Science.gov

Sample records for large extended formulation

  1. Hamiltonian formulation of the extended Green-Naghdi equations

    NASA Astrophysics Data System (ADS)

    Matsuno, Yoshimasa

    2015-05-01

    A novel method is developed for extending the Green-Naghdi (GN) shallow-water model equation to the general system which incorporates the arbitrary higher-order dispersive effects. As an illustrative example, we derive a model equation which is accurate to the fourth power of the shallowness parameter while preserving the full nonlinearity of the GN equation, and obtain its solitary wave solutions by means of a singular perturbation analysis. We show that the extended GN equations have the same Hamiltonian structure as that of the GN equation. We also demonstrate that Zakharov's Hamiltonian formulation of surface gravity waves is equivalent to that of the extended GN system by rewriting the former system in terms of the momentum density instead of the velocity potential at the free surface.

  2. Extended-release formulations for the treatment of epilepsy.

    PubMed

    Bialer, Meir

    2007-01-01

    This review analyses the concept of extended-release (ER) formulations in epilepsy and evaluates ER formulations of carbamazepine, valproic acid and a modified-release (MR) formulation of oxcarbazepine. ER formulations are usually designed to reduce dose frequency and maintain relatively constant or flat plasma drug concentration. It is questionable whether flat plasma concentrations of an antiepileptic drug (AED) improve antiepileptic efficacy compared with fluctuating plasma concentrations. More certainly, they minimise concentration-related adverse effects, and the dosing flexibility and consistency of plasma concentrations may simplify the management of antiepileptic drug therapy. Neurologists would like ER formulations that can be administered once- and/or twice-daily to tailor therapy for the individual patient; however, switching dosage schedules from multiple dosages per day to once daily, although more convenient, will not generally improve therapeutic coverage (maintenance of effective drug concentration in biological fluids and tissue). Pharmacokinetically, the impact of a missed dose is greater the larger the dose and the less frequent the administration. Therefore, the risk of breakthrough seizure is higher during AED once-daily administration than twice-daily administration. Consequently, the increased compliance observed with fewer dosages per day should be weighed against the impact or forgiveness of omitted dose(s) and the shorter 'forgiveness' period associated with once-daily administration. Currently, the trend is to treat patients with epilepsy with ER formulations because of the better compliance, convenience and flat plasma concentration versus time curve. Thus, it seems that the term 'flatter is better' for AED plasma profiles has precipitated in the last 10-15 years among neurologists and epilepsy caregivers, and is being promoted by marketing forces of pharmaceutical companies. Data from the literature support the trend to treat epileptic

  3. An Extended Self-Consistent Viscoplastic Polycrystal Formulation: Application to Polycrystals with Voids

    SciTech Connect

    Lebensohn, Ricardo A.; Tomé, Carlos N.; Maudlin, Paul J.

    2003-08-01

    In this work we consider the presence of ellipsoidal voids inside polycrystals submitted to large strain deformation. For this purpose, the originally incompressible viscoplastic self-consistent (VPSC) formulation of Lebensohn and Tomé (1993) has been extended to compressible polycrystals. In doing this, both the deviatoric and the spherical components of strain rate and stress are accounted for. Such an extended model allows us to account for the presence of voids and for porosity evolution, while preserving the anisotropy and crystallographic capabilities of the VPSC model. The formulation is adjusted to match Gurson model in the limit of rateindependent isotropic media and spherical voids. We present several applications of this extended VPSC model that address the coupling between texture, plastic anisotropy, void shape, triaxiality, and porosity evolution. This report contains a detailed and comprehensive derivation of the VPSC polycrystal model and of the equations associated with the theory. Such description is meant to serve as a general reference source for the VPSC formulation and is not limited to the particular case of voided polycrystals.

  4. Sustained-release, extended-release, and other time-release formulations in neuropsychiatry.

    PubMed

    Andrade, Chittaranjan

    2015-08-01

    Pills and capsules may release their contents within minutes of ingestion; these are immediate-release formulations. Pills and capsules may also release their contents after a time lag, or a little at a time, or in some other predetermined way; these are time-release formulations. Many drugs in psychiatry have been time-release formulated to reduce their local adverse effects in the gastrointestinal tract, to reduce adverse effects associated with peak blood levels, or to artificially extend their half-life. Time-release formulations are associated with the added advantages of convenience of dosing, improved compliance, and less fluctuation in blood levels across the course of the day. A disadvantage of time-release formulations is that they may be incompletely absorbed; this is a serious issue in patients with acute or chronic intestinal hurry disorders, such as gastroenteritis or irritable bowel syndrome. Time-release formulations may also be more expensive than immediate-release formulations.

  5. Formulation and Evaluation of Trimetazidine Dihydrochloride Extended Release Tablets by Melt Congealing Method

    PubMed Central

    Javeer, S. D.; Pandit, Reshma; Jain, S. P.; Amin, Purnima

    2010-01-01

    Trimetazidine dihydrochloride, a cellular antiischemic agent indicated in the management and prophylaxis of angina pectoris is given as 20 mg thrice daily in the conventional dosage regimen. The purpose of the present study was to formulate and evaluate twice a day extended release tablets containing 30 mg trimetazidine dihydrochloride. The method developed to formulate these extended release tablets was melt congealing followed by wet granulation which exhibited uniform sustained release action and overcame the drawbacks of multidosing. The formulation was developed with Methocel® K100M and stearic acid as release retardant. PMID:21969741

  6. Formulation Development and Stability Studies of Norfloxacin Extended-Release Matrix Tablets

    PubMed Central

    Oliveira, Paulo Renato; Klein, Lilian; Sangoi, Maximiliano da Silva; Bernardi, Larissa Sakis; Silva, Marcos Antônio Segatto

    2013-01-01

    The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX). Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide) as hydrophilic polymers, with different molecular weights (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6 months at 40 ± 2°C and 75 ± 5% relative humidity), and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30%) of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo. PMID:24083235

  7. Drug Formulation Advances in Extended-Release Medications for Pain Control.

    PubMed

    Jones, Mark R; Carney, Martin J; Kaye, Rachel J; Prabhakar, Amit; Kaye, Alan D

    2016-06-01

    Prescription opioid abusers frequently tamper with opioid tablets in order to either accelerate the delivery of the euphoria-inducing agent or to alter the route of delivery, such that it may be delivered intranasally or intravenously. As one strategy to combat the opioid epidemic in the USA, drug manufacturers have begun to explore formulations which resist such tampering by abusers. Techniques to prevent tampering consist of physical barriers to crushing, chewing, and drug extraction, or aversive or antagonistic agents, incorporated within the formulation itself. Recent years have seen the development of numerous extended-release opioid agents, which are described in this review. This article provides a comprehensive summary of the pharmacology, benefits, risks, and processes behind the development of currently available extended-release opioid drugs, as well as a glimpse into promising future formulations. PMID:27084375

  8. Nonlinear formulation for flexible multibody system with large deformation

    NASA Astrophysics Data System (ADS)

    Liu, Jinyang; Hong, Jiazhen

    2007-02-01

    In this paper, nonlinear modeling for flexible multibody system with large deformation is investigated. Absolute nodal coordinates are employed to describe the displacement, and variational motion equations of a flexible body are derived on the basis of the geometric nonlinear theory, in which both the shear strain and the transverse normal strain are taken into account. By separating the inner and the boundary nodal coordinates, the motion equations of a flexible multibody system are assembled. The advantage of such formulation is that the constraint equations and the forward recursive equations become linear because the absolute nodal coordinates are used. A spatial double pendulum connected to the ground with a spherical joint is simulated to investigate the dynamic performance of flexible beams with large deformation. Finally, the resultant constant total energy validates the present formulation.

  9. Effects of Discrete Damping on the Dynamic Behaviour of Rotating Shaft through Extended Lagrangian Formulation

    NASA Astrophysics Data System (ADS)

    Rastogi, Vikas

    2016-09-01

    The main focus of the paper is touted as effects of discrete damping on the dynamic analysis of rotating shaft. The whole analysis is being carried out through extended Lagrangian formulation for a discrete - continuous system. The variation formulation for this system is possible, considering the continuous system as one-dimensional. The generalized formulation for one dimensional continuous rotary shaft with discrete external damper has been obtained through principle of variation. Using this extended formulation, the invariance of umbra-Lagrangian density through extended Noether's theorem is achieved. Rayleigh beam model is used to model the shaft. Amplitude equation of rotor is obtained theoretically and validated through simulation results. The simulation results reveal the important phenomena of limiting dynamics of the rotor shaft, which is due to an imbalance of material damping and stiffness of the rotor shaft. The regenerative energy in the rotor shaft, induced due to elasticity/stiffness of the rotor shaft, is dissipated partially through the in-span discrete damper and also through the dissipative coupling between drive and the rotor shaft. In such cases, the shaft speed will not increase with increase in excitation frequency of the rotor but the slip between the drive and the shaft increases due to loading of drive.

  10. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations.

    PubMed

    Ena, Javier; Amador, Concepción; Benito, Conxa; Pasquau, Francisco

    2012-01-01

    We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase-inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment-naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release) that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment-naïve patients, and TRANxITION, a study carried out in antiretroviral treatment-experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.

  11. Risk based in vitro performance assessment of extended release abuse deterrent formulations.

    PubMed

    Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N; Khan, Mansoor A

    2016-03-16

    High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products. PMID:26784976

  12. Extending the Principles of Intensive Writing to Large Macroeconomics Classes

    ERIC Educational Resources Information Center

    Docherty, Peter; Tse, Harry; Forman, Ross; McKenzie, Jo

    2010-01-01

    The authors report on the design and implementation of a pilot program to extend the principles of intensive writing outlined by W. Lee Hansen (1998), Murray S. Simpson and Shireen E. Carroll (1999) and David Carless (2006) to large macroeconomics classes. The key aspect of this program was its collaborative nature, with staff from two specialist…

  13. Safety and efficacy considerations due to misuse of extended-release formulations of stimulant medications.

    PubMed

    Jain, Rakesh; Stark, Jeffrey G

    2016-09-01

    Amphetamine or methylphenidate are first-line options for treating attention-deficit/hyperactivity disorder (ADHD). Deviations from suggested routes of administration such as crushing, chewing, intravenous administration, or snorting stimulant medication may alter the release rate, absorption, and bioavailability of the active drug. Additionally, the pharmacokinetic (PK) profiles of extended-release formulations of certain medications (e.g., some opioids) are known to be dangerously altered when consumed with alcohol; specifically, there is an unintended, rapid release of a significant portion of the drug (dose dumping). In vitro data suggest some extended-release stimulants dose dump in the presence of alcohol, which is of concern because the ADHD patient population is at risk for alcohol abuse. This article reviews the available scientific literature concerning modifications to routes of administration that may alter PK properties of stimulant-based medication for treating ADHD. These modifications are of clinical interest because they may pose safety hazards and affect efficacy. Electronic databases were searched for appropriate studies using relevant search terms. The misuse and abuse potential for stimulants and the efforts to prevent misuse are also discussed. Future research should be focused on determining the PK ramifications of stimulant misuse, along with developing new formulations with abuse-deterrent properties. PMID:27467139

  14. An extended finite element formulation for modeling the response of polycrystalline materials to shock loading

    NASA Astrophysics Data System (ADS)

    Robbins, Joshua; Voth, Thomas

    2007-06-01

    The eXtended Finite Element Method (X-FEM) is a finite element based discretization technique developed originally to model dynamic crack propagation [1]. Since that time the method has been used for modeling physics ranging from static mesoscale material failure to dendrite growth. Here we adapt the recent advances of Benson et al. [2] and Belytchko et al. [3] to model shock loading of polycrystalline material. Through several demonstration problems we evaluate the method for modeling the shock response of polycrystalline materials at the mesoscale. Specifically, we use the X-FEM to model grain boundaries. This approach allows us to i) eliminate ad-hoc mixture rules for multi-material elements and ii) avoid explicitly meshing grain boundaries. ([1] N. Moes, J. Dolbow, J and T. Belytschko, 1999,``A finite element method for crack growth without remeshing,'' International Journal for Numerical Methods in Engineering, 46, 131-150. [2] E. Vitali, and D. J. Benson, 2006, ``An extended finite element formulation for contact in multi-material arbitrary Lagrangian-Eulerian calculations,'' International Journal for Numerical Methods in Engineering, 67, 1420-1444. [3] J-H Song, P. M. A. Areias and T. Belytschko, 2006, ``A method for dynamic crack and shear band propagation with phantom nodes,'' International Journal for Numerical Methods in Engineering, 67, 868-893.)

  15. Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation.

    PubMed

    Chen, W; Desai, D; Good, D; Crison, J; Timmins, P; Paruchuri, S; Wang, J; Ha, K

    2016-08-01

    A computational fluid dynamic (CFD) model was developed to predict metformin release from a hydroxypropylmethylcellulose (HPMC) matrix-based extended-release formulation that took into consideration the physical and chemical properties of the drug substance, composition, as well as size and shape of the tablet. New high dose strength (1000 mg) tablet geometry was selected based on the surface area/volume (SA/V) approach advocated by Lapidus/Lordi/Reynold to obtain the desired equivalent metformin release kinetics. Maintaining a similar SA/V ratio across all extended-release metformin hydrochloride (Met XR) tablet strengths that had different geometries provided similar simulations of dissolution behavior. Experimental dissolution profiles of three lots of high-strength tablets agreed with the simulated release kinetics. Additionally, a pharmacokinetic absorption model was developed using GastroPlus™ software and known physicochemical, pharmacokinetic, and in vitro dissolution properties of metformin to predict the clinical exposure of the new high strength (1000 mg) tablet prior to conducting a human clinical bioequivalence study. In vitro metformin release kinetics were utilized in the absorption model to predict exposures in humans for new 1000-mg Met XR tablets, and the absorption model correctly projected equivalent in vivo exposure across all dose strengths. A clinical bioequivalence study was pursued based on the combined modeling results and demonstrated equivalent exposure as predicted by the simulations. PMID:26729531

  16. Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation.

    PubMed

    Nadaf, Sameer; Nnamani, Petra; Jadhav, Namdeo

    2015-06-01

    In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12 h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs. PMID:25523143

  17. Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation.

    PubMed

    Nadaf, Sameer; Nnamani, Petra; Jadhav, Namdeo

    2015-06-01

    In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12 h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs.

  18. Extending large-scale forest inventories to assess urban forests.

    PubMed

    Corona, Piermaria; Agrimi, Mariagrazia; Baffetta, Federica; Barbati, Anna; Chiriacò, Maria Vincenza; Fattorini, Lorenzo; Pompei, Enrico; Valentini, Riccardo; Mattioli, Walter

    2012-03-01

    Urban areas are continuously expanding today, extending their influence on an increasingly large proportion of woods and trees located in or nearby urban and urbanizing areas, the so-called urban forests. Although these forests have the potential for significantly improving the quality the urban environment and the well-being of the urban population, data to quantify the extent and characteristics of urban forests are still lacking or fragmentary on a large scale. In this regard, an expansion of the domain of multipurpose forest inventories like National Forest Inventories (NFIs) towards urban forests would be required. To this end, it would be convenient to exploit the same sampling scheme applied in NFIs to assess the basic features of urban forests. This paper considers approximately unbiased estimators of abundance and coverage of urban forests, together with estimators of the corresponding variances, which can be achieved from the first phase of most large-scale forest inventories. A simulation study is carried out in order to check the performance of the considered estimators under various situations involving the spatial distribution of the urban forests over the study area. An application is worked out on the data from the Italian NFI.

  19. Wall-models for large eddy simulation based on a generic additive-filter formulation

    NASA Astrophysics Data System (ADS)

    Sanchez Rocha, Martin

    resolved, results are only weakly affected by the characteristics of the blending function. Unfortunately, for practical applications the hybrid terms cannot be exactly computed. Consequently, a reconstruction procedure is proposed to approximate these terms. Results show, that the model proposed is able to mimic the exact hybrid terms, enhancing the accuracy of current hybrid RANS/LES approaches. In a second effort, the Two Level Simulation (TLS) approach is proposed as a nearwall model for LES simulations. Here, TLS is first extended to compressible flows by deriving the small-scale equations required by the model. The new compressible TLS formulation, is validated simulating the flow over a flat-plate turbulent boundary layer. Overall, results are found in reasonable agreement with experimental data and LES calculations. Here, issues related with the integration criteria of the TLS small-scale equations are commented. Finally, TLS is implemented in the additive-filter formulation by replacing the RANS operator with the TLS large-scale operator. The new hybrid TLS/LES approach, is evaluated on the turbulent boundary layer case, in general, results are found in good agreement with experimental data and LES calculations. Here, the dependency of hybrid TLS/LES formulation on the blending function is similar to the hybrid RANS/LES approach when the hybrid terms are neglected. However, contrary to the hybrid RANS/LES case, including the hybrid terms in the TLS/LES formulation does not seem to improve the predictions. The low impact of the hybrid terms in the accuracy of the calculations, is explained by the similarity exhibited between the large-scale TLS operator and the LES space filter. Here, both operators represent space filters, therefore, the difference between TLS and LES variables is almost negligible, reducing drastically the importance of the hybrid terms.

  20. Large-scale crystallization of proteins for purification and formulation.

    PubMed

    Hekmat, Dariusch

    2015-07-01

    Since about 170 years, salts were used to create supersaturated solutions and crystallize proteins. The dehydrating effect of salts as well as their kosmotropic or chaotropic character was revealed. Even the suitability of organic solvents for crystallization was already recognized. Interestingly, what was performed during the early times is still practiced today. A lot of effort was put into understanding the underlying physico-chemical interaction mechanisms leading to protein crystallization. However, it was understood that already the solvation of proteins is a highly complex process not to mention the intricate interrelation of electrostatic and hydrophobic interactions taking place. Although many basic questions are still unanswered, preparative protein crystallization was attempted as illustrated in the presented case studies. Due to the highly variable nature of crystallization, individual design of the crystallization process is needed in every single case. It was shown that preparative crystallization from impure protein solutions as a capture step is possible after applying adequate pre-treatment procedures like precipitation or extraction. Protein crystallization can replace one or more chromatography steps. It was further shown that crystallization can serve as an attractive alternative means for formulation of therapeutic proteins. Crystalline proteins can offer enhanced purity and enable highly concentrated doses of the active ingredient. Easy scalability of the proposed protein crystallization processes was shown using the maximum local energy dissipation as a suitable scale-up criterion. Molecular modeling and target-oriented protein engineering may allow protein crystallization to become part of a platform purification process in the near future.

  1. Formulation and Evaluation of Cephalexin Extended-release Matrix Tablets Using Hydroxy Propyl Methyl Cellulose as Rate-controlling Polymer

    PubMed Central

    Vijay, J; Sahadevan, JT; Prabhakaran, R; Gilhotra, R Mehra

    2012-01-01

    The present investigation reports the design and evaluation of six-hour extended release film-coated matrix tablets of cephalexin using different grades of hydrophilic polymer hydroxypropylmethylcellulose (HPMC) employing direct compression method. The preformulation studies performed included the physical compatibility studies, Differential Scanning Calorimetry analysis, drug characterization using Fourier Transform Infra Red spectroscopic analysis and particle size analysis using sieve method. The tablets were evaluated for weight variation, hardness, thickness and friability. Results of the studies indicate that the polymers used have significant release-retarding effect on the formulation. The dissolution profile comparison of the prepared batches P1 to P8 and market preparation (Sporidex AF 375) was done by using Food and Drug Administration-recommended similarity factor (f2) determination. The formulation P8 (10% HPMC K4M, 15% HPMC 15cps) with a similarity factor (f2) of 77.75 was selected as the optimized formulae for scale-up batches. The dissolution data of the best formulation P8 was fitted into zero order, first order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. The results of the accelerated stability study of best formulation P8 for three months revealed that storage conditions were not found to have made any significant changes in final formulation F3. The release of cephalexin was prolonged for 6 h by using polymer combinations of HPMC and a twice daily matrix tablet was formulated. PMID:22523453

  2. A finite element formulation for scattering from electrically large 2-dimensional structures

    NASA Technical Reports Server (NTRS)

    Ross, Daniel C.; Volakis, John L.

    1992-01-01

    A finite element formulation is given using the scattered field approach with a fictitious material absorber to truncate the mesh. The formulation includes the use of arbitrary approximation functions so that more accurate results can be achieved without any modification to the software. Additionally, non-polynomial approximation functions can be used, including complex approximation functions. The banded system that results is solved with an efficient sparse/banded iterative scheme and as a consequence, large structures can be analyzed. Results are given for simple cases to verify the formulation and also for large, complex geometries.

  3. Finite element formulations for problems of large elastic-plastic deformation

    NASA Technical Reports Server (NTRS)

    Mcmeeking, R. M.; Rice, J. R.

    1974-01-01

    An Eulerian finite element formulation is presented for problems of large elastic-plastic flow. The method is based on Hill's variational principle for incremental deformations, and is suited to isotropically hardening Prandtl-Reuss materials. The formulation is given in a manner which allows any conventional finite element program, for "small strain" elasticplastic analysis, to be simply and rigorously adapted to problems involving arbitrary amounts of deformation and arbitrary levels of stress in comparison to plastic deformation moduli. The method is applied to a necking bifurcation analysis of a bar in plane-strain tension. A unified general formulation of finite element equations, both Lagrangian and Eulerian, for large deformations, with arbitrary choice of the conjugate stress and strain measures, and a discussion is given of other proposed formulations for elastic-plastic finite element analysis at large strain.

  4. Finite-element formulations for problems of large elastic-plastic deformation

    NASA Technical Reports Server (NTRS)

    Mcmeeking, R. M.; Rice, J. R.

    1975-01-01

    An Eulerian finite element formulation is presented for problems of large elastic-plastic flow. The method is based on Hill's variational principle for incremental deformations, and is ideally suited to isotropically hardening Prandtl-Reuss materials. Further, the formulation is given in a manner which allows any conventional finite element program, for 'small strain' elastic-plastic analysis, to be simply and rigorously adapted to problems involving arbitrary amounts of deformation and arbitrary levels of stress in comparison to plastic deformation moduli. The method is applied to a necking bifurcation analysis of a bar in plane-strain tension. The paper closes with a unified general formulation of finite element equations, both Lagrangian and Eulerian, for large deformations, with arbitrary choice of the conjugate stress and strain measures. Further, a discussion is given of other proposed formulations for elastic-plastic finite element analysis at large strain, and the inadequacies of some of these are commented upon.

  5. Post-buckling and Large Amplitude Free Vibration Analysis of Composite Beams: Simple Intuitive Formulation

    NASA Astrophysics Data System (ADS)

    Gunda, Jagadish Babu; Venkateswara Rao, Gundabathula

    2016-04-01

    Post-buckling and large amplitude free vibration analysis of composite beams with axially immovable ends is investigated in the present study using a simple intuitive formulation. Geometric nonlinearity of Von-Karman type is considered in the analysis which accounts for mid-plane stretching action of the beam. Intuitive formulation uses only two parameters: the critical bifurcation point and the axial stretching force developed due to membrane stretching action of the beam. Hinged-hinged, clamped-clamped and clamped-hinged boundary conditions are considered. Numerical accuracy of the proposed analytical closed-form solutions obtained from the intuitive formulation are compared to available finite element solutions for symmetric and asymmetric layup schemes of laminated composite beam which indicates the confidence gained on the present formulation.

  6. Optimised process and formulation conditions for extended release dry polymer powder-coated pellets.

    PubMed

    Terebesi, Ildikó; Bodmeier, Roland

    2010-05-01

    The objective of this study was to improve the film formation and permeability characteristics of extended release ethylcellulose coatings prepared by dry polymer powder coating for the release of drugs of varying solubility. Ethylcellulose (7 and 10 cp viscosity grades) and Eudragit(R) RS were used for dry powder coating of pellets in a fluidised bed ball coater. Pre-plasticised ethylcellulose powder was prepared by spray-drying aqueous ethylcellulose dispersions (Surelease(R) and Aquacoat(R)) or by hot melt extrusion/cryogenic grinding of plasticised ethylcellulose. Chlorpheniramine maleate and theophylline were used as model drugs of different solubilities. The film formation process, polymeric films and coated pellets were characterised by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), scanning electron microscopy (SEM) and dissolution testing. Film formation and extended drug release was achieved with ethylcellulose, a polymer with a high glass transition temperature (T(g)) without the use of water, which is usually required in dry powder coating. DMA-measurements revealed that plasticised ethylcellulose had a modulus of elasticity (E') similar to the low T(g) Eudragit(R) RS. With increasing plasticiser concentration, the T(g) of ethylcellulose was reduced and the mechanical properties improved, thus facilitating coalescence of the polymer particles. SEM-pictures revealed the formation of a dense, homogeneous film. The lower viscosity grade ethylcellulose (7 cp) resulted in better film formation than the higher viscosity grade (10 cp) and required less stringent curing conditions. Successful extended release ethylcellulose coatings were also obtained by coating with pre-plasticised spray-dried ethylcellulose powders as an alternative to the separate application of pure ethylcellulose powder and plasticiser. The permeability of the extended release coating could be controlled by using powder blends of ethylcellulose with the

  7. An Extended Finite Element Method Formulation for Modeling the Response of Polycrystalline Materials to Dynamic Loading

    NASA Astrophysics Data System (ADS)

    Robbins, Joshua; Voth, Thomas E.

    2007-12-01

    The eXtended Finite Element Method (X-FEM) is a finite-element based discretization technique developed originally to model dynamic crack propagation [1]. Since that time the method has been used for modeling physics ranging from static meso-scale material failure to dendrite growth. Here we adapt the recent advances of Vitali and Benson [2] and Song et al. [3] to model dynamic loading of a polycrystalline material. We use demonstration problems to examine the method's efficacy for modeling the dynamic response of polycrystalline materials at the meso-scale. Specifically, we use the X-FEM to model grain boundaries. This approach allows us to i) eliminate ad-hoc mixture rules for multi-material elements and ii) avoid explicitly meshing grain boundaries.

  8. The biopharmaceutic drug classification and drugs administered in extended release (ER) formulations.

    PubMed

    Corrigan, O I

    1997-01-01

    A biopharmaceutic drug classification scheme for correlating the in-vitro drug product dissolution and in-vivo bioavailability for IR products was proposed by Amidon et al (1995). The classification arose from drug dissolution and absorption models which identified the key parameters controlling drug absorption as the dimensionless numbers; the Absorption number (A(n)), the Dissolution number (Dn) and the Dose number (D(o)). This led to a biopharmaceutic classification of drugs into four groups, the establishment of a basis for determining the conditions under which in-vitro-in-vivo (IVIV) correlation's are expected and the use of the classification to set drug bioavailability standards for IR products. These developments raise the issue of whether the biopharmaceutic classification has relevance to ER products. In contrast to IR products, drugs selected for ER products should have good gastrointestinal (GI) permeability and an extended site of absorption. However their permeability(Papp) may change depending on the site. Solubility(Cs), effective fluid volume and hence D(o) may also vary with site. Of particular relevance to both permeability and solubility is the degree of ionization of the drug. Residence time at each site, pH changes and the potential for drug degradation at different sites, the latter resulting in a restricted absorption window, will influence the time frame over which an IVIV relationship is possible. Of the drugs available in ER dosage forms approximately 63% are bases, 15% acids and the remainder either unionizable or small inorganic ions. Acidic drugs will tend to have lower solubility's high up in the gastrointestinal tract (GIT), with solubility increasing down the GIT. In contrast with increased ionization permeability should fall. Thus with acids, as the dosage form moves to a more alkaline environment down the GIT, absorption may change from dissolution control to membrane control depending on the pK.a of the drug. In contrast bases

  9. Effect of combination of acrylic polymers on the release of nevirapine formulated as extended release matrix pellets using extrusion and spheronization technique.

    PubMed

    Sharma, Anshuli; Prasad, Anjaneya; Dua, Kamal; Singh, Gurvinder

    2014-01-01

    The aim of the present research work was to formulate and evaluate the extended release matrix pellets of nevirapine using extrusion and spheronization technique which will be an alternative technique for making extended release dosage forms and to compare the drug release profiles of the formulations with the reference product. In vitro dissolutions were carried out in 0.04M Phosphate buffer pH 6.8 with 2% w/v SLS (sodium lauryl sulphate) for 24 hours with USP type I apparatus at 75rpm. The drug release from the optimised formulation was comparable to that of the reference product and follows first order kinetics followed by non-fickian transport mechanism of drug release which confirms the drug release pattern involves complex mixture of diffusion and erosion. The similarity factor, f2 value of optimised formulation was found to be 70, which shows that the developed formulation was comparable to that of the reference product.

  10. Dosage form design and in vitro/in vivo evaluation of cevimeline extended-release tablet formulations.

    PubMed

    Tajiri, Shinichiro; Kanamaru, Taro; Kamada, Makoto; Makoto, Kamada; Konno, Tsutomu; Nakagami, Hiroaki

    2010-01-01

    The objective of the present work is to develop an extended-release dosage form of cevimeline. Two types of extended-release tablets (simple matrix tablets and press-coated tablets) were prepared and their potential as extended-release dosage forms were assessed. Simple matrix tablets have a large amount of hydroxypropylcellulose as a rate-controlling polymer and the matrix is homogeneous throughout the tablet. The press-coated tablets consisted of a matrix core tablet, which was completely surrounded by an outer shell containing a large amount of hydroxypropylcellulose. The simple matrix tablets could not sustain the release of cevimeline effectively. In contrast, the press-coated tablets showed a slower dissolution rate compared with simple matrix tablets and the release curve was nearly linear. The dissolution of cevimeline from the press-coated tablets was not markedly affected by the pH of the dissolution medium or by a paddle rotating speed over the range of 50-200 rpm. Furthermore, cevimeline was constantly released from the press-coated tablets in the gastrointestinal tract and the steady-state plasma drug levels were maintained in beagle dogs. These results suggested that the designed PC tablets have a potential for extended-release dosage forms. PMID:19747964

  11. Parallel Domain Decomposition Formulation and Software for Large-Scale Sparse Symmetrical/Unsymmetrical Aeroacoustic Applications

    NASA Technical Reports Server (NTRS)

    Nguyen, D. T.; Watson, Willie R. (Technical Monitor)

    2005-01-01

    The overall objectives of this research work are to formulate and validate efficient parallel algorithms, and to efficiently design/implement computer software for solving large-scale acoustic problems, arised from the unified frameworks of the finite element procedures. The adopted parallel Finite Element (FE) Domain Decomposition (DD) procedures should fully take advantages of multiple processing capabilities offered by most modern high performance computing platforms for efficient parallel computation. To achieve this objective. the formulation needs to integrate efficient sparse (and dense) assembly techniques, hybrid (or mixed) direct and iterative equation solvers, proper pre-conditioned strategies, unrolling strategies, and effective processors' communicating schemes. Finally, the numerical performance of the developed parallel finite element procedures will be evaluated by solving series of structural, and acoustic (symmetrical and un-symmetrical) problems (in different computing platforms). Comparisons with existing "commercialized" and/or "public domain" software are also included, whenever possible.

  12. Extended molecular Ornstein-Zernike integral equation for fully anisotropic solute molecules: Formulation in a rectangular coordinate system

    NASA Astrophysics Data System (ADS)

    Ishizuka, Ryosuke; Yoshida, Norio

    2013-08-01

    An extended molecular Ornstein-Zernike (XMOZ) integral equation is formulated to calculate the spatial distribution of solvent around a solute of arbitrary shape and solid surfaces. The conventional MOZ theory employs spherical harmonic expansion technique to treat the molecular orientation of components of solution. Although the MOZ formalism is fully exact analytically, the truncation of the spherical harmonic expansion requires at a finite order for numerical calculation and causes the significant error for complex molecules. The XMOZ integral equation is the natural extension of the conventional MOZ theory to a rectangular coordinate system, which is free from the truncation of spherical harmonic expansion with respect to solute orientation. In order to show its applicability, we applied the XMOZ theory to several systems using the hypernetted-chain (HNC) and Kovalenko-Hirata approximations. The quality of results obtained within our theory is discussed by comparison with values from the conventional MOZ theory, molecular dynamics simulation, and three-dimensional reference interaction site model theory. The spatial distributions of water around the complex of non-charged sphere and dumbbell were calculated. Using this system, the approximation level of the XMOZ and other methods are discussed. To assess our theory, we also computed the excess chemical potentials for three realistic molecules (water, methane, and alanine dipeptide). We obtained the qualitatively reasonable results by using the XMOZ/HNC theory. The XMOZ theory covers a wide variety of applications in solution chemistry as a useful tool to calculate solvation thermodynamics.

  13. Development of corotational formulated FEM for application to 30m class large deployable reflector

    NASA Astrophysics Data System (ADS)

    Ozawa, Satoru; Fujiwara, Yuuichi; Tsujihata, Akio

    2010-06-01

    JAXA, Japan Aerospace Exploration Agency, is now developing a corotational formulated finite element analysis method and its software "Origami/ETS" for the development of 30m class large deployable reflectors. For the reason that the deployable reflector is composed of beams, cables and mesh, this analysis method is generalized for finite elements with multiple nodes, which are commonly used in linear finite element analyses. The large displacement and rotation are taken into account by the corotational formulation. The tangent stiffness matrix for finite elements with multiple nodes is obtained as follows; the geometric stiffness matrix of two node elements is derived by taking variation of the element's corotational matrix from the virtual work of finite elements with large displacement; similarly the geometric stiffness matrix for three node elements is derived; as the extension of two and three node element theories, the geometric stiffness matrix for multiple node elements is derived; with the geometric stiffness matrix for multiple node elements, the tangent stiffness matrix is obtained. The analysis method is applied for the deployment analysis and static structural analysis of the 30m class large deployable reflector. In the deployment analysis, it is confirmed that this method stably analyzes the deployment motion from the deployment configuration to the stowed configuration of the reflector. In the static analysis, it is confirmed that the mesh structure is analyzed successfully. The 30m class large deployable reflector is now still being developed and is about to undergo several tests with its prototypes. This analysis method will be used in the tests and verifications of the reflector.

  14. Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

    PubMed

    Lin, Zhongqiang; Zhou, Deliang; Hoag, Stephen; Qiu, Yihong

    2016-03-01

    Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory

  15. Performance of Extended Local Clustering Organization (LCO) for Large Scale Job-Shop Scheduling Problem (JSP)

    NASA Astrophysics Data System (ADS)

    Konno, Yohko; Suzuki, Keiji

    This paper describes an approach to development of a solution algorithm of a general-purpose for large scale problems using “Local Clustering Organization (LCO)” as a new solution for Job-shop scheduling problem (JSP). Using a performance effective large scale scheduling in the study of usual LCO, a solving JSP keep stability induced better solution is examined. In this study for an improvement of a performance of a solution for JSP, processes to a optimization by LCO is examined, and a scheduling solution-structure is extended to a new solution-structure based on machine-division. A solving method introduced into effective local clustering for the solution-structure is proposed as an extended LCO. An extended LCO has an algorithm which improves scheduling evaluation efficiently by clustering of parallel search which extends over plural machines. A result verified by an application of extended LCO on various scale of problems proved to conduce to minimizing make-span and improving on the stable performance.

  16. The finite element absolute nodal coordinate formulation incorporated with surface stress effect to model elastic bending nanowires in large deformation

    NASA Astrophysics Data System (ADS)

    He, Jin; Lilley, Carmen M.

    2009-08-01

    Surface stress was incorporated into the finite element absolute nodal coordinate formulation in order to model elastic bending of nanowires in large deformation. The absolute nodal coordinate formulation is a numerical method to model bending structures in large deformation. The generalized Young-Laplace equation was employed to model the surface stress effect on bending nanowires. Effects from surface stress and large deformation on static bending nanowires are presented and discussed. The results calculated with the absolute nodal coordinate formulation incorporated with surface stress show that the surface stress effect makes the bending nanowires behave like softer or stiffer materials depending on the boundary condition. The surface stress effect diminishes as the dimensions of the bending structures increase beyond the nanoscale. The developed algorithm is consistent with the classical absolute nodal coordinate formulation at the macroscale.

  17. Models of population-based analyses for data collected from large extended families

    PubMed Central

    Lee, Elisa T.; Howard, Barbara V.; Fabsitz, Richard R.; Devereux, Richard B.; MacCluer, Jean W.; Laston, Sandra; Comuzzie, Anthony G.; Shara, Nawar M.; Welty, Thomas K.

    2014-01-01

    Large studies of extended families usually collect valuable phenotypic data that may have scientific value for purposes other than testing genetic hypotheses if the families were not selected in a biased manner. These purposes include assessing population-based associations of diseases with risk factors/covariates and estimating population characteristics such as disease prevalence and incidence. Relatedness among participants however, violates the traditional assumption of independent observations in these classic analyses. The commonly used adjustment method for relatedness in population-based analyses is to use marginal models, in which clusters (families) are assumed to be independent (unrelated) with a simple and identical covariance (family) structure such as those called independent, exchangeable and unstructured covariance structures. However, using these simple covariance structures may not be optimally appropriate for outcomes collected from large extended families, and may under- or over-estimate the variances of estimators and thus lead to uncertainty in inferences. Moreover, the assumption that families are unrelated with an identical family structure in a marginal model may not be satisfied for family studies with large extended families. The aim of this paper is to propose models incorporating marginal models approaches with a covariance structure for assessing population-based associations of diseases with their risk factors/covariates and estimating population characteristics for epidemiological studies while adjusting for the complicated relatedness among outcomes (continuous/categorical, normally/non-normally distributed) collected from large extended families. We also discuss theoretical issues of the proposed models and show that the proposed models and covariance structure are appropriate for and capable of achieving the aim. PMID:20882324

  18. An approach to extend seismic vulnerability relationships for large diameter pipelines

    SciTech Connect

    Honegger, D.G.

    1995-12-31

    The most common approach to determining vulnerability is to rely solely upon damage data from past earthquakes as a predictor of future performance. Relying upon past damage data is not an option when data does not exist for a particular type of pipeline. An option discussed in this paper and recently implemented for a large diameter water supply pipelines, relies upon engineering characterization of the relative strength of pipelines to extend existing damage data.

  19. Large eddy simulation models for incompressible magnetohydrodynamics derived from the variational multiscale formulation

    SciTech Connect

    Sondak, David; Oberai, Assad A.

    2012-10-15

    Novel large eddy simulation (LES) models are developed for incompressible magnetohydrodynamics (MHD). These models include the application of the variational multiscale formulation of LES to the equations of incompressible MHD. Additionally, a new residual-based eddy viscosity model is introduced for MHD. A mixed LES model that combines the strengths of both of these models is also derived. The new models result in a consistent numerical method that is relatively simple to implement. The need for a dynamic procedure in determining model coefficients is no longer required. The new LES models are tested on a decaying Taylor-Green vortex generalized to MHD and benchmarked against classical LES turbulence models. The LES simulations are run in a periodic box of size [-{pi}, {pi}]{sup 3} with 32 modes in each direction and are compared to a direct numerical simulation (DNS) with 512 modes in each direction. The new models are able to account for the essential MHD physics which is demonstrated via comparisons of energy spectra. We also compare the performance of our models to a DNS simulation by Pouquet et al.['The dynamics of unforced turbulence at high Reynolds number for Taylor-Green vortices generalized to MHD,' Geophys. Astrophys. Fluid Dyn. 104, 115-134 (2010)], for which the ratio of DNS modes to LES modes is 262:144.

  20. Nonlinear finite element formulation for the large displacement analysis in multibody system dynamics

    NASA Technical Reports Server (NTRS)

    Rismantab-Sany, J.; Chang, B.; Shabana, A. A.

    1989-01-01

    A total Lagrangian finite element formulation for the deformable bodies in multibody mechanical systems that undergo finite relative rotations is developed. The deformable bodies are discretized using finite element methods. The shape functions that are used to describe the displacement field are required to include the rigid body modes that describe only large translational displacements. This does not impose any limitations on the technique because most commonly used shape functions satisfy this requirement. The configuration of an element is defined using four sets of coordinate systems: Body, Element, Intermediate element, Global. The body coordinate system serves as a unique standard for the assembly of the elements forming the deformable body. The element coordinate system is rigidly attached to the element and therefore it translates and rotates with the element. The intermediate element coordinate system, whose axes are initially parallel to the element axes, has an origin which is rigidly attached to the origin of the body coordinate system and is used to conveniently describe the configuration of the element in undeformed state with respect to the body coordinate system.

  1. EXTENDED STAR FORMATION IN THE INTERMEDIATE-AGE LARGE MAGELLANIC CLOUD STAR CLUSTER NGC 2209

    SciTech Connect

    Keller, Stefan C.; Mackey, A. Dougal; Da Costa, Gary S.

    2012-12-10

    We present observations of the 1 Gyr old star cluster NGC 2209 in the Large Magellanic Cloud made with the GMOS imager on the Gemini South Telescope. These observations show that the cluster exhibits a main-sequence turnoff that spans a broader range in luminosity than can be explained by a single-aged stellar population. This places NGC 2209 amongst a growing list of intermediate-age (1-3 Gyr) clusters that show evidence for extended or multiple epochs of star formation of between 50 and 460 Myr in extent. The extended main-sequence turnoff observed in NGC 2209 is a confirmation of the prediction in Keller et al. made on the basis of the cluster's large core radius. We propose that secondary star formation is a defining feature of the evolution of massive star clusters. Dissolution of lower mass clusters through evaporation results in only clusters that have experienced secondary star formation surviving for a Hubble time, thus providing a natural connection between the extended main-sequence turnoff phenomenon and the ubiquitous light-element abundance ranges seen in the ancient Galactic globular clusters.

  2. Comparison of Deconvolution-Based and Absorption Modeling IVIVC for Extended Release Formulations of a BCS III Drug Development Candidate.

    PubMed

    Kesisoglou, Filippos; Xia, Binfeng; Agrawal, Nancy G B

    2015-11-01

    In vitro-in vivo correlations (IVIVC) are predictive mathematical models describing the relationship between dissolution and plasma concentration for a given drug compound. The traditional deconvolution/convolution-based approach is the most common methodology to establish a level A IVIVC that provides point to point relationship between the in vitro dissolution and the in vivo input rate. The increasing application of absorption physiologically based pharmacokinetic model (PBPK) has provided an alternative IVIVC approach. The current work established and compared two IVIVC models, via the traditional deconvolution/convolution method and via absorption PBPK modeling, for two types of modified release (MR) formulations (matrix and multi-particulate tablets) of MK-0941, a BCS III drug development candidate. Three batches with distinct release rates were studied for each formulation technology. A two-stage linear regression model was used for the deconvolution/convolution approach while optimization of the absorption scaling factors (a model parameter that relates permeability and input rate) in Gastroplus(TM) Advanced Compartmental Absorption and Transit model was used for the absorption PBPK approach. For both types of IVIVC models established, and for either the matrix or the multiparticulate formulations, the average absolute prediction errors for AUC and C max were below 10% and 15%, respectively. Both the traditional deconvolution/convolution-based and the absorption/PBPK-based level A IVIVC model adequately described the compound pharmacokinetics to guide future formulation development. This case study highlights the potential utility of absorption PBPK model to complement the traditional IVIVC approaches for MR products.

  3. ENDLESS: An extended nonperiodic domain large-eddy simulation approach for scalar plumes

    NASA Astrophysics Data System (ADS)

    Chen, Bicheng; Yang, Di; Meneveau, Charles; Chamecki, Marcelo

    2016-05-01

    Large-eddy simulation (LES) has proven to be a valuable tool for high-fidelity modeling of environmental and geophysical turbulent flows. An important application of LES is to study the transport of effluents (e.g. oils from a subsea blowout) in the ocean mixed layer (OML). Oil plumes being transported in the OML experience the action of shear-generated turbulence, Langmuir circulations, Ekman transport and submesoscale quasi-geostrophic eddies. To resolve such turbulent processes, grid sizes of a few meters are desirable while horizontal domain sizes of LES are typically restricted from hundreds of meters to a few kilometers, for LES to remain practically affordable. Yet transported oil plumes evolve to large scales extending to tens or even hundreds of kilometers. In this study, the Extended Nonperiodic Domain LES for Scalar transport (ENDLESS) is proposed as a multi-scale approach to tackle this challenge while being computationally affordable. The basic idea is to simulate the shear turbulence and Langmuir circulations on a small horizontal domain with periodic boundary conditions while the resulting transport velocity field is replicated periodically following adaptively the large-scale plume as it evolves spatially towards much larger scales. This approach also permits the superposition of larger-scale quasi two-dimensional flow motions on the oil advection, allowing for coupling with regional circulation models. A validation case and two sample applications to oil plume evolution in the OML are presented in order to demonstrate key features and computational speedup associated with the ENDLESS method.

  4. Applying SDDP to very large hydro-economic models with a simplified formulation for irrigation: the case of the Tigris-Euphrates river basin.

    NASA Astrophysics Data System (ADS)

    Rougé, Charles; Tilmant, Amaury

    2015-04-01

    extended to any type of consumptive use of water beyond irrigation, e.g., municipal, industrial, etc This slightly different version of SDDP is applied to a large portion of the Tigris-Euphrates river basin. It comprises 24 state variables representing storage in reservoirs, 28 hydrologic state variables, and 51 demand nodes. It is the largest yet to simultaneously consider hydropower and irrigation within the same river system, and the proposed formulation almost halves the number of state variables to be considered.

  5. Recent Enhancements of the Phased Array Mirror Extendible Large Aperture (PAMELA) Telescope Testbed at MSFC

    NASA Technical Reports Server (NTRS)

    Rakoczy, John; Burdine, Robert (Technical Monitor)

    2001-01-01

    Recent incremental upgrades to the Phased Array Mirror Extendible Large Aperture (PAMELA) telescope testbed have enabled the demonstration of phasing (with a monochromatic source) of clusters of primary mirror segments down to the diffraction limit. PAMELA upgrades include in improved Shack-Hartmann wavefront sensor, passive viscoelastic damping treatments for the voice-coil actuators, mechanical improvement of mirror surface figures, and optical bench baffling. This report summarizes the recent PAMELA upgrades, discusses the lessons learned, and presents a status of this unique testbed for wavefront sensing and control. The Marshall Space Flight Center acquired the Phased Array Mirror Extendible Large Aperture (PAMELA) telescope in 1993 after Kaman Aerospace was unable to complete integration and testing under the limited SDIO and DARPA funding. The PAMELA is a 36-segment, half-meter aperture, adaptive telescope which utilizes a Shack-Hartmann wavefront sensor, inductive coil edge sensors, voice coil actuators, imaging CCD cameras and interferometry for figure alignment, wavefront sensing and control. MSFC originally obtained the PAMELA to supplement its research in the interactions of control systems with flexible structures. In August 1994, complete tip, tilt and piston control was successfully demonstrated using the Shack-Hartmann wavefront sensor and the inductive edge sensors.

  6. Characteristics of large three-dimensional heaps of particles produced by ballistic deposition from extended sources

    NASA Astrophysics Data System (ADS)

    Topic, Nikola; Gallas, Jason A. C.; Pöschel, Thorsten

    2013-11-01

    This paper reports a detailed numerical investigation of the geometrical and structural properties of three-dimensional heaps of particles. Our goal is the characterization of very large heaps produced by ballistic deposition from extended circular dropping areas. First, we provide an in-depth study of the formation of monodisperse heaps of particles. We find very large heaps to contain three new geometrical characteristics: they may display two external angles of repose, one internal angle of repose, and four distinct packing fraction (density) regions. Such features are found to be directly connected with the size of the dropping zone. We derive a differential equation describing the boundary of an unexpected triangular packing fraction zone formed under the dropping area. We investigate the impact that noise during the deposition has on the final heap structure. In addition, we perform two complementary experiments designed to test the robustness of the novel features found. The first experiment considers changes due to polydispersity. The second checks what happens when letting the extended dropping zone to become a point-like source of particles, the more common type of source.

  7. An Eulerian formulation for large deformations of anisotropic elastic and viscoelastic solids and viscous fluids

    NASA Astrophysics Data System (ADS)

    Rubin, M. B.; Nadler, B.

    2016-03-01

    An Eulerian formulation has been developed for the constitutive response of a group of materials that includes anisotropic elastic and viscoelastic solids and viscous fluids. The material is considered to be a composite of an elastic solid and a viscous fluid. Evolution equations are proposed for a triad of vectors m i that represent the stretches and orientations of material line elements in the solid component. Evolution equations for an orthonormal triad of vectors s i are also proposed to characterize anisotropy of the fluid component. In particular, for an elastic solid it is shown that the material response is totally characterized by the functional form of the strain energy and by the current values of m i , which are measurable in the current state of the material. Moreover, it is shown that the proposed Eulerian formulation removes unphysical arbitrariness of the choice of the reference configuration in the standard formulation of constitutive equations for anisotropic elastic solids.

  8. Phase field approach with anisotropic interface energy and interface stresses: Large strain formulation

    NASA Astrophysics Data System (ADS)

    Levitas, Valery I.; Warren, James A.

    2016-06-01

    A thermodynamically consistent, large-strain, multi-phase field approach (with consequent interface stresses) is generalized for the case with anisotropic interface (gradient) energy (e.g. an energy density that depends both on the magnitude and direction of the gradients in the phase fields). Such a generalization, if done in the "usual" manner, yields a theory that can be shown to be manifestly unphysical. These theories consider the gradient energy as anisotropic in the deformed configuration, and, due to this supposition, several fundamental contradictions arise. First, the Cauchy stress tensor is non-symmetric and, consequently, violates the moment of momentum principle, in essence the Herring (thermodynamic) torque is imparting an unphysical angular momentum to the system. In addition, this non-symmetric stress implies a violation of the principle of material objectivity. These problems in the formulation can be resolved by insisting that the gradient energy is an isotropic function of the gradient of the order parameters in the deformed configuration, but depends on the direction of the gradient of the order parameters (is anisotropic) in the undeformed configuration. We find that for a propagating nonequilibrium interface, the structural part of the interfacial Cauchy stress is symmetric and reduces to a biaxial tension with the magnitude equal to the temperature- and orientation-dependent interface energy. Ginzburg-Landau equations for the evolution of the order parameters and temperature evolution equation, as well as the boundary conditions for the order parameters are derived. Small strain simplifications are presented. Remarkably, this anisotropy yields a first order correction in the Ginzburg-Landau equation for small strains, which has been neglected in prior works. The next strain-related term is third order. For concreteness, specific orientation dependencies of the gradient energy coefficients are examined, using published molecular dynamics

  9. Experimental instrumentation system for the Phased Array Mirror Extendible Large Aperture (PAMELA) test program

    NASA Technical Reports Server (NTRS)

    Boykin, William H., Jr.

    1993-01-01

    Adaptive optics are used in telescopes for both viewing objects with minimum distortion and for transmitting laser beams with minimum beam divergence and dance. In order to test concepts on a smaller scale, NASA MSFC is in the process of setting up an adaptive optics test facility with precision (fraction of wavelengths) measurement equipment. The initial system under test is the adaptive optical telescope called PAMELA (Phased Array Mirror Extendible Large Aperture). Goals of this test are: assessment of test hardware specifications for PAMELA application and the determination of the sensitivities of instruments for measuring PAMELA (and other adaptive optical telescopes) imperfections; evaluation of the PAMELA system integration effort and test progress and recommended actions to enhance these activities; and development of concepts and prototypes of experimental apparatuses for PAMELA.

  10. Pharmacokinetic Studies in Healthy Subjects for the Development of an Extended-Release Tablet Formulation of Guaifenesin: A 505(b)(2) New Drug Application Approval.

    PubMed

    Vilson, Lineau; Owen, Joel S

    2013-01-01

    Guaifenesin is an expectorant used to improve mucociliary clearance (MCC) and relieve chest congestion from upper respiratory tract infections. Immediate-release (IR) guaifenesin requires dosing every 4 hours to maintain efficacy because of the drug's short half-life. Extended-release (ER) guaifenesin has been developed to prolong efficacy and reduce dosing frequency. As part of the 505(b)(2) new drug application (NDA), the pharmacokinetics (PK) of an ER bi-layer tablet formulation of guaifenesin (Mucinex®) and bioequivalence to an over-the-counter (OTC) monograph IR formulation were evaluated in healthy subjects. In one study, subjects received 1,200 mg ER guaifenesin every 12 hours or 400 mg IR guaifenesin every 4 hours for 6 days. Steady-state exposures were equivalent between the two products, as demonstrated by AUC and Cmax . In another study, subjects received a single dose of 600 mg (fasted) or 1,200 mg (fasted or fed) ER bi-layer tablet formulations. AUC and Cmax were equivalent between both states for the 1,200 mg ER dose. However, Tmax of 1,200 mg ER guaifenesin was later in the fed than the fasted state. ER guaifenesin is bioequivalent to corresponding OTC monograph doses of IR guaifenesin. ER guaifenesin offers a convenient 12-hour dosing alternative to 4-hour dosing of IR guaifenesin. PMID:27121557

  11. Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

    PubMed

    Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

    2014-11-01

    Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes.

  12. Compartmental absorption modeling and site of absorption studies to determine feasibility of an extended-release formulation of an HIV-1 attachment inhibitor phosphate ester prodrug.

    PubMed

    Brown, Jonathan; Chien, Caly; Timmins, Peter; Dennis, Andrew; Doll, Walter; Sandefer, Erik; Page, Richard; Nettles, Richard E; Zhu, Li; Grasela, Dennis

    2013-06-01

    BMS-663068 is a phosphonooxymethyl ester prodrug under development for the treatment of HIV/AIDS. The prodrug is designed to overcome the solubility-limited bioavailability of the active moiety, BMS-626529. BMS-663068 is not absorbed from the gastrointestinal (GI) tract and requires enzymatic conversion by alkaline phosphatase to BMS-626529 immediately before absorption. In the light of the known short in vivo half-life of BMS-626529, compartmental absorption modeling was used to predict the potential feasibility of extended-release (ER) delivery to achieve target Cmax :Cmin ratios. To further refine the model with respect to colonic absorption, the regional absorption of BMS-626529 following delivery of BMS-663068 to upper and lower GI sites was characterized through a site of absorption study in human subjects. A refined model was subsequently applied to guide the development of ER tablet formulations. Comparisons of results from the refined model to the in vivo human pharmacokinetic data for three selected ER formulations demonstrate the utility of the model in predicting feasibility of ER delivery and in directing formulation development.

  13. Evaluation of a single-dose, extended-release epidural morphine formulation for pain control after lumbar spine surgery.

    PubMed

    Vineyard, Joseph C; Toohey, John S; Neidre, Arvo; Fogel, Guy; Joyner, Robert

    2014-01-01

    DepoDur, an extended-release epidural morphine, has been used effectively for postoperative pain control following many orthopaedic and general surgery procedures and has provided prolonged analgesia when compared with Duramorph. The goal of this article was to compare the safety and analgesic efficacy of DepoDur versus Duramorph after lumbar spine surgery. A prospective, randomized, double-blind clinical study was completed at a single extended-stay ambulatory surgery center. All patients over 18 undergoing posterior lumbar spine fusions were considered for the study. Sixty patients were randomly assigned to a control or treatment group. The control group received DepoDur before surgery, while the treatment group received Duramorph. Although results show no significant differences between the two groups in postoperative visual analog pain scale scores, use of pain medication, and adverse events, subjects receiving DepoDur were less likely to receive Naloxone and oxygen supplementation, experience nausea or fever, and were more likely to experience hypotension. DepoDur proved to be safe and effective, offering similar prolonged analgesic activity when compared with Duramorph.

  14. In vivo performance evaluation and establishment of IVIVC for osmotic pump based extended release formulation of milnacipran HCl.

    PubMed

    Parejiya, Punit B; Barot, Bhavesh S; Patel, Hetal K; Chorawala, Mehul R; Shelat, Pragna K; Shukla, Arunkumar

    2013-05-01

    The objective of the present study was to carry out a pharmacokinetics evaluation of an oral modified release formulation [Aquarius EKX 19102 SRX-2 based osmotic pump (OP)] containing highly soluble milnacipran HCl (MH) as a model drug. It was also aimed at developing an in vitro-in vivo correlation (IVIVC) model for a developed OP. In vivo plasma concentration data were obtained from six healthy male New Zealand albino rabbits after administration of immediate-release milnacipran HCl solution (IRMHSOL) and milnacipran HCl osmotic pump (MHOP). In vitro samples were analysed using an in house developed spectrophotometry method and in vivo samples were analysed using a RP-HPLC method developed by the author. A deconvolution based Level A model was attempted through a correlation of the percent in vivo input obtained through deconvolution and the percent in vitro dissolution obtained experimentally. A good correlation between the percentages dissolved vs absorbed (R(2) = 0.978) was obtained using level A correlation. Evaluation of the internal predictability of level A correlation was calculated in terms of the percent prediction error, which was found to be below 15%. In a nutshell, the success of the present study warrants further studies in patient volunteers to assess the ability of the MHOP to provide an effective therapy for depression. PMID:23463628

  15. A multiscale overlapped coupling formulation for large-deformation strain localization

    NASA Astrophysics Data System (ADS)

    Sun, WaiChing; Mota, Alejandro

    2014-09-01

    We generalize the multiscale overlapped domain framework to couple multiple rate-independent standard dissipative material models in the finite deformation regime across different length scales. We show that a fully coupled multiscale incremental boundary-value problem can be recast as the stationary point that optimizes the partitioned incremental work of a three-field energy functional. We also establish inf-sup tests to examine the numerical stability issues that arise from enforcing weak compatibility in the three-field formulation. We also devise a new block solver for the domain coupling problem and demonstrate the performance of the formulation with one-dimensional numerical examples. These simulations indicate that it is sufficient to introduce a localization limiter in a confined region of interest to regularize the partial differential equation if loss of ellipticity occurs.

  16. Comparative effects of autologous and homologous seminal plasma on the viability of largely extended boar spermatozoa.

    PubMed

    Caballero, I; Vazquez, J M; Centurión, F; Rodríguez-Martinez, H; Parrilla, I; Roca, J; Cuello, C; Martinez, E A

    2004-10-01

    Sperm handling, associated to artificial reproduction technologies (ART) such as in vitro fertilization (IVF) or the use of flow cytometry for cell analysis or sorting imposes volumetric extension of the sperm suspension and decreases sperm viability, presumably because of the removal of seminal plasma (SP) components. This study evaluated whether a 10% v/v of autologous SP (retrieved from the same donor boar) or homologous SP (e.g. from any of the four fertile boars included, other than the one providing the spermatozoa) would differently affect the viability of boar spermatozoa subjected to large extension in a simple saline medium [phosphate-buffered saline and 0.1% ethylenediaminetetraacetic acid (EDTA), PBSm] to a concentration of 0.3 x 10(6) spermatozoa/ml and incubated for 2 h at 30 degrees C. Sperm viability was monitored as membrane integrity [using the fluorophore carboxyfluorescein diacetate (C-FDA) and propidium iodide (PI)], mitochondrial function (using the fluorophore R-123) and motility characteristics [using Computer Assisted Sperm Analysis (CASA)]. Substraction of the SP and extension followed by incubation in PBSm significantly (p < 0.05) decreased sperm viability, which could be restored by addition of autologous SP. Furthermore, exposure of the extended spermatozoa to homologous SP (from any other individual boar) significantly (p < 0.05) varied with the source of the sire; some boars exerting beneficial effects (even surpassing the effects of the autologous SP; p < 0.05) while at least one boar negatively (p < 0.05) influencing the viability of the incubated spermatozoa. It is concluded that SP should be present when incubating highly extended spermatozoa. As a result of the obvious differences among boars, it would be advantageous to examine the ability of SP to maintain sperm viability prior to the use of SP pools during sperm handling in vitro. PMID:15367272

  17. Extended-release Formulation of Minocycline in the Treatment of Moderate-to-severe Acne Vulgaris in Patients Over the Age of 12 Years.

    PubMed

    Torok, Helen M

    2013-07-01

    Oral antibiotics continue to play an important role in the treatment of moderate-to-severe acne. Minocycline is widely used in moderate-to-severe acne. Minocycline has anti-inflammatory properties, activity against Propionibacterium acnes and lipophilicity. An extended-release formulation of minocycline has been introduced. Extended-release minocycline is not bioequivalent to nonmodified release minocycline products and exhibits dose-proportional pharmacokinetics. Food or dairy products did not influence absorption. Efficacy is not dose-dependent, while the incidence of acute vestibular adverse events increases with dose suggesting an optimal dose of 1mg/kg. In two Phase 3 clinical trials, mean percent improvement in inflammatory lesions after 12 weeks of treatment with extended-release minocycline was 43.1 and 45.8 percent compared to 31.7 and 30.8 percent with placebo (P=0.001 and P<0.001, respectively) while the incidence of acute vestibular adverse events was comparable to placebo.

  18. Effects of food and alcohol on the pharmacokinetics of an oral, extended-release formulation of hydrocodone in healthy volunteers

    PubMed Central

    Farr, Stephen J; Robinson, Cynthia Y; Rubino, Christopher M

    2015-01-01

    Background The purpose of this study was to evaluate the pharmacokinetics, bioavailability, and safety of oral extended-release hydrocodone (HC-ER) when administered with food or alcohol. Methods Two single-center, open-label, randomized, crossover studies were conducted in healthy volunteers. In a two-period food-interaction study, 12 subjects received HC-ER 20 mg after an overnight fast and a high-fat meal. In a three-period alcohol-interaction study, 30 naltrexone-blocked subjects received HC-ER 50 mg with a 0%, 20%, or 40% alcohol/orange juice solution after an overnight fast. Pharmacokinetic parameters were derived from plasma concentrations of hydrocodone and its metabolites. Results Exposure to hydrocodone after HC-ER 20 mg was similar in the fed and fasted states, as assessed by area under the plasma concentration versus time curve from time of dosing to time of last detectable concentration (AUC0–t; 316.14 versus 311.94 ng · h/mL); relative bioavailability (Frel) was 101.74%. Differences (fed versus fasted) in hydrocodone mean maximum plasma concentration (Cmax; 28.86 versus 22.74 ng/mL) and median time to Cmax (tmax; 6 versus 8 hours) were not clinically significant. Administration of 20% alcohol with HC-ER 50 mg did not increase systemic exposure relative to 0% alcohol (AUC0–t 878 versus 832 ng · h/mL; Frel 105%) or result in clinically meaningful changes in Cmax (51.8 versus 46.3 ng/mL) or tmax (5.44 versus 6.16 hours). Administration with 40% alcohol increased AUC0–t (1,008 ng · h/mL versus 832 ng · h/mL; Frel 120%) and Cmax (109 versus 46.3 ng/mL), and shortened tmax (2.43 versus 6.16 hours). Adverse events occurred in 10.0%, 24.1%, and 66.7% of subjects after 0%, 20%, and 40% alcohol, respectively. Conclusion HC-ER can be administered without regard to meals. While there was no evidence of “dose-dumping” (an unintended, rapid release in a short time period of all or most of the hydrocodone from HC-ER), even with 40% alcohol, as with all

  19. Collective phenomena in large-eddy simulations of extended wind farms

    NASA Astrophysics Data System (ADS)

    Stevens, Richard; Meneveau, Charles

    2012-11-01

    A major issue with respect to the incorporation of large wind farms in power grids is that their power output strongly fluctuates over time. Understanding these fluctuations, especially its spatio-temporal characteristics, is important for the design of the backup power that must be available. The power fluctuations of the turbines depend on the effect of the wakes, created by a prior row of turbines, on the operation of the turbines, the inter-turbine correlations, and the interaction between the turbines and the atmospheric boundary layer (ABL). We analyze the power fluctuations in large eddy simulations of extended wind-parks in the ABL. We consider various aggregates of wind turbines such as the total average power signal, or sub-averages within the wind farm. In particular, we find that the power variations of the total wind park decreases more than one would expect if one assumes the power output of the turbines to be uncorrelated. The non-trivial correlations are due to the interactions between turbines placed down-stream from each other. Surprisingly, the frequency spectra of the total wind-farm output show a decay that follows approximately a -5/3 power-law scaling regime, qualitatively consistent with observations made in field-scale operational wind parks (Apt, 2007). RS is supported by a ``Fellowship for Young Energy Scientists'' (YES!) of the Foundation for Fundamental Research on Matter (FOM), which is supported by the Netherlands Organization for Scientific Research (NWO). CM is supported by NSF-CBET 1133800.

