-excited states with dissociative character, the method is capable of closely reproducing the main features for one-dimensional test systems, compared to the quantum-mechanical formulation. Due to the good accuracy combined with the relatively low computational cost, the method has great potential of being used for complex systems with many degrees of freedom, such as liquids and surface adsorbates.

Ancient Indian concepts about phenomenology, biology, and therapeutics of epilepsy.

PubMed

Arya, Ravindra

2018-01-01

This article discusses etiology, pathogenesis, symptoms, and treatment of epilepsy, as described in Charaka Samhitā (translation: Charaka's Compendium) and Sushruta Samhitā, the two core texts of Ayurveda, an ancient system of medicine. Ayurveda emphasized amnesia and loss of consciousness as core features of epileptic seizures (Sanskrit: apasmar; translation: apa negation, smaran memory) and recognized that seizures occur due to a disturbance in brain function or flow of "humors" to the brain. Semiology of various seizure types was well described. Epilepsy was attributed to both internal and multiple exogenous factors. Treatment of epilepsy with formulations of naturally occurring substances, their compounding and use, is described in remarkable detail. Lifestyle modifications to protect people with epilepsy are also documented. Cognitive comorbidities of epilepsy were recognized. Although none of the Ayurveda formulations have any empirical evidence supporting their safety or efficacy in the treatment of epilepsy, studies are needed to generate relevant evidence, to recognize their hazards, and to integrate traditional and complementary systems of medicine with modern health care in an informed and safe manner.

Posttest analysis of a laboratory-cast monolith of salt-saturated concrete. Final report

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

Wakeley, L.D.; Poole, T.S.

A salt-saturated concrete was formulated for laboratory testing of cementitious mixtures with potential for use in disposal of radioactive wastes in a geologic repository in halite rock. Cores were taken from a laboratory-cast concrete monolith on completion of tests of permeability, strain, and stress. The cores were analyzed for physical and chemical evidence of brine migration through the concrete, and other features with potential impact on installation of crete plugs at the Waste Isolation Pilot Plant (WIPP) in New Mexico. The posttest analyses of the cores provided evidence of brine movement along the interface between concrete and pipe, and littlemore » indication of permeability through the monolith itself. There may also have been diffusion of chloride into the monolith without actual brine flow.« less

Planetary exploration through year 2000, a core program: Mission operations

NASA Technical Reports Server (NTRS)

1986-01-01

In 1980 the NASA Advisory Council created the Solar System Exploratory Committee (SSEC) to formulate a long-range program of planetary missions that was consistent with likely fiscal constraints on total program cost. The SSEC had as its primary goal the establishment of a scientifically valid, affordable program that would preserve the nation's leading role in solar system exploration, capitalize on two decades of investment, and be consistent with the coordinated set of scientific stategies developed earlier by the Committe on Planetary and Lunar Exploration (COMPLEX). The result of the SSEC effort was the design of a Core Program of planetary missions to be launched by the year 2000, together with a realistic and responsible funding plan. The Core Program Missions, subcommittee activities, science issues, transition period assumptions, and recommendations are discussed.

Reversible, on-demand generation of aqueous two-phase microdroplets

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

Collier, Charles Patrick; Retterer, Scott Thomas; Boreyko, Jonathan Barton

The present invention provides methods of on-demand, reversible generation of aqueous two-phase microdroplets core-shell microbeads, microparticle preparations comprising the core-shell microbeads, and drug delivery formulation comprising the microparticle preparations. Because these aqueous microdroplets have volumes comparable to those of cells, they provide an approach to mimicking the dynamic microcompartmentation of biomaterial that naturally occurs within the cytoplasm of cells. Hence, the present methods generate femtoliter aqueous two-phase droplets within a microfluidic oil channel using gated pressure pulses to generate individual, stationary two-phase microdroplets with a well-defined time zero for carrying out controlled and sequential phase transformations over time. Reversible phasemore » transitions between single-phase, two-phase, and core-shell microbead states are obtained via evaporation-induced dehydration and water rehydration.« less

Traditional medicine in north Côte-d'Ivoire: screening of 50 medicinal plants for antibacterial activity.

PubMed

Koné, W M; Atindehou, K Kamanzi; Terreaux, C; Hostettmann, K; Traoré, D; Dosso, M

2004-07-01

Sixty-seven crude ethanol extracts from 50 plants (31 families), which are used in North Côte-d'Ivoire as traditional remedies for bacterial diseases, were screened for in vitro activity against Gram negative (Escherichia coli and Pseudomonas aeruginosa) and Gram positive (Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes and Bacillus subtilis) bacteria. Thirty-one extracts showed antibacterial activity only on Gram positive bacteria. Of these, 10 extracts from 10 plant species had a promising level of activity against bacteria including strains resistant to antibiotics such as aminosides, penicillin M, macrolides, lincosamide and streptrogramin B. The most active was Erythrina senegalensis DC (Fabaceae) followed by Bobgunnia madagascariensis (Desv.) J.H. Kirkbr. & Wiersema (Caesalpinaceae), Waltheria lanceolata R. Br. ex Mast. (Sterculiaceae), Uapaca togoensis Pax. (Euphorbiaceae), Ximenia americana L. (Olacaceae), Khaya senegalensis (Ders.) A. Juss. (Meliaceae), Lannea acida A. Rich. (Anacardiaceae), Cissus populnea Guill. & Perr. (Vitaceae), Keetia hispida (Benth.) Bridson (Rubiaceae) and Ficus thonningii (Miq.) A. Rich. (Moraceae). This is the first report of the antibacterial potency of these 10 plant species on a range of bacteria. The results provided evidence that some of the studied plants might indeed be potential sources of new antibacterial agents, also against some antibiotic-resistant strains.

Design and Synthesis of Self-Assembled Polymeric Nanoparticles for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Logie, Jennifer

Current chemotherapeutics are plagued by poor solubility and selectivity, requiring toxic excipients in formulations and causing a number of dose limiting side effects. Nanoparticle delivery has emerged as a strategy to more effectively deliver chemotherapeutics to the tumour site. Specifically, polymeric micelles enable the solubilization of hydrophobic small molecule drugs within the core and mitigate the necessity of excipients. Notwithstanding the significant progress made in polymeric micelle delivery, translation is limited by poor stability and low drug loading. In this work, a rational design approach is used to chemically modify poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG) in order to overcome these limitations and effectively deliver drug to tumours. The PEG density of the polymer system was optimized to enhance the stability of our polymeric micelles. Higher PEG densities permitted the lyophilization of micelles and enhanced the serum stability of the system. To increase the drug loading of our system, we facilitated specific intermolecular interactions within the micelle core. For drugs that form colloidal aggregates, such as pentyl-PABC doxazolidine, polymers were used to stabilize the colloidal core against aggregation and protein adsorption. For more challenging molecules, where self-assembly cannot be controlled, such as docetaxel, we modified the polymeric backbone with a peptide from the binding site of the drug to achieve loadings five times higher than those achieved in conventional micelle systems. This novel docetaxel nanoparticle was assessed in vivo in an orthotopic mouse model of breast cancer, where it showed a wider therapeutic index than the conventional ethanolic polysorbate 80 formulation. The improved tolerability of this formulation enabled higher dosing regimens and led to heightened efficacy and survival in this mouse model. Combined, these studies validated P(LA-co-TMCC)-g-PEG nanoparticles as an effective delivery vehicle for two chemotherapeutics, and presents approaches amenable to the delivery of many other clinically relevant hydrophobic drugs or drug combinations.

Transformable liquid-metal nanomedicine

PubMed Central

Lu, Yue; Hu, Quanyin; Lin, Yiliang; Pacardo, Dennis B.; Wang, Chao; Sun, Wujin; Ligler, Frances S.; Dickey, Michael D.; Gu, Zhen

2015-01-01

To date, numerous inorganic nanocarriers have been explored for drug delivery systems (DDSs). However, the clinical application of inorganic formulations has often been hindered by their toxicity and failure to biodegrade. We describe here a transformable liquid-metal nanomedicine, based on a core–shell nanosphere composed of a liquid-phase eutectic gallium-indium core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-mediated method with bioconjugation flexibility. The resulting nanoparticles loaded with doxorubicin (Dox) have an average diameter of 107 nm and demonstrate the capability to fuse and subsequently degrade under a mildly acidic condition, which facilitates release of Dox in acidic endosomes after cellular internalization. Equipped with hyaluronic acid, a tumour-targeting ligand, this formulation displays enhanced chemotherapeutic inhibition towards the xenograft tumour-bearing mice. This liquid metal-based DDS with fusible and degradable behaviour under physiological conditions provides a new strategy for engineering theranostic agents with low toxicity. PMID:26625944

Doxorubicin loaded magneto-niosomes for targeted drug delivery.

PubMed

Tavano, Lorena; Vivacqua, Marco; Carito, Valentina; Muzzalupo, Rita; Caroleo, Maria Cristina; Nicoletta, Fiore

2013-02-01

In chemotherapy the magnetic drug targeting to a specific organ or tissue is proposed on the assumption that magnetic fields are harmless to biological systems. In this light we have vehiculated doxorubicin as model drug by novel magneto-niosomes in order to evaluate the physico-chemical properties of the obtained formulations and the in vitro release profile. Tween 60 and Pluronic L64 have been used as surfactants and the formulation cytotoxicity has been performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolum bromide and trypan blue dye esclusion tests. Results show that niosome dimensions and doxorubicin entrapment efficiencies are influenced by bilayer composition. In addition, formulations are able to control the deliver and release of the drug active form in a retarded manner. No additional toxicity, due to the encapsulation of ferrofluid into niosomes core, has been detected. Copyright © 2012 Elsevier B.V. All rights reserved.

What could a strengthened right to health bring to the post-2015 health development agenda?: interrogating the role of the minimum core concept in advancing essential global health needs

PubMed Central

2013-01-01

Background Global health institutions increasingly recognize that the right to health should guide the formulation of replacement goals for the Millennium Development Goals, which expire in 2015. However, the right to health’s contribution is undercut by the principle of progressive realization, which links provision of health services to available resources, permitting states to deny even basic levels of health coverage domestically and allowing international assistance for health to remain entirely discretionary. Discussion To prevent progressive realization from undermining both domestic and international responsibilities towards health, international human rights law institutions developed the idea of non-derogable “minimum core” obligations to provide essential health services. While minimum core obligations have enjoyed some uptake in human rights practice and scholarship, their definition in international law fails to specify which health services should fall within their scope, or to specify wealthy country obligations to assist poorer countries. These definitional gaps undercut the capacity of minimum core obligations to protect essential health needs against inaction, austerity and illegitimate trade-offs in both domestic and global action. If the right to health is to effectively advance essential global health needs in these contexts, weaknesses within the minimum core concept must be resolved through innovative research on social, political and legal conceptualizations of essential health needs. Summary We believe that if the minimum core concept is strengthened in these ways, it will produce a more feasible and grounded conception of legally prioritized health needs that could assist in advancing health equity, including by providing a framework rooted in legal obligations to guide the formulation of new health development goals, providing a baseline of essential health services to be protected as a matter of right against governmental claims of scarcity and inadequate international assistance, and empowering civil society to claim fulfillment of their essential health needs from domestic and global decision-makers. PMID:24289096

Multi-functional Magnetic Nanoparticles for Magnetic Resonance Imaging and Cancer Therapy

PubMed Central

Yallapu, Murali M.; Othman, Shadi F.; Curtis, Evan T.; Gupta, Brij K.; Jaggi, Meena; Chauhan, Subhash C.

2010-01-01

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapuetic agent for cancer therapy. PMID:21167595

Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy.

PubMed

Yallapu, Murali M; Othman, Shadi F; Curtis, Evan T; Gupta, Brij K; Jaggi, Meena; Chauhan, Subhash C

2011-03-01

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapeutic agent for cancer therapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

A survey of the core-congruential formulation for geometrically nonlinear TL finite elements

NASA Technical Reports Server (NTRS)

Felippa, Carlos A.; Crivelli, Luis A.; Haugen, Bjorn

1994-01-01

This article presents a survey of the core-congruential formulation (CCF) for geometrically nonlinear mechanical finite elements based on the total Lagrangian (TL) kinematic description. Although the key ideas behind the CCF can be traced back to Rajasekaran and Murray in 1973, it has not subsequently received serious attention. The CCF is distinguished by a two-phase development of the finite element stiffness equations. The initial phase developed equations for individual particles. These equations are expressed in terms of displacement gradients as degrees of freedom. The second phase involves congruential-type transformations that eventually binds the element particles of an individual element in terms of its node-displacement degrees of freedom. Two versions of the CCF, labeled direct and generalized, are distinguished. The direct CCF (DCCF) is first described in general form and then applied to the derivation of geometrically nonlinear bar, and plane stress elements using the Green-Lagrange strain measure. The more complex generalized CCF (GCCF) is described and applied to the derivation of 2D and 3D Timoshenko beam elements. Several advantages of the CCF, notably the physically clean separation of material and geometric stiffnesses, and its independence with respect to the ultimate choice of shape functions and element degrees of freedom, are noted. Application examples involving very large motions solved with the 3D beam element display the range of applicability of this formulation, which transcends the kinematic limitations commonly attributed to the TL description.

Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo.

PubMed

Klippstein, Rebecca; Wang, Julie Tzu-Wen; El-Gogary, Riham I; Bai, Jie; Mustafa, Falisa; Rubio, Noelia; Bansal, Sukhvinder; Al-Jamal, Wafa T; Al-Jamal, Khuloud T

2015-09-01

Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half-life and poor water solubility. Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic-co-glycolic acid) (PLGA)-based polymeric oil-cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico-chemical properties, and shelf-life stability. The results indicate that castor oil-cored PLGA-based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin-loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non-PEGylated NC, and accumulates in the subcutaneous CT26-tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization of chlorophyll derivatives in micelles of polymeric surfactants aiming photodynamic applications

NASA Astrophysics Data System (ADS)

Gerola, Adriana Passarella; de Morais, Flavia Amanda Pedroso; Costa, Paulo Fernando A.; Kimura, Elza; Caetano, Wilker; Hioka, Noboru

2017-02-01

The spectrophotometric properties of chlorophylls' derivatives (Chls) formulated in the Pluronics® F-127 and P-123 were evaluated and the results have shown that the Chls were efficiently solubilized in these drug delivery systems as monomers. The relative location of the Chls in the Pluronics® was estimated from the Stokes shift and micropolarity of the micellar environment. Chls with phytyl chain were located in the micellar core, where the micropolarity is similar to ethanol, while phorbides' derivatives (without phytyl chain) were located in the outer shell of the micelle, i.e., more polar environment. In addition, the thermal stability of the micellar formulations was evaluated through electronic absorption, fluorescence emission and resonance light scattering with lowering the temperature. The Chls promote the stability of the micelles at temperatures below the Critical Micellar Temperature (CMT) of these surfactants. For F-127 formulations, the water molecules drive through inside the nano-structure at temperatures below the CMT, which increased the polarity of this microenvironment and directly affected the spectrophotometric properties of the Chls with phytyl chain. The properties of the micellar microenvironment of P-123, with more hydrophobic core due to the small PEO/PPO fraction, were less affected by lowering the temperature than for F-127. These results enable us to better understand the Chls behavior in micellar copolymers and allowed us to design new drug delivery system that maintains the photosensitizer's properties for photodynamic applications.

Development and optimization of buspirone oral osmotic pump tablet

PubMed Central

Derakhshandeh, K.; berenji, M. Ghasemnejad

2014-01-01

The aim of the current study was to design a porous osmotic pump–based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance. PMID:25657794

Development and optimization of buspirone oral osmotic pump tablet.

PubMed

Derakhshandeh, K; Berenji, M Ghasemnejad

2014-01-01

The aim of the current study was to design a porous osmotic pump-based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance.

Ballistic Resistance of Honeycomb Sandwich Panels under In-Plane High-Velocity Impact

PubMed Central

Yang, Shu; Wang, Dong; Yang, Li-Jun

2013-01-01

The dynamic responses of honeycomb sandwich panels (HSPs) subjected to in-plane projectile impact were studied by means of explicit nonlinear finite element simulations using LS-DYNA. The HSPs consisted of two identical aluminum alloy face-sheets and an aluminum honeycomb core featuring three types of unit cell configurations (regular, rectangular-shaped, and reentrant hexagons). The ballistic resistances of HSPs with the three core configurations were first analyzed. It was found that the HSP with the reentrant auxetic honeycomb core has the best ballistic resistance, due to the negative Poisson's ratio effect of the core. Parametric studies were then carried out to clarify the influences of both macroscopic (face-sheet and core thicknesses, core relative density) and mesoscopic (unit cell angle and size) parameters on the ballistic responses of the auxetic HSPs. Numerical results show that the perforation resistant capabilities of the auxetic HSPs increase as the values of the macroscopic parameters increase. However, the mesoscopic parameters show nonmonotonic effects on the panels' ballistic capacities. The empirical equations for projectile residual velocities were formulated in terms of impact velocity and the structural parameters. It was also found that the blunter projectiles result in higher ballistic limits of the auxetic HSPs. PMID:24187526

Diametral and compressive strength of dental core materials.

PubMed

Cho, G C; Kaneko, L M; Donovan, T E; White, S N

1999-09-01

Strength greatly influences the selection of core materials. Many disparate material types are now recommended for use as cores. Cores must withstand forces due to mastication and parafunction for many years. This study compared the compressive and diametral tensile strengths of 8 core materials of various material classes and formulations (light-cured hybrid composite, autocured titanium containing composite, amalgam, glass ionomer, glass ionomer cermet, resin-modified glass ionomer, and polyurethane). Materials were manipulated according to manufacturers' instructions for use as cores. Mean compressive and diametral strengths with associated standard errors were calculated for each material (n = 10). Analyses of variance were computed (P <.0001) and multiple comparisons tests discerned many differences among materials. Compressive strengths varied widely from 61.1 MPa for a polyurethane to 250 MPa for a resin composite. Diametral tensile strengths ranged widely from 18.3 MPa for a glass ionomer cermet to 55.1 MPa for a resin composite. Some resin composites had compressive and tensile strengths equal to those of amalgam. Light-cured hybrid resin composites were stronger than autocured titanium containing composites. The strengths of glass ionomer-based materials and of a polyurethane material were considerably lower than for resin composites or amalgam.

Ballistic resistance of honeycomb sandwich panels under in-plane high-velocity impact.

PubMed

Qi, Chang; Yang, Shu; Wang, Dong; Yang, Li-Jun

2013-01-01

The dynamic responses of honeycomb sandwich panels (HSPs) subjected to in-plane projectile impact were studied by means of explicit nonlinear finite element simulations using LS-DYNA. The HSPs consisted of two identical aluminum alloy face-sheets and an aluminum honeycomb core featuring three types of unit cell configurations (regular, rectangular-shaped, and reentrant hexagons). The ballistic resistances of HSPs with the three core configurations were first analyzed. It was found that the HSP with the reentrant auxetic honeycomb core has the best ballistic resistance, due to the negative Poisson's ratio effect of the core. Parametric studies were then carried out to clarify the influences of both macroscopic (face-sheet and core thicknesses, core relative density) and mesoscopic (unit cell angle and size) parameters on the ballistic responses of the auxetic HSPs. Numerical results show that the perforation resistant capabilities of the auxetic HSPs increase as the values of the macroscopic parameters increase. However, the mesoscopic parameters show nonmonotonic effects on the panels' ballistic capacities. The empirical equations for projectile residual velocities were formulated in terms of impact velocity and the structural parameters. It was also found that the blunter projectiles result in higher ballistic limits of the auxetic HSPs.

A core syllabus for the teaching of neuroanatomy to medical students.

PubMed

Moxham, Bernard; McHanwell, Stephen; Plaisant, Odile; Pais, Diogo

2015-09-01

There is increasingly a call for clinical relevance in the teaching of biomedical sciences within all health care courses. However, this presupposes that there is a clear understanding of what can be considered core material within the curricula. To date, the anatomical sciences have been relatively poorly served by the development of core syllabuses, particularly for specialized core syllabuses such as neuroanatomy. One of the aims of the International Federation of Associations of Anatomists (IFAA) and of the European Federation for Experimental Morphology (EFEM) is to formulate, on an international scale, core syllabuses for all branches of the anatomical sciences using Delphi Panels consisting of anatomists, scientists, and clinicians to initially evaluate syllabus content. In this article, the findings of a Delphi Panel for neuroanatomy are provided. These findings will subsequently be published on the IFAA website to enable anatomical (and other cognate learned) societies and individual anatomists, clinicians, and students to freely comment upon, and elaborate and amend, the syllabuses. The aim is to set internationally recognized standards and thus to provide guidelines concerning neuroanatomical knowledge when engaged in course development. © 2015 Wiley Periodicals, Inc.

Synthesis and evaluation of mesoporous carbon/lipid bilayer nanocomposites for improved oral delivery of the poorly water-soluble drug, nimodipine.

PubMed

Zhang, Yanzhuo; Zhao, Qinfu; Zhu, Wufu; Zhang, Lihua; Han, Jin; Lin, Qisi; Ai, Fengwei

2015-07-01

A novel mesoporous carbon/lipid bilayer nanocomposite (MCLN) with a core-shell structure was synthesized and characterized as an oral drug delivery system for poorly water-soluble drugs. The objective of this study was to investigate the potential of MCLN-based formulation to modulate the in vitro release and in vivo absorption of a model drug, nimodipine (NIM). NIM-loaded MCLN was prepared by a procedure involving a combination of thin-film hydration and lyophilization. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), specific surface area analysis, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were employed to characterize the NIM-loaded MCLN formulation. The effect of MCLN on cell viability was assessed using the MTT assay. In addition, the oral bioavailability of NIM-loaded MCLN in beagle dogs was compared with that of the immediate-release formulation, Nimotop®. Our results demonstrate that the NIM-loaded MCLN formulation exhibited a typical sustained release pattern. The NIM-loaded MCLN formulation achieved a greater degree of absorption and longer lasting plasma drug levels compared with the commercial formulation. The relative bioavailability of NIM for NIM-loaded MCLN was 214%. MCLN exhibited negligible toxicity. The data reported herein suggest that the MCLN matrix is a promising carrier for controlling the drug release rate and improving the oral absorption of poorly water-soluble drugs.

Multiple-layer compression-coated tablets: formulation and humidity studies of novel chewable amoxicillin/clavulanate tablet formulations.

PubMed

Wardrop, J; Jaber, A B; Ayres, J W

1998-08-01

The purpose of this study was to produce novel multiple-layer, compression-coated, chewable tablet formulations containing amoxicillin trihydrate, and clavulanic acid as potassium clavulanate, and to test in vitro dissolution characteristics and the effect of humidity stability compared to Augmentin chewable tablets as a reference. Double- and triple-layer tablets were manufactured on a laboratory scale by multiple-layer dry compression, and dissolution profiles of both active ingredients were determined. Tablets were subjected to stability evaluation in laboratory-scale humidity tanks maintained at constant humidity. Assay of content was determined by HPLC or UV spectroscopy. Physical characteristics of the powder mixture, such as angle of repose, and of tablets for hardness and friability, were also determined. Chewable tablets showed similar dissolution profiles in vitro for both active ingredients, compared to the marketed reference, Augmentin. The stability of clavulanic acid, but not amoxicillin, was increased in the novel triple or bilayer formulation. The tablets showed suitable friability, hardness, and angle of repose for starting materials to suggest that industrial scale-up is feasible. This approach to formulation of drugs containing multiple or moisture-sensitive ingredients has been shown to increase the stability of the central core drug without changing the dissolution pattern of the active ingredients. This formulation is expected to be bioequivalent in vivo based on these in vitro results.

EFFECT OF MAGNESIUM STEARATE CONCENTRATION ON DISSOLUTION PROPERTIES OF RANITIDINE HYDROCHLORIDE COATED TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2007-01-01

Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmaco-peial test for similarity of dissolution profiles (f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response. PMID:17848158

Characterization of the coating and tablet core roughness by means of 3D optical coherence tomography.

PubMed

Markl, Daniel; Wahl, Patrick; Pichler, Heinz; Sacher, Stephan; Khinast, Johannes G

2018-01-30

This study demonstrates the use of optical coherence tomography (OCT) to simultaneously characterize the roughness of the tablet core and coating of pharmaceutical tablets. OCT is a high resolution non-destructive and contactless imaging methodology to characterize structural properties of solid dosage forms. Besides measuring the coating thickness, it also facilitates the analysis of the tablet core and coating roughness. An automated data evaluation algorithm extracts information about coating thickness, as well as tablet core and coating roughness. Samples removed periodically from a pan coating process were investigated, on the basis of thickness and profile maps of the tablet core and coating computed from about 480,000 depth measurements (i.e., 3D data) per sample. This data enables the calculation of the root mean square deviation, the skewness and the kurtosis of the assessed profiles. Analyzing these roughness parameters revealed that, for the given coating formulation, small valleys in the tablet core are filled with coating, whereas coarse features of the tablet core are still visible on the final film-coated tablet. Moreover, the impact of the tablet core roughness on the coating thickness is analyzed by correlating the tablet core profile and the coating thickness map. The presented measurement method and processing could be in the future transferred to in-line OCT measurements, to investigate core and coating roughness during the production of film-coated tablets. Copyright © 2017. Published by Elsevier B.V.

Truth Matters: Teaching Young Students to Search for the Most Reasonable Answer

ERIC Educational Resources Information Center

Reznitskaya, Alina; Wilkinson, Ian A. G.

2018-01-01

Learning how to formulate, comprehend, and evaluate arguments is an essential part of helping students develop the ability to make better, more reasonable judgments. The Common Core identified argumentation as a fundamental life skill that is broadly important for the literate person. According to the authors, having students engage in an inquiry…

Insight in Frontotemporal Dementia: Conceptual Analysis and Empirical Evaluation of the Consensus Criterion ''Loss of Insight'' in Frontotemporal Dementia

ERIC Educational Resources Information Center

Evers, Kathinka; Kilander, Lena; Lindau, Maria

2007-01-01

The objective of this study was to suggest a new formulation of the core research diagnostic consensus criterion ''loss of insight'' in frontotemporal dementia (FTD). Eight patients with FTD (diagnoses made by interviews, medical and neuropsychological examination, CT scan, and regional cerebral glucose metabolism measured by positron emission…

Method of forming low cost, formable High T(subc) superconducting wire

NASA Technical Reports Server (NTRS)

Smialek, James L. (Inventor)

1989-01-01

A ceramic superconductivity part, such as a wire, is produced through the partial oxidation of a specially formulated copper alloy in a core. The alloys contains low level of quantities of rare earth and alkaline earth dopant elements. Upon oxidation at high temperatures, and superconducting oxide phases are formed as a thin film.

A Grassroots Approach to Formulating a Multicultural, Interdisciplinary Core Curriculum.

ERIC Educational Resources Information Center

Carrier, Henry N.; Williams, Donald A.

This paper reports on the study at Brevard Community College in Florida to discover how faculty and students can learn from each other. By examining the diverse elements of the college population and making the findings widely available, the disparate liberal arts courses and the diversity of participating faculty and students can become mutually…

Low-Skilled Workers and Adult Vocational Skills-Upgrading Strategies in Denmark and South Korea

ERIC Educational Resources Information Center

Gvaramadze, Irakli

2010-01-01

The main objective of the paper was to address the relevance of adult vocational skills-upgrading strategies for low-skilled workers. The research was based on an identification of core elements such as time, cost and access which define and impact on formulation and implementation of adult vocational skills-upgrading strategies. The literature…

Fractographic logging for determination of pre-core and core-induced fractures: Nicholas Combs No. 7239 well, Hazard, Kentucky

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

Kulander, B.R.; Dean, S.L.; Barton, C.C.

1977-01-01

Methods results, and conclusions formulated during a prototype fractographic logging study of seventy-five feet of oriented Devonian shale core are summarized. The core analyzed is from the Nicholas Combs No. 7239 well located twelve miles due north of Hazard, Kentucky. The seventy-five foot core length was taken from a cored section lying between 2369.0 feet (subsea) and 2708.0 feet (subsea). Total core length is 339.0 feet. The core was extracted from the upper Devonian Ohio and Olentangy shale formations. Results indicate that there are few tectonic (pre-core) fractures within the studied core section. The region may nevertheless be cut atmore » core sample depth by well-defined vertical or inclined tectonic fractures that the vertically drilled test core didn't intersect. This is likely since surface Plateau systematic fractures in other Plateau areas are vertical to sub-vertical and seldom have a frequency of less than one major fracture per foot. The remarkable directional preference of set three fractures about strikes of N 40/sup 0/ E, N 10/sup 0/ W, N 45/sup 0/ W, suggests some incipient pre-core rock anisotropy or stored directional strain energy. If this situation exists, the anisotropy strike change or stored strain variance from N 40/sup 0/ E to N 45/sup 0/ W downcore remains an unanswered question. Tectonic features, indicating local and/or regional movement plans, are present on and within the tectonichorizontal fracture set one. Slickensides had a preferred orientation within several core levels, and fibrous-nonfibrous calcite serves as fracture fillings.« less

Thermal Hydraulics Design and Analysis Methodology for a Solid-Core Nuclear Thermal Rocket Engine Thrust Chamber

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Canabal, Francisco; Chen, Yen-Sen; Cheng, Gary; Ito, Yasushi

2013-01-01

Nuclear thermal propulsion is a leading candidate for in-space propulsion for human Mars missions. This chapter describes a thermal hydraulics design and analysis methodology developed at the NASA Marshall Space Flight Center, in support of the nuclear thermal propulsion development effort. The objective of this campaign is to bridge the design methods in the Rover/NERVA era, with a modern computational fluid dynamics and heat transfer methodology, to predict thermal, fluid, and hydrogen environments of a hypothetical solid-core, nuclear thermal engine the Small Engine, designed in the 1960s. The computational methodology is based on an unstructured-grid, pressure-based, all speeds, chemically reacting, computational fluid dynamics and heat transfer platform, while formulations of flow and heat transfer through porous and solid media were implemented to describe those of hydrogen flow channels inside the solid24 core. Design analyses of a single flow element and the entire solid-core thrust chamber of the Small Engine were performed and the results are presented herein

Two-proton capture on the 68Se nucleus with a new self-consistent cluster model

NASA Astrophysics Data System (ADS)

Hove, D.; Garrido, E.; Jensen, A. S.; Sarriguren, P.; Fynbo, H. O. U.; Fedorov, D. V.; Zinner, N. T.

2018-07-01

We investigate the two-proton capture reaction of the prominent rapid proton capture waiting point nucleus, 68Se, that produces the borromean nucleus 70Kr (68Se + p + p). We apply a recently formulated general model where the core nucleus, 68Se, is treated in the mean-field approximation and the three-body problem of the two valence protons and the core is solved exactly. We compare using two popular Skyrme interactions, SLy4 and SkM*. We calculate E2 electromagnetic two-proton dissociation and capture cross sections, and derive the temperature dependent capture rates. We vary the unknown 2+ resonance energy without changing any of the structures computed self-consistently for both core and valence particles. We find rates increasing quickly with temperature below 2-4 GK after which we find rates varying by about a factor of two independent of 2+ resonance energy. The capture mechanism is sequential through the f5/2 proton-core resonance, but the continuum background contributes significantly.

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

Huang, Tingting; Chang, Chin -Yuan; Lohman, Jeremy R.

Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site-directed mutagenesis of the conserved residues lining this site allowed us tomore » propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase-associated enzymes, into an enzyme-sequestered enediyne core intermediate. In conclusion, these findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.« less

A new equation of state Based on Nuclear Statistical Equilibrium for Core-Collapse Simulations

NASA Astrophysics Data System (ADS)

Furusawa, Shun; Yamada, Shoichi; Sumiyoshi, Kohsuke; Suzuki, Hideyuki

2012-09-01

We calculate a new equation of state for baryons at sub-nuclear densities for the use in core-collapse simulations of massive stars. The formulation is the nuclear statistical equilibrium description and the liquid drop approximation of nuclei. The model free energy to minimize is calculated by relativistic mean field theory for nucleons and the mass formula for nuclei with atomic number up to ~ 1000. We have also taken into account the pasta phase. We find that the free energy and other thermodynamical quantities are not very different from those given in the standard EOSs that adopt the single nucleus approximation. On the other hand, the average mass is systematically different, which may have an important effect on the rates of electron captures and coherent neutrino scatterings on nuclei in supernova cores.

Analysis of an optimization-based atomistic-to-continuum coupling method for point defects

DOE PAGES

Olson, Derek; Shapeev, Alexander V.; Bochev, Pavel B.; ...

2015-11-16

Here, we formulate and analyze an optimization-based Atomistic-to-Continuum (AtC) coupling method for problems with point defects. Application of a potential-based atomistic model near the defect core enables accurate simulation of the defect. Away from the core, where site energies become nearly independent of the lattice position, the method switches to a more efficient continuum model. The two models are merged by minimizing the mismatch of their states on an overlap region, subject to the atomistic and continuum force balance equations acting independently in their domains. We prove that the optimization problem is well-posed and establish error estimates.

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.

pH Responsive Microcapsules for Corrosion Control

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Li, Wenyan; Muehlberg, Aaron; Boraas, Samuel; Webster, Dean; JohnstonGelling, Victoria; Croll, Stuart; Taylor, S Ray; Contu, Francesco

2008-01-01

The best coatings for corrosion protection provide not only barriers to the environment, but also a controlled release of a corrosion inhibitor, as demanded by the presence of corrosion or mechanical damage. NASA has developed pH sensitive microcapsules (patent pending) that can release their core contents when corrosion starts. The objectives of the research presented here were to encapsulate non-toxic corrosion inhibitors, to incorporate the encapsulated inhibitors into paint formulations, and to test the ability of the paints to control corrosion. Results showed that the encapsulated corrosion inhibitors, specifically Ce(NO3)3 , are effective to control corrosion over long periods of time when incorporated at relatively high pigment volume concentrations into a paint formulation.

Emotion-focused therapy in a case of anorexia nervosa.

PubMed

Dolhanty, Joanne; Greenberg, Leslie S

2009-01-01

An emotion-focused approach to the treatment of eating disorders and to case formulation is described in an individual with anorexia nervosa (AN). The basic theory of emotion-focused therapy (EFT), the steps of case formulation and an outline of the tasks and course of treatment of an individual recently hospitalized on an inpatient unit for eating disorders highlight key aspects of the approach. The transformation in this individual, in terms of gaining access to her internal experience, understanding and tolerating her emotions, and working through her core themes of insecure attachment and worthlessness, is described. Weight and scores on self-report measures at the outset of treatment and at 18 months are provided.

A 3-D Finite-Volume Non-hydrostatic Icosahedral Model (NIM)

NASA Astrophysics Data System (ADS)

Lee, Jin

2014-05-01

The Nonhydrostatic Icosahedral Model (NIM) formulates the latest numerical innovation of the three-dimensional finite-volume control volume on the quasi-uniform icosahedral grid suitable for ultra-high resolution simulations. NIM's modeling goal is to improve numerical accuracy for weather and climate simulations as well as to utilize the state-of-art computing architecture such as massive parallel CPUs and GPUs to deliver routine high-resolution forecasts in timely manner. NIM dynamic corel innovations include: * A local coordinate system remapped spherical surface to plane for numerical accuracy (Lee and MacDonald, 2009), * Grid points in a table-driven horizontal loop that allow any horizontal point sequence (A.E. MacDonald, et al., 2010), * Flux-Corrected Transport formulated on finite-volume operators to maintain conservative positive definite transport (J.-L, Lee, ET. Al., 2010), *Icosahedral grid optimization (Wang and Lee, 2011), * All differentials evaluated as three-dimensional finite-volume integrals around the control volume. The three-dimensional finite-volume solver in NIM is designed to improve pressure gradient calculation and orographic precipitation over complex terrain. NIM dynamical core has been successfully verified with various non-hydrostatic benchmark test cases such as internal gravity wave, and mountain waves in Dynamical Cores Model Inter-comparisons Projects (DCMIP). Physical parameterizations suitable for NWP are incorporated into NIM dynamical core and successfully tested with multimonth aqua-planet simulations. Recently, NIM has started real data simulations using GFS initial conditions. Results from the idealized tests as well as real-data simulations will be shown in the conference.

Bromelain-Functionalized Multiple-Wall Lipid-Core Nanocapsules: Formulation, Chemical Structure and Antiproliferative Effect Against Human Breast Cancer Cells (MCF-7).

PubMed

Oliveira, Catiúscia P; Prado, Willian A; Lavayen, Vladimir; Büttenbender, Sabrina L; Beckenkamp, Aline; Martins, Bruna S; Lüdtke, Diogo S; Campo, Leandra F; Rodembusch, Fabiano S; Buffon, Andréia; Pessoa, Adalberto; Guterres, Silvia S; Pohlmann, Adriana R

2017-02-01

This study was conducted a promising approach to surface functionalization developed for lipid-core nanocapsules and the merit to pursue new strategies to treat solid tumors. Bromelain-functionalized multiple-wall lipid-core nanocapsules (Bro-MLNC-Zn) were produced by self-assembling following three steps of interfacial reactions. Physicochemical and structural characteristics, in vitro proteolytic activity (casein substrate) and antiproliferative activity (breast cancer cells, MCF-7) were determined. Bro-MLNC-Zn had z-average diameter of 135 nm and zeta potential of +23 mV. The complex is formed by a Zn-N chemical bond and a chelate with hydroxyl and carboxyl groups. Bromelain complexed at the nanocapsule surface maintained its proteolytic activity and showed anti-proliferative effect against human breast cancer cells (MCF-7) (72.6 ± 1.2% at 1.250 μg mL -1 and 65.5 ± 5.5% at 0.625 μg mL -1 ). Comparing Bro-MLNC-Zn and bromelain solution, the former needed a dose 160-folds lower than the latter for a similar effect. Tripan blue dye assay corroborated the results. The surface functionalization approach produced an innovative formulation having a much higher anti-proliferative effect than the bromelain solution, even though both in vitro proteolytic activity were similar, opening up a great opportunity for further studies in nanomedicine.

Refined hierarchical kinematics quasi-3D Ritz models for free vibration analysis of doubly curved FGM shells and sandwich shells with FGM core

NASA Astrophysics Data System (ADS)

Fazzolari, Fiorenzo A.; Carrera, Erasmo

2014-02-01

In this paper, the Ritz minimum energy method, based on the use of the Principle of Virtual Displacements (PVD), is combined with refined Equivalent Single Layer (ESL) and Zig Zag (ZZ) shell models hierarchically generated by exploiting the use of Carrera's Unified Formulation (CUF), in order to engender the Hierarchical Trigonometric Ritz Formulation (HTRF). The HTRF is then employed to carry out the free vibration analysis of doubly curved shallow and deep functionally graded material (FGM) shells. The PVD is further used in conjunction with the Gauss theorem to derive the governing differential equations and related natural boundary conditions. Donnell-Mushtari's shallow shell-type equations are given as a particular case. Doubly curved FGM shells and doubly curved sandwich shells made up of isotropic face sheets and FGM core are investigated. The proposed shell models are widely assessed by comparison with the literature results. Two benchmarks are provided and the effects of significant parameters such as stacking sequence, boundary conditions, length-to-thickness ratio, radius-to-length ratio and volume fraction index on the circular frequency parameters and modal displacements are discussed.

Intravenous paracetamol as an antipyretic and analgesic medication: the significance of drug metabolism.

PubMed

Giamarellos-Bourboulis, Evangelos J; Spyridaki, Aikaterini; Savva, Athina; Georgitsi, Marianna; Tsaganos, Thomas; Mouktaroudi, Maria; Raftogiannis, Maria; Antonopoulou, Anastasia; Papaziogas, Vassilios; Baziaka, Fotini; Sereti, Kalliopi; Christopoulos, Petros; Marioli, Androniki; Kanni, Theodora; Maravitsa, Panagiota; Pantelidou, Ilianna; Leventogiannis, Konstantinos; Tsiaoussis, Panagiotis; Lymberopoulou, Korina; Koutelidakis, Ioannis M

2014-01-01

One prospective, open-label, non-randomized study was conducted in 100 patients to define the antipyretic and analgesic effect of a new intravenous formulation of 1 g of paracetamol; 71 received paracetamol for the management of fever and 29 received paracetamol for pain relief after abdominal surgery or for neoplastic pain. Serial follow-up measurements of core temperature and of pain intensity were done for 6 h. Additional rescue medications were recorded for 5 days. Blood was sampled for the measurement of free paracetamol (APAP) and of glucuronide-APAP and N-sulfate-APAP by an HPLC assay. Defervescence, defined as core temperature below or equal to 37.1°C, was achieved in 52 patients (73.2%) within a median time of 3 h. Patients failing to become afebrile with the first dose of paracetamol became afebrile when administered other agents as rescue medications. Analgesia was achieved in 25 patients (86.4%) within a median time of 2 h. Serum levels of glucuronide-APAP were greater among non-responders to paracetamol. The presented results suggest that the intravenous formulation of paracetamol is clinically effective depending on drug metabolism.

An evaluation of the pharmacokinetics of methylphenidate for the treatment of attention-deficit/ hyperactivity disorder.

PubMed

Frölich, Jan; Banaschewski, Tobias; Döpfner, Manfred; Görtz-Dorten, Anja

2014-08-01

Methylphenidate (MPH) plays a principal role in the multimodal treatment of attention-deficit/hyperactivity disorder (ADHD). Controlled studies have demonstrated an effective reduction in the core symptoms of the disorder following MPH therapy, although long-term studies also demonstrate that the therapeutic benefits dissipate in the absence of combined psychosocial interventions. This review article focuses on the pharmacological characteristics of MPH, examining its effects on brain metabolism and the neurotransmitter system. Neuropsychological and clinical effects of different immediate and extended release MPH formulations are discussed to aid clinicians in choosing the appropriate formulation. The drug's addictive potency and abuse potential is also discussed. Data came from a literature search of relevant studies performed using the PubMed database up to June 2013. MPH is effective in the treatment of the core symptoms of ADHD. Considerable clinical expertise is required to identify an individually well-adapted dosage which will produce the optimal clinical effects with potential side effects minimized. Due to low adherence to medication, especially in adolescents, motivation to treatment and attentive clinical monitoring is mandatory, as is the consideration of risks of abuse or the presence of a comorbid addictive disorder.

Elucidation of Compression-Induced Surface Crystallization in Amorphous Tablets Using Sum Frequency Generation (SFG) Microscopy.

PubMed

Mah, Pei T; Novakovic, Dunja; Saarinen, Jukka; Van Landeghem, Stijn; Peltonen, Leena; Laaksonen, Timo; Isomäki, Antti; Strachan, Clare J

2017-05-01

To investigate the effect of compression on the crystallization behavior in amorphous tablets using sum frequency generation (SFG) microscopy imaging and more established analytical methods. Tablets containing neat amorphous griseofulvin with/without excipients (silica, hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC) and polyethylene glycol (PEG)) were prepared. They were analyzed upon preparation and storage using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM) and SFG microscopy. Compression-induced crystallization occurred predominantly on the surface of the neat amorphous griseofulvin tablets, with minimal crystallinity being detected in the core of the tablets. The presence of various types of excipients was not able to mitigate the compression-induced surface crystallization of the amorphous griseofulvin tablets. However, the excipients affected the crystallization rate of amorphous griseofulvin in the core of the tablet upon compression and storage. SFG microscopy can be used in combination with ATR-FTIR spectroscopy and SEM to understand the crystallization behaviour of amorphous tablets upon compression and storage. When selecting excipients for amorphous formulations, it is important to consider the effect of the excipients on the physical stability of the amorphous formulations.

A novel heterogeneous algorithm to simulate multiphase flow in porous media on multicore CPU-GPU systems

NASA Astrophysics Data System (ADS)

McClure, J. E.; Prins, J. F.; Miller, C. T.

2014-07-01

Multiphase flow implementations of the lattice Boltzmann method (LBM) are widely applied to the study of porous medium systems. In this work, we construct a new variant of the popular "color" LBM for two-phase flow in which a three-dimensional, 19-velocity (D3Q19) lattice is used to compute the momentum transport solution while a three-dimensional, seven velocity (D3Q7) lattice is used to compute the mass transport solution. Based on this formulation, we implement a novel heterogeneous GPU-accelerated algorithm in which the mass transport solution is computed by multiple shared memory CPU cores programmed using OpenMP while a concurrent solution of the momentum transport is performed using a GPU. The heterogeneous solution is demonstrated to provide speedup of 2.6 × as compared to multi-core CPU solution and 1.8 × compared to GPU solution due to concurrent utilization of both CPU and GPU bandwidths. Furthermore, we verify that the proposed formulation provides an accurate physical representation of multiphase flow processes and demonstrate that the approach can be applied to perform heterogeneous simulations of two-phase flow in porous media using a typical GPU-accelerated workstation.

A matrix-algebraic formulation of distributed-memory maximal cardinality matching algorithms in bipartite graphs

DOE PAGES

Azad, Ariful; Buluç, Aydın

2016-05-16

We describe parallel algorithms for computing maximal cardinality matching in a bipartite graph on distributed-memory systems. Unlike traditional algorithms that match one vertex at a time, our algorithms process many unmatched vertices simultaneously using a matrix-algebraic formulation of maximal matching. This generic matrix-algebraic framework is used to develop three efficient maximal matching algorithms with minimal changes. The newly developed algorithms have two benefits over existing graph-based algorithms. First, unlike existing parallel algorithms, cardinality of matching obtained by the new algorithms stays constant with increasing processor counts, which is important for predictable and reproducible performance. Second, relying on bulk-synchronous matrix operations,more » these algorithms expose a higher degree of parallelism on distributed-memory platforms than existing graph-based algorithms. We report high-performance implementations of three maximal matching algorithms using hybrid OpenMP-MPI and evaluate the performance of these algorithm using more than 35 real and randomly generated graphs. On real instances, our algorithms achieve up to 200 × speedup on 2048 cores of a Cray XC30 supercomputer. Even higher speedups are obtained on larger synthetically generated graphs where our algorithms show good scaling on up to 16,384 cores.« less

A Preliminary Core Domain Set for Clinical Trials of Shoulder Disorders: A Report from the OMERACT 2016 Shoulder Core Outcome Set Special Interest Group.

PubMed

Buchbinder, Rachelle; Page, Matthew J; Huang, Hsiaomin; Verhagen, Arianne P; Beaton, Dorcas; Kopkow, Christian; Lenza, Mario; Jain, Nitin B; Richards, Bethan; Richards, Pamela; Voshaar, Marieke; van der Windt, Danielle; Gagnier, Joel J

2017-12-01

The Outcome Measures in Rheumatology (OMERACT) Shoulder Core Outcome Set Special Interest Group (SIG) was established to develop a core outcome set (COS) for clinical trials of shoulder disorders. In preparation for OMERACT 2016, we systematically examined all outcome domains and measurement instruments reported in 409 randomized trials of interventions for shoulder disorders published between 1954 and 2015. Informed by these data, we conducted an international Delphi consensus study including shoulder trial experts, clinicians, and patients to identify key domains that should be included in a shoulder disorder COS. Findings were discussed at a stakeholder premeeting of OMERACT. At OMERACT 2016, we sought consensus on a preliminary core domain set and input into next steps. There were 13 and 15 participants at the premeeting and the OMERACT 2016 SIG meeting, respectively (9 attended both meetings). Consensus was reached on a preliminary core domain set consisting of an inner core of 4 domains: pain, physical function/activity, global perceived effect, and adverse events including death. A middle core consisted of 3 domains: emotional well-being, sleep, and participation (recreation and work). An outer core of research required to inform the final COS was also formulated. Our next steps are to (1) analyze whether participation (recreation and work) should be in the inner core, (2) conduct a third Delphi round to finalize definitions and wording of domains and reach final endorsement for the domains, and (3) determine which instruments fulfill the OMERACT criteria for measuring each domain.

Development of w/o microemulsion for transdermal delivery of iodide ions.

PubMed

Lou, Hao; Qiu, Ni; Crill, Catherine; Helms, Richard; Almoazen, Hassan

2013-03-01

The objective of this study was to develop a water-in-oil (w/o) microemulsion which can be utilized as a transdermal delivery for iodide ions. Several w/o microemulsion formulations were prepared utilizing Span 20, ethanol, Capryol 90®, and water. The selected formulations had 5%, 10%, 15%, 20%, and a maximum of 23% w/w water content. Potassium iodide (KI) was incorporated in all formulations at 5% w/v. Physicochemical characterizations were conducted to evaluate the structure and stability. These studies included: mean droplet size, pH, viscosity, conductivity, and chemical stability tests. In vitro human skin permeation studies were conducted to evaluate the diffusion of the iodide ion through human skin. The w/o microemulsion formulations were stable and compatible with iodide ions with water content ranging from 5% to 23% w/w. The addition of KI influenced the physicochemical properties of microemulsion as compared to blank microemulsion formulations. In vitro human skin permeation studies indicated that selected formulations improved iodide ion diffusion significantly as compared to control (KI solution; P value<0.05). Iodide ions were entrapped within the aqueous core of w/o microemulsion. Span 20, ethanol and Capryol 90 protected the iodide ions against oxidation and formed a stable microemulsion. It is worth to note that according to Hofmeister series, iodide ions tend to lower the interfacial tension between water and oil and consequently enhance overall stability. This work illustrates that microemulsion system can be utilized as a vehicle for the transdermal administration of iodide.

Method of fabricating a monolithic core for a solid oxide fuela cell

DOEpatents

Zwick, S.A.; Ackerman, J.P.

1983-10-12

A method is disclosed for forming a core for use in a solid oxide fuel cell that electrochemically combines fuel and oxidant for generating galvanic output. The core has an array of electrolyte and interconnect walls that are substantially devoid of any composite inert materials for support consisting instead only of the active anode, cathode, electrolyte and interconnect materials. Each electrolyte wall consists of cathode and anode materials sandwiching electrolyte material therebetween, and each interconnect wall consists of the cathode and anode materials sandwiching interconnect material therebetween. The electrolyte and interconnect walls define a plurality of substantially parallel core passageways alternately having respectively the inside faces thereof with only the anode material or with only the cathode material exposed. In the wall structure, the electrolyte and interconnect materials are only 0.002 to 0.01 cm thick; and the cathode and anode materials are only 0.002 to 0.05 cm thick. The method consists of building up the electrolyte and interconnect walls by depositing each material on individually and endwise of the wall itself, where each material deposit is sequentially applied for one cycle; and where the depositing cycle is repeated many times until the material buildup is sufficient to formulate the core. The core is heat cured to become dimensionally and structurally stable.

Method of fabricating a monolithic core for a solid oxide fuel cell

DOEpatents

Zwick, Stanley A.; Ackerman, John P.

1985-01-01

A method is disclosed for forming a core for use in a solid oxide fuel cell that electrochemically combines fuel and oxidant for generating galvanic output. The core has an array of electrolyte and interconnect walls that are substantially devoid of any composite inert materials for support consisting instead only of the active anode, cathode, electrolyte and interconnect materials. Each electrolyte wall consists of cathode and anode materials sandwiching electrolyte material therebetween, and each interconnect wall consists of the cathode and anode materials sandwiching interconnect material therebetween. The electrolyte and interconnect walls define a plurality of substantially parallel core passageways alternately having respectively the inside faces thereof with only the anode material or with only the cathode material exposed. In the wall structure, the electrolyte and interconnect materials are only 0.002-0.01 cm thick; and the cathode and anode materials are only 0.002-0.05 cm thick. The method consists of building up the electrolyte and interconnect walls by depositing each material on individually and endwise of the wall itself, where each material deposit is sequentially applied for one cycle; and where the depositing cycle is repeated many times until the material buildup is sufficient to formulate the core. The core is heat cured to become dimensionally and structurally stable.

Preparation and evaluation of celecoxib-loaded microcapsules with self-microemulsifying core.

PubMed

Homar, Miha; Dreu, Rok; Kerc, Janez; Gasperlin, Mirjana

2009-09-01

The purpose of this study was to prepare alginate microcapsules with a self-microemulsifying system (SMES) containing celecoxib in the core. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to prepare the microcapsules. The encapsulated SMES was shown to increase celecoxib solubility over that of the pure drug more than 400-fold. Microcapsules prepared with a high SMES:celecoxib ratio exhibited distinct core vesicles containing liquid SMES. By modifying the SMES and including an additional chitosan coating, drug loading in the range from 12-40% could be achieved with the degree of encapsulation ranging from 60-82%. Alginate microcapsules loaded with SMES and celecoxib showed increased dissolution rate of celecoxib over that of alginate microcapsules loaded with celecoxib or of the celecoxib alone. Compared to the previous report, drug loading capacity was significantly improved, enabling the formulation of dosage forms which are of suitable size for peroral application.

Mucoadhesive Microparticles in a Rapidly Dissolving Tablet for Sustained Drug Delivery to the Eye

PubMed Central

Choy, Young Bin; Patel, Samirkumar R.; Park, Jung-Hwan; McCarey, Bernard E.; Edelhauser, Henry F.

2011-01-01

Purpose. To test the hypothesis that mucoadhesive microparticles formulated in a rapidly dissolving tablet can achieve sustained drug delivery to the eye. Methods. Mucoadhesive microparticles, smaller than 5 μm were fabricated with poly(lactic-co-glycolic acid) and poly(ethylene glycol) as a core material and mucoadhesion promoter, respectively, and encapsulated pilocarpine as a model drug. These microparticles were embedded in a poly(vinyl alcohol) matrix to form a dry tablet designed to reduce rapid clearance of the microparticles on initial application to the eye. Results. This in vitro drug release study exhibited that for all formulations, approximately 90% of pilocarpine was released during the first 10 minutes, and the remaining 10% was released slowly for 3 hours. In vivo mucoadhesion test on the rabbit eye indicated that mucoadhesive microparticles adhered significantly better to the preocular surface than other formulations. To assess the pharmacodynamics, the most prolonged pilocarpine-induced pupil constriction was observed in rabbit eyes in vivo using a tablet with mucoadhesive microparticles; it lasted up to 330 minutes. Conclusions. The authors conclude that mucoadhesive microparticles formulated into a dry dosage form is a promising system for sustained drug delivery to the eye. PMID:21245405

Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization.

PubMed

Sokar, M; Hanafy, A; Elkamel, A; El-Gamal, S

2015-01-01

The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time after which the highest, complete % drug release at pH 6.8 was obtained. In addition, a good partitioning of valsartan, between the aqueous and organic phases in a ratio of 1:7, was observed. The selected formula was stable for at least 3 months under standard long-term and accelerated storage conditions. In conclusion, in vitro studies revealed that the novel time-clock system could be used successfully to deliver valsartan in a pulsatile pH-independent manner. It provided a desirable lag time followed by a rapid and complete drug release accompanied by an expected effective permeation through the biological membranes upon release in the duodenum; the window of absorption, as indicated by the two phase release study.

Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization

PubMed Central

Sokar, M.; Hanafy, A.; Elkamel, A.; El-Gamal, S.

2015-01-01

The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time after which the highest, complete % drug release at pH 6.8 was obtained. In addition, a good partitioning of valsartan, between the aqueous and organic phases in a ratio of 1:7, was observed. The selected formula was stable for at least 3 months under standard long-term and accelerated storage conditions. In conclusion, in vitro studies revealed that the novel time-clock system could be used successfully to deliver valsartan in a pulsatile pH-independent manner. It provided a desirable lag time followed by a rapid and complete drug release accompanied by an expected effective permeation through the biological membranes upon release in the duodenum; the window of absorption, as indicated by the two phase release study. PMID:26664064

Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals

PubMed Central

Farazuddin, Mohammad; Dua, Bhavyata; Zia, Qamar; Khan, Aijaz Ahmad; Joshi, Beenu; Owais, Mohammad

2014-01-01

Curcumin (diferuloylmethane) is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver. Unfortunately, the poor bioavailability and hydrophobicity of curcumin pose a major hurdle to its use as a potent anticancer agent. To circumvent some of these problems, we developed a novel, dual-core microcell formulation of curcumin. The encapsulation of curcumin in microcells increases its solubility and bioavailability, and facilitates slow release kinetics over extended periods. Besides being safe, these formulations do not bear any toxicity constraints, as revealed by in vitro and in vivo studies. Histopathological analysis revealed that curcumin-bearing microcells helped in regression of hepatocellular carcinoma and the maintenance of cellular architecture in liver tissue. Free curcumin had a very mild effect on cancer suppression. Empty (sham) microcells and microparticles failed to inhibit cancer cells. The novel curcumin formulation was found to suppress hepatocellular carcinoma efficiently in Swiss albino mice. PMID:24627632

Instability of the cored barotropic disc: the linear eigenvalue formulation

NASA Astrophysics Data System (ADS)

Polyachenko, E. V.

