DEKFIS user's guide: Discrete Extended Kalman Filter/Smoother program for aircraft and rotorcraft data consistency

NASA Technical Reports Server (NTRS)

1979-01-01

The computer program DEKFIS (discrete extended Kalman filter/smoother), formulated for aircraft and helicopter state estimation and data consistency, is described. DEKFIS is set up to pre-process raw test data by removing biases, correcting scale factor errors and providing consistency with the aircraft inertial kinematic equations. The program implements an extended Kalman filter/smoother using the Friedland-Duffy formulation.

Efficient kinetic method for fluid simulation beyond the Navier-Stokes equation.

PubMed

Zhang, Raoyang; Shan, Xiaowen; Chen, Hudong

2006-10-01

We present a further theoretical extension to the kinetic-theory-based formulation of the lattice Boltzmann method of Shan [J. Fluid Mech. 550, 413 (2006)]. In addition to the higher-order projection of the equilibrium distribution function and a sufficiently accurate Gauss-Hermite quadrature in the original formulation, a regularization procedure is introduced in this paper. This procedure ensures a consistent order of accuracy control over the nonequilibrium contributions in the Galerkin sense. Using this formulation, we construct a specific lattice Boltzmann model that accurately incorporates up to third-order hydrodynamic moments. Numerical evidence demonstrates that the extended model overcomes some major defects existing in conventionally known lattice Boltzmann models, so that fluid flows at finite Knudsen number Kn can be more quantitatively simulated. Results from force-driven Poiseuille flow simulations predict the Knudsen's minimum and the asymptotic behavior of flow flux at large Kn.

ASRM propellant and igniter propellant development and process scale-up

NASA Technical Reports Server (NTRS)

Landers, L. C.; Booth, D. W.; Stanley, C. B.; Ricks, D. W.

1993-01-01

A program of formulation and process development for ANB-3652 motor propellant was conducted to validate design concepts and screen critical propellant composition and process parameters. Design experiments resulted in the selection of a less active grade of ferric oxide to provide better burning rate control, the establishment of AP fluidization conditions that minimized the adverse effects of particle attrition, and the selection of a higher mix temperature to improve mechanical properties. It is shown that the propellant can be formulated with AP and aluminum powder from various producers. An extended duration pilot plant run demonstrated stable equipment operation and excellent reproducibility of propellant properties. A similar program of formulation and process optimization culminating in large batch scaleup was conducted for ANB-3672 igniter propellant. The results for both ANB-3652 and ANB 37672 confirmed that their processing characteristics are compatible with full-scale production.

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 multiple independent variables on the event rate. Both the Cox and Weibull formulations were tested. The Cox formulation is more commonly used in survival analysis because of its flexibility. The best Cox model included fixed effects at the multi-reactor site level. The Weibull parametric formulation has the same base hazard rate as the Crow/AMSAA model. This theoretical connection was confirmed through a series of tests that demonstrated both models predicted the same base hazard rates. The Weibull formulation produced a model with most of the same statistically significant variables as the Cox model. The beneficial effect of extended power up-rates was predicted in the proportional hazards models as well as the Crow/AMSAA model. The Weibull model also indicated an effect that can be traced back to a plant’s construction. Performance was also found to improve in plants that had been divested from their original owners. This research developed a consistent evaluation toolkit for nuclear power plant performance using either a univariate method that allows for simple graphical evaluation at its heart or a more complex multivariate method that includes the effects of several independent variables with data that are available from public sources. Utilities or regulators with access to proprietary data may be able to expand upon this research with additional data that is not readily available to an academic researcher. Even without access to special data, the methods developed are valuable tools in evaluating and predicting nuclear power plant reliability performance.

Review of extended-release formulations of Tramadol for the management of chronic non-cancer pain: focus on marketed formulations

PubMed Central

Kizilbash, Arshi; Ngô-Minh, Cường

2014-01-01

Patients with chronic non-malignant pain report impairments of physical, social, and psychological well-being. The goal of pain management should include reducing pain and improving quality of life. Patients with chronic pain require medications that are able to provide adequate pain relief, have minimum dosing intervals to maintain efficacy, and avoid breakthrough pain. Tramadol has proven efficacy and a favourable safety profile. The positive efficacy and safety profile has been demonstrated historically in numerous published clinical studies as well as from post-marketing experience. It is a World Health Organization “Step 2” opioid analgesic that has been shown to be effective, well-tolerated, and valuable, where treatment with strong opioids is not required. A number of extended release formulations of Tramadol are available in Canada and the United States. An optimal extended release Tramadol formulation would be expected to provide consistent pain control with once daily dosing, few sleep interruptions, flexible dosing schedules, and no limitation on taking with meals. Appropriate treatment options should be based on the above proposed attributes. A comparative review of available extended release Tramadol formulations shows that these medications are not equivalent in their pharmacokinetic profile and this may have implications for selecting the optimal therapy for patients with pain syndromes where Tramadol is an appropriate analgesic agent. Differences in pharmacokinetics amongst the formulations may also translate into varied clinical responses in patients. Selection of the appropriate formulation by the health care provider should therefore be based on the patient’s chronic pain condition, needs, and lifestyle. PMID:24711710

Extended release amoxicillin/clavulanate: optimizing a product for respiratory infections based on pharmacodynamic principles.

PubMed

Jacobs, Michael R

2005-06-01

Acute bacterial respiratory tract infections cause a great deal of human morbidity and mortality. Treatment guidelines for these infections include macrolides, doxycycline, beta-lactams and beta-lactam/beta-lactamase inhibitor combinations such as amoxicillin/clavulanic acid to provide coverage for the common respiratory pathogens, including penicillin and macrolide nonsusceptible Streptococcus pneumoniae, as well as beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis. In response to recent guidelines recommending higher dose amoxicillin to extend coverage to a higher percentage of S. pneumoniae, a new formulation of amoxicillin/clavulanic acid was developed. This formulation includes a higher amoxicillin dose, with part of the amoxicillin dose being in an extended release formulation, without increasing the clavulanate dose, for twice-daily oral treatment of these infections. Clinical studies of community-acquired pneumonia and acute rhinosinusitis have shown that the new formulation is well tolerated and highly efficacious, with clinical outcomes equivalent to comparators.

Flow resistance and suspended load in sand-bed rivers: Simplified stratification model

USGS Publications Warehouse

Wright, S.; Parker, G.

2004-01-01

New methods are presented for the prediction of the flow depth, grain-size specific near-bed concentration, and bed-material suspended sediment transport rate in sand-bed rivers. The salient improvements delineated here all relate to the need to modify existing formulations in order to encompass the full range of sand-bed rivers, and in particular large, low-slope sand-bed rivers. They can be summarized as follows: (1) the inclusion of density stratification effects in a simplified manner, which have been shown in the companion paper to be particularly relevant for large, low-slope, sand-bed rivers; (2) a new predictor for near-bed entrainment rate into suspension which extends a previous relation to the range of large, low-slope sand-bed rivers; and (3) a new predictor for form drag which again extends a previous relation to include large, low-slope sand-bed rivers. Finally, every attempt has been made to cast the relations in the simplest form possible, including the development of software, so that practicing engineers may easily use the methods. ?? ASCE.

Semi-preparative HPLC preparation and HPTLC quantification of tetrahydroamentoflavone as marker in Semecarpus anacardium and its polyherbal formulations.

PubMed

Aravind, S G; Arimboor, Ranjith; Rangan, Meena; Madhavan, Soumya N; Arumughan, C

2008-11-04

Application of modern scientific knowledge coupled with sensitive analytical technique is important for the quality evaluation and standardization of polyherbal formulations. Semecarpus anacardium, an important medicinal plant with wide medicinal properties, is frequently used in a large number of traditional herbal preparations. Tetrahydroamentoflavone (THA), a major bioactive biflavonoid was selected as a chemical marker of S. anacardium and RP-semi-preparative HPLC conditions were optimized for the isolation of tetrahydroamentoflavone. HPTLC analytical method was developed for the fingerprinting of S. anacardium flavonoids and quantification of tetrahydroamentoflavone. The method was validated in terms of their linearity, LOD, LOQ, precision and accuracy and compared with RP-HPLC-DAD method. The methods were demonstrated for the chemical fingerprinting of S. anacardium plant parts and some commercial polyherbal formulations and the amount of tetrahydroamentoflavone was quantified. HPTLC analysis showed that S. anacardium seed contained approximately 10 g kg(-1) of tetrahydroamentoflavone. The methods were able to identify and quantify tetrahydroamentoflavone from complex mixtures of phytochemicals and could be extended to the marker-based standardization of polyherbal formulations, containing S. anacardium.

From diets to foods: using linear programming to formulate a nutritious, minimum-cost porridge mix for children aged 1 to 2 years.

PubMed

De Carvalho, Irene Stuart Torrié; Granfeldt, Yvonne; Dejmek, Petr; Håkansson, Andreas

2015-03-01

Linear programming has been used extensively as a tool for nutritional recommendations. Extending the methodology to food formulation presents new challenges, since not all combinations of nutritious ingredients will produce an acceptable food. Furthermore, it would help in implementation and in ensuring the feasibility of the suggested recommendations. To extend the previously used linear programming methodology from diet optimization to food formulation using consistency constraints. In addition, to exemplify usability using the case of a porridge mix formulation for emergency situations in rural Mozambique. The linear programming method was extended with a consistency constraint based on previously published empirical studies on swelling of starch in soft porridges. The new method was exemplified using the formulation of a nutritious, minimum-cost porridge mix for children aged 1 to 2 years for use as a complete relief food, based primarily on local ingredients, in rural Mozambique. A nutritious porridge fulfilling the consistency constraints was found; however, the minimum cost was unfeasible with local ingredients only. This illustrates the challenges in formulating nutritious yet economically feasible foods from local ingredients. The high cost was caused by the high cost of mineral-rich foods. A nutritious, low-cost porridge that fulfills the consistency constraints was obtained by including supplements of zinc and calcium salts as ingredients. The optimizations were successful in fulfilling all constraints and provided a feasible porridge, showing that the extended constrained linear programming methodology provides a systematic tool for designing nutritious foods.

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.

Fast and exact Newton and Bidirectional fitting of Active Appearance Models.

PubMed

Kossaifi, Jean; Tzimiropoulos, Yorgos; Pantic, Maja

2016-12-21

Active Appearance Models (AAMs) are generative models of shape and appearance that have proven very attractive for their ability to handle wide changes in illumination, pose and occlusion when trained in the wild, while not requiring large training dataset like regression-based or deep learning methods. The problem of fitting an AAM is usually formulated as a non-linear least squares one and the main way of solving it is a standard Gauss-Newton algorithm. In this paper we extend Active Appearance Models in two ways: we first extend the Gauss-Newton framework by formulating a bidirectional fitting method that deforms both the image and the template to fit a new instance. We then formulate a second order method by deriving an efficient Newton method for AAMs fitting. We derive both methods in a unified framework for two types of Active Appearance Models, holistic and part-based, and additionally show how to exploit the structure in the problem to derive fast yet exact solutions. We perform a thorough evaluation of all algorithms on three challenging and recently annotated inthe- wild datasets, and investigate fitting accuracy, convergence properties and the influence of noise in the initialisation. We compare our proposed methods to other algorithms and show that they yield state-of-the-art results, out-performing other methods while having superior convergence properties.

New Formulations of Methylphenidate for the Treatment of Attention-Deficit/Hyperactivity Disorder: Pharmacokinetics, Efficacy, and Tolerability.

PubMed

Cortese, Samuele; D'Acunto, Giulia; Konofal, Eric; Masi, Gabriele; Vitiello, Benedetto

2017-02-01

Psychostimulants are the recommended first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). Methylphenidate is one of the most commonly used psychostimulants worldwide. Given that immediate-release and/or tablet/capsule formulations may decrease adherence to methylphenidate treatment, several drug companies have been developing novel long-acting and/or liquid/chewable formulations that may improve adherence as well as (for long-acting formulations) reduce abuse potential, decrease stigma associated with multiple administrations per day, and decrease the potential for adverse effects related to dosage peak. Here, we review the pharmacokinetics, efficacy, and tolerability of novel formulations of methylphenidate that are in development or have been approved by the US FDA or European Medicines Agency (EMA) in the last 5 years. We searched the websites of the FDA, EMA, ClinicalTrials.gov, and the pertinent drug companies. We also searched PubMed, Ovid databases (MEDLINE, PsycINFO, Embase + Embase classic), and ISI Web of Knowledge (Web of Science [Science Citation Index Expanded], Biological Abstracts, Biosis, Food Science and Technology Abstracts) to retrieve any additional pertinent information. We found data from trials for the following compounds: (1) methylphenidate extended-release oral suspension (MEROS; NWP06, Quillivant™); (2) methylphenidate extended-release chewable capsules (NWP09, QuilliChew ER™); (3) methylphenidate hydrochloride extended-release capsules (Aptensio XR™); (4) methylphenidate extended-release orally disintegrating tablets (XR-ODT; NT-0102, Cotempla™); (5) ORADUR technology (once-daily tamper-resistant formulation) methylphenidate sustained release (SR); and (6) methylphenidate modified-release (HLD-200; Bejorna™). Overall, available evidence based on trials suggests these compounds have good efficacy and tolerability. Future research should further explore the effectiveness and tolerability of these new formulations as well as their potential to improve adherence to treatment in the 'real world' via pragmatic trials.

SLI381 (Adderall XR), a two-component, extended-release formulation of mixed amphetamine salts: bioavailability of three test formulations and comparison of fasted, fed, and sprinkled administration.

PubMed

Tulloch, Simon J; Zhang, Yuxin; McLean, Angus; Wolf, Kathleen N

2002-11-01

To assess the bioavailability of three test formulations of a single dose of extended-release Adderall 20-mg capsules compared with two doses of immediate-release Adderall 10-mg tablets, and to assess the bioequivalence of a single 30-mg dose of the chosen extended-release Adderall formulation (designated as SLI381) administered in applesauce (sprinkled) and the same dose administered as an intact capsule with or without food. Randomized, open-label, crossover study. Clinical research unit. Forty-one healthy adults. Study A had four treatment sequences: three test formulations (A, B, and C) of a single dose of extended-release Adderall 20 mg, and two 10-mg doses of Adderall given 4 hours apart. Study B had three treatment sequences: a single dose of SLI381 30 mg as an intact capsule after overnight fast, an intact capsule after a high-fat breakfast, and the contents of a capsule sprinkled in 1 tablespoon of applesauce. The 20-mg test formulation A had comparable pharmacokinetic profiles and bioequivalence in rate and extent of drug absorption to Adderall 10 mg twice/day for both d- and l-amphetamine. Formulations B and C had statistically significant differences from the reference drug in some pharmacokinetic parameters. A 30-mg dose of SLI381 showed no significant differences in rate and extent of absorption of d- and l-amphetamine for fasted or sprinkled conditions compared with the high-fat meal condition. SLI381 20 mg/day is bioequivalent to Adderall 10 mg twice/day. SLI381 30 mg administered in applesauce is bioequivalent in terms of both rate and extent of absorption to the same dose administered as an intact capsule in both fasted and fed states.

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.

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

PubMed Central

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

2014-01-01

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

Quantum kinetic expansion in the spin-boson model: Matrix formulation and system-bath factorized initial state.

PubMed

Gong, Zhihao; Tang, Zhoufei; Wang, Haobin; Wu, Jianlan

2017-12-28

Within the framework of the hierarchy equation of motion (HEOM), the quantum kinetic expansion (QKE) method of the spin-boson model is reformulated in the matrix representation. The equivalence between the two formulations (HEOM matrices and quantum operators) is numerically verified from the calculation of the time-integrated QKE rates. The matrix formulation of the QKE is extended to the system-bath factorized initial state. Following a one-to-one mapping between HEOM matrices and quantum operators, a quantum kinetic equation is rederived. The rate kernel is modified by an extra term following a systematic expansion over the site-site coupling. This modified QKE is numerically tested for its reliability by calculating the time-integrated rate and non-Markovian population kinetics. For an intermediate-to-strong dissipation strength and a large site-site coupling, the population transfer is found to be significantly different when the initial condition is changed from the local equilibrium to system-bath factorized state.

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

Stochastic dual dynamic programming (SDDP) is an optimization algorithm well-suited for the study of large-scale water resources systems comprising reservoirs - and hydropower plants - as well as irrigation nodes. It generates intertemporal allocation policies that balance the present and future marginal value of water while taking into account hydrological uncertainty. It is scalable, in the sense that the time and memory required for computation do not grow exponentially with the number of state variables. Still, this scalability relies on the sampling of a few relevant trajectories for the system, and the approximation of the future value of water through cuts -i.e., hyperplanes - at points along these trajectories. Therefore, the accuracy of this approximation arguably decreases as the number of state variables increases, and it is important not to have more than necessary. In previous formulations, SDDP had three types of state variables, namely storage in each reservoir, inflow at each node and water accumulated during the irrigation season for each crop at each node. We present a simplified formulation for irrigation that does not require using the latter type of state variable. It also requires only two decision variables for each irrigation site, where the previous formulation had four per crop - and there may be several crops at the same site. This reduction in decision variables effectively reduces computation time, since SDDP decomposes the stochastic, multiperiodic, non-linear maximization problem into a series of linear ones. The proposed formulation, while computationally simpler, is mathematically equivalent to the previous one, and therefore the model gives the same results. A corollary of this formulation is that marginal utility of water at an irrigation site is effectively related to consumption at that site, through a piecewise linear function representing the net benefits from irrigation. Last but not least, the proposed formulation can be 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.

Exceptional Form of D=11 Supergravity

NASA Astrophysics Data System (ADS)

Hohm, Olaf; Samtleben, Henning

2013-12-01

Eleven-dimensional supergravity reveals large exceptional symmetries upon reduction, in accordance with the U-duality groups of M theory, but their higher-dimensional geometric origin has remained a mystery. In this Letter, we show that D=11 supergravity can be extended to be fully covariant under the exceptional groups En(n), n=6, 7, 8. Motivated by a similar formulation of double field theory we introduce an extended “exceptional spacetime.” We illustrate the construction by giving the explicit E6(6) covariant form: the full D=11 supergravity, in a 5+6 splitting of coordinates but without truncation, embeds into an E6(6) covariant 5+27 dimensional theory. We argue that this covariant form likewise comprises type IIB supergravity.

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

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.

Numerical simulation using vorticity-vector potential formulation

NASA Technical Reports Server (NTRS)

Tokunaga, Hiroshi

1993-01-01

An accurate and efficient computational method is needed for three-dimensional incompressible viscous flows in engineering applications. On solving the turbulent shear flows directly or using the subgrid scale model, it is indispensable to resolve the small scale fluid motions as well as the large scale motions. From this point of view, the pseudo-spectral method is used so far as the computational method. However, the finite difference or the finite element methods are widely applied for computing the flow with practical importance since these methods are easily applied to the flows with complex geometric configurations. However, there exist several problems in applying the finite difference method to direct and large eddy simulations. Accuracy is one of most important problems. This point was already addressed by the present author on the direct simulations on the instability of the plane Poiseuille flow and also on the transition to turbulence. In order to obtain high efficiency, the multi-grid Poisson solver is combined with the higher-order, accurate finite difference method. The formulation method is also one of the most important problems in applying the finite difference method to the incompressible turbulent flows. The three-dimensional Navier-Stokes equations have been solved so far in the primitive variables formulation. One of the major difficulties of this method is the rigorous satisfaction of the equation of continuity. In general, the staggered grid is used for the satisfaction of the solenoidal condition for the velocity field at the wall boundary. However, the velocity field satisfies the equation of continuity automatically in the vorticity-vector potential formulation. From this point of view, the vorticity-vector potential method was extended to the generalized coordinate system. In the present article, we adopt the vorticity-vector potential formulation, the generalized coordinate system, and the 4th-order accurate difference method as the computational method. We present the computational method and apply the present method to computations of flows in a square cavity at large Reynolds number in order to investigate its effectiveness.

Evaluation of new creosote formulations after extended exposures in fungal cellar tests and field plot tests

Treesearch

Douglas M. Crawford; Patricia K. Lebow; Rodney DeGroot

2000-01-01

This paper compares two new formulations of creosote and one pigment-emulsified creosote (PEC) with a formulation of creosote that met requirements of the AWPA standard P1/P13. Two softwood and two hardwood species were treated to four retention levels with each formulation. The evaluation of the four creosote formulations was done using (1) soil-block tests, (2)...

A reciprocity formulation for the EM scattering by an obstacle within a large open cavity

NASA Technical Reports Server (NTRS)

Pathak, Prabhakar H.; Burkholder, Robert J.

1993-01-01

A formulation based on a generalized reciprocity theorem is developed for analyzing the external high frequency EM scattering by a complex obstacle inside a relatively arbitrary open-ended waveguide cavity when it is illuminated by an external source. This formulation is also extended to include EM fields whose time dependence may be nonperiodic. A significant advantage of this formulation is that it allows one to break up the analysis into two independent parts; one deals with the waveguide cavity shape alone and the other with the obstacle alone. The external scattered field produced by the obstacle (in the presence of the waveguide cavity structure) is given in terms of a generalized reciprocity integral over a surface S(T) corresponding to the interior waveguide cavity cross section located conveniently but sufficiently close to the obstacle. Furthermore, the fields coupled into the cavity from the source in the exterior region generally need to propagate only one-way via the open front end (which is directly illuminated) to the interior surface S(T) in this approach, and not back, in order to find the external field scattered by the obstacle.

New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control.

PubMed

Nelson, Anita

2010-08-09

To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women's desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors.

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.

Final Technical Report for Quantum Embedding for Correlated Electronic Structure in Large Systems and the Condensed Phase

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

Chan, Garnet Kin-Lic

2017-04-30

This is the final technical report. We briefly describe some selected results below. Developments in density matrix embedding. DMET is a quantum embedding theory that we introduced at the beginning of the last funding period, around 2012-2013. Since the first DMET papers, which demonstrated proof-of- principle calculations on the Hubbard model and hydrogen rings, we have carried out a number of different developments, including: Extending the DMET technology to compute broken symmetry phases, including magnetic phases and super- conductivity (Pub. 13); Calibrating the accuracy of DMET and its cluster size convergence against other methods, and formulation of a dynamical clustermore » analog (Pubs. 4, 10) (see Fig. 1); Implementing DMET for ab-initio molecular calculations, and exploring different self-consistency criteria (Pubs. 9, 14); Using embedding to defi ne quantum classical interfaces Pub. 2; Formulating DMET for spectral functions (Pub. 7) (see Fig. 1); Extending DMET to coupled fermion-boson problems (Pub. 12). Together with these embedding developments, we have also implemented a wide variety of impurity solvers within our DMET framework, including DMRG (Pub. 3), AFQMC (Pub. 10), and coupled cluster theory (CC) (Pub. 9).« less

In vitro-in vivo correlation for nevirapine extended release tablets.

PubMed

Macha, Sreeraj; Yong, Chan-Loi; Darrington, Todd; Davis, Mark S; MacGregor, Thomas R; Castles, Mark; Krill, Steven L

2009-12-01

An in vitro-in vivo correlation (IVIVC) for four nevirapine extended release tablets with varying polymer contents was developed. The pharmacokinetics of extended release formulations were assessed in a parallel group study with healthy volunteers and compared with corresponding in vitro dissolution data obtained using a USP apparatus type 1. In vitro samples were analysed using HPLC with UV detection and in vivo samples were analysed using a HPLC-MS/MS assay; the IVIVC analyses comparing the two results were performed using WinNonlin. A Double Weibull model optimally fits the in vitro data. A unit impulse response (UIR) was assessed using the fastest ER formulation as a reference. The deconvolution of the in vivo concentration time data was performed using the UIR to estimate an in vivo drug release profile. A linear model with a time-scaling factor clarified the relationship between in vitro and in vivo data. The predictability of the final model was consistent based on internal validation. Average percent prediction errors for pharmacokinetic parameters were <10% and individual values for all formulations were <15%. Therefore, a Level A IVIVC was developed and validated for nevirapine extended release formulations providing robust predictions of in vivo profiles based on in vitro dissolution profiles. Copyright 2009 John Wiley & Sons, Ltd.

Variational treatment of entanglement in the Dicke model

NASA Astrophysics Data System (ADS)

Bakemeier, L.; Alvermann, A.; Fehske, H.

2015-10-01

We introduce a variational ansatz for the Dicke model that extends mean-field theory through the inclusion of spin-oscillator correlations. The correlated variational state is obtained from the mean-field product state via a unitary transformation. The ansatz becomes correct in the limit of large oscillator frequency and in the limit of a large spin, for which it captures the leading quantum corrections to the classical limit exactly including the spin-oscillator entanglement entropy. We explain the origin of the unitary transformation before we show that the ansatz improves substantially upon mean-field theory, giving near exact results for the ground state energy and very good results for other observables. We then discuss why the ansatz still encounters problems in the transition regime at moderate spin lengths, where it fails to capture the precursors of the superradiant quantum phase transition faithfully. This observation illustrates the principal limits of semi-classical formulations, even after they are extended with correlations and entanglement.

Numerical computation of spherical harmonics of arbitrary degree and order by extending exponent of floating point numbers

NASA Astrophysics Data System (ADS)

Fukushima, Toshio

2012-04-01

By extending the exponent of floating point numbers with an additional integer as the power index of a large radix, we compute fully normalized associated Legendre functions (ALF) by recursion without underflow problem. The new method enables us to evaluate ALFs of extremely high degree as 232 = 4,294,967,296, which corresponds to around 1 cm resolution on the Earth's surface. By limiting the application of exponent extension to a few working variables in the recursion, choosing a suitable large power of 2 as the radix, and embedding the contents of the basic arithmetic procedure of floating point numbers with the exponent extension directly in the program computing the recurrence formulas, we achieve the evaluation of ALFs in the double-precision environment at the cost of around 10% increase in computational time per single ALF. This formulation realizes meaningful execution of the spherical harmonic synthesis and/or analysis of arbitrary degree and order.

A Cosserat crystal plasticity and phase field theory for grain boundary migration

NASA Astrophysics Data System (ADS)

Ask, Anna; Forest, Samuel; Appolaire, Benoit; Ammar, Kais; Salman, Oguz Umut

2018-06-01

The microstructure evolution due to thermomechanical treatment of metals can largely be described by viscoplastic deformation, nucleation and grain growth. These processes take place over different length and time scales which present significant challenges when formulating simulation models. In particular, no overall unified field framework exists to model concurrent viscoplastic deformation and recrystallization and grain growth in metal polycrystals. In this work a thermodynamically consistent diffuse interface framework incorporating crystal viscoplasticity and grain boundary migration is elaborated. The Kobayashi-Warren-Carter (KWC) phase field model is extended to incorporate the full mechanical coupling with material and lattice rotations and evolution of dislocation densities. The Cosserat crystal plasticity theory is shown to be the appropriate framework to formulate the coupling between phase field and mechanics with proper distinction between bulk and grain boundary behaviour.

Risk based In Vitro Performance Assessment of Extended Release Abuse Deterrent Formulations

PubMed Central

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

2016-01-01

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

Finite Nilpotent BRST Transformations in Hamiltonian Formulation

NASA Astrophysics Data System (ADS)

Rai, Sumit Kumar; Mandal, Bhabani Prasad

2013-10-01

We consider the finite field dependent BRST (FFBRST) transformations in the context of Hamiltonian formulation using Batalin-Fradkin-Vilkovisky method. The non-trivial Jacobian of such transformations is calculated in extended phase space. The contribution from Jacobian can be written as exponential of some local functional of fields which can be added to the effective Hamiltonian of the system. Thus, FFBRST in Hamiltonian formulation with extended phase space also connects different effective theories. We establish this result with the help of two explicit examples. We also show that the FFBRST transformations is similar to the canonical transformations in the sector of Lagrange multiplier and its corresponding momenta.

Development of extended-release solid dispersion granules of tacrolimus: evaluation of release mechanism and human oral bioavailability.

PubMed

Tsunashima, Daisuke; Yamashita, Kazunari; Ogawara, Ken-Ichi; Sako, Kazuhiro; Hakomori, Tadashi; Higaki, Kazutaka

2017-12-01

We aimed to prepare a once-daily modified-release oral formulation of tacrolimus by utilizing an extended-release granules (ERG). Extended-release granules were prepared using ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC) and lactose via a solvent evaporation method with ethanol. Physicochemical and biopharmaceutical studies were performed to determine the formulation with optimum release profile of tacrolimus from ERG. Tacrolimus existed in an amorphous state in ERG. Tacrolimus release from ERG was attenuated by EC and facilitated by lactose, suggesting that drug release kinetics could adequately be regulated by these components. Those release profiles were consistent with Higuchi's equation, suggesting a diffusion-type release mechanism. Smooth surface of ERG changed to the structure with pores after the release test, likely derived from the dissolution of HPMC and lactose. But ERG structure formed by EC was still maintained after the release test, leading to the longer maintenance of diffusion-type release. Two ERG formulations selected by blood concentration simulation successfully provided long-term retention of tacrolimus in blood in a human absorption study. We successfully developed the formulation exhibiting a significant reduction in C max , the longer mean residence time and AUC close to that of an immediate-release tacrolimus formulation, being preferred from the viewpoint of safe and effective immunosuppressant pharmacotherapy. © 2017 Royal Pharmaceutical Society.

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.

New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control

PubMed Central

Nelson, Anita

2010-01-01

Aim: To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. Methods: This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. Results: The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. Conclusion: The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women’s desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors. PMID:21072303

The quest for solvable multistate Landau-Zener models

DOE PAGES

Sinitsyn, Nikolai A.; Chernyak, Vladimir Y.

2017-05-24

Recently, integrability conditions (ICs) in mutistate Landau-Zener (MLZ) theory were proposed. They describe common properties of all known solved systems with linearly time-dependent Hamiltonians. Here we show that ICs enable efficient computer assisted search for new solvable MLZ models that span complexity range from several interacting states to mesoscopic systems with many-body dynamics and combinatorially large phase space. This diversity suggests that nontrivial solvable MLZ models are numerous. Additionally, we refine the formulation of ICs and extend the class of solvable systems to models with points of multiple diabatic level crossing.

Local finite element enrichment strategies for 2D contact computations and a corresponding post-processing scheme

NASA Astrophysics Data System (ADS)

Sauer, Roger A.

2013-08-01

Recently an enriched contact finite element formulation has been developed that substantially increases the accuracy of contact computations while keeping the additional numerical effort at a minimum reported by Sauer (Int J Numer Meth Eng, 87: 593-616, 2011). Two enrich-ment strategies were proposed, one based on local p-refinement using Lagrange interpolation and one based on Hermite interpolation that produces C 1-smoothness on the contact surface. Both classes, which were initially considered for the frictionless Signorini problem, are extended here to friction and contact between deformable bodies. For this, a symmetric contact formulation is used that allows the unbiased treatment of both contact partners. This paper also proposes a post-processing scheme for contact quantities like the contact pressure. The scheme, which provides a more accurate representation than the raw data, is based on an averaging procedure that is inspired by mortar formulations. The properties of the enrichment strategies and the corresponding post-processing scheme are illustrated by several numerical examples considering sliding and peeling contact in the presence of large deformations.

Numerical Hydrodynamics in General Relativity.

PubMed

Font, José A

2003-01-01

The current status of numerical solutions for the equations of ideal general relativistic hydrodynamics is reviewed. With respect to an earlier version of the article, the present update provides additional information on numerical schemes, and extends the discussion of astrophysical simulations in general relativistic hydrodynamics. Different formulations of the equations are presented, with special mention of conservative and hyperbolic formulations well-adapted to advanced numerical methods. A large sample of available numerical schemes is discussed, paying particular attention to solution procedures based on schemes exploiting the characteristic structure of the equations through linearized Riemann solvers. A comprehensive summary of astrophysical simulations in strong gravitational fields is presented. These include gravitational collapse, accretion onto black holes, and hydrodynamical evolutions of neutron stars. The material contained in these sections highlights the numerical challenges of various representative simulations. It also follows, to some extent, the chronological development of the field, concerning advances on the formulation of the gravitational field and hydrodynamic equations and the numerical methodology designed to solve them. Supplementary material is available for this article at 10.12942/lrr-2003-4.

Gaussian-windowed frame based method of moments formulation of surface-integral-equation for extended apertures

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

Shlivinski, A., E-mail: amirshli@ee.bgu.ac.il; Lomakin, V., E-mail: vlomakin@eng.ucsd.edu

2016-03-01

Scattering or coupling of electromagnetic beam-field at a surface discontinuity separating two homogeneous or inhomogeneous media with different propagation characteristics is formulated using surface integral equation, which are solved by the Method of Moments with the aid of the Gabor-based Gaussian window frame set of basis and testing functions. The application of the Gaussian window frame provides (i) a mathematically exact and robust tool for spatial-spectral phase-space formulation and analysis of the problem; (ii) a system of linear equations in a transmission-line like form relating mode-like wave objects of one medium with mode-like wave objects of the second medium; (iii)more » furthermore, an appropriate setting of the frame parameters yields mode-like wave objects that blend plane wave properties (as if solving in the spectral domain) with Green's function properties (as if solving in the spatial domain); and (iv) a representation of the scattered field with Gaussian-beam propagators that may be used in many large (in terms of wavelengths) systems.« less

Least-squares finite element solution of 3D incompressible Navier-Stokes problems

NASA Technical Reports Server (NTRS)

Jiang, Bo-Nan; Lin, Tsung-Liang; Povinelli, Louis A.

1992-01-01

Although significant progress has been made in the finite element solution of incompressible viscous flow problems. Development of more efficient methods is still needed before large-scale computation of 3D problems becomes feasible. This paper presents such a development. The most popular finite element method for the solution of incompressible Navier-Stokes equations is the classic Galerkin mixed method based on the velocity-pressure formulation. The mixed method requires the use of different elements to interpolate the velocity and the pressure in order to satisfy the Ladyzhenskaya-Babuska-Brezzi (LBB) condition for the existence of the solution. On the other hand, due to the lack of symmetry and positive definiteness of the linear equations arising from the mixed method, iterative methods for the solution of linear systems have been hard to come by. Therefore, direct Gaussian elimination has been considered the only viable method for solving the systems. But, for three-dimensional problems, the computer resources required by a direct method become prohibitively large. In order to overcome these difficulties, a least-squares finite element method (LSFEM) has been developed. This method is based on the first-order velocity-pressure-vorticity formulation. In this paper the LSFEM is extended for the solution of three-dimensional incompressible Navier-Stokes equations written in the following first-order quasi-linear velocity-pressure-vorticity formulation.

Extension and Validation of a Hybrid Particle-Finite Element Method for Hypervelocity Impact Simulation. Chapter 2

NASA Technical Reports Server (NTRS)

Fahrenthold, Eric P.; Shivarama, Ravishankar

2004-01-01

The hybrid particle-finite element method of Fahrenthold and Horban, developed for the simulation of hypervelocity impact problems, has been extended to include new formulations of the particle-element kinematics, additional constitutive models, and an improved numerical implementation. The extended formulation has been validated in three dimensional simulations of published impact experiments. The test cases demonstrate good agreement with experiment, good parallel speedup, and numerical convergence of the simulation results.

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

PubMed

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

2016-12-01

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

Semi-empirical formulation of multiple scattering for the Gaussian beam model of heavy charged particles stopping in tissue-like matter.

PubMed

Kanematsu, Nobuyuki

2009-03-07

Dose calculation for radiotherapy with protons and heavier ions deals with a large volume of path integrals involving a scattering power of body tissue. This work provides a simple model for such demanding applications. There is an approximate linearity between RMS end-point displacement and range of incident particles in water, empirically found in measurements and detailed calculations. This fact was translated into a simple linear formula, from which the scattering power that is only inversely proportional to the residual range was derived. The simplicity enabled the analytical formulation for ions stopping in water, which was designed to be equivalent with the extended Highland model and agreed with measurements within 2% or 0.02 cm in RMS displacement. The simplicity will also improve the efficiency of numerical path integrals in the presence of heterogeneity.

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

Kapil, Sanjay; Oberst, R. D.; Bieker, Jill Marie

Chemical disinfection and inactivation of viruses is largely understudied, but is very important especially in the case of highly infectious viruses. The purpose of this LDRD was to determine the efficacy of the Sandia National Laboratories developed decontamination formulations against Bovine Coronavirus (BCV) as a surrogate for the coronavirus that causes Severe Acute Respiratory Syndrome (SARS) in humans. The outbreak of SARS in late 2002 resulted from a highly infectious virus that was able to survive and remain infectious for extended periods. For this study, preliminary testing with Escherichia coli MS-2 (MS-2) and Escherichia coli T4 (T4) bacteriophages was conductedmore » to develop virucidal methodology for verifying the inactivation after treatment with the test formulations following AOAC germicidal methodologies. After the determination of various experimental parameters (i.e. exposure, concentration) of the formulations, final testing was conducted on BCV. All experiments were conducted with various organic challenges (horse serum, bovine feces, compost) for results that more accurately represent field use condition. The MS-2 and T4 were slightly more resistant than BCV and required a 2 minute exposure while BCV was completely inactivated after a 1 minute exposure. These results were also consistent for the testing conducted in the presence of the various organic challenges indicating that the test formulations are highly effective for real world application.« less

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

2015-09-08

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.

Spectrally formulated user-defined element in conventional finite element environment for wave motion analysis in 2-D composite structures

NASA Astrophysics Data System (ADS)

Khalili, Ashkan; Jha, Ratneshwar; Samaratunga, Dulip

2016-11-01

Wave propagation analysis in 2-D composite structures is performed efficiently and accurately through the formulation of a User-Defined Element (UEL) based on the wavelet spectral finite element (WSFE) method. The WSFE method is based on the first-order shear deformation theory which yields accurate results for wave motion at high frequencies. The 2-D WSFE model is highly efficient computationally and provides a direct relationship between system input and output in the frequency domain. The UEL is formulated and implemented in Abaqus (commercial finite element software) for wave propagation analysis in 2-D composite structures with complexities. Frequency domain formulation of WSFE leads to complex valued parameters, which are decoupled into real and imaginary parts and presented to Abaqus as real values. The final solution is obtained by forming a complex value using the real number solutions given by Abaqus. Five numerical examples are presented in this article, namely undamaged plate, impacted plate, plate with ply drop, folded plate and plate with stiffener. Wave motions predicted by the developed UEL correlate very well with Abaqus simulations. The results also show that the UEL largely retains computational efficiency of the WSFE method and extends its ability to model complex features.