  20. Large-scale pattern of mantle evolution through rifting in hyper-extended margins

    NASA Astrophysics Data System (ADS)

    Picazo, Suzanne; Müntener, Othmar; Manatschal, Gianreto; Bauville, Arthur

    2016-04-01

    New ideas and concepts have been developed to understand and be able to give a simplified large-scale view of the evolution of the mantle lithosphere in hyper-extended magma-poor rifted margins based on the ancient Alpine Tethys rifted margin. In contrast to the classical assumption assuming a simple, isotropic mantle lithosphere, these new models integrate observations from exposed and drilled mantle rocks and propose that the mantle lithosphere evolved and was modified during an extensional cycle from post-orogenic collapse through several periods of rifting to embryonic oceanic (ultra-) slow seafloor spreading. But it is, at present, unclear how far these ideas can be generalized at Atlantic type rifted margins. In our presentation, we review the available mantle data from dredged samples in the North Atlantic and from ophiolite massifs and xenoliths in preserved and reactivated passive margins i.e. the Alpine Tethys, the Pyrenean domain, and the Dinarides and Hellenides. We revisit the available terminology concerning mantle massifs and xenoliths and compile the available data to identify different mantle domains. We define chemical and petrological characteristics of mantle domains based on clinopyroxene and spinel compositions and compile them on present-day and paleo-geographic maps of Western Europe. Finally we link the observed distribution of mantle domains to the post-Variscan extensional cycle and link domains to processes related to the late post-Variscan extension, the rift evolution and refertilization associated to hyper-extension and the development of embryonic oceanic domains.

  1. Response to "Comment on `Application of the extended Lie group analysis to the Hopf functional formulation of the Burgers equation'" [J. Math. Phys. 57, 034102 (2016)

    NASA Astrophysics Data System (ADS)

    Wacławczyk, Marta; Oberlack, Martin

    2016-03-01

    We address the criticism of Frewer et al. concerning the paper "Application of the extended Lie group analysis to the Hopf functional formulation of the Burgers equation" [J. Math. Phys. 54, 072901 (2013)]. Most importantly, we stress that we never claimed that any new statistical symmetries were found in this paper. The aim of this paper was to apply the Lie group analysis to an equation with functional derivatives and derive invariant solutions for this equation. These results still stand as they are, most important, mathematically correct. We address also other critical statements of Frewer et al. and show that there is a connection between the translational invariance of statistics and transformations of the functional Φ. To sum up, key ideas and fundamental result in the work of Wacławczyk and Oberlack are still unaffected.

  2. Finite-element formulation for the analysis of interfaces, nonlinear and large displacement problems in geotechnical engineering

    NASA Astrophysics Data System (ADS)

    Zeevaert, A. E.

    1980-03-01

    A mathematical formulation to model the behavior under load of a reinforced soil system, where a fabric is placed over a soft soil and covered with stone for use as a temporary haul road is discussed. This approach is used to improve the behavior of temporary roadways, particularly where very soft soils are encountered. The stress distribution and the load-deformation characteristics of the soil-fabric system for varying geometries and material properties are defined. Included in the mathematical formulation are such features as: nonlinear behavior of the soil and fabric materials, friction parameters of the interface, tension characteristics of the fabric materials, large displacements in finite deformation, "no tension" conditions of the cohesionless materials, and yielding of plastic materials. The mathematical model is a more complete approximation of the actual fabric-soil system than is presently available.

  3. Symbolic Formulation of Large-scale Open-loop Multibody Systems for Vibration Analysis Using Absolute Joint Coordinates

    NASA Astrophysics Data System (ADS)

    Jiang, Wei; Chen, Xuedong; Luo, Xin; Huang, Qingjiu

    A novel symbolic formulation is presented to model dynamics of large-scale open-loop holonomic multibody systems, by using absolute joint coordinates and via matrix transformation, instead of solving constraint equations. The resulting minimal set of second-order linear ordinary differential equations (ODEs) can be used for linear vibration analysis and control directly. The ODEs are generated in three steps. Firstly, a set of linearized ODEs are formulated in terms of absolute coordinates without considering any constraint. Secondly, an overall transform matrix representing constraint topology for the entire constrained system is generated. Finally, matrices for a minimal set of ODEs for the open-loop holonomic multibody system are obtained via matrix transformation. The correctness and efficiency of the presented algorithm are verified by numerical experiments on various cases of holonomic multibody systems with different open-loop topologies, including chain topology and tree topology. It is indicated that the proposed method can significantly improve efficiency without losing computational accuracy.

  4. Extended release microparticle-in-gel formulation of octreotide: Effect of polymer type on acylation of peptide during in vitro release.

    PubMed

    Vaishya, Ravi D; Mandal, Abhirup; Patel, Sulabh; Mitra, Ashim K

    2015-12-30

    Polymeric microparticles (MPs)-in-gel formulations for extended delivery of octreotide were developed. We investigated influence of polymer composition on acylation of octreotide and kinetics of release during in vitro release from biodegradable polymeric formulations. Polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA) and polyethylene glycol (PEG) based triblock (TB≈PCL10k-PEG2k-PCL10k) and pentablock (PBA≈PLA3k-PCL7k-PEG2k-PCL7k-PLA3k and PBB≈PGA3k-PCL7k-PEG2k-PCL7k-PGA3k) polymers were investigated. Octreotide was encapsulated in MPs using methanol-oil/water emulsion solvent evaporation method. The particles were characterized for size, morphology, encapsulation efficiency, drug loading and in vitro release. Release samples were subjected to HPLC analysis for quantitation and HPLC-MS analysis for identification of native and chemically modified octreotide adducts. Entrapment efficiency of methanol-oil/water method with TB, PBA and PBB polymers were 45%, 60%, and 82%, respectively. A significant fraction of released octreotide was acylated from lactide and glycolide based PBA (53%) and PBB (92%) polymers. Substantial amount of peptide was not released from PBB polymers after 330 days of incubation. Complete release of octreotide was achieved from TB polymer over a period of 3 months with minimal acylation of peptide (13%). PCL based polymers resulted in minimal acylation of peptide and hence may be suitable for extended peptide and protein delivery. Conversely, polymers having PLA and PGA blocks may not be appropriate for peptide delivery due to acylation and incomplete release.

  5. Population pharmacodynamic modeling of various extended-release formulations of methylphenidate in children with attention deficit hyperactivity disorder via meta-analysis.

    PubMed

    Kimko, Holly; Gibiansky, Ekaterina; Gibiansky, Leonid; Starr, H Lynn; Berwaerts, Joris; Massarella, Joseph; Wiegand, Frank

    2012-04-01

    Placebo and pharmacodynamic (PD) models were developed which link temporal measures of efficacy in children with attention deficit hyperactivity disorder (ADHD) and methylphenidate (MPH) plasma concentrations from adults. These models can be used to predict daily pediatric clinical measure profiles following administration of different MPH formulations in children without conducting pediatric pharmacokinetic (PK) or PD studies by using more easily obtained adult PK data. Mean PK data from various extended-release MPH formulations studied in adults and mean PD data from nine pediatric efficacy studies were obtained from the literature. The individual time-course of the clinical measures from three pediatric trials were also analyzed after being combined with the meta-analysis data. The clinical measure profiles following placebo administration were described by indirect response models with time-varying elimination rates. MPH pharmacodynamic effect was described by E(max) models, which included time-dependent tolerance. Internal and external evaluations using a visual predictive check technique confirmed the prediction capability of the models. This modeling exercise demonstrated that time courses of MPH concentrations in adults with different drug release patterns can be used to predict time courses of clinical efficacy parameters in pediatrics by employing the models developed by meta-analysis.

  6. Formulation and in vitro, in vivo evaluation of extended- release matrix tablet of zidovudine: influence of combination of hydrophilic and hydrophobic matrix formers.

    PubMed

    Kuksal, Atul; Tiwary, Ashok K; Jain, Narendra K; Jain, Subheet

    2006-01-01

    The aim of the present study was to prepare and characterize extended-release matrix tablets of zidovudine using hydrophilic Eudragit RLPO and RSPO alone or their combination with hydrophobic ethyl cellulose. Release kinetics was evaluated by using United States Pharmacopeia (USP)-22 type I dissolution apparatus. Scanning electron microscopy was used to visualize the effect of dissolution medium on matrix tablet surface. Furthermore, the in vitro and in vivo newly formulated sustained-release zidovudine tablets were compared with conventional marketed tablet (Zidovir, Cipla Ltd, Mumbai, India). The in-vitro drug release study revealed that either Eudragit preparation was able to sustain the drug release only for 6 hours (94.3% +/- 4.5% release). Combining Eudragit with ethyl cellulose sustained the drug release for 12 hours (88.1% +/- 4.1% release). Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release. In vivo investigation in rabbits showed sustained-release pharmacokinetic profile of zidovudine from the matrix tablets formulated using combination of Eudragits and ethylcellulose. In conclusion, the results suggest that the developed sustained-release tablets of zidovudine could perform therapeutically better than conventional dosage forms, leading to improve efficacy and better patient compliance. PMID:16584139

  7. Transfering spin into an extended π orbital of a large molecule

    NASA Astrophysics Data System (ADS)

    Esat, Taner; Deilmann, Thorsten; Lechtenberg, Benedikt; Wagner, Christian; Krüger, Peter; Temirov, Ruslan; Anders, Frithjof B.; Rohlfing, Michael; Tautz, F. Stefan

    2015-04-01

    By means of low-temperature scanning tunneling microscopy (STM) and spectroscopy (STS), we have investigated the adsorption of single Au atoms on a PTCDA monolayer physisorbed on the Au(111) surface. A chemical reaction between the Au atom and the PTCDA molecule leads to the formation of a radical that has an unpaired electron in its highest occupied orbital. This orbital is a π orbital that extends over the whole Au-PTCDA complex. Because of the large Coulomb repulsion in this orbital, the unpaired electron generates a local moment when the molecule is adsorbed on the Au(111) surface. We demonstrate the formation of the radical and the existence of the local moment after adsorption by observing a zero-bias differential conductance peak that originates from the Kondo effect. By temperature dependent measurements of the zero-bias differential conductance, we determine the Kondo temperature to be TK=(38 ±8 ) K . For the theoretical description of the properties of the Au-PTCDA complex we use a hierarchy of methods, ranging from density functional theory (DFT) including a van der Waals correction to many-body perturbation theory (MBPT) and the numerical renormalization group (NRG) approach. Regarding the high-energy orbital spectrum, we obtain an excellent agreement with experiments by both spin-polarized DFT/MBPT and NRG. Moreover, the NRG provides an accurate description of the low-energy excitation spectrum of the spin degree of freedom, predicting a Kondo temperature very close to the experimental value. This is achieved by a detailed analysis of the universality of various definitions of TK and by taking into account the full energy dependence of the coupling function between the molecule-metal complex and the metallic substrate.

  8. General-Purpose Heat Source development: Extended series test program large fragment tests

    SciTech Connect

    Cull, T.A.

    1989-08-01

    General-Purpose Heat Source radioisotope thermoelectric generators (GPHS-RTGs) will provide electric power for the NASA Galileo and European Space Agency Ulysses missions. Each GPHS-RTG comprises two major components: GPHS modules, which provide thermal energy, and a thermoelectric converter, which converts the thermal energy into electric power. Each of the 18 GPHS modules in a GPHS-RTG contains four /sup 238/PuO/sub 2/-fueled capsules. LANL conducted a series of safety verification tests on the GPHS-RTG before the scheduled May 1986 launch of the Galileo spacecraft to assess the ability of the GPHS modules to contain the plutonia in potential accident environments. As a result of the Challenger 51-L accident in January 1986, NASA postponed the launch of Galileo; the launch vehicle was reconfigured and the spacecraft trajectory was modified. These actions prompted NASA to reevaluate potential mission accidents, and an extended series safety test program was initiated. The program included a series of large fragment tests that simulated the collision of solid rocket booster (SRB) fragments, generated in an SRB motor case rupture or resulting from a range safety officer SRB destruct action, with the GPHS-RTG. The tests indicated that fueled clads, inside a converter, will not breach or release fuel after a square (142 cm on a side) SRB fragment impacts flat-on at velocities up to 212 m/s, and that only the leading fueled capsules breach and release fuel after the square SRB fragment impacts the modules, inside the converter, edge-on at 95 m/s. 8 refs., 32 figs., 7 tabs.

  9. THE LARGE APEX BOLOMETER CAMERA SURVEY OF THE EXTENDED CHANDRA DEEP FIELD SOUTH

    SciTech Connect

    Weiss, A.; Kovacs, A.; Menten, K. M.; Coppin, K.; Smail, Ian; Greve, T. R.; Walter, F.; Dannerbauer, H.; Dunlop, J. S.; Ivison, R. J.; Knudsen, K. K.; Bertoldi, F.; Alexander, D. M.; Brandt, W. N.; Chapman, S. C.; Cox, P.; De Breuck, C.; Gawiser, E.; Lutz, D.; Koekemoer, A. M.

    2009-12-20

    We present a sensitive 870 mum survey of the Extended Chandra Deep Field South (ECDFS) combining 310 hr of observing time with the Large Apex BOlometer Camera (LABOCA) on the APEX telescope. The LABOCA ECDFS Submillimetre Survey (LESS) covers the full 30' x 30' field size of the ECDFS and has a uniform noise level of sigma{sub 870{sub m}}u{sub m} approx 1.2 mJy beam{sup -1}. LESS is thus the largest contiguous deep submillimeter survey undertaken to date. The noise properties of our map show clear evidence that we are beginning to be affected by confusion noise. We present a catalog of 126 submillimeter galaxies (SMGs) detected with a significance level above 3.7sigma, at which level we expect five false detections given our map area of 1260 arcmin{sup 2}. The ECDFS exhibits a deficit of bright SMGs relative to previously studied blank fields but not of normal star-forming galaxies that dominate the extragalactic background light (EBL). This is in line with the underdensities observed for optically defined high redshift source populations in the ECDFS (BzKs, DRGs, optically bright active galactic nucleus, and massive K-band-selected galaxies). The differential source counts in the full field are well described by a power law with a slope of alpha = -3.2, comparable to the results from other fields. We show that the shape of the source counts is not uniform across the field. Instead, it steepens in regions with low SMG density. Towards the highest overdensities we measure a source-count shape consistent with previous surveys. The integrated 870 mum flux densities of our source-count models down to S{sub 870{sub m}}u{sub m} = 0.5 mJy account for >65% of the estimated EBL from COBE measurements. We have investigated the clustering of SMGs in the ECDFS by means of a two-point correlation function and find evidence for strong clustering on angular scales <1' with a significance of 3.4sigma. Assuming a power-law dependence for the correlation function and a typical

  10. An embedded boundary formulation for large-eddy simulation of turbulent flows interacting with moving boundaries

    NASA Astrophysics Data System (ADS)

    Yang, Jianming

    2005-11-01

    A non-boundary-conforming formulation for simulating transitional and turbulent flows with complex geometries and dynamically moving boundaries on fixed orthogonal grids is developed. The underlying finite-difference solver for the filtered incompressible Navier-Stokes equations in both Cartesian and cylindrical coordinates is based on a second-order fractional step method on staggered grid. To satisfy the boundary conditions on an arbitrary immersed interface, the velocity field at the grid points near the interface is reconstructed locally without smearing the sharp interface. The complications caused by the Eulerian grid points emerging from a moving solid body into the fluid phase are treated with a novel "field-extension" strategy. To treat the two-way interactions between the fluid and structure, a strong coupling scheme based on Hamming's fourth-order predictor-corrector method has been developed. The fluid and the structure are treated as elements of a single dynamical system, and all of the governing equations are integrated simultaneously, and iteratively in the time-domain. A variety of two and three-dimensional fluid-structure interaction problems of increasing complexity have been considered to demonstrate the accuracy and the range of applicability of the method. In particular, forced vibrations of a rigid circular cylinder including the harmonic in-line vibrations in a quiescent fluid and the transverse vibrations in a free-stream, and the vortex-induced vibrations of an elastic cylinder with one and two degrees of freedom in a free-stream are presented and compared with reference simulations and experiments. Three-dimensional DNS and LES of fluid flows involving stationary complex geometries include the flow past a sphere at Re = 50 ˜ 1,000, the transitional flow past an airfoil with a 10° attack angle at Re = 10,000. Then, the turbulent flow over a traveling wavy wall at Re = 10,170 are simulated are compared with the detailed DNS using body

  11. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

    PubMed

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

  12. Space-based assembly sequence formulation for evaluation of large orbital assemblies

    NASA Astrophysics Data System (ADS)

    Jolly, Steve

    Some necessary and sufficient conditions for judging a conceptual design of a large orbital assembly to be constructible are identified. A methodology which can be 'mechanized' (to some extent) in a computer aided engineering (CAE) platform for both research purposes and later for CAE tools is formed. The model-based reasoning (MBR) approach to perform interface estimations allows easy examination of how a given interface was estimated. It is also possible to 'tune' the performance of the MBR estimates without any resulting simulation instabilities by merely changing the heuristics to meet a particular 'expert' opinion. The blackboard metaphor paradigm allows any number of knowledge sources to be participants in the spacecraft decomposition, and the controller can be adjusted to represent certain project biases, policies, or tendencies.

  13. Mapping composition in dust-producing regions: Extending geochemical measurements over large scales with remote sensing

    NASA Astrophysics Data System (ADS)

    Tollerud, H. J.; Elmore, A. J.; Fantle, M. S.

    2009-12-01

    Dust is a critical, yet understudied, component of geochemical cycles. Dust inputs to the ocean have been deemed especially significant in the iron cycle, for instance, since dust stimulates natural iron fertilization and thus potentially affects climate. Dust may also be important to the cycles of other elements, such as calcium (Ca). To determine the importance of dust relative to other geochemical inputs, some estimate must be made of the mass flux of Ca from dust-producing regions. However, understanding the spatial distribution of Ca within terrain known to generate dust has been problematic. Remote sensing may offer a critical perspective with measurement at landscape scales instead of extrapolation from a few point measurements, allowing for investigation closer to the scale at which dust is produced. This study investigates the elemental geochemistry of surface sediments and the distribution of non-silicate bound Ca in a large playa system (Black Rock Desert) in northwestern Nevada (USA). We used satellite-derived hyperspectral data, field-collected ground spectra, surface sediment samples, and Synthetic Aperture Radar (SAR) in our analysis. We collected approximately 50 samples and their spectra from the Black Rock Desert in July/August 2007. We measured the bulk and soluble Ca by ICP-OES and mineralogy by x-ray diffraction (XRD). Assuming all Ca in weak HCl (0.5 N) leaches is derived from calcite, we found that calcite concentrations in a subset of collected samples range from 5 to 15 wt. %. Acid-soluble calcite, which was generally 90 to 100 mol % of the total Ca in sediments (determined by lithium metaborate fusion), correlates well with the relative abundance of calcite determined by XRD analyses. Using hyperspectral measurements of surface reflectance, we found that acid soluble Ca concentration is correlated with the depth of a calcite absorption feature at 2335 nm. We then mapped this depth in satellite hyperspectral data from the Hyperion

  14. Effects of Renal Impairment and Hepatic Impairment on the Pharmacokinetics of Hydrocodone After Administration of a Hydrocodone Extended-Release Tablet Formulated With Abuse-Deterrence Technology.

    PubMed

    Darwish, Mona; Yang, Ronghua; Tracewell, William; Robertson, Philmore; Bond, Mary

    2016-03-01

    Two open-label, single-dose, parallel-group studies assessed effects of renal and hepatic impairment on the pharmacokinetics of a hydrocodone extended-release (ER) formulation developed with the CIMA Abuse-Deterrence Technology platform. Forty-eight subjects with normal renal function or varying degrees of renal impairment received hydrocodone ER 45 mg (study 1); 16 subjects with normal hepatic function or moderate hepatic impairment received hydrocodone ER 15 mg (study 2). Blood samples were obtained predose and through 144 hours postdose. Mean maximum observed plasma hydrocodone concentration (Cmax ) in subjects with normal renal function, mild, moderate, and severe impairment, and end-stage renal disease was 28.6, 33.4, 42.4, 36.5, and 31.6 ng/mL, and mean area under the plasma hydrocodone concentration-versus-time curve from time 0 to infinity (AUC0-∞ ) was 565, 660, 973, 983, and 638 ng·h/mL, respectively. Incidence of adverse events was 57%, 38%, 44%, 33%, and 56%, respectively. Mean Cmax with normal hepatic function and moderate impairment was 10.1 and 13.0 ng/mL, and mean AUC0-∞ was 155 and 269 ng·h/mL, respectively. Incidence of adverse events was 38% in both groups. Altered systemic exposure in renally or hepatically impaired populations (up to ∼70% higher) should be considered when titrating to an effective dose of hydrocodone ER. PMID:27138027

  15. Mathematical formulation to predict the harmonics of the superconducting Large Hadron Collider magnets

    NASA Astrophysics Data System (ADS)

    Sammut, Nicholas; Bottura, Luca; Micallef, Joseph

    2006-01-01

    CERN is currently assembling the LHC (Large Hadron Collider) that will accelerate and bring in collision 7 TeV protons for high energy physics. Such a superconducting magnet-based accelerator can be controlled only when the field errors of production and installation of all magnetic elements are known to the required accuracy. The ideal way to compensate the field errors obviously is to have direct diagnostics on the beam. For the LHC, however, a system solely based on beam feedback may be too demanding. The present baseline for the LHC control system hence requires an accurate forecast of the magnetic field and the multipole field errors to reduce the burden on the beam-based feedback. The field model is the core of this magnetic prediction system, that we call the field description for the LHC (FIDEL). The model will provide the forecast of the magnetic field at a given time, magnet operating current, magnet ramp rate, magnet temperature, and magnet powering history. The model is based on the identification and physical decomposition of the effects that contribute to the total field in the magnet aperture of the LHC dipoles. Each effect is quantified using data obtained from series measurements, and modeled theoretically or empirically depending on the complexity of the physical phenomena involved. This paper presents the developments of the new finely tuned magnetic field model and, using the data accumulated through series tests to date, evaluates its accuracy and predictive capabilities over a sector of the machine.

  16. No evidence for large-scale outflows in the extended ionized halo of ULIRG Mrk273

    NASA Astrophysics Data System (ADS)

    Spence, R. A. W.; Zaurín, J. Rodríguez; Tadhunter, C. N.; Rose, M.; Cabrera-Lavers, A.; Spoon, H.; Muñoz-Tuñón, C.

    2016-06-01

    We present deep new Gran Telescopio Canarias (GTC) narrow-band images and William Herschel Telescope (WHT) long-slit spectroscopy of the merging system Mrk273 that show a spectacular extended halo of warm ionized gas out to a radius of ˜45 kpc from the system nucleus. Outside of the immediate nuclear regions (r > 6 kpc), there is no evidence for kinematic disturbance in the ionized gas: in the extended regions covered by our spectroscopic slits the emission lines are relatively narrow (full width at half-maximum, FWHM ≲ 350 km s-1) and velocity shifts small (|ΔV| ≲ 250 km s-1). This is despite the presence of powerful near-nuclear outflows (FWHM > 1000 km s-1; |ΔV| > 400 km s-1; r < 6 kpc). Diagnostic ratio plots are fully consistent with Seyfert 2 photoionization to the NE of the nuclear region, however to the SW the plots are more consistent with low-velocity radiative shock models. The kinematics of the ionized gas, combined with the fact that the main structures are aligned with low-surface-brightness tidal continuum features, are consistent with the idea that the ionized halo represents tidal debris left over from a possible triple-merger event, rather than a reservoir of outflowing gas.

  17. An extended basis inexact shift-invert Lanczos for the efficient solution of large-scale generalized eigenproblems

    NASA Astrophysics Data System (ADS)

    Rewieński, M.; Lamecki, A.; Mrozowski, M.

    2013-09-01

    This paper proposes a technique, based on the Inexact Shift-Invert Lanczos (ISIL) method with Inexact Jacobi Orthogonal Component Correction (IJOCC) refinement, and a preconditioned conjugate-gradient (PCG) linear solver with multilevel preconditioner, for finding several eigenvalues for generalized symmetric eigenproblems. Several eigenvalues are found by constructing (with the ISIL process) an extended projection basis. Presented results of numerical experiments confirm the technique can be effectively applied to challenging, large-scale problems characterized by very dense spectra, such as resonant cavities with spatial dimensions which are large with respect to wavelengths of the resonating electromagnetic fields. It is also shown that the proposed scheme based on inexact linear solves delivers superior performance, as compared to methods which rely on exact linear solves, indicating tremendous potential of the 'inexact solve' concept. Finally, the scheme which generates an extended projection basis is found to provide a cost-efficient alternative to classical deflation schemes when several eigenvalues are computed.

  18. An Atypically Large, Free-Floating Thrombus Extending From the Lung to the Left Atrium via a Pulmonary Vein

    PubMed Central

    Wang, Wei; Li, Xuechang; Song, Weian; Zhang, Yunshan; Yue, Caiying; Shang, Liqun; Li, Jun; Wen, Feng; Liu, Junqiang; Zha, Peng

    2015-01-01

    Abstract An atypically large, free-floating thrombus extending from primary pulmonary malignancy into the left atrium (LA) is a rare phenomenon. Here, we report a 61-year-old man presenting with a large mass in the lower lobe of the left lung, extending to LA via the left inferior pulmonary vein. The thrombus remained clinically silent and was detected by computed tomography (CT) and transthoracic echocardiography. To prevent life-threatening complications including systemic embolism and sudden death, the patient underwent surgical excision of the mass under cardiopulmonary bypass. Pathology of the tumor and the embolus was confirmed as moderately differentiated squamous cell carcinoma. Furthermore, immunohistochemical studies demonstrated consistency of the tumor cells in this pathological category. The patient tolerated the surgery well and his condition began to improve gradually after the operation. PMID:26579798

  19. Purification and Characterization of Enzymes from Yeast: An Extended Undergraduate Laboratory Sequence for Large Classes

    ERIC Educational Resources Information Center

    Johanson, Kelly E.; Watt, Terry J.; McIntyre, Neil R.; Thompson, Marleesa

    2013-01-01

    Providing a project-based experience in an undergraduate biochemistry laboratory class can be complex with large class sizes and limited resources. We have designed a 6-week curriculum during which students purify and characterize the enzymes invertase and phosphatase from bakers yeast. Purification is performed in two stages via ethanol…

  20. Coherent-backscatter effect - A vector formulation accounting for polarization and absorption effects and small or large scatterers

    NASA Technical Reports Server (NTRS)

    Peters, Kenneth J.

    1992-01-01

    Previous theoretical work on the coherent-backscatter effect in the context of speckle time autocorrelation has gone beyond the diffusion approximation and the assumption of isotropic (point) scatterers. This paper extends the theory to include the effects of polarization and absorption, and to give the angular line shape. The results are expressions for angular variations valid for small and large scatterers and linear and circular polarizations, in lossless or lossy media. Calculations show that multiple anisotropic scattering results in the preservation of incident polarization. Application to a problem in radar astronomy is considered. It is shown that the unusual radar measurements (high reflectivity and polarization ratios) of Jupiter's icy Galilean satellites can be explained by coherent backscatter from anisotropic (forward) scatterers.

  1. Surface charging by large multivalent molecules. Extending the standard Gouy-Chapman treatment.

    PubMed Central

    Stankowski, S

    1991-01-01

    Traditionally, Gouy-Chapman theory has been used to calculate the distribution of ions in the diffuse layer next to a charged surface. In recent years, the same theory has found application to adsorption (incorporation, partitioning) of charged peptides, hormones, or drugs at the membrane-water interface. Empirically it has been found that an effective charge, smaller than the physical charge, must often be used in the Gouy-Chapman formula. In addition, the large size of these molecules can be expected to influence their adsorption isotherms. To improve evaluation techniques for such experiments, comparatively simple extensions of the standard Gouy-Chapman formalism have been studied which are based on a discrete charge virial expansion. The model allows for the mobility of charged groups at the interface. It accounts for finite size of the adsorbed macromolecules and for discrete charge effects arising from pair interactions in the interface plane. In contrast to previous discrete charge treatments this model nearly coincides with the Gouy-Chapman formalism in the case where the adsorbing molecules are univalent. Large discrepancies are found for multivalent molecules. This could explain the reduced effective charges needed in the standard Gouy-Chapman treatment. The reduction factor can be predicted. The model is mainly limited to low surface coverage, typical for the adsorption studies in question. PMID:1912277

  2. Large scale ab initio calculations of extended defects in materials: screw dislocations in bcc metals

    NASA Astrophysics Data System (ADS)

    Dézerald, Lucile; Ventelon, Lisa; Willaime, François; Clouet, Emmanuel; Rodney, David

    2014-06-01

    Ab initio methods, based on the Density Functional Theory (DFT), have been extensively used to study point defects and defect clusters in materials. Present HPC resources and DFT codes now allow similar investigations to be performed on dislocations. The study of these extended defects requires not only larger simulation cells but also a higher accuracy because the energy differences, which are involved, are rather small, typically 50-to-100 meV for supercells containing 50-to-500 atoms. The topology of the Peierls potential of screw dislocations with 1/2 <111>Burgers vector, i.e. the 2D energy landscape seen by these dislocations, is being completely revisited by DFT calculations. From results obtained in all body-centered cubic (bcc) transition metals, except Cr (V, Nb, Ta, Mo, W and Fe), using the PWSCF code, which is part of the Quantum-Espresso package, we concluded that the 2D Peierls potentials have two common features: the single-hump shape of the barrier between two minima of the potential, and the presence of a maximum - and not a minimum as predicted by most empirical potentials - around the split core. In iron, the topology of the Peierls potential is reversed compared to the classical sinusoidal picture: the location of the saddle point and the maximum are indeed inverted with unexpected flat regions. The first results obtained within the framework of the PRACE project, DIMAIM (DIslocations in Metals using Ab Initio Methods), started at the beginning of 2013, will also be presented. In particular, in order to address the twinning-antitwinning asymmetry often observed in bcc metals and regarded as the major contribution to the breakdown of Schmid's law, we have determined the crystal orientation dependence of the Peierls stress, i.e. the critical stress required for dislocation motion. These computationally most expensive simulations were performed on the PRACE Tier-0 system at Barcelona Supercomputing Center (Marenostrum III). The scalability results

  3. Fermi Large Area Telescope Detection of Extended Gamma-Ray Emission from the Radio Galaxy Fornax A

    NASA Astrophysics Data System (ADS)

    Ackermann, M.; Ajello, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bellazzini, R.; Bissaldi, E.; Blandford, R. D.; Bloom, E. D.; Bonino, R.; Brandt, T. J.; Bregeon, J.; Bruel, P.; Buehler, R.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Caragiulo, M.; Caraveo, P. A.; Cavazzuti, E.; Cecchi, C.; Charles, E.; Chekhtman, A.; Cheung, C. C.; Chiaro, G.; Ciprini, S.; Cohen, J. M.; Cohen-Tanugi, J.; Costanza, F.; Cutini, S.; D’Ammando, F.; Davis, D. S.; de Angelis, A.; de Palma, F.; Desiante, R.; Digel, S. W.; Di Lalla, N.; Di Mauro, M.; Di Venere, L.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Focke, W. B.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Georganopoulos, M.; Giglietto, N.; Giordano, F.; Giroletti, M.; Godfrey, G.; Green, D.; Grenier, I. A.; Guiriec, S.; Hays, E.; Hewitt, J. W.; Hill, A. B.; Jogler, T.; Jóhannesson, G.; Kensei, S.; Kuss, M.; Larsson, S.; Latronico, L.; Li, J.; Li, L.; Longo, F.; Loparco, F.; Lubrano, P.; Magill, J. D.; Maldera, S.; Manfreda, A.; Mayer, M.; Mazziotta, M. N.; McConville, W.; McEnery, J. E.; Michelson, P. F.; Mitthumsiri, W.; Mizuno, T.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Negro, M.; Nuss, E.; Ohno, M.; Ohsugi, T.; Orienti, M.; Orlando, E.; Ormes, J. F.; Paneque, D.; Perkins, J. S.; Pesce-Rollins, M.; Piron, F.; Pivato, G.; Porter, T. A.; Rainò, S.; Rando, R.; Razzano, M.; Reimer, A.; Reimer, O.; Schmid, J.; Sgrò, C.; Simone, D.; Siskind, E. J.; Spada, F.; Spandre, G.; Spinelli, P.; Stawarz, Ł.; Takahashi, H.; Thayer, J. B.; Thompson, D. J.; Torres, D. F.; Tosti, G.; Troja, E.; Vianello, G.; Wood, K. S.; Wood, M.; Zimmer, S.

    2016-07-01

    We report the Fermi Large Area Telescope detection of extended γ-ray emission from the lobes of the radio galaxy Fornax A using 6.1 years of Pass 8 data. After Centaurus A, this is now the second example of an extended γ-ray source attributed to a radio galaxy. Both an extended flat disk morphology and a morphology following the extended radio lobes were preferred over a point-source description, and the core contribution was constrained to be \\lt 14% of the total γ-ray flux. A preferred alignment of the γ-ray elongation with the radio lobes was demonstrated by rotating the radio lobes template. We found no significant evidence for variability on ˜0.5 year timescales. Taken together, these results strongly suggest a lobe origin for the γ-rays. With the extended nature of the \\gt 100 {{MeV}} γ-ray emission established, we model the source broadband emission considering currently available total lobe radio and millimeter flux measurements, as well as X-ray detections attributed to inverse Compton (IC) emission off the cosmic microwave background (CMB). Unlike the Centaurus A case, we find that a leptonic model involving IC scattering of CMB and extragalactic background light (EBL) photons underpredicts the γ-ray fluxes by factors of about ˜2–3, depending on the EBL model adopted. An additional γ-ray spectral component is thus required, and could be due to hadronic emission arising from proton–proton collisions of cosmic rays with thermal plasma within the radio lobes.

  4. Fermi Large Area Telescope Detection of Extended Gamma-Ray Emission from the Radio Galaxy Fornax A

    NASA Astrophysics Data System (ADS)

    Ackermann, M.; Ajello, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bellazzini, R.; Bissaldi, E.; Blandford, R. D.; Bloom, E. D.; Bonino, R.; Brandt, T. J.; Bregeon, J.; Bruel, P.; Buehler, R.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Caragiulo, M.; Caraveo, P. A.; Cavazzuti, E.; Cecchi, C.; Charles, E.; Chekhtman, A.; Cheung, C. C.; Chiaro, G.; Ciprini, S.; Cohen, J. M.; Cohen-Tanugi, J.; Costanza, F.; Cutini, S.; D'Ammando, F.; Davis, D. S.; de Angelis, A.; de Palma, F.; Desiante, R.; Digel, S. W.; Di Lalla, N.; Di Mauro, M.; Di Venere, L.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Focke, W. B.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Georganopoulos, M.; Giglietto, N.; Giordano, F.; Giroletti, M.; Godfrey, G.; Green, D.; Grenier, I. A.; Guiriec, S.; Hays, E.; Hewitt, J. W.; Hill, A. B.; Jogler, T.; Jóhannesson, G.; Kensei, S.; Kuss, M.; Larsson, S.; Latronico, L.; Li, J.; Li, L.; Longo, F.; Loparco, F.; Lubrano, P.; Magill, J. D.; Maldera, S.; Manfreda, A.; Mayer, M.; Mazziotta, M. N.; McConville, W.; McEnery, J. E.; Michelson, P. F.; Mitthumsiri, W.; Mizuno, T.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Negro, M.; Nuss, E.; Ohno, M.; Ohsugi, T.; Orienti, M.; Orlando, E.; Ormes, J. F.; Paneque, D.; Perkins, J. S.; Pesce-Rollins, M.; Piron, F.; Pivato, G.; Porter, T. A.; Rainò, S.; Rando, R.; Razzano, M.; Reimer, A.; Reimer, O.; Schmid, J.; Sgrò, C.; Simone, D.; Siskind, E. J.; Spada, F.; Spandre, G.; Spinelli, P.; Stawarz, Ł.; Takahashi, H.; Thayer, J. B.; Thompson, D. J.; Torres, D. F.; Tosti, G.; Troja, E.; Vianello, G.; Wood, K. S.; Wood, M.; Zimmer, S.

    2016-07-01

    We report the Fermi Large Area Telescope detection of extended γ-ray emission from the lobes of the radio galaxy Fornax A using 6.1 years of Pass 8 data. After Centaurus A, this is now the second example of an extended γ-ray source attributed to a radio galaxy. Both an extended flat disk morphology and a morphology following the extended radio lobes were preferred over a point-source description, and the core contribution was constrained to be \\lt 14% of the total γ-ray flux. A preferred alignment of the γ-ray elongation with the radio lobes was demonstrated by rotating the radio lobes template. We found no significant evidence for variability on ˜0.5 year timescales. Taken together, these results strongly suggest a lobe origin for the γ-rays. With the extended nature of the \\gt 100 {{MeV}} γ-ray emission established, we model the source broadband emission considering currently available total lobe radio and millimeter flux measurements, as well as X-ray detections attributed to inverse Compton (IC) emission off the cosmic microwave background (CMB). Unlike the Centaurus A case, we find that a leptonic model involving IC scattering of CMB and extragalactic background light (EBL) photons underpredicts the γ-ray fluxes by factors of about ˜2-3, depending on the EBL model adopted. An additional γ-ray spectral component is thus required, and could be due to hadronic emission arising from proton-proton collisions of cosmic rays with thermal plasma within the radio lobes.

  5. Large apparent electric size of solid-state nanopores due to spatially extended surface conduction.

    PubMed

    Lee, Choongyeop; Joly, Laurent; Siria, Alessandro; Biance, Anne-Laure; Fulcrand, Rémy; Bocquet, Lydéric

    2012-08-01

    Ion transport through nanopores drilled in thin membranes is central to numerous applications, including biosensing and ion selective membranes. This paper reports experiments, numerical calculations, and theoretical predictions demonstrating an unexpectedly large ionic conduction in solid-state nanopores, taking its origin in anomalous entrance effects. In contrast to naive expectations based on analogies with electric circuits, the surface conductance inside the nanopore is shown to perturb the three-dimensional electric current streamlines far outside the nanopore in order to meet charge conservation at the pore entrance. This unexpected contribution to the ionic conductance can be interpreted in terms of an apparent electric size of the solid-state nanopore, which is much larger than its geometric counterpart whenever the number of charges carried by the nanopore surface exceeds its bulk counterpart. This apparent electric size, which can reach hundreds of nanometers, can have a major impact on the electrical detection of translocation events through nanopores, as well as for ionic transport in biological nanopores.

  6. Extended temperature-accelerated dynamics: Enabling long-time full-scale modeling of large rare-event systems

    SciTech Connect

    Bochenkov, Vladimir; Suetin, Nikolay; Shankar, Sadasivan

    2014-09-07

    A new method, the Extended Temperature-Accelerated Dynamics (XTAD), is introduced for modeling long-timescale evolution of large rare-event systems. The method is based on the Temperature-Accelerated Dynamics approach [M. Sørensen and A. Voter, J. Chem. Phys. 112, 9599 (2000)], but uses full-scale parallel molecular dynamics simulations to probe a potential energy surface of an entire system, combined with the adaptive on-the-fly system decomposition for analyzing the energetics of rare events. The method removes limitations on a feasible system size and enables to handle simultaneous diffusion events, including both large-scale concerted and local transitions. Due to the intrinsically parallel algorithm, XTAD not only allows studies of various diffusion mechanisms in solid state physics, but also opens the avenue for atomistic simulations of a range of technologically relevant processes in material science, such as thin film growth on nano- and microstructured surfaces.

  7. The Ĝ Infrared Search for Extraterrestrial Civilizations with Large Energy Supplies. III. The Reddest Extended Sources in WISE

    NASA Astrophysics Data System (ADS)

    Griffith, Roger L.; Wright, Jason T.; Maldonado, Jessica; Povich, Matthew S.; Sigurđsson, Steinn; Mullan, Brendan

    2015-04-01

    Nearby Type iii (galaxy-spanning) Kardashev supercivilizations would have high mid-infrared (MIR) luminosities. We have used the Wide-field Infrared Survey Explorer (WISE) to survey ∼ 1× {{10}5} galaxies for extreme MIR emission, 1 × 103 times more galaxies than the only previous such search. We have calibrated the WISE All-sky Catalog pipeline products to improve their photometry for extended sources. We present 563 extended sources with |b|≥slant 10 and red MIR colors, having visually vetted them to remove artifacts. No galaxies in our sample host an alien civilization reprocessing more than 85% of its starlight into the MIR, and only 50 galaxies, including Arp 220, have MIR luminosities consistent with \\gt 50% reprocessing. Ninety of these (likely) extragalactic sources have little literature presence; in most cases, they are likely barely resolved galaxies or pairs of galaxies undergoing large amounts of star formation. Five are new to science and deserve further study. The Be star 48 Librae sits within a MIR nebula, and we suggest that it may be creating dust. WISE, 2MASS, and Spitzer imagery shows that IRAS 04287+6444 is consistent with a previously unnoticed, heavily extinguished cluster of young stellar objects. We identify five “passive” (i.e., red) spiral galaxies with unusually high MIR and low NUV luminosity. We search a set of H i dark galaxies for MIR emission and find none. These 90 poorly understood sources and 5 anomalous passive spirals deserve follow-up via both SETI and conventional astrophysics.

  8. Formation of Large Regular Satellites of Giant Planets in an Extended Gaseous Nebula. 2; Satellite Migration And Survival

    NASA Technical Reports Server (NTRS)

    Mosqueira, I.; Estrada, P. R.

    2000-01-01

    Using an optically thick inner disk and an extended, optically thin outer disk as described in Mosqueira and Estrada, we compute the torque as a function of position in the subnebula, and show that although the torque exerted on the satellite is generally negative, which leads to inward migration as expected, there are regions of the disk where the torque is positive. For our model these regions of positive torque correspond roughly to the locations of Callisto and Iapetus. Though the outer location of zero torque depends on the (unknown) size of the transition region between the inner and outer disks, the result that Saturn's is found much farther out (at approximately 3r(sub c, sup S) where r(sub c, sup S) is Saturn's centrifugal radius) than Jupiter's (at approximately 2r(sub c, sup J), where r(sub c, sup J) is Jupiter's centrifugal radius) is mostly due to Saturn's less massive outer disk, and larger Hill radius. For a satellite to survive in the disk the timescale of satellite migration must be longer than the timescale for gas dissipation. For large satellites (approximately 1000 km) migration is dominated by the gas torque. We consider the possibility that the feedback reaction of the gas disk caused by the redistribution of gas surface density around satellites with masses larger than the inertial mass causes a large drop in the drift velocity of such objects, thus improving the likelihood that they will be left stranded following gas dissipation. We adapt the inviscid inertial mass criterion to include gas drag, and m-dependent non-local deposition of angular momentum.

  9. THE VERY LARGE ARRAY 1.4 GHz SURVEY OF THE EXTENDED CHANDRA DEEP FIELD SOUTH: SECOND DATA RELEASE

    SciTech Connect

    Miller, Neal A.; Bonzini, Margherita; Mainieri, Vincenzo; Padovani, Paolo; Rosati, Piero; Fomalont, Edward B.; Kellermann, Kenneth I.; Tozzi, Paolo; Vattakunnel, Shaji

    2013-04-01

    Deep radio observations at 1.4 GHz for the Extended Chandra Deep Field South were performed in 2007 June through September and presented in a first data release. The survey was made using six separate pointings of the Very Large Array with over 40 hr of observation per pointing. In the current paper, we improve on the data reduction to produce a second data release (DR2) mosaic image. This DR2 image covers an area of about a third of a square degree, reaches a best rms sensitivity of 6 {mu}Jy, and has a typical sensitivity of 7.4 {mu}Jy per 2.''8 by 1.''6 beam. We also present a more comprehensive catalog, including sources down to peak flux densities of five or more times the local rms noise along with information on source sizes and relevant pointing data. We discuss in some detail the consideration of whether sources are resolved under the complication of a radio image created as a mosaic of separate pointings each suffering some degree of bandwidth smearing, and the accurate evaluation of the flux densities of such sources. Finally, the radio morphologies and optical/near-IR counterpart identifications are used to identify 17 likely multiple-component sources and arrive at a catalog of 883 radio sources, which is roughly double the number of sources contained in the first data release.

  10. An Analysis of the Population of Extended Main Sequence Turn-off Clusters in the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Piatti, Andrés E.; Bastian, Nate

    2016-08-01

    We combine a number of recent studies of the extended main sequence turn-off (eMSTO) phenomenon in intermediate age stellar (1 - 2 Gyr) clusters in the Large Magellanic Cloud (LMC) in order to investigate its origin. By employing the largest sample of eMSTO LMC clusters so far used, we show that cluster core radii, masses, and dynamical state are not related to the genesis of eMSTOs. Indeed, clusters in our sample have core radii, masses and age-relaxation time ratios in the range ≈ 2-6 pc, 3.35- 5.50 (log(Mcls/M⊙) and 0.2-8.0, respectively. These results imply that the eMSTO phenomenon is not caused by actual age spreads within the clusters. Furthermore, we confirm from a larger cluster sample recent results including young eMSTO LMC clusters, that the FWHM at the MSTOs correlates most strongly with cluster age, suggesting that a stellar evolutionary effect is the underlying cause.

  11. THE EXTENDED MAIN-SEQUENCE TURNOFF CLUSTERS OF THE LARGE MAGELLANIC CLOUD-MISSING LINKS IN GLOBULAR CLUSTER EVOLUTION

    SciTech Connect

    Keller, Stefan C.; Mackey, A. Dougal; Da Costa, Gary S.

    2011-04-10

    Recent observations of intermediate-age (1-3 Gyr) massive star clusters in the Large Magellanic Cloud have revealed that the majority possess bifurcated or extended main-sequence turnoff (EMSTO) morphologies. This effect can be understood to arise from subsequent star formation among the stellar population with age differences between constituent stars amounting to 50-300 Myr. Age spreads of this order are similarly invoked to explain the light-element abundance variations witnessed in ancient globular clusters (GCs). In this paper, we explore the proposition that the clusters exhibiting the EMSTO phenomenon are a general phase in the evolution of massive clusters, one that naturally leads to the particular chemical properties of the ancient GC population. We show that the isolation of EMSTO clusters to intermediate ages is the consequence of observational selection effects. In our proposed scenario, the EMSTO phenomenon is identical to that which establishes the light-element abundance variations that are ubiquitous in the ancient GC population. Our scenario makes a strong prediction: EMSTO clusters will exhibit abundance variations in the light-elements characteristic of the ancient GC population.

  12. Extending ALE3D, an Arbitrarily Connected hexahedral 3D Code, to Very Large Problem Size (U)

    SciTech Connect

    Nichols, A L

    2010-12-15

    As the number of compute units increases on the ASC computers, the prospect of running previously unimaginably large problems is becoming a reality. In an arbitrarily connected 3D finite element code, like ALE3D, one must provide a unique identification number for every node, element, face, and edge. This is required for a number of reasons, including defining the global connectivity array required for domain decomposition, identifying appropriate communication patterns after domain decomposition, and determining the appropriate load locations for implicit solvers, for example. In most codes, the unique identification number is defined as a 32-bit integer. Thus the maximum value available is 231, or roughly 2.1 billion. For a 3D geometry consisting of arbitrarily connected hexahedral elements, there are approximately 3 faces for every element, and 3 edges for every node. Since the nodes and faces need id numbers, using 32-bit integers puts a hard limit on the number of elements in a problem at roughly 700 million. The first solution to this problem would be to replace 32-bit signed integers with 32-bit unsigned integers. This would increase the maximum size of a problem by a factor of 2. This provides some head room, but almost certainly not one that will last long. Another solution would be to replace all 32-bit int declarations with 64-bit long long declarations. (long is either a 32-bit or a 64-bit integer, depending on the OS). The problem with this approach is that there are only a few arrays that actually need to extended size, and thus this would increase the size of the problem unnecessarily. In a future computing environment where CPUs are abundant but memory relatively scarce, this is probably the wrong approach. Based on these considerations, we have chosen to replace only the global identifiers with the appropriate 64-bit integer. The problem with this approach is finding all the places where data that is specified as a 32-bit integer needs to be

  13. Exergy and extended exergy accounting of very large complex systems with an application to the province of Siena, Italy.

    PubMed

    Sciubba, Enrico; Bastianoni, Simone; Tiezzi, Enzo

    2008-01-01

    This paper describes the application of exergy and extended exergy analyses to large complex systems. The system to be analysed is assumed to be at steady state, and the input and output fluxes of matter and energy are expressed in units of exergy. Human societies of any reasonable extent are indeed Very Large Complex Systems and can be represented as interconnected networks of N elementary "components", their Subsystems; the detail of the disaggregation depends on the type and quality of the available data. The structural connectivity of the "model" of the System must correctly describe the interactions of each mass or energy flow with each sector of the society: since it is seldom the case that all of these fluxes are available in detail, some preliminary mass- and energy balances must be completed and constitute in fact a part of the initial assumptions. Exergy accounting converts the total amount of resources inflow into their equivalent exergetic form with the help of a table of "raw exergy data" available in the literature. The quantification of each flow on a homogeneous exergetic basis paves the way to the evaluation of the efficiency of each energy and mass transfer between the N sectors and makes it possible to quantify the irreversible losses and identify their sources. The advantage of the EEA, compared to a classical exergy accounting, is the inclusion in the system balance of the exergetic equivalents of three additional "Production Factors": human Labour, Capital and Environmental Remediation costs. EEA has an additional advantage: it allows for the calculation of the efficiency of the domestic sector (impossible to evaluate with any other energy- or exergy-based method) by considering the working hours as its product. As implied in the title, an application of the method was made to a model of the province of Siena (on a year 2000 database): the results show that the sectors of this Province have values of efficiency close to the Italian average

  14. Time-dependent restricted-active-space self-consistent-field theory for laser-driven many-electron dynamics. II. Extended formulation and numerical analysis

    NASA Astrophysics Data System (ADS)

    Miyagi, Haruhide; Madsen, Lars Bojer

    2014-06-01

    The time-dependent restricted-active-space self-consistent-field (TD-RASSCF) method is formulated based on the TD variational principle. The SCF based TD orbitals contributing to the expansion of the wave function are classified into three groups, between which orbital excitations are considered with the RAS scheme. In analogy with the configuration-interaction singles (CIS), singles-and-doubles (CISD), and singles-doubles-and-triples (CISDT) methods in quantum chemistry, the TD-RASSCF-S, -SD, and -SDT methods are introduced as extensions of the TD-RASSCF-doubles (-D) method [Phys. Rev. A 87, 062511 (2013), 10.1103/PhysRevA.87.062511]. Based on an analysis of the numerical cost and test calculations for one-dimensional (1D) models of atomic helium, beryllium, and carbon, it is shown that the TD-RASSCF-S and -D methods are computationally feasible for systems with many electrons and more accurate than the TD Hartree-Fock (TDHF) and TDCIS methods. In addition to the discussion of methodology, an analysis of electron dynamics in the high-order harmonic generation (HHG) process is presented. For the 1D beryllium atom, a state-resolved analysis of the HHG spectrum based on the time-independent HF orbitals shows that while only single-orbital excitations are needed in the region below the cutoff, single- and double-orbital excitations are essential beyond, where accordingly the single-active-electron (SAE) approximation and the TDCIS method break down. On the other hand, the TD-RASSCF-S and -D methods accurately describe the multiorbital excitation processes throughout the entire region of the HHG spectrum. For the 1D carbon atom, our calculations show that multiorbital excitations are essential in the HHG process even below the cutoff. Hence, in this test system a very accurate treatment of electron correlation is required. The TD-RASSCF-S and -D approaches meet this demand, while the SAE approximation and the TDCIS method are inadequate.

  15. Physiologically Based Pharmacokinetic Modeling for Substitutability Analysis of Venlafaxine Hydrochloride Extended-Release Formulations Using Different Release Mechanisms: Osmotic Pump Versus Openable Matrix.

    PubMed

    Lin, Ho-Pi; Sun, Dajun; Zhang, Xinyuan; Wen, Hong

    2016-10-01

    A Food and Drug Administration-approved generic oral product of venlafaxine hydrochloride (HCl) extended-release (ER) tablets has used a release mechanism based on an openable matrix, which is different from the push-pull osmotic pump system of its reference-listed drug. In an extreme case, a delay in the bursting of the openable matrix may be considered a product failure mode that alters the intended profile of systemic exposure. A physiologically based pharmacokinetic absorption model was established and verified to simulate the pharmacokinetic profiles after a single-dose oral administration of ER venlafaxine HCl tablets based on an osmotic pump or openable matrix design. This model adequately predicted the observed human mean pharmacokinetic metrics with <20% difference between the predicted and observed data. Based on the modeling and simulation results, Cmax and AUCt of the venlafaxine openable matrix tablets were entirely within the bioequivalence acceptance limits (i.e., 80%-125%) when the lag time varied from 0 to 4 h and using drug-release profiles under most dissolution conditions. The results indicated that a bioinequivalence risk is minimal for a delayed onset of drug release from the approved generic venlafaxine HCl ER tablets with an openable matrix design, supporting its substitutability to the reference product. PMID:27449228

  16. An Extended Lagrangian Method

    NASA Technical Reports Server (NTRS)

    Liou, Meng-Sing

    1995-01-01

    A unique formulation of describing fluid motion is presented. The method, referred to as 'extended Lagrangian method,' is interesting from both theoretical and numerical points of view. The formulation offers accuracy in numerical solution by avoiding numerical diffusion resulting from mixing of fluxes in the Eulerian description. The present method and the Arbitrary Lagrangian-Eulerian (ALE) method have a similarity in spirit-eliminating the cross-streamline numerical diffusion. For this purpose, we suggest a simple grid constraint condition and utilize an accurate discretization procedure. This grid constraint is only applied to the transverse cell face parallel to the local stream velocity, and hence our method for the steady state problems naturally reduces to the streamline-curvature method, without explicitly solving the steady stream-coordinate equations formulated a priori. Unlike the Lagrangian method proposed by Loh and Hui which is valid only for steady supersonic flows, the present method is general and capable of treating subsonic flows and supersonic flows as well as unsteady flows, simply by invoking in the same code an appropriate grid constraint suggested in this paper. The approach is found to be robust and stable. It automatically adapts to flow features without resorting to clustering, thereby maintaining rather uniform grid spacing throughout and large time step. Moreover, the method is shown to resolve multi-dimensional discontinuities with a high level of accuracy, similar to that found in one-dimensional problems.

  17. Epidemiologic and Molecular Pathophysiology of Chronic Opioid Dependence and the Place of Naltrexone Extended-Release Formulations in its Clinical Management

    PubMed Central

    Reece, Albert Stuart

    2012-01-01

    Naltrexone implants and depot injections (NI) are a novel form of treatment for opiate dependence (OD). Major questions relate to their absolute and relative efficacy and safety. Opportunely, six recent clinical trial data from several continents have uniformly provided dramatic evidence of the potent, dose-related and highly significant efficacy of NI, with minimal or manageable accompanying toxicity and safety concerns. The opiate-free lifestyle is attained significantly more often with NI adjusted O.R. = 6.00 (95% C.I. 3.86–9.50), P < 10−10. Other drug use and drug craving are also rapidly reduced. The optimum manner in which to commence NI remains to be established. Of particular relevance is the relative safety of NI compared to the chronic opiate agonists (COA) usually employed, as the long-term toxicity of COA is only just being elucidated. Large population-based studies have found elevated rates of cardiovascular disease, six cancers, liver and respiratory disease, and all-cause mortality in COA. Whilst opiates have been shown to trigger numerous molecular pathways, the most interesting is the demonstration that the opiate morphinan’s nucleus binds to the endotoxin groove of the TLR4-MD2 heterodimer. This has the effect of triggering a low grade endotoxaemic-like state, which over time may account for these protean clinical findings, an effect which is reversed by opiate antagonists. This emerging evidence suggests an exciting new treatment paradigm for OD and a corresponding increase in the role of NI in treatment. PMID:23055738

  18. Mathematical formulation to predict the harmonics of the superconducting Large Hadron Collider magnets. II. Dynamic field changes and scaling laws

    NASA Astrophysics Data System (ADS)

    Sammut, Nicholas J.; Bottura, Luca; Bauer, Pierre; Velev, George; Pieloni, Tatiana; Micallef, Joseph

    2007-08-01

    A superconducting particle accelerator like the LHC (Large Hadron Collider) at CERN, can only be controlled well if the effects of the magnetic field multipoles on the beam are compensated. The demands on a control system solely based on beam feedback may be too high for the requirements to be reached at the specified bandwidth and accuracy. Therefore, we designed a suitable field description for the LHC (FIDEL) as part of the machine control baseline to act as a feed-forward magnetic field prediction system. FIDEL consists of a physical and empirical parametric field model based on magnetic measurements at warm and in cryogenic conditions. The performance of FIDEL is particularly critical at injection when the field decays, and in the initial part of the acceleration when the field snaps back. These dynamic components are both current and time dependent and are not reproducible from cycle to cycle since they also depend on the magnet powering history. In this paper a qualitative and quantitative description of the dynamic field behavior substantiated by a set of scaling laws is presented.

  19. Characteristics of oxidative homolytic alkylation of imidazoles and organic-inorganic hybrid extended networks from large aromatic building blocks

    NASA Astrophysics Data System (ADS)

    Li, Kunhao

    The discovery of the dramatic in vitro antimalarial activity of 2-iodo-L-histidine and 2-fluoro-L-histidine, as well as their in vivo limitations, has prompted a systematic search for novel 2-substituted imidazoles and bioimidazoles as agents against human malaria. Previous research has shown that the regioselective alkyl free radical substitution on imidazoles and bioimidazoles could serve as a simple and efficient route to a wide variety of 2-alkylimidazoles. In this research, this methodology was successfully extended to include alkyl radicals substituted with various functional groups such as amide or ester. While this novel methodology should be of some synthetic utility when tertiary radicals are used, poorer yields are usually encountered in the cases of primary radicals. In the second part of this dissertation, a series of novel ligands containing multiple ortho-bis(organothio) groups were synthesized and their coordination and network forming properties were studied in the context of crystalline organic-inorganic hybrid extended networks. For the syntheses of HRTTs [2,3,6,7,10,11-hexakis(alkylthio)triphenylenes], a simpler, safer and higher yielding one-pot process was developed. Quenching the hexa-anions (formed when sodium methylthiolate was refluxed with hexabromotriphenylene) with alkyl halides or acid chlorides afforded HRTTs. This newly developed process was also successfully expanded to the pyrene system. In the syntheses of unsymmetrically substituted triphenlyenes, it was shown for the first time that the oxidative cyclization process is applicable to thioether containing systems, pointing to a novel strategy for the preparation of this type of unsymmetrically substituted triphenlyenes. Treating these novel ligands with various metal salts [i.e. bismuth(III) chloride and bismuth(III) bromide] under carefully controlled conditions resulted in a series of air-stable semiconductive coordination networks. Their single crystal structures were

  20. Transmesocolic robotic extended pyelolithotomy of a large gas-containing renal stone: Case report and review of the literature

    PubMed Central

    Manny, Ted B.; Manny, Julia S.; Hemal, Ashok K.

    2013-01-01

    We present the fifth case in the world literature of a gas-containing urinary stone. Our patient is a 31-year-old woman referred for left flank pain and gross hematuria who was noted on imaging to have a 6.5 cm left renal pelvis stone containing gas. Cultures revealed Escherichia coli from the urine and stone material. Chemistry revealed underlying gouty diathesis. The stone was removed using robotic extended pyelolithotomy. Overall, renal function remained unchanged while drainage improved on nucleotide renography. Review of the world literature suggests that gas-containing renal stones are invariably associated with emphysematous pyelonephritis commonly caused by E. coli and Klebsiella. Contributing factors to gas-containing stone formation include urinary stasis, metabolic mineral derangement and, in a minority of the cases, diabetes. PMID:23798875

  1. Transmesocolic robotic extended pyelolithotomy of a large gas-containing renal stone: Case report and review of the literature.

    PubMed

    Manny, Ted B; Manny, Julia S; Hemal, Ashok K

    2013-04-01

    We present the fifth case in the world literature of a gas-containing urinary stone. Our patient is a 31-year-old woman referred for left flank pain and gross hematuria who was noted on imaging to have a 6.5 cm left renal pelvis stone containing gas. Cultures revealed Escherichia coli from the urine and stone material. Chemistry revealed underlying gouty diathesis. The stone was removed using robotic extended pyelolithotomy. Overall, renal function remained unchanged while drainage improved on nucleotide renography. Review of the world literature suggests that gas-containing renal stones are invariably associated with emphysematous pyelonephritis commonly caused by E. coli and Klebsiella. Contributing factors to gas-containing stone formation include urinary stasis, metabolic mineral derangement and, in a minority of the cases, diabetes. PMID:23798875

  2. A Stabilized Sparse-Matrix U-D Square-Root Implementation of a Large-State Extended Kalman Filter

    NASA Technical Reports Server (NTRS)

    Boggs, D.; Ghil, M.; Keppenne, C.

    1995-01-01

    The full nonlinear Kalman filter sequential algorithm is, in theory, well-suited to the four-dimensional data assimilation problem in large-scale atmospheric and oceanic problems. However, it was later discovered that this algorithm can be very sensitive to computer roundoff, and that results may cease to be meaningful as time advances. Implementations of a modified Kalman filter are given.

  3. Pharmacokinetics of the evogliptin/metformin extended-release (5/1,000 mg) fixed-dose combination formulation compared to the corresponding loose combination, and food effect in healthy subjects.

    PubMed

    Rhee, Su-Jin; Lee, SeungHwan; Yoon, Seo Hyun; Cho, Joo-Youn; Jang, In-Jin; Yu, Kyung-Sang

    2016-01-01

    A new fixed-dose combination formulation of evogliptin 5 mg and metformin extended-release (XR) 1,000 mg (FDC_EVO5/MET1000) was developed to improve medication adherence for type 2 diabetes mellitus. The pharmacokinetics of FDC_EVO5/MET1000 was compared to the corresponding loose combination in a randomized, open-label, crossover study in 36 healthy male subjects (Part 1), and the food effect on FDC_EVO5/MET1000 was assessed (under fasted or fed conditions) in a randomized, open-label, crossover study in 28 healthy male subjects (Part 2). Serial blood samples for pharmacokinetic analysis were collected up to 72 hours, and pharmacokinetic parameters of evogliptin and metformin were calculated using non-compartmental methods. The geometric mean ratios (fixed-dose combination to loose combination) and 90% confidence intervals of pharmacokinetic parameters for evogliptin and metformin were all within 0.800-1.250, suggesting bioequivalent pharmacokinetic. After a single oral dose of FDC_EVO5/MET1000, food did not significantly affect evogliptin pharmacokinetic while systemic exposure of metformin was increased about 47.5% under the fed condition, which is consistent with the already established food effect on metformin XR. FDC_EVO5/MET1000 was generally well tolerated without any drug-related serious adverse events. In conclusion, FDC_EVO5/MET1000 can be substituted for the loose combination of FDC_EVO5/MET1000, providing better compliance with convenient administration. PMID:27110098

  4. Single-dose evaluation of safety, tolerability and pharmacokinetics of newly formulated hydromorphone immediate-release and hydrophilic matrix extended-release tablets in healthy Japanese subjects without co-administration of an opioid antagonist.