2018-05-01

Gaseous rotating razor-thin discs are a testing ground for theories of spiral structure that try to explain appearance and diversity of disc galaxy patterns. These patterns are believed to arise spontaneously under the action of gravitational instability, but calculations of its characteristics in the gas are mostly obscured. The paper suggests a new method for finding the spiral patterns based on an expansion of small amplitude perturbations over Lagrange polynomials in small radial elements. The final matrix equation is extracted from the original hydrodynamical equations without the use of an approximate theory and has a form of the linear algebraic eigenvalue problem. The method is applied to a galactic model with the cored exponential density profile.

Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent.

PubMed

Wehbe, Mohamed; Anantha, Malathi; Shi, Minghan; Leung, Ada Wai-Yin; Dragowska, Wieslawa H; Sanche, Léon; Bally, Marcel B

2017-01-01

Copper diethyldithiocarbamate (Cu(DDC) 2 ) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC) 2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC) 2 because of the inherent aqueous insolubility of the complex. Here, we describe an injectable Cu(DDC) 2 formulation prepared through a method that involves synthesis of Cu(DDC) 2 inside the aqueous core of liposomes. Convection-enhanced delivery of a Cu(DDC) 2 formulation prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol liposomes into a rat model of F98 glioma engendered a 25% increase in median survival time relative to vehicle-treated animals. In a murine subcutaneous MV-4-11 model, treatment resulted in a 45% reduction in tumor burden when compared to controls. Pharmacokinetic studies indicated that the Cu(DDC) 2 was rapidly eliminated after intravenous administration while the liposomes remained in circulation. To test whether liposomal lipid composition could increase Cu(DDC) 2 circulation lifetime, a number of different formulations were evaluated. Studies demonstrated that liposomes composed of DSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-(carboxy[polyethylene glycol]-2000) (95:5) enhanced Cu(DDC) 2 concentrations in the circulation as reflected by a 4.2-fold increase in plasma AUC (0-∞) relative to the DSPC/cholesterol formulation. The anticancer activity of this Cu(DDC) 2 formulation was subsequently evaluated in the MV-4-11 model. At its maximum tolerated dose, this formulation exhibited comparable activity to the DSPC/cholesterol formulation. This is the first report demonstrating the therapeutic effects of an injectable Cu(DDC) 2 formulation in vivo.

Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent

PubMed Central

Wehbe, Mohamed; Anantha, Malathi; Shi, Minghan; Leung, Ada Wai-yin; Dragowska, Wieslawa H; Sanche, Léon; Bally, Marcel B

2017-01-01

Copper diethyldithiocarbamate (Cu(DDC)2) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC)2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC)2 because of the inherent aqueous insolubility of the complex. Here, we describe an injectable Cu(DDC)2 formulation prepared through a method that involves synthesis of Cu(DDC)2 inside the aqueous core of liposomes. Convection-enhanced delivery of a Cu(DDC)2 formulation prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol liposomes into a rat model of F98 glioma engendered a 25% increase in median survival time relative to vehicle-treated animals. In a murine subcutaneous MV-4–11 model, treatment resulted in a 45% reduction in tumor burden when compared to controls. Pharmacokinetic studies indicated that the Cu(DDC)2 was rapidly eliminated after intravenous administration while the liposomes remained in circulation. To test whether liposomal lipid composition could increase Cu(DDC)2 circulation lifetime, a number of different formulations were evaluated. Studies demonstrated that liposomes composed of DSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-(carboxy[polyethylene glycol]-2000) (95:5) enhanced Cu(DDC)2 concentrations in the circulation as reflected by a 4.2-fold increase in plasma AUC(0−∞) relative to the DSPC/cholesterol formulation. The anticancer activity of this Cu(DDC)2 formulation was subsequently evaluated in the MV-4–11 model. At its maximum tolerated dose, this formulation exhibited comparable activity to the DSPC/cholesterol formulation. This is the first report demonstrating the therapeutic effects of an injectable Cu(DDC)2 formulation in vivo. PMID:28615941

Dendrimers in Medicine: Therapeutic Concepts and Pharmaceutical Challenges.

PubMed

Wu, Lin-Ping; Ficker, Mario; Christensen, Jørn B; Trohopoulos, Panagiotis N; Moghimi, Seyed Moein

2015-07-15

Dendrimers are three-dimensional macromolecular structures originating from a central core molecule and surrounded by successive addition of branching layers (generation). These structures exhibit a high degree of molecular uniformity, narrow molecular weight distribution, tunable size and shape characteristics, as well as multivalency. Collectively, these physicochemical characteristics together with advancements in design of biodegradable backbones have conferred many applications to dendrimers in formulation science and nanopharmaceutical developments. These have included the use of dendrimers as pro-drugs and vehicles for solubilization, encapsulation, complexation, delivery, and site-specific targeting of small-molecule drugs, biopharmaceuticals, and contrast agents. We briefly review these advances, paying particular attention to attributes that make dendrimers versatile for drug formulation as well as challenging issues surrounding the future development of dendrimer-based medicines.

X-ray Raman scattering from molecules and solids in the framework of the Mahan-Nozières-De Dominicis model

NASA Astrophysics Data System (ADS)

Privalov, Timofei; Gel'mukhanov, Faris; Ågren, Hans

2001-10-01

We have developed a formulation of resonant x-ray Raman scattering of molecules and solids based on the Mahan-Nozières-De Dominicis model. A key step in the formulation is given by a reduction of the Keldysh-Dyson equations for the Green's function to a set of linear algebraic equations. This gave way for a tractable scheme that can be used to analyze the resonant x-ray scattering in the whole time domain. The formalism is used to investigate the role of core-hole relaxation, interference, band filling, detuning, and size of the scattering target. Numerical applications are performed with a one-dimensional tight-binding model.

A combined vector potential-scalar potential method for FE computation of 3D magnetic fields in electrical devices with iron cores

NASA Technical Reports Server (NTRS)

Wang, R.; Demerdash, N. A.

1991-01-01

A method of combined use of magnetic vector potential based finite-element (FE) formulations and magnetic scalar potential (MSP) based formulations for computation of three-dimensional magnetostatic fields is introduced. In this method, the curl-component of the magnetic field intensity is computed by a reduced magnetic vector potential. This field intensity forms the basic of a forcing function for a global magnetic scalar potential solution over the entire volume of the region. This method allows one to include iron portions sandwiched in between conductors within partitioned current-carrying subregions. The method is most suited for large-scale global-type 3-D magnetostatic field computations in electrical devices, and in particular rotating electric machinery.

Lattice Boltzmann model for numerical relativity.

PubMed

Ilseven, E; Mendoza, M

2016-02-01

In the Z4 formulation, Einstein equations are written as a set of flux conservative first-order hyperbolic equations that resemble fluid dynamics equations. Based on this formulation, we construct a lattice Boltzmann model for numerical relativity and validate it with well-established tests, also known as "apples with apples." Furthermore, we find that by increasing the relaxation time, we gain stability at the cost of losing accuracy, and by decreasing the lattice spacings while keeping a constant numerical diffusivity, the accuracy and stability of our simulations improve. Finally, in order to show the potential of our approach, a linear scaling law for parallelization with respect to number of CPU cores is demonstrated. Our model represents the first step in using lattice kinetic theory to solve gravitational problems.

Evaluation of hypericin-loaded solid lipid nanoparticles: physicochemical properties, photostability and phototoxicity.

PubMed

Youssef, Tareq; Fadel, Maha; Fahmy, Rania; Kassab, Kawser

2012-01-01

Hypericin (HYP), a natural photosensitizer, has powerful photo-oxidizing ability, tumor-seeking characteristics, and minimal dark toxicity; nevertheless, it has proven high lipid solubility compared to its sparingly water soluble nature. Therefore, its formulation into solid lipid nanoparticles (SLNs) has attracted increasing attention as a potential drug-delivery carrier. Two HYP-loaded SLNs formulations were prepared utilizing microemulsion-based technique. Thereafter, the physicochemical properties of the formulations were investigated and evaluated. HYP-loaded SLNs showed spherical shape with mean particle size ranging from 200-300 nm for both formulations (FA and FB). The encapsulation efficiencies reached above 80% and FA showed significant higher encapsulation than FB (P<0.05), also, the thermal analysis using differential scanning calorimetry (DSC) indicated good compatibility between hypericin and lipids forming the cores in both formulations. Spectroscopic measurements of the photostability study showed that hypericin encapsulation into SLNs improved its photostability, compared to free HYP in 0.1% ethanolic solution. However, photocytotoxicity studies on HepG2 cells revealed an evident inhibition of the photodynamic efficacy of HYP-loaded SLNs, compared to free HYP. In conclusion, although the elevated entrapment efficiency of HYP into SLNs increased its photostability, it decreased its phototoxicity which might be due to the quenching deactivation of HYP molecules resulting from SLN compactness and thickness structure. © 2012 Informa Healthcare USA, Inc.

Disk-Planet Torques from Radiation-Hydrodynamics Calculations with Spatially-Resolved Planetary Envelopes Undergoing Solids' Accretion

NASA Astrophysics Data System (ADS)

D'Angelo, G.

2016-12-01

D'Angelo & Bodenheimer (2013, ApJ, 778, 77) performed global 3D radiation-hydrodynamics disk-planet simulations aimed at studying envelope formation around planetary cores, during the phase of sustained planetesimal accretion. The calculations modeled cores of 5, 10, and 15 Earth masses orbiting a sun-like star in a protoplanetary disk extending from ap/2 to 2ap in radius, ap=5 or 10 AU being the core's orbital radius. The gas equation of state - for a solar mixture of H2, H, He - accounted for translational, rotational, and vibrational states, for molecular dissociation and atomic ionization, and for radiation energy. Dust opacity calculations applied the Mie theory to multiple grain species whose size distributions ranged from 5e-6 to 1 mm. Mesh refinement via grid nesting allowed the planets' envelopes to be resolved at the core-radius length scale. Passive tracers were used to determine the volume of gas bound to a core, defining the envelope, and resulting in planet radii comparable to the Bondi radius. The energy budjet included contributions from the accretion of solids on the cores, whose rates were self-consistently computed with a 1D planet formation code. At this stage of the planet's growth, gravitational energy released in the envelope by solids' accretion far exceeds that released by gas accretion. These models are used to determine the gravitational torques exerted by the disk's gas on the planet and the resulting orbital migration rates. Since the envelope radius is a direct product of the models, they allow for a non-ambiguous assessment of the torques exerted by gas not bound to the planet. Additionally, since planets' envelopes are fully resolved, thermal and dynamical effects on the surrounding disk's gas are accurately taken into account. The computed migration rates are compared to those obtained from existing semi-analytical formulations for planets orbiting in isothermal and adiabatic disks. Because these formulations do not account for thermodynamical interactions between the planet's envelope and the disk's gas, the numerical models are also used to quanitfy the impact of short-scale tidal interactions on the total torque acting on the planet. Computing resources were provided by the NASA High-End Computing Program through the NASA Advanced Supercomputing Division at Ames Research Center.

Structure and properties of barium tin boro-phosphate glass systems with very low photoelastic constant

NASA Astrophysics Data System (ADS)

Itadani, M.; Tricot, G.; Doumert, B.; Takebe, H.; Saitoh, A.

2017-08-01

Glasses in the BaO-SnO-P2O5-B2O3 system were prepared and evaluated in order to formulate preform glasses suitable for the fabrication of fiber cores with a very low photoelastic constant. A first glass system (I: xBaO-(60-x)SnO-40P2O5) was designed with a constant P2O5 content and various BaO contents (0-40 mol. %). Introduction of 3 mol. % of B2O3 to enhance the glass stability leads to the second glass system (II: x'BaO-(57-x')SnO-40P2O5-3B2O3) with 33-38 mol. % BaO. The structure of both systems was investigated by 1D/2D magic-angle spinning nuclear magnetic resonance, Raman, and Fourier transform infrared spectroscopic techniques. 31P NMR showed the presence of Q2 and Q1 units in the first system and correlation 11B/31P NMR indicated that boron enters into the network as B(OP)4 structural units. The photoelastic constant was determined and the stability of the best formulations as well as their refractive index dispersion was established. The drawing temperature and isothermal heating time (without crystal precipitation) parameters were also accurately measured by using experimental time-temperature-transition. Considering that the refractive indices of the core and the cladding materials must match, detailed core and cladding compositions for a fiber enabling single-mode waveguide transmission were proposed.

The maximum vector-angular margin classifier and its fast training on large datasets using a core vector machine.

PubMed

Hu, Wenjun; Chung, Fu-Lai; Wang, Shitong

2012-03-01

Although pattern classification has been extensively studied in the past decades, how to effectively solve the corresponding training on large datasets is a problem that still requires particular attention. Many kernelized classification methods, such as SVM and SVDD, can be formulated as the corresponding quadratic programming (QP) problems, but computing the associated kernel matrices requires O(n2)(or even up to O(n3)) computational complexity, where n is the size of the training patterns, which heavily limits the applicability of these methods for large datasets. In this paper, a new classification method called the maximum vector-angular margin classifier (MAMC) is first proposed based on the vector-angular margin to find an optimal vector c in the pattern feature space, and all the testing patterns can be classified in terms of the maximum vector-angular margin ρ, between the vector c and all the training data points. Accordingly, it is proved that the kernelized MAMC can be equivalently formulated as the kernelized Minimum Enclosing Ball (MEB), which leads to a distinctive merit of MAMC, i.e., it has the flexibility of controlling the sum of support vectors like v-SVC and may be extended to a maximum vector-angular margin core vector machine (MAMCVM) by connecting the core vector machine (CVM) method with MAMC such that the corresponding fast training on large datasets can be effectively achieved. Experimental results on artificial and real datasets are provided to validate the power of the proposed methods. Copyright © 2011 Elsevier Ltd. All rights reserved.

Illegal "no prescription" internet access to narrow therapeutic index drugs.

PubMed

Liang, Bryan A; Mackey, Tim K; Lovett, Kimberly M

2013-05-01

Narrow therapeutic index (NTI) drugs, because of proximity of therapeutic amounts to toxic amounts, require close professional oversight, particularly when switching formulations. However, safe use may be compromised by unsupervised switching through access to online "no prescription" Web sites. We assessed no prescription online availability of NTI drugs, using an academically published list (core NTI drugs). Using the Google search term "buy DRUG no prescription," we reviewed the first 5 search result pages for marketing of no prescription NTI drugs. We further assessed if National Association of Boards of Pharmacy (NABP) Not Recommended vendors were marketing NTI drugs. Searches were conducted from November 3, 2012 to January 3, 2013. For core NTI drugs, we found 13 of 14 NTI drugs (92%) marketed as available without prescription, all from NABP Not Recommended vendors. On the basis of these initial findings, we expanded our core list to 12 additional NTI drugs; 11 of 12 of these drugs (92%) were available from no prescription Web sites. Overall, 24 of 26 NTI drugs (92%) were illegally marketed as available online without the need for a prescription. Suspect online NTI drug access from no prescription vendors represents a significant patient safety risk because of potential patient drug switching and risk of counterfeit versions. Further, state health care exchanges with coverage limitations may drive patients to seek formulations online. Food and Drug Administration harmonization with tighter international NTI drug standards should be considered, and aggressive action against suspect online marketers should be a regulatory and public health priority. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

An Etiological Approach to Sexual Offender Assessment: CAse Formulation Incorporating Risk Assessment (CAFIRA).

PubMed

Craig, Leam A; Rettenberger, Martin

2018-05-19

Case formulations (CF) have been the cornerstone of effective practice in clinical psychology since the 1950s and now form one of the core competencies in clinical and forensic assessment. The use of CFs within forensic settings is becoming more relevant when working with offenders who have experienced significant trauma, suffered from personality disorder, and have displayed sexually abusive behavior. Furthermore, most North American and European jurisdictions insist that expert witnesses adopt an idiosyncratic approach to risk assessment and consider the characteristics of the individual as part of a wider formulation of the problem behavior. This article focuses specifically on CF incorporating risk assessment procedures of sexual offenders. While empirical support for the use of risk analysis and formulation in managing offending behavior generally, and sexual offending behavior in particular, is limited, there is mounting evidence to suggest that CF can improve understanding of an individual's problem sexual behaviors. We argue that by integrating risk formulations into the CF provides a conceptually robust link between the etiologically development of the problem sexual behavior and effective assessment and risk management of sexual offenders. As forensic treatment programs increasingly moved toward strength-based approaches, in keeping with the Risk-Need-Responsivity principles Andrews and Bonta (2004), and the Good Lives Model Ward and Stewart (Prof Psychol Res Pract 34:353-60, 2003) of offender rehabilitation, the use of CFs in the assessment, treatment, and management of sexual offenders is indispensable. We present an etiological framework for understanding risk in an individual sexual offender by integrating a case formulation model to include the use of (static, stable, and acute) actuarial and clinical risk assessment measures as well as protective risk factors, referred to as the CAse Formulation Incorporating Risk Assessment (CAFIRA) model.

Assessment of antimalarial activity against Plasmodium falciparum and phytochemical screening of some Yemeni medicinal plants

PubMed Central

Alshawsh, Mohammed A.; Al-shamahy, Hassan A.; Alsllami, Salah F.; Lindequist, Ulrike

2009-01-01

Developing countries, where malaria is one of the most prevalent diseases, still rely on traditional medicine as a source for the treatment of this disease. In the present study, six selected plants (Acalypha fruticosa, Azadirachta indica, Cissus rotundifolia, Echium rauwalfii, Dendrosicyos socotrana and Boswellia elongata) commonly used in Yemen by traditional healers for the treatment of malaria as well as other diseases, were collected from different localities of Yemen, dried and extracted with methanol and water successfully. The antiplasmodial activity of the extracts was evaluated against fresh clinical isolates of Plasmodium falciparum. The selectivity parameters to evaluate the efficacy of these medicinal plants were measured by in vitro micro test (Mark III) according to World Health Organization (WHO) 1996 & WHO 2001 protocols of antimalarial drug tests. Among the investigated 12 extracts, three were found to have significant antiplasmodial activity with IC50 values less than 4 µg/ml, namely the water extracts of A. fruticosa, A. indica and D. socotrana. Six extracts showed moderate activity with IC50 values ranging from 10 to 30 µg/ml and three appeared to be inactive with IC50 values more than 30 µg/ml. In addition, preliminary phytochemical screening of the methanolic and aqueous extracts indicated the presence of saponins, tannins, flavonoids, terpenoids, polysaccharides and peptides. PMID:18955251

A Review of Natural Stimulant and Non‐stimulant Thermogenic Agents

PubMed Central

Badmaev, Vladimir

2016-01-01

Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non‐stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non‐stimulatory thermogenic agents include p‐synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd. PMID:26856274

A Review of Natural Stimulant and Non-stimulant Thermogenic Agents.

PubMed

Stohs, Sidney J; Badmaev, Vladimir

2016-05-01

Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non-stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non-stimulatory thermogenic agents include p-synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd. © 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd.

Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027

DOE PAGES

Huang, Tingting; Chang, Chin -Yuan; Lohman, Jeremy R.; ...

2016-10-01

Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site-directed mutagenesis of the conserved residues lining this site allowed us tomore » propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase-associated enzymes, into an enzyme-sequestered enediyne core intermediate. In conclusion, these findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.« less

A thermodynamic recipe for baking the Earth's lower mantle and core as a whole

NASA Astrophysics Data System (ADS)

Tirone, Max; Faak, Kathi

2016-04-01

A rigorous understanding of the thermal and dynamic evolution of the core and the interaction with the silicate mantle cannot preclude a non-empirical petrological description of the problem which takes the form of a thermodynamic model. Because the Earth's core is predominantly made of iron such model may seem relatively straightforward, simply delivering a representation of the phase transformations in the P,T space. However due to well known geophysical considerations, a certain amount of light elements should be added. With the Occam's razor principle in mind, potential candidates could be the most abundant and easily accessible elements in the mantle, O, Si and Mg. Given these premises, the challenging problems on developing this type of model are: - a thermodynamic formulation should not simply describe phase equilibrium relations at least in the Fe-Si-O system (a formidable task itself) but should be also consistently applicable to evaluate thermophysical properties of liquid components and solids phases at extreme conditions (P=500-2000 kbar, T=1000-5000 K). Presently these properties are unknown for certain mineral and liquid components or partially available from scattered sources. - experimental data on the phase relations for iron rich liquid are extremely difficult to obtain and could not cover the entire P,T,X spectrum. - interaction of the outer core with the silicate mantle requires a melt model that is capable of describing a vast range of compositions ranging from metal-rich liquids to silicate liquids. The compound energy formalism for liquids with variable tendency to ionization developed by Hillert and coworkers is a sublattice model with varying stoichiometry that includes vacancies and neutral species in one site. It represents the ideal candidate for the task in hand. The thermodynamic model unfortunately is rather complex and a detailed description of the formulation for practical applications like chemical equilibrium calculations is nowhere to be found, while the model is only accessible on few commercial thermodynamic programs. The latest developments regarding all these related issues will be discussed in this contribution. In particular some self-consistent but preliminary results will be presented addressing the following topics: - some details regarding the implementation of the liquid model for Gibbs free energy minimizations, - the physically consistent behavior of thermodynamic properties of certain solid phases like (Fe,O,Si) BCC, FCC, HCP and liquid components, - selected phase diagrams at core conditions in the system Fe-Si-O, - derived geotherms linking the inner-outer core with the core-mantle boundary. - brief outline of the future geodynamic applications.

Dynamics of axial torsional libration under the mantle-inner core gravitational interaction

NASA Astrophysics Data System (ADS)

Chao, B. F.

2017-01-01

The aims of this paper are (i) formulating the dynamics of the mantle-inner core gravitational (MICG) interaction in terms of the spherical-harmonic multipoles of mass density. The modeled MICG system is composed of two concentric rigid bodies (mantle and inner core) of near-spherical but otherwise heterogeneous configuration, with a fluid outer core in between playing a passive role. We derive the general equation of motion for the vector rotation but only focus on the polar component that describes the MICG axial torsional libration. The torsion constant and hence the square of the natural frequency of the libration is proportional to the product of the equatorial ellipticities of the mantle and inner-core geoid embodied in their multipoles (of two different types) of degree 2 and order 2 (such as the Large Low-Shear-Velocity Provinces above the core-mantle boundary) and (ii) studying the geophysical implications upon equating the said MICG libration to the steady 6 year oscillation that are observed in the Earth's spin rate or the length-of-day variation (ΔLOD). In particular, the MICG torsion constant is found to be Γ>˜z = CIC σz2 ≈ 6.5 × 1019 N m, while the inner core's (BIC - AIC) ≈ 1.08 × 1031 kg m2 gives the inner core triaxiality (BIC - AIC)/CIC ≈ 1.8 × 10-4, about 8 times the whole-Earth value. It is also asserted that the required inner-core ellipticity amounts to no more than 140 m in geoid height, much smaller than the sensitivity required for the seismic wave travel time to resolve the variation of the inner core.

A Safer Formulation Concept for Flame-Generated Engineered Nanomaterials

PubMed Central

Gass, Samuel; Cohen, Joel M.; Pyrgiotakis, Georgios; Sotiriou, Georgios A.; Pratsinis, Sotiris E.; Demokritou, Philip

2013-01-01

The likely success or failure of the nanotechnology industry depends on the environmental health and safety of engineered nanomaterials (ENMs). While efforts toward engineering safer ENMs are sparse, such efforts are considered crucial to the sustainability of the nanotech industry. A promising approach in this regard is to coat potentially toxic nanomaterials with a biologically inert layer of amorphous SiO2. Core-shell particles exhibit the surface properties of their amorphous SiO2 shell while maintaining specific functional properties of their core material. A major challenge in the development of functional core-shell particles is the design of scalable high-yield processes that can meet large-scale industrial demand. Here, we present a safer formulation concept for flame-generated ENMs based on a one-step, in flight SiO2 encapsulation process, which was recently introduced by the authors as a means for a scalable manufacturing of SiO2 coated ENMs. Firstly, the versatility of the SiO2-coating process is demonstrated by applying it to four ENMs (CeO2, ZnO, Fe2O3, Ag) marked by their prevalence in consumer products as well as their range in toxicity. The ENM-dependent coating fundamentals are assessed and process parameters are optimized for each ENM investigated. The effects of the SiO2-coating on core material structure, composition and morphology, as well as the coating efficiency on each nanostructured material, are evaluated using state-of-the-art analytical methods (XRD, N2 adsorption, TEM, XPS, isopropanol chemisorption). Finally, the biological interactions of SiO2-coated vs. uncoated ENMs are evaluated using cellular bioassays, providing valuable evidence for reduced toxicity for the SiO2-coated ENMs. Results indicate that the proposed ‘safer by design’ concept bears great promise for scaled-up application in industry in order to reduce the toxicological profile of ENMs for certain applications. PMID:23961338

Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

PubMed

Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R

2012-04-02

This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.

What are the core ideas behind the Precautionary Principle?

PubMed

Persson, Erik

2016-07-01

The Precautionary Principle is both celebrated and criticized. It has become an important principle for decision making, but it is also subject to criticism. One problem that is often pointed out with the principle is that is not clear what it actually says and how to use it. I have taken on this problem by performing an analysis of some of the most influential formulations of the principle in an attempt to identify the core ideas behind it, with the purpose of producing a formulation of the principle that is clear and practically applicable. It was found that what is called the Precautionary Principle is not a principle that tells us what do to achieve extra precaution or how to handle situations when extra precaution is called for. Instead, it was found to be a list of circumstances that each justify extra precaution. An analysis of some of the most common and influential formulations of the Precautionary Principle identified four such circumstances: (1) When we deal with important values that tend to be systematically downplayed by traditional decision methods - such as human health and the environment. (2) When we suspect that the decision might lead to irreversible and severe consequences and the values at stake are also irreplaceable, (3) When timing is at least as important as being right. (4) When it is more important to avoid false negatives than false positives. This interpretation of the Precautionary Principle does not say anything about what kind of actions to take when extra precaution is called for, but it does provide a clear and practically useful list of circumstances that call for extra precaution and that is not subject to the most common objections to the Precautionary Principle. Copyright © 2016 Elsevier B.V. All rights reserved.

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

PubMed Central

Charão, Mariele Feiffer; Souto, Caroline; Brucker, Natália; Barth, Anelise; Jornada, Denise S; Fagundez, Daiandra; Ávila, Daiana Silva; Eifler-Lima, Vera L; Guterres, Silvia S; Pohlmann, Adriana R; Garcia, Solange Cristina

2015-01-01

Caenorhabditis elegans is an alternative in vivo model that is being successfully used to assess the pharmacological and toxic effects of drugs. The exponential growth of nanotechnology requires the use of alternative in vivo models to assess the toxic effects of theses nanomaterials. The use of polymeric nanocapsules has shown promising results for drug delivery. Moreover, these formulations have not been used in cases of intoxication, such as in treatment of paraquat (PQ) poisoning. Thus, the use of drugs with properties improved by nanotechnology is a promising approach to overcome the toxic effects of PQ. This research aimed to evaluate the absorption of rhodamine B-labeled melatonin (Mel)-loaded lipid-core nanocapsules (LNC) by C. elegans, the application of this model in nanotoxicology, and the protection of Mel-LNC against PQ damage. The formulations were prepared by self-assembly and characterized by particle sizing, zeta potential, drug content, and encapsulation efficiency. The results demonstrated that the formulations had narrow size distributions. Rhodamine B-labeled Mel-LNC were orally absorbed and distributed in the worms. The toxicity assessment of LNC showed a lethal dose 50% near the highest dose tested, indicating low toxicity of the nanocapsules. Moreover, pretreatment with Mel-LNC significantly increased the survival rate, reduced the reactive oxygen species, and maintained the development in C. elegans exposed to PQ compared to those worms that were either untreated or pretreated with free Mel. These results demonstrated for the first time the uptake and distribution of Mel-LNC by a nematode, and indicate that while LNC is not toxic, Mel-LNC prevents the effects of PQ poisoning. Thus, C. elegans may be an interesting alternative model to test the nanocapsules toxicity and efficacy. PMID:26300641

New proteoliposome vaccine formulation from N. meningitidis serogroup B, without aluminum hydroxide, retains its antimeningococcal protectogenic potential as well as Th-1 adjuvant capacity

PubMed Central

2013-01-01

Proteoliposomes purified from the Outer Membrane of Neisseria meningitidis B, have been successfully used as core for adjuvants and vaccine formulations. We have tried to increase their structural definition and to conserve their efficacy and stability avoiding the addition of the aluminum hydroxide to the final formulation. Liposomal particle systems were prepared from components of defined molecular structure, such as a Neisseria meningitidis B protein complex, extracted and purified without forming vesicle structures. Liposomes were prepared from a mixture of dioleoyl phosphatidyl serine and cholesterol, using the classical dehydration-rehydration method. Transmission Electron Microscopy (TEM) was used to characterize the liposomes. BALB/c mice were used for animal testing procedures. Analysis of specific IgG response, serum bactericidal activity as well as DTH reaction was carried out. Isolation and purification of mRNA and real-time PCR, was performed to determine the dominating Th lymphokine pattern. The new antimeningococcal formulation without aluminum hydroxide prepared with components of defined molecular structure assembled itself into Neoproteoliposomes (NPL) ranging from 50 to 70 nm in diameter. The extraction and purification of selected membrane proteins to provide the antigen for this new formulation (PD-Tp), as well as the NPL-formulation favors a Th1 response pattern, suggested by the higher percentages of DTH, increased expression of proinflamatory lymphokine mRNAs when administered by intramuscular and intranasal routes. It stimulates a systemic bactericidal antibody response against Neisseria meningitidis B and immunologic memory similar to the Cuban VA-MENGOC-BC® vaccine, even at lower dosages and is less reactogenic at the injection site in comparison with the formulation with aluminum hydroxide. This new adjuvant formulation could be applicable to the development of new and improved vaccines against meningococcal disease, and eventually as modulators of the immune response against other diseases. PMID:23458443

The Shock and Vibration Digest. Volume 15, Number 3

DTIC Science & Technology

1983-03-01

High Temperature Gas-Cooled Reactor Core with Block-type Fuel (2nd Report: An Analytical Method of Two-dmentmnal Vibration of Interacting CohunM) T...Computer-aided techniquei, Detign techniquei A wite of computer programs hat been developed which allow« advanced fatigue analyiit procedures to be...valuei with those developed by bearing analysis computer programs were used to formulate an understanding of the mechanisms that induce ball skidding

JOMAR: Joint Operations with Mobile Autonomous Robots

DTIC Science & Technology

2015-12-21

AFRL-AFOSR-JP-TR-2015-0009 JOMAR: Joint Operations with Mobile Autonomous Robots Edwin Olson UNIVERSITY OF MICHIGAN Final Report 12/21/2015...SUBTITLE JOMAR: Joint Operations with Mobile Autonomous Robots 5a. CONTRACT NUMBER FA23861114024 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...14. ABSTRACT Under this grant, we formulated and implemented a variety of novel algorithms that address core problems in multi- robot systems. These

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.

The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

PubMed Central

Chen, Jian; Huang, Gui-Dong; Tan, Si-Rong; Guo, Jiao; Su, Zheng-Quan

2013-01-01

This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs. PMID:24351818

Multifunctional antitumor magnetite/chitosan- l-glutamic acid (core/shell) nanocomposites

NASA Astrophysics Data System (ADS)

Santos, Daniela P.; Ruiz, M. Adolfina; Gallardo, Visitación; Zanoni, Maria Valnice B.; Arias, José L.

2011-09-01

The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan- l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.

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

Ethnomedicinal plants to cure skin diseases-an account of the traditional knowledge in the coastal parts of Central Western Ghats, Karnataka, India.

PubMed

Bhat, Pradeep; Hegde, Ganesh R; Hegde, Gurumurthi; Mulgund, Gangadhar S

2014-01-01

Documentation of ethnomedicinal knowledge pertaining to the treatment of different types of skin diseases from the Central Western Ghats of India, a rich habitat of different ethnic communities. Frequent field surveys were carried out to invent the 'key informants' in the treatment of skin diseases in the study area. The information was collected through semi-structured open ended interviews with questionnaire in their local Kannada language. All medicinal plants recorded for the treatment of skin diseases were photographed in the field; voucher specimens were made subsequently and are deposited in the Herbarium, P.G. Department of Botany, Karnatak University, Dharwad. The information such as botanical name, status, family, vernacular name, habit and habitat, analysis like percentage of parts used, percentage of drug preparations, use value (UV), informants consensus factor (ICF), fidelity level (FL) and correlation between UV and use mention (Np) of the plants are provided. In all, 48 informants were interviewed. Amongst which 38 were the 'key informants' who gave the information exclusively about the treatment of skin diseases. Among 102 plant species collected, seven species are endemic to India and eleven species have their nativity outside India. Twelve species could be considered as new claims for skin diseases as their use has not been mentioned in Ayurveda or any other research articles surveyed. Of all the drug formulations, paste is the most preferred method (50%) followed by oil extraction (18.89%), juice (14.44%), ash (4.44%) etc. The highest UV is for Pongamia pinnata, Naregamia alata, Randia dumetorum and Girardinia diversifolia (1.50 each). The treatment for different types of skin diseases by the herbal healers are classified into 13 categories, out of which ringworm scored the highest ICF value. Similarly, the 100% FL value scored was in the order of 10 plants for boils, 4 plants for different types of sore, 2 plants for ringworm, intertrigo, eczema and pruritus respectively. As Caesalpinia mimosoides and Basella alba in the treatment of boils, Hygrophila schulli for inter trigo, Cissus discolor for ringworm, Mammea suriga for eczema scored high FL and high Np value, they can be considered as important species. The documentation and data analysis of the ethnomedicinal knowledge in the coastal regions of Uttara Kannada district of Central Western Ghats have provided the information about important plants in the treatment of different types of skin diseases. Further scientific analysis of such plants may provide novel compounds for the treatment of skin diseases. © 2013 The Authors. Published by Elsevier Ireland Ltd All rights reserved.

Two-photon excitation cross section in light and intermediate atoms in frozen-core LS-coupling approximation

NASA Technical Reports Server (NTRS)

Omidvar, K.

1980-01-01

Using the method of explicit summation over the intermediate states two-photon absorption cross sections in light and intermediate atoms based on the simplistic frozen-core approximation and LS coupling have been formulated. Formulas for the cross section in terms of integrals over radial wave functions are given. Two selection rules, one exact and one approximate, valid within the stated approximations are derived. The formulas are applied to two-photon absorptions in nitrogen, oxygen, and chlorine. In evaluating the radial integrals, for low-lying levels, the Hartree-Fock wave functions, and for high-lying levels, hydrogenic wave functions obtained by the quantum-defect method have been used. A relationship between the cross section and the oscillator strengths is derived.

VCE testbed program planning and definition study

NASA Technical Reports Server (NTRS)

Westmoreland, J. S.; Godston, J.

1978-01-01

The flight definition of the Variable Stream Control Engine (VSCE) was updated to reflect design improvements in the two key components: (1) the low emissions duct burner, and (2) the coannular exhaust nozzle. The testbed design was defined and plans for the overall program were formulated. The effect of these improvements was evaluated for performance, emissions, noise, weight, and length. For experimental large scale testing of the duct burner and coannular nozzle, a design definition of the VCE testbed configuration was made. This included selecting the core engine, determining instrumentation requirements, and selecting the test facilities, in addition to defining control system and assembly requirements. Plans for a comprehensive test program to demonstrate the duct burner and nozzle technologies were formulated. The plans include both aeroacoustic and emissions testing.

Evaluation of damage progression and mechanical behavior under compression of bone cements containing core-shell nanoparticles by using acoustic emission technique.

PubMed

Pacheco-Salazar, O F; Wakayama, Shuichi; Sakai, Takenobu; Cauich-Rodríguez, J V; Ríos-Soberanis, C R; Cervantes-Uc, J M

2015-06-01

In this work, the effect of the incorporation of core-shell particles on the fracture mechanisms of the acrylic bone cements by using acoustic emission (AE) technique during the quasi-static compression mechanical test was investigated. Core-shell particles were composed of a poly(butyl acrylate) (PBA) rubbery core and a methyl methacrylate/styrene copolymer (P(MMA-co-St)) outer glassy shell. Nanoparticles were prepared with different core-shell ratio (20/80, 30/70, 40/60 and 50/50) and were incorporated into the solid phase of bone cement at several percentages (5, 10 and 15 wt%). It was observed that the particles exhibited a spherical morphology averaging ca. 125 nm in diameter, and the dynamic mechanical analysis (DMA) thermograms revealed the desired structuring pattern of phases associated with core-shell structures. A fracture mechanism was proposed taking into account the detected AE signals and the scanning electron microscopy (SEM) micrographs. In this regard, core-shell nanoparticles can act as both additional nucleation sites for microcracks (and crazes) and to hinder the microcrack propagation acting as a barrier to its growth; this behavior was presented by all formulations. Cement samples containing 15 wt% of core-shell nanoparticles, either 40/60 or 50/50, were fractured at 40% deformation. This fact seems related to the coalescence of microcracks after they surround the agglomerates of core-shell nanoparticles to continue growing up. This work also demonstrated the potential of the AE technique to be used as an accurate and reliable detection tool for quasi-static compression test in acrylic bone cements. Copyright © 2015 Elsevier Ltd. All rights reserved.

Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line.

PubMed

Yurgel, Virginia C; Oliveira, Catiuscia P; Begnini, Karine R; Schultze, Eduarda; Thurow, Helena S; Leon, Priscila M M; Dellagostin, Odir A; Campos, Vinicius F; Beck, Ruy C R; Guterres, Silvia S; Collares, Tiago; Pohlmann, Adriana R; Seixas, Fabiana K

2014-01-01

Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors.

Methotrexate diethyl ester-loaded lipid-core nanocapsules in aqueous solution increased antineoplastic effects in resistant breast cancer cell line

PubMed Central

Yurgel, Virginia C; Oliveira, Catiuscia P; Begnini, Karine R; Schultze, Eduarda; Thurow, Helena S; Leon, Priscila MM; Dellagostin, Odir A; Campos, Vinicius F; Beck, Ruy CR; Guterres, Silvia S; Collares, Tiago; Pohlmann, Adriana R; Seixas, Fabiana K

2014-01-01

Breast cancer is the most frequent cancer affecting women. Methotrexate (MTX) is an antimetabolic drug that remains important in the treatment of breast cancer. Its efficacy is compromised by resistance in cancer cells that occurs through a variety of mechanisms. This study evaluated apoptotic cell death and cell cycle arrest induced by an MTX derivative (MTX diethyl ester [MTX(OEt)2]) and MTX(OEt)2-loaded lipid-core nanocapsules in two MTX-resistant breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231. The formulations prepared presented adequate granulometric profile. The treatment responses were evaluated through flow cytometry. Relying on the mechanism of resistance, we observed different responses between cell lines. For MCF-7 cells, MTX(OEt)2 solution and MTX(OEt)2-loaded lipid-core nanocapsules presented significantly higher apoptotic rates than untreated cells and cells incubated with unloaded lipid-core nanocapsules. For MDA-MB-231 cells, MTX(OEt)2-loaded lipid-core nanocapsules were significantly more efficient in inducing apoptosis than the solution of the free drug. S-phase cell cycle arrest was induced only by MTX(OEt)2 solution. The drug nanoencapsulation improved apoptosis induction for the cell line that presents MTX resistance by lack of transport receptors. PMID:24741306

Multiphysics Computational Analysis of a Solid-Core Nuclear Thermal Engine Thrust Chamber

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Canabal, Francisco; Cheng, Gary; Chen, Yen-Sen

2007-01-01

The objective of this effort is to develop an efficient and accurate computational heat transfer methodology to predict thermal, fluid, and hydrogen environments for a hypothetical solid-core, nuclear thermal engine - the Small Engine. In addition, the effects of power profile and hydrogen conversion on heat transfer efficiency and thrust performance were also investigated. The computational methodology is based on an unstructured-grid, pressure-based, all speeds, chemically reacting, computational fluid dynamics platform, while formulations of conjugate heat transfer were implemented to describe the heat transfer from solid to hydrogen inside the solid-core reactor. The computational domain covers the entire thrust chamber so that the afore-mentioned heat transfer effects impact the thrust performance directly. The result shows that the computed core-exit gas temperature, specific impulse, and core pressure drop agree well with those of design data for the Small Engine. Finite-rate chemistry is very important in predicting the proper energy balance as naturally occurring hydrogen decomposition is endothermic. Locally strong hydrogen conversion associated with centralized power profile gives poor heat transfer efficiency and lower thrust performance. On the other hand, uniform hydrogen conversion associated with a more uniform radial power profile achieves higher heat transfer efficiency, and higher thrust performance.

Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

PubMed

Tan, Angel; Rao, Shasha; Prestidge, Clive A

2013-12-01

The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

Chronotherapeutically Modulated Pulsatile System of Valsartan Nanocrystals-an In Vitro and In Vivo Evaluation.

PubMed

Biswas, Nikhil; Kuotsu, Ketousetuo

2017-02-01

The objective was to improve the dissolution of valsartan by developing valsartan nanocrystals and design a pulsed release system for the chronotherapy of hypertension. Valsartan nanocrystals were prepared by sonication-anti-solvent precipitation method and lyophilized to obtain dry powder. Nanocrystals were directly compressed to minitablets and coated to achieve pulsatile valsartan release. Pharmacokinetic profiles of optimized and commercial formulations were compared in rabbit model. The mean particle size and PDI of the optimized nanocrystal batch V4 was reported as 211 nm and 0.117, respectively. DSC and PXRD analysis confirmed the crystalline nature of valsartan in nanocrystals. The dissolution extent of valsartan was markedly enhanced with both nanocrystals and minitablets as compared to pure valsartan irrespective of pH of the medium. Core minitablet V4F containing 5% w/w polyplasdone XL showed quickest release of valsartan, over 90% within 15 min. Coated formulation CV4F showed two spikes in release profile after successive lag times of 235 and 390 min. The pharmacokinetic study revealed that the bioavailability of optimized formulation (72.90%) was significantly higher than the commercial Diovan tablet (30.18%). The accelerated stability studies showed no significant changes in physicochemical properties, release behavior, and bioavialability of CV4F formulation. The formulation was successfully designed to achieve enhanced bioavailability and dual pulsatile release. Bedtime dosing will more efficiently control the circadian spikes of hypertension in the morning.

Principles of quasi-equivalence and Euclidean geometry govern the assembly of cubic and dodecahedral cores of pyruvate dehydrogenase complexes.

PubMed

Izard, T; Aevarsson, A; Allen, M D; Westphal, A H; Perham, R N; de Kok, A; Hol, W G

1999-02-16

The pyruvate dehydrogenase multienzyme complex (Mr of 5-10 million) is assembled around a structural core formed of multiple copies of dihydrolipoyl acetyltransferase (E2p), which exhibits the shape of either a cube or a dodecahedron, depending on the source. The crystal structures of the 60-meric dihydrolipoyl acyltransferase cores of Bacillus stearothermophilus and Enterococcus faecalis pyruvate dehydrogenase complexes were determined and revealed a remarkably hollow dodecahedron with an outer diameter of approximately 237 A, 12 large openings of approximately 52 A diameter across the fivefold axes, and an inner cavity with a diameter of approximately 118 A. Comparison of cubic and dodecahedral E2p assemblies shows that combining the principles of quasi-equivalence formulated by Caspar and Klug [Caspar, D. L. & Klug, A. (1962) Cold Spring Harbor Symp. Quant. Biol. 27, 1-4] with strict Euclidean geometric considerations results in predictions of the major features of the E2p dodecahedron matching the observed features almost exactly.

Film stability in a vertical rotating tube with a core-gas flow.

NASA Technical Reports Server (NTRS)

Sarma, G. S. R.; Lu, P. C.; Ostrach, S.

1971-01-01

The linear hydrodynamic stability of a thin-liquid layer flowing along the inside wall of a vertical tube rotating about its axis in the presence of a core-gas flow is examined. The stability problem is formulated under the conditions that the liquid film is thin, the density and viscosity ratios of gas to liquid are small and the relative (axial) pressure gradient in the gas is of the same order as gravity. The resulting eigenvalue problem is first solved by a perturbation method appropriate to axisymmetric long-wave disturbances. The damped nature (to within the thin-film and other approximations made) of the nonaxisymmetric and short-wave disturbances is noted. In view of the limitations on a truncated perturbation solution when the disturbance wavenumber is not small, an initial value method using digital computer is presented. Stability characteristics of neutral, growing, and damped modes are presented showing the influences of rotation, surface tension, and the core-gas flow. Energy balance in a neutral mode is also illustrated.

Simulation of drift wave instability in field-reversed configurations using global magnetic geometry

NASA Astrophysics Data System (ADS)

Fulton, D. P.; Lau, C. K.; Lin, Z.; Tajima, T.; Holod, I.; the TAE Team

2016-10-01

Minimizing transport in the field-reversed configuration (FRC) is essential to enable FRC-based fusion reactors. Recently, significant progress on advanced beam-driven FRCs in C-2 and C-2U (at Tri Alpha Energy) provides opportunities to study transport properties using Doppler backscattering (DBS) measurements of turbulent fluctuations and kinetic particle-in-cell simulations of driftwaves in realistic equilibria via the Gyrokinetic Toroidal Code (GTC). Both measurements and simulations indicate relatively small fluctuations in the scrape-off layer (SOL). In the FRC core, local, single flux surface simulations reveal strong stabilization, while experiments indicate quiescent but finite fluctuations. One possible explanation is that turbulence may originate in the SOL and propagate at very low levels across the separatrix into the core. To test this hypothesis, a significant effort has been made to develop A New Code (ANC) based on GTC physics formulations, but using cylindrical coordinates which span the magnetic separatrix, including both core and SOL. Here, we present first results from global ANC simulations.

Determination of dryout localization using a five-equation model of annular flow for boiling in minichannels

NASA Astrophysics Data System (ADS)

Wajs, Jan; Mikielewicz, Dariusz

2017-03-01

Detailed studies have suggested that the critical heat flux in the form of dryout in minichannels occurs when the combined effects of entrainment, deposition, and evaporation of the film make the film flow rate go gradually and smoothly to zero. Most approaches so far used the mass balance equation for the liquid film with appropriate formulations for the rate of deposition and entrainment respectively. It must be acknowledged that any discrepancy in determination of deposition and entrainment rates, together with cross-correlations between them, leads to the loss of accuracy of model predictions. Conservation equations relating the primary parameters are established for the liquid film and vapor core. The model consists of three mass balance equations, for liquid in the film as well as two-phase core and the gas phase itself. These equations are supplemented by the corresponding momentum equations for liquid in the film and the two-phase core. Applicability of the model has been tested on some experimental data.

Plasma-wall interaction data needs critical to a Burning Core Experiment (BCX)

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

Not Available

1985-11-01

The Division of Development and Technology has sponsored a four day US-Japan workshop ''Plasma-Wall Interaction Data Needs Critical to a Burning Core Experiment (BCX)'', held at Sandia National Laboratories, Livermore, California on June 24 to 27, 1985. The workshop, which brought together fifty scientists and engineers from the United States, Japan, Germany, and Canada, considered the plasma-material interaction and high heat flux (PMI/HHF) issues for the next generation of magnetic fusion energy devices, the Burning Core Experiment (BCX). Materials options were ranked, and a strategy for future PMI/HHF research was formulated. The foundation for international collaboration and coordination of thismore » research was also established. This volume contains the last three of the five technical sessions. The first of the three is on plasma materials interaction issues, the second is on research facilities and the third is from smaller working group meetings on graphite, beryllium, advanced materials and future collaborations.« less

Preparation and in-vivo pharmacokinetic study of a novel extended release compression coated tablets of fenoterol hydrobromide.

PubMed

Elshafeey, Ahmed H; Sami, Elshaimaa I

2008-01-01

The aim of this study was to formulate extended release compression coated core tablets of fenoterol hydrobromide, a selective beta(2) adrenergic receptor agonist, in an attempt to prevent nocturnal asthma. Two hydrophilic polymers viz Kollidon SR, Polyox WSR 303 and a hydrophobic one (Precirol ATO5) were employed. Compression coated tablets were formulated by preparing a core tablet containing 7.5 mg drug and various amounts of polymer and Emcompress then compressed coated with the same polymeric materials. For comparison purpose different matrix tablets were also prepared employing the same polymers. In-vitro release studies were carried out at different pH (1.2 and 6.8). Pharmacokinetics of extended release tablets as well as commercially available immediate release tablets (Berotec) were studied after oral administration to beagle dogs using a new developed LC-MS/MS method with a lower limit of quantification of 1 ng/ml. Fenoterol release from compression coated tablets was significantly lower than matrix tablets. The mechanism of release was changed with the nature and content of polymer. The release pattern of drug from F16 containing 40 mg Kollidon SR divided in the core tablet (15 mg) and the rest in the compressed coat (25 mg) showed a typical zero order release kinetic that could extend drug release >10 h and reasonable time for 75% to be released (t(75)) (8.92 h). When compared to immediate release Berotec tablet the MRT was significantly extended from 7.03 +/- 0.76 to 10.93 +/- 1.25 h (P < 0.001) and HVD(t 50%Cmax) was also significantly extended from 2.71 +/- 0.68 to 6.81 +/- 0.67 h with expected prevention of nocturnal asthma.

A new description of Earth's wobble modes using Clairaut coordinates: 1. Theory

NASA Astrophysics Data System (ADS)

Rochester, M. G.; Crossley, D. J.; Zhang, Y. L.

2014-09-01

This paper presents a novel mathematical reformulation of the theory of the free wobble/nutation of an axisymmetric reference earth model in hydrostatic equilibrium, using the linear momentum description. The new features of this work consist in the use of (i) Clairaut coordinates (rather than spherical polars), (ii) standard spherical harmonics (rather than generalized spherical surface harmonics), (iii) linear operators (rather than J-square symbols) to represent the effects of rotational and ellipticity coupling between dependent variables of different harmonic degree and (iv) a set of dependent variables all of which are continuous across material boundaries. The resulting infinite system of coupled ordinary differential equations is given explicitly, for an elastic solid mantle and inner core, an inviscid outer core and no magnetic field. The formulation is done to second order in the Earth's ellipticity. To this order it is shown that for wobble modes (in which the lowest harmonic in the displacement field is degree 1 toroidal, with azimuthal order m = ±1), it is sufficient to truncate the chain of coupled displacement fields at the toroidal harmonic of degree 5 in the solid parts of the earth model. In the liquid core, however, the harmonic expansion of displacement can in principle continue to indefinitely high degree at this order of accuracy. The full equations are shown to yield correct results in three simple cases amenable to analytic solution: a general earth model in rigid rotation, the tiltover mode in a homogeneous solid earth model and the tiltover and Chandler periods for an incompressible homogeneous solid earth model. Numerical results, from programmes based on this formulation, are presented in part II of this paper.

RAFT Dispersion Alternating Copolymerization of Styrene with N-Phenylmaleimide: Morphology Control and Application as an Aqueous Foam Stabilizer

PubMed Central

2016-01-01

We report a new nonaqueous polymerization-induced self-assembly (PISA) formulation based on the reversible addition–fragmentation chain transfer (RAFT) dispersion alternating copolymerization of styrene with N-phenylmaleimide using a nonionic poly(N,N-dimethylacrylamide) stabilizer in a 50/50 w/w ethanol/methyl ethyl ketone (MEK) mixture. The MEK cosolvent is significantly less toxic than the 1,4-dioxane cosolvent reported previously [YangP.; Macromolecules2013, 46, 8545−8556]. The core-forming alternating copolymer block has a relatively high glass transition temperature (Tg), which leads to vesicular morphologies being observed during PISA, as well as the more typical sphere and worm phases. Each of these copolymer morphologies has been characterized by transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) studies. TEM studies reveal micrometer-sized elliptical particles with internal structure, with SAXS analysis suggesting an oligolamellar vesicle morphology. This structure differs from that previously reported for a closely related PISA formulation utilizing a poly(methacrylic acid) stabilizer block for which unilamellar platelet-like particles are observed by TEM and SAXS. This suggests that interlamellar interactions are governed by the nature of the steric stabilizer layer. Moreover, using the MEK cosolvent also enables access to a unilamellar vesicular morphology, despite the high Tg of the alternating copolymer core-forming block. This was achieved by simply conducting the PISA synthesis at a higher temperature for a longer reaction time (80 °C for 24 h). Presumably, MEK solvates the core-forming block more than the previously utilized 1,4-dioxane cosolvent, which leads to greater chain mobility. Finally, preliminary experiments indicate that the worms are much more efficient stabilizers for aqueous foams than either the spheres or the oligolamellar elliptical vesicles. PMID:27708458

Formulation and evaluation of delayed-onset extended-release tablets of metoprolol tartrate using hydrophilic-swellable polymers.

PubMed

Dadarwal, Subhash Chand; Madan, Sarika; Agrawal, Shyam Sunder

2012-03-01

In view of the circadian rhythm of cardiovascular diseases, a delayed-onset extended-release (DOER) formulation of metoprolol tartrate (MT) was prepared. This was achieved through dissolution-guided optimization of the proportion of Methocel K4M and Methocel K15M. Core erosion ratio was greater than 50 %, thereby showing steady release of the drug after the lag time until complete dissolution. Optimized formulation produced a lag phase of 6 h followed by complete release of 98.7 ± 2.1 % in 24 h. Water uptake study revealed that Methocel K15M has lower water uptake (30 ± 1 %) than Methocel K4M (40 ± 2 %) after 24 h. Axial swelling of polymers was higher than swelling in the radial direction. Drug-polymer interaction study precludes any interaction between drug and polymer. Such a drug delivery system may provide a viable alternative for effective management of hypertension and other related disorders. This work also proposes an approach to attain DOER for a hydrophilic drug by using a hydrophilic swellable polymer in press coat.

Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles.

PubMed

Bachar, Michal; Mandelbaum, Amitai; Portnaya, Irina; Perlstein, Hadas; Even-Chen, Simcha; Barenholz, Yechezkel; Danino, Dganit

2012-06-10

β-casein is an amphiphilic protein that self-organizes into well-defined core-shell micelles. We developed these micelles as efficient nanocarriers for oral drug delivery. Our model drug is celecoxib, an anti-inflammatory hydrophobic drug utilized for treatment of rheumatoid arthritis and osteoarthritis, now also evaluated as a potent anticancer drug. This system is unique as it enables encapsulation loads >100-fold higher than other β-casein/drug formulations, and does not require additives as do other formulations that have high loadings. This is combined with the ability to lyophilize the formulation without a cryoprotectant, long-term physical and chemical stability of the resulting powder, and fully reversible reconstitution of the structures by rehydration. The dry dosage form, in which >95% of the drug is encapsulated, meets the daily dose. Cryo-TEM and DLS prove that drug encapsulation results in micelle swelling, and X-ray diffraction shows that the encapsulated drug is amorphous. Altogether, our novel dosage form is highly advantageous for oral administration. Copyright © 2012 Elsevier B.V. All rights reserved.