The Effects of Potato Puree and Bread Crumbs on Some Quality Characteristics of Low Fat Meatballs

PubMed Central

Ergezer, Haluk; Akcan, Tolga; Serdaroğlu, Meltem

2014-01-01

The purpose of this study was to determine the effects of using different amounts of potato puree (PP) (10 or 20%) and 10% bread crumbs (BC) as an extender and also control samples (C) with no added extender on chemical composition, energy values, cooking analyses, colour measurements, water holding capacity (WHC), penetration values, thiobarbituric acid value (TBA) and sensory analyses of meatballs. Meatball samples were cooked in a pre-heated 180℃ electric oven. Uncooked meatballs formulated with 20% PP had the highest moisture content. No significant differences were recorded for protein contents of uncooked samples. The highest cooking yield was found in samples extended with 10% BC. Increasing PP from 10% to 20% increased cooking yield of meatballs. 20% PP increased moisture and fat retention values and water holding capacity of meatballs. Meatballs with 10% BC had the lowest (the hardness in the texture) and meatballs with the 20% PP had the highest (the softness in the texture) penetration values. Formulating meatballs at a level of 20% resulted lower L* values. TBA values of control samples were higher than in PP added samples at the end of the storage period. Flavour scores for meatballs formulated with PP were higher than control and meatballs formulated with BC. Meatballs formulated with 10% PP had similar overall acceptability with meatballs added with 10% BC. PMID:26761488

The Effects of Potato Puree and Bread Crumbs on Some Quality Characteristics of Low Fat Meatballs.

PubMed

Ergezer, Haluk; Akcan, Tolga; Serdaroğlu, Meltem

2014-01-01

The purpose of this study was to determine the effects of using different amounts of potato puree (PP) (10 or 20%) and 10% bread crumbs (BC) as an extender and also control samples (C) with no added extender on chemical composition, energy values, cooking analyses, colour measurements, water holding capacity (WHC), penetration values, thiobarbituric acid value (TBA) and sensory analyses of meatballs. Meatball samples were cooked in a pre-heated 180℃ electric oven. Uncooked meatballs formulated with 20% PP had the highest moisture content. No significant differences were recorded for protein contents of uncooked samples. The highest cooking yield was found in samples extended with 10% BC. Increasing PP from 10% to 20% increased cooking yield of meatballs. 20% PP increased moisture and fat retention values and water holding capacity of meatballs. Meatballs with 10% BC had the lowest (the hardness in the texture) and meatballs with the 20% PP had the highest (the softness in the texture) penetration values. Formulating meatballs at a level of 20% resulted lower L* values. TBA values of control samples were higher than in PP added samples at the end of the storage period. Flavour scores for meatballs formulated with PP were higher than control and meatballs formulated with BC. Meatballs formulated with 10% PP had similar overall acceptability with meatballs added with 10% BC.

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

PubMed

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

2015-06-01

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

Synthesis and optimization of four bar mechanism with six design parameters

NASA Astrophysics Data System (ADS)

Jaiswal, Ankur; Jawale, H. P.

2018-04-01

Function generation is synthesis of mechanism for specific task, involves complexity for specially synthesis above five precision of coupler points. Thus pertains to large structural error. The methodology for arriving to better precision solution is to use the optimization technique. Work presented herein considers methods of optimization of structural error in closed kinematic chain with single degree of freedom, for generating functions like log(x), ex, tan(x), sin(x) with five precision points. The equation in Freudenstein-Chebyshev method is used to develop five point synthesis of mechanism. The extended formulation is proposed and results are obtained to verify existing results in literature. Optimization of structural error is carried out using least square approach. Comparative structural error analysis is presented on optimized error through least square method and extended Freudenstein-Chebyshev method.

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.

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.

Next generation extended Lagrangian first principles molecular dynamics

NASA Astrophysics Data System (ADS)

Niklasson, Anders M. N.

2017-08-01

Extended Lagrangian Born-Oppenheimer molecular dynamics [A. M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] is formulated for general Hohenberg-Kohn density-functional theory and compared with the extended Lagrangian framework of first principles molecular dynamics by Car and Parrinello [Phys. Rev. Lett. 55, 2471 (1985)]. It is shown how extended Lagrangian Born-Oppenheimer molecular dynamics overcomes several shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while improving or maintaining important features of Car-Parrinello simulations. The accuracy of the electronic degrees of freedom in extended Lagrangian Born-Oppenheimer molecular dynamics, with respect to the exact Born-Oppenheimer solution, is of second-order in the size of the integration time step and of fourth order in the potential energy surface. Improved stability over recent formulations of extended Lagrangian Born-Oppenheimer molecular dynamics is achieved by generalizing the theory to finite temperature ensembles, using fractional occupation numbers in the calculation of the inner-product kernel of the extended harmonic oscillator that appears as a preconditioner in the electronic equations of motion. Material systems that normally exhibit slow self-consistent field convergence can be simulated using integration time steps of the same order as in direct Born-Oppenheimer molecular dynamics, but without the requirement of an iterative, non-linear electronic ground-state optimization prior to the force evaluations and without a systematic drift in the total energy. In combination with proposed low-rank and on the fly updates of the kernel, this formulation provides an efficient and general framework for quantum-based Born-Oppenheimer molecular dynamics simulations.

Next generation extended Lagrangian first principles molecular dynamics.

PubMed

Niklasson, Anders M N

2017-08-07

Extended Lagrangian Born-Oppenheimer molecular dynamics [A. M. N. Niklasson, Phys. Rev. Lett. 100, 123004 (2008)] is formulated for general Hohenberg-Kohn density-functional theory and compared with the extended Lagrangian framework of first principles molecular dynamics by Car and Parrinello [Phys. Rev. Lett. 55, 2471 (1985)]. It is shown how extended Lagrangian Born-Oppenheimer molecular dynamics overcomes several shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while improving or maintaining important features of Car-Parrinello simulations. The accuracy of the electronic degrees of freedom in extended Lagrangian Born-Oppenheimer molecular dynamics, with respect to the exact Born-Oppenheimer solution, is of second-order in the size of the integration time step and of fourth order in the potential energy surface. Improved stability over recent formulations of extended Lagrangian Born-Oppenheimer molecular dynamics is achieved by generalizing the theory to finite temperature ensembles, using fractional occupation numbers in the calculation of the inner-product kernel of the extended harmonic oscillator that appears as a preconditioner in the electronic equations of motion. Material systems that normally exhibit slow self-consistent field convergence can be simulated using integration time steps of the same order as in direct Born-Oppenheimer molecular dynamics, but without the requirement of an iterative, non-linear electronic ground-state optimization prior to the force evaluations and without a systematic drift in the total energy. In combination with proposed low-rank and on the fly updates of the kernel, this formulation provides an efficient and general framework for quantum-based Born-Oppenheimer molecular dynamics simulations.

Metformin extended release: metformin gastric retention, metformin GR, metformin XR.

PubMed

2005-01-01

Metformin extended release [Glumetza, metformin hydrochloride, metformin gastric retention, metformin GR] is a proprietary once-a-day formulation of metformin hydrochloride under development with Depomed for the treatment of diabetes mellitus. In May 2002, Depomed licensed manufacturing and marketing rights for its proprietary formulation of metformin extended release (500mg dose) to Biovail Corporation for the US (including Puerto Rico) and Canada. Under the terms of the agreement, Biovail will pay DepoMed a 25 million dollars milestone fee upon approval of the 500mg dosage and also customary royalties on the net sales in the US and Canada. Biovail also agreed to acquire approximately 2.4 million of additionally issued Depomed shares for 12.3 million dollars. Biovail has subsequently developed a 1000mg dose of metformin extended release [metformin XR] using its proprietary Smartcoat delivery technology allowing a graduated release of the active drug from the tablet. In April 2004, Depomed and Biovail amended their original license agreement of May 2002. Under the terms of the amended agreement, Depomed will receive royalties on sales of Biovail's 1000mg tablet in the US and Canada. In turn, Biovail acquired access to Depomed's clinical data for the metformin 500mg tablet that will be used to accelerate regulatory filings for Biovail's 1000mg tablet and establish equivalence between the two dosages. Biovail is seeking marketing partners for metformin extended release (Glumetza) in the US. The company anticipates signing an agreement for the US during the second half of 2005. In Canada, Biovail Corporation will market Glumetzatrade mark through its Canadian division, Bioval Pharmaceuticals Canada. Depomed has an agreement with LG Life Sciences for the commercialisation and distribution of metformin extended release in Korea. Metformin GR is available for partnership in Europe and Asia. Biovail Corporation and Depomed announced in June 2005 that the US FDA has approved metformin extended release (Glumetza) 500mg and 1000mg tablets for the treatment of type 2 diabetes mellitus. Biovail plans launching the product in the fourth quarter of 2005. In July 2005, Biovail paid Depomed a 25 million dollars milestone payment following approval of metformin extended release in the US for type 2 diabetes. In March 2005, Biovail Corporation and Depomed announced that they have received an approvable letter from the FDA for the once-daily, extended-release formulation of metformin extended release (Glumetza) 500mg and 1000mg tablets. The letter specified an issue related to finalising one manufacturing specification. There were no clinical labeling issues identified in the letter. Both companies filed a response to a specified issue at the FDA on 8 April 2005. The companies believed that the response will be classified as a Class I response with a 60-day review period. The 500mg dosage was developed by Depomed using its patented drug delivery GR technology, while Biovail developed metformin 1000mg dose using its proprietary Smartcoat delivery technology. Biovail's NDA for a once-daily, extended-release formulation of metformin HCl for the treatment of type II diabetes was filed in April 2004 and accepted for review in June 2004 by the FDA. Depomed completed two double-blind, pivotal, phase III clinical trials with metformin extended release 500mg at 60 sites in the US in more than 1000 patients with type 2 diabetes. In three different dosing regimens, metformin extended release significantly decreased the glycosylated haemoglobin level similarly to that of metformin immediate-release. Biovail successfully compared metformin extended release 1000mg dose with Depomed's 500mg dose in multiple equivalence studies. In these studies, metformin extended release was well tolerated and demonstrated an excellent safety profile in terms of gastrointestinal adverse events. On 1 June 2005, Depomed and Biovail Comporation, the licensee, announced that the Therapeutic Products Directorate in Canada issued a Notice of Compliance for metformin extended release (Glumetza) 500mg and 1000mg for the treatment of type 2 diabetes. Biovail Pharmaceuticals Canada plans to launch the product in the fourth quarter of 2005. Biovail has submitted an application for metformin extended release with the Therapeutic Products Directorate in Canada. and received notification of acceptance for review in August 2004. Bristol-Myers Squibb is marketing a proprietary, once-daily extended-release formulation of metformin (Glucophage XR). Several companies are developing controlled-release and extended-release formulations of metformin.

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

PubMed

Gonçalves de Lima, L; Rossi de Campos, D

2016-05-01

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

Computing Evans functions numerically via boundary-value problems

NASA Astrophysics Data System (ADS)

Barker, Blake; Nguyen, Rose; Sandstede, Björn; Ventura, Nathaniel; Wahl, Colin

2018-03-01

The Evans function has been used extensively to study spectral stability of travelling-wave solutions in spatially extended partial differential equations. To compute Evans functions numerically, several shooting methods have been developed. In this paper, an alternative scheme for the numerical computation of Evans functions is presented that relies on an appropriate boundary-value problem formulation. Convergence of the algorithm is proved, and several examples, including the computation of eigenvalues for a multi-dimensional problem, are given. The main advantage of the scheme proposed here compared with earlier methods is that the scheme is linear and scalable to large problems.

The metamorphosis of hydromorphone.

PubMed

Reisfield, Gary M; Wilson, George R

2005-01-01

Hydromorphone, one of the oldest and most potent of opioids, is an effective alternative to morphine. With a variety of routes of administration, it has an efficacy similar to that of morphine. The FDA has recently approved the first commercially available extended-release formulation, a once-daily hydromorphone for the management of moderate to severe pain in opioid tolerant individuals with an anticipated extended period of use. The formulation exhibits less peak-to-trough fluctuation in plasma concentration, while providing analgesia statistically indistinguishable from its immediate-release counterpart. The manufacturer and the FDA have articulated a plan to minimize unskillful prescribing and abuse/diversion through education, supply-chain integrity, and surveillance. It is anticipated that Palladone will be a valuable addition to the limited armamentarium of extended-release opioids.

In vitro biorelevant models for evaluating modified release mesalamine products to forecast the effect of formulation and meal intake on drug release.

PubMed

Andreas, Cord J; Chen, Ying-Chen; Markopoulos, Constantinos; Reppas, Christos; Dressman, Jennifer

2015-11-01

Postprandial administration of solid oral dosage forms greatly changes the dissolution environment compared to fasted state administration. The aims of this study were to investigate and forecast the effect of co-administration of a meal on drug release for delayed and/or extended release mesalamine formulations as well as design of in vitro tests to distinguish among formulations in a biorelevant way. Five different mesalamine formulations (Asacol® 400 mg, Mezavant® 1200 mg, Pentasa® 500 mg and Salofalk® in the 250 mg and 500 mg strengths) were investigated with biorelevant dissolution methods using the USP apparatus III and USP apparatus IV (open loop mode) under both fasted and fed state conditions, as well as with the dissolution methods described in pharmacopeia for delayed and extended release mesalamine products. Using the biorelevant experimental conditions proposed in this study, changes in release in the proximal gut due to meal intake are forecast to be minimal for Asacol®, Mezavant®, Pentasa® and Salofalk® 500 mg, while for Salofalk® 250 mg release was predicted to occur much earlier under fed state conditions. The USP apparatus III generally tended to result in faster dissolution rates and forecast more pronounced food effects for Salofalk® 250 mg than the USP apparatus IV. The biorelevant dissolution gradients were also able to reflect the in vivo behavior of the formulations. In vitro biorelevant models can be useful in the comparison of the release behavior from different delayed and extended release mesalamine formulations as well as forecasting effects of concomitant meal intake on drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of In Vitro-In Vivo Correlation for Potassium Chloride Extended Release Tablet Formulation Using Urinary Pharmacokinetic Data.

PubMed

Mittapalli, Rajendar K; Marroum, Patrick; Qiu, Yihong; Apfelbaum, Kathleen; Xiong, Hao

2017-07-01

To develop and validate a Level A in vitro-in vivo correlation (IVIVC) for potassium chloride extended-release (ER) formulations. Three prototype ER formulations of potassium chloride with different in vitro release rates were developed and their urinary pharmacokinetic profiles were evaluated in healthy subjects. A mathematical model between in vitro dissolution and in vivo urinary excretion, a surrogate for measuring in vivo absorption, was developed using time-scale and time-shift parameters. The IVIVC model was then validated based on internal and external predictability. With the established IVIVC model, there was a good correlation between the observed fraction of dose excreted in urine and the time-scaled and time-shifted fraction of the drug dissolved, and between the in vitro dissolution time and the in vivo urinary excretion time for the ER formulations. The percent prediction error (%PE) on cumulative urinary excretion over the 24 h interval (A e0-24h ) and maximum urinary excretion rate (R max ) was less than 15% for the individual formulations and less than 10% for the average of the two formulations used to develop the model. Further, the %PE values using external predictability were below 10%. A novel Level A IVIVC was successfully developed and validated for the new potassium chloride ER formulations using urinary pharmacokinetic data. This successful IVIVC may facilitate future development or manufacturing changes to the potassium chloride ER formulation.

Filling of High-Concentration Monoclonal Antibody Formulations into Pre-filled Syringes: Investigating Formulation-Nozzle Interactions To Minimize Nozzle Clogging.

PubMed

Shieu, Wendy; Stauch, Oliver B; Maa, Yuh-Fun

2015-01-01

Syringe filling of high-concentration/viscosity monoclonal antibody formulations is a complex process that is not fully understood. This study, which builds on a previous investigation that used a bench-top syringe filling unit to examine formulation drying at the filling nozzle tip and subsequent nozzle clogging, further explores the impact of formulation-nozzle material interactions on formulation drying and nozzle clogging. Syringe-filling nozzles made of glass, stainless steel, or plastic (polypropylene, silicone, and Teflon®), which represent a full range of materials with hydrophilic and hydrophobic properties as quantified by contact angle measurements, were used to fill liquids of different viscosity, including a high-concentration monoclonal antibody formulation. Compared with hydrophilic nozzles, hydrophobic nozzles offered two unique features that discouraged formulation drying and nozzle clogging: (1) the liquid formulation is more likely to be withdrawn into the hydrophobic nozzle under the same suck-back conditions, and (2) the residual liquid film left on the nozzle wall when using high suck-back settings settles to form a liquid plug away from the hydrophobic nozzle tip. Making the tip of the nozzle hydrophobic (silicone-coating on glass and Teflon-coating stainless steel) could achieve the same suck-back performance as plastic nozzles. This study demonstrated that using hydrophobic nozzles are most effective in reducing the risk of nozzle clogging by drying of high-concentration monoclonal antibody formulation during extended nozzle idle time in a large-scale filling facility and environment. Syringe filling is a well-established manufacturing process and has been implemented by numerous contract manufacturing organizations and biopharmaceutical companies. However, its technical details and associated critical process parameters are rarely published. Information on high-concentration/viscosity formulation filling is particularly lacking. This study is the continuation of a previous investigation with a focus on understanding the impact of nozzle material on the suck-back function of liquid formulations. The findings identified the most critical parameter-nozzle material hydrophobicity-in alleviating formulation drying at the nozzle tip and eventually limiting the occurrence of nozzle clogging during the filling process. The outcomes of this study will benefit scientists and engineers who develop pre-filled syringe products by providing a better understanding of high-concentration formulation filling principles and challenges. © PDA, Inc. 2015.

Treatment Planning and Image Guidance for Radiofrequency Ablations of Large Tumors

PubMed Central

Ren, Hongliang; Campos-Nanez, Enrique; Yaniv, Ziv; Banovac, Filip; Abeledo, Hernan; Hata, Nobuhiko; Cleary, Kevin

2014-01-01

This article addresses the two key challenges in computer-assisted percutaneous tumor ablation: planning multiple overlapping ablations for large tumors while avoiding critical structures, and executing the prescribed plan. Towards semi-automatic treatment planning for image-guided surgical interventions, we develop a systematic approach to the needle-based ablation placement task, ranging from pre-operative planning algorithms to an intra-operative execution platform. The planning system incorporates clinical constraints on ablations and trajectories using a multiple objective optimization formulation, which consists of optimal path selection and ablation coverage optimization based on integer programming. The system implementation is presented and validated in phantom studies and on an animal model. The presented system can potentially be further extended for other ablation techniques such as cryotherapy. PMID:24235279

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.

Buccal drug delivery.

PubMed

Smart, John D

2005-05-01

Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Evolution of the treatment of attention-deficit/hyperactivity disorder in children: a review.

PubMed

Findling, Robert L

2008-05-01

Efficacious and well-tolerated medications are available for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulants such as methylphenidate (MPH) and amphetamines are the most widely used medications approved by the US Food and Drug Administration for the treatment of ADHDin children. This article reviews the literature on the development and use of medications for the treatment of ADHD in children. A search of MEDLINE was conducted toidentify relevant studies and critical reviews on the treatment of ADHD in children. The main criteria for inclusion of a study were that it have a controlled design, enroll >100 subjects if a clinical trial and >20 subjects if a classroom study, assess symptoms with the most widely used scales and tests,and be published from 2000 to 2008.A few older pivotal studies were also included. Many studies have reported the long-term efficacy and tolerability of immediate-release formulations of MPH. The disadvantages of such formulations include the need for multiple daily dosing and a potential for abuse. Various extended-release formulations of MPH have been found effective in controlled studies enrolling large numbers of children with ADHD. The efficacy and tolerability of dexmethylphenidate, the active D-isomer of MPH, in an extended-release formulation have also been reported. An extended-release formulation of mixed amphetamine salts (MMAS-XR) that is dosed once daily has been found to be efficacious and well tolerated. The non-stimulant atomoxetine has been reported to be well tolerated and efficacious, although it may not be as effective as stimulants; this formulation is, however, less likely than stimulants to be associated with abuse and diversion. A recently approved prodrug stimulant, lisdexamfetamine dimesylate (LDX), was developed to provide a long duration of effect that is consistent throughout the day, with a reduced potential for abuse. In a placebo-controlled study in children with ADHD, less intersubject variability in T(max), C(max), and AUC from time zero to the last quantifiable concentration was seen in the 8 subjects who received LDX (percent coefficient of variation, 15.3, 20.3, and 21.6, respectively) compared with the 9 subjects who received MAS-XR (52.8, 44.0, and 42.8).In 2 clinical trials, significantly greater improvements in teacher and parent ratings of ADHD symptoms were seen with LDX compared with placebo (P<0.001).A study of the abuse potential of LDX evaluated subjective responses to the effects of oral LDX and immediate-release d-amphetamine in adults with a history of stimulant abuse. LDX was associated with a significantly lower abuse-related liking effect than d-aamphetamine (P = 0.039). Currently available treatments for ADHD in children are efficacious and well tolerated, but many of them are limited by the requirement for multiple daily dosing and abuse potential. LDX, a long-acting prodrug of d-amphetamine, has been reported to be effective and appears to overcome some of these limitations.

Extending the shelf-life of Myrothecium verrucaria, a bioherbicide

USDA-ARS?s Scientific Manuscript database

The bioherbicidal efficacy of freshly fermented Myrothecium verrucaria IMI 368023 (MV) mycelia formulations and MV mycelia preparations that had been freeze-dried and then stored at -20 °C for 8 years were compared. Two concentrations of each formulation (1x and 0.5x) were tested, utilizing bioassa...

Water-based and biocompatible 2D crystal inks for all-inkjet-printed heterostructures

NASA Astrophysics Data System (ADS)

McManus, Daryl; Vranic, Sandra; Withers, Freddie; Sanchez-Romaguera, Veronica; Macucci, Massimo; Yang, Huafeng; Sorrentino, Roberto; Parvez, Khaled; Son, Seok-Kyun; Iannaccone, Giuseppe; Kostarelos, Kostas; Fiori, Gianluca; Casiraghi, Cinzia

2017-05-01

Exploiting the properties of two-dimensional crystals requires a mass production method able to produce heterostructures of arbitrary complexity on any substrate. Solution processing of graphene allows simple and low-cost techniques such as inkjet printing to be used for device fabrication. However, the available printable formulations are still far from ideal as they are either based on toxic solvents, have low concentration, or require time-consuming and expensive processing. In addition, none is suitable for thin-film heterostructure fabrication due to the re-mixing of different two-dimensional crystals leading to uncontrolled interfaces and poor device performance. Here, we show a general approach to achieve inkjet-printable, water-based, two-dimensional crystal formulations, which also provide optimal film formation for multi-stack fabrication. We show examples of all-inkjet-printed heterostructures, such as large-area arrays of photosensors on plastic and paper and programmable logic memory devices. Finally, in vitro dose-escalation cytotoxicity assays confirm the biocompatibility of the inks, extending their possible use to biomedical applications.

On the structure-bounded growth processes in plant populations.

PubMed

Kilian, H G; Kazda, M; Király, F; Kaufmann, D; Kemkemer, R; Bartkowiak, D

2010-07-01

If growing cells in plants are considered to be composed of increments (ICs) an extended version of the law of mass action can be formulated. It evidences that growth of plants runs optimal if the reaction-entropy term (entropy times the absolute temperature) matches the contact energy of ICs. Since these energies are small, thermal molecular movements facilitate via relaxation the removal of structure disturbances. Stem diameter distributions exhibit extra fluctuations likely to be caused by permanent constraints. Since the signal-response system enables in principle perfect optimization only within finite-sized cell ensembles, plants comprising relatively large cell numbers form a network of size-limited subsystems. The maximal number of these constituents depends both on genetic and environmental factors. Accounting for logistical structure-dynamics interrelations, equations can be formulated to describe the bimodal growth curves of very different plants. The reproduction of the S-bended growth curves verifies that the relaxation modes with a broad structure-controlled distribution freeze successively until finally growth is fully blocked thus bringing about "continuous solidification".

Long-term safety and efficacy of budesonide in the treatment of ulcerative colitis

PubMed Central

Iborra, Marisa; Álvarez-Sotomayor, Diego; Nos, Pilar

2014-01-01

Ulcerative colitis (UC) is a chronic, relapsing, and remitting inflammatory disease involving the large intestine (colon). Treatment seeks to break recurrent inflammation episodes by inducing and maintaining remission. Historically, oral systemic corticosteroids played an important role in inducing remission of this chronic disease; however, their long-term use is limited and can lead to adverse events. Budesonide is a synthetic steroid with potent local anti-inflammatory effects and low systemic bioavailability due to high first-pass hepatic metabolism. Several studies have demonstrated oral budesonide’s usefulness in treating active mild to moderate ileocecal Crohn’s disease and microscopic colitis and in an enema formulation for left sided UC. However, there is limited information regarding oral budesonide’s efficacy in UC. A novel oral budesonide formulation using a multimatrix system (budesonide-MMX) to extend drug release throughout the colon has been developed recently and seems to be an effective treatment in active left sided UC patients. This article summarizes budesonide’s long-term safety and efficacy in treating UC. PMID:24523594

Statistical nature of infrared dynamics on de Sitter background

NASA Astrophysics Data System (ADS)

Tokuda, Junsei; Tanaka, Takahiro

2018-02-01

In this study, we formulate a systematic way of deriving an effective equation of motion(EoM) for long wavelength modes of a massless scalar field with a general potential V(phi) on de Sitter background, and investigate whether or not the effective EoM can be described as a classical stochastic process. Our formulation gives an extension of the usual stochastic formalism to including sub-leading secular growth coming from the nonlinearity of short wavelength modes. Applying our formalism to λ phi4 theory, we explicitly derive an effective EoM which correctly recovers the next-to-leading secularly growing part at a late time, and show that this effective EoM can be seen as a classical stochastic process. Our extended stochastic formalism can describe all secularly growing terms which appear in all correlation functions with a specific operator ordering. The restriction of the operator ordering will not be a big drawback because the commutator of a light scalar field becomes negligible at large scales owing to the squeezing.

User manual for EXCALIBUR: A FE-BI numerical laboratory for cavity-backed antennas in a circular cylinder, version 1.2

NASA Technical Reports Server (NTRS)

Kempel, Leo C.

1994-01-01

The Finite Element-Boundary Integral (FE-BI) technique was used to analyze the scattering and radiation properties of cavity-backed patch antennas recessed in a metallic groundplane. A program, CAVITY3D, was written and found to yield accurate results for large arrays without the usual high memory and computational demand associated with competing formulations. Recently, the FE-BI approach was extended to cavity-backed antennas recessed in an infinite, metallic circular cylinder. EXCALIBUR is a computer program written in the Radiation Laboratory of the University of Michigan which implements this formulation. This user manual gives a brief introduction to EXCALIBUR and some hints as to its proper use. As with all computational electromagnetics programs (especially finite element programs), skilled use and best performance are only obtained through experience. However, several important aspects of the program such as portability, geometry generation, interpretation of results, and custom modification are addressed.

Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

PubMed

Lamba, Manisha; Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C

2016-11-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers. Study A characterized single-dose and steady-state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single-dose and steady-state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high-fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half-life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) after single- and multiple-dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. C max increased by 27% under the fed state. On repeat administration, negligible accumulation (<20%) of systemic exposures was observed for both formulations. Steady state was achieved within 48 hours of dosing with the XR formulation. Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. © 2016, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Phase-field modelling of ductile fracture: a variational gradient-extended plasticity-damage theory and its micromorphic regularization

PubMed Central

Teichtmeister, S.; Aldakheel, F.

2016-01-01

This work outlines a novel variational-based theory for the phase-field modelling of ductile fracture in elastic–plastic solids undergoing large strains. The phase-field approach regularizes sharp crack surfaces within a pure continuum setting by a specific gradient damage modelling. It is linked to a formulation of gradient plasticity at finite strains. The framework includes two independent length scales which regularize both the plastic response as well as the crack discontinuities. This ensures that the damage zones of ductile fracture are inside of plastic zones, and guarantees on the computational side a mesh objectivity in post-critical ranges. PMID:27002069

Enriched reproducing kernel particle method for fractional advection-diffusion equation

NASA Astrophysics Data System (ADS)

Ying, Yuping; Lian, Yanping; Tang, Shaoqiang; Liu, Wing Kam

2018-06-01

The reproducing kernel particle method (RKPM) has been efficiently applied to problems with large deformations, high gradients and high modal density. In this paper, it is extended to solve a nonlocal problem modeled by a fractional advection-diffusion equation (FADE), which exhibits a boundary layer with low regularity. We formulate this method on a moving least-square approach. Via the enrichment of fractional-order power functions to the traditional integer-order basis for RKPM, leading terms of the solution to the FADE can be exactly reproduced, which guarantees a good approximation to the boundary layer. Numerical tests are performed to verify the proposed approach.

Microstructural Modeling of Dynamic Intergranular and Transgranular Fracture Modes in Zircaloys

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

Mohammed, I.; Zikry, M.A.; Ziaei, S.

2017-04-01

In this time period, we have continued to focus on (i) refining the thermo-mechanical fracture model for zirconium (Zr) alloys subjected to large deformations and high temperatures that accounts for the cracking of ZrH and ZrH2 hydrides, (ii) formulating a framework to account intergranular fracture due to iodine diffusion and pit formation in grain-boundaries (GBs). Our future objectives are focused on extending to a combined population of ZrH and ZrH2 populations and understanding how thermo-mechanical behavior affects hydride reorientation and cracking. We will also refine the intergranular failure mechanisms for grain boundaries with pits.

Shape invariant potentials in higher dimensions

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

Sandhya, R., E-mail: saudhamini@yahoo.com; Sree Ranjani, S., E-mail: s.sreeranjani@gmail.com; Faculty of Science and Technology, ICFAI foundation for Higher Education,

2015-08-15

In this paper we investigate the shape invariance property of a potential in one dimension. We show that a simple ansatz allows us to reconstruct all the known shape invariant potentials in one dimension. This ansatz can be easily extended to arrive at a large class of new shape invariant potentials in arbitrary dimensions. A reformulation of the shape invariance property and possible generalizations are proposed. These may lead to an important extension of the shape invariance property to Hamiltonians that are related to standard potential problems via space time transformations, which are found useful in path integral formulation ofmore » quantum mechanics.« less

Advanced data assimilation in strongly nonlinear dynamical systems

NASA Technical Reports Server (NTRS)

Miller, Robert N.; Ghil, Michael; Gauthiez, Francois

1994-01-01

Advanced data assimilation methods are applied to simple but highly nonlinear problems. The dynamical systems studied here are the stochastically forced double well and the Lorenz model. In both systems, linear approximation of the dynamics about the critical points near which regime transitions occur is not always sufficient to track their occurrence or nonoccurrence. Straightforward application of the extended Kalman filter yields mixed results. The ability of the extended Kalman filter to track transitions of the double-well system from one stable critical point to the other depends on the frequency and accuracy of the observations relative to the mean-square amplitude of the stochastic forcing. The ability of the filter to track the chaotic trajectories of the Lorenz model is limited to short times, as is the ability of strong-constraint variational methods. Examples are given to illustrate the difficulties involved, and qualitative explanations for these difficulties are provided. Three generalizations of the extended Kalman filter are described. The first is based on inspection of the innovation sequence, that is, the successive differences between observations and forecasts; it works very well for the double-well problem. The second, an extension to fourth-order moments, yields excellent results for the Lorenz model but will be unwieldy when applied to models with high-dimensional state spaces. A third, more practical method--based on an empirical statistical model derived from a Monte Carlo simulation--is formulated, and shown to work very well. Weak-constraint methods can be made to perform satisfactorily in the context of these simple models, but such methods do not seem to generalize easily to practical models of the atmosphere and ocean. In particular, it is shown that the equations derived in the weak variational formulation are difficult to solve conveniently for large systems.

Methylphenidate and dexmethylphenidate formulations for children with attention-deficit/hyperactivity disorder.

PubMed

Sugrue, David; Bogner, Robin; Ehret, Megan J

2014-07-15

Current literature on the safety and efficacy of various intermediate- and long-acting preparations of methylphenidate and dexmethylphenidate for pediatric attention-deficit/hyperactivity disorder (ADHD) is reviewed. The efficacy of methylphenidate in controlling ADHD symptoms is firmly established. Given the drug's relatively short half-life in pediatric patients (about 2.5 hours), a number of intermediate- and long-acting products have been developed; these extended-release methylphenidate products provide the same efficacy as immediate-release (IR) formulations, with the convenience of less frequent dosing. Intermediate-acting methylphenidate preparations have effects lasting as long as 8 hours, but peak concentrations are not attained for up to 5 hours, and many patients may require twice-daily dosing. Long-acting methylphenidate products developed to address these challenges include a controlled-release tablet and bimodal-delivery capsules containing mixtures of IR and extended-release beads (durations of effect, 8-12 hours). Options for patients with difficulty swallowing tablets or capsules include a once-daily transdermal delivery system and a once-daily liquid formulation. Dexmethylphenidate (the more pharmacologically active d-isomer of racemic methylphenidate) can provide efficacy comparable to that of IR methylphenidate at half the dose; an extended-release form of dexmethylphenidate can provide less fluctuation in peak and trough concentrations than the IR form. Methylphenidate and dexmethylphenidate products in capsule form can be opened and sprinkled on applesauce. The various formulations of IR and intermediate- and extended-release methylphenidate and dexmethylphenidate can be useful options in satisfying patients' individual needs in the management of ADHD. All are equally efficacious in controlling ADHD symptoms. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

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.

Discovery of the Kalman filter as a practical tool for aerospace and industry

NASA Technical Reports Server (NTRS)

Mcgee, L. A.; Schmidt, S. F.

1985-01-01

The sequence of events which led the researchers at Ames Research Center to the early discovery of the Kalman filter shortly after its introduction into the literature is recounted. The scientific breakthroughs and reformulations that were necessary to transform Kalman's work into a useful tool for a specific aerospace application are described. The resulting extended Kalman filter, as it is now known, is often still referred to simply as the Kalman filter. As the filter's use gained in popularity in the scientific community, the problems of implementation on small spaceborne and airborne computers led to a square-root formulation of the filter to overcome numerical difficulties associated with computer word length. The work that led to this new formulation is also discussed, including the first airborne computer implementation and flight test. Since then the applications of the extended and square-root formulations of the Kalman filter have grown rapidly throughout the aerospace industry.

A rigorous approach to the formulation of extended Born-Oppenheimer equation for a three-state system

NASA Astrophysics Data System (ADS)

Sarkar, Biplab; Adhikari, Satrajit

If a coupled three-state electronic manifold forms a sub-Hilbert space, it is possible to express the non-adiabatic coupling (NAC) elements in terms of adiabatic-diabatic transformation (ADT) angles. Consequently, we demonstrate: (a) Those explicit forms of the NAC terms satisfy the Curl conditions with non-zero Divergences; (b) The formulation of extended Born-Oppenheimer (EBO) equation for any three-state BO system is possible only when there exists coordinate independent ratio of the gradients for each pair of ADT angles leading to zero Curls at and around the conical intersection(s). With these analytic advancements, we formulate a rigorous EBO equation and explore its validity as well as necessity with respect to the approximate one (Sarkar and Adhikari, J Chem Phys 2006, 124, 074101) by performing numerical calculations on two different models constructed with different chosen forms of the NAC elements.

On large time step TVD scheme for hyperbolic conservation laws and its efficiency evaluation

NASA Astrophysics Data System (ADS)

Qian, ZhanSen; Lee, Chun-Hian

2012-08-01

A large time step (LTS) TVD scheme originally proposed by Harten is modified and further developed in the present paper and applied to Euler equations in multidimensional problems. By firstly revealing the drawbacks of Harten's original LTS TVD scheme, and reasoning the occurrence of the spurious oscillations, a modified formulation of its characteristic transformation is proposed and a high resolution, strongly robust LTS TVD scheme is formulated. The modified scheme is proven to be capable of taking larger number of time steps than the original one. Following the modified strategy, the LTS TVD schemes for Yee's upwind TVD scheme and Yee-Roe-Davis's symmetric TVD scheme are constructed. The family of the LTS schemes is then extended to multidimensional by time splitting procedure, and the associated boundary condition treatment suitable for the LTS scheme is also imposed. The numerical experiments on Sod's shock tube problem, inviscid flows over NACA0012 airfoil and ONERA M6 wing are performed to validate the developed schemes. Computational efficiencies for the respective schemes under different CFL numbers are also evaluated and compared. The results reveal that the improvement is sizable as compared to the respective single time step schemes, especially for the CFL number ranging from 1.0 to 4.0.

Co-rotational thermo-mechanically coupled multi-field framework and finite element for the large displacement analysis of multi-layered shape memory alloy beam-like structures

NASA Astrophysics Data System (ADS)

Solomou, Alexandros G.; Machairas, Theodoros T.; Karakalas, Anargyros A.; Saravanos, Dimitris A.

2017-06-01

A thermo-mechanically coupled finite element (FE) for the simulation of multi-layered shape memory alloy (SMA) beams admitting large displacements and rotations (LDRs) is developed to capture the geometrically nonlinear effects which are present in many SMA applications. A generalized multi-field beam theory implementing a SMA constitutive model based on small strain theory, thermo-mechanically coupled governing equations and multi-field kinematic hypotheses combining first order shear deformation assumptions with a sixth order polynomial temperature field through the thickness of the beam section are extended to admit LDRs. The co-rotational formulation is adopted, where the motion of the beam is decomposed to rigid body motion and relative small deformation in the local frame. A new generalized multi-layered SMA FE is formulated. The nonlinear transient spatial discretized equations of motion of the SMA structure are synthesized and solved using the Newton-Raphson method combined with an implicit time integration scheme. Correlations of models incorporating the present beam FE with respective results of models incorporating plane stress SMA FEs, demonstrate excellent agreement of the predicted LDRs response, temperature and phase transformation fields, as well as, significant gains in computational time.

Algorithms for bilevel optimization

NASA Technical Reports Server (NTRS)

Alexandrov, Natalia; Dennis, J. E., Jr.

1994-01-01

General multilevel nonlinear optimization problems arise in design of complex systems and can be used as a means of regularization for multi-criteria optimization problems. Here, for clarity in displaying our ideas, we restrict ourselves to general bi-level optimization problems, and we present two solution approaches. Both approaches use a trust-region globalization strategy, and they can be easily extended to handle the general multilevel problem. We make no convexity assumptions, but we do assume that the problem has a nondegenerate feasible set. We consider necessary optimality conditions for the bi-level problem formulations and discuss results that can be extended to obtain multilevel optimization formulations with constraints at each level.

Effective Field Theory on Manifolds with Boundary

NASA Astrophysics Data System (ADS)

Albert, Benjamin I.

In the monograph Renormalization and Effective Field Theory, Costello made two major advances in rigorous quantum field theory. Firstly, he gave an inductive position space renormalization procedure for constructing an effective field theory that is based on heat kernel regularization of the propagator. Secondly, he gave a rigorous formulation of quantum gauge theory within effective field theory that makes use of the BV formalism. In this work, we extend Costello's renormalization procedure to a class of manifolds with boundary and make preliminary steps towards extending his formulation of gauge theory to manifolds with boundary. In addition, we reorganize the presentation of the preexisting material, filling in details and strengthening the results.

Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential

PubMed Central

Immordino, Maria Laura; Dosio, Franco; Cattel, Luigi

2006-01-01

Among several promising new drug-delivery systems, liposomes represent an advanced technology to deliver active molecules to the site of action, and at present several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles (“first-generation liposomes”) to “second-generation liposomes”, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol) (PEG) in liposome composition. The presence of PEG on the surface of the liposomal carrier has been shown to extend blood-circulation time while reducing mononuclear phagocyte system uptake (stealth liposomes). This technology has resulted in a large number of liposome formulations encapsulating active molecules, with high target efficiency and activity. Further, by synthetic modification of the terminal PEG molecule, stealth liposomes can be actively targeted with monoclonal antibodies or ligands. This review focuses on stealth technology and summarizes pre-clinical and clinical data relating to the principal liposome formulations; it also discusses emerging trends of this promising technology. PMID:17717971

Convex Formulations of Learning from Crowds

NASA Astrophysics Data System (ADS)

Kajino, Hiroshi; Kashima, Hisashi

It has attracted considerable attention to use crowdsourcing services to collect a large amount of labeled data for machine learning, since crowdsourcing services allow one to ask the general public to label data at very low cost through the Internet. The use of crowdsourcing has introduced a new challenge in machine learning, that is, coping with low quality of crowd-generated data. There have been many recent attempts to address the quality problem of multiple labelers, however, there are two serious drawbacks in the existing approaches, that are, (i) non-convexity and (ii) task homogeneity. Most of the existing methods consider true labels as latent variables, which results in non-convex optimization problems. Also, the existing models assume only single homogeneous tasks, while in realistic situations, clients can offer multiple tasks to crowds and crowd workers can work on different tasks in parallel. In this paper, we propose a convex optimization formulation of learning from crowds by introducing personal models of individual crowds without estimating true labels. We further extend the proposed model to multi-task learning based on the resemblance between the proposed formulation and that for an existing multi-task learning model. We also devise efficient iterative methods for solving the convex optimization problems by exploiting conditional independence structures in multiple classifiers.

Crystallization of glass-forming liquids: Specific surface energy

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

Schmelzer, Jürn W. P., E-mail: juern-w.schmelzer@uni-rostock.de; Abyzov, Alexander S.

2016-08-14

A generalization of the Stefan-Skapski-Turnbull relation for the melt-crystal specific interfacial energy is developed in terms of the generalized Gibbs approach extending its standard formulation to thermodynamic non-equilibrium states. With respect to crystal nucleation, this relation is required in order to determine the parameters of the critical crystal clusters being a prerequisite for the computation of the work of critical cluster formation. As one of its consequences, a relation for the dependence of the specific surface energy of critical clusters on temperature and pressure is derived applicable for small and moderate deviations from liquid-crystal macroscopic equilibrium states. Employing the Stefan-Skapski-Turnbullmore » relation, general expressions for the size and the work of formation of critical crystal clusters are formulated. The resulting expressions are much more complex as compared to the respective relations obtained via the classical Gibbs theory. Latter relations are retained as limiting cases of these more general expressions for moderate undercoolings. By this reason, the formulated, here, general relations for the specification of the critical cluster size and the work of critical cluster formation give a key for an appropriate interpretation of a variety of crystallization phenomena occurring at large undercoolings which cannot be understood in terms of the Gibbs’ classical treatment.« less

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

PubMed

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

2012-03-01

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

Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product.

PubMed

Pergolizzi, Joseph V; Taylor, Robert; LeQuang, Jo Ann; Raffa, Robert B

2018-01-01

Proper management of severe pain represents one of the most challenging clinical dilemmas. Two equally important goals must be attained: the humanitarian/medical goal to relieve suffering and the societal/legal goal to not contribute to the drug abuse problem. This is an age-old problem, and the prevailing emphasis placed on one or the other goal has resulted in pendulum swings that have resulted in either undertreatment of pain or the current epidemic of misuse and abuse. In an effort to provide efficacious strong pain relievers (opioids) that are more difficult to abuse by the most dangerous routes of administration, pharmaceutical companies are developing products in which the opioid is manufactured in a formulation that is designed to be tamper resistant. Such a product is known as an abuse-deterrent formulation (ADF). ADF opioid products are designed to deter or resist abuse by making it difficult to tamper with the product and extracting the opioid for inhalation or injection. To date, less than a dozen opioid formulations have been approved by the US Food and Drug Administration to carry specific ADF labeling, but this number will likely increase in the coming years. Most of these products are extended-release formulations.

Membrane triangles with corner drilling freedoms. I - The EFF element

NASA Technical Reports Server (NTRS)

Alvin, Ken; De La Fuente, Horacio M.; Haugen, Bjorn; Felippa, Carlos A.

1992-01-01

The formulation of 3-node 9-DOF membrane elements with normal-to-element-plane rotations (drilling freedoms) is examined in the context of parametrized variational principles. In particular, attention is given to the application of the extended free formulation (EFF) to the construction of a triangular membrane element with drilling freedoms that initially has complete quadratic polynomial expansions in each displacement component. The main advantage of the EFF over the free formulation triangle is that an explicit form is obtained for the higher-order stiffness.

Self-similar cosmological solutions with dark energy. I. Formulation and asymptotic analysis

NASA Astrophysics Data System (ADS)

Harada, Tomohiro; Maeda, Hideki; Carr, B. J.

2008-01-01

Based on the asymptotic analysis of ordinary differential equations, we classify all spherically symmetric self-similar solutions to the Einstein equations which are asymptotically Friedmann at large distances and contain a perfect fluid with equation of state p=(γ-1)μ with 0<γ<2/3. This corresponds to a “dark energy” fluid and the Friedmann solution is accelerated in this case due to antigravity. This extends the previous analysis of spherically symmetric self-similar solutions for fluids with positive pressure (γ>1). However, in the latter case there is an additional parameter associated with the weak discontinuity at the sonic point and the solutions are only asymptotically “quasi-Friedmann,” in the sense that they exhibit an angle deficit at large distances. In the 0<γ<2/3 case, there is no sonic point and there exists a one-parameter family of solutions which are genuinely asymptotically Friedmann at large distances. We find eight classes of asymptotic behavior: Friedmann or quasi-Friedmann or quasistatic or constant-velocity at large distances, quasi-Friedmann or positive-mass singular or negative-mass singular at small distances, and quasi-Kantowski-Sachs at intermediate distances. The self-similar asymptotically quasistatic and quasi-Kantowski-Sachs solutions are analytically extendible and of great cosmological interest. We also investigate their conformal diagrams. The results of the present analysis are utilized in an accompanying paper to obtain and physically interpret numerical solutions.

Self-similar cosmological solutions with dark energy. I. Formulation and asymptotic analysis

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

Harada, Tomohiro; Maeda, Hideki; Centro de Estudios Cientificos

2008-01-15

Based on the asymptotic analysis of ordinary differential equations, we classify all spherically symmetric self-similar solutions to the Einstein equations which are asymptotically Friedmann at large distances and contain a perfect fluid with equation of state p=({gamma}-1){mu} with 0<{gamma}<2/3. This corresponds to a 'dark energy' fluid and the Friedmann solution is accelerated in this case due to antigravity. This extends the previous analysis of spherically symmetric self-similar solutions for fluids with positive pressure ({gamma}>1). However, in the latter case there is an additional parameter associated with the weak discontinuity at the sonic point and the solutions are only asymptotically 'quasi-Friedmann',more » in the sense that they exhibit an angle deficit at large distances. In the 0<{gamma}<2/3 case, there is no sonic point and there exists a one-parameter family of solutions which are genuinely asymptotically Friedmann at large distances. We find eight classes of asymptotic behavior: Friedmann or quasi-Friedmann or quasistatic or constant-velocity at large distances, quasi-Friedmann or positive-mass singular or negative-mass singular at small distances, and quasi-Kantowski-Sachs at intermediate distances. The self-similar asymptotically quasistatic and quasi-Kantowski-Sachs solutions are analytically extendible and of great cosmological interest. We also investigate their conformal diagrams. The results of the present analysis are utilized in an accompanying paper to obtain and physically interpret numerical solutions.« less

Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults

PubMed Central

Yang, Xiaoxia; Duan, John; Fisher, Jeffrey

2016-01-01

A previously presented physiologically-based pharmacokinetic model for immediate release (IR) methylphenidate (MPH) was extended to characterize the pharmacokinetic behaviors of oral extended release (ER) MPH formulations in adults for the first time. Information on the anatomy and physiology of the gastrointestinal (GI) tract, together with the biopharmaceutical properties of MPH, was integrated into the original model, with model parameters representing hepatic metabolism and intestinal non-specific loss recalibrated against in vitro and in vivo kinetic data sets with IR MPH. A Weibull function was implemented to describe the dissolution of different ER formulations. A variety of mathematical functions can be utilized to account for the engineered release/dissolution technologies to achieve better model performance. The physiological absorption model tracked well the plasma concentration profiles in adults receiving a multilayer-release MPH formulation or Metadate CD, while some degree of discrepancy was observed between predicted and observed plasma concentration profiles for Ritalin LA and Medikinet Retard. A local sensitivity analysis demonstrated that model parameters associated with the GI tract significantly influenced model predicted plasma MPH concentrations, albeit to varying degrees, suggesting the importance of better understanding the GI tract physiology, along with the intestinal non-specific loss of MPH. The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations. PMID:27723791

Can dosage form-dependent food effects be predicted using biorelevant dissolution tests? Case example extended release nifedipine.

PubMed

Andreas, Cord J; Tomaszewska, Irena; Muenster, Uwe; van der Mey, Dorina; Mueck, Wolfgang; Dressman, Jennifer B

2016-08-01

Food intake is known to have various effects on gastrointestinal luminal conditions in terms of transit times, hydrodynamic forces and/or luminal fluid composition and can therefore affect the dissolution behavior of solid oral dosage forms. The aim of this study was to investigate and detect the dosage form-dependent food effect that has been observed for two extended-release formulations of nifedipine using in vitro dissolution tests. Two monolithic extended release formulations, the osmotic pump Adalat® XL 60mg and matrix-type Adalat® Eins 30mg formulation, were investigated with biorelevant dissolution methods using the USP apparatus III and IV under both simulated prandial states, and their corresponding quality control dissolution method. In vitro data were compared to published and unpublished in vivo data using deconvolution-based in vitro - in vivo correlation (IVIVC) approaches. Quality control dissolution methods tended to overestimate the dissolution rate due to the excessive solubilizing capabilities of the sodium dodecyl sulfate (SDS)-containing dissolution media. Using Level II biorelevant media the dosage form dependent food effect for nifedipine was described well when studied with the USP apparatus III, whereas the USP apparatus IV failed to detect the positive food effect for the matrix-type dosage form. It was demonstrated that biorelevant methods can serve as a useful tool during formulation development as they were able to qualitatively reflect the in vivo data. Copyright © 2016 Elsevier B.V. All rights reserved.

Gauge symmetries of the free bosonic string field theory

NASA Astrophysics Data System (ADS)

Neveu, A.; Schwarz, J.; West, P. C.

1985-12-01

The gauge covariant local formulations of free bosonic string theories that contained a finite number of supplementary fields are extended to include an infinite number of supplementary fields. These new formulations allow the generators of the Virasoro algebra to appear on a more equal footing. Permanent address: King's College, Physics Department, London WC2R 2LS, UK.

Response of female Ceratitis capitata (Diptera: Tephritidae) to a spinosad bait and polymer matrix mixture with extended residual effect in Hawaii.

PubMed

Piñero, Jaime C; Souder, Steven K; Gomez, Luis E; Mau, Ronald F L; Vargas, Roger I

2011-12-01

The effectiveness of foliar applications of protein baits against pestiferous fruit flies (Tephritidae) can be adversely affected by a rapid loss of attractive volatile compounds and by rainfall due to the high water solubility of the baits. In a large coffee, Coffea arabica L., plantation in Hawaii with high and low populations of Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), the relative attractiveness of GF-120 NF Naturalyte Fruit Fly Bait as either a 40% (vol:vol) spray solution (= GF-120 NF) or as a formulated proprietary amorphous polymer matrix (= GF-120 APM) was compared. The GF-120 APM formulations contained either, 25, 50, or 75% of GF-120 NF (wt:wt). All baits were tested in association with visually attractive yellow bait stations as a way of standardizing the evaluations. With both high and low C. capitata populations, significantly more females were attracted to the fresh sprayed GF-120 NF than to any of the three fresh GF-120 APM formulations. The attractiveness of GF-120 sprayed decreased significantly after 1 wk, whereas 1-wk-old GF-120 APM formulations were as attractive as similar fresh formulations. GF-120 APM 75% aged for 3 wk outperformed similarly-aged sprayed GF-120 NF with comparatively high C. capitata populations. With low populations, both GF-120 APM 75% and GF-120 APM 50% aged for 2 wk outperformed the similarly aged sprayed GF-120 NF. Combined findings indicate that APM mixed with either 50 or 75% GF-120 applied to bait stations can be attractive to female C. capitata for up to 3 wk longer than the standard sprayed GF-120 NF.

A Variational Formulation of Macro-Particle Algorithms for Kinetic Plasma Simulations

NASA Astrophysics Data System (ADS)

Shadwick, B. A.

2013-10-01

Macro-particle based simulations methods are in widespread use in plasma physics; their computational efficiency and intuitive nature are largely responsible for their longevity. In the main, these algorithms are formulated by approximating the continuous equations of motion. For systems governed by a variational principle (such as collisionless plasmas), approximations of the equations of motion is known to introduce anomalous behavior, especially in system invariants. We present a variational formulation of particle algorithms for plasma simulation based on a reduction of the distribution function onto a finite collection of macro-particles. As in the usual Particle-In-Cell (PIC) formulation, these macro-particles have a definite momentum and are spatially extended. The primary advantage of this approach is the preservation of the link between symmetries and conservation laws. For example, nothing in the reduction introduces explicit time dependence to the system and, therefore, the continuous-time equations of motion exactly conserve energy; thus, these models are free of grid-heating. In addition, the variational formulation allows for constructing models of arbitrary spatial and temporal order. In contrast, the overall accuracy of the usual PIC algorithm is at most second due to the nature of the force interpolation between the gridded field quantities and the (continuous) particle position. Again in contrast to the usual PIC algorithm, here the macro-particle shape is arbitrary; the spatial extent is completely decoupled from both the grid-size and the ``smoothness'' of the shape; smoother particle shapes are not necessarily larger. For simplicity, we restrict our discussion to one-dimensional, non-relativistic, un-magnetized, electrostatic plasmas. We comment on the extension to the electromagnetic case. Supported by the US DoE under contract numbers DE-FG02-08ER55000 and DE-SC0008382.

On the performance of infrared sensors in earth observations

NASA Technical Reports Server (NTRS)

Johnson, L. F.

1972-01-01

The performance of infrared sensing systems is dependent upon the radiative properties of targets in addition to constraints imposed by system components. The unclassified state-of-the-art of infrared system performance figures is reviewed to indicate the relevance to system performance of target radiative properties. A theory of rough surface scattering is developed which allows the formulation of the reflective characteristics of extended targets. The thermal radiation emission from extended targets is formulated on the basis of internal radiation characteristics of natural materials and the transmissive scattering effects at the surface. Finally, the total radiative characteristics may be expressed as functions of material properties and incident and received directions, although the expressions are extremely complex functions and do not account for the effects of shadowing or multiple scattering. It is believed that the theory may be extended to include these effects and to incorporate the local radii of curvature of the surface.

The dynamics and control of large flexible space structures - 13

NASA Technical Reports Server (NTRS)

Bainum, Peter M.; Li, Feiyue; Xu, Jianke

1990-01-01

The optimal control of three-dimensional large angle maneuvers and vibrations of a Shuttle-mast-reflector system is considered. The nonlinear equations of motion are formulated by using Lagrange's formula, with the mast modeled as a continuous beam subject to three-dimensional deformations. Pontryagin's Maximum Principle is applied to the slewing problem, to derive the necessary conditions for the optimal controls, which are bounded by given saturation levels. The resulting two point boundary value problem is then solved by using the quasilinearization algorithm and the method of particular solutions. The study of the large angle maneuvering of the Shuttle-beam-reflector spacecraft in the plane of a circular earth orbit is extended to consider the effects of the structural offset connection, the axial shortening, and the gravitational torque on the slewing motion. Finally the effect of additional design parameters (such as related to additional payload requirement) on the linear quadratic regulator based design of an orbiting control/structural system is examined.

Multi-disciplinary optimization of aeroservoelastic systems

NASA Technical Reports Server (NTRS)

Karpel, Mardechay

1992-01-01

The purpose of the research project was to continue the development of new methods for efficient aeroservoelastic analysis and optimization. The main targets were as follows: to complete the development of analytical tools for the investigation of flutter with large stiffness changes; to continue the work on efficient continuous gust response and sensitivity derivatives; and to advance the techniques of calculating dynamic loads with control and unsteady aerodynamic effects. An efficient and highly accurate mathematical model for time-domain analysis of flutter during which large structural changes occur was developed in cooperation with Carol D. Wieseman of NASA LaRC. The model was based on the second-year work 'Modal Coordinates for Aeroelastic Analysis with Large Local Structural Variations'. The work on continuous gust response was completed. An abstract of the paper 'Continuous Gust Response and Sensitivity Derivatives Using State-Space Models' was submitted for presentation in the 33rd Israel Annual Conference on Aviation and Astronautics, Feb. 1993. The abstract is given in Appendix A. The work extends the optimization model to deal with continuous gust objectives in a way that facilitates their inclusion in the efficient multi-disciplinary optimization scheme. Currently under development is a work designed to extend the analysis and optimization capabilities to loads and stress considerations. The work is on aircraft dynamic loads in response to impulsive and non-impulsive excitation. The work extends the formulations of the mode-displacement and summation-of-forces methods to include modes with significant local distortions, and load modes. An abstract of the paper,'Structural Dynamic Loads in Response to Impulsive Excitation' is given in appendix B. Another work performed this year under the Grant was 'Size-Reduction Techniques for the Determination of Efficient Aeroservoelastic Models' given in Appendix C.

Plasma concentrations of remoxipride and the gastrointestinal transit of 111In-marked extended-release coated spheres

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

Graffner, C.; Wagner, Z.; Nilsson, M.I.

1990-01-01

To explore the oral absorption of remoxipride, spheres of remoxipride were labeled with indium-111 colloid before coating with a release-controlling ethylcellulose membrane. Since the labeling remained inside the coating, it was suitable as a marker. Eight healthy volunteers were given a single dose of 100 mg remoxipride in 111In-marked spheres as a multiple-unit capsule. The radioactivity and the position of the spheres (microcapsules) were followed externally for 30 hr by gamma scintigraphy. Parallel to this, plasma concentrations were drawn for 48 hr to confirm the extended dissolution and absorption of remoxipride. The hard gelatin, multiple-unit capsule released the microcapsules withinmore » the stomach. These were then rapidly emptied into the small intestine, within 0.5-1 hr. There was then an immediate distribution in the upper small intestine before collection in the lower portion, within 2-5 hr. After passing into the large intestine, there was again extended distribution of the microcapsules. A mean Cmax of 2.7 microM remoxipride was achieved 4 hr after drug administration and a mean AUC of 26.1 mumol.L-1.hr was achieved. Judging from the absorption versus time profile, calculated according to the Wagner-Nelson method, and the scintigraphic images, it is concluded that the main absorption occurs from the small intestine. Data from four volunteers, however, indicated a comparatively good absorption also from the large intestine. Due to the good absorption properties, it is reasonable to expect a low variation in the extent of bioavailability of remoxipride after administration in an extended-release, multiple-unit capsule formulation.« less

On the development of a semi-nonparametric generalized multinomial logit model for travel-related choices

PubMed Central

Ye, Xin; Pendyala, Ram M.; Zou, Yajie

2017-01-01

A semi-nonparametric generalized multinomial logit model, formulated using orthonormal Legendre polynomials to extend the standard Gumbel distribution, is presented in this paper. The resulting semi-nonparametric function can represent a probability density function for a large family of multimodal distributions. The model has a closed-form log-likelihood function that facilitates model estimation. The proposed method is applied to model commute mode choice among four alternatives (auto, transit, bicycle and walk) using travel behavior data from Argau, Switzerland. Comparisons between the multinomial logit model and the proposed semi-nonparametric model show that violations of the standard Gumbel distribution assumption lead to considerable inconsistency in parameter estimates and model inferences. PMID:29073152

On the development of a semi-nonparametric generalized multinomial logit model for travel-related choices.

PubMed

Wang, Ke; Ye, Xin; Pendyala, Ram M; Zou, Yajie

2017-01-01

A semi-nonparametric generalized multinomial logit model, formulated using orthonormal Legendre polynomials to extend the standard Gumbel distribution, is presented in this paper. The resulting semi-nonparametric function can represent a probability density function for a large family of multimodal distributions. The model has a closed-form log-likelihood function that facilitates model estimation. The proposed method is applied to model commute mode choice among four alternatives (auto, transit, bicycle and walk) using travel behavior data from Argau, Switzerland. Comparisons between the multinomial logit model and the proposed semi-nonparametric model show that violations of the standard Gumbel distribution assumption lead to considerable inconsistency in parameter estimates and model inferences.

Computation of Pressurized Gas Bearings Using CE/SE Method

NASA Technical Reports Server (NTRS)

Cioc, Sorin; Dimofte, Florin; Keith, Theo G., Jr.; Fleming, David P.

2003-01-01

The space-time conservation element and solution element (CE/SE) method is extended to compute compressible viscous flows in pressurized thin fluid films. This numerical scheme has previously been used successfully to solve a wide variety of compressible flow problems, including flows with large and small discontinuities. In this paper, the method is applied to calculate the pressure distribution in a hybrid gas journal bearing. The formulation of the problem is presented, including the modeling of the feeding system. the numerical results obtained are compared with experimental data. Good agreement between the computed results and the test data were obtained, and thus validate the CE/SE method to solve such problems.

Phase-field modelling of ductile fracture: a variational gradient-extended plasticity-damage theory and its micromorphic regularization.

PubMed

Miehe, C; Teichtmeister, S; Aldakheel, F

2016-04-28

This work outlines a novel variational-based theory for the phase-field modelling of ductile fracture in elastic-plastic solids undergoing large strains. The phase-field approach regularizes sharp crack surfaces within a pure continuum setting by a specific gradient damage modelling. It is linked to a formulation of gradient plasticity at finite strains. The framework includes two independent length scales which regularize both the plastic response as well as the crack discontinuities. This ensures that the damage zones of ductile fracture are inside of plastic zones, and guarantees on the computational side a mesh objectivity in post-critical ranges. © 2016 The Author(s).

Galilean invariant resummation schemes of cosmological perturbations

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

Peloso, Marco; Pietroni, Massimo, E-mail: peloso@physics.umn.edu, E-mail: massimo.pietroni@unipr.it

2017-01-01

Many of the methods proposed so far to go beyond Standard Perturbation Theory break invariance under time-dependent boosts (denoted here as extended Galilean Invariance, or GI). This gives rise to spurious large scale effects which spoil the small scale predictions of these approximation schemes. By using consistency relations we derive fully non-perturbative constraints that GI imposes on correlation functions. We then introduce a method to quantify the amount of GI breaking of a given scheme, and to correct it by properly tailored counterterms. Finally, we formulate resummation schemes which are manifestly GI, discuss their general features, and implement them inmore » the so called Time-Flow, or TRG, equations.« less

Robust Rocket Engine Concept

NASA Technical Reports Server (NTRS)

Lorenzo, Carl F.

1995-01-01

The potential for a revolutionary step in the durability of reusable rocket engines is made possible by the combination of several emerging technologies. The recent creation and analytical demonstration of life extending (or damage mitigating) control technology enables rapid rocket engine transients with minimum fatigue and creep damage. This technology has been further enhanced by the formulation of very simple but conservative continuum damage models. These new ideas when combined with recent advances in multidisciplinary optimization provide the potential for a large (revolutionary) step in reusable rocket engine durability. This concept has been named the robust rocket engine concept (RREC) and is the basic contribution of this paper. The concept also includes consideration of design innovations to minimize critical point damage.

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

PubMed

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

2016-12-01

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

Assimilating data into open ocean tidal models

NASA Astrophysics Data System (ADS)

Kivman, Gennady A.

The problem of deriving tidal fields from observations by reason of incompleteness and imperfectness of every data set practically available has an infinitely large number of allowable solutions fitting the data within measurement errors and hence can be treated as ill-posed. Therefore, interpolating the data always relies on some a priori assumptions concerning the tides, which provide a rule of sampling or, in other words, a regularization of the ill-posed problem. Data assimilation procedures used in large scale tide modeling are viewed in a common mathematical framework as such regularizations. It is shown that they all (basis functions expansion, parameter estimation, nudging, objective analysis, general inversion, and extended general inversion), including those (objective analysis and general inversion) originally formulated in stochastic terms, may be considered as utilizations of one of the three general methods suggested by the theory of ill-posed problems. The problem of grid refinement critical for inverse methods and nudging is discussed.

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…

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.

Global localization of 3D point clouds in building outline maps of urban outdoor environments.

PubMed

Landsiedel, Christian; Wollherr, Dirk

2017-01-01

This paper presents a method to localize a robot in a global coordinate frame based on a sparse 2D map containing outlines of building and road network information and no location prior information. Its input is a single 3D laser scan of the surroundings of the robot. The approach extends the generic chamfer matching template matching technique from image processing by including visibility analysis in the cost function. Thus, the observed building planes are matched to the expected view of the corresponding map section instead of to the entire map, which makes a more accurate matching possible. Since this formulation operates on generic edge maps from visual sensors, the matching formulation can be expected to generalize to other input data, e.g., from monocular or stereo cameras. The method is evaluated on two large datasets collected in different real-world urban settings and compared to a baseline method from literature and to the standard chamfer matching approach, where it shows considerable performance benefits, as well as the feasibility of global localization based on sparse building outline data.

Adjacent-Categories Mokken Models for Rater-Mediated Assessments

PubMed Central

Wind, Stefanie A.

2016-01-01

Molenaar extended Mokken’s original probabilistic-nonparametric scaling models for use with polytomous data. These polytomous extensions of Mokken’s original scaling procedure have facilitated the use of Mokken scale analysis as an approach to exploring fundamental measurement properties across a variety of domains in which polytomous ratings are used, including rater-mediated educational assessments. Because their underlying item step response functions (i.e., category response functions) are defined using cumulative probabilities, polytomous Mokken models can be classified as cumulative models based on the classifications of polytomous item response theory models proposed by several scholars. In order to permit a closer conceptual alignment with educational performance assessments, this study presents an adjacent-categories variation on the polytomous monotone homogeneity and double monotonicity models. Data from a large-scale rater-mediated writing assessment are used to illustrate the adjacent-categories approach, and results are compared with the original formulations. Major findings suggest that the adjacent-categories models provide additional diagnostic information related to individual raters’ use of rating scale categories that is not observed under the original formulation. Implications are discussed in terms of methods for evaluating rating quality. PMID:29795916

Transdermal glimepiride delivery system based on optimized ethosomal nano-vesicles: Preparation, characterization, in vitro, ex vivo and clinical evaluation.

PubMed

Ahmed, Tarek A; El-Say, Khalid M; Aljaeid, Bader M; Fahmy, Usama A; Abd-Allah, Fathy I

2016-03-16

This work aimed to develop an optimized ethosomal formulation of glimepiride then loading into transdermal films to offer lower drug side effect, extended release behavior and avoid first pass effect. Four formulation factors were optimized for their effects on vesicle size (Y1), entrapment efficiency (Y2) and vesicle flexibility (Y3). Optimum desirability was identified and, an optimized formulation was prepared, characterized and loaded into transdermal films. Ex-vivo permeation study for the prepared films was conducted and, the permeation parameters and drug permeation mechanism were identified. Penetration through rat skin was studied using confocal laser microscope. In-vivo study was performed following transdermal application on human volunteers. The percent of alcohol was significantly affecting all the studied responses while the other factors and their interaction effects were varied on their effects on each response. The optimized ethosomal formulation showed observed values for Y1, Y2 and Y3 of 61 nm, 97.12% and 54.03, respectively. Ex-vivo permeation of films loaded with optimized ethosomal formulation was superior to that of the corresponding pure drug transdermal films and this finding was also confirmed after confocal laser microscope study. Permeation of glimepiride from the prepared films was in favor of Higushi-diffusion model and exhibited non-Fickian or anomalous release mechanism. In-vivo study revealed extended drug release behavior and lower maximum drug plasma level from transdermal films loaded with drug ethosomal formulation. So, the ethosomal formulation could be considered a suitable drug delivery system especially when loaded into transdermal vehicle with possible reduction in side effects and controlling the drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2004-01-01

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

Preparation and in vitro and in vivo evaluation of HupA PLGA microsphere.

PubMed

Ye, Liang; Fu, Fenghua; Liu, Wanhui; Sun, Kaoxiang; Li, Youxin; He, Jie; Yu, Xin; Yu, Pengfei; Tian, Jingwei

2013-03-01

Acetylcholinesterase inhibitors (AChEIs), including Huperzine A (HupA), have been the mainstay of treatment for Alzheimer's disease (AD). However, AChEIs can cause gastrointestinal side effects, which has been related to the high Cmax and short tmax after oral administration. Clinical trials have verified that extended-release formulation with lower Cmax and prolonged tmax, such as rivastigmine patch, could perform a similar efficacy with significantly improved tolerability compared with the oral formulations. In this study, we developed an extended-release microspheres formulation of HupA (called as HAM) with poly(lactide-co-glycolide) (PLGA) as drug carrier. HAM has showed the loading rate as 1.35% (w/w) and yielded 42% with mean particle size at 72.6 μm. In vitro and in vivo pharmacokinetics studies have showed that HAM produced a relatively smooth and continuous drug concentration in 14 days. Furthermore, in vivo pharmacokinetics data have demonstrated that the Cmax was lower and the tmax was considerably later in single intramuscular administration of HAM (1,000 μg/kg) than the counterparts in single intragastric administration of HAT (75 μg/kg/d). Meanwhile, HAM has performed a continuous inhibition to brain AChE activity in normal rats and improvement of memory deficit in Aβ1-40 i.c.v. infused AD rat model for 14 days. The results have suggested that HAM has performed good extended-release properties and good prolonged pharmacological efficacy in vivo in the 2-week period, and could exert a similar efficacy with significantly lowered gastrointestinal side effects as compared with oral formulation.

Bilayer tablets of Paliperidone for Extended release osmotic drug delivery

NASA Astrophysics Data System (ADS)

Chowdary, K. Sunil; Napoleon, A. A.

2017-11-01

The purpose of this study is to develop and optimize the formulation of paliperidone bilayer tablet core and coating which should meet in vitro performance of trilayered Innovator sample Invega. Optimization of core formulations prepared by different ratio of polyox grades and optimization of coating of (i) sub-coating build-up with hydroxy ethyl cellulose (HEC) and (ii).enteric coating build-up with cellulose acetate (CA). Some important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviours of Paliperidone. In vitro dissolution studies of Innovator sample (Invega) with formulations of different release rate which ever close release pattern during the whole 24 h test is finalized.

A T Matrix Method Based upon Scalar Basis Functions

NASA Technical Reports Server (NTRS)

Mackowski, D.W.; Kahnert, F. M.; Mishchenko, Michael I.

2013-01-01

A surface integral formulation is developed for the T matrix of a homogenous and isotropic particle of arbitrary shape, which employs scalar basis functions represented by the translation matrix elements of the vector spherical wave functions. The formulation begins with the volume integral equation for scattering by the particle, which is transformed so that the vector and dyadic components in the equation are replaced with associated dipole and multipole level scalar harmonic wave functions. The approach leads to a volume integral formulation for the T matrix, which can be extended, by use of Green's identities, to the surface integral formulation. The result is shown to be equivalent to the traditional surface integral formulas based on the VSWF basis.

Heterogeneity in the pharmacodynamics of two long-acting methylphenidate formulations for children with attention deficit/hyperactivity disorder. A growth mixture modelling analysis.

PubMed

Sonuga-Barke, Edmund J S; Van Lier, Pol; Swanson, James M; Coghill, David; Wigal, Sharon; Vandenberghe, Mieke; Hatch, Simon

2008-06-01

To use growth mixture modelling (GMM) to identify subgroups of children with attention deficit hyperactive disorder (ADHD) who have different pharmacodynamic profiles in response to extended release methylphenidate as assessed in a laboratory classroom setting. GMM analysis was performed on data from the COMACS study (Comparison of Methylphenidates in the Analog Classroom Setting): a large (n = 184) placebo-controlled cross-over study comparing three treatment conditions in the Laboratory School Protocol (with a 1.5-h cycle of attention and deportment assessments). Two orally administered, once-daily methylphenidate (MPH) bioequivalent formulations [Metadate CD/Equasym XL (MCD-EQXL) and Concerta XL (CON)] were compared with placebo (PLA). Three classes of children with distinct severity profiles in the PLA condition were identified. For both MCD-EQXL and CON, the more severe their PLA symptoms the better, the children's response. However, the formulations produced different growth curves by class, with CON having essentially a flat profile for all three classes (i.e. no effect of PLA severity) and MCD-EQXL showing a marked decline in symptoms immediately post-dosing in the two most severe classes compared with the least severe. Comparison of daily doses matched for immediate-release (IR) components accounted for this difference. The results suggest considerable heterogeneity in the pharmacodynamics of MPH response by children with ADHD. When treatment response for near-equal, bioequivalent daily doses the two formulations was compared, marked differences were seen for children in the most severe classes with a strong curvilinear trajectory for MCD-EQXL related to the greater IR component.

A Class of High-Resolution Explicit and Implicit Shock-Capturing Methods

NASA Technical Reports Server (NTRS)

Yee, H. C.

1994-01-01

The development of shock-capturing finite difference methods for hyperbolic conservation laws has been a rapidly growing area for the last decade. Many of the fundamental concepts, state-of-the-art developments and applications to fluid dynamics problems can only be found in meeting proceedings, scientific journals and internal reports. This paper attempts to give a unified and generalized formulation of a class of high-resolution, explicit and implicit shock capturing methods, and to illustrate their versatility in various steady and unsteady complex shock waves, perfect gases, equilibrium real gases and nonequilibrium flow computations. These numerical methods are formulated for the purpose of ease and efficient implementation into a practical computer code. The various constructions of high-resolution shock-capturing methods fall nicely into the present framework and a computer code can be implemented with the various methods as separate modules. Included is a systematic overview of the basic design principle of the various related numerical methods. Special emphasis will be on the construction of the basic nonlinear, spatially second and third-order schemes for nonlinear scalar hyperbolic conservation laws and the methods of extending these nonlinear scalar schemes to nonlinear systems via the approximate Riemann solvers and flux-vector splitting approaches. Generalization of these methods to efficiently include real gases and large systems of nonequilibrium flows will be discussed. Some perbolic conservation laws to problems containing stiff source terms and terms and shock waves are also included. The performance of some of these schemes is illustrated by numerical examples for one-, two- and three-dimensional gas-dynamics problems. The use of the Lax-Friedrichs numerical flux to obtain high-resolution shock-capturing schemes is generalized. This method can be extended to nonlinear systems of equations without the use of Riemann solvers or flux-vector splitting approaches and thus provides a large savings for multidimensional, equilibrium real gases and nonequilibrium flow computations.

Flux Jacobian Matrices For Equilibrium Real Gases

NASA Technical Reports Server (NTRS)

Vinokur, Marcel

1990-01-01

Improved formulation includes generalized Roe average and extension to three dimensions. Flux Jacobian matrices derived for use in numerical solutions of conservation-law differential equations of inviscid flows of ideal gases extended to real gases. Real-gas formulation of these matrices retains simplifying assumptions of thermodynamic and chemical equilibrium, but adds effects of vibrational excitation, dissociation, and ionization of gas molecules via general equation of state.

Large time-step stability of explicit one-dimensional advection schemes

NASA Technical Reports Server (NTRS)

Leonard, B. P.

1993-01-01

There is a wide-spread belief that most explicit one-dimensional advection schemes need to satisfy the so-called 'CFL condition' - that the Courant number, c = udelta(t)/delta(x), must be less than or equal to one, for stability in the von Neumann sense. This puts severe limitations on the time-step in high-speed, fine-grid calculations and is an impetus for the development of implicit schemes, which often require less restrictive time-step conditions for stability, but are more expensive per time-step. However, it turns out that, at least in one dimension, if explicit schemes are formulated in a consistent flux-based conservative finite-volume form, von Neumann stability analysis does not place any restriction on the allowable Courant number. Any explicit scheme that is stable for c is less than 1, with a complex amplitude ratio, G(c), can be easily extended to arbitrarily large c. The complex amplitude ratio is then given by exp(- (Iota)(Nu)(Theta)) G(delta(c)), where N is the integer part of c, and delta(c) = c - N (less than 1); this is clearly stable. The CFL condition is, in fact, not a stability condition at all, but, rather, a 'range restriction' on the 'pieces' in a piece-wise polynomial interpolation. When a global view is taken of the interpolation, the need for a CFL condition evaporates. A number of well-known explicit advection schemes are considered and thus extended to large delta(t). The analysis also includes a simple interpretation of (large delta(t)) total-variation-diminishing (TVD) constraints.

The cost effectiveness of long-acting/extended-release antipsychotics for the treatment of schizophrenia: a systematic review of economic evaluations.

PubMed

Achilla, Evanthia; McCrone, Paul

2013-04-01

Antipsychotic medication is the mainstay of treatment in schizophrenia. Long-acting medication has potential advantages over daily medication in improving compliance and thus reducing hospitalization and relapse rates. The high acquisition and administration costs of such formulations raise the need for pharmacoeconomic evaluation. The aim of this article is to provide a comprehensive review of the available evidence on the cost effectiveness of long-acting/extended-release antipsychotic medication and critically appraise the strength of evidence reported in the studies from a methodological viewpoint. Relevant studies were identified by searching five electronic databases: PsycINFO, MEDLINE, EMBASE, the NHS Economic Evaluation Database and the Health Technology Assessment database (HTA). Search terms included, but were not limited to, 'long-acting injection', 'economic evaluation', 'cost-effectiveness' and 'cost-utility'. No limits were applied for publication dates and language. Full economic evaluations on long-acting/extended-release antipsychotics were eligible for inclusion. Observational studies and clinical trials were also checked for cost-effectiveness information. Conference abstracts and poster presentations on the cost effectiveness of long-acting antipsychotics were excluded. Thirty-two percent of identified studies met the selection criteria. Pertinent abstracts were reviewed independently by two reviewers. Relevant studies underwent data extraction by one reviewer and were checked by a second, with any discrepancies being clarified during consensus meetings. Eligible studies were assessed for methodological quality using the quality checklist for economic studies recommended by the NICE guideline on interventions in the treatment and management of schizophrenia. After applying the selection criteria, the final sample consisted of 28 studies. The majority of studies demonstrated that risperidone long-acting injection, relative to oral or other long-acting injectable drugs, was associated with cost savings and additional clinical benefits and was the dominant strategy in terms of cost effectiveness. However, olanzapine in either oral or long-acting injectable formulation dominated risperidone long-acting injection in a Slovenian and a US study. Furthermore, in two UK studies, the use of long-acting risperidone increased the hospitalization days and overall healthcare costs, relative to other atypical or typical long-acting antipsychotics. Finally, paliperidone extended-release was the most cost-effective treatment compared with atypical oral or typical long-acting formulations. From a methodological viewpoint, most studies employed decision analytic models, presented results using average cost-effectiveness ratios and conducted comprehensive sensitivity analyses to test the robustness of the results. Variations in study methodologies restrict consistent and direct comparisons across countries. The exclusion of a large body of potentially relevant conference abstracts as well as some papers being unobtainable may have increased the likelihood of misrepresenting the overall cost effectiveness of long-acting antipsychotics. Finally, the review process was restricted to qualitative assessment rather than a quantitative synthesis of results, which could provide more robust conclusions. Atypical long-acting (especially risperidone)/extended-release antipsychotic medication is likely to be a cost-effective, first-line strategy for managing schizophrenia, compared with long-acting haloperidol and other oral or depot formulations, irrespective of country-specific differences. However, inconsistencies in study methodologies and in the reporting of study findings suggest caution needs to be applied in interpreting these findings.