    PubMed

    Toyama, Kaoru; Uchida, Naoki; Ishizuka, Hitoshi; Sambe, Takehiko; Kobayashi, Shinichi

    2015-09-01

    This single dose, open-label study investigated the safety, tolerability and pharmacokinetics of single oral doses of newly formulated immediate-release (IR) and hydrophilic matrix extended-release (ER) hydromorphone tablets in healthy Japanese subjects without co-administration of an opioid antagonist under fasting and fed conditions. Plasma and urinary concentrations of hydromorphone and metabolites were measured by liquid-chromatography tandem mass-spectroscopy. Following administration of the ER tablet, plasma concentrations of hydromorphone slowly increased with a median tmax of 5.0 h and the Cmax decreased to 37% of the IR tablet, while the AUC0-inf was comparable with that of the IR tablet when administered at the same dose. The degree of fluctuation in the plasma concentration for the ER tablet was much lower than that of the IR tablet and certain levels of plasma concentrations were maintained after 24 h of ER dosing. The AUC0-inf and Cmax increased with food for both IR and ER tablets. The AUC0-inf of hydromorphone-3-glucoside was one-tenth of that of hydromorphone-3-glucuronide. A single oral administration of the hydromorphone tablets would be well-tolerated in healthy Japanese subjects despite a lack of co-administration of an opioid antagonist and the newly developed ER hydromorphone tablets may have the appropriate PK characteristics for once-daily dosing.

  5. A straightforward strategy toward large BN-embedded π-systems: synthesis, structure, and optoelectronic properties of extended BN heterosuperbenzenes.

    PubMed

    Wang, Xiao-Ye; Zhuang, Fang-Dong; Wang, Rui-Bo; Wang, Xin-Chang; Cao, Xiao-Yu; Wang, Jie-Yu; Pei, Jian

    2014-03-12

    A straightforward strategy has been used to construct large BN-embedded π-systems simply from azaacenes. BN heterosuperbenzene derivatives, the largest BN heteroaromatics to date, have been synthesized in three steps. The molecules exhibit curved π-surfaces, showing two different conformations which are self-organized into a sandwich structure and further packed into a π-stacking column. The assembled microribbons exhibit good charge transport properties and photoconductivity, representing an important step toward the optoelectronic applications of BN-embedded aromatics.

  6. Formation of Large Regular Satellites of Giant Planets in an Extended Gaseous Nebula: Subnebula Model and Accretion of Satellites

    NASA Technical Reports Server (NTRS)

    Mosqueira, I.; Estrada, P. R.

    2000-01-01

    We model the subnebulae of Jupiter and Saturn wherein satellite accretion took place. We expect a giant planet subnebula to be composed of an optically thick (given gaseous opacity) inner region inside of the planet's centrifugal radius (located at r(sub c, sup J) = l5R(sub J) for Jupiter and r(sub c, sup S) = 22R(sub S) for Saturn), and an optically thin, extended outer disk out to a fraction of the planet's Roche lobe, which we choose to be R(sub roche)/5 (located at approximately 150R(sub J) near the inner irregular satellites for Jupiter, and approximately 200R(sub S) near Phoebe for Saturn). This places Titan and Ganymede in the inner disk, Callisto and Iapetus in the outer disk, and Hyperion in the transition region. The inner disk is the leftover of the gas accreted by the protoplanet. The outer disk results from the solar torque on nebula gas flowing into the protoplanet during the time of giant planet gap opening. For the sake of specificity, we use a cosmic mixture 'minimum mass' model to constrain the gas densities of the inner disks of Jupiter and Saturn (and also Uranus). For the total mass of the outer disk we use the simple scaling M(sub disk) = M(sub P)tau(sub gap)/tau(sub acc), where M(sub P) is the mass of the giant planet, tau(sub gap) is the gap opening timescale, and tau(sub acc) is the giant planet accretion time. This gives a total outer disk mass of approximately 100M(sub Callisto) for Jupiter and possibly approximately 200M(sub Iapetus) for Saturn (which contain enough condensables to form Callisto and Iapetus respectively). Our model has Ganymede at a subnebula temperature of approximately 250 K and Titan at approximately 100 K. The outer disks of Jupiter and Saturn have constant temperatures of 130 K and 90 K respectively.

  7. The Need for Pediatric Formulations to Treat Children with HIV

    PubMed Central

    2016-01-01

    Over 3.2 million children worldwide are infected with HIV, but only 24% of these children receive antiretroviral therapy (ART). ART adherence among children is a crucial part of managing human-immunodeficiency virus (HIV) infection and extending the life and health of infected children. Important causes of poor adherence are formulation- and regimen-specific properties, including poor palatability, large pill burden, short dosing intervals, and the complex storage and transportation of drugs. This review aims to summarize the various regimen- and formulation-based barriers to ART adherence among children to support the need for new and innovative pediatric formulations for antiretroviral therapy (ART). Detailing the arguments both for and against investing in the development of pediatric HIV medications, as well as highlighting recent advances in pediatric ART formulation research, provides a synopsis of the current data related to pediatric ART formulations and adherence. PMID:27413548

  8. Extended general relativity: Large-scale antigravity and short-scale gravity with ω=-1 from five-dimensional vacuum

    NASA Astrophysics Data System (ADS)

    Madriz Aguilar, José Edgar; Bellini, Mauricio

    2009-08-01

    Considering a five-dimensional (5D) Riemannian spacetime with a particular stationary Ricci-flat metric, we obtain in the framework of the induced matter theory an effective 4D static and spherically symmetric metric which give us ordinary gravitational solutions on small (planetary and astrophysical) scales, but repulsive (anti gravitational) forces on very large (cosmological) scales with ω=-1. Our approach is an unified manner to describe dark energy, dark matter and ordinary matter. We illustrate the theory with two examples, the solar system and the great attractor. From the geometrical point of view, these results follow from the assumption that exists a confining force that make possible that test particles move on a given 4D hypersurface.

  9. Granulated decontamination formulations

    DOEpatents

    Tucker, Mark D.

    2007-10-02

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field.

  10. Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain

    PubMed Central

    Hale, Martin E; Laudadio, Charles; Yang, Ronghua; Narayana, Arvind; Malamut, Richard

    2015-01-01

    This double-blind, placebo-controlled study evaluated the efficacy and safety of hydrocodone extended release (ER) developed with abuse-deterrence technology to provide sustained pain relief and limit effects of alcohol and tablet manipulation on drug release. Eligible patients with chronic moderate-to-severe low back or osteoarthritis pain were titrated to an analgesic dose of hydrocodone ER (15–90 mg) and randomized to placebo or hydrocodone ER every 12 hours. The primary efficacy measure was change from baseline to week 12 in weekly average pain intensity (API; 0=no pain, 10=worst pain imaginable). Secondary measures included percentage of patients with >33% and >50% increases from baseline in weekly API, change from baseline in weekly worst pain intensity, supplemental opioid usage, aberrant drug-use behaviors, and adverse events. Overall, 294 patients were randomized and received ≥1 dose of placebo (n=148) or hydrocodone ER (n=146). Weekly API did not differ significantly between hydrocodone ER and placebo at week 12 (P=0.134); although, in post hoc analyses, the change in weekly API was significantly lower with hydrocodone ER when excluding the lowest dose (15 mg; least squares mean, −0.20 vs 0.40; P=0.032). Significantly more patients had >33% and >50% increase in weekly API with placebo (P<0.05), and mean weekly worst pain intensity was significantly lower with hydrocodone ER at week 12 (P=0.026). Supplemental medication usage was higher with placebo (86%) than hydrocodone ER (79%). Incidence of aberrant drug-use behaviors was low, and adverse events were similar between groups. This study did not meet the primary endpoint, although results support the effectiveness of this hydrocodone ER formulation in managing chronic low back or osteoarthritis pain. Use of the hydrocodone ER 15-mg dose, a robust placebo response, and use of supplemental analgesics, particularly in the placebo group, may have limited detection of a statistically significant

  11. A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone

    PubMed Central

    Kopecky, Ernest A.; Smith, Michael D.; Fleming, Alison B.

    2016-01-01

    Objective. Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein “DETERx”). Design. Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting. Clinical research site. Subjects. There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. Methods. The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx—administered as either a crushed intranasal (IN) or an intact oral (PO) preparation—with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control. Results. For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO (P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. Conclusions. Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested. PMID:26814256

  12. Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain.

    PubMed

    Hale, Martin E; Laudadio, Charles; Yang, Ronghua; Narayana, Arvind; Malamut, Richard

    2015-01-01

    This double-blind, placebo-controlled study evaluated the efficacy and safety of hydrocodone extended release (ER) developed with abuse-deterrence technology to provide sustained pain relief and limit effects of alcohol and tablet manipulation on drug release. Eligible patients with chronic moderate-to-severe low back or osteoarthritis pain were titrated to an analgesic dose of hydrocodone ER (15-90 mg) and randomized to placebo or hydrocodone ER every 12 hours. The primary efficacy measure was change from baseline to week 12 in weekly average pain intensity (API; 0=no pain, 10=worst pain imaginable). Secondary measures included percentage of patients with >33% and >50% increases from baseline in weekly API, change from baseline in weekly worst pain intensity, supplemental opioid usage, aberrant drug-use behaviors, and adverse events. Overall, 294 patients were randomized and received ≥1 dose of placebo (n=148) or hydrocodone ER (n=146). Weekly API did not differ significantly between hydrocodone ER and placebo at week 12 (P=0.134); although, in post hoc analyses, the change in weekly API was significantly lower with hydrocodone ER when excluding the lowest dose (15 mg; least squares mean, -0.20 vs 0.40; P=0.032). Significantly more patients had >33% and >50% increase in weekly API with placebo (P<0.05), and mean weekly worst pain intensity was significantly lower with hydrocodone ER at week 12 (P=0.026). Supplemental medication usage was higher with placebo (86%) than hydrocodone ER (79%). Incidence of aberrant drug-use behaviors was low, and adverse events were similar between groups. This study did not meet the primary endpoint, although results support the effectiveness of this hydrocodone ER formulation in managing chronic low back or osteoarthritis pain. Use of the hydrocodone ER 15-mg dose, a robust placebo response, and use of supplemental analgesics, particularly in the placebo group, may have limited detection of a statistically significant treatment

  13. A Hunter Patient with a Severe Phenotype Reveals Two Large Deletions and Two Duplications Extending 1.2 Mb Distally to IDS Locus.

    PubMed

    Zanetti, Alessandra; Tomanin, Rosella; Rampazzo, Angelica; Rigon, Chiara; Gasparotto, Nicoletta; Cassina, Matteo; Clementi, Maurizio; Scarpa, Maurizio

    2014-01-01

    Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is an X-linked lysosomal storage disorder caused by the deficit of iduronate 2-sulfatase (IDS), an enzyme involved in the glycosaminoglycans (GAGs) degradation. We here report the case of a 9-year-old boy who was diagnosed with an extremely severe form of MPS II at 10 months of age. Sequencing of the IDS gene revealed the deletion of exons 1-7, extending distally and removing the entire pseudogene IDSP1. The difficulty to define the boundaries of the deletion and the particular severity of the patient phenotype suggested to verify the presence of pathological copy number variations (CNVs) in the genome, by the array CGH (aCGH) technology. The examination revealed the presence of two deletions alternate with two duplications, overall affecting a region of about 1.2 Mb distally to IDS gene. This is the first complex rearrangement involving IDS and extending to a large region located distally to it described in a severe Hunter patient, as evidenced by the CNVs databases interrogated. The analysis of the genes involved in the rearrangement and of the disorders correlated with them did not help to clarify the phenotype observed in our patient, except for the deletion of the IDS gene, which explains per se the Hunter phenotype. However, this cannot exclude a potential "contiguous gene syndrome" as well as the future rising of additional pathological symptoms associated with the other extra genes involved in the identified rearrangement.

  14. A Numerical Combination of Extended Boundary Condition Method and Invariant Imbedding Method Applied to Light Scattering by Large Spheroids and Cylinders

    NASA Technical Reports Server (NTRS)

    Bi, Lei; Yang, Ping; Kattawar, George W.; Mishchenko, Michael I.

    2013-01-01

    The extended boundary condition method (EBCM) and invariant imbedding method (IIM) are two fundamentally different T-matrix methods for the solution of light scattering by nonspherical particles. The standard EBCM is very efficient but encounters a loss of precision when the particle size is large, the maximum size being sensitive to the particle aspect ratio. The IIM can be applied to particles in a relatively large size parameter range but requires extensive computational time due to the number of spherical layers in the particle volume discretization. A numerical combination of the EBCM and the IIM (hereafter, the EBCM+IIM) is proposed to overcome the aforementioned disadvantages of each method. Even though the EBCM can fail to obtain the T-matrix of a considered particle, it is valuable for decreasing the computational domain (i.e., the number of spherical layers) of the IIM by providing the initial T-matrix associated with an iterative procedure in the IIM. The EBCM+IIM is demonstrated to be more efficient than the IIM in obtaining the optical properties of large size parameter particles beyond the convergence limit of the EBCM. The numerical performance of the EBCM+IIM is illustrated through representative calculations in spheroidal and cylindrical particle cases.

  15. Extended BCDM

    NASA Astrophysics Data System (ADS)

    Occhionero, Franco; Baccigalupi, Carlo; Amendola, Luca

    1999-05-01

    We propose a new inflationary toy model that produces two episodes of phase transitions. With the first one, super-horizon-sized bubbles are nucleated, which are seen from inside as open universes, thereby reconciling inflation with the recent observations of a low Ω0. With the second transition, a distribution of sub-horizon voids, of sizes typically around 10-100 Mpc/h are generated inside the open universes. These primordial voids can be the seeds of the present large scale voids that are detected in redshift surveys, and provide a non-Gaussian signal on the microwave background. The model realizes this sequence along the same slow-rolling path, by modulating the energy difference between the vacuum states. In this model, that we call extended Bubbly CDM, openness and bubblyness, rather than flatness and homogeneity, are the main products of inflation.

  16. Cationic Lipid-Formulated DNA Vaccine against Hepatitis B Virus: Immunogenicity of MIDGE-Th1 Vectors Encoding Small and Large Surface Antigen in Comparison to a Licensed Protein Vaccine

    PubMed Central

    Endmann, Anne; Klünder, Katharina; Kapp, Kerstin; Riede, Oliver; Oswald, Detlef; Talman, Eduard G.; Schroff, Matthias; Kleuss, Christiane; Ruiters, Marcel H. J.; Juhls, Christiane

    2014-01-01

    Currently marketed vaccines against hepatitis B virus (HBV) based on the small (S) hepatitis B surface antigen (HBsAg) fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L) protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals. PMID:24992038

  17. Combining very large quadratic and cubic nonlinear optical responses in extended, tris-chelate metallochromophores with six pi-conjugated pyridinium substituents.

    PubMed

    Coe, Benjamin J; Fielden, John; Foxon, Simon P; Brunschwig, Bruce S; Asselberghs, Inge; Clays, Koen; Samoc, Anna; Samoc, Marek

    2010-03-17

    We describe a series of nine new complex salts in which electron-rich Ru(II) or Fe(II) centers are connected via pi-conjugated bridges to six electron-accepting N-methyl-/N-arylpyridinium groups. This work builds upon our previous preliminary studies (Coe , B. J. J. Am. Chem. Soc. 2005, 127, 13399-13410; J. Phys. Chem. A 2007, 111, 472-478), with the aims of achieving greatly enhanced NLO properties and also combining large quadratic and cubic effects in potentially redox-switchable molecules. Characterization has involved various techniques, including electronic absorption spectroscopy and cyclic voltammetry. The complexes display intense, visible d --> pi* metal-to-ligand charge-transfer (MLCT) bands, and their pi --> pi* intraligand charge-transfer (ILCT) absorptions in the near-UV region show molar extinction coefficients as high as ca. 3.5 x 10(5) M(-1) cm(-1). Molecular quadratic nonlinear optical (NLO) responses beta have been determined by using hyper-Rayleigh scattering at 800 and 1064 nm and also via Stark (electroabsorption) spectroscopic studies. The directly and indirectly derived beta values are very large, with the Stark-based static first hyperpolarizabilities beta(0) reaching as high as ca. 10(-27) esu, and generally increase on extending the pi-conjugation and enhancing the electron-accepting strength of the ligands. Cubic NLO properties have also been measured by using the Z-scan technique, revealing relatively high two-photon absorption cross sections of up to 2500 GM at 750 nm.

  18. Combining very large quadratic and cubic nonlinear optical responses in extended, tris-chelate metallochromophores with six pi-conjugated pyridinium substituents.

    PubMed

    Coe, Benjamin J; Fielden, John; Foxon, Simon P; Brunschwig, Bruce S; Asselberghs, Inge; Clays, Koen; Samoc, Anna; Samoc, Marek

    2010-03-17

    We describe a series of nine new complex salts in which electron-rich Ru(II) or Fe(II) centers are connected via pi-conjugated bridges to six electron-accepting N-methyl-/N-arylpyridinium groups. This work builds upon our previous preliminary studies (Coe , B. J. J. Am. Chem. Soc. 2005, 127, 13399-13410; J. Phys. Chem. A 2007, 111, 472-478), with the aims of achieving greatly enhanced NLO properties and also combining large quadratic and cubic effects in potentially redox-switchable molecules. Characterization has involved various techniques, including electronic absorption spectroscopy and cyclic voltammetry. The complexes display intense, visible d --> pi* metal-to-ligand charge-transfer (MLCT) bands, and their pi --> pi* intraligand charge-transfer (ILCT) absorptions in the near-UV region show molar extinction coefficients as high as ca. 3.5 x 10(5) M(-1) cm(-1). Molecular quadratic nonlinear optical (NLO) responses beta have been determined by using hyper-Rayleigh scattering at 800 and 1064 nm and also via Stark (electroabsorption) spectroscopic studies. The directly and indirectly derived beta values are very large, with the Stark-based static first hyperpolarizabilities beta(0) reaching as high as ca. 10(-27) esu, and generally increase on extending the pi-conjugation and enhancing the electron-accepting strength of the ligands. Cubic NLO properties have also been measured by using the Z-scan technique, revealing relatively high two-photon absorption cross sections of up to 2500 GM at 750 nm. PMID:20166735

  19. A three-dimensional, extended field of view ultrasound method for estimating large strain mechanical properties of the cervix during pregnancy

    PubMed Central

    House, Michael; Feltovich, Helen; Hall, Timothy J; Stack, Trevor; Patel, Atur; Socrate, Simona

    2015-01-01

    Cervical shortening and cervical insufficiency contribute to a significant number of preterm births. However, the deformation mechanisms that control how the cervix changes its shape from long and closed to short and dilated are not clear. Investigation of the biomechanical problem is limited by 1) lack of thorough characterization of the three-dimensional anatomical changes associated with cervical deformation and 2) difficulty measuring cervical tissue properties in vivo. The objective of the present study was to explore the feasibility of using three-dimensional ultrasound and fundal pressure to obtain anatomically accurate numerical models of large-strain cervical deformation during pregnancy and enable non-invasive assessment of cervical tissue compliance. Healthy subjects (n=6) and one subject with acute cervical insufficiency in the midtrimester were studied. Extended field of view ultrasound images were obtained of the entire uterus and cervix. These images aided construction of anatomically accurate numerical models. Cervical loading was achieved with fundal pressure, which was quantified with a vaginal pressure catheter. In one subject, the anatomical response to fundal pressure was matched by a model-based simulation of the deformation response, thereby deriving the corresponding cervical mechanical properties and showing the feasibility of non-invasive assessment of compliance. The results of this pilot study demonstrate the feasibility of a biomechanical modeling framework for estimating cervical mechanical properties in vivo. An improved understanding of cervical biomechanical function will clarify the pathophysiology of cervical shortening. PMID:22655487

  20. Epidemiology and risk factors for isolation of Escherichia coli producing CTX-M-type extended-spectrum β-lactamase in a large U.S. Medical Center.

    PubMed

    Hayakawa, Kayoko; Gattu, Sureka; Marchaim, Dror; Bhargava, Ashish; Palla, Mohan; Alshabani, Khaled; Gudur, Uma Mahesh; Pulluru, Harish; Bathina, Pradeep; Sundaragiri, Pranathi Rao; Sarkar, Moumita; Kakarlapudi, Hari; Ramasamy, Balaji; Nanjireddy, Priyanka; Mohin, Shah; Dasagi, Meenakshi; Datla, Satya; Kuchipudi, Vamsi; Reddy, Swetha; Shahani, Shobha; Upputuri, Vijaya; Marrey, Satya; Gannamani, Vedavyas; Madhanagopal, Nandhini; Annangi, Srinadh; Sudha, Busani; Muppavarapu, Kalyan Srinivas; Moshos, Judy A; Lephart, Paul R; Pogue, Jason M; Bush, Karen; Kaye, Keith S

    2013-08-01

    A case-case-control study was conducted to identify independent risk factors for recovery of Escherichia coli strains producing CTX-M-type extended-spectrum β-lactamases (CTX-M E. coli) within a large Southeastern Michigan medical center. Unique cases with isolation of ESBL-producing E. coli from February 2010 through July 2011 were analyzed by PCR for blaCTX-M, blaTEM, and blaSHV genes. Patients with CTX-M E. coli were compared to patients with E. coli strains not producing CTX-M-type ESBLs (non-CTX-M E. coli) and uninfected controls. Of 575 patients with ESBL-producing E. coli, 491 (85.4%) isolates contained a CTX-M ESBL gene. A total of 319 (84.6%) patients with CTX-M E. coli (282 [74.8%] CTX-M-15 type) were compared to 58 (15.4%) non-CTX-M E. coli patients and to uninfected controls. Independent risk factors for CTX-M E. coli isolation compared to non-CTX-M E. coli included male gender, impaired consciousness, H2 blocker use, immunosuppression, and exposure to penicillins and/or trimethoprim-sulfamethoxazole. Compared to uninfected controls, independent risk factors for isolation of CTX-M E. coli included presence of a urinary catheter, previous urinary tract infection, exposure to oxyimino-cephalosporins, dependent functional status, non-home residence, and multiple comorbid conditions. Within 48 h of admission, community-acquired CTX-M E. coli (n = 51 [16%]) and non-CTX-M E coli (n = 11 [19%]) strains were isolated from patients with no recent health care contacts. CTX-M E. coli strains were more resistant to multiple antibiotics than non-CTX-M E. coli strains. CTX-M-encoding genes, especially bla(CTX-M-15) type, represented the most common ESBL determinants from ESBL-producing E. coli, the majority of which were present upon admission. Septic patients with risk factors for isolation of CTX-M E. coli should be empirically treated with appropriate agents. Regional infection control efforts and judicious antibiotic use are needed to control the spread of these

  1. Epidemiology and Risk Factors for Isolation of Escherichia coli Producing CTX-M-Type Extended-Spectrum β-Lactamase in a Large U.S. Medical Center

    PubMed Central

    Gattu, Sureka; Marchaim, Dror; Bhargava, Ashish; Palla, Mohan; Alshabani, Khaled; Gudur, Uma Mahesh; Pulluru, Harish; Bathina, Pradeep; Sundaragiri, Pranathi Rao; Sarkar, Moumita; Kakarlapudi, Hari; Ramasamy, Balaji; Nanjireddy, Priyanka; Mohin, Shah; Dasagi, Meenakshi; Datla, Satya; Kuchipudi, Vamsi; Reddy, Swetha; Shahani, Shobha; Upputuri, Vijaya; Marrey, Satya; Gannamani, Vedavyas; Madhanagopal, Nandhini; Annangi, Srinadh; Sudha, Busani; Muppavarapu, Kalyan Srinivas; Moshos, Judy A.; Lephart, Paul R.; Pogue, Jason M.; Bush, Karen; Kaye, Keith S.

    2013-01-01

    A case-case-control study was conducted to identify independent risk factors for recovery of Escherichia coli strains producing CTX-M-type extended-spectrum β-lactamases (CTX-M E. coli) within a large Southeastern Michigan medical center. Unique cases with isolation of ESBL-producing E. coli from February 2010 through July 2011 were analyzed by PCR for blaCTX-M, blaTEM, and blaSHV genes. Patients with CTX-M E. coli were compared to patients with E. coli strains not producing CTX-M-type ESBLs (non-CTX-M E. coli) and uninfected controls. Of 575 patients with ESBL-producing E. coli, 491 (85.4%) isolates contained a CTX-M ESBL gene. A total of 319 (84.6%) patients with CTX-M E. coli (282 [74.8%] CTX-M-15 type) were compared to 58 (15.4%) non-CTX-M E. coli patients and to uninfected controls. Independent risk factors for CTX-M E. coli isolation compared to non-CTX-M E. coli included male gender, impaired consciousness, H2 blocker use, immunosuppression, and exposure to penicillins and/or trimethoprim-sulfamethoxazole. Compared to uninfected controls, independent risk factors for isolation of CTX-M E. coli included presence of a urinary catheter, previous urinary tract infection, exposure to oxyimino-cephalosporins, dependent functional status, non-home residence, and multiple comorbid conditions. Within 48 h of admission, community-acquired CTX-M E. coli (n = 51 [16%]) and non-CTX-M E coli (n = 11 [19%]) strains were isolated from patients with no recent health care contacts. CTX-M E. coli strains were more resistant to multiple antibiotics than non-CTX-M E. coli strains. CTX-M-encoding genes, especially blaCTX-M-15 type, represented the most common ESBL determinants from ESBL-producing E. coli, the majority of which were present upon admission. Septic patients with risk factors for isolation of CTX-M E. coli should be empirically treated with appropriate agents. Regional infection control efforts and judicious antibiotic use are needed to control the spread of these

  2. The Parallelized Large-Eddy Simulation Model (PALM) version 4.0 for atmospheric and oceanic flows: model formulation, recent developments, and future perspectives

    NASA Astrophysics Data System (ADS)

    Maronga, B.; Gryschka, M.; Heinze, R.; Hoffmann, F.; Kanani-Sühring, F.; Keck, M.; Ketelsen, K.; Letzel, M. O.; Sühring, M.; Raasch, S.

    2015-02-01

    In this paper we present the current version of the Parallelized Large-Eddy Simulation Model (PALM) whose core has been developed at the Institute of Meteorology and Climatology at Leibniz Universität Hannover (Germany). PALM is a Fortran 95-based code with some Fortran 2003 extensions and has been applied for the simulation of a variety of atmospheric and oceanic boundary layers for more than 15 years. PALM is optimized for use on massively parallel computer architectures and was recently ported to general-purpose graphics processing units. In the present paper we give a detailed description of the current version of the model and its features, such as an embedded Lagrangian cloud model and the possibility to use Cartesian topography. Moreover, we discuss recent model developments and future perspectives for LES applications.

  3. The Parallelized Large-Eddy Simulation Model (PALM) version 4.0 for atmospheric and oceanic flows: model formulation, recent developments, and future perspectives

    NASA Astrophysics Data System (ADS)

    Maronga, B.; Gryschka, M.; Heinze, R.; Hoffmann, F.; Kanani-Sühring, F.; Keck, M.; Ketelsen, K.; Letzel, M. O.; Sühring, M.; Raasch, S.

    2015-08-01

    In this paper we present the current version of the Parallelized Large-Eddy Simulation Model (PALM) whose core has been developed at the Institute of Meteorology and Climatology at Leibniz Universität Hannover (Germany). PALM is a Fortran 95-based code with some Fortran 2003 extensions and has been applied for the simulation of a variety of atmospheric and oceanic boundary layers for more than 15 years. PALM is optimized for use on massively parallel computer architectures and was recently ported to general-purpose graphics processing units. In the present paper we give a detailed description of the current version of the model and its features, such as an embedded Lagrangian cloud model and the possibility to use Cartesian topography. Moreover, we discuss recent model developments and future perspectives for LES applications.

  4. Decontamination formulation with sorbent additive

    DOEpatents

    Tucker; Mark D. , Comstock; Robert H.

    2007-10-16

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a bleaching activator, a sorbent additive, and water. The highly adsorbent, water-soluble sorbent additive (e.g., sorbitol or mannitol) is used to "dry out" one or more liquid ingredients, such as the liquid bleaching activator (e.g., propylene glycol diacetate or glycerol diacetate) and convert the activator into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field.

  5. A large βzzz of π-extended molecules tetra-substituted by meta-positioned donor-acceptor pairs

    NASA Astrophysics Data System (ADS)

    Tomonari, Mutsumi; Ookubo, Norio

    2003-07-01

    We computationally studied hyperpolarizability β of C 2v fused-ring molecules substituted by two pairs of meta- or para-positioned donor (D)-acceptor (A). In two types of meta-substituted isomers, the meta1-type showed small βzzz, being plausible since the meta-positioned D-A pairs indicated the resonance structures not preferable for the large charge transfer (CT). Nevertheless, the meta2-type showed a large βzzz resulting from a large forward CT associated with the HOMO-LUMO transition. This βzzz increased with the number of fused-rings (the x-extension) and decreased slightly with small structural changes by the geometry optimization, but these changes did not vary the dominant CT structure. The x-extension was ineffective to the large βzzz for the para-substituted isomer.

  6. Indications for Pelvic Nodal Treatment in Prostate Cancer Should Change. Validation of the Roach Formula in a Large Extended Nodal Dissection Series

    SciTech Connect

    Abdollah, Firas; Cozzarini, Cesare; Suardi, Nazareno; Gallina, Andrea; Capitanio, Umberto; Bianchi, Marco; Tutolo, Manuela; Salonia, Andrea; La Macchia, Mariangela; Di Muzio, Nadia; Rigatti, Patrizio; Montorsi, Francesco; Briganti, Alberto

    2012-06-01

    Purpose: Previous studies have criticized the predicting ability of the Roach formula in assessing the risk of lymph node invasion (LNI) in contemporary patients with prostate cancer (PCa) due to a significant overestimation of LNI rates. However, all those studies included patients treated with limited pelvic lymph node dissection (PLND), which is associated with high rates of false negative findings. We hypothesized that the Roach formula is still an accurate tool for LNI predictions if an extended PLND (ePLND) is performed. Methods and Materials: We included 3,115 consecutive patients treated with radical prostatectomy and ePLND between 2000 and 2010 at a single tertiary referral center. Extended PLND consisted of removal of obturator, external iliac, and hypogastric lymph nodes. We externally validated the Roach formula by using the area under the receiver operating characteristics curve and calibration plot method. Moreover, we tested the performance characteristics of different formula-generated cutoff values ranging from 1% to 20%. Results: The accuracy of the Roach formula was 80.3%. The calibration showed only a minor underestimation of the LNI risk in high-risk patients (6.7%). According to the Roach formula, the use of 15% cut off would have allowed 74.2% (2,311/3,115) of patients to avoid nodal irradiation, while up to 32.7% (111/336) of all patients with LNI would have been missed. When the cut off was lowered to 6%, nodal treatment would have been spared in 1,541 (49.5%) patients while missing 41 LNI patients. The sensitivity, specificity, and negative predictive values associated with the 6% cut off were 87.9%, 54%, and 97.3%, respectively. Conclusions: The Roach formula is still accurate and does not overestimate the rate of LNI in contemporary prostate cancer patients if they are treated with ePLND. However, the recommended cut off of 15% would miss approximately one-third of patients with LNI. Based on our results, the cut off should be lowered to

  7. Large retroperitoneal abscess extended to the inferior right limb secondary to a perforated ileal Crohn’s disease: the importance of the multidisciplinary approach

    PubMed Central

    MASCOLINO, A.; SCERRINO, G.; GULLO, R.; GENOVA, C.; MELFA, G.I.; RASPANTI, C.; FONTANA, T.; FALCO, N.; PORRELLO, C.; GULOTTA, G.

    2016-01-01

    The typical complications of Crohn’s disease concerns small and large bowel. The full thickness inflammation of the intestinal wall develops in strictures, fistulas and abdominal abscesses. Nowadays the most accepted therapeutic for intra-abdominal abscess option is antibiotic therapy and, in case of need, percutaneous drainage of the abscess. If the abscess passes through the pelvic foramen the abscess can involve the inferior limbs. We report a case a perforation of terminal ileum in Crohn’s disease complicated by a large abscess of the right iliac fossa reaching the spaces between the anterior lateral muscles of the right thigh as far as the anterior lateral pre-tibial region. We discuss the diagnostic and therapeutic options in a multidisciplinary context. PMID:27142824

  8. An Extended Duopoly Game.

    ERIC Educational Resources Information Center

    Eckalbar, John C.

    2002-01-01

    Illustrates how principles and intermediate microeconomic students can gain an understanding for strategic price setting by playing a relatively large oligopoly game. Explains that the game extends to a continuous price space and outlines appropriate applications. Offers the Mathematica code to instructors so that the assumptions of the game can…

  9. Towards Extended Vantage Theory

    ERIC Educational Resources Information Center

    Glaz, Adam

    2010-01-01

    The applicability of Vantage Theory (VT), a model of (colour) categorization, to linguistic data largely depends on the modifications and adaptations of the model for the purpose. An attempt to do so proposed here, called Extended Vantage Theory (EVT), slightly reformulates the VT conception of vantage by capitalizing on some of the entailments of…

  10. Susceptibility of different developmental stages of large pine weevil Hylobius abietis (Coleoptera: Curculionidae) to entomopathogenic fungi and effect of fungal infection to adult weevils by formulation and application methods.

    PubMed

    Ansari, Minshad A; Butt, Tariq M

    2012-09-15

    The large pine weevil, Hylobius abietis, is a major pest in European conifer forests causing millions of Euros of damage annually. Larvae develop in the stumps of recently felled trees; the emerging adults feed on the bark of seedlings and may kill them. This study investigated the susceptibility of different developmental stages of H. abietis to commercial and commercially viable isolates of entomopathogenic fungi, Metarhizium and Beauveria. All the developmental stages of H. abietis can be killed by Metarhizium robertsii, Metarhizium brunneum, and Beauveria bassiana. The most virulent isolate of M. robertsii ARSEF4556 caused 100% mortality of pupae, larvae and adults on day 4, 6 and 12, respectively. This strain was further tested against adult weevils in different concentrations (10(5)-10(8) conidia cm(-2) or ml(-1)) using two types of fungal formulation: 'dry' conidia and 'wet' conidia (suspended in 0.03% aq. Tween 80) applied on different substrates (tissue paper, peat and Sitka spruce seedlings). 'Dry' conidia were more effective than 'wet' conidia on tissue paper and on spruce or 'dry' conidia premixed in peat. The LC(50) value for 'dry' conidia of isolate ARSEF4556 was three folds lower than 'wet' conidia on tissue paper. This study showed that 'dry' conidia are more effective than 'wet' conidia, causing 100% adult mortality within 12 days. Possible strategies for fungal applications are discussed in light of the high susceptibility of larvae and pupae to fungal pathogen.

  11. Storage characteristics, nutritive value, and fermentation characteristics of alfalfa packaged in large-round bales and wrapped in stretch film after extended time delays.

    PubMed

    Coblentz, W K; Coffey, K P; Chow, E A

    2016-05-01

    The production of baled silage is attractive to producers because it offers advantages over dry hay, particularly by limiting risks associated with wet or unstable weather conditions. Our objectives were to test the effects of delayed wrapping on silage fermentation, storage characteristics, and the nutritive value of baled alfalfa silages. To accomplish this, large-round bales of alfalfa were wrapped in plastic film within 4h of baling (d 0), or after delays of 1, 2, or 3 d. A secondary objective was to evaluate a prototype bale wrap containing an O2-limiting barrier (OB) against an identical polyethylene wrap without the O2 barrier (SUN). Sixty-four 1.19×1.25-m bales of alfalfa were made from 4 field blocks at a mean moisture concentration of 59.1±4.3% with a mean initial wet bale weight of 473±26.4kg. Two bales per field block were assigned to each combination of bale wrap (SUN or OB) and wrapping time (0, 1, 2, or 3 d postbaling), and one bale of each pair was fitted with a thermocouple placed in the geometric center of each bale. All bales were sampled after a 97-d storage period. Internal bale temperatures, recorded at the time bales were wrapped, were greater for all bales with wrapping delays compared with bales wrapped on d 0 (54.9 vs. 34.9°C), and increased to a maximum of 63.9°C after a 3-d delay exhibiting a linear effect of time delay. Total silage fermentation acids (lactic, acetic, propionic, butyric, and isobutyric) were greatest when bales were wrapped on d 0 compared with all bales wrapped with time delays (4.64 vs. 2.26% of DM), and declined with linear and quadratic effects of wrapping delay. Total fermentation acids also were related quadratically to internal bale temperature by regression [y (% of DM)=0.0042x(2) - 0.50x + 17.1; R(2)=0.725]. Similar responses were observed for lactic acid, except that trends were linear, both for orthogonal contrasts evaluating length of wrapping delay, and in regressions on internal bale temperature [y

  12. The Extended Mind: Coupling Environment and Brain

    NASA Astrophysics Data System (ADS)

    Vrobel, Susie

    2010-11-01

    This paper describes embodiment and cognitive extension as examples of strong anticipation as defined by Dubois. Clark and Chalmers formulated a thesis which states that parts of the environment, if coupled successfully, can become part of the extended mind. This coupling, be it deliberate or unintentional, shifts the observer-world boundary outwards when the observer encompasses parts of his environment. The resulting extended observer forms a new systemic whole, which consists of both the assimilated context and the recalibrated version of the original observer. Recalibration occurs when conditioning and adaptation lead to corresponding changes on the neural level, for instance, when an agent compensates for delays in a control loop. Plasticity is a prerequisite for any successful incorporation of external structures. However, uncoupled parts of the observer must remain inviolate in order to preserve the boundary. Neither the extended mind nor the core observer are absolute concepts. Depending on whether we focus on local-scale interactions or on large-scale behaviour, boundaries are formed at different interfacial cuts, which lead to either an endo- or an exo-perspective or endo- or exo-anticipation, respectively. For biological extended agents which undergo a transition from exo- to endo-states, a tell-tale sign of a successful exo-endo transition is invisibility. This invisibility occurs when the agent is no longer aware of the delay originally introduced into the control loop by the assimilated part of the environment. Explaining the world in terms of effective causality is not sufficient to account for extended minds. The latter require explanations in terms of final causation. For extended minds, this ordering principle comes in the shape of nested hierarchical layers. The interfaces of these layers may have merged for an endo-observer, whereas an exo-observer can make out the detailed structure, including artificially introduced delays. A sufficient

  13. Formulation of Nematodes.

    PubMed

    Peters, Arne

    2016-01-01

    The enduring stages of entomopathogenic nematodes of the genera Steinernema and Heterorhabditis are infective juveniles, which require a high humidity and sufficient ventilation for survival. Formulations must account for these requirements. Nematodes may be formulated inside the insects in which they reproduced or they need to be cleaned and mixed with a suitable binder to maintain humidity but allowing for gas exchange. Another method for formulation is the encapsulation in beads of Ca-alginate. Generic procedures for these formulation techniques are described. PMID:27565496

  14. Psychiatrists' use of formulation

    PubMed Central

    Hughes, Patricia M.

    2016-01-01

    Both psychologists and psychiatrists are trained to write formulations of their patients' illnesses, with some differences in how they do this. Psychologists focus on psychological understanding, while psychiatrists' formulation brings together aetiology, functioning and a management plan. Mohtashemi et al's study records how some psychiatrists understand formulation and its usefulness. Time pressure was an important barrier to making a full formulation, and some believed the medical role of the psychiatrist was a priority. The study illustrates some of the challenges facing psychiatrists working in the NHS in terms of maintaining high clinical standards and a holistic approach to patient care. PMID:27512593

  15. Formulation to Enhance the Insecticidal Activity of Entomopathogenic Nematodes for Control of Insect Pests of Orchards

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Extended shelf life and rapid dispersion of entomopathogenic nematode (EPN) infective juveniles (IJs) in spray suspensions were the principal objectives of earlier EPN formulation development. Subsequently, formulation of EPNs for enhanced insecticidal control in greenhouses and field has been inves...

  16. Topological vs Global Penalty Formulations for Real-Time Flexible Multibody Dynamics

    NASA Astrophysics Data System (ADS)

    Cuadrado, Javier; Lugrís, Urbano; Dopico, Daniel; González, Manuel

    The simulation of flexible multibody systems is a very demanding task that needs improvements in efficiency in order to achieve real-time performance. One of the possible improvements may be the use of topological formulations, which have provided good results in the simulation of large rigid multibody systems. In this work, a topological formulation for rigid bodies is extended to the flexible case, and tests are carried out in order to compare its performance with that of a global formulation. Two systems are simulated, a double four-bar mechanism and a vehicle suspension. As it happened in the rigid case for these two examples, the topological formulation shows lower performance than its global counterpart for such small systems, but the difference decreases as more bodies are modeled as flexible. Since in the rigid case the topological formulation became faster for large systems, further tests must be performed in order to check whether this advantage is kept or even increased in the flexible case.

  17. Audits of radiopharmaceutical formulations

    SciTech Connect

    Castronovo, F.P. Jr. )

    1992-03-01

    A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expert knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team.

  18. Formulation of natural shampoos.

    PubMed

    Mainkar, A R; Jolly, C I

    2001-02-01

    Formulating cosmetics using completely natural raw materials is a difficult task. The challenge lies in selecting materials that can be rationally justified as 'natural' and formulating them into cosmetics whose functionality is comparable with their synthetic counterparts. The present paper focuses on the formulation of completely natural shampoos, their evaluation and comparison with commercial herbal shampoos. Attention is drawn to the fact that, due to the ambiguous definition of the word 'natural', several so-called natural cosmetics are available in the Indian market. It is up to the cosmetic chemists themselves to promote and encourage the development and use of truly natural cosmetics.

  19. Reactive decontamination formulation

    DOEpatents

    Giletto, Anthony; White, William; Cisar, Alan J.; Hitchens, G. Duncan; Fyffe, James

    2003-05-27

    The present invention provides a universal decontamination formulation and method for detoxifying chemical warfare agents (CWA's) and biological warfare agents (BWA's) without producing any toxic by-products, as well as, decontaminating surfaces that have come into contact with these agents. The formulation includes a sorbent material or gel, a peroxide source, a peroxide activator, and a compound containing a mixture of KHSO.sub.5, KHSO.sub.4 and K.sub.2 SO.sub.4. The formulation is self-decontaminating and once dried can easily be wiped from the surface being decontaminated. A method for decontaminating a surface exposed to chemical or biological agents is also disclosed.

  20. Hamiltonian dynamics of extended objects

    NASA Astrophysics Data System (ADS)

    Capovilla, R.; Guven, J.; Rojas, E.

    2004-12-01

    We consider relativistic extended objects described by a reparametrization-invariant local action that depends on the extrinsic curvature of the worldvolume swept out by the object as it evolves. We provide a Hamiltonian formulation of the dynamics of such higher derivative models which is motivated by the ADM formulation of general relativity. The canonical momenta are identified by looking at boundary behaviour under small deformations of the action; the relationship between the momentum conjugate to the embedding functions and the conserved momentum density is established. The canonical Hamiltonian is constructed explicitly; the constraints on the phase space, both primary and secondary, are identified and the role they play in the theory is described. The multipliers implementing the primary constraints are identified in terms of the ADM lapse and shift variables and Hamilton's equations are shown to be consistent with the Euler Lagrange equations.

  1. Extended service 5w-40 motor oil

    SciTech Connect

    Schiemen, R.D.

    1983-09-06

    An extended drain 5W-40 motor oil composition for internal combustion engines comprises a base oil component of one or more solvent extracted mineral oils and a high refractory mineral oil, a V.I. improver, and preferably other suitable lube oil additives. The finished oil formulation has characteristics of minimal viscosity at low temperatures, low volatility at higher temperatures, and stable viscosity over extended use.

  2. Topological defects in extended inflation

    NASA Technical Reports Server (NTRS)

    Copeland, Edmund J.; Kolb, Edward W.; Liddle, Andrew R.

    1990-01-01

    The production of topological defects, especially cosmic strings, in extended inflation models was considered. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of bubbles when they collide. This mechanism allows a natural combination of inflation and large scale structure via cosmic strings.

  3. CONSIDERATIONS FOR GROUT FORMULATIONS FOR FACILITY CLOSURES USING IN SITU STRATEGIES

    SciTech Connect

    Gladden, J.; Serrato, M.; Langton, C.; Long, T.; Blankenship, J.; Hannah, G.; Stubblefield, R.; Szilagyi, A.

    2010-08-25

    The U.S. Department of Energy (DOE) is conducting in situ closures (entombment) at a large number of facilities throughout the complex. Among the largest closure actions currently underway are the closures of the P and R Reactors at the Savannah River Site (SRS), near Aiken, South Carolina. In these facilities, subgrade open spaces are being stabilized with grout; this ensures the long term structural integrity of the facilities and permanently immobilizes and isolates residual contamination. The large size and structural complexity of these facilities present a wide variety of challenges for the identification and selection of appropriate fill materials. Considerations for grout formulations must account for flowability, long term stability, set times, heat generation and interactions with materials within the structure. The large size and configuration of the facility necessitates that grout must be pumped from the exterior to the spaces to be filled, which requires that the material must retain a high degree of flowability to move through piping without clogging while achieving the required leveling properties at the pour site. Set times and curing properties must be controlled to meet operations schedules, while not generating sufficient heat to compromise the properties of the fill material. The properties of residual materials can result in additional requirements for grout formulations. If significant quantities of aluminum are present in the facility, common formulations of highly alkaline grouts may not be appropriate because of the potential for hydrogen generation with the resultant risks. SRS is developing specialized inorganic grout formulations that are designed to address this issue. One circum-neutral chemical grout formulation identified for initial consideration did not possess the proper chemical characteristics, having exceptionally short set times and high heat of hydration. Research efforts are directed toward developing grout formulations

  4. Advanced protein formulations.

    PubMed

    Wang, Wei

    2015-07-01

    It is well recognized that protein product development is far more challenging than that for small-molecule drugs. The major challenges include inherent sensitivity to different types of stresses during the drug product manufacturing process, high rate of physical and chemical degradation during long-term storage, and enhanced aggregation and/or viscosity at high protein concentrations. In the past decade, many novel formulation concepts and technologies have been or are being developed to address these product development challenges for proteins. These concepts and technologies include use of uncommon/combination of formulation stabilizers, conjugation or fusion with potential stabilizers, site-specific mutagenesis, and preparation of nontraditional types of dosage forms-semiaqueous solutions, nonfreeze-dried solid formulations, suspensions, and other emerging concepts. No one technology appears to be mature, ideal, and/or adequate to address all the challenges. These gaps will likely remain in the foreseeable future and need significant efforts for ultimate resolution.

  5. Advanced protein formulations

    PubMed Central

    Wang, Wei

    2015-01-01

    It is well recognized that protein product development is far more challenging than that for small-molecule drugs. The major challenges include inherent sensitivity to different types of stresses during the drug product manufacturing process, high rate of physical and chemical degradation during long-term storage, and enhanced aggregation and/or viscosity at high protein concentrations. In the past decade, many novel formulation concepts and technologies have been or are being developed to address these product development challenges for proteins. These concepts and technologies include use of uncommon/combination of formulation stabilizers, conjugation or fusion with potential stabilizers, site-specific mutagenesis, and preparation of nontraditional types of dosage forms—semiaqueous solutions, nonfreeze-dried solid formulations, suspensions, and other emerging concepts. No one technology appears to be mature, ideal, and/or adequate to address all the challenges. These gaps will likely remain in the foreseeable future and need significant efforts for ultimate resolution. PMID:25858529

  6. Formulation of Automotive Lubricants

    NASA Astrophysics Data System (ADS)

    Atkinson, D.; Brown, A. J.; Jilbert, D.; Lamb, G.

    The formulation of lubricants for current light- and heavy-duty vehicles (passenger cars and trucks) and also motorcycles/small engines is described in terms of engine types and meeting European, US and Japanese emission control requirements. Trends in the formulation of lubricants are discussed and the importance of high and low 'SAPS' for future developments emphasised. Specification and evaluation of lubricant performance for light-vehicle gasoline and diesel, and also heavy-duty diesel engines are described. Emphasis is given to diesel engine cleanliness by soot and deposit control and the effect of emission controls on lubricant formulation. The lubricant requirements for motorcycle and small engines, primarily two-stroke cycle, and their specifications are described.

  7. Effects of formulation design on niacin therapeutics: mechanism of action, metabolism, and drug delivery.

    PubMed

    Cooper, Dustin L; Murrell, Derek E; Roane, David S; Harirforoosh, Sam

    2015-07-25

    Niacin is a highly effective, lipid regulating drug associated with a number of metabolically induced side effects such as prostaglandin (PG) mediated flushing and hepatic toxicity. In an attempt to reduce the development of these adverse effects, scientists have investigated differing methods of niacin delivery designed to control drug release and alter metabolism. However, despite successful formulation of various orally based capsule and tablet delivery systems, patient adherence to niacin therapy is still compromised by adverse events such as PG-induced flushing. While the primary advantage of orally dosed formulations is ease of use, alternative delivery options such as transdermal delivery or polymeric micro/nanoparticle encapsulation for oral administration have shown promise in niacin reformulation. However, the effectiveness of these alternative delivery options in reducing inimical effects of niacin and maintaining drug efficacy is still largely unknown and requires more in-depth investigation. In this paper, we present an overview of niacin applications, its metabolic pathways, and current drug delivery formulations. Focus is placed on oral immediate, sustained, and extended release niacin delivery as well as combined statin and/or prostaglandin antagonist niacin formulation. We also examine and discuss current findings involving transdermal niacin formulations and polymeric micro/nanoparticle encapsulated niacin delivery.

  8. Extended Hamiltonian approach to continuous tempering

    NASA Astrophysics Data System (ADS)

    Gobbo, Gianpaolo; Leimkuhler, Benedict J.

    2015-06-01

    We introduce an enhanced sampling simulation technique based on continuous tempering, i.e., on continuously varying the temperature of the system under investigation. Our approach is mathematically straightforward, being based on an extended Hamiltonian formulation in which an auxiliary degree of freedom, determining the effective temperature, is coupled to the physical system. The physical system and its temperature evolve continuously in time according to the equations of motion derived from the extended Hamiltonian. Due to the Hamiltonian structure, it is easy to show that a particular subset of the configurations of the extended system is distributed according to the canonical ensemble for the physical system at the correct physical temperature.

  9. Ising formulations of many NP problems

    NASA Astrophysics Data System (ADS)

    Lucas, Andrew

    2014-02-01

    We provide Ising formulations for many NP-complete and NP-hard problems, including all of Karp's 21 NP-complete problems. This collects and extends mappings to the Ising model from partitioning, covering and satisfiability. In each case, the required number of spins is at most cubic in the size of the problem. This work may be useful in designing adiabatic quantum optimization algorithms.

  10. Second-quantized formulation of geometric phases

    SciTech Connect

    Deguchi, Shinichi; Fujikawa, Kazuo

    2005-07-15

    The level crossing problem and associated geometric terms are neatly formulated by the second-quantized formulation. This formulation exhibits a hidden local gauge symmetry related to the arbitrariness of the phase choice of the complete orthonormal basis set. By using this second-quantized formulation, which does not assume adiabatic approximation, a convenient exact formula for the geometric terms including off-diagonal geometric terms is derived. The analysis of geometric phases is then reduced to a simple diagonalization of the Hamiltonian, and it is analyzed both in the operator and path-integral formulations. If one diagonalizes the geometric terms in the infinitesimal neighborhood of level crossing, the geometric phases become trivial (and thus no monopole singularity) for arbitrarily large but finite time interval T. The integrability of Schroedinger equation and the appearance of the seemingly nonintegrable phases are thus consistent. The topological proof of the Longuet-Higgins' phase-change rule, for example, fails in the practical Born-Oppenheimer approximation where a large but finite ratio of two time scales is involved and T is identified with the period of the slower system. The difference and similarity between the geometric phases associated with level crossing and the exact topological object such as the Aharonov-Bohm phase become clear in the present formulation. A crucial difference between the quantum anomaly and the geometric phases is also noted.

  11. Extended-release hydrocodone (Hysingla ER) for pain.

    PubMed

    2015-05-11

    Hysingla ER, the second single-ingredient extended-release hydrocodone product to become available in the US, is formulated for once-daily use. Zohydro ER is dosed twice daily and costs more. Both Hysingla ER and the new formulation of Zohydro ER have abuse-deterrent properties, but they will still be subject to misuse. PMID:25941956

  12. Applications of a quadratic extended interior penalty function for structural optimization

    NASA Technical Reports Server (NTRS)

    Haftka, R. T.; Starnes, J. H., Jr.

    1975-01-01

    A quadratic extended interior penalty function formulation especially well suited for second-order unconstrained optimization procedures is presented. Analytical derivatives of constraints and an approximate analysis technique are used. Minimum-mass design results are presented which indicate that the combination of these procedures can help make mathematical programming a useful optimization tool for large-order structural design problems with a large number of design variables and multiple constraints. Examples include statically loaded high- and low-aspect-ratio wings simultaneously subjected to stress, displacement, minimum gage and, in some cases, maximum strain constraints.

  13. Large deviations and portfolio optimization

    NASA Astrophysics Data System (ADS)

    Sornette, Didier

    Risk control and optimal diversification constitute a major focus in the finance and insurance industries as well as, more or less consciously, in our everyday life. We present a discussion of the characterization of risks and of the optimization of portfolios that starts from a simple illustrative model and ends by a general functional integral formulation. A major item is that risk, usually thought of as one-dimensional in the conventional mean-variance approach, has to be addressed by the full distribution of losses. Furthermore, the time-horizon of the investment is shown to play a major role. We show the importance of accounting for large fluctuations and use the theory of Cramér for large deviations in this context. We first treat a simple model with a single risky asset that exemplifies the distinction between the average return and the typical return and the role of large deviations in multiplicative processes, and the different optimal strategies for the investors depending on their size. We then analyze the case of assets whose price variations are distributed according to exponential laws, a situation that is found to describe daily price variations reasonably well. Several portfolio optimization strategies are presented that aim at controlling large risks. We end by extending the standard mean-variance portfolio optimization theory, first within the quasi-Gaussian approximation and then using a general formulation for non-Gaussian correlated assets in terms of the formalism of functional integrals developed in the field theory of critical phenomena.

  14. Extended chameleon models

    NASA Astrophysics Data System (ADS)

    Brax, Philippe; Tamanini, Nicola

    2016-05-01

    We extend the chameleon models by considering scalar-fluid theories where the coupling between matter and the scalar field can be represented by a quadratic effective potential with density-dependent minimum and mass. In this context, we study the effects of the scalar field on Solar System tests of gravity and show that models passing these stringent constraints can still induce large modifications of Newton's law on galactic scales. On these scales we analyze models which could lead to a percent deviation of Newton's law outside the virial radius. We then model the dark matter halo as a Navarro-Frenk-White profile and explicitly find that the fifth force can give large contributions around the galactic core in a particular model where the scalar field mass is constant and the minimum of its potential varies linearly with the matter density. At cosmological distances, we find that this model does not alter the growth of large scale structures and therefore would be best tested on galactic scales, where interesting signatures might arise in the galaxy rotation curves.

  15. Extended Ewald summation technique

    NASA Astrophysics Data System (ADS)

    Kylänpää, Ilkka; Räsänen, Esa

    2016-09-01

    We present a technique to improve the accuracy and to reduce the computational labor in the calculation of long-range interactions in systems with periodic boundary conditions. We extend the well-known Ewald method by using a linear combination of screening Gaussian charge distributions instead of only one. This enables us to find faster converging real-space and reciprocal space summations. The combined simplicity and efficiency of our method is demonstrated, and the scheme is readily applicable to large-scale periodic simulations, classical as well as quantum. Moreover, apart from the required a priori optimization the method is straightforward to include in most routines based on the Ewald method within, e.g., density-functional, molecular dynamics, and quantum Monte Carlo calculations.

  16. Distribution of HLA-G extended haplotypes and one HLA-E polymorphism in a large-scale study of mother-child dyads with and without severe preeclampsia and eclampsia.

    PubMed

    Nilsson, L L; Djurisic, S; Andersen, A-M N; Melbye, M; Bjerre, D; Ferrero-Miliani, L; Hackmon, R; Geraghty, D E; Hviid, T V F

    2016-10-01

    The etiological pathways and pathogenesis of preeclampsia have rendered difficult to disentangle. Accumulating evidence points toward a maladapted maternal immune system, which may involve aberrant placental expression of immunomodulatory human leukocyte antigen (HLA) class Ib molecules during pregnancy. Several studies have shown aberrant or reduced expression of HLA-G in the placenta and in maternal blood in cases of preeclampsia compared with controls. Unlike classical HLA class Ia loci, the nonclassical HLA-G has limited polymorphic variants. Most nucleotide variations are clustered in the 5'-upstream regulatory region (5'URR) and 3'-untranslated regulatory region (3'UTR) of HLA-G and reflect a stringent expressional control. Based on genotyping and full gene sequencing of HLA-G in a large number of cases and controls (n > 900), the present study, which to our knowledge is the largest and most comprehensive performed, investigated the association between the HLA-G 14-bp ins/del (rs66554220) and HLA-E polymorphisms in mother and newborn dyads from pregnancies complicated by severe preeclampsia/eclampsia and from uncomplicated pregnancies. Furthermore, results from extended HLA-G haplotyping in the newborns are presented in order to assess whether a combined contribution of nucleotide variations spanning the 5'URR, coding region, and 3'UTR of HLA-G describes the genetic association with severe preeclampsia more closely. In contrast to earlier findings, the HLA-G 14-bp ins/del polymorphism was not associated with severe preeclampsia. Furthermore, the polymorphism (rs1264457) defining the two nonsynonymous HLA-E alleles, HLA-E*01:01:xx:xx and HLA-E*01:03:xx:xx, were not associated with severe preeclampsia. Finally, no specific HLA-G haplotypes were significantly associated with increased risk of developing severe preeclampsia/eclampsia. PMID:27596021

  17. Distribution of HLA-G extended haplotypes and one HLA-E polymorphism in a large-scale study of mother-child dyads with and without severe preeclampsia and eclampsia.

    PubMed

    Nilsson, L L; Djurisic, S; Andersen, A-M N; Melbye, M; Bjerre, D; Ferrero-Miliani, L; Hackmon, R; Geraghty, D E; Hviid, T V F

    2016-10-01

    The etiological pathways and pathogenesis of preeclampsia have rendered difficult to disentangle. Accumulating evidence points toward a maladapted maternal immune system, which may involve aberrant placental expression of immunomodulatory human leukocyte antigen (HLA) class Ib molecules during pregnancy. Several studies have shown aberrant or reduced expression of HLA-G in the placenta and in maternal blood in cases of preeclampsia compared with controls. Unlike classical HLA class Ia loci, the nonclassical HLA-G has limited polymorphic variants. Most nucleotide variations are clustered in the 5'-upstream regulatory region (5'URR) and 3'-untranslated regulatory region (3'UTR) of HLA-G and reflect a stringent expressional control. Based on genotyping and full gene sequencing of HLA-G in a large number of cases and controls (n > 900), the present study, which to our knowledge is the largest and most comprehensive performed, investigated the association between the HLA-G 14-bp ins/del (rs66554220) and HLA-E polymorphisms in mother and newborn dyads from pregnancies complicated by severe preeclampsia/eclampsia and from uncomplicated pregnancies. Furthermore, results from extended HLA-G haplotyping in the newborns are presented in order to assess whether a combined contribution of nucleotide variations spanning the 5'URR, coding region, and 3'UTR of HLA-G describes the genetic association with severe preeclampsia more closely. In contrast to earlier findings, the HLA-G 14-bp ins/del polymorphism was not associated with severe preeclampsia. Furthermore, the polymorphism (rs1264457) defining the two nonsynonymous HLA-E alleles, HLA-E*01:01:xx:xx and HLA-E*01:03:xx:xx, were not associated with severe preeclampsia. Finally, no specific HLA-G haplotypes were significantly associated with increased risk of developing severe preeclampsia/eclampsia.

  18. Population Parameters of Intermediate-age Star Clusters in the Large Magellanic Cloud. III. Dynamical Evidence for a Range of Ages Being Responsible for Extended Main-sequence Turnoffs

    NASA Astrophysics Data System (ADS)

    Goudfrooij, Paul; Puzia, Thomas H.; Chandar, Rupali; Kozhurina-Platais, Vera

    2011-08-01

    We present a new analysis of 11 intermediate-age (1-2 Gyr) star clusters in the Large Magellanic Cloud based on Hubble Space Telescope imaging data. Seven of the clusters feature main-sequence turnoff (MSTO) regions that are wider than can be accounted for by a simple stellar population, whereas their red giant branches (RGBs) indicate a single value of [Fe/H]. The star clusters cover a range in present-day mass from about 1 × 104 M sun to 2 × 105 M sun. We compare radial distributions of stars in the upper and lower parts of the MSTO region, and calculate cluster masses and escape velocities from the present time back to a cluster age of 10 Myr. Our main result is that for all clusters in our sample with estimated escape velocities v esc >~ 15 km s-1 at an age of 10 Myr, the stars in the brightest half of the MSTO region are significantly more centrally concentrated than the stars in the faintest half and more massive RGB and asymptotic giant branch stars. This is not the case for clusters with v esc <~ 10 km s-1 at an age of 10 Myr. We argue that the wide MSTO region of such clusters is caused mainly by a ~200-500 Myr range in the ages of cluster stars due to extended star formation within the cluster from material shed by first-generation stars featuring slow stellar winds. Dilution of this enriched material by accretion of ambient interstellar matter is deemed plausible if the spread of [Fe/H] in this ambient gas was very small when the second-generation stars were formed in the cluster. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555.

  19. From the Berkovits formulation to the Witten formulation in open superstring field theory

    NASA Astrophysics Data System (ADS)

    Iimori, Yuki; Noumi, Toshifumi; Okawa, Yuji; Torii, Shingo

    2014-03-01

    The Berkovits formulation of open superstring field theory is based on the large Hilbert space of the superconformal ghost sector. We discuss its relation to the Witten formulation based on the small Hilbert space. We introduce a one-parameter family of conditions for partial gauge fixing of the Berkovits formulation such that the cubic interaction of the theory under the partial gauge fixing reduces to that of the Witten formulation in a singular limit. The local picture-changing operator at the open-string midpoint in the Witten formulation is regularized in our approach, and the divergence in on-shell four-point amplitudes coming from collision of picture-changing operators is resolved. The quartic interaction inherited from the Berkovits formulation plays a role of adjusting different behaviors of the picture-changing operators in the s channel and in the t channel of Feynman diagrams with two cubic vertices, and correct amplitudes in the world-sheet theory are reproduced. While gauge invariance at the second order in the coupling constant is obscured in the Witten formulation by collision of picture-changing operators, it is well defined in our approach and is recovered by including the quartic interaction inherited from the Berkovits formulation.

  20. Perfume formulation: words and chats.

    PubMed

    Ellena, Céline

    2008-06-01

    What does it mean to create fragrances with materials from chemistry and/or from nature? How are they used to display their characteristic differences, their own personality? Is it easier to create with synthetic raw materials or with essential oils? This review explains why a perfume formulation corresponds in fact to a conversation, an interplay between synthetic and natural perfumery materials. A synthetic raw material carries a single information, and usually is very linear. Its smell is uniform, clear, and faithful. Natural raw materials, on the contrary, provide a strong, complex and generous image. While a synthetic material can be seen as a single word, a natural one such as rose oil could be compared to chatting: cold, warm, sticky, heavy, transparent, pepper, green, metallic, smooth, watery, fruity... full of information. Yet, if a very small amount of the natural material is used, nothing happens, the fragrance will not change. However, if a large amount is used, the rose oil will swallow up everything else. The fragrance will smell of nothing else except rose! To formulate a perfume is not to create a culinary recipe, with only dosing the ingredients in well-balanced amounts. To formulate rather means to flexibly knit materials together with a lively stitch, meeting or repelling each other, building a pleasant form, which is neither fixed, nor solid, nor rigid. A fragrance has an overall structure, which ranges from a clear sound, made up of stable, unique, and linear items, to a background chat, comfortable and reassuring. But that does, of course, not mean that there is only one way of creating a fragrance!