Negotiating treatment preferences: Physicians' formulations of patients' stance.

PubMed

Landmark, Anne Marie Dalby; Svennevig, Jan; Gulbrandsen, Pål

2016-01-01

Eliciting patients' values and treatment preferences is an essential element in models of shared decision making, yet few studies have investigated the interactional realizations of how physicians do this in authentic encounters. Drawing on video-recorded encounters from Norwegian secondary care, the present study uses the fine-grained empirical methodology of conversation analysis (CA) to identify one conversational practice physicians use, namely, formulations of patients' stance, in which physicians summarize or paraphrase their understanding of the patient's stance towards treatment. The purpose of this study is twofold: (1) to explore what objectives formulations of patients' stance achieve while negotiating treatment and (2) to discuss these objectives in relation to core requirements in shared decision making. Our analysis demonstrates that formulating the patient's stance is a practice physicians use in order to elicit, check, and establish patients' attitudes towards treatment. This practice is in line with general recommendations for making shared decisions, such as exploring and checking patients' preferences and values. However, the formulations may function as a device for doing more than merely checking and establishing common ground and bringing up patients' preferences and views: Accompanied by subtle deprecating expressions, they work to delegitimize the patients' stances and indirectly convey the physicians' opposing stance. Once established, these positions can be used as a basis for challenging and potentially altering the patient's attitude towards the decision, thereby making it more congruent with the physician's view. Therefore, in addition to bringing up patients' views towards treatment, we argue that physicians may use formulations of patients' stance as a resource for directing the patient towards decisions that are congruent with the physician's stance in situations with potential disagreement, whilst (ostensibly) avoiding a more authoritarian or paternalistic approach. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design Tools for Accelerating Development and Usage of Multi-Core Computing Platforms

DTIC Science & Technology

2014-04-01

Government formulated or supplied the drawings, specifications, or other data does not license the holder or any other person or corporation ; or convey...multicore PDSP platforms. The GPU- based capabilities of TDIF are currently oriented towards NVIDIA GPUs, based on the Compute Unified Device Architecture...CUDA) programming language [ NVIDIA 2007], which can be viewed as an extension of C. The multicore PDSP capabilities currently in TDIF are oriented

Formulation of a Production Strategy for a Software Product Line

DTIC Science & Technology

2009-08-01

chooses to develop its products) as a series of scenarios • identifying the production factors critical to the success of the organization’s...line approach to achieve its business goals. AGM, a subsidiary of a multinational corporation, produces a series of software-intensive products deli...days from time of request. 2 The core assets mentioned in this example are available at http://www.sei.cmu.edu/productlines/ ppl . 19 | CMU/SEI

Heat Transfer in Adhesively Bonded Honeycomb Core Panels

NASA Technical Reports Server (NTRS)

Daryabeigi, Kamran

2001-01-01

The Swann and Pittman semi-empirical relationship has been used as a standard in aerospace industry to predict the effective thermal conductivity of honeycomb core panels. Recent measurements of the effective thermal conductivity of an adhesively bonded titanium honeycomb core panel using three different techniques, two steady-state and one transient radiant step heating method, at four laboratories varied significantly from each other and from the Swann and Pittman predictions. Average differences between the measurements and the predictions varied between 17 and 61% in the temperature range of 300 to 500 K. In order to determine the correct values of the effective thermal conductivity and determine which set of the measurements or predictions were most accurate, the combined radiation and conduction heat transfer in the honeycomb core panel was modeled using a finite volume numerical formulation. The transient radiant step heating measurements provided the best agreement with the numerical results. It was found that a modification of the Swann and Pittman semi-empirical relationship which incorporated the facesheets and adhesive layers in the thermal model provided satisfactory results. Finally, a parametric study was conducted to investigate the influence of adhesive thickness and thermal conductivity on the overall heat transfer through the panel.

Learning experiences in population education: proposed guidelines and core messages.

PubMed

1984-01-01

As a result of the 1984 Regional Workshop for the Development of Packages of Adequate Learning Requirements in Population Education, the participants tackled the problem of non-institutionalization of population education into the formal and non-formal educational curricula in their countries. Based on their deliberations, several sets of guidelines and core messages were formulated to provide countries with a more definite direction that will hopefully ensure the functional and effective integration of population education in their respective national school and out-of-school curriculum system. Useful packages of learning materials in population education should help realize the country's population policy and goals within the broader framework of socioeconomic development, and the content of the package should comprehensively cover the core messages of the country's Population Information, Education and Communication (IEC) Program. The population knowledge base of the package should be accurate and relevant; the package should provide for graphic and visual presentation and for assessment of effects on the target groups. Proposed core messages in population education discuss the advantages of small family size and delayed marriage, and aspects of responsible parenthood. Other messages discuss population resource development and population-related beliefs and values.

A core syllabus for the teaching of embryology and teratology to medical students.

PubMed

Fakoya, Francis A; Emmanouil-Nikoloussi, Elpida; Sharma, Deepak; Moxham, Bernard J

2017-03-01

Clinical relevance in the teaching of biomedical sciences within health care courses presupposes that there is internationally agreed core material within the curricula. However, with the exception of a syllabus for neuroanatomy and gross anatomy of the head and neck for medical students, core syllabuses within many of the specialized anatomical sciences have yet to be developed. The International Federation of Associations of Anatomists aims to formulate internationally accepted core syllabuses for all anatomical sciences disciplines initially using Delphi Panels that comprise anatomists, scientists, and clinicians who evaluate syllabus content. Here, the suggestions of a Delphi Panel for embryology and teratology are presented prior to their publication on the website of the International Federation of Associations of Anatomists. Hence, to obtain a more definitive syllabus, it is required that anatomical and embryological/teratological societies, as well as individual anatomists, embryologists and clinicians, freely comment upon, elaborate and amend, this draft syllabus. The goal is to set internationally recognized standards and thereby provide guidelines concerning embryological and teratological knowledge when involved with course development. Clin. Anat. 30:159-167, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Taking the lead from our colleagues in medical education: the use of images of the in-vivo setting in teaching concepts of pharmaceutical science.

PubMed

Curley, Louise E; Kennedy, Julia; Hinton, Jordan; Mirjalili, Ali; Svirskis, Darren

2017-01-01

Despite pharmaceutical sciences being a core component of pharmacy curricula, few published studies have focussed on innovative methodologies to teach the content. This commentary identifies imaging techniques which can visualise oral dosage forms in-vivo and observe formulation disintegration in order to achieve a better understanding of in-vivo performance. Images formed through these techniques can provide students with a deeper appreciation of the fate of oral formulations in the body compared to standard disintegration and dissolution testing, which is conducted in-vitro. Such images which represent the in-vivo setting can be used in teaching to give context to both theory and experimental work, thereby increasing student understanding and enabling teaching of pharmaceutical sciences supporting students to correlate in-vitro and in-vivo processes.

Preliminary control system design and analysis for the Space Station Furnace Facility thermal control system

NASA Technical Reports Server (NTRS)

Jackson, M. E.

1995-01-01

This report presents the Space Station Furnace Facility (SSFF) thermal control system (TCS) preliminary control system design and analysis. The SSFF provides the necessary core systems to operate various materials processing furnaces. The TCS is defined as one of the core systems, and its function is to collect excess heat from furnaces and to provide precise cold temperature control of components and of certain furnace zones. Physical interconnection of parallel thermal control subsystems through a common pump implies the description of the TCS by coupled nonlinear differential equations in pressure and flow. This report formulates the system equations and develops the controllers that cause the interconnected subsystems to satisfy flow rate tracking requirements. Extensive digital simulation results are presented to show the flow rate tracking performance.

Occurrence of coring in insulin vials and possibility of rubber piece contamination by self-injection.

PubMed

Asakura, T; Seino, H; Nozaki, S; Abe, R

2001-06-01

Coring is reported to occur because rubber pieces are shaved off from a rubber stopper when a needle is inserted into the rubber stopper of transfusion liquid formulation. We verified whether coring really occurs in insulin vials of self-injecting patients. We collected insulin cartridges from 30 hospitalized patients and used the primary injection (trial injection), the secondary injection and the cartridge remaining preparation as samples. We observed the rubber pieces using a microscope and measured the shape, number of pieces. The occurrence rate of coring was 73% for the primary injection, 47% for the secondary injection and 97% for the cartridge remaining preparation. The rubber pieces in the primary injection and the secondary injection which went through the needle are mostly in aggregate shape and the rubber pieces in the cartridge remaining preparation which did not go through the needle are mostly in needle-like shape. A number of small rubber pieces are found in both the primary injection and the secondary injection, indicating a high possibility that rubber pieces may be injected under subcutaneous tissue. The coring is considered to occur because needles are repeatedly inserted and rotated at the same spot. It is required to improve the structure to mount a needle to the pen-type injector in future. Coring is a very serious problem from the medical and pharmaceutical points of view. Further study should be made on the implication to latex allergy and lipodystrophy.

The Variation Test and Extraction Equipment to Optimum Asphalt by Using Gasoline Solvent

NASA Astrophysics Data System (ADS)

Soehardi, Fitridawati

2017-12-01

Based on the Binamarga Specification 2010 at third revision, the extraction test should be carried out using the specimen from the loose asphalt mixture extracted from the back of the finisher bitumen machine. The purpose of this research is to find out the result of pretest and posttest extraction asphalt content. The Extraction test using two equipment, they are Soklet and Centrifuge. The specimens was used AMP, Asphalt Finisher and Core, which involved gasoline solvent. Based on the asphalt level extraction test results, the appropriate equipment was used centrifuge with the level accuracy as requirement of Binamarga Specification 2010 at third revision and the level of ease used as equipment in the field study. The asphalt content obtained for AMP 5,51%, Asphalt Finisher5,46% and Core 5.34%. As for the socket asphalt content obtained is AMP 5.55%, Asphalt Finisher 5.50% and Core core 5. 41%. The extract test value of asphalt content decreased, so it can be formulated KA JMF

T1 relaxivity of core-encapsulated gadolinium liposomal contrast agents--effect of liposome size and internal gadolinium concentration.

PubMed

Ghaghada, Ketan; Hawley, Catherine; Kawaji, Keigo; Annapragada, Ananth; Mukundan, Srinivasan

2008-10-01

Long circulating core-encapsulated gadolinium (CE-Gd) liposomal nanoparticles that have surface conjugated polyethylene glycol are a promising platform technology for use as blood pool T1-based magnetic resonance (MR) contrast agents. The objective of this study was to investigate the effect of liposome size and internal (core) Gd concentration on the T1 relaxivity of CE-Gd liposomes. Twelve different liposomal formulations were synthesized and characterized, resulting in a size (50, 100, 200, and 400 nm) and core Gd-concentration (200, 350, and 500 mM) "matrix" of test samples. Subsequently, CE-Gd liposomes were diluted in deionized water (four diluted samples) and molar T1 relaxivity (r1) measurements were performed at 2- and 7-T MR field strengths. The r1 of CE-Gd liposomes was inversely related to the liposome size. The largest change in r1 was observed between liposomes that were extruded through 50- and 100-nm filter membranes. At both field strengths, the variation in internal gadolinium concentration did not show any significant correlation (alpha < or = 0.05) with r1. The size of CE-Gd liposomal nanoparticles significantly affects the T1 relaxivity. An inverse relation was observed between liposome size and T1 relaxivity. The T1 relaxivity did not change significantly with core Gd concentration over the measured concentration range.

Formulation and characterization of hydrophilic drug diclofenac sodium-loaded solid lipid nanoparticles based on phospholipid complexes technology.

PubMed

Liu, Dongfei; Chen, Li; Jiang, Sunmin; Zhu, Shuning; Qian, Yong; Wang, Fengzhen; Li, Rui; Xu, Qunwei

2014-03-01

To successfully prepare the diclofenac sodium (DS)-loaded solid lipid nanoparticles (SLNs), phospholipid complexes (PCs) technology was applied here to improve the liposolubility of DS. Solid lipid nanoparticles (SLNs) loaded with phospholipid complexes (PCs) were prepared by the modified emulsion/solvent evaporation method. DS could be solubilized effectively in the organic solvents with the existence of phospholipid and apparent partition coefficient of DS in PCs increased significantly. X-ray diffraction analysis suggested that DS in PCs was either molecularly dispersed or in an amorphous form. However, no significant difference was observed between the Fourier transform infrared spectroscopy (FT-IR) spectra of physical mixture and that of PCs. Particles with small sizes, narrow polydispersity indexes and high entrapment efficiencies could be obtained with the addition of PCs. Furthermore, according to the transmission electron microscopy, a core-shell structure was likely to be formed. The presence of PCs caused the change of zeta potential and retarded the drug release of SLNs, which indicated that phospholipid formed multilayers around the solid lipid core of SLNs. Both FT-IR and differential scanning calorimetry analysis also illustrated that some weak interactions between DS and lipid materials might take place during the preparation of SLNs. In conclusion, the model hydrophilic drug-DS can be formulated into the SLNs with the help of PCs.

Results of comparative RBMK neutron computation using VNIIEF codes (cell computation, 3D statics, 3D kinetics). Final report

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

Grebennikov, A.N.; Zhitnik, A.K.; Zvenigorodskaya, O.A.

1995-12-31

In conformity with the protocol of the Workshop under Contract {open_quotes}Assessment of RBMK reactor safety using modern Western Codes{close_quotes} VNIIEF performed a neutronics computation series to compare western and VNIIEF codes and assess whether VNIIEF codes are suitable for RBMK type reactor safety assessment computation. The work was carried out in close collaboration with M.I. Rozhdestvensky and L.M. Podlazov, NIKIET employees. The effort involved: (1) cell computations with the WIMS, EKRAN codes (improved modification of the LOMA code) and the S-90 code (VNIIEF Monte Carlo). Cell, polycell, burnup computation; (2) 3D computation of static states with the KORAT-3D and NEUmore » codes and comparison with results of computation with the NESTLE code (USA). The computations were performed in the geometry and using the neutron constants presented by the American party; (3) 3D computation of neutron kinetics with the KORAT-3D and NEU codes. These computations were performed in two formulations, both being developed in collaboration with NIKIET. Formulation of the first problem maximally possibly agrees with one of NESTLE problems and imitates gas bubble travel through a core. The second problem is a model of the RBMK as a whole with imitation of control and protection system controls (CPS) movement in a core.« less

Measurement of Global Precipitation: Introduction to International GPM Program

NASA Technical Reports Server (NTRS)

Hwang, P.

2004-01-01

The Global Precipitation Measurement (GPM) Program is an international cooperative effort whose objectives are to (a) obtain better understanding of rainfall processes, and (b) make frequent rainfall measurements on a global basis. The National Aeronautics and Space Administration (NASA) of the United States and the Japanese Aviation and Exploration Agency (JAXA) have entered into a cooperative agreement for the formulation and development of GPM. This agreement is a continuation of the partnership that developed the highly successful Tropical Rainfall Measuring Mission (TRMM) that was launched in November 1997; this mission continues to provide valuable scientific and meteorological information on rainfall and the associated processes. International collaboration on GPM from other space agencies has been solicited, and discussions regarding their participation are currently in progress. NASA has taken lead responsibility for the planning and formulation of GPM. Key elements of the Program to be provided by NASA include a Core satellite instrumented with a multi-channel microwave radiometer, a Ground Validation System and a ground-based Precipitation Processing System (PPS). JAXA will provide a Dual-frequency Precipitation Radar for installation on the Core satellite and launch services. Other United States agencies and international partners may participate in a number of ways, such as providing rainfall measurements obtained from their own national space-borne platforms, providing local rainfall measurements to support the ground validation activities, or providing hardware or launch services for GPM constellation spacecraft.

Chitosan-carboxymethylcellulose based microcapsules formulation for controlled release of active ingredients from cosmeto textile

NASA Astrophysics Data System (ADS)

Roy, J. C.; Ferri, A.; Salaün, F.; Giraud, S.; Chen, G.; Jinping, G.

2017-10-01

Chitosan-based emulsions were prepared at pH from 4.0 to 6.0. The zeta potential and droplet size were monitored at different pH. Double emulsions (wateroil- water) were observed due to the stiff conformation of chitosan at pH 4.0. At pH 5.0, the emulsion droplets were the smallest (2.9 μm) of the experimental pH range. The emulsion droplets were well dispersed due to high surface charge of chitosan (for example, +50 mV at pH 5.5) in entire pH range. The emulsion was treated with carboxymethyl cellulose (CMC) for neutralizing the charged chitosan on the surface of emulsion droplets. Above 10×10-2 mg/ml of CMC, no change in zeta potential was observed indicating no more free chitosan existed after neutralization with CMC. The emulsion was then crosslinked with different amount of glutaraldehyde. Upon increasing the amount of glutaraldehyde, the amount of core content inside the microcapsule and encapsulation efficiency of shell materials decreased gradually. The Dynamic Scanning Calorimetry data confirmed no interaction between core and shell material in the microencapsulation process. The thermal degradation of the microcapsules was examined by thermogravimetric analysis and a gradual decrease in the degradation temperature upon increasing glutaraldehyde concentration was found. The tuning of CMC concentration can provide valuable information regarding stable emulsion and efficient microcapsule formulation via coacervation.

Mini-tablets versus pellets as promising multiparticulate modified release delivery systems for highly soluble drugs.

PubMed

Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

2015-07-05

Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkably higher coating thickness was required for pellets to provide equivalent retardation. Ethyl cellulose in the core ensured faster release due to polymer migration to the surface and pore formation in the coat. mini-tablets showed higher stability to pellets upon storage. Industrially speaking, mini-tablets proved to be superior to pellets in terms of manufacturing, product quality and economical aspects. Results point out the urgent need for standardized evaluation procedures for mini-tablets. Copyright © 2015. Published by Elsevier B.V.

The Nonisothermal Stage of Magnetic Star Formation. I. Formulation of the Problem and Method of Solution

NASA Astrophysics Data System (ADS)

Kunz, Matthew W.; Mouschovias, Telemachos Ch.

2009-03-01

We formulate the problem of the formation and subsequent evolution of fragments (or cores) in magnetically supported, self-gravitating molecular clouds in two spatial dimensions. The six-fluid (neutrals, electrons, molecular and atomic ions, positively charged, negatively charged, and neutral grains) physical system is governed by the radiation, nonideal magnetohydrodynamic equations. The magnetic flux is not assumed to be frozen in any of the charged species. Its evolution is determined by a newly derived generalized Ohm's law, which accounts for the contributions of both elastic and inelastic collisions to ambipolar diffusion and Ohmic dissipation. The species abundances are calculated using an extensive chemical-equilibrium network. Both MRN and uniform grain size distributions are considered. The thermal evolution of the protostellar core and its effect on the dynamics are followed by employing the gray flux-limited diffusion approximation. Realistic temperature-dependent grain opacities are used that account for a variety of grain compositions. We have augmented the publicly available Zeus-MP code to take into consideration all these effects and have modified several of its algorithms to improve convergence, accuracy, and efficiency. Results of magnetic star formation simulations that accurately track the evolution of a protostellar fragment from a density sime103 cm-3 to a density sime1015 cm-3, while rigorously accounting for both nonideal MHD processes and radiative transfer, are presented in a separate paper.

An examination of three methods of psychodynamic formulation based on the same videotaped interview.

PubMed

Perry, J C; Luborsky, L; Silberschatz, G; Popp, C

1989-08-01

While psychodynamic theory and therapy are approaching their centennial, the science of psychodynamics is still in an earlier developmental stage. Any scientific field generates the most controversy and excitement when it is still developing. For psychodynamic psychology this means that its basic units of observation as well as its rules for justifying clinical inference in formulating and testing dynamic hypotheses require more development. In short, we are still evaluating different methods for both discovering and validating psychodynamic propositions. This is especially true for central features of dynamic psychology, including intrapsychic conflict, relationships, and transference patterns. This report compares three different methods for making a dynamic case formulation: 1) the Core Conflictual Relationship Theme (CCRT) of Luborsky (Crits-Christoph and Luborsky 1985a,b; Luborsky 1976, 1977, 1984, and companion paper in this issue; Levine and Luborsky 1981), 2) the Plan Diagnosis (PD) method of Silberschatz, Curtis and colleagues of the Mount Zion group (Caston 1986; Curtis and Silberschatz 1986; Rosenberg et al. 1986; Curtis et al. 1988) and, 3) the Idiographic Conflict Formulation (ICF) of Perry and Cooper (1985, 1986, and companion paper in this issue). Each has a slightly different focus. The CCRT focuses on relationship patterns as the central feature of individual dynamics and transference in or out of the treatment situation. The Plan Diagnosis focuses on dynamic features related to transference, resistance and insight in therapy. The Idiographic Conflict Formulation focuses on stress and internal conflict, and the individual's adaptation to them in or out of treatment.

Colon Targeted Guar Gum Compression Coated Tablets of Flurbiprofen: Formulation, Development, and Pharmacokinetics

PubMed Central

Bontha, Vijaya Kumar

2013-01-01

The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The C max of colon targeted tablets was 11956.15 ng/mL at T max of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen. PMID:24260738

Colon targeted guar gum compression coated tablets of flurbiprofen: formulation, development, and pharmacokinetics.

PubMed

Vemula, Sateesh Kumar; Bontha, Vijaya Kumar

2013-01-01

The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The C(max) of colon targeted tablets was 11956.15 ng/mL at T max of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen.

Development and Applications of Orthogonality Constrained Density Functional Theory for the Accurate Simulation of X-Ray Absorption Spectroscopy

NASA Astrophysics Data System (ADS)

Derricotte, Wallace D.

The aim of this dissertation is to address the theoretical challenges of calculating core-excited states within the framework of orthogonality constrained density functional theory (OCDFT). OCDFT is a well-established variational, time independent formulation of DFT for the computation of electronic excited states. In this work, the theory is first extended to compute core-excited states and generalized to calculate multiple excited state solutions. An initial benchmark is performed on a set of 40 unique core-excitations, highlighting that OCDFT excitation energies have a mean absolute error of 1.0 eV. Next, a novel implementation of the spin-free exact-two-component (X2C) one-electron treatment of scalar relativistic effects is presented and combined with OCDFT in an effort to calculate core excited states of transition metal complexes. The X2C-OCDFT spectra of three organotitanium complexes (TiCl4, TiCpCl3, and TiCp2Cl2) are shown to be in good agreement with experimental results and show a maximum absolute error of 5-6 eV. Next the issue of assigning core excited states is addressed by introducing an automated approach to analyzing the excited state MO by quantifying its local contributions using a unique orbital basis known as localized intrinsic valence virtual orbitals (LIVVOs). The utility of this approach is highlighted by studying sulfur core-excitations in ethanethiol and benzenethiol, as well as the hydrogen bonding in the water dimer. Finally, an approach to selectively target specic core-excited states in OCDFT based on atomic orbital subspace projection is presented in an effort to target core excited states of chemisorbed organic molecules. The core excitation spectrum of pyrazine chemisorbed on Si(100) is calculated using OCDFT and further characterized using the LIVVO approach.

[Social participation in mental health: space of construction of citizenship, policy formulation and decision making].

PubMed

Guimarães, José Maria Ximenes; Jorge, Maria Salete Bessa; Maia, Regina Claudia Furtado; de Oliveira, Lucia Conde; Morais, Ana Patrícia Pereira; Lima, Marcos Paulo de Oliveira; Assis, Marluce Maria Araújo; dos Santos, Adriano Maia

2010-07-01

The article approaches the comprehension of professionals that act in the mental health area about the movement of construction of social participation in the health system of Fortaleza, Ceará State. The methodology adopted is based upon qualitative approach. The study was developed with semi-structured interviews with 17 mental health professionals of the city above mentioned. The empirical data was analyzed through the technique of thematic content analysis, where it was identified three cores of analysis: social participation as space of citizenship and policy formulation; oriented to attention of collective needs; and decision taking. The study reveals that social participation represents a possibility of amplifying X the relations between the Civil Society and the State, which makes possible the social intervention in proposals of the health policies. It is highlighted the right to health linked to the consolidation of democracy in the attention to the needs and collective edification.

Cultural competencies for graduate nursing education.

PubMed

Clark, Lauren; Calvillo, Evelyn; Dela Cruz, Felicitas; Fongwa, Marie; Kools, Susan; Lowe, John; Mastel-Smith, Beth

2011-01-01

Nursing is challenged to meet the health needs of ethnic and socioculturally diverse populations. To this end, American Association of Colleges of Nursing (AACN) charged an expert nursing faculty advisory group to formulate competencies for graduate nursing education, expanding them to integrate leadership and scholarship. The Cultural Competency in Baccalaureate Nursing Education served as the springboard for the initiative. In formulating the graduate cultural competencies and the toolkit, the advisory group reviewed all AACN Essentials documents and the cultural competency literature, drew upon their collective experiences with cultural diversity, and used cultural humility as the supporting framework. Six core competencies were formulated and endorsed by the AACN board of directors and key professional nursing organizations. A companion toolkit was compiled to provide resources for the implementation of the competencies. A 1-day conference was held in California to launch the cultural competencies and toolkit. Dissemination to graduate nursing programs is in process, with emphasis on faculty readiness to undertake this graduate educational transformation. The AACN Cultural Competencies for Graduate Nursing Education set national standards to prepare culturally competent nurses at the graduate level who will contribute to the elimination of health disparities through education, clinical practice, research, scholarship, and policy. 2011 Elsevier Inc. All rights reserved.

Rapid microwave-assisted synthesis of sub-30nm lipid nanoparticles.

PubMed

Dunn, Stuart S; Beckford Vera, Denis R; Benhabbour, S Rahima; Parrott, Matthew C

2017-02-15

Accessing the phase inversion temperature by microwave heating may enable the rapid synthesis of small lipid nanoparticles. Nanoparticle formulations consisted of surfactants Brij 78 and Vitamin E TPGS, and trilaurin, trimyristin, or miglyol 812 as nanoparticle lipid cores. Each formulation was placed in water and heated by microwave irradiation at temperatures ranging from 65°C to 245°C. We observed a phase inversion temperature (PIT) for these formulations based on a dramatic decrease in particle Z-average diameters. Subsequently, nanoparticles were manufactured above and below the PIT and studied for (a) stability toward dilution, (b) stability over time, (c) fabrication as a function of reaction time, and (d) transmittance of lipid nanoparticle dispersions. Lipid-based nanoparticles with distinct sizes down to 20-30nm and low polydispersity could be attained by a simple, one-pot microwave synthesis. This was carried out by accessing the phase inversion temperature using microwave heating. Nanoparticles could be synthesized in just one minute and select compositions demonstrated high stability. The notable stability of these particles may be explained by the combination of van der Waals interactions and steric repulsion. 20-30nm nanoparticles were found to be optically transparent. Published by Elsevier Inc.

Carbamazepine parenteral nanoemulsions prepared by spontaneous emulsification process.

PubMed

Kelmann, Regina G; Kuminek, Gislaine; Teixeira, Helder F; Koester, Letícia S

2007-09-05

Carbamazepine (CBZ), a widely used anticonvulsant drug, is a poorly soluble drug with no parenteral treatment available for patients. This study was aimed at developing a nanoemulsion for CBZ intravenous delivery. The spontaneous emulsification method was used to prepare different formulations containing 2mg/mL CBZ. Likewise, a 2(2) full factorial experimental design was applied to study the influence of two independent variables (type of oil and type of lipophilic emulsifier) on emulsion physicochemical characteristics. The nanoemulsions were evaluated concerning droplet size, zeta potential, viscosity, drug content and association to oily phase. The formulation, which presented the best characteristics required for intravenous administration was selected and refined with respect to the lipophilic emulsifier content (increase from 5% to 6% of soy lecithin). This formulation was characterized and kept its properties in a satisfactory range over the evaluated period (3 months), i.e. droplet size around 150 nm, drug content around 95% and zeta potential around -40 mV. The transmission electron microscopy revealed emulsion droplets almost spherical in shape with an amorphous core, whereas the in vitro release profile assessed by dialysis bags demonstrated a release kinetics square root time dependent, with 95% of ca. having been released within 11h.

Effect of Monomer Solubility on the Evolution of Copolymer Morphology during Polymerization-Induced Self-Assembly in Aqueous Solution

PubMed Central

2017-01-01

Polymerization-induced self-assembly (PISA) has become a widely used technique for the rational design of diblock copolymer nano-objects in concentrated aqueous solution. Depending on the specific PISA formulation, reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization typically provides straightforward access to either spheres, worms, or vesicles. In contrast, RAFT aqueous emulsion polymerization formulations often lead to just kinetically-trapped spheres. This limitation is currently not understood, and only a few empirical exceptions have been reported in the literature. In the present work, the effect of monomer solubility on copolymer morphology is explored for an aqueous PISA formulation. Using 2-hydroxybutyl methacrylate (aqueous solubility = 20 g dm–3 at 70 °C) instead of benzyl methacrylate (0.40 g dm–3 at 70 °C) for the core-forming block allows access to an unusual “monkey nut” copolymer morphology over a relatively narrow range of target degrees of polymerization when using a poly(methacrylic acid) RAFT agent at pH 5. These new anisotropic nanoparticles have been characterized by transmission electron microscopy, dynamic light scattering, aqueous electrophoresis, shear-induced polarized light imaging (SIPLI), and small-angle X-ray scattering. PMID:28216792

Mathematical modelling of powder material motion and transportation in high-temperature flow core during plasma coatings application

NASA Astrophysics Data System (ADS)

Bogdanovich, V. I.; Giorbelidze, M. G.

2018-03-01

A problem of mathematical modelling of powder material motion and transportation in gas thermal flow core has been addressed. Undertaken studies indicate significant impact on dynamics of motion of sprayed particles of phenomenological law for drag coefficient and accounting momentum loss of a plasma jet upon acceleration of these particles and their diameter. It is determined that at great dispersion of spraying particles, they reach detail surface at different velocity and significant particles separation takes place at spraying spot. According to the results of mathematical modelling, requirements for admissible dispersion of diameters of particles used for spraying have been formulated. Research has also allowed reducing separation of particles at the spraying spot due to the selection of the method of powder feed to the anode channel of the plasma torch.

Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

PubMed

Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

2008-01-01

The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

Development of a Jet Noise Prediction Method for Installed Jet Configurations

NASA Technical Reports Server (NTRS)

Hunter, Craig A.; Thomas, Russell H.

2003-01-01

This paper describes development of the Jet3D noise prediction method and its application to heated jets with complex three-dimensional flow fields and installation effects. Noise predictions were made for four separate flow bypass ratio five nozzle configurations tested in the NASA Langley Jet Noise Laboratory. These configurations consist of a round core and fan nozzle with and without pylon, and an eight chevron core nozzle and round fan nozzle with and without pylon. Predicted SPL data were in good agreement with experimental noise measurements up to 121 inlet angle, beyond which Jet3D under predicted low frequency levels. This is due to inherent limitations in the formulation of Lighthill's Acoustic Analogy used in Jet3D, and will be corrected in ongoing development. Jet3D did an excellent job predicting full scale EPNL for nonchevron configurations, and captured the effect of the pylon, correctly predicting a reduction in EPNL. EPNL predictions for chevron configurations were not in good agreement with measured data, likely due to the lower mixing and longer potential cores in the CFD simulations of these cases.

A case study of full integration of the arts into core subject area instruction in one East Texas secondary school

NASA Astrophysics Data System (ADS)

Leysath, Maggie

This exploratory phenomenological case study investigated the influence the full integration of the arts into core subject instruction has on classroom environment, student academic achievement, and student engagement as perceived by administrators, teachers, and students in one East Texas secondary school. Participant interviews were analyzed using Creswell's (2012) six-step method for analyzing phenomenological studies. The researcher implemented three learning activities in which ceramics learning objectives were fully integrated with chemistry learning objectives. The first activity combined clay properties and pottery wheel throwing with significant numbers. The second activity combined glaze formulation with moles. The third combined stoichiometry with the increased glaze formula for students to glaze the bowls they made. Findings suggest the full integration of art in core subject area instruction has numerous positive effects. Participants reported improved academic achievement for all students including reluctant learners. Students, teachers, and the administrator reported greater participation in the art integrated activities. Participants perceived a need for further training for teachers and administrators for greater success.

Shock Initiated Reactions of Reactive Multiphase Blast Explosives

NASA Astrophysics Data System (ADS)

Wilson, Dennis; Granier, John; Johnson, Richard; Littrell, Donald

2015-06-01

This paper describes a new class of reactive multiphase blast explosives (RMBX) and characterization of their blast characteristics. These RMBXs are non-ideal explosive compositions of perfluoropolyether (PFPE), nano aluminum, and a micron-size high-density reactive metal - Tantalum, Zirconium, or Zinc in mass loadings of 66 to 83 percent. Unlike high explosives, these PFPE-metal compositions release energy via a fast self-oxidized combustion wave (rather than a true self-sustaining detonation) that is shock dependent, and can be overdriven to control energy release rate. The term ``reactive multiphase blast'' refers to the post-dispersion blast behavior: multiphase in that there are a gas phase that imparts pressure and a solid (particulate) phase that imparts momentum; and reactive in that the hot metal particles react with atmospheric oxygen and the explosive gas products to give an extended pressure pulse. The RMBX formulations were tested in two spherical core-shell geometries - an RMBX shell exploded by a high explosive core, and an RMBX core imploded by a high explosive shell. The fireball and blast characteristics were compared to a C-4 baseline charge.

Shock initiated reactions of reactive multi-phase blast explosives

NASA Astrophysics Data System (ADS)

Wilson, Dennis; Granier, John; Johnson, Richard; Littrell, Donald

2017-01-01

This paper describes a new class of non-ideal explosive compositions made of perfluoropolyether (PFPE), nanoaluminum, and a micron-size, high mass density, reactive metal. Unlike high explosives, these compositions release energy via a fast self-oxidized combustion wave rather than a true self-sustaining detonation. Their reaction rates are shock dependent and they can be overdriven to change their energy release rate. These compositions are fuel rich and have an extended aerobic energy release phase. The term "reactive multiphase blast" refers to the post-dispersion blast behavior: multiphase in that there are a gas phase that imparts pressure and a solid (particulate) phase that imparts energy and momentum [1]; and reactive in that the hot metal particles react with atmospheric oxygen and the explosive gas products to give an extended pressure pulse. Tantalum-based RMBX formulations were tested in two spherical core-shell configurations - an RMBX shell exploded by a high explosive core, and an RMBX core imploded by a high explosive shell. The fireball and blast characteristics were compared to a C-4 baseline charge.

Permeability of bacterial spores. IV. Water content, uptake, and distribution.

PubMed

BLACK, S H; GERHARDT, P

1962-05-01

Black, S. H. (The University of Michigan, Ann Arbor) and Philipp Gerhardt. Permeability of bacterial spores. IV. Water content, uptake, and distribution. J. Bacteriol. 83:960-967. 1962.-Dormant and germinated spores of Bacillus cereus strain terminalis were examined for water properties. Respectively, they exhibited a mean density of 1.28 and 1.11 g/ml, a water content of 64.8 and 73.0%, and a total water uptake of 66.6 and 75.6%, based on spore weight, or 86.0 and 83.9%, based on spore volume. The results confirmed a previous report that internal and external water are in virtually complete equilibrium, but refuted a prevailing hypothesis that heat resistance is attributable to a dry core. A model of spore ultrastructure that evolved from the cumulative results pictures a moist, dense, heteroporous core. A new hypothesis is formulated as an explanation for thermostability in spores and possibly in other instances; it postulates the occurrence of an insolubly gelled core with cross-linking between macromolecules through stable but reversible bonds so as to form a high-polymer matrix with entrapped free water.

A new baryonic equation of state at sub-nuclear densities for core-collapse simulations

NASA Astrophysics Data System (ADS)

Furusawa, Shun; Yamada, Shoichi; Sumiyoshi, Kohsuke; Suzuki, Hideyuki

2012-11-01

We construct a new equation of state for baryons at sub-nuclear densities for the use in core-collapse simulations of massive stars. The formulation is based on the nuclear statistical equilibrium description and the liquid drop approximation of nuclei. The model free energy to minimize is calculated by using relativistic mean field theory for nucleons and the mass formula for nuclei with atomic number up to ~ 1000. We have also taken into account the pasta phase. We find that the free energy and other thermodynamical quantities are not very different from those given in the standard EOSs that adopt the single nucleus approximation. On the other hand, the average mass is systematically different, which may have an important effect to the rates of electron captures and coherent neutrino scatterings on nuclei in supernova cores. It is also interesting that the root mean square of the mass number is not very different from the average mass number, since the former is important for the evaluation of coherent scattering rates on nuclei but has been unavailable so far.

Developing Creative and Critical Thinkers

DTIC Science & Technology

2009-12-01

competitive advantage and long-term success. Strategic thinking meshes anticipated requirements with future organizational capabilities to ensure the organization wins in the future. Examples of failures in strategic thinking abound. They include the recent failures of U.S. auto companies to understand the key factors facing their industry. Of greater significance is our own failure of strategic thinking in the formulation and acceptance of the many pre-war assumptions about Iraq. The core elements of strategic thinking are the ability to think creatively and critically

Harmonics suppression of vacuum chamber eddy current induced fields with application to the Superconducting Super Collider (SSC) Low Energy Booster (LEB) Magnets

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

Schlueter, R.D.; Halbach, K.

1991-12-04

This memo presents the formulation of an expression for eddy currents induced in a thin-walled conductor due to a time-dependent electromagnet field excitation. Then follows an analytical development for prediction of vacuum chamber eddy current induced field harmonics in iron-core electromagnets. A passive technique for harmonics suppression is presented with specific application to the design of the Superconducting Super Collider (SSC) Low Energy B (LEB) Magnets.

Analysis of Counterfeit Coated Tablets and Multi-Layer Packaging Materials Using Infrared Microspectroscopic Imaging.

PubMed

Winner, Taryn L; Lanzarotta, Adam; Sommer, André J

2016-06-01

An effective method for detecting and characterizing counterfeit finished dosage forms and packaging materials is described in this study. Using attenuated total internal reflection Fourier transform infrared spectroscopic imaging, suspect tablet coating and core formulations as well as multi-layered foil safety seals, bottle labels, and cigarette tear tapes were analyzed and compared directly with those of a stored authentic product. The approach was effective for obtaining molecular information from structures as small as 6 μm.

Survivability of a Propellant Fire inside a Simulated Military Vehicle Crew Compartment: Part 2 - Hazard Mitigation Strategies and Their Effectiveness

DTIC Science & Technology

2013-06-01

Weapons Propulsion Group where his work initially focussed on R&D relating to cast- composite rocket motors. The emphasis of his work then shifted to gun...Relative humidity RHS Rectangular Hollow Section t Time (s) T1 Ambient room temperature, ceiling-height (K) T2 Ambient room temperature...propellant and a centre- core igniter train. The BCM and UNCLASSIFIED DSTO-RR-0393 UNCLASSIFIED 2 TCM contain the same propellant formulation and

The hygroscopicity of moisture barrier film coatings.

PubMed

Mwesigwa, Enosh; Buckton, Graham; Basit, Abdul W

2005-12-01

The hygroscopicity of three commercial moisture-barrier film coatings, namely, Eudragit L30 D-55 (methacrylic acid-ethyl acrylate copolymer), Opadry AMB (polyvinyl alcohol based system), and Sepifilm LP 014 (hypromellose, microcrystalline cellulose, and stearic acid based formulation), was investigated using a dynamic vapor sorption apparatus. Moisture uptake by cast films and uncoated and coated tablet cores, which were designed to be hygroscopic, low hygroscopic, and waxy, was measured following exposure to repeat relative humidity (RH) cycles of 0-50-0-50-0%, 0-75-0-75-0%, and 0-90-0-90-0% RH at 25 degrees C. Eudragit cast film exhibited the fastest equilibration but was also the least hygroscopic. Sepifilm had the fastest sorption and took up the greatest mass of water. The rate of uptake for Opadry film was similar to Sepifilm. However, this film continued to sorb moisture for a longer period. When returned to 0% RH it retained moisture in the film showing that it had a high affinity for moisture within the film. The data for the different cores indicated that there was very little benefit in using a moisture barrier film on cores with low hygroscopicity, the mass gain being a sum of that which would be expected to sorb to the film and that which sorbs to the uncoated core. There was, however, some advantage for hygroscopic cores where, even though the barrier coatings allowed substantial water sorption into the core, the extent of this was less and the rate of uptake lower than for the uncoated sample.

Physical properties of self-, dual-, and light-cured direct core materials.

PubMed

Rüttermann, Stefan; Alberts, Ian; Raab, Wolfgang H M; Janda, Ralf R

2011-08-01

The objective of this study is to evaluate flexural strength, flexural modulus, compressive strength, curing temperature, curing depth, volumetric shrinkage, water sorption, and hygroscopic expansion of two self-, three dual-, and three light-curing resin-based core materials. Flexural strength and water sorption were measured according to ISO 4049, flexural modulus, compressive strength, curing temperature, and curing depth according to well-proven, literature-known methods, and the volumetric behavior was determined by the Archimedes' principle. ANOVA was calculated to find differences between the materials' properties, and correlation of water sorption and hygroscopic expansion was analysed according to Pearson (p < 0.05). Clearfil Photo Core demonstrated the highest flexural strength (125 ± 12 MPa) and curing depth (15.2 ± 0.1 mm) and had the highest flexural modulus (≈12.6 ± 1.2 GPa) concertedly with Multicore HB. The best compressive strength was measured for Voco Rebilda SC and Clearfil DC Core Auto (≈260 ± 10 MPa). Encore SuperCure Contrast had the lowest water sorption (11.8 ± 3.3 µg mm(-3)) and hygroscopic expansion (0.0 ± 0.2 vol.%). Clearfil Photo Core and Encore SuperCure Contrast demonstrated the lowest shrinkage (≈2.1 ± 0.1 vol.%). Water sorption and hygroscopic expansion had a very strong positive correlation. The investigated core materials significantly differed in the tested properties. The performance of the materials depended on their formulation, as well as on the respective curing process.

Synthesis of polymer-lipid nanoparticles for image-guided delivery of dual modality therapy.

PubMed

Mieszawska, Aneta J; Kim, YongTae; Gianella, Anita; van Rooy, Inge; Priem, Bram; Labarre, Matthew P; Ozcan, Canturk; Cormode, David P; Petrov, Artiom; Langer, Robert; Farokhzad, Omid C; Fayad, Zahi A; Mulder, Willem J M

2013-09-18

For advanced treatment of diseases such as cancer, multicomponent, multifunctional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly(lactic-co-glycolic) acid (PLGA) polymer is formulated into a polymer-lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near-infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics-based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine-tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near-infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging.

Development of an Insect Repellent Spray for Textile Based on Permethrin-Loaded Lipid-Core Nanocapsules.

PubMed

Forgearini, Joana C; Michalowski, Cecília B; Assumpção, Evelise; Pohlmann, Adriana R; Guterres, Silvia S

2016-02-01

The aim of this study was to prepare and characterize permethrin-loaded lipid core nanocapsules (P-LNC) in order to produce a long last insect repellent spray formulation for clothes. P-LNC were prepared by self-assembling in aqueous solution showing a mean diameter of 201 +/- 4 nm with a monomodal distribution, a permethrin content of 4.6 +/- 0.1 mg/mL and zeta potential of--16.7 +/- 4 mV. P-LNC (0.46%), as well as the commercial product (0.46%) and the hydroalcoholic solution (0.50%) of permethrin were separately sprayed onto cotton or polyester, followed by successive washes of the fabric. The results showed that the fabrics treated with P-LNC are more resistant than other solutions in terms of remaining permethrin content. After twenty washes, the cotton treated with P-LNC, presented a concentration of 566 +/- 27 mg/M2 of impregnated permethrin, while for the treatment with the substance hydroalcoholic solution and with the commercial product the concentrations values were of 340 +/- 7 mg/M2 and 224 +/- 74 mg/M2, respectively. When the test was performed using polyester, this fiber was less adhesive than cotton, resulting in a final concentration of permethrin (after 20 washes) of 81 +/- 10 mg/m2 for P-LNC suspension, 94 +/- 8 mg/M2 for the substance hydroalcoolic solution and 22 +/- 3 mg/M2 for the commercial product. After impregnating cotton with the formulations and submitting to a temperature of 200 degrees C, the P-LNC also demonstrated higher adherence compared to the other formulations (407 +/- 67 mg/m2 for P-LNC, 236 +/- 72 mg/m2 for the substance hydroalcoholic solution and 158 +/- 62 mg/m2 for commercial product). These results showed that the repellent spray composed of P-LNC developed in this work is a promising and innovative product for the individual protection against insects, useful for impregnation onto cotton garments.

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

PubMed

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

2006-03-01

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

Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer.

PubMed

Kim, Soo-Yeon; Lee, Sang-Jin; Kim, Jin-Ki; Choi, Han-Gon; Lim, Soo-Jeong

2017-01-01

Cationic lipid-based nanoparticles enhance viral gene transfer by forming electrostatic complexes with adenoviral vectors. We recently demonstrated the superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) emulsion compared with a liposomal counterpart but the cytotoxicity of DOTAP emulsions remained a challenge. The present study is aimed at formulating an emulsion capable of acting as a highly effective viral gene transfer vehicle with reduced cytotoxicity and to physicochemically characterize the structures of virus-emulsion complexes in comparison with virus-liposome complexes when the only difference between emulsions and liposomes was the presence or absence of inner oil core. The emulsion formulation was performed by 1) reducing the content of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2) optimizing the oil content. The complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to those of emulsions containing DOTAP alone while displaying significantly lower cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were serum-compatible and were monitored in a variety of cell types, whereas its liposomal counterpart was totally ineffective. Characterization by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering studies indicated that the optimized emulsions spontaneously surrounded the virus particles to generate emulsions that encapsulated the viral particles, whereas viral particles merely attached to the surfaces of the counterpart liposomes to form multiviral aggregates. Overall, these studies demonstrated that optimized DOTAP:DMPC mixed emulsions are potentially useful for adenoviral gene delivery due to less cytotoxicity and the unique ability to encapsulate the viral particle, highlighting the importance of nanoparticle formulation.

Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer

PubMed Central

Kim, Soo-Yeon; Lee, Sang-Jin; Kim, Jin-Ki; Choi, Han-Gon; Lim, Soo-Jeong

2017-01-01

Cationic lipid-based nanoparticles enhance viral gene transfer by forming electrostatic complexes with adenoviral vectors. We recently demonstrated the superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) emulsion compared with a liposomal counterpart but the cytotoxicity of DOTAP emulsions remained a challenge. The present study is aimed at formulating an emulsion capable of acting as a highly effective viral gene transfer vehicle with reduced cytotoxicity and to physicochemically characterize the structures of virus-emulsion complexes in comparison with virus–liposome complexes when the only difference between emulsions and liposomes was the presence or absence of inner oil core. The emulsion formulation was performed by 1) reducing the content of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2) optimizing the oil content. The complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to those of emulsions containing DOTAP alone while displaying significantly lower cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were serum-compatible and were monitored in a variety of cell types, whereas its liposomal counterpart was totally ineffective. Characterization by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering studies indicated that the optimized emulsions spontaneously surrounded the virus particles to generate emulsions that encapsulated the viral particles, whereas viral particles merely attached to the surfaces of the counterpart liposomes to form multiviral aggregates. Overall, these studies demonstrated that optimized DOTAP:DMPC mixed emulsions are potentially useful for adenoviral gene delivery due to less cytotoxicity and the unique ability to encapsulate the viral particle, highlighting the importance of nanoparticle formulation. PMID:29070949

Controlled delivery of Gemcitabine Hydrochloride using mannosylated poly(propyleneimine) dendrimers

NASA Astrophysics Data System (ADS)

Soni, Namrata; Jain, Keerti; Gupta, Umesh; Jain, N. K.

2015-11-01

The aim of the present investigation was to deliver Gemcitabine Hydrochloride (GmcH), an anticancer bioactive, specifically to lung tumor cells using mannosylated 4.0G poly(propyleneimine) dendrimers (M-PPI). 4.0G poly(propyleneimine) (PPI) dendrimers was synthesized using ethylenediamine as core and conjugated with mannose by ring opening reactions, followed by Schiff's reaction in the presence of sodium acetate buffer (pH 4.0). Synthesized PPI dendrimers and mannose-conjugated dendrimers were characterized using IR, NMR spectroscopy, and scanning electron microscopy. GmcH was loaded into PPI and M-PPI dendrimers using equilibrium dialysis method to develop the formulations, GmcH-PPI and GmcH-M-PPI, respectively. The developed formulations were evaluated for drug loading, in vitro release kinetics, in vitro stability, hemolytic toxicity, cytotoxicity, pharmacokinetic, and biodistribution studies. The dendrimeric formulation of GmcH showed pH-sensitive release with faster release at acidic pH, i.e., pH 4.0 in comparison with physiological pH 7.4. M-PPI conjugate showed significant reduction in hemolytic toxicity as compared to plain 4.0G PPI dendrimers towards human erythrocytes. In the cytotoxicity studies with A-549 lung adenocarcinoma cell line, the GmcH-M-PPI formulation showed the lowest IC50 value. Further, the pharmacokinetic and tissue distribution studies of free drug GmcH, GmcH-PPI, and GmcH-M-PPI in albino rats of Sprague-Dawley strain suggested the mean residence time of GmcH-M-PPI conjugate to be significantly higher (24.85 h) than free GmcH and GmcH-PPI. Deposition of drug (396.1 ± 4.7 after 2 h) in lung was found to be significantly higher with GmcH-M-PPI formulation in comparison with Gmch and GmcH-PPI.

Core stability exercises for low back pain in athletes: a systematic review of the literature.

PubMed

Stuber, Kent J; Bruno, Paul; Sajko, Sandy; Hayden, Jill A

2014-11-01

The aim of this study was to systematically review the evidence for the effectiveness of core stability exercises for treating athletes with low back pain (LBP). We searched several databases (Medline, AMED, CINAHL, SportDiscus, and EMBASE). Our eligibility criteria consisted of articles published in a peer-reviewed journal in English, using any prospective clinical study design, where athletes with nonspecific LBP were treated with core stability exercises in at least 1 study arm, and back pain intensity and/or disability were used as outcome measures. All included randomized controlled trials (RCTs) were assessed for risk of bias using the Cochrane Risk of Bias tool, whereas non-RCT studies were assessed for quality using the Downs and Black checklist. Five studies including 151 participants met the inclusion criteria, including 2 RCTs. The quality of the literature on this topic was deemed to be low overall, with only 1 non-RCT having a moderate quality score, and 1 RCT having a lower risk of bias. Four studies reported statistically significant decreases in back pain intensity in their core stability intervention group. The quantity and quality of literature on the use of core stability exercises for treating LBP in athletes is low. The existing evidence has been conducted on small and heterogeneous study populations using interventions that vary drastically with only mixed results and short-term follow-up. This precludes the formulation of strong conclusions, and additional high quality research is clearly needed.

Maintenance and assessment of cell viability in formulation of non-sporulating bacterial inoculants.

PubMed

Berninger, Teresa; González López, Óscar; Bejarano, Ana; Preininger, Claudia; Sessitsch, Angela

2018-03-01

The application of beneficial, plant-associated microorganisms is a sustainable approach to improving crop performance in agriculture. However, microbial inoculants are often susceptible to prolonged periods of storage and deleterious environmental factors, which negatively impact their viability and ultimately limit efficacy in the field. This particularly concerns non-sporulating bacteria. To overcome this challenge, the availability of protective formulations is crucial. Numerous parameters influence the viability of microbial cells, with drying procedures generally being among the most critical ones. Thus, technological advances to attenuate the desiccation stress imposed on living cells are key to successful formulation development. In this review, we discuss the core aspects important to consider when aiming at high cell viability of non-sporulating bacteria to be applied as microbial inoculants in agriculture. We elaborate the suitability of commonly applied drying methods (freeze-drying, vacuum-drying, spray-drying, fluidized bed-drying, air-drying) and potential measures to prevent cell damage from desiccation (externally applied protectants, stress pre-conditioning, triggering of exopolysaccharide secretion, 'helper' strains). Furthermore, we point out methods for assessing bacterial viability, such as colony counting, spectrophotometry, microcalorimetry, flow cytometry and viability qPCR. Choosing appropriate technologies for maintenance of cell viability and evaluation thereof will render formulation development more efficient. This in turn will aid in utilizing the vast potential of promising, plant beneficial bacteria as sustainable alternatives to standard agrochemicals. © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres.

PubMed

Alli, Sk Md Athar

2011-01-01

Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f(1)), the similarity factor (f(2)), and the Rescigno index (ξ(1) and ξ(2)) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations.

Celecoxib Encapsulation in β-Casein Micelles: Structure, Interactions, and Conformation.

PubMed

Turovsky, Tanya; Khalfin, Rafail; Kababya, Shifi; Schmidt, Asher; Barenholz, Yechezkel; Danino, Dganit

2015-07-07

β-Casein is a 24 kDa natural protein that has an open conformation and almost no folded or secondary structure, and thus is classified as an intrinsically unstructured protein. At neutral pH, β-casein has an amphiphilic character. Therefore, in contrast to most unstructured proteins that remain monomeric in solution, β-casein self-assembles into well-defined core-shell micelles. We recently developed these micelles as potential carriers for oral administration of poorly water-soluble pharmaceuticals, using celecoxib as a model drug. Herein we present deep and precise insight into the physicochemical characteristics of the protein-drug formulation, both in bulk solution and in dry form, emphasizing drug conformation, packing properties and aggregation state. In addition, the formulation is extensively studied in terms of structure and morphology, protein/drug interactions and physical stability. Particularly, NMR measurements indicated strong drug-protein interactions and noncrystalline drug conformation, which is expected to improve drug solubility and bioavailability. Small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) were combined for nanostructural characterization, proving that drug-protein interactions lead to well-defined spheroidal micelles that become puffier and denser upon drug loading. Dynamice light scattering (DLS), turbidity measurements, and visual observations complemented the analysis for determining formulation structure, interactions, and stability. Additionally, it was shown that the loaded micelles retain their properties through freeze-drying and rehydration, providing long-term physical and chemical stability. Altogether, the formulation seems greatly promising for oral drug delivery.

Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres

PubMed Central

Alli, Sk Md Athar

2011-01-01

Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f1), the similarity factor (f2), and the Rescigno index (ξ1 and ξ2) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations. PMID:21674019

Nanoparticles of lipid monolayer shell and biodegradable polymer core for controlled release of paclitaxel: effects of surfactants on particles size, characteristics and in vitro performance.

PubMed

Liu, Yutao; Pan, Jie; Feng, Si-Shen

2010-08-16

This work developed a system of nanoparticles of lipid monolayer shell and biodegradable polymer core for controlled release of anticancer drugs with paclitaxel as a model drug, in which the emphasis was given to the effects of the surfactant type and the optimization of the emulsifier amount used in the single emulsion solvent evaporation/extraction process for the nanoparticle preparation on the particle size, characters and in vitro performance. The drug loaded nanoparticles were characterized by laser light scattering (LLS) for size and size distribution, field-emission scanning electron microscopy (FESEM) for surface morphology, X-ray photoelectron spectroscopy (XPS) for surface chemistry, zetasizer for surface charge, and high performance liquid chromatography (HPLC) for drug encapsulation efficiency and in vitro drug release kinetics. MCF-7 breast cancer cells were employed to evaluate the cellular uptake and cytotoxicity. It was found that phospholipids of short chains such as 1,2-dilauroylphosphatidylocholine (DLPC) have great advantages over the traditional emulsifier poly(vinyl alcohol) (PVA), which is used most often in the literature, in preparation of nanoparticles of biodegradable polymers such as poly(D,L-lactide-co-glycolide) (PLGA) for desired particle size, character and in vitro cellular uptake and cytotoxicity. After incubation with MCF-7 cells at 0.250 mg/ml NP concentration, the coumarin-6 loaded PLGA NPs of DLPC shell showed more effective cellular uptake versus those of PVA shell. The analysis of IC(50), i.e. the drug concentration at which 50% of the cells are killed, demonstrated that our DLPC shell PLGA core NP formulation of paclitaxel could be 5.88-, 5.72-, 7.27-fold effective than the commercial formulation Taxol after 24, 48, 72h treatment, respectively. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Physiotherapy in rheumatoid arthritis: development of a practice guideline.