XFEM modeling of hydraulic fracture in porous rocks with natural fractures

NASA Astrophysics Data System (ADS)

Wang, Tao; Liu, ZhanLi; Zeng, QingLei; Gao, Yue; Zhuang, Zhuo

2017-08-01

Hydraulic fracture (HF) in porous rocks is a complex multi-physics coupling process which involves fluid flow, diffusion and solid deformation. In this paper, the extended finite element method (XFEM) coupling with Biot theory is developed to study the HF in permeable rocks with natural fractures (NFs). In the recent XFEM based computational HF models, the fluid flow in fractures and interstitials of the porous media are mostly solved separately, which brings difficulties in dealing with complex fracture morphology. In our new model the fluid flow is solved in a unified framework by considering the fractures as a kind of special porous media and introducing Poiseuille-type flow inside them instead of Darcy-type flow. The most advantage is that it is very convenient to deal with fluid flow inside the complex fracture network, which is important in shale gas extraction. The weak formulation for the new coupled model is derived based on virtual work principle, which includes the XFEM formulation for multiple fractures and fractures intersection in porous media and finite element formulation for the unified fluid flow. Then the plane strain Kristianovic-Geertsma-de Klerk (KGD) model and the fluid flow inside the fracture network are simulated to validate the accuracy and applicability of this method. The numerical results show that large injection rate, low rock permeability and isotropic in-situ stresses tend to lead to a more uniform and productive fracture network.

Self-organizing map analysis using multivariate data from theophylline tablets predicted by a thin-plate spline interpolation.

PubMed

Yasuda, Akihito; Onuki, Yoshinori; Obata, Yasuko; Yamamoto, Rie; Takayama, Kozo

2013-01-01

The "quality by design" concept in pharmaceutical formulation development requires the establishment of a science-based rationale and a design space. We integrated thin-plate spline (TPS) interpolation and Kohonen's self-organizing map (SOM) to visualize the latent structure underlying causal factors and pharmaceutical responses. As a model pharmaceutical product, theophylline tablets were prepared based on a standard formulation. The tensile strength, disintegration time, and stability of these variables were measured as response variables. These responses were predicted quantitatively based on nonlinear TPS. A large amount of data on these tablets was generated and classified into several clusters using an SOM. The experimental values of the responses were predicted with high accuracy, and the data generated for the tablets were classified into several distinct clusters. The SOM feature map allowed us to analyze the global and local correlations between causal factors and tablet characteristics. The results of this study suggest that increasing the proportion of microcrystalline cellulose (MCC) improved the tensile strength and the stability of tensile strength of these theophylline tablets. In addition, the proportion of MCC has an optimum value for disintegration time and stability of disintegration. Increasing the proportion of magnesium stearate extended disintegration time. Increasing the compression force improved tensile strength, but degraded the stability of disintegration. This technique provides a better understanding of the relationships between causal factors and pharmaceutical responses in theophylline tablet formulations.

Bounded Hamiltonian in the Fourth-Order Extension of the Chern-Simons Theory

NASA Astrophysics Data System (ADS)

Abakumova, V. A.; Kaparulin, D. S.; Lyakhovich, S. L.

2018-04-01

The problem of constructing alternative Hamiltonian formulations in the extended Chern-Simons theory with higher derivatives is considered. It is shown that the fourth-order extended theory admits a four-parameter series of alternative Hamiltonians which can be bounded from below, even if the canonical energy of the model is unbounded from below.

Terminology challenges: defining modified release dosage forms in veterinary medicine.

PubMed

Martinez, Marilyn N; Lindquist, Danielle; Modric, Sanja

2010-08-01

Terminologies for describing dosage form release characteristics for human pharmaceuticals have been addressed by bodies such as the US Food and Drug Administration (FDA), the International Conference on Harmonization (ICH), and the US Pharmacopeia (USP). While the definition for terms such as "immediate release," "modified release," "extended release," and "delayed release" are now well accepted for human pharmaceuticals, confusion still exists within the veterinary community. In part, this confusion is attributable to differences between human and veterinary dosage forms (such as the preponderance of parenteral vs. oral extended release products for use in animals vs. the focus on oral extended release formulations for human use) which reflect interspecies differences in physiology and conditions of use. It also simply reflects a lack of attention to existing definitions. In an effort to remedy this problem, this manuscript reflects an initial effort to suggest definitions that may be appropriate for describing formulation effects in veterinary medicine. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Extended Lagrangian Excited State Molecular Dynamics

DOE PAGES

Bjorgaard, Josiah August; Sheppard, Daniel Glen; Tretiak, Sergei; ...

2018-01-09

In this work, an extended Lagrangian framework for excited state molecular dynamics (XL-ESMD) using time-dependent self-consistent field theory is proposed. The formulation is a generalization of the extended Lagrangian formulations for ground state Born–Oppenheimer molecular dynamics [Phys. Rev. Lett. 2008 100, 123004]. The theory is implemented, demonstrated, and evaluated using a time-dependent semiempirical model, though it should be generally applicable to ab initio theory. The simulations show enhanced energy stability and a significantly reduced computational cost associated with the iterative solutions of both the ground state and the electronically excited states. Relaxed convergence criteria can therefore be used both formore » the self-consistent ground state optimization and for the iterative subspace diagonalization of the random phase approximation matrix used to calculate the excited state transitions. In conclusion, the XL-ESMD approach is expected to enable numerically efficient excited state molecular dynamics for such methods as time-dependent Hartree–Fock (TD-HF), Configuration Interactions Singles (CIS), and time-dependent density functional theory (TD-DFT).« less

Extended Lagrangian Excited State Molecular Dynamics

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

Bjorgaard, Josiah August; Sheppard, Daniel Glen; Tretiak, Sergei

In this work, an extended Lagrangian framework for excited state molecular dynamics (XL-ESMD) using time-dependent self-consistent field theory is proposed. The formulation is a generalization of the extended Lagrangian formulations for ground state Born–Oppenheimer molecular dynamics [Phys. Rev. Lett. 2008 100, 123004]. The theory is implemented, demonstrated, and evaluated using a time-dependent semiempirical model, though it should be generally applicable to ab initio theory. The simulations show enhanced energy stability and a significantly reduced computational cost associated with the iterative solutions of both the ground state and the electronically excited states. Relaxed convergence criteria can therefore be used both formore » the self-consistent ground state optimization and for the iterative subspace diagonalization of the random phase approximation matrix used to calculate the excited state transitions. In conclusion, the XL-ESMD approach is expected to enable numerically efficient excited state molecular dynamics for such methods as time-dependent Hartree–Fock (TD-HF), Configuration Interactions Singles (CIS), and time-dependent density functional theory (TD-DFT).« less

Extended Lagrangian Excited State Molecular Dynamics.

PubMed

Bjorgaard, J A; Sheppard, D; Tretiak, S; Niklasson, A M N

2018-02-13

An extended Lagrangian framework for excited state molecular dynamics (XL-ESMD) using time-dependent self-consistent field theory is proposed. The formulation is a generalization of the extended Lagrangian formulations for ground state Born-Oppenheimer molecular dynamics [Phys. Rev. Lett. 2008 100, 123004]. The theory is implemented, demonstrated, and evaluated using a time-dependent semiempirical model, though it should be generally applicable to ab initio theory. The simulations show enhanced energy stability and a significantly reduced computational cost associated with the iterative solutions of both the ground state and the electronically excited states. Relaxed convergence criteria can therefore be used both for the self-consistent ground state optimization and for the iterative subspace diagonalization of the random phase approximation matrix used to calculate the excited state transitions. The XL-ESMD approach is expected to enable numerically efficient excited state molecular dynamics for such methods as time-dependent Hartree-Fock (TD-HF), Configuration Interactions Singles (CIS), and time-dependent density functional theory (TD-DFT).

Nonlinear programming extensions to rational function approximation methods for unsteady aerodynamic forces

NASA Technical Reports Server (NTRS)

Tiffany, Sherwood H.; Adams, William M., Jr.

1988-01-01

The approximation of unsteady generalized aerodynamic forces in the equations of motion of a flexible aircraft are discussed. Two methods of formulating these approximations are extended to include the same flexibility in constraining the approximations and the same methodology in optimizing nonlinear parameters as another currently used extended least-squares method. Optimal selection of nonlinear parameters is made in each of the three methods by use of the same nonlinear, nongradient optimizer. The objective of the nonlinear optimization is to obtain rational approximations to the unsteady aerodynamics whose state-space realization is lower order than that required when no optimization of the nonlinear terms is performed. The free linear parameters are determined using the least-squares matrix techniques of a Lagrange multiplier formulation of an objective function which incorporates selected linear equality constraints. State-space mathematical models resulting from different approaches are described and results are presented that show comparative evaluations from application of each of the extended methods to a numerical example.

Universal Local Symmetries and Nonsuperposition in Classical Mechanics

NASA Astrophysics Data System (ADS)

Gozzi, Ennio; Pagani, Carlo

2010-10-01

In the Hilbert space formulation of classical mechanics, pioneered by Koopman and von Neumann, there are potentially more observables than in the standard approach to classical mechanics. In this Letter, we show that actually many of those extra observables are not invariant under a set of universal local symmetries which appear once the Koopman and von Neumann formulation is extended to include the evolution of differential forms. Because of their noninvariance, those extra observables have to be removed. This removal makes the superposition of states in the Koopman and von Neumann formulation, and as a consequence also in classical mechanics, impossible.

Thermal and quantum fluctuations of confined Bose–Einstein condensate beyond the Bogoliubov approximation

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

Nakamura, Y., E-mail: yusuke.n@asagi.waseda.jp; Nagano Prefectural Kiso Seiho High School, Nagano 397-8571; Kawaguchi, T., E-mail: pionelish30@toki.waseda.jp

The formulation for zero mode of a Bose–Einstein condensate beyond the Bogoliubov approximation at zero temperature [Y. Nakamura et al., Phys. Rev. A 89 (2014) 013613] is extended to finite temperature. Both thermal and quantum fluctuations are considered in a manner consistent with a concept of spontaneous symmetry breakdown for a finite-size system. Therefore, we need a proper treatment of the zero mode operators, which invoke non-trivial enhancements in depletion condensate and thermodynamical quantities such as the specific heat. The enhancements are visible in the weak interaction case. Our approach reproduces the results of a homogeneous system in the Bogoliubovmore » approximation in a large particle number limit.« less

Saliva Preservative for Diagnostic Purposes

NASA Technical Reports Server (NTRS)

Pierson, Duane L.; Mehta, Satish K.

2012-01-01

Saliva is an important body fluid for diagnostic purposes. Glycoproteins, glucose, steroids, DNA, and other molecules of diagnostic value are found in saliva. It is easier to collect as compared to blood or urine. Unfortunately, saliva also contains large numbers of bacteria that can release enzymes, which can degrade proteins and nucleic acids. These degradative enzymes destroy or reduce saliva s diagnostic value. This innovation describes the formulation of a chemical preservative that prevents microbial growth and inactivates the degradative enzymes. This extends the time that saliva can be stored or transported without losing its diagnostic value. Multiple samples of saliva can be collected if needed without causing discomfort to the subject and it does not require any special facilities to handle after it is collected.

Comparing Consider-Covariance Analysis with Sigma-Point Consider Filter and Linear-Theory Consider Filter Formulations

NASA Technical Reports Server (NTRS)

Lisano, Michael E.

2007-01-01

Recent literature in applied estimation theory reflects growing interest in the sigma-point (also called unscented ) formulation for optimal sequential state estimation, often describing performance comparisons with extended Kalman filters as applied to specific dynamical problems [c.f. 1, 2, 3]. Favorable attributes of sigma-point filters are described as including a lower expected error for nonlinear even non-differentiable dynamical systems, and a straightforward formulation not requiring derivation or implementation of any partial derivative Jacobian matrices. These attributes are particularly attractive, e.g. in terms of enabling simplified code architecture and streamlined testing, in the formulation of estimators for nonlinear spaceflight mechanics systems, such as filter software onboard deep-space robotic spacecraft. As presented in [4], the Sigma-Point Consider Filter (SPCF) algorithm extends the sigma-point filter algorithm to the problem of consider covariance analysis. Considering parameters in a dynamical system, while estimating its state, provides an upper bound on the estimated state covariance, which is viewed as a conservative approach to designing estimators for problems of general guidance, navigation and control. This is because, whether a parameter in the system model is observable or not, error in the knowledge of the value of a non-estimated parameter will increase the actual uncertainty of the estimated state of the system beyond the level formally indicated by the covariance of an estimator that neglects errors or uncertainty in that parameter. The equations for SPCF covariance evolution are obtained in a fashion similar to the derivation approach taken with standard (i.e. linearized or extended) consider parameterized Kalman filters (c.f. [5]). While in [4] the SPCF and linear-theory consider filter (LTCF) were applied to an illustrative linear dynamics/linear measurement problem, in the present work examines the SPCF as applied to nonlinear sequential consider covariance analysis, i.e. in the presence of nonlinear dynamics and nonlinear measurements. A simple SPCF for orbit determination, exemplifying an algorithm hosted in the guidance, navigation and control (GN&C) computer processor of a hypothetical robotic spacecraft, was implemented, and compared with an identically-parameterized (standard) extended, consider-parameterized Kalman filter. The onboard filtering scenario examined is a hypothetical spacecraft orbit about a small natural body with imperfectly-known mass. The formulations, relative complexities, and performances of the filters are compared and discussed.

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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

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.

LATDYN - PROGRAM FOR SIMULATION OF LARGE ANGLE TRANSIENT DYNAMICS OF FLEXIBLE AND RIGID STRUCTURES

NASA Technical Reports Server (NTRS)

Housner, J. M.

1994-01-01

LATDYN is a computer code for modeling the Large Angle Transient DYNamics of flexible articulating structures and mechanisms involving joints about which members rotate through large angles. LATDYN extends and brings together some of the aspects of Finite Element Structural Analysis, Multi-Body Dynamics, and Control System Analysis; three disciplines that have been historically separate. It combines significant portions of their distinct capabilities into one single analysis tool. The finite element formulation for flexible bodies in LATDYN extends the conventional finite element formulation by using a convected coordinate system for constructing the equation of motion. LATDYN's formulation allows for large displacements and rotations of finite elements subject to the restriction that deformations within each are small. Also, the finite element approach implemented in LATDYN provides a convergent path for checking solutions simply by increasing mesh density. For rigid bodies and joints LATDYN borrows extensively from methodology used in multi-body dynamics where rigid bodies may be defined and connected together through joints (hinges, ball, universal, sliders, etc.). Joints may be modeled either by constraints or by adding joint degrees of freedom. To eliminate error brought about by the separation of structural analysis and control analysis, LATDYN provides symbolic capabilities for modeling control systems which are integrated with the structural dynamic analysis itself. Its command language contains syntactical structures which perform symbolic operations which are also interfaced directly with the finite element structural model, bypassing the modal approximation. Thus, when the dynamic equations representing the structural model are integrated, the equations representing the control system are integrated along with them as a coupled system. This procedure also has the side benefit of enabling a dramatic simplification of the user interface for modeling control systems. Three FORTRAN computer programs, the LATDYN Program, the Preprocessor, and the Postprocessor, make up the collective LATDYN System. The Preprocessor translates user commands into a form which can be used while the LATDYN program provides the computational core. The Postprocessor allows the user to interactively plot and manage a database of LATDYN transient analysis results. It also includes special facilities for modeling control systems and for programming changes to the model which take place during analysis sequence. The documentation includes a Demonstration Problem Manual for the evaluation and verification of results and a Postprocessor guide. Because the program should be viewed as a byproduct of research on technology development, LATDYN's scope is limited. It does not have a wide library of finite elements, and 3-D Graphics are not available. Nevertheless, it does have a measure of "user friendliness". The LATDYN program was developed over a period of several years and was implemented on a CDC NOS/VE & Convex Unix computer. It is written in FORTRAN 77 and has a virtual memory requirement of 1.46 MB. The program was validated on a DEC MICROVAX operating under VMS 5.2.

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…

An Extended Optional Infinitive Stage in German-Speaking Children with Specific Language Impairment.

ERIC Educational Resources Information Center

Rice, Mabel L.; Noll, Karen Ruff; Grimm, Hannelore

1997-01-01

Predictions were formulated for extended Optional Infinitives (OIs) stage in German-speaking children with specific language impairment and evaluated in clinical sample of 8 SLI German-speaking children, ages 4; 0 to 4; 8; and control group of 8 younger utterance-equivalent children, ages 2; 1 to 2; 7. Samples reveal that affected group more…

Pharmacokinetics of dinalbuphine sebacate and nalbuphine in human after intramuscular injection of dinalbuphine sebacate in an extended-release formulation.

PubMed

Tien, Yu En; Huang, Wen-Chuan; Kuo, Hui-Yuan; Tai, Lily; Uang, Yow-Shieng; Chern, Wendy H; Huang, Jin-Ding

2017-11-01

Nalbuphine is a semi-synthetic opioid indicated for the relief of moderate to severe pain. Its short half-life requires frequent injections in clinical practice, resulting in a greater incidence of adverse events. A prodrug of nalbuphine has been developed, dinalbuphine sebacate (DNS), dissolved in a simple oil-based injectable formulation, which could deliver and maintain an effective blood level of nalbuphine. An open-label, prospective, two-period study was performed in healthy volunteers to verify the extended blood concentration profile of nalbuphine. Twelve healthy Taiwanese were randomized to receive an intramuscular injection of 20 mg nalbuphine HCl and 150 mg DNS sequentially with a washout period of 5 days. To prevent DNS hydrolysis during sample analysis, the effect of four esterase inhibitors was evaluated in the quantitation of DNS in human whole blood and thenoyltrifluoroacetone was chosen. The bioavailability of nalbuphine from intramuscularly injected DNS relative to that from nalbuphine HCl was 85.4%. The mean absorption time of nalbuphine from DNS was 145.2 h. It took approximately 6 days for the complete release of DNS into the blood stream where DNS was rapidly hydrolysed to nalbuphine; suggesting a single injection of 150 mg DNS in our extended-release formulation could provide long-lasting pain relief. Copyright © 2017 John Wiley & Sons, Ltd.

Assessment of the bioequivalence of two formulations of clarithromycin extended-release 500-mg tablets under fasting and fed conditions: a single-dose, randomized, open-label, two-period, two-way crossover study in healthy Jordanian male volunteers.

PubMed

Alkhalidi, Bashar A; Tamimi, Jaafar J; Salem, Isam I; Ibrahim, Husain; Sallam, Alsayed Alarabi I

2008-10-01

Clarithromycin extended-release tablets are indicated for the treatment of adults with acute maxillary sinusitis caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae; acute bacterial exacerbation of chronic bronchitis due to H influenzae, Haemophilus parainfluenzae, M catarrhalis, or S pneumoniae; or community acquired pneumonia due to H influenzae, H parainfluenzae, M catarrhalis, S pneumoniae, Chlamydia pneumoniae, or Mycoplasma pneumoniae. This study was conducted to assess the bioequivalence of test and reference formulations of clarithromycin extended-release 500-mg tablets under fasting and fed conditions. This was a single-dose, randomized, open-label, 2-period, 2-way crossover study with a 1-week washout period between doses. Separate bioequivalence studies (fasting and fed) were performed in 2 groups of healthy male Jordanian volunteers. Eighteen blood samples were obtained from each volunteer over 38 hours after drug administration. Clarithromycin concentrations were determined in plasma using a validated high-performance liquid chromatography method with electrochemical detection. Pharmacokinetic parameters of clarithromycin (C(max), T(max), AUC(0-t), AUC(0-infinity), lambda(z) [first-order elimination rate constant], and t((1/2))) were calculated and analyzed statistically. Tolerability was assessed based on changes in vital signs and laboratory tests, and by questioning subjects about adverse events. Thirty-eight volunteers each participated in the fasting and fed studies. The mean ages of participants in the fasting and fed studies were 26.7 and 27.6 years, respectively; their mean weight was 71.2 and 70.9 kg and mean height was 171.3 and 179.0 cm. Under fasting conditions, the arithmetic mean (SD) C(max) was 569.4 (189.3) ng/mL for the test formulation and 641.2 (202.0) ng/mL for the reference formulation, with a geometric mean ratio of 0.88. The arithmetic mean AUC(0-t) was 8602.9 (4105.1) and 8245.3 (4122.4) ng . h/mL in the respective formulations, with a geometric mean ratio of 1.06. The arithmetic mean T(max) was 8.0 (5.6) and 6.1 (3.8) hours. In the fed study, the C(max) and AUC of both formulations were significantly increased relative to the fasting study (P < 0.05). The arithmetic mean C(max) of the 2 formulations was 1183.0 (637.5) and 1199.6 (496.3) ng/mL, with a geometric mean ratio of 0.93. The arithmetic mean AUC(0-t) was 12,981.2 (7849.0) and 11,822.9 (5790.2) ng . h/mL, with a geometric mean ratio of 1.06. The arithmetic mean T(max) was 5.7 (2.8) and 6.7 (2.5) hours. The 90% CI for the ratio (test:reference) of log-transformed C(max) and AUC values was within the acceptance range of 0.80 to 1.25. The 2 formulations were both well tolerated, and no adverse events were reported during the study. In these fasting and fed studies in healthy male Jordanian volunteers, the 2 formulations of clarithromycin extended-release 500-mg tablets were found to be bioequivalent according to the US Food and Drug Administration regulatory definition. Administration with food significantly increased the rate and extent of absorption of both products, with no significant effect on their bioequivalence.

Generic products of antiepileptic drugs: a perspective on bioequivalence, bioavailability, and formulation switches using Monte Carlo simulations.

PubMed

Karalis, Vangelis; Macheras, Panos; Bialer, Meir

2014-01-01

Generic products of antiepileptic drugs (AEDs) are currently a controversial topic as neurologists and patients are reluctant to switch from brand products to generics and to switch between generics. The aim of this study was to provide enlightenment on issues of bioequivalence (BE) and interchangeability of AED products. Monte Carlo simulations of the classic 2 × 2 BE studies were performed to study the effect of sample size, within-subject variability, and the true difference in pharmacokinetic values of the products under comparison on BE acceptance of generic AED products. Simulations were extended to study the comparative performance of two generic AED products against the same innovative product. The simulated results are compared with literature data on AEDs. The question with regard to bioavailability (BA) is whether two formulations are different, while for BE the question is whether two formulations are sufficiently similar in terms of extent and rate of absorption. Therefore, the criteria for BA and BE and the statistical analysis involved in their analysis are different. Two generic formulations that meet regulatory approval requirements for generics by being bioequivalent to the same innovative AED may not be bioequivalent to one another and therefore should not be regarded as equal or as therapeutically equivalent products. A switch from a standard or an immediate-release formulation to a modified-release product, which comprises extended-release or delayed-release formulations, should not be regarded as a switch between generics, but rather as a switch between different formulation types. Switches between bioequivalent generic AED products could potentially lead to larger changes in plasma levels and exposure than the brand-to-generic switch. The simulation work verified the clinical findings that not all generic AED products bioequivalent to the same innovative product are bioequivalent to one another. Two generic formulations that meet regulatory approval requirements for generics, by being bioequivalent to the innovative AED, may not be bioequivalent to one another. Additional BE criteria are needed for a formulation switch, particularly in epilepsy, where a breakthrough seizure may change a patient's status from seizure-free to refractory.

Equine spermatozoal motility and fertility associated with the incorporation of d-(+)-mannose into semen extender.

PubMed

King, Sheryl S; Speiser, Stephanie A; Jones, Karen L; Apgar, Gary A; Wessels, Sarah E

2006-04-01

Mannose is capable of decreasing bacterial attachment to the uterine mucosa in mares. Bacteria gain entry into the mare's uterus during breeding; therefore, a practical method to deliver mannose to the uterus is to incorporate it into semen extenders. The effect of mannose on spermatozoal motility and subsequent sperm fertilizing capability is unknown. The present study evaluated progressive spermatozoal motility in semen extender formulations incorporating mannose and assessed the fertility of mares inseminated with a mannose-containing semen extender. In Experiment 1, progressive spermatozoal motility in extender mixtures containing 0 mannose (control), 25, 37 or 49 mg/mL mannose was evaluated at 20 degrees C or 5 degrees C holding temperatures for 0, 12, 24 and 48 h post-dilution. Measures were repeated three times using five stallions of proven fertility. High concentrations of mannose in the extender affected progressive motility beyond the time and temperature effects noted in the controls. Extender containing only mannose sugar (49 mg/mL) displayed an immediate depression in progressive motility compared with controls (45.5% versus 62.9%, respectively; P<0.001). The 37 mg/mL mannose extender had a less dramatic decrease in motility (P<0.05) and only after storage at 5 degrees C for > or =12h (48.7% versus 58.0%, respectively). Extender with 25 mg/mL mannose performed no differently than the control formulation under all conditions. In Experiment 2, two groups of mares (n=11 each) were inseminated with 500 x 10(6) progressively motile spermatozoa extended in a traditional skim milk (control) extender or the 37 mg/mL mannose extender preparation. A single-cycle pregnancy rate of 72% was achieved by both groups. Present data suggest that a semen extender containing up to 37 mg/mL mannose could maintain motile spermatozoa for on-farm use and 25 mg/mL mannose concentrations preserved motility during long-term cooling. Likewise, sperm extended with up to 37 mg/mL of mannose had the same fertilizing capability as sperm in traditional extender mixtures.

Decentralized diagnostics based on a distributed micro-genetic algorithm for transducer networks monitoring large experimental systems.

PubMed

Arpaia, P; Cimmino, P; Girone, M; La Commara, G; Maisto, D; Manna, C; Pezzetti, M

2014-09-01

Evolutionary approach to centralized multiple-faults diagnostics is extended to distributed transducer networks monitoring large experimental systems. Given a set of anomalies detected by the transducers, each instance of the multiple-fault problem is formulated as several parallel communicating sub-tasks running on different transducers, and thus solved one-by-one on spatially separated parallel processes. A micro-genetic algorithm merges evaluation time efficiency, arising from a small-size population distributed on parallel-synchronized processors, with the effectiveness of centralized evolutionary techniques due to optimal mix of exploitation and exploration. In this way, holistic view and effectiveness advantages of evolutionary global diagnostics are combined with reliability and efficiency benefits of distributed parallel architectures. The proposed approach was validated both (i) by simulation at CERN, on a case study of a cold box for enhancing the cryogeny diagnostics of the Large Hadron Collider, and (ii) by experiments, under the framework of the industrial research project MONDIEVOB (Building Remote Monitoring and Evolutionary Diagnostics), co-funded by EU and the company Del Bo srl, Napoli, Italy.

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

PubMed

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

2012-03-01

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

Trichotomous processes in early memory development, aging, and neurocognitive impairment: a unified theory.

PubMed

Brainerd, C J; Reyna, V F; Howe, M L

2009-10-01

One of the most extensively investigated topics in the adult memory literature, dual memory processes, has had virtually no impact on the study of early memory development. The authors remove the key obstacles to such research by formulating a trichotomous theory of recall that combines the traditional dual processes of recollection and familiarity with a reconstruction process. The theory is then embedded in a hidden Markov model that measures all 3 processes with low-burden tasks that are appropriate for even young children. These techniques are applied to a large corpus of developmental studies of recall, yielding stable findings about the emergence of dual memory processes between childhood and young adulthood and generating tests of many theoretical predictions. The techniques are extended to the study of healthy aging and to the memory sequelae of common forms of neurocognitive impairment, resulting in a theoretical framework that is unified over 4 major domains of memory research: early development, mainstream adult research, aging, and neurocognitive impairment. The techniques are also extended to recognition, creating a unified dual process framework for recall and recognition.

A minimalistic approach to static and dynamic electron correlations: Amending generalized valence bond method with extended random phase approximation correlation correction

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

Chatterjee, Koushik; Jawulski, Konrad; Pastorczak, Ewa

A perfect-pairing generalized valence bond (GVB) approximation is known to be one of the simplest approximations, which allows one to capture the essence of static correlation in molecular systems. In spite of its attractive feature of being relatively computationally efficient, this approximation misses a large portion of dynamic correlation and does not offer sufficient accuracy to be generally useful for studying electronic structure of molecules. We propose to correct the GVB model and alleviate some of its deficiencies by amending it with the correlation energy correction derived from the recently formulated extended random phase approximation (ERPA). On the examples ofmore » systems of diverse electronic structures, we show that the resulting ERPA-GVB method greatly improves upon the GVB model. ERPA-GVB recovers most of the electron correlation and it yields energy barrier heights of excellent accuracy. Thanks to a balanced treatment of static and dynamic correlation, ERPA-GVB stays reliable when one moves from systems dominated by dynamic electron correlation to those for which the static correlation comes into play.« less

Advanced Analgesic Drug Delivery and Nanobiotechnology.

PubMed

Stoicea, Nicoleta; Fiorda-Diaz, Juan; Joseph, Nicholas; Shabsigh, Muhammad; Arias-Morales, Carlos; Gonzalez-Zacarias, Alicia A; Mavarez-Martinez, Ana; Marjoribanks, Stephen; Bergese, Sergio D

2017-07-01

Transdermal administration of analgesic medications offers several benefits over alternative routes of administration, including a decreased systemic drug load with fewer side effects, and avoidance of drug degradation by the gastrointestinal tract. Transdermal administration also offers a convenient mode of drug administration over an extended period of time, particularly desirable in pain medicine. A transdermal administration route may also offer increased safety for drugs with a narrow therapeutic window. The primary barrier to transdermal drug absorption is the skin itself. Transdermal nanotechnology offers a novel method of achieving enhanced dermal penetration with an extended delivery profile for analgesic drugs, due to their small size and relatively large surface area. Several materials have been used to enhance drug duration and transdermal penetration. The application of nanotechnology in transdermal delivery of analgesics has raised new questions regarding safety and ethical issues. The small molecular size of nanoparticles enables drug delivery to previously inaccessible body sites. To ensure safety, the interaction of nanoparticles with the human body requires further investigation on an individual drug basis, since different formulations have unique properties and side effects.

The Fermi-Pasta-Ulam Problem and Its Underlying Integrable Dynamics: An Approach Through Lyapunov Exponents

NASA Astrophysics Data System (ADS)

Benettin, G.; Pasquali, S.; Ponno, A.

2018-05-01

FPU models, in dimension one, are perturbations either of the linear model or of the Toda model; perturbations of the linear model include the usual β -model, perturbations of Toda include the usual α +β model. In this paper we explore and compare two families, or hierarchies, of FPU models, closer and closer to either the linear or the Toda model, by computing numerically, for each model, the maximal Lyapunov exponent χ . More precisely, we consider statistically typical trajectories and study the asymptotics of χ for large N (the number of particles) and small ɛ (the specific energy E / N), and find, for all models, asymptotic power laws χ ˜eq Cɛ ^a, C and a depending on the model. The asymptotics turns out to be, in general, rather slow, and producing accurate results requires a great computational effort. We also revisit and extend the analytic computation of χ introduced by Casetti, Livi and Pettini, originally formulated for the β -model. With great evidence the theory extends successfully to all models of the linear hierarchy, but not to models close to Toda.

Are in situ formulations the keys for the therapeutic future of S-nitrosothiols?

PubMed

Parent, Marianne; Boudier, Ariane; Dupuis, François; Nouvel, Cécile; Sapin, Anne; Lartaud, Isabelle; Six, Jean-Luc; Leroy, Pierre; Maincent, Philippe

2013-11-01

S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) were formulated into in situ forming implants (ISI) and microparticles (ISM) using PLGA and either N-methyl-2-pyrrolidone (NMP) or triacetin. Physicochemical characterization was carried out, including the study of matrix structure and degradation. A strong correlation between drug hydrophobicity and the in vitro release profiles was observed: whatever the formulation, GSNO and SNAP were completely released after ca. 1 day and 1 week, respectively. Then, selected formulations (i.e., SNAP-loaded NMP formulations) demonstrated the ability to sustain the vasodilation effect of SNAP, as shown by monitoring the arterial pressure (telemetry) of Wistar rats after subcutaneous injection. Both ISI and ISM injections resulted in a 3-fold extended decrease in pulse arterial pressure compared with the unloaded drug, without significant decrease in the mean arterial pressure. Hence, the results emphasize the suitability of these formulations as drug delivery systems for S-nitrosothiols, widening their therapeutic potential. Copyright © 2013 Elsevier B.V. All rights reserved.

Improved photostability of NREL-developed EVA pottant formulations for PV module encapsulation

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

Pern, F.J.; Glick, S.H.

1997-12-31

Several new formulations of ethylene vinyl acetate (EVA)-based encapsulant have been developed at NREL and have greatly improved photostability against UV-induced discoloration. The new EVA formulations use stabilizers and a curing agent entirely different from any of those used in existing formulations known to the authors. No discoloration was observed for the laminated and cured samples that were exposed to a {approximately}5-sun UV light (300--400 nm) from a solar simulator at a black panel temperature (BPT) of 44 {+-} 2 C for {approximately}3250 h followed by at 85 C for {approximately}850 h, an equivalent of approximately 9.4 years for anmore » average 6-h daily, 1-sun solar exposure in Golden, Colorado. Under the same conditions, substantial discoloration and premature delamination were observed for two commercial EVA formulations. Encapsulation with the new EVA formulations should extend the long-term stability for PV modules in the field, especially when coupled with UV-filtering, Ce-containing glass superstrates.« less

An integral equation formulation for the diffraction from convex plates and polyhedra.

PubMed

Asheim, Andreas; Svensson, U Peter

2013-06-01

A formulation of the problem of scattering from obstacles with edges is presented. The formulation is based on decomposing the field into geometrical acoustics, first-order, and multiple-order edge diffraction components. An existing secondary-source model for edge diffraction from finite edges is extended to handle multiple diffraction of all orders. It is shown that the multiple-order diffraction component can be found via the solution to an integral equation formulated on pairs of edge points. This gives what can be called an edge source signal. In a subsequent step, this edge source signal is propagated to yield a multiple-order diffracted field, taking all diffraction orders into account. Numerical experiments demonstrate accurate response for frequencies down to 0 for thin plates and a cube. No problems with irregular frequencies, as happen with the Kirchhoff-Helmholtz integral equation, are observed for this formulation. For the axisymmetric scattering from a circular disc, a highly effective symmetric formulation results, and results agree with reference solutions across the entire frequency range.

Dirac structures in nonequilibrium thermodynamics

NASA Astrophysics Data System (ADS)

Gay-Balmaz, François; Yoshimura, Hiroaki

2018-01-01

Dirac structures are geometric objects that generalize both Poisson structures and presymplectic structures on manifolds. They naturally appear in the formulation of constrained mechanical systems. In this paper, we show that the evolution equations for nonequilibrium thermodynamics admit an intrinsic formulation in terms of Dirac structures, both on the Lagrangian and the Hamiltonian settings. In the absence of irreversible processes, these Dirac structures reduce to canonical Dirac structures associated with canonical symplectic forms on phase spaces. Our geometric formulation of nonequilibrium thermodynamic thus consistently extends the geometric formulation of mechanics, to which it reduces in the absence of irreversible processes. The Dirac structures are associated with the variational formulation of nonequilibrium thermodynamics developed in the work of Gay-Balmaz and Yoshimura, J. Geom. Phys. 111, 169-193 (2017a) and are induced from a nonlinear nonholonomic constraint given by the expression of the entropy production of the system.

Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

PubMed

Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

2002-01-01

Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p < 0.0001). By contrast, methylphenidate concentrations over the same 8 h were unaffected by breakfast, providing consistent levels of early drug exposure. Therefore, as a child's or adult's eating pattern varies, methylphenidate exposure over the first 8 h would be expected to have less day-to-day variation compared with amphetamine exposure. The osmotic-controlled OROS tablet provides a reliable and consistent delivery of methylphenidate HCI, independent of food, for patients with ADHD.

Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy.

PubMed

Sattler, Annika; Schaefer, Marion; May, Theodor W

2015-09-01

To evaluate the relationship between serum concentrations of mono-hydroxy-carbazepine (MHD), the main metabolite of oxcarbazepine (OXC), and the occurrence of adverse effects (AE) in a large group of patients on OXC monotherapy. An antiepileptic drug (AED) therapeutic drug monitoring (TDM) database was analyzed especially with regard to OXC dosage, MHD serum concentration, and the occurrence of AE. In total, 893 blood samples of 442 patients were included in this retrospective study. The statistical evaluation was performed by means of Kaplan-Meier estimates, log-rank tests and generalized estimating equations (GEE). At least one AE was reported in 78 (17.6%) of the 442 patients. At MHD serum concentrations of 30.0 μg/ml and 43.7 μg/ml and OXC dosages of 33.1 mg/kg and 62.3 mg/kg, 25% and 75% of patients, respectively, experienced at least one AE. Log-rank tests indicated that younger patients (<18 years) may be able to tolerate higher MHD serum levels (p = 0.006) and higher OXC dosages per body weight (p < 0.001) compared to adult patients (≥ 18 years). Furthermore, AEs occurred at higher body-weight adjusted OXC dosages of extended release formulations compared to immediate-release formulations (p = 0.010), whereas MHD serum levels at which AEs occurred did not differ significantly between formulations (p = 0.125). Multivariate GEE confirmed the results. The occurrence of AEs is significantly (and non-linearly) dependent on MHD serum level, whereas the dependence of OXC dosage is less distinctive. But, tolerability of OXC seems to depend on age of the patients as well as on pharmaceutical formulation of OXC. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

pyomocontrib_simplemodel v. 1.0

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

Hart, William

2017-03-02

Pyomo supports the formulation and analysis of mathematical models for complex optimization applications. This library extends the API of Pyomo to include a simple modeling representation: a list of objectives and constraints.