  1. Liposomal formulations for inhalation.

    PubMed

    Cipolla, David; Gonda, Igor; Chan, Hak-Kim

    2013-08-01

    No marketed inhaled products currently use sustained release formulations such as liposomes to enhance drug disposition in the lung, but that may soon change. This review focuses on the interaction between liposomal formulations and the inhalation technology used to deliver them as aerosols. There have been a number of dated reviews evaluating nebulization of liposomes. While the information they shared is still accurate, this paper incorporates data from more recent publications to review the factors that affect aerosol performance. Recent reviews have comprehensively covered the development of dry powder liposomes for aerosolization and only the key aspects of those technologies will be summarized. There are now at least two inhaled liposomal products in late-stage clinical development: ARIKACE(®) (Insmed, NJ, USA), a liposomal amikacin, and Pulmaquin™ (Aradigm Corp., CA, USA), a liposomal ciprofloxacin, both of which treat a variety of patient populations with lung infections. This review also highlights the safety of inhaled liposomes and summarizes the clinical experience with liposomal formulations for pulmonary application. PMID:23919478

  2. Extended-release methylphenidate (Ritalin LA).

    PubMed

    Lyseng-Williamson, Katherine A; Keating, Gillian M

    2002-01-01

    An extended-release formulation of methylphenidate (Ritalin LA), a CNS stimulant that inhibits dopamine and noradrenaline (norepinephrine) reuptake into presynaptic neurons, has been developed for use in patients with attention deficit/hyperactivity disorder (ADHD). In children with ADHD and healthy male adults, extended-release methylphenidate 20mg was rapidly absorbed and demonstrated two distinct peak plasma concentrations approximately 4 hours apart. The absorption pharmacokinetics of extended-release methylphenidate 20mg, which closely mimics those of immediate-release methylphenidate 10mg given in two doses 4 hours apart, permits once-daily administration. In a 2-week randomised, double-blind, placebo-controlled trial in 134 evaluable children aged 6 to 12 years with ADHD, symptoms improved to a significantly greater extent with extended-release methylphenidate 10 to 40mg once daily than with placebo. Extended-release methylphenidate improved both inattention and hyperactivity symptoms and was effective in children with combined- (inattentive and hyperactive/impulsive) type or predominantly inattentive-type ADHD. In clinical trials, the safety and tolerability profiles of extended-release methylphenidate were consistent with that of the immediate-release formulation.

  3. Lyα Emitter Galaxies at z∼ 2.8 in the Extended Chandra Deep Field South. I. Tracing the Large-scale Structure via Lyα Imaging

    NASA Astrophysics Data System (ADS)

    Zheng, Zhen-Ya; Malhotra, Sangeeta; Rhoads, James E.; Finkelstein, Steven L.; Wang, Jun-Xian; Jiang, Chun-Yan; Cai, Zheng

    2016-10-01

    We present a narrowband survey with three adjacent filters for z = 2.8–2.9 Lyman alpha (Lyα) emitter (LAE) galaxies in the Extended Chandra Deep Field South (ECDFS), along with spectroscopic follow-up. With a complete sample of 96 LAE candidates in the narrowband NB466, we confirm the large-scale structure at z ∼ 2.8 suggested by previous spectroscopic surveys. Compared to the blank field detected with the other two narrowband filters NB470 and NB475, the LAE-density excess in NB466 (900 arcmin2) is ∼ 6.0 ± 0.8 times the standard deviation expected at z ∼ 2.8, assuming a linear bias of 2. The overdense large-scale structure in NB466 can be decomposed into four protoclusters, whose overdensities (each within an equivalent comoving volume 153 Mpc3) relative to the blank field (NB470+NB475) are in the range of 4.6–6.6. These four protoclusters are expected to evolve into a Coma-like cluster (M ≥ 1015 M ⊙) at z ∼ 0. We also investigate the various properties of LAEs at z = 2.8–2.9 and their dependence on the environment. The average star formation rates derived from the Lyα, rest-frame UV, and X-ray bands are ∼4, 10, and <16 M ⊙ yr‑1, respectively, implying a Lyα escape fraction of 25% ≲ {f}{{ESC}}{Lyα } ≲ 40% and a UV continuum escape fraction of {f}{{ESC}}{{UV,cont}} ≳ 62% for LAEs at z ∼ 2.8. The Lyα photon density calculated from the integrated Lyα luminosity function in the overdense field (NB466) is ∼50% higher than that in the blank field (NB470+NB475), and more bright LAEs are found in the overdense field. The three brightest LAEs, including a quasar at z = 2.81, are all detected in the X-ray band and in NB466. These three LAE-active galactic nuclei contribute an extra 20%–30% Lyα photon density compared to other LAE galaxies. Furthermore, we find that LAEs in overdense regions have larger equivalent width values, bluer U ‑ B and V ‑ R (∼2–3σ) colors compared with those in lower density regions, indicating

  4. Kit systems for granulated decontamination formulations

    DOEpatents

    Tucker, Mark D.

    2010-07-06

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field. The formulation can be pre-mixed and pre-packaged as a multi-part kit system, where one or more of the parts are packaged in a powdered, granulated form for ease of handling and mixing in the field.

  5. Oral supplementation with a nutraceutical formulation containing omega-3 fatty acids, vitamins, minerals, and antioxidants in a large series of patients with dry eye symptoms: results of a prospective study

    PubMed Central

    Gatell-Tortajada, Jordi

    2016-01-01

    Purpose To assess the benefits and tolerability of a dietary supplement based on omega-3 fatty acids to relieve dry eye symptoms. Methods A total of 1,419 patients (74.3% women, mean age 58.9 years) with dry eye syndrome using artificial tears participated in a 12-week prospective study. Patients were instructed to take 3 capsules/day of the nutraceutical formulation (Brudysec® 1.5 g). Study variables were dry eye symptoms (scratchy and stinging sensation, eye redness, grittiness, painful and tired eyes, grating sensation, and blurry vision), conjunctival hyperemia, tear breakup time (TBUT), Schrimer I test, and Oxford grading scheme. Results At 12 weeks, each dry eye symptom improved significantly (P<0.001), and the use of artificial tears decreased significantly from 3.77 (standard deviation [SD] =2.08) at baseline to 3.45 (SD =1.72) (P<0.01). In addition, the Schirmer test scores and the TBUT increased significantly, and there was an increase in patients grading 0–I in the Oxford scale and a decrease of those grading IV–V. Significant differences in improvements of dry eye symptoms were also found in compliant versus noncompliant patients as well as in those with moderate/severe versus none/mild conjunctival hyperemia. Conclusion Oral ω-3 fatty acids supplementation was an effective treatment for dry eye symptoms. PMID:27279739

  6. The formulation makes the honey bee poison.

    PubMed

    Mullin, Christopher A; Chen, Jing; Fine, Julia D; Frazier, Maryann T; Frazier, James L

    2015-05-01

    Dr. Fumio Matsumura's legacy embraced a passion for exploring environmental impacts of agrochemicals on non-target species such as bees. Why most formulations are more toxic to bees than respective active ingredients and how pesticides interact to cause pollinator decline cannot be answered without understanding the prevailing environmental chemical background to which bees are exposed. Modern pesticide formulations and seed treatments, particularly when multiple active ingredients are blended, require proprietary adjuvants and inert ingredients to achieve high efficacy for targeted pests. Although we have found over 130 different pesticides and metabolites in beehive samples, no individual pesticide or amount correlates with recent bee declines. Recently we have shown that honey bees are sensitive to organosilicone surfactants, nonylphenol polyethoxylates and the solvent N-methyl-2-pyrrolidone (NMP), widespread co-formulants used in agrochemicals and frequent pollutants within the beehive. Effects include learning impairment for adult bees and chronic toxicity in larval feeding bioassays. Multi-billion pounds of formulation ingredients like NMP are used and released into US environments. These synthetic organic chemicals are generally recognized as safe, have no mandated tolerances, and residues remain largely unmonitored. In contrast to finding about 70% of the pesticide active ingredients searched for in our pesticide analysis of beehive samples, we have found 100% of the other formulation ingredients targeted for analysis. These 'inerts' overwhelm the chemical burden from active pesticide, drug and personal care ingredients with which they are formulated. Honey bees serve as an optimal terrestrial bioindicator to determine if 'the formulation and not just the dose makes the poison'. PMID:25987217

  7. The formulation makes the honey bee poison.

    PubMed

    Mullin, Christopher A; Chen, Jing; Fine, Julia D; Frazier, Maryann T; Frazier, James L

    2015-05-01

    Dr. Fumio Matsumura's legacy embraced a passion for exploring environmental impacts of agrochemicals on non-target species such as bees. Why most formulations are more toxic to bees than respective active ingredients and how pesticides interact to cause pollinator decline cannot be answered without understanding the prevailing environmental chemical background to which bees are exposed. Modern pesticide formulations and seed treatments, particularly when multiple active ingredients are blended, require proprietary adjuvants and inert ingredients to achieve high efficacy for targeted pests. Although we have found over 130 different pesticides and metabolites in beehive samples, no individual pesticide or amount correlates with recent bee declines. Recently we have shown that honey bees are sensitive to organosilicone surfactants, nonylphenol polyethoxylates and the solvent N-methyl-2-pyrrolidone (NMP), widespread co-formulants used in agrochemicals and frequent pollutants within the beehive. Effects include learning impairment for adult bees and chronic toxicity in larval feeding bioassays. Multi-billion pounds of formulation ingredients like NMP are used and released into US environments. These synthetic organic chemicals are generally recognized as safe, have no mandated tolerances, and residues remain largely unmonitored. In contrast to finding about 70% of the pesticide active ingredients searched for in our pesticide analysis of beehive samples, we have found 100% of the other formulation ingredients targeted for analysis. These 'inerts' overwhelm the chemical burden from active pesticide, drug and personal care ingredients with which they are formulated. Honey bees serve as an optimal terrestrial bioindicator to determine if 'the formulation and not just the dose makes the poison'.

  8. Extending the extended V-Y flap.

    PubMed

    Prowse, Phoebe; Morton, Jonathan

    2012-06-01

    This case report demonstrates a modification of the so-called 'Extended V-Y Flap' used to simultaneously reconstruct a defect involving the upper lip, floor of nose and alar rim following tumour excision. We hope that this case serves as a reminder of the versatility of the V-Y flap in the nasolabial region, and its considerable capacity for augmentation. PMID:22018837

  9. Structural design using equilibrium programming formulations

    NASA Technical Reports Server (NTRS)

    Scotti, Stephen J.

    1995-01-01

    Solutions to increasingly larger structural optimization problems are desired. However, computational resources are strained to meet this need. New methods will be required to solve increasingly larger problems. The present approaches to solving large-scale problems involve approximations for the constraints of structural optimization problems and/or decomposition of the problem into multiple subproblems that can be solved in parallel. An area of game theory, equilibrium programming (also known as noncooperative game theory), can be used to unify these existing approaches from a theoretical point of view (considering the existence and optimality of solutions), and be used as a framework for the development of new methods for solving large-scale optimization problems. Equilibrium programming theory is described, and existing design techniques such as fully stressed design and constraint approximations are shown to fit within its framework. Two new structural design formulations are also derived. The first new formulation is another approximation technique which is a general updating scheme for the sensitivity derivatives of design constraints. The second new formulation uses a substructure-based decomposition of the structure for analysis and sensitivity calculations. Significant computational benefits of the new formulations compared with a conventional method are demonstrated.

  10. Extending earthquakes' reach through cascading.

    PubMed

    Marsan, David; Lengliné, Olivier

    2008-02-22

    Earthquakes, whatever their size, can trigger other earthquakes. Mainshocks cause aftershocks to occur, which in turn activate their own local aftershock sequences, resulting in a cascade of triggering that extends the reach of the initial mainshock. A long-lasting difficulty is to determine which earthquakes are connected, either directly or indirectly. Here we show that this causal structure can be found probabilistically, with no a priori model nor parameterization. Large regional earthquakes are found to have a short direct influence in comparison to the overall aftershock sequence duration. Relative to these large mainshocks, small earthquakes collectively have a greater effect on triggering. Hence, cascade triggering is a key component in earthquake interactions.

  11. Functional Extended Redundancy Analysis

    ERIC Educational Resources Information Center

    Hwang, Heungsun; Suk, Hye Won; Lee, Jang-Han; Moskowitz, D. S.; Lim, Jooseop

    2012-01-01

    We propose a functional version of extended redundancy analysis that examines directional relationships among several sets of multivariate variables. As in extended redundancy analysis, the proposed method posits that a weighed composite of each set of exogenous variables influences a set of endogenous variables. It further considers endogenous…

  12. Extended or Restricted Childhood?

    ERIC Educational Resources Information Center

    Richards, Colin

    2005-01-01

    This article discusses the Government's proposals for "extended" primary schools, an important element in the recently-published five-year plan for education. The author expresses concern that extended primary schools will not provide a variety of experiences, including "play" experiences for young children.

  13. Extended conformal field theories

    NASA Astrophysics Data System (ADS)

    Taormina, Anne

    1990-08-01

    Some extended conformal field theories are briefly reviewed. They illustrate how non minimal models of the Virasoro algebra (c≥1) can become minimal with respect to a larger algebra. The accent is put on N-extended superconformal algebras, which are relevant in superstring compactification.

  14. Lagrangian formulation of turbulent premixed combustion.

    PubMed

    Pagnini, Gianni; Bonomi, Ernesto

    2011-07-22

    The lagrangian point of view is adopted to study turbulent premixed combustion. The evolution of the volume fraction of combustion products is established by the Reynolds transport theorem. It emerges that the burned-mass fraction is led by the turbulent particle motion, by the flame front velocity, and by the mean curvature of the flame front. A physical requirement connecting particle turbulent dispersion and flame front velocity is obtained from equating the expansion rates of the flame front progression and of the unburned particles spread. The resulting description compares favorably with experimental data. In the case of a zero-curvature flame, with a non-markovian parabolic model for turbulent dispersion, the formulation yields the Zimont equation extended to all elapsed times and fully determined by turbulence characteristics. The exact solution of the extended Zimont equation is calculated and analyzed to bring out different regimes.

  15. Plutonium Immobilization Project Baseline Formulation

    SciTech Connect

    Ebbinghaus, B.

    1999-02-01

    A key milestone for the Immobilization Project (AOP Milestone 3.2a) in Fiscal Year 1998 (FY98) is the definition of the baseline composition or formulation for the plutonium ceramic form. The baseline formulation for the plutonium ceramic product must be finalized before the repository- and plant-related process specifications can be determined. The baseline formulation that is currently specified is given in Table 1.1. In addition to the baseline formulation specification, this report provides specifications for two alternative formulations, related compositional specifications (e.g., precursor compositions and mixing recipes), and other preliminary form and process specifications that are linked to the baseline formulation. The preliminary specifications, when finalized, are not expected to vary tremendously from the preliminary values given.

  16. Explosive Formulation Code Naming SOP

    SciTech Connect

    Martz, H. E.

    2014-09-19

    The purpose of this SOP is to provide a procedure for giving individual HME formulations code names. A code name for an individual HME formulation consists of an explosive family code, given by the classified guide, followed by a dash, -, and a number. If the formulation requires preparation such as packing or aging, these add additional groups of symbols to the X-ray specimen name.

  17. Baseline LAW Glass Formulation Testing

    SciTech Connect

    Kruger, Albert A.; Mooers, Cavin; Bazemore, Gina; Pegg, Ian L.; Hight, Kenneth; Lai, Shan Tao; Buechele, Andrew; Rielley, Elizabeth; Gan, Hao; Muller, Isabelle S.; Cecil, Richard

    2013-06-13

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements.

  18. Bimodal Gastroretentive Drug Delivery Systems of Lamotrigine: Formulation and Evaluation

    PubMed Central

    Poonuru, R. R.; Gonugunta, C. S. R

    2014-01-01

    Gastroretentive bimodal drug delivery systems of lamotrigine were developed using immediate release and extended release segments incorporated in a hydroxypropyl methylcellulose capsule and in vitro and in vivo evaluations were conducted. In vivo radiographic studies were carried out for the optimized formulation in healthy human volunteers with replacement of drug polymer complex by barium sulphate and the floating time was noted. Here the immediate release segment worked as loading dose and extended release segment as maintenance dose. The results of release studies of formulations with hydrophillic matrix to formulations with dual matrix hydroxypropyl methylcellulose acetate succinate shown that as the percentage of polymer increased, the release decreased. Selected formulation F2 having F-Melt has successfully released the drug within one hour and hydrophillic matrix composing polyethylene oxide with 5% hydroxypropyl methylcellulose acetate succinate showed a lag time of one hour and then extended its release up to 12th hour with 99.59% drug release following zero order kinetics with R2 value of 0.989. The Korsmeyer-Peppas equation showed the R2 value to be 0.941 and n value was 1.606 following non-Fickian diffusion pattern with supercase II relaxation mechanism. Here from extended release tablet the drug released slowly from the matrix while floating. PMID:25593380

  19. Extended-release niacin for modifying the lipoprotein profile.

    PubMed

    Guyton, John R

    2004-06-01

    Niacin (nicotinic acid) favourably modifies all aspects of the lipoprotein profile; it raises high-density lipoprotein cholesterol (HDL-C) levels, lowers triglyceride, low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) levels and reduces atherogenic small, dense LDL particles. One large monotherapy trial and multiple trials of niacin in combination with other lipid-modifying drugs show remarkable consistency in the ability of niacin to improve angiographic and clinical outcomes. In practice, however, the use of regular, immediate-release niacin (niacin IR) has been limited by the side effect of flushing. Sustained-release (SR) formulations, developed in order to reduce flushing, were found to cause serious hepatotoxicity at varying frequencies. Extended-release niacin (niacin ER; Niaspan), Kos Pharmaceuticals, Inc.) is a prescription formulation of niacin, administered once-daily at bedtime. Niacin ER is as effective in modifying lipoprotein levels as an equal daily dose of niacin IR and it causes less flushing. In addition, niacin ER administered once-daily is not associated with the increased hepatotoxicity reported with SR formulations. Niacin ER has been studied extensively in combination therapy with statins, including lovastatin in a recently introduced combination tablet. Myopathy has not been a substantial problem in statin/niacin ER combination therapy. Finally, a study of niacin ER given to diabetic patients showed only mild trends towards increased glycosylated haemoglobin concentrations and a need for additional antidiabetic medication. Thus, niacin ER represents an effective and safe option in the management of low levels of HDL-C and other lipoprotein abnormalities in a variety of settings.

  20. Gurson's Model: ALE Formulation and Strain Localization

    NASA Astrophysics Data System (ADS)

    da Cunda, Luiz A. B.; Creus, Guillermo J.

    2007-05-01

    This paper presents a brief review of Gurson's damage model, employed to describes the strength degradation in ductile metals submitted to large plastic deformations. The damage model is applied using finite elements and an Arbitrary Lagrangian-Eulerian formulation (ALE), to ensure a better quality to the finite elements mesh. The study of the combined application of ALE and Gurson approach to damage modeling and strain localization is the object of this paper.

  1. Gurson's Model: ALE Formulation and Strain Localization

    SciTech Connect

    Cunda, Luiz A. B. da; Creus, Guillermo J.

    2007-05-17

    This paper presents a brief review of Gurson's damage model, employed to describes the strength degradation in ductile metals submitted to large plastic deformations. The damage model is applied using finite elements and an Arbitrary Lagrangian-Eulerian formulation (ALE), to ensure a better quality to the finite elements mesh. The study of the combined application of ALE and Gurson approach to damage modeling and strain localization is the object of this paper.

  2. Extending mine life

    SciTech Connect

    Not Available

    1984-06-01

    Mine layouts, new machines and techniques, research into problem areas of ground control and so on, are highlighted in this report on extending mine life. The main resources taken into account are coal mining, uranium mining, molybdenum and gold mining.

  3. Saltstone Clean Cap Formulation

    SciTech Connect

    Langton, C

    2005-04-22

    The current operation strategy for using Saltstone Vault 4 to receive 0.2 Ci/gallon salt solution waste involves pouring a clean grout layer over the radioactive grout prior to initiating pour into another cell. This will minimize the radiating surface area and reduce the dose rate at the vault and surrounding area. The Clean Cap will be used to shield about four feet of Saltstone poured into a Z-Area vault cell prior to moving to another cell. The minimum thickness of the Clean Cap layer will be determined by the cesium concentration and resulting dose levels and it is expected to be about one foot thick based on current calculations for 0.1 Ci Saltstone that is produced in the Saltstone process by stabilization of 0.2 Ci salt solution. This report documents experiments performed to identify a formulation for the Clean Cap. Thermal transient calculations, adiabatic temperature rise measurements, pour height, time between pour calculations and shielding calculations were beyond the scope and time limitations of this study. However, data required for shielding calculations (composition and specific gravity) are provided for shielding calculations. The approach used to design a Clean Cap formulation was to produce a slurry from the reference premix (10/45/45 weight percent cement/slag/fly ash) and domestic water that resembled as closely as possible the properties of the Saltstone slurry. In addition, options were investigated that may offer advantages such as less bleed water and less heat generation. The options with less bleed water required addition of dispersants. The options with lower heat contained more fly ash and less slag. A mix containing 10/45/45 weight percent cement/slag/fly ash with a water to premix ratio of 0.60 is recommended for the Clean Cap. Although this mix may generate more than 3 volume percent standing water (bleed water), it has rheological, mixing and flow properties that are similar to previously processed Saltstone. The recommended

  4. Nondestructive construction error detection in large space structures

    NASA Technical Reports Server (NTRS)

    Stubbs, Norris; Broome, Taft H.; Osegueda, Roberto

    1988-01-01

    Continuum modeling of large space structures is extended to the problem of detecting construction errors in large space structures such as the proposed space station. First-order dynamic sensitivity equations for structures involving eigenfrequencies, modal masses, modal stiffnesses, and modal damping are presented. Matrix equations relating changes in element parameters to dynamic sensitivities are summarized. The sensitivity equations for the entire dynamical system are rearranged as a system of algebraic equations with unknowns of stiffness losses at selected locations. The feasibility of the formulation is numerically demonstrated on a simply-supported Euler-Bernouilli beam with simulated construction defects. The method is next extended to large space structures modelled as equivalent continua with simulated construction defects.

  5. Operator Formulation of Classical Mechanics.

    ERIC Educational Resources Information Center

    Cohn, Jack

    1980-01-01

    Discusses the construction of an operator formulation of classical mechanics which is directly concerned with wave packets in configuration space and is more similar to that of convential quantum theory than other extant operator formulations of classical mechanics. (Author/HM)

  6. Overview of extended release tacrolimus in solid organ transplantation

    PubMed Central

    Patel, Neha; Cook, Abigail; Greenhalgh, Elizabeth; Rech, Megan A; Rusinak, Joshua; Heinrich, Lynley

    2016-01-01

    Tacrolimus (Prograf©, Astellas Pharma Europe Ltd, Staines, United Kingdom; referred to as tacrolimus-BID) is an immunosuppressive agent to prevent and treat allograft rejection in kidney transplant recipients in combination with mycophenolate mofetil, corticosteroids, with or without basiliximab induction. The drug has also been studied in liver, heart and lung transplant; however, these are currently off-label indications. An extended release tacrolimus formulation (Advagraf©, Astagraf XL©) allows for once-daily dosing, with the potential to improve adherence. Extended release tacrolimus has similar absorption, distribution, metabolism and excretion to tacrolimus-BID. Phase I pharmacokinetic trials comparing extended release tacrolimus and tacrolimus-BID have demonstrated a decreased maximum concentration (Cmax) and delayed time to maximum concentration (tmax) with the extended release formulation; however, AUC0-24 was comparable between formulations. Overall extended release tacrolimus has a very similar safety and efficacy profile to tacrolimus-BID. It is not recommended in the use of liver transplant patient’s due to the increased risk of mortality in female recipients. There has been minimal data regarding the use of extended release tacrolimus in heart and lung transplant recipients. With the current data available for all organ groups the extended release tacrolimus should be dosed in a 1:1 fashion, the exception may be the cystic fibrosis population where their initial dose may need to be higher. PMID:27011912

  7. Overview of extended release tacrolimus in solid organ transplantation.

    PubMed

    Patel, Neha; Cook, Abigail; Greenhalgh, Elizabeth; Rech, Megan A; Rusinak, Joshua; Heinrich, Lynley

    2016-03-24

    Tacrolimus (Prograf(©), Astellas Pharma Europe Ltd, Staines, United Kingdom; referred to as tacrolimus-BID) is an immunosuppressive agent to prevent and treat allograft rejection in kidney transplant recipients in combination with mycophenolate mofetil, corticosteroids, with or without basiliximab induction. The drug has also been studied in liver, heart and lung transplant; however, these are currently off-label indications. An extended release tacrolimus formulation (Advagraf(©), Astagraf XL(©)) allows for once-daily dosing, with the potential to improve adherence. Extended release tacrolimus has similar absorption, distribution, metabolism and excretion to tacrolimus-BID. Phase I pharmacokinetic trials comparing extended release tacrolimus and tacrolimus-BID have demonstrated a decreased maximum concentration (Cmax) and delayed time to maximum concentration (tmax) with the extended release formulation; however, AUC0-24 was comparable between formulations. Overall extended release tacrolimus has a very similar safety and efficacy profile to tacrolimus-BID. It is not recommended in the use of liver transplant patient's due to the increased risk of mortality in female recipients. There has been minimal data regarding the use of extended release tacrolimus in heart and lung transplant recipients. With the current data available for all organ groups the extended release tacrolimus should be dosed in a 1:1 fashion, the exception may be the cystic fibrosis population where their initial dose may need to be higher.

  8. Extended lifetime railgap switch

    SciTech Connect

    Cohn, D.B.; Mendoza, P.J.

    1988-02-02

    In a railgap switch of the type having an elongate blade electrode made of conductive material, an elongate housing made of insulating material for supporting the blade electrode and plate electrode in opposed relation extending in the same direction with the blade centered over the plate and separated therefrom by a gap, and a gas filling the housing and the gap, the gas being selected to breakdown and switch from a highly insulative state to a highly conductive state upon application of a high voltage across the blade and plate electrodes, the improvement is described comprising: forming the blade with laterally extending transverse wing portions at the edge of the blade and adjacent the gap so as to extend in spaced parallel relation to the surface of the plate, the blade generally following the contour thereof to form an inverted T-shape structure with the wing portions extending transversely of the elongate dimension of the blade. The wing portions terminating in a pair of spaced parallel edges extending along the elongate direction of the blade to thereby create two spaced elongate edges along which arcs form serving to divide the erosion effects of discharge between them, the current through each edge being one-half of that in single-edge devices with ablation wear reduced accordingly to give significantly larger switch lifetime. The blade and wing portions limiting ablation erosion of the edges in a direction generally align with the plate contour so that the edge-to-plate separation remains substantially constant.

  9. Extending quantum mechanics entails extending special relativity

    NASA Astrophysics Data System (ADS)

    Aravinda, S.; Srikanth, R.

    2016-05-01

    The complementarity between signaling and randomness in any communicated resource that can simulate singlet statistics is generalized by relaxing the assumption of free will in the choice of measurement settings. We show how to construct an ontological extension for quantum mechanics (QMs) through the oblivious embedding of a sound simulation protocol in a Newtonian spacetime. Minkowski or other intermediate spacetimes are ruled out as the locus of the embedding by virtue of hidden influence inequalities. The complementarity transferred from a simulation to the extension unifies a number of results about quantum non-locality, and implies that special relativity has a different significance for the ontological model and for the operational theory it reproduces. Only the latter, being experimentally accessible, is required to be Lorentz covariant. There may be certain Lorentz non-covariant elements at the ontological level, but they will be inaccessible at the operational level in a valid extension. Certain arguments against the extendability of QM, due to Conway and Kochen (2009) and Colbeck and Renner (2012), are attributed to their assumption that the spacetime at the ontological level has Minkowski causal structure.

  10. On the formulation, parameter identification and numerical integration of the EMMI model :plasticity and isotropic damage.

    SciTech Connect

    Bammann, Douglas J.; Johnson, G. C. (University of California, Berkeley, CA); Marin, Esteban B.; Regueiro, Richard A.

    2006-01-01

    In this report we present the formulation of the physically-based Evolving Microstructural Model of Inelasticity (EMMI) . The specific version of the model treated here describes the plasticity and isotropic damage of metals as being currently applied to model the ductile failure process in structural components of the W80 program . The formulation of the EMMI constitutive equations is framed in the context of the large deformation kinematics of solids and the thermodynamics of internal state variables . This formulation is focused first on developing the plasticity equations in both the relaxed (unloaded) and current configurations. The equations in the current configuration, expressed in non-dimensional form, are used to devise the identification procedure for the plasticity parameters. The model is then extended to include a porosity-based isotropic damage state variable to describe the progressive deterioration of the strength and mechanical properties of metals induced by deformation . The numerical treatment of these coupled plasticity-damage constitutive equations is explained in detail. A number of examples are solved to validate the numerical implementation of the model.

  11. Extendable pipe crawler

    DOEpatents

    Hapstack, Mark

    1991-01-01

    A pipe crawler having a front leg assembly and a back leg assembly connected together by two air cylinders, each leg assembly having four extendable legs and a pair of actuators for sliding the extendable legs radially outward to increase the range of the legs when the pipe crawler enters a section of a pipe having a larger diameter. The crawler crawls by "inchworm"-like motion, the front leg assembly and back leg assembly alternately engaging and disengaging the wall of the pipe to hold the pipe crawler as the air cylinders alternately advance the front leg assembly and bring up the rear leg assembly. The pair of actuators of each leg assembly are parallel, adjacent and opposing acting so that each slides two adjacent extendable legs radially outward.

  12. Extendable pipe crawler

    DOEpatents

    Hapstack, M.

    1991-05-28

    A pipe crawler is described having a front leg assembly and a back leg assembly connected together by two air cylinders, each leg assembly having four extendable legs and a pair of actuators for sliding the extendable legs radially outward to increase the range of the legs when the pipe crawler enters a section of a pipe having a larger diameter. The crawler crawls by inchworm'-like motion, the front leg assembly and back leg assembly alternately engaging and disengaging the wall of the pipe to hold the pipe crawler as the air cylinders alternately advance the front leg assembly and bring up the rear leg assembly. The pair of actuators of each leg assembly are parallel, adjacent and opposing acting so that each slides two adjacent extendable legs radially outward. 5 figures.

  13. Renormalization of Extended QCD2

    NASA Astrophysics Data System (ADS)

    Fukaya, Hidenori; Yamamura, Ryo

    2015-10-01

    Extended QCD (XQCD), proposed by Kaplan [D. B. Kaplan, arXiv:1306.5818], is an interesting reformulation of QCD with additional bosonic auxiliary fields. While its partition function is kept exactly the same as that of original QCD, XQCD naturally contains properties of low-energy hadronic models. We analyze the renormalization group flow of 2D (X)QCD, which is solvable in the limit of a large number of colors N_c, to understand what kind of roles the auxiliary degrees of freedom play and how the hadronic picture emerges in the low-energy region.

  14. Earth Observing-1 Extended Mission

    USGS Publications Warehouse

    ,

    2005-01-01

    Since November 2000, the National Aeronautics and Space Administration (NASA) Earth Observing-1 (EO-1) mission has demonstrated the capabilities of a dozen spacecraft sensor and communication innovations. Onboard the EO-1 spacecraft are two land remote sensing instruments. The Advanced Land Imager (ALI) acquires data in spectral bands and at resolutions similar to Landsat. The Hyperion instrument, which is the first civilian spaceborne hyperspectral imager, acquires data in 220 10-nanometer bands covering the visible, near, and shortwave-infrared bands. The initial one-year technology demonstration phase of the mission included a detailed comparison of ALI with the Landsat Enhanced Thematic Mapper Plus (ETM+) instrument. Specifications for the Operational Land Imager (OLI), the planned successor to ETM+, were formulated in part from performance characteristics of ALI. Recognizing the remarkable performance of the satellite's instruments and the exceptional value of the data, the U.S. Geological Survey (USGS) and NASA agreed in December 2001 to share responsibility for operating EO-1. The extended mission continues, on a cost-reimbursable basis, as long as customer sales fully recover flight and ground operations costs. As of May 2005, more than 17,800 scenes from each instrument have been acquired, indexed, archived, and made available to the public.

  15. Novel Formulations for Antimicrobial Peptides

    PubMed Central

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  16. Modelling extended chromospheres

    NASA Technical Reports Server (NTRS)

    Linsky, J. L.

    1986-01-01

    Attention is given to the concept that the warm, partially ionized plasma (presently called chromosphere) associated with such stars as Alpha Boo and Rho Per extends outwards at least several photospheric radii. Calculations are presented for the Mg II K line in light of two input model atmospheres. Specific predictions are deduced from the results obtained by each of the two models.

  17. Extended artistic appreciation.

    PubMed

    Wilson, Robert A

    2013-04-01

    I propose that in at least some cases, objects of artistic appreciation are best thought of not simply as causes of artistic appreciation, but as parts of the cognitive machinery that drives aesthetic appreciation. In effect, this is to say that aesthetic appreciation operates via extended cognitive systems.

  18. Simple formulation of magnetoplasmadynamic acceleration

    SciTech Connect

    Sasoh, A. )

    1994-03-01

    A simple formulation of magnetoplasmadynamic acceleration has been made based on energy conservation relations and a generalized Ohm's law. An exhaust velocity is expressed using three characteristic parameters: (1) a dimensionless characteristic velocity [ital [tilde U

  19. The algebras of large N matrix mechanics

    SciTech Connect

    Halpern, M.B.; Schwartz, C.

    1999-09-16

    Extending early work, we formulate the large N matrix mechanics of general bosonic, fermionic and supersymmetric matrix models, including Matrix theory: The Hamiltonian framework of large N matrix mechanics provides a natural setting in which to study the algebras of the large N limit, including (reduced) Lie algebras, (reduced) supersymmetry algebras and free algebras. We find in particular a broad array of new free algebras which we call symmetric Cuntz algebras, interacting symmetric Cuntz algebras, symmetric Bose/Fermi/Cuntz algebras and symmetric Cuntz superalgebras, and we discuss the role of these algebras in solving the large N theory. Most important, the interacting Cuntz algebras are associated to a set of new (hidden!) local quantities which are generically conserved only at large N. A number of other new large N phenomena are also observed, including the intrinsic nonlocality of the (reduced) trace class operators of the theory and a closely related large N field identification phenomenon which is associated to another set (this time nonlocal) of new conserved quantities at large N.

  20. Formulation Optimization of Arecoline Patches

    PubMed Central

    Wu, Pao-Chu; Tsai, Pi-Ju; Lin, Shin-Chen; Huang, Yaw-Bin

    2014-01-01

    The response surface methodology (RSM) including polynomial equations has been used to design an optimal patch formulation with appropriate adhesion and flux. The patch formulations were composed of different polymers, including Eudragit RS 100 (ERS), Eudragit RL 100 (ERL) and polyvinylpyrrolidone K30 (PVP), plasticizers (PEG 400), and drug. In addition, using terpenes as enhancers could increase the flux of the drug. Menthol showed the highest enhancement effect on the flux of arecoline. PMID:24707220

  1. Attempted suicide: an operant formulation.

    PubMed

    Bostock, T; Williams, C L

    1975-06-01

    An alternative formulation of attempted suicide is offered, in which the phenomenon is considered within the context of social learning theory. The suicidal behaviour is viewed as an operant which is reinforced and maintained by the consequent interpersonal contingencies. The modification of the suicidal behaviour then involves alteration of the contingent consequences. This theoretical formulation is elaborated and the treatment principles and practice are outlined.

  2. Preparation and Characterization of Azadirachtin Alginate-Biosorbent Based Formulations: Water Release Kinetics and Photodegradation Study.

    PubMed

    Flores-Céspedes, Francisco; Martínez-Domínguez, Gerardo P; Villafranca-Sánchez, Matilde; Fernández-Pérez, Manuel

    2015-09-30

    The botanical insecticide azadirachtin was incorporated in alginate-based granules to obtain controlled release formulations (CRFs). The basic formulation [sodium alginate (1.47%) - azadirachtin (0.28%) - water] was modified by the addition of biosorbents, obtaining homogeneous hybrid hydrogels with high azadirachtin entrapment efficiency. The effect on azadirachtin release rate caused by the incorporation of biosorbents such as lignin, humic acid, and olive pomace in alginate formulation was studied by immersion of the granules in water under static conditions. The addition of the biosorbents to the basic alginate formulation reduces the rate of release because the lignin-based formulation produces a slower release. Photodegradation experiments showed the potential of the prepared formulations in protecting azadirachtin against simulated sunlight, thus improving its stability. The results showed that formulation prepared with lignin provided extended protection. Therefore, this study provides a new procedure to encapsulate the botanical insecticide azadirachtin, improving its delivery and photostability. PMID:26345112

  3. Memantine extended release (28 mg once daily): a review of its use in Alzheimer's disease.

    PubMed

    Plosker, Greg L

    2015-05-01

    Memantine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that is a well-established treatment option for moderate to severe dementia of the Alzheimer's type, either alone or in combination with cholinesterase inhibitors. The immediate-release (IR) formulations of memantine (tablets and oral solution) have been available in numerous countries, including the USA, for more than a decade and are administered orally twice daily at a maximum recommended total daily dosage of 20 mg/day. The memantine extended-release (ER) (Namenda XR(®)) 28 mg once-daily capsule formulation was approved in the USA in 2010 and became available more recently. The potential advantages of memantine ER over the IR formulation include a more convenient dosage regimen and lower pill burden that may improve adherence to therapy; also, memantine ER capsules may be opened and the contents sprinkled on applesauce for patients who have difficulty swallowing. Memantine ER provides a higher total daily dosage than the recommended memantine IR regimen and pharmacokinetic data indicate greater exposure with the ER formulation, but the clinical implications of this are unclear, as the two formulations have not been assessed in a comparative clinical trial. The efficacy of memantine ER 28 mg once daily was demonstrated in a large, multinational, phase III trial, which showed that the addition of memantine ER to ongoing oral cholinesterase inhibitors improved key outcomes compared with cholinesterase inhibitor monotherapy, including measures of cognition and global status, which were the co-primary endpoints of the study. The most common adverse events were headache, diarrhoea and dizziness.

  4. Pharmacokinetics of 3 Formulations of Meloxicam in Cynomolgus Macaques (Macaca fascicularis)

    PubMed Central

    Bauer, Cassondra; Frost, Patrice; Kirschner, Stephen

    2014-01-01

    Meloxicam is a commonly used COX2-preferential NSAID in both human and veterinary patients. Minimal information has been published regarding appropriate dosing in nonhuman primates. Here we investigated the pharmacokinetic parameters of 3 formulations of meloxicam in cynomolgus macaques. A single dose of meloxicam SR, an extended-release formulation purported to provide therapeutic levels for as long as 72 h, was compared with the intramuscular and oral formulations dosed for 3 consecutive days and as a single dose. The oral formulation, both over 3 d and as a single dose, yielded lower plasma levels and a shorter duration than did intramuscular and sustained-release subcutaneous formulations. The intramuscular formulation, both over 3 d and as a single dose, provided lower plasma levels and a shorter duration than did a sustained-release subcutaneous formulation. The sustained-release formulations generated the highest plasma concentrations for the longest periods of time. None of the formulations caused significant effects on kidney or liver function. Our results indicate that the sustained-release formulation of meloxicam can achieve an adequate steady-state plasma concentration for 2 to 3 d in nonhuman primates. The standard intramuscular formulation provides adequate plasma concentrations for 12 to 24 h, with waxing and waning levels associated with daily dosing. The oral formulation has limited utility in nonhuman primates because of low circulating levels of drug. PMID:25255073

  5. Geometric formulation of the uncertainty principle

    NASA Astrophysics Data System (ADS)

    Bosyk, G. M.; Osán, T. M.; Lamberti, P. W.; Portesi, M.

    2014-03-01

    A geometric approach to formulate the uncertainty principle between quantum observables acting on an N-dimensional Hilbert space is proposed. We consider the fidelity between a density operator associated with a quantum system and a projector associated with an observable, and interpret it as the probability of obtaining the outcome corresponding to that projector. We make use of fidelity-based metrics such as angle, Bures, and root infidelity to propose a measure of uncertainty. The triangle inequality allows us to derive a family of uncertainty relations. In the case of the angle metric, we recover the Landau-Pollak inequality for pure states and show, in a natural way, how to extend it to the case of mixed states in arbitrary dimension. In addition, we derive and compare alternative uncertainty relations when using other known fidelity-based metrics.

  6. Reparametrization of the Relativistic Infinitely Extended Charged Particle Action

    NASA Astrophysics Data System (ADS)

    Saadat, Hassan; Pourhassan, Behnam

    2016-09-01

    In this letter, relativistic infinitely extended particles formulated. Correct form of action with possibility of reparametrization obtained and effect of electric field considered. It may be one of the first step to re-introduce theory of every things given by Nakano and Hessaby many years ago.

  7. Propelling Extended Objects

    ERIC Educational Resources Information Center

    Humbert, Richard

    2010-01-01

    A force acting on just part of an extended object (either a solid or a volume of a liquid) can cause all of it to move. That motion is due to the transmission of the force through the object by its material. This paper discusses how the force is distributed to all of the object by a gradient of stress or pressure in it, which creates the local…

  8. Social Groupwork. A Model for Goal Formulation.

    ERIC Educational Resources Information Center

    Tompkins, Rosamond P.; Gallo, Frank T.

    1978-01-01

    A conceptual model for goal formulation in social groupwork, discussion of existing models and their limitations, and an attempt to formulate an encompassing groupwork model that facilitates goal formulation. (Author/PD)

  9. 40 CFR 152.43 - Alternate formulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Registration Procedures § 152.43 Alternate formulations... label text of the alternate formulation product must be identical to that of the basic formulation....

  10. 40 CFR 152.43 - Alternate formulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Registration Procedures § 152.43 Alternate formulations... label text of the alternate formulation product must be identical to that of the basic formulation....

  11. Surface-integral formulation of scattering theory

    SciTech Connect

    Kadyrov, A.S. Bray, I.; Mukhamedzhanov, A.M.; Stelbovics, A.T.

    2009-07-15

    We formulate scattering theory in the framework of a surface-integral approach utilizing analytically known asymptotic forms of the two-body and three-body scattering wavefunctions. This formulation is valid for both short-range and long-range Coulombic interactions. New general definitions for the potential scattering amplitude are presented. For the Coulombic potentials, the generalized amplitude gives the physical on-shell amplitude without recourse to a renormalization procedure. New post and prior forms for the Coulomb three-body breakup amplitude are derived. This resolves the problem of the inability of the conventional scattering theory to define the post form of the breakup amplitude for charged particles. The new definitions can be written as surface-integrals convenient for practical calculations. The surface-integral representations are extended to amplitudes of direct and rearrangement scattering processes taking place in an arbitrary three-body system. General definitions for the wave operators are given that unify the currently used channel-dependent definitions.

  12. Extended frequency turbofan model

    NASA Technical Reports Server (NTRS)

    Mason, J. R.; Park, J. W.; Jaekel, R. F.

    1980-01-01

    The fan model was developed using two dimensional modeling techniques to add dynamic radial coupling between the core stream and the bypass stream of the fan. When incorporated into a complete TF-30 engine simulation, the fan model greatly improved compression system frequency response to planar inlet pressure disturbances up to 100 Hz. The improved simulation also matched engine stability limits at 15 Hz, whereas the one dimensional fan model required twice the inlet pressure amplitude to stall the simulation. With verification of the two dimensional fan model, this program formulated a high frequency F-100(3) engine simulation using row by row compression system characteristics. In addition to the F-100(3) remote splitter fan, the program modified the model fan characteristics to simulate a proximate splitter version of the F-100(3) engine.

  13. Parallelized solvers for heat conduction formulations

    NASA Technical Reports Server (NTRS)

    Padovan, Joe; Kwang, Abel

    1991-01-01

    Based on multilevel partitioning, this paper develops a structural parallelizable solution methodology that enables a significant reduction in computational effort and memory requirements for very large scale linear and nonlinear steady and transient thermal (heat conduction) models. Due to the generality of the formulation of the scheme, both finite element and finite difference simulations can be treated. Diverse model topologies can thus be handled, including both simply and multiply connected (branched/perforated) geometries. To verify the methodology, analytical and numerical benchmark trends are verified in both sequential and parallel computer environments.

  14. The effect of essential oil formulations for potato sprout suppression.

    PubMed

    Owolabi, Moses S; Lajide, Labunmi; Oladimeji, Matthew O; Setzer, William N

    2010-04-01

    The concerns over safety and environmental impact of synthetic pesticides such as chlorpropham (CIPC) has stimulated interest in finding environmentally benign, natural sprout suppressants, including essential oils. The effects of Chenopodium ambrosioides and Lippia multiflora essential oils on sprout growth and decay of stored potatoes has been investigated. Formulations of essential oils with alumina, bentonite, or kaolin, both with and without Triton X-100 additive, were tested. These formulations have been compared to the pulverized plant materials themselves as well as wick-volatilized essential oils. The results showed that the tested oils possess compositions that make them suitable for application as sprout suppressants. Additionally, the formulation seems to be able to reduce the volatility of the essential oil and artificially extend dormancy of stored potatoes.

  15. Repellent effects of Melaleuca alternifolia (tea tree) oil against cattle tick larvae (Rhipicephalus australis) when formulated as emulsions and in β-cyclodextrin inclusion complexes.

    PubMed

    Yim, Wei Tsun; Bhandari, Bhesh; Jackson, Louise; James, Peter

    2016-07-30

    Rhipicephalus australis (formerly Boophilus microplus) is a one host tick responsible for major economic loss in tropical and subtropical cattle production enterprises. Control is largely dependent on the application of acaricides but resistance has developed to most currently registered chemical groups. Repellent compounds that prevent initial attachment of tick larvae offer a potential alternative to control with chemical toxicants. The repellent effects of Melaleuca alternifolia oil (TTO) emulsions and two β-cyclodextrin complex formulations, a slow release form (SR) and a modified faster release form (FR), were examined in a series of laboratory studies. Emulsions containing 4% and 5% TTO applied to cattle hair in laboratory studies completely repelled ascending tick larvae for 24h whereas 2% and 3% formulations provided 80% protection. At 48h, 5% TTO provided 78% repellency but lower concentrations repelled less than 60% of larvae. In a study conducted over 15 days, 3% TTO emulsion applied to cattle hair provided close to 100% repellency for 2 days, but then protection fell to 23% by day 15. The FR formulation gave significantly greater repellency than the emulsion and the SR formulation from day 3 until the end of the study (P<0.05), providing almost complete repellency at day 3 (99.5%), then decreasing over the period of the study to 49% repellency at day 15. Proof of concept is established for the use of appropriately designed controlled-release formulations to extend the period of repellency provided by TTO against R. australis larvae. PMID:27369582

  16. Extended Testability Analysis Tool

    NASA Technical Reports Server (NTRS)

    Melcher, Kevin; Maul, William A.; Fulton, Christopher

    2012-01-01

    The Extended Testability Analysis (ETA) Tool is a software application that supports fault management (FM) by performing testability analyses on the fault propagation model of a given system. Fault management includes the prevention of faults through robust design margins and quality assurance methods, or the mitigation of system failures. Fault management requires an understanding of the system design and operation, potential failure mechanisms within the system, and the propagation of those potential failures through the system. The purpose of the ETA Tool software is to process the testability analysis results from a commercial software program called TEAMS Designer in order to provide a detailed set of diagnostic assessment reports. The ETA Tool is a command-line process with several user-selectable report output options. The ETA Tool also extends the COTS testability analysis and enables variation studies with sensor sensitivity impacts on system diagnostics and component isolation using a single testability output. The ETA Tool can also provide extended analyses from a single set of testability output files. The following analysis reports are available to the user: (1) the Detectability Report provides a breakdown of how each tested failure mode was detected, (2) the Test Utilization Report identifies all the failure modes that each test detects, (3) the Failure Mode Isolation Report demonstrates the system s ability to discriminate between failure modes, (4) the Component Isolation Report demonstrates the system s ability to discriminate between failure modes relative to the components containing the failure modes, (5) the Sensor Sensor Sensitivity Analysis Report shows the diagnostic impact due to loss of sensor information, and (6) the Effect Mapping Report identifies failure modes that result in specified system-level effects.

  17. Extended Wordsearches in Chemistry

    NASA Astrophysics Data System (ADS)

    Cotton, Simon

    1998-04-01

    Students can be encouraged to develop their factual knowledge by use of puzzles. One strategy described here is the extended wordsearch, where the wordsearch element generates a number of words or phrases from which the answers to a series of questions are selected. The wordsearch can be generated with the aid of computer programs, though in order to make them suitable for students with dyslexia or other learning difficulties, a simpler form is more appropriate. These problems can be employed in a variety of contexts, for example, as topic tests and classroom end-of-lesson fillers. An example is provided in the area of calcium chemistry. Sources of suitable software are listed.

  18. Extended-release morphine sulfate in treatment of severe acute and chronic pain

    PubMed Central

    Balch, Robert J; Trescot, Andrea

    2010-01-01

    Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolism, pharmacodynamics, formulations, and efficacy of the currently available extended-release morphine medications. PMID:21197323

  19. The influence of frusemide formulation on diuretic effect and efficiency

    PubMed Central

    Wakelkamp, Monique; Blechert, Åsa; Eriksson, Maria; Gjellan, Kirsti; Graffner, Christina

    1999-01-01

    Aims Changes in drug delivery rate may result in clinically important changes in drug effects. For the loop diuretic frusemide, it would be desirable to develop controlled release preparations, that could maintain an effective urinary excretion rate over a prolonged period of time. The aim of this study was to investigate the influence of frusemide formulation on frusemide recovery, diuretic effect and efficiency. Methods Twelve subjects were given 60 mg of four different frusemide controlled release formulations in a single-dose, double-blind, randomized 4-way cross-over design. The formulations were three study drugs with different extended dissolution rates (ER1Tab, ER2Tab and ER3Caps) and one reference drug (LR). Urinary volume and contents of frusemide in urine were measured in samples collected over 24 h. Results Substantial differences in frusemide recovery and diuretic efficiency were observed between LR and all other formulations. At 24 h, mean total frusemide recoveries of ER1Tab, ER2Tab and ER3Caps were 52%, 36% and 57% lower, respectively, compared with LR (P < 0.01). Also at 24 h, mean total diuretic efficiency for ER1Tab, ER2Tab and ER3Caps was 83%, 31% and 135% higher, respectively, compared to LR. The rapid dissolution and absorption of LR resulted in a high diuretic response from 0 to 3 h after dosing. However, from 0 to 24 h, there were no differences in diuretic response between the formulations. Conclusions Controlled release formulations of frusemide with a low and extended rate of dissolution lead to a more prolonged absorption and subsequent diuresis, but still maintain a similar cumulative response, due to their higher diuretic efficiency. PMID:10510147

  20. Extended suicide with a pet.

    PubMed

    Cooke, Brian K

    2013-01-01

    The combination of the killing of a pet and a suicide is a perplexing scenario that is largely unexplored in the literature. Many forensic psychiatrists and psychologists may be unaccustomed to considering the significance of the killing of a pet. The subject is important, however, because many people regard their pets as members of their family. A case is presented of a woman who killed her pet dog and herself by carbon monoxide poisoning. The purpose of this article is to provide an initial exploration of the topic of extended suicide with a pet. Forensic mental health evaluations may have a role in understanding the etiology of this event and in opining as to the culpability of individuals who attempt to or successfully kill a pet and then commit suicide. Because the scientific literature is lacking, there is a need to understand this act from a variety of perspectives. First, a social and anthropological perspective will be presented that summarizes the history of the practice of killing of one's pet, with a focus on the ancient Egyptians. A clinical context will examine what relationship animals have to mental illness. A vast body of existing scientific data showing the relevance of human attachment to pets suggests that conclusions from the phenomena of homicide-suicide and filicide-suicide are applicable to extended suicide with a pet. Finally, recommendations will be proposed for both clinical and forensic psychiatrists faced with similar cases. PMID:24051598

  1. General formulation of transverse hydrodynamics

    SciTech Connect

    Ryblewski, Radoslaw; Florkowski, Wojciech

    2008-06-15

    General formulation of hydrodynamics describing transversally thermalized matter created at the early stages of ultrarelativistic heavy-ion collisions is presented. Similarities and differences with the standard three-dimensionally thermalized relativistic hydrodynamics are discussed. The role of the conservation laws as well as the thermodynamic consistency of two-dimensional thermodynamic variables characterizing transversally thermalized matter is emphasized.

  2. Covariant Formulation of Hooke's Law.

    ERIC Educational Resources Information Center

    Gron, O.

    1981-01-01

    Introducing a four-vector strain and a four-force stress, Hooke's law is written as a four-vector equation. This formulation is shown to clarify seemingly paradoxical results in connection with uniformly accelerated motion, and rotational motion with angular acceleration. (Author/JN)

  3. Case Formulation in TADS CBT

    ERIC Educational Resources Information Center

    Rogers, Gregory M.; Reinecke, Mark A.; Curry, John F.

    2005-01-01

    For the Treatment for Adolescents With Depression Study (TADS), a cognitive-behavioral therapy (CBT) manual was developed with the aim of balancing standardization and flexibility. In this article, we describe the manual's case formulation procedures, which served as one major mechanism of flexibility in TADS CBT. We first describe the essential…

  4. Reduced Extended MHD

    NASA Astrophysics Data System (ADS)

    Morrison, P. J.; Abdelhamid, H. M.; Grasso, D.; Hazeltine, R. D.; Lingam, M.; Tassi, E.

    2015-11-01

    Over the years various reduced fluid models have been obtained for modeling plasmas, with the goal of capturing important physics while maintaining computability. Such models have included the physics contained in various generalizations of Ohm's law, including Hall drift and electron inertia. In a recent publication it was shown that full 3D extended MHD is a Hamiltonian system by finding its noncanonical Poisson bracket. Subsequently, this bracket was shown to be derivable from that for Hall MHD by a series of remarkable transformations, which greatly simplifies the proof of the Jacobi identity and allows one to immediately obtain generalizations of the helicity and cross helicity. In this poster we use this structure to obtain exact reduced fluid models with the effects of full two-fluid theory. Results of numerical computations of collisionless reconnection using an exact reduced 4-field model will be presented and analytical comparisons of mode structure of previous reduced models will be made.

  5. Stars with Extended Atmospheres

    NASA Astrophysics Data System (ADS)

    Sterken, C.

    2002-12-01

    This Workshop consisted of a full-day meeting of the Working Group "Sterren met Uitgebreide Atmosferen" (SUA, Working Group Stars with Extended Atmospheres), a discussion group founded in 1979 by Kees de Jager, Karel van der Hucht and Pik Sin The. This loose association of astronomers and astronomy students working in the Dutch-speaking part of the Low Countries (The Netherlands and Flanders) organised at regular intervals one-day meetings at the Universities of Utrecht, Leiden, Amsterdam and Brussels. These meetings consisted of the presentation of scientific results by junior as well as senior members of the group, and by discussions between the participants. As such, the SUA meetings became a forum for the exchange of ideas, and for asking questions and advice in an informal atmosphere. Kees de Jager has been chairman of the WG SUA from the beginning in 1979 till today, as the leading source of inspiration. At the occasion of Prof. Kees de Jager's 80th birthday, we decided to collect the presented talks in written form as a Festschrift in honour of this well-respected and much beloved scientist, teacher and friend. The first three papers deal with the personality of Kees de Jager, more specifically with his role as a supervisor and mentor of young researchers and as a catalyst in the research work of his colleagues. And also about his remarkable role in the establishment of astronomy education and research at the University of Brussels. The next presentation is a very detailed review of solar research, a field in which Cees was prominently active for many years. Then follow several papers dealing with stars about which Kees is a true expert: massive stars and extended atmospheres.

  6. A DENSITY-INDEPENDENT FORMULATION OF SMOOTHED PARTICLE HYDRODYNAMICS

    SciTech Connect

    Saitoh, Takayuki R.; Makino, Junichiro

    2013-05-01

    The standard formulation of the smoothed particle hydrodynamics (SPH) assumes that the local density distribution is differentiable. This assumption is used to derive the spatial derivatives of other quantities. However, this assumption breaks down at the contact discontinuity. At the contact discontinuity, the density of the low-density side is overestimated while that of the high-density side is underestimated. As a result, the pressure of the low-density (high-density) side is overestimated (underestimated). Thus, unphysical repulsive force appears at the contact discontinuity, resulting in the effective surface tension. This tension suppresses fluid instabilities. In this paper, we present a new formulation of SPH, which does not require the differentiability of density. Instead of the mass density, we adopt the internal energy density (pressure) and its arbitrary function, which are smoothed quantities at the contact discontinuity, as the volume element used for the kernel integration. We call this new formulation density-independent SPH (DISPH). It handles the contact discontinuity without numerical problems. The results of standard tests such as the shock tube, Kelvin-Helmholtz and Rayleigh-Taylor instabilities, point-like explosion, and blob tests are all very favorable to DISPH. We conclude that DISPH solved most of the known difficulties of the standard SPH, without introducing additional numerical diffusion or breaking the exact force symmetry or energy conservation. Our new SPH includes the formulation proposed by Ritchie and Thomas as a special case. Our formulation can be extended to handle a non-ideal gas easily.

  7. Extended duration local anesthetic agent in a rat paw model.

    PubMed

    Ickowicz, D E; Golovanevski, L; Domb, A J; Weiniger, C F

    2014-07-01

    Encapsulated local anesthetics extend postoperative analgesic effect following site-directed nerve injection; potentially reducing postoperative complications. Our study aim was to investigate efficacy of our improved extended duration formulation - 15% bupivacaine in poly(DL-lactic acid co castor oil) 3:7 synthesized by ring opening polymerization. In vitro, around 70% of bupivacaine was released from the p(DLLA-CO) 3:7 after 10 days. A single injection of the optimal formulation of 15% bupivacaine-polymer or plain (0.5%) bupivacaine (control), was injected via a 22G needle beside the sciatic nerve of Sprague-Dawley rats under anesthesia; followed (in some animals) by a 1cm longitudinal incision through the skin and fascia of the paw area. Behavioral tests for sensory and motor block assessment were done using Hargreave's hot plate score, von Frey filaments and rearing count. The 15% bupivacaine formulation significantly prolonged sensory block duration up to at least 48 h. Following surgery, motor block was observed for 48 h following administration of bupivacaine-polymer formulation and rearing was reduced (returning to baseline after 48 h). No significant differences in mechanical nociceptive response were observed. The optimized bupivacaine-polymer formulation prolonged duration of local anesthesia effect in our animal model up to at least 48 h. PMID:24726301

  8. A numerically stable formulation of the Green's function parabolic equation: Subtracting the surface-wave pole.

    PubMed

    Gilbert, Kenneth E

    2015-01-01

    The original formulation of the Green's function parabolic equation (GFPE) can have numerical accuracy problems for large normalized surface impedances. To solve the accuracy problem, an improved form of the GFPE has been developed. The improved GFPE formulation is similar to the original formulation, but it has the surface-wave pole "subtracted." The improved GFPE is shown to be accurate for surface impedances varying over 2 orders of magnitude, with the largest having a magnitude exceeding 1000. Also, the improved formulation is slightly faster than the original formulation because the surface-wave component does not have to be computed separately.

  9. Geometric nonlinear formulation for thermal-rigid-flexible coupling system

    NASA Astrophysics Data System (ADS)

    Fan, Wei; Liu, Jin-Yang

    2013-10-01

    This paper develops geometric nonlinear hybrid formulation for flexible multibody system with large deformation considering thermal effect. Different from the conventional formulation, the heat flux is the function of the rotational angle and the elastic deformation, therefore, the coupling among the temperature, the large overall motion and the elastic deformation should be taken into account. Firstly, based on nonlinear strain-displacement relationship, variational dynamic equations and heat conduction equations for a flexible beam are derived by using virtual work approach, and then, Lagrange dynamics equations and heat conduction equations of the first kind of the flexible multibody system are obtained by leading into the vectors of Lagrange multiplier associated with kinematic and temperature constraint equations. This formulation is used to simulate the thermal included hub-beam system. Comparison of the response between the coupled system and the uncoupled system has revealed the thermal chattering phenomenon. Then, the key parameters for stability, including the moment of inertia of the central body, the incident angle, the damping ratio and the response time ratio, are analyzed. This formulation is also used to simulate a three-link system applied with heat flux. Comparison of the results obtained by the proposed formulation with those obtained by the approximate nonlinear model and the linear model shows the significance of considering all the nonlinear terms in the strain in case of large deformation. At last, applicability of the approximate nonlinear model and the linear model are clarified in detail.

  10. Sports Teams Extend Reach

    ERIC Educational Resources Information Center

    Shah, Nirvi

    2012-01-01

    Unlike traditional high school athletic teams, Unified Sports teams are designed to immerse students with intellectual disabilities in a facet of school culture that has largely eluded them. Nationwide, more than 2,000 schools in 42 states have the teams, where the ideal is for about half the athletes on each team to be students with intellectual…

  11. Extending ultra-short pulse laser texturing over large area

    NASA Astrophysics Data System (ADS)

    Mincuzzi, G.; Gemini, L.; Faucon, M.; Kling, R.

    2016-11-01

    Surface texturing by Ultra-Short Pulses Laser (UPL) for industrial applications passes through the use of both fast beam scanning systems and high repetition rate, high average power P, UPL. Nevertheless unwanted thermal effects are expected when P exceeds some tens of W. An interesting strategy for a reliable heat management would consists in texturing with a low fluence values (slightly higher than the ablation threshold) and utilising a Polygon Scanner Heads delivering laser pulses with unrepeated speed. Here we show for the first time that with relatively low fluence it is possible over stainless steel, to obtain surface texturing by utilising a 2 MHz femtosecond laser jointly with a polygonal scanner head in a relatively low fluence regime (0.11 J cm-2). Different surface textures (Ripples, micro grooves and spikes) can be obtained varying the scan speed from 90 m s-1 to 25 m s-1. In particular, spikes formation process has been shown and optimised at 25 m s-1 and a full morphology characterization by SEM has been carried out. Reflectance measurements with integrating sphere are presented to compare reference surface with high scan rate textures. In the best case we show a black surface with reflectance value < 5%.

  12. Passive stabilization for large space systems

    NASA Technical Reports Server (NTRS)

    Sesak, J. R.; Gronet, M. J.; Marinos, G. M.

    1987-01-01

    The optimal tuning of multiple tuned-mass dampers for the transient vibration damping of large space structures is investigated. A multidisciplinary approach is used. Structural dynamic techniques are applied to gain physical insight into absorber/structure interaction and to optimize specific cases. Modern control theory and parameter optimization techniques are applied to the general optimization problem. A design procedure for multi-absorber multi-DOF vibration damping problems is presented. Classical dynamic models are extended to investigate the effects of absorber placement, existing structural damping, and absorber cross-coupling on the optimal design synthesis. The control design process for the general optimization problem is formulated as a linear output feedback control problem via the development of a feedback control canonical form. The techniques are applied to sample micro-g and pointing problems on the NASA dual keel space station.

  13. Uncertainty formulations for multislit interferometry

    NASA Astrophysics Data System (ADS)

    Biniok, Johannes C. G.

    2014-12-01

    In the context of (far-field) multislit interferometry we investigate the utility of two formulations of uncertainty in accounting for the complementarity of spatial localization and fringe width. We begin with a characterization of the relevant observables and general considerations regarding the suitability of different types of measures. The detailed analysis shows that both of the discussed uncertainty formulations yield qualitatively similar results, confirming that they correctly capture the relevant tradeoff. One approach, based on an idea of Aharonov and co-workers, is intuitively appealing and relies on a modification of the Heisenberg uncertainty relation. The other approach, developed by Uffink and Hilgevoord for single- and double-slit experiments, is readily applied to multislits. However, it is found that one of the underlying concepts requires generalization and that the choice of the parameters requires more consideration than was known.

  14. Effects of the oceans on polar motion: Extended investigations

    NASA Technical Reports Server (NTRS)

    Dickman, Steven R.

    1987-01-01

    Matrix formulation of the tide equations (pole tide in nonglobal oceans); matrix formulation of the associated boundary conditions (constraints on the tide velocity at coastlines); and FORTRAN encoding of the tide equations excluding boundary conditions were completed. The need for supercomputer facilities was evident. Large versions of the programs were successfully run on the CYBER, submitting the jobs from SUNY through the BITNET network. The code was also restructured to include boundary constraints.