PubMed

Hurkmans, E J; van der Giesen, F J; Bloo, H; Boonman, D C; van der Esch, M; Fluit, M; Hilberdink, W K; Peter, W F; van der Stegen, H P; Veerman, E A; Verhoef, J; Vermeulen, H M; Hendriks, H M; Schoones, J W; Vliet Vlieland, T P

2011-01-01

To improve the quality of the physiotherapy management in patients with rheumatoid arthritis (RA) a Dutch practice guideline, based on current scientific evidence and best practice, was developed. This guideline comprised all elements of a structured approach (assessment, treatment and evaluation) and was based on the Internatio-nal Classification of Functioning, disability and Health (ICF) and the ICF core sets for RA. A guideline steering committee, comprising 10 expert physiotherapists, selected topics concerning the guideline chapters initial assessment, treatment and evaluation. With respect to treatment a systematic literature search was performed using various databases, and the evidence was graded (1-4). For the initial assessment and evaluation mainly review papers and textbooks were used. Based on evidence and expert opinion, recommendations were formulated. A first draft of the guideline was reviewed by 10 experts from different professional backgrounds resulting in the final guideline. In total 7 topics were selected. For the initial assessment, three recommendations were made. Based on the ICF core sets for RA a list of health problems relevant for the physiotherapist was made and completed with red flags and points of attention. Concerning treatment, three recommendations were formulated; both exercise therapy and education on physiotherapy were recommended, whereas passive interventions (delivery of heat or cold, mechanical, electric and electromagnetic energy, massage, passive mobilization/manipulation and balneotherapy) were neither recommended nor discouraged. For treatment evaluation at the level of activities and participation, the Health Assessment Questionnaire was recommended. For evaluating specific body structures and functions the handheld dynamometer, 6-minute walk test or Ästrand bicycle test (including Borg-scale for rating the perceived exertion), Escola Paulista de Medicina Range of Motion Scale and a Visual Analog Scale for pain and morning stiffness were recommended. This physiotherapy practice guideline for RA included seven recommendations on the initial assessment, treatment and evaluation, which were all based on the ICF and the ICF Core Set for RA. The implementation of the guideline in clinical practice needs further evaluation.

Docetaxel-Loaded Nanoparticles Assembled from β-Cyclodextrin/Calixarene Giant Surfactants: Physicochemical Properties and Cytotoxic Effect in Prostate Cancer and Glioblastoma Cells.

PubMed

Gallego-Yerga, Laura; Posadas, Inmaculada; de la Torre, Cristina; Ruiz-Almansa, Jesús; Sansone, Francesco; Ortiz Mellet, Carmen; Casnati, Alessandro; García Fernández, José M; Ceña, Valentín

2017-01-01

Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA 4 ) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities. Indeed, the release kinetics profiles evidenced an initial fast release of the drug, which likely accounts for the fraction hosted on the surface, followed by a slow and sustained release rate, corresponding to diffusion of DTX in the core, which can be finely tuned by modification of the giant amphiphile chemical structure. The ability of the docetaxel-loaded nanoparticles to induce cellular death in different prostate (human LnCap and PC3) and glioblastoma (human U87 and rat C6) cells was also explored. Giant amphiphile-based DTX formulations surpassing or matching the antitumoral activity of the free DTX formulation were identified in all cases with no need to employ any organic co-solvent, thus overcoming the DTX water solubility problems. Moreover, the presence of the βCD shell at the surface of the assemblies is intended to impart stealth properties against serum proteins while permitting nanoparticle surface decoration by supramolecular approaches, paving the way for a new generation of molecularly well-defined antitumoral drug delivery systems with improved specificity and efficiency. Altogether, the results provide a proof of concept of the suitability of the approach based on βCD-CA 4 giant amphiphiles to access DTX carriers with tunable properties.

Core/shell PLGA microspheres with controllable in vivo release profile via rational core phase design.

PubMed

Yu, Meiling; Yao, Qing; Zhang, Yan; Chen, Huilin; He, Haibing; Zhang, Yu; Yin, Tian; Tang, Xing; Xu, Hui

2018-02-27

Highly soluble drugs tend to release from preparations at high speeds, which make them need to be taken at frequent intervals. Additionally, some drugs need to be controlled to release in vivo at certain periods, so as to achieve therapeutic effects. Thus, the objective of this study is to design injectable microparticulate systems with controllable in vivo release profile. Biodegradable PLGA was used as the matrix material to fabricate microspheres using the traditional double emulsification-solvent evaporation method as well as improved techniques, with gel (5% gelatine or 25% F127) or LP powders as the inner phases. Their physicochemical properties were systemically investigated. Microspheres prepared by modified methods had an increase in drug loading (15.50, 16.72, 15.66%, respectively) and encapsulation efficiencies (73.46, 79.42, 74.40%, respectively) when compared with traditional methods (12.01 and 57.06%). The morphology of the particles was characterized by optical microscope (OM) and scanning electron microscopy (SEM), and the amorphous nature of the encapsulated drug was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. To evaluate their release behaviour, the in vitro degradation, in vitro release and in vivo pharmacodynamics were subsequently studied. Traditional microspheres prepared in this study with water as the inner phase had a relatively short release period within 16 d when compared with modified microspheres with 5% gelatine as the inner phase, which resulted in a smooth release profile and appropriate plasma LP concentrations over 21 d. Thus this type of modified microspheres can be better used in drugs requiring sustained release. The other two formulations containing 25% F127 and LP micropowders presented two-stage release profiles, resulting in fluctuant plasma LP concentrations which may be suitable for drugs requiring controlled release. All the results suggested that drug release rates from the microspheres prepared by various methods were mainly controlled by either the porosity inside the microspheres or the degradation of materials, which could, therefore, lead to different release behaviours. This results indicated great potential of the PLGA microsphere formulation as an injectable depot for controllable in vivo release profile via rational core phase design. Core/shell microspheres fabricated by modified double emulsification-solvent evaporation methods, with various inner phases, to obtain high loading drugs system, as well as appropriate release behaviours. Accordingly, control in vivo release profile via rational core phase design.

Possible long-acting risperidone-induced hypothermia precipitating phenytoin toxicity in an elderly patient.

PubMed

Brandon Bookstaver, P; Miller, A D

2011-06-01

Thermodysregulation, including hypothermia, is recognized as a potential adverse effect secondary to atypical antipsychotics. We report the first known case of hypothermia possibly associated with long-acting risperidone depot injection, precipitating further adverse events secondary to supratherapeutic phenytoin concentrations. A 75-year-old African-American female presented as a transfer from an outpatient psychiatric center with hypothermia (35·1 °C), bradycardia, altered mental status and a series of witnessed tonic-clonic seizures. The patient was discovered to be profoundly neutropenic (absolute neutrophil count = 266 × 10(9) /L) and a corrected phenytoin concentration was 147·708 μm. During the 3 months preceding admission, phenytoin dosing was stable and consecutive therapeutic concentrations were documented. The only recent change in medication regimen was a switch from oral risperidone to the long-acting injectable formulation. Upon discontinuation of the risperidone and phenytoin, the patient's mental status and laboratory abnormalities returned to baseline. The patient did not experience additional seizure activity. This unintentional significant drop in core body temperature may have resulted in altered metabolism of phenytoin leading to supratherapeutic concentrations and subsequent tonic-clonic seizures, bradycardia and neutropenia. Low core body temperatures can alter the pharmacokinetic profiles of hepatically metabolized medications, prompting careful patient assessment especially in those receiving medications with a narrow-therapeutic index. Hypothermia should be recognized as a potential adverse event with the long-acting injectable formulation of risperidone. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Space charge induced resonance excitation in high intensity rings

NASA Astrophysics Data System (ADS)

Cousineau, S.; Lee, S. Y.; Holmes, J. A.; Danilov, V.; Fedotov, A.

2003-03-01

We present a particle core model study of the space charge effect on high intensity synchrotron beams, with specific emphasis on the Proton Storage Ring (PSR) at Los Alamos National Laboratory. Our particle core model formulation includes realistic lattice focusing and dispersion. We transport both matched and mismatched beams through real lattice structure and compare the results with those of an equivalent uniform-focusing approximation. The effects of lattice structure and finite momentum spread on the resonance behavior are specifically targeted. Stroboscopic maps of the mismatched envelope are constructed and show high-order resonances and stochastic effects that dominate at high mismatch or high intensity. We observe the evolution of the envelope phase-space structure during a high intensity PSR beam accumulation. Finally, we examine the envelope-particle parametric resonance condition and discuss the possibility for halo growth in synchrotron beams due to this mechanism.

Axisymmetric contour dynamics for buoyant vortex rings

NASA Astrophysics Data System (ADS)

Chang, Ching; Llewellyn Smith, Stefan

2017-11-01

Vortex rings are important in many fluid flows in engineering and environmental applications. A family of steady propagating vortex rings including thin-core rings and Hill's spherical vortex was obtained by Norbury (1973). However, the dynamics of vortex rings in the presence of buoyancy has not been investigated yet in detail. When the core of a ring is thin, we may formulate reduced equations using momentum balance for vortex filaments, but that is not the case for ``fat'' rings. In our study, we use contour dynamics to study the time evolution of axisymmetric vortex rings when the density of the fluid inside the ring differs from that of the ambient. Axisymmetry leads to an almost-conserved material variable when the Boussinesq approximation is made. A set of integro-differential equations is solved numerically for these buoyant vortex rings. The same physical settings are also used to run a DNS code and compare to the results from contour dynamics.

Bismaleimide resins for flame resistant honeycomb sandwich panels

NASA Technical Reports Server (NTRS)

Stenzenberger, H. D.

1978-01-01

Bismaleimide resins are prime candidates for nonflammable aircraft interior panels. Three resin types with different structures and processing characteristics were formulated. Resin M 751 was used to fabricate 100 kg of glass fabric prepregs which were used for the preparation of face sheets for honeycomb sandwich panels. Prepreg characteristics and curing cycles for laminate fabrication are provided. In order to advance beyond the current solvent resin technology for fibre and fabric impregnation, a hot melt solvent-less resin system was prepared and characterized. Preliminary tests were performed to develop a wet bonding process for the fabrication of advanced sandwich honeycomb panels by use of polybismaleimide glass fabric face sheets and polybismaleimide Nomex honeycomb core. B-stage material was used for both the core and the face sheet, providing flatwise tensile properties equivalent to those obtained by the state-of-the-art 3-step process which includes an epoxy adhesive resin.

Tenofovir Containing Thiolated Chitosan Core/Shell Nanofibers: In Vitro and in Vivo Evaluations.

PubMed

Meng, Jianing; Agrahari, Vivek; Ezoulin, Miezan J; Zhang, Chi; Purohit, Sudhaunshu S; Molteni, Agostino; Dim, Daniel; Oyler, Nathan A; Youan, Bi-Botti C

2016-12-05

It is hypothesized that thiolated chitosan (TCS) core/shell nanofibers (NFs) can enhance the drug loading of tenofovir, a model low molecular weight and highly water-soluble drug molecule, and improve its mucoadhesivity and in vivo safety. To test this hypothesis, poly(ethylene oxide) (PEO) core with TCS and polylactic acid (PLA) shell NFs are fabricated by a coaxial electrospinning technique. The morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of the NFs are analyzed using scanning and transmission electron microscopies, liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines and Lactobacilli crispatus, fluorescence imaging and periodic acid colorimetric method, respectively. In vivo safety studies are performed in C57BL/6 mice followed by H&E and immunohistochemical (CD45) staining analysis of genital tract. The mean diameters of PEO, PEO/TCS, and PEO/TCS-PLA NFs are 118.56, 9.95, and 99.53 nm, respectively. The NFs exhibit smooth surface. The drug loading (13%-25%, w/w) increased by 10-fold compared to a nanoparticle formulation due to the application of the electrospinning technique. The NFs are noncytotoxic at the concentration of 1 mg/mL. The PEO/TCS-PLA core/shell NFs mostly exhibit a release kinetic following Weibull model (r 2 = 0.9914), indicating the drug release from a matrix system. The core/shell NFs are 40-60-fold more bioadhesive than the pure PEO based NFs. The NFs are nontoxic and noninflammatory in vivo after daily treatment for up to 7 days. Owing to their enhanced drug loading and preliminary safety profile, the TCS core/shell NFs are promising candidates for the topical delivery of HIV/AIDS microbicides such as tenofovir.

Integrated core-log petrofacies analysis in the construction of a reservoir geomodel: A case study of a mature Mississippian carbonate reservoir using limited data

USGS Publications Warehouse

Bhattacharya, S.; Doveton, J.H.; Carr, T.R.; Guy, W.R.; Gerlach, P.M.

2005-01-01

Small independent operators produce most of the Mississippian carbonate fields in the United States mid-continent, where a lack of integrated characterization studies precludes maximization of hydrocarbon recovery. This study uses integrative techniques to leverage extant data in an Osagian and Meramecian (Mississippian) cherty carbonate reservoir in Kansas. Available data include petrophysical logs of varying vintages, limited number of cores, and production histories from each well. A consistent set of assumptions were used to extract well-level porosity and initial saturations, from logs of different types and vintages, to build a geomodel. Lacking regularly recorded well shut-in pressures, an iterative technique, based on material balance formulations, was used to estimate average reservoir-pressure decline that matched available drillstem test data and validated log-analysis assumptions. Core plugs representing the principal reservoir petrofacies provide critical inputs for characterization and simulation studies. However, assigning plugs among multiple reservoir petrofacies is difficult in complex (carbonate) reservoirs. In a bottom-up approach, raw capillary pressure (Pc) data were plotted on the Super-Pickett plot, and log- and core-derived saturation-height distributions were reconciled to group plugs by facies, to identify core plugs representative of the principal reservoir facies, and to discriminate facies in the logged interval. Pc data from representative core plugs were used for effective pay evaluation to estimate water cut from completions, in infill and producing wells, and guide-selective perforations for economic exploitation of mature fields. The results from this study were used to drill 22 infill wells. Techniques demonstrated here can be applied in other fields and reservoirs. Copyright ?? 2005. The American Association of Petroleum Geologists. All rights reserved.

A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity

PubMed Central

Hasani-Ranjbar, Shirin; Nayebi, Neda; Larijani, Bagher; Abdollahi, Mohammad

2009-01-01

This review focuses on the efficacy and safety of effective herbal medicines in the management of obesity in humans and animals. PubMed, Scopus, Google Scholar, Web of Science, and IranMedex databases were searched up to December 30, 2008. The search terms were “obesity” and (“herbal medicine” or “plant”, “plant medicinal” or “medicine traditional”) without narrowing or limiting search elements. All of the human and animal studies on the effects of herbs with the key outcome of change in anthropometric measures such as body weight and waist-hip circumference, body fat, amount of food intake, and appetite were included. In vitro studies, reviews, and letters to editors were excluded. Of the publications identified in the initial database, 915 results were identified and reviewed, and a total of 77 studies were included (19 human and 58 animal studies). Studies with Cissus quadrangularis (CQ), Sambucus nigra, Asparagus officinalis, Garcinia atroviridis, ephedra and caffeine, Slimax (extract of several plants including Zingiber officinale and Bofutsushosan) showed a significant decrease in body weight. In 41 animal studies, significant weight loss or inhibition of weight gain was found. No significant adverse effects or mortality were observed except in studies with supplements containing ephedra, caffeine and Bofutsushosan. In conclusion, compounds containing ephedra, CQ, ginseng, bitter melon, and zingiber were found to be effective in the management of obesity. Attention to these natural compounds would open a new approach for novel therapeutic and more effective agents. PMID:19575486

Ethno-veterinary control of bovine dermatophilosis and ticks in Zhombe, Njelele and Shamrock resettlement in Zimbabwe.

PubMed

Ndhlovu, Daud Nyosi; Masika, Patrick J

2013-02-01

A structured questionnaire survey was conducted to determine the ethno-veterinary practices and other control methods used by smallholder farmers for the management of bovine dermatophilosis and ticks. A total of 153 farmers were interviewed from Njelele, Zhombe communal and Shamrock resettlement areas. Crop production contributed most to livelihoods (83.2 %) while livestock contributed 9.0 %. Over 90 % of the respondents had attended school up to primary level, with 11.4 % undergoing animal health and husbandry training. Treatment of livestock diseases was practised by 96 % of the farmers, and 49.7 % of these farmers used ethno-veterinary medicines. Across the study sites, dermatophilosis was controlled using the following plants: Cissus quadrangularis (59.7 %), Catunaregam spinosa (10.5 %), Pterocarpus angolensis (10.5 %), Kalanchoe lanceolata (5.3 %), Aloe chabaudii (3.5 %), Cassia abbreviata (1.8 %), Dichrostachys cinerea (1.8 %), Urginea sanguinea (1.8 %), Ximenia caffra (1.8 %) and a plant locally called umfanawembila (1.8 %). Carica papaya and two plants, locally called mugimbura and umdungudungu, were used for tick control, and these were reported once from Njelele communal. Other control methods, besides plants or conventional drugs, were used by 28 % of the farmers for the treatment of dermatophilosis and ticks. Some farmers (14.4 %) claimed that ethno-veterinary medicines performed better than conventional drugs. The study revealed that farmers used ethno-veterinary medical practices for the treatment of dermatophilosis but rarely for tick control.

Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

PubMed

Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

2017-05-19

Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

Co-extrusion as a processing technique to manufacture a dual sustained release fixed-dose combination product.

PubMed

Vynckier, An-Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris

2016-05-01

This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed. Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams.

PubMed

Zhao, Yanjun; Brown, Marc B; Jones, Stuart A

2010-01-04

Nanocarriers may act as useful tools to deliver therapeutic agents to the skin. However, balancing the drug-particle interactions; to ensure adequate drug loading, with the drug-vehicle interactions; to allow efficient drug release, presents a significant challenge using traditional semi-solid vehicles. The aim of this study was to determine how the physicochemical properties of nanoparticles influenced minoxidil release pre and post dose application when formulated as a simple aqueous suspension compared to dynamic hydrofluoroalkane (HFA) foams. Minoxidil loaded lipid nanoparticles (LN, 1.4 mg/ml, 50 nm) and polymeric nanoparticles with a lipid core (PN, 0.6 mg/ml, 260 nm) were produced and suspended in water to produce the aqueous suspensions. These aqueous suspensions were emulsified with HFA using pluronic surfactant to generate the foams. Approximately 60% of the minoxidil loaded into the PN and 80% of the minoxidil loaded into the LN was released into the external aqueous phase 24h after production. Drug permeation was superior from the PN, i.e. it was the particle that retained the most drugs, irrespective of the formulation method. Premature drug release, i.e. during storage, resulted in the performance of the topical formulation being dictated by the thermodynamic activity of the solubilised drug not the particle properties.

Computer-Assisted Drug Formulation Design: Novel Approach in Drug Delivery.

PubMed

Metwally, Abdelkader A; Hathout, Rania M

2015-08-03

We hypothesize that, by using several chemo/bio informatics tools and statistical computational methods, we can study and then predict the behavior of several drugs in model nanoparticulate lipid and polymeric systems. Accordingly, two different matrices comprising tripalmitin, a core component of solid lipid nanoparticles (SLN), and PLGA were first modeled using molecular dynamics simulation, and then the interaction of drugs with these systems was studied by means of computing the free energy of binding using the molecular docking technique. These binding energies were hence correlated with the loadings of these drugs in the nanoparticles obtained experimentally from the available literature. The obtained relations were verified experimentally in our laboratory using curcumin as a model drug. Artificial neural networks were then used to establish the effect of the drugs' molecular descriptors on the binding energies and hence on the drug loading. The results showed that the used soft computing methods can provide an accurate method for in silico prediction of drug loading in tripalmitin-based and PLGA nanoparticulate systems. These results have the prospective of being applied to other nano drug-carrier systems, and this integrated statistical and chemo/bio informatics approach offers a new toolbox to the formulation science by proposing what we present as computer-assisted drug formulation design (CADFD).

Formulation Development of High Strength Gel System and Evaluation on Profile Control Performance for High Salinity and Low Permeability Fractured Reservoir

PubMed Central

Zhang, Chengli; Qu, Guodong

2017-01-01

For the large pores and cracks of reservoirs with low temperatures, high salinity, and low permeability, a new type of high strength gel ABP system is developed in this paper. The defects of conventional gels such as weak gel strength, no gelling, and easy dehydration are overcome under the conditions of low temperature and high salinity. The temperature and salt resistance, plugging characteristics, and EOR of the gel system are studied. Under the condition of 32°C and 29500 mg/L salinity, the ABP system formulation is for 0.3% crosslinking agent A + 0.09% coagulant B + 3500 mg/L polymer solution P. The results show that when the temperature was increased, the delayed crosslinking time of the system was shortened and the gel strength was increased. The good plugging characteristics of the ABP system were reached, and the plugging rate was greater than 99% in cores with different permeability. A good profile control performance was achieved, and the recovery rate was improved by 19.27% on the basis of water flooding. In the practical application of the gel system, the salinity of formation water and the permeability of fractures are necessary to determine the appropriate formulation. PMID:28592971

Formulation and evaluation of metoclopramide solid lipid nanoparticles for rectal suppository.

PubMed

Mohamed, Radwa A; Abass, Haidy A; Attia, Mohamed A; Heikal, Ola A

2013-11-01

The purpose of this study was to formulate and characterize metoclopramide solid lipid nanoparticles (MCP-SLNs) and incorporating it into suppository bases for treatment of nausea and vomiting, produced with chemotherapeutic agents, using one dose per day. MCP-SLNs was prepared using high shear homogenization (hot homogenization) technique using different surfactants (tween 80, poloxamer 407, poloxamer 188 and cremophore) in two different concentrations (2.5% and 5%) then solid lipid nanoparticle (SLN), whose release percentage above 50%, was incorporated into suppository for treatment of nausea and vomiting. The prepared SLN and suppositories were then evaluated and characterized. Formulation of poloxamer 407 with compritol and drug (F9) produced highest in-vitro % release (80%). Transmission electron microscopy showed that SLN had round and spherical shape in form of solid dispersion or drug-enriched core. Particle size analysis of SLN showed a size range of 24.99-396.8 nm. Negative zeta potential proves complete drug entrapment. In-vivo study of MCP-SLN suppositories produced the same %GE as the market metoclopramide (MCP) suppository (Primperan) with sustained release effect. MCP-SLN suppositories (formula F) can reverse decrease in %GE because of emesis with sustained release effect. So it succeeded to be an alternative to MCP suppositories with no multiple dosing. © 2013 Royal Pharmaceutical Society.

Poly(dimethylsiloxane) coatings for controlled drug release--polymer modifications.

PubMed

Schulze Nahrup, J; Gao, Z M; Mark, J E; Sakr, A

2004-02-11

Modifications of endhydroxylated poly(dimethylsiloxane) (PDMS) formulations were studied for their ability to be applied onto tablet cores in a spray-coating process and to control drug release in zero-order fashion. Modifications of the crosslinker from the most commonly used tetraethylorthosilicate (TEOS) to the trifunctional 3-(2,3-epoxypropoxy)propyltrimethoxysilane (SIG) and a 1:1 mixture of the two were undertaken. Addition of methylpolysiloxane-copolymers were studied. Lactose, microcrystalline cellulose (MCC) and polyethylene glycol 8000 (PEG) were the channeling agents applied. The effects on dispersion properties were characterized by particle size distribution and viscosity. Mechanical properties of resulting free films were studied to determine applicability in a pan-coating process. Release of hydrochlorothiazide (marker drug) was studied from tablets coated in a lab-size conventional coating pan. All dispersions were found suitable for a spray-coating process. Preparation of free films showed that copolymer addition was not possible due to great decline in mechanical properties. Tablets coated with formulations containing PEG were most suitable to control drug release, at only 5% coating weight. Constant release rates could be achieved for formulations with up to 25% PEG; higher amounts resulted in a non-linear release pattern. Upon adding 50% PEG, a drug release of 63% over 24 h could be achieved.

Optmization and Fabrication Studies in the Development of Structurally Integrated Thermal Protection System Technology

NASA Technical Reports Server (NTRS)

Stephens, Craig A.

2009-01-01

NASA HYP M&S is pursuing the development of SITPS: 1) Working with HYP MDAO to formulate methodology to incorporate SITPS into hypersonic vehicle design trades. 2) SITPS-0 to SITPS-1 (FY10): a) Manufacturing development and weight reduction (5.8 to 3.1 lb(sub m)/sq ft); b) Structural testing to mature SITPS model. 3) SITPS-2 (FY11): a) Focus on panel closeout, panel-to-panel load transfer, and panel curvature. 4) Extend fabrication technology to include alternate cores and insulations (FY12).

Crystallization of dense neutron matter

NASA Technical Reports Server (NTRS)

Canuto, V.; Chitre, S. M.

1974-01-01

The equation of state for cold neutron matter at high density is studied in the t-matrix formulation, and it is shown that energetically it is convenient to have neutrons in a crystalline configuration rather than in a liquid state for values of the density exceeding 1600 Tg/cu cm. The study of the mechanical properties indicates that the system is stable against shearing stresses. A solid core in the deep interior of heavy neutron stars appears to offer the most plausible explanation of speed-ups observed in the Vela pulsar.

Numerical parametric studies of spray combustion instability

NASA Technical Reports Server (NTRS)

Pindera, M. Z.

1993-01-01

A coupled numerical algorithm has been developed for studies of combustion instabilities in spray-driven liquid rocket engines. The model couples gas and liquid phase physics using the method of fractional steps. Also introduced is a novel, efficient methodology for accounting for spray formation through direct solution of liquid phase equations. Preliminary parametric studies show marked sensitivity of spray penetration and geometry to droplet diameter, considerations of liquid core, and acoustic interactions. Less sensitivity was shown to the combustion model type although more rigorous (multi-step) formulations may be needed for the differences to become apparent.

Multiphysics Thrust Chamber Modeling for Nuclear Thermal Propulsion

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Cheng, Gary; Chen, Yen-Sen

2006-01-01

The objective of this effort is to develop an efficient and accurate thermo-fluid computational methodology to predict environments for a solid-core, nuclear thermal engine thrust chamber. The computational methodology is based on an unstructured-grid, pressure-based computational fluid dynamics formulation. A two-pronged approach is employed in this effort: A detailed thermo-fluid analysis on a multi-channel flow element for mid-section corrosion investigation; and a global modeling of the thrust chamber to understand the effect of heat transfer on thrust performance. Preliminary results on both aspects are presented.

On numerical solution of the Schrödinger equation: the shooting method revisited

NASA Astrophysics Data System (ADS)

Indjin, D.; Todorović, G.; Milanović, V.; Ikonić, Z.

1995-09-01

An alternative formulation of the "shooting" method for a numerical solution of the Schrödinger equation is described for cases of general asymmetric one-dimensional potential (planar geometry), and spherically symmetric potential. The method relies on matching the asymptotic wavefunctions and the potential core region wavefunctions, in course of finding bound states energies. It is demonstrated in the examples of Morse and Kratzer potentials, where a high accuracy of the calculated eigenvalues is found, together with a considerable saving of the computation time.

The development of a core syllabus for the teaching of oral anatomy, histology, and embryology to dental students via an international 'Delphi Panel'.

PubMed

Moxham, Bernard John; McHanwell, Stephen; Berkovitz, Barry

2018-03-01

The formulation of core syllabuses for the biomedical sciences within medical and dental courses is partially driven by the need to cope with decreased time allocations for these subjects as a result of major curricular changes taking place worldwide. There is also a requirement to deal with the request for increased clinical relevance. In response to such demands, the International Federation of Associations of Anatomists (IFAA) is devising core syllabuses for the anatomical sciences relating to the education and training of both scientific and clinical professions. The process initially involves using Delphi Panels consisting of a team of anatomists, scientists, and clinicians who evaluate syllabus content in detail and accord each element/topic 'essential,' 'important,' 'acceptable,' or 'not required' status. Their conjectures, published on the IFAA website, provide merely a framework to enable other stakeholders to comment. The approach is international in scope, is conceptually 'democratic,' and is developmentally fluid in being readily available for amendment. The aim is to set internationally recognized standards and thus to provide guidelines concerning anatomical knowledge when engaged in course development. This article presents the deliberations of an IFAA Delphi Panel into a core syllabus for oral anatomy, histology, and embryology within the dental curriculum. Clin. Anat. 31:231-249, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The Utilization of the Microflora Indigenous to and Present in Oil-Bearing Formations to Selectively Plug the More Porous Zones Thereby Increasing Oil Recovery During Waterflooding

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

Brown, Lewis R.; Stephens, James O.; Vadie, Alex A.

The objective of this work is to demonstrate the use of indigenous microbes as a method of profile control in waterfloods. It is expected that as the microbial population is induced to increase, that the expanded biomass will selectively block the more permeable zones of the reservoir thereby forcing injection water to flow through the less permeable zones which will result in improved sweep efficiency. This increase in microbial population will be accomplished by injecting a nutrient solution into four injectors. Four other injectors will act as control wells. During Phase I, two wells will be cored through the zonemore » of interest. The core will be subjected to special core analyses in order to arrive at the optimum nutrient formulation. During Phase II, nutrient injection will begin, the results monitored, and adjustments to the nutrient composition made, if necessary. Phase II also will include the drilling of three wells for post-mortem core analysis. Phase III will focus on technology transfer of the results. It should be pointed out that one expected outcome of this new technology will be a prolongation of economical waterflooding operations, i.e. economical oil recovery should continue for much longer periods in the producing wells subjected to this selective plugging technique.« less

Surface passivation and self-regulated shell growth in selective area-grown GaN-(Al,Ga)N core-shell nanowires.

PubMed

Hetzl, Martin; Winnerl, Julia; Francaviglia, Luca; Kraut, Max; Döblinger, Markus; Matich, Sonja; Fontcuberta I Morral, Anna; Stutzmann, Martin

2017-06-01

The large surface-to-volume ratio of GaN nanowires implicates sensitivity of the optical and electrical properties of the nanowires to their surroundings. The implementation of an (Al,Ga)N shell with a larger band gap around the GaN nanowire core is a promising geometry to seal the GaN surface. We investigate the luminescence and structural properties of selective area-grown GaN-(Al,Ga)N core-shell nanowires grown on Si and diamond substrates. While the (Al,Ga)N shell allows a suppression of yellow defect luminescence from the GaN core, an overall intensity loss due to Si-related defects at the GaN/(Al,Ga)N interface has been observed in the case of Si substrates. Scanning transmission electron microscopy measurements indicate a superior crystal quality of the (Al,Ga)N shell along the nanowire side facets compared to the (Al,Ga)N cap at the top facet. A nucleation study of the (Al,Ga)N shell reveals a pronounced bowing of the nanowires along the c-direction after a short deposition time which disappears for longer growth times. This is assigned to an initially inhomogeneous shell nucleation. A detailed study of the proceeding shell growth allows the formulation of a strain-driven self-regulating (Al,Ga)N shell nucleation model.

Solubilization Behavior of Polyene Antibiotics in Nanomicellar System: Insights from Molecular Dynamics Simulation of the Amphotericin B and Nystatin Interactions with Polysorbate 80.

PubMed

Mobasheri, Meysam; Attar, Hossein; Rezayat Sorkhabadi, Seyed Mehdi; Khamesipour, Ali; Jaafari, Mahmoud Reza

2015-12-24

Amphotericin B (AmB) and Nystatin (Nys) are the drugs of choice for treatment of systemic and superficial mycotic infections, respectively, with their full clinical potential unrealized due to the lack of high therapeutic index formulations for their solubilized delivery. In the present study, using a coarse-grained (CG) molecular dynamics (MD) simulation approach, we investigated the interaction of AmB and Nys with Polysorbate 80 (P80) to gain insight into the behavior of these polyene antibiotics (PAs) in nanomicellar solution and derive potential implications for their formulation development. While the encapsulation process was predominantly governed by hydrophobic forces, the dynamics, hydration, localization, orientation, and solvation of PAs in the micelle were largely controlled by hydrophilic interactions. Simulation results rationalized the experimentally observed capability of P80 in solubilizing PAs by indicating (i) the dominant kinetics of drugs encapsulation over self-association; (ii) significantly lower hydration of the drugs at encapsulated state compared with aggregated state; (iii) monomeric solubilization of the drugs; (iv) contribution of drug-micelle interactions to the solubilization; (v) suppressed diffusivity of the encapsulated drugs; (vi) high loading capacity of the micelle; and (vii) the structural robustness of the micelle against drug loading. Supported from the experimental data, our simulations determined the preferred location of PAs to be the core-shell interface at the relatively shallow depth of 75% of micelle radius. Deeper penetration of PAs was impeded by the synergistic effects of (i) limited diffusion of water; and (ii) perpendicular orientation of these drug molecules with respect to the micelle radius. PAs were solvated almost exclusively in the aqueous poly-oxyethylene (POE) medium due to the distance-related lack of interaction with the core, explaining the documented insensitivity of Nys solubilization to drug-core compatibility in detergent micelles. Based on the obtained results, the dearth of water at interior sites of micelle and the large lateral occupation space of PAs lead to shallow insertion, broad radial distribution, and lack of core interactions of the amphiphilic drugs. Hence, controlled promotion of micelle permeability and optimization of chain crowding in palisade layer may help to achieve more efficient solubilization of the PAs.

Core concepts of human rights and inclusion of vulnerable groups in the mental health policies of Malawi, Namibia, and Sudan

PubMed Central

2013-01-01

Background One of the most crucial steps towards delivering judicious and comprehensive mental health care is the formulation of a policy and plan that will navigate mental health systems. For policy-makers, the challenges of a high-quality mental health system are considerable: the provision of mental health services to all who need them, in an equitable way, in a mode that promotes human rights and health outcomes. Method EquiFrame, a novel policy analysis framework, was used to evaluate the mental health policies of Malawi, Namibia, and Sudan. The health policies were assessed in terms of their coverage of 21 predefined Core Concepts of human rights (Core Concept Coverage), their stated quality of commitment to said Core Concepts (Core Concept Quality), and their inclusion of 12 Vulnerable Groups (Vulnerable Group Coverage). In relation to these summary indices, each policy was also assigned an Overall Summary Ranking, in terms of it being of High, Moderate, or Low quality. Results Substantial variability was identified across EquiFrame’s summary indices for the mental health policies of Malawi, Namibia, and Sudan. However, all three mental health policies scored high on Core Concept Coverage. Particularly noteworthy was the Sudanese policy, which scored 86% on Core Concept Coverage, and 92% on Vulnerable Group Coverage. Particular deficits were evident in the Malawian mental health policy, which scored 33% on Vulnerable Group Coverage and 47% on Core Concept Quality, and was assigned an Overall Summary Ranking of Low accordingly. The Overall Summary Ranking for the Namibian Mental Health Policy was High; for the Sudanese Mental Health Policy was Moderate; and for the Malawian Mental Health Policy was Low. Conclusions If human rights and equity underpin policy formation, it is more likely that they will be inculcated in health service delivery. EquiFrame may provide a novel and valuable tool for mental health policy analysis in relation to core concepts of human rights and inclusion of vulnerable groups, a key practical step in the successful realization of the Millennium Development Goals. PMID:23406583

Application of Genetic Algorithm for Discovery of Core Effective Formulae in TCM Clinical Data

PubMed Central

Yang, Ming; Poon, Josiah; Wang, Shaomo; Jiao, Lijing; Poon, Simon; Cui, Lizhi; Chen, Peiqi; Sze, Daniel Man-Yuen; Xu, Ling

2013-01-01

Research on core and effective formulae (CEF) does not only summarize traditional Chinese medicine (TCM) treatment experience, it also helps to reveal the underlying knowledge in the formulation of a TCM prescription. In this paper, CEF discovery from tumor clinical data is discussed. The concepts of confidence, support, and effectiveness of the CEF are defined. Genetic algorithm (GA) is applied to find the CEF from a lung cancer dataset with 595 records from 161 patients. The results had 9 CEF with positive fitness values with 15 distinct herbs. The CEF have all had relative high average confidence and support. A herb-herb network was constructed and it shows that all the herbs in CEF are core herbs. The dataset was divided into CEF group and non-CEF group. The effective proportions of former group are significantly greater than those of latter group. A Synergy index (SI) was defined to evaluate the interaction between two herbs. There were 4 pairs of herbs with high SI values to indicate the synergy between the herbs. All the results agreed with the TCM theory, which demonstrates the feasibility of our approach. PMID:24288577

Generalized Higher Order Orthogonal Iteration for Tensor Learning and Decomposition.

PubMed

Liu, Yuanyuan; Shang, Fanhua; Fan, Wei; Cheng, James; Cheng, Hong

2016-12-01

Low-rank tensor completion (LRTC) has successfully been applied to a wide range of real-world problems. Despite the broad, successful applications, existing LRTC methods may become very slow or even not applicable for large-scale problems. To address this issue, a novel core tensor trace-norm minimization (CTNM) method is proposed for simultaneous tensor learning and decomposition, and has a much lower computational complexity. In our solution, first, the equivalence relation of trace norm of a low-rank tensor and its core tensor is induced. Second, the trace norm of the core tensor is used to replace that of the whole tensor, which leads to two much smaller scale matrix TNM problems. Finally, an efficient alternating direction augmented Lagrangian method is developed to solve our problems. Our CTNM formulation needs only O((R N +NRI)log(√{I N })) observations to reliably recover an N th-order I×I×…×I tensor of n -rank (r,r,…,r) , compared with O(rI N-1 ) observations required by those tensor TNM methods ( I > R ≥ r ). Extensive experimental results show that CTNM is usually more accurate than them, and is orders of magnitude faster.

Dynamic characteristics of a novel damped outrigger system

NASA Astrophysics Data System (ADS)

Tan, Ping; Fang, Chuangjie; Zhou, Fulin

2014-06-01

This paper presents exact analytical solutions for a novel damped outrigger system, in which viscous dampers are vertically installed between perimeter columns and the core of a high-rise building. An improved analytical model is developed by modeling the effect of the damped outrigger as a general rotational spring acting on a Bernoulli-Euler beam. The equivalent rotational spring stiffness incorporating the combined effects of dampers and axial stiffness of perimeter columns is derived. The dynamic stiffness method (DSM) is applied to formulate the governing equation of the damped outrigger system. The accuracy and efficiency are verified in comparison with those obtained from compatibility equations and boundary equations. Parametric analysis of three non-dimensional factors is conducted to evaluate the influences of various factors, such as the stiffness ratio of the core to the beam, position of the damped outrigger, and the installed damping coefficient. Results show that the modal damping ratio is significantly influenced by the stiffness ratio of the core to the column, and is more sensitive to damping than the position of the damped outrigger. The proposed analytical model in combination with DSM can be extended to the study of structures with more outriggers.

Polypeptide nanogels with hydrophobic moieties in the cross-linked ionic cores: Synthesis, characterization and implications for anticancer drug delivery

PubMed Central

Kim, Jong Oh; Oberoi, Hardeep S.; Desale, Swapnil; Kabanov, Alexander V.; Bronich, Tatiana K.

2014-01-01

Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(L-glutamic acid), hydrophobically modified with L-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70 nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics. PMID:23998716

A statistical model of the human core-temperature circadian rhythm

NASA Technical Reports Server (NTRS)

Brown, E. N.; Choe, Y.; Luithardt, H.; Czeisler, C. A.

2000-01-01

We formulate a statistical model of the human core-temperature circadian rhythm in which the circadian signal is modeled as a van der Pol oscillator, the thermoregulatory response is represented as a first-order autoregressive process, and the evoked effect of activity is modeled with a function specific for each circadian protocol. The new model directly links differential equation-based simulation models and harmonic regression analysis methods and permits statistical analysis of both static and dynamical properties of the circadian pacemaker from experimental data. We estimate the model parameters by using numerically efficient maximum likelihood algorithms and analyze human core-temperature data from forced desynchrony, free-run, and constant-routine protocols. By representing explicitly the dynamical effects of ambient light input to the human circadian pacemaker, the new model can estimate with high precision the correct intrinsic period of this oscillator ( approximately 24 h) from both free-run and forced desynchrony studies. Although the van der Pol model approximates well the dynamical features of the circadian pacemaker, the optimal dynamical model of the human biological clock may have a harmonic structure different from that of the van der Pol oscillator.

Application of quality by design (QbD) to formulation and processing of naproxen pellets by extrusion-spheronization.

PubMed

Wang, Junlin; Kan, Shuling; Chen, Tong; Liu, Jianping

2015-03-01

The aim of this research was to apply quality by design (QbD) to the development of naproxen loaded core pellets which can be used as the potential core for colon-specific pellets. In the early stages of this study, prior knowledge and preliminary studies were systematically incorporated into the risk assessment using failure mode and effect analysis (FMEA) and fishbone diagram. Then Plackett-Burman design was used to screen eight potential high risk factors (spheronization speed, spheronization time, extrusion speed, drying method, CCMC-Na concentration, lactose concentration, water concentration and Tween 80 concentration) obtained from the above risk assessment. It was discovered that out of the eight potential high risk factors only three factors (spheronization speed, extrusion speed and CCMC-Na concentration) had significant effects on the quality of the pellets. This allowed the use of Box-Behnken design (BBD) to fully elucidate the relationship between the variables and critical quality attribute (CQA). Finally, the final control space was established within which the quality of the pellets can meet the requirement of colon-specific drug delivery system. This study demonstrated that naproxen loaded core pellets were successfully designed using QbD principle.

Unifying Inference of Meso-Scale Structures in Networks.

PubMed

Tunç, Birkan; Verma, Ragini

2015-01-01

Networks are among the most prevalent formal representations in scientific studies, employed to depict interactions between objects such as molecules, neuronal clusters, or social groups. Studies performed at meso-scale that involve grouping of objects based on their distinctive interaction patterns form one of the main lines of investigation in network science. In a social network, for instance, meso-scale structures can correspond to isolated social groupings or groups of individuals that serve as a communication core. Currently, the research on different meso-scale structures such as community and core-periphery structures has been conducted via independent approaches, which precludes the possibility of an algorithmic design that can handle multiple meso-scale structures and deciding which structure explains the observed data better. In this study, we propose a unified formulation for the algorithmic detection and analysis of different meso-scale structures. This facilitates the investigation of hybrid structures that capture the interplay between multiple meso-scale structures and statistical comparison of competing structures, all of which have been hitherto unavailable. We demonstrate the applicability of the methodology in analyzing the human brain network, by determining the dominant organizational structure (communities) of the brain, as well as its auxiliary characteristics (core-periphery).

Development of biodegradable hyperbranched core-multishell nanocarriers for efficient topical drug delivery.

PubMed

Du, Fang; Hönzke, Stefan; Neumann, Falko; Keilitz, Juliane; Chen, Wei; Ma, Nan; Hedtrich, Sarah; Haag, Rainer

2016-11-28

The topical application of drugs allows for a local application in skin disease and can reduce side effects. Here we present biodegradable core-multishell (CMS) nanocarriers which are composed of a hyperbranched polyglycerol core functionalized with diblock copolymers consisting of polycaprolactone (PCL) and poly(ethylene glycol) (mPEG) as the outer shell. The anti-inflammatory drug Dexamethasone (Dexa) was loaded into these CMS nanocarriers. DLS results suggested that Dexa loaded nanoparticles mostly act as a unimolecular carrier system. With longer PCL segments, a better transport capacity is observed. In vitro skin permeation studies showed that CMS nanocarriers could improve the Nile red penetration through the skin by up to 7 times, compared to a conventional cream formulation. Interestingly, covalently FITC-labeled CMS nanocarriers remain in the stratum corneum layer. This suggests the enhancement is due to the release of cargo after being transported into the stratum corneum by the CMS nanocarriers. In addition, the hPG-PCL-mPEG CMS nanocarriers exhibited good stability, low cytotoxicity, and their production can easily be scaled up, which makes them promising nanocarriers for topical drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanomedicines for Inflammatory Arthritis: Head-To-Head Comparison of Glucocorticoid-Containing Polymers, Micelles and Liposomes

PubMed Central

Crielaard, Bart J.; Dusad, Anand; Lele, Subodh M.; Rijcken, Cristianne J. F.; Metselaar, Josbert M; Kostková, Hana; Etrych, Tomáš; Ulbrich, Karel; Kiessling, Fabian; Mikuls, Ted R.; Hennink, Wim E.; Storm, Gert; Lammers, Twan; Wang, Dong

2014-01-01

As an emerging research direction, nanomedicine has been increasingly utilized to treat inflammatory diseases. In this head-to-head comparison study, four established nanomedicine formulations of dexamethasone, including liposomes (L-Dex), core-crosslinked micelles (M-Dex), slow releasing polymeric prodrugs (P-Dex-slow) and fast releasing polymeric prodrugs (P-Dex-fast), were evaluated in an adjuvant-induced arthritis rat model with an equivalent dose treatment design. It was found that after a single i.v. injection, the formulations with the slower drug release kinetics (i.e. M-Dex and P-Dex-slow) maintained longer duration of therapeutic activity than those with relatively faster drug release kinetics, resulting in better joint protection. This finding will be instructional in the future development and optimization of nanomedicines for the clinical management of rheumatoid arthritis. The outcome of this study also illustrates the value of such head-to-head comparison studies in translational nanomedicine research. PMID:24341611

Formulation and evaluation of press coated tablets for pulsatile drug delivery using hydrophilic and hydrophobic polymers.

PubMed

Rane, Ashish Babulal; Gattani, Surendra Ganeshlal; Kadam, Vinayak Dinkar; Tekade, Avinash Ramrao

2009-11-01

The aim of present investigation was to develop press coated tablet for pulsatile drug delivery of ketoprofen using hydrophilic and hydrophobic polymers. The drug delivery system was designed to deliver the drug at such a time when it could be most needful to patient of rheumatoid arthritis. The press coated tablets containing ketoprofen in the inner core was formulated with an outer shell by different weight ratio of hydrophobic polymer (micronized ethyl cellulose powder) and hydrophilic polymers (glycinemax husk or sodium alginate). The release profile of press coated tablet exhibited a lag time followed by burst release, in which outer shell ruptured into two halves. Authors also investigated factors influencing on lag time such as particle size and viscosity of ethyl cellulose, outer coating weight and paddle rpm. The surface morphology of the tablet was examined by a scanning electron microscopy. Differential scanning calorimeter and Fourier transformed infrared spectroscopy study showed compatibility between ketoprofen and coating material.

Gel in core carbosomes as novel ophthalmic vehicles with enhanced corneal permeation and residence.

PubMed

Moustafa, Mona A; El-Refaie, Wessam M; Elnaggar, Yosra S R; Abdallah, Ossama Y

2018-05-17

Carbopol is a good bio-adhesive polymer that increases the residence time in the eye. However, the effect of blinking and lacrimation still reduce the amount of polymer and the incorporated drug available for bioadhesion. Gel-core liposomes are advanced systems offering benefits making it a good tool for improved ocular drug delivery and residence time. Incorporation of carbopol in gel-core liposomes and their potential in ocular delivery have not so far been investigated. Fluconazole (FLZ) was selected as a challenging important ocular antifungal suffering from poor corneal permeation and short residence time. In this study, gel-core carbosomes have been elaborated as novel carbopol-based ophthalmic vehicles to solve ocular delivery obstacles of FLZ and to sustain its effect. Full in vitro appraisal was performed considering gel-core structure, entrapment efficiency, particle size and stability of the vesicles as quality attributes. Structure elucidation of the nanocarrier was performed using optical, polarizing and transmission electron microscopy before and after Triton-X100 addition. Ex-vivo ocular permeation and in vivo performance were investigated on male albino rabbits. Optimized formulation (CBS5) showed gel-core structure, nanosize (339.00 ± 5.50 nm) and not defined before (62.00% ± 1.73) entrapment efficiency. Cumulative amount of CBS5 permeated ex-vivo after 6 h, was 2.43 and 3.43 folds higher than that of conventional liposomes and FLZ suspension, respectively. In-vivo corneal permeation of CBS5 showed significantly higher AUC0-24 h (487.12 ± 74.80) compared to that of FLZ suspension (204.34 ± 7.46) with longer residence time in the eye lasts for more than 18 h. In conclusion, novel gel-core carbosomes could successfully be used as a promising delivery system for chronic ocular diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Relationships between core factors of knowledge management in hospital nursing organisations and outcomes of nursing performance.

PubMed

Lee, Eun Ju; Kim, Hong Soon; Kim, Hye Young

2014-12-01

The study was conducted to investigate the levels of implementation of knowledge management and outcomes of nursing performance, to examine the relationships between core knowledge management factors and nursing performance outcomes and to identify core knowledge management factors affecting these outcomes. Effective knowledge management is very important to achieve strong organisational performance. The success or failure of knowledge management depends on how effectively an organisation's members share and use their knowledge. Because knowledge management plays a key role in enhancing nursing performance, identifying the core factors and investigating the level of knowledge management in a given hospital are priorities to ensure a high quality of nursing for patients. The study employed a descriptive research procedure. The study sample consisted of 192 nurses registered in three large healthcare organisations in South Korea. The variables demographic characteristics, implementation of core knowledge management factors and outcomes of nursing performance were examined and analysed in this study. The relationships between the core knowledge management factors and outcomes of nursing performance as well as the factors affecting the performance outcomes were investigated. A knowledge-sharing culture and organisational learning were found to be core factors affecting nursing performance. The study results provide basic data that can be used to formulate effective knowledge management strategies for enhancing nursing performance in hospital nursing organisations. In particular, prioritising the adoption of a knowledge-sharing culture and organisational learning in knowledge management systems might be one method for organisations to more effectively manage their knowledge resources and thus to enhance the outcomes of nursing performance and achieve greater business competitiveness. The study results can contribute to the development of effective and efficient knowledge management systems and strategies for enhancing knowledge-sharing culture and organisational learning that can improve both the productivity and competitiveness of healthcare organisations. © 2014 John Wiley & Sons Ltd.

Polymeric nanocarriers for transport modulation across the pulmonary epithelium: dendrimers, polymeric nanoparticles, and their nanoblends.

PubMed

Bharatwaj, Balaji; Dimovski, Radovan; Conti, Denise S; da Rocha, Sandro R P

2014-05-01

The purpose of this study was to (a) Determine the cellular transport and uptake of amine-terminated generation 3 (G3) poly(amido amine) (PAMAM) dendrimers across an in vitro model of the pulmonary epithelium, and the ability to modulate their transport by forming nanoblends of the dendrimers with biodegradable solid polymeric nanoparticles (NPs) and (b) to formulate dendrimer nanocarriers in portable oral inhalation devices and evaluate their aerosol characteristics. To that end, fluorescein isothiocyanate (FITC)-labeled G3 PAMAM dendrimer nanocarriers (DNCs) were synthesized, and also encapsulated within poly lactide-co-glycolide nanoparticles (NPs). Transport and uptake of both DNCs encapsulated within NPs (nanoblends) and unencapsulated DNCs were tracked across polarized monolayers of airway epithelial cells, Calu-3. DNCs were also formulated as core-shell microparticles in pressurized metered-dose inhalers (pMDIs) and their aerodynamic properties evaluated by Andersen cascade impaction. The apparent permeability of DNCs across the airway epithelial model was similar to that of a paracellular marker of comparable molar mass--order of 10(-7) cm s(-1). The transport and cellular internalization of the DNCs can be modulated by formulating them as nanoblends. The transport of the DNCs across the lung epithelium was completely suppressed within the time of the experiment (5 h) when formulated as blends. The encapsulation also prevents saturation of the cellular internalization profile. Nanoblending may be a potential strategy to modulate the rate of transport and cellular uptake of DNCs, and thus be used as a design strategy to achieve enhanced local or systemic drug delivery.

Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers.

PubMed

Niu, Zhigao; Tedesco, Erik; Benetti, Federico; Mabondzo, Aloïse; Montagner, Isabella Monia; Marigo, Ilaria; Gonzalez-Touceda, David; Tovar, Sulay; Diéguez, Carlos; Santander-Ortega, Manuel J; Alonso, María J

2017-10-10

The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected based on their penetration enhancing properties. Insulin was adopted as a model peptide to assess the performance of the NCs. After screening numerous formulation variables, including different oils and surfactants, we defined a composition consisting of oleic acid, sodium deoxycholate (SDC) and Span 80. This selected NCs composition, produced by the solvent displacement technique, exhibited the following key features: (i) an average size of 180nm and a low polydispersity (0.1), (ii) a high insulin association efficacy (80-90% AE), (iii) a good colloidal stability upon incubation in simulated intestinal fluids (SIF, FaSSIF-V2, FeSSIF-V2), and (iv) the capacity to control the release of the associated insulin for >4h. Furthermore, using the Caco-2 model cell line, PARG nanocapsules were able to interact with the enterocytes, and reversibly modify the TEER of the monolayer. Both cell adhesion and membrane permeabilization could account for the pronounced transport of the NCs-associated insulin (3.54%). This improved interaction was also visualized by confocal fluorescent microscopy following oral administration of PARG nanocapsulesto mice. Finally, in vivo efficacy studies performed in normoglycemic rats showed a significant decrease in their plasma glucose levels after treatment. In conclusion, here we disclose key formulation elements for making possible the oral administration of peptides. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Measurement of Global Precipitation

NASA Technical Reports Server (NTRS)

Flaming, Gilbert Mark

2004-01-01

The Global Precipitation Measurement (GPM) Program is an international cooperative effort whose objectives are to (a) obtain increased understanding of rainfall processes, and (b) make frequent rainfall measurements on a global basis. The National Aeronautics and Space Administration (NASA) of the United States and the Japanese Aviation and Exploration Agency (JAXA) have entered into a cooperative agreement for the formulation and development of GPM. This agreement is a continuation of the partnership that developed the highly successful Tropical Rainfall Measuring Mission (TRMM) that was launched in November 1997; this mission continues to provide valuable scientific and meteorological information on rainfall and the associated processes. International collaboration on GPM from other space agencies has been solicited, and discussions regarding their participation are currently in progress. NASA has taken lead responsibility for the planning and formulation of GPM, Key elements of the Program to be provided by NASA include a Core satellite bus instrumented with a multi-channel microwave radiometer, a Ground Validation System and a ground-based Precipitation Processing System (PPS). JAXA will provide a Dual-frequency Precipitation Radar for installation on the Core satellite and launch services. Other United States agencies and international partners may participate in a number of ways, such as providing rainfall measurements obtained from their own national space-borne platforms, providing local rainfall measurements to support the ground validation activities, or providing hardware or launch services for GPM constellation spacecraft. This paper will present an overview of the current planning for the GPM Program, and discuss in more detail the status of the lead author's primary responsibility, development and acquisition of the GPM Microwave Imager.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico.

PubMed

Larenas Linnemann, D E S; Del Río Navarro, B E; Luna Pech, J A; Romero Lombard, J; Villaverde Rosas, J; Cano Salas, M C; Fernández Vega, M; Ortega Martell, J A; López Estrada, E C; Mayorga Butrón, J L; Salas Hernández, J; Vázquez García, J C; Ortiz Aldana, I; Vargas Becerra, M H; Bedolla Barajas, M; Rodríguez Pérez, N; Aguilar Aranda, A; Jiménez González, C A; García Bolaños, C; Garrido Galindo, C; Mendoza Hernández, D A; Mendoza López, E; López Pérez, G; Wakida Kuzonoki, G H; Ruiz Gutiérrez, H H; León Molina, H; Martínez de la Lanza, H; Stone Aguilar, H; Gómez Vera, J; Olvera Salinas, J; Oyoqui Flores, J J; Gálvez Romero, J L; Lozano Saenz, J S; Salgado Gama, J I; Jiménez Chobillon, M A; García Avilés, M A; Guinto Balanzar, M P; Medina Ávalos, M A; Camargo Angeles, R; García Torrentera, R; Toral Freyre, S; Montes Narvaez, G; Solorio Gómez, H; Rosas Peña, J; Romero Tapia, S J; Reyes Herrera, A; Cuevas Schacht, F; Esquer Flores, J; Sacre Hazouri, J A; Compean Martínez, L; Medina Sánchez, P J; Garza Salinas, S; Baez Loyola, C; Romero Alvarado, I; Miguel Reyes, J L; Huerta Espinosa, L E; Correa Flores, M Á; Castro Martínez, R

With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma. Copyright © 2017. Published by Elsevier España, S.L.U.