Recursive estimators of mean-areal and local bias in precipitation products that account for conditional bias

NASA Astrophysics Data System (ADS)

Zhang, Yu; Seo, Dong-Jun

2017-03-01

This paper presents novel formulations of Mean field bias (MFB) and local bias (LB) correction schemes that incorporate conditional bias (CB) penalty. These schemes are based on the operational MFB and LB algorithms in the National Weather Service (NWS) Multisensor Precipitation Estimator (MPE). By incorporating CB penalty in the cost function of exponential smoothers, we are able to derive augmented versions of recursive estimators of MFB and LB. Two extended versions of MFB algorithms are presented, one incorporating spatial variation of gauge locations only (MFB-L), and the second integrating both gauge locations and CB penalty (MFB-X). These two MFB schemes and the extended LB scheme (LB-X) are assessed relative to the original MFB and LB algorithms (referred to as MFB-O and LB-O, respectively) through a retrospective experiment over a radar domain in north-central Texas, and through a synthetic experiment over the Mid-Atlantic region. The outcome of the former experiment indicates that introducing the CB penalty to the MFB formulation leads to small, but consistent improvements in bias and CB, while its impacts on hourly correlation and Root Mean Square Error (RMSE) are mixed. Incorporating CB penalty in LB formulation tends to improve the RMSE at high rainfall thresholds, but its impacts on bias are also mixed. The synthetic experiment suggests that beneficial impacts are more conspicuous at low gauge density (9 per 58,000 km2), and tend to diminish at higher gauge density. The improvement at high rainfall intensity is partly an outcome of the conservativeness of the extended LB scheme. This conservativeness arises in part from the more frequent presence of negative eigenvalues in the extended covariance matrix which leads to no, or smaller incremental changes to the smoothed rainfall amounts.

A stochastic electricity market clearing formulation with consistent pricing properties

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

Zavala, Victor M.; Kim, Kibaek; Anitescu, Mihai

We argue that deterministic market clearing formulations introduce arbitrary distortions between day-ahead and expected real-time prices that bias economic incentives. We extend and analyze a previously proposed stochastic clearing formulation in which the social surplus function induces penalties between day-ahead and real-time quantities. We prove that the formulation yields price bounded price distortions, and we show that adding a similar penalty term to transmission flows and phase angles ensures boundedness throughout the network. We prove that when the price distortions are zero, day-ahead quantities equal a quantile of their real-time counterparts. The undesired effects of price distortions suggest that stochasticmore » settings provide significant benefits over deterministic ones that go beyond social surplus improvements. Finally, we propose additional metrics to evaluate these benefits.« less

A stochastic electricity market clearing formulation with consistent pricing properties

DOE PAGES

Zavala, Victor M.; Kim, Kibaek; Anitescu, Mihai; ...

2017-03-16

We argue that deterministic market clearing formulations introduce arbitrary distortions between day-ahead and expected real-time prices that bias economic incentives. We extend and analyze a previously proposed stochastic clearing formulation in which the social surplus function induces penalties between day-ahead and real-time quantities. We prove that the formulation yields price bounded price distortions, and we show that adding a similar penalty term to transmission flows and phase angles ensures boundedness throughout the network. We prove that when the price distortions are zero, day-ahead quantities equal a quantile of their real-time counterparts. The undesired effects of price distortions suggest that stochasticmore » settings provide significant benefits over deterministic ones that go beyond social surplus improvements. Finally, we propose additional metrics to evaluate these benefits.« less

Thermal shock induced dynamics of a spacecraft with a flexible deploying boom

NASA Astrophysics Data System (ADS)

Shen, Zhenxing; Li, Huijian; Liu, Xiaoning; Hu, Gengkai

2017-12-01

The dynamics in the process of deployment of a flexible extendible boom as a deployable structure on the spacecraft is studied. For determining the thermally induced vibrations of the boom subjected to an incident solar heat flux, an axially moving thermal-dynamic beam element based on the absolute nodal coordinate formulation which is able to precisely describe the large displacement, rotation and deformation of flexible body is presented. For the elastic forces formulation of variable-length beam element, the enhanced continuum mechanics approach is adopted, which can eliminate the Poisson locking effect, and take into account the tension-bending-torsion coupling deformations. The main body of the spacecraft, modeled as a rigid body, is described using the natural coordinates method. In the derived nonlinear thermal-dynamic equations of rigid-flexible multibody system, the mass matrix is time-variant, and a pseudo damping matrix which is without actual energy dissipation, and a heat conduction matrix which is relative to the moving speed and the number of beam element are arisen. Numerical results give the dynamic and thermal responses of the nonrotating and spinning spacecraft, respectively, and show that thermal shock has a significant influence on the dynamics of spacecraft.

LES models for incompressible magnetohydrodynamics derived from the variational multiscale formulation

NASA Astrophysics Data System (ADS)

Sondak, David; Oberai, Assad

2012-10-01

Novel large eddy simulation (LES) models are developed for incompressible magnetohydrodynamics (MHD). These models include the application of the variational multiscale formulation (VMS) of LES to the equations of incompressible MHD, a new residual-based eddy viscosity model (RBEVM,) and a mixed LES model that combines the strengths of both of these models. The new models result in a consistent numerical method that is relatively simple to implement. A dynamic procedure for 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 and state-of-the art LES turbulence models as well as direct numerical simulations (DNS). These 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 A. Pouquet et al., for which the ratio of DNS modes to LES modes is 262,144. Additionally, we extend these models to a finite element setting in which boundary conditions play a role. A classic problem on which we test these models is turbulent channel flow, which in the case of MHD, is called Hartmann flow.

Optimal guidance law development for an advanced launch system

NASA Technical Reports Server (NTRS)

Calise, Anthony J.; Hodges, Dewey H.

1990-01-01

A regular perturbation analysis is presented. Closed-loop simulations were performed with a first order correction including all of the atmospheric terms. In addition, a method was developed for independently checking the accuracy of the analysis and the rather extensive programming required to implement the complete first order correction with all of the aerodynamic effects included. This amounted to developing an equivalent Hamiltonian computed from the first order analysis. A second order correction was also completed for the neglected spherical Earth and back-pressure effects. Finally, an analysis was begun on a method for dealing with control inequality constraints. The results on including higher order corrections do show some improvement for this application; however, it is not known at this stage if significant improvement will result when the aerodynamic forces are included. The weak formulation for solving optimal problems was extended in order to account for state inequality constraints. The formulation was tested on three example problems and numerical results were compared to the exact solutions. Development of a general purpose computational environment for the solution of a large class of optimal control problems is under way. An example, along with the necessary input and the output, is given.

Newmark local time stepping on high-performance computing architectures

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

Rietmann, Max, E-mail: max.rietmann@erdw.ethz.ch; Institute of Geophysics, ETH Zurich; Grote, Marcus, E-mail: marcus.grote@unibas.ch

In multi-scale complex media, finite element meshes often require areas of local refinement, creating small elements that can dramatically reduce the global time-step for wave-propagation problems due to the CFL condition. Local time stepping (LTS) algorithms allow an explicit time-stepping scheme to adapt the time-step to the element size, allowing near-optimal time-steps everywhere in the mesh. We develop an efficient multilevel LTS-Newmark scheme and implement it in a widely used continuous finite element seismic wave-propagation package. In particular, we extend the standard LTS formulation with adaptations to continuous finite element methods that can be implemented very efficiently with very strongmore » element-size contrasts (more than 100x). Capable of running on large CPU and GPU clusters, we present both synthetic validation examples and large scale, realistic application examples to demonstrate the performance and applicability of the method and implementation on thousands of CPU cores and hundreds of GPUs.« less

PEVC-FMDF for Large Eddy Simulation of Compressible Turbulent Flows

NASA Astrophysics Data System (ADS)

Nouri Gheimassi, Arash; Nik, Mehdi; Givi, Peyman; Livescu, Daniel; Pope, Stephen

2017-11-01

The filtered density function (FDF) closure is extended to a ``self-contained'' format to include the subgrid scale (SGS) statistics of all of the hydro-thermo-chemical variables in turbulent flows. These are the thermodynamic pressure, the specific internal energy, the velocity vector, and the composition field. In this format, the model is comprehensive and facilitates large eddy simulation (LES) of flows at both low and high compressibility levels. A transport equation is developed for the joint ``pressure-energy-velocity-composition filtered mass density function (PEVC-FMDF).'' In this equation, the effect of convection appears in closed form. The coupling of the hydrodynamics and thermochemistry is modeled via a set of stochastic differential equation (SDE) for each of the transport variables. This yields a self-contained SGS closure. For demonstration, LES is conducted of a turbulent shear flow with transport of a passive scalar. The consistency of the PEVC-FMDF formulation is established, and its overall predictive capability is appraised via comparison with direct numerical simulation (DNS) data.

Open Group Transformations

NASA Astrophysics Data System (ADS)

Batalin, Igor; Marnelius, Robert

Open groups whose generators are in arbitrary involutions may be quantized within a ghost extended framework in terms of a nilpotent BFV-BRST charge operator. Previously we have shown that generalized quantum Maurer-Cartan equations for arbitrary open groups may be extracted from the quantum connection operators and that they also follow from a simple quantum master equation involving an extended nilpotent BFV-BRST charge and a master charge. Here we give further details of these results. In addition we establish the general structure of the solutions of the quantum master equation. We also construct an extended formulation whose properties are determined by the extended BRST charge in the master equation.

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.

Complete characterization of fourth-order symplectic integrators with extended-linear coefficients.

PubMed

Chin, Siu A

2006-02-01

The structure of symplectic integrators up to fourth order can be completely and analytically understood when the factorization (split) coefficients are related linearly but with a uniform nonlinear proportional factor. The analytic form of these extended-linear symplectic integrators greatly simplified proofs of their general properties and allowed easy construction of both forward and nonforward fourth-order algorithms with an arbitrary number of operators. Most fourth-order forward integrators can now be derived analytically from this extended-linear formulation without the use of symbolic algebra.

Doxazosin in the current treatment of hypertension.

PubMed

Wykretowicz, Andrzej; Guzik, Przemyslaw; Wysocki, Henryk

2008-03-01

Evidence from various studies has shown that even a very small reduction in the blood pressure explains the majority of benefits in cardiovascular outcomes. Although doxazosin is a relatively old drug, it is a very effective add-on therapeutic agent. It has been used in a variety of clinical trials, including different groups of hypertensive patients such as diabetics, the elderly, patients with benign prostatic hyperplasia or hypercholesterolaemia, the obese or Afro-Americans and in combination with all major groups of antihypertensive drugs such as: calcium channel antagonists, diuretics, beta-adrenoreceptor antagonists, angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers. The purpose of this article is to review the role of doxazosin in the current treatment of hypertension. English-language reports published in 1986 - 2007 were retrieved. Data extraction was based on articles reporting at least 15 or more patients treated with combination of doxazosin with other antihypertensive drugs. In these studies doxazosin in either standard or extended-release formulation was added as a second- or third-line agent. The two formulations of doxazosin, although chemically identical, appear to differ in some other effects. A large proportion of patients demonstrated a favourable blood pressure response with relatively few treatment-associated side effects showing that this drug appears to be a valuable add-on antihypertensive treatment option. Doxazosin reduces blood pressure and additionally influences other risk factors of coronary heart disease. However, it should be clearly stated that the clinical role of 'beyond blood pressure' effects of doxazosin are largely undetermined.

Maximizing algebraic connectivity in air transportation networks

NASA Astrophysics Data System (ADS)

Wei, Peng

In air transportation networks the robustness of a network regarding node and link failures is a key factor for its design. An experiment based on the real air transportation network is performed to show that the algebraic connectivity is a good measure for network robustness. Three optimization problems of algebraic connectivity maximization are then formulated in order to find the most robust network design under different constraints. The algebraic connectivity maximization problem with flight routes addition or deletion is first formulated. Three methods to optimize and analyze the network algebraic connectivity are proposed. The Modified Greedy Perturbation Algorithm (MGP) provides a sub-optimal solution in a fast iterative manner. The Weighted Tabu Search (WTS) is designed to offer a near optimal solution with longer running time. The relaxed semi-definite programming (SDP) is used to set a performance upper bound and three rounding techniques are discussed to find the feasible solution. The simulation results present the trade-off among the three methods. The case study on two air transportation networks of Virgin America and Southwest Airlines show that the developed methods can be applied in real world large scale networks. The algebraic connectivity maximization problem is extended by adding the leg number constraint, which considers the traveler's tolerance for the total connecting stops. The Binary Semi-Definite Programming (BSDP) with cutting plane method provides the optimal solution. The tabu search and 2-opt search heuristics can find the optimal solution in small scale networks and the near optimal solution in large scale networks. The third algebraic connectivity maximization problem with operating cost constraint is formulated. When the total operating cost budget is given, the number of the edges to be added is not fixed. Each edge weight needs to be calculated instead of being pre-determined. It is illustrated that the edge addition and the weight assignment can not be studied separately for the problem with operating cost constraint. Therefore a relaxed SDP method with golden section search is developed to solve both at the same time. The cluster decomposition is utilized to solve large scale networks.

The Lunch-Wheel Spin.

ERIC Educational Resources Information Center

Mason, Julia A.; Jones, Graham A.

1994-01-01

Describes a problem formulated by fourth-grade students about having more pizza for lunch, and the clarifying, predicting, modeling, simulating, comparing, and extending activities that occurred in addressing the problem from a probabilistic perspective. (MKR)

Ramizol® encapsulation into extended release PLGA micro- and nanoparticle systems for subcutaneous and intramuscular administration: in vitro and in vivo evaluation.

PubMed

Wright, Leah; Rao, Shasha; Thomas, Nicky; Boulos, Ramiz A; Prestidge, Clive A

2018-04-11

Novel antibiotic Ramizol ® is advancing to clinical trials for the treatment of gastrointestinal Clostridium difficile associated disease. Despite this, previous studies have shown a rapid plasma clearance upon intravenous administration and low oral bioavailability indicating pure drug is unsuitable for systemic infection treatment following oral dosing. The current study aims to investigate the development of poly-lactic-(co-glycolic) acid (PLGA) particles to overcome this limitation and increase the systemic half-life following subcutaneous and intramuscular dosing. The development of new antibiotic treatments will help in combatting the rising incidence of antimicrobial resistance. Ramizol ® was encapsulated into PLGA nano and microparticles using nanoprecipitation and emulsification solvent evaporation techniques. Formulations were analyzed for particle size, loading level and encapsulation efficiency as well as in vitro drug release profiles. Final formulation was advanced to in vivo pharmacokinetic studies in Sprague-Dawley rats. Formulation technique showed major influence on particle size and loading levels with optimal loading of 9.4% and encapsulation efficiency of 92.06%, observed using emulsification solvent evaporation. Differences in formulation technique were also linked with subsequent differences in release profiles. Pharmacokinetic studies in Sprague-Dawley rats confirmed extended absorption and enhanced bioavailability following subcutaneous and intramuscular dosing with up to an 8-fold increase in T max and T 1/2 when compared to the oral and IV routes. Subcutaneous and intramuscular dosing of PLGA particles successfully increased systemic half-life and bioavailability of Ramizol ® . This formulation will allow further development of Ramizol ® for systemic infection eradication.

An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

PubMed

Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

2015-04-30

Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Spotlight on amoxicillin/clavulanic acid 2000 mg/125 mg extended release (XR) in respiratory tract infections in adults.

PubMed

McCormack, Paul L; Keating, Gillian M

2005-01-01

Amoxicillin/clavulanic acid 2000 mg/125 mg extended release (Augmentin XR), referred to herein as amoxicillin/clavulanic acid XR, is a pharmacokinetically enhanced formulation designed to provide more effective therapy in adults and adolescents than conventional formulations against community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae, with reduced susceptibility to amoxicillin.Amoxicillin/clavulanic acid XR maintains plasma amoxicillin concentrations >4 microg/mL for a mean of 49% of the dosing interval indicating that it would be highly effective against S. pneumoniae strains with minimum inhibitory concentrations (MICs) above the National Committee for Clinical Laboratory Standard's amoxicillin +/- clavulanic acid susceptibility breakpoint of < or = 2 microg/mL. Amoxicillin/clavulanic acid XR is at least as effective as conventional amoxicillin/clavulanic acid formulations, levofloxacin, and clarithromycin in treating community-acquired pneumonia, acute bacterial sinusitis, or acute exacerbations of chronic bronchitis, and has a tolerability profile comparable to that of conventional amoxicillin/clavulanic acid formulations. While the incidence of amoxicillin- or multidrug-resistant S. pneumoniae is not currently sufficient in most regions to warrant the routine empiric use of amoxicillin/clavulanic acid XR, the drug would be extremely useful in those regions with a high incidence of resistant pathogens or in selected patients (i.e. those with S. pneumoniae isolates having amoxicillin MICs > or = 2 microg/mL but < or = 4 microg/mL).

Amoxicillin/clavulanic acid 2000mg/125mg extended release (XR): a review of its use in the treatment of respiratory tract infections in adults.

PubMed

McCormack, Paul L; Keating, Gillian M

2005-01-01

Amoxicillin/clavulanic acid 2000mg/125mg extended release (Augmentin XR), referred to herein as amoxicillin/clavulanic acid XR, is a pharmacokinetically enhanced formulation designed to provide more effective therapy in adults and adolescents than conventional formulations against community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae, with reduced susceptibility to amoxicillin. Amoxicillin/clavulanic acid XR maintains plasma amoxicillin concentrations above 4 microg/mL for a mean of 49% of the dosing interval indicating that it would be highly effective against S. pneumoniae strains with minimum inhibitory concentrations (MICs) above the National Committee for Clinical Laboratory Standard's amoxicillin +/- clavulanic acid susceptibility breakpoint of < or =2 microg/mL. Amoxicillin/clavulanic acid XR is at least as effective as conventional amoxicillin/clavulanic acid formulations, levofloxacin and clarithromycin in treating community-acquired pneumonia, acute bacterial sinusitis or acute exacerbations of chronic bronchitis, and has a tolerability profile comparable to that of conventional amoxicillin/clavulanic acid formulations. While the incidence of amoxicillin- or multidrug-resistant S. pneumoniae is not currently sufficient in most regions to warrant the routine empirical use of amoxicillin/clavulanic acid XR, the drug would be extremely useful in those regions with a high incidence of resistant pathogens or in selected patients (i.e. those with S. pneumoniae isolates having amoxicillin MICs > or =2 microg/mL but < or =4 microg/mL).

On the apparent insignificance of the randomness of flexible joints on large space truss dynamics

NASA Technical Reports Server (NTRS)

Koch, R. M.; Klosner, J. M.

1993-01-01

Deployable periodic large space structures have been shown to exhibit high dynamic sensitivity to period-breaking imperfections and uncertainties. These can be brought on by manufacturing or assembly errors, structural imperfections, as well as nonlinear and/or nonconservative joint behavior. In addition, the necessity of precise pointing and position capability can require the consideration of these usually negligible and unknown parametric uncertainties and their effect on the overall dynamic response of large space structures. This work describes the use of a new design approach for the global dynamic solution of beam-like periodic space structures possessing parametric uncertainties. Specifically, the effect of random flexible joints on the free vibrations of simply-supported periodic large space trusses is considered. The formulation is a hybrid approach in terms of an extended Timoshenko beam continuum model, Monte Carlo simulation scheme, and first-order perturbation methods. The mean and mean-square response statistics for a variety of free random vibration problems are derived for various input random joint stiffness probability distributions. The results of this effort show that, although joint flexibility has a substantial effect on the modal dynamic response of periodic large space trusses, the effect of any reasonable uncertainty or randomness associated with these joint flexibilities is insignificant.

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.

Upwind and symmetric shock-capturing schemes

NASA Technical Reports Server (NTRS)

Yee, H. C.

1987-01-01

The development of numerical methods for hyperbolic conservation laws has been a rapidly growing area for the last ten years. Many of the fundamental concepts and state-of-the-art developments can only be found in meeting proceedings or internal reports. This review paper attempts to give an overview and a unified formulation of a class of shock-capturing methods. Special emphasis is on the construction of the basic nonlinear scalar second-order schemes and the methods of extending these nonlinear scalar schemes to nonlinear systems via the extact Riemann solver, approximate Riemann solvers, and flux-vector splitting approaches. Generalization of these methods to efficiently include real gases and large systems of nonequilibrium flows is discussed. The performance of some of these schemes is illustrated by numerical examples for one-, two- and three-dimensional gas dynamics problems.

A unified electrostatic and cavitation model for first-principles molecular dynamics in solution

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

Scherlis, D A; Fattebert, J; Gygi, F

2005-11-14

The electrostatic continuum solvent model developed by Fattebert and Gygi is combined with a first-principles formulation of the cavitation energy based on a natural quantum-mechanical definition for the surface of a solute. Despite its simplicity, the cavitation contribution calculated by this approach is found to be in remarkable agreement with that obtained by more complex algorithms relying on a large set of parameters. The model allows for very efficient Car-Parrinello simulations of finite or extended systems in solution, and demonstrates a level of accuracy as good as that of established quantum-chemistry continuum solvent methods. They apply this approach to themore » study of tetracyanoethylene dimers in dichloromethane, providing valuable structural and dynamical insights on the dimerization phenomenon.« less

Big Data Ecosystems Enable Scientific Discovery

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

Critchlow, Terence J.; Kleese van Dam, Kerstin

Over the past 5 years, advances in experimental, sensor and computational technologies have driven the exponential growth in the volumes, acquisition rates, variety and complexity of scientific data. As noted by Hey et al in their 2009 e-book The Fourth Paradigm, this availability of large-quantities of scientifically meaningful data has given rise to a new scientific methodology - data intensive science. Data intensive science is the ability to formulate and evaluate hypotheses using data and analysis to extend, complement and, at times, replace experimentation, theory, or simulation. This new approach to science no longer requires scientists to interact directly withmore » the objects of their research; instead they can utilize digitally captured, reduced, calibrated, analyzed, synthesized and visualized results - allowing them carry out 'experiments' in data.« less

Simultaneous analysis and design

NASA Technical Reports Server (NTRS)

Haftka, R. T.

1984-01-01

Optimization techniques are increasingly being used for performing nonlinear structural analysis. The development of element by element (EBE) preconditioned conjugate gradient (CG) techniques is expected to extend this trend to linear analysis. Under these circumstances the structural design problem can be viewed as a nested optimization problem. There are computational benefits to treating this nested problem as a large single optimization problem. The response variables (such as displacements) and the structural parameters are all treated as design variables in a unified formulation which performs simultaneously the design and analysis. Two examples are used for demonstration. A seventy-two bar truss is optimized subject to linear stress constraints and a wing box structure is optimized subject to nonlinear collapse constraints. Both examples show substantial computational savings with the unified approach as compared to the traditional nested approach.

Accurate and Efficient Parallel Implementation of an Effective Linear-Scaling Direct Random Phase Approximation Method.

PubMed

Graf, Daniel; Beuerle, Matthias; Schurkus, Henry F; Luenser, Arne; Savasci, Gökcen; Ochsenfeld, Christian

2018-05-08

An efficient algorithm for calculating the random phase approximation (RPA) correlation energy is presented that is as accurate as the canonical molecular orbital resolution-of-the-identity RPA (RI-RPA) with the important advantage of an effective linear-scaling behavior (instead of quartic) for large systems due to a formulation in the local atomic orbital space. The high accuracy is achieved by utilizing optimized minimax integration schemes and the local Coulomb metric attenuated by the complementary error function for the RI approximation. The memory bottleneck of former atomic orbital (AO)-RI-RPA implementations ( Schurkus, H. F.; Ochsenfeld, C. J. Chem. Phys. 2016 , 144 , 031101 and Luenser, A.; Schurkus, H. F.; Ochsenfeld, C. J. Chem. Theory Comput. 2017 , 13 , 1647 - 1655 ) is addressed by precontraction of the large 3-center integral matrix with the Cholesky factors of the ground state density reducing the memory requirements of that matrix by a factor of [Formula: see text]. Furthermore, we present a parallel implementation of our method, which not only leads to faster RPA correlation energy calculations but also to a scalable decrease in memory requirements, opening the door for investigations of large molecules even on small- to medium-sized computing clusters. Although it is known that AO methods are highly efficient for extended systems, where sparsity allows for reaching the linear-scaling regime, we show that our work also extends the applicability when considering highly delocalized systems for which no linear scaling can be achieved. As an example, the interlayer distance of two covalent organic framework pore fragments (comprising 384 atoms in total) is analyzed.

Local spectrum analysis of field propagation in an anisotropic medium. Part II. Time-dependent fields.

PubMed

Tinkelman, Igor; Melamed, Timor

2005-06-01

In Part I of this two-part investigation [J. Opt. Soc. Am. A 22, 1200 (2005)], we presented a theory for phase-space propagation of time-harmonic electromagnetic fields in an anisotropic medium characterized by a generic wave-number profile. In this Part II, these investigations are extended to transient fields, setting a general analytical framework for local analysis and modeling of radiation from time-dependent extended-source distributions. In this formulation the field is expressed as a superposition of pulsed-beam propagators that emanate from all space-time points in the source domain and in all directions. Using time-dependent quadratic-Lorentzian windows, we represent the field by a phase-space spectral distribution in which the propagating elements are pulsed beams, which are formulated by a transient plane-wave spectrum over the extended-source plane. By applying saddle-point asymptotics, we extract the beam phenomenology in the anisotropic environment resulting from short-pulsed processing. Finally, the general results are applied to the special case of uniaxial crystal and compared with a reference solution.

Micromorphic approach for gradient-extended thermo-elastic-plastic solids in the logarithmic strain space

NASA Astrophysics Data System (ADS)

Aldakheel, Fadi

2017-11-01

The coupled thermo-mechanical strain gradient plasticity theory that accounts for microstructure-based size effects is outlined within this work. It extends the recent work of Miehe et al. (Comput Methods Appl Mech Eng 268:704-734, 2014) to account for thermal effects at finite strains. From the computational viewpoint, the finite element design of the coupled problem is not straightforward and requires additional strategies due to the difficulties near the elastic-plastic boundaries. To simplify the finite element formulation, we extend it toward the micromorphic approach to gradient thermo-plasticity model in the logarithmic strain space. The key point is the introduction of dual local-global field variables via a penalty method, where only the global fields are restricted by boundary conditions. Hence, the problem of restricting the gradient variable to the plastic domain is relaxed, which makes the formulation very attractive for finite element implementation as discussed in Forest (J Eng Mech 135:117-131, 2009) and Miehe et al. (Philos Trans R Soc A Math Phys Eng Sci 374:20150170, 2016).

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.

Characterization of cationic liposome formulations designed to exhibit extended plasma residence times and tumor vasculature targeting properties.

PubMed

Ho, Emmanuel A; Ramsay, Euan; Ginj, Mihaela; Anantha, Malathi; Bregman, Isaiah; Sy, Jonathan; Woo, Janet; Osooly-Talesh, Maryam; Yapp, Donald T; Bally, Marcel B

2010-06-01

Cationic liposomes exhibit a propensity to selectively target tumor-associated blood vessels demonstrating potential value as anti-cancer drug delivery vehicles. Their utility however, is hampered by their biological instability and rapid elimination following i.v. administration. Efforts to circumvent rapid plasma elimination have, to date, focused on decreasing cationic lipid content and incorporating polyethylene glycol (PEG)-modified lipids. In this study we wanted to determine whether highly charged cationic liposomes with surface-associated PEG could be designed to exhibit extended circulation lifetimes, while retaining tumor vascular targeting properties in an HT29 colorectal cancer xenograft model. Cationic liposomes prepared of DSPC, cationic lipids (DODAC, DOTAP, or DC-CHOL), and DSPE-PEG(2000) were studied. Our results demonstrate that formulations prepared with 50 mol% DODAC or DC-CHOL, and 20 mol% DSPE-PEG(2000) exhibited circulation half-lives ranging from 6.5 to 12.5 h. Biodistribution studies demonstrated that DC-CHOL formulations prepared with DSPE-PEG(2000) accumulated threefold higher in s.c. HT29 tumors than its PEG-free counterpart. Fluorescence microscopy studies suggested that the presence of DSPE-PEG(2000) did not adversely affect liposomal tumor vasculature targeting. We show for the first time that it is achievable to design highly charged, highly pegylated (20 mol% DSPE-PEG(2000)) cationic liposomes which exhibit both extended circulation lifetimes and tumor vascular targeting properties. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Relaxation model for extended magnetohydrodynamics: Comparison to magnetohydrodynamics for dense Z-pinches

DOE PAGES

Seyler, C. E.; Martin, M. R.

2011-01-14

In this study, it is shown that the two-fluid model under a generalized Ohm’s law formulation and the resistive magnetohydrodynamics (MHD) can both be described as relaxation systems. In the relaxation model, the under-resolved stiff source terms constrain the dynamics of a set of hyperbolic equations to give the correct asymptotic solution. When applied to the collisional two-fluid model, the relaxation of fast time scales associated with displacement current and finite electron mass allows for a natural transition from a system where Ohm’s law determines the current density to a system where Ohm’s law determines the electric field. This resultmore » is used to derive novel algorithms, which allow for multiscale simulation of low and high frequency extended-MHD physics. This relaxation formulation offers an efficient way to implicitly advance the Hall term and naturally simulate a plasma-vacuum interface without invoking phenomenological models. The relaxation model is implemented as an extended-MHD code, which is used to analyze pulsed power loads such as wire arrays and ablating foils. Two-dimensional simulations of pulsed power loads are compared for extended-MHD and MHD. For these simulations, it is also shown that the relaxation model properly recovers the resistive-MHD limit.« less

On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing.

PubMed

Okwuosa, Tochukwu C; Soares, Cindy; Gollwitzer, Verena; Habashy, Rober; Timmins, Peter; Alhnan, Mohamed A

2018-06-15

A method for the production of liquid capsules with the potential of modifying drug dose and release is presented. For the first time, the co-ordinated use of fused deposition modelling (FDM), 3D printing and liquid dispensing to fabricate individualised dosage form on demand in a fully automated fashion has been demonstrated. Polymethacrylate shells (Eudragit EPO and RL) for immediate and extended release were fabricated using FDM 3D printing and simultaneously filled using a computer-controlled liquid dispenser loaded with model drug solution (theophylline) or suspension (dipyridamole). The impact of printing modes: simultaneous shell printing and filling (single-phase) or sequential 3D printing of shell bottom, filling and shell cap (multi-phase), nozzle size, syringe volume, and shell structure has been reported. The use of shell thickness of 1.6 mm, and concentric architecture allowed successful containment of liquid core whilst maintaining the release properties of the 3D printed liquid capsule. The linear relationship between the theoretical and the actual volumes from the dispenser reflected its potential for accurate dosing (R 2  = 0.9985). Modifying the shell thickness of Eudragit RL capsule allowed a controlled extended drug release without the need for formulation change. Owing to its low cost and versatility, this approach can be adapted to wide spectrum of liquid formulations such as small and large molecule solutions and obviate the need for compatibility with the high temperature of FDM 3D printing process. In a clinical setting, health care staff will be able to instantly manufacture in small volumes liquid capsules with individualised dose contents and release pattern in response to specific patient's needs. Copyright © 2018 Elsevier B.V. All rights reserved.

A post-market surveillance analysis of the safety of hydroxyapatite-derived products as bone graft extenders or substitutes for spine fusion.

PubMed

Barbanti Brodano, G; Griffoni, C; Zanotti, B; Gasbarrini, A; Bandiera, S; Ghermandi, R; Boriani, S

2015-10-01

Iliac crest bone graft (ICBG) is considered the gold standard for spine surgical procedures to achieve a successful fusion, because of its known osteoinductive and osteoconductive properties. Considering its autogenous origin, the use of ICBG has not been associated to an increase of intraoperative or postoperative complications directly related to the surgery. However, complications related to the harvesting procedure and to the donor site morbidity have been largely reported in the literature, favoring the development of a wide range of alternative products to be used as bone graft extenders or substitutes for spine fusion. The family of ceramic-based bone grafts has been widely used and studied during the last years for spine surgical procedures in order to reduce the need for iliac crest bone grafting and the consequent morbidity associated to the harvesting procedures. We report here the results of a post-market surveillance analysis performed on four independent cohorts of patients (115 patients) to evaluate the safety of three different formulations of hydroxyapatite-derived products used as bone graft extenders/substitutes for lumbar arthrodesis. No intraoperative or post-operative complications related to the use of hydroxyapatite-derived products were detected, during medium and long follow up period (minimum 12 months-maximum 5 years). This post-market surveillance analysis evidenced the safety of ceramic products as bone graft extenders or substitutes for spine fusion. Moreover, the evidence of the safety of hydroxyapatite-derived products allows to perform clinical studies aimed at evaluating the fusion rates and the clinical outcomes of these materials as bone graft extenders/substitutes, in order to support their use as an alternative to ICBG for spine fusion.

Beta-lactam antibiotics: newer formulations and newer agents.

PubMed

Martin, Stanley I; Kaye, Kenneth M

2004-09-01

beta-Lactam antibiotics share a common structure and mechanism of action, although they differ in their spectrum of antimicrobial activity and utility in treating different infections. The current classes include the penicillins, the penicillinase-resistant penicillins, the extended- spectrum penicillins, the cephalosporins, the carbapenems, and the monobactams. This article discusses some of the newest beta-lactams available for use in the United States: ertapenem, cefditoren, and cefepime. A new formulation of amoxicillin-clavulanate, which contains higher doses of amoxicillin, is also discussed.

A note on ‘gaugings’ in four spacetime dimensions and electric-magnetic duality

NASA Astrophysics Data System (ADS)

Henneaux, Marc; Julia, Bernard; Lekeu, Victor; Ranjbar, Arash

2018-02-01

The variety of consistent ‘gauging’ deformations of supergravity theories in four dimensions depends on the choice of Lagrangian formulation. One important goal is to get the most general deformations without making hidden assumptions. Ignoring supersymmetry we consider in this paper n v abelian vector potentials in four spacetime dimensions with non-minimal kinetic coupling to n s uncharged (possibly nonlinear) scalar fields. As in the case of extended supergravities, one model may possess different formulations related by \

Paliperidone for the treatment of schizoaffective disorder.

PubMed

Alphs, Larry; Fu, Dong-Jing; Turkoz, Ibrahim

2016-01-01

Schizoaffective disorder (SCA) is a complex mental illness characterized by psychosis and affective symptoms. Treatment usually involves concomitant therapy with antipsychotics, mood stabilizers, and/or antidepressants. Effective treatment must address acute symptoms, maintain long-term stability, promote recovery, and improve patient functioning. Data from 3 pivotal studies evaluating the acute and maintenance treatment of SCA with paliperidone are reviewed. Two formulations of paliperidone have been studied for these indications: an extended-release oral formulation (NCT00397033, NCT00412373) and long-acting injectable once-monthly paliperidone palmitate (NCT01193153). The reported effects of these formulations on psychotic, depressive, and manic symptoms are discussed. Both formulations were found to be safe and effective for the acute and maintenance treatment of SCA. Of critical importance for this treatment population is that rapid improvement was seen in all major symptoms of SCA, including psychosis, depression, and mania. Mediation analyses suggest that the known antipsychotic effects of paliperidone occur independently of its antidepressant effects. Both formulations of the drug are effective when used as monotherapy or adjunctively with antidepressants or mood stabilizers. Beyond symptom control, both formulations improved patient functioning and increased patient satisfaction.

Automatic query formulations in information retrieval.

PubMed

Salton, G; Buckley, C; Fox, E A

1983-07-01

Modern information retrieval systems are designed to supply relevant information in response to requests received from the user population. In most retrieval environments the search requests consist of keywords, or index terms, interrelated by appropriate Boolean operators. Since it is difficult for untrained users to generate effective Boolean search requests, trained search intermediaries are normally used to translate original statements of user need into useful Boolean search formulations. Methods are introduced in this study which reduce the role of the search intermediaries by making it possible to generate Boolean search formulations completely automatically from natural language statements provided by the system patrons. Frequency considerations are used automatically to generate appropriate term combinations as well as Boolean connectives relating the terms. Methods are covered to produce automatic query formulations both in a standard Boolean logic system, as well as in an extended Boolean system in which the strict interpretation of the connectives is relaxed. Experimental results are supplied to evaluate the effectiveness of the automatic query formulation process, and methods are described for applying the automatic query formulation process in practice.

Canonical-ensemble extended Lagrangian Born-Oppenheimer molecular dynamics for the linear scaling density functional theory.

PubMed

Hirakawa, Teruo; Suzuki, Teppei; Bowler, David R; Miyazaki, Tsuyoshi

2017-10-11

We discuss the development and implementation of a constant temperature (NVT) molecular dynamics scheme that combines the Nosé-Hoover chain thermostat with the extended Lagrangian Born-Oppenheimer molecular dynamics (BOMD) scheme, using a linear scaling density functional theory (DFT) approach. An integration scheme for this canonical-ensemble extended Lagrangian BOMD is developed and discussed in the context of the Liouville operator formulation. Linear scaling DFT canonical-ensemble extended Lagrangian BOMD simulations are tested on bulk silicon and silicon carbide systems to evaluate our integration scheme. The results show that the conserved quantity remains stable with no systematic drift even in the presence of the thermostat.

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 added value to both deterministic and probability forecast compared to raw SME's and this better skill is probably flows from large spread and improved spread-error relationship. CGMME system is currently capable of generating ER prediction in real time and successfully delivering its experimental operational ER forecast of ISM for the last few years.

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 condition for an endo-observer to turn into an extended mind is the formation of a new systemic whole as a result of shifting the interfacial cut between exo-and endo-world outwards. However, this is only a necessary condition for an extended agent with strong anticipatory properties. It is invisibility which is a sufficient condition for strong or endo-anticipation.

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.

Dual formulation of covariant nonlinear duality-symmetric action of kappa-symmetric D3-brane

NASA Astrophysics Data System (ADS)

Vanichchapongjaroen, Pichet

2018-02-01

We study the construction of covariant nonlinear duality-symmetric actions in dual formulation. Essentially, the construction is the PST-covariantisation and nonlinearisation of Zwanziger action. The covariantisation made use of three auxiliary scalar fields. Apart from these, the construction proceed in a similar way to that of the standard formulation. For example, the theories can be extended to include interactions with external fields, and that the theories possess two local PST symmetries. We then explicitly demonstrate the construction of covariant nonlinear duality-symmetric actions in dual formulation of DBI theory, and D3-brane. For each of these theories, the twisted selfduality condition obtained from duality-symmetric actions are explicitly shown to match with the duality relation between field strength and its dual from the one-potential actions. Their on-shell actions between the duality-symmetric and the one-potential versions are also shown to match. We also explicitly prove kappa-symmetry of the covariant nonlinear duality-symmetric D3-brane action in dual formulation.