  15. Giotto Extended Mission (GEM)

    NASA Technical Reports Server (NTRS)

    Wilkins, D. E. B.; Grensemann, M.

    1991-01-01

    The primary objectives of the Giotto Extended Mission (GEM), are to determine the composition and physical state of the Grigg Skjellerup Comet's nucleus; to determine the processes that govern the composition and distribution of neutral and ionized species in the cometary atmosphere. Giotto consists of a single European Space Agency (ESA) spacecraft that was launched in 1985 from Center Spatial Guyanis in French Guiana on an Ariane launch vehicle. After a successful launch into geostationary orbit and a heliocentric transfer trajectory, the spacecraft successfully encountered Halley's Comet in 1986. One month after encountering Halley's Comet, Mar. 1986, the spacecraft was placed in hibernation in a heliocentric orbit slightly less than 1 AU. Between Feb. and Jul. 1990 the spacecraft was successfully reactivated, checked out, and placed on a trajectory course to intercept comet Grigg Skjellerup. The spacecraft has been in hibernation since Jul. 1990. Information is presented in tabular form in the following areas: coverage goals, Deep Space Network Support, frequency assignments, telemetry, command, and tracking support responsibility.

  16. New formulation of leading order anisotropic hydrodynamics

    NASA Astrophysics Data System (ADS)

    Tinti, Leonardo

    2015-05-01

    Anisotropic hydrodynamics is a reorganization of the relativistic hydrodynamics expansion, with the leading order already containing substantial momentum-space anisotropies. The latter are a cause of concern in the traditional viscous hydrodynamics, since large momentum anisotropies generated in ultrarelativistic heavy-ion collisions are not consistent with the hypothesis of small deviations from an isotropic background, i.e., from the local equilibrium distribution. We discuss the leading order of the expansion, presenting a new formulation for the (1+1)- dimensional case, namely, for the longitudinally boost invariant and cylindrically symmetric flow. This new approach is consistent with the well established framework of Israel and Stewart in the close to equilibrium limit (where we expect viscous hydrodynamics to work well). If we consider the (0+1)-dimensional case, that is, transversally homogeneous and longitudinally boost invariant flow, the new form of anisotropic hydrodynamics leads to better agreement with known solutions of the Boltzmann equation than the previous formulations, especially when we consider massive particles.

  17. Extending Beowulf Clusters

    USGS Publications Warehouse

    Steinwand, Daniel R.; Maddox, Brian; Beckmann, Tim; Hamer, George

    2003-01-01

    Beowulf clusters can provide a cost-effective way to compute numerical models and process large amounts of remote sensing image data. Usually a Beowulf cluster is designed to accomplish a specific set of processing goals, and processing is very efficient when the problem remains inside the constraints of the original design. There are cases, however, when one might wish to compute a problem that is beyond the capacity of the local Beowulf system. In these cases, spreading the problem to multiple clusters or to other machines on the network may provide a cost-effective solution.

  18. Deformation modes in the finite element absolute nodal coordinate formulation

    NASA Astrophysics Data System (ADS)

    Sugiyama, Hiroyuki; Gerstmayr, Johannes; Shabana, Ahmed A.

    2006-12-01

    The objective of this study is to provide interpretation of the deformation modes in the finite element absolute nodal coordinate formulation using several strain definitions. In this finite element formulation, the nodal coordinates consist of absolute position coordinates and gradients that can be used to define a unique rotation and deformation fields within the element as well as at the nodal points. The results obtained in this study clearly show cross-section deformation modes eliminated when the number of the finite element nodal coordinates is systematically and consistently reduced. Using the procedure discussed in this paper one can obtain a reduced order dynamic model, eliminate position vector gradients that introduce high frequencies to the solution of some problems, achieve the continuity of the remaining gradients at the nodal points, and obtain a formulation that automatically satisfies the principle of work and energy. Furthermore, the resulting dynamic model, unlike large rotation finite element formulations, leads to a unique rotation field, and as a consequence, the obtained formulation does not suffer from the problem of coordinate redundancy that characterizes existing large deformation finite element formulations. In order to accurately define strain components that can have easy physical interpretation, a material coordinate system is introduced to define the material element rotation and deformation. Using the material coordinate system, the Timoshenko-Reissner and Euler -Bernoulli beam models can be systematically obtained as special cases of the absolute nodal coordinate formulation beam models. While a constraint approach is used in this study to eliminate the cross-section deformation modes, it is important to point out as mentioned in this paper that lower-order finite elements, some of which already presented in previous investigations, can be efficiently used in thin and stiff structure applications.

  19. Note about Hamiltonian formulation of modified F(R) Horava-Lifshitz gravities and their healthy extension

    SciTech Connect

    Kluson, J.

    2010-08-15

    This note is devoted to the study of Hamiltonian formulation of modified F(R) Horava-Lifshitz theories of gravity that were proposed recently by Chaichian and collaborators [arXiv:1001.4102]. We also study Hamiltonian formulation of the healthy extended Horava-Lifshitz gravities and show that these theories have the Hamiltonian structure that is different from Hamiltonian formulation general relativity.

  20. Action principles for extended magnetohydrodynamic models

    SciTech Connect

    Keramidas Charidakos, I.; Lingam, M.; Morrison, P. J.; White, R. L.; Wurm, A.

    2014-09-15

    The general, non-dissipative, two-fluid model in plasma physics is Hamiltonian, but this property is sometimes lost or obscured in the process of deriving simplified (or reduced) two-fluid or one-fluid models from the two-fluid equations of motion. To ensure that the reduced models are Hamiltonian, we start with the general two-fluid action functional, and make all the approximations, changes of variables, and expansions directly within the action context. The resulting equations are then mapped to the Eulerian fluid variables using a novel nonlocal Lagrange-Euler map. Using this method, we recover Lüst's general two-fluid model, extended magnetohydrodynamic (MHD), Hall MHD, and electron MHD from a unified framework. The variational formulation allows us to use Noether's theorem to derive conserved quantities for each symmetry of the action.

  1. Extended Range Prediction of Indian Summer Monsoon: Current status

    NASA Astrophysics Data System (ADS)

    Sahai, A. K.; Abhilash, S.; Borah, N.; Joseph, S.; Chattopadhyay, R.; S, S.; Rajeevan, M.; Mandal, R.; Dey, A.

    2014-12-01

    The main focus of this study is to develop forecast consensus in the extended range prediction (ERP) of monsoon Intraseasonal oscillations using a suit of different variants of Climate Forecast system (CFS) model. In this CFS based Grand MME prediction system (CGMME), the ensemble members are generated by perturbing the initial condition and using different configurations of CFSv2. This is to address the role of different physical mechanisms known to have control on the error growth in the ERP in the 15-20 day time scale. The final formulation of CGMME is based on 21 ensembles of the standalone Global Forecast System (GFS) forced with bias corrected forecasted SST from CFS, 11 low resolution CFST126 and 11 high resolution CFST382. Thus, we develop the multi-model consensus forecast for the ERP of Indian summer monsoon (ISM) using a suite of different variants of CFS model. This coordinated international effort lead towards the development of specific tailor made regional forecast products over Indian region. Skill of deterministic and probabilistic categorical rainfall forecast as well the verification of large-scale low frequency monsoon intraseasonal oscillations has been carried out using hindcast from 2001-2012 during the monsoon season in which all models are initialized at every five days starting from 16May to 28 September. The skill of deterministic forecast from CGMME is better than the best participating single model ensemble configuration (SME). The CGMME approach is believed to quantify the uncertainty in both initial conditions and model formulation. Main improvement is attained in probabilistic forecast which is because of an increase in the ensemble spread, thereby reducing the error due to over-confident ensembles in a single model configuration. For probabilistic forecast, three tercile ranges are determined by ranking method based on the percentage of ensemble members from all the participating models falls in those three categories. CGMME further

  2. Resurgence in extended hydrodynamics

    NASA Astrophysics Data System (ADS)

    Aniceto, Inês; Spaliński, Michał

    2016-04-01

    It has recently been understood that the hydrodynamic series generated by the Müller-Israel-Stewart theory is divergent and that this large-order behavior is consistent with the theory of resurgence. Furthermore, it was observed that the physical origin of this is the presence of a purely damped nonhydrodynamic mode. It is very interesting to ask whether this picture persists in cases where the spectrum of nonhydrodynamic modes is richer. We take the first step in this direction by considering the simplest hydrodynamic theory which, instead of the purely damped mode, contains a pair of nonhydrodynamic modes of complex conjugate frequencies. This mimics the pattern of black brane quasinormal modes which appear on the gravity side of the AdS/CFT description of N =4 supersymmetric Yang-Mills plasma. We find that the resulting hydrodynamic series is divergent in a way consistent with resurgence and precisely encodes information about the nonhydrodynamic modes of the theory.

  3. Mathematical programming formulations for satellite synthesis

    NASA Technical Reports Server (NTRS)

    Bhasin, Puneet; Reilly, Charles H.

    1987-01-01

    The problem of satellite synthesis can be described as optimally allotting locations and sometimes frequencies and polarizations, to communication satellites so that interference from unwanted satellite signals does not exceed a specified threshold. In this report, mathematical programming models and optimization methods are used to solve satellite synthesis problems. A nonlinear programming formulation which is solved using Zoutendijk's method and a gradient search method is described. Nine mixed integer programming models are considered. Results of computer runs with these nine models and five geographically compatible scenarios are presented and evaluated. A heuristic solution procedure is also used to solve two of the models studied. Heuristic solutions to three large synthesis problems are presented. The results of our analysis show that the heuristic performs very well, both in terms of solution quality and solution time, on the two models to which it was applied. It is concluded that the heuristic procedure is the best of the methods considered for solving satellite synthesis problems.

  4. Formulations to the patient: explicit and implicit.

    PubMed

    Cooper, A M

    1994-12-01

    Many of our formulations to the patient are conveyed through the day-to-day unremarkable actions, verbal and nonverbal, occurring between analyst and patient as the analyst attempts to understand his patient within the analytic setting. The analyst's confidence, even intensity, concerning the value of analysis is significant in enabling him to communicate successfully with his patient. Unlike what may have been the case in the past, this analytic fervour is not in the service of a single theory or an attempt to prove an analytic proposition, but is aimed at deepening introspective curiosity and opening avenues of communication. Within our characterologic and procedural limits, we use ourselves in a large variety of ways in an attempt to further the analytic process. This use of ourselves, conveyed to the patient in innumerable interactions, becomes a central analytic fact that fosters the patient's participation in his analysis. Clinical vignettes are provided to illustrate these propositions. PMID:7713649

  5. Liposomal extended-release bupivacaine for postsurgical analgesia

    PubMed Central

    Lambrechts, Mark; O’Brien, Michael J; Savoie, Felix H; You, Zongbing

    2013-01-01

    When physicians consider which analgesia to use postsurgery, the primary goal is to relieve pain with minimal adverse side effects. Bupivacaine, a commonly used analgesic, has been formulated into an aqueous suspension of multivesicular liposomes that provide long-lasting analgesia for up to 72 hours, while avoiding the adverse side effects of opioids. The increased efficacy of liposomal extended-release bupivacaine, compared to bupivacaine hydrochloride, has promoted its usage in a variety of surgeries including hemorrhoidectomy, bunionectomy, inguinal hernia repair, total knee arthroplasty, and augmentation mammoplasty. However, like other bupivacaine formulations, the liposomal extended-release bupivacaine does have some side effects. In this brief review, we provide an update of the current knowledge in the use of bupivacaine for postsurgical analgesia. PMID:24043932

  6. Liposomal extended-release bupivacaine for postsurgical analgesia.

    PubMed

    Lambrechts, Mark; O'Brien, Michael J; Savoie, Felix H; You, Zongbing

    2013-09-06

    When physicians consider which analgesia to use postsurgery, the primary goal is to relieve pain with minimal adverse side effects. Bupivacaine, a commonly used analgesic, has been formulated into an aqueous suspension of multivesicular liposomes that provide long-lasting analgesia for up to 72 hours, while avoiding the adverse side effects of opioids. The increased efficacy of liposomal extended-release bupivacaine, compared to bupivacaine hydrochloride, has promoted its usage in a variety of surgeries including hemorrhoidectomy, bunionectomy, inguinal hernia repair, total knee arthroplasty, and augmentation mammoplasty. However, like other bupivacaine formulations, the liposomal extended-release bupivacaine does have some side effects. In this brief review, we provide an update of the current knowledge in the use of bupivacaine for postsurgical analgesia.

  7. Generalized extended Lagrangian Born-Oppenheimer molecular dynamics

    SciTech Connect

    Niklasson, Anders M. N. Cawkwell, Marc J.

    2014-10-28

    Extended Lagrangian Born-Oppenheimer molecular dynamics based on Kohn-Sham density functional theory is generalized in the limit of vanishing self-consistent field optimization prior to the force evaluations. The equations of motion are derived directly from the extended Lagrangian under the condition of an adiabatic separation between the nuclear and the electronic degrees of freedom. We show how this separation is automatically fulfilled and system independent. The generalized equations of motion require only one diagonalization per time step and are applicable to a broader range of materials with improved accuracy and stability compared to previous formulations.

  8. 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.

  9. Formulation and Stability of Solutions.

    PubMed

    Akers, Michael J

    2016-01-01

    Ready-to-use solutions are the most preferable and most common dosage forms for injectable and topical ophthalmic products. Drugs formulated as solution almost always have chemical and physical stability challenges as well as solubility limitations and the need to prevent inadvertent microbial contamination issues. The first in this series of articles took us through a discussion of optimizing the physical stability of solutions. This article concludes this series of articles with a discussion on foreign particles, protein aggregation, and immunogenicity; optimizing microbiological activity; and osmolality (tonicity) agents, and discusses how these challenges and issues are addressed. PMID:27326440

  10. Mixed-Integer Formulations for Constellation Scheduling

    NASA Astrophysics Data System (ADS)

    Valicka, C.; Hart, W.; Rintoul, M.

    Remote sensing systems have expanded the set of capabilities available for and critical to national security. Cooperating, high-fidelity sensing systems and growing mission applications have exponentially increased the set of potential schedules. A definitive lack of advanced tools places an increased burden on operators, as planning and scheduling remain largely manual tasks. This is particularly true in time-critical planning activities where operators aim to accomplish a large number of missions through optimal utilization of single or multiple sensor systems. Automated scheduling through identification and comparison of alternative schedules remains a challenging problem applicable across all remote sensing systems. Previous approaches focused on a subset of sensor missions and do not consider ad-hoc tasking. We have begun development of a robust framework that leverages the Pyomo optimization modeling language for the design of a tool to assist sensor operators planning under the constraints of multiple concurrent missions and uncertainty. Our scheduling models have been formulated to address the stochastic nature of ad-hoc tasks inserted under a variety of scenarios. Operator experience is being leveraged to select appropriate model objectives. Successful development of the framework will include iterative development of high-fidelity mission models that consider and expose various schedule performance metrics. Creating this tool will aid time-critical scheduling by increasing planning efficiency, clarifying the value of alternative modalities uniquely provided by multi-sensor systems, and by presenting both sets of organized information to operators. Such a tool will help operators more quickly and fully utilize sensing systems, a high interest objective within the current remote sensing operations community. Preliminary results for mixed-integer programming formulations of a sensor scheduling problem will be presented. Assumptions regarding sensor geometry

  11. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

    PubMed Central

    Mitragotri, Samir; Burke, Paul A.; Langer, Robert

    2015-01-01

    The formulation and delivery of biopharmaceutical drugs, such as monoclonal antibodies and recombinant proteins, poses substantial challenges owing to their large size and susceptibility to degradation. In this Review we highlight recent advances in formulation and delivery strategies — such as the use of microsphere-based controlled-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, and genetic manipulation of biopharmaceutical drugs — and discuss their advantages and limitations. We also highlight current and emerging delivery routes that provide an alternative to injection, including transdermal, oral and pulmonary delivery routes. In addition, the potential of targeted and intracellular protein delivery is discussed. PMID:25103255

  12. Abuse deterrent formulations and the Controlled Substances Act (CSA).

    PubMed

    Sapienza, Frank L

    2006-06-01

    The Controlled Substances Act (CSA) has reduced the diversion of controlled substances at the manufacturing and distribution levels. Recent increased diversion has occurred at the retail level. Levels of diversion and abuse of controlled substances with similar abuse potential and therapeutic indications often parallel availability for medical use, while rates of diversion and abuse may be influenced by factors related to specific products, including their formulations and risk management plans. Abuse deterrent formulations may reduce abuse and attendant adverse health consequences even if the products are diverted. Their development should consider how, to what extent and by whom products containing the targeted substance are abused. It should take into consideration all potential types of abuse including "as is", multiple doses, alternate routes of administration, physical or chemical separation of the active ingredient, compromised extended release mechanisms and abuse in combination with other substances. Industry incentives for developing abuse-resistant formulations include enhanced corporate image and potentially less restrictive scheduling or risk management plans. Scheduling is substance specific, but the CSA includes products/formulations that are differentially scheduled. Issues to be considered for differential scheduling under the CSA include: (1) whether there is legal authority to do so; (2) application of standard scheduling criteria to individual products; (3) product specific data for "eight factor analyses"; (4) development of predictive data and standards accepted by the scientific and regulatory communities; (5) use of predictive data or post marketing surveillance data; (6) international treaty obligations. These issues must be addressed before differential scheduling can be considered.

  13. Bioconvection in spatially extended domains

    NASA Astrophysics Data System (ADS)

    Karimi, A.; Paul, M. R.

    2013-05-01

    We numerically explore gyrotactic bioconvection in large spatially extended domains of finite depth using parameter values from available experiments with the unicellular alga Chlamydomonas nivalis. We numerically integrate the three-dimensional, time-dependent continuum model of Pedley [J. Fluid Mech.10.1017/S0022112088002393 195, 223 (1988)] using a high-order, parallel, spectral-element approach. We explore the long-time nonlinear patterns and dynamics found for layers with an aspect ratio of 10 over a range of Rayleigh numbers. Our results yield the pattern wavelength and pattern dynamics which we compare with available theory and experimental measurement. There is good agreement for the pattern wavelength at short times between numerics, experiment, and a linear stability analysis. At long times we find that the general sequence of patterns given by the nonlinear evolution of the governing equations correspond qualitatively to what has been described experimentally. However, at long times the patterns in numerics grow to larger wavelengths, in contrast to what is observed in experiment where the wavelength is found to decrease with time.

  14. Primal and dual formulations of sequential gradient-restoration algorithms for trajectory optimization problems

    NASA Technical Reports Server (NTRS)

    Miele, A.; Wang, T.; Basapur, V. K.

    1986-01-01

    One of the most effective first-order algorithms for solving trajectory optimization problems is the sequential gradient-restoration algorithm (SGRA). Originally developed in the primal formulation, this algorithm is extended to incorporate a dual formulation. Both the primal formulation and the dual formulation involve a sequence of two-phase cycles, each cycle including a gradient phase and a restoration phase. In turn, each iteration of the gradient phase and the restoration phase requires the solution of an auxiliary minimization problem (AMP). In the primal formulation, the AMP is solved with respect to the variations of the state, the control, and the parameter. In the dual formulation, the AMP is solved with respect to the Lagrange multipliers. A characteristic of the dual formulation is that the AMPs associated with the gradient phase and the restoration phase of SGRA can be reduced to mathematical programming problems involving a finite number of parameters as unknowns. A comparison of the primal formulation and the dual formulation is presented. The comparison is done in terms of several trajectory optimization problems having current aerospace interest.

  15. Formulation, Preparation, and Characterization of Polyurethane Foams

    ERIC Educational Resources Information Center

    Pinto, Moises L.

    2010-01-01

    Preparation of laboratory-scale polyurethane foams is described with formulations that are easy to implement in experiments for undergraduate students. Particular attention is given to formulation aspects that are based on the main chemical reactions occurring in polyurethane production. This allows students to develop alternative formulations to…

  16. ANTI-RHEUMATIC FORMULATIONS FROM AYURVEDA

    PubMed Central

    Raut, A. A.; Joshi, A. D.; Antarkar, D. S.; Joshi, V. R.; Vaidya, A. B.

    1991-01-01

    Rheumatic disorders like Amavata, Sandhivata and Vatarakta are elaborately described in ayurvedic literature. Preliminary survey of literature shows that about 247 formulations are recommended for these rheumatic disorders. These formulations generally include guggulu compounds, compounds of plant powders, decoctions, medicated ghees, oils, electuaries etc. Therapeutic potential of ayurvedic concepts and a brief review of Ayurvedic formulations are also discussed. PMID:22556565

  17. NAIF Toolkit - Extended

    NASA Technical Reports Server (NTRS)

    Acton, Charles H., Jr.; Bachman, Nathaniel J.; Semenov, Boris V.; Wright, Edward D.

    2010-01-01

    The Navigation Ancillary Infor ma tion Facility (NAIF) at JPL, acting under the direction of NASA s Office of Space Science, has built a data system named SPICE (Spacecraft Planet Instrument Cmatrix Events) to assist scientists in planning and interpreting scientific observations (see figure). SPICE provides geometric and some other ancillary information needed to recover the full value of science instrument data, including correlation of individual instrument data sets with data from other instruments on the same or other spacecraft. This data system is used to produce space mission observation geometry data sets known as SPICE kernels. It is also used to read SPICE kernels and to compute derived quantities such as positions, orientations, lighting angles, etc. The SPICE toolkit consists of a subroutine/ function library, executable programs (both large applications and simple utilities that focus on kernel management), and simple examples of using SPICE toolkit subroutines. This software is very accurate, thoroughly tested, and portable to all computers. It is extremely stable and reusable on all missions. Since the previous version, three significant capabilities have been added: Interactive Data Language (IDL) interface, MATLAB interface, and a geometric event finder subsystem.

  18. Solute drag on perfect and extended dislocations

    NASA Astrophysics Data System (ADS)

    Sills, R. B.; Cai, W.

    2016-04-01

    The drag force exerted on a moving dislocation by a field of mobile solutes is studied in the steady state. The drag force is numerically calculated as a function of the dislocation velocity for both perfect and extended dislocations. The sensitivity of the non-dimensionalized force-velocity curve to the various controlling parameters is assessed, and an approximate analytical force-velocity expression is given. A non-dimensional parameter S characterizing the strength of the solute-dislocation interaction, the background solute fraction ?, and the dislocation character angle ?, are found to have the strongest influence on the force-velocity curve. Within the model considered here, a perfect screw dislocation experiences no solute drag, but an extended screw dislocation experiences a non-zero drag force that is about 10 to 30% of the drag on an extended edge dislocation. The solutes can change the spacing between the Shockley partials in both stationary and moving extended dislocations, even when the stacking fault energy remains unaltered. Under certain conditions, the solutes destabilize an extended dislocation by either collapsing it into a perfect dislocation or causing the partials to separate unboundedly. It is proposed that the latter instability may lead to the formation of large faulted areas and deformation twins in low stacking fault energy materials containing solutes, consistent with experimental observations of copper and stainless steel containing hydrogen.

  19. Aerodynamic Shape Optimization of Complex Aircraft Configurations via an Adjoint Formulation

    NASA Technical Reports Server (NTRS)

    Reuther, James; Jameson, Antony; Farmer, James; Martinelli, Luigi; Saunders, David

    1996-01-01

    This work describes the implementation of optimization techniques based on control theory for complex aircraft configurations. Here control theory is employed to derive the adjoint differential equations, the solution of which allows for a drastic reduction in computational costs over previous design methods (13, 12, 43, 38). In our earlier studies (19, 20, 22, 23, 39, 25, 40, 41, 42) it was shown that this method could be used to devise effective optimization procedures for airfoils, wings and wing-bodies subject to either analytic or arbitrary meshes. Design formulations for both potential flows and flows governed by the Euler equations have been demonstrated, showing that such methods can be devised for various governing equations (39, 25). In our most recent works (40, 42) the method was extended to treat wing-body configurations with a large number of mesh points, verifying that significant computational savings can be gained for practical design problems. In this paper the method is extended for the Euler equations to treat complete aircraft configurations via a new multiblock implementation. New elements include a multiblock-multigrid flow solver, a multiblock-multigrid adjoint solver, and a multiblock mesh perturbation scheme. Two design examples are presented in which the new method is used for the wing redesign of a transonic business jet.

  20. The extended Touschek lifetime

    SciTech Connect

    Bizek, H.M.

    1996-02-01

    With the advent of synchrotron radiation sources, the issue of beam lifetime becomes increasingly important. Users of these machines need to perform experiments which seldom last 15 minutes, but require hours for their completion. Therefore, the beam should circulate stably for hours. The beam of the Advanced Photon Source (APS) storage ring at Argonne National Laboratory is assumed to circulate stably for a minimum of 10 hours. The main contributions to the total beam lifetime (which is the inverse of the loss rate) come from residual gas scattering and Touschek scattering. The residual gas scattering is comprised of single Coulomb scattering and bremsstrahlung. The single-Coulomb scattering involves elastic collisions, while bremsstrahlung involves inelastic collisions, between the bunch and the surrounding residual gas. In the calculation the authors take the gas to be nitrogen at a pressure of 1 nTorr. Touschek scattering involves scattering of particles within the bunch, transferring energy among themselves. Such an energy transfer, if large enough, may eject the particle out of the bunch, thus causing it to be lost. Let us not forget the residual-gas lifetime. As pointed out, the calculation of this lifetime is done for the very low pressure of 1 nTorr. If the pressure is higher, the residual-gas lifetime will be smaller. This will further reduce the total beam lifetime, causing it to slip deeper below the minimum lifetime for stable storage ring operation. They begin this article by reviewing the Touschek integral and the associated limits of integration. The program ZAP has been altered to take into account the possible loss due to induced betatron oscillations. At each lattice position the energy loss required to produce, by coupling, a vertical oscillation that exceeds the vertical aperture is calculated. When this energy loss is less than the rf bucket half-height, it replaces the rf bucket half-height in the Touschek integral.

  1. Generalized massive gravity in arbitrary dimensions and its Hamiltonian formulation

    SciTech Connect

    Huang, Qing-Guo; Zhang, Ke-Chao; Zhou, Shuang-Yong E-mail: zkc@itp.ac.cn

    2013-08-01

    We extend the four-dimensional de Rham-Gabadadze-Tolley (dRGT) massive gravity model to a general scalar massive-tensor theory in arbitrary dimensions, coupling a dRGT massive graviton to multiple scalars and allowing for generic kinetic and mass matrix mixing between the massive graviton and the scalars, and derive its Hamiltonian formulation and associated constraint system. When passing to the Hamiltonian formulation, two different sectors arise: a general sector and a special sector. Although obtained via different ways, there are two second class constraints in either of the two sectors, eliminating the BD ghost. However, for the special sector, there are still ghost instabilities except for the case of two dimensions. In particular, for the special sector with one scalar, there is a ''second BD ghost''.

  2. Metaplectic Formulation of the Wigner Transform and Applications

    NASA Astrophysics Data System (ADS)

    Dias, Nuno Costa; de Gosson, Maurice A.; Prata, João Nuno

    2013-11-01

    We show that the cross Wigner function can be written in the form W(ψ , φ ) = \\hat S (ψ ⊗ /line{\\hat φ }) where {\\hat φ } is the Fourier transform of ϕ and \\Scirc is a metaplectic operator that projects onto a linear symplectomorphism S consisting of a rotation along an ellipse in phase space (or in the time-frequency space). This formulation can be extended to generic Weyl symbols and yields an interesting fractional generalization of the Weyl-Wigner formalism. It also provides a suitable approach to study the Bopp phase space representation of quantum mechanics, familiar from deformation quantization. Using the "metaplectic formulation" of the Wigner transform, we construct a complete set of intertwiners relating the Weyl and the Bopp pseudo-differential operators. This is an important result that allows us to prove the spectral and dynamical equivalence of the Schrödinger and the Bopp representations of quantum mechanics.

  3. Canonical formulation and path integral for local vacuum energy sequestering

    NASA Astrophysics Data System (ADS)

    Bufalo, R.; KlusoÅ, J.; Oksanen, M.

    2016-08-01

    We establish the Hamiltonian analysis and the canonical path integral for a local formulation of vacuum energy sequestering. In particular, by considering the state of the Universe as a superposition of vacuum states corresponding to different values of the cosmological and gravitational constants, the path integral is extended to include integrations over the cosmological and gravitational constants. The result is an extension of the Ng-van Dam form of the path integral of unimodular gravity. It is argued to imply a relation between the fraction of the most likely values of the gravitational and cosmological constants and the average values of the energy density and pressure of matter over spacetime. Finally, we construct and analyze a Becchi-Rouet-Stora-Tyutin-exact formulation of the theory, which can be considered as a topological field theory.

  4. Levomilnacipran extended release: first global approval.

    PubMed

    Hair, Philip; Cameron, Fiona; Garnock-Jones, Karly P

    2013-09-01

    Pierre Fabre and Forest Laboratories are developing levomilnacipran extended release (ER) [FETZIMA™], an enantiomer of milnacipran, for the treatment of major depressive disorder (MDD). In addition, Pierre Fabre (the originator of the compound) is developing the drug to improve recovery in patients with ischaemic stroke. Levomilnacipran ER exerts its effects by selectively inhibiting the reuptake of norepinephrine and serotonin (two neurotransmitters known to play an essential role in regulating mood) without directly affecting the uptake of dopamine or other neurotransmitters. The agent is being developed as an extended-release capsule formulation for once-daily dosing. Levomilnacipran ER is approved and launched in the US for the treatment of MDD; phase III development in this indication was completed in the US and Canada. In Europe, a phase II trial for MDD was completed, and development is in progress for improving functional recovery of patients with ischaemic stroke. A completed phase II trial in the US investigated levomilnacipran ER for the treatment of fatigue associated with MDD. This article summarizes the milestones in the development of levomilnacipran ER leading to the first approval for major depressive disorder.

  5. Levomilnacipran extended release: first global approval.

    PubMed

    Hair, Philip; Cameron, Fiona; Garnock-Jones, Karly P

    2013-09-01

    Pierre Fabre and Forest Laboratories are developing levomilnacipran extended release (ER) [FETZIMA™], an enantiomer of milnacipran, for the treatment of major depressive disorder (MDD). In addition, Pierre Fabre (the originator of the compound) is developing the drug to improve recovery in patients with ischaemic stroke. Levomilnacipran ER exerts its effects by selectively inhibiting the reuptake of norepinephrine and serotonin (two neurotransmitters known to play an essential role in regulating mood) without directly affecting the uptake of dopamine or other neurotransmitters. The agent is being developed as an extended-release capsule formulation for once-daily dosing. Levomilnacipran ER is approved and launched in the US for the treatment of MDD; phase III development in this indication was completed in the US and Canada. In Europe, a phase II trial for MDD was completed, and development is in progress for improving functional recovery of patients with ischaemic stroke. A completed phase II trial in the US investigated levomilnacipran ER for the treatment of fatigue associated with MDD. This article summarizes the milestones in the development of levomilnacipran ER leading to the first approval for major depressive disorder. PMID:24000002

  6. Parallel computing using a Lagrangian formulation

    NASA Technical Reports Server (NTRS)

    Liou, May-Fun; Loh, Ching Yuen

    1991-01-01

    A new Lagrangian formulation of the Euler equation is adopted for the calculation of 2-D supersonic steady flow. The Lagrangian formulation represents the inherent parallelism of the flow field better than the common Eulerian formulation and offers a competitive alternative on parallel computers. The implementation of the Lagrangian formulation on the Thinking Machines Corporation CM-2 Computer is described. The program uses a finite volume, first-order Godunov scheme and exhibits high accuracy in dealing with multidimensional discontinuities (slip-line and shock). By using this formulation, a better than six times speed-up was achieved on a 8192-processor CM-2 over a single processor of a CRAY-2.

  7. Multivariate analysis of identity of imported technical PCN formulation.

    PubMed

    Falandysz, J; Chudzyński, K; Takekuma, M; Yamamoto, T; Noma, Y; Hanari, N; Yamashita, N

    2008-10-01

    Chloronaphthalenes form a class of compounds consisting of 8 CN homologue groups and altogether of 75 congeners, which used have been most extensively in 1930--1950. An investigation have been performed on the possible origin of unidentified by name technical chloronaphthalene formulation unlawfully imported recently from the United Kingdom to Japan. Principal component analysis (PCA) and Cluster Analysis of chloronaphthalene congener isomer-specific and homologue classes' compositional HRGC/HRMS data of imported CN formulation and of certain brands of technical CN formulation called Halowax (Halowax 1000, 1001 and 1031) enabled to identify that unnamed product is not Halowax 1001. A less accurate multivariate examination based on CN homologue classes patter did indicate on large similarity between unlawfully imported technical CN formulation and Halowax 1001 (manufactured by the Koppers Ind. Co., USA), while a more accurate based on CN congeners pattern differentiated them as to of various origin mixtures. Based on chlorine content of imported CN formulation (50-52%) and its no similarity to Halowax 1001 it seems reasonable to conclude that unnamed CN mixture examined could be a sample of stockpiled Seekay wax R93.

  8. Meclizine metabolism and pharmacokinetics: formulation on its absorption.

    PubMed

    Wang, Zhijun; Lee, Benjamin; Pearce, Daniel; Qian, Shuai; Wang, Yanfeng; Zhang, Qizhi; Chow, Moses S S

    2012-09-01

    Meclizine, an antihistamine, has been widely used for prophylactic treatment and management of motion sickness. However, the onset of action of meclizine was about 1 hour for the treatment of motion sickness and vertigo. A new suspension formulation of meclizine (MOS) was developed with the intention to achieve a rapid effect. To investigate the pharmacokinetics of the new MOS formulation versus the marketed meclizine oral tablet (MOT), a phase 1 pharmacokinetic study was performed in 20 healthy volunteers. In addition, an in vitro metabolic study using human hepatic microsome and recombinant CYP enzyme was also performed to determine the metabolic pathway in the human body. The plasma concentration of MOS appeared more rapidly in comparison to the MOT. The geometric mean ratios (90% confidence interval) of AUC(0-24) and AUC(0-∞) indicated no significant difference in bioavailability between the 2 formulations. CYP2D6 was found to be the dominant enzyme for metabolism of meclizine, and its genetic polymorphism could contribute to the large interindividual variability. In view of the similar bioavailability with a much shorter peak time of the plasma meclizine concentration from the MOS formulation, this new formulation is expected to produce a much quicker onset of action when used for the management of motion sickness. PMID:21903894

  9. Street Men, Family Men: Race and Men's Extended Family Integration

    ERIC Educational Resources Information Center

    Sarkisian, Natalia

    2007-01-01

    Disorganization theories postulate that black men have largely abandoned their familial roles. Using the NSFH data, this article refutes the hypothesis of black men's familial disengagement by focusing on extended family integration. Black men are more likely than white men to live with or near extended kin, as well as to frequently see kin in…

  10. Hamiltonian formulation of general relativity.

    NASA Astrophysics Data System (ADS)

    Teitelboim, Claudio

    The following sections are included: * INTRODUCTION * HAMILTONIAN FORMULATION OF GAUGE THEORIES (PRE-BRST) * BRST HAMILTONIAN FORMULATION OF GAUGE THEORIES * DYNAMICS OF GRAVITATIONAL FIELD * DOES THE HAMILTONIAN VANISH? GENERAL COVARIANCE AS AN "ORDINARY" GAUGE INVARIANCE * GENERALLY COVARIANT SYSTEMS * TIME AS A CANONICAL VARIABLE. ZERO HAMILTONIAN * Parametrized Systems * Zero Hamiltonian * Parametrization and Explicit Time Dependence * TIME REPARAMETRIZATION INVARIANCE * Form of Gauge Transformations * Must the Hamiltonian be Zero for a Generally Covariant System? * Simple Example of a Generally Covariant System with a Nonzero Hamiltonian * "TRUE DYNAMICS" VERSUS GAUGE TRANSFORMATIONS * Interpretation of the Formalism * Reduced Phase Space * MUST TIME FLOW? * GAUGE INDEPENDENCE OF PATH INTEGRAL FOR A PARAMETRIZED SYSTEM ILLUSTRATED. EQUIVALENCE OF THE GAUGES t = τ AND t = 0 * Reduced Phase Space Transition Amplitude as a Reduced Phase Space Path Integral * Canonical Gauge Conditions * Gauge t = 0 * Gauge t α τ * BRST CHARGE OF GRAVITATIONAL FIELD * ELEMENTS OF BRST THEORY * THE GHOST, YOU'VE COME A LONG WAY BABY * Introduction * Quantum mechanics, the art of finding and combining simple elementary processes * Ghosts necessary to keep elementary processes simple * BRST symmetry: ghosts and matter become different components of single geometrical object * BRST SYMMETRY IN CLASSICAL MECHANICS * Ghosts have role in classical mechanics * Gauge invariance and constraints * Classical mechanics over Grassmann algebra necessary * Higher order structure functions * Rank defined. Open algebras * Ghosts. Ghost number. BRST generator as generating function for structure functions * A belianization of constraints. Existence of Ω * Uniqueness of Ω * Classical BRST cohomology * QUANTUM BRST THEORY * States and operators * Ghost number * BRST invariant states * Quantum BRST cohomology * Equivalence of the BRST physical subspace with the conventional gauge

  11. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2014-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  12. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2016-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  13. Extended active disturbance rejection controller

    NASA Technical Reports Server (NTRS)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2012-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  14. New formulations of monotonically convergent quantum control algorithms

    NASA Astrophysics Data System (ADS)

    Maday, Yvon; Turinici, Gabriel

    2003-05-01

    Most of the numerical simulation in quantum (bilinear) control have used one of the monotonically convergent algorithms of Krotov (introduced by Tannor et al.) or of Zhu and Rabitz. However, until now no explicit relationship has been revealed between the two algorithms in order to understand their common properties. Within this framework, we propose in this paper a unified formulation that comprises both algorithms and that extends to a new class of monotonically convergent algorithms. Numerical results show that the newly derived algorithms behave as well as (and sometimes better than) the well-known algorithms cited above.

  15. [ALCHEMI formulated for delocalization and anti-site defects

    SciTech Connect

    Anderson, I.M.; Bentley, J.

    1994-06-01

    ALCHEMI (atom location by channeling enhanced microanalysis) provides a useful method for determining the site distributions of impurity atoms in crystals with multiple sublattices. Delocalization of low energy excitations and the dubious statistical confidence level of the technique are problems; a recent formulation of ALCHEMI analysis (Walls, 1992) addresses both problems. This paper extends this analysis for the distribution of atoms over two sublattices; expressions are derived for the fit parameters that are exact given the assumptions of the model, which allows for arbitrary localization constants, and for the possibility of anti-site defects.

  16. Orally delivered microencapsulated probiotic formulation favorably impacts polyp formation in APC (Min/+) model of intestinal carcinogenesis.

    PubMed

    Urbanska, Aleksandra Malgorzata; Bhathena, Jasmine; Cherif, Sofiane; Prakash, Satya

    2016-01-01

    The development of intestinal polyps in an orthotopic colorectal mouse model, receiving a probiotic yogurt formulation containing microencapsulated live Lactobacillus acidophilus cells was investigated. The expression of various immunohistochemical markers namely CD8, Mac-1, Ki-67, and cleaved caspase-3, was evaluated. Results suggest that the probiotic formulation decreases overall intestinal inflammation. Mice receiving the probiotic formulation were found to develop almost two-fold fewer tumors in the small intestines. In the large intestine, however, there was no significant difference observed among polyp numbers. The formulation appears to have potential application in the prevention of various GI pathological conditions. PMID:25060720

  17. Autoplan: A self-processing network model for an extended blocks world planning environment

    NASA Technical Reports Server (NTRS)

    Dautrechy, C. Lynne; Reggia, James A.; Mcfadden, Frank

    1990-01-01

    Self-processing network models (neural/connectionist models, marker passing/message passing networks, etc.) are currently undergoing intense investigation for a variety of information processing applications. These models are potentially very powerful in that they support a large amount of explicit parallel processing, and they cleanly integrate high level and low level information processing. However they are currently limited by a lack of understanding of how to apply them effectively in many application areas. The formulation of self-processing network methods for dynamic, reactive planning is studied. The long-term goal is to formulate robust, computationally effective information processing methods for the distributed control of semiautonomous exploration systems, e.g., the Mars Rover. The current research effort is focusing on hierarchical plan generation, execution and revision through local operations in an extended blocks world environment. This scenario involves many challenging features that would be encountered in a real planning and control environment: multiple simultaneous goals, parallel as well as sequential action execution, action sequencing determined not only by goals and their interactions but also by limited resources (e.g., three tasks, two acting agents), need to interpret unanticipated events and react appropriately through replanning, etc.

  18. Symmetric Galerkin boundary formulations employing curved elements

    NASA Technical Reports Server (NTRS)

    Kane, J. H.; Balakrishna, C.

    1993-01-01

    Accounts of the symmetric Galerkin approach to boundary element analysis (BEA) have recently been published. This paper attempts to add to the understanding of this method by addressing a series of fundamental issues associated with its potential computational efficiency. A new symmetric Galerkin theoretical formulation for both the (harmonic) heat conduction and the (biharmonic) elasticity problem that employs regularized singular and hypersingular boundary integral equations (BIEs) is presented. The novel use of regularized BIEs in the Galerkin context is shown to allow straightforward incorporation of curved, isoparametric elements. A symmetric reusable intrinsic sample point (RISP) numerical integration algorithm is shown to produce a Galerkin (i.e., double) integration strategy that is competitive with its counterpart (i.e., singular) integration procedure in the collocation BEA approach when the time saved in the symmetric equation solution phase is also taken into account. This new formulation is shown to be capable of employing hypersingular BIEs while obviating the requirement of C 1 continuity, a fact that allows the employment of the popular continuous element technology. The behavior of the symmetric Galerkin BEA method with regard to both direct and iterative equation solution operations is also addressed. A series of example problems are presented to quantify the performance of this symmetric approach, relative to the more conventional unsymmetric BEA, in terms of both accuracy and efficiency. It is concluded that appropriate implementations of the symmetric Galerkin approach to BEA indeed have the potential to be competitive with, if not superior to, collocation-based BEA, for large-scale problems.

  19. Extension of the approximate two-dimensional electron gas formulation

    NASA Astrophysics Data System (ADS)

    Pierret, R. F.

    1985-07-01

    The functional two-dimensional electron gas (2DEG) formalism employed in the analysis of modulation-doped field-effect transistors is extended to properly account for the bulk charge and to more accurately model sub- and near-threshold behavior. The implemented changes basically transform the functional formulation from an above-threshold formalism for lightly doped structures to one of additional utility which automatically approaches expected limits under widely divergent conditions. Sample computations of the surface carrier concentration, relevant energy level positionings, and the semiconductor depletion width as a function of surface potential and doping are also presented and examined. These computations exhibit the general utility of the extended theory and provide an indirect evaluation of the standard two-level 2DEG theory.

  20. Effects of aerosol formulation to amino acids and fatty acids contents in Haruan extract.

    PubMed

    Febriyenti; Bai-Baie, Saringat Bin; Laila, Lia

    2012-01-01

    Haruan (Channa striatus) extract was formulated to aerosol for wound and burn treatment. Haruan extract is containing amino acids and fatty acids that important for wound healing process. The purpose of this study is to observe the effect of formulation and other excipients in the formula to amino acids and fatty acids content in Haruan extract before and after formulated into aerosol. Precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) method is used for amino acids analysis. Fatty acids in Haruan extract were esterified using transesterification method to form FAMEs before analyzed using GC. Boron trifluoride-methanol reagent is used for transesterification. Tyrosine and methionine concentrations were different after formulated. The concentrations were decrease. There are six fatty acids have amount that significantly different after formulated into concentrate and aerosol. Contents of these fatty acids were increase. Generally, fatty acids which had content increased after formulated were the long-chain fatty acids. This might be happen because of chain extension process. Saponification and decarboxylation would give the chain extended product. Therefore contents of long-chain fatty acids were increase. Generally, the aerosol formulation did not affect the amino acids concentrations in Haruan extract while some long-chain fatty acids concentrations were increase after formulated into concentrate and aerosol.

  1. Novel Approaches in Formulation of Entomopathogenic Fungi for Control of Insects in Soil, Foliar, and Structural Habitats: Thinking Outside the Box and Expecting the Unexpected

    Technology Transfer Automated Retrieval System (TEKTRAN)

    By and large, mycoinsecticide formulations have involved sprayable products, typically oil flowables, emulsifiable suspensions, wettable powders, and water dispersable granules. Various nutritive or inert carriers have been used to create granular formulations for use against soil pests. Sometime...

  2. A method of teaching psychodynamic case formulation.

    PubMed

    Ivey, Gavin

    2006-01-01

    In light of the paucity of literature discussing the systematic instruction of trainee psychologists in psychodynamic case formulation, the author introduces an eight-step method for teaching the theory and application of psychodynamic case formulation. The method involves clarifying the nature of psychodynamic formulations, outlining the characteristics of competent formulations, presenting a conceptually simple structure for organizing case material, exposing trainees to carefully selected written and video-recorded cases, and getting trainees to use their subjective responses to video-recorded initial clinical interviews as a source of useful hypotheses. A case study from the literature is used to demonstrate this formulation methodology. The paper concludes with a discussion of both the prerequisites for, and characteristics of, competent case formulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  3. Cognitive Transformations and Extended Expertise

    ERIC Educational Resources Information Center

    Menary, Richard; Kirchhoff, Michael

    2014-01-01

    Expertise is extended by becoming immersed in cultural practices. We look at an example of mathematical expertise in which immersion in cognitive practices results in the transformation of expert performance.

  4. Potential formulation of sleep dynamics

    NASA Astrophysics Data System (ADS)

    Phillips, A. J. K.; Robinson, P. A.

    2009-02-01

    A physiologically based model of the mechanisms that control the human sleep-wake cycle is formulated in terms of an equivalent nonconservative mechanical potential. The potential is analytically simplified and reduced to a quartic two-well potential, matching the bifurcation structure of the original model. This yields a dynamics-based model that is analytically simpler and has fewer parameters than the original model, allowing easier fitting to experimental data. This model is first demonstrated to semiquantitatively match the dynamics of the physiologically based model from which it is derived, and is then fitted directly to a set of experimentally derived criteria. These criteria place rigorous constraints on the parameter values, and within these constraints the model is shown to reproduce normal sleep-wake dynamics and recovery from sleep deprivation. Furthermore, this approach enables insights into the dynamics by direct analogies to phenomena in well studied mechanical systems. These include the relation between friction in the mechanical system and the timecourse of neurotransmitter action, and the possible relation between stochastic resonance and napping behavior. The model derived here also serves as a platform for future investigations of sleep-wake phenomena from a dynamical perspective.

  5. Postmodern string theory: Stochastic formulation

    NASA Astrophysics Data System (ADS)

    Aurilia, A.; Spallucci, E.; Vanzetta, I.

    1994-11-01

    In this paper we study the dynamics of a statistical ensemble of strings, building on a recently proposed gauge theory of the string geodesic field. We show that this stochastic approach is equivalent to the Carathéodory formulation of the Nambu-Goto action, supplemented by an averaging procedure over the family of classical string world sheets which are solutions of the equation of motion. In this new framework, the string geodesic field is reinterpreted as the Gibbs current density associated with the string statistical ensemble. Next, we show that the classical field equations derived from the string gauge action can be obtained as the semiclassical limit of the string functional wave equation. For closed strings, the wave equation itself is completely analogous to the Wheeler-DeWitt equation used in quantum cosmology. Thus, in the string case, the wave function has support on the space of all possible spatial loop configurations. Finally, we show that the string distribution induces a multiphase, or cellular structure on the spacetime manifold characterized by domains with a purely Riemannian geometry separated by domain walls over which there exists a predominantly Weyl geometry.

  6. A formulation for aircraft rotation

    SciTech Connect

    Boland, N.

    1994-12-31

    The aircraft rotation problem arises in airline operations: the flight legs to be flown by a particular type of aircraft must be sequenced, with the intention that any one aircraft could fly through the entire sequence and end up positioned so as to begin the sequence again, hence the use of the term {open_quotes}rotation{close_quotes}. A rotation must be constructed so that at regular intervals the aircraft can undergo maintenance. This requires a particular location and duration of time. For each pair of legs which can be adjacent in the rotation, there is an associated value, called the {open_quotes}through-value{close_quotes}, which represents the revenue possibilities of providing one-stop service on these legs. We model this problem on a digraph: we need to find a Hamiltonian cycle that maximizes total through-value, subject to the side constraints arising from the maintenance requirements. We present a set partitioning formulation in which column generation involves finding a shortest path in a network, subject to side constraints.

  7. A new formulation of longitudinal coherent instabilities

    SciTech Connect

    Zhang, S.Y.; Weng, W.T.

    1993-01-01

    The quadrature response of longitudinal impedance is shown to be the effective impedance for the beam instability. The results of the application of this formulation are compared with that obtained using the Robinson-Pedersen approach and the Sacherer integral equation. The formulation is further generalized to the rigid bunch motion using signal analysis method, where a form factor shows up naturally. Finally, the formulation is applied to solve the coupled bunch instabilities. Examples of the AGS Booster and the AGS coupled bunch instabilities are used to illustrate the applications of the formulation.

  8. A new formulation of longitudinal coherent instabilities

    SciTech Connect

    Zhang, S.Y.; Weng, W.T.

    1993-06-01

    The quadrature response of longitudinal impedance is shown to be the effective impedance for the beam instability. The results of the application of this formulation are compared with that obtained using the Robinson-Pedersen approach and the Sacherer integral equation. The formulation is further generalized to the rigid bunch motion using signal analysis method, where a form factor shows up naturally. Finally, the formulation is applied to solve the coupled bunch instabilities. Examples of the AGS Booster and the AGS coupled bunch instabilities are used to illustrate the applications of the formulation.

  9. Slow-roll extended quintessence

    SciTech Connect

    Chiba, Takeshi; Siino, Masaru; Yamaguchi, Masahide

    2010-04-15

    We derive the slow-roll conditions for a nonminimally coupled scalar field (extended quintessence) during the radiation/matter dominated era extending our previous results for thawing quintessence. We find that the ratio {phi}e/3H{phi} becomes constant but negative, in sharp contrast to the ratio for the minimally coupled scalar field. We also find that the functional form of the equation of state of the scalar field asymptotically approaches that of the minimally coupled thawing quintessence.

  10. Extender for securing a closure

    SciTech Connect

    Thomas, II, Patrick A.

    2012-10-02

    An apparatus for securing a closure such as door or a window that opens and closes by movement relative to a fixed structure such as a wall or a floor. Many embodiments provide a device for relocating a padlock from its normal location where it secures a fastener (such as a hasp) to a location for the padlock that is more accessible for locking and unlocking the padlock. Typically an extender is provided, where the extender has a hook at a first end that is disposed through the eye of the staple of the hasp, and at an opposing second end the extender has an annulus, such as a hole in the extender or a loop or ring affixed to the extender. The shackle of the padlock may be disposed through the annulus and may be disposed through the eye of a second staple to secure the door or window in a closed or open position. Some embodiments employ a rigid sheath to enclose at least a portion of the extender. Typically the rigid sheath has an open state where the hook is exposed outside the sheath and a closed state where the hook is disposed within the sheath.

  11. Critical appraisal of extended-release hydrocodone for chronic pain: patient considerations

    PubMed Central

    Gould, Harry J; Paul, Dennis

    2015-01-01

    Opioid analgesics are currently the most effective pharmacologic option for the management of both acute and chronic forms of moderate-to-severe pain. Although the “as-needed” use of immediate-release formulations is considered optimum for treating acute, painful episodes of limited duration, the scheduled dosing of extended-release formulations with immediate-release supplementation for breakthrough pain is regarded to be most effective for managing chronic conditions requiring around-the-clock treatment. The recent introduction of extended-release formulations of the opioid analgesic hydrocodone potentially broadened the possibility of providing pain relief for individuals for whom current formulations are either ineffective or not tolerated. However, reaction to the approval of the new formulations has fueled controversy over the general safety and need for opioid medications, in light of their potential for misuse, abuse, diversion, and addiction. Here, we discuss how the approval of extended-release formulations of hydrocodone and the emotionally charged controversy over their release may affect physician prescribing and the care available to patients in need of chronic opioid therapy for the management of pain. PMID:26543371

  12. Critical appraisal of extended-release hydrocodone for chronic pain: patient considerations.

    PubMed

    Gould, Harry J; Paul, Dennis

    2015-01-01

    Opioid analgesics are currently the most effective pharmacologic option for the management of both acute and chronic forms of moderate-to-severe pain. Although the "as-needed" use of immediate-release formulations is considered optimum for treating acute, painful episodes of limited duration, the scheduled dosing of extended-release formulations with immediate-release supplementation for breakthrough pain is regarded to be most effective for managing chronic conditions requiring around-the-clock treatment. The recent introduction of extended-release formulations of the opioid analgesic hydrocodone potentially broadened the possibility of providing pain relief for individuals for whom current formulations are either ineffective or not tolerated. However, reaction to the approval of the new formulations has fueled controversy over the general safety and need for opioid medications, in light of their potential for misuse, abuse, diversion, and addiction. Here, we discuss how the approval of extended-release formulations of hydrocodone and the emotionally charged controversy over their release may affect physician prescribing and the care available to patients in need of chronic opioid therapy for the management of pain. PMID:26543371

  13. Extended Source/Galaxy All Sky 2

    NASA Technical Reports Server (NTRS)

    2003-01-01

    This panoramic view encompasses the entire sky and reveals the distribution of galaxies beyond the Milky Way galaxy, which astronomers call extended sources, as observed by Two Micron All-Sky Survey. The image is assembled from a database of over 1.6 million galaxies listed in the survey's All-Sky Survey Extended Source Catalog,; more than half of the galaxies have never before been catalogued. The colors represent how the many galaxies appear at three distinct wavelengths of infrared light (blue at 1.2 microns, green at 1.6 microns, and red at 2.2 microns). Quite evident are the many galactic clusters and superclusters, as well as some streamers composing the large-scale structure of the nearby universe. The blue overlay represents the very close and bright stars from our own Milky Way galaxy. In this projection, the bluish Milky Way lies predominantly toward the upper middle and edges of the image.

  14. Optimizing Extender Code for NCSX Analyses

    SciTech Connect

    M. Richman, S. Ethier, and N. Pomphrey

    2008-01-22

    Extender is a parallel C++ code for calculating the magnetic field in the vacuum region of a stellarator. The code was optimized for speed and augmented with tools to maintain a specialized NetCDF database. Two parallel algorithms were examined. An even-block work-distribution scheme was comparable in performance to a master-slave scheme. Large speedup factors were achieved by representing the plasma surface with a spline rather than Fourier series. The accuracy of this representation and the resulting calculations relied on the density of the spline mesh. The Fortran 90 module db access was written to make it easy to store Extender output in a manageable database. New or updated data can be added to existing databases. A generalized PBS job script handles the generation of a database from scratch

  15. From Self-Organized to Extended Criticality

    PubMed Central

    Lovecchio, Elisa; Allegrini, Paolo; Geneston, Elvis; West, Bruce J.; Grigolini, Paolo

    2012-01-01

    We address the issue of criticality that is attracting the attention of an increasing number of neurophysiologists. Our main purpose is to establish the specific nature of some dynamical processes that although physically different, are usually termed as “critical,” and we focus on those characterized by the cooperative interaction of many units. We notice that the term “criticality” has been adopted to denote both noise-induced phase transitions and Self-Organized Criticality (SOC) with no clear connection with the traditional phase transitions, namely the transformation of a thermodynamic system from one state of matter to another. We notice the recent attractive proposal of extended criticality advocated by Bailly and Longo, which is realized through a wide set of critical points rather than emerging as a singularity from a unique value of the control parameter. We study a set of cooperatively firing neurons and we show that for an extended set of interaction couplings the system exhibits a form of temporal complexity similar to that emerging at criticality from ordinary phase transitions. This extended criticality regime is characterized by three main properties: (i) In the ideal limiting case of infinitely large time period, temporal complexity corresponds to Mittag-Leffler complexity; (ii) For large values of the interaction coupling the periodic nature of the process becomes predominant while maintaining to some extent, in the intermediate time asymptotic region, the signature of complexity; (iii) Focusing our attention on firing neuron avalanches, we find two of the popular SOC properties, namely the power indexes 2 and 1.5 respectively for time length and for the intensity of the avalanches. We derive the main conclusion that SOC emerges from extended criticality, thereby explaining the experimental observation of Plenz and Beggs: avalanches occur in time with surprisingly regularity, in apparent conflict with the temporal complexity of physical

  16. THE EXTENDED OPTICAL DISK OF M101

    SciTech Connect

    Mihos, J. Christopher; Harding, Paul; Spengler, Chelsea E.; Rudick, Craig S.; Feldmeier, John J. E-mail: paul.harding@case.edu E-mail: craig.rudick@phys.ethz.ch

    2013-01-10

    We have used deep, wide-field optical imaging to study the faint outskirts of the luminous spiral galaxy M101 (NGC 5457) as well as its surrounding environment. Over 6 deg{sup 2}, our imaging has a limiting surface brightness of {mu} {sub B} {approx} 29.5 mag arcsec{sup -2}, and has revealed the stellar structure of M101's disk out to nearly 25' (50 kpc), 3 times our measured R {sub 25} isophotal size of the optical disk. At these radii, the well-known asymmetry of the inner disk slews 180 Degree-Sign , resulting in an asymmetric plume of light at large radius which follows the very extended H I disk to the northeast of M101. This plume has very blue colors (B - V {approx} 0.2), suggesting that it is the somewhat more evolved (few hundred Myr to {approx}1 Gyr) counterpart of the young far-ultraviolet emitting population traced by Galaxy Evolution Explorer imaging. We also detect another, redder spur of extended light to the east of the disk, and both structures are reminiscent of features produced during fly-by galaxy interactions. However, we see no evidence of very extended tidal tails around M101 or any of its companions which might be expected from a recent encounter with a massive companion. We consider the properties of M101's outer disk in light of possible past interactions with the nearby companion galaxies NGC 5477 and NGC 5474. The detection of optical starlight at such large radii gives us the ability to study star formation histories and stellar populations in outer disks over longer timescales than those traced by the UV or H{alpha} emitting populations. Our data suggest an ongoing buildup of M101's outer disk due to encounters in the group environment triggering extended star formation and tidal heating of existing disk populations.

  17. Glass Ceramic Formulation Data Package

    SciTech Connect

    Crum, Jarrod V.; Rodriguez, Carmen P.; McCloy, John S.; Vienna, John D.; Chung, Chul-Woo

    2012-06-17

    A glass ceramic waste form is being developed for treatment of secondary waste streams generated by aqueous reprocessing of commercial used nuclear fuel (Crum et al. 2012b). The waste stream contains a mixture of transition metals, alkali, alkaline earths, and lanthanides, several of which exceed the solubility limits of a single phase borosilicate glass (Crum et al. 2009; Caurant et al. 2007). A multi-phase glass ceramic waste form allows incorporation of insoluble components of the waste by designed crystallization into durable heat tolerant phases. The glass ceramic formulation and processing targets the formation of the following three stable crystalline phases: (1) powellite (XMoO4) where X can be (Ca, Sr, Ba, and/or Ln), (2) oxyapatite Yx,Z(10-x)Si6O26 where Y is alkaline earth, Z is Ln, and (3) lanthanide borosilicate (Ln5BSi2O13). These three phases incorporate the waste components that are above the solubility limit of a single-phase borosilicate glass. The glass ceramic is designed to be a single phase melt, just like a borosilicate glass, and then crystallize upon slow cooling to form the targeted phases. The slow cooling schedule is based on the centerline cooling profile of a 2 foot diameter canister such as the Hanford High-Level Waste canister. Up to this point, crucible testing has been used for glass ceramic development, with cold crucible induction melter (CCIM) targeted as the ultimate processing technology for the waste form. Idaho National Laboratory (INL) will conduct a scaled CCIM test in FY2012 with a glass ceramic to demonstrate the processing behavior. This Data Package documents the laboratory studies of the glass ceramic composition to support the CCIM test. Pacific Northwest National Laboratory (PNNL) measured melt viscosity, electrical conductivity, and crystallization behavior upon cooling to identify a processing window (temperature range) for melter operation and cooling profiles necessary to crystallize the targeted phases in the

  18. Usage of humic materials for formulation of stable microbial inoculants

    NASA Astrophysics Data System (ADS)

    Kydralieva, K. A.; Khudaibergenova, B. M.; Elchin, A. A.; Gorbunova, N. V.; Muratov, V. S.; Jorobekova, Sh. J.

    2009-04-01

    Some microbes have been domesticated for environment service, for example in a variety of novel applications, including efforts to reduce environmental problems. For instance, antagonistic organisms can be used as biological control agents to reduce the use of chemical pesticides, or efficient degraders can be applied as bioprophylactics to minimise the spread of chemical pollutants. Microorganisms can also be used for the biological clean-up of polluted soil or as plant growth-promoting bacteria that stimulate nutrient uptake. Many microbial applications require large-scale cultivation of the organisms. The biomass production must then be followed by formulation steps to ensure long-term stability and convenient use. However, there remains a need to further develop knowledge on how to optimise fermentation of "non-conventional microorganisms" for environmental applications involving the intact living cells. The goal of presented study is to develop fermentation and formulation techniques for termolabile rhizobacteria isolates - Pseudomonas spp. with major biotechnical potential. Development of efficient and cost-effective media and process parameters giving high cell yields are important priorities. This also involves establishing fermentation parameters yielding cells well adapted to subsequent formulation procedures. Collectively, these strategies will deliver a high proportion of viable cells with good long-term survival. Our main efforts were focused on development of more efficient drying techniques for microorganisms, particularly spray drying and fluidised bed-drying. The advantages of dry formulations are that storage and delivery costs are much lower than for liquid formulations and that long-term survival can be very high if initial packaging is carefully optimised. In order to improve and optimise formulations various kinds of humics-based excipients have been added that have beneficial effects on the viability of the organisms and the storage stability

  19. Bioavailability of sustained-release theophylline formulations.

    PubMed

    Bonora Regazzi, M; Rondanelli, R; Vidale, E; Cristiani, D

    1983-05-01

    Sustained-release formulations of theophylline as well as of other drugs are designed to effect a delayed but constant release of the active principle in the gastrointestinal tract, thus ensuring more prolonged blood level curves. This study was made to assess the bioavailability of two sustained-release microencapsulated formulations and one sustained-release Diffucaps formulation, in comparison with an equivalent dose of theophylline solution. As regards bioavailability, none of the three formulations differed significantly from the reference formulation. The blood levels at steady state were estimated on the basis of data obtained after a single-dose study. All three sustained release formulations showed good results after prolonged administration in terms of peaks and troughs. The time duration at which the theophylline plasma levels remain higher than 75% of the maximum steady-state levels, following 12-h dosing interval, was evaluated: for the sustained-release microencapsulated formulations this time duration reaches 100% of the dosing interval. A multiple-dose administration of the sustained-release formulations used in this study should guarantee almost complete time coverage, with blood levels sharply exceeding the minimum threshold level of the theophylline therapeutic range.

  20. Highly concentrated foam formulation for blast mitigation

    DOEpatents

    Tucker, Mark D.; Gao, Huizhen

    2010-12-14

    A highly concentrated foam formulation for blast suppression and dispersion mitigation for use in responding to a terrorism incident involving a radiological dispersion device. The foam formulation is more concentrated and more stable than the current blast suppression foam (AFC-380), which reduces the logistics burden on the user.