Analysis of Monolith Cores from an Engineering Scale Demonstration of a Prospective Cast Stone Process

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

Crawford, C. L.; Cozzi, A. D.; Hill, K. A.

2016-06-01

The primary disposition path of Low Activity Waste (LAW) at the DOE Hanford Site is vitrification. A cementitious waste form is one of the alternatives being considered for the supplemental immobilization of the LAW that will not be treated by the primary vitrification facility. Washington River Protection Solutions (WRPS) has been directed to generate and collect data on cementitious or pozzolanic waste forms such as Cast Stone. This report documents the coring and leach testing of monolithic samples cored from an engineering-scale demonstration (ES Demo) with non-radioactive simulants. The ES Demo was performed at SRNL in October of 2013 usingmore » the Scaled Continuous Processing Facility (SCPF) to fill an 8.5 ft. diameter x 3.25 ft. high container with simulated Cast Stone grout. The Cast Stone formulation was chosen from the previous screening tests. Legacy salt solution from previous Hanford salt waste testing was adjusted to correspond to the average LAW composition generated from the Hanford Tank Waste Operation Simulator (HTWOS). The dry blend materials, ordinary portland cement (OPC), Class F fly ash, and ground granulated blast furnace slag (GGBFS or BFS), were obtained from Lafarge North America in Pasco, WA. In 2014 core samples originally obtained approximately six months after filling the ES Demo were tested along with bench scale molded samples that were collected during the original pour. A latter set of core samples were obtained in late March of 2015, eighteen months after completion of the original ES Demo. Core samples were obtained using a 2” diameter x 11” long coring bit. The ES Demo was sampled in three different regions consisting of an outer ring, a middle ring and an inner core zone. Cores from these three lateral zones were further segregated into upper, middle and lower vertical segments. Monolithic core samples were tested using the Environmental Protection Agency (EPA) Method 1315, which is designed to provide mass transfer rates (release rates) of inorganic analytes contained in monolithic material under diffusion controlled release conditions as a function of leaching time. Compressive strength measurements and drying tests were also performed on the 2015 samples. Leachability indices reported are based on analyte concentrations determined from dissolution of the dried samples.« less

Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.

PubMed

Cherniakov, Irina; Izgelov, Dvora; Barasch, Dinorah; Davidson, Elyad; Domb, Abraham J; Hoffman, Amnon

2017-11-28

Nowadays, therapeutic indications for cannabinoids, specifically Δ 9 -tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is that its composition of materials is approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (10.8mg, 10mg respectively) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments. Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has in serving as a standardized oral cannabinoid formulation. Moreover, the concept of improving oral bioavailability described here, can pave the way for other potential lipophilic active compounds requiring enhancement of their oral bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

Cytotoxicity assessment of functionalized CdSe, CdTe and InP quantum dots in two human cancer cell models.

PubMed

Liu, Jing; Hu, Rui; Liu, Jianwei; Zhang, Butian; Wang, Yucheng; Liu, Xin; Law, Wing-Cheung; Liu, Liwei; Ye, Ling; Yong, Ken-Tye

2015-12-01

The toxicity of quantum dots (QDs) has been extensively studied over the past decade. Some common factors that originate the QD toxicity include releasing of heavy metal ions from degraded QDs and the generation of reactive oxygen species on the QD surface. In addition to these factors, we should also carefully examine other potential QD toxicity causes that will play crucial roles in impacting the overall biological system. In this contribution, we have performed cytotoxicity assessment of four types of QD formulations in two different human cancer cell models. The four types of QD formulations, namely, mercaptopropionic acid modified CdSe/CdS/ZnS QDs (CdSe-MPA), PEGylated phospholipid encapsulated CdSe/CdS/ZnS QDs (CdSe-Phos), PEGylated phospholipid encapsulated InP/ZnS QDs (InP-Phos) and Pluronic F127 encapsulated CdTe/ZnS QDs (CdTe-F127), are representatives for the commonly used QD formulations in biomedical applications. Both the core materials and the surface modifications have been taken into consideration as the key factors for the cytotoxicity assessment. Through side-by-side comparison and careful evaluations, we have found that the toxicity of QDs does not solely depend on a single factor in initiating the toxicity in biological system but rather it depends on a combination of elements from the particle formulations. More importantly, our toxicity assessment shows different cytotoxicity trend for all the prepared formulations tested on gastric adenocarcinoma (BGC-823) and neuroblastoma (SH-SY5Y) cell lines. We have further proposed that the cellular uptake of these nanocrystals plays an important role in determining the final faith of the toxicity impact of the formulation. The result here suggests that the toxicity of QDs is rather complex and it cannot be generalized under a few assumptions reported previously. We suggest that one have to evaluate the QD toxicity on a case to case basis and this indicates that standard procedures and comprehensive protocols are urgently needed to be developed and employed for fully assessing and understanding the origins of the toxicity arising from different QD formulations. Copyright © 2015. Published by Elsevier B.V.

IceChrono1: a probabilistic model to compute a common and optimal chronology for several ice cores

NASA Astrophysics Data System (ADS)

Parrenin, F.; Bazin, L.; Capron, E.; Landais, A.; Lemieux-Dudon, B.; Masson-Delmotte, V.

2015-05-01

Polar ice cores provide exceptional archives of past environmental conditions. The dating of ice cores and the estimation of the age-scale uncertainty are essential to interpret the climate and environmental records that they contain. It is, however, a complex problem which involves different methods. Here, we present IceChrono1, a new probabilistic model integrating various sources of chronological information to produce a common and optimized chronology for several ice cores, as well as its uncertainty. IceChrono1 is based on the inversion of three quantities: the surface accumulation rate, the lock-in depth (LID) of air bubbles and the thinning function. The chronological information integrated into the model are models of the sedimentation process (accumulation of snow, densification of snow into ice and air trapping, ice flow), ice- and air-dated horizons, ice and air depth intervals with known durations, depth observations (depth shift between synchronous events recorded in the ice and in the air) and finally air and ice stratigraphic links in between ice cores. The optimization is formulated as a least squares problem, implying that all densities of probabilities are assumed to be Gaussian. It is numerically solved using the Levenberg-Marquardt algorithm and a numerical evaluation of the model's Jacobian. IceChrono follows an approach similar to that of the Datice model which was recently used to produce the AICC2012 (Antarctic ice core chronology) for four Antarctic ice cores and one Greenland ice core. IceChrono1 provides improvements and simplifications with respect to Datice from the mathematical, numerical and programming point of views. The capabilities of IceChrono1 are demonstrated on a case study similar to the AICC2012 dating experiment. We find results similar to those of Datice, within a few centuries, which is a confirmation of both IceChrono1 and Datice codes. We also test new functionalities with respect to the original version of Datice: observations as ice intervals with known durations, correlated observations, observations as air intervals with known durations and observations as mixed ice-air stratigraphic links. IceChrono1 is freely available under the General Public License v3 open source license.

Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles.

PubMed

Ebrahimi, Hossein Ali; Javadzadeh, Yousef; Hamidi, Mehrdad; Jalali, Mohammad Barzegar

2015-09-21

Repaglinide is an efficient anti-diabetic drug which is prescribed widely as multi-dosage oral daily regimens. Due to the low compliance inherent to each multi-dosage regimen, development of prolonged-release formulations could enhance the overall drug efficacy in patient populations. Repaglinide-loaded solid lipid nanoparticles (SLNs) were developed and characterized in vitro. Various surfactants were used in this study during the nanocarrier preparation procedure and their corresponding effects on some physicochemical properties of SLNs such as size, zeta potential; drug loading parameters and drug release profiles was investigated. Stearic acid and glyceryl mono stearate (GMS) were used as lipid phase and phosphatidylcholin, Tween80, Pluronic F127, poly vinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) were used as surfactant/stabilizer. The results showed some variations between formulations; where the Tween80-based SLNs showed smallest size, the phosphatidylcholin-based SLNs indicated most prolonged drug release time and the highest loading capacity. SEM images of these formulations showed morphological variations and also confirmed the nanoscale size of these particles. The FTIR and DSC results demonstrated no interaction between drug and excipients. The invitro release profiles of different formulations were studied and observed slow release of drug from all formulations. However significant differences were found among them in terms of their initial burst release as well as the whole drug release profile. From fitting these data to various statistical models, the Peppas model was proposed as the best model to describe the statistical indices and, therefore, mechanism of drug release. The results of this study confirmed the effect of surfactant type on SLNs physicochemical properties such as morphological features, loading parameters, particle sizes and drug release kinetic. With respect to the outcome data, the mixture of phosphatidylcholin/Pluronic F127 was selected as the best surfactant/stabilizer to coat the lipid core comprising stearic acid and GMS.

Core Dynamics Analysis for Reactivity Insertion and Loss of Coolant Flow Tests Using the High Temperature Engineering Test Reactor

NASA Astrophysics Data System (ADS)

Takamatsu, Kuniyoshi; Nakagawa, Shigeaki; Takeda, Tetsuaki

Safety demonstration tests using the High Temperature Engineering Test Reactor (HTTR) are in progress to verify its inherent safety features and improve the safety technology and design methodology for High-temperature Gas-cooled Reactors (HTGRs). The reactivity insertion test is one of the safety demonstration tests for the HTTR. This test simulates the rapid increase in the reactor power by withdrawing the control rod without operating the reactor power control system. In addition, the loss of coolant flow tests has been conducted to simulate the rapid decrease in the reactor power by tripping one, two or all out of three gas circulators. The experimental results have revealed the inherent safety features of HTGRs, such as the negative reactivity feedback effect. The numerical analysis code, which was named-ACCORD-, was developed to analyze the reactor dynamics including the flow behavior in the HTTR core. We have modified this code to use a model with four parallel channels and twenty temperature coefficients. Furthermore, we added another analytical model of the core for calculating the heat conduction between the fuel channels and the core in the case of the loss of coolant flow tests. This paper describes the validation results for the newly developed code using the experimental results. Moreover, the effect of the model is formulated quantitatively with our proposed equation. Finally, the pre-analytical result of the loss of coolant flow test by tripping all gas circulators is also discussed.

Modifications to WRF's dynamical core to improve the treatment of moisture for large-eddy simulations: WRF DY-CORE MOISTURE TREATMENT

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

Xiao, Heng; Endo, Satoshi; Wong, May

Yamaguchi and Feingold (2012) note that the cloud fields in their Weather Research and Forecasting (WRF) large-eddy simulations (LESs) of marine stratocumulus exhibit a strong sensitivity to time stepping choices. In this study, we reproduce and analyze this sensitivity issue using two stratocumulus cases, one marine and one continental. Results show that (1) the sensitivity is associated with spurious motions near the moisture jump between the boundary layer and the free atmosphere, and (2) these spurious motions appear to arise from neglecting small variations in water vapor mixing ratio (qv) in the pressure gradient calculation in the acoustic sub­stepping portionmore » of the integration procedure. We show that this issue is remedied in the WRF dynamical core by replacing the prognostic equation for the potential temperature θ with one for the moist potential temperature θm=θ(1+1.61qv), which allows consistent treatment of moisture in the calculation of pressure during the acoustic sub­steps. With this modification, the spurious motions and the sensitivity to the time stepping settings (i.e., the dynamic time step length and number of acoustic sub­steps) are eliminated in both of the example stratocumulus cases. This modification improves the applicability of WRF for LES applications, and possibly other models using similar dynamical core formulations, and also permits the use of longer time steps than in the original code.« less

Methods of information geometry in computational system biology (consistency between chemical and biological evolution).

PubMed

Astakhov, Vadim

2009-01-01

Interest in simulation of large-scale metabolic networks, species development, and genesis of various diseases requires new simulation techniques to accommodate the high complexity of realistic biological networks. Information geometry and topological formalisms are proposed to analyze information processes. We analyze the complexity of large-scale biological networks as well as transition of the system functionality due to modification in the system architecture, system environment, and system components. The dynamic core model is developed. The term dynamic core is used to define a set of causally related network functions. Delocalization of dynamic core model provides a mathematical formalism to analyze migration of specific functions in biosystems which undergo structure transition induced by the environment. The term delocalization is used to describe these processes of migration. We constructed a holographic model with self-poetic dynamic cores which preserves functional properties under those transitions. Topological constraints such as Ricci flow and Pfaff dimension were found for statistical manifolds which represent biological networks. These constraints can provide insight on processes of degeneration and recovery which take place in large-scale networks. We would like to suggest that therapies which are able to effectively implement estimated constraints, will successfully adjust biological systems and recover altered functionality. Also, we mathematically formulate the hypothesis that there is a direct consistency between biological and chemical evolution. Any set of causal relations within a biological network has its dual reimplementation in the chemistry of the system environment.

Aeroacoustics of Flight Vehicles: Theory and Practice. Volume 1: Noise Sources

NASA Technical Reports Server (NTRS)

Hubbard, Harvey H. (Editor)

1991-01-01

Methodology recommended to evaluate aeroacoustic related problems is provided, and approaches to their solutions are suggested without extensive tables, nomographs, and derivations. Orientation is toward flight vehicles and emphasis is on underlying physical concepts. Theoretical, experimental, and applied aspects are covered, including the main formulations and comparisons of theory and experiment. The topics covered include: propeller and propfan noise, rotor noise, turbomachinery noise, jet noise classical theory and experiments, noise from turbulent shear flows, jet noise generated by large-scale coherent motion, airframe noise, propulsive lift noise, combustion and core noise, and sonic booms.

Well-Being With Soul: Science in Pursuit of Human Potential.

PubMed

Ryff, Carol D

2018-03-01

This essay examines core contributions of a model of psychological well-being that has had widespread scientific impact. It drew on distant formulations to identify new dimensions and measures for assessing what it means to be well. Key themes among the more than 750 studies using the model are sketched, followed by reflections about why there has been so much interest in this eudaimonic approach to well-being. A final section looks to the future, proposing new directions to illuminate the forces that work against the realization of human potential as well as those that nurture human flourishing and self-realization.

Borderline Brenner tumor of the ovary: a case report with immunohistochemical and molecular study.

PubMed

De Cecio, Rossella; Cantile, Monica; Collina, Francesca; Marra, Laura; Santonastaso, Clemente; Scaffa, Cono; Botti, Gerardo; Losito, Nunzia Simona

2014-10-29

Borderline Brenner tumor of the ovary is a rare entity characterized by papillary structures with a fibro-vascular core, covered by a transitional epithelium, and by the absence of stromal infiltration. It is associated, by definition, with a benign component of Brenner tumor. We report a case of a 68-year-old woman, with a right ovarian mass, whose morphology and immuno-profile were consistent with the diagnosis of a borderline Brenner tumor. Immunohistochemistry carried out on selected markers may help to formulate the diagnosis, more than the molecular analyses.

Vortex breakdown simulation - A circumspect study of the steady, laminar, axisymmetric model

NASA Technical Reports Server (NTRS)

Salas, M. D.; Kuruvila, G.

1989-01-01

The incompressible axisymmetric steady Navier-Stokes equations are written using the streamfunction-vorticity formulation. The resulting equations are discretized using a second-order central-difference scheme. The discretized equations are linearized and then solved using an exact LU decomposition, Gaussian elimination, and Newton iteration. Solutions are presented for Reynolds numbers (based on vortex core radius) 100-1800 and swirl parameter 0.9-1.1. The effects of inflow boundary conditions, the location of farfield and outflow boundaries, and mesh refinement are examined. Finally, the stability of the steady solutions is investigated by solving the time-dependent equations.

Numerical studies of interacting vortices

NASA Technical Reports Server (NTRS)

Liu, G. C.; Hsu, C. H.

1985-01-01

To get a basic understanding of the physics of flowfields modeled by vortex filaments with finite vortical cores, systematic numerical studies of the interactions of two dimensional vortices and pairs of coaxial axisymmetric circular vortex rings were made. Finite difference solutions of the unsteady incompressible Navier-Stokes equations were carried out using vorticity and stream function as primary variables. Special emphasis was placed on the formulation of appropriate boundary conditions necessary for the calculations in a finite computational domain. Numerical results illustrate the interaction of vortex filaments, demonstrate when and how they merge with each other, and establish the region of validity for an asymptotic analysis.

Solid Lipid Nanoparticle Formulations of Docetaxel Prepared with High Melting Point Triglycerides: In Vitro and in Vivo Evaluation

PubMed Central

2015-01-01

Docetaxel (DCX) is a second generation taxane. It is approved by the U.S. Food and Drug Administration for the treatment of various types of cancer, including breast, non-small cell lung, and head and neck cancers. However, side effects, including those related to Tween 80, an excipient in current DCX formulations, can be severe. In the present study, we developed a novel solid lipid nanoparticle (SLN) composition of DCX. Trimyristin was selected from a list of high melting point triglycerides as the core lipid component of the SLNs, based on the rate at which the DCX was released from the SLNs and the stability of the SLNs. The trimyristin-based, PEGylated DCX-incorporated SLNs (DCX-SLNs) showed significantly higher cytotoxicity against various human and murine cancer cells in culture, as compared to DCX solubilized in a Tween 80/ethanol solution. Moreover, in a mouse model with pre-established tumors, the new DCX-SLNs were significantly more effective than DCX solubilized in a Tween 80/ethanol solution in inhibiting tumor growth without toxicity, likely because the DCX-SLNs increased the concentration of DCX in tumor tissues, but decreased the levels of DCX in major organs such as liver, spleen, heart, lung, and kidney. DCX-incorporated SLNs prepared with one or more high-melting point triglycerides may represent an improved DCX formulation. PMID:24621456

Development and optimization of press coated floating pulsatile drug delivery of sumatriptan succinate.

PubMed

Jagdale, Swati C; Pawar, Chandrakala R

2014-01-01

Floating pulsatile is combined approach designed according to circadian rhythm to deliver the drug at right time, in right quantity and at right site as per pathophysiological need of disease with prolong gastric residence and lag phase followed by burst release. As the migraine follows circadian rhythm in which headache is more painful at the awakening time, the dosage form should be given during night time to release drug when pain get worsen. Present work deals with formulation and optimization of floating pulsatile tablet of sumatriptan succinate. Core tablet containing crospovidone as superdisintegrant (10%) showed burst release. Lag time was maintained using swellable polymer as polyoxN12K and xanthum gum. 3(2) experimental design was carried out. Developed formulations were evaluated for physical characteristics, in vitro and in vivo study. Optimized batch F2 with concentration of polyox N12K (73.43%) and xanthum gum (26.56%) of total polymer weight showed floating lag time 15±2 sec, drug content 99.58±0.2 %, hardness 6±0.2 Kg/cm(2) and drug release 99.54±2% with pulsatile manner followed lag period of 7±0.1h. In vivo x-ray study confirms prolong gastric residence of system. Programmable pulsatile release has been achieved by formulation F2 which meet demand of chronotherapeutic objective of migraine.

Nano-suspension coating as a technique to modulate the drug release from controlled porosity osmotic pumps for a soluble agent.

PubMed

Bahari, Leila Azharshekoufeh; Javadzadeh, Yousef; Jalali, Mohammad Barzegar; Johari, Peyvand; Nokhodchi, Ali; Shokri, Javad

2017-05-01

In controlled porosity osmotic pumps (CPOP), usually finding a single solvent with a capability to dissolve both film former (hydrophobic) and pore former (hydrophilic) is extremely challenging. Therefore, the aim of the present investigation was to tackle the issue associated with controlled porosity osmotic pump (CPOP) system using nano-suspension coating method. In the present study 4-Amino pyridine was used as a highly water soluble drug. In this method, a hydrophilic pore former (sucrose or mannitol) in nano range was suspended in polymeric coating solution using ball-mill. The performance of the prepared formulations was assessed in terms of D 12h (cumulative release percent after 12h), Dev zero (mean percent deviation of drug release from zero order kinetic), t L (lag time of the drug release) and RSQ zero . The results revealed that gelling agent amount (HPMC E 15LV ) in core and pore former concentration in SPM had crucial effect on SPM integrity. All the optimised formulations showed a burst drug release due to fast dissolving nature of the pore formers. Results obtained from scanning electron microscopy demonstrated the formation of nanopores in the membrane where the drug release takes place via these nanopores. Nano suspension coating method can be introduced as novel method in formulation of CPOPs. Copyright © 2017 Elsevier B.V. All rights reserved.

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%.

Formulation and evaluation of novel coated floating tablets of bergenin and cetirizine dihydrochloride for gastric delivery.

PubMed

He, Shuang; Li, Feng; Zhou, Dan; Du, Junrong; Huang, Yuan

2012-10-01

A novel coated gastric floating drug-delivery system (GFDDS) of bergenin (BN) and cetirizine dihydrochloride (CET) was developed. First, the pharmacodynamic studies were performed and the results revealed that the new compounds of bergenin/cetirizine dihydrochloride had comparative efficacy as commercial products (bergenin/chlorphenamine maleate) but with fewer side effects on central nervous system (CNS). Subsequently, bergenin was formulated as an extended-release core tablet while cetirizine dihydrochloride was incorporated into the gastric coating film for immediate release. The formulation of GFDDS was optimized by CET content uniformity test, in vitro buoyancy and drug release. Herein, the effects of sodium bicarbonate (effervescent), hydroxypropyl methylcellulose (HPMC, matrix polymer) and coating weight gain were investigated respectively. The optimized GFDDS exhibited good floating properties (buoyancy lag time < 2 min; floating duration > 10 h) and satisfactory drug-release profiles (immediate release of CET in 10 min and sustained release of BN for 12 h). In vivo gamma scintigraphy proved that the optimized GFDDS could retain in the stomach with a prolonged gastric retention time (GRT) of 5 h, and the coating layer showed no side effect for gastric retention. The novel coated gastric floating drug-delivery system offers a new approach to enhance BN's absorption at its absorption site and the efficacy of both CET and BN.

Development of a Mouse Model for Assessing Fatigue during Chemotherapy

PubMed Central

Ray, Maria A; Trammell, Rita A; Verhulst, Steve; Ran, Sophia; Toth, Linda A

2011-01-01

Fatigue and disturbed sleep are common problems for cancer patients and affect both quality of life and compliance with treatment. Fatigue may be associated with cancer itself and with the treatment, particularly for therapies with neurotoxic side effects. To develop a model system for evaluation of chemotherapy-related fatigue, we studied mice treated with either a commonly used formulation of the chemotherapeutic agent paclitaxel (paclitaxel; Taxol), which is known to have neurotoxic properties, or a nanoparticle formulation of paclitaxel (nab-paclitaxel; Abraxane) that is reported to have greater potency and efficacy yet fewer side effects than does paclitaxel. Mice were treated with 1 of these 2 agents (10 mg/kg IV daily for 5 consecutive days) and were monitored from 1 wk before through 4 wk after treatment. Dependent measures included running wheel activity, locomotor activity on the cage floor, core temperature, sleep patterns, CBC count, serum cytokine and chemokine concentrations, and neurologic assessment. For both drugs, mice showed the most severe perturbations of activity during the first recovery week after drug administration. Mice treated with paclitaxel showed greater neutropenia and motor deficits than did mice treated with nab-paclitaxel. However, deficits had largely resolved by 4 wk after administration of either drug. We conclude that these measures provide an assessment of chemotherapy-related fatigue that potentially can distinguish toxicity associated with different formulations of the same agent. PMID:21535922

[Trade-offs in the development of various dosage form (overview)].

PubMed

Uchida, Takahiro

2015-01-01

In this symposium we focused on trade-offs which might occur in the process of development of many types of formulation and corresponding dissolution methods. Firstly, we focused on a solubility-permeability trade-off in the case of micelle with surfactant or molecular complex with CyD. The micelle would be successful in increasing drug solubility, however it rather decreased permeability of model drug progesterone (Biopharmaceutics Classfication System (BCS) Class II) as an overall flux. Secondly in order to reduce bitterness of branched chain amino acid (BCAA), increasing particle sizes of each amino acid crystals involved in formulation was effective since the release rate of amino acid was restricted efficiently. Thirdly, in the case of injection of paclitaxel (BCS Class II)formulation, the drug was adsorbed to albumin. Thereby the risk of allergy was dramatically decreased compared to the case when non-ionic surfactant was used as an additive. Fourth, anticancer drug was incorporated into the internal (core) phase of an orally disintegrating tablet (ODT), this is also merit to avoid exposure of the drug to a nursing person or individual working person in manufacturing process. Fifth, the convenient syringe type kit pharmaceutical preparation for administration of total parenteral nutrition (TPN) to avoid incompatibility and its risk management effect was briefly discussed. Finally, the risk of an additive such as alcohol for a preterm infant was described.

A Galleria Boundary Element Method for two-dimensional nonlinear magnetostatics

NASA Astrophysics Data System (ADS)

Brovont, Aaron D.

The Boundary Element Method (BEM) is a numerical technique for solving partial differential equations that is used broadly among the engineering disciplines. The main advantage of this method is that one needs only to mesh the boundary of a solution domain. A key drawback is the myriad of integrals that must be evaluated to populate the full system matrix. To this day these integrals have been evaluated using numerical quadrature. In this research, a Galerkin formulation of the BEM is derived and implemented to solve two-dimensional magnetostatic problems with a focus on accurate, rapid computation. To this end, exact, closed-form solutions have been derived for all the integrals comprising the system matrix as well as those required to compute fields in post-processing; the need for numerical integration has been eliminated. It is shown that calculation of the system matrix elements using analytical solutions is 15-20 times faster than with numerical integration of similar accuracy. Furthermore, through the example analysis of a c-core inductor, it is demonstrated that the present BEM formulation is a competitive alternative to the Finite Element Method (FEM) for linear magnetostatic analysis. Finally, the BEM formulation is extended to analyze nonlinear magnetostatic problems via the Dual Reciprocity Method (DRBEM). It is shown that a coarse, meshless analysis using the DRBEM is able to achieve RMS error of 3-6% compared to a commercial FEM package in lightly saturated conditions.

Design and evaluation of artificial cornea with core-skirt design using polyhydroxyethyl methacrylate and graphite.

PubMed

Sinha, Mukty; Gupte, Tanvi

2017-06-10

Artificial cornea is the effective treatment option for corneal blindness. One of the challenges with the artificial cornea is limited, or no tissue integration necessitates reimplantation due to necrosis or corneal melting. We propose here a new formulation approach for core-skirt incorporating graphite in the outer skirt region to improve cell adhesion. Hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate were procured from Sigma-Aldrich. Polyhydroxyethyl methacrylate (PHEMA) was synthesized by free radical polymerization of HEMA. PHEMA hydrogel core with graphite incorporated skirt was developed with the help of mould and spacer. Pores were introduced into the skirt by salt leaching technique using sodium chloride as porogen. The porous skirt was improved for its aesthetic appeal of black colour and mechanical strength to sustain intraocular pressure by incorporating graphite. The material properties of the newly developed design were evaluated in terms of wetting behaviour, mechanical strength, water vapour permeability, degradation profile and cell adhesion. The polymerization of HEMA was confirmed by thin layer chromatography and FTIR. Water content of the polymeric film was optimized at 50% where maximum transparency with required refractive index of 1.4 was obtained. The concentration of salt vital for the essential porosity was also optimized using optical microscopy and scanning electron microscopy. Other properties, namely mechanical strength, water vapour transmission rate and degradation behaviour, showed that the developed design is suitable for ocular applications. Furthermore, cell adhesion study confirmed tissue adhesion in the skirt region but absent in the core. The core-skirt design may offer an efficient cornea replacement alternative with enhanced tissue integration in addition to desired mechanical behaviour with a clear and aesthetic vision.

STRUCTURAL GLITCHES NEAR THE CORES OF RED GIANTS REVEALED BY OSCILLATIONS IN G-MODE PERIOD SPACINGS FROM STELLAR MODELS

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

Cunha, M. S.; Avelino, P. P.; Stello, D.

2015-06-01

With recent advances in asteroseismology it is now possible to peer into the cores of red giants, potentially providing a way to study processes such as nuclear burning and mixing through their imprint as sharp structural variations—glitches—in the stellar cores. Here we show how such core glitches can affect the oscillations we observe in red giants. We derive an analytical expression describing the expected frequency pattern in the presence of a glitch. This formulation also accounts for the coupling between acoustic and gravity waves. From an extensive set of canonical stellar models we find glitch-induced variation in the period spacingmore » and inertia of non-radial modes during several phases of red giant evolution. Significant changes are seen in the appearance of mode amplitude and frequency patterns in asteroseismic diagrams such as the power spectrum and the échelle diagram. Interestingly, along the red giant branch glitch-induced variation occurs only at the luminosity bump, potentially providing a direct seismic indicator of stars in that particular evolution stage. Similarly, we find the variation at only certain post-helium-ignition evolution stages, namely, in the early phases of helium core burning and at the beginning of helium shell burning, signifying the asymptotic giant branch bump. Based on our results, we note that assuming stars to be glitch-free, while they are not, can result in an incorrect estimate of the period spacing. We further note that including diffusion and mixing beyond classical Schwarzschild could affect the characteristics of the glitches, potentially providing a way to study these physical processes.« less

IceChrono v1: a probabilistic model to compute a common and optimal chronology for several ice cores

NASA Astrophysics Data System (ADS)

Parrenin, Frédéric

2015-04-01

Polar ice cores provide exceptional archives of past environmental conditions. The dating of ice cores is essential to interpret the paleo records that they contain, but it is a complicated problem since it involves different dating methods. Here I present IceChrono v1, a new probabilistic model to combine different kinds of chronological information to obtain a common and optimized chronology for several ice cores, as well as its uncertainty. It is based on the inversion of three quantities: the surface accumulation rate, the Lock-In Depth (LID) of air bubbles and the vertical thinning function. The chronological information used are: models of the sedimentation process (accumulation of snow, densification of snow into ice and air trapping, ice flow), ice and gas dated horizons, ice and gas dated depth intervals, Δdepth observations (depth shift between synchronous events recorded in the ice and in the air), stratigraphic links in between ice cores (ice-ice, air-air or mix ice-air and air-ice links). The optimization problem is formulated as a least squares problems, that is, all densities of probabilities are assumed gaussian. It is numerically solved using the Levenberg-Marquardt algorithm and a numerical evaluation of the model's Jacobian. IceChrono is similar in scope to the Datice model, but has differences from the mathematical, numerical and programming point of views. I apply IceChrono on an AICC2012-like experiment and I find similar results than Datice within a few centuries, which is a confirmation of both IceChrono and Datice codes. IceChrono v1 is freely available under the GPL v3 open source license.

Meteor research program

NASA Technical Reports Server (NTRS)

Southworth, R. B.; Mccrosky, R. E.

1970-01-01

An overview of research on radio and radar meteors accomplished during the past decade is presented, and the work of the past year is highlighted. Velocity distribution and mass flux data are obtained for meteors in the range 10 to 0.0001 g, the size believed to be the principal hazard to space missions. The physical characteristics of mass, structure and density, luminosity, and ablation are briefly described, and the formulation of a theory for interactions of ionization and excitation during collision of atomic particles is mentioned. Five classes of meteoroids are identified, including the two of iron and stone meteorites. Stream meteors associated with known comets are Classes A or C, and parent comets of Class B streams are not observed. Class A meteoroids are identified with the core of a cometary nucleus, Class C with less dense surface of the nucleus after sublimation of ices, and Class B with less dense cores of smaller cometary nuclei. Atmospheric meteor phenomena associated with winds and gravity waves, density and temperature, atomic oxygen, and meteor rate changes are mentioned.

Multipoint to multipoint routing and wavelength assignment in multi-domain optical networks

NASA Astrophysics Data System (ADS)

Qin, Panke; Wu, Jingru; Li, Xudong; Tang, Yongli

2018-01-01

In multi-point to multi-point (MP2MP) routing and wavelength assignment (RWA) problems, researchers usually assume the optical networks to be a single domain. However, the optical networks develop toward to multi-domain and larger scale in practice. In this context, multi-core shared tree (MST)-based MP2MP RWA are introduced problems including optimal multicast domain sequence selection, core nodes belonging in which domains and so on. In this letter, we focus on MST-based MP2MP RWA problems in multi-domain optical networks, mixed integer linear programming (MILP) formulations to optimally construct MP2MP multicast trees is presented. A heuristic algorithm base on network virtualization and weighted clustering algorithm (NV-WCA) is proposed. Simulation results show that, under different traffic patterns, the proposed algorithm achieves significant improvement on network resources occupation and multicast trees setup latency in contrast with the conventional algorithms which were proposed base on a single domain network environment.

Forced nutations of the earth: Influence of inner core dynamics. I - Theory. II - Numerical results and comparisons. III - Very long interferometry data analysis

NASA Technical Reports Server (NTRS)

Mathews, P. M.; Buffett, Bruce A.; Herring, Thomas A.; Shapiro, Irwin I.

1991-01-01

A treatment is presented of the nutation problem for an oceanless, elastic, spheroidally stratified earth, with the dynamical role of the inner core explicitly included in the formulation. Solving the enlarged system of equations shows that a new almost diurnal eigenfrequency emerges. A rough estimate places it not far from the prograde annual tidal excitation frequency, so that possible resonance effects on nutation amplitudes need careful consideration. Tables are provided that exhibit the sensitivities of various relevant quantities, the eigenfrequencies and the coefficients which appear in the resonance expansion, as well as the nutation amplitudes at important tidal frequencies, to possible errors in the earth parameters which enter the theory set forth. Finally, the analysis of 798 VLBI experiments performed between July 1980 and February 1989 and the determination from this analysis of corrections to selected coefficients in the International Astronomical Union 1980 theory of the nutations of the earth are discussed.

Non-LTE CO, revisited

NASA Technical Reports Server (NTRS)

Ayres, Thomas R.; Wiedemann, Gunter R.

1989-01-01

A more extensive and detailed non-LTE simulation of the Delta v = 1 bands of CO than attempted previously is reported. The equations of statistical equilibrium are formulated for a model molecule containing 10 bound vibrational levels, each split into 121 rotational substates and connected by more than 1000 radiative transitions. Solutions are obtained for self-consistent populations and radiation fields by iterative application of the 'Lambda-operator' to an initial LTE distribution. The formalism is used to illustrate models of the sun and Arcturus. For the sun, negligible departures from LTE are found in either a theoretical radiative-equilibrium photosphere with outwardly falling temperatures in its highest layers or in a semiempirical hot chromosphere that reproduces the spatially averaged emission cores of Ca II H and K. The simulations demonstrate that the puzzling 'cool cores' of the CO Delta V = 1 bands observed in limb spectra of the sun and in flux spectra of Arcturus cannot be explained simply by non-LTE scattering effects.

Kinetic simulation of edge instability in fusion plasmas

NASA Astrophysics Data System (ADS)

Fulton, Daniel Patrick

In this work, gyrokinetic simulations in edge plasmas of both tokamaks and field reversed. configurations (FRC) have been carried out using the Gyrokinetic Toroidal Code (GTC) and A New Code (ANC) has been formulated for cross-separatrix FRC simulation. In the tokamak edge, turbulent transport in the pedestal of an H-mode DIII-D plasma is. studied via simulations of electrostatic driftwaves. Annulus geometry is used and simulations focus on two radial locations corresponding to the pedestal top with mild pressure gradient and steep pressure gradient. A reactive trapped electron instability with typical ballooning mode structure is excited in the pedestal top. At the steep gradient, the electrostatic instability exhibits unusual mode structure, peaking at poloidal angles theta=+- pi/2. Simulations find this unusual mode structure is due to steep pressure gradients in the pedestal but not due to the particular DIII-D magnetic geometry. Realistic DIII-D geometry has a stabilizing effect compared to a simple circular tokamak geometry. Driftwave instability in FRC is studied for the first time using gyrokinetic simulation. GTC. is upgraded to treat realistic equilibrium calculated by an MHD equilibrium code. Electrostatic local simulations in outer closed flux surfaces find ion-scale modes are stable due to the large ion gyroradius and that electron drift-interchange modes are excited by electron temperature gradient and bad magnetic curvature. In the scrape-off layer (SOL) ion-scale modes are excited by density gradient and bad curvature. Collisions have weak effects on instabilities both in the core and SOL. Simulation results are consistent with density fluctuation measurements in the C-2 experiment using Doppler backscattering (DBS). The critical density gradients measured by the DBS qualitatively agree with the linear instability threshold calculated by GTC simulations. One outstanding critical issue in the FRC is the interplay between turbulence in the FRC. core and SOL regions. While the magnetic flux coordinates used by GTC provide a number of computational advantages, they present unique challenges at the magnetic field separatrix. To address this limitation, a new code, capable of coupled core-SOL simulations, is formulated, implemented, and successfully verified.

Impact of an irregular friction formulation on dynamics of a minimal model for brake squeal

NASA Astrophysics Data System (ADS)

Stender, Merten; Tiedemann, Merten; Hoffmann, Norbert; Oberst, Sebastian

2018-07-01

Friction-induced vibrations are of major concern in the design of reliable, efficient and comfortable technical systems. Well-known examples for systems susceptible to self-excitation can be found in fluid structure interaction, disk brake squeal, rotor dynamics, hip implants noise and many more. While damping elements and amplitude reduction are well-understood in linear systems, nonlinear systems and especially self-excited dynamics still constitute a challenge for damping element design. Additionally, complex dynamical systems exhibit deterministic chaotic cores which add severe sensitivity to initial conditions to the system response. Especially the complex friction interface dynamics remain a challenging task for measurements and modeling. Today, mostly simple and regular friction models are investigated in the field of self-excited brake system vibrations. This work aims at investigating the effect of high-frequency irregular interface dynamics on the nonlinear dynamical response of a self-excited structure. Special focus is put on the characterization of the system response time series. A low-dimensional minimal model is studied which features self-excitation, gyroscopic effects and friction-induced damping. Additionally, the employed friction formulation exhibits temperature as inner variable and superposed chaotic fluctuations governed by a Lorenz attractor. The time scale of the irregular fluctuations is chosen one order smaller than the overall system dynamics. The influence of those fluctuations on the structural response is studied in various ways, i.e. in time domain and by means of recurrence analysis. The separate time scales are studied in detail and regimes of dynamic interactions are identified. The results of the irregular friction formulation indicate dynamic interactions on multiple time scales, which trigger larger vibration amplitudes as compared to regular friction formulations conventionally studied in the field of friction-induced vibrations.

Immunogenicity and efficacy following sequential parenterally-administered doses of Salmonella Enteritidis COPS:FliC glycoconjugates in infant and adult mice.

PubMed

Baliban, Scott M; Curtis, Brittany; Toema, Deanna; Tennant, Sharon M; Levine, Myron M; Pasetti, Marcela F; Simon, Raphael

2018-05-23

In sub-Saharan Africa, invasive nontyphoidal Salmonella (iNTS) infections with serovars S. Enteritidis, S. Typhimurium and I 4,[5],12:i:- are widespread in children < 5 years old. Development of an efficacious vaccine would provide an important public health tool to prevent iNTS disease in this population. Glycoconjugates of S. Enteritidis core and O-polysaccharide (COPS) coupled to the homologous serovar phase 1 flagellin protein (FliC) were previously shown to be immunogenic and protected adult mice against death following challenge with a virulent Malian S. Enteritidis blood isolate. This study extends these observations to immunization of mice in early life and also assesses protection with partial and full regimens. Anti-COPS and anti-FliC serum IgG titers were assessed in infant and adult mice after immunization with 1, 2 or 3 doses of S. Enteritidis COPS:FliC alone or co-formulated with aluminum hydroxide or monophosphoryl lipid A (MPL) adjuvants. S. Enteritidis COPS:FliC was immunogenic in both age groups, although the immune responses were quantitatively lower in infants. Kinetics of antibody production were similar for the native and adjuvanted formulations after three doses; conjugates formulated with MPL elicited significantly increased anti-COPS IgG titers in adult but not infant mice. Nevertheless, robust protection against S. Enteritidis challenge was seen for all three formulations when three doses were given either during infancy or as adults. We further found that significant protection could be achieved with two COPS:FliC doses, despite elicitation of modest serum anti-COPS IgG antibody titers. These findings guide potential immunization strategies that may be translated to develop a human pediatric iNTS vaccine for sub-Saharan Africa.

Modeling of high pressure arc-discharge with a fully-implicit Navier-Stokes stabilized finite element flow solver

NASA Astrophysics Data System (ADS)

Sahai, A.; Mansour, N. N.; Lopez, B.; Panesi, M.

2017-05-01

This work addresses the modeling of high pressure electric discharge in an arc-heated wind tunnel. The combined numerical solution of Poisson’s equation, radiative transfer equations, and the set of Favre-averaged thermochemical nonequilibrium Navier-Stokes equations allows for the determination of the electric, radiation, and flow fields, accounting for their mutual interaction. Semi-classical statistical thermodynamics is used to determine the plasma thermodynamic properties, while transport properties are obtained from kinetic principles with the Chapman-Enskog method. A multi-temperature formulation is used to account for thermal non-equilibrium. Finally, the turbulence closure of the flow equations is obtained by means of the Spalart-Allmaras model, which requires the solution of an additional scalar transport equation. A Streamline upwind Petrov-Galerkin stabilized finite element formulation is employed to solve the Navier-Stokes equation. The electric field equation is solved using the standard Galerkin formulation. A stable formulation for the radiative transfer equations is obtained using the least-squares finite element method. The developed simulation framework has been applied to investigate turbulent plasma flows in the 20 MW Aerodynamic Heating Facility at NASA Ames Research Center. The current model is able to predict the process of energy addition and re-distribution due to Joule heating and thermal radiation, resulting in a hot central core surrounded by colder flow. The use of an unsteady three-dimensional treatment also allows the asymmetry due to a dynamic electric arc attachment point in the cathode chamber to be captured accurately. The current work paves the way for detailed estimation of operating characteristics for arc-heated wind tunnels which are critical in testing thermal protection systems.

Novel polymeric micelles for insect pest control: encapsulation of essential oil monoterpenes inside a triblock copolymer shell for head lice control.

PubMed

Lucia, Alejandro; Toloza, Ariel Ceferino; Guzmán, Eduardo; Ortega, Francisco; Rubio, Ramón G

2017-01-01

Essential oil components (EOCs) are molecules with interesting application in pest control, these have been evaluated against different insect pest from more than 100 years, but their practical use is rather limited. Thus, the enhancement of their bioavailability and manageability due to their dispersion in water can open new perspective for the preparation of formulations for the control of insect pest. In this work, we studied the encapsulation of different monoterpenes in a poloxamer shell in order to prepare aqueous formulations that can be used for the development of platforms used in pest control. Micellar systems containing a 5 wt% of poloxamer 407 and 1.25 wt% of the different monoterpenes were prepared. Dynamic Light Scattering (DLS) experiments were carried out to characterize the dispersion of the EOCs in water. The pediculicidal activity of these micellar systems was tested on head lice using an ex vivo immersion test. The poloxamers allowed the dispersion of EOCs in water due to their encapsulation inside the hydrophobic core of the copolymer micelles. From this study, we concluded that it is possible to make stable micellar systems containing water (>90 wt%), 1.25 wt% of different monoterpenes and a highly safe polymer (5wt% Poloxamer 407). These formulations were effective against head lice with mortality ranging from 30 to 60%, being the most effective emulsions those containing linalool, 1,8-cineole, α -terpineol, thymol, eugenol, geraniol and nonyl alcohol which lead to mortalities above 50%. Since these systems showed good pediculicidal activity and high physicochemical stability, they could be a new route for the green fabrication of biocompatible and biosustainable insecticide formulations.

Highly efficient photodynamic therapy colloidal system based on chloroaluminum phthalocyanine/pluronic micelles.

PubMed

Py-Daniel, Karen R; Namban, Joy S; de Andrade, Laise R; de Souza, Paulo E N; Paterno, Leonardo G; Azevedo, Ricardo B; Soler, Maria A G

2016-06-01

Phthalocyanine derivatives comprise the second generation of photosensitizer molecules employed in photodynamic therapy (PDT) and have attracted much attention due to their outstanding photosensitizing performance. Most phthalocyanines are hydrophobic compounds that require association to drug delivery systems for clinical use. In this study, formulations of Pluronic F127 micelles incorporated with chloroaluminum phthalocyanine, or else F127/AlClPc, were produced at optimized conditions aiming at efficient and biocompatible PDT colloidal systems. Absorption/emission spectroscopies, as well as dynamic light scattering were performed to evaluate the optimum conditions for the F127 micelle formation and AlClPc incorporation. The micelles formation was attained with F127 concentrations ranging from 50 to 150mgmL(-1). At these conditions, AlClPc photosensitizer molecules were encapsulated into the hydrophobic micelle core and, therefore, readily solubilized in physiological medium (PBS pH 7.2). Encapsulation efficiency of about 90% resulted from different AlClPc concentrations. Identification of singlet oxygen production by irradiated F127/AlClPc formulations indicated good applicability for PDT. In vitro tests conducted with A549 human lung carcinoma cell line incubated with the F127/AlClPc formulations, at different AlClPc loadings, followed by only 18min of light irradiation (660nm LED, fluence of 25.3J/cm(2)), showed a cellular damage as high as 90% for rather low dosages of AlClPc (0.1-5.0μgmL(-1)). Further, no cytotoxicity occurred on non-irradiated cells. These findings suggest those F127/AlClPc formulations are highly promising for PDT applications, since they are easily prepared and the incubation and irradiation times are significantly shortened. Copyright © 2016 Elsevier B.V. All rights reserved.

Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform.

PubMed

Choudhury, Hira; Gorain, Bapi; Karmakar, Sanmoy; Biswas, Easha; Dey, Goutam; Barik, Rajib; Mandal, Mahitosh; Pal, Tapan Kumar

2014-01-02

Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug. Copyright © 2013 Elsevier B.V. All rights reserved.

Feasibility studies of concomitant administration of optimized formulation of probiotic-loaded Vancomycin hydrochloride pellets for colon delivery.

PubMed

Avachat, Amelia M; Shinde, Amol S

2016-01-01

Objective of this study was to develop Vancomycin HCl pellets loaded with Saccharomyces boulardii (S.b.) for pH-dependent system and CODES™ for augmenting the efficacy of Vancomycin HCl in the treatment of colitis. Pellets were prepared by extrusion-spheronization. In the pH-dependent system, the pellets were coated with Eudragit FS 30D. These pellets exhibited spherical form and a uniform surface coating. The CODES™ system consisted of three components: core containing mannitol, drug and probiotic, an inner acid-soluble coating layer, and an outer layer of enteric coating material. Statistical factorial design was used to optimize both formulations. Scanning electron micrographs of coated pellets revealed uniform coating. In vitro drug release of these coated pellets was studied sequentially in various buffers with (2%) and without rat cecal content for a period of 12 h. From the optimized pH-dependent formulation, F6 (20% w/w coating level and 15% w/v concentration of polymer), higher amount of probiotic was released in earlier time phase (first 5 h) as compared to the CODES™ and so R5 [containing acid-soluble inner coating layer (15% w/w coating level and 12% w/v concentration of Eudragit E100), and an outer layer of enteric coating material (12% w/w coating level and 10% w/v concentration of Eudragit L100)] was considered as the best formulation after confirming in vivo X-ray studies conducted on rabbits, suggesting that Vancomycin HCl and S.b. may be co-administered as pellets [CODES™] to enhance the effectiveness of Vancomycin HCl in the treatment of colitis without its associated side effects, which can only be confirmed after clinical trials.

Novel polymeric micelles for insect pest control: encapsulation of essential oil monoterpenes inside a triblock copolymer shell for head lice control

PubMed Central

Guzmán, Eduardo; Ortega, Francisco; Rubio, Ramón G.

2017-01-01

Background Essential oil components (EOCs) are molecules with interesting application in pest control, these have been evaluated against different insect pest from more than 100 years, but their practical use is rather limited. Thus, the enhancement of their bioavailability and manageability due to their dispersion in water can open new perspective for the preparation of formulations for the control of insect pest. In this work, we studied the encapsulation of different monoterpenes in a poloxamer shell in order to prepare aqueous formulations that can be used for the development of platforms used in pest control. Methods Micellar systems containing a 5 wt% of poloxamer 407 and 1.25 wt% of the different monoterpenes were prepared. Dynamic Light Scattering (DLS) experiments were carried out to characterize the dispersion of the EOCs in water. The pediculicidal activity of these micellar systems was tested on head lice using an ex vivo immersion test. Results The poloxamers allowed the dispersion of EOCs in water due to their encapsulation inside the hydrophobic core of the copolymer micelles. From this study, we concluded that it is possible to make stable micellar systems containing water (>90 wt%), 1.25 wt% of different monoterpenes and a highly safe polymer (5wt% Poloxamer 407). These formulations were effective against head lice with mortality ranging from 30 to 60%, being the most effective emulsions those containing linalool, 1,8-cineole, α-terpineol, thymol, eugenol, geraniol and nonyl alcohol which lead to mortalities above 50%. Discussion Since these systems showed good pediculicidal activity and high physicochemical stability, they could be a new route for the green fabrication of biocompatible and biosustainable insecticide formulations. PMID:28439460

In-vitro and in-vivo assessment of dextran-appended cellulose acetate phthalate nanoparticles for transdermal delivery of 5-fluorouracil.

PubMed

Garg, Ashish; Rai, Gopal; Lodhi, Santram; Jain, Alok P; Yadav, Awesh K

2016-06-01

The aim of this research was transdermal delivery of 5-fluorouracil (5-FU) using dextran-coated cellulose acetate phthalate (CAP) nanoparticulate formulation. CAP nanoparticles were prepared using drug-polymer ratio (1:1 to 1:3) and surfactant ratio (2.5, 5 and 10%). Dextran coating was made using aminodextran. The results showed that the optimized CAP nanoparticles (CNs) and dextran-coated CAP nanoparticles represented core-corona nanoparticles with the mean diameter of 75 ± 3 and 79 ± 2 nm, respectively, and entrapment efficiency was 82.5 ± 0.06 and 78.2 ± 0.12, respectively. Dextran-coated nanoparticles (FDCNs) and CAP nanoparticles (FCNs) showed in vitro 5-FU release upto 31 h and 8 h, respectively. Moreover, the cumulative amount of 5-FU penetrated through excised skin from FDCNs was 2.94 folds than that of the FU cream. Concentration of 5-FU in epidermis and dermis were also studied. In dermis, concentration of 5-FU was found higher in case of FDCN formulation than plain FU cream. FDCNs were found more hemocompatible in comparison to FCNs. The hematological data recommended that FDCNs formulation was less immunogenic compared to FU creams formulation. In blood level study, FDCNs exhibited 153, 12, 16.66 and 16.24-fold higher values for area under the curve, Tmax, Cmax and mean residence time (MRT) compared with those of FU cream, respectively. The in-vitro cytotoxicity was assessed using the MCF-7 by the MTT test and was compared to the plain 5-FU solution. All the detailed evidence showed that FDCNs could provide a promising tuning as a transdermal delivery system of 5-FU.

Repellent activity screening of 11 kinds of essential oils against Aedes albopictus Skuse: microcapsule preparation of Herba Schizonepetae oil and repellent bioassay on hand skin.

PubMed

Wu, H; Fu, C C; Yu, D D; Feng, J T; Zhang, X; Ma, Z Q

2013-08-01

The main ingredient of most repellents on the market is DEET, an effective compound that has the disadvantages of toxic reactions as well as damaging effects on plastic and synthetic fabric. DEET alternatives are urgently needed. The repellent activities of 11 kinds of essential oils were tested against Aedes albopictus Skuse by a Y-tube olfactometer. Using essential oils with high repellent activity as core material and gelatin and gum arabic as wall materials, we prepared microcapsules of essential oils and optimized the preparation process. The microcapsule formulation was then subjected to repellent bioassay on hand skin. when the dosage of essential oils was 5 µL, the cinnamon oil repellent rate was 87.5% within 10 min and the Herba Schizonepetae oil (HSO) repellent rate was 98.0% within 3 min. Up to 1.5% (w/v) gelatin and 1.5% (w/v) gum arabic (as wall materials), and HSO (as core material) were used to form microcapsules with a 1:1 ratio of core material to wall material. The ointment preparations effectively protected hand skin exposed to a high-density A. albopictus Skuse rearing cage for 4-5 h. The HSO microcapsule repellent has broad application and development prospects.

Hard sphere packings within cylinders.

PubMed

Fu, Lin; Steinhardt, William; Zhao, Hao; Socolar, Joshua E S; Charbonneau, Patrick

2016-03-07

Arrangements of identical hard spheres confined to a cylinder with hard walls have been used to model experimental systems, such as fullerenes in nanotubes and colloidal wire assembly. Finding the densest configurations, called close packings, of hard spheres of diameter σ in a cylinder of diameter D is a purely geometric problem that grows increasingly complex as D/σ increases, and little is thus known about the regime for D > 2.873σ. In this work, we extend the identification of close packings up to D = 4.00σ by adapting Torquato-Jiao's adaptive-shrinking-cell formulation and sequential-linear-programming (SLP) technique. We identify 17 new structures, almost all of them chiral. Beyond D ≈ 2.85σ, most of the structures consist of an outer shell and an inner core that compete for being close packed. In some cases, the shell adopts its own maximum density configuration, and the stacking of core spheres within it is quasiperiodic. In other cases, an interplay between the two components is observed, which may result in simple periodic structures. In yet other cases, the very distinction between the core and shell vanishes, resulting in more exotic packing geometries, including some that are three-dimensional extensions of structures obtained from packing hard disks in a circle.

SANTA BARBARA CLUSTER COMPARISON TEST WITH DISPH

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

Saitoh, Takayuki R.; Makino, Junichiro, E-mail: saitoh@elsi.jp

2016-06-01

The Santa Barbara cluster comparison project revealed that there is a systematic difference between entropy profiles of clusters of galaxies obtained by Eulerian mesh and Lagrangian smoothed particle hydrodynamics (SPH) codes: mesh codes gave a core with a constant entropy, whereas SPH codes did not. One possible reason for this difference is that mesh codes are not Galilean invariant. Another possible reason is the problem of the SPH method, which might give too much “protection” to cold clumps because of the unphysical surface tension induced at contact discontinuities. In this paper, we apply the density-independent formulation of SPH (DISPH), whichmore » can handle contact discontinuities accurately, to simulations of a cluster of galaxies and compare the results with those with the standard SPH. We obtained the entropy core when we adopt DISPH. The size of the core is, however, significantly smaller than those obtained with mesh simulations and is comparable to those obtained with quasi-Lagrangian schemes such as “moving mesh” and “mesh free” schemes. We conclude that both the standard SPH without artificial conductivity and Eulerian mesh codes have serious problems even with such an idealized simulation, while DISPH, SPH with artificial conductivity, and quasi-Lagrangian schemes have sufficient capability to deal with it.« less

Larvicidal potential of some plants from West Africa against Culex quinquefasciatus (Say) and Anopheles gambiae Giles (Diptera: Culicidae).