Generalized extended Lagrangian Born-Oppenheimer molecular dynamics

DOE PAGES

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

2014-10-29

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.

Life extending control for rocket engines

NASA Technical Reports Server (NTRS)

Lorenzo, C. F.; Saus, J. R.; Ray, A.; Carpino, M.; Wu, M.-K.

1992-01-01

The concept of life extending control is defined. A brief discussion of current fatigue life prediction methods is given and the need for an alternative life prediction model based on a continuous functional relationship is established. Two approaches to life extending control are considered: (1) the implicit approach which uses cyclic fatigue life prediction as a basis for control design; and (2) the continuous life prediction approach which requires a continuous damage law. Progress on an initial formulation of a continuous (in time) fatigue model is presented. Finally, nonlinear programming is used to develop initial results for life extension for a simplified rocket engine (model).

A spray flamelet/progress variable approach combined with a transported joint PDF model for turbulent spray flames

NASA Astrophysics Data System (ADS)

Hu, Yong; Olguin, Hernan; Gutheil, Eva

2017-05-01

A spray flamelet/progress variable approach is developed for use in spray combustion with partly pre-vaporised liquid fuel, where a laminar spray flamelet library accounts for evaporation within the laminar flame structures. For this purpose, the standard spray flamelet formulation for pure evaporating liquid fuel and oxidiser is extended by a chemical reaction progress variable in both the turbulent spray flame model and the laminar spray flame structures, in order to account for the effect of pre-vaporised liquid fuel for instance through use of a pilot flame. This new approach is combined with a transported joint probability density function (PDF) method for the simulation of a turbulent piloted ethanol/air spray flame, and the extension requires the formulation of a joint three-variate PDF depending on the gas phase mixture fraction, the chemical reaction progress variable, and gas enthalpy. The molecular mixing is modelled with the extended interaction-by-exchange-with-the-mean (IEM) model, where source terms account for spray evaporation and heat exchange due to evaporation as well as the chemical reaction rate for the chemical reaction progress variable. This is the first formulation using a spray flamelet model considering both evaporation and partly pre-vaporised liquid fuel within the laminar spray flamelets. Results with this new formulation show good agreement with the experimental data provided by A.R. Masri, Sydney, Australia. The analysis of the Lagrangian statistics of the gas temperature and the OH mass fraction indicates that partially premixed combustion prevails near the nozzle exit of the spray, whereas further downstream, the non-premixed flame is promoted towards the inner rich-side of the spray jet since the pilot flame heats up the premixed inner spray zone. In summary, the simulation with the new formulation considering the reaction progress variable shows good performance, greatly improving the standard formulation, and it provides new insight into the local structure of this complex spray flame.

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models.

PubMed

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible.

Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers.

PubMed

Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

2014-01-01

This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22-48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC(0-24h)), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC(0-24h) were contained within the conventional bioequivalence range of 0.80-1.25 (0.94 [0.88-1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC(0-24h) was not affected. There were no serious adverse events and both formulations were generally well tolerated. At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability.

Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

PubMed Central

Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

2014-01-01

Background This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were generally well tolerated. Conclusion At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability. PMID:24470753

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

PubMed Central

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer–Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible. PMID:28442890

Change in formulation and its potential clinical and pharmacoeconomic value: example of extended release venlafaxine.

PubMed

Haeusler, Jean-Marc C

2009-05-01

The 505(b)(2) route of a New Drug Application (NDA) allows published literature or previous FDA findings of safety and effectiveness to be used for approval. Such drugs are not therapeutic equivalents (i.e., generics); instead, the FDA calls them pharmaceutical alternatives. A recent example is the approval of venlafaxine extended-release (ER) tablets, developed as an alternative to the widely used ER venlafaxine capsules. The smaller size of the tablets makes them available in a 225-mg strength, which is the approved maximum dose in major depressive disorder after up-titration but currently unavailable in the capsule formulation, requiring patients on this dose to take two or three capsules; in addition, the tablets are priced at a discount compared to the capsules. The objective of this review was to investigate how the change in formulation of ER venlafaxine from capsules to tablets, as an example of such a change in formulation, can potentially offer value to patients and society, with a specific focus on pill burden, drug cost, and adherence. Based on a MEDLINE literature search, the pertinent literature was reviewed in a qualitative manner. Simplifying treatment regimens, reducing pill burden, and reducing drug costs are recognized strategies for improving adherence. This can be of particular benefit in psychiatric illness because of high rates of nonadherence to treatment. Lack of adherence may negatively impact treatment outcomes and increase disease cost. As such, the ER venlafaxine tablets have the potential to reduce pill burden, improve adherence and outcomes, and reduce cost to patients and society. These preliminary findings need to be corroborated with more primary research and a systematic review of formulation changes. A change in formulation of established therapies such as ER venlafaxine has the potential to offer clinical and pharmacoeconomic benefits to patients and society.

A Mixed Integer Linear Program for Solving a Multiple Route Taxi Scheduling Problem

NASA Technical Reports Server (NTRS)

Montoya, Justin Vincent; Wood, Zachary Paul; Rathinam, Sivakumar; Malik, Waqar Ahmad

2010-01-01

Aircraft movements on taxiways at busy airports often create bottlenecks. This paper introduces a mixed integer linear program to solve a Multiple Route Aircraft Taxi Scheduling Problem. The outputs of the model are in the form of optimal taxi schedules, which include routing decisions for taxiing aircraft. The model extends an existing single route formulation to include routing decisions. An efficient comparison framework compares the multi-route formulation and the single route formulation. The multi-route model is exercised for east side airport surface traffic at Dallas/Fort Worth International Airport to determine if any arrival taxi time savings can be achieved by allowing arrivals to have two taxi routes: a route that crosses an active departure runway and a perimeter route that avoids the crossing. Results indicate that the multi-route formulation yields reduced arrival taxi times over the single route formulation only when a perimeter taxiway is used. In conditions where the departure aircraft are given an optimal and fixed takeoff sequence, accumulative arrival taxi time savings in the multi-route formulation can be as high as 3.6 hours more than the single route formulation. If the departure sequence is not optimal, the multi-route formulation results in less taxi time savings made over the single route formulation, but the average arrival taxi time is significantly decreased.

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. © The Author(s) 2013.

Advagraf® with or without an induction therapy for de novo kidney-transplant recipients.

PubMed

Noble, Johan; Jouve, Thomas; Rostaing, Lionel; Malvezzi, Paolo

2018-06-01

Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company). Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i.e., basiliximab) in de novo kidney-transplant recipients. To achieve this, we searched for suitable articles through PubMed. Expert commentary: Phases-III and -IV studies comparing Advagraf®/Astagraf XL® to Prograf® in association with mycophenolate mofetil (more than 2,500 patients) have demonstrated overall similar results with regards to patient/graft survival, biopsy-proven acute-rejection rate, and renal function (p > 0.05). A randomized controlled study in maintenance kidney transplant patients has shown (using electronic monitoring) that, as compared to Prograf®, Advagraf® significantly improved adherence to medication. Other studies report that Advagraf®-treated patients receiving a mTOR-inhibitor agent (sirolimus or everolimus) instead of MMF: this was associated with good allograft outcome, and might also prevent late-onset cytomegalovirus infection. Advagraf®-based immunosuppression given to de novo kidney-transplant recipients, with or without an induction therapy, provided excellent results compared to Prograf®; it also increased patients' adherence to treatment.

Aeroelastic Stability Investigations for Large-scale Vertical Axis Wind Turbines

NASA Astrophysics Data System (ADS)

Owens, B. C.; Griffith, D. T.

2014-06-01

The availability of offshore wind resources in coastal regions, along with a high concentration of load centers in these areas, makes offshore wind energy an attractive opportunity for clean renewable electricity production. High infrastructure costs such as the offshore support structure and operation and maintenance costs for offshore wind technology, however, are significant obstacles that need to be overcome to make offshore wind a more cost-effective option. A vertical-axis wind turbine (VAWT) rotor configuration offers a potential transformative technology solution that significantly lowers cost of energy for offshore wind due to its inherent advantages for the offshore market. However, several potential challenges exist for VAWTs and this paper addresses one of them with an initial investigation of dynamic aeroelastic stability for large-scale, multi-megawatt VAWTs. The aeroelastic formulation and solution method from the BLade Aeroelastic STability Tool (BLAST) for HAWT blades was employed to extend the analysis capability of a newly developed structural dynamics design tool for VAWTs. This investigation considers the effect of configuration geometry, material system choice, and number of blades on the aeroelastic stability of a VAWT, and provides an initial scoping for potential aeroelastic instabilities in large-scale VAWT designs.

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

Kim, G. H.; Pesaran, A.; Spotnitz, R.

To understand further the thermal abuse behavior of large format Li-ion batteries for automotive applications, the one-dimensional modeling approach formulated by Hatchard et al. was reproduced. Then it was extended to three dimensions so we could consider the geometrical features, which are critical in large cells for automotive applications. The three-dimensional model captures the shapes and dimensions of cell components and the spatial distributions of materials and temperatures, and is used to simulate oven tests, and to determine how a local hot spot can propagate through the cell. In simulations of oven abuse testing of cells with cobalt oxide cathodemore » and graphite anode with standard LiPF6 electrolyte, the three-dimensional model predicts that thermal runaway will occur sooner or later than the lumped model, depending on the size of the cell. The model results showed that smaller cells reject heat faster than larger cells; this may prevent them from going into thermal runaway under identical abuse conditions. In simulations of local hot spots inside a large cylindrical cell, the three-dimensional model predicts that the reactions initially propagate in the azimuthal and longitudinal directions to form a hollow cylinder-shaped reaction zone.« less

Interferometric synthetic aperture radar phase unwrapping based on sparse Markov random fields by graph cuts

NASA Astrophysics Data System (ADS)

Zhou, Lifan; Chai, Dengfeng; Xia, Yu; Ma, Peifeng; Lin, Hui

2018-01-01

Phase unwrapping (PU) is one of the key processes in reconstructing the digital elevation model of a scene from its interferometric synthetic aperture radar (InSAR) data. It is known that two-dimensional (2-D) PU problems can be formulated as maximum a posteriori estimation of Markov random fields (MRFs). However, considering that the traditional MRF algorithm is usually defined on a rectangular grid, it fails easily if large parts of the wrapped data are dominated by noise caused by large low-coherence area or rapid-topography variation. A PU solution based on sparse MRF is presented to extend the traditional MRF algorithm to deal with sparse data, which allows the unwrapping of InSAR data dominated by high phase noise. To speed up the graph cuts algorithm for sparse MRF, we designed dual elementary graphs and merged them to obtain the Delaunay triangle graph, which is used to minimize the energy function efficiently. The experiments on simulated and real data, compared with other existing algorithms, both confirm the effectiveness of the proposed MRF approach, which suffers less from decorrelation effects caused by large low-coherence area or rapid-topography variation.

Legal liability perspectives on abuse-deterrent opioids in the treatment of chronic pain.

PubMed

Brushwood, David B; Rich, Ben A; Coleman, John J; Bolen, Jennifer; Wong, Winston

2010-12-01

Abuse-deterrent opioid analgesic formulations can help reduce the risk of opioid diversion and abuse. Not all opioid analgesics are available as both extended- and immediate-release dosage forms in abuse-deterrent formulations. Clinicians may have to balance the clinical benefit of a product that does not use abuse-deterrent technology versus the regulatory benefit of using a product with this technology. There is the possibility that a health care professional may be held legally liable when a product without abuse-deterrent qualities is used and a person suffers harm that would not have occurred had an abuse-deterrent formulation been provided. This article reviews legal precedents that inform an understanding of the need to reduce malpractice exposure by identifying patients who are at high risk of opioid diversion and/or abuse and considering the use of an abuse-deterrent formulation for these patients.

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.

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

PubMed

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

2008-10-01

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

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

PubMed

Elshafeey, Ahmed H; Sami, Elshaimaa I

2008-01-01

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

Discrete velocity computations with stochastic variance reduction of the Boltzmann equation for gas mixtures

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

Clarke, Peter; Varghese, Philip; Goldstein, David

We extend a variance reduced discrete velocity method developed at UT Austin [1, 2] to gas mixtures with large mass ratios and flows with trace species. The mixture is stored as a collection of independent velocity distribution functions, each with a unique grid in velocity space. Different collision types (A-A, A-B, B-B, etc.) are treated independently, and the variance reduction scheme is formulated with different equilibrium functions for each separate collision type. The individual treatment of species enables increased focus on species important to the physics of the flow, even if the important species are present in trace amounts. Themore » method is verified through comparisons to Direct Simulation Monte Carlo computations and the computational workload per time step is investigated for the variance reduced method.« less

A multiscale strength model for tantalum over an extended range of strain rates

NASA Astrophysics Data System (ADS)

Barton, N. R.; Rhee, M.

2013-09-01

A strength model for tantalum is developed and exercised across a range of conditions relevant to various types of experimental observations. The model is based on previous multiscale modeling work combined with experimental observations. As such, the model's parameterization includes a hybrid of quantities that arise directly from predictive sub-scale physics models and quantities that are adjusted to align the model with experimental observations. Given current computing and experimental limitations, the response regions for sub-scale physics simulations and detailed experimental observations have been largely disjoint. In formulating the new model and presenting results here, attention is paid to integrated experimental observations that probe strength response at the elevated strain rates where a previous version of the model has generally been successful in predicting experimental data [Barton et al., J. Appl. Phys. 109(7), 073501 (2011)].

Mixed-strategy Nash equilibrium for a discontinuous symmetric N-player game

NASA Astrophysics Data System (ADS)

Hilhorst, H. J.; Appert-Rolland, C.

2018-03-01

We consider a game in which each player must find a compromise between more daring strategies that carry a high risk for him to be eliminated, and more cautious ones that, however, reduce his final score. For two symmetric players this game was originally formulated in 1961 by Dresher, who modeled a duel between two opponents. The game has also been of interest in the description of athletic competitions. We extend here the two-player game to an arbitrary number N of symmetric players. We show that there is a mixed-strategy Nash equilibrium and find its exact analytic expression, which we analyze in particular in the limit of large N, where mean-field behavior occurs. The original game with N  =  2 arises as a singular limit of the general case.

Use of Vitelline Protein B as a Microencapsulating Additive

NASA Technical Reports Server (NTRS)

Ficht, Allison R. (Inventor); Carson, Ken (Inventor); Waite, John Herbert (Inventor); Sheffield, Cynthia (Inventor)

2017-01-01

The present invention includes compositions and methods for the use of an encapsulation additive having between about 0.1 to about 30 percent isolated and purified vitelline protein B to provide for mixed and extended release formulations.

An extended-release formulation of oxybutynin chloride for the treatment of overactive urinary bladder.

PubMed

Goldenberg, M M

1999-04-01

Detrusor instability, or urinary incontinence, is common in elderly patients, particularly elderly women. The clinical symptoms of overactive, or unstable, urinary bladder include urge urinary incontinence, urgency, and frequency. Mixed urinary incontinence, which comprises urge urinary incontinence and stress incontinence, is manifested by increased intraabdominal pressure on coughing or sneezing. The detrusor muscle of the bladder is under the control of the parasympathetic, or muscarinic, nervous system. The drug of choice in this condition is oxybutynin chloride, which has the ability to block acetylcholine released from parasympathetic nerves in the urinary bladder, preventing contractions of the muscle and exerting a direct spasmolytic effect on the bladder. A new extended-release oral tablet formulation, OROS oxybutynin, uses osmotic pressure to deliver the drug at a controlled rate over approximately 24 hours. It resembles a conventional tablet but has a two-part core consisting of a drug layer and below it, a "push" layer containing osmotically active components, the whole surrounded by a semipermeable membrane with a laser-drilled opening in the drug side. Water in the gastrointestinal tract enters the tablet and mixes with the drug to form a suspension. The "push" layer expands and pushes the suspended drug out of the orifice and into the gastrointestinal tract for eventual absorption. Pharmacokinetic studies have indicated a slow rise in mean plasma concentration of the isomer R-oxybutynin for 4 to 6 hours after a single dose of OROS oxybutynin, followed by maintenance of steady concentrations for up to 24 hours, minimizing the fluctuations between peak and trough associated with TID dosing of 5-mg immediate-release oxybutynin tablets. Efficacy and safety studies comparing the extended-release with the immediate-release formulation of oxybutynin demonstrated equivalent efficacy in patients with overactive urinary bladder. The adverse-event profile of oxybutynin is similar to that of a typical anticholinergic agent such as atropine--dry mouth, constipation, somnolence, blurred vision, headache, and gastrointestinal pain--although in 2 clinical studies, the incidence of dry mouth was less with the extended-release formulation. Once-daily dosing with OROS oxybutynin appears to be well tolerated and effective, as well as convenient, for the treatment of overactive bladder, particularly for elderly patients using multiple medications.

Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis.

PubMed

Rençber, Seda; Karavana, Sinem Yaprak; Yılmaz, Fethiye Ferda; Eraç, Bayri; Nenni, Merve; Özbal, Seda; Pekçetin, Çetin; Gurer-Orhan, Hande; Hoşgör-Limoncu, Mine; Güneri, Pelin; Ertan, Gökhan

2016-01-01

This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT(®) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis.

Intramuscular administration of paliperidone palmitate extended-release injectable microsuspension induces a subclinical inflammatory reaction modulating the pharmacokinetics in rats.

PubMed

Darville, Nicolas; van Heerden, Marjolein; Vynckier, An; De Meulder, Marc; Sterkens, Patrick; Annaert, Pieter; Van den Mooter, Guy

2014-07-01

The present study aims at elucidating the intricate nature of the drug release and absorption following intramuscular (i.m.) injection of sustained-release prodrug nanocrystals/microcrystals. A paliperidone palmitate (PPP) long-acting suspension was characterized with regard to particle size (Dv,50 = 1.09 μm) and morphology prior to i.m. injection in rats. The local disposition was rigorously investigated by means of (immuno)histochemistry and transmission electron microscopy while the concurrent multiphasic pharmacokinetics was linked to the microanatomy. A transient (24 h) trauma-induced inflammation promptly evolved into a subclinical but chronic granulomatous inflammatory reaction initiated by the presence of solid material. The dense inflammatory envelope (CD68(+) macrophages) led to particle agglomeration with subsequent drop in dissolution rate beyond 24 h postinjection. This was associated with a decrease in apparent paliperidone (PP) absorption (near-zero order) until 96 h and a delayed time of occurrence of observed maximum drug plasma concentration (168 h). The infiltrating macrophages phagocytosed large fractions of the depot, thereby influencing the (pro)drug release. Radial angiogenesis (CD31(+)) was observed throughout the inflammatory rim from 72 h onwards and presumably contributed to the sustained systemic PP concentrations by maintaining a sufficient absorptive capacity. No solid-state transitions of the retrieved formulation were recorded with X-ray diffraction analysis. In summary, the initial formulation-driven prodrug (PPP) dissolution and drug (PP) absorption were followed by a complex phase determined by the relative contribution of formulation factors and dynamic physiological variables. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

A LES-CMC formulation for premixed flames including differential diffusion

NASA Astrophysics Data System (ADS)

Farrace, Daniele; Chung, Kyoungseoun; Bolla, Michele; Wright, Yuri M.; Boulouchos, Konstantinos; Mastorakos, Epaminondas

2018-05-01

A finite volume large eddy simulation-conditional moment closure (LES-CMC) numerical framework for premixed combustion developed in a previous studyhas been extended to account for differential diffusion. The non-unity Lewis number CMC transport equation has an additional convective term in sample space proportional to the conditional diffusion of the progress variable, that in turn accounts for diffusion normal to the flame front and curvature-induced effects. Planar laminar simulations are first performed using a spatially homogeneous non-unity Lewis number CMC formulation and validated against physical-space fully resolved reference solutions. The same CMC formulation is subsequently used to numerically investigate the effects of curvature for laminar flames having different effective Lewis numbers: a lean methane-air flame with Leeff = 0.99 and a lean hydrogen-air flame with Leeff = 0.33. Results suggest that curvature does not affect the conditional heat release if the effective Lewis number tends to unity, so that curvature-induced transport may be neglected. Finally, the effect of turbulence on the flame structure is qualitatively analysed using LES-CMC simulations with and without differential diffusion for a turbulent premixed bluff body methane-air flame exhibiting local extinction behaviour. Overall, both the unity and the non-unity computations predict the characteristic M-shaped flame observed experimentally, although some minor differences are identified. The findings suggest that for the high Karlovitz number (from 1 to 10) flame considered, turbulent mixing within the flame weakens the differential transport contribution by reducing the conditional scalar dissipation rate and accordingly the conditional diffusion of the progress variable.

Time-Accurate Local Time Stepping and High-Order Time CESE Methods for Multi-Dimensional Flows Using Unstructured Meshes

NASA Technical Reports Server (NTRS)

Chang, Chau-Lyan; Venkatachari, Balaji Shankar; Cheng, Gary

2013-01-01

With the wide availability of affordable multiple-core parallel supercomputers, next generation numerical simulations of flow physics are being focused on unsteady computations for problems involving multiple time scales and multiple physics. These simulations require higher solution accuracy than most algorithms and computational fluid dynamics codes currently available. This paper focuses on the developmental effort for high-fidelity multi-dimensional, unstructured-mesh flow solvers using the space-time conservation element, solution element (CESE) framework. Two approaches have been investigated in this research in order to provide high-accuracy, cross-cutting numerical simulations for a variety of flow regimes: 1) time-accurate local time stepping and 2) highorder CESE method. The first approach utilizes consistent numerical formulations in the space-time flux integration to preserve temporal conservation across the cells with different marching time steps. Such approach relieves the stringent time step constraint associated with the smallest time step in the computational domain while preserving temporal accuracy for all the cells. For flows involving multiple scales, both numerical accuracy and efficiency can be significantly enhanced. The second approach extends the current CESE solver to higher-order accuracy. Unlike other existing explicit high-order methods for unstructured meshes, the CESE framework maintains a CFL condition of one for arbitrarily high-order formulations while retaining the same compact stencil as its second-order counterpart. For large-scale unsteady computations, this feature substantially enhances numerical efficiency. Numerical formulations and validations using benchmark problems are discussed in this paper along with realistic examples.

The Application of Deterministic Spectral Domain Method to the Analysis of Planar Circuit Discontinuities on Open Substrates

DTIC Science & Technology

1990-08-01

the spectral domain is extended to include the effects of two-dimensional, two-component current flow in planar transmission line discontinuities 6n...PROFESSOR: Tatsuo Itoh A deterministic formulation of the method of moments carried out in the spectral domain is extended to include the effects of...two-dimensional, two- component current flow in planar transmission line discontinuities on open substrates. The method includes the effects of space

Learning to rank for blind image quality assessment.

PubMed

Gao, Fei; Tao, Dacheng; Gao, Xinbo; Li, Xuelong

2015-10-01

Blind image quality assessment (BIQA) aims to predict perceptual image quality scores without access to reference images. State-of-the-art BIQA methods typically require subjects to score a large number of images to train a robust model. However, subjective quality scores are imprecise, biased, and inconsistent, and it is challenging to obtain a large-scale database, or to extend existing databases, because of the inconvenience of collecting images, training the subjects, conducting subjective experiments, and realigning human quality evaluations. To combat these limitations, this paper explores and exploits preference image pairs (PIPs) such as the quality of image Ia is better than that of image Ib for training a robust BIQA model. The preference label, representing the relative quality of two images, is generally precise and consistent, and is not sensitive to image content, distortion type, or subject identity; such PIPs can be generated at a very low cost. The proposed BIQA method is one of learning to rank. We first formulate the problem of learning the mapping from the image features to the preference label as one of classification. In particular, we investigate the utilization of a multiple kernel learning algorithm based on group lasso to provide a solution. A simple but effective strategy to estimate perceptual image quality scores is then presented. Experiments show that the proposed BIQA method is highly effective and achieves a performance comparable with that of state-of-the-art BIQA algorithms. Moreover, the proposed method can be easily extended to new distortion categories.

Formulation of detailed consumables management models for the development (preoperational) period of advanced space transportation system: Executive summary

NASA Technical Reports Server (NTRS)

Torian, J. G.

1976-01-01

Formulation of models required for the mission planning and scheduling function and establishment of the relation of those models to prelaunch, onboard, ground support, and postmission functions for the development phase of space transportation systems (STS) was conducted. The preoperational space shuttle is used as the design baseline for the subject model formulations. Analytical models were developed which consist of a mission planning processor with appropriate consumables data base and a method of recognizing potential constraint violations in both the planning and flight operations functions. A flight data file for storage/retrieval of information over an extended period which interfaces with a flight operations processor for monitoring of the actual flights was examined.

Toughened uni-piece, fibrous, reinforced, oxidization-resistant composite

NASA Technical Reports Server (NTRS)

Stewart, David A. (Inventor); Leiser, Daniel B. (Inventor)

2008-01-01

A composite thermal protection structure, for applications such as atmospheric re-entry vehicles, that can withstand temperatures as high as 3600.degree. F. The structure includes an exposed surface cap having a specially formulated coating, an insulator base adjacent to the cap with another specially formulated coating, and one or more pins that extend from the cap through the insulator base to tie the cap and base together, through ceramic bonding and mechanical attachment. The cap and insulator base have corresponding depressions and projections that mate and allow for differences in thermal expansion of the cap and base. A thin coating of a reaction cured glass formulation is optionally provided on the structure to allow reduce oxidization and/or to reduce catalytic efficiency.

Tamarind seed gum-hydrolyzed polymethacrylamide-g-gellan beads for extended release of diclofenac sodium using 32 full factorial design.

PubMed

Nandi, Gouranga; Nandi, Amit Kumar; Khan, Najim Sarif; Pal, Souvik; Dey, Sibasish

2018-07-15

Development of tamarind seed gum (TSG)-hydrolyzed polymethacrylamide-g-gellan (h-Pmaa-g-GG) composite beads for extended release of diclofenac sodium using 3 2 full factorial design is the main purpose of this study. The ratio of h-Pmaa-g-GG and TSG and concentration of cross-linker CaCl 2 were taken as independent factors with three different levels of each. Effects of polymer ratio and CaCl 2 on drug entrapment efficiency (DEE), drug release, bead size and swelling were investigated. Responses such as DEE and different drug release parameters were statistically analyzed by 3 2 full factorial design using Design-Expert software and finally the formulation factors were optimized to obtain USP-reference release profile. Drug release rate was found to decrease with decrease in the ratio of h-Pmaa-g-GG:TSG and increase in the concentration of Ca 2+ ions in cross-linking medium. The optimized formulation showed DEE of 93.25% and an extended drug release profile over a period of 10h with f 2 =80.13. Kinetic modeling unveiled case-I-Fickian diffusion based drug release mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

Application of hot-melt extrusion technology in immediate-release abuse-deterrent formulations.

PubMed

Wening, Klaus; Schwier, Sebastian; Stahlberg, Hans-J; Galia, Eric

Hot-melt extrusion (HME) technology has been used for manufacturing extended-release abuse-deterrent formulations (ADFs) of opioid-type analgesics with improved tamper-resistant properties. Our objective was to describe application of this technology to immediate-release (IR) ADFs. For development of a sample IR ADF (hydrocodone 10 mg/acetaminophen 325 mg) based on HME, feasibility studies were performed using different excipients. The formulation selected for further development was evaluated via in vitro test battery. Moreover, in vivo performance of IR ADF technologies was investigated in an open-label, randomized, cross-over, phase 1, relative oral bioavailability study with another opioid (model compound). Single-center bioavailability trial. Twenty-four healthy white male subjects. ADF IR formulation of an opioid and marketed IR formulation. For feasibility and in vitro studies, dissolution profiles, syringeability, particle size distribution after physical manipulation, and extractability were evaluated. For the phase 1 study, pharmacokinetic parameters were evaluated and compared for ADF IR and a marketed IR formulation. After manipulation, the majority of particles from the ADF IR formulation were >500µm and, thus, not considered suitable for intranasal abuse, while the majority of particles for the reference marketed IR formulation were <500µm. The ADF IR formulation was resistant to syringing and preparation for potential intravenous injection. In healthy subjects, pharmacokinetics of an ADF and marketed IR formulation of an opioid were nearly identical. Application of HME to IR formulations led to development of products with improved mechanical resistance to manipulation for intranasal or intravenous preparation, but similar bioavailability.

Application of the Extended Completeness Relation to the Absorbing Boundary Condition

NASA Astrophysics Data System (ADS)

Iwasaki, Masataka; Otani, Reiji; Ito, Makoto

The strength function of the linear response by the external field is calculated in the formalism of the absorbing boundary condition (ABC). The dipole excitation of a schematic two-body system is treated in the present study. The extended completeness relation, which is assumed on the analogy of the formulation in the complex scaling method (CSM), is applied to the calculation of the strength function. The calculation of the strength function is successful in the present formalism and hence, the extended completeness relation seems to work well in the ABC formalism. The contributions from the resonance and the non-resonant continuum are also analyzed according to the decomposition of the energy levels in the extended completeness relation.

Transformation of nonlinear discrete-time system into the extended observer form

NASA Astrophysics Data System (ADS)

Kaparin, V.; Kotta, Ü.

2018-04-01

The paper addresses the problem of transforming discrete-time single-input single-output nonlinear state equations into the extended observer form, which, besides the input and output, also depends on a finite number of their past values. Necessary and sufficient conditions for the existence of both the extended coordinate and output transformations, solving the problem, are formulated in terms of differential one-forms, associated with the input-output equation, corresponding to the state equations. An algorithm for transformation of state equations into the extended observer form is proposed and illustrated by an example. Moreover, the considered approach is compared with the method of dynamic observer error linearisation, which likewise is intended to enlarge the class of systems transformable into an observer form.

Mono- and biphasic plasma concentration-time curves of mesalazine from a 500 mg suppository in healthy male volunteers controlled by the time of defecation before dosing.

PubMed

Vree, T B; Dammers, E; Exler, P S; Maes, R A

2000-06-01

This study was based on data from a bioequivalence study (n=24) of two different formulations of suppositories containing 500 mg mesalazine (formulation I and II), with a similar dissolution profile in phosphate buffer pH 6.8. There was a large intra- and intersubject variability in the plasma concentration-time curves of mesalazine from both suppositories. The aim of the investigation was to identify the parameters that caused the observed large variations in release and absorption of mesalazine in the rectum. Plasma mesalazine and acetylmesalazine, and urine acetylmesalazine concentrations were determined according to validated methods involving HPLC analysis with coulometric detection. Lower limit of quantitation values were respectively 10.4 and 19.4 ng mL(-1) in plasma and 0.96 microg mL(-1) in urine. The time of defecation before and after insertion was recorded. There was a clear distinction between subjects who showed monophasic mesalazine release/absorption and those who showed biphasic and more extended release/absorption. With formulation I there was a correlation between time of defecation before dosing and the type of absorption, monophasic and biphasic absorbers showed a significant difference in the time of defecation, e.g. 9.7+/-5.6 h vs 18.8+/-11.9 h (P = 0.0218). The impact of time of defecation before dosing was non-significant with formulation II, 16.7+/-7.2 h vs 15.1+/-4.2 h (P = 0.67). The impact of the time elapsed between administration and time of defecation after the insertion of the suppository was not significant for the type of release/absorption. The plasma concentration-time curves of the metabolite ran parallel to that of the parent drug, the more parent drug was released/absorbed, the more was acetylated (P = 0.0013) and excreted into the urine (P = 0.0004). After absorption the compound was metabolized into acetylmesalazine, and renally excreted (12-13% of the dose). Monophasic release/ absorption resulted in 7.1% metabolite with I and 10.3% with II (P = 0.0004), while biphasic release/absorption gave 16.8% metabolite with I and 15.5% with II. The renal clearance of the metabolite acetylmesalazine was independent of the observed defecation patterns (300 mL min(-1), P > 0.8), stool composition, and type of absorption.

Formulation of consumables management models: Mission planning processor payload interface definition

NASA Technical Reports Server (NTRS)

Torian, J. G.

1977-01-01

Consumables models required for the mission planning and scheduling function are formulated. The relation of the models to prelaunch, onboard, ground support, and postmission functions for the space transportation systems is established. Analytical models consisting of an orbiter planning processor with consumables data base is developed. A method of recognizing potential constraint violations in both the planning and flight operations functions, and a flight data file storage/retrieval of information over an extended period which interfaces with a flight operations processor for monitoring of the actual flights is presented.

An Ellipsoidal Particle-Finite Element Method for Hypervelocity Impact Simulation. Chapter 1

NASA Technical Reports Server (NTRS)

Shivarama, Ravishankar; Fahrenthold, Eric P.

2004-01-01

A number of coupled particle-element and hybrid particle-element methods have been developed for the simulation of hypervelocity impact problems, to avoid certain disadvantages associated with the use of pure continuum based or pure particle based methods. To date these methods have employed spherical particles. In recent work a hybrid formulation has been extended to the ellipsoidal particle case. A model formulation approach based on Lagrange's equations, with particles entropies serving as generalized coordinates, avoids the angular momentum conservation problems which have been reported with ellipsoidal smooth particle hydrodynamics models.

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

NASA Astrophysics Data System (ADS)

Sumihara, K.

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

Frequency domain, waveform inversion of laboratory crosswell radar data

USGS Publications Warehouse

Ellefsen, Karl J.; Mazzella, Aldo T.; Horton, Robert J.; McKenna, Jason R.

2010-01-01

A new waveform inversion for crosswell radar is formulated in the frequency-domain for a 2.5D model. The inversion simulates radar waves using the vector Helmholtz equation for electromagnetic waves. The objective function is minimized using a backpropagation method suitable for a 2.5D model. The inversion is tested by processing crosswell radar data collected in a laboratory tank. The estimated model is consistent with the known electromagnetic properties of the tank. The formulation for the 2.5D model can be extended to inversions of acoustic and elastic data.

Soft, chewable gelatin-based pharmaceutical oral formulations: a technical approach.

PubMed

Dille, Morten J; Hattrem, Magnus N; Draget, Kurt I

2018-06-01

Hard tablets and capsules for oral drug delivery cause problems for people experiencing dysphagia. This work describes the formulation and properties of a gelatin based, self-preserved, and soft chewable tablet as an alternative and novel drug delivery format. Gelatin (8.8-10% in 24.7-29% water) constituted the matrix of the soft, semi-solid tablets. Three different pharmaceuticals (Ibuprofen 10%, Acetaminophen 15%, and Meloxicam 1.5%) were tested in this formulation. Microbial stability was controlled by lowering the water activity with a mixture of sorbitol and xylitol (45.6-55%). Rheological properties were tested applying small strain oscillation measurements. Taste masking of ibuprofen soft-chew tablets was achieved by keeping the ibuprofen insoluble at pH 4.5 and keeping the processing temperature below the crystalline-to-amorphous transition temperature. Soft-chew formulations showed good stability for all three pharmaceuticals (up to 24 months), and the ibuprofen containing formulation exhibited comparable dissolution to a standard oral tablet as well as good microbial stability. The rheological properties of the ibuprofen/gelatin formulation had the fingerprint of a true gelatin gel, albeit higher moduli, and melting temperature. The results suggest that easy-to-swallow and well taste-masked soft chewable tablet formulations with extended shelf life are within reach for several active pharmaceutical ingredients (APIs).

Controlled-release of Bacillus thurigiensis formulations encapsulated in light-resistant colloidosomal microcapsules for the management of lepidopteran pests of Brassica crops.

PubMed

Bashir, Oumar; Claverie, Jerome P; Lemoyne, Pierre; Vincent, Charles

2016-01-01

Bacillus thuringiensis ( B. t. ) based formulations have been widely used to control lepidopteran pests in agriculture and forestry. One of their weaknesses is their short residual activity when sprayed in the field. Using Pickering emulsions, mixtures of spores and crystals from three B. t. serovars were successfully encapsulated in colloïdosomal microparticles (50 μm) using innocuous chemicals (acrylic particles, sunflower oil, iron oxide nanoparticles, ethanol and water). A pH trigger mechanism was incorporated within the particles so that B. t. release occurred only at pH > 8.5 which corresponds to the midgut pH of the target pests. Laboratory assays performed on Trichoplusia ni ( T. ni ) larvae demonstrated that the microencapsulation process did not impair B. t. bioactivity. The best formulations were field-tested on three key lepidopteran pests that attack Brassica crops, i.e., the imported cabbageworm, the cabbage looper and the diamondback moth. After 12 days, the mean number of larvae was significantly lower in microencapsulated formulations than in a commercial B. t. formulation, and the effect of microencapsulated formulations was comparable to a chemical pesticide (lambda-cyhalothrin). Therefore, colloïdosomal microcapsule formulations successfully extend the bioactivity of B. t. for the management of lepidopteran pests of Brassica crops.

In Vitro Drug Release After Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations.

PubMed

Mayock, Stephen P; Saim, Said; Fleming, Alison B

2017-12-01

Extended-release (ER) opioids are associated with high rates of abuse. Recreational opioid users often manipulate ER formulations to achieve a high plasma concentration in a short amount of time, resulting in a more rapid and intense high. Patients may also manipulate ER tablets to facilitate swallowing, without recognizing that manipulation could increase release rate. The goal of this study was to assess the ability of oxycodone DETERx (Xtampza ® ER, Collegium Pharmaceutical, Inc., Canton, MA, USA) and other commercially available ER opioid formulations with and without physicochemical abuse-deterrent characteristics to be manipulated by crushing in an in vitro setting. In vitro dissolution techniques were used to compare the opioid release from a variety of ER opioid formulations. Dissolution was assessed for intact and crushed dosage forms. Opioid release was quantified using high-performance liquid chromatography. Intact formulations exhibited drug release rates characteristic of 12- or 24-h dosage forms. After crushing using commonly available household tools, only Xtampza ER maintained ER of opioid. Xtampza ER maintained its ER characteristics after crushing, unlike many other commercially available opioid formulations, including some formulated with abuse-deterrent properties. As such, Xtampza ER may be less appealing to abusers and offer a margin of safety for patients who manipulate dosage forms to facilitate swallowing.

Gacs quantum algorithmic entropy in infinite dimensional Hilbert spaces

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

Benatti, Fabio, E-mail: benatti@ts.infn.it; Oskouei, Samad Khabbazi, E-mail: kh.oskuei@ut.ac.ir; Deh Abad, Ahmad Shafiei, E-mail: shafiei@khayam.ut.ac.ir

We extend the notion of Gacs quantum algorithmic entropy, originally formulated for finitely many qubits, to infinite dimensional quantum spin chains and investigate the relation of this extension with two quantum dynamical entropies that have been proposed in recent years.

Extending residence time and stability of peptides by Protected Graft Copolymer (PGC) excipient: GLP-1 example

PubMed Central

Castillo, Gerardo M.; Reichstetter, Sandra; Bolotin, Elijah M.