  1. Quantitative measures of osteoinductivity of a porous poly(propylene fumarate) bone graft extender.

    PubMed

    Lewandrowski, Kai-Uwe; Hile, David D; Thompson, Benjamin M J; Wise, Donald L; Tomford, William W; Trantolo, Debra J

    2003-02-01

    Bioresorbable bone graft substitutes could alleviate disadvantages associated with the use of autografts, allografts, and other synthetic materials. However, little is known about the minimum autograft/extender ratio for a given material at which a sufficient osteoinductive effect is still seen. Therefore, we investigated a bioresorbable bone graft substitute made from the unsaturated polyester poly(propylene fumarate), PPF, at various mixing ratios with autograft. The bone graft extender is cross-linked in the presence of a hydroxylapatite filler and effervescent foaming agents citric acid and sodium bicarbonate. The porous bone graft extender material develops porosity in vivo by generating carbon dioxide during the effervescent reaction, resulting in foam formation and expansion with respective pore sizes of 50 to 1000 microm. In an attempt to determine how much cancellous autograft bone could be extended with the poly(propylene fumarate) material and at which ratio the autograft/extender combination remained supportive of the overall structural integrity of the repairing defect site, we studied the amount of new bone formation on implantation of the materials in 3-mm holes made in the anteromedial tibial metaphysis of Sprague-Dawley rats. The extender formulation was analyzed at high autograft/extender (75% autograft/25% extender) and low autograft/extender (25% autograft/75% extender) mixing ratios and compared with negative (extender alone) and positive (autograft alone) controls. Animals from each of the formulations were killed in groups of eight at 6 weeks postoperatively. Hence, a total of 32 animals were included in this study. Histologic analysis of the healing process revealed enhanced in vivo osteoinduction with the bone graft extender regardless of the autograft loading. Histomorphometry did not show any statistically significant difference between the high and low autograft/extender ratios. All formulations maintained implant integrity and did not

  2. Inherent formulation issues of kinase inhibitors.

    PubMed

    Herbrink, M; Schellens, J H M; Beijnen, J H; Nuijen, B

    2016-10-10

    The small molecular Kinase Inhibitor (smKI) drug class is very promising and rapidly expanding. All of these drugs are administered orally. The clear relationship between structure and function has led to drugs with a general low intrinsic solubility. The majority of the commercial pharmaceutical formulations of the smKIs are physical mixtures that are limited by the low drug solubility of a salt form. This class of drugs is therefore characterized by an impaired and variable bioavailability rendering them costly and their therapies suboptimal. New formulations are sparingly being reported in literature and patents. The presented data suggests that continued research into formulation design can help to develop more efficient and cost-effective smKI formulation. Moreover, it may also be of help in the future design of the formulations of new smKIs.

  3. "True enough" formulations: the MAPS approach.

    PubMed

    Goldman, Stuart

    2012-01-01

    Clinical case formulation is at the core of competent care. When appropriately constructed it is grounded in best practices and serves as an explanatory model, a prescriptive road map, and a yardstick for all interventions. Despite the key role of formulations, many clinicians struggle with their construction and usage. The author offers a new model described as the MAPS approach. This framework, which is pragmatic, driven by clinical data, and process oriented, helps clinicians develop a "true enough" core formulation focusing on the most salient clinical elements that must be addressed. Its graphic nature helps reinforce the interrelated systems nature of psychiatric work and directs the clinician to a restricted number of specific areas that both inform the "core formulation" and serve as the targets for care. This comprehensive model, which includes evaluation, formulation, treatment planning, and treatment monitoring, readily complements and dovetails with the full range of treatment approaches.

  4. A complex dietary supplement extends longevity of mice.

    PubMed

    Lemon, Jennifer A; Boreham, Douglas R; Rollo, C David

    2005-03-01

    Key factors implicated in aging include reactive oxygen species, inflammatory processes, insulin resistance, and mitochondrial dysfunction. All are exaggerated in transgenic growth hormone mice (TGM), which display a syndrome resembling accelerated aging. We formulated a complex dietary supplement containing 31 ingredients known to ameliorate all of the above features. We previously showed that this supplement completely abolished the severe age-related cognitive decline expressed by untreated TGM. Here we report that longevity of both TGM and normal mice is extended by this supplement. Treated TGM showed a 28% increase (p < .00008) in mean longevity. An 11% increase in mean longevity was also significant (p < .002093) for treated normal mice, compared to untreated normal mice. These data support the hypothesis that TGM are a model of accelerated aging, and demonstrate that complex dietary supplements may be effective in ameliorating aging or age-related pathologies where simpler formulations have generally failed.

  5. Extended cognition in science communication.

    PubMed

    Ludwig, David

    2014-11-01

    The aim of this article is to propose a methodological externalism that takes knowledge about science to be partly constituted by the environment. My starting point is the debate about extended cognition in contemporary philosophy and cognitive science. Externalists claim that human cognition extends beyond the brain and can be partly constituted by external devices. First, I show that most studies of public knowledge about science are based on an internalist framework that excludes the environment we usually utilize to make sense of science and does not allow the possibility of extended knowledge. In a second step, I argue that science communication studies should adopt a methodological externalism and accept that knowledge about science can be partly realized by external information resources such as Wikipedia.

  6. An Extended Keyword Extraction Method

    NASA Astrophysics Data System (ADS)

    Hong, Bao; Zhen, Deng

    Among numerous Chinese keyword extraction methods, Chinese characteristics were shortly considered. This phenomenon going against the precision enhancement of the Chinese keyword extraction. An extended term frequency based method(Extended TF) is proposed in this paper which combined Chinese linguistic characteristics with basic TF method. Unary, binary and ternary grammars for the candidate keyword extraction as well as other linguistic features were all taken into account. The method establishes classification model using support vector machine. Tests show that the proposed extraction method improved key words precision and recall rate significantly. We applied the key words extracted by the extended TF method into the text file classification. Results show that the key words extracted by the proposed method contributed greatly to raising the precision of text file classification.

  7. Complex-extended Bohmian mechanics.

    PubMed

    Chou, Chia-Chun; Wyatt, Robert E

    2010-04-01

    Complex-extended Bohmian mechanics is investigated by analytically continuing the wave function in polar form into the complex plane. We derive the complex-extended version of the quantum Hamilton-Jacobi equation and the continuity equation in Bohmian mechanics. Complex-extended Bohmian mechanics recovers the standard real-valued Bohmian mechanics on the real axis. The trajectories on the real axis are in accord with the standard real-valued Bohmian trajectories. The trajectories launched away from the real axis never intersect the real axis, and they display symmetry with respect to the real axis. Trajectories display hyperbolic deflection around nodes of the wave function in the complex plane. PMID:20387916

  8. A novel extended state observer.

    PubMed

    Xiong, Shaofeng; Wang, Weihong; Liu, Xiaodong; Chen, Zengqiang; Wang, Sen

    2015-09-01

    A novel extended state observer, which feeds back the output estimation error via both nonlinear and switching terms, is put forward for the first time in this paper. No longer neglecting the lumped uncertainty׳s first time derivative, the problem of disturbance observer design is transformed into the problem of state observer design in the presence of external disturbance. The switching term of the output estimation error is employed to counteract the adverse effect of external disturbance. The newly developed extended state observer provides an attractive solution to the issue of high precision motion control system. Both numerical simulation and experimentation on a speed turntable with temperature box are implemented to verify the performance of the proposed newly developed extended state observer. PMID:26275404

  9. Formulation and bioavailability of controlled release salbutamol sulphate tablets using natural additives.

    PubMed

    Nouh, A T; Abd El-Gawad, A H; Guda, T K

    2010-04-01

    Salbutamol sulphate granules and physical mixtures were prepared using mastic with various natural additives. The prepared granules and physical mixtures were examined using IR and DSC. The obtained results indicate that there is no interaction between salbutamol sulphate and the formulation ingredients used. The physical properties and release behavior of the formulated tablets prepared from granules and physical mixtures were evaluated and showed good physical properties. The rate of drug release from tablets prepared from granules was found to be lower than that prepared from physical mixtures at fixed mastic concentration and the same additive. The rate of drug release decreased with increased mastic concentration in formulated tablets. Pectin and sodium alginate allowed the best controlled release rate of the drug. On the basis of the results obtained from the controlled release studies, selected sulbutamol formulations were subjected to an in vivo comparison with commercial sulbutamol tablets. The pharmacokinetic parameters AUC(0-24), C(max), and T(max) of sulbutamol from the selected formulation were determined after administration of a single oral dose of 8 mg and compared statistically using an ANOVA test. There was no significant difference in the AUC(0-24). On the other hand, there was a significant difference in the C(max) and T(max) between the commercial and the formulated tablets. These results demonstrate that the formulated tablets extended the time of the drug effect.

  10. An Evaluation of the Difference Formulation for Photon Transport in a Two Level System

    SciTech Connect

    Daffin, F D; McKinley, M S; Brooks, E D; Szoke, A

    2004-05-20

    In this paper we extend the difference formulation for radiation transport to the case of a single atomic line. We examine the accuracy, performance and stability of the difference formulation within the framework of the Symbolic Implicit Monte Carlo method. The difference formulation, introduced for thermal radiation by some of the authors, has the unique property that the transport equation is written in terms that become small for thick systems. We find that the difference formulation has a significant advantage over the standard formulation for a thick system. The correct treatment of the line profile, however, requires that the difference formulation in the core of the line be mixed with the standard formulation in the wings and this may limit the advantage of the method. We bypass this problem by using the gray approximation. We develop three Monte Carlo solution methods based on different degrees of implicitness for the treatment of the source terms, and we find only conditional stability unless the source terms are treated fully implicitly.

  11. An Evaluation of the Difference Formulation for Photon Transport in a Two Level System

    SciTech Connect

    Daffin, F C; McKinley, M S; Brooks, E D; Szoke, A

    2005-03-02

    In this paper we extend the difference formulation for radiation transport to the case of a single atomic line. We examine the accuracy, performance and stability of the difference formulation within the framework of the Symbolic Implicit Monte Carlo method. The difference formulation, introduced for thermal radiation by some of the authors, has the unique property that the transport equation is written in terms that become small for thick systems. We find that the difference formulation has a significant advantage over the standard formulation for a thick system. The correct treatment of the line profile, however, requires that the difference formulation in the core of the line be mixed with the standard formulation in the wings, and this may limit the advantage of the method. We bypass this problem by using the gray approximation. We develop three Monte Carlo solution methods based on different degrees of implicitness for the treatment of the source terms, and we find only conditional stability unless the source terms are treated fully implicitly.

  12. An Evaluation of the Difference Formulation for Photon Transport in a Two Level System

    SciTech Connect

    Daffin, F C; McKinley, M S; Brooks, E D; Szoke, A

    2004-11-23

    In this paper we extend the difference formulation for radiation transport to the case of a single atomic line. We examine the accuracy, performance and stability of the difference formulation within the framework of the Symbolic Implicit Monte Carlo method. The difference formulation, introduced for thermal radiation by some of the authors, has the unique property that the transport equation is written in terms that become small for thick systems. We find that the difference formulation has a significant advantage over the standard formulation for a thick system. The correct treatment of the line profile, however, requires that the difference formulation in the core of the line be mixed with the standard formulation in the wings, and this may limit the advantage of the method. We bypass this problem by using the gray approximation. We develop three Monte Carlo solution methods based on different degrees of implicitness for the treatment of the source terms, and we find only conditional stability unless the source terms are treated fully implicitly.

  13. Extending the applicability of multigrid methods

    SciTech Connect

    Brannick, J; Brezina, M; Falgout, R; Manteuffel, T; McCormick, S; Ruge, J; Sheehan, B; Xu, J; Zikatanov, L

    2006-09-25

    Multigrid methods are ideal for solving the increasingly large-scale problems that arise in numerical simulations of physical phenomena because of their potential for computational costs and memory requirements that scale linearly with the degrees of freedom. Unfortunately, they have been historically limited by their applicability to elliptic-type problems and the need for special handling in their implementation. In this paper, we present an overview of several recent theoretical and algorithmic advances made by the TOPS multigrid partners and their collaborators in extending applicability of multigrid methods. Specific examples that are presented include quantum chromodynamics, radiation transport, and electromagnetics.

  14. Extendable retractable telescopic mast for deployable structures

    NASA Technical Reports Server (NTRS)

    Schmid, M.; Aguirre, M.

    1986-01-01

    The Extendable and Retractable Mast (ERM) which is presently developed by Dornier in the frame of an ESA-contract, will be used to deploy and retract large foldable structures. The design is based on a telescopic carbon-fiber structure with high stiffness, strength and pointing accuracy. To verify the chosen design, a breadboard model of an ERM was built and tested under thermal vacuum (TV)-conditions. It is planned as a follow-on development to manufacture and test an Engineering Model Mast. The Engineering Model will be used to establish the basis for an ERM-family covering a wide range of requirements.

  15. Formation of extended conducting channels in atmosphere

    SciTech Connect

    Apollonov, V V; Pletnev, N V

    2012-02-28

    Some mechanisms of the formation of an extended ({approx}1 km) conducting channel in atmosphere using the laser engine technology (Impul'sar program) are considered. The electric conductivity of a channel formed by electric explosion of a 90-{mu}m copper wire up to {approx}1.6 m long (in electric breakdown) at a voltage not higher than 10 kV is studied. The requirements to the products of laser engine exhaust to atmosphere for producing a conducting channel, containing dispersion and condensation aerosols of hot particles of copper oxides (CuO, Cu{sub 2}O) and copper with an oxidised surface (from 50 nm to 300 {mu}m in diameter), are formulated. Possible mechanisms of electric breakdown at the field strength E {>=} 52 V cm{sup -1} in the discharge gap are discussed. The electric conductivity of the channel formed by the laser plasma upon focusing the solid-state laser radiation on targets made of different materials has also been studied.

  16. Constrained Stochastic Extended Redundancy Analysis.

    PubMed

    DeSarbo, Wayne S; Hwang, Heungsun; Stadler Blank, Ashley; Kappe, Eelco

    2015-06-01

    We devise a new statistical methodology called constrained stochastic extended redundancy analysis (CSERA) to examine the comparative impact of various conceptual factors, or drivers, as well as the specific predictor variables that contribute to each driver on designated dependent variable(s). The technical details of the proposed methodology, the maximum likelihood estimation algorithm, and model selection heuristics are discussed. A sports marketing consumer psychology application is provided in a Major League Baseball (MLB) context where the effects of six conceptual drivers of game attendance and their defining predictor variables are estimated. Results compare favorably to those obtained using traditional extended redundancy analysis (ERA). PMID:24327066

  17. Adjustable extender for instrument module

    DOEpatents

    Sevec, J.B.; Stein, A.D.

    1975-11-01

    A blank extender module used to mount an instrument module in front of its console for repair or test purposes has been equipped with a rotatable mount and means for locking the mount at various angles of rotation for easy accessibility. The rotatable mount includes a horizontal conduit supported by bearings within the blank module. The conduit is spring-biased in a retracted position within the blank module and in this position a small gear mounted on the conduit periphery is locked by a fixed pawl. The conduit and instrument mount can be pulled into an extended position with the gear clearing the pawl to permit rotation and adjustment of the instrument.

  18. Constrained Stochastic Extended Redundancy Analysis.

    PubMed

    DeSarbo, Wayne S; Hwang, Heungsun; Stadler Blank, Ashley; Kappe, Eelco

    2015-06-01

    We devise a new statistical methodology called constrained stochastic extended redundancy analysis (CSERA) to examine the comparative impact of various conceptual factors, or drivers, as well as the specific predictor variables that contribute to each driver on designated dependent variable(s). The technical details of the proposed methodology, the maximum likelihood estimation algorithm, and model selection heuristics are discussed. A sports marketing consumer psychology application is provided in a Major League Baseball (MLB) context where the effects of six conceptual drivers of game attendance and their defining predictor variables are estimated. Results compare favorably to those obtained using traditional extended redundancy analysis (ERA).

  19. WFRC patrners: our extended family

    USGS Publications Warehouse

    Thorsteinson, Lyman

    2007-01-01

    For more than five decades the Western Fisheries Research Center (WFRC) has worked with partners to provide research findings to managers of aquatic resources. Those partners form an extended family, a network of clients, colleagues, co-investigators, and customers. Our partners include numerous clients in other Department of Interior bureaus such as the U.S. Fish and Wildlife Service, the U.S. Bureau of Reclamation, and the National Park Service. But there is much more--we have partners in other federal agencies, state agencies, and universities. The extended family includes tribal governments, and non-government organizations such as the Nature Conservancy and the Lower Columbia River Estuary Program.

  20. Extending the ICRF to Higher Radio Frequencies

    NASA Technical Reports Server (NTRS)

    Jacobs, C. S.; Jones, D. L.; Lanyi, G. E.; Lowe, S. T.; Naudet, C. J.; Resch, G. M.; Steppe, J. A.; Zhang, L. D.; Ulvestad, J. S.; Taylor, G. B.

    2002-01-01

    The ICRF forms the basis for all astrometry including use as the inertial coordinate system for navigating deep space missions. This frame was defined using S/X-band observations over the past 20+ years. In January 2002, the VLBA approved our proposal for observing time to extend the ICRF to K-band (24 GHz) and Q-band (43 GHz). The first step will be observations at K- and Q-bands on a subset of ICRF sources. Eventually, K- and Q-band multi-epoch observations will be used to estimate positions, flux density and source structure for a large fraction of the current S/X-band ICRF source list. This work will benefit the radio astronomy community by extending the VLBA calibrator list at these bands. In the longer term, we would also like to extend the ICRF to Ka-band (32 GHz). A celestial reference frame will be needed at this frequency to support deep space navigation. A navigation demonstration is being considered for NASA's Mars 2005 mission. The initial K- and Q-band work will serve to identify candidate sources at Ka-band for use with that mission.

  1. On extended thermonuclear functions through pathway model

    NASA Astrophysics Data System (ADS)

    Kumar, Dilip

    when α → 1. The beauty of the result is that these different families of three different functional forms are covered through the pathway parameter α. In a physical set up if f (x) in (3) is the stable or limiting form, the Maxwell-Boltzmann approach to thermonuclear functions, then f (x) in (1) and (2) will contain a large variety of unstable or chaotic situations which will all tend to (3) in the limit. Thus we get a clear idea of all the stable and unstable situations around the Maxwell-Boltzmann approach. Thus the current theory is given a mathematical extension and physical interpretations can be found to situations in (1) and (2). Incidently Tsallis statistics is a special case of (1) for γ = 0, a = 1, δ = 1, η = 1. The Beck-Cohen superstatistics, discussed in current statistical mechanics literature is a special case of (2) for a = 1, η = 1, α > 1. The main purpose of the present paper is to investigate in some more detail, mathematically, the extended thermonuclear functions for Maxwell-Boltzmann statistics and in the cut-off case. The extended thermonuclear functions will be evaluated in closed form for all convenient values of the parameter by means of residue calculus. A comparison of the standard thermonuclear functions with the extended thermonuclear functions is also done. The results and derivations in this paper are new and these will be of interest to physicists, mathematicians, probabilists, and statisticians.

  2. Evaluating sludge minimization caused by predation and viral infection based on the extended activated sludge model No. 2d.

    PubMed

    Hao, Xiaodi; Wang, Qilin; Cao, Yali; van Loosdrecht, Mark C M

    2011-10-15

    The Activated Sludge Model No. 2d (ASM2d) was extended to incorporate the processes of both predation and viral infection. The extended model was used to evaluate the contributions of predation and viral infection to sludge minimization in a sequencing batch reactor (SBR) system enriching polyphosphate-accumulating organisms (PAOs). Three individual decay processes formulated according to the general model rules were used in the extended model. The model was firstly calibrated and validated by different experimental results. It was used to evaluate the potential extent of predation and viral infection on sludge minimization. Simulations indicate that predation contributes roughly two times more to sludge minimization than viral infection in the SBR system enriching PAOs. The sensitivity analyses of the selected key parameters reveal that there are thresholds on both predation and viral infection rates, if they are too large a minimal sludge retention time is obtained and the effluent quality is deteriorating. Due to the thresholds, the contributions of predation and viral infection to sludge minimization are limited to a maximal extent of about 21% and 9%, respectively. However, it should be noted that the parameters concerning predation and viral infection were not calibrated separately by independent experiment in our study due to the lack of an effective method, especially for the parameters regarding viral infection. Therefore, it is essential to better evaluate these parameters in the future.

  3. Liquid-Liquid Phase Separation in a Dual Variable Domain Immunoglobulin Protein Solution: Effect of Formulation Factors and Protein-Protein Interactions.

    PubMed

    Raut, Ashlesha S; Kalonia, Devendra S

    2015-09-01

    Dual variable domain immunoglobulin proteins (DVD-Ig proteins) are large molecules (MW ∼ 200 kDa) with increased asymmetry because of their extended Y-like shape, which results in increased formulation challenges. Liquid-liquid phase separation (LLPS) of protein solutions into protein-rich and protein-poor phases reduces solution stability at intermediate concentrations and lower temperatures, and is a serious concern in formulation development as therapeutic proteins are generally stored at refrigerated conditions. In the current work, LLPS was studied for a DVD-Ig protein molecule as a function of solution conditions by measuring solution opalescence. LLPS of the protein was confirmed by equilibrium studies and by visually observing under microscope. The protein does not undergo any structural change after phase separation. Protein-protein interactions were measured by light scattering (kD) and Tcloud (temperature that marks the onset of phase separation). There is a good agreement between kD measured in dilute solution with Tcloud measured in the critical concentration range. Results indicate that the increased complexity of the molecule (with respect to size, shape, and charge distribution on the molecule) increases contribution of specific and nonspecific interactions in solution, which are affected by formulation factors, resulting in LLPS for DVD-Ig protein.

  4. Optimization in development of acetaminophen syrup formulation.

    PubMed

    Worakul, Nimit; Wongpoowarak, Wibul; Boonme, Prapaporn

    2002-03-01

    Formulation of acetaminophen syrup could be developed by an optimization technique to reduce the time and cost of study. Cosolvents were used in the formulation because of the low solubility of acetaminophen in water. They were composed of polyethylene glycol 4000, propylene glycol, sorbitol solution, and glycerin. Their effects on the solubility of acetaminophen and the pH of formulations were investigated. Effects on taste and price were calculated based on their properties. Simulation study of the effect of cosolvents upon the formulation scores was performed, using an algorithm based upon a simulated annealing concept to achieve the global optima and heuristic optimization concept to accelerate convergence. The program written as a Visual Basic module within Microsoft Access 97 was used to simulate and assess the optimal cosolvent amounts to achieve the most desirable formulations automatically according to the specified criteria. Formulators could customize the optimal formulation according to their needs and cost constraints by redefining the desirable outcomes in the source code of the program. PMID:12026227

  5. Volatilization of alachlor from polymeric formulations.

    PubMed

    Dailey, Oliver D

    2004-11-01

    Pesticides may be dispersed throughout the environment by several means, including groundwater contamination, surface water contamination, and volatilization with subsequent atmospheric transport and deposition. In earlier research primarily directed at reducing the potential for groundwater contamination, a number of herbicides were microencapsulated within several different polymers. These polymeric formulations were evaluated for efficacy in the greenhouse. In the studies described in this paper, three polymeric alachlor formulations that were the most effective in the greenhouse were evaluated in laboratory volatility studies using pure alachlor and a commercial formulation (Lasso 4EC) for comparison purposes. In a given experiment, technical alachlor, Lasso 4EC, and two polymeric formulations were applied to soil and evaluated in a contained system under 53% humidity with a fixed flow rate. Evolved alachlor was collected in ethylene glycol, recovered with C18 solid phase extraction cartridges, and analyzed by reverse-phase high-performance thin-layer chromatography with densitometry. Duration of the studies ranged from 32 to 39 days. In studies in which all formulations were uniformly incorporated in the soil, total alachlor volatilization from the polymeric microcapsules was consistently lower than that from the alachlor and Lasso 4EC formulations. In studies in which the polymeric formulations were sprinkled on the surface of the soil, microcapsules prepared with the polymer cellulose acetate butyrate released the smallest quantity of volatilized alachlor.

  6. Lightweight extendable and retractable pole

    DOEpatents

    Warren, J.L.; Brandt, J.E.

    1994-08-02

    A lightweight extendable and retractable telescopic pole is disclosed comprising a plurality of non-metallic telescoping cylinders with sliding and sealing surfaces between the cylinders, a first plug member on the upper end of the smallest cylinder, and a second plug member on the lower end of the largest cylinder, whereby fluid pressure admitted to the largest cylinder will cause the telescoping cylinders to slide relative to one another causing the pole to extend. An elastomeric member connects the first plug member with one of the intermediate cylinders to urge the cylinders back into a collapsed position when the fluid pressure in the cylinders is vented. Annular elastomer members are provided which seal one cylinder to another when the pole is fully extended and further serve to provide a cushion to prevent damage to the cylinders when the pole is urged back into its retractable position by the elastomeric members and the venting of the pressure. A value mechanism associated with the pole is provided to admit a fluid under pressure to the interior of the telescoping cylinders of the pole while pressurizing a pressure relief port having an opening larger than the inlet port in a closed position whereby removal of the pressure on the relief port will cause the relief port to open to quickly lower the pressure in the interior of the telescoping cylinders to thereby assist in the rapid retraction of the extended pole. 18 figs.

  7. Lightweight extendable and retractable pole

    DOEpatents

    Warren, John L.; Brandt, James E.

    1994-01-01

    A lightweight extendable and retractable telescopic pole is disclosed comprising a plurality of non-metallic telescoping cylinders with sliding and sealing surfaces between the cylinders, a first plug member on the upper end of the smallest cylinder, and a second plug member on the lower end of the largest cylinder, whereby fluid pressure admitted to the largest cylinder will cause the telescoping cylinders to slide relative to one another causing the pole to extend. An elastomeric member connects the first plug member with one of the intermediate cylinders to urge the cylinders back into a collapsed position when the fluid pressure in the cylinders is vented. Annular elastomer members are provided which seal one cylinder to another when the pole is fully extended and further serve to provide a cushion to prevent damage to the cylinders when the pole is urged back into its retractable position by the elastomeric members and the venting of the pressure. A value mechanism associated with the pole is provided to admit a fluid under pressure to the interior of the telescoping cylinders of the pole while pressurizing a pressure relief port having an opening larger than the inlet port in a closed position whereby removal of the pressure on the relief port will cause the relief port to open to quickly lower the pressure in the interior of the telescoping cylinders to thereby assist in the rapid retraction of the extended pole.

  8. Engage, Enhance, and Extend Learning!

    ERIC Educational Resources Information Center

    Keren-Kolb, Liz

    2013-01-01

    Educators often say that technology is more than a gimmick or add-on, and that it should engage, enhance, or extend learning in ways that traditional tools do not. Yet they seldom stop to define these terms, and they can be confusing, especially for teachers and preservice teachers. Recently, while collaborating on an English language arts and…

  9. Extended Duration Orbiter Medical Project

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Pool, S. L.; Sawin, C. F.; Nicogossian, A. E.

    1990-01-01

    The Extended Duration Orbiter (EDO) program addresses a need for more time to perform experiments and other tasks during Space Shuttle missions. As a part of this program, the Extended Duration Orbiter Medical Project (EDOMP) has been instituted to obtain information about physiologic effects of extending mission duration and the effectiveness of countermeasures against factors that might compromise crew health, safety, or performance on extended-duration missions. Only those investigations that address and characterize operational problems, develop countermeasures, or evaluate the effectiveness of countermeasures will be pursued. The EDOMP investigations will include flight-associated Detailed Supplementary Objectives as well as ground-based studies simulating the influence of microgravity. Investigator teams have been formed in the following areas: biomedical physiology, cardiovascular and fluid/electrolyte physiology, environmental health, muscle and exercise physiology, and neurophysiology. Major operational questions must be answered in each of these areas, and investigations have been designed to answer them. The EDO program will proceed only after countermeasures have been shown to be effective in preventing or mitigating the adverse changes they have been designed to attenuate. The program is underway and will continue on each Shuttle flight as the manifest builds toward a 16-day orbital flight.

  10. Extended range chemical sensing apparatus

    DOEpatents

    Hughes, Robert C.; Schubert, W. Kent

    1994-01-01

    An apparatus for sensing chemicals over extended range of concentrations. In particular, first and second sensors each having separate, but overlapping ranges for sensing concentrations of hydrogen are provided. Preferably, the first sensor is a MOS solid state device wherein the metal electrode or gate is a nickel alloy. The second sensor is a chemiresistor comprising a nickel alloy.

  11. On the formulation of a crystal plasticity model.

    SciTech Connect

    Marin, Esteban B.

    2006-08-01

    This report presents the formulation of a crystal elasto-viscoplastic model and the corresponding integration scheme. The model is suitable to represent the isothermal, anisotropic, large deformation of polycrystalline metals. The formulation is an extension of a rigid viscoplastic model to account for elasticity effects, and incorporates a number of changes with respect to a previous formulation [Marin & Dawson, 1998]. This extension is formally derived using the well-known multiplicative decomposition of the deformation gradient into an elastic and plastic components, where the elastic part is additionally decomposed into the elastic stretch V{sup e} and the proper orthogonal R{sup e} tensors. The constitutive equations are written in the intermediate, stress-free configuration obtained by unloading the deformed crystal through the elastic stretch V{sup e-}. The model is framed in a thermodynamic setting, and developed initially for large elastic strains. The crystal equations are then specialized to the case of small elastic strains, an assumption typically valid for metals. The developed integration scheme is implicit and proceeds by separating the spherical and deviatoric crystal responses. An ''approximate'' algorithmic material moduli is also derived for applications in implicit numerical codes. The model equations and their integration procedure have been implemented in both a material point simulator and a commercial finite element code. Both implementations are validated by solving a number of examples involving aggregates of either face centered cubic (FCC) or hexagonal close-packed (HCP) crystals subjected to different loading paths.

  12. IP-Based Video Modem Extender Requirements

    SciTech Connect

    Pierson, L G; Boorman, T M; Howe, R E

    2003-12-16

    Visualization is one of the keys to understanding large complex data sets such as those generated by the large computing resources purchased and developed by the Advanced Simulation and Computing program (aka ASCI). In order to be convenient to researchers, visualization data must be distributed to offices and large complex visualization theaters. Currently, local distribution of the visual data is accomplished by distance limited modems and RGB switches that simply do not scale to hundreds of users across the local, metropolitan, and WAN distances without incurring large costs in fiber plant installation and maintenance. Wide Area application over the DOE Complex is infeasible using these limited distance RGB extenders. On the other hand, Internet Protocols (IP) over Ethernet is a scalable well-proven technology that can distribute large volumes of data over these distances. Visual data has been distributed at lower resolutions over IP in industrial applications. This document describes requirements of the ASCI program in visual signal distribution for the purpose of identifying industrial partners willing to develop products to meet ASCI's needs.

  13. Phentermine and topiramate extended release (Qsymia™): first global approval.

    PubMed

    Cameron, Fiona; Whiteside, Glenn; McKeage, Kate

    2012-10-22

    Vivus' proprietary oral capsule containing phentermine and extended-release (ER) topiramate has been approved in the US for the treatment of obesity. Phentermine is an appetite suppressant, while topiramate is an anti-epileptic medication. The once-daily formulation, known as Qsymia™, is designed to produce weight loss by decreasing appetite and increasing satiety. The product is also in clinical development for sleep apnoea syndrome and type 2 diabetes mellitus. This article summarizes the milestones in the development of phentermine/topiramate ER leading to this first approval for obesity.

  14. Heat transfer through an extended surface containing He II

    SciTech Connect

    Van Sciver, S.W.

    1999-02-01

    A semi-analytic solution for the heat transfer process between a He II pressurized bath and a saturated tube-type heat exchanger is presented. The problem is modeled with an extended surface heat transfer formulation analogous to that in conventional conduction. The process is governed by Kapitza conductance and counterflow within the bulk fluid in the tube. The resulting nonlinear differential equation may be integrated for the special case of constant properties, yielding a simple solution applicable to design and analysis of practical heat exchangers.

  15. Phentermine and topiramate extended release (Qsymia™): first global approval.

    PubMed

    Cameron, Fiona; Whiteside, Glenn; McKeage, Kate

    2012-10-22

    Vivus' proprietary oral capsule containing phentermine and extended-release (ER) topiramate has been approved in the US for the treatment of obesity. Phentermine is an appetite suppressant, while topiramate is an anti-epileptic medication. The once-daily formulation, known as Qsymia™, is designed to produce weight loss by decreasing appetite and increasing satiety. The product is also in clinical development for sleep apnoea syndrome and type 2 diabetes mellitus. This article summarizes the milestones in the development of phentermine/topiramate ER leading to this first approval for obesity. PMID:23039320

  16. Recent advances in materials for extended-release antibiotic delivery system.

    PubMed

    Gao, Ping; Nie, Xin; Zou, Meijuan; Shi, Yijie; Cheng, Gang

    2011-09-01

    To maintain antimicrobial activity, frequent administration of conventional formulations of many antibiotics with short half-life is necessary. Otherwise, concentration under MIC occurs frequently in the course of anti-infective treatment, which induces antibiotic resistance. By maintaining a constant plasma drug concentration over MIC for a prolonged period, extended-release dosage forms maximize the therapeutic effect of antibiotics while minimizing antibiotic resistance. Another undoubted advantage of extended-release formulation is improved patient compliance. For better release properties, many materials have been introduced into the matrix and coating extended-release system in the past few years. Materials that have been widely used in industry are hydrophilic matrix materials such as hydroxypropylmethylcellulose. The excellent biocompatibility and extensive laboratory studies provide biodegradable polymers great potential for industrial applications. In addition, it seems like the researches on tailored materials that are obtained by chemical modification of the existing materials or combination of different carriers in physical mixtures have a long way to go. Meanwhile, with the development of polymers and inorganic porous nanocarriers, nanotechnology is applied increasingly for the extended delivery of antibiotics. This review highlights the development of materials used in extended-release formulation and nanoparticles for antibiotic delivery. We also provide an overview of the antibiotic extended-release products that have provided clinical benefit or are undergoing the clinical trial.

  17. Extended SQL for manipulating clinical warehouse data.

    PubMed

    Johnson, S B; Chatziantoniou, D

    1999-01-01

    Health care institutions are beginning to collect large amounts of clinical data through patient care applications. Clinical data warehouses make these data available for complex analysis across patient records, benefiting administrative reporting, patient care and clinical research. Data gathered for patient care purposes are difficult to manipulate for analytic tasks; the schema presents conceptual difficulties for the analyst, and many queries perform poorly. An extension to SQL is presented that enables the analyst to designate groups of rows. These groups can then be manipulated and aggregated in various ways to solve a number of useful analytic problems. The extended SQL is concise and runs in linear time, while standard SQL requires multiple statements with polynomial performance. The extensions are extremely powerful for performing aggregations on large amounts of data, which is useful in clinical data mining applications.

  18. Algorithmic Perspectives on Problem Formulations in MDO

    NASA Technical Reports Server (NTRS)

    Alexandrov, Natalia M.; Lewis, Robert Michael

    2000-01-01

    This work is concerned with an approach to formulating the multidisciplinary optimization (MDO) problem that reflects an algorithmic perspective on MDO problem solution. The algorithmic perspective focuses on formulating the problem in light of the abilities and inabilities of optimization algorithms, so that the resulting nonlinear programming problem can be solved reliably and efficiently by conventional optimization techniques. We propose a modular approach to formulating MDO problems that takes advantage of the problem structure, maximizes the autonomy of implementation, and allows for multiple easily interchangeable problem statements to be used depending on the available resources and the characteristics of the application problem.

  19. Decontamination formulations for disinfection and sterilization

    DOEpatents

    Tucker, Mark D.; Engler, Daniel E.

    2007-09-18

    Aqueous decontamination formulations that neutralize biological pathogens for disinfection and sterilization applications. Examples of suitable applications include disinfection of food processing equipment, disinfection of areas containing livestock, mold remediation, sterilization of medical instruments and direct disinfection of food surfaces, such as beef carcasses. The formulations include at least one reactive compound, bleaching activator, inorganic base, and water. The formulations can be packaged as a two-part kit system, and can have a pH value in the range of 7-8.

  20. Measurements of Aluminum Combustion in Energetic Formulations

    NASA Astrophysics Data System (ADS)

    Miller, J. Scott; Pangilinan, G. I.

    2004-07-01

    Aluminum combustion plays an important role in tailoring energy release rates of energetic materials. The intimate mixing between Al and oxidizers from the formulation itself or from the surrounding atmosphere is key to effecting combustion. We infer combustion processes in detonated aluminized energetic formulations PBXIH-135 and PBXN-111 in air using time-resolved spectroscopy. We recorded spectral emissions from Al and AlO emanating from the surface of each sample for up to 100 μs. We observe differences in metal combustion between the oxidizer deficient PBXIH-135 and the oxygen-rich PBXN-111. We will discuss phases of combustion that each formulation exhibits and possible reaction processes.

  1. Extended recency effect extended: blocking, presentation mode, and retention interval.

    PubMed

    Glidden, L M; Pawelski, C; Mar, H; Zigman, W

    1979-07-01

    The effect of blocking of stimulus items on the free recall of EMR adolescents was examined. In Experiment 1 a multitrial free-recall list of 15 pictures was presented either simultaneously in groups of 3, or sequentially, one at a time. Consistent ordering was used in both conditions, so that on each trial, each item in each set of 3 pictures was presented contiguously with the other 2 items from that set. In addition, recall came immediately or after a filled or unfilled delay of 24.5 seconds. Results showed that simultaneous presentation led to higher recall, subjective organization, and clustering than did sequential presentation, but analysis of serial-position curves showed a much reduced extended recency effect in comparison with previous studies. Experiment 2 was designed to determine whether the cause of the reduced extended recency was the use of pictures rather than words as stimuli. Stimuli were presented either as pictures, as pictures with auditory labels, or as words with auditory labels, with both simultaneous and consistent ordering for all conditions. Results indicated a strong extended recency effect for all groups, eliminating presentation mode as a causal factor in the data of Experiment 1. We concluded that blocking leads to increased organization and recall over a variety of presentation modes, rates, and block sizes.

  2. EMPIRICAL MODEL FOR FORMULATION OF CRYSTAL-TOLERANT HLW GLASSES

    SciTech Connect

    KRUGER AA; MATYAS J; HUCKLEBERRY AR; VIENNA JD; RODRIGUEZ CA

    2012-03-07

    Historically, high-level waste (HLW) glasses have been formulated with a low liquideus temperature (T{sub L}), or temperature at which the equilibrium fraction of spinel crystals in the melt is below 1 vol % (T{sub 0.01}), nominally below 1050 C. These constraints cannot prevent the accumulation of large spinel crystals in considerably cooler regions ({approx} 850 C) of the glass discharge riser during melter idling and significantly limit the waste loading, which is reflected in a high volume of waste glass, and would result in high capital, production, and disposal costs. A developed empirical model predicts crystal accumulation in the riser of the melter as a function of concentration of spinel-forming components in glass, and thereby provides guidance in formulating crystal-tolerant glasses that would allow high waste loadings by keeping the spinel crystals small and therefore suspended in the glass.

  3. EMPIRICAL MODEL FOR FORMULATION OF CRYSTAL-TOLERANT HLW GLASSES

    SciTech Connect

    Matyas, Josef; Huckleberry, Adam R.; Rodriguez, Carmen P.; Vienna, John D.; Kruger, Albert A.

    2012-11-07

    Historically, high-level waste (HLW) glasses have been formulated with a low liquidus temperature (TL), or temperature at which the equilibrium fraction of spinel crystals in the melt is below 1 vol % (T0.01), nominally below 1050°C. These constraints cannot prevent the accumulation of large spinel crystals in considerably cooler regions (~ 850°C) of the glass discharge riser during melter idling and significantly limit the waste loading, which is reflected in a high volume of waste glass, and would result in high capital, production, and disposal costs. A developed empirical model predicts crystal accumulation in the riser of the melter as a function of concentration of spinel-forming components in glass, and thereby provides guidance in formulating crystal-tolerant glasses that would allow high waste loadings by keeping the spinel crystals small and therefore suspended in the glass.

  4. Alternative ways for formulation of hybrid stress elements

    NASA Technical Reports Server (NTRS)

    Pian, T. H. H.; Chen, D.-P.

    1982-01-01

    An element stiffness matrix can be derived by the conventional potential energy principle and, indirectly, also by generalized variational principles, such as the Hu-Washizu principle and the Hellinger-Reissner principle. The present investigation has the objective to show an approach which is concerned with the formulation of incompatible elements for solid continuum and for plate bending problems by the Hellinger-Reissner principle. It is found that the resulting scheme is equivalent to that considered by Tong (1982) for the construction of hybrid stress elements. In Tong's scheme the inversion of a large flexibility matrix can be avoided. It is concluded that the introduction of additional internal displacement modes in mixed finite element formulations by the Hellinger-Reissner principle and the Hu-Washizu principle can lead to element stiffness matrices which are equivalent to the assumed stress hybrid method.

  5. Large Array Channel Capacity in the Presence of Interference

    NASA Technical Reports Server (NTRS)

    Vilnrotter, V.; Srinivasan, M.

    2006-01-01

    We develop a model for a large array ground receiver system for use in deep-space communications, and analyze the resulting array channel capacity. The model includes effects of array geometry, time-dependent spacecraft orbital trajectory, point and extended interference sources, and elevation-dependent noise and tropospheric channel variations. Channel capacity is expressed as the ratio of determinants of covariance matrices characterizing source, interference, and additive noise, and then reduced to a simpler quadratic form more amenable to analysis and numerical computation. This formulation facilitates inclusion of array and channel characteristics into the model, as well as comparison of optimal, suboptimal, and equivalent single antenna configurations on achievable throughput. Realistic examples of ground array channel capacity calculations are presented, demonstrating the impact of array geometry, planetary interference sources, and array combining algorithm design upon the achievable data throughput.

  6. Estimating Power System Dynamic States Using Extended Kalman Filter

    SciTech Connect

    Huang, Zhenyu; Schneider, Kevin P.; Nieplocha, Jaroslaw; Zhou, Ning

    2014-10-31

    Abstract—The state estimation tools which are currently deployed in power system control rooms are based on a steady state assumption. As a result, the suite of operational tools that rely on state estimation results as inputs do not have dynamic information available and their accuracy is compromised. This paper investigates the application of Extended Kalman Filtering techniques for estimating dynamic states in the state estimation process. The new formulated “dynamic state estimation” includes true system dynamics reflected in differential equations, not like previously proposed “dynamic state estimation” which only considers the time-variant snapshots based on steady state modeling. This new dynamic state estimation using Extended Kalman Filter has been successfully tested on a multi-machine system. Sensitivity studies with respect to noise levels, sampling rates, model errors, and parameter errors are presented as well to illustrate the robust performance of the developed dynamic state estimation process.

  7. Universal Formulation For Symmetries In Computed Flows

    NASA Technical Reports Server (NTRS)

    Pao, S. Paul; Abdol-Hamid, Khaled S.

    1995-01-01

    Universal formulation for high-order symmetries in boundary conditions on flows devised. Eliminates need for special procedures to incorporate symmetries and corresponding boundary conditions into computer codes solving Navier-Stokes and Euler equations of flow.

  8. Paclitaxel Albumin-stabilized Nanoparticle Formulation

    Cancer.gov

    This page contains brief information about paclitaxel albumin-stabilized nanoparticle formulation and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

  9. Formulating and Solving Problems in Computational Chemistry.

    ERIC Educational Resources Information Center

    Norris, A. C.

    1980-01-01

    Considered are the main elements of computational chemistry problems and how these elements can be used to formulate the problems mathematically. Techniques that are useful in devising an appropriate solution are also considered. (Author/TG)

  10. FIRE I - Extended Time Observations Data Sets

    Atmospheric Science Data Center

    2013-08-01

    FIRE I - Extended Time Observations Data Sets First ISCCP Regional Experiment (FIRE) I - Extended Time Observations were conducted in Utah. Relevant Documents:  FIRE Project Guide FIRE I - Extended Time Observations Home Page SCAR-B Block:  ...

  11. Assessment of extended-release opioid analgesics for the treatment of chronic pain.

    PubMed

    Gudin, Jeffrey A

    2013-03-01

    Approximately 3.8 million patients annually receive extended-release (ER) or long-acting opioid prescriptions in the outpatient setting, around half of which are written by primary care physicians. Compared with short-acting, immediate-release (IR) formulations, ER and oral long-acting opioid analgesics are associated with clinical advantages, such as extended periods of time during which drug plasma levels are within the therapeutic range, decreased peak-to-trough fluctuations, and prolonged analgesia over the dosing period. Additionally, ER opioids offer a more convenient, less frequent dosing regimen to chronic pain patients who are often taking several concomitant medications. The increased utilization of ER opioids has been accompanied by a rise in the misuse and abuse of these formulations. Certain pharmacokinetic parameters (e.g., longer time to maximum drug plasma concentration, lower maximum drug plasma concentration) may decrease the abuse potential of intact ER opioids by limiting the positive subjective and reinforcing effects relative to IR formulations. Putative abuse-deterrent formulations have also recently been introduced to impede physical manipulation of these formulations, or reduce the harm resulting from such behavior. Such formulations may represent an incremental advance to reduce non-oral forms of abuse. This article reviews the pharmacokinetic profiles and abuse-deterrent features of newer ER opioid analgesics for the treatment of moderate to severe chronic pain.

  12. Formulating liquid ethers for microtubular SOFCs

    NASA Astrophysics Data System (ADS)

    Kendall, Kevin; Slinn, Matthew; Preece, John

    One of the key problems of applying solid oxide fuel cells (SOFCs) in transportation is that conventional fuels like kerosene and diesel do not operate directly in SOFCs without prereforming to hydrogen and carbon monoxide which can be handled by the nickel cermet anode. SOFCs can internally reform certain hydrocarbon molecules such as methanol and methane. However, other liquid fuels usable in petrol or diesel internal combustion engines (ICEs) have not easily been reformable directly on the anode. This paper describes a search for liquid fuels which can be mixed with petrol or diesel and also injected directly into an SOFC without destroying the nickel anode. When fuel molecules such as octane are injected onto the conventional nickel/yttria stabilised zirconia (Ni/YSZ) SOFC fuel electrode, the anode rapidly becomes blocked by carbon deposition and the cell power drops to near zero in minutes. This degeneration of the anode can be inhibited by injection of air or water into the anode or by some upstream reforming just before entry to the SOFC. Some smaller molecules such as methane, methanol and methanoic acid produce a slight tendency to carbon deposition but not sufficient to prevent long term operation. In this project we have investigated a large number of molecules and now found that some liquid ethers do not significantly damage the anode when directly injected. These molecules and formulations with other components have been evaluated in this study. The theory put forward in this paper is that carbon-carbon bonds in the fuel are the main reason for anode damage. By testing a number of fuels without such bonds, particularly liquid ethers such as methyl formate and dimethoxy methane, it has been shown that SOFCs can run without substantial carbon formation. The proposal is that conventional fuels can be doped with these molecules to allow hybrid operation of an ICE/SOFC device.

  13. Liquid-Spray Formulation Of Scopolamine

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Cintron, Nitza M.

    1992-01-01

    Scopolamine, fast-acting anticholinergic drug, formulated into drops administered intranasally. Formulation very useful for people who need immediate relief from motion sickness, and they can administer it to themselves. Also used in other clinical situations in which fast-acting anticholinergic medication required. Modified into such other forms as gel preparation, aqueous-base ointment, or aerosol spray or mist; also dispensed in metered-dose delivery system.

  14. Project Integration Architecture: Formulation of Semantic Parameters

    NASA Technical Reports Server (NTRS)

    Jones, William Henry

    2005-01-01

    One of several key elements of the Project Integration Architecture (PIA) is the intention to formulate parameter objects which convey meaningful semantic information. In so doing, it is expected that a level of automation can be achieved in the consumption of information content by PIA-consuming clients outside the programmatic boundary of a presenting PIA-wrapped application. This paper discusses the steps that have been recently taken in formulating such semantically-meaningful parameters.

  15. The Boltzmann equation in the difference formulation

    SciTech Connect

    Szoke, Abraham; Brooks III, Eugene D.

    2015-05-06

    First we recall the assumptions that are needed for the validity of the Boltzmann equation and for the validity of the compressible Euler equations. We then present the difference formulation of these equations and make a connection with the time-honored Chapman - Enskog expansion. We discuss the hydrodynamic limit and calculate the thermal conductivity of a monatomic gas, using a simplified approximation for the collision term. Our formulation is more consistent and simpler than the traditional derivation.

  16. Steady-State Clinical Pharmacokinetics of Bupropion Extended-Release In Youths

    ERIC Educational Resources Information Center

    Daviss, W. Burleson; Perel, James M.; Birmaher, Boris; Rudolph, George R.; Melhem, Imad; Axelson, David A.; Brent, David A.

    2006-01-01

    Objective: To examine in children and adolescents the 24-hour, steady-state clinical pharmacokinetics of an extended-release (XL) formulation of bupropion (Wellbutrin XL). Method: Subjects were six male and four female patients (ages 11.5-16.2 years) prescribed bupropion XL in morning daily doses of either 150 mg (n = 5) or 300 mg (n = 5) for at…

  17. Extended Mixed-Efects Item Response Models with the MH-RM Algorithm

    ERIC Educational Resources Information Center

    Chalmers, R. Philip

    2015-01-01

    A mixed-effects item response theory (IRT) model is presented as a logical extension of the generalized linear mixed-effects modeling approach to formulating explanatory IRT models. Fixed and random coefficients in the extended model are estimated using a Metropolis-Hastings Robbins-Monro (MH-RM) stochastic imputation algorithm to accommodate for…

  18. Stress Formulation in Three-Dimensional Elasticity

    NASA Technical Reports Server (NTRS)

    Patnaik, Surya N.; Hopkins, Dale A.

    2001-01-01

    The theory of elasticity evolved over centuries through the contributions of eminent scientists like Cauchy, Navier, Hooke Saint Venant, and others. It was deemed complete when Saint Venant provided the strain formulation in 1860. However, unlike Cauchy, who addressed equilibrium in the field and on the boundary, the strain formulation was confined only to the field. Saint Venant overlooked the compatibility on the boundary. Because of this deficiency, a direct stress formulation could not be developed. Stress with traditional methods must be recovered by backcalculation: differentiating either the displacement or the stress function. We have addressed the compatibility on the boundary. Augmentation of these conditions has completed the stress formulation in elasticity, opening up a way for a direct determination of stress without the intermediate step of calculating the displacement or the stress function. This Completed Beltrami-Michell Formulation (CBMF) can be specialized to derive the traditional methods, but the reverse is not possible. Elasticity solutions must be verified for the compliance of the new equation because the boundary compatibility conditions expressed in terms of displacement are not trivially satisfied. This paper presents the variational derivation of the stress formulation, illustrates the method, examines attributes and benefits, and outlines the future course of research.

  19. Microbiological quality of pediatric oral liquid formulations.

    PubMed

    Cabañas Poy, Maria Josep; Cañete Ramírez, Carme; González di Lauro, Sabina X; Rodríguez Garrido, Virginia; Roig Carbajosa, Gloria; Fernández-Polo, Aurora; Clemente Bautista, Susana

    2016-09-01

    The oral administration of drugs to the pediatric population involves the extemporaneous preparation of liquid formulations. These formulations have studies on their physicochemical stability, but they often lack microbiological studies. The objective of this study is to check the microbiological quality of five oral liquid formulations prepared with different excipients, which represent five major combinations, in two conditions: kept unopened until the day of the test, and in a multi-dose vial opened daily. The formulations were prepared according to standard operating procedures. Half of each batch was packaged in vials that remained closed until the day of testing, and the other half in a single container which was opened daily. Both the vials and the containers had been previously sterilized. Microbiological tests were performed weekly during the first month of the study, and then every two weeks, until the expiration date. The microbiological quality of oral liquid formulations is determined by the Royal Spanish Pharmacopoeia. The conclusion was that none of the formulations prepared that were packaged in sterilized containers became contaminated, either in unopened vials or in multi-dose containers when they were opened daily.

  20. A generalized anisotropic deformation formulation for geomaterials

    NASA Astrophysics Data System (ADS)

    Lei, Z.; Rougier, Esteban; Knight, E. E.; Munjiza, A.; Viswanathan, H.

    2016-04-01

    In this paper, the combined finite-discrete element method (FDEM) has been applied to analyze the deformation of anisotropic geomaterials. In the most general case geomaterials are both non-homogeneous and non-isotropic. With the aim of addressing anisotropic material problems, improved 2D FDEM formulations have been developed. These formulations feature the unified hypo-hyper elastic approach combined with a multiplicative decomposition-based selective integration for volumetric and shear deformation modes. This approach is significantly different from the co-rotational formulations typically encountered in finite element codes. Unlike the co-rotational formulation, the multiplicative decomposition-based formulation naturally decomposes deformation into translation, rotation, plastic stretches, elastic stretches, volumetric stretches, shear stretches, etc. This approach can be implemented for a whole family of finite elements from solids to shells and membranes. This novel 2D FDEM based material formulation was designed in such a way that the anisotropic properties of the solid can be specified in a cell by cell basis, therefore enabling the user to seed these anisotropic properties following any type of spatial variation, for example, following a curvilinear path. In addition, due to the selective integration, there are no problems with volumetric or shear locking with any type of finite element employed.

  1. Extended-Synaptotagmins (E-Syts); the extended story.

    PubMed

    Herdman, Chelsea; Moss, Tom

    2016-05-01

    The Extended-Synaptotagmin (E-Syt) membrane proteins were only recently discovered, but have already been implicated in a range of interrelated cellular functions, including calcium and receptor signaling, and membrane lipid transport. However, despite their evolutionary conservation and detailed studies of their molecular actions, we still have little idea of how and when these proteins are required in cellular and organism physiology. Here we review our present understanding of the E-Syts and discuss the molecular functions and in vivo requirements for these proteins. PMID:26926095

  2. Dark energy and extended dark matter halos

    NASA Astrophysics Data System (ADS)

    Chernin, A. D.; Teerikorpi, P.; Valtonen, M. J.; Dolgachev, V. P.; Domozhilova, L. M.; Byrd, G. G.

    2012-03-01

    The cosmological mean matter (dark and baryonic) density measured in the units of the critical density is Ωm = 0.27. Independently, the local mean density is estimated to be Ωloc = 0.08-0.23 from recent data on galaxy groups at redshifts up to z = 0.01-0.03 (as published by Crook et al. 2007, ApJ, 655, 790 and Makarov & Karachentsev 2011, MNRAS, 412, 2498). If the lower values of Ωloc are reliable, as Makarov & Karachentsev and some other observers prefer, does this mean that the Local Universe of 100-300 Mpc across is an underdensity in the cosmic matter distribution? Or could it nevertheless be representative of the mean cosmic density or even be an overdensity due to the Local Supercluster therein. We focus on dark matter halos of groups of galaxies and check how much dark mass the invisible outer layers of the halos are able to host. The outer layers are usually devoid of bright galaxies and cannot be seen at large distances. The key factor which bounds the size of an isolated halo is the local antigravity produced by the omnipresent background of dark energy. A gravitationally bound halo does not extend beyond the zero-gravity surface where the gravity of matter and the antigravity of dark energy balance, thus defining a natural upper size of a system. We use our theory of local dynamical effects of dark energy to estimate the maximal sizes and masses of the extended dark halos. Using data from three recent catalogs of galaxy groups, we show that the calculated mass bounds conform with the assumption that a significant amount of dark matter is located in the invisible outer parts of the extended halos, sufficient to fill the gap between the observed and expected local matter density. Nearby groups of galaxies and the Virgo cluster have dark halos which seem to extend up to their zero-gravity surfaces. If the extended halo is a common feature of gravitationally bound systems on scales of galaxy groups and clusters, the Local Universe could be typical or even

  3. New formulations between spherical aberration and spherical aberration coefficient using the Abbe sine condition

    NASA Astrophysics Data System (ADS)

    Kang, Songgao; Lu, Kaichang; Zhu, Yafei

    1991-12-01

    The relationship between aberration and the aberration coefficient is the basic formulation in the field of aberration theory. The Seidel's formulations can only be used in the case of low performance (small aperture and small field), so that a set of correct relations between spherical aberration (SA) and spherical aberration coefficient (SAC) must be derived for the application of large aperture and small viewing field.

  4. The Formulation of Bacteriophage in a Semi Solid Preparation for Control of Propionibacterium acnes Growth

    PubMed Central

    Brown, Teagan L.; Petrovski, Steve; Dyson, Zoe A.; Seviour, Robert; Tucci, Joseph

    2016-01-01

    Aims To isolate and characterise phage which could lyse P. acnes and to formulate the phage into a delivery form for potential application in topical treatment of acne infection. Methods and Results Using standard phage isolation techniques, ten phage capable of lysing P. acnes were isolated from human skin microflora. Their genomes showed high homology to previously reported P. acnes phage. These phage were formulated into cetomacrogol cream aqueous at a concentration of 2.5x108 PFU per gram, and shown to lyse underlying P. acnes cells grown as lawn cultures. These phage formulations remained active for at least 90 days when stored at four degrees Celsius in a light protected container. Conclusions P. acnes phage formulated into cetomacrogol cream aqueous will lyse surrounding and underlying P. acnes bacteria, and are effective for at least 90 days if stored appropriately. Significance and Impact of the Study There are few reports of phage formulation into semi solid preparations for application as phage therapy. The formulation method described here could potentially be applied topically to treat human acne infections. The potential exists for this model to be extended to other phage applied to treat other bacterial skin infections. PMID:26964063

  5. An alternative Biot's displacement formulation for porous materials.

    PubMed

    Dazel, Olivier; Brouard, Bruno; Depollier, Claude; Griffiths, Stéphane

    2007-06-01

    This paper proposes an alternative displacement formulation of Biot's linear model for poroelastic materials. Its advantage is a simplification of the formalism without making any additional assumptions. The main difference between the method proposed in this paper and the original one is the choice of the generalized coordinates. In the present approach, the generalized coordinates are chosen in order to simplify the expression of the strain energy, which is expressed as the sum of two decoupled terms. Hence, new equations of motion are obtained whose elastic forces are decoupled. The simplification of the formalism is extended to Biot and Willis thought experiments, and simpler expressions of the parameters of the three Biot waves are also provided. A rigorous derivation of equivalent and limp models is then proposed. It is finally shown that, for the particular case of sound-absorbing materials, additional simplifications of the formalism can be obtained.

  6. New Formulation of the Governing Equations for Analyzing Outrigger Structures

    NASA Astrophysics Data System (ADS)

    Er, Guo-Kang

    2010-05-01

    In this paper, an easily comprehensible solution procedure is proposed for the analysis of outrigger-braced structures. The idea is based on the compatibility of the columns' axial deformation. The unknowns are selected to be the axial forces in the columns. The resulted governing equations and the equations for the optimum analysis of the outrigger locations are different from the conventional ones, but numerical analysis shows that the results obtained with the new equations are same as those obtained with conventional equations. The relations between the new equations and the conventional ones are also figured out. The new procedure of formulating the governing equations can be easily extended to more complicated cases of outrigger-braced structures.

  7. Thinking large.

    PubMed

    Devries, Egbert

    2016-05-01

    Egbert Devries was brought up on a farm in the Netherlands and large animal medicine has always been his area of interest. After working in UK practice for 12 years he joined CVS and was soon appointed large animal director with responsibility for building a stronger large animal practice base. PMID:27154956

  8. A random matrix formulation of fidelity decay

    NASA Astrophysics Data System (ADS)

    Gorin, T.; Prosen, T.; Seligman, T. H.

    2004-02-01

    We propose to study echo dynamics in a random-matrix framework, where we assume that the perturbation is time-independent, random and orthogonally invariant. This allows us to use a basis in which the unperturbed Hamiltonian is diagonal and its properties are thus largely determined by its spectral statistics. We concentrate on the effect of spectral correlations usually associated with chaos and disregard secular variations in spectral density. We obtain analytical results for the fidelity decay in the linear-response regime. To extend the domain of validity, we heuristically exponentiate the linear-response result. The resulting expressions, exact in the perturbative limit, are accurate approximations in the transition region between the 'Fermi golden rule' and the perturbative regimes, as verified by example for a deterministic chaotic system. To sense the effect of spectral stiffness, we apply our model also to the extreme cases of random spectra and equidistant spectra. In our analytical approximations as well as in extensive Monte Carlo calculations, we find that fidelity decay is fastest for random spectra and slowest for equidistant ones, while the classical ensembles lie in between. We conclude that spectral stiffness systematically enhances fidelity.

  9. A dual potential formulation of the Navier-Stokes equations

    NASA Technical Reports Server (NTRS)

    Gegg, S. G.; Pletcher, R. H.; Steger, J. L.

    1989-01-01

    A dual potential formulation for numerically solving the Navier-Stokes equations is developed and presented. The velocity field is decomposed using a scalar and vector potential. Vorticity and dilatation are used as the dependent variables in the momentum equations. Test cases in two dimensions verify the capability to solve flows using approximations from potential flow to full Navier-Stokes simulations. A three-dimensional incompressible flow formulation is also described. An interesting feature of this approach to solving the Navier-Stokes equations is the decomposition of the velocity field into a rotational part (vector potential) and an irrotational part (scalar potential). The Helmholtz decomposition theorem allows this splitting of the velocity field. This approach has had only limited use since it increases the number of dependent variables in the solution. However, it has often been used for incompressible flows where the solution scheme is known to be fast and accurate. This research extends the usage of this method to fully compressible Navier-Stokes simulations by using the dilatation variable along with vorticity. A time-accurate, iterative algorithm is used for the uncoupled solution of the governing equations. Several levels of flow approximation are available within the framework of this method. Potential flow, Euler and full Navier-Stokes solutions are possible using the dual potential formulation. Solution efficiency can be enhanced in a straightforward way. For some flows, the vorticity and/or dilatation may be negligible in certain regions (e.g., far from a viscous boundary in an external flow). It is possible to drop the calculation of these variables then and optimize the solution speed. Also, efficient Poisson solvers are available for the potentials. The relative merits of non-primitive variables versus primitive variables for solution of the Navier-Stokes equations are also discussed.

  10. Optimization Testbed Cometboards Extended into Stochastic Domain

    NASA Technical Reports Server (NTRS)

    Patnaik, Surya N.; Pai, Shantaram S.; Coroneos, Rula M.; Patnaik, Surya N.

    2010-01-01

    COMparative Evaluation Testbed of Optimization and Analysis Routines for the Design of Structures (CometBoards) is a multidisciplinary design optimization software. It was originally developed for deterministic calculation. It has now been extended into the stochastic domain for structural design problems. For deterministic problems, CometBoards is introduced through its subproblem solution strategy as well as the approximation concept in optimization. In the stochastic domain, a design is formulated as a function of the risk or reliability. Optimum solution including the weight of a structure, is also obtained as a function of reliability. Weight versus reliability traced out an inverted-S-shaped graph. The center of the graph corresponded to 50 percent probability of success, or one failure in two samples. A heavy design with weight approaching infinity could be produced for a near-zero rate of failure that corresponded to unity for reliability. Weight can be reduced to a small value for the most failure-prone design with a compromised reliability approaching zero. The stochastic design optimization (SDO) capability for an industrial problem was obtained by combining three codes: MSC/Nastran code was the deterministic analysis tool, fast probabilistic integrator, or the FPI module of the NESSUS software, was the probabilistic calculator, and CometBoards became the optimizer. The SDO capability requires a finite element structural model, a material model, a load model, and a design model. The stochastic optimization concept is illustrated considering an academic example and a real-life airframe component made of metallic and composite materials.

  11. Optimization of hyaluronan-based eye drop formulations.

    PubMed

    Salzillo, Rosanna; Schiraldi, Chiara; Corsuto, Luisana; D'Agostino, Antonella; Filosa, Rosanna; De Rosa, Mario; La Gatta, Annalisa

    2016-11-20

    Hyaluronan (HA) is frequently incorporated in eye drops to extend the pre-corneal residence time, due to its viscosifying and mucoadhesive properties. Hydrodynamic and rheological evaluations of commercial products are first accomplished revealing molecular weights varying from about 360 to about 1200kDa and viscosity values in the range 3.7-24.2mPa s. The latter suggest that most products could be optimized towards resistance to drainage from the ocular surface. Then, a study aiming to maximize the viscosity and mucoadhesiveness of HA-based preparations is performed. The effect of polymer chain length and concentration is investigated. For the whole range of molecular weights encountered in commercial products, the concentration maximizing performance is identified. Such concentration varies from 0.3 (wt%) for a 1100kDa HA up to 1.0 (wt%) for a 250kDa HA, which is 3-fold higher than the highest concentration on the market. The viscosity and mucoadhesion profiles of optimized formulations are superior than commercial products, especially under conditions simulating in vivo blinking. Thus longer retention on the corneal epithelium can be predicted. An enhanced capacity to protect corneal porcine epithelial cells from dehydration is also demonstrated in vitro. Overall, the results predict formulations with improved efficacy.