PubMed

Azokou, Alain; Koné, Mamidou W; Koudou, Benjamin G; Tra Bi, Honora F

2013-01-01

Mosquitoes increased resistance to insecticides, and environmental concerns about the use of insecticides, pose a major challenge in the search for new molecules to deplete and incapacitate mosquito populations. Plants are the valuable source as practices consisting in exploiting plant materials as repellents, and are still in wide use throughout developing countries. The aim of the present study was to screen plants from Cτte d'Ivoire for larvicidal activity against mosquitoes. Resistant and sensitive larvae (III and IV instar) of Anopheles gambiae and Culex quinquefasciatus were exposed to crude ethanol extracts (90%) of 45 plants and viability observed after 30 min, 6, 12 and 24 h postincubation. After partition of active extracts, each fraction (hexane and chloroform washed with NaCl 1%, tannins and aqueous) was tested using the same protocol at various concentrations (1000- 31.2 ppm). Of 49 extracts tested, 7 exhibited high potential (LC50 = 80 to 370 ppm) against resistant and sensitive III and IV instar larvae of An. gambiae and Cx. quinquefasciatus. These extracts were from Cissus populnea, Cochlospermum planchonii, Heliotropium indicum, Phyllanthus amarus, Vitex grandifolia and Alchornea cordifolia. However, three most active plant species (LC50 = 80- 180 ppm) were Cs. populnea, Cm. planchonii and P. amarus Their hexane and chloroform fractions showed high larvicidal activity. This study demonstrated that plants from Cτte d'Ivoire have a real potential for malaria, yellow fever, filarial and dengue vector control. Those could be used as sources or provide lead compounds for the development of safe plant-based biocides.

Colloid release and clogging in porous media: Effects of solution ionic strength and flow velocity.

PubMed

Torkzaban, Saeed; Bradford, Scott A; Vanderzalm, Joanne L; Patterson, Bradley M; Harris, Brett; Prommer, Henning

2015-10-01

The release and retention of in-situ colloids in aquifers play an important role in the sustainable operation of managed aquifer recharge (MAR) schemes. The processes of colloid release, retention, and associated permeability changes in consolidated aquifer sediments were studied by displacing native groundwater with reverse osmosis-treated (RO) water at various flow velocities. Significant amounts of colloid release occurred when: (i) the native groundwater was displaced by RO-water with a low ionic strength (IS), and (ii) the flow velocity was increased in a stepwise manner. The amount of colloid release and associated permeability reduction upon RO-water injection depended on the initial clay content of the core. The concentration of released colloids was relatively low and the permeability reduction was negligible for the core sample with a low clay content of about 1.3%. In contrast, core samples with about 6 and 7.5% clay content exhibited: (i) close to two orders of magnitude increase in effluent colloid concentration and (ii) more than 65% permeability reduction. Incremental improvement in the core permeability was achieved when the flow velocity increased, whereas a short flow interruption provided a considerable increase in the core permeability. This dependence of colloid release and permeability changes on flow velocity and colloid concentration was consistent with colloid retention and release at pore constrictions due to the mechanism of hydrodynamic bridging. A mathematical model was formulated to describe the processes of colloid release, transport, retention at pore constrictions, and subsequent permeability changes. Our experimental and modeling results indicated that only a small fraction of the in-situ colloids was released for any given change in the IS or flow velocity. Comparison of the fitted and experimentally measured effluent colloid concentrations and associated changes in the core permeability showed good agreement, indicating that the essential physics were accurately captured by the model. Copyright © 2015 Elsevier B.V. All rights reserved.

Climate Proxies: An Inquiry-Based Approach to Discovering Climate Change on Antarctica

NASA Astrophysics Data System (ADS)

Wishart, D. N.

2016-12-01

An attractive way to advance climate literacy in higher education is to emphasize its relevance while teaching climate change across the curriculum to science majors and non-science majors. An inquiry-based pedagogical approach was used to engage five groups of students on a "Polar Discovery Project" aimed at interpreting the paleoclimate history of ice cores from Antarctica. Learning objectives and student learning outcomes were clearly defined. Students were assigned several exercises ranging from examination of Antarctic topography to the application of physical and chemical measurements as proxies for climate change. Required materials included base and topographic maps of Antarctica; graph sheets for construction of topographic cross-sectional profiles from profile lines of the Western Antarctica Ice Sheet (WAIS) Divide and East Antarctica; high-resolution photographs of Antarctic ice cores; stratigraphic columns of ice cores; borehole and glaciochemical data (i.e. anions, actions, δ18O, δD etc.); and isotope data on greenhouse gases (CH4, O2, N2) extracted from gas bubbles in ice cores. The methodology was to engage students in (2) construction of topographic profiles; (2) suggest directions for ice flow based on simple physics; (3) formulate decisions on suitable locations for drilling ice cores; (4) visual ice stratigraphy including ice layer counting; (5) observation of any insoluble particles (i.e. meteoritic and volcanic material); (6) analysis of borehole temperature profiles; and (7) the interpretation of several datasets to derive a paleoclimate history of these areas of the continent. The overall goal of the project was to improve the students analytical and quantitative skills; their ability to evaluate relationships between physical and chemical properties in ice cores, and to advance the understanding the impending consequences of climate change while engaging science, technology, engineering and mathematics (STEM). Student learning outcomes were assessed at the completion of the `Polar Discovery Project' for their curiosity, analytical strength, creativity, group collaboration, problem-solving, innovation, and interest in level climate change and the implications of the its effects on polar regions.

The antiproliferative effect of indomethacin-loaded lipid-core nanocapsules in glioma cells is mediated by cell cycle regulation, differentiation, and the inhibition of survival pathways

PubMed Central

Bernardi, Andressa; Frozza, Rudimar L; Hoppe, Juliana B; Salbego, Christianne; Pohlmann, Adriana R; Battastini, Ana Maria O; Guterres, Sílvia S

2013-01-01

Despite recent advances in radiotherapy, chemotherapy, and surgical techniques, glioblastoma multiforme (GBM) prognosis remains dismal. There is an urgent need for new therapeutic strategies. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted intense interest in recent years because they can provide sustained, controlled, and targeted delivery. Here, we investigate the mechanisms involved in the antiproliferative effect of indomethacin-loaded lipid-core nanocapsules (IndOH-LNC) in glioma cells. IndOH-LNC were able to reduce cell viability by inducing apoptotic cell death in C6 and U138-MG glioma cell lines. Interestingly, IndOH-LNC did not affect the viability of primary astrocytes, suggesting that this formulation selectively targeted transformed cells. Mechanistically, IndOH-LNC induced inhibition of cell growth and cell-cycle arrest to be correlated with the inactivation of AKT and β-catenin and the activation of GSK-3β. IndOH-LNC also induced G0/G1 and/or G2/M phase arrest, which was accompanied by a decrease in the levels of cyclin D1, cyclin B1, pRb, and pcdc2 and an increase in the levels of Wee1 CDK inhibitor p21WAF1. Additionally, IndOH-LNC promoted GBM cell differentiation, observed as upregulation of glial fibrillary acidic protein (GFAP) protein and downregulation of nestin and CD133. Taken together, the crosstalk among antiproliferative effects, cell-cycle arrest, apoptosis, and cell differentiation should be considered when tailoring pharmacological interventions aimed at reducing glioma growth by using formulations with multiples targets, such as IndOH-LNC. PMID:23440594

A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

PubMed

Vemula, Sateesh Kumar

2015-12-01

A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

Thermostability of the coating, antigen and immunostimulator in an adjuvanted oral capsule vaccine formulation.

PubMed

Longet, Stephanie; Aversa, Vincenzo; O'Donnell, Daire; Tobias, Joshua; Rosa, Monica; Holmgren, Jan; Coulter, Ivan S; Lavelle, Ed C

2017-12-20

Oral vaccines present an attractive alternative to injectable vaccines for enteric diseases due to ease of delivery and the induction of intestinal immunity at the site of infection. However, susceptibility to gastrointestinal proteolysis, limited transepithelial uptake and a lack of clinically acceptable adjuvants present significant challenges. A further challenge to mass vaccination in developing countries is the very expensive requirement to maintain the cold chain. We recently described the effectiveness of a Single Multiple Pill ® (SmPill ® ) adjuvanted capsule approach to enhance the effectiveness of a candidate enterotoxigenic Escherichia coli (ETEC) oral vaccine. Here it was demonstrated that this delivery system maintains the antigenicity of ETEC colonisation factor antigen I (CFA/I) and the immunostimulatory activity of the orally active α-Galactosylceramide (α-GalCer) adjuvant after storage of SmPill ® minispheres under room temperature and extreme storage conditions for several months. In addition, the internal structure of the cores of SmPill ® minispheres and antigen release features at intestinal pH were found to be preserved under all these conditions. However, changes in the surface morphology of SmPill ® minispheres leading to the antigen release at gastric pH were observed after a few weeks of storage under extreme conditions. Those modifications were prevented by the introduction of an Opadry ® White film coating layer between the core of SmPill ® minispheres and the enteric coating. Under these conditions, protection against antigen release at gastric pH was maintained even under high temperature and humidity conditions. These results support the potential of the SmPill ® minisphere approach to maintain the stability of an adjuvanted whole cell killed oral vaccine formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of tablet formulation and subsequent film coating on the supersaturated dissolution behavior of amorphous solid dispersions.

PubMed

Sakai, Toshiro; Hirai, Daiki; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-04-05

The effects of tablet preparation and subsequent film coating with amorphous solid dispersion (ASD) particles that were composed of a drug with poor water solubility and hydrophilic polymers were investigated. ASD particles were prepared with a drug and vinylpyrrolidone-vinyl acetate copolymer (PVPVA) or polyvinylpyrrolidone (PVP) at a weight ratio of 1:1 or 1:2 using a melt extrusion technique. Tablets were prepared by conventional direct compression followed by pan coating. A mathematical model based on the Noyes-Whitney equation assuming that stable crystals precipitated at the changeable surface area of the solid-liquid interface used to estimate drug dissolution kinetics in a non-sink dissolution condition. All the ASD particles showed a maximum dissolution concentration approximately ten times higher than that of the crystalline drug. The ASD particles with PVPVA showed higher precipitation rate with lower polymer ratio, while PVP did not precipitate within 960 min regardless of the polymer ratio, suggesting the ASD particles of 1:1 drug:PVPVA (ASD-1) were the most unstable among the ASD particles considered. The dissolution of a core tablet with ASD-1 showed less supersaturation and a much higher precipitation rate than those of ASD-1 particles. However, a film-coated tablet or core tablet with a trace amount of hydroxypropylmethylcellulose (HPMC) showed a similar dissolution profile to that of the ASD-1 particles, indicating HPMC had a remarkable precipitation inhibition effect. Overall, these results suggest that tablet preparation with ASD may adversely affect the maintenance of supersaturation; however, this effect can be mitigated by adding an appropriate precipitation inhibitor to the formulation. Copyright © 2018 Elsevier B.V. All rights reserved.

Self-consistent predictor/corrector algorithms for stable and efficient integration of the time-dependent Kohn-Sham equation

NASA Astrophysics Data System (ADS)

Zhu, Ying; Herbert, John M.

2018-01-01

The "real time" formulation of time-dependent density functional theory (TDDFT) involves integration of the time-dependent Kohn-Sham (TDKS) equation in order to describe the time evolution of the electron density following a perturbation. This approach, which is complementary to the more traditional linear-response formulation of TDDFT, is more efficient for computation of broad-band spectra (including core-excited states) and for systems where the density of states is large. Integration of the TDKS equation is complicated by the time-dependent nature of the effective Hamiltonian, and we introduce several predictor/corrector algorithms to propagate the density matrix, one of which can be viewed as a self-consistent extension of the widely used modified-midpoint algorithm. The predictor/corrector algorithms facilitate larger time steps and are shown to be more efficient despite requiring more than one Fock build per time step, and furthermore can be used to detect a divergent simulation on-the-fly, which can then be halted or else the time step modified.

Liposomal adjuvant development for leishmaniasis vaccines.

PubMed

Askarizadeh, Anis; Jaafari, Mahmoud Reza; Khamesipour, Ali; Badiee, Ali

2017-08-01

Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to fatality. Since long-lasting protection is induced upon recovery from cutaneous leishmaniasis, development of an effective vaccine is promising. However, there is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the use of particulate adjuvants such as liposomes for effective delivery to the antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis vaccine efficacy. The extraordinary versatility of liposomes because of their unique amphiphilic and biphasic nature allows for using antigens or immunostimulators within the core, on the surface or within the bilayer, and modulates both the magnitude and the T-helper bias of the immune response. In this review article, we attempt to summarize the role of liposomal adjuvants in the development of Leishmania vaccines and describe the main physicochemical properties of liposomes like phospholipid composition, surface charge, and particle size during formulation design. We also suggest potentially useful formulation strategies in order for future experiments to have a chance to succeed as liposomal vaccines against leishmaniasis.

Liposomal adjuvant development for leishmaniasis vaccines

PubMed Central

Askarizadeh, Anis; Jaafari, Mahmoud Reza; Khamesipour, Ali; Badiee, Ali

2017-01-01

Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to fatality. Since long-lasting protection is induced upon recovery from cutaneous leishmaniasis, development of an effective vaccine is promising. However, there is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the use of particulate adjuvants such as liposomes for effective delivery to the antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis vaccine efficacy. The extraordinary versatility of liposomes because of their unique amphiphilic and biphasic nature allows for using antigens or immunostimulators within the core, on the surface or within the bilayer, and modulates both the magnitude and the T-helper bias of the immune response. In this review article, we attempt to summarize the role of liposomal adjuvants in the development of Leishmania vaccines and describe the main physicochemical properties of liposomes like phospholipid composition, surface charge, and particle size during formulation design. We also suggest potentially useful formulation strategies in order for future experiments to have a chance to succeed as liposomal vaccines against leishmaniasis. PMID:29201374

Controlling the energy of defects and interfaces in the amplitude expansion of the phase-field crystal model

NASA Astrophysics Data System (ADS)

Salvalaglio, Marco; Backofen, Rainer; Voigt, Axel; Elder, Ken R.

2017-08-01

One of the major difficulties in employing phase-field crystal (PFC) modeling and the associated amplitude (APFC) formulation is the ability to tune model parameters to match experimental quantities. In this work, we address the problem of tuning the defect core and interface energies in the APFC formulation. We show that the addition of a single term to the free-energy functional can be used to increase the solid-liquid interface and defect energies in a well-controlled fashion, without any major change to other features. The influence of the newly added term is explored in two-dimensional triangular and honeycomb structures as well as bcc and fcc lattices in three dimensions. In addition, a finite-element method (FEM) is developed for the model that incorporates a mesh refinement scheme. The combination of the FEM and mesh refinement to simulate amplitude expansion with a new energy term provides a method of controlling microscopic features such as defect and interface energies while simultaneously delivering a coarse-grained examination of the system.

An Improved TA-SVM Method Without Matrix Inversion and Its Fast Implementation for Nonstationary Datasets.

PubMed

Shi, Yingzhong; Chung, Fu-Lai; Wang, Shitong

2015-09-01

Recently, a time-adaptive support vector machine (TA-SVM) is proposed for handling nonstationary datasets. While attractive performance has been reported and the new classifier is distinctive in simultaneously solving several SVM subclassifiers locally and globally by using an elegant SVM formulation in an alternative kernel space, the coupling of subclassifiers brings in the computation of matrix inversion, thus resulting to suffer from high computational burden in large nonstationary dataset applications. To overcome this shortcoming, an improved TA-SVM (ITA-SVM) is proposed using a common vector shared by all the SVM subclassifiers involved. ITA-SVM not only keeps an SVM formulation, but also avoids the computation of matrix inversion. Thus, we can realize its fast version, that is, improved time-adaptive core vector machine (ITA-CVM) for large nonstationary datasets by using the CVM technique. ITA-CVM has the merit of asymptotic linear time complexity for large nonstationary datasets as well as inherits the advantage of TA-SVM. The effectiveness of the proposed classifiers ITA-SVM and ITA-CVM is also experimentally confirmed.

Predicting MHC-II binding affinity using multiple instance regression

PubMed Central

EL-Manzalawy, Yasser; Dobbs, Drena; Honavar, Vasant

2011-01-01

Reliably predicting the ability of antigen peptides to bind to major histocompatibility complex class II (MHC-II) molecules is an essential step in developing new vaccines. Uncovering the amino acid sequence correlates of the binding affinity of MHC-II binding peptides is important for understanding pathogenesis and immune response. The task of predicting MHC-II binding peptides is complicated by the significant variability in their length. Most existing computational methods for predicting MHC-II binding peptides focus on identifying a nine amino acids core region in each binding peptide. We formulate the problems of qualitatively and quantitatively predicting flexible length MHC-II peptides as multiple instance learning and multiple instance regression problems, respectively. Based on this formulation, we introduce MHCMIR, a novel method for predicting MHC-II binding affinity using multiple instance regression. We present results of experiments using several benchmark datasets that show that MHCMIR is competitive with the state-of-the-art methods for predicting MHC-II binding peptides. An online web server that implements the MHCMIR method for MHC-II binding affinity prediction is freely accessible at http://ailab.cs.iastate.edu/mhcmir. PMID:20855923

Explicit formulation of second and third order optical nonlinearity in the FDTD framework

NASA Astrophysics Data System (ADS)

Varin, Charles; Emms, Rhys; Bart, Graeme; Fennel, Thomas; Brabec, Thomas

2018-01-01

The finite-difference time-domain (FDTD) method is a flexible and powerful technique for rigorously solving Maxwell's equations. However, three-dimensional optical nonlinearity in current commercial and research FDTD softwares requires solving iteratively an implicit form of Maxwell's equations over the entire numerical space and at each time step. Reaching numerical convergence demands significant computational resources and practical implementation often requires major modifications to the core FDTD engine. In this paper, we present an explicit method to include second and third order optical nonlinearity in the FDTD framework based on a nonlinear generalization of the Lorentz dispersion model. A formal derivation of the nonlinear Lorentz dispersion equation is equally provided, starting from the quantum mechanical equations describing nonlinear optics in the two-level approximation. With the proposed approach, numerical integration of optical nonlinearity and dispersion in FDTD is intuitive, transparent, and fully explicit. A strong-field formulation is also proposed, which opens an interesting avenue for FDTD-based modelling of the extreme nonlinear optics phenomena involved in laser filamentation and femtosecond micromachining of dielectrics.

Nanocapsules of perfluorooctyl bromide for theranostics: from formulation to targeting

NASA Astrophysics Data System (ADS)

Diou, O.; Fattal, E.; Payen, T.; Bridal, S. L.; Valette, J.; Tsapis, N.

2014-03-01

The need to detect cancer at its early stages, as well as, to deliver chemotherapy to targeted site motivates many researchers to build theranostic platforms which combine diagnostic and therapy. Among imaging modalities, ultrasonography and Magnetic Resonance Imaging (MRI) are widely available, non invasive and complement each other. Both techniques often require the use of contrast agents. We have developed nanocapsules of perfluorooctyl bromide as dual contrast agent for both imaging modalities. The soft, amorphous polymer shell provides echogenicity, while the high-density perfluorinated liquid core allows detection by 19F MRI. We have used a shell of poly(lactide-co-glycolide) (PLGA) since this polymer is biodegradable, biocompatible and can be loaded with drugs. These capsules were shown to be efficient in vitro as contrast agents for both 19F MRI and ultrasonography. In addition, for in vivo applications a poly(ethyleneglycol) (PEG) coating promotes stability and prolonged circulation. Being stealth, nanocapsule can accumulate passively into implanted tumors by the EPR effect. We will present nanocapsule formulation and characterization, and will show promising in vivo results obtained for both ultrasonography and 19F MRI.

Analysis of Alternatives for Dismantling of the Equipment in Building 117/1 at Ignalina NPP - 13278

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

Poskas, Povilas; Simonis, Audrius; Poskas, Gintautas

2013-07-01

Ignalina NPP was operating two RBMK-1500 reactors which are under decommissioning now. In this paper dismantling alternatives of the equipment in Building 117/1 are analyzed. After situation analysis and collection of the primary information related to components' physical and radiological characteristics, location and other data, two different alternatives for dismantling of the equipment are formulated - the first (A1), when major components (vessels and pipes of Emergency Core Cooling System - ECCS) are segmented/halved in situ using flame cutting (oxy-acetylene) and the second one (A2), when these components are segmented/halved at the workshop using CAMC (Contact Arc Metal Cutting) technique.more » To select the preferable alternative MCDA method - AHP (Analytic Hierarchy Process) is applied. Hierarchical list of decision criteria, necessary for assessment of alternatives performance, are formulated. Quantitative decision criteria values for these alternatives are calculated using software DECRAD, which was developed by Lithuanian Energy Institute Nuclear engineering laboratory. While qualitative decision criteria are evaluated using expert judgment. Analysis results show that alternative A1 is better than alternative A2. (authors)« less

IceChrono1: a probabilistic model to compute a common and optimal chronology for several ice cores

NASA Astrophysics Data System (ADS)

Parrenin, Frédéric; Bazin, Lucie; Capron, Emilie; Landais, Amaëlle; Lemieux-Dudon, Bénédicte; Masson-Delmotte, Valérie

2016-04-01

Polar ice cores provide exceptional archives of past environmental conditions. The dating of ice cores and the estimation of the age scale uncertainty are essential to interpret the climate and environmental records that they contain. It is however a complex problem which involves different methods. Here, we present IceChrono1, a new probabilistic model integrating various sources of chronological information to produce a common and optimized chronology for several ice cores, as well as its uncertainty. IceChrono1 is based on the inversion of three quantities: the surface accumulation rate, the Lock-In Depth (LID) of air bubbles and the thinning function. The chronological information integrated into the model are: models of the sedimentation process (accumulation of snow, densification of snow into ice and air trapping, ice flow), ice and air dated horizons, ice and air depth intervals with known durations, Δdepth observations (depth shift between synchronous events recorded in the ice and in the air) and finally air and ice stratigraphic links in between ice cores. The optimization is formulated as a least squares problem, implying that all densities of probabilities are assumed to be Gaussian. It is numerically solved using the Levenberg-Marquardt algorithm and a numerical evaluation of the model's Jacobian. IceChrono follows an approach similar to that of the Datice model which was recently used to produce the AICC2012 chronology for 4 Antarctic ice cores and 1 Greenland ice core. IceChrono1 provides improvements and simplifications with respect to Datice from the mathematical, numerical and programming point of views. The capabilities of IceChrono is demonstrated on a case study similar to the AICC2012 dating experiment. We find results similar to those of Datice, within a few centuries, which is a confirmation of both IceChrono and Datice codes. We also test new functionalities with respect to the original version of Datice: observations as ice intervals with known durations, correlated observations, observations as gas intervals with known durations and observations as mixed ice-air stratigraphic links. IceChrono1 is freely available under the GPL v3 open source license.

Implementation strategies to promote community-engaged efforts to counter tobacco marketing at the point of sale.

PubMed

Leeman, Jennifer; Myers, Allison; Grant, Jennifer C; Wangen, Mary; Queen, Tara L

2017-09-01

The US tobacco industry spends $8.2 billion annually on marketing at the point of sale (POS), a practice known to increase tobacco use. Evidence-based policy interventions (EBPIs) are available to reduce exposure to POS marketing, and nationwide, states are funding community-based tobacco control partnerships to promote local enactment of these EBPIs. Little is known, however, about what implementation strategies best support community partnerships' success enacting EBPI. Guided by Kingdon's theory of policy change, Counter Tools provides tools, training, and other implementation strategies to support community partnerships' performance of five core policy change processes: document local problem, formulate policy solutions, engage partners, raise awareness of problems and solutions, and persuade decision makers to enact new policy. We assessed Counter Tools' impact at 1 year on (1) partnership coordinators' self-efficacy, (2) partnerships' performance of core policy change processes, (3) community progress toward EBPI enactment, and (4) salient contextual factors. Counter Tools provided implementation strategies to 30 partnerships. Data on self-efficacy were collected using a pre-post survey. Structured interviews assessed performance of core policy change processes. Data also were collected on progress toward EBPI enactment and contextual factors. Analysis included descriptive and bivariate statistics and content analysis. Following 1-year exposure to implementation strategies, coordinators' self-efficacy increased significantly. Partnerships completed the greatest proportion of activities within the "engage partners" and "document local problem" core processes. Communities made only limited progress toward policy enactment. Findings can inform delivery of implementation strategies and tests of their effects on community-level efforts to enact EBPIs.

New Equations of State Based on the Liquid Drop Model of Heavy Nuclei and Quantum Approach to Light Nuclei for Core-collapse Supernova Simulations

NASA Astrophysics Data System (ADS)

Furusawa, Shun; Sumiyoshi, Kohsuke; Yamada, Shoichi; Suzuki, Hideyuki

2013-08-01

We construct new equations of state for baryons at subnuclear densities for the use in core-collapse simulations of massive stars. The abundance of various nuclei is obtained together with thermodynamic quantities. A model free energy is constructed, based on the relativistic mean field theory for nucleons and the mass formula for nuclei with the proton number up to ~1000. The formulation is an extension of the previous model, in which we adopted the liquid drop model to all nuclei under the nuclear statistical equilibrium. We reformulate the new liquid drop model so that the temperature dependences of bulk energies could be taken into account. Furthermore, we extend the region in the nuclear chart, in which shell effects are included, by using theoretical mass data in addition to experimental ones. We also adopt a quantum-theoretical mass evaluation of light nuclei, which incorporates the Pauli- and self-energy shifts that are not included in the ordinary liquid drop model. The pasta phases for heavy nuclei are taken into account in the same way as in the previous model. We find that the abundances of heavy nuclei are modified by the shell effects of nuclei and temperature dependence of bulk energies. These changes may have an important effect on the rates of electron captures and coherent neutrino scatterings on nuclei in supernova cores. The abundances of light nuclei are also modified by the new mass evaluation, which may affect the heating and cooling rates of supernova cores and shocked envelopes.

A 3-D mathematical model to identify organ-specific risks in rats during thermal stress.

PubMed

Rakesh, Vineet; Stallings, Jonathan D; Helwig, Bryan G; Leon, Lisa R; Jackson, David A; Reifman, Jaques

2013-12-01

Early prediction of the adverse outcomes associated with heat stress is critical for effective management and mitigation of injury, which may sometimes lead to extreme undesirable clinical conditions, such as multiorgan dysfunction syndrome and death. Here, we developed a computational model to predict the spatiotemporal temperature distribution in a rat exposed to heat stress in an attempt to understand the correlation between heat load and differential organ dysfunction. The model includes a three-dimensional representation of the rat anatomy obtained from medical imaging and incorporates the key mechanisms of heat transfer during thermoregulation. We formulated a novel approach to estimate blood temperature by accounting for blood mixing from the different organs and to estimate the effects of the circadian rhythm in body temperature by considering day-night variations in metabolic heat generation and blood perfusion. We validated the model using in vivo core temperature measurements in control and heat-stressed rats and other published experimental data. The model predictions were within 1 SD of the measured data. The liver demonstrated the greatest susceptibility to heat stress, with the maximum temperature reaching 2°C higher than the measured core temperature and 95% of its volume exceeding the targeted experimental core temperature. Other organs also attained temperatures greater than the core temperature, illustrating the need to monitor multiple organs during heat stress. The model facilitates the identification of organ-specific risks during heat stress and has the potential to aid in the development of improved clinical strategies for thermal-injury prevention and management.

Bacteriophage-resistant mutants in Yersinia pestis: identification of phage receptors and attenuation for mice.

PubMed

Filippov, Andrey A; Sergueev, Kirill V; He, Yunxiu; Huang, Xiao-Zhe; Gnade, Bryan T; Mueller, Allen J; Fernandez-Prada, Carmen M; Nikolich, Mikeljon P

2011-01-01

Bacteriophages specific for Yersinia pestis are routinely used for plague diagnostics and could be an alternative to antibiotics in case of drug-resistant plague. A major concern of bacteriophage therapy is the emergence of phage-resistant mutants. The use of phage cocktails can overcome this problem but only if the phages exploit different receptors. Some phage-resistant mutants lose virulence and therefore should not complicate bacteriophage therapy. The purpose of this work was to identify Y. pestis phage receptors using site-directed mutagenesis and trans-complementation and to determine potential attenuation of phage-resistant mutants for mice. Six receptors for eight phages were found in different parts of the lipopolysaccharide (LPS) inner and outer core. The receptor for R phage was localized beyond the LPS core. Most spontaneous and defined phage-resistant mutants of Y. pestis were attenuated, showing increase in LD₅₀ and time to death. The loss of different LPS core biosynthesis enzymes resulted in the reduction of Y. pestis virulence and there was a correlation between the degree of core truncation and the impact on virulence. The yrbH and waaA mutants completely lost their virulence. We identified Y. pestis receptors for eight bacteriophages. Nine phages together use at least seven different Y. pestis receptors that makes some of them promising for formulation of plague therapeutic cocktails. Most phage-resistant Y. pestis mutants become attenuated and thus should not pose a serious problem for bacteriophage therapy of plague. LPS is a critical virulence factor of Y. pestis.

Bacteriophage-Resistant Mutants in Yersinia pestis: Identification of Phage Receptors and Attenuation for Mice

PubMed Central

Filippov, Andrey A.; Sergueev, Kirill V.; He, Yunxiu; Huang, Xiao-Zhe; Gnade, Bryan T.; Mueller, Allen J.; Fernandez-Prada, Carmen M.; Nikolich, Mikeljon P.

2011-01-01

Background Bacteriophages specific for Yersinia pestis are routinely used for plague diagnostics and could be an alternative to antibiotics in case of drug-resistant plague. A major concern of bacteriophage therapy is the emergence of phage-resistant mutants. The use of phage cocktails can overcome this problem but only if the phages exploit different receptors. Some phage-resistant mutants lose virulence and therefore should not complicate bacteriophage therapy. Methodology/Principal Findings The purpose of this work was to identify Y. pestis phage receptors using site-directed mutagenesis and trans-complementation and to determine potential attenuation of phage-resistant mutants for mice. Six receptors for eight phages were found in different parts of the lipopolysaccharide (LPS) inner and outer core. The receptor for R phage was localized beyond the LPS core. Most spontaneous and defined phage-resistant mutants of Y. pestis were attenuated, showing increase in LD50 and time to death. The loss of different LPS core biosynthesis enzymes resulted in the reduction of Y. pestis virulence and there was a correlation between the degree of core truncation and the impact on virulence. The yrbH and waaA mutants completely lost their virulence. Conclusions/Significance We identified Y. pestis receptors for eight bacteriophages. Nine phages together use at least seven different Y. pestis receptors that makes some of them promising for formulation of plague therapeutic cocktails. Most phage-resistant Y. pestis mutants become attenuated and thus should not pose a serious problem for bacteriophage therapy of plague. LPS is a critical virulence factor of Y. pestis. PMID:21980477

Accurate Estimate of Some Propagation Characteristics for the First Higher Order Mode in Graded Index Fiber with Simple Analytic Chebyshev Method

NASA Astrophysics Data System (ADS)

Dutta, Ivy; Chowdhury, Anirban Roy; Kumbhakar, Dharmadas

2013-03-01

Using Chebyshev power series approach, accurate description for the first higher order (LP11) mode of graded index fibers having three different profile shape functions are presented in this paper and applied to predict their propagation characteristics. These characteristics include fractional power guided through the core, excitation efficiency and Petermann I and II spot sizes with their approximate analytic formulations. We have shown that where two and three Chebyshev points in LP11 mode approximation present fairly accurate results, the values based on our calculations involving four Chebyshev points match excellently with available exact numerical results.

The Stanford how things work project

NASA Technical Reports Server (NTRS)

Fikes, Richard; Gruber, Tom; Iwasaki, Yumi

1994-01-01

We provide an overview of the Stanford How Things Work (HTW) project, an ongoing integrated collection of research activities in the Knowledge Systems Laboratory at Stanford University. The project is developing technology for representing knowledge about engineered devices in a form that enables the knowledge to be used in multiple systems for multiple reasoning tasks and reasoning methods that enable the represented knowledge to be effectively applied to the performance of the core engineering task of simulating and analyzing device behavior. The central new capabilities currently being developed in the project are automated assistance with model formulation and with verification that a design for an electro-mechanical device satisfies its functional specification.

Vibrations and structureborne noise in space station

NASA Technical Reports Server (NTRS)

Vaicaitis, R.

1985-01-01

Theoretical models were developed capable of predicting structural response and noise transmission to random point mechanical loads. Fiber reinforced composite and aluminum materials were considered. Cylindrical shells and circular plates were taken as typical representatives of structural components for space station habitability modules. Analytical formulations include double wall and single wall constructions. Pressurized and unpressurized models were considered. Parametric studies were conducted to determine the effect on structural response and noise transmission due to fiber orientation, point load location, damping in the core and the main load carrying structure, pressurization, interior acoustic absorption, etc. These analytical models could serve as preliminary tools for assessing noise related problems, for space station applications.

Should psychoanalysis become a science?

PubMed

Appelbaum, Jerome

2011-03-01

I wish to formulate in broad outline an approach to the conceptualization of psychoanalysis that is divested from theory. This view sees the core of psychoanalysis as a humanistic practice, first and foremost guided by the individuality of the dyadic encounter, rather than as a science. I will not argue for any particular view of psychoanalysis. Instead I marshal a series of considerations from the humanities, to frame a conceptualization of psychoanalysis as a clinically based interpretive discipline having a unique mission. Finally, I will present a futuristic hypothetical scenario whose aim is to show why psychoanalysis will remain a viable enterprise basically as conceived by Freud.

Earthicle: The Design of a Conceptually New Type of Particle.

PubMed

Uskoković, Vuk; Pernal, Sebastian; Wu, Victoria M

2017-01-18

The conception and the steps made in the design of a conceptually new type of composite particle, so-called "earthicle", are being described. This particle is meant to roughly mimic the layered structure of the Earth, having zerovalent iron core, silicate mantle, and a thin carbonaceous crust resembling the biosphere and its geological remnants. Particles are made in a stable colloidal form in an aqueous medium, involving chemical precipitation and pyrolysis of citric acid in the solution. The effects of various synthesis parameters were studied, including borohydride and oleate concentrations, APTES/TEOS molar ratio, chemical nature of the carbon precursors, and others. XRD analysis confirmed the predominantly zerovalent iron composition of the core, amorphous silica and crystalline iron silicate/silicide composition of the mesolayer, and the carbonaceous, amorphous graphitic composition of the surface coating. The atomically thin carbon shell was also detected as a distinct shoulder on the broad n-π* absorption resonance and the peak at ∼300 nm, a signature of sp 2 hybridized electronic orbitals and the result of the interband π-π* transition characteristic of graphitic structures. The irregularity of the shape of generally round Fe 0 particles has caused the uniformity of the silica shell to be directly proportional to the particle size. The size of the earthicles ranged from 60 to 500 nm depending on the ionic concentration of the precursors and additives. Silica layer effectively prevented the aggregation of the iron core and increased the biocompatibility of the particles. The point of zero charge first increased from the acidic to the neutral range after coating Fe 0 core with the APTES-functionalized, aminated silica shell and then restored its low value after depositing the carboxylated carbonic crust in a charge-reversal process designed to facilitate the formation of core-multishell structures. Tested on K7M2 osteosarcoma cell line and primary kidney and lung fibroblasts, cytotoxicity was cell-line dependent; however, the trend assessed in both planar and 3D cell culture with respect to the three types of particles, Fe 0 , Fe/SiO 2 , and Fe/SiO 2 /C, was general and independent of the cell line. Thus, the pronounced toxicity of Fe 0 alone became neutralized after the silica layer was coated around Fe 0 . The further addition of the carbonic layer reduced the viability as compared to Fe/SiO 2 , albeit in a statistically significant manner only for K7M2 cell line when compared against the untreated control. Cell response also varied depending on the formulation: while some formulations exhibited lethal effects on kidney fibroblasts, were harmless to lung fibroblasts, and boosted the proliferation of K7M2 osteosarcoma cells, other formulations exhibited the opposite behavior despite being similar in terms of their core/double-shell structure. Compared across three different cancerous cell lines, K7M2 osteosarcoma and U87 and E297 glioblastoma, a similar cell-line dependency in response was observed, yet the viability reduction was consistent for all Fe/SiO 2 /C particles, ranging from 80% to 85% of the untreated control. Carbon surface layer, albeit of graphitic structural nature, was of a markedly more viable character than that of nanosized graphene oxide. The viability of lung fibroblasts incubated with Fe/SiO 2 /C particles was reduced in the presence of the alternating magnetic field of 312.75 A/m and 1 MHz, while the viability reduction caused by Fe/SiO 2 /C particles in kidney fibroblasts and K7M2 cells was converted from statistically insignificant to significant, suggesting that the composite particles could be used for hyperthermia treatments, although their properties should be optimized for a more intense effect. A single-cell immunofluorescent analysis of the interaction of primary kidney fibroblasts and K7M2 osteosarcoma cells with Fe/SiO 2 /C particles demonstrated that the cell uptake and perinuclear localization may be responsible for the necrotic effects. This analysis also showed that composite Fe/SiO 2 /C particles may have the ability to cause the rupture of the cancer cell nucleus while having a harmless effect on the primary cells. Such a promising and selective anticancer activity will be investigated in more detail in future studies.

Composite fluorescent nanoparticles for biomedical imaging.

PubMed

Pansare, Vikram J; Bruzek, Matthew J; Adamson, Douglas H; Anthony, John; Prud'homme, Robert K

2014-04-01

In the rapidly expanding field of biomedical imaging, there is a need for nontoxic, photostable, and nonquenching fluorophores for fluorescent imaging. We have successfully encapsulated a new, extremely hydrophobic, pentacene-based fluorescent dye within polymeric nanoparticles (NPs) or nanocarriers (NCs) via the Flash NanoPrecipitation (FNP) process. Nanoparticles and dye-loaded micelles were formulated by FNP and characterized by dynamic light scattering, fluorescence spectroscopy, UV-VIS absorbance spectroscopy, and confocal microscopy. These fluorescent particles were loaded from less than 1% to 78% by weight core loading and the fluorescence maximum was found to be at 2.3 wt.%. The particles were also stably formed at 2.3% core loading from 20 up to 250 nm in diameter with per-particle fluorescence scaling linearly with the NC core volume. The major absorption peaks are at 458, 575, and 625 nm, and the major emission peaks at 635 and 695 nm. In solution, the Et-TP5 dye displays a strong concentration-dependent ratio of the emission intensities of the first two emission peaks, whereas in the nanoparticle core the spectrum is independent of concentration over the entire concentration range. A model of the fluorescence quenching was consistent with Förster resonant energy transfer as the cause of the quenching observed for Et-TP5. The Förster radius calculated from the absorption and emission spectra of Et-TP5 is 4.1 nm, whereas the average dye spacing in the particles at the maximum fluorescence is 3.9 nm. We have successfully encapsulated Et-TP5, a pentacene derivative dye previously only used in light-emitting diode applications, within NCs via the FNP process. The extreme hydrophobicity of the dye keeps it encapsulated in the NC core, its extended pentacene structure gives it relatively long wavelength emission at 695 nm, and the pentacene structure, without oxygen or nitrogen atoms in its core, makes it highly resistant to photobleaching. Its bulky side groups minimize self-quenching and localization within the nanoparticle core prevents interaction of the dye with biological surfaces, or molecules in diagnostic assays. Loading of dye in the NP core allows 25 times more dye to be delivered than if it were conjugated onto the nanocarrier surface. The utility of the dye for quantifying nanoparticle binding is demonstrated. Studies to extend the wavelength range of these pentacene dyes into the near infra-red are underway.

Resource use and cost implications of switching among warfarin formulations in atrial fibrillation patients.

PubMed

Kwong, Winghan Jacqueline; Kamat, Siddhesh; Fang, Christy

2012-12-01

Despite the uncertainty surrounding the safety of switching warfarin formulations, limited data exist on the resource use and costs associated with this switching pattern. To evaluate health care resource use and costs associated with switching warfarin formulations among patients with atrial fibrillation (AF) in a managed care organization. Patients diagnosed with AF (ICD-9 427.31) between July 2004 and August 2008 and who received warfarin therapy were identified in the HealthCore Integrated Research Database and categorized into 3 groups: users of generic warfarin formulations from a single drug manufacturer (generic-only group), users of branded warfarin formulations only (brand-only group), and patients who used generic and branded warfarin therapy interchangeably or who may have used generic drugs from 1 or more manufacturers (generic/brand switching group). Patients were followed 12 months or longer after their index warfarin prescription date to compare all-cause resource use and costs using multivariable regression analysis. The analysis included 12,908 patients: 71.82% were in the genericonly group, 9.61% were in the brand-only group, and 18.57% were in the generic/brand switching group. Patients in the generic/brand switching group were more likely to be hospitalized (relative risk [RR] = 1.43, p < 0.0001) or to use emergency department services (RR = 1.20, p < 0.01), compared to the brand-only users. Hospitalizations were more likely (RR = 1.26, p < 0.001) to occur among generic-only users versus brand-only users. Adjusted mean pharmacy costs per member per month were lower in the generic/brand switching group compared to the brand-only group ($257 vs $273, p = 0.038), but inpatient costs were higher ($1250 vs $972, p < 0.001), resulting in higher ($2125 vs $1847, p < 0.001) total costs. Generic-only users had lower pharmacy costs compared to brand-only users ($246 vs $273, p < 0.001), but total health care costs trended to be higher in the generic-only group ($1957 vs $1847, p = 0.053). The use of both generic and branded formulations of warfarin interchangeably, or the use of generics from more than 1 manufacturer, was associated with increased use of all-cause health care resources and total costs in patients with AF.

Formulation and process considerations affecting the stability of solid dosage forms formulated with methacrylate copolymers.

PubMed

Petereit, H U; Weisbrod, W

1999-01-01

General considerations concerning the stability of coated dosage forms are discussed, in order to avoid predictable interactions which may cause long-term stability problems. As polymers themselves maintain a high chemical stability and a low reactivity, instability phenomena mainly have to be explained by interactions of low molecular weight substances or physical changes. Possible interactions of functional groups can be predicted easily and insulating subcoates are proper countermeasures. Impurities, remaining in the polymeric material from the manufacturing process, may accelerate the hydrolysis of sensitive drugs. Instabilities of coated dosage forms are mainly based on physical interactions, caused by improper formulations of coating suspensions (i.e. plasticizers or pigments) or the film coating process. Residual moisture or solvents, probably enclosed in the core and migrating over time, may increase the permeability of coatings, due to plasticizing effects. The functionality of coatings from aqueous dispersions is linked to coalescence of latex particles. Thus any incomplete film formation, caused by too high or too low coating temperatures, may result in high permeable coatings. During storage, preferably under stress conditions this process will continue and thus change the release profile. Therefore bed temperatures of 10-20 degrees C above MFT must ensure the formation of homogeneous polymer layers during the coating process. Stability test procedures and packaging materials also need to be adapted to the physicochemical properties of the dosage form, in order to get meaningful results in stability tests.

Development and evaluation of controlled porosity osmotic pump for Nifedipine and Metoprolol combination

PubMed Central

2011-01-01

Background A system that can deliver multi-drug at a prolonged rate is very important for the treatment of various chronic diseases such as diabetes, asthma and heart disease. Controlled porosity osmotic pump tablet (CPOP) system was designed to deliver Nifedipine (NP) and Metoprolol (MP) in a controlled manner up to 12 h. It was prepared by incorporating drugs in the core and coated with various types (PVP, PEG-400 and HPMC) and levels (30, 40 and 50% w/w of polymer) of pore former at a weight gain of 8, 12 & 15%. Results Formulation variables like type and level of pore former and percent weight gain of membrane was found to affect the drug release from the developed formulations. Drug release was inversely proportional to the membrane weight but directly related to the level of pore former. Burst strength of the exhausted shell was inversely proportional to the level of pore former, but directly affected by the membrane weight. Results of scanning electron microscopy (SEM) studies showed the formation of pores in the membrane from where the drug release occurred. Dissolution models were applied to drug release data in order to establish the mechanism of drug release kinetics. In vitro release kinetics was subjected to superposition method to predict in vivo performance of the developed formulation. Conclusion The developed osmotic system is effective in the multi-drug therapy of hypertension by delivering both drugs in a controlled manner. PMID:21477386

Formulation of Granules for Site-Specific Delivery of an Antimicrobial Essential Oil to the Animal Intestinal Tract.

PubMed

Ma, Yin-Hing; Wang, Qi; Gong, Joshua; Wu, Xiao Yu

2016-03-01

Owing to proliferation of antibiotic-resistant bacteria, the use of antibiotics for livestock growth promotion is banned in many countries and alternatives to in-feed antibiotics are needed. Cinnamon essential oil exhibits strong in vitro antibacterial activity; however, direct addition of essential oils to animal feed has limited practicality due to their high volatility, odor, fast decomposition, and poor availability in the lower intestines. To solve these problems, we formulated trans-cinnamaldehyde (CIN) with an adsorbent powder and fatty acid via a melt-solidification technique. Core granules of an optimized composition contained up to 48% wt/wt CIN. The granules were then coated with an enteric polymer to impart site-specific release of CIN. CIN was mostly retained in simulated gastric fluid and released rapidly (>80% under 2 h) in simulated intestinal fluids. Rapid CIN autoxidation into cinnamic acid was inhibited by adding 1% vol/vol eugenol, which maintained CIN stability for at least 1 y. The granule formulation increased the antimicrobial activity of CIN against Escherichia coli K88 slightly with a minimum bactericidal concentration of 450 μg/mL for CIN in lauric acid-based granules compared with 550-600 μg/mL for palmitic acid-based granules and free CIN, respectively. These results encourage the potential use of encapsulated CIN for control of animal enteric pathogens by oral in-feed administration. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Evolution of Flexible Multibody Dynamics for Simulation Applications Supporting Human Spaceflight

NASA Technical Reports Server (NTRS)

Huynh, An; Brain, Thomas A.; MacLean, John R.; Quiocho, Leslie J.

2016-01-01

During the course of transition from the Space Shuttle and International Space Station programs to the Orion and Journey to Mars exploration programs, a generic flexible multibody dynamics formulation and associated software implementation has evolved to meet an ever changing set of requirements at the NASA Johnson Space Center (JSC). Challenging problems related to large transitional topologies and robotic free-flyer vehicle capture/ release, contact dynamics, and exploration missions concept evaluation through simulation (e.g., asteroid surface operations) have driven this continued development. Coupled with this need is the requirement to oftentimes support human spaceflight operations in real-time. Moreover, it has been desirable to allow even more rapid prototyping of on-orbit manipulator and spacecraft systems, to support less complex infrastructure software for massively integrated simulations, to yield further computational efficiencies, and to take advantage of recent advances and availability of multi-core computing platforms. Since engineering analysis, procedures development, and crew familiarity/training for human spaceflight is fundamental to JSC's charter, there is also a strong desire to share and reuse models in both the non-realtime and real-time domains, with the goal of retaining as much multibody dynamics fidelity as possible. Three specific enhancements are reviewed here: (1) linked list organization to address large transitional topologies, (2) body level model order reduction, and (3) parallel formulation/implementation. This paper provides a detailed overview of these primary updates to JSC's flexible multibody dynamics algorithms as well as a comparison of numerical results to previous formulations and associated software.

Chitosan nanoparticles for the linear release of model cationic Peptide.

PubMed

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

2015-07-01

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

Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation

PubMed Central

Almeida, Freya M Freyre; Blanco, Aracelys; Trujillo, Heidy; Hernández, Dunia; García, Daymir; Alba, José S; Abad, Matilde López; Merino, Nelson; Lobaina, Yadira

2016-01-01

ABSTRACT The development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys. Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study. How to cite this article Freyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation. Euroasian J Hepato-Gastroenterol 2016;6(1):25-30. PMID:29201720

Few-body semiclassical approach to nucleon transfer and emission reactions

NASA Astrophysics Data System (ADS)

Sultanov, Renat A.; Guster, D.

2014-04-01

A three-body semiclassical model is proposed to describe the nucleon transfer and emission reactions in a heavy-ion collision. In this model the two heavy particles, i.e. nuclear cores A1(ZA1, MA1) and A2(ZA2, MA2), move along classical trajectories {{R}_1}( t ) and {{R}_2}( t ) respectively, while the dynamics of the lighter neutron (n) is considered from a quantum mechanical point of view. Here, Mi are the nucleon masses and Zi are the Coulomb charges of the heavy nuclei (i = 1, 2). A Faddeev-type semiclassical formulation using realistic paired nuclear-nuclear potentials is applied so that all three channels (elastic, rearrangement and break-up) are described in a unified manner. In order to solve the time-dependent equations the Faddeev components of the total three-body wave-function are expanded in terms of the input and output channel target eigenfunctions. In the special case, when the nuclear cores are identical (A1 ≡ A2) and also the two-level approximation in the expansion over the target (subsystem) functions is used, the time-dependent semiclassical Faddeev equations are resolved in an explicit way. To determine the realistic {{R}_1}( t ) and {{R}_2}( t ) trajectories of the nuclear cores, a self-consistent approach based on the Feynman path integral theory is applied.

A transmission line model for propagation in elliptical core optical fibers

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

Georgantzos, E.; Boucouvalas, A. C.; Papageorgiou, C.

The calculation of mode propagation constants of elliptical core fibers has been the purpose of extended research leading to many notable methods, with the classic step index solution based on Mathieu functions. This paper seeks to derive a new innovative method for the determination of mode propagation constants in single mode fibers with elliptic core by modeling the elliptical fiber as a series of connected coupled transmission line elements. We develop a matrix formulation of the transmission line and the resonance of the circuits is used to calculate the mode propagation constants. The technique, used with success in the casemore » of cylindrical fibers, is now being extended for the case of fibers with elliptical cross section. The advantage of this approach is that it is very well suited to be able to calculate the mode dispersion of arbitrary refractive index profile elliptical waveguides. The analysis begins with the deployment Maxwell’s equations adjusted for elliptical coordinates. Further algebraic analysis leads to a set of equations where we are faced with the appearance of harmonics. Taking into consideration predefined fixed number of harmonics simplifies the problem and enables the use of the resonant circuits approach. According to each case, programs have been created in Matlab, providing with a series of results (mode propagation constants) that are further compared with corresponding results from the ready known Mathieu functions method.« less

State interference in resonance Auger and x-ray emission

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

Cesar, A.; Agren, H.

1992-03-01

Starting from a scattering-theory formulation, cross sections for Auger and x-ray decay from energetically shifted inner-shell states are derived. Two situations are studied: (i) when there are several close-lying intermediate core-hole states with no vibrational excitations, in which case a {ital state} {ital interference} effect is identified; and (ii) when there are several close-lying intermediate states with vibrational excitations, in which case a {ital vibronic} {ital interference} effect is identified. In the latter case, the present formalism is a many-state generalization of the {ital vibrational} {ital interference} {ital effects} derived from the same type of scattering formalism in our previousmore » paper (A. Cesar, H. Agren, and V. Carravetta, Phys. Rev. A 40, 187 (1989)). Applications are carried out for spectra of some few-state model systems. It is found that a conventional analysis in terms of discrete noninteracting (noninterfering) states, such as the one-center decomposition model, is only valid when the ratio ({ital R}) between energy shift and lifetime is sufficiently large. For states with small {ital R}, a more complete theoretical account must be undertaken, including, e.g., the calculation of phases of the respective transition moments. The presented formalism applies to resonance Auger or x-ray emission spectra, to Auger and x-ray emission from core-electron shake-up states, and also, under certain circumstances, to emission from chemically shifted core-hole states.« less

Biocompatibility and safety of a hybrid core-shell nanoparticulate OP-1 delivery system intramuscularly administered in rats.

PubMed

Haidar, Ziyad S; Hamdy, Reggie C; Tabrizian, Maryam

2010-04-01

A hybrid, localized and release-controlled delivery system for bone growth factors consisting of a liposomal core incorporated into a shell of alternating layer-by-layer self-assembled natural polyelectrolytes has been formulated. Hydrophilic, monodisperse, spherical and stable cationic nanoparticles (< or =350 nm) with an extended shelf-life resulted. Cytocompatibility was previously assayed with MC3T3-E1.4 mouse preosteoblasts showing no adverse effects on cell viability. In this study, the in vivo biocompatibility of unloaded and loaded nanoparticles with osteogenic protein-1 or OP-1 was investigated. Young male Wistar rats were injected intramuscularly and monitored over a period of 10 weeks for signs of inflammation and/or adverse reactions. Blood samples (600 microL/collection) were withdrawn followed by hematological and biochemical analysis. Body weight changes over the treatment period were noted. Major organs were harvested, weighed and examined histologically for any pathological changes. Finally, the injection site was identified and examined immunohistochemically. Overall, all animals showed no obvious toxic health effects, immune responses and/or change in organ functions. This hybrid core-shell nanoparticulate delivery system localizes the effect of the released bioactive load within the site of injection in muscle with no significant tissue distress. Hence, a safe and promising carrier for therapeutic growth factors and possibly other biomolecules is presented. 2009 Elsevier Ltd. All rights reserved.

Computational studies on self-assembled paclitaxel structures: templates for hierarchical block copolymer assemblies and sustained drug release.

PubMed

Guo, Xin D; Tan, Jeremy P K; Kim, Sung H; Zhang, Li J; Zhang, Ying; Hedrick, James L; Yang, Yi Y; Qian, Yu

2009-11-01

Paclitaxel-loaded poly(ethylene oxide)-b-poly(lactide) (PEO-b-PLA) systems have been observed to assemble into fiber structures with remarkably different properties using different chirality and molecular weight of PLA segments. In this study, dissipative particle dynamics (DPD) simulations were carried out to elaborate the microstructures and properties of pure paclitaxel and paclitaxel-loaded PEO-b-PLA systems. Paclitaxel molecules formed ribbon or fiber like structures in water. With the addition of PEO-b-PDLA, PEO-b-PLLA and their stereocomplex, paclitaxel acted as a template and polymer molecules assembled around the paclitaxel structure to form core/shell structured fibers having a PEO shell. For PEO19-b-PDLA27 and PEO19-b-PLLA27 systems, PLA segments and paclitaxel molecules were distributed homogeneously in the core of fibers based on the hydrophobic interactions. In the stereocomplex formulation, paclitaxel molecules were more concentrated in the inner PLA stereocomplex core, which led to slower release of paclitaxel. By increasing the length of PLA segments (e.g. 8,16,22 and 27), the crystalline structure of paclitaxel was gradually weakened and destroyed, which was further proved by X-ray diffraction studies. All the simulation results agreed well with experimental data, suggesting that the DPD simulations may provide a powerful tool for designing drug delivery systems.

[Kampo Medicine in the New Model Core Curriculum of Pharmaceutical Education].

PubMed

Kobayashi, Yoshinori

2016-01-01

What should we educate for Kampo medicine in the model core curriculum of pharmaceutical education? The curricular core should be discussed considering the points mentioned below. (1) Positioning of Kampo medicine in the Japanese medical care system. Kampo medicine is an authorized medical care category in the National Health Insurance (NHI) program in Japan. The NHI drug price list carries 148 Kampo formulations. According to the report of the Japan Kampo Medicines Manufacturers Association in 2011, approximately 90% of Japanese physicians prescribe Kampo medicines. (2) Differences between Kampo medicine and western medicine: In Kampo medicine, the most suitable formula among various Kampo formulas to normalize the psychophysical state of individual patients is selected. In other words, if there is a complaint, there are always some treatments. (3) A strong point of Kampo medicine: Kampo medicine enables physicians to deal with difficult-to-treat conditions by western medicine alone. Also, by using the scale of Kampo medicine, each patient can grasp his or her own systemic state and improve their lifestyle. To extend healthy life expectancy, a basic knowledge of Kampo medicine may play a significant role in integrated health care. "The guide book of the approval standards for OTC Kampo products", "the pharmaceutical advanced educational guideline", and "the manual of the exam questions preparation for registered sales clerks" should also be consulted before selecting the area and contents that should be covered.