2011-01-01

Purpose The purpose of this study is to determine whether a Protected Graft Copolymer (PGC) containing fatty acid can be used as a stabilizing excipient for GLP-1 and whether PGC/GLP-1 given once a week can be an effective treatment for diabetes. Methods To create a PGC excipient, polylysine was grafted with methoxypolyethyleneglycol and fatty acid at the epsilon amino groups. We performed evaluation of 1) the binding of excipient to GLP-1, 2) the DPP IV sensitivity of GLP-1 formulated with PGC as the excipient, 3) the in vitro bio-activity of excipient-formulated GLP-1, 4) the in vivo pharmacokinetics of excipient-formulated GLP-1, and 5) the efficacy of the excipient-formulated GLP-1 in diabetic rats. Results We showed reproducible synthesis of PGC excipient, showed high affinity binding of PGC to GLP-1, slowed protease degradation of excipient-formulated GLP-1, and showed that excipient-formulated GLP-1 induced calcium influx in INS cells. Excipient-formulated GLP-1 stays in the blood for at least 4 days. When excipient-formulated GLP-1 was given subcutaneously once a week to diabetic ZDF rats, a significant reduction of HbA1c compared to control was observed. The reduction is similar to diabetic ZDF rats given exendin twice a day. Conclusions PGC can be an ideal in vivo stabilizing excipient for biologically labile peptides. PMID:21830140

Administration of a Sol-Gel Formulation of Phenylephrine Using Low-Temperature Hollow Microneedle for Treatment of Intermittent Fecal Incontinence.

PubMed

Lee, Hyunji; Park, Jung-Hwan; Park, Jung Ho

2017-12-01

A low temperature hollow microneedle system was devised to deliver sol-gel transition formulation near the surface of the skin for extended release and local delivery of drug by a non-invasive method. This new system can improve treatment of intermittent fecal incontinence. The low-temperature system was integrated with a hollow microneedle to maintain the low temperature of the sol formulation. Various sol-gel formulations using Pluronic F-127 (PF-127) and Hydroxy-propyl-methyl-cellulose (HPMC) were prepared, and their gelation temperature, flow property, and diffusion retardation were observed. Resting anal sphincter pressure in response to a phenylephrine (PE) sol-gel formulation was measured using an air-charged catheter. The biocompatibility of the sol-gel PE formulation was evaluated by observing the immunological response. When the PF-127 25%, HPMC 1% and PE formulation (PF25-HPMC1-PE) was injected through the peri-anal skin of the rat in vivo, the highest pressure on the anal sphincter muscle occurred at 6-8 h and anal pressure increased and lasted twice as long as with the phosphate-buffered saline (PBS)-PE formulation. There was no significant difference in the number of mast cells after administration into the rat in vivo between the PF25-HPMC1-PE formulation and the PBS-PE formulation. The combination of a low-pain hollow microneedle system and an injectable sol-gel formulation improved the efficacy of treatment of intermittent fecal incontinence. A low-temperature hollow microneedle system using a sol-gel formulation has many applications in medical treatments that require depot effect, local targeting, and pain control.

Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy.

PubMed

Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Fadaeinasab, Mehran; Khaing, Si Lay; Chung, Lip Yong; Mohamad Haron, Didi Erwandi B; Noordin, Mohamed Ibrahim

2017-01-01

This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153 Sm 2 O 3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time ( T max ) at which the maximum concentration of metformin HCl in the blood ( C max ) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. C max and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region.

Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy

PubMed Central

Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Fadaeinasab, Mehran; Khaing, Si Lay; Chung, Lip Yong; Mohamad Haron, Didi Erwandi B; Noordin, Mohamed Ibrahim

2017-01-01

This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153Sm2O3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time (Tmax) at which the maximum concentration of metformin HCl in the blood (Cmax) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. Cmax and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region. PMID:28031701

Analysis of Online Information Searching for Cardiovascular Diseases on a Consumer Health Information Portal

PubMed Central

Jadhav, Ashutosh; Sheth, Amit; Pathak, Jyotishman

2014-01-01

Since the early 2000’s, Internet usage for health information searching has increased significantly. Studying search queries can help us to understand users “information need” and how do they formulate search queries (“expression of information need”). Although cardiovascular diseases (CVD) affect a large percentage of the population, few studies have investigated how and what users search for CVD. We address this knowledge gap in the community by analyzing a large corpus of 10 million CVD related search queries from MayoClinic.com. Using UMLS MetaMap and UMLS semantic types/concepts, we developed a rule-based approach to categorize the queries into 14 health categories. We analyzed structural properties, types (keyword-based/Wh-questions/Yes-No questions) and linguistic structure of the queries. Our results show that the most searched health categories are ‘Diseases/Conditions’, ‘Vital-Sings’, ‘Symptoms’ and ‘Living-with’. CVD queries are longer and are predominantly keyword-based. This study extends our knowledge about online health information searching and provides useful insights for Web search engines and health websites. PMID:25954380

Printable Transparent Conductive Films for Flexible Electronics.

PubMed

Li, Dongdong; Lai, Wen-Yong; Zhang, Yi-Zhou; Huang, Wei

2018-03-01

Printed electronics are an important enabling technology for the development of low-cost, large-area, and flexible optoelectronic devices. Transparent conductive films (TCFs) made from solution-processable transparent conductive materials, such as metal nanoparticles/nanowires, carbon nanotubes, graphene, and conductive polymers, can simultaneously exhibit high mechanical flexibility, low cost, and better photoelectric properties compared to the commonly used sputtered indium-tin-oxide-based TCFs, and are thus receiving great attention. This Review summarizes recent advances of large-area flexible TCFs enabled by several roll-to-roll-compatible printed techniques including inkjet printing, screen printing, offset printing, and gravure printing using the emerging transparent conductive materials. The preparation of TCFs including ink formulation, substrate treatment, patterning, and postprocessing, and their potential applications in solar cells, organic light-emitting diodes, and touch panels are discussed in detail. The rational combination of a variety of printed techniques with emerging transparent conductive materials is believed to extend the opportunities for the development of printed electronics within the realm of flexible electronics and beyond. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Naming game with biased assimilation over adaptive networks

NASA Astrophysics Data System (ADS)

Fu, Guiyuan; Zhang, Weidong

2018-01-01

The dynamics of two-word naming game incorporating the influence of biased assimilation over adaptive network is investigated in this paper. Firstly an extended naming game with biased assimilation (NGBA) is proposed. The hearer in NGBA accepts the received information in a biased manner, where he may refuse to accept the conveyed word from the speaker with a predefined probability, if the conveyed word is different from his current memory. Secondly, the adaptive network is formulated by rewiring the links. Theoretical analysis is developed to show that the population in NGBA will eventually reach global consensus on either A or B. Numerical simulation results show that the larger strength of biased assimilation on both words, the slower convergence speed, while larger strength of biased assimilation on only one word can slightly accelerate the convergence; larger population size can make the rate of convergence slower to a large extent when it increases from a relatively small size, while such effect becomes minor when the population size is large; the behavior of adaptively reconnecting the existing links can greatly accelerate the rate of convergence especially on the sparse connected network.

Use of partial AUC to demonstrate bioequivalence of Zolpidem Tartrate Extended Release formulations.

PubMed

Lionberger, Robert A; Raw, Andre S; Kim, Stephanie H; Zhang, Xinyuan; Yu, Lawrence X

2012-04-01

FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times. Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations. The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test. In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien CR: onset of sleep and sleep maintenance.

ALPS - A LINEAR PROGRAM SOLVER

NASA Technical Reports Server (NTRS)

Viterna, L. A.

1994-01-01

Linear programming is a widely-used engineering and management tool. Scheduling, resource allocation, and production planning are all well-known applications of linear programs (LP's). Most LP's are too large to be solved by hand, so over the decades many computer codes for solving LP's have been developed. ALPS, A Linear Program Solver, is a full-featured LP analysis program. ALPS can solve plain linear programs as well as more complicated mixed integer and pure integer programs. ALPS also contains an efficient solution technique for pure binary (0-1 integer) programs. One of the many weaknesses of LP solvers is the lack of interaction with the user. ALPS is a menu-driven program with no special commands or keywords to learn. In addition, ALPS contains a full-screen editor to enter and maintain the LP formulation. These formulations can be written to and read from plain ASCII files for portability. For those less experienced in LP formulation, ALPS contains a problem "parser" which checks the formulation for errors. ALPS creates fully formatted, readable reports that can be sent to a printer or output file. ALPS is written entirely in IBM's APL2/PC product, Version 1.01. The APL2 workspace containing all the ALPS code can be run on any APL2/PC system (AT or 386). On a 32-bit system, this configuration can take advantage of all extended memory. The user can also examine and modify the ALPS code. The APL2 workspace has also been "packed" to be run on any DOS system (without APL2) as a stand-alone "EXE" file, but has limited memory capacity on a 640K system. A numeric coprocessor (80X87) is optional but recommended. The standard distribution medium for ALPS is a 5.25 inch 360K MS-DOS format diskette. IBM, IBM PC and IBM APL2 are registered trademarks of International Business Machines Corporation. MS-DOS is a registered trademark of Microsoft Corporation.

Voluntary Running-Wheel Activity, Arterial Blood Gases, and Thermal Antinociception in Rats after 3 Buprenorphine Formulations

PubMed Central

Johnson, Rebecca A

2016-01-01

Buprenorphine HCl (BUP) is a μ-opioid agonist used in laboratory rodents. New formulations of buprenorphine (for example, sustained-released buprenorphine [BUP SR], extended-release buprenorphine [BUP ER]) have been developed to extend the analgesic duration. In a crossover design, 8 adult rats were injected subcutaneously with either BUP, BUP SR, BUP ER, or saline, after which voluntary running-wheel activity, arterial blood gases, and thermal withdrawal latency were assessed. Wheel running was decreased at 24 h compared with baseline in all treatment groups but returned to baseline by 48 h. Arterial pH, HCO3–, and CO2 were not changed between groups or over time. However, arterial oxygen was lower than baseline in the BUP (–8 ± 2 mm Hg), BUP SR (–7 ± 1 mm Hg), and BUP ER (–17 ± 2 mm Hg) groups compared with saline controls (3 ± 2 mm Hg); the BUP ER group showed the greatest decrease when all time points were combined. BUP increased the withdrawal latency at 1 h (15% ± 3%), whereas BUP ER increased latencies at 4, 8, 12, and 48 h (35% ± 11%, 21% ± 7%, 26% ± 7%, and 22% ± 9%, respectively) and BUP SR prolonged latencies at 24, 48, and 72 h (15% ± 6%, 18% ± 5%, and 20% ± 8%, respectively). The duration of thermal analgesia varied between buprenorphine formulations, but all 3 formulations reduced voluntary-running activity at 24 h after injection and might cause hypoxemia in normal adult rats. PMID:27177564

An abuse-deterrent, microsphere-in-capsule formulation of extended-release oxycodone: alternative modes of administration to facilitate pain management in patients with dysphagia.

PubMed

McCarberg, Bill H; Kopecky, Ernest A; O'Connor, Melinda; Marseilles, Ann; Varanasi, Ravi K; Thompson, Christy; Fleming, Alison B

2016-12-01

Patients with chronic pain may experience difficulty swallowing, in part due to worsening disease, comorbid conditions, iatrogenic etiology, or age. Patients or caregivers may manipulate extended-release (ER) opioid formulations to facilitate oral dosing due to a lack of therapeutic options that allow for sprinkle or enteral feeding tube administration. If crushed or broken, current oral ER opioids can be associated with adverse sequelae, including risk of potentially fatal overdose. To review the safety, in vitro dissolution data, and in vivo pharmacokinetic data that support alternative modes of administration of oxycodone DETERx (Xtampza ER) via sprinkling onto soft foods for oral ingestion or via enteral feeding tubes. A review of oxycodone DETERx data from in vitro and in vivo studies was conducted to demonstrate support for alternative routes and modes of administration. There was no difference in the dissolution profile when administered with various soft foods or when mixed with various liquid vehicles and administered via nasogastric (NG) or gastrostomy (G) tubes, based on in vitro studies. When sprinkled onto applesauce and administered orally, the microspheres were bioequivalent to the intact oxycodone capsules. When crushed or chewed, the formulation maintained its pharmacokinetic profile; no bolus dose of opioid was released. The sprinkle-dose study was limited by the single-dose study design, as well as the small sample size. Oxycodone DETERx is the first ER oxycodone formulation that can be administered either intact, sprinkled onto soft foods, or via NG/G tubes, thereby providing options for treating pain in patients who have difficulty swallowing.

Procedures and equipment for staining large numbers of plant root samples for endomycorrhizal assay.

PubMed

Kormanik, P P; Bryan, W C; Schultz, R C

1980-04-01

A simplified method of clearing and staining large numbers of plant roots for vesicular-arbuscular (VA) mycorrhizal assay is presented. Equipment needed for handling multiple samples is described, and two formulations for the different chemical solutions are presented. Because one formulation contains phenol, its use should be limited to basic studies for which adequate laboratory exhaust hoods are available and great clarity of fungal structures is required. The second staining formulation, utilizing lactic acid instead of phenol, is less toxic, requires less elaborate laboratory facilities, and has proven to be completely satisfactory for VA assays.

Generalized Fractional Derivative Anisotropic Viscoelastic Characterization.

PubMed

Hilton, Harry H

2012-01-18

Isotropic linear and nonlinear fractional derivative constitutive relations are formulated and examined in terms of many parameter generalized Kelvin models and are analytically extended to cover general anisotropic homogeneous or non-homogeneous as well as functionally graded viscoelastic material behavior. Equivalent integral constitutive relations, which are computationally more powerful, are derived from fractional differential ones and the associated anisotropic temperature-moisture-degree-of-cure shift functions and reduced times are established. Approximate Fourier transform inversions for fractional derivative relations are formulated and their accuracy is evaluated. The efficacy of integer and fractional derivative constitutive relations is compared and the preferential use of either characterization in analyzing isotropic and anisotropic real materials must be examined on a case-by-case basis. Approximate protocols for curve fitting analytical fractional derivative results to experimental data are formulated and evaluated.

Evaluating Descent and Ascent Trajectories Near Non-Spherical Bodies

NASA Technical Reports Server (NTRS)

Werner, Robert A.

2010-01-01

Spacecraft landing on small bodies pass through regions where conventional gravitation formulations using exterior spherical harmonics are inaccurate. An investigation shows that a formulation using interior solid spherical harmonics might be satisfactory. Interior spherical harmonic expansions are usable inside an imaginary, empty sphere. For this application, such a sphere could be positioned in empty space above the intended landing site and rotating with the body. When the spacecraft is inside this sphere, the interior harmonic expansion would be used instead of the conventional, exterior harmonic expansion. Coefficients can be determined by a least-squares fit to gravitation measurements synthesized from conventional formulations. Due to their unfamiliarity, recurrences for interior, as well as exterior, expansions are derived. Hotine's technique for partial derivatives of exterior spherical harmonics is extended to interior harmonics.

Generalized cable equation model for myelinated nerve fiber.

PubMed

Einziger, Pinchas D; Livshitz, Leonid M; Mizrahi, Joseph

2005-10-01

Herein, the well-known cable equation for nonmyelinated axon model is extended analytically for myelinated axon formulation. The myelinated membrane conductivity is represented via the Fourier series expansion. The classical cable equation is thereby modified into a linear second order ordinary differential equation with periodic coefficients, known as Hill's equation. The general internal source response, expressed via repeated convolutions, uniformly converges provided that the entire periodic membrane is passive. The solution can be interpreted as an extended source response in an equivalent nonmyelinated axon (i.e., the response is governed by the classical cable equation). The extended source consists of the original source and a novel activation function, replacing the periodic membrane in the myelinated axon model. Hill's equation is explicitly integrated for the specific choice of piecewise constant membrane conductivity profile, thereby resulting in an explicit closed form expression for the transmembrane potential in terms of trigonometric functions. The Floquet's modes are recognized as the nerve fiber activation modes, which are conventionally associated with the nonlinear Hodgkin-Huxley formulation. They can also be incorporated in our linear model, provided that the periodic membrane point-wise passivity constraint is properly modified. Indeed, the modified condition, enforcing the periodic membrane passivity constraint on the average conductivity only leads, for the first time, to the inclusion of the nerve fiber activation modes in our novel model. The validity of the generalized transmission-line and cable equation models for a myelinated nerve fiber, is verified herein through a rigorous Green's function formulation and numerical simulations for transmembrane potential induced in three-dimensional myelinated cylindrical cell. It is shown that the dominant pole contribution of the exact modal expansion is the transmembrane potential solution of our generalized model.

A stable fixed-dose combination tablet of pseudoephedrine and KOB extracts for the extended release.

PubMed

Hwang, C-J; Park, M-H; Jung, H-W; Park, Y-K; Kim, Y-H; Kang, J-S; Cho, C-W

2013-11-01

Allergic rhinitis (AR) is characterized by inflammation of the nasal mucosa with hypersensitivity resulting from seasonal or perennial responses to specific environmental allergens and by symptoms like nasal rubbing, sneezing, rhinorrhea, lacrimation, nasal congestion and obstruction, and less frequently cough. KOB extracts, which is a polyherbal medicine consisting of 5 different herbs (Atractylodes macrocephala, Astragalus membranaceus, Saposhnikovia divaricata, Ostericum koreanum and Scutellaria baicalensis) had commonly been used for the treatment of various allergic diseases showed an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis, recently. On the other hand, pseudoephedrine is a sympathomimetic amine commonly used to relieve congestion in patients with allergic rhinitis and common colds. Considering the KOB's therapeutic mechanism, the combination with pseudoephedrine would be suitable for allergic rhinitis. This study is to obtain an effective extended release formulation using pseudoephedrine and KOB extracts to reduce side effects of drug due to repeated dosing and improve the compliance of patients for treatment of rhinitis and nasal decongestion. So, the fixed-dose combination tablet of pseudoephedrine and KOB extracts was prepared by direct compression and characterized by drug content, flowing characteristics and dissolution test. The drug content of baicalin of KOB extracts was within the range of 95-105% except for T1 formulation. The hardness and friability values of all formulations ranged from 9 to 13 kp and less than 1%, respectively. Taken together, T4 or T8 could be a stable fixed-dose combination tablet for extended release of pseudoephedrine and KOB extracts for nasal rhinitis. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of an Extended-Release, Abuse-Deterrent, Microsphere-in-Capsule Analgesic for the Management of Patients with Chronic Pain With Dysphagia (CPD).

PubMed

Fleming, Alison B; Carlson, Douglas R; Varanasi, Ravi K; Grima, Michael; Mayock, Stephen P; Saim, Said; Kopecky, Ernest A

2016-03-01

Patients who have chronic pain with dysphagia (difficulty swallowing) (CPD) often have difficulty taking oral medication and, as such, alter their medications by crushing or chewing in an attempt to make it easier to swallow. Such manipulation of currently marketed, extended-release (ER) opioid analgesics can significantly alter the pharmacokinetic (PK) properties of the formulations, resulting in poor treatment outcome or serious adverse events. There is an unmet medical need for oral ER opioid formulations suitable for patients with CPD. The primary objectives of this study were to conduct in vitro studies to evaluate alternate means of administration of a new, extended-release (ER), abuse-deterrent, microsphere-in-capsule formulation of oxycodone for patients with CPD. Specifically, these studies investigated the in vitro equivalence of drug release rates from Oxycodone DETERx® ER intact capsules (control condition) and administration via alternate modes-opening the capsule and sprinkling the microspheres onto soft foods or administration through enteral tubes. Secondary objectives were to compare alternate modes of administration of Oxycodone DETERx® to a commercially available ER-morphine product. Soft food study: Oxycodone DETERx® microspheres were sprinkled onto and mixed with several soft foods (ie, applesauce, vanilla pudding, strawberry jam, yogurt, and vanilla ice cream); the effect of drug contact time (0, 30, and 60 minutes) on drug release was studied. Enteral tube study: Oxycodone DETERx® microspheres were administered through varying sizes of nasogastric (10 and 12 Fr.) tubes and a 16 Fr. gastrostomy tube using 5 different delivery vehicles (ie, water, liquid nutritional feeds [Jevity®, Ensure®], and milk [whole milk and 2% milk]). Drug release rate was characterized using a standard in vitro dissolution methodology; dissolution of intact Oxycodone DETERx® capsules served as the control for both the soft food and enteral tube studies. Oxycodone concentration was measured using a standardized high-performance liquid chromatography (HPLC) assay. Similarity factor (f2) analysis was used to compare similarity of the dissolution profiles of test and control conditions. The mean dissolution profile of Oxycodone DETERx® microspheres sprinkled onto and mixed with each of the soft foods were similar (f2 > 50) to that of the control. Study drug-food contact time did not impact dissolution profiles. The dissolution data obtained from Oxycodone DETERx® microspheres passed through enteral feeding tubes of varying sizes were similar (f2 > 50) to that of the control. Unlike a marketed morphine sulfate ER pellet formulation, Oxycodone DETERx® did not clog any of the studied enteral tubes. A new ER, abuse-deterrent, microsphere-in-capsule formulation of oxycodone can be administered by sprinkling onto soft food without affecting the drug release profile of the formulation. The formulation can also be administered directly via enteral tubes without affecting drug release and without clogging enteral tubes. Oxycodone DETERx® may offer physicians and patients with CPD an alternate treatment option, especially in those patients who have dysphagia or an aversion to swallowing monolithic tablet/capsule formulations and for whom analgesic patches or other opioid formulations are not a viable therapeutic option. © 2015 World Institute of Pain.

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

USDA-ARS?s Scientific Manuscript database

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...

Unit-Dose Bags For Formulating Intravenous Solutions

NASA Technical Reports Server (NTRS)

Finley, Mike; Kipp, Jim; Scharf, Mike; Packard, Jeff; Owens, Jim

1993-01-01

Smaller unit-dose flowthrough bags devised for use with large-volume parenteral (LVP) bags in preparing sterile intravenous solutions. Premeasured amount of solute stored in such unit-dose bag flushed by predetermined amount of water into LVP bag. Relatively small number of LVP bags used in conjunction with smaller unit-dose bags to formulate large number of LVP intravenous solutions in nonsterile environment.

A contact layer element for large deformations

NASA Astrophysics Data System (ADS)

Weißenfels, C.; Wriggers, P.

2015-05-01

In many contact situations the material behavior of one contact member strongly influences the force acting between the two bodies. Unfortunately standard friction models cannot reproduce all of these material effects at the contact layer and often continuum interface elements are used instead. These elements are intrinsically tied to the fixed grid and hence cannot be used in large sliding simulations. Due to the shortcomings of the standard contact formulations and of the interface elements a new type of a contact layer element is developed in this work. The advantages of this element are the direct implementation of continuum models into the contact formulation and the application to arbitrary large deformations. Showing a relation between continuum and contact kinematics based on the solid-shell concept the new contact element is at the end a natural extension of the standard contact formulations into 3D. Two examples show that the continuum behavior can be exactly reproduced at the contact surface even in large sliding situations using this contact layer element. For the discretization of the new contact element the Mortar method is chosen exemplary, but it can be combined with all kinds of contact formulations.

Putting Ideas on Paper

ERIC Educational Resources Information Center

Allen, Jared; Rogers, Meredith Park

2015-01-01

Many students find it easier to express their ideas about science through talking rather than writing. However, writing in science promotes new learning, helps students consolidate and review their scientific ideas, and aids in reformulating and extending their scientific knowledge. These practices lead to formulating and defending scientific…

Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

PubMed Central

Campos, Michel Leandro; Rosa, Talita Atanazio; Padilha, Elias Carvalho; Alzate, Alejandro Henao; Rolim, Larissa Araújo; Rolim-Neto, Pedro José

2016-01-01

Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentration in vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease. PMID:26883698

Local spectrum analysis of field propagation in an anisotropic medium. Part I. Time-harmonic fields.

PubMed

Tinkelman, Igor; Melamed, Timor

2005-06-01

The phase-space beam summation is a general analytical framework for local analysis and modeling of radiation from extended source distributions. In this formulation, the field is expressed as a superposition of beam propagators that emanate from all points in the source domain and in all directions. In this Part I of a two-part investigation, the theory is extended to include propagation in anisotropic medium characterized by a generic wave-number profile for time-harmonic fields; in a companion paper [J. Opt. Soc. Am. A 22, 1208 (2005)], the theory is extended to time-dependent fields. The propagation characteristics of the beam propagators in a homogeneous anisotropic medium are considered. With use of Gaussian windows for the local processing of either ordinary or extraordinary electromagnetic field distributions, the field is represented by a phase-space spectral distribution in which the propagating elements are Gaussian beams that are formulated by using Gaussian plane-wave spectral distributions over the extended source plane. By applying saddle-point asymptotics, we extract the Gaussian beam phenomenology in the anisotropic environment. The resulting field is parameterized in terms of the spatial evolution of the beam curvature, beam width, etc., which are mapped to local geometrical properties of the generic wave-number profile. The general results are applied to the special case of uniaxial crystal, and it is found that the asymptotics for the Gaussian beam propagators, as well as the physical phenomenology attached, perform remarkably well.

Koopmans-Compliant Spectral Functionals for Extended Systems

NASA Astrophysics Data System (ADS)

Nguyen, Ngoc Linh; Colonna, Nicola; Ferretti, Andrea; Marzari, Nicola

2018-04-01

Koopmans-compliant functionals have been shown to provide accurate spectral properties for molecular systems; this accuracy is driven by the generalized linearization condition imposed on each charged excitation, i.e., on changing the occupation of any orbital in the system, while accounting for screening and relaxation from all other electrons. In this work, we discuss the theoretical formulation and the practical implementation of this formalism to the case of extended systems, where a third condition, the localization of Koopmans's orbitals, proves crucial to reach seamlessly the thermodynamic limit. We illustrate the formalism by first studying one-dimensional molecular systems of increasing length. Then, we consider the band gaps of 30 paradigmatic solid-state test cases, for which accurate experimental and computational results are available. The results are found to be comparable with the state of the art in many-body perturbation theory, notably using just a functional formulation for spectral properties and the generalized-gradient approximation for the exchange and correlation functional.

Ethnic Enclaves and the Earnings of Immigrants

PubMed Central

Xie, Yu; Gough, Margaret

2011-01-01

A large literature in sociology concerns the implications of immigrants’ participation in ethnic enclaves for their economic and social well-being. The “enclave thesis” speculates that immigrants benefit from working in ethnic enclaves. Previous research concerning the effects of enclave participation on immigrants’ economic outcomes has come to mixed conclusions as to whether enclave effects are positive or negative. In this article, we seek to extend and improve upon past work by formulating testable hypotheses based on the enclave thesis and testing them with data from the 2003 New Immigrant Survey (NIS), employing both residence-based and workplace-based measures of the ethnic enclave. We compare the economic outcomes of immigrants working in ethnic enclaves with those of immigrants working in the mainstream economy. Our research yields minimal support for the enclave thesis. Our results further indicate that for some immigrant groups, ethnic enclave participation actually has a negative effect on economic outcomes. PMID:21863367

Concept Design of Cryogenic Propellant Storage and Transfer for Space Exploration

NASA Technical Reports Server (NTRS)

Free, James M.; Motil, Susan M.; Kortes, Trudy F.; Meyer, Michael L.; taylor, William J.

2012-01-01

NASA is in the planning and investigation process of developing innovative paths for human space exploration that strengthen the capability to extend human and robotic presence beyond low Earth orbit and throughout the solar system. NASA is establishing the foundations to enable humans to safely reach multiple potential destinations, including the Moon, asteroids, Lagrange points, and Mars and its environs through technology and capability development. To achieve access to these destinations within a reasonable flight time will require the use of high performance cryogenic propulsion systems. Therefore NASA is examining mission concepts for a Cryogenic Propellant Storage and Transfer (CPST) Flight Demonstration which will test and validate key capabilities and technologies required for future exploration elements such as large cryogenic propulsion stages and propellant depots. The CPST project will perform key ground testing in fiscal year 2012 and execute project formulation and implementation leading to a flight demonstration in 2017.

A universal pathway for kinesin stepping.

PubMed

Clancy, Bason E; Behnke-Parks, William M; Andreasson, Johan O L; Rosenfeld, Steven S; Block, Steven M

2011-08-14

Kinesin-1 is an ATP-driven, processive motor that transports cargo along microtubules in a tightly regulated stepping cycle. Efficient gating mechanisms ensure that the sequence of kinetic events proceeds in the proper order, generating a large number of successive reaction cycles. To study gating, we created two mutant constructs with extended neck-linkers and measured their properties using single-molecule optical trapping and ensemble fluorescence techniques. Owing to a reduction in the inter-head tension, the constructs access an otherwise rarely populated conformational state in which both motor heads remain bound to the microtubule. ATP-dependent, processive backstepping and futile hydrolysis were observed under moderate hindering loads. On the basis of measurements, we formulated a comprehensive model for kinesin motion that incorporates reaction pathways for both forward and backward stepping. In addition to inter-head tension, we found that neck-linker orientation is also responsible for ensuring gating in kinesin.

Maxwellians and the Remaking of Maxwell's Equations

NASA Astrophysics Data System (ADS)

Hunt, Bruce

2012-02-01

Although James Clerk Maxwell first formulated his theory of the electromagnetic field in the early 1860s, it went through important changes before it gained general acceptance in the 1890s. Those changes were largely the work of a group of younger physicists, the Maxwellians, led by G. F. FitzGerald in Ireland, Oliver Lodge and Oliver Heaviside in England, and Heinrich Hertz in Germany. Together, they extended, refined, tested, and confirmed Maxwell's theory, and recast it into the set of four vector equations known ever since as ``Maxwell's equations.'' By tracing how the Maxwellians remade and disseminated Maxwell's theory between the late 1870s and the mid-1890s, we can gain a clearer understanding not just of how the electromagnetic field was understood at the end of the 19th century, but of the collaborative nature of work at the frontiers of physics.

Trends in life science grid: from computing grid to knowledge grid.

PubMed

Konagaya, Akihiko

2006-12-18

Grid computing has great potential to become a standard cyberinfrastructure for life sciences which often require high-performance computing and large data handling which exceeds the computing capacity of a single institution. This survey reviews the latest grid technologies from the viewpoints of computing grid, data grid and knowledge grid. Computing grid technologies have been matured enough to solve high-throughput real-world life scientific problems. Data grid technologies are strong candidates for realizing "resourceome" for bioinformatics. Knowledge grids should be designed not only from sharing explicit knowledge on computers but also from community formulation for sharing tacit knowledge among a community. Extending the concept of grid from computing grid to knowledge grid, it is possible to make use of a grid as not only sharable computing resources, but also as time and place in which people work together, create knowledge, and share knowledge and experiences in a community.

Trends in life science grid: from computing grid to knowledge grid

PubMed Central

Konagaya, Akihiko

2006-01-01

Background Grid computing has great potential to become a standard cyberinfrastructure for life sciences which often require high-performance computing and large data handling which exceeds the computing capacity of a single institution. Results This survey reviews the latest grid technologies from the viewpoints of computing grid, data grid and knowledge grid. Computing grid technologies have been matured enough to solve high-throughput real-world life scientific problems. Data grid technologies are strong candidates for realizing "resourceome" for bioinformatics. Knowledge grids should be designed not only from sharing explicit knowledge on computers but also from community formulation for sharing tacit knowledge among a community. Conclusion Extending the concept of grid from computing grid to knowledge grid, it is possible to make use of a grid as not only sharable computing resources, but also as time and place in which people work together, create knowledge, and share knowledge and experiences in a community. PMID:17254294

Theoretical and software considerations for nonlinear dynamic analysis

NASA Technical Reports Server (NTRS)

Schmidt, R. J.; Dodds, R. H., Jr.

1983-01-01

In the finite element method for structural analysis, it is generally necessary to discretize the structural model into a very large number of elements to accurately evaluate displacements, strains, and stresses. As the complexity of the model increases, the number of degrees of freedom can easily exceed the capacity of present-day software system. Improvements of structural analysis software including more efficient use of existing hardware and improved structural modeling techniques are discussed. One modeling technique that is used successfully in static linear and nonlinear analysis is multilevel substructuring. This research extends the use of multilevel substructure modeling to include dynamic analysis and defines the requirements for a general purpose software system capable of efficient nonlinear dynamic analysis. The multilevel substructuring technique is presented, the analytical formulations and computational procedures for dynamic analysis and nonlinear mechanics are reviewed, and an approach to the design and implementation of a general purpose structural software system is presented.

A Bayesian Account of Vocal Adaptation to Pitch-Shifted Auditory Feedback

PubMed Central

Hahnloser, Richard H. R.

2017-01-01

Motor systems are highly adaptive. Both birds and humans compensate for synthetically induced shifts in the pitch (fundamental frequency) of auditory feedback stemming from their vocalizations. Pitch-shift compensation is partial in the sense that large shifts lead to smaller relative compensatory adjustments of vocal pitch than small shifts. Also, compensation is larger in subjects with high motor variability. To formulate a mechanistic description of these findings, we adapt a Bayesian model of error relevance. We assume that vocal-auditory feedback loops in the brain cope optimally with known sensory and motor variability. Based on measurements of motor variability, optimal compensatory responses in our model provide accurate fits to published experimental data. Optimal compensation correctly predicts sensory acuity, which has been estimated in psychophysical experiments as just-noticeable pitch differences. Our model extends the utility of Bayesian approaches to adaptive vocal behaviors. PMID:28135267

Efficient Construction of Discrete Adjoint Operators on Unstructured Grids by Using Complex Variables

NASA Technical Reports Server (NTRS)

Nielsen, Eric J.; Kleb, William L.

2005-01-01

A methodology is developed and implemented to mitigate the lengthy software development cycle typically associated with constructing a discrete adjoint solver for aerodynamic simulations. The approach is based on a complex-variable formulation that enables straightforward differentiation of complicated real-valued functions. An automated scripting process is used to create the complex-variable form of the set of discrete equations. An efficient method for assembling the residual and cost function linearizations is developed. The accuracy of the implementation is verified through comparisons with a discrete direct method as well as a previously developed handcoded discrete adjoint approach. Comparisons are also shown for a large-scale configuration to establish the computational efficiency of the present scheme. To ultimately demonstrate the power of the approach, the implementation is extended to high temperature gas flows in chemical nonequilibrium. Finally, several fruitful research and development avenues enabled by the current work are suggested.

Efficient Construction of Discrete Adjoint Operators on Unstructured Grids Using Complex Variables

NASA Technical Reports Server (NTRS)

Nielsen, Eric J.; Kleb, William L.

2005-01-01

A methodology is developed and implemented to mitigate the lengthy software development cycle typically associated with constructing a discrete adjoint solver for aerodynamic simulations. The approach is based on a complex-variable formulation that enables straightforward differentiation of complicated real-valued functions. An automated scripting process is used to create the complex-variable form of the set of discrete equations. An efficient method for assembling the residual and cost function linearizations is developed. The accuracy of the implementation is verified through comparisons with a discrete direct method as well as a previously developed handcoded discrete adjoint approach. Comparisons are also shown for a large-scale configuration to establish the computational efficiency of the present scheme. To ultimately demonstrate the power of the approach, the implementation is extended to high temperature gas flows in chemical nonequilibrium. Finally, several fruitful research and development avenues enabled by the current work are suggested.

Design and Realization of Online Monitoring System of Distributed New Energy and Renewable Energy

NASA Astrophysics Data System (ADS)

Tang, Yanfen; Zhou, Tao; Li, Mengwen; Zheng, Guotai; Li, Hao

2018-01-01

Aimed at difficult centralized monitoring and management of current distributed new energy and renewable energy generation projects due to great varieties, different communication protocols and large-scale difference, this paper designs a online monitoring system of new energy and renewable energy characterized by distributed deployment, tailorable functions, extendible applications and fault self-healing performance. This system is designed based on international general standard for grid information data model, formulates unified data acquisition and transmission standard for different types of new energy and renewable energy generation projects, and can realize unified data acquisition and real-time monitoring of new energy and renewable energy generation projects, such as solar energy, wind power, biomass energy, etc. within its jurisdiction. This system has applied in Beijing. At present, 576 projects are connected to the system. Good effect is achieved and stability and reliability of the system have been validated.

A study of the solar wind angular momentum including proton thermal anisotropy. Ph.D. Thesis - Catholic Univ. of Am., 1973

NASA Technical Reports Server (NTRS)

Acuna, M. H.

1974-01-01

The solution to the steady state magnetohydrodynamic equations governing the supersonic expansion of the solar corona into interplanetary space is obtained for various assumptions regarding the form in which proton thermal energy is carried away from the sun. The one-fluid, inviscid, formulation of the MHD equations is considered assuming that thermal energy is carried away by conduction from a heat source located at the base of the corona. Angular motion of the solar wind led to the existence of three critical points through which the numerical solutions must pass to extend from the sun's surface to large heliocentric distances. The results show that the amount of magnetic field energy converted into kinetic energy in the solar wind is only a small fraction of the total expansion energy flux and has little effect upon the final radial expansion velocity.

5D Tempest simulations of kinetic edge turbulence

NASA Astrophysics Data System (ADS)

Xu, X. Q.; Xiong, Z.; Cohen, B. I.; Cohen, R. H.; Dorr, M. R.; Hittinger, J. A.; Kerbel, G. D.; Nevins, W. M.; Rognlien, T. D.; Umansky, M. V.; Qin, H.

2006-10-01

Results are presented from the development and application of TEMPEST, a nonlinear five dimensional (3d2v) gyrokinetic continuum code. The simulation results and theoretical analysis include studies of H-mode edge plasma neoclassical transport and turbulence in real divertor geometry and its relationship to plasma flow generation with zero external momentum input, including the important orbit-squeezing effect due to the large electric field flow-shear in the edge. In order to extend the code to 5D, we have formulated a set of fully nonlinear electrostatic gyrokinetic equations and a fully nonlinear gyrokinetic Poisson's equation which is valid for both neoclassical and turbulence simulations. Our 5D gyrokinetic code is built on 4D version of Tempest neoclassical code with extension to a fifth dimension in binormal direction. The code is able to simulate either a full torus or a toroidal segment. Progress on performing 5D turbulence simulations will be reported.

Formulation of human-structure interaction system models for vertical vibration

NASA Astrophysics Data System (ADS)

Caprani, Colin C.; Ahmadi, Ehsan

2016-09-01

In this paper, human-structure interaction system models for vibration in the vertical direction are considered. This work assembles various moving load models from the literature and proposes extension of the single pedestrian to a crowd of pedestrians for the FE formulation for crowd-structure interaction systems. The walking pedestrian vertical force is represented as a general time-dependent force, and the pedestrian is in turn modelled as moving force, moving mass, and moving spring-mass-damper. The arbitrary beam structure is modelled using either a formulation in modal coordinates or finite elements. In each case, the human-structure interaction (HSI) system is first formulated for a single walking pedestrian and then extended to consider a crowd of pedestrians. Finally, example applications for single pedestrian and crowd loading scenarios are examined. It is shown how the models can be used to quantify the interaction between the crowd and bridge structure. This work should find use for the evaluation of existing and new footbridges.