  12. Optimization of hyaluronan-based eye drop formulations.

    PubMed

    Salzillo, Rosanna; Schiraldi, Chiara; Corsuto, Luisana; D'Agostino, Antonella; Filosa, Rosanna; De Rosa, Mario; La Gatta, Annalisa

    2016-11-20

    Hyaluronan (HA) is frequently incorporated in eye drops to extend the pre-corneal residence time, due to its viscosifying and mucoadhesive properties. Hydrodynamic and rheological evaluations of commercial products are first accomplished revealing molecular weights varying from about 360 to about 1200kDa and viscosity values in the range 3.7-24.2mPa s. The latter suggest that most products could be optimized towards resistance to drainage from the ocular surface. Then, a study aiming to maximize the viscosity and mucoadhesiveness of HA-based preparations is performed. The effect of polymer chain length and concentration is investigated. For the whole range of molecular weights encountered in commercial products, the concentration maximizing performance is identified. Such concentration varies from 0.3 (wt%) for a 1100kDa HA up to 1.0 (wt%) for a 250kDa HA, which is 3-fold higher than the highest concentration on the market. The viscosity and mucoadhesion profiles of optimized formulations are superior than commercial products, especially under conditions simulating in vivo blinking. Thus longer retention on the corneal epithelium can be predicted. An enhanced capacity to protect corneal porcine epithelial cells from dehydration is also demonstrated in vitro. Overall, the results predict formulations with improved efficacy. PMID:27561497

  13. Sterile Filtration of Highly Concentrated Protein Formulations: Impact of Protein Concentration, Formulation Composition, and Filter Material.

    PubMed

    Allmendinger, Andrea; Mueller, Robert; Huwyler, Joerg; Mahler, Hanns-Christian; Fischer, Stefan

    2015-10-01

    Differences in filtration behavior of concentrated protein formulations were observed during aseptic drug product manufacturing of biologics dependent on formulation composition. The present study investigates filtration forces of monoclonal antibody formulations in a small-scale set-up using polyvinylidene difluoride (PVDF) or polyethersulfone (PES) filters. Different factors like formulation composition and protein concentration related to differences in viscosity, as well as different filtration rates were evaluated. The present study showed that filtration behavior was influenced by the presence or absence of a surfactant in the formulation, which defines the interaction between filter membrane and surface active formulation components. This can lead to a change in filter resistance (PES filter) independent on the buffer system used. Filtration behavior was additionally defined by rheological non-Newtonian flow behavior. The data showed that high shear rates resulting from small pore sizes and filtration pressure up to 1.0 bar led to shear-thinning behavior for highly concentrated protein formulations. Differences in non-Newtonian behavior were attributed to ionic strength related to differences in repulsive and attractive interactions. The present study showed that the interplay of formulation composition, filter material, and filtration rate can explain differences in filtration behavior/filtration flux observed for highly concentrated protein formulations thus guiding filter selection.

  14. Psychiatrists' use of formulation: Commentary on … Psychiatrists' understanding and use of psychological formulation.

    PubMed

    Hughes, Patricia M

    2016-08-01

    Both psychologists and psychiatrists are trained to write formulations of their patients' illnesses, with some differences in how they do this. Psychologists focus on psychological understanding, while psychiatrists' formulation brings together aetiology, functioning and a management plan. Mohtashemi et al's study records how some psychiatrists understand formulation and its usefulness. Time pressure was an important barrier to making a full formulation, and some believed the medical role of the psychiatrist was a priority. The study illustrates some of the challenges facing psychiatrists working in the NHS in terms of maintaining high clinical standards and a holistic approach to patient care.

  15. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

    PubMed

    Kawakami, Kohsaku

    2009-09-01

    Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

  16. Sterile Filtration of Highly Concentrated Protein Formulations: Impact of Protein Concentration, Formulation Composition, and Filter Material.

    PubMed

    Allmendinger, Andrea; Mueller, Robert; Huwyler, Joerg; Mahler, Hanns-Christian; Fischer, Stefan

    2015-10-01

    Differences in filtration behavior of concentrated protein formulations were observed during aseptic drug product manufacturing of biologics dependent on formulation composition. The present study investigates filtration forces of monoclonal antibody formulations in a small-scale set-up using polyvinylidene difluoride (PVDF) or polyethersulfone (PES) filters. Different factors like formulation composition and protein concentration related to differences in viscosity, as well as different filtration rates were evaluated. The present study showed that filtration behavior was influenced by the presence or absence of a surfactant in the formulation, which defines the interaction between filter membrane and surface active formulation components. This can lead to a change in filter resistance (PES filter) independent on the buffer system used. Filtration behavior was additionally defined by rheological non-Newtonian flow behavior. The data showed that high shear rates resulting from small pore sizes and filtration pressure up to 1.0 bar led to shear-thinning behavior for highly concentrated protein formulations. Differences in non-Newtonian behavior were attributed to ionic strength related to differences in repulsive and attractive interactions. The present study showed that the interplay of formulation composition, filter material, and filtration rate can explain differences in filtration behavior/filtration flux observed for highly concentrated protein formulations thus guiding filter selection. PMID:26149748

  17. HIGH-LEVEL WASTE GLASS FORMULATION MODEL SENSITIVITY STUDY 2009 GLASS FORMULATION MODEL VERSUS 1996 GLASS FORMULATION MODEL

    SciTech Connect

    BELSHER JD; MEINERT FL

    2009-12-07

    This document presents the differences between two HLW glass formulation models (GFM): The 1996 GFM and 2009 GFM. A glass formulation model is a collection of glass property correlations and associated limits, as well as model validity and solubility constraints; it uses the pretreated HLW feed composition to predict the amount and composition of glass forming additives necessary to produce acceptable HLW glass. The 2009 GFM presented in this report was constructed as a nonlinear optimization calculation based on updated glass property data and solubility limits described in PNNL-18501 (2009). Key mission drivers such as the total mass of HLW glass and waste oxide loading are compared between the two glass formulation models. In addition, a sensitivity study was performed within the 2009 GFM to determine the effect of relaxing various constraints on the predicted mass of the HLW glass.

  18. The Clinical Applications of Extended-Release Abuse-Deterrent Opioids.

    PubMed

    Vadivelu, Nalini; Schermer, Erika; Kodumudi, Gopal; Berger, Jack M

    2016-07-01

    Opioids are the mainstay for treatment of acute pain and cancer pain, and also have a role in the treatment of chronic non-malignant pain. There has been, however, a growing public health problem stemming from the misuse of opioid analgesics leading to serious consequences. To deter abuse, new formulations of extended-release opioid analgesics and tamper-resistant opioids have recently been developed. The concept of abuse-deterrent extended-release opioids is relatively new and, although abuse may not be completely prevented, the utilization of such abuse-deterrent extended-release opioids could reduce this risk. Extended-release abuse-deterrent opioids have been found to have important clinical applications in cancer, acute pain, and chronic non-malignant pain for analgesia control with decreased incidence of tampering and abuse. In this review, different extended-release formulations of opioids available for clinical applications are presented with descriptions of the formulations, their physical properties, and the clinical studies performed to provide physicians with a better understanding of their uses. PMID:27290716

  19. Decision-Tree Formulation With Order-1 Lateral Execution

    NASA Technical Reports Server (NTRS)

    James, Mark

    2007-01-01

    A compact symbolic formulation enables mapping of an arbitrarily complex decision tree of a certain type into a highly computationally efficient multidimensional software object. The type of decision trees to which this formulation applies is that known in the art as the Boolean class of balanced decision trees. Parallel lateral slices of an object created by means of this formulation can be executed in constant time considerably less time than would otherwise be required. Decision trees of various forms are incorporated into almost all large software systems. A decision tree is a way of hierarchically solving a problem, proceeding through a set of true/false responses to a conclusion. By definition, a decision tree has a tree-like structure, wherein each internal node denotes a test on an attribute, each branch from an internal node represents an outcome of a test, and leaf nodes represent classes or class distributions that, in turn represent possible conclusions. The drawback of decision trees is that execution of them can be computationally expensive (and, hence, time-consuming) because each non-leaf node must be examined to determine whether to progress deeper into a tree structure or to examine an alternative. The present formulation was conceived as an efficient means of representing a decision tree and executing it in as little time as possible. The formulation involves the use of a set of symbolic algorithms to transform a decision tree into a multi-dimensional object, the rank of which equals the number of lateral non-leaf nodes. The tree can then be executed in constant time by means of an order-one table lookup. The sequence of operations performed by the algorithms is summarized as follows: 1. Determination of whether the tree under consideration can be encoded by means of this formulation. 2. Extraction of decision variables. 3. Symbolic optimization of the decision tree to minimize its form. 4. Expansion and transformation of all nested conjunctive

  20. A new SMA shell element based on the corotational formulation

    NASA Astrophysics Data System (ADS)

    Bisegna, P.; Caselli, F.; Marfia, S.; Sacco, E.

    2014-11-01

    Aim of this paper is to develop a new shape memory alloy (SMA) facet-shell finite element accounting for material and geometric nonlinearities. A corotational formulation is exploited, able to filter out large rigid-body motions from the element transformation. Accordingly, a geometrically linear core-element is employed, along with a SMA constitutive model formulated in the small strain framework. In particular, in accordance with the formulation of the classical thin shell theory, a plane-stress SMA model accounting for the pseudo-elastic as well as the shape memory effect is adopted. The time integration of the evolutive equation is performed developing a step-by-step backward-Euler numerical procedure. A highly efficient implementation of the corotational machinery is used, endowed with a fully consistent tangent stiffness. Applications are carried out for assessing the performances of the developed computational procedure and to investigate on some interesting engineering examples. The numerical results show the effectiveness of the proposed shell element, whose simplicity makes it attractive for the design of new advanced SMA-based devices undergoing significant configuration changes during their operation.

  1. Electromagnetic interactions of extended nucleons

    SciTech Connect

    Ohta, K. )

    1989-09-01

    An electromagnetic current operator is deduced from the most general form of the extended pion-nucleon vertex function using the minimal substitution prescription. It is proved that the sum of the obtained current operator and the isolated-pole contribution satisfies the Ward-Takahashi identity derived for the pion photoproduction. The minimal-coupling interaction is applied to the calculation of the one-pion exchange current regularized by the pion-nucleon form factors. It is found that the one-pion exchange current operator including hadronic and electromagnetic form factors satisfies the Ward-Takahashi equation for the nucleon-nucleon interaction.

  2. On implementation of the extended interior penalty function. [optimum structural design

    NASA Technical Reports Server (NTRS)

    Cassis, J. H.; Schmit, L. A., Jr.

    1976-01-01

    The extended interior penalty function formulation is implemented. A rational method for determining the transition between the interior and extended parts is set forth. The formulation includes a straightforward method for avoiding design points with some negative components, which are physically meaningless in structural analysis. The technique, when extended to problems involving parametric constraints, can facilitate closed form integration of the penalty terms over the most important parts of the parameter interval. The method lends itself well to the use of approximation concepts, such as design variable linking, constraint deletion and Taylor series expansions of response quantities in terms of design variables. Examples demonstrating the algorithm, in the context of planar orthogonal frames subjected to ground motion, are included.

  3. 38 CFR 21.57 - Extended evaluation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Extended evaluation. 21... Initial and Extended Evaluation § 21.57 Extended evaluation. (a) Purpose. The purpose of an extended evaluation for a veteran with a serious employment handicap is to determine the current feasibility of...

  4. [Pharmaceutical and formulation aspects of Petroselinum crispum extract].

    PubMed

    Pápay, Zsófia Edit; Kósa, Annamária; Boldizsár, Imre; Ruszkai, Akos; Balogh, Emese; Klebovich, Imre; Antal, István

    2012-01-01

    Parsley (Petroselinum crispum L.) is a very popular spice and vegetable in Europe, it is widely spread and easy to grow. It's herb and fruits are known to be diuretic, smooth muscle relaxant and hepatoprotective. The most important identified active ingredients are flavonoids, cumarins and vitamin C. Apigenin and its glycosides are the main flavonoids in parsley, it can be found relatively large amounts in the leaves. The bioactive flavonoid apigenin has antiinflammatory, antioxidant and anticancer activities. The objectives of this study were the preparation and detemination of the apigenin content of the parsley extract and the formulation using inert pellets by layering the apigenin in fluid-bed process.

  5. Matrix formulation of a universal microbial transcript profiling system

    SciTech Connect

    Fitch, J P; Ng, J; Sokhansanj, B A

    2000-11-01

    DNA chips and microarrays are used to profile gene transcription. Unfortunately, the initial fabrication cost for a chip and the reagent costs to amplify thousands of open reading frames for a microarray are over $100K for a typical 4 Mbase bacterial genome. To avoid these expensive steps, a matrix formulation of a universal hybrid chip-microarray approach to transcript profiling is demonstrated for synthetic data. Initial considerations for application to the 4.3 Mbase bacterium Yersinia pestis are also presented. This approach can be applied to arbitrary bacteria by recalculating a matrix and pseudoinverse. This approach avoids the large upfront expenses associated with DNA chips and microarrays.

  6. Subscale Testing of Prompt Agent Defeat Formulations

    NASA Astrophysics Data System (ADS)

    Milby, Christopher; Stamatis, Demitrios; Daniels, Amber; Svingala, Forrest; Lightstone, Jim; Miller, Kendra; Bensman, Misty; Bohmke, Matthew

    2015-06-01

    There is a need to improve the current bioagent defeat systems with formulations that produce lower peak pressure, impulse, sustained high temperatures, and release of biocidal species for prompt defeat applications. In this work, explosive charge configurations similar to fuel-air explosives were detonated in a semi-enclosed chamber configuration. Binder type and fuel-to-oxidizer ratios were varied to observe the effects on combustion performance. Thermocouple measurements and high-speed video were used to monitor the combustion of the dispersed formulation. The down-selected formulations were then tested in a sub-scale vented agent defeat system developed to evaluate performance of formulations against aerosolized Bacillus thuringiensis (BT) spores. Diagnostics such as thermocouples, piezoelectric pressure gauges, and pyrometry were utilized to characterize the detonation event. Biological sampling with surface coupons, liquid impingement, and filters of the post detonation environment were utilized to determine spore survivability and rank the relative effectiveness of each formulation. Distribution Statement A: Approved for Public Release; Distribution is Unlimited

  7. Formulation development of allopurinol suppositories and injectables.

    PubMed

    Lee, D K; Wang, D P

    1999-11-01

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

  8. A new oral testosterone undecanoate formulation.

    PubMed

    Köhn, Frank-Michael; Schill, Wolf-Bernhard

    2003-11-01

    Testosterone undecanoate has been available on the market for more than 20 years. This testosterone ester is used worldwide for oral treatment of male hypogonadism. So far, testosterone undecanoate has been dissolved in oleic acid, leading to inconvenient storage conditions. It will now be available in a new formulation with castor oil and propylene glycol laurate instead of oleic acid, thus improving storage conditions markedly (stable at room temperature for approximately 3 years). Pharmacokinetic and pharmacodynamic studies have demonstrated bioequivalence of the old and the new formulation of testosterone undecanoate. Therefore, the results of studies that were performed with the old formulation can be transferred to the clinical use of the new formulation. Controlled studies have shown its efficacy in the treatment of symptoms associated with reduced serum testosterone levels. In these cases testosterone undecanoate improves bone mineral density, quality of life, muscle mass, libido and mood. Further studies will help evaluate the efficacy and safety of the new formulation in the treatment of elderly men with late-onset hypogonadism. PMID:14579074

  9. Formulation and optimization of potassium iodide tablets

    PubMed Central

    Al-Achi, Antoine; Patel, Binit

    2014-01-01

    The use of potassium iodide (KI) as a protective agent against accidental radioactive exposure is well established. In this study, we aimed to prepare a KI tablet formulation using a direct compression method. We utilized Design of Experiment (DoE)/mixture design to define the best formulation with predetermined physical qualities as to its dissolution, hardness, assay, disintegration, and angle of repose. Based on the results from the DoE, the formulation had the following components (%w/w): Avicel 48.70%, silicon dioxide 0.27%, stearic acid (1.00%), magnesium stearate 2.45%, and dicalcium phosphate 18.69%, in addition to potassium iodide 28.89% (130 mg/tablet). This formulation was scaled-up using two tablet presses, a single-punch press and a rotary mini tablet press. The final scaled-up formulation was subjected to a variety of quality control tests, including photo-stability testing. The results indicate that potassium iodide tablets prepared by a rotary mini tablet press had good pharmaceutical characteristics and a shelf-life of 25 days when stored at room temperature protected from light. PMID:25685048

  10. Long Term Storage of Lyophilized Liposomal Formulations

    PubMed Central

    Payton, N.M.; Wempe, M.F.; Xu, Y.; Anchordoquy, T.J.

    2014-01-01

    Because aqueous liposomal formulations containing multiply unsaturated lipids are susceptible to chemical degradation, these formulations are often lyophilized. Despite their limited chemical stability, interest in the use of multiply unsaturated lipids to promote intracellular delivery has increased considerably in recent years. The goal of the current study was to examine the long term storage stability of lyophilized formulations containing lipids with increasing levels of unsaturation, and various strategies which can be employed to improve stability. Aqueous lipid-trehalose formulations containing 1,2-dilinolenoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLinPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) were lyophilized and stored at temperatures ranging from 4°C to 60°C. We observed that the lipid degradation rate increased as the storage temperature and unsaturation level were increased. Even the cleanest sugars which are available commercially contain iron contaminants, and it was observed that the chelation of these iron contaminants significantly improved the stability of DLPC during storage. However, the glass transition temperature of the sugar which was included in the formulation, the reduction of the oxygen in the aqueous sample prior to lyophilization, the inclusion of helper lipids (i.e., cholesterol), and the rate of freezing did not significantly improve stability. PMID:25308534

  11. Formulation and optimization of potassium iodide tablets.

    PubMed

    Al-Achi, Antoine; Patel, Binit

    2015-01-01

    The use of potassium iodide (KI) as a protective agent against accidental radioactive exposure is well established. In this study, we aimed to prepare a KI tablet formulation using a direct compression method. We utilized Design of Experiment (DoE)/mixture design to define the best formulation with predetermined physical qualities as to its dissolution, hardness, assay, disintegration, and angle of repose. Based on the results from the DoE, the formulation had the following components (%w/w): Avicel 48.70%, silicon dioxide 0.27%, stearic acid (1.00%), magnesium stearate 2.45%, and dicalcium phosphate 18.69%, in addition to potassium iodide 28.89% (130 mg/tablet). This formulation was scaled-up using two tablet presses, a single-punch press and a rotary mini tablet press. The final scaled-up formulation was subjected to a variety of quality control tests, including photo-stability testing. The results indicate that potassium iodide tablets prepared by a rotary mini tablet press had good pharmaceutical characteristics and a shelf-life of 25 days when stored at room temperature protected from light. PMID:25685048

  12. Self-Setting Calcium Orthophosphate Formulations

    PubMed Central

    Dorozhkin, Sergey V.

    2013-01-01

    In early 1980s, researchers discovered self-setting calcium orthophosphate cements, which are bioactive and biodegradable grafting bioceramics in the form of a powder and a liquid. After mixing, both phases form pastes, which set and harden forming either a non-stoichiometric calcium deficient hydroxyapatite or brushite. Since both of them are remarkably biocompartible, bioresorbable and osteoconductive, self-setting calcium orthophosphate formulations appear to be promising bioceramics for bone grafting. Furthermore, such formulations possess excellent molding capabilities, easy manipulation and nearly perfect adaptation to the complex shapes of bone defects, followed by gradual bioresorption and new bone formation. In addition, reinforced formulations have been introduced, which might be described as calcium orthophosphate concretes. The discovery of self-setting properties opened up a new era in the medical application of calcium orthophosphates and many commercial trademarks have been introduced as a result. Currently such formulations are widely used as synthetic bone grafts, with several advantages, such as pourability and injectability. Moreover, their low-temperature setting reactions and intrinsic porosity allow loading by drugs, biomolecules and even cells for tissue engineering purposes. In this review, an insight into the self-setting calcium orthophosphate formulations, as excellent bioceramics suitable for both dental and bone grafting applications, has been provided. PMID:24956191

  13. Multi-field variational formulations and related finite elements for piezoelectric shells

    NASA Astrophysics Data System (ADS)

    Lammering, Rolf; Mesecke-Rischmann, Simone

    2003-12-01

    Smart structures technology characterized by structurally integrated sensors and actuators has recently expanded significantly especially as regards lightweight constructions in aeronautics and robotics, e.g. to allow vibration suppression and noise attenuation. In order to be capable of solving these complex issues the finite element method as a well established design tool has to be extended. This paper focuses on shallow sandwich composite shell structures with thin piezoelectric patches bonded to the surfaces. For the proper design of plate and shell structures with integrated piezoelectric materials, various variational formulations and corresponding finite elements are presented. The starting point is the well known two-field variational formulation where the linear piezoelectric effect is taken into account so that the displacements and the electric potential serve as independent variables. Here, the mostly assumed linear variation of the electric potential through the thickness is assumed. Next, it is shown that a quadratic variation of the electric potential through the thickness can be deduced directly from the charge conservation condition. This quadratic variation of the electric potential in the thickness direction is compared with the linear gradient of the first two-field variational formulation. Moreover, in order to allow the implementation of alternative formulations of the constitutive equations by switching of the independent variables and nonlinear material behaviour, a three-field variational formulation is presented in analogy to the Hu-Washizu principle. Adopting this variational principle a hybrid finite element is derived where the dielectric displacement is formulated as an additional degree of freedom. This independent variable can be condensed on the element level and does not enter the system of equations. For the first time all these different variational formulations are developed for a Reissner-Mindlin shallow shell element

  14. Extended Source/Galaxy All Sky 1

    NASA Technical Reports Server (NTRS)

    2003-01-01

    This panoramic view of the entire sky reveals the distribution of galaxies beyond our Milky Way galaxy, which astronomers call extended sources, as observed by Two Micron All-Sky Survey. The image is constructed from a database of over 1.6 million galaxies listed in the survey's Extended Source Catalog; more than half of the galaxies have never before been catalogued. The image is a representation of the relative brightnesses of these million-plus galaxies, all observed at a wavelength of 2.2 microns.

    The brightest and nearest galaxies are represented in blue, and the faintest, most distant ones are in red. This color scheme gives insights into the three dimensional large-scale structure of the nearby universe with the brightest, closest clusters and superclusters showing up as the blue and bluish-white features. The dark band in this image shows the area of the sky where our Milky Way galaxy blocks our view of distant objects, which, in this projection, lies predominantly along the edges of the image.

  15. Extended Duration Orbiter Medical Project

    NASA Technical Reports Server (NTRS)

    Sawin, Charles F. (Editor); Taylor, Gerald R. (Editor); Smith, Wanda L. (Editor); Brown, J. Travis (Technical Monitor)

    1999-01-01

    Biomedical issues have presented a challenge to flight physicians, scientists, and engineers ever since the advent of high-speed, high-altitude airplane flight in the 1940s. In 1958, preparations began for the first manned space flights of Project Mercury. The medical data and flight experience gained through Mercury's six flights and the Gemini, Apollo, and Skylab projects, as well as subsequent space flights, comprised the knowledge base that was used to develop and implement the Extended Duration Orbiter Medical Project (EDOMP). The EDOMP yielded substantial amounts of data in six areas of space biomedical research. In addition, a significant amount of hardware was developed and tested under the EDOMP. This hardware was designed to improve data gathering capabilities and maintain crew physical fitness, while minimizing the overall impact to the microgravity environment. The biomedical findings as well as the hardware development results realized from the EDOMP have been important to the continuing success of extended Space Shuttle flights and have formed the basis for medical studies of crew members living for three to five months aboard the Russian space station, Mir. EDOMP data and hardware are also being used in preparation for the construction and habitation of International Space Station. All data sets were grouped to be non-attributable to individuals, and submitted to NASA s Life Sciences Data Archive.

  16. Implications of Extended Solar Minima

    NASA Technical Reports Server (NTRS)

    Adams, Mitzi L.; Davis, J. M.

    2009-01-01

    Since the discovery of periodicity in the solar cycle, the historical record of sunspot number has been carefully examined, attempting to make predictions about the next cycle. Much emphasis has been on predicting the maximum amplitude and length of the next cycle. Because current space-based and suborbital instruments are designed to study active phenomena, there is considerable interest in estimating the length and depth of the current minimum. We have developed criteria for the definition of a minimum and applied it to the historical sunspot record starting in 1749. In doing so, we find that 1) the current minimum is not yet unusually long and 2) there is no obvious way of predicting when, using our definition, the current minimum may end. However, by grouping the data into 22- year cycles there is an interesting pattern of extended minima that recurs every fourth or fifth 22-year cycle. A preliminary comparison of this pattern with other records, suggests the possibility of a correlation between extended minima and lower levels of solar irradiance.

  17. Extended Operation of Stirling Convertors

    NASA Technical Reports Server (NTRS)

    Roth, Mary Ellen; Schreiber, Jeffery G.; Pepper, Stephen V.

    2004-01-01

    A high-efficiency 110 W Stirling Radioisotope Generator 110 (SRG110) is being developed for potential NASA exploration missions. The SRG system efficiency is greater than 20%, making it an attractive candidate power system for deep space missions and unmanned rovers. The Department of Energy SRG110 Project team consists of the System Integrator, Lockheed Martin (LM), Stirling Technology Company (STC), and NASA Glenn Research Center (GRC). One of the GRC roles is to provide Independent Verification and Validation of the Stirling TDC s. At the request of LM, a part of this effort includes the Extended Operation of the TDC s in the dynamically balanced dual-opposed configuration. Performance data of Stirling Convertors over time is required to demonstrate that an SRG110 can meet long-duration mission requirements. A test plan and test system were developed to evaluate TDC s #13 and #14 steady-state performance for a minimum of 5000 hours. Hardware, software and TDC preparation processes were developed to support this test and insure safe, round-the-clock operation of the TDC s. This paper will discuss the design and development, and status of the Extended Operation Test.

  18. Extended Operation of Stirling Convertors

    NASA Technical Reports Server (NTRS)

    Roth, Mary Ellen; Schreiber, Jeffrey G.; Pepper, Stephen V.

    2004-01-01

    A high-efficiency 110 watt Stirling Radioisotope Generator 110 (SRG110) is being developed for potential NASA exploration missions. The SRG system efficiency is greater than 20%, making it an attractive candidate power system for deep space missions and unmanned rovers. The Department of Energy SRG110 Project team consists of the System Integrator, Lockheed Martin (LM), Stirling Technology Company (STC), and NASA Glenn Research Center (GRC). One of the GRC roles is to provide Independent Verification and Validation of the Stirling TDC's. At the request of LM, a part of this effort includes the extended operation of the TDC's in the dynamically balanced dual-opposed configuration. Performance data of the Stirling Converters over time is required to demonstrate that an SRG110 can meet long-duration mission requirements. A test plan and test system were developed to evaluate TDC's #13 and #14 steady-state performance for a minimum of 5000 hours and insure safe, round-the-clock operation of the TDC's. This paper will discuss the design and development, and status of the Extended Operation Test.

  19. Reasoning over Extended ER Models

    NASA Astrophysics Data System (ADS)

    Artale, A.; Calvanese, D.; Kontchakov, R.; Ryzhikov, V.; Zakharyaschev, M.

    We investigate the computational complexity of reasoning over various fragments of the Extended Entity-Relationship (EER) language, which includes a number of constructs: isa between entities and relationships, disjointness and covering of entities and relationships, cardinality constraints for entities in relationships and their refinements as well as multiplicity constraints for attributes. We extend the known ExpTime-completeness result for UML class diagrams [5] and show that reasoning over EER diagrams with isa between relationships is ExpTime-complete even without relationship covering. Surprisingly, reasoning becomes NP-complete when we drop isa between relationships (while still allowing all types of constraints on entities). If we further omit disjointness and covering over entities, reasoning becomes polynomial. Our lower complexity bound results are proved by direct reductions, while the upper bounds follow from the correspondences with expressive variants of the description logic DL-Lite, which we establish in this paper. These correspondences also show the usefulness of DL-Lite as a language for reasoning over conceptual models and ontologies.

  20. Pipe crawler with extendable legs

    DOEpatents

    Zollinger, W.T.

    1992-06-16

    A pipe crawler for moving through a pipe in inchworm fashion having front and rear leg assemblies separated by air cylinders to increase and decrease the spacing between assemblies. Each leg of the four legs of an assembly is moved between a wall-engaging, extended position and a retracted position by a separate air cylinder. The air cylinders of the leg assemblies are preferably arranged in pairs of oppositely directed cylinders with no pair lying in the same axial plane as another pair. Therefore, the cylinders can be as long as a leg assembly is wide and the crawler can crawl through sections of pipes where the diameter is twice that of other sections. The crawler carries a valving system, a manifold to distribute air supplied by a single umbilical air hose to the various air cylinders in a sequence controlled electrically by a controller. The crawler also utilizes a rolling mechanism, casters in this case, to reduce friction between the crawler and pipe wall thereby further extending the range of the pipe crawler. 8 figs.

  1. Pipe crawler with extendable legs

    DOEpatents

    Zollinger, William T.

    1992-01-01

    A pipe crawler for moving through a pipe in inchworm fashion having front and rear leg assemblies separated by air cylinders to increase and decrease the spacing between assemblies. Each leg of the four legs of an assembly is moved between a wall-engaging, extended position and a retracted position by a separate air cylinder. The air cylinders of the leg assemblies are preferably arranged in pairs of oppositely directed cylinders with no pair lying in the same axial plane as another pair. Therefore, the cylinders can be as long a leg assembly is wide and the crawler can crawl through sections of pipes where the diameter is twice that of other sections. The crawler carries a valving system, a manifold to distribute air supplied by a single umbilical air hose to the various air cylinders in a sequence controlled electrically by a controller. The crawler also utilizes a rolling mechanism, casters in this case, to reduce friction between the crawler and pipe wall thereby further extending the range of the pipe crawler.

  2. Angular momentum dependent orbital-free density functional theory: Formulation and implementation

    NASA Astrophysics Data System (ADS)

    Ke, Youqi; Libisch, Florian; Xia, Junchao; Carter, Emily A.

    2014-04-01

    Orbital-free density functional theory (OFDFT) directly solves for the ground-state electron density. It scales linearly with respect to system size, providing a promising tool for large-scale material simulations. Removal of the orbitals requires use of approximate noninteracting kinetic energy density functionals. If replacing ionic cores with pseudopotentials, removal of the orbitals also requires these pseudopotentials to be local. These are two severe challenges to the capabilities of conventional OFDFT. While main group elements are often well described within conventional OFDFT, transition metals remain intractable due to their localized d electrons. To advance the accuracy and general applicability of OFDFT, we have recently reported a general angular momentum dependent formulation as a next-generation OFDFT. In this formalism, we incorporate the angular momenta of electrons by devising a hybrid scheme based on a muffin tin geometry: inside spheres centered at the ionic cores, the electron density is expanded in a set of atom-centered basis functions combined with an onsite density matrix. The explicit treatment of the angular momenta of electrons provides an important basis for accurately describing the important ionic core region, which is not possible in conventional OFDFT. In addition to the conventional OFDFT total energy functional, we introduce a nonlocal energy term containing a set of angular momentum dependent energies to correct the errors due to the approximate kinetic energy density functional and local pseudopotentials. Our approach greatly increases the accuracy of OFDFT while largely preserving its numerical simplicity. Here, we provide details of the theoretical formulation and practical implementation, including the hybrid scheme, the derivation of the nonlocal energy term, the choice of basis functions, the direct minimization of the total energy, the procedure to determine the angular momentum dependent energies, the force formula with

  3. Relic gravitational waves and extended inflation

    NASA Technical Reports Server (NTRS)

    Turner, Michael S.; Wilczek, Frank

    1990-01-01

    In extended inflation, a new version of inflation where the transition from the false-vacuum phase to a radiation-dominated Universe is accomplished by bubble nucleation and percolation, bubble collisions supply a potent-and potentially detectable-source of gravitational waves. The present energy density in relic gravity waves from bubble collisions is expected to be about 10(exp -5) of closure density-many orders of magnitude greater than that of the gravity waves produced by quantum fluctuations. Their characteristic wavelength depends upon the reheating temperature T(sub RH): lambda is approximately 10(exp 4) cm (10(exp 14) GeV/T(sub RH)). If large numbers of black holes are produced, a not implausible outcome, they will evaporate producing comparable amounts of shorter wavelength waves, lambda is approximately 10(exp -6) cm (T(sub RH)/10(exp 14) GeV).

  4. An extended cure model and model selection.

    PubMed

    Peng, Yingwei; Xu, Jianfeng

    2012-04-01

    We propose a novel interpretation for a recently proposed Box-Cox transformation cure model, which leads to a natural extension of the cure model. Based on the extended model, we consider an important issue of model selection between the mixture cure model and the bounded cumulative hazard cure model via the likelihood ratio test, score test and Akaike's Information Criterion (AIC). Our empirical study shows that AIC is informative and both the score test and the likelihood ratio test have adequate power to differentiate between the mixture cure model and the bounded cumulative hazard cure model when the sample size is large. We apply the tests and AIC methods to leukemia and colon cancer data to examine the appropriateness of the cure models considered for them in the literature.

  5. Formulations for children: problems and solutions

    PubMed Central

    Batchelor, Hannah K; Marriott, John F

    2015-01-01

    Paediatric formulation design is complex as there is a need to understand the developmental physiological changes that occur during childhood and their impact on the absorption of drugs. Paediatric dose adjustments are usually based on achieving pharmacokinetic or pharmacodynamic profiles equivalent to those achieved in adult populations. However, differences in the way in which children handle adult products or the use of bespoke paediatric formulations can result in unexpected pharmacokinetic drug profiles with altered clinical efficacy. Differences in drug formulations need to be understood by healthcare professionals involved in the prescribing, administration or dispensing of drugs to children such that appropriate advice is given to ensure that therapeutic outcomes are achieved. This issue is not confined to oral medicines but is applicable for all routes of administration encountered in paediatric therapy. PMID:25855822

  6. Majorization formulation of uncertainty in quantum mechanics

    SciTech Connect

    Partovi, M. Hossein

    2011-11-15

    Heisenberg's uncertainty principle is formulated for a set of generalized measurements within the framework of majorization theory, resulting in a partial uncertainty order on probability vectors that is stronger than those based on quasientropic measures. The theorem that emerges from this formulation guarantees that the uncertainty of the results of a set of generalized measurements without a common eigenstate has an inviolable lower bound which depends on the measurement set but not the state. A corollary to this theorem yields a parallel formulation of the uncertainty principle for generalized measurements corresponding to the entire class of quasientropic measures. Optimal majorization bounds for two and three mutually unbiased bases in two dimensions are calculated. Similarly, the leading term of the majorization bound for position and momentum measurements is calculated which provides a strong statement of Heisenberg's uncertainty principle in direct operational terms. Another theorem provides a majorization condition for the least-uncertain generalized measurement of a given state with interesting physical implications.

  7. A citation-based assessment of the performance of U.S. boiling water reactors following extended power up-rates

    NASA Astrophysics Data System (ADS)

    Heidrich, Brenden J.

    Nuclear power plants produce 20 percent of the electricity generated in the U.S. Nuclear generated electricity is increasingly valuable to a utility because it can be produced at a low marginal cost and it does not release any carbon dioxide. It can also be a hedge against uncertain fossil fuel prices. The construction of new nuclear power plants in the U.S. is cautiously moving forward, restrained by high capital costs. Since 1998, nuclear utilities have been increasing the power output of their reactors by implementing extended power up-rates. Power increases of up to 20 percent are allowed under this process. The equivalent of nine large power plants has been added via extended power up-rates. These up-rates require the replacement of large capital equipment and are often performed in concert with other plant life extension activities such as license renewals. This dissertation examines the effect of these extended power up-rates on the safety performance of U.S. boiling water reactors. Licensing event reports are submitted by the utilities to the Nuclear Regulatory Commission, the federal nuclear regulator, for a wide range of abnormal events. Two methods are used to examine the effect of extended power up-rates on the frequency of abnormal events at the reactors. The Crow/AMSAA model, a univariate technique is used to determine if the implementation of an extended power up-rate affects the rate of abnormal events. The method has a long history in the aerospace industry and in the military. At a 95-percent confidence level, the rate of events requiring the submission of a licensing event report decreases following the implementation of an extended power up-rate. It is hypothesized that the improvement in performance is tied to the equipment replacement and refurbishment that is performed as part of the up-rate process. The reactor performance is also analyzed using the proportional hazards model. This technique allows for the estimation of the effects of

  8. The local symmetries of M-theory and their formulation in generalised geometry

    NASA Astrophysics Data System (ADS)

    Berman, David S.; Godazgar, Hadi; Godazgar, Mahdi; Perry, Malcolm J.

    2012-01-01

    In the doubled field theory approach to string theory the T-duality group is promoted to a manifest symmetry at the expense of replacing ordinary Riemannian geometry with generalised geometry on a doubled space. The local symmetries are then given by a generalised Lie derivative and its associated algebra. This paper constructs an analogous structure for the extended geometry of M-theory. A crucial by-product of this construction is the derivation of the physical section condition for M-theory formulated in an extended space.

  9. Modeling of ocean dynamics with large variations in sea level

    NASA Astrophysics Data System (ADS)

    Ibrayev, R. A.; Dyakonov, G. S.

    2016-07-01

    The formulation and the algorithm of solving an ocean model for the prediction and assimilation of the observed data which makes it possible to reconstruct the circulation in the deep-water parts of the sea and at a shallow water shelf, as well as to describe the large time-space variability in the surface level, are considered. The model uses a vertical hybrid σ- z coordinate system: the several upper tens of meters of the ocean are described in the σ-coordinate system and the rest of the water column is described in the z coordinates. Such hybridization extends the possibilities of models for reconstructing thermo-hydrodynamic processes in different sea basins and the World Ocean. The differential formulation of the model in the σ- z coordinate system is presented; the simplified records of several operators that are allowable in the case of a small thickness of the ocean σ-layer are described. The construction of a computational grid, approximation of the bottom topography on it, and discretization of equations and boundary conditions of the models are considered; an approach to describing the bottom friction at shallow waters is offered. The results of the comparative experiments in the z and σ- z coordinate models are analyzed.

  10. Nanoparticle formulation of ormeloxifene for pancreatic cancer

    PubMed Central

    Khan, Sheema; Chauhan, Neeraj; Yallapu, Murali M.; Ebeling, Mara C.; Balakrishna, Swathi; Ellis, Robert T.; Thompson, Paul A.; Balabathula, Pavan; Behrman, Stephen W.; Zafar, Nadeem; Singh, Man Mohan; Halaweish, Fathi T.; Jaggi, Meena; Chauhan, Subhash C.

    2015-01-01

    Pancreatic cancer is the fourth most prevalent cancer with about an 85% mortality rate; thus, an utmost need exists to discover new therapeutic modalities that would enhance therapy outcomes of this disease with minimal or no side effects. Ormeloxifene (ORM), a synthetic molecule, has exhibited potent anti-cancer effects through inhibition of important oncogenic and proliferation signaling pathways. However, the anti-cancer efficacy of ORM can be further improved by developing its nanoformulation, which will also offer tumor specific targeted delivery. Therefore, we have developed a novel ORM encapsulated poly(lactic-co-glycolic acid) nanoparticle (NP) formulation (PLGA-ORM NP). This formulation was characterized for particle size, chemical composition, and drug loading efficiency, using various physico-chemical methods (TEM, FT-IR, DSC, TGA, and HPLC). Because of its facile composition, this novel formulation is compatible with antibody/aptamer conjugation to achieve tumor specific targeting. The particle size analysis of this PLGA-ORM formulation (~ 100 nm) indicates that this formulation can preferentially reach and accumulate in tumors by the Enhanced Permeability and Retention (EPR) effect. Cellular uptake and internalization studies demonstrate that PLGA-ORM NPs escape lysosomal degradation, providing efficient endosomal release to cytosol. PLGA-ORM NPs showed remarkable anti-cancer potential in various pancreatic cancer cells (HPAF-II, BxPC-3, Panc-1, MiaPaca) and a BxPC-3 xenograft mice model resulting in increased animal survival. PLGA-ORM NPs suppressed pancreatic tumor growth via suppression of Akt phosphorylation and expression of MUC1, HER2, PCNA, CK19 and CD31. This study suggests that the PLGA-ORM formulation is highly efficient for the inhibition of pancreatic tumor growth and thus can be valuable for the treatment of pancreatic cancer in the future. PMID:25890768

  11. Effects of Formulation Variables and Storage Conditions on Light Protected Vitamin B12 Mixed Parenteral Formulations

    PubMed Central

    Monajjemzadeh, Farnaz; Ebrahimi, Fatemeh; Zakeri-Milani, Parvin; Valizadeh, Hadi

    2014-01-01

    Purpose: In this research the effect of vitamin B1 and B6 on cyanocobalamin stability in commercial light protected parenteral formulations and upon adding stabilizing agents will be investigated and best formulation composition and proper storage condition will be introduced. Methods: In this research some additives such as co solvents and tonicity adjusters, surfactants, antioxidants and chelating agents as well as buffer solutions, were used to improve the stability of the parenteral mixed formulations of B12 in the presence of other B vitamins (B1 and B6). Screening tests and accelerated stability tests were performed according to ICH guidelines Q1A (R2). Results: Shelf life evaluation revealed the best formulation and the proper storage condition. The results indicated the first kinetic models for all tested formulations and the optimum pH value was determined to be 5.8. There was no evidence of B12 loss when mixed with B1 and B6 in a medical syringe at room temperature for maximum of 8 hours. Conclusion: It is necessary to formulate vitamin B12 mixed parenteral solutions using proper phosphate buffers (pH=5.8) and to indicate “Store in refrigerator” on the mixed parenteral formulations of vitamin B12 with other B vitamins, which has not been expressed on the label of tested Brand formulations at the time of this study. PMID:25436187

  12. Nonlocal formulation of spin Coulomb drag

    NASA Astrophysics Data System (ADS)

    D'Amico, I.; Ullrich, C. A.

    2013-10-01

    The spin Coulomb drag (SCD) effect occurs in materials and devices where charged carriers with different spins exchange momentum via Coulomb scattering. This causes frictional forces between spin-dependent currents that lead to intrinsic dissipation, which may limit spintronics applications. A nonlocal formulation of SCD is developed which is valid for strongly inhomogeneous systems such as nanoscale spintronics devices. This nonlocal formulation of SCD is successfully applied to linewidths of intersubband spin plasmons in semiconductor quantum wells, where experiments have shown that the local approximation fails.

  13. Boson formulation of fermion field theories

    SciTech Connect

    Ha, Y.K.

    1984-04-15

    The nonperturbative connection between a canonical Fermi field and a canonical Bose field in two dimensions is developed and its validity verified according to the tenets of quantum field theory. We advocate the point of view that a boson formulation offers a unifying theme in understanding the structure of many theories. This is illustrated by the boson formulation of a multifermion theory with chiral and internal symmetries. Many features of the massless theory, such as dynamical mass generation with asymptotic-freedom behavior, hidden chiral symmetry, and connections with models of apparently different internal symmetries, are readily transparent through such fermion-boson metamorphosis.

  14. Formulation of custom sized LX-15 granules

    SciTech Connect

    Stull, T.W.

    1980-04-01

    LX-15 is a booster explosive formulation consisting of 95% HNS I and 5% Kel F-800 developed by Lawrence Livermore Laboratory. The purpose of this effort was to develop formulation techniques for the production of custom size granules that are amenable for processing in automatic weighing equipment. This report details processes whereby 0.4 and 1.5 kg size batches are produced, meeting those requirements. Efforts to date have found that granule size is dependent on batch/vessel size, water-to-solvent ratio and the degree of vessel agitation.

  15. From Molecular Insights to Novel Catalysts Formulation

    NASA Astrophysics Data System (ADS)

    Nikolla, Eranda; Linic, Suljo

    First-principles methods can be utilized to obtain elementary step mechanisms for chemical reactions on model systems. In this chapter, we will illustrate how this molecular information can be employed to motivate novel heterogeneous catalyst formulations. We will discuss a few examples where first-principles studies on idealized model systems were utilized, along with various experimental tools, to identify alloy catalysts that exhibit improved performance in a number of catalytic processes. We will emphasize the role of molecular approaches in the formulation of these catalysts.

  16. Renewal-reward process formulation of motor protein dynamics.

    PubMed

    Krishnan, Arjun; Epureanu, Bogdan I

    2011-10-01

    Renewal-reward processes are used to provide a framework for the mathematical description of single-molecule bead-motor assays for processive motor proteins. The formulation provides a more powerful, general approach to the fluctuation analysis of bead-motor assays begun by Svoboda et al. (Proc. Natl. Acad. Sci. USA 91(25):11782, 1994). Fluctuation analysis allows one to gain insight into the mechanochemical cycle of motor proteins purely by measuring the statistics of the displacement of the cargo (e.g., bead) the protein transports. The statistical parameters of interest are shown to be the steady-state slopes (in time) of the cumulants of the bead (the cumulant rates). The first two cumulant rates are the steady-state velocity and slope of the variance. The cumulant rates are shown to be insensitive to experimental disturbances such as the initial state of the enzyme and from the viewpoint of modeling, unaffected by substeps. Two existing models--Elston (J. Math. Biol. 41(3):189-206, 2000) and Peskin and Oster (Biophys. J. 68(4):202S-211S, 1995)--are formulated as renewal-reward processes to demonstrate the insight that the formulation affords. A key contribution of the approach is the possibility of accounting for wasted hydrolyses and backward steps in the fluctuation analysis. For example, the randomness parameter defined in the first fluctuation analysis of optical trap based bead-motor assays (Svoboda et al. in Proc. Natl. Acad. Sci. USA 91(25):11782, 1994), loses its original purpose of estimating the number of rate-determining steps in the chemical cycle when backward steps and wasted hydrolyses are present. As a simple application of our formulation, we extend the randomness parameter's scope by showing how it can be used to infer the presence of wasted hydrolyses and backward steps with certainty. A more powerful fluctuation analysis using higher cumulant rate measurements is proposed: the method allows one to estimates the number of intermediate

  17. Analytical Formulation of the Single-visit Completeness Joint Probability Density Function

    NASA Astrophysics Data System (ADS)

    Garrett, Daniel; Savransky, Dmitry

    2016-09-01

    We derive an exact formulation of the multivariate integral representing the single-visit obscurational and photometric completeness joint probability density function for arbitrary distributions for planetary parameters. We present a derivation of the region of nonzero values of this function, which extends previous work, and discuss the time and computational complexity costs and benefits of the method. We present a working implementation and demonstrate excellent agreement between this approach and Monte Carlo simulation results.

  18. First-order nonadiabatic coupling matrix elements between excited states: A Lagrangian formulation at the CIS, RPA, TD-HF, and TD-DFT levels

    SciTech Connect

    Li, Zhendong; Liu, Wenjian

    2014-07-07

    Analytic expressions for the first-order nonadiabatic coupling matrix elements between electronically excited states are first formulated exactly via both time-independent equation of motion and time-dependent response theory, and are then approximated at the configuration interaction singles, particle-hole/particle-particle random phase approximation, and time-dependent density functional theory/Hartree-Fock levels of theory. Note that, to get the Pulay terms arising from the derivatives of basis functions, the standard response theory designed for electronic perturbations has to be extended to nuclear derivatives. The results are further recast into a Lagrangian form that is similar to that for excited-state energy gradients and allows to use atomic orbital based direct algorithms for large molecules.

  19. Extending Medicare immunosuppressive medication coverage.

    PubMed

    Beaubrun, Anne Christine

    2012-02-01

    African Americans and the poor are at a high risk of suffering from kidney disease and are at an extreme disadvantage when it comes to obtaining the resources needed to maintain a functioning kidney post-transplant. Medicare currently covers 80% of the cost of immunosuppressive therapy for up to three years following a Medicare-covered transplant for patients whose Medicare entitlement was based solely on their end-stage renal disease diagnosis. Adequate insurance coverage has the potential to prevent graft failure and retransplantation resulting from cost-related immunosuppressive medication nonadherence. Given the multifactorial nature of medication nonadherence, extending insurance coverage in an attempt to reduce graft failures should be coupled with intensive interventions to prevent the socioeconomic and various other factors associated with medication nonadherence. Lifetime Medicare coverage for all kidney-transplant recipients, coupled with medication adherence promotion, has the potential to minimize poor outcomes associated with graft failure, especially among minorities and the impoverished.

  20. Extended uncertainty from first principles

    NASA Astrophysics Data System (ADS)

    Costa Filho, Raimundo N.; Braga, João P. M.; Lira, Jorge H. S.; Andrade, José S.

    2016-04-01

    A translation operator acting in a space with a diagonal metric is introduced to describe the motion of a particle in a quantum system. We show that the momentum operator and, as a consequence, the uncertainty relation now depend on the metric. It is also shown that, for any metric expanded up to second order, this formalism naturally leads to an extended uncertainty principle (EUP) with a minimum momentum dispersion. The Ehrenfest theorem is modified to include an additional term related to a tidal force arriving from the space curvature introduced by the metric. For one-dimensional systems, we show how to map a harmonic potential to an effective potential in Euclidean space using different metrics.

  1. Extended mission life support systems

    NASA Technical Reports Server (NTRS)

    Quattrone, P. D.

    1985-01-01

    Extended manned space missions which include interplanetary missions require regenerative life support systems. Manned mission life support considerations are placed in perspective and previous manned space life support system technology, activities and accomplishments in current supporting research and technology (SR&T) programs are reviewed. The life support subsystem/system technologies required for an enhanced duration orbiter (EDO) and a space operations center (SOC), regenerative life support functions and technology required for manned interplanetary flight vehicles, and future development requirements are outlined. The Space Shuttle Orbiters (space transportation system) is space cabin atmosphere is maintained at Earth ambient pressure of 14.7 psia (20% O2 and 80% N2). The early Shuttle flights will be seven-day flights, and the life support system flight hardware will still utilize expendables.

  2. Learning Extended Finite State Machines

    NASA Technical Reports Server (NTRS)

    Cassel, Sofia; Howar, Falk; Jonsson, Bengt; Steffen, Bernhard

    2014-01-01

    We present an active learning algorithm for inferring extended finite state machines (EFSM)s, combining data flow and control behavior. Key to our learning technique is a novel learning model based on so-called tree queries. The learning algorithm uses the tree queries to infer symbolic data constraints on parameters, e.g., sequence numbers, time stamps, identifiers, or even simple arithmetic. We describe sufficient conditions for the properties that the symbolic constraints provided by a tree query in general must have to be usable in our learning model. We have evaluated our algorithm in a black-box scenario, where tree queries are realized through (black-box) testing. Our case studies include connection establishment in TCP and a priority queue from the Java Class Library.

  3. Extended MHD Simulations of Spheromaks

    NASA Astrophysics Data System (ADS)

    Howell, E. C.; Sovinec, C. R.

    2012-10-01

    Nonlinear extended MHD simulations of a spheromak in a cylindrical flux conserver are performed using the NIMROD code (JCP 195, 2004). An idealized series of simulations starting from a Grad-Shafranov equilibrium and small non-axisymmetric perturbations are performed to model the sustained decay phase. The resulting confinement leads to steep resistivity gradients. Strong current gradients develop, driving tearing modes that dominate the evolution of the spheromak. Absent in these simulations are the remains of n=1 fluctuations created during the formation process. A second series of simulations start from vacuum fields and model the full spheromak evolution, including the formation process where the n=1 fluctuations dominate. To understand the role of pressure driven instabilities in the evolution of the spheromak, a numerical diagnostic is developed to calculate the Mercier stability criterion from the axisymmetric fields.

  4. Dicyanometallates as Model Extended Frameworks

    PubMed Central

    2016-01-01

    We report the structures of eight new dicyanometallate frameworks containing molecular extra-framework cations. These systems include a number of hybrid inorganic–organic analogues of conventional ceramics, such as Ruddlesden–Popper phases and perovskites. The structure types adopted are rationalized in the broader context of all known dicyanometallate framework structures. We show that the structural diversity of this family can be understood in terms of (i) the charge and coordination preferences of the particular metal cation acting as framework node, and (ii) the size, shape, and extent of incorporation of extra-framework cations. In this way, we suggest that dicyanometallates form a particularly attractive model family of extended frameworks in which to explore the interplay between molecular degrees of freedom, framework topology, and supramolecular interactions. PMID:27057759

  5. Stellar structures in Extended Gravity

    NASA Astrophysics Data System (ADS)

    Capozziello, S.; De Laurentis, M.

    2016-09-01

    Stellar structures are investigated by considering the modified Lané-Emden equation coming out from Extended Gravity. In particular, this equation is obtained in the Newtonian limit of f ( R) -gravity by introducing a polytropic relation between the pressure and the density into the modified Poisson equation. The result is an integro-differential equation, which, in the limit f ( R) → R , becomes the standard Lané-Emden equation usually adopted in the stellar theory. We find the radial profiles of gravitational potential by solving for some values of the polytropic index. The solutions are compatible with those coming from General Relativity and could be physically relevant in order to address peculiar and extremely massive objects.

  6. Extended Klein edges in graphene.

    PubMed

    He, Kuang; Robertson, Alex W; Lee, Sungwoo; Yoon, Euijoon; Lee, Gun-Do; Warner, Jamie H

    2014-12-23

    Graphene has three experimentally confirmed periodic edge terminations, zigzag, reconstructed 5-7, and arm-chair. Theory predicts a fourth periodic edge of graphene called the extended Klein (EK) edge, which consists of a series of single C atoms protruding from a zigzag edge. Here, we confirm the existence of EK edges in both graphene nanoribbons and on the edge of bulk graphene using atomic resolution imaging by aberration-corrected transmission electron microscopy. The formation of the EK edge stems from sputtering and reconstruction of the zigzag edge. Density functional theory reveals minimal energy for EK edge reconstruction and bond distortion both in and out of plane, supporting our TEM observations. The EK edge can now be included as the fourth member of observed periodic edge structures in graphene.

  7. THE EXTENDED VIRGO CLUSTER CATALOG

    SciTech Connect

    Kim, Suk; Rey, Soo-Chang; Lee, Youngdae; Chung, Jiwon; Pak, Mina; Yi, Wonhyeong; Lee, Woong; Jerjen, Helmut; Lisker, Thorsten; Sung, Eon-Chang

    2015-01-01

    We present a new catalog of galaxies in the wider region of the Virgo cluster, based on the Sloan Digital Sky Survey (SDSS) Data Release 7. The Extended Virgo Cluster Catalog (EVCC) covers an area of 725 deg{sup 2} or 60.1 Mpc{sup 2}. It is 5.2 times larger than the footprint of the classical Virgo Cluster Catalog (VCC) and reaches out to 3.5 times the virial radius of the Virgo cluster. We selected 1324 spectroscopically targeted galaxies with radial velocities less than 3000 km s{sup –1}. In addition, 265 galaxies that have been overlooked in the SDSS spectroscopic survey but have available redshifts in the NASA Extragalactic Database are also included. Our selection process secured a total of 1589 galaxies, 676 of which are not included in the VCC. The certain and possible cluster members are defined by means of redshift comparison with a cluster infall model. We employed two independent and complementary galaxy classification schemes: the traditional morphological classification based on the visual inspection of optical images and a characterization of galaxies from their spectroscopic features. SDSS u, g, r, i, and z passband photometry of all EVCC galaxies was performed using Source Extractor. We compare the EVCC galaxies with the VCC in terms of morphology, spatial distribution, and luminosity function. The EVCC defines a comprehensive galaxy sample covering a wider range in galaxy density that is significantly different from the inner region of the Virgo cluster. It will be the foundation for forthcoming galaxy evolution studies in the extended Virgo cluster region, complementing ongoing and planned Virgo cluster surveys at various wavelengths.

  8. Extended optical model for fission

    DOE PAGES

    Sin, M.; Capote, R.; Herman, M. W.; Trkov, A.

    2016-03-07

    A comprehensive formalism to calculate fission cross sections based on the extension of the optical model for fission is presented. It can be used for description of nuclear reactions on actinides featuring multi-humped fission barriers with partial absorption in the wells and direct transmission through discrete and continuum fission channels. The formalism describes the gross fluctuations observed in the fission probability due to vibrational resonances, and can be easily implemented in existing statistical reaction model codes. The extended optical model for fission is applied for neutron induced fission cross-section calculations on 234,235,238U and 239Pu targets. A triple-humped fission barrier ismore » used for 234,235U(n,f), while a double-humped fission barrier is used for 238U(n,f) and 239Pu(n,f) reactions as predicted by theoretical barrier calculations. The impact of partial damping of class-II/III states, and of direct transmission through discrete and continuum fission channels, is shown to be critical for a proper description of the measured fission cross sections for 234,235,238U(n,f) reactions. The 239Pu(n,f) reaction can be calculated in the complete damping approximation. Calculated cross sections for 235,238U(n,f) and 239Pu(n,f) reactions agree within 3% with the corresponding cross sections derived within the Neutron Standards least-squares fit of available experimental data. Lastly, the extended optical model for fission can be used for both theoretical fission studies and nuclear data evaluation.« less

  9. Group-theoretical construction of extended baryon operators

    SciTech Connect

    S. Basak; R. Edwards; R. Fiebig; G. T. Fleming; U. M. Heller; C. Morningstar; D. Richards; I. Sato; S. Wallace

    2004-06-01

    The design and implementation of large sets of spatially extended baryon operators for use in lattice simulations are described. The operators are constructed to maximize overlaps with the low-lying states of interest, while minimizing the number of sources needed in computing the required quark propagators.

  10. Detail section extending from shore. Note the paired support pilings, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail section extending from shore. Note the paired support pilings, concrete curbs with rectangular openings for drainage, and large-diameter metal pipe suspended under the deck. USS MISSOURI in background - U.S. Naval Base, Pearl Harbor, Gasoline Wharf, Offshore, near the intersection of Hornet Avenue & Curtis Street, Ford Island, Pearl City, Honolulu County, HI

  11. How Far Is Leadership Distributed in Extended Services Provision?

    ERIC Educational Resources Information Center

    Fuller, Kay; Parsons, Sarah; MacNab, Natasha; Thomas, Hywel

    2013-01-01

    This study focuses on the leadership engagement of children, young people (CYP) and their families in six school-based extended services (ES) clusters in a single, large, urban local authority in England. Empirical research was carried out in two strands of activity that focused on outcomes and experiences for CYP and leaders and leadership.…

  12. Granulation of increasingly hydrophobic formulations using a twin screw granulator.

    PubMed

    Yu, Shen; Reynolds, Gavin K; Huang, Zhenyu; de Matas, Marcel; Salman, Agba D

    2014-11-20

    The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has not yet been established. Hence, the current work investigated the granulation behaviour of three formulations containing increasing amounts of hydrophobic components using a Consigma™-1 twin screw granulator. Process conditions including powder feed rate, liquid to solid ratio, granulation liquid composition and screw configuration were also evaluated. The size of the wet granules was measured in order to enable exploration of granulation behaviour in isolation without confounding effects from downstream processes such as drying. The experimental observations indicated that the granulation process was not sensitive to the powder feed rate. The hydrophobicity led to heterogeneous liquid distribution and hence a relatively large proportion of un-wetted particles. Increasing numbers of kneading elements led to high shear and prolonged residence time, which acted to enhance the distribution of liquid and feeding materials. The bimodal size distributions considered to be characteristic of twin screw granulation were primarily ascribed to the breakage of relatively large granules by the kneading elements. PMID:25124058

  13. Enhanced element-specific modal formulations for flexible multibody dynamics

    NASA Technical Reports Server (NTRS)

    Ryan, Robert R.

    1989-01-01

    The accuracy of current flexible multibody formalisms based on assumed modes is examined in the context of standard spacecraft motions involving structural components undergoing both slow and fast overall translational and rotational motions as well as small deformations. Limitations of current techniques in treating: (1) element-specific coupling behavior of large motion and small deformation, and (2) motion-induced structural stiffness variations, are noted. The roles of nonlinear and linear elastic structural theories in accurately predicting transient large-displacement dynamic behavior of flexible multibody systems are examined in detail. Coupling effects between deformation and overall motion are carefully scrutinized in the context of assumed-mode discretization techniques. Consistently linearized beam, plate, and shell formulations involving in-plane stretch variables are proposed and shown to yield very accurate simulation results and extremely fast modal convergence for most motions involving small strains. In some particular cases, however, in which membrane stiffness dominates bending stiffness, a nonlinear strain formulation is required in order to capture proper coupling between deformation and overall motion.

  14. Dissolution of three insensitive munitions formulations.

    PubMed

    Taylor, Susan; Park, Eileen; Bullion, Katherine; Dontsova, Katerina

    2015-01-01

    The US military fires live munitions during training. To save soldiers lives both during training and war, the military is developing insensitive munitions (IM) that minimize unintentional detonations. Some of the compounds in the IM formulation are, however, very soluble in water, raising environmental concerns about their fate and transport. We measured the dissolution of three of these IM formulations, IMX101, IMX104 and PAX21 using laboratory drip tests and studied the accompanying changes in particle structure using micro computed tomography. Our laboratory drip tests mimic conditions on training ranges, where spatially isolated particles of explosives scattered by partial detonations are dissolved by rainfall. We found that the constituents of these IM formulations dissolve sequentially and in the order predicted by their aqueous solubility. The order of magnitude differences in solubility among their constituents produce water solutions whose compositions and concentrations vary with time. For IMX101 and IMX104, that contain 3-nitro-1,2,4-triazol-5-one (NTO), the solutions also vary in pH. The good mass balances measured for the drip tests indicate that the formulations are not being photo-or bio-transformed under laboratory conditions. PMID:25043961

  15. A Generalized Fluid Formulation for Turbomachinery Computations

    NASA Technical Reports Server (NTRS)

    Merkle, Charles L.; Sankaran, Venkateswaran; Dorney, Daniel J.; Sondak, Douglas L.

    2003-01-01

    A generalized formulation of the equations of motion of an arbitrary fluid are developed for the purpose of defining a common iterative algorithm for computational procedures. The method makes use of the equations of motion in conservation form with separate pseudo-time derivatives used for defining the numerical flux for a Riemann solver and the convergence algorithm. The partial differential equations are complemented by an thermodynamic and caloric equations of state of a complexity necessary for describing the fluid. Representative solutions with a new code based on this general equation formulation are provided for three turbomachinery problems. The first uses air as a working fluid while the second uses gaseous oxygen in a regime in which real gas effects are of little importance. These nearly perfect gas computations provide a basis for comparing with existing perfect gas code computations. The third case is for the flow of liquid oxygen through a turbine where real gas effects are significant. Vortex shedding predictions with the LOX formulations reduce the discrepancy between perfect gas computations and experiment by approximately an order of magnitude, thereby verifying the real gas formulation as well as providing an effective case where its capabilities are necessary.

  16. 40 CFR 152.85 - Formulators' exemption.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Formulators' exemption. 152.85 Section 152.85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Satisfaction of Data Requirements and Protection...