Enteric-coated sustained-release nanoparticles by coaxial electrospray: preparation, characterization, and in vitro evaluation

NASA Astrophysics Data System (ADS)

Hao, Shilei; Wang, Bochu; Wang, Yazhou; Xu, Yingqian

2014-02-01

Enteric-coated formulations can delay the release of drugs until they have passed through the stomach. However, high concentration of drugs caused by rapidly released in the small intestine leads to the intestinal damage, and frequent administration would increase the probability of missing medication and reduce the patient compliance. To solve the above-mentioned problems, aspirin-loaded enteric-coated sustained-release nanoparticles with core-shell structure were prepared via one-step method using coaxial electrospray in this study. Eudragit L100-55 as pH-sensitive polymer and Eudragit RS as sustained-release polymer were used for the outer coating and inner core of the nanoparticles, respectively. The maximum loading capacity of nanoparticles was 23.66 % by changing the flow rate ratio of outer/inner solutions, and the entrapment efficiency was nearly 100 %. Nanoparticles with core-shell structure were observed via fluorescence microscope and transmission electron microscope. And pH-sensitive and sustained drug release profiles were observed in the media with different pH values (1.2 and 6.8). In addition, mild cytotoxicity in vitro was detected, and the nanoparticles could be taken up by Caco-2 cells within 1.0 h in cellular uptake study. These results indicate that prepared enteric-coated sustained-release nanoparticles would be a more safety and effective carrier for oral drug delivery.

Questions about Mercury's role in comparative planetary geophysics

NASA Technical Reports Server (NTRS)

Chapman, C. R.; Weidenschilling, S. J.; Davis, D. R.; Greenberg, R.; Leake, M. A.

1985-01-01

Problems which have arisen in formulating a mutually consistent picture of Mercury's evolution are outlined. It appears that one or more of the following widely adopted assumptions are wrong about Mercury: (1) its original composition at least approximately resulted from equilibrium condensation; (2) its magnetic field arises from a still-active dynamo; (3) its thermal evolution should have yielded early core formation followed by cooling and a global contraction approaching 20 km in the planet's radius; (4) Mercury's surface is basaltic and the intercrater plains are of volcanic origin. It is suggested that Mercury's role in comparative planetology be reevaluated in the context of an alternative timescale based on the possibility that Mercury was subjected to a continuing source of cratering projectiles over recent aeons, which have not impacted the other terrestrial planets. Although such vulcanoids have not yet been discovered, the evolution of Mercury's orbit due to secular perturbations could well have led to a prolonged period of sweeping out any intra-Mercurian planetesimals that were originally present. Mercury's surface could be younger than previously believed, which explains why Mercury's core is still molten.

Synthesis of Polylactide-Based Core-Shell Interface Cross-Linked Micelles for Anticancer Drug Delivery.

PubMed

Chen, Chih-Kuang; Lin, Wei-Jen; Hsia, Yu; Lo, Leu-Wei

2017-03-01

Well-defined poly(ethylene glycol)-b-allyl functional polylactide-b-polylactides (PEG-APLA-PLAs) are synthesized through sequential ring-opening polymerization. PEG-APLA-PLAs that have amphiphilic properties and reactive allyl side chains on their intermediate blocks are successfully transferred to core-shell interface cross-linked micelles (ICMs) by micellization and UV-initiated irradiation. ICMs have demonstrated enhanced colloidal stability in physiological-mimicking media. Hydrophobic molecules such as Nile Red or doxorubicin (Dox) are readily loaded into ICMs; the resulting drug-ICM formulations possess slow and sustained drug release profiles under physiological-mimicking conditions. ICMs exhibit negligible cytotoxicity in human uterine sarcoma cancer cells by using biodegradable aliphatic polyester as the hydrophobic segments. Relative to free Dox, Dox-loaded ICMs show a reduced cytotoxicity due to the late intracellular release of Dox from ICMs. Overall, ICMs represent a new type of biodegradable cross-linked micelle and can be employed as a promising platform for delivering a broad variety of hydrophobic drugs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microfluidic Bioprinting for Engineering Vascularized Tissues and Organoids.

PubMed

Zhang, Yu Shrike; Pi, Qingmeng; van Genderen, Anne Metje

2017-08-11

Engineering vascularized tissue constructs and organoids has been historically challenging. Here we describe a novel method based on microfluidic bioprinting to generate a scaffold with multilayer interlacing hydrogel microfibers. To achieve smooth bioprinting, a core-sheath microfluidic printhead containing a composite bioink formulation extruded from the core flow and the crosslinking solution carried by the sheath flow, was designed and fitted onto the bioprinter. By blending gelatin methacryloyl (GelMA) with alginate, a polysaccharide that undergoes instantaneous ionic crosslinking in the presence of select divalent ions, followed by a secondary photocrosslinking of the GelMA component to achieve permanent stabilization, a microfibrous scaffold could be obtained using this bioprinting strategy. Importantly, the endothelial cells encapsulated inside the bioprinted microfibers can form the lumen-like structures resembling the vasculature over the course of culture for 16 days. The endothelialized microfibrous scaffold may be further used as a vascular bed to construct a vascularized tissue through subsequent seeding of the secondary cell type into the interstitial space of the microfibers. Microfluidic bioprinting provides a generalized strategy in convenient engineering of vascularized tissues at high fidelity.

Stellar structure and compact objects before 1940: Towards relativistic astrophysics

NASA Astrophysics Data System (ADS)

Bonolis, Luisa

2017-06-01

Since the mid-1920s, different strands of research used stars as "physics laboratories" for investigating the nature of matter under extreme densities and pressures, impossible to realize on Earth. To trace this process this paper is following the evolution of the concept of a dense core in stars, which was important both for an understanding of stellar evolution and as a testing ground for the fast-evolving field of nuclear physics. In spite of the divide between physicists and astrophysicists, some key actors working in the cross-fertilized soil of overlapping but different scientific cultures formulated models and tentative theories that gradually evolved into more realistic and structured astrophysical objects. These investigations culminated in the first contact with general relativity in 1939, when J. Robert Oppenheimer and his students George Volkoff and Hartland Snyder systematically applied the theory to the dense core of a collapsing neutron star. This pioneering application of Einstein's theory to an astrophysical compact object can be regarded as a milestone in the path eventually leading to the emergence of relativistic astrophysics in the early 1960s.

The linguistic demands of the Common Core State Standards for reading and writing informational text in the primary grades.

PubMed

Roberts, Kathryn L

2012-05-01

Forty-five states and four U.S. territories have committed to implementing the new Common Core State Standards, with the goal of graduating students from our K-12 programs who are ready for college and careers. For many, the new standards represent a shift in genre focus, giving much more specific attention to informational genres. Beginning in the primary grades, the standards set high expectations for students' interaction with informational text, many of which are significantly more linguistically demanding than the standards that they replace. These increased demands are likely to pose difficulties not only for students currently receiving language support, but also for students without identified delays or disabilities. This article describes several of the kindergarten through fifth-grade standards related to informational text, highlighting the linguistic demands that each poses. In addition, instructional strategies are provided that teachers and speech-language pathologists can use to support the understanding and formulation of informational text for listening, reading, speaking, and writing. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Modeling of Advanced BWR Fuel Designs with the NRC Fuel Depletion Codes PARCS/PATHS

DOE PAGES

Ward, Andrew; Downar, Thomas J.; Xu, Y.; ...

2015-04-22

The PATHS (PARCS Advanced Thermal Hydraulic Solver) code was developed at the University of Michigan in support of U.S. Nuclear Regulatory Commission research to solve the steady-state, two-phase, thermal-hydraulic equations for a boiling water reactor (BWR) and to provide thermal-hydraulic feedback for BWR depletion calculations with the neutronics code PARCS (Purdue Advanced Reactor Core Simulator). The simplified solution methodology, including a three-equation drift flux formulation and an optimized iteration scheme, yields very fast run times in comparison to conventional thermal-hydraulic systems codes used in the industry, while still retaining sufficient accuracy for applications such as BWR depletion calculations. Lastly, themore » capability to model advanced BWR fuel designs with part-length fuel rods and heterogeneous axial channel flow geometry has been implemented in PATHS, and the code has been validated against previously benchmarked advanced core simulators as well as BWR plant and experimental data. We describe the modifications to the codes and the results of the validation in this paper.« less

Reviewing the quality of strategic environmental assessment reports for English spatial plan core strategies

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

Fischer, Thomas B., E-mail: fischer@liverpool.ac.u

This paper summarises the results of a research project from early 2008, involving the author of this paper, as well as 18 post-graduate University of Liverpool students, in which the quality of European Directive based strategic environmental assessment (SEA) reports of English spatial plan core strategies (conducted within the context of the spatial planning sustainability appraisal-SA-regime) was reviewed. The project aimed at establishing the extensiveness of emerging spatial plan related SEA practice, as well as highlighting shortcomings and problems. Overall, it was found that whilst some aspects of assessment were done well, others were not of a satisfactory quality. Shortcomingsmore » were connected particularly with the practice of listing potentially relevant baseline documents and data without distinguishing sufficiently between those that are important in terms of significant impacts and those that are not. Problems were also found to exist with the evaluation of options and impacts, the consideration of substantive aspects, such as health, as well as regarding the formulation of final recommendations and monitoring.« less

Diagnosis and Management of Paediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement.

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego; Baumann, Ulrich; Czubkowski, Piotr; Debray, Dominique; Dezsofi, Antal; Fischler, Björn; Gupte, Girish; Hierro, Loreto; Indolfi, Giuseppe; Jahnel, Jörg; Smets, Françoise; Verkade, Henkjan J; Hadzic, Nedim

2017-11-03

Paediatric autoimmune liver disease is characterised by inflammatory liver histology, circulating autoantibodies and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. Two types of paediatric AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibodies (anti-LKM-1/anti-LC-1; AIH-2).Pertinent issues addressing the diagnosis, treatment and long term follow up were formulated by a core group of ESPGHAN members. They have commissioned the first authors with execution of this project. Initially, they have performed a systematic literature search on MEDLINE, ResearchGate and Mendeley databases over the last 30 years and produced a document focusing on prospective and retrospective studies in children. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique.

A matrix approach to guide IHC-based tissue biomarker development in oncology drug discovery.

PubMed

Smith, Neil R; Womack, Christopher

2014-01-01

Immunohistochemistry (IHC) is a core platform for the analysis of tissue samples, and there is an increasing demand for reliable and quantitative IHC-based tissue biomarkers in oncology clinical research and development (R&D) environments. Biomarker assay and drug development proceed in parallel. Furthermore, biomarker assay requirements change with each phase of drug development. We have therefore developed a matrix tool to enable researchers to evaluate whether a particular IHC biomarker assay is fit for purpose. Experience gained from the development of 130 IHC biomarkers, supporting a large number of oncology drug projects, was used to formulate a practical approach to IHC assay development. The resultant matrix grid and accompanying work flow incorporates 16 core decision points that link antibody and assay specificity and sensitivity, and assay performance in preclinical and clinical samples, with stages of drug development. The matrix provides a means to ensure that relevant information on an IHC assay in development is recorded and communicated consistently and that minimum assay validation requirements are met. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Lyophilized sustained release mucoadhesive chitosan sponges for buccal buspirone hydrochloride delivery: formulation and in vitro evaluation.

PubMed

Kassem, Mohamed A A; ElMeshad, Aliaa N; Fares, Ahmed R

2015-06-01

This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 3(2) factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.

The Effect of Drought on Stomatal Conductance in the Biosphere 2 Rainforest

NASA Astrophysics Data System (ADS)

Gay, J. D.; Van Haren, J. L. M.

2015-12-01

Drought is a major climate change concern for the Earth's rainforests; however little is currently known about how these forests and individual plants will respond to water stress. At the individual level, the ability of plants to regulate their stomatal conductance is an important preservation mechanism that helps to cool leaves, regulate water loss, and uptake carbon dioxide. At the ecosystem level, transpiration in rainforests is a major contributor to the positive feedback loop that returns moisture to the atmosphere for continued precipitation cycles. Nearly 60% of atmospheric moisture in the Amazon rain forests has been traced back to origins of transpiration from its plants. In relation to current climatic conditions, stomatal conductance rates are highly variable across rainforest species and environmental conditions. It is still unknown to what extent these rates will decrease at leaf and forest level in response to periods of drought. The University of Arizona's Biosphere 2 (B2) served as the study site for a simulated 4-week long drought because of its ability to mimic the micrometeorology of an Amazonian rainforest. Three species of plants were chosen at various levels in the canopy: Clitoria racemosa, Cissus sicyoides, and Hibiscus elatus. These plants were selected based on their relative abundance and distribution in the B2 forest. It was revealed that two out of the three species exhibited decreases in H20 efflux at each elevation, while one species (C. racemosa) proved much more resistant, at each elevation, to H20 loss. These results may be useful for future integrative modeling of how individual leaf level responses extend to entire ecosystem scales. It will be important to better understand how rainforests conserve, recycle, and lose water to gauge their response to warming climate, and increased periods of drought in the tropics.

L-arginine supplementation prevents increases in intestinal permeability and bacterial translocation in male Swiss mice subjected to physical exercise under environmental heat stress.

PubMed

Costa, Kátia Anunciação; Soares, Anne Danieli Nascimento; Wanner, Samuel Penna; Santos, Rosana das Graças Carvalho dos; Fernandes, Simone Odília Antunes; Martins, Flaviano dos Santos; Nicoli, Jacques Robert; Coimbra, Cândido Celso; Cardoso, Valbert Nascimento

2014-02-01

Dietary supplementation with l-arginine has been shown to improve the intestinal barrier in many experimental models. This study investigated the effects of arginine supplementation on the intestinal permeability and bacterial translocation (BT) induced by prolonged physical exercise under heat stress. Under anesthesia, male Swiss mice (5-wk-old) were implanted with an abdominal sensor to record their core body temperature (T(core)). After recovering from surgery, the mice were divided into 3 groups: a non-supplemented group that was fed the standard diet formulated by the American Institute of Nutrition (AIN-93G; control), a non-supplemented group that was fed the AIN-93G diet and subjected to exertional hyperthermia (H-NS), and a group supplemented with l-arginine at 2% and subjected to exertional hyperthermia (H-Arg). After 7 d of treatment, the H-NS and H-Arg mice were forced to run on a treadmill (60 min, 8 m/min) in a warm environment (34°C). The control mice remained at 24°C. Thirty min before the exercise or control trials, the mice received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with technetium-99m ((99m)Tc-DTPA) or (99m)Tc-Escherichia coli by gavage to assess intestinal permeability and BT, respectively. The H-NS mice terminated the exercise with T(core) values of ∼40°C, and, 4 h later, presented a 12-fold increase in the blood uptake of (99m)Tc-DTPA and higher bacterial contents in the blood and liver than the control mice. Although supplementation with arginine did not change the exercise-induced increase in T(core), it prevented the increases in intestinal permeability and BT caused by exertional hyperthermia. Our results indicate that dietary l-arginine supplementation preserves the integrity of the intestinal epithelium during exercise under heat stress, acting through mechanisms that are independent of T(core) regulation.

Using collaborative technology to enhance pre-service teachers' pedagogical content knowledge in Science

NASA Astrophysics Data System (ADS)

Donnelly, Dermot Francis; Hume, Anne

2015-01-01

Background:Supporting pre-service teacher (PT) collaboration as a means of professional learning is a challenging but essential task for effective practice. However, teacher placements or practicums in schools, which is common practice within teacher education programmes, can often isolate PTs from sharing their experiences with each other. Further, the articulation of effective pedagogical practices by high-quality teachers is limited, restricting PTs' ability to access such professional knowledge. Purpose:This study investigates how the introduction of a collaborative technology, a wiki, may enhance existing and new opportunities for pre-service teachers' (PTs) to develop pedagogical content knowledge (PCK). Sample:Seven PT chemistry teachers of varied backgrounds participated in this study. Design and method:The PTs were learning to collaboratively formulate and document their early topic-specific teaching knowledge using a pedagogical tool known as Content Representation (CoRe) design. Once scaffolded into this process, the PTs continued and extended this collaborative work online through the introduction of a wiki. Data were collected for qualitative analysis through the CoRe artefacts, a semi-structured focus group interview, and PTs' reflective essays about their collaborative experiences representing their teaching knowledge in CoRes through the wiki. Results:Data analysis highlighted that while wiki use showed some potential for collaborative representation when participants were not face-to-face, the PTs were hesitant in critiquing each other's work. As such, the online representations remained relatively static without face-to-face interaction. However, developing artefacts online was favoured over established practice and the access to artefacts of their peers on the wiki enhanced PTs' consideration for their own PCK. Conclusion:Wikis show some potential in the hosting of CoRes, but issues in simultaneous posting and lack of chat functionality may hinder PTs' ability to easily critique each others' work. However, the PTs in this study also demonstrated a broader unwillingness to critique each other's CoRes that teacher educators need to challenge. The use of technology to support PTs' CoRes and critiquing warrants further research.

Truncation effects in computing free wobble/nutation modes explored using a simple Earth model

NASA Astrophysics Data System (ADS)

Seyed-Mahmoud, Behnam; Rochester, Michael G.; Rogers, Christopher M.

2017-06-01

The displacement field accompanying the wobble/nutation of the Earth is conventionally represented by an infinite chain of toroidal and spheroidal vector spherical harmonics, coupled by rotation and ellipticity. Numerical solutions for the eigenperiods require truncation of that chain, and the standard approaches using the linear momentum description (LMD) of deformation during wobble/nutation have truncated it at very low degrees, usually degree 3 or 4, and at most degree 5. The effects of such heavy truncation on the computed eigenperiods have hardly been examined. We here investigate the truncation effects on the periods of the free wobble/nutation modes using a simplified Earth model consisting of a homogeneous incompressible inviscid liquid outer core with a rigid (but not fixed) inner core and mantle. A novel Galerkin method is implemented using a Clairaut coordinate system to solve the classic Poincaré problem in the liquid core and, to close the problem, we use the Lagrangean formulation of the Liouville equation for each of the solid parts of the Earth model. We find that, except for the free inner core nutation (FICN), the periods of the free rotational modes converge rather quickly. The period of the tiltover mode is found to excellent accuracy. The computed periods of the Chandler wobble and free core nutation are nearly identical to the values cited in the literature for similar Earth models, but that for the inner core wobble is slightly different. Truncation at low-degree harmonics causes the FICN period to fluctuate over a range as large as 90 sd, with different values at different truncation levels. For example, truncation at degree 6 gives a period of 752 sd (almost identical with the value cited in the literature for such an Earth model) but truncation at degree 24 is required to obtain convergence, and the resulting period is 746 ± 1 sd, as more terms are included, with no guarantee that its proximity to earlier values is other than fortuitous. We conclude that the heavy truncation necessitated by the conventional LMD is unsatisfactory for the FICN.

Truncation Effects in Computing Free Wobble/Nutation Modes Explored Using a Simple Earth Model

NASA Astrophysics Data System (ADS)

Seyed-Mahmoud, B.; Rochester, M. G.; Rogers, C. M.

2016-12-01

The displacement field accompanying the wobble/nutation of the Earth is conventionally represented by an infinite chain of toroidal and spheroidal vector spherical harmonics, coupled by rotation and ellipticity. Numerical solutions for the eigenperiods require truncation of that chain, and the standard approaches using the linear momentum description (LMD) of deformation during wobble/nutation have truncated it at very low degrees, usually degree 3 or 4, and at most degree 5. The effects of such heavy truncation on the computed eigenperiods have hardly been examined. We here investigate the truncation effects on the periods of the free wobble/nutation modes using a simplified Earth model consisting of a homogeneous incompressible inviscid liquid outer core with a rigid (but not fixed) inner core and mantle. A novel Galerkin method is implemented using a Clairaut coordinate system to solve the classic Poincare problem in the liquid core and, to close the problem, we use the Lagrangean formulation of the Liouville equation for each of the solid parts of the Earth model. We find that, except for the free inner core nutation (FICN), the periods of the free rotational modes converge rather quickly. The period of the tiltover mode (TOM) is found to excellent accuracy. The computed periods of the Chandler wobble (CW) and free core nutation (FCN) are nearly identical to the values cited in the literature for similar Earth models, but that for the inner core wobble (ICW) is slightly different. Truncation at low-degree harmonics causes the FICN period to fluctuate over a range as large as 90 sd, with different values at different truncation levels. For example, truncation at degree 6 gives a period of 752 sd (almost identical with the value cited in the literature for such an Earth model) but truncation at degree 24 is required to obtain convergence, and the resulting period is 746 sd, with no guarantee that its proximity to earlier values is other than fortuitous. We conclude that the heavy truncation necessitated by the conventional LMD is unsatisfactory for the FICN.

Histidine-rich stabilized polyplexes for cMet-directed tumor-targeted gene transfer

NASA Astrophysics Data System (ADS)

Kos, Petra; Lächelt, Ulrich; Herrmann, Annika; Mickler, Frauke Martina; Döblinger, Markus; He, Dongsheng; Krhač Levačić, Ana; Morys, Stephan; Bräuchle, Christoph; Wagner, Ernst

2015-03-01

Overexpression of the hepatocyte growth factor receptor/c-Met proto oncogene on the surface of a variety of tumor cells gives an opportunity to specifically target cancerous tissues. Herein, we report the first use of c-Met as receptor for non-viral tumor-targeted gene delivery. Sequence-defined oligomers comprising the c-Met binding peptide ligand cMBP2 for targeting, a monodisperse polyethylene glycol (PEG) for polyplex surface shielding, and various cationic (oligoethanamino) amide cores containing terminal cysteines for redox-sensitive polyplex stabilization, were assembled by solid-phase supported syntheses. The resulting oligomers exhibited a greatly enhanced cellular uptake and gene transfer over non-targeted control sequences, confirming the efficacy and target-specificity of the formed polyplexes. Implementation of endosomal escape-promoting histidines in the cationic core was required for gene expression without additional endosomolytic agent. The histidine-enriched polyplexes demonstrated stability in serum as well as receptor-specific gene transfer in vivo upon intratumoral injection. The co-formulation with an analogous PEG-free cationic oligomer led to a further compaction of pDNA polyplexes with an obvious change of shape as demonstrated by transmission electron microscopy. Such compaction was critically required for efficient intravenous gene delivery which resulted in greatly enhanced, cMBP2 ligand-dependent gene expression in the distant tumor.Overexpression of the hepatocyte growth factor receptor/c-Met proto oncogene on the surface of a variety of tumor cells gives an opportunity to specifically target cancerous tissues. Herein, we report the first use of c-Met as receptor for non-viral tumor-targeted gene delivery. Sequence-defined oligomers comprising the c-Met binding peptide ligand cMBP2 for targeting, a monodisperse polyethylene glycol (PEG) for polyplex surface shielding, and various cationic (oligoethanamino) amide cores containing terminal cysteines for redox-sensitive polyplex stabilization, were assembled by solid-phase supported syntheses. The resulting oligomers exhibited a greatly enhanced cellular uptake and gene transfer over non-targeted control sequences, confirming the efficacy and target-specificity of the formed polyplexes. Implementation of endosomal escape-promoting histidines in the cationic core was required for gene expression without additional endosomolytic agent. The histidine-enriched polyplexes demonstrated stability in serum as well as receptor-specific gene transfer in vivo upon intratumoral injection. The co-formulation with an analogous PEG-free cationic oligomer led to a further compaction of pDNA polyplexes with an obvious change of shape as demonstrated by transmission electron microscopy. Such compaction was critically required for efficient intravenous gene delivery which resulted in greatly enhanced, cMBP2 ligand-dependent gene expression in the distant tumor. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06556e

Effect of chitosan and thiolated chitosan coating on the inhibition behaviour of PIBCA nanoparticles against intestinal metallopeptidases

NASA Astrophysics Data System (ADS)

Bravo-Osuna, Irene; Vauthier, Christine; Farabollini, Alessandra; Millotti, Gioconda; Ponchel, Gilles

2008-12-01

Surface modified nanoparticles composed of poly(isobutylcyanoacrylate) (PIBCA) cores surrounded by a chitosan and thiolated chitosan gel layer were prepared and characterized in previous works. The presence of such biopolymers on the nanoparticle surface conferred those nanosystems interesting characteristics that might partially overcome the gastrointestinal enzymatic barrier, improving the oral administration of pharmacologically active peptides. In the present work, the antiprotease behaviour of this family of core-shell nanoparticles was in vitro tested against two model metallopeptidases present in the gastrointestinal tract (GIT): Carboxypeptidase A -CP A- (luminal protease) and Leucine Aminopeptidase M -LAP M- (membrane protease). As previous step, the zinc-binding capacity of these nanoparticles was evaluated. Interestingly, an improvement of both the zinc-binding capacity and the antiprotease effect of chitosan was observed when the biopolymers (chitosan and thiolated chitosan) were used as coating component of the core-shell nanoparticles, in comparison with their behaviour in solution, thanks to the different biopolymer chains rearrangement. The presence of amino, hydroxyl and thiol groups on the nanoparticle surface promoted zinc binding and hence the inhibition of the metallopeptidases analysed. On the contrary, the occurrence of a cross-linked structure in the gel layer surrounding the PIBCA cores of thiolated formulations, due to the formation of interchain and intrachain disulphide bonds, partially limited the inhibition of the proteases. The low accessibility of cations to the active groups of the cross-linked polymeric shell was postulated as a possible explanation of this behaviour. Results obtained in this work make this family of surface-modified nanocarriers promising candidates for the successfull administration of pharmacologically active peptides and proteins by the oral route.

A two-pronged approach to detecting ICB Stoneley modes

NASA Astrophysics Data System (ADS)

Jasperson, H. A.; Ye, J.; Shi, J.; De Hoop, M. V.

2017-12-01

Stoneley modes are special kinds of normal modes that are confined to the boundary between a fluid layer and a solid layer inside the Earth. Thus, these modes theoretically occur at the core-mantle boundary (CMB) and inner core boundary (ICB). CMB Stoneley modes were identified in observational data by Koelemeijer, et al. in 2013, but ICB Stoneley modes have remained relatively unexplored. Here we use a joint numerical and data-driven approach to identify ICB Stoneley modes from the deep 2013 Mw 8.3 Sea of Okhotsk earthquake. For the data-driven portion, we use 50 stacked traces from the USArray to identify potential occurrences of ICB Stoneley modes. Next, we verify each occurrence by comparing the spectrum to its equivalent from the shallow 2011 Mw 9.1 Tohoku earthquake. We also develop a novel computational approach to compute normal modes in a spherically symmetric non-rotating Earth building on the work of Wiggins (1976) and Buland and Gilbert (1984). We successfully resolve the clustering eigenvalue problem with non-orthogonal eigenfunctions from which Mineos suffers. By choosing the displacement/pressure formulation in the fluid outer core and handling boundary conditions properly, we remarkably project out the essential spectrum and provide the correct point spectrum. The utilization of weak variational form to perform the Rayleigh-Ritz procedure contributes to preserving the high accuracy across the solid-fluid boundary, which makes it possible to capture Stoneley modes' exponentially decaying behavior across the solid-fluid boundary, leading to more accurate and reliable eigenvalues and eigenfunctions. This allows us to compare the observation data and numerical computations. With this approach, we eliminate false signals from consideration, leaving only true ICB Stoneley mode peaks. In the future, information from these modes can be used to study the properties of the ICB and inner core.

Optimization and validation of a high performance liquid chromatography method for rapid determination of sinafloxacin, a novel fluoroquinolone in rat plasma using a fused-core C(18)-silica column.

PubMed

Wang, Shuowen; Wen, Jun; Cui, Lijun; Zhang, Xiurong; Wei, Hua; Xie, Rui; Feng, Bo; Wu, Yutian; Fan, Guorong

2010-03-11

A novel, simple and rapid high performance liquid chromatographic method has been developed and validated for the determination of sinafloxacin, a new fluoroquinolone, in rat plasma using 96-well protein precipitation, fused-core C(18)-silica column (4.6mmx50mm, 2.7microm) packed with a new solid support, which is made of 2.7microm particles that consist of a 1.7microm solid core covered with a 0.5microm thick shell of porous silica.The chromatographic separation was achieved with a mobile phase of 20:80 (v/v) of acetonitrile and phosphate buffer (pH=3.0) at a flow rate of 1mlmin(-1). Fluorescence detection was employed with lambda(ex) 295nm and lambda(em) 505nm. Lomefloxacin was used as internal standard (IS). The total analysis time was as short as 3min. The method was sensitive with a limit of detection (LOD) of 2ngml(-1), with good linearity (R(2)=0.9996) over the linear range of 5-500ngml(-1). The intra-day and inter-day precision was less than 5.8% and accuracy ranged from 100.3% to 103.5% for quality control (QC) samples at three concentrations of 10, 50 and 400ngml(-1).The fused-core C(18)-silica column method offered high sample throughput, low injection volume and low consumption of organic solvents. The method was successfully employed in the pharmacokinetic study of sinafloxacin formulation product after tail vein injection to healthy rats. Copyright 2009 Elsevier B.V. All rights reserved.

Going beyond the second virial coefficient in the hadron resonance gas model

NASA Astrophysics Data System (ADS)

Bugaev, K. A.; Sagun, V. V.; Ivanytskyi, A. I.; Yakimenko, I. P.; Nikonov, E. G.; Taranenko, A. V.; Zinovjev, G. M.

2018-02-01

We develop a novel formulation of the hadron resonance gas model which, besides a hard-core repulsion, explicitly accounts for the surface tension induced by the interaction between the particles. Such an equation of state allows us to go beyond the Van der Waals approximation for any number of different hard-core radii. A comparison with the Carnahan-Starling equation of state shows that the new model is valid for packing fractions 0.2-0.22, while the usual Van der Waals model is inapplicable at packing fractions above 0.1-0.11. Moreover, it is shown that the equation of state with induced surface tension is softer than the one of hard spheres and remains causal at higher particle densities. The great advantage of our model is that there are only two equations to be solved and neither their number nor their form depend on the values of the hard-core radii used for different hadronic resonances. Such an advantage leads to a significant mathematical simplification compared to other versions of truly multi-component hadron resonance gas models. Using this equation of state we obtain a high-quality fit of the ALICE hadron multiplicities measured at the center-of-mass energy 2.76 TeV per nucleon and we find that the dependence of χ2 / ndf on the temperature has a single global minimum in the traditional hadron resonance gas model with the multi-component hard-core repulsion. Also we find two local minima of χ2 / ndf in the model in which the proper volume of each hadron is proportional to its mass. However, it is shown that in the latter model a second local minimum located at higher temperatures always appears far above the limit of its applicability.

The Planetary Data System (PDS) Data Dictionary Tool (LDDTool)

NASA Astrophysics Data System (ADS)

Raugh, Anne C.; Hughes, John S.

2017-10-01

One of the major design goals of the PDS4 development effort was to provide an avenue for discipline specialists and large data preparers such as mission archivists to extend the core PDS4 Information Model (IM) to include metadata definitions specific to their own contexts. This capability is critical for the Planetary Data System - an archive that deals with a data collection that is diverse along virtually every conceivable axis. Amid such diversity, it is in the best interests of the PDS archive and its users that all extensions to the core IM follow the same design techniques, conventions, and restrictions as the core implementation itself. Notwithstanding, expecting all mission and discipline archivist seeking to define metadata for a new context to acquire expertise in information modeling, model-driven design, ontology, schema formulation, and PDS4 design conventions and philosophy is unrealistic, to say the least.To bridge that expertise gap, the PDS Engineering Node has developed the data dictionary creation tool known as “LDDTool”. This tool incorporates the same software used to maintain and extend the core IM, packaged with an interface that enables a developer to create his contextual information model using the same, open standards-based metadata framework PDS itself uses. Through this interface, the novice dictionary developer has immediate access to the common set of data types and unit classes for defining attributes, and a straight-forward method for constructing classes. The more experienced developer, using the same tool, has access to more sophisticated modeling methods like abstraction and extension, and can define very sophisticated validation rules.We present the key features of the PDS Local Data Dictionary Tool, which both supports the development of extensions to the PDS4 IM, and ensures their compatibility with the IM.

Harnessing Data to Assess Equity of Care by Race, Ethnicity and Language

PubMed Central

Gracia, Amber; Cheirif, Jorge; Veliz, Juana; Reyna, Melissa; Vecchio, Mara; Aryal, Subhash

2015-01-01

Objective: Determine any disparities in care based on race, ethnicity and language (REaL) by utilizing inpatient (IP) core measures at Texas Health Resources, a large, faith-based, non-profit health care delivery system located in a large, ethnically diverse metropolitan area in Texas. These measures, which were established by the U.S. Centers for Medicare and Medicaid Services (CMS) and The Joint Commission (TJC), help to ensure better accountability for patient outcomes throughout the U.S. health care system. Methods: Sample analysis to understand the architecture of race, ethnicity and language (REaL) variables within the Texas Health clinical database, followed by development of the logic, method and framework for isolating populations and evaluating disparities by race (non-Hispanic White, non-Hispanic Black, Native American/Native Hawaiian/Pacific Islander, Asian and Other); ethnicity (Hispanic and non-Hispanic); and preferred language (English and Spanish). The study is based on use of existing clinical data for four inpatient (IP) core measures: Acute Myocardial Infarction (AMI), Congestive Heart Failure (CHF), Pneumonia (PN) and Surgical Care (SCIP), representing 100% of the sample population. These comprise a high number of cases presenting in our acute care facilities. Findings are based on a sample of clinical data (N = 19,873 cases) for the four inpatient (IP) core measures derived from 13 of Texas Health’s wholly-owned facilities, formulating a set of baseline data. Results: Based on applied method, Texas Health facilities consistently scored high with no discernable race, ethnicity and language (REaL) disparities as evidenced by a low percentage difference to the reference point (non-Hispanic White) on IP core measures, including: AMI (0.3%–1.2%), CHF (0.7%–3.0%), PN (0.5%–3.7%), and SCIP (0–0.7%). PMID:26703665

Investigation of Chemical-Foam Design as a Novel Approach toward Immiscible Foam Flooding for Enhanced Oil Recovery

PubMed Central

2017-01-01

Strong foam can be generated in porous media containing oil, resulting in incremental oil recovery; however, oil recovery factor is restricted. A large fraction of oil recovered by foam flooding forms an oil-in-water emulsion, so that costly methods may need to be used to separate the oil. Moreover, strong foam could create a large pressure gradient, which may cause fractures in the reservoir. This study presents a novel chemical-foam flooding process for enhanced oil recovery (EOR) from water-flooded reservoirs. The presented method involved the use of chemically designed foam to mobilize the remaining oil after water flooding and then to displace the mobilized oil to the production well. A blend of two anionic surfactant formulations was formulated for this method: (a) IOS, for achieving ultralow interfacial tension (IFT), and (b) AOS, for generating a strong foam. Experiments were performed using Bentheimer sandstone cores, where X-ray CT images were taken during foam generation to find the stability of the advancing front of foam propagation and to map the gas saturation for both the transient and the steady-state flow regimes. Then the proposed chemical-foam strategy for incremental oil recovery was tested through the coinjection of immiscible nitrogen gas and surfactant solutions with three different formulation properties in terms of IFT reduction and foaming strength capability. The discovered optimal formulation contains a foaming agent surfactant, a low IFT surfactant, and a cosolvent, which has a high foam stability and a considerably low IFT (1.6 × 10–2 mN/m). Coinjection resulted in higher oil recovery and much less MRF than the same process with only using a foaming agent. The oil displacement experiment revealed that coinjection of gas with a blend of surfactants, containing a cosolvent, can recover a significant amount of oil (33% OIIP) over water flooding with a larger amount of clean oil and less emulsion. PMID:29093612

Investigation of Chemical-Foam Design as a Novel Approach toward Immiscible Foam Flooding for Enhanced Oil Recovery.

PubMed

Hosseini-Nasab, S M; Zitha, P L J

2017-10-19

Strong foam can be generated in porous media containing oil, resulting in incremental oil recovery; however, oil recovery factor is restricted. A large fraction of oil recovered by foam flooding forms an oil-in-water emulsion, so that costly methods may need to be used to separate the oil. Moreover, strong foam could create a large pressure gradient, which may cause fractures in the reservoir. This study presents a novel chemical-foam flooding process for enhanced oil recovery (EOR) from water-flooded reservoirs. The presented method involved the use of chemically designed foam to mobilize the remaining oil after water flooding and then to displace the mobilized oil to the production well. A blend of two anionic surfactant formulations was formulated for this method: (a) IOS, for achieving ultralow interfacial tension (IFT), and (b) AOS, for generating a strong foam. Experiments were performed using Bentheimer sandstone cores, where X-ray CT images were taken during foam generation to find the stability of the advancing front of foam propagation and to map the gas saturation for both the transient and the steady-state flow regimes. Then the proposed chemical-foam strategy for incremental oil recovery was tested through the coinjection of immiscible nitrogen gas and surfactant solutions with three different formulation properties in terms of IFT reduction and foaming strength capability. The discovered optimal formulation contains a foaming agent surfactant, a low IFT surfactant, and a cosolvent, which has a high foam stability and a considerably low IFT (1.6 × 10 -2 mN/m). Coinjection resulted in higher oil recovery and much less MRF than the same process with only using a foaming agent. The oil displacement experiment revealed that coinjection of gas with a blend of surfactants, containing a cosolvent, can recover a significant amount of oil (33% OIIP) over water flooding with a larger amount of clean oil and less emulsion.

Petermann I and II spot size: Accurate semi analytical description involving Nelder-Mead method of nonlinear unconstrained optimization and three parameter fundamental modal field

NASA Astrophysics Data System (ADS)

Roy Choudhury, Raja; Roy Choudhury, Arundhati; Kanti Ghose, Mrinal

2013-01-01

A semi-analytical model with three optimizing parameters and a novel non-Gaussian function as the fundamental modal field solution has been proposed to arrive at an accurate solution to predict various propagation parameters of graded-index fibers with less computational burden than numerical methods. In our semi analytical formulation the optimization of core parameter U which is usually uncertain, noisy or even discontinuous, is being calculated by Nelder-Mead method of nonlinear unconstrained minimizations as it is an efficient and compact direct search method and does not need any derivative information. Three optimizing parameters are included in the formulation of fundamental modal field of an optical fiber to make it more flexible and accurate than other available approximations. Employing variational technique, Petermann I and II spot sizes have been evaluated for triangular and trapezoidal-index fibers with the proposed fundamental modal field. It has been demonstrated that, the results of the proposed solution identically match with the numerical results over a wide range of normalized frequencies. This approximation can also be used in the study of doped and nonlinear fiber amplifier.

Optimization of propranolol HCl release kinetics from press coated sustained release tablets.

PubMed

Ali, Adel Ahmed; Ali, Ahmed Mahmoud

2013-01-01

Press-coated sustained release tablets offer a valuable, cheap and easy manufacture alternative to the highly expensive, multi-step manufacture and filling of coated beads. In this study, propranolol HCl press-coated tablets were prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material together with carbopol 971P and compressol as release modifiers. The prepared formulations were optimized for zero-order release using artificial neural network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero-order release kinetics with extended release profile for more than 12 h was obtained. The most important variables considered by the program in optimizing formulations were type and proportion of polymer mixture in the coat layer and distribution ratio of drug between core and coat. The key elements found were; incorporation of 31-38 % of the drug in the coat, fixing the amount of polymer in coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when 2.5-10 % carbopol and 25-42.5% compressol were incorporated into the 50 % HPMC coat layer.

Usability requirements for buildings: a case study on primary schools.

PubMed

Duca, Gabriella

2012-01-01

This paper concerns an applied research aimed at applying the concept of usability, as derived form the standard ISO 9241/11, in the filed of building design, namely primary schools. Starting from the concept that space characteristics play a very relevant role in learning performances, the study presented here developed an original methodology for the assessment of effectiveness, efficiency and satisfaction of buildings hosting primary schools, in order to create a school environment better supporting users in their tasks. Research core is the framework of usability requirements and their related markers, indicators and technical specification that has been formulated in order to check compliance of urban area, building, rooms and architectural details with users needs. Therefore, a detailed task analysis of pupils and teacher tasks has been carried out and two questionnaires addressed to a significant users panel have been formulated for satisfaction survey. Lastly, a matrix for an overall reading of gathered data has been set-up and criteria for usability assessment based on that data has been defined. The whole study has been developed within the case study of a primary school in the Naples city centre, whose contents and results are discussed.

Comparison of monolithic and microparticulate columns for reversed-phase liquid chromatography of tryptic digests of industrial enzymes in cleaning products.

PubMed

Beneito-Cambra, M; Herrero-Martínez, J M; Ramis-Ramos, G; Lindner, W; Lämmerhofer, M

2011-10-14

Enzymes of several classes used in the formulations of cleaning products were characterized by trypsin digestion followed by HPLC with UV detection. A polymeric monolithic column (ProSwift) was used to optimize the separation of both the intact enzymes and their tryptic digests. This column was adequate for the quality control of raw industrial enzyme concentrates. Then, monolithic and microparticulate columns were compared for peptide analysis. Under optimized conditions, the analysis of tryptic digests of enzymes of different classes commonly used in the formulation of cleaning products was carried out. Number of peaks, peak capacity and global resolution were obtained in order to evaluate the chromatographic performance of each column. Particulate shell-core C18 columns (Kinetex, 2.6 μm) showed the best performance, followed by a silica monolithic column (Chromolith RP-18e) and the conventional C18 packings (Gemini, 5 μm or 3 μm). A polymeric monolithic column (ProSwift) gave the worst performances. The proposed method was satisfactorily applied to the characterization of the enzymes present in spiked detergent bases and commercial cleaners. Copyright © 2011 Elsevier B.V. All rights reserved.

An integrated system for dissolution studies and magnetic resonance imaging of controlled release, polymer-based dosage forms-a tool for quantitative assessment of hydrogel formation processes.

PubMed

Kulinowski, Piotr; Dorozyński, Przemysław; Jachowicz, Renata; Weglarz, Władysław P

2008-11-04

Controlled release (CR) dosage forms are often based on polymeric matrices, e.g., sustained-release tablets and capsules. It is crucial to visualise and quantify processes of the hydrogel formation during the standard dissolution study. A method for imaging of CR, polymer-based dosage forms during dissolution study in vitro is presented. Imaging was performed in a non-invasive way by means of the magnetic resonance imaging (MRI). This study was designed to simulate in vivo conditions regarding temperature, volume, state and composition of dissolution media. Two formulations of hydrodynamically balanced systems (HBS) were chosen as model CR dosage forms. HBS release active substance in stomach while floating on the surface of the gastric content. Time evolutions of the diffusion region, hydrogel formation region and "dry core" region were obtained during a dissolution study of L-dopa as a model drug in two simulated gastric fluids (i.e. in fed and fasted state). This method seems to be a very promising tool for examining properties of new formulations of CR, polymer-based dosage forms or for comparison of generic and originator dosage forms before carrying out bioequivalence studies.

Efficient molecular dynamics simulations with many-body potentials on graphics processing units

NASA Astrophysics Data System (ADS)

Fan, Zheyong; Chen, Wei; Vierimaa, Ville; Harju, Ari

2017-09-01

Graphics processing units have been extensively used to accelerate classical molecular dynamics simulations. However, there is much less progress on the acceleration of force evaluations for many-body potentials compared to pairwise ones. In the conventional force evaluation algorithm for many-body potentials, the force, virial stress, and heat current for a given atom are accumulated within different loops, which could result in write conflict between different threads in a CUDA kernel. In this work, we provide a new force evaluation algorithm, which is based on an explicit pairwise force expression for many-body potentials derived recently (Fan et al., 2015). In our algorithm, the force, virial stress, and heat current for a given atom can be accumulated within a single thread and is free of write conflicts. We discuss the formulations and algorithms and evaluate their performance. A new open-source code, GPUMD, is developed based on the proposed formulations. For the Tersoff many-body potential, the double precision performance of GPUMD using a Tesla K40 card is equivalent to that of the LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator) molecular dynamics code running with about 100 CPU cores (Intel Xeon CPU X5670 @ 2.93 GHz).

A finite element approach to self-consistent field theory calculations of multiblock polymers

NASA Astrophysics Data System (ADS)

Ackerman, David M.; Delaney, Kris; Fredrickson, Glenn H.; Ganapathysubramanian, Baskar

2017-02-01

Self-consistent field theory (SCFT) has proven to be a powerful tool for modeling equilibrium microstructures of soft materials, particularly for multiblock polymers. A very successful approach to numerically solving the SCFT set of equations is based on using a spectral approach. While widely successful, this approach has limitations especially in the context of current technologically relevant applications. These limitations include non-trivial approaches for modeling complex geometries, difficulties in extending to non-periodic domains, as well as non-trivial extensions for spatial adaptivity. As a viable alternative to spectral schemes, we develop a finite element formulation of the SCFT paradigm for calculating equilibrium polymer morphologies. We discuss the formulation and address implementation challenges that ensure accuracy and efficiency. We explore higher order chain contour steppers that are efficiently implemented with Richardson Extrapolation. This approach is highly scalable and suitable for systems with arbitrary shapes. We show spatial and temporal convergence and illustrate scaling on up to 2048 cores. Finally, we illustrate confinement effects for selected complex geometries. This has implications for materials design for nanoscale applications where dimensions are such that equilibrium morphologies dramatically differ from the bulk phases.

Formulation of an organic carbon trajectory over a 10-year period on a restored spoil island in south-central Florida

NASA Astrophysics Data System (ADS)

Schafer, T.; Ellis, R.; Osborne, T.; Hicks Pries, C.

2015-12-01

Long-term monitoring of restoration projects aims to determine long-term sustainability and stability of restored systems. In coastal wetlands, one indicator of restoration of ecosystem function can be seen with organic matter (specifically carbon) accretion. SL-15, a spoil island in Fort Pierce, Fl was restored in 2005, and has been monitored for return to natural condition over the last 10 years.. To assess sediment carbon accretion, sediment cores were collected in a set of eight plots, located on the SL-15 mangrove island and the surrounding seagrass recruitment area. These were analyzed for organic carbon, microbial biomass carbon, extractable carbon, and total nitrogen. The biogeochemical data collected in the previous year was compared to data collected in 2005-2007. Vegetation surveys were also completed to show the build-up of organic material in accordance with vegetation shift over the 9-year period. From this information, a trajectory has been formulated on organic carbon accretion and vegetation shift from the time of orginal restoration activities. By comparison to control sites nearby, realistic estimates of time required to reach natural levels of carbon and vegetation community structure can be calculated..

Preliminary model and validation of molten carbonate fuel cell kinetics under sulphur poisoning

NASA Astrophysics Data System (ADS)

Audasso, E.; Nam, S.; Arato, E.; Bosio, B.

2017-06-01

MCFC represents an effective technology to deal with CO2 capture and relative applications. If used for these purposes, due to the working conditions and the possible feeding, MCFC must cope with a different number of poisoning gases such as sulphur compounds. In literature, different works deal with the development of kinetic models to describe MCFC performance to help both industrial applications and laboratory simulations. However, in literature attempts to realize a proper model able to consider the effects of poisoning compounds are scarce. The first aim of the present work is to provide a semi-empirical kinetic formulation capable to take into account the effects that sulphur compounds (in particular SO2) have on the MCFC performance. The second aim is to provide a practical example of how to effectively include the poisoning effects in kinetic models to simulate fuel cells performances. To test the reliability of the proposed approach, the obtained formulation is implemented in the kinetic core of the SIMFC (SIMulation of Fuel Cells) code, an MCFC 3D model realized by the Process Engineering Research Team (PERT) of the University of Genova. Validation is performed through data collected at the Korea Institute of Science and Technology in Seoul.

Emotional Valence and the Free-Energy Principle

PubMed Central

Joffily, Mateus; Coricelli, Giorgio

2013-01-01

The free-energy principle has recently been proposed as a unified Bayesian account of perception, learning and action. Despite the inextricable link between emotion and cognition, emotion has not yet been formulated under this framework. A core concept that permeates many perspectives on emotion is valence, which broadly refers to the positive and negative character of emotion or some of its aspects. In the present paper, we propose a definition of emotional valence in terms of the negative rate of change of free-energy over time. If the second time-derivative of free-energy is taken into account, the dynamics of basic forms of emotion such as happiness, unhappiness, hope, fear, disappointment and relief can be explained. In this formulation, an important function of emotional valence turns out to regulate the learning rate of the causes of sensory inputs. When sensations increasingly violate the agent's expectations, valence is negative and increases the learning rate. Conversely, when sensations increasingly fulfil the agent's expectations, valence is positive and decreases the learning rate. This dynamic interaction between emotional valence and learning rate highlights the crucial role played by emotions in biological agents' adaptation to unexpected changes in their world. PMID:23785269

Retrofitting the AutoBayes Program Synthesis System with Concrete Syntax

NASA Technical Reports Server (NTRS)

Fischer, Bernd; Visser, Eelco

2004-01-01

AutoBayes is a fully automatic, schema-based program synthesis system for statistical data analysis applications. Its core component is a schema library. i.e., a collection of generic code templates with associated applicability constraints which are instantiated in a problem-specific way during synthesis. Currently, AutoBayes is implemented in Prolog; the schemas thus use abstract syntax (i.e., Prolog terms) to formulate the templates. However, the conceptual distance between this abstract representation and the concrete syntax of the generated programs makes the schemas hard to create and maintain. In this paper we describe how AutoBayes is retrofitted with concrete syntax. We show how it is integrated into Prolog and describe how the seamless interaction of concrete syntax fragments with AutoBayes's remaining legacy meta-programming kernel based on abstract syntax is achieved. We apply the approach to gradually mitigate individual schemas without forcing a disruptive migration of the entire system to a different First experiences show that a smooth migration can be achieved. Moreover, it can result in a considerable reduction of the code size and improved readability of the code. In particular, abstracting out fresh-variable generation and second-order term construction allows the formulation of larger continuous fragments.

Large-scale optimization-based non-negative computational framework for diffusion equations: Parallel implementation and performance studies

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

Chang, Justin; Karra, Satish; Nakshatrala, Kalyana B.

It is well-known that the standard Galerkin formulation, which is often the formulation of choice under the finite element method for solving self-adjoint diffusion equations, does not meet maximum principles and the non-negative constraint for anisotropic diffusion equations. Recently, optimization-based methodologies that satisfy maximum principles and the non-negative constraint for steady-state and transient diffusion-type equations have been proposed. To date, these methodologies have been tested only on small-scale academic problems. The purpose of this paper is to systematically study the performance of the non-negative methodology in the context of high performance computing (HPC). PETSc and TAO libraries are, respectively, usedmore » for the parallel environment and optimization solvers. For large-scale problems, it is important for computational scientists to understand the computational performance of current algorithms available in these scientific libraries. The numerical experiments are conducted on the state-of-the-art HPC systems, and a single-core performance model is used to better characterize the efficiency of the solvers. Furthermore, our studies indicate that the proposed non-negative computational framework for diffusion-type equations exhibits excellent strong scaling for real-world large-scale problems.« less

A Micelle Self-Assembled from Doxorubicin-Arabinoxylan Conjugates with pH-Cleavable Bond for Synergistic Antitumor Therapy

NASA Astrophysics Data System (ADS)

Wang, Jie; Li, Yanli; Dong, Xia; Wang, Ying; Chong, Xiaodan; Yu, Tai; Zhang, Fulei; Chen, Di; Zhang, Li; Gao, Jie; Yang, Cheng; Han, Jun; Li, Wei

2017-01-01

Nanomedicine offers new hope to overcome the low solubility and high side toxicity to normal tissue appeared in traditional chemotherapy. The biocompatibility and intracellular drug accumulation is still a big challenge for the nano-based formulations. Herein, a medical-used biocompatible arabinoxylan (AX) is used to develop to delivery chemodrug doxorubicin (DOX). The solubility of DOX is obviously enhanced via the hydrogen bond formed with AX which results in an amphiphilic AX-DOX. A micelle with pH-cleavable bond is thus self-assembled from such AX-DOX with DOX core and AX shell. The inner DOX can be easily released out at low intracellular pH, which obviously enhanced its in vitro cytotoxicity against breast cancer cells (MCF-7). Interestingly, an unexpected apoptosis is evoked except for the proliferation inhibition. Moreover, the therapeutic effects are further synergistically promoted by the enhanced permeability and retention (EPR) and intracellular pH-triggered drug release. Consequently, the in vivo intratumor accumulation of DOX, the tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing MCF-7 tumors. These in vitro/vivo results indicated that the AX-DOX micellular formulation holds high potential in cancer therapy.

PKPD model of interleukin-21 effects on thermoregulation in monkeys--application and evaluation of stochastic differential equations.

PubMed

Overgaard, Rune Viig; Holford, Nick; Rytved, Klaus A; Madsen, Henrik

2007-02-01

To describe the pharmacodynamic effects of recombinant human interleukin-21 (IL-21) on core body temperature in cynomolgus monkeys using basic mechanisms of heat regulation. A major effort was devoted to compare the use of ordinary differential equations (ODEs) with stochastic differential equations (SDEs) in pharmacokinetic pharmacodynamic (PKPD) modelling. A temperature model was formulated including circadian rhythm, metabolism, heat loss, and a thermoregulatory set-point. This model was formulated as a mixed-effects model based on SDEs using NONMEM. The effects of IL-21 were on the set-point and the circadian rhythm of metabolism. The model was able to describe a complex set of IL-21 induced phenomena, including 1) disappearance of the circadian rhythm, 2) no effect after first dose, and 3) high variability after second dose. SDEs provided a more realistic description with improved simulation properties, and further changed the model into one that could not be falsified by the autocorrelation function. The IL-21 induced effects on thermoregulation in cynomolgus monkeys are explained by a biologically plausible model. The quality of the model was improved by the use of SDEs.

Emotional valence and the free-energy principle.

PubMed

Joffily, Mateus; Coricelli, Giorgio

2013-01-01

The free-energy principle has recently been proposed as a unified Bayesian account of perception, learning and action. Despite the inextricable link between emotion and cognition, emotion has not yet been formulated under this framework. A core concept that permeates many perspectives on emotion is valence, which broadly refers to the positive and negative character of emotion or some of its aspects. In the present paper, we propose a definition of emotional valence in terms of the negative rate of change of free-energy over time. If the second time-derivative of free-energy is taken into account, the dynamics of basic forms of emotion such as happiness, unhappiness, hope, fear, disappointment and relief can be explained. In this formulation, an important function of emotional valence turns out to regulate the learning rate of the causes of sensory inputs. When sensations increasingly violate the agent's expectations, valence is negative and increases the learning rate. Conversely, when sensations increasingly fulfil the agent's expectations, valence is positive and decreases the learning rate. This dynamic interaction between emotional valence and learning rate highlights the crucial role played by emotions in biological agents' adaptation to unexpected changes in their world.

A finite element approach to self-consistent field theory calculations of multiblock polymers

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

Ackerman, David M.; Delaney, Kris; Fredrickson, Glenn H.

Self-consistent field theory (SCFT) has proven to be a powerful tool for modeling equilibrium microstructures of soft materials, particularly for multiblock polymers. A very successful approach to numerically solving the SCFT set of equations is based on using a spectral approach. While widely successful, this approach has limitations especially in the context of current technologically relevant applications. These limitations include non-trivial approaches for modeling complex geometries, difficulties in extending to non-periodic domains, as well as non-trivial extensions for spatial adaptivity. As a viable alternative to spectral schemes, we develop a finite element formulation of the SCFT paradigm for calculating equilibriummore » polymer morphologies. We discuss the formulation and address implementation challenges that ensure accuracy and efficiency. We explore higher order chain contour steppers that are efficiently implemented with Richardson Extrapolation. This approach is highly scalable and suitable for systems with arbitrary shapes. We show spatial and temporal convergence and illustrate scaling on up to 2048 cores. Finally, we illustrate confinement effects for selected complex geometries. This has implications for materials design for nanoscale applications where dimensions are such that equilibrium morphologies dramatically differ from the bulk phases.« less

Large-scale optimization-based non-negative computational framework for diffusion equations: Parallel implementation and performance studies

DOE PAGES

Chang, Justin; Karra, Satish; Nakshatrala, Kalyana B.