  17. Update on tamper-resistant drug formulations.

    PubMed

    Romach, M K; Schoedel, K A; Sellers, E M

    2013-06-01

    An expert panel convened in 2005 by the College on Problems of Drug Dependence (CPDD) to consider strategies to reduce the risk of prescription medication abuse concluded that drug formulation plays a significant role in determining risk of abuse. Efforts on the part of the pharmaceutical industry to develop drugs that deter abuse have focused primarily on opioid formulations resistant to common forms of tampering, most notably crushing or dissolving the tablet to accelerate release. Several opioid formulations developed to be tamper resistant have been approved, but the US Food and Drug Administration has not approved explicit label claims of abuse deterrence and has stated that any such claim will require substantial postmarketing data. Drug development efforts in this area raise questions about the relative impact of abuse-deterrent formulations, not only on individuals who might abuse a medication, but also on patients who are compliant with therapy. This review discusses progress since the 2005 CPDD meeting with an emphasis on opioids. Articles cited in the review were identified via a PubMed search covering the period between January 1, 2000, and October 5, 2011. Scientific work presented by the authors and their colleagues at meetings held through May 2012 also was included. Published literature suggests that development of abuse-deterrent products will require broad public health support and continued encouragement from regulatory authorities so that such products will become the expected standard of care for certain drug classes.

  18. Dissolution of three insensitive munitions formulations.

    PubMed

    Taylor, Susan; Park, Eileen; Bullion, Katherine; Dontsova, Katerina

    2015-01-01

    The US military fires live munitions during training. To save soldiers lives both during training and war, the military is developing insensitive munitions (IM) that minimize unintentional detonations. Some of the compounds in the IM formulation are, however, very soluble in water, raising environmental concerns about their fate and transport. We measured the dissolution of three of these IM formulations, IMX101, IMX104 and PAX21 using laboratory drip tests and studied the accompanying changes in particle structure using micro computed tomography. Our laboratory drip tests mimic conditions on training ranges, where spatially isolated particles of explosives scattered by partial detonations are dissolved by rainfall. We found that the constituents of these IM formulations dissolve sequentially and in the order predicted by their aqueous solubility. The order of magnitude differences in solubility among their constituents produce water solutions whose compositions and concentrations vary with time. For IMX101 and IMX104, that contain 3-nitro-1,2,4-triazol-5-one (NTO), the solutions also vary in pH. The good mass balances measured for the drip tests indicate that the formulations are not being photo-or bio-transformed under laboratory conditions.

  19. State-Space Formulation for Circuit Analysis

    ERIC Educational Resources Information Center

    Martinez-Marin, T.

    2010-01-01

    This paper presents a new state-space approach for temporal analysis of electrical circuits. The method systematically obtains the state-space formulation of nondegenerate linear networks without using concepts of topology. It employs nodal/mesh systematic analysis to reduce the number of undesired variables. This approach helps students to…

  20. Beyond antigens and adjuvants: formulating future vaccines.

    PubMed

    Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J

    2016-03-01

    The need to optimize vaccine potency while minimizing toxicity in healthy recipients has motivated studies of the formulation of vaccines to control how, when, and where antigens and adjuvants encounter immune cells and other cells/tissues following administration. An effective subunit vaccine must traffic to lymph nodes (LNs), activate both the innate and adaptive arms of the immune system, and persist for a sufficient time to promote a mature immune response. Here, we review approaches to tailor these three aspects of vaccine function through optimized formulations. Traditional vaccine adjuvants activate innate immune cells, promote cell-mediated transport of antigen to lymphoid tissues, and promote antigen retention in LNs. Recent studies using nanoparticles and other lymphatic-targeting strategies suggest that direct targeting of antigens and adjuvant compounds to LNs can also enhance vaccine potency without sacrificing safety. The use of formulations to regulate biodistribution and promote antigen and inflammatory cue co-uptake in immune cells may be important for next-generation molecular adjuvants. Finally, strategies to program vaccine kinetics through novel formulation and delivery strategies provide another means to enhance immune responses independent of the choice of adjuvant. These technologies offer the prospect of enhanced efficacy while maintaining high safety profiles necessary for successful vaccines.

  1. 40 CFR 152.85 - Formulators' exemption.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., toxicology, residue chemistry, exposure, environmental fate, and ecological effects. (2) The data to which... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Formulators' exemption. 152.85 Section 152.85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE...

  2. A Logarithmic Complexity Floating Frame of Reference Formulation with Interpolating Splines for Articulated Multi-Flexible-Body Dynamics

    PubMed Central

    Ahn, W.; Anderson, K.S.; De, S.

    2013-01-01

    An interpolating spline-based approach is presented for modeling multi-flexible-body systems in the divide-and-conquer (DCA) scheme. This algorithm uses the floating frame of reference formulation and piecewise spline functions to construct and solve the non-linear equations of motion of the multi-flexible-body system undergoing large rotations and translations. The new approach is compared with the flexible DCA (FDCA) that uses the assumed modes method [1]. The FDCA, in many cases, must resort to sub-structuring to accurately model the deformation of the system. We demonstrate, through numerical examples, that the interpolating spline-based approach is comparable in accuracy and superior in efficiency to the FDCA. The present approach is appropriate for modeling flexible mechanisms with thin 1D bodies undergoing large rotations and translations, including those with irregular shapes. As such, the present approach extends the current capability of the DCA to model deformable systems. The algorithm retains the theoretical logarithmic complexity inherent in the DCA when implemented in parallel. PMID:24124265

  3. Large area plasma source

    NASA Technical Reports Server (NTRS)

    Foster, John (Inventor); Patterson, Michael (Inventor)

    2008-01-01

    An all permanent magnet Electron Cyclotron Resonance, large diameter (e.g., 40 cm) plasma source suitable for ion/plasma processing or electric propulsion, is capable of producing uniform ion current densities at its exit plane at very low power (e.g., below 200 W), and is electrodeless to avoid sputtering or contamination issues. Microwave input power is efficiently coupled with an ionizing gas without using a dielectric microwave window and without developing a throat plasma by providing a ferromagnetic cylindrical chamber wall with a conical end narrowing to an axial entrance hole for microwaves supplied on-axis from an open-ended waveguide. Permanent magnet rings are attached inside the wall with alternating polarities against the wall. An entrance magnet ring surrounding the entrance hole has a ferromagnetic pole piece that extends into the chamber from the entrance hole to a continuing second face that extends radially across an inner pole of the entrance magnet ring.

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

    PubMed

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

    2015-11-10

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

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

    PubMed

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

    2015-11-10

    The aim of the current work was to explore continuous dry powder mixing and direct compression for manufacturing of extended release (ER) matrix tablets. The study was span out with a challenging formulation design comprising ibuprofen compositions with varying particle size and a relatively low amount of the matrix former hydroxypropyl methylcellulose (HPMC). Standard grade HPMC (CR) was compared to a recently developed direct compressible grade (DC2). The work demonstrate that ER tablets with desired quality attributes could be manufactured via integrated continuous mixing and direct compression. The most robust tablet quality (weight, assay, tensile strength) was obtained using high mixer speed and large particle size ibuprofen and HPMC DC2 due to good powder flow. At low mixer speed it was more difficult to achieve high quality low dose tablets. Notably, with HPMC DC2 the processing conditions had a significant effect on drug release. Longer processing time and/or faster mixer speed was needed to achieve robust release with compositions containing DC2 compared with those containing CR. This work confirms the importance of balancing process parameters and material properties to find consistent product quality. Also, adaptive control is proven a pivotal means for control of continuous manufacturing systems. PMID:26320548

  6. "Loyola Values": Extending the Brand

    ERIC Educational Resources Information Center

    Rosen, Jeffrey; Shannon, Kelly

    2008-01-01

    Loyola University Chicago had long used the tag line, "Chicago's Jesuit University," to highlight the institution's local origins and its ties to a 450-year tradition of academic excellence. By the turn of this century, this reference was unfamiliar to a large percentage of prospective students, particularly adult students, and the Chicago focus…

  7. Re-analysis procedure based on the mixed formulation

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Peters, Jeanne M.

    1987-01-01

    An analysis procedure is presented for large-scale structural systems, with large numbers of degrees of freedom and design variables. The procedure uses a mixed formulation with the fundamental unknowns consisting of both stress and displacement parameters. Other elements of the procedure include: (1) lumping the design variables into a single tracing parameter; (2) operator splitting or additive decomposition of different arrays in the finite element equations into the corresponding arrays of the original structure plus correction terms; and (3) application of a reduction method through the use of the finite element method and the classical Bubnov-Galerkin technique. The re-analysis procedure is applied to the linear static and free vibration problems of plate and shell structures.

  8. Application of the Absolute Nodal Co-Ordinate Formulation to Multibody System Dynamics

    NASA Astrophysics Data System (ADS)

    Escalona, J. L.; Hussien, H. A.; Shabana, A. A.

    1998-07-01

    The floating frame of reference formulation is currently the most widely used approach in flexible multibody simulations. The use of this approach, however, has been limited to small deformation problems. In this investigation, the computer implementation of the newabsolute nodal co-ordinate formulationand its use in the small and large deformation analysis of flexible multibody systems that consist of interconnected bodies are discussed. While in the floating frame of reference formulation a mixed set of absolute reference and local elastic co-ordinates are used, in the absolute nodal co-ordinate formulation only absolute co-ordinates are used. In the absolute nodal co-ordinate formulation, new interpretation of the nodal co-ordinates of the finite elements is used. No infinitesimal or finite rotations are used as nodal co-ordinates from beams and plates, instead, global slopes are used to define the element nodal co-ordinates. Using this interpretation of the element co-ordinates, beams and plates can be considered as isoparametric elements, and as a result, exact modelling of the rigid body dynamics can be obtained using the element shape function and the absolute nodal co-ordinates. Unlike the floating frame of reference approach, no co-ordinate transformation is required in order to determine the element inertia. The mass matrix of the finite elements is a constant matrix, and therefore, the centrifugal and Coriolis forces are equal to zero when the absolute nodal co-ordinate formulation is used. Another advantage of using the absolute nodal co-ordinate formulation in the dynamic simulation of multibody systems is its simplicity in imposing some of the joint constraints and also its simplicity in formulating the generalized forces due to spring-damper elements. The results obtained in this investigation show an excellent agreement with the results obtained using the floating frame of reference formulation when large rotation-small deformation problems are

  9. The highest limiting Z in the extended periodic table

    NASA Astrophysics Data System (ADS)

    Gambhir, Y. K.; Bhagwat, A.; Gupta, M.

    2015-12-01

    The problem of finding the highest limiting Z in the extended periodic table is discussed. The upper limit suggested by the atomic many body theory at Z = 172 may be reached much earlier due to nuclear instabilities. Therefore, an extensive set of calculations based on the relativistic mean field formulation are carried out for the ground state properties of nuclei with Z = 100 to 180 and N/Z ratio ranging from 1.19 to 2.70. This choice of Z and N extends far beyond the corresponding values of all the known heavy to superheavy elements. To facilitate the analysis of the huge quantity of calculated results, various filters depending upon the pairing energies, one and two nucleon separation energies, binding energy per particle (BE/A) and α-decay plus fission half lives, are introduced. The limiting value of Z is found to be 146. For the specific filter with {BE}/A = 5.5 MeV a few nuclei with Z = 180 also appear. No evidence for the limiting Z value 172 is found. We stress the need to bridge the atomic and nuclear findings and to arrive at an acceptable limiting value of highest Z (or rather combination of Z and N) of the extended periodic table.

  10. Aerosol characterization of nebulized intranasal glucocorticoid formulations.

    PubMed

    Berlinski, A; Waldrep, J C

    2001-01-01

    Inhaled glucocorticoids (GCs) are the mainstay of long-term therapy for asthma. The lack of suitable preparations in the United States has induced clinicians to use intranasal (IN) GC formulations as "nebulizer suspensions" for off-label therapy. However, no data are available regarding aerosol production and characteristics. The aim of this study was to characterize drug outputs and aerodynamic profiles of four nebulized IN GC formulations with further analysis of flunisolide (Flu), and to test the influence of different delivery system/formulation combinations. The aerodynamic profiles and drug outputs were determined by impaction and chemical analysis. The solution output was determined by the gravimetric technique. Triamcinole acetonide (TAA), fluticasone propionate (Flut), beclomethasone dipropionate (Bec), and Flu (550, 500, 840, and 250 microg, respectively) diluted to 4 mL with saline solution were tested with the Sidestream (SID) and Aero-Tech II (AT2) nebulizers. Subsequently, Flu was tested with four additional nebulizers (Pari LC + [PARI] Acorn II, Hudson T Up-draft II, and Raindrop). All the aerosols were heterodisperse and had a particle size range optimal for peripheral airway deposition (1.85 to 3.67 microm). Flu had the highest drug output in the respirable range (22.8 and 20.3 microg/min with the AT and SID, respectively). Flu was 5-11 times more efficiently nebulized than the other formulations tested. No differences were detected in the solution outputs (0.25 to 0.3 mL/min). In subsequent testing of Flu, the PARI, AT, and SID showed the best performances. The LC+ achieved the highest drug and solution output (27.4 microg/min and 0.89 mL/min, respectively). In conclusion, Flu showed the best aerosol performance characteristics. These data do not endorse the off-label utilization of nebulized IN GC, but underscores the importance of in vitro testing before selecting any formulation/nebulizer combinations for clinical use.

  11. Characterization of Amorphous and Co-Amorphous Simvastatin Formulations Prepared by Spray Drying.

    PubMed

    Craye, Goedele; Löbmann, Korbinian; Grohganz, Holger; Rades, Thomas; Laitinen, Riikka

    2015-01-01

    In this study, spray drying from aqueous solutions, using the surface-active agent sodium lauryl sulfate (SLS) as a solubilizer, was explored as a production method for co-amorphous simvastatin-lysine (SVS-LYS) at 1:1 molar mixtures, which previously have been observed to form a co-amorphous mixture upon ball milling. In addition, a spray-dried formulation of SVS without LYS was prepared. Energy-dispersive X-ray spectroscopy (EDS) revealed that SLS coated the SVS and SVS-LYS particles upon spray drying. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) showed that in the spray-dried formulations the remaining crystallinity originated from SLS only. The best dissolution properties and a "spring and parachute" effect were found for SVS spray-dried from a 5% SLS solution without LYS. Despite the presence of at least partially crystalline SLS in the mixtures, all the studied formulations were able to significantly extend the stability of amorphous SVS compared to previous co-amorphous formulations of SVS. The best stability (at least 12 months in dry conditions) was observed when SLS was spray-dried with SVS (and LYS). In conclusion, spray drying of SVS and LYS from aqueous surfactant solutions was able to produce formulations with improved physical stability for amorphous SVS. PMID:26633346

  12. Evaluation of soyscreen in an oil-based formulation for UV protection of Beauveria bassiana conidia.

    PubMed

    Behle, Robert W; Compton, David L; Laszlo, Joseph A; Shapiro-Ilan, David I

    2009-10-01

    Soyscreen oil was studied as a formulation ingredient to protect Beauveria bassiana (Balsamo) Vuillemin conidia from UV degradation. Feruloylated soy glycerides, referred to as Soyscreen oil, are biobased UV-absorbing molecules made by combining molecules of soybean oil with ferulic acid. Conidia stored in Soyscreen oil for 28 wk at 25, 30, and 35 degrees C retained viability as well as conidia stored in sunflower oil, demonstrating that Soyscreen did not adversely affect viability with prolonged storage. For samples applied to glass and exposed to simulated sunlight (xenon light), conidia in sunflower oil with or without sunscreens (Soyscreen or oxyl methoxycinnimate) had similar conidia viability after exposure. These oil formulations retained conidia viability better than conidia applied as an aqueous treatment. However, the 10% Soyscreen oil formulation applied to field grown cabbage (Brassica oleracea L.) and bean (Phaseolus vulgaris L.) plants, did not improve residual insecticidal activity compared with aqueous applications of unformulated conidia or two commercial formulations when assayed against Trichoplusia ni (Hübner) larvae. Our results suggest that the oil applications lose UV protection because the oil was absorbed by the leaf. This conclusion was supported in subsequent laboratory exposures of conidia in oil-based formulations with UV screens applied to cabbage leaves or balsa wood, which lost protection as measured by decreased viability of conidia when exposed to simulated sunlight. As a result, additional formulation techniques such as encapsulation to prevent separation of the protective oil from the conidia may be required to extend protection when oil formulations are applied in the field.

  13. Continuous twin screw granulation of controlled release formulations with various HPMC grades.

    PubMed

    Vanhoorne, V; Janssens, L; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

    2016-09-25

    HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC. PMID:27521702

  14. Pair extended coupled cluster doubles

    SciTech Connect

    Henderson, Thomas M.; Scuseria, Gustavo E.; Bulik, Ireneusz W.

    2015-06-07

    The accurate and efficient description of strongly correlated systems remains an important challenge for computational methods. Doubly occupied configuration interaction (DOCI), in which all electrons are paired and no correlations which break these pairs are permitted, can in many cases provide an accurate account of strong correlations, albeit at combinatorial computational cost. Recently, there has been significant interest in a method we refer to as pair coupled cluster doubles (pCCD), a variant of coupled cluster doubles in which the electrons are paired. This is simply because pCCD provides energies nearly identical to those of DOCI, but at mean-field computational cost (disregarding the cost of the two-electron integral transformation). Here, we introduce the more complete pair extended coupled cluster doubles (pECCD) approach which, like pCCD, has mean-field cost and reproduces DOCI energetically. We show that unlike pCCD, pECCD also reproduces the DOCI wave function with high accuracy. Moreover, pECCD yields sensible albeit inexact results even for attractive interactions where pCCD breaks down.

  15. Earth Observing-1 Extended Mission

    USGS Publications Warehouse

    ,

    2003-01-01

    From its beginning in November 2000, the NASA Earth Observing-1 (EO-1) mission demonstrated the feasibility and performance of a dozen innovative sensor, spacecraft, and operational technologies. The 1-year mission tested a variety of technologies, some of which may be included on the planned 2007 Landsat Data Continuity Mission. Onboard the spacecraft are two land remote sensing instruments: the Advanced Land Imager (ALI), which acquires data in spectral bands and at resolutions similar to Landsat, and Hyperion, which acquires data in 220 10-nanometer-wide bands covering the visible, near-, and shortwave-infrared bands. Recognizing the remarkable performance of the satellite's instruments and the exceptional value of the data, the U.S. Geological Survey (USGS) and NASA agreed in December 2001 to share responsibility for operating EO-1 on a cost-reimbursable basis as long as customer sales are sufficient to recover flight and ground operations costs. The EO-1 extended mission operates within constraints imposed by its technology-pioneering origins, but it also provides unique and valuable capabilities. The spacecraft can acquire a target scene three times in a 16-day period. The ALI instrument has additional spectral coverage and greater radiometric dynamic range compared with the sensors on Landsat 7. Hyperion is the first civilian spaceborne hyperspectral imager. As of January 2003, more than 5,000 scenes had been acquired, indexed, and archived.

  16. The Extended Mission Rover (EMR)

    NASA Astrophysics Data System (ADS)

    Shields, W.; Halecki, Anthony; Chung, Manh; Clarke, Ken; Frankle, Kevin; Kassemkhani, Fariba; Kuhlhoff, John; Lenzini, Josh; Lobdell, David; Morgan, Sam

    A key component in ensuring America's status as a leader in the global community is its active pursuit of space exploration. On the twentieth anniversary of Apollo 11, President George Bush challenged the nation to place a man on the moon permanently and to conduct human exploration of Mars in the 21st century. The students of the FAMU/FSU College of Engineering hope to make a significant contribution to this challenge, America's Space Exploration Initiative (SEI), with their participation in the NASA/USRA Advanced Design Program. The project selected by the 1991/1992 Aerospace Design group is the design of an Extended Mission Rover (EMR) for use on the lunar surface. This vehicle will serve as a mobile base to provide future astronauts with a 'shirt-sleeve' living and working environment. Some of the proposed missions are planetary surface exploration, construction and maintenance, hardware setup, and in situ resource experimentation. This vehicle will be put into use in the 2010-2030 time frame.

  17. Extended attention span training system

    NASA Technical Reports Server (NTRS)

    Pope, Alan T.; Bogart, Edward H.

    1991-01-01

    Attention Deficit Disorder (ADD) is a behavioral disorder characterized by the inability to sustain attention long enough to perform activities such as schoolwork or organized play. Treatments for this disorder include medication and brainwave biofeedback training. Brainwave biofeedback training systems feed back information to the trainee showing him how well he is producing the brainwave pattern that indicates attention. The Extended Attention Span Training (EAST) system takes the concept a step further by making a video game more difficult as the player's brainwaves indicate that attention is waning. The trainee can succeed at the game only by maintaining an adequate level of attention. The EAST system is a modification of a biocybernetic system that is currently being used to assess the extent to which automated flight management systems maintain pilot engagement. This biocybernetic system is a product of a program aimed at developing methods to evaluate automated flight deck designs for compatibility with human capabilities. The EAST technology can make a contribution in the fields of medical neuropsychology and neurology, where the emphasis is on cautious, conservative treatment of youngsters with attention disorders.

  18. The Extended Mission Rover (EMR)

    NASA Technical Reports Server (NTRS)

    Shields, W.; Halecki, Anthony; Chung, Manh; Clarke, Ken; Frankle, Kevin; Kassemkhani, Fariba; Kuhlhoff, John; Lenzini, Josh; Lobdell, David; Morgan, Sam

    1992-01-01

    A key component in ensuring America's status as a leader in the global community is its active pursuit of space exploration. On the twentieth anniversary of Apollo 11, President George Bush challenged the nation to place a man on the moon permanently and to conduct human exploration of Mars in the 21st century. The students of the FAMU/FSU College of Engineering hope to make a significant contribution to this challenge, America's Space Exploration Initiative (SEI), with their participation in the NASA/USRA Advanced Design Program. The project selected by the 1991/1992 Aerospace Design group is the design of an Extended Mission Rover (EMR) for use on the lunar surface. This vehicle will serve as a mobile base to provide future astronauts with a 'shirt-sleeve' living and working environment. Some of the proposed missions are planetary surface exploration, construction and maintenance, hardware setup, and in situ resource experimentation. This vehicle will be put into use in the 2010-2030 time frame.

  19. 38 CFR 21.74 - Extended evaluation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Extended evaluation. 21... Duration of Rehabilitation Programs § 21.74 Extended evaluation. (a) General. An extended evaluation may be... evaluation are listed in § 21.57(b) of this part. (Authority: 38 U.S.C. 3105(a), 3106(a)) (b) Duration....

  20. Reconnection in compressible plasmas: Extended conversion region

    SciTech Connect

    Birn, J.; Hesse, M.; Zenitani, S.

    2011-11-15

    The classical Sweet-Parker approach to steady-state magnetic reconnection is extended into the regime of large resistivity (small magnetic Reynolds or Lundquist number) when the aspect ratio between the outflow and inflow scale, {delta} = d/L, approaches unity. In a previous paper [Paper I, Hesse et al., Phys. Plasmas 18, 042104 (2011)], the vicinity of the dissipation site (''diffusion region'') was investigated. In this paper, the approach is extended to cover larger sites, in which the energy transfer and conversion is not confined to the diffusion region. Consistent with the results of Paper I, we find that increasing aspect ratio {delta} is associated with increasing compression, increasing reconnection rate for low {beta}, but slightly decreasing rate for higher {beta}, decreasing outflow speed, and increasing outflow magnetic field. These trends are stronger for lower {beta}. Deviations from the traditional Sweet-Parker limit {delta}{yields} 0 become significant for R{sub m}<{approx}10, where R{sub m} is the magnetic Reynolds number (Lundquist number) based on the half-thickness of the current layer responsible for the Ohmic dissipation. They are also more significant for small {gamma}, that is, for increasing compressibility. In contrast to the results of Paper I, but consistent with earlier results for {delta}<<1, we find that in this limit the outflow speed is given by the Alfven speed {nu}{sub A} in the inflow region and the energy conversion is given by an even split of Poynting flux into enthalpy flux and bulk kinetic energy flux. However, with increasing {delta} the conversion to enthalpy flux becomes more and more dominant.

  1. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis.

    PubMed

    Cilfone, N A; Pienaar, E; Thurber, G M; Kirschner, D E; Linderman, J J

    2015-03-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  2. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis

    PubMed Central

    Cilfone, NA; Pienaar, E; Thurber, GM; Kirschner, DE; Linderman, JJ

    2015-01-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  3. Dynamics and Control of Flexible Multibody Systems - Part I: General Formulation with an Order N Forward Dynamics

    NASA Astrophysics Data System (ADS)

    Nagata, Takashi; Modi, Vinod J.; Matsuo, Hiroki

    2001-12-01

    This paper presents a rather general recursive formulation of flexible multibody systems. It accounts for an arbitrary level of topological branching, character of the structural members, slewing, deployment, orbital perturbations, etc. By introducing the concept of equivalent disconnected system, it leads to an efficient order n algorithm. Validity and efficiency of the formulation are assessed through several numerical examples of flexible multibody systems, which show high accuracy in terms of system energy and angular momentum conservation. A simple and unified methodology for extending the formulation to systems in general topology is also given. A companion paper describes a numerical simulation code which has been developed based upon the formulation, and illustrates versatility of the approach through parametric studies of several particular systems.

  4. CLOSURE OF HLW TANKS FORMULATION FOR A COOLING COIL GROUT

    SciTech Connect

    Harbour, J; Vickie Williams, V; Erich Hansen, E

    2008-05-23

    The Tank Closure and Technology Development Groups are developing a strategy for closing the High Level Waste (HLW) tanks at the Savannah River Site (SRS). Two Type IV tanks, 17 and 20 in the F-Area Tank Farm, have been successfully filled with grout. Type IV tanks at SRS do not contain cooling coils; on the other hand, the majority of the tanks (Type I, II, III and IIIA) do contain cooling coils. The current concept for closing tanks equipped with cooling coils is to pump grout into the cooling coils to prevent pathways for infiltrating water after tank closure. This task addresses the use of grout to fill intact cooling coils present in most of the remaining HLW tanks on Site. The overall task was divided into two phases. Phase 1 focused on the development of a grout formulation (mix design) suitable for filling the HLW tank cooling coils. Phase 2 will be a large-scale demonstration of the filling of simulated cooling coils under field conditions using the cooling coil grout mix design recommended from Phase 1. This report summarizes the results of Phase 1, the development of the cooling coil grout formulation. A grout formulation is recommended for the full scale testing at Clemson Environmental Technology Laboratory (CETL) that is composed by mass of 90% Masterflow (MF) 816 (a commercially available cable grout) and 10% blast furnace slag, with a water to cementitious material (MF 816 + slag) ratio of 0.33. This formulation produces a grout that meets the fresh and cured grout requirements detailed in the Task Technical Plan (2). The grout showed excellent workability under continuous mixing with minimal change in rheology. An alternative formulation using 90% MF 1341 and 10% blast furnace slag with a water to cementitious material ratio of 0.29 is also acceptable and generates less heat per gram than the MF 816 plus slag mix. However this MF 1341 mix has a higher plastic viscosity than the MF 816 mix due to the presence of sand in the MF 1341 cable grout and a

  5. Cyclosporine A-Nanosuspension: Formulation, Characterization and In Vivo Comparison with a Marketed Formulation

    PubMed Central

    Nakarani, Mahendra; Patel, Priyal; Patel, Jayvadan; Patel, Pankaj; Murthy, Rayasa S. R.; Vaghani, Subhash S.

    2010-01-01

    Cyclosporine A-nanosuspensions were prepared using zirconium oxide beads as a milling media, Poloxamer 407 as a stabilizer and distilled water as an aqueous medium using the Pearl Milling technique. The optimized formulation was characterized in terms of particle size distribution, surface morphology, drug-surfactant interaction, drug content, saturation solubility, osmolarity, and stability. The nanoparticles consisting of Poloxamer-bound cyclosporin A with a mean diameter of 213 nm revealed a spherical shape and 5.69 fold increased saturation solubility as compared to the parent drug. The formulation was found to be iso-osmolar with blood and stable up to 3 months at 2–8°C. In-vivo studies were carried out in albino rats and the pharmacokinetic parameters were compared with a marketed formulation, which indicated better results of the prepared formulation than the marketed one. PMID:21179351

  6. Cyclosporine a-nanosuspension: formulation, characterization and in vivo comparison with a marketed formulation.

    PubMed

    Nakarani, Mahendra; Patel, Priyal; Patel, Jayvadan; Patel, Pankaj; Murthy, Rayasa S R; Vaghani, Subhash S

    2010-01-01

    Cyclosporine A-nanosuspensions were prepared using zirconium oxide beads as a milling media, Poloxamer 407 as a stabilizer and distilled water as an aqueous medium using the Pearl Milling technique. The optimized formulation was characterized in terms of particle size distribution, surface morphology, drug-surfactant interaction, drug content, saturation solubility, osmolarity, and stability. The nanoparticles consisting of Poloxamer-bound cyclosporin A with a mean diameter of 213 nm revealed a spherical shape and 5.69 fold increased saturation solubility as compared to the parent drug. The formulation was found to be iso-osmolar with blood and stable up to 3 months at 2â8ÂC. In-vivo studies were carried out in albino rats and the pharmacokinetic parameters were compared with a marketed formulation, which indicated better results of the prepared formulation than the marketed one. PMID:21179351

  7. A hybrid-mixed finite element formulation for the geometrically exact analysis of three-dimensional framed structures

    NASA Astrophysics Data System (ADS)

    Santos, H. A. F. A.; Pimenta, P. M.; Almeida, J. P. M.

    2011-11-01

    This paper addresses the development of a hybrid-mixed finite element formulation for the quasi-static geometrically exact analysis of three-dimensional framed structures with linear elastic behavior. The formulation is based on a modified principle of stationary total complementary energy, involving, as independent variables, the generalized vectors of stress-resultants and displacements and, in addition, a set of Lagrange multipliers defined on the element boundaries. The finite element discretization scheme adopted within the framework of the proposed formulation leads to numerical solutions that strongly satisfy the equilibrium differential equations in the elements, as well as the equilibrium boundary conditions. This formulation consists, therefore, in a true equilibrium formulation for large displacements and rotations in space. Furthermore, this formulation is objective, as it ensures invariance of the strain measures under superposed rigid body rotations, and is not affected by the so-called shear-locking phenomenon. Also, the proposed formulation produces numerical solutions which are independent of the path of deformation. To validate and assess the accuracy of the proposed formulation, some benchmark problems are analyzed and their solutions compared with those obtained using the standard two-node displacement/ rotation-based formulation.

  8. IRAS observations of extended dust envelopes around evolved stars

    NASA Technical Reports Server (NTRS)

    Hawkins, George

    1990-01-01

    Deconvolved IRAS profiles, with resolution 2-3 time better than detector sizes 1.5 and 3 arcmin at 60 and 100 microns, are presented for a number of evolved stars with extended emission. These include VY UMa, Mu Cep, S Sct, U Hya, Y CVn, U Ant, alpha Ori, Y Pav, UU aur, IRC + 10216, RZ Sgr, and R Lyr. Simple models suggest that extended IRAS emission results from stars which greater mass loss rates in the past, rather than from stars with large current mass loss rates.

  9. Advances in Nanotechnology for Efficacious and Stable Formulation Development

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshimi

    2012-01-01

    Current operational medical kits aboard the International Space Station (ISS) include an array of medications intended for the treatment of minor ambulatory care symptoms, first aid, and basic life support. All medications contained in the flight kits are commercially available off-the-shelf formulations used for treatment of illnesses on Earth. However, transport and stowage of supplies including medications for space missions are exposed to adverse environmental conditions and extended shelf-life demands. Proposed missions to Mars and near-Earth objects such as asteroid 1999 AO10 will present crew health risk that is different both quantitatively and qualitatively from those encountered on ISS missions. Few drug options are available at the present time for mitigation of crew health risk of planned space exploration missions. Alternatives to standard oral formulations that include sustained and targeted delivery technologies for preventive healthcare in space will be a welcome addition to the space formulary and may include controlled release topical, sub-cutaneous, intranasal and inhalation dosage forms. An example of such a technology development endeavor can be nanotechnology-based multi-stage drug cocktail and vaccine delivery systems. Nanostructures also have the ability to protect drugs encapsulated within them from physiologic degradation, target their delivery with sustained release and are suitable for per oral routes of administration. The use of nanostructures such as polymeric nanoparticles offers a non-invasive approach for penetrating the blood brain barrier. Finally, nanotechnology offers great potential for the development of safe and efficacious drug delivery systems for preventive health care in space and on Earth.

  10. Dynamical and Hamiltonian Formulation of General Relativity

    NASA Astrophysics Data System (ADS)

    Giulini, Domenico

    Einstein's theory of General Relativity describes spacetime as a solution of a set of non-linear partial differential equations. These equations are initially not in the form of evolution equations and it is hence not clear how to formulate and solve initial-value problems, as would be physically highly desirable. In this contribution it will be shown how to cast Einstein's equations into the form of a constrained Hamiltonian system. This will allow to formulate and solve initial-value problems, integrate Einstein's equations by numerical codes, characterize dynamical degrees of freedom, and characterize isolated systems and their conserved quantities, like energy, momentum, and angular momentum. Moreover, this reformulation of General Relativity is also the starting point for various attempts to subject the gravitational field to the program of canonical quantization. The exposition given here is, to some degree, self contained. It attempts to comprehensively account for all the relevant geometric constructions, including the relevant symplectic geometry of constrained Hamiltonian systems.

  11. Gauge-Invariant Formulation of Circular Dichroism.

    PubMed

    Raimbault, Nathaniel; de Boeij, Paul L; Romaniello, Pina; Berger, J A

    2016-07-12

    Standard formulations of magnetic response properties, such as circular dichroism spectra, are plagued by gauge dependencies, which can lead to unphysical results. In this work, we present a general gauge-invariant and numerically efficient approach for the calculation of circular dichroism spectra from the current density. First we show that in this formulation the optical rotation tensor, the response function from which circular dichroism spectra can be obtained, is independent of the origin of the coordinate system. We then demonstrate that its trace is independent of the gauge origin of the vector potential. We also show how gauge invariance can be retained in practical calculations with finite basis sets. As an example, we explain how our method can be applied to time-dependent current-density-functional theory. Finally, we report gauge-invariant circular dichroism spectra obtained using the adiabatic local-density approximation. The circular dichroism spectra we thus obtain are in good agreement with experiment. PMID:27295541

  12. Coherent states formulation of polymer field theory

    SciTech Connect

    Man, Xingkun; Villet, Michael C.; Delaney, Kris T.; Orland, Henri; Fredrickson, Glenn H.

    2014-01-14

    We introduce a stable and efficient complex Langevin (CL) scheme to enable the first direct numerical simulations of the coherent-states (CS) formulation of polymer field theory. In contrast with Edwards’ well-known auxiliary-field (AF) framework, the CS formulation does not contain an embedded nonlinear, non-local, implicit functional of the auxiliary fields, and the action of the field theory has a fully explicit, semi-local, and finite-order polynomial character. In the context of a polymer solution model, we demonstrate that the new CS-CL dynamical scheme for sampling fluctuations in the space of coherent states yields results in good agreement with now-standard AF-CL simulations. The formalism is potentially applicable to a broad range of polymer architectures and may facilitate systematic generation of trial actions for use in coarse-graining and numerical renormalization-group studies.

  13. Orodispersible drug formulations for children and elderly.

    PubMed

    Slavkova, Marta; Breitkreutz, Jörg

    2015-07-30

    Various orodispersible drug formulations have been recently introduced into the market. Oral lyophilisates and orodispersible granules, tablets or films have enriched the therapeutic options. In particular, the paediatric and geriatric population may profit from the advantages like convenient administration, lack of swallowing, ease of use. Until now, only a few novel products made it to the market as the development and production usually is more expensive than for conventional oral drug dosage forms like tablets or capsules. The review reports the recent advances, existing and upcoming products, and the significance of formulating patient-friendly oral dosage forms. The preparation of the medicines can be performed both in pharmaceutical industry and in community pharmacies. Recent advances, e.g. drug printing technologies, may facilitate this process for community or hospital pharmacies. Still, regulatory guidelines and pharmacopoeial monographs lack appropriate methods, specifications and global harmonization to foster the development of innovative orodispersible drug dosage forms.

  14. New Variational Formulations of Hybrid Stress Elements

    NASA Technical Reports Server (NTRS)

    Pian, T. H. H.; Sumihara, K.; Kang, D.

    1984-01-01

    In the variational formulations of finite elements by the Hu-Washizu and Hellinger-Reissner principles the stress equilibrium condition is maintained by the inclusion of internal displacements which function as the Lagrange multipliers for the constraints. These versions permit the use of natural coordinates and the relaxation of the equilibrium conditions and render considerable improvements in the assumed stress hybrid elements. These include the derivation of invariant hybrid elements which possess the ideal qualities such as minimum sensitivity to geometric distortions, minimum number of independent stress parameters, rank sufficient, and ability to represent constant strain states and bending moments. Another application is the formulation of semiLoof thin shell elements which can yield excellent results for many severe test cases because the rigid body nodes, the momentless membrane strains, and the inextensional bending modes are all represented.

  15. Use of the cultural formulation with refugees.

    PubMed

    Rohlof, Hans; Knipscheer, Jeroen W; Kleber, Rolf J

    2009-09-01

    This article discusses the experiences of mental health professionals who applied the Cultural Formulation (CF) of the DSM-IV for assessment of psychopathology and treatment needs of refugees in the Netherlands. The CF approach proved to be a useful tool in the assessment and diagnostic phase of clinical treatment. However, patients reported problems with defining their own culture and providing explanations of illness and therapists had difficulty identifying culturally-based difficulties in the clinical relationship. Additional information was needed about working with interpreters, therapists' attitudes towards the culture of the patient and towards their own culture, patients' previous experiences with discrimination and inaccessibility of care, gender issues, and specific cultures and subcultures. A more structured approach to conducting the CF is recommended. We developed the "Cultural Formulation Interview" for this purpose. The adaptations are aimed at improving the CF for use with refugee populations, as well as for more general use in transcultural psychiatry.

  16. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

    PubMed

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R

    2014-07-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single

  17. Formulation and Characterization of Echogenic Lipid–Pluronic Nanobubbles

    PubMed Central

    Krupka, Tianyi M.; Solorio, Luis; Wilson, Robin E.; Wu, Hanping; Azar, Nami; Exner, Agata A.

    2012-01-01

    The advent of microbubble contrast agents has enhanced the capabilities of ultrasound as a medical imaging modality and stimulated innovative strategies for ultrasound-mediated drug and gene delivery. While the utilization of microbubbles as carrier vehicles has shown encouraging results in cancer therapy, their applicability has been limited by a large size which typically confines them to the vasculature. To enhance their multifunctional contrast and delivery capacity, it is critical to reduce bubble size to the nanometer range without reducing echogenicity. In this work, we present a novel strategy for formulation of nanosized, echogenic lipid bubbles by incorporating the surfactant Pluronic, a triblock copolymer of ethylene oxide copropylene oxide coethylene oxide into the formulation. Five Pluronics (L31, L61, L81, L64 and P85) with a range of molecular weights (Mw: 1100 to 4600 Da) were incorporated into the lipid shell either before or after lipid film hydration and before addition of perfluorocarbon gas. Results demonstrate that Pluronic–lipid interactions lead to a significantly reduced bubble size. Among the tested formulations, bubbles made with Pluronic L61 were the smallest with a mean hydrodynamic diameter of 207.9 ± 74.7 nm compared to the 880.9 ± 127.6 nm control bubbles. Pluronic L81 also significantly reduced bubble size to 406.8 ± 21.0 nm. We conclude that Pluronic is effective in lipid bubble size control, and Pluronic Mw, hydrophilic–lipophilic balance (HLB), and Pluronic/ lipid ratio are critical determinants of the bubble size. Most importantly, our results have shown that although the bubbles are nanosized, their stability and in vitro and in vivo echogenicity are not compromised. The resulting nanobubbles may be better suited for contrast enhanced tumor imaging and subsequent therapeutic delivery. PMID:19957968

  18. Intrinsic formulation of the equation of Szebehely

    NASA Astrophysics Data System (ADS)

    Puel, F.

    1984-03-01

    The first-order linear partial differential equation developed by Szebehely (1974) for the potentials generating one-given-parameter family of plane orbits, expanded by Broucke (1980), Mertens (1981), and Erdi (1982) to the 3D case, is investigated analytically. An intrinsic formulation permitting the use of various coordinate systems is obtained for the plane case, and analogous techniques are applied in separate treatments of the 3D and N-dimensional cases.

  19. Supergroup formulation of Plebanski theory of gravity

    SciTech Connect

    Ramirez, C.; Rosales, E.

    2009-04-20

    General relativity can be formulated as a SU(2) BF-theory with constraints, as shown by Plebanski. Jacobson has given a SL(2, C) invariant fermionic extension of it, from which supergravity turns out [6]. We present a supersymmetric, Sp(2|1) invariant extension of the theory of Plebanski. Consistency requires that the constraints are properly generalized, resulting as well the action of supergravity.

  20. Calixarene cleansing formulation for uranium skin contamination.

    PubMed

    Phan, Guillaume; Semili, Naïma; Bouvier-Capely, Céline; Landon, Géraldine; Mekhloufi, Ghozlene; Huang, Nicolas; Rebière, François; Agarande, Michelle; Fattal, Elias

    2013-10-01

    An oil-in-water cleansing emulsion containing calixarene molecule, an actinide specific chelating agent, was formulated in order to improve the decontamination of uranium from the skin. Commonly commercialized cosmetic ingredients such as surfactants, mineral oil, or viscosifying agents were used in preparing the calixarene emulsion. The formulation was characterized in terms of size and apparent viscosity measurements and then was tested for its ability to limit uranyl ion permeation through excoriated pig-ear skin explants in 24-h penetration studies. Calixarene emulsion effectiveness was compared with two other reference treatments consisting of DTPA and EHBP solutions. Application of calixarene emulsion induced the highest decontamination effect with an 87% decrease in uranium diffusion flux. By contrast, EHBP and DTPA solutions only allowed a 50% and 55% reduction of uranium permeation, respectively, and had the same effect as a simple dilution of the contamination by pure water. Uranium diffusion decrease was attributed to uranyl ion-specific chelation by calixarene within the formulation, since no significant effect was obtained after application of the same emulsion without calixarene. Thus, calixarene cleansing emulsion could be considered as a promising treatment in case of accidental contamination of the skin by highly diffusible uranium compounds. PMID:23982616

  1. Formulation of benzoporphyrin derivatives in Pluronics.

    PubMed

    Chowdhary, Rubinah K; Chansarkar, Namrata; Sharif, Isha; Hioka, Noboru; Dolphin, David

    2003-03-01

    This study investigates the potential of Pluronics for the formulation of tetrapyrrole-based photosensitizers, with a particular focus on B-ring benzoporphyrin derivatives. The B-ring derivatives have a high tendency to aggregate in aqueous solutions, and this poses a significant formulation problem. Pluronics are ABA-type triblock copolymers composed of a central hydrophobic polypropylene oxide section with two hydrophilic polyethylene oxide sections of equal length at either end. Out of a range of different commercially available block copolymers studied, it was found that the longer the hydrophobic block, the better the stabilization of tetrapyrrolic drugs in monomeric form in aqueous suspensions. Of these the best performance was observed in the micelle-forming Pluronic P123. Micelle size determination by laser light scattering confirmed that particle size in stable Pluronic formulations was around 20 nm. Pluronics such as L122 formed emulsions spontaneously without the need for emulsion stabilizers; emulsions were highly stable at ambient temperatures over several days and also highly effective as potential drug delivery agents.

  2. Three-dimensional formulation of dislocation climb

    NASA Astrophysics Data System (ADS)

    Gu, Yejun; Xiang, Yang; Quek, Siu Sin; Srolovitz, David J.

    2015-10-01

    We derive a Green's function formulation for the climb of curved dislocations and multiple dislocations in three-dimensions. In this new dislocation climb formulation, the dislocation climb velocity is determined from the Peach-Koehler force on dislocations through vacancy diffusion in a non-local manner. The long-range contribution to the dislocation climb velocity is associated with vacancy diffusion rather than from the climb component of the well-known, long-range elastic effects captured in the Peach-Koehler force. Both long-range effects are important in determining the climb velocity of dislocations. Analytical and numerical examples show that the widely used local climb formula, based on straight infinite dislocations, is not generally applicable, except for a small set of special cases. We also present a numerical discretization method of this Green's function formulation appropriate for implementation in discrete dislocation dynamics (DDD) simulations. In DDD implementations, the long-range Peach-Koehler force is calculated as is commonly done, then a linear system is solved for the climb velocity using these forces. This is also done within the same order of computational cost as existing discrete dislocation dynamics methods.

  3. Formulation of benzoporphyrin derivatives in Pluronics.

    PubMed

    Chowdhary, Rubinah K; Chansarkar, Namrata; Sharif, Isha; Hioka, Noboru; Dolphin, David

    2003-03-01

    This study investigates the potential of Pluronics for the formulation of tetrapyrrole-based photosensitizers, with a particular focus on B-ring benzoporphyrin derivatives. The B-ring derivatives have a high tendency to aggregate in aqueous solutions, and this poses a significant formulation problem. Pluronics are ABA-type triblock copolymers composed of a central hydrophobic polypropylene oxide section with two hydrophilic polyethylene oxide sections of equal length at either end. Out of a range of different commercially available block copolymers studied, it was found that the longer the hydrophobic block, the better the stabilization of tetrapyrrolic drugs in monomeric form in aqueous suspensions. Of these the best performance was observed in the micelle-forming Pluronic P123. Micelle size determination by laser light scattering confirmed that particle size in stable Pluronic formulations was around 20 nm. Pluronics such as L122 formed emulsions spontaneously without the need for emulsion stabilizers; emulsions were highly stable at ambient temperatures over several days and also highly effective as potential drug delivery agents. PMID:12685658

  4. Phytoconstituents as photoprotective novel cosmetic formulations

    PubMed Central

    Saraf, S.; Kaur, C. D.

    2010-01-01

    Phytoconstituents are gaining popularity as ingredients in cosmetic formulations as they can protect the skin against exogenous and endogenous harmful agents and can help remedy many skin conditions. Exposure of skin to sunlight and other atmospheric conditions causes the production of reactive oxygen species, which can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of antioxidant system. Such injuries damage regulation pathways of skin and lead to photoaging and skin cancer development. The effects of aging include wrinkles, roughness, appearance of fine lines, lack of elasticity, and de- or hyperpigmentation marks. Herbal extracts act on these areas and produce healing, softening, rejuvenating, and sunscreen effects. We have selected a few photoprotective phytoconstituents, such as curcumin, resveratrol, tea polyphenols, silymarin, quercetin and ascorbic acid, and have discussed the considerations to be undertaken for the development of herbal cosmetic formulations that could reduce the occurrence of skin cancer and delay the process of photoaging. This article is aimed at providing specific and compiled knowledge for the successful preparation of photoprotective herbal cosmetic formulations. PMID:22228936

  5. Formulation, pharmacokinetics and pharmacodynamics of topical microbicides.

    PubMed

    Adams, Jessica L; Kashuba, Angela D M

    2012-08-01

    The development of safe topical microbicides that effectively prevent human immunodeficiency virus (HIV) infection is a major goal in curbing the human immunodeficiency virus pandemic. A number of past failures resulting from mucosal toxicity or lack of efficacy have informed the field. Products that caused toxicity to the female genital tract mucosa, and thereby increased the likelihood of HIV acquisition, included nonoxynol 9, cellulose sulfate, and C31 G vaginal gel Savvy. Topical products that were ineffective in preventing HIV infection include BufferGel, Carraguard, and PRO 2000. Antiretroviral drugs such as tenofovir and dapivirine formulated into microbicide products have shown promise, but there is much to learn about ideal product formulation and acceptability, and drug distribution and disposition (pharmacokinetics). Current formulations for water-soluble molecules include vaginally or rectally applied gels, vaginal rings, films and tablets. Dosing strategies (e.g. coitally dependent or independent) will be based on the pharmacokinetics of the active ingredient and the tolerance for less than perfect adherence. PMID:22306523

  6. A formulation and analysis of combat games

    NASA Technical Reports Server (NTRS)

    Heymann, M.; Ardema, M. D.; Rajan, N.

    1984-01-01

    Combat which is formulated as a dynamical encounter between two opponents, each of whom has offensive capabilities and objectives is outlined. A target set is associated with each opponent in the event space in which he endeavors to terminate the combat, thereby winning. If the combat terminates in both target sets simultaneously, or in neither, a joint capture or a draw, respectively, occurs. Resolution of the encounter is formulated as a combat game; as a pair of competing event constrained differential games. If exactly one of the players can win, the optimal strategies are determined from a resulting constrained zero sum differential game. Otherwise the optimal strategies are computed from a resulting nonzero sum game. Since optimal combat strategies may frequently not exist, approximate or delta combat games are also formulated leading to approximate or delta optimal strategies. The turret game is used to illustrate combat games. This game is sufficiently complex to exhibit a rich variety of combat behavior, much of which is not found in pursuit evasion games.

  7. A formulation and analysis of combat games

    NASA Technical Reports Server (NTRS)

    Heymann, M.; Ardema, M. D.; Rajan, N.

    1985-01-01

    Combat is formulated as a dynamical encounter between two opponents, each of whom has offensive capabilities and objectives. With each opponent is associated a target in the event space in which he endeavors to terminate the combat, thereby winning. If the combat terminates in both target sets simultaneously or in neither, a joint capture or a draw, respectively, is said to occur. Resolution of the encounter is formulated as a combat game; namely, as a pair of competing event-constrained differential games. If exactly one of the players can win, the optimal strategies are determined from a resulting constrained zero-sum differential game. Otherwise the optimal strategies are computed from a resulting non-zero-sum game. Since optimal combat strategies frequencies may not exist, approximate of delta-combat games are also formulated leading to approximate or delta-optimal strategies. To illustrate combat games, an example, called the turret game, is considered. This game may be thought of as a highly simplified model of air combat, yet it is sufficiently complex to exhibit a rich variety of combat behavior, much of which is not found in pursuit-evasion games.

  8. Calixarene cleansing formulation for uranium skin contamination.

    PubMed

    Phan, Guillaume; Semili, Naïma; Bouvier-Capely, Céline; Landon, Géraldine; Mekhloufi, Ghozlene; Huang, Nicolas; Rebière, François; Agarande, Michelle; Fattal, Elias

    2013-10-01

    An oil-in-water cleansing emulsion containing calixarene molecule, an actinide specific chelating agent, was formulated in order to improve the decontamination of uranium from the skin. Commonly commercialized cosmetic ingredients such as surfactants, mineral oil, or viscosifying agents were used in preparing the calixarene emulsion. The formulation was characterized in terms of size and apparent viscosity measurements and then was tested for its ability to limit uranyl ion permeation through excoriated pig-ear skin explants in 24-h penetration studies. Calixarene emulsion effectiveness was compared with two other reference treatments consisting of DTPA and EHBP solutions. Application of calixarene emulsion induced the highest decontamination effect with an 87% decrease in uranium diffusion flux. By contrast, EHBP and DTPA solutions only allowed a 50% and 55% reduction of uranium permeation, respectively, and had the same effect as a simple dilution of the contamination by pure water. Uranium diffusion decrease was attributed to uranyl ion-specific chelation by calixarene within the formulation, since no significant effect was obtained after application of the same emulsion without calixarene. Thus, calixarene cleansing emulsion could be considered as a promising treatment in case of accidental contamination of the skin by highly diffusible uranium compounds.

  9. On the spectral formulation of Granger causality.

    PubMed

    Chicharro, D

    2011-12-01

    Spectral measures of causality are used to explore the role of different rhythms in the causal connectivity between brain regions. We study several spectral measures related to Granger causality, comprising the bivariate and conditional Geweke measures, the directed transfer function, and the partial directed coherence. We derive the formulation of dependence and causality in the spectral domain from the more general formulation in the information-theory framework. We argue that the transfer entropy, the most general measure derived from the concept of Granger causality, lacks a spectral representation in terms of only the processes associated with the recorded signals. For all the spectral measures we show how they are related to mutual information rates when explicitly considering the parametric autoregressive representation of the processes. In this way we express the conditional Geweke spectral measure in terms of a multiple coherence involving innovation variables inherent to the autoregressive representation. We also link partial directed coherence with Sims' criterion of causality. Given our results, we discuss the causal interpretation of the spectral measures related to Granger causality and stress the necessity to explicitly consider their specific formulation based on modeling the signals as linear Gaussian stationary autoregressive processes.

  10. Femtosecond pulse propagation in nitrogen: Numerical study of (3+1)-dimensional extended nonlinear Schroedinger equation with shock-term correction

    SciTech Connect

    Ando, Taro; Fujimoto, Masatoshi

    2005-08-01

    We develop an accurate and efficient method for calculating evolution due to the extended nonlinear Schroedinger equation, which describes the propagation behavior of a femtosecond light pulse in a nonlinear medium. Applying Suzuki's exponential operator expansion to the evolution operator based on the finite-differential formulation, we realize the accurate and fast calculation that can be performed without large-scale computing systems even for (3+1)-dimensional problems. To study the correspondence between experiments and calculations, we calculate the propagation behavior of a femtosecond light pulse that is weakly focused in nitrogen gas of various pressures and compare the calculation results to the experimental ones. The calculation results reproduce the relative behavior of the spatial light pattern observed during the propagation. Additionally, the multiple-cone formation and interaction between two collimated pulses in nitrogen gas are also demonstrated as applications of the developed method.

  11. A thermo-sensitive polymeric gel containing a gadolinium (Gd) compound encapsulated into liposomes significantly extended the retention of the Gd in tumors.

    PubMed

    Le, Uyen Minh; Shaker, Dalia S; Sloat, Brian R; Cui, Zhengrong

    2008-04-01

    Gadolinium neutron capture therapy (Gd-NCT) is a promising approach to fight cancer. One key factor for the success of Gd-NCT is to deliver and maintain a sufficient amount of Gd inside tumors. A large amount of Gd can be readily introduced into tumors by direct intratumor injection. However, an innovative approach is needed to maintain the Gd in the tumors. We encapsulated a Gd compound into a liposome formulation and then dispersed the liposomes into a thermo-sensitive polymeric gel. In murine tumor models, we showed that this liposome-in-thermo-sensitive gel system significantly extended the retention of the Gd compound in tumors. This similar concept may be applied to prolong the retention of other cytotoxic chemicals in tumors, and thus, improve their anti-tumor efficacy. PMID:18401783

  12. Heparin penetration into and permeation through human skin from aqueous and liposomal formulations in vitro.

    PubMed

    Betz, G; Nowbakht, P; Imboden, R; Imanidis, G

    2001-10-01

    The transport of unfractionated (UH) and low molecular weight Heparin (LMWH) in human skin was investigated in vitro using heat separated epidermal membrane and dermis and the effect of liposomal formulations with Phospholipon(R) 80 (PL80) and Sphingomyelin (SM) was assessed. The distribution of Heparin within skin tissue was studied by the tape stripping method. Heparin concentrations were measured with a biological assay. Transepidermal water loss was determined to characterize barrier properties of skin. No consistent permeation of Heparin through epidermal membrane was detected. Penetration into the epidermal membrane was for LMWH significantly greater than for UH. Accumulation of UH was largely restricted to the outermost layers of the stratum corneum while LMWH penetrated into deeper epidermal layers. UH penetration into epidermis was detected for the PL80 liposomal formulation only. The extent of LMWH penetration was independent of the formulation, LMWH, however, showed a trend to accumulate in deeper epidermal layers for the PL80 compared to the aqueous formulation. Thus, molecular weight and liposomal formulations influenced the penetration pattern of Heparin in the epidermis. It can not be concluded whether the concentration of LMWH achieved at the blood capillaries is sufficient to exert a pharmacological effect. UH permeated readily through dermis irrespectively of formulation and its accumulation in the dermis was significantly enhanced and its lag time of permeation increased in the presence of SM liposomes.

  13. On the Electrostatic Born-Infeld Equation with Extended Charges

    NASA Astrophysics Data System (ADS)

    Bonheure, Denis; d'Avenia, Pietro; Pomponio, Alessio

    2016-09-01

    In this paper, we deal with the electrostatic Born-Infeld equation -operatorname{div} (nablaφ/√{1-|nabla φ|^2} )= ρ quad{in} {R}^N, lim_{|x|to ∞} φ(x)= 0,. quad quad quad quad ({{BI}}) where {ρ} is an assigned extended charge density. We are interested in the existence and uniqueness of the potential {φ} and finiteness of the energy of the electrostatic field {-nabla φ}. We first relax the problem and treat it with the direct method of the Calculus of Variations for a broad class of charge densities. Assuming {ρ} is radially distributed, we recover the weak formulation of {({{BI}})} and the regularity of the solution of the Poisson equation (under the same smoothness assumptions). In the case of a locally bounded charge, we also recover the weak formulation without assuming any symmetry. The solution is even classical if {ρ} is smooth. Then we analyze the case where the density {ρ} is a superposition of point charges and discuss the results in (Kiessling, Commun Math Phys 314:509-523, 2012). Other models are discussed, as for instance a system arising from the coupling of the nonlinear Klein-Gordon equation with the Born-Infeld theory.

  14. Profile of extended-release oxycodone/acetaminophen for acute pain.

    PubMed

    Bekhit, Mary Hanna

    2015-01-01

    This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER) formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA)-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone) with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen), are available solely in immediate-release (IR) formulations. PMID:26527898

  15. Profile of extended-release oxycodone/acetaminophen for acute pain

    PubMed Central

    Bekhit, Mary Hanna

    2015-01-01

    This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER) formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA)-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone) with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen), are available solely in immediate-release (IR) formulations. PMID:26527898

  16. [Oral formulation of choice for children].

    PubMed

    Lajoinie, A; Henin, E; Kassai, B

    2015-08-01

    Selecting the most appropriate oral formulation is very challenging when developing medicines for children and in routine practice. Research in pediatric pharmacology has focused on oral drug formulation, determining whether the active pharmaceutical ingredient can be successfully delivered to children. Pediatric expert committees (EMA, EuFPI) recommend that children's medicines be safe, well tolerated, easy to use (palatable and requiring minimal handling), transportable, easily produced, cost effective, commercially viable, with a minimal impact on children's life-style. Oral liquid drug formulations (OLFs: solutions, syrups, suspensions) are historically considered as the most appropriate oral formulation for children, since they are easy to swallow for younger infants and palatable for children. However, OLFs present numerous disadvantages, such as low stability, potentially toxic excipients for children, and low transportability. In the long-term, dose volume and frequency of administration might lead to non-compliance. Multiple preparation steps and volume calculations are also among risk factors for medicine errors in children. An alternative to OLFs is the conventional solid oral dosage form (OSF), such as tablets and capsules. These offer the advantages of greater stability, easy dose selection, improved transportability, and ease of storage. They also allow the modification of drug pharmacokinetic parameters, minimizing administration frequency. Finally, OSFs are less costly than OLFs, since they are easier to develop, manufacture, transport, store, and deliver. Controlled study results suggest that the use of OSFs in children would be associated with greater acceptability by children, greater preference on the part of caregivers, and higher drug compliance than OLFs. Recent controlled studies, confirming that OSFs with an acceptable size for children (mini-tablets), should shift the current paradigm of OLFs as the reference for children's oral medicine

  17. Three-dimensional simulation of wave-induced circulation: Comparison of three radiation stress formulations

    NASA Astrophysics Data System (ADS)

    Sheng, Y. Peter; Liu, Tianyi

    2011-05-01

    A three-dimensional current-wave modeling system, Curvilinear-grid Hydrodynamics 3D (CH3D)-Simulating Waves Nearshore (SWAN), has been used to simulate wave-induced circulation and compare the performances of three radiation stress (RS) formulations: two depth-dependent formulations (M08 by Mellor (2008) and X04 by Xia et al. (2004)) and one depth-independent formulation (LHS by Longuet-Higgins and Stewart (1964)). While all are based on linear wave theory, LHS uses the vertically integrated equations of motion, and M08 and X04 consider the three-dimensional equations of motion. Results of CH3D-SWAN with three RS formulations are compared with steady state wave setup, observed data in an undertow experiment by Ting and Kirby (1994) (TK94), and observed data in a laboratory fringing reef. All three RS formulations reproduce the analytical solution of wave setup very well. Simulated wave-induced currents and turbulence for TK94 are the best when M08 is used and worst when X04 is used, apparently due to the errors in the X04 formulation. All three RS formulations give good simulation of wave setup in the fringing reef. Wave-induced currents in the fringing reef simulated by the three RS formulations are quite different: M08 produces a single large clockwise gyre in the x-z plane, LHS produces a weaker gyre, and X04 produces a clockwise gyre plus a counterclockwise gyre inside the surf zone. Using the CH3D-Storm Surge Modeling System and M08, storm surge and currents in the Outer Banks and Chesapeake Bay during Hurricane Isabel are simulated. Compared to the earlier simulation obtained with the LHS, M08 produces similar storm surge but slightly improved the wave-induced currents.

  18. Application of Extended Kalman Filter Techniques for Dynamic Model Parameter Calibration

    SciTech Connect

    Huang, Zhenyu; Du, Pengwei; Kosterev, Dmitry; Yang, Bo

    2009-07-26

    Abstract -Phasor measurement has previously been used for sub-system model validation, which enables rigorous comparison of model simulation and recorded dynamics and facilitates identification of problematic model components. Recent work extends the sub-system model validation approach with a focus on how model parameters may be calibrated to match recorded dynamics. In this paper, a calibration method using Extended Kalman Filter (EKF) technique is proposed. This paper presents the formulation as well as case studies to show the validity of the EKF-based parameter calibration method. The proposed calibration method is expected to be a cost-effective means complementary to traditional equipment testing for improving dynamic model quality.

  19. Formulation and Stabilization of Francisella tularensis Live Vaccine Strain

    PubMed Central

    OHTAKE, SATOSHI; MARTIN, RUSSELL A.; SAXENA, ATUL; LECHUGA-BALLESTEROS, DAVID; SANTIAGO, ARACELI E; BARRY, EILEEN M.; TRUONG-LE, VU

    2012-01-01

    Francisella tularensis live vaccine strain (F. tularensis LVS), a promising vaccine candidate for protection against F. tularensis exposure, is a particularly thermolabile vaccine and difficult to stabilize sufficiently for storage under refrigerated conditions. Our preliminary data show that F. tularensis LVS can be stabilized in the dried state using foam drying, a modified freeze drying method, with sugar-based formulations. The process was conducted under mild drying conditions, which resulted in a good titer retention following processing. The inclusion of osmolytes in the growth media resulted in an acceleration of growth kinetics, although no change in osmotolerance was observed. The optimized F. tularensis formulation, which contained trehalose, gelatin, and Pluronic F68 demonstrated stability for approximately 1.5 weeks at 37°C (i.e., time required for the vaccine to decrease in potency by 1 log10 colony forming unit) and for 12 weeks at 25°C. At refrigerator storage condition (4°C), stabilized F. tularensis LVS vaccine exhibited no activity loss for at least 12 weeks. This stabilization method utilizes conventional freeze dryers and pharmaceutically approved stabilizers, and thus can be readily implemented at many manufacturing sites for large-scale production of stabilized vaccines. The improved heat stability of the F. tularensis LVS could mitigate risks of vaccine potency loss during long-term storage, shipping, and distribution. PMID:21491457

  20. Formulation strategies for drug delivery of tacrolimus: An overview

    PubMed Central

    Patel, Pranav; Patel, Hitesh; Panchal, Shital; Mehta, Tejal

    2012-01-01

    Tacrolimus (FK 506) is a potent macrolide lactone immunosuppressive agent used for prophylaxis of organ rejection after transplantation and graft-versus-host disease after bone marrow transplantation in patients. Moreover, tacrolimus is a drug of choice in the treatment of atopic dermatitis for decreasing side effects associated with the use of topical corticosteroids. In spite of its success in ensuring graft survival, therapeutic use of tacrolimus is complicated due to its narrow therapeutic index (between 5 and 15 ng/ml). Tacrolimus has a large inter-/intra-patient variability in pharmacokinetics profile and a poor oral bioavailability because of its poor solubility, P-gp efflux, marked pre-systemic metabolism by CYP3A in the enterocytes and liver first pass effect. Several formulation approaches such as oily solution, solid dispersions, complexation with cyclodextrins, liposomes etc., have been investigated to improve oral delivery of FK 506. In this review, we have discussed various formulation approaches that have been undertaken by various researchers to solve the problems related to the drug delivery of tacrolimus. PMID:23580932