2016-07-26

It is well-known that the standard Galerkin formulation, which is often the formulation of choice under the finite element method for solving self-adjoint diffusion equations, does not meet maximum principles and the non-negative constraint for anisotropic diffusion equations. Recently, optimization-based methodologies that satisfy maximum principles and the non-negative constraint for steady-state and transient diffusion-type equations have been proposed. To date, these methodologies have been tested only on small-scale academic problems. The purpose of this paper is to systematically study the performance of the non-negative methodology in the context of high performance computing (HPC). PETSc and TAO libraries are, respectively, usedmore » for the parallel environment and optimization solvers. For large-scale problems, it is important for computational scientists to understand the computational performance of current algorithms available in these scientific libraries. The numerical experiments are conducted on the state-of-the-art HPC systems, and a single-core performance model is used to better characterize the efficiency of the solvers. Furthermore, our studies indicate that the proposed non-negative computational framework for diffusion-type equations exhibits excellent strong scaling for real-world large-scale problems.« less

The Importance of Three-Body Interactions in Molecular Dynamics Simulations of Water with the Fragment Molecular Orbital Method

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

Pruitt, Spencer R.; Nakata, Hiroya; Nagata, Takeshi

2016-04-12

The analytic first derivative with respect to nuclear coordinates is formulated and implemented in the framework of the three-body fragment molecular orbital (FMO) method. The gradient has been derived and implemented for restricted Hartree-Fock, second-order Møller-Plesset perturbation, and density functional theories. The importance of the three-body fully analytic gradient is illustrated through the failure of the two-body FMO method during molecular dynamics simulations of a small water cluster. The parallel implementation of the fragment molecular orbital method, its parallel efficiency, and its scalability on the Blue Gene/Q architecture up to 262,144 CPU cores, are also discussed.

[Core principles for the regulation of placement subject to public law in psychiatric hospitals - with explanations].

PubMed

2016-03-01

While the provisions of the highest courts concerning the involuntary commitment and treatment in psychiatric hospitals of people unable to give their consent are being implemented, in many federal states corresponding adjustments to the rules governing involuntary commitment in accordance with the mental health laws and laws on involuntary commitment are still pending. In states where new regulations do exist, legal experts express doubts that they conform to the Constitution and the UN Convention on the Rights of Persons with Disabilities. The DGPPN has formulated key parameters for involuntary commitment from a clinical perspective, which should be taken into account in the new regulations of the individual federal states.

A users guide for A344: A program using a finite difference method to analyze transonic flow over oscillating airfoils

NASA Technical Reports Server (NTRS)

Weatherill, W. H.; Ehlers, F. E.

1979-01-01

The design and usage of a pilot program for calculating the pressure distributions over harmonically oscillating airfoils in transonic flow are described. The procedure used is based on separating the velocity potential into steady and unsteady parts and linearizing the resulting unsteady differential equations for small disturbances. The steady velocity potential which must be obtained from some other program, was required for input. The unsteady equation, as solved, is linear with spatially varying coefficients. Since sinusoidal motion was assumed, time was not a variable. The numerical solution was obtained through a finite difference formulation and either a line relaxation or an out of core direct solution method.

Diverse realities: sexually transmitted infections and HIV in India.

PubMed

Hawkes, S; Santhya, K G

2002-04-01

There are many features that make India a vulnerable country as far as a sexually transmitted infection (STI)/HIV epidemic is concerned. These include the lack of a strong evidence base on which to formulate decision making, a pluralistic and often unregulated health sector, and a highly vulnerable population. Nonetheless, India has shown strong commitment to other areas of a comprehensive reproductive health care programme, and may be able to do so in the field of STI/HIV control. Vast numbers of people in India are severely disadvantaged in terms of income, education, power structures, and gender. Addressing these basic issues of human rights lies at the core of achieving better health outcomes.

Verbal problem solving in high functioning autistic individuals.

PubMed

Minshew, N J; Siegel, D J; Goldstein, G; Weldy, S

1994-01-01

The verbal problem-solving and abstract reasoning ability of 25 high-functioning autistic individuals ages 11 to 41 was compared with normal controls individually matched on age, gender, race, IQ, and educational level. The Twenty Questions Procedure was administered using a grid of 42 common objects. Time to complete the task, number of correct solutions, and number and type of questions asked were analyzed. Results indicated that controls were more often successful in achieving solutions, and in formulating constraint seeking questions that conceptually grouped, ordered, and sorted the objects. In contrast, the autistics relied primarily on guessing. Findings are consistent with prior studies reporting a core deficit in autism involving abstract reasoning ability.

A study of microbial profile modification

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

Bae, J.H.; Lee, H.O.

1995-12-31

A microbial profile modification method using spores was investigated. A halotolerant, spore-forming, biopolymer-producing mesophile was used in Berea cores with a specifically formulated nutrient package to reduce the permeability of the rock. The degree of permeability reduction varied widely depending on the stimulation protocols used. The incubation period had a significant impact on permeability reduction, and there appeared to be an optimum incubation time for maximum permeability reduction. The reduction persisted for many PV of brine injection and appeared very stable. For our microbes used in this study, the permeability reduction was about the same when the NaCl concentration wasmore » above 2 wt% in the range from 0 wt% to 10 wt%.« less

Off-design temperature effects on nuclear fuel pins for an advanced space-power-reactor concept

NASA Technical Reports Server (NTRS)

Bowles, K. J.

1974-01-01

An exploratory out-of-reactor investigation was made of the effects of short-time temperature excursions above the nominal operating temperature of 990 C on the compatibility of advanced nuclear space-power reactor fuel pin materials. This information is required for formulating a reliable reactor safety analysis and designing an emergency core cooling system. Simulated uranium mononitride (UN) fuel pins, clad with tungsten-lined T-111 (Ta-8W-2Hf) showed no compatibility problems after heating for 8 hours at 2400 C. At 2520 C and above, reactions occurred in 1 hour or less. Under these conditions free uranium formed, redistributed, and attacked the cladding.

Electronic structure and optical properties of the thiolate-protected Au28(SMe)20 cluster.

PubMed

Knoppe, Stefan; Malola, Sami; Lehtovaara, Lauri; Bürgi, Thomas; Häkkinen, Hannu

2013-10-10

The recently reported crystal structure of the Au28(TBBT)20 cluster (TBBT: p-tert-butylbenzenethiolate) is analyzed with (time-dependent) density functional theory (TD-DFT). Bader charge analysis reveals a novel trimeric Au3(SR)4 binding motif. The cluster can be formulated as Au14(Au2(SR)3)4(Au3(SR)4)2. The electronic structure of the Au14(6+) core and the ligand-protected cluster were analyzed, and their stability can be explained by formation of distorted eight-electron superatoms. Optical absorption and circular dichroism (CD) spectra were calculated and compared to the experiment. Assignment of handedness of the intrinsically chiral cluster is possible.

Effect of formulation and processing variables on the characteristics of microspheres for water-soluble drugs prepared by w/o/o double emulsion solvent diffusion method.

PubMed

Lee, J; Park, T G; Choi, H

2000-02-25

80% except for acetaminophen, due to its lower solubility in water and higher solubility in corn oil. The release profile of the drug was pH dependent. In acidic medium, the release rate was much slower, however, the drug was released quickly at pH 7.4. Tacrine showed unexpected release profiles, probably due to ionic interaction with polymer matrix and the shell structure and the highest release rate was obtained at pH 2.0. The prepared microspheres had a sponge-like inner structure with or without central hollow core and the surface was dense with no apparent pores.

Multilayer engineered nanoliposomes as a novel tool for oral delivery of lipopeptide-based vaccines against group A Streptococcus.

PubMed

Marasini, Nirmal; Giddam, Ashwini K; Ghaffar, Khairunnisa A; Batzloff, Michael R; Good, Michael F; Skwarczynski, Mariusz; Toth, Istvan

2016-05-01

To develop an oral nanovaccine delivery system for lipopeptide-based vaccine candidate against group A Streptococcus. Lipid-core peptide-1-loaded nanoliposomes were prepared as a template and coated with opposite-charged polyelectrolytes to produce particles with size <200 nm. Efficacy of this oral nanovaccine delivery system was evaluated in mice model. Polymer-coated liposomes produced significantly higher antigen-specific mucosal IgA and systemic IgG titers in comparison to vaccine formulated with a strong mucosal adjuvant upon oral immunization in mice. Moreover, high levels of systemic antibody titers were retained even at day 185 postprimary immunization. Efficient oral delivery platform for lipopeptide-based vaccines has been developed.

Computational Psychosomatics and Computational Psychiatry: Toward a Joint Framework for Differential Diagnosis.

PubMed

Petzschner, Frederike H; Weber, Lilian A E; Gard, Tim; Stephan, Klaas E

2017-09-15

This article outlines how a core concept from theories of homeostasis and cybernetics, the inference-control loop, may be used to guide differential diagnosis in computational psychiatry and computational psychosomatics. In particular, we discuss 1) how conceptualizing perception and action as inference-control loops yields a joint computational perspective on brain-world and brain-body interactions and 2) how the concrete formulation of this loop as a hierarchical Bayesian model points to key computational quantities that inform a taxonomy of potential disease mechanisms. We consider the utility of this perspective for differential diagnosis in concrete clinical applications. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Amended Safety Assessment of Isethionate Salts as Used in Cosmetics.

PubMed

Burnett, Christina L; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) rereviewed the safety of 12 isethionate salts as used in cosmetics and concluded that these ingredients are safe in the present practices of use and concentration, when formulated to be nonirritating. These isethionate salts are reported to function mostly as surfactants and cleansing agents in cosmetic products. The Panel reviewed the available animal and clinical data as well as information from previous CIR reports. Although there are data gaps, the shared chemical core structure, expected similarities in physicochemical properties, and similar functions and concentrations in cosmetics enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each ingredient.

Enhanced Core Noise Modeling for Turbofan Engines

NASA Technical Reports Server (NTRS)

Stone, James R.; Krejsa, Eugene A.; Clark, Bruce J.

2011-01-01

This report describes work performed by MTC Technologies (MTCT) for NASA Glenn Research Center (GRC) under Contract NAS3-00178, Task Order No. 15. MTCT previously developed a first-generation empirical model that correlates the core/combustion noise of four GE engines, the CF6, CF34, CFM56, and GE90 for General Electric (GE) under Contract No. 200-1X-14W53048, in support of GRC Contract NAS3-01135. MTCT has demonstrated in earlier noise modeling efforts that the improvement of predictive modeling is greatly enhanced by an iterative approach, so in support of NASA's Quiet Aircraft Technology Project, GRC sponsored this effort to improve the model. Since the noise data available for correlation are total engine noise spectra, it is total engine noise that must be predicted. Since the scope of this effort was not sufficient to explore fan and turbine noise, the most meaningful comparisons must be restricted to frequencies below the blade passage frequency. Below the blade passage frequency and at relatively high power settings jet noise is expected to be the dominant source, and comparisons are shown that demonstrate the accuracy of the jet noise model recently developed by MTCT for NASA under Contract NAS3-00178, Task Order No. 10. At lower power settings the core noise became most apparent, and these data corrected for the contribution of jet noise were then used to establish the characteristics of core noise. There is clearly more than one spectral range where core noise is evident, so the spectral approach developed by von Glahn and Krejsa in 1982 wherein four spectral regions overlap, was used in the GE effort. Further analysis indicates that the two higher frequency components, which are often somewhat masked by turbomachinery noise, can be treated as one component, and it is on that basis that the current model is formulated. The frequency scaling relationships are improved and are now based on combustor and core nozzle geometries. In conjunction with the Task Order No. 10 jet noise model, this core noise model is shown to provide statistical accuracy comparable to the jet noise model for frequencies below blade passage. This model is incorporated in the NASA FOOTPR code and a user s guide is provided.

Single dose sublingual testosterone and oral sildenafil vs. a dual route/dual release fixed dose combination tablet: a pharmacokinetic comparison

PubMed Central

van Rooij, Kim; de Leede, Leo; Frijlink, Henderik W.; Koppeschaar, Hans P. F.; Olivier, Berend; Tuiten, Adriaan

2016-01-01

Aim The aim was to compare the pharmacokinetic profiles of two formulations of a combination drug product containing 0.5 mg testosterone and 50 mg sildenafil for female sexual interest/arousal disorder. The prototype (formulation 1) consists of a testosterone solution for sublingual administration and a sildenafil tablet that is administered 2.5 h later. The dual route/dual release fixed dose combination tablet (formulation 2) employs a sublingual and an oral route for systemic uptake. This tablet has an inner core of sildenafil with a polymeric time delay coating and an outer polymeric coating containing testosterone. It was designed to increase dosing practicality and decrease potential temporal non‐adherence through circumventing the relatively complex temporal dosing scheme. Methods Twelve healthy premenopausal subjects received both formulations randomly on separate days. Blood was sampled frequently to determine the pharmacokinetics of free testosterone, total testosterone, dihydrotestosterone, sildenafil and N‐desmethyl‐sildenafil. Results Formulation 2 had a higher maximum concentration (C max) for testosterone, 8.06 ng ml–1 (95% confidence interval [CI] 6.84, 9.28) and higher area under the plasma concentration–time curve (AUC), 7.69 ng ml–1 h (95% CI 6.22, 9.16) than formulation 1, 5.66 ng ml–1 (95% CI 4.63, 6.69) and 5.12 ng ml–1 h (95% CI 4.51, 5.73), respectively. Formulation 2 had a lower C max for sildenafil, 173 ng ml–1 (95% CI 126, 220) and a lower AUC, 476 ng ml–1 h (95% CI 401, 551) than formulation 1, 268 ng ml–1 (95% CI 188, 348) and 577 ng ml–1 h (95% CI 462, 692), respectively. Formulation 2 released sildenafil after 2.75 h (95% CI 2.40, 3.10). Conclusions The dual route/dual release fixed dose combination tablet fulfilled its design criteria and is considered suitable for further clinical testing. What is Already Known about this Subject Female sexual interest/arousal disorder (FSIAD) is a significant problem impacting psychological well‐being, but the pharmacotherapeutic options for this problem are lacking.The combined, on‐demand, sublingual administration of low dose sublingual testosterone and oral administration of sildenafil is a novel pharmacotherapeutic option under development for FSIAD.In proof‐of‐concept trials, these compounds were successfully administered via different dosage forms (sublingual and oral) at different time points (separated by 2.5 h) because of their markedly different pharmacokinetic–pharmacodynamic profiles. For future larger scale studies and the clinical practice, this raises obvious adherence issues. What this Study Adds A newly developed dual route/dual release fixed dose combination tablet containing testosterone and sildenafil mimics the pharmacokinetic profile of these components when they are administered as different dosage forms, 2.5 h apart.This combination tablet is a suitable final pharmaceutical drug product that will be used in future studies. PMID:26804967

Formulation and process strategies to minimize coat damage for compaction of coated pellets in a rotary tablet press: A mechanistic view.

PubMed

Xu, Min; Heng, Paul Wan Sia; Liew, Celine Valeria

2016-02-29

Compaction of multiple-unit pellet system (MUPS) tablets has been extensively studied in the past few decades but with marginal success. This study aims to investigate the formulation and process strategies for minimizing pellet coat damage caused by compaction and elucidate the mechanism of damage sustained during the preparation of MUPS tablets in a rotary tablet press. Blends containing ethylcellulose-coated pellets and cushioning agent (spray dried aggregates of micronized lactose and mannitol), were compacted into MUPS tablets in a rotary tablet press. The effects of compaction pressure and dwell time on the physicomechanical properties of resultant MUPS tablets and extent of pellet coat damage were systematically examined. The coated pellets from various locations at the axial and radial peripheral surfaces and core of the MUPS tablets were excavated and assessed for their coat damage individually. Interestingly, for a MUPS tablet formulation which consolidates by plastic deformation, the tablet mechanical strength could be enhanced without exacerbating pellet coat damage by extending the dwell time in the compaction cycle during rotary tableting. However, the increase in compaction pressure led to faster drug release rate. The location of the coated pellets in the MUPS tablet also contributed to the extent of their coat damage, possibly due to uneven force distribution within the compact. To ensure viability of pellet coat integrity, the formation of a continuous percolating network of cushioning agent is critical and the applied compaction pressure should be less than the pellet crushing strength. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation design of an HPMC-based sustained release tablet for pyridostigmine bromide as a highly hygroscopic model drug and its in vivo/in vitro dissolution properties.

PubMed

Huang, Yuh-Tyng; Tsai, Tong-Rong; Cheng, Chun-Jen; Cham, Thau-Ming; Lai, Tsun-Fwu; Chuo, Wen-Ho

2007-11-01

Pyridostigmine bromide (PB), a highly hygroscopic drug was selected as the model drug. A sustained-release (SR) tablet prepared by direct compression of wet-extruded and spheronized core pellets with HPMC excipients and exhibited a zero-order sustained release (SR) profile. The 2(3) full factorial design was utilized to search an optimal SR tablet formulation. This optimal formulation was followed zero-order mechanism and had specific release rate at different time intervals (released % of 1, 6, and 12 hr were 15.84, 58.56, and 93.10%). The results of moisture absorption by Karl Fischer meter showed the optimum SR tablet could improve the hygroscopic defect of the pure drug (PB). In the in vivo study, the results of the bioavailability data showed the T(max) was prolonged (from 0.65 +/- 0.082 hr to 4.83 +/- 1.60 hr) and AUC(0-t) (from 734.88 +/- 230.68 ng/ml.hr to 1153.34 +/- 488.08 ng/ml.hr) and was increased respectively for optimum PB-SR tablets when compared with commercial immediate release (IR) tablets. Furthermore, the percentages of in vitro dissolution and in vivo absorption in the rabbits have good correlation. We believe that PB-SR tablets designed in our study would improve defects of PB, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in war or terrorist attacks in the future.

Oleanolic acid liposomes with polyethylene glycol modification: promising antitumor drug delivery

PubMed Central

Gao, Dawei; Tang, Shengnan; Tong, Qi

2012-01-01

Background Oleanolic acid is a pentacyclic triterpene present in many fruits and vegetables, and has received much attention on account of its biological properties. However, its poor solubility and low bioavailability limit its use. The objective of this study was to encapsulate oleanolic acid into nanoliposomes using the modified ethanol injection method. Methods The liposomes contain a hydrophobic oleanolic acid core, an amphiphilic soybean lecithin monolayer, and a protective hydrophilic polyethylene glycol (PEG) coating. During the preparation process, the formulations described were investigated by designing 34 orthogonal experiments as well as considering the effects of different physical characteristics. The four factors were the ratios of drug to soybean phosphatidylcholine (w/w), cholesterol (w/w), PEG-2000 (w/w), and temperature of phosphate-buffered saline at three different levels. We identified the optimized formulation which showed the most satisfactory lipid stability and particle formation. The morphology of the liposomes obtained was determined by transmission electron microscopy and atomic force microscopy. The existence of PEG in the liposome component was validated by Fourier transform infrared spectrum analysis. Results The PEGylated liposomes dispersed individually and had diameters of around 110–200 nm. Encapsulation efficiency was more than 85%, as calculated by high-performance liquid chromatography and Sephadex® gel filtration. Furthermore, when compared with native oleanolic acid, the liposomal formulations showed better stability in vitro. Finally, the cytotoxicity of the oleanolic acid liposomes was evaluated using a microtiter tetrazolium assay. Conclusion These results suggest that PEGylated liposomes would serve as a potent delivery vehicle for oleanolic acid in future cancer therapy. PMID:22848175

Rational design of protamine nanocapsules as antigen delivery carriers.

PubMed

González-Aramundiz, José Vicente; Presas, Elena; Dalmau-Mena, Inmaculada; Martínez-Pulgarín, Susana; Alonso, Covadonga; Escribano, José M; Alonso, María J; Csaba, Noemi Stefánia

2017-01-10

Current challenges in global immunization indicate the demand for new delivery strategies, which could be applied to the development of new vaccines against emerging diseases, as well as to improve safety and efficacy of currently existing vaccine formulations. Here, we report a novel antigen nanocarrier consisting of an oily core and a protamine shell, further stabilized with pegylated surfactants. These nanocarriers, named protamine nanocapsules, were rationally designed to promote the intracellular delivery of antigens to immunocompetent cells and to trigger an efficient and long-lasting immune response. Protamine nanocapsules have nanometric size, positive zeta potential and high association capacity for H1N1 influenza hemagglutinin, a protein that was used here as a model antigen. The new formulation shows an attractive stability profile both, as an aqueous suspension or a freeze-dried powder formulation. In vitro studies showed that protamine nanocapsules were efficiently internalized by macrophages without eliciting significant toxicity. In vivo studies indicate that antigen-loaded nanocapsules trigger immune responses comparable to those achieved with alum, even when using significantly lower antigen doses, thus indicating their adjuvant properties. These promising in vivo data, alongside with their versatility for the loading of different antigens and oily immunomodulators and their excellent stability profile, make these nanocapsules a promising platform for the delivery of antigens. Protamine sulphate (PubChem SID: 7849283), Sodium Cholate (PubChem CID: 23668194), Miglyol (PubChem CID: 53471835), α tocopherol (PubChem CID: 14985), Tween® 20(PubChem CID: 443314), Tween® 80(PubChem CID: 5281955), TPGS (PubChem CID: 71406). Copyright © 2016 Elsevier B.V. All rights reserved.

pH-Controlled Bacillus thuringiensis Cry1Ac Protoxin Loading and Release from Polyelectrolyte Microcapsules

PubMed Central

Yang, Wenhui; He, Kanglai; Zhang, Jie; Guo, Shuyuan

2012-01-01

Crystal proteins synthesized by Bacillus thuringiensis (Bt) have been used as biopesticides because of their toxicity to the insect larval hosts. To protect the proteins from environmental stress to extend their activity, we have developed a new microcapsule formulation. Poly (acrylic acid) (PAH) and poly (styrene sulfonate) (PSS) were fabricated through layer-by-layer self-assembly based on a CaCO3 core. Cry1Ac protoxins were loaded into microcapsules through layer-by-layer self-assembly at low pH, and the encapsulated product was stored in water at 4°C. Scanning electron microscopy (SEM) was used to observe the morphology of the capsules. To confirm the successful encapsulation, the loading results were observed with a confocal laser scattering microscope (CLSM), using fluorescein-labeled Cry1Ac protoxin (FITC-Cry1Ac). The protoxins were released from the capsule under the alkaline condition corresponding to the midgut of certain insects, a condition which seldom exists elsewhere in the environment. The following bioassay experiment demonstrated that the microcapsules with Cry1Ac protoxins displayed approximately equivalent insecticidal activity to the Asian corn borer compared with free Cry1Ac protoxins, and empty capsules proved to have no effect on insects. Further result also indicated that the formulation could keep stable under the condition of heat and desiccation. These results suggest that this formulation provides a promising methodology that protects protoxins from the environment and releases them specifically in the target insects’ midgut, which has shown potential as biopesticide in the field. PMID:23024810

Understanding and practice of evidence based search strategy among postgraduate dental students: a preliminary study.

PubMed

Qureshi, Ambrina; Bokhari, Syed Akhtar Hussain; Pirvani, Madiha; Dawani, Narendar

2015-06-01

One of the core attributes of competent practice is the ability to locate and analyze high-quality evidence. Research on information seeking knowledge of dental graduates is scarce. The objective was to evaluate pertinent knowledge and skills on formulation of answerable questions and searching skills through the understanding and application of EBP. Participants' understanding and abilities to develop answerable questions in application of EBP were assessed through a quasi-experimental study design among freshly inducted postgraduate dental students at Dow University of Health Sciences. Pre and post workshop activity sessions were conducted and assessment was made through a tool that was an adaptation of the Fresno Test. The assessments performed were calculated for mean scores and standard deviations to draw descriptive results for the participants' understanding of the search items and clinical question formulation skills. Wilcoxon-signed rank test was performed to compare the pre and post workshop mean scores. Forty two participants (females = 20, males = 22) attended the workshop. Pre-workshop knowledge and understanding about the terminologies used in EBP was low among participants. Post-workshop performance of the participants to formulate a question, find evidence and search on PubMed was improved to a "Limited" level. The improvements were statistically significant but could not attain "Strong" and "Excellent" grades as far as the EBP skills were concerned. This study observed a potential to improve search skills of dental graduates after their training and exposure to search strategies available on databases. Copyright © 2015 Elsevier Inc. All rights reserved.

Time-Accurate Local Time Stepping and High-Order Time CESE Methods for Multi-Dimensional Flows Using Unstructured Meshes

NASA Technical Reports Server (NTRS)

Chang, Chau-Lyan; Venkatachari, Balaji Shankar; Cheng, Gary

2013-01-01

With the wide availability of affordable multiple-core parallel supercomputers, next generation numerical simulations of flow physics are being focused on unsteady computations for problems involving multiple time scales and multiple physics. These simulations require higher solution accuracy than most algorithms and computational fluid dynamics codes currently available. This paper focuses on the developmental effort for high-fidelity multi-dimensional, unstructured-mesh flow solvers using the space-time conservation element, solution element (CESE) framework. Two approaches have been investigated in this research in order to provide high-accuracy, cross-cutting numerical simulations for a variety of flow regimes: 1) time-accurate local time stepping and 2) highorder CESE method. The first approach utilizes consistent numerical formulations in the space-time flux integration to preserve temporal conservation across the cells with different marching time steps. Such approach relieves the stringent time step constraint associated with the smallest time step in the computational domain while preserving temporal accuracy for all the cells. For flows involving multiple scales, both numerical accuracy and efficiency can be significantly enhanced. The second approach extends the current CESE solver to higher-order accuracy. Unlike other existing explicit high-order methods for unstructured meshes, the CESE framework maintains a CFL condition of one for arbitrarily high-order formulations while retaining the same compact stencil as its second-order counterpart. For large-scale unsteady computations, this feature substantially enhances numerical efficiency. Numerical formulations and validations using benchmark problems are discussed in this paper along with realistic examples.

Mucoadhesive properties of low molecular weight chitosan- or glycol chitosan- and corresponding thiomer-coated poly(isobutylcyanoacrylate) core-shell nanoparticles.

PubMed

Palazzo, Claudio; Trapani, Giuseppe; Ponchel, Gilles; Trapani, Adriana; Vauthier, Christine

2017-08-01

The aim of the present work was to evaluate the mucoadhesive properties of poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles (NPs) coated with Low Molecular Weight (LMW) chitosan (CS)- and glycol chitosan (GCS)-based thiomers as well as with the corresponding LMW unmodified polysaccharides. For this purpose, all the CS- and GCS-based thiomers were prepared under simple and mild conditions starting from the LMW unmodified polymers CS and GCS. The resulting NPs were of spherical shape with diameters ranging from 400 to 600nm and 187 to 309nm, for CS- and GCS-based NPs, respectively. The mucoadhesive characteristics of these core shell NPs were studied in Ussing chambers measuring the percentage of NPs stuck on the mucosal of fresh intestinal tissue after 2h of incubation. Moreover, incubation of nanoparticle formulations with the intestinal tissue induced changes in transmucosal electrical resistance which were measured to gain information into the opening of tight junctions and to control the integrity of the mucosa. Thus, it was found that PIBCA NPs coated with the GCS-Glutathione conjugate (GCGPIBCA NPs) possessed the most favorable mucoadhesive performances. Moreover, both GCGPIBCA- and GCS-N-acetyl-cysteine (GCNPIBCA)-core-shell NPs might induced an enlargement of the epithelial cell tight junctions. In conclusion, coating of PIBCA NPs with GCS-based thiomers may be useful for improving the mucoadhesive and permeation properties of these nanocarriers. Copyright © 2017 Elsevier B.V. All rights reserved.

Modifications to WRFs dynamical core to improve the treatment of moisture for large-eddy simulations

DOE PAGES

Xiao, Heng; Endo, Satoshi; Wong, May; ...

2015-10-29

Yamaguchi and Feingold (2012) note that the cloud fields in their large-eddy simulations (LESs) of marine stratocumulus using the Weather Research and Forecasting (WRF) model exhibit a strong sensitivity to time stepping choices. In this study, we reproduce and analyze this sensitivity issue using two stratocumulus cases, one marine and one continental. Results show that (1) the sensitivity is associated with spurious motions near the moisture jump between the boundary layer and the free atmosphere, and (2) these spurious motions appear to arise from neglecting small variations in water vapor mixing ratio (qv) in the pressure gradient calculation in themore » acoustic sub-stepping portion of the integration procedure. We show that this issue is remedied in the WRF dynamical core by replacing the prognostic equation for the potential temperature θ with one for the moist potential temperature θm=θ(1+1.61qv), which allows consistent treatment of moisture in the calculation of pressure during the acoustic sub-steps. With this modification, the spurious motions and the sensitivity to the time stepping settings (i.e., the dynamic time step length and number of acoustic sub-steps) are eliminated in both of the example stratocumulus cases. In conclusion, this modification improves the applicability of WRF for LES applications, and possibly other models using similar dynamical core formulations, and also permits the use of longer time steps than in the original code.« less

Moisture sorption and permeability characteristics of polymer films: implications for their use as barrier coatings for solid dosage forms containing hydrolyzable drug substances.

PubMed

Mwesigwa, Enosh; Basit, Abdul W; Buckton, Graham

2008-10-01

Moisture sorption and permeability characteristics of polymer films were studied and their effectiveness to protect a hydrolyzable drug assessed. Cast films were prepared from Eudragit L30 D-55, Eudragit EPO, Opadry AMB and Sepifilm LP dispersions, which were also applied onto tablet cores formulated with aspirin as a model moisture sensitive active ingredient. Sorption studies were undertaken using dynamic vapour sorption, ranging between 0% and 90% RH at 25 degrees C. Cast films exhibited fast equilibration (

Tetranuclear clusters containing a CrIII-doped MnIII4O2 core: syntheses, structures, and magnetic properties.

PubMed

Ma, Yun-Sheng; Li, Yi-Zhi; Song, You; Zheng, Li-Min

2008-06-02

The oxidation of MnII carboxylates by (NBu4)Cr2O7 in the presence of different phosphonic acids and chelating ligands results in six CrIII-doped tetranuclear manganese clusters formulated [Mn3CrO2(O2CCH3)4(O3PC5H4N)2(bpy)2] (1), [Mn3CrO2(O2CCH3)4(O3PC5H4N)2(phen)2] (2), [Mn3CrO2(O2CPh)4(O3PC5H4NO)2(phen)2] (3), [Mn3CrO2(O2CPh)4(O3PC6H11)2(bpy)2] (4), [Mn 3CrO2(O2CPh)4(O3PC6H11)2(phen) 2] (5), and [Mn3CrO2(O2CCH3)4(O3PC6H11)2(bpy)2] (6). Single-crystal X-ray analyses reveal that all the compounds contain similar [M4O2]8+ cores with the four metal sites arranged in planar topologies. The metal ions within the core are bridged by both carboxylate and phosphonate ligands. Temperature-dependent magnetic measurements show that in all cases dominant antiferromagnetic interactions are propagated between the metal centers. The ac magnetic measurements on compounds 5 and 6 reveal that both the in-phase and the out-of-phase signals are frequency dependent, characteristic of single-molecule magnet behaviors.

Spray-dried casein-based micelles as a vehicle for solubilization and controlled delivery of flutamide: formulation, characterization, and in vivo pharmacokinetics.

PubMed

Elzoghby, Ahmed O; Helmy, Maged W; Samy, Wael M; Elgindy, Nazik A

2013-08-01

Novel casein (CAS)-based micelles loaded with the poorly soluble anti-cancer drug, flutamide (FLT), were successfully developed in a powdered form via spray-drying technique. Genipin (GNP) was used to crosslink CAS micelles as demonstrated by color variation of the micelles. Drug solubilization was enhanced by incorporation within the hydrophobic micellar core which was confirmed by solubility study and UV spectra. Spherical core-shell micelles were obtained with a particle size below 100 nm and zeta potential around -30 mV. At low drug loading, FLT was totally incorporated within micellar core as revealed by thermal analysis. However, at higher loading, excess non-incorporated drug at micelle surface caused a significant reduction in the surface charge density. Turbidity measurements demonstrated the high physical stability of micelles for 2 weeks dependent on GNP-crosslinking degree. In a dry powdered form, the micelles were stable for 6 months with no significant changes in drug content or particle size. A sustained drug release from CAS micelles up to 5 days was observed. After i.v. administration into rats, CAS micelles exhibited a prolonged plasma circulation of FLT compared to drug solution. Furthermore, a more prolonged drug systemic circulation was observed for GNP-crosslinked micelles. Overall, this study reports the application of spray-dried natural protein-based micelles for i.v. delivery of hydrophobic anti-cancer drugs such as FLT. Copyright © 2013 Elsevier B.V. All rights reserved.

Magnetic and pH-sensitive nanoparticles for antitumor drug delivery.

PubMed

Yu, Shufang; Wu, Guolin; Gu, Xin; Wang, Jingjing; Wang, Yinong; Gao, Hui; Ma, Jianbiao

2013-03-01

A dually responsive nanocarrier with multilayer core-shell architecture was prepared based on Fe(3)O(4)@SiO(2) nanoparticles coated with mPEG-poly(l-Asparagine). Imidazole groups (pK(a)∼6.0) were tethered to the side chains of poly(l-Asparagine) segments by aminolysis. These nanoparticles were expected to be sensitive to both magnetic field and pH environment. The obtained materials were characterized with FTIR, dynamic light scattering, ζ-potential, TEM, TGA and hysteresis loop analysis. It was found that this Fe(3)O(4)@SiO(2)-polymer complex can form nano-scale core-shell-corona trilayer particles (∼250 nm) in aqueous solution. The Fe(3)O(4)@SiO(2), poly(L-Asparagine) and mPEG segments serve as a super-paramagnetic core, a pH-sensitive shell, and a hydrophilic corona, respectively. An antitumor agent, doxorubicin (DOX), was successfully loaded into the nanocarrier via combined actions of hydrophobic interaction and hydrogen bonding. The drug release profiles displayed a pH-dependent behavior. DOX release rate increased significantly as the ambient pH dropped from the physiological pH (7.4) to acidic (5.5). This is most likely due to protonation and a change in hydrophilicity of the imidazole groups in the poly(l-Asparagine) segments. This new approach may serve as a promising platform to formulate magnetic targeted drug delivery systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Modeled Seasonal Variations of Firn Density Induced by Steady State Surface Air Temperature Cycle

NASA Technical Reports Server (NTRS)

Jun, Li; Zwally, H. Jay; Koblinsky, Chester J. (Technical Monitor)

2001-01-01

Seasonal variations of firn density in ice-sheet firn layers have been attributed to variations in deposition processes or other processes within the upper firn. A recent high-resolution (mm scale) density profile, measured along a 181 m core from Antarctica, showed small-scale density variations with a clear seasonal cycle that apparently was not-related to seasonal variations in deposition or known near-surface processes (Gerland and others 1999). A recent model of surface elevation changes (Zwally and Li, submitted) produced a seasonal variation in firn densification, and explained the seasonal surface elevation changes observed by satellite radar altimeters. In this study, we apply our 1-D time-dependent numerical model of firn densification that includes a temperature-dependent formulation of firn densification based on laboratory measurements of grain growth. The model is driven by a steady-state seasonal surface temperature and a constant accumulation rate appropriate for the measured Antarctic ice core. The modeled seasonal variations in firn density show that the layers of snow deposited during spring to mid-summer with the highest temperature history compress to the highest density, and the layers deposited during later summer to autumn with the lowest temperature history compress to the lowest density. The initial amplitude of the seasonal difference of about 0.13 reduces to about 0.09 in five years and asymptotically to 0.92 at depth, which is consistent with the core measurements.

Microencapsulation of Clostridium difficile specific bacteriophages using microfluidic glass capillary devices for colon delivery using pH triggered release

PubMed Central

Vinner, Gurinder K.; Vladisavljević, Goran T.; Clokie, Martha R. J.

2017-01-01

The prevalence of pathogenic bacteria acquiring multidrug antibiotic resistance is a global health threat to mankind. This has motivated a renewed interest in developing alternatives to conventional antibiotics including bacteriophages (viruses) as therapeutic agents. The bacterium Clostridium difficile causes colon infection and is particularly difficult to treat with existing antibiotics; phage therapy may offer a viable alternative. The punitive environment within the gastrointestinal tract can inactivate orally delivered phages. C. difficile specific bacteriophage, myovirus CDKM9 was encapsulated in a pH responsive polymer (Eudragit® S100 with and without alginate) using a flow focussing glass microcapillary device. Highly monodispersed core-shell microparticles containing phages trapped within the particle core were produced by in situ polymer curing using 4-aminobenzoic acid dissolved in the oil phase. The size of the generated microparticles could be precisely controlled in the range 80 μm to 160 μm through design of the microfluidic device geometry and by varying flow rates of the dispersed and continuous phase. In contrast to free ‘naked’ phages, those encapsulated within the microparticles could withstand a 3 h exposure to simulated gastric fluid at pH 2 and then underwent a subsequent pH triggered burst release at pH 7. The significance of our research is in demonstrating that C. difficile specific phage can be formulated and encapsulated in highly uniform pH responsive microparticles using a microfluidic system. The microparticles were shown to afford significant protection to the encapsulated phage upon prolonged exposure to an acid solution mimicking the human stomach environment. Phage encapsulation and subsequent release kinetics revealed that the microparticles prepared using Eudragit® S100 formulations possess pH responsive characteristics with phage release triggered in an intestinal pH range suitable for therapeutic purposes. The results reported here provide proof-of-concept data supporting the suitability of our approach for colon targeted delivery of phages for therapeutic purposes. PMID:29023522

Fabrication and Evaluation of Graphite Fiber-Reinforced Polyimide Composite Tube Forms Using Modified Resin Transfer Molding

NASA Technical Reports Server (NTRS)

Exum, Daniel B.; Ilias, S.; Avva, V. S.; Sadler, Bob

1997-01-01

The techniques necessary for the fabrication of a complex three-dimensional tubular form using a PMR-type resin have been developed to allow for the construction of several tubes with good physical and mechanical properties. Employing established resin transfer molding practices, the relatively non-hazardous AMB-21 in acetone formulation was used to successfully impregnate four layers of AS4 braided graphite fiber preform previously loaded around an aluminum cylindrical core in an enclosed mold cavity. Using heat and vacuum, the solvent was evaporated to form a prepreg followed by a partial imidization and removal of condensation products. The aluminum core was replaced by a silicone rubber bladder and the cure cycle continued to the final stage of 550 F with a bladder internal pressure of 200 lbs/sq in while simultaneously applying a strong vacuum to the prepreg for removal of any additional imidization products. A combination of several modifications to the standard resin transfer molding methodology enabled the mold to 'breathe', allowing the imidization products a pathway for escape. AMB-21 resin was chosen because of the carcinogenic nature of the primary commercial polyimide PMR-15. The AMB-21 resin was formulated using commercially available monomers or monomer precursors and dissolved in a mixture of methyl alcohol and acetone. The viscosity of the resulting monomer solution was checked by use of a Brookfield rheometer and adjusted by adding acetone to an easily pumpable viscosity of about 600 cP. In addition, several types of chromatographic and thermal analyses were of the braids, and excess handling of the preforms broke some of the microscopic fibers, needlessly decreasing the strength of the finished part. In addition, three dimensional braided preforms with fibers along the length of the tube will be significantly stronger in tension than the braided preforms used in this study.

Hesperetin-loaded lipid-core nanocapsules in polyamide: a new textile formulation for topical drug delivery

PubMed Central

Menezes, Paula dos Passos; Frank, Luiza Abrahão; Lima, Bruno dos Santos; de Carvalho, Yasmim Maria Barbosa Gomes; Serafini, Mairim Russo; Quintans-Júnior, Lucindo José; Pohlmann, Adriana Raffin; Guterres, Sílvia Stanisçuaski; Araújo, Adriano Antunes de Souza

2017-01-01

Chronic venous insufficiency is characterized by chronic reflux disorder of blood from the peripheral to the central vein, with subsequent venous hypertension and resulting changes in the skin. Traditionally, nonsurgical treatments relied on the use of compression therapy, and more recently a variety of flavonoids have been shown to have positive effects. There have also been developments of more effective drug delivery systems using various textiles and nanotechnology to provide new therapeutic options. Our objective was to use nanotechnology to develop a new formulation containing hesperetin (Hst), a substance not previously used in the treatment of chronic venous insufficiency, impregnated into textile fibers as a possible alternative treatment of venous diseases. We prepared the nanocapsules using the interfacial deposition of preformed polymer method with an Hst concentration of 0.5 mg/mL and then characterized the size and distribution of particles. To quantify the Hst in the samples, we developed an analytical method using high-performance liquid chromatography. Studies of encapsulation efficiency (98.81%±0.28%), microscopy, drug release (free-Hst: 104.96%±12.83%; lipid-core nanocapsule-Hst: 69.90%±1.33%), penetration/permeation, drug content (0.46±0.01 mg/mL) and the effect of washing the textile after drug impregnation were performed as part of the study. The results showed that nanoparticles of a suitable size and distribution with controlled release of the drug and penetration/permeation into the skin layers were achieved. Furthermore, it was established that polyamide was able to hold more of the drug, with a 2.54 times higher content than the cotton fiber; after one wash and after five washes, this relation was 2.80 times higher. In conclusion, this is a promising therapeutic alternative to be further studied in clinical trials. PMID:28352176

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.

PubMed

Mathes, C; Melero, A; Conrad, P; Vogt, T; Rigo, L; Selzer, D; Prado, W A; De Rossi, C; Garrigues, T M; Hansen, S; Guterres, S S; Pohlmann, A R; Beck, R C R; Lehr, C-M; Schaefer, U F

2016-02-10

The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

An enhanced beam model for constrained layer damping and a parameter study of damping contribution

NASA Astrophysics Data System (ADS)

Xie, Zhengchao; Shepard, W. Steve, Jr.

2009-01-01

An enhanced analytical model is presented based on an extension of previous models for constrained layer damping (CLD) in beam-like structures. Most existing CLD models are based on the assumption that shear deformation in the core layer is the only source of damping in the structure. However, previous research has shown that other types of deformation in the core layer, such as deformations from longitudinal extension and transverse compression, can also be important. In the enhanced analytical model developed here, shear, extension, and compression deformations are all included. This model can be used to predict the natural frequencies and modal loss factors. The numerical study shows that compared to other models, this enhanced model is accurate in predicting the dynamic characteristics. As a result, the model can be accepted as a general computation model. With all three types of damping included and the formulation used here, it is possible to study the impact of the structure's geometry and boundary conditions on the relative contribution of each type of damping. To that end, the relative contributions in the frequency domain for a few sample cases are presented.

Optimising a curriculum for clinical haematology and biochemistry in sports medicine: a Delphi approach

PubMed Central

Fallon, K E; Trevitt, A C

2006-01-01

Objectives To investigate issues of curriculum in the context of a postgraduate sports medicine training programme, specifically in the field of clinical biochemistry and haematology. Methods Following the Delphi methodology, a series of sequential questionnaires was administered to curriculum developers, clinical teachers, examiners, and registrars. Results Agreement on a core syllabus for this subject with an indication of the core aims and objectives of teaching and learning in this field and the associated required skills and competencies. An indication of current and ideal teaching and learning methods and reasons for these preferences. A consensus of key features of a teaching module for this field and of appropriate methods of examination. Conclusions The data derived from this study, as well as the experience of engaging in it, will better inform curriculum developers, teachers, and students of one another's perceptions as to what is important in and appropriate to teaching and learning in this field of sports medicine. Engagement in the exercise and broader consideration of the outcomes by those who develop the curriculum, teach, and formulate the examination process will facilitate attainment of the ideal of well aligned teaching, learning, and examination in this specific field. PMID:16432001

Unlocking reflective practice for nurses: innovations in working with master of nursing students in Hong Kong.

PubMed

Joyce-McCoach, Joanne T; Parrish, Dominique R; Andersen, Patrea R; Wall, Natalie

2013-09-01

Being reflective is well established as an important conduit of practice development, a desirable tertiary graduate quality and a core competency of health professional membership. By assisting students to be more effective in their ability to reflect, they are better able to formulate strategies to manage issues experienced within a professional context, which ultimately assists them to be better service providers. However, some students are challenged by the practice of reflection and these challenges are even more notable for international students. This paper presents a teaching initiative that focused specifically on enhancing the capacity of an international cohort of nursing students, to engage in reflective practice. The initiative centered on an evaluation of a reflective practice core subject, which was taught in a Master of Nursing programme delivered in Hong Kong. A learning-centered framework was used to evaluate the subject and identify innovative strategies that would better assist international students to develop reflective practices. The outcomes of curriculum and teaching analysis and proposed changes and innovations in teaching practice to support international students are presented and discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

New release cell for NMR microimaging of tablets. Swelling and erosion of poly(ethylene oxide).

PubMed

Abrahmsén-Alami, Susanna; Körner, Anna; Nilsson, Ingvar; Larsson, Anette

2007-09-05

A small release cell, in the form of a rotating disc, has been constructed to fit into the MRI equipment. The present work show that both qualitative and quantitative information of the swelling and erosion behavior of hydrophilic extended release (ER) matrix tablets may be obtained using this release cell and non-invasive magnetic resonance imaging (MRI) studies at different time-points during matrix dissolution. The tablet size, core size and the gel layer thickness of ER matrix formulations based on poly(ethylene oxide) have been determined. The dimensional changes as a function of time were found to correspond well to observations made with texture analysis (TA) methodology. Most importantly, the results of the present study show that both the erosion (displacement of the gel-dissolution media interface) and the swelling (decrease of dry tablet core size) proceed with a faster rate in radial than in axial direction using the rotating disk set-up. This behavior was attributed to the higher shear forces experienced in the radial direction. The results also indicate that front synchronization (constant gel layer thickness) is associated with the formation of an almost constant polymer concentration profile through the gel layer at different time-points.

Dispersion characteristics of plasmonic waveguides for THz waves

NASA Astrophysics Data System (ADS)

Markides, Christos; Viphavakit, Charusluk; Themistos, Christos; Komodromos, Michael; Kalli, Kyriacos; Quadir, Anita; Rahman, Azizur

2013-05-01

Today there is an increasing surge in Surface Plasmon based research and recent studies have shown that a wide range of plasmon-based optical elements and techniques have led to the development of a variety of active switches, passive waveguides, biosensors, lithography masks, to name just a few. The Terahertz (THz) frequency region of the electromagnetic spectrum is located between the traditional microwave spectrum and the optical frequencies, and offers a significant scientific and technological potential in many fields, such as in sensing, in imaging and in spectroscopy. Waveguiding in this intermediate spectral region is a major challenge. Amongst the various THz waveguides suggested, the metal-clad waveguides supporting surface plasmon modes waves and specifically hollow core structures, coated with insulating material are showing the greatest promise as low-loss waveguides for their use in active components and as well as passive waveguides. The H-field finite element method (FEM) based full-vector formulation is used to study the vectorial modal field properties and the complex propagation characteristics of Surface Plasmon modes of a hollow-core dielectric coated rectangular waveguide structure. Additionally, the finite difference time domain (FDTD) method is used to estimate the dispersion parameters and the propagation loss of the rectangular waveguide.

Anatomy of funded research in science

PubMed Central

Ma, Athen; Mondragón, Raúl J.; Latora, Vito

2015-01-01

Seeking research funding is an essential part of academic life. Funded projects are primarily collaborative in nature through internal and external partnerships, but what role does funding play in the formulation of these partnerships? Here, by examining over 43,000 scientific projects funded over the past three decades by one of the major government research agencies in the world, we characterize how the funding landscape has changed and its impacts on the underlying collaboration networks across different scales. We observed rising inequality in the distribution of funding and that its effect was most noticeable at the institutional level—the leading universities diversified their collaborations and increasingly became the knowledge brokers in the collaboration network. Furthermore, it emerged that these leading universities formed a rich club (i.e., a cohesive core through their close ties) and this reliance among them seemed to be a determining factor for their research success, with the elites in the core overattracting resources but also rewarding in terms of both research breadth and depth. Our results reveal how collaboration networks organize in response to external driving forces, which can have major ramifications on future research strategy and government policy. PMID:26504240

Dual pH/redox responsive and CD44 receptor targeting hybrid nano-chrysalis based on new oligosaccharides of hyaluronan conjugates.

PubMed

Chen, Daquan; Dong, Xue; Qi, Mengjiao; Song, Xiaoyan; Sun, Jingfang

2017-02-10

A smart hybrid microenvironment-mediated dual pH/redox-responsive polymeric nanoparticles combined with inorganic calcium phosphate (CaP) was fabricated, which we term as armored nano-chrysalis inspired by butterfly pupa. The nano-chrysalis has an inner core composed of specially designed oligosaccharides of hyaluronan (oHA) targeting CD44 receptor. The inner core has two functions, i.e., the dual pH/redox responsive polymeric conjugate and the fluorescent curcumin-prodrug function. The prepared nano-chrysalis possessed a smaller size (102.5±4.6nm) than the unarmored nano-chrysalis (122.5±6.6nm). Interestingly, while the nano-chrysalis were stable under pH 7.4, when incubated under the tumor acidic conditions (pH 6.5) the outer CaP armor would dissolve in a pH-dependent, sustained manner. Moreover, nano-chrysalis was demonstrated to present the most effective antitumor efficacy than other formulations. This study provides a promising smart nano-carrier platform to enhance the stability, decrease the side effects, and improve the therapeutic efficacy of anticancer drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation and in vitro/in vivo evaluation of gestodene (GEST) intravaginal ring.

PubMed

Li, Chunxiao; Ning, Meiying; Yao, Xiaodong; Wang, Yankun; Liu, Ying

2016-09-01

Preparation and in vitro/in vivo evaluation of gestodene (GEST) intravaginal ring (IVR) formulations which can release a constant dose of GEST during 3 weeks were investigated. In present study a reservoir gestodene intravaginal ring, including a gestodene silicone elastomer core and the non-active silicone layer, was reported, which was manufactured by reaction injection moulding at 80°C for 20 min. The raw materials compatibility experiments showed that the silicone elastomer core carrier wouldn't interact with drugs. In vitro release samples were determined by HPLC and the experiment was performed under sink conditions. The equation of cumulative release verse time was Y=64.76χ+5.44 (r=0.9998), performing zero-order release at about the target dose of 60 µg/day over 21 days. Drug release increased with temperature elevating from 45 to 55°C, which could be attributed to optimizing the prescription. In addition, the pharmacokinetic and safety studies of gestodene intravaginal ring were evaluated in female New Zealand White rabbits. The GEST in plasma was analyzed by LC-MS/MS and the results proved that the correlation between in vitro and in vivo was relatively well.

Kinematic validation of a quasi-geostrophic model for the fast dynamics in the Earth's outer core

NASA Astrophysics Data System (ADS)

Maffei, S.; Jackson, A.

2017-09-01

We derive a quasi-geostrophic (QG) system of equations suitable for the description of the Earth's core dynamics on interannual to decadal timescales. Over these timescales, rotation is assumed to be the dominant force and fluid motions are strongly invariant along the direction parallel to the rotation axis. The diffusion-free, QG system derived here is similar to the one derived in Canet et al. but the projection of the governing equations on the equatorial disc is handled via vertical integration and mass conservation is applied to the velocity field. Here we carefully analyse the properties of the resulting equations and we validate them neglecting the action of the Lorentz force in the momentum equation. We derive a novel analytical solution describing the evolution of the magnetic field under these assumptions in the presence of a purely azimuthal flow and an alternative formulation that allows us to numerically solve the evolution equations with a finite element method. The excellent agreement we found with the analytical solution proves that numerical integration of the QG system is possible and that it preserves important physical properties of the magnetic field. Implementation of magnetic diffusion is also briefly considered.

Flight Guidance System Validation Using SPIN

NASA Technical Reports Server (NTRS)

Naydich, Dimitri; Nowakowski, John

1998-01-01

To verify the requirements for the mode control logic of a Flight Guidance System (FGS) we applied SPIN, a widely used software package that supports the formal verification of distributed systems. These requirements, collectively called the FGS specification, were developed at Rockwell Avionics & Communications and expressed in terms of the Consortium Requirements Engineering (CoRE) method. The properties to be verified are the invariants formulated in the FGS specification, along with the standard properties of consistency and completeness. The project had two stages. First, the FGS specification and the properties to be verified were reformulated in PROMELA, the input language of SPIN. This involved a semantics issue, as some constructs of the FGS specification do not have well-defined semantics in CoRE. Then we attempted to verify the requirements' properties using the automatic model checking facilities of SPIN. Due to the large size of the state space of the FGS specification an exhaustive state space analysis with SPIN turned out to be impossible. So we used the supertrace model checking procedure of SPIN that provides for a partial analysis of the state space. During this process, we found some subtle errors in the FGS specification.

Mismatch Considerations in Excitation of Single-Mode Circular Core Parabolic Index Fiber by Laser Diode via Upside Down Tapered Hemispherical Microlens on the Tip of the Fiber

NASA Astrophysics Data System (ADS)

Das, Bishuddhananda; Middya, Tapas Ranjan; Gangopadhyay, Sankar

2017-12-01

We report the theoretical investigation of the coupling optics involving laser diode to single-mode circular core parabolic index fiber via upside down tapered hemispherical microlens on the tip of the fiber in the presence of possible transverse and angular mismatches. Using the relevant ABCD matrix for such tapered hemispherical microlens, we formulate analytical expressions for the coupling efficiencies in the presence of the said two mismatches. Further, the transmitted spot size of the source via the hemispherical lens and the tapered region should match with the spot size of the fiber for obtaining maximum coupling. The investigations have been made for two practical wavelengths, namely 1.3 and 1.5 μm in order to find the tolerance of this coupling device with respect to the said kinds of mismatches at the concerned wavelengths. Although our simple method predicts the concerned coupling optics excellently, the evaluation of the concerned efficiencies and associated losses involve little computations. Thus this user-friendly technique and also the results found thereof will benefit the designers and packagers who are working in the field of optical technology.

Discrete Event Modeling and Massively Parallel Execution of Epidemic Outbreak Phenomena

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

Perumalla, Kalyan S; Seal, Sudip K

2011-01-01

In complex phenomena such as epidemiological outbreaks, the intensity of inherent feedback effects and the significant role of transients in the dynamics make simulation the only effective method for proactive, reactive or post-facto analysis. The spatial scale, runtime speed, and behavioral detail needed in detailed simulations of epidemic outbreaks make it necessary to use large-scale parallel processing. Here, an optimistic parallel execution of a new discrete event formulation of a reaction-diffusion simulation model of epidemic propagation is presented to facilitate in dramatically increasing the fidelity and speed by which epidemiological simulations can be performed. Rollback support needed during optimistic parallelmore » execution is achieved by combining reverse computation with a small amount of incremental state saving. Parallel speedup of over 5,500 and other runtime performance metrics of the system are observed with weak-scaling execution on a small (8,192-core) Blue Gene / P system, while scalability with a weak-scaling speedup of over 10,000 is demonstrated on 65,536 cores of a large Cray XT5 system. Scenarios representing large population sizes exceeding several hundreds of millions of individuals in the largest cases are successfully exercised to verify model scalability.« less

Treating depression with antidepressants: drug-placebo efficacy debates limit broader considerations.

PubMed

Yapko, Michael D

2013-01-01

The core issue regarding antidepressants for many clinicians is whether they perform significantly better than placebos. However, this article suggests eight additional concerns beyond drug efficacy alone to consider regarding antidepressants including: (1) formulating only a one-dimensional, biological view of depression; (2) defining the client's role as passive in treatment; (3) economic corruption of the research and reporting; (4) false or misleading consumer advertising; (5) conflicting data that confuse practitioners and consumers alike; (6) over- and under-prescription of medications; (7) drug side-effects; and (8) harm to the environment. The enhanced effects of psychotherapy utilizing hypnosis offer a means of avoiding most, if not all, of the problems associated with the use of antidepressants as a primary form of treatment.