Kinetic and dynamic probability-density-function descriptions of disperse turbulent two-phase flows

NASA Astrophysics Data System (ADS)

Minier, Jean-Pierre; Profeta, Christophe

2015-11-01

This article analyzes the status of two classical one-particle probability density function (PDF) descriptions of the dynamics of discrete particles dispersed in turbulent flows. The first PDF formulation considers only the process made up by particle position and velocity Zp=(xp,Up) and is represented by its PDF p (t ;yp,Vp) which is the solution of a kinetic PDF equation obtained through a flux closure based on the Furutsu-Novikov theorem. The second PDF formulation includes fluid variables into the particle state vector, for example, the fluid velocity seen by particles Zp=(xp,Up,Us) , and, consequently, handles an extended PDF p (t ;yp,Vp,Vs) which is the solution of a dynamic PDF equation. For high-Reynolds-number fluid flows, a typical formulation of the latter category relies on a Langevin model for the trajectories of the fluid seen or, conversely, on a Fokker-Planck equation for the extended PDF. In the present work, a new derivation of the kinetic PDF equation is worked out and new physical expressions of the dispersion tensors entering the kinetic PDF equation are obtained by starting from the extended PDF and integrating over the fluid seen. This demonstrates that, under the same assumption of a Gaussian colored noise and irrespective of the specific stochastic model chosen for the fluid seen, the kinetic PDF description is the marginal of a dynamic PDF one. However, a detailed analysis reveals that kinetic PDF models of particle dynamics in turbulent flows described by statistical correlations constitute incomplete stand-alone PDF descriptions and, moreover, that present kinetic-PDF equations are mathematically ill posed. This is shown to be the consequence of the non-Markovian characteristic of the stochastic process retained to describe the system and the use of an external colored noise. Furthermore, developments bring out that well-posed PDF descriptions are essentially due to a proper choice of the variables selected to describe physical systems and guidelines are formulated to emphasize the key role played by the notion of slow and fast variables.

Viability of Listeria monocytogenes on uncured turkey breast commercially prepared with and without buffered vinegar during extended storage at 4 and 10°C.

PubMed

Porto-Fett, Anna C S; Campano, Stephen G; Shoyer, Bradley A; Wadsworth, Sarah; Luchansky, John B

2014-06-01

We determined the viability of Listeria monocytogenes on uncured turkey breast containing buffered vinegar (BV) and surface treated with a stabilized solution of sodium chlorite in vinegar (VSC). Commercially produced, uncured, deli-style turkey breast was formulated with BV (0.0, 2.0, 2.5, or 3.0%), sliced (ca. 100 g and ca. 1.25 cm thick), and subsequently surface inoculated (ca. 4.3 log CFU per slice) in each of two trials with a five-strain cocktail of L. monocytogenes. Next, 1 ml per side of a 2 or 10% solution of VSC was added to each package before vacuum sealing and storing at 4 or 10°C. Without antimicrobials, L. monocytogenes numbers increased by ca. 6.2 log CFU per slice after 90 and 48 days of storage at 4 or 10°C, respectively. At 4°C, L. monocytogenes numbers increased by ca. 0.4 to 1.9 log CFU per slice on turkey breast formulated with 2.0 or 2.5% BV and treated or not with 2% VSC, whereas when treated with 10% VSC, L. monocytogenes levels remained relatively unchanged over 90 days. However, when turkey breast was formulated with 3.0% BV and treated or not with VSC, pathogen numbers decreased by ca. 0.7 to 1.3 log CFU per slice. At 10°C, L. monocytogenes numbers increased by ca. 1.5 to 5.6 log CFU per slice after 48 days when formulated with 2.0 to 3.0% BV and treated or not with 2% VSC. When formulated with 2.0% BV and treated with 10% VSC, L. monocytogenes numbers increased by ca. 3.3 log CFU per slice, whereas when formulated with 2.5 or 3.0% BV and treated with 10% VSC, L. monocytogenes decreased by ca. 0.3 log CFU per slice. Inclusion of BV as an ingredient in uncured turkey breast, alone or in combination with VSC added to the package, appreciably suppressed outgrowth of L. monocytogenes during an extended refrigerated shelf life.

Evaluation of the resistance of a geopolymer-based drug delivery system to tampering.

PubMed

Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne

2014-04-25

Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users. Copyright © 2014 Elsevier B.V. All rights reserved.

Elasticity of smectic liquid crystals with in-plane orientational order and dispiration asymmetry

NASA Astrophysics Data System (ADS)

Alageshan, Jaya Kumar; Chakrabarti, Buddhapriya; Hatwalne, Yashodhan

2017-02-01

The Nelson-Peliti formulation of the elasticity theory of isolated fluid membranes with orientational order emphasizes the interplay between geometry, topology, and thermal fluctuations. Fluid layers of lamellar liquid crystals such as smectic-C , hexatic smectics, and smectic-C* are endowed with in-plane orientational order. We extend the Nelson-Peliti formulation so as to bring these smectics within its ambit. Using the elasticity theory of smectics-C*, we show that positive and negative dispirations (topological defects in Smectic-C* liquid crystals) with strengths of equal magnitude have disparate energies—a result that is amenable to experimental tests.

Toughened uni-piece, fibrous, reinforced, oxidization-resistant composite

NASA Technical Reports Server (NTRS)

Stewart, David A. (Inventor); Leiser, Daniel B. (Inventor)

2008-01-01

A composite thermal protection structure, for applications such as atmospheric re-entry vehicles, that can withstand temperatures as high as 3600.degree F. The structure includes an exposed surface cap having a specially formulated coating, an insulator base adjacent to the cap with another specially formulated coating, and one or more pins that extend from the cap through the insulator base to tie the cap and base together, through ceramic bonding and mechanical attachment. The cap and insulator base have corresponding depressions and projections that mate and allow for differences in thermal expansion of the cap and base.

A Green's function formulation for a nonlinear potential flow solution applicable to transonic flow

NASA Technical Reports Server (NTRS)

Baker, A. J.; Fox, C. H., Jr.

1977-01-01

Routine determination of inviscid subsonic flow fields about wing-body-tail configurations employing a Green's function approach for numerical solution of the perturbation velocity potential equation is successfully extended into the high subsonic subcritical flow regime and into the shock-free supersonic flow regime. A modified Green's function formulation, valid throughout a range of Mach numbers including transonic, that takes an explicit accounting of the intrinsic nonlinearity in the parent governing partial differential equations is developed. Some considerations pertinent to flow field predictions in the transonic flow regime are discussed.

Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids.

PubMed

Aradi, Bálint; Niklasson, Anders M N; Frauenheim, Thomas

2015-07-14

A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born-Oppenheimer molecular dynamics. For systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can be applied to a broad range of problems in materials science, chemistry, and biology.

Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.

PubMed

Wang, Tina; Tsui, Brian; Kreisberg, Jason F; Robertson, Neil A; Gross, Andrew M; Yu, Michael Ku; Carter, Hannah; Brown-Borg, Holly M; Adams, Peter D; Ideker, Trey

2017-03-28

Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1 df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers.

Nonlinear programming extensions to rational function approximations of unsteady aerodynamics

NASA Technical Reports Server (NTRS)

Tiffany, Sherwood H.; Adams, William M., Jr.

1987-01-01

This paper deals with approximating unsteady generalized aerodynamic forces in the equations of motion of a flexible aircraft. Two methods of formulating these approximations are extended to include both the same flexibility in constraining them and the same methodology in optimizing nonlinear parameters as another currently used 'extended least-squares' method. Optimal selection of 'nonlinear' parameters is made in each of the three methods by use of the same nonlinear (nongradient) optimizer. The objective of the nonlinear optimization is to obtain rational approximations to the unsteady aerodynamics whose state-space realization is of lower order than that required when no optimization of the nonlinear terms is performed. The free 'linear' parameters are determined using least-squares matrix techniques on a Lagrange multiplier formulation of an objective function which incorporates selected linear equality constraints. State-space mathematical models resulting from the different approaches are described, and results are presented which show comparative evaluations from application of each of the extended methods to a numerical example. The results obtained for the example problem show a significant (up to 63 percent) reduction in the number of differential equations used to represent the unsteady aerodynamic forces in linear time-invariant equations of motion as compared to a conventional method in which nonlinear terms are not optimized.

A novel phosphorylcholine-coated contact lens for extended wear use.

PubMed

Court, J L; Redman, R P; Wang, J H; Leppard, S W; Obyrne, V J; Small, S A; Lewis, A L; Jones, S A; Stratford, P W

2001-12-01

The preparation and characterisation of a new phosphorylcholine (PC)-coated silicone hydrogel contact lens for use in extended wear is described. The Michael-type addition of amines to acrylates forms the basis of the synthesis of a novel silicone-based macromer with hydrophilic functionality. It is demonstrated that this macromer can be combined with other silicone-based monomers, hydrophilic monomers and crosslinker to produce a contact lenses formulation. Examples of lenses with water contents of 33% and 46% are illustrated and their properties compared to other commercially available lenses. Materials with comparatively low modulus (<0.3 MPa) and adequate tear strength (>2-4MPa) with excellent elongation to break (>200%) can be obtained using this technology. In addition to the mechanical aspects. both the oxygen and solute permeabilities of the material can be controlled by the hydrophilic: hydrophobic monomer balance in the formulation. to obtain materials with attributes suitable for extended wear use. The PC coating is achieved by means of an in-mould coating (IMC) technique that produces a uniform and stable surface as determined by staining and XPS. The coating imparts both improved lens wettability (advancing contact angle of approximately 50 with virtually no hysteresis) and lower protein adsorption relative to the uncoated lens.

f(T) teleparallel gravity and cosmology.

PubMed

Cai, Yi-Fu; Capozziello, Salvatore; De Laurentis, Mariafelicia; Saridakis, Emmanuel N

2016-10-01

Over recent decades, the role of torsion in gravity has been extensively investigated along the main direction of bringing gravity closer to its gauge formulation and incorporating spin in a geometric description. Here we review various torsional constructions, from teleparallel, to Einstein-Cartan, and metric-affine gauge theories, resulting in extending torsional gravity in the paradigm of f (T) gravity, where f (T) is an arbitrary function of the torsion scalar. Based on this theory, we further review the corresponding cosmological and astrophysical applications. In particular, we study cosmological solutions arising from f (T) gravity, both at the background and perturbation levels, in different eras along the cosmic expansion. The f (T) gravity construction can provide a theoretical interpretation of the late-time universe acceleration, alternative to a cosmological constant, and it can easily accommodate with the regular thermal expanding history including the radiation and cold dark matter dominated phases. Furthermore, if one traces back to very early times, for a certain class of f (T) models, a sufficiently long period of inflation can be achieved and hence can be investigated by cosmic microwave background observations-or, alternatively, the Big Bang singularity can be avoided at even earlier moments due to the appearance of non-singular bounces. Various observational constraints, especially the bounds coming from the large-scale structure data in the case of f (T) cosmology, as well as the behavior of gravitational waves, are described in detail. Moreover, the spherically symmetric and black hole solutions of the theory are reviewed. Additionally, we discuss various extensions of the f (T) paradigm. Finally, we consider the relation with other modified gravitational theories, such as those based on curvature, like f (R) gravity, trying to illuminate the subject of which formulation, or combination of formulations, might be more suitable for quantization ventures and cosmological applications.

A framework for evaluation of flood management strategies.

PubMed

Hansson, K; Danielson, M; Ekenberg, L

2008-02-01

The resulting impact of disasters on society depends on the affected country's economic strength prior to the disaster. The larger the disaster and the smaller the economy, the more significant is the impact. This is clearest seen in developing countries, where weak economies become even weaker afterwards. Deliberate strategies for the sharing of losses from hazardous events may aid a country or a community in efficiently using scarce prevention and mitigation resources, thus being better prepared for the effects of a disaster. Nevertheless, many governments lack an adequate institutional system for applying cost effective and reliable technologies for disaster prevention, early warnings, and mitigation. Modelling by event analyses and strategy models is one way of planning ahead, but these models have so far not been linked together. An approach to this problem was taken during a large study in Hungary, the Tisza case study, where a number of policy strategies for spreading of flood loss were formulated. In these strategies, a set of parameters of particular interest were extracted from interviews with stakeholders in the region. However, the study was focused on emerging economies, and, in particular, on insurance strategies. The scope is now extended to become a functional framework also for developing countries. In general, they have a higher degree of vulnerability. The paper takes northern Vietnam as an example of a developing region. We identify important parameters and discuss their importance for flood strategy formulations. Based on the policy strategies in the Tisza case, we extract data from the strategies and propose a framework for loss spread in developing and emerging economies. The parameter set can straightforwardly be included in a simulation and decision model for policy formulation and evaluation, taking multiple stakeholders into account.

On-Orbit 3-Dimensional Electrostatic Detumble for Generic Spacecraft Geometries

NASA Astrophysics Data System (ADS)

Bennett, Trevor J.

In recent years, there is a growing interest in active debris removal and on-orbit servicing of Earth orbiting assets. The growing need for such approaches is often exemplified by the Iridium-Kosmos collision in 2009 that generated thousands of debris fragments. There exists a variety of active debris removal and on-orbit servicing technologies in development. Conventional docking mechanisms and mechanical capture by actuated manipulators, exemplified by NASA's Restore-L mission, require slow target tumble rates or more aggressive circumnavigation rate matching. The tumble rate limitations can be overcome with flexible capture systems such nets, harpoons, or tethers yet these systems require complex deployment, towing, and/or interfacing strategies to avoid servicer and target damage. Alternatively, touchless methods overcome the tumble rate limitations by provide detumble control prior to a mechanical interface. This thesis explores electrostatic detumble technology to touchlessly reduce large target rotation rates of Geostationary satellites and debris. The technical challenges preceding flight implementation largely reside in the long-duration formation flying guidance, navigation, and control of a servicer spacecraft equipped with electrostatic charge transfer capability. Leveraging prior research into the electrostatic charging of spacecraft, electrostatic detumble control formulations are developed for both axisymmetric and generic target geometries. A novel relative position vector and associated relative orbit control approach is created to manage the long-duration proximity operations. Through detailed numerical simulations, the proposed detumble and relative motion control formulations demonstrate detumble of several thousand kilogram spacecraft tumbling at several degrees per second in only several days. The availability, either through modeling or sensing, of the relative attitude, relative position, and electrostatic potential are among key concerns with implementation of electrostatic detumble control on-orbit. Leveraging an extended Kalman filter scheme, the relative position information is readily obtained. In order to touchlessly acquire the target electrostatic potential, a nested two-time scale Kalman filter is employed to provide real-time estimates of both relative position and electrostatic potential while on-orbit. The culmination of the presented control formulations for generic spacecraft geometries, the proximity and formation flying control capability, and the availability of necessary state information provide significant contributions towards the viability of electrostatic detumble mission concepts.

Modeling of fatigue crack induced nonlinear ultrasonics using a highly parallelized explicit local interaction simulation approach

NASA Astrophysics Data System (ADS)

Shen, Yanfeng; Cesnik, Carlos E. S.

2016-04-01

This paper presents a parallelized modeling technique for the efficient simulation of nonlinear ultrasonics introduced by the wave interaction with fatigue cracks. The elastodynamic wave equations with contact effects are formulated using an explicit Local Interaction Simulation Approach (LISA). The LISA formulation is extended to capture the contact-impact phenomena during the wave damage interaction based on the penalty method. A Coulomb friction model is integrated into the computation procedure to capture the stick-slip contact shear motion. The LISA procedure is coded using the Compute Unified Device Architecture (CUDA), which enables the highly parallelized supercomputing on powerful graphic cards. Both the explicit contact formulation and the parallel feature facilitates LISA's superb computational efficiency over the conventional finite element method (FEM). The theoretical formulations based on the penalty method is introduced and a guideline for the proper choice of the contact stiffness is given. The convergence behavior of the solution under various contact stiffness values is examined. A numerical benchmark problem is used to investigate the new LISA formulation and results are compared with a conventional contact finite element solution. Various nonlinear ultrasonic phenomena are successfully captured using this contact LISA formulation, including the generation of nonlinear higher harmonic responses. Nonlinear mode conversion of guided waves at fatigue cracks is also studied.

Characterization of Amorphous and Co-Amorphous Simvastatin Formulations Prepared by Spray Drying.

PubMed

Craye, Goedele; Löbmann, Korbinian; Grohganz, Holger; Rades, Thomas; Laitinen, Riikka

2015-12-03

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.

Reliability of emerging bonded interface materials for large-area attachments

DOE PAGES

Paret, Paul P.; DeVoto, Douglas J.; Narumanchi, Sreekant

2015-12-30

In this study, conventional thermal interface materials (TIMs), such as greases, gels, and phase change materials, pose bottlenecks to heat removal and have long caused reliability issues in automotive power electronics packages. Bonded interface materials (BIMs) with superior thermal performance have the potential to be a replacement to the conventional TIMs. However, due to coefficient of thermal expansion mismatches between different components in a package and resultant thermomechanical stresses, fractures or delamination could occur, causing serious reliability concerns. These defects manifest themselves in increased thermal resistance in the package. In this paper, the results of reliability evaluation of emerging BIMsmore » for large-area attachments in power electronics packaging are reported. Thermoplastic (polyamide) adhesive with embedded near-vertical-aligned carbon fibers, sintered silver, and conventional lead solder (Sn 63Pb 37) materials were bonded between 50.8 mm x 50.8 mm cross-sectional footprint silicon nitride substrates and copper base plate samples, and were subjected to accelerated thermal cycling until failure or 2500 cycles. Damage in the BIMs was monitored every 100 cycles by scanning acoustic microscopy. Thermoplastic with embedded carbon fibers performed the best with no defects, whereas sintered silver and lead solder failed at 2300 and 1400 thermal cycles, respectively. Besides thermal cycling, additional lead solder samples were subjected to thermal shock and thermal cycling with extended dwell periods. A finite element method (FEM)-based model was developed to simulate the behavior of lead solder under thermomechanical loading. Strain energy density per cycle results were calculated from the FEM simulations. A predictive lifetime model was formulated for lead solder by correlating strain energy density results extracted from modeling with cycles-to-failure obtained from experimental accelerated tests. A power-law-based approach was used to formulate the - redictive lifetime model.« less

Development of a Novel Simplified PBPK Absorption Model to Explain the Higher Relative Bioavailability of the OROS® Formulation of Oxybutynin.

PubMed

Olivares-Morales, Andrés; Ghosh, Avijit; Aarons, Leon; Rostami-Hodjegan, Amin

2016-11-01

A new minimal Segmented Transit and Absorption model (mSAT) model has been recently proposed and combined with intrinsic intestinal effective permeability (P eff,int ) to predict the regional gastrointestinal (GI) absorption (f abs ) of several drugs. Herein, this model was extended and applied for the prediction of oral bioavailability and pharmacokinetics of oxybutynin and its enantiomers to provide a mechanistic explanation of the higher relative bioavailability observed for oxybutynin's modified-release OROS® formulation compared to its immediate-release (IR) counterpart. The expansion of the model involved the incorporation of mechanistic equations for the prediction of release, transit, dissolution, permeation and first-pass metabolism. The predicted pharmacokinetics of oxybutynin enantiomers after oral administration for both the IR and OROS® formulations were in close agreement with the observed data. The predicted absolute bioavailability for the IR formulation was within 5% of the observed value, and the model adequately predicted the higher relative bioavailability observed for the OROS® formulation vs. the IR counterpart. From the model predictions, it can be noticed that the higher bioavailability observed for the OROS® formulation was mainly attributable to differences in the intestinal availability (F G ) rather than due to a higher colonic f abs , thus confirming previous hypotheses. The predicted f abs was almost 70% lower for the OROS® formulation compared to the IR formulation, whereas the F G was almost eightfold higher than in the IR formulation. These results provide further support to the hypothesis of an increased F G as the main factor responsible for the higher bioavailability of oxybutynin's OROS® formulation vs. the IR.

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

PubMed

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

2016-10-10

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

Approaches in highly parameterized inversion - PEST++, a Parameter ESTimation code optimized for large environmental models

USGS Publications Warehouse

Welter, David E.; Doherty, John E.; Hunt, Randall J.; Muffels, Christopher T.; Tonkin, Matthew J.; Schreuder, Willem A.

2012-01-01

An object-oriented parameter estimation code was developed to incorporate benefits of object-oriented programming techniques for solving large parameter estimation modeling problems. The code is written in C++ and is a formulation and expansion of the algorithms included in PEST, a widely used parameter estimation code written in Fortran. The new code is called PEST++ and is designed to lower the barriers of entry for users and developers while providing efficient algorithms that can accommodate large, highly parameterized problems. This effort has focused on (1) implementing the most popular features of PEST in a fashion that is easy for novice or experienced modelers to use and (2) creating a software design that is easy to extend; that is, this effort provides a documented object-oriented framework designed from the ground up to be modular and extensible. In addition, all PEST++ source code and its associated libraries, as well as the general run manager source code, have been integrated in the Microsoft Visual Studio® 2010 integrated development environment. The PEST++ code is designed to provide a foundation for an open-source development environment capable of producing robust and efficient parameter estimation tools for the environmental modeling community into the future.

Update on tolterodine extended-release for treatment of overactive bladder

PubMed Central

Omotosho, Tola; Chen, Chi Chiung Grace

2010-01-01

Overactive bladder is a prevalent condition which negatively impacts quality of life and puts a significant economical burden on society. First-line therapy often includes pharmacotherapy with antimuscarinic medications, and numerous research studies have demonstrated that tolterodine extended-release (ER) is an efficacious and tolerable formulation of this class of medication. This review provides an update on the clinical use of tolterodine ER, detailing the current literature on its efficacy, tolerability, adverse effects, and comparability with other commonly prescribed medications for the treatment of overactive bladder. PMID:24198627

Applied Routh approximation

NASA Technical Reports Server (NTRS)

Merrill, W. C.

1978-01-01

The Routh approximation technique for reducing the complexity of system models was applied in the frequency domain to a 16th order, state variable model of the F100 engine and to a 43d order, transfer function model of a launch vehicle boost pump pressure regulator. The results motivate extending the frequency domain formulation of the Routh method to the time domain in order to handle the state variable formulation directly. The time domain formulation was derived and a characterization that specifies all possible Routh similarity transformations was given. The characterization was computed by solving two eigenvalue-eigenvector problems. The application of the time domain Routh technique to the state variable engine model is described, and some results are given. Additional computational problems are discussed, including an optimization procedure that can improve the approximation accuracy by taking advantage of the transformation characterization.

Pointless strings

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

Periwal, V.

1988-01-01

The author proves that bosonic string perturbation theory diverges and is not Borel summable. This is an indication of a non-perturbative instability of the bosonic string vacuum. He formulates two-dimensional sigma models in terms of algebras of functions. He extends this formulation to general C* algebras. He illustrates the utility of these algebraic notions by calculating some determinants of interest in the study of string propagation in orbifold backgrounds. He studies the geometry of spaces of field theories and show that the vanishing of the curvature of the natural Gel'fand-Naimark-Segal metric on such spaces is exactly the strong associativity conditionmore » of the operator product expansion.He shows that string scattering amplitudes arise as invariants of renormalization, when he formulates renormalization in terms of rescalings of the metric on the string world-sheet.« less

The thermal response of HMX-TATB charges

NASA Astrophysics Data System (ADS)

Drake, R. C.

2017-01-01

One approach to achieving charge safety and performance requirements is to prepare formulations containing two (or more) explosives. The intention of this approach is that by judicious choice of explosives and binder the formulation will have the desirable features of the constituent materials. HMX and TATB have very different properties. In an attempt to achieve a formulation which has the safety and performance characteristics of TATB and HMX, respectively, a range of formulations were prepared. The thermal response of the formulations were measured in the One-Dimensional Time To Explosion (ODTX) configuration and compared to those of formulations containing only HMX and TATB. The response of the mixed formulations was found to be largely determined by the HMX component with the binder making a small contribution. A formulation with a Kel-F 800 binder had a much higher critical temperature than would have been expected based on the critical temperatures of formulations with HTPB-IPDI as the binder.

Evidence for Coseismic Rupture Beyond the Base of the Seismogenic Layer

NASA Astrophysics Data System (ADS)

Zielke, O.; Wesnousky, S.

2010-12-01

For scientific reasons and hazard assessment it is important to better understand the physics and rupture characteristics of large, destructive earthquakes. However, those events occur infrequently, severely obstructing their analysis. Smaller but more frequent earthquakes are usually studied and their characteristics are extrapolated to assess large earthquake behavior, assuming that small and large events are associated with the same physical processes and parameters. For small and moderate size earthquakes it was observed and independently derived from elastic models that coseismic stress drop is independent of earthquake size and that slip is proportional to the smallest rupture dimension. It is therefore assumed that large earthquake stress drops are essentially equal to the stress drop of their smaller size siblings. It is further assumed that the slip amount of large events does not further increase once it ruptures the full seismogenic layer--the base of the seismogenic layer is commonly thought to limit the earthquake down-dip rupture extend and thus defines the smallest rupture dimension. However, slip observations for many large strike-slip events show how offset gradually increases with rupture length. Two explanations have been formulated: If the rupture width of those events were indeed limited by the base of the seismogenic layer, the observations would imply larger stress drops and possibly other processes involved in large earthquake rupture, questioning the validity of the aforementioned extrapolation from small to large earthquakes. On the other hand, if rupture width of large earthquakes were not limited by the base of the seismogenic layer but were allowed to extend further down (as suggested by recent studies), the increased slip amount may be explained without an increase in stress drop or additional rupture mechanisms for large earthquakes. For the study we present here, we analyzed seismic data constraining the depth extent of large earthquakes relative to the depth of the seismogenic base. We utilized time series data of aftershock depths for a number of large strike-slip earthquakes, generating aftershock time vs. depth histograms to investigate the temporal variation in depth distribution. Based on hypocenter depth of small earthquakes along the Landers fault (causing the 1992 M7.3 Landers earthquake), we identified the base of the seismogenic layer at ~10km. Aftershocks that occurred only days after the Landers earthquake had maximum depths of ~18km, suggesting that rupture of the main shock extended this far down and therefore went well below the base of the seismogenic layer. Maximum aftershock depth then decayed roughly logarithmically, reaching the previous value of ~10km after about 5.5years. We argue that these observations are a logical consequence of the visco-elastic rheology of crustal rocks: Coseismically highly increased strains elevate the crustal stiffness, temporarily lowering the base of the seismogenic layer and permitting initiation of slip instabilities at depths that are otherwise characterized by viscous behavior. Extrapolation from small to large earthquakes is therefore permitted. No additional stress drop or rupture mechanism is required to explain the data.

Estimation of three-dimensional radar tracking using modified extended kalman filter

NASA Astrophysics Data System (ADS)

Aditya, Prima; Apriliani, Erna; Khusnul Arif, Didik; Baihaqi, Komar

2018-03-01

Kalman filter is an estimation method by combining data and mathematical models then developed be extended Kalman filter to handle nonlinear systems. Three-dimensional radar tracking is one of example of nonlinear system. In this paper developed a modification method of extended Kalman filter from the direct decline of the three-dimensional radar tracking case. The development of this filter algorithm can solve the three-dimensional radar measurements in the case proposed in this case the target measured by radar with distance r, azimuth angle θ, and the elevation angle ϕ. Artificial covariance and mean adjusted directly on the three-dimensional radar system. Simulations result show that the proposed formulation is effective in the calculation of nonlinear measurement compared with extended Kalman filter with the value error at 0.77% until 1.15%.

Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics.

PubMed

Martínez, Enrique; Cawkwell, Marc J; Voter, Arthur F; Niklasson, Anders M N

2015-04-21

Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached at each time step. The thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.

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

PubMed

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

2015-11-10

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

Extended multi-configuration quasi-degenerate perturbation theory: the new approach to multi-state multi-reference perturbation theory.

PubMed

Granovsky, Alexander A

2011-06-07

The distinctive desirable features, both mathematically and physically meaningful, for all partially contracted multi-state multi-reference perturbation theories (MS-MR-PT) are explicitly formulated. The original approach to MS-MR-PT theory, called extended multi-configuration quasi-degenerate perturbation theory (XMCQDPT), having most, if not all, of the desirable properties is introduced. The new method is applied at the second order of perturbation theory (XMCQDPT2) to the 1(1)A(')-2(1)A(') conical intersection in allene molecule, the avoided crossing in LiF molecule, and the 1(1)A(1) to 2(1)A(1) electronic transition in cis-1,3-butadiene. The new theory has several advantages compared to those of well-established approaches, such as second order multi-configuration quasi-degenerate perturbation theory and multi-state-second order complete active space perturbation theory. The analysis of the prevalent approaches to the MS-MR-PT theory performed within the framework of the XMCQDPT theory unveils the origin of their common inherent problems. We describe the efficient implementation strategy that makes XMCQDPT2 an especially useful general-purpose tool in the high-level modeling of small to large molecular systems. © 2011 American Institute of Physics

Prediction of scaling physics laws for proton acceleration with extended parameter space of the NIF ARC

NASA Astrophysics Data System (ADS)

Bhutwala, Krish; Beg, Farhat; Mariscal, Derek; Wilks, Scott; Ma, Tammy

2017-10-01

The Advanced Radiographic Capability (ARC) laser at the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory is the world's most energetic short-pulse laser. It comprises four beamlets, each of substantial energy ( 1.5 kJ), extended short-pulse duration (10-30 ps), and large focal spot (>=50% of energy in 150 µm spot). This allows ARC to achieve proton and light ion acceleration via the Target Normal Sheath Acceleration (TNSA) mechanism, but it is yet unknown how proton beam characteristics scale with ARC-regime laser parameters. As theory has also not yet been validated for laser-generated protons at ARC-regime laser parameters, we attempt to formulate the scaling physics of proton beam characteristics as a function of laser energy, intensity, focal spot size, pulse length, target geometry, etc. through a review of relevant proton acceleration experiments from laser facilities across the world. These predicted scaling laws should then guide target design and future diagnostics for desired proton beam experiments on the NIF ARC. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344 and funded by the LLNL LDRD program under tracking code 17-ERD-039.

Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial.

PubMed

Bunnapradist, S; Ciechanowski, K; West-Thielke, P; Mulgaonkar, S; Rostaing, L; Vasudev, B; Budde, K

2013-03-01

Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4-15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Long-term liquid storage and reproductive evaluation of an innovative boar semen extender (Formula12®) containing a non-reducing disaccharide and an enzymatic agent.

PubMed

Bresciani, Carla; Bianchera, Annalisa; Bettini, Ruggero; Buschini, Annamaria; Marchi, Laura; Cabassi, Clotilde Silvia; Sabbioni, Alberto; Righi, Federico; Mazzoni, Claudio; Parmigiani, Enrico

2017-05-01

There are no reports of saccharolytic enzymes being used in the preparation of formulations for animal semen extenders. In the present study, the use of an innovative semen extender (Formula12 ® ) in the long-term liquid storage of boar semen at 17°C was evaluated. The formulation included use of a disaccharide (sucrose) as the energy source precursor coupled to an enzymatic agent (invertase). The innovative extender was evaluated and compared in vitro to a commercial extender (Vitasem LD ® ) for the following variables: Total Motility (TM), Forward Progressive Motility (FPM), sperm morphology, membrane integrity, acrosome integrity, and chromatin instability. Boar sperm diluted in Formula12 ® and stored for 12 days at 17°C maintained a commercially acceptable FPM (>70%). Using the results from the in vitro study, an AI field trial was performed. A total of 170 females were inseminated (135 with Formula12 ® and 35 with Vitasem LD ® ). The pregnancy rates were 97.8% compared with 91.4%, and the farrowing rates were 96.3% compared with 88.6% when Formula12 ® and Vitasem LD ® were used, respectively. The mean number of piglets born/sow were 14.92±0.46 compared with 13.83±0.70, and the number of piglets born alive/sow were 14.07±0.46 compared with 12.12±0.70 (P<0.05). The results obtained in this study demonstrated that use of the innovative concept to provide a precursor of glucose and fructose as energy sources for an enzymatic agent in an extender allowed for meeting the metabolic requirements of boar sperm during storage at 17°C. It is suggested that there was a beneficial effect on fertilizing capacity of boar sperm in the female reproductive tract with use of these technologies. Copyright © 2017 Elsevier B.V. All rights reserved.

The influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine

PubMed Central

Stout, Stephen M.; Nielsen, Jace; Welage, Lynda S.; Shea, Michael; Brook, Robert; Kerber, Kevin; Bleske, Barry E.

2010-01-01

Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used β-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4 phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate release (IR) tartrate and extended release (ER) succinate metoprolol formulations. Ten healthy subjects received metoprolol IR (50 mg) and ER (100 mg) with and without paroxetine coadministration. Blood samples were collected over 24 hours for determination of metoprolol plasma enantiomer concentrations. Paroxetine coadministration significantly increased S and R metoprolol AUC0–24h by 4 and 5 fold, respectively for IR, and 3 and 4 fold, respectively for ER. S/R AUC ratios significantly decreased. These results demonstrate a pharmacokinetic interaction between paroxetine and both formulations of metoprolol. The interaction is greater with R metoprolol and stereoselective metabolism is lost. This could theoretically result in greater β-blockade and lost cardioselectivity. The magnitude of the interaction was similar between metoprolol formulations, which may be attributable to low doses / drug input rates employed. PMID:20400652

Repellent effect of microencapsulated essential oil in lotion formulation against mosquito bites.

PubMed

Misni, Norashiqin; Nor, Zurainee Mohamed; Ahmad, Rohani

2017-01-01

Many essential oils have been reported as natural sources of insect repellents; however, due to high volatility, they present low repellent effect. Formulation technique by using microencapsulation enables to control the volatility of essential oil and thereby extends the duration of repellency. In this study, the effectiveness of microencapsulated essential oils of Alpinia galanga, Citrus grandis and C. aurantifolia in the lotion formulations were evaluated against mosquito bites. Essential oils and N,N-Diethyl-3-methylbenzamide (DEET) were encapsulated by using interfacial pre- cipitation techniques before incorporation into lotion base to form microencapsulated (ME) formulation. The pure essential oil and DEET were also prepared into lotion base to produce non-encapsulated (NE) formulation. All the prepared formulations were assessed for their repellent activity against Culex quinquefasciatus under laboratory condition. Field evaluations also were conducted in three different study sites in Peninsular Malaysia. In addi- tion, Citriodiol® (Mosiquard®) and citronella-based repellents (KAPS®, MozAway® and BioZ Natural®) were also included for comparison. In laboratory conditions, the ME formulations of the essential oils showed no significant difference with regard to the duration of repellent effect compared to the microencapsulated DEET used at the highest con- centration (20%). It exhibited >98% repellent effect for duration of 4 h (p = 0.06). In the field conditions, these formulations demonstrated comparable repellent effect (100% for a duration of 3 h) to Citriodiol® based repellent (Mosiguard®) (p = 0.07). In both test conditions, the ME formulations of the essential oils presented longer duration of 100% repellent effect (between 1 and 2 h) compared to NE formulations. The findings of the study demonstrate that the application of the microencapsulation technique during the preparation of the formulations significantly increases the duration of the repellent effect of the essential oils, suggesting that the ME formulation of essential oils have potential to be commercialized as an alternative plant-based repellent in the market against the mosquitoes.

Multiphase flows of N immiscible incompressible fluids: A reduction-consistent and thermodynamically-consistent formulation and associated algorithm

NASA Astrophysics Data System (ADS)

Dong, S.

2018-05-01

We present a reduction-consistent and thermodynamically consistent formulation and an associated numerical algorithm for simulating the dynamics of an isothermal mixture consisting of N (N ⩾ 2) immiscible incompressible fluids with different physical properties (densities, viscosities, and pair-wise surface tensions). By reduction consistency we refer to the property that if only a set of M (1 ⩽ M ⩽ N - 1) fluids are present in the system then the N-phase governing equations and boundary conditions will exactly reduce to those for the corresponding M-phase system. By thermodynamic consistency we refer to the property that the formulation honors the thermodynamic principles. Our N-phase formulation is developed based on a more general method that allows for the systematic construction of reduction-consistent formulations, and the method suggests the existence of many possible forms of reduction-consistent and thermodynamically consistent N-phase formulations. Extensive numerical experiments have been presented for flow problems involving multiple fluid components and large density ratios and large viscosity ratios, and the simulation results are compared with the physical theories or the available physical solutions. The comparisons demonstrate that our method produces physically accurate results for this class of problems.

An oral multi-particulate, modified release, hydrocortisone replacement therapy that provides physiological cortisol exposure

PubMed Central

Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J.

2013-01-01

Objective It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multi-particulate technology. Design and Measurements Screening by in-vitro dissolution profiles, pharmacokinetic testing in dexamethasone suppressed dogs and humans, and comparison to a reference population. Setting Field laboratories and clinical research facility. Results Formulations were generated using an enteric (delayed-release) design configuration with an extended (sustained-release) dissolution profile. In-vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained release functionality. Pharmacokinetic characterisation of DIURF-006 showed that, despite absence of a sustained release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n=16) receiving a twice daily ‘toothbrush’ regimen (20mg at 23:00h and 10mg at 07:00h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 hr*nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8.5h vs clock time 08:12 hours for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89% and cortisol levels increased linearly with doses between 5 and 30mg. Conclusion A multi-particulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a ‘toothbrush’ regimen provides physiological cortisol exposure. PMID:23980724

An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.

PubMed

Whitaker, Martin; Debono, Miguel; Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J

2014-04-01

It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure. © 2013 John Wiley & Sons Ltd.

Development of metoprolol tartrate extended-release matrix tablet formulations for regulatory policy consideration.

PubMed

Nellore, R V; Rekhi, G S; Hussain, A S; Tillman, L G; Augsburger, L L

1998-01-02

This research study was designed to develop model extended-release (ER) matrix tablet formulations for metoprolol tartrate (100 mg) sufficiently sensitive to manufacturing variable and to serve as the scientific basis for regulatory policy development on scale-up and post approval changes for modified-release dosage forms (SUPAC-MR). Several grades and levels of hydroxypropyl methylcellulose (Methocel K4M, K15M, K100M and K100LV), fillers and binders and studied. Three granulation processes were evaluated; direct compression, fluid-bed or high-shear granulation. Lubrication was performed in a V-blender and tablets were compressed on an instrumented rotary tablet press. Direct compression formulations exhibited poor flow, picking and sticking problems during tableting. High-shear granulation resulted in the formation of hard granules that were difficult to mill but yielded good tablets. Fluid-bed granulations were made using various binders and appeared to be satisfactory in terms of flow and tableting performance. In vitro drug release testing was performed in pH 6.8 phosphate buffer using USP apparatus 2 (paddle) at 50 rpm. At a fixed polymer level, drug release from the higher viscosity grades (K100M) was slower as compared to the lower viscosity grades (K100LV). In addition, release from K100LV was found to be more sensitive to polymer level changes. Increased in polymer level from 10 to 40% and/or filler change from lactose to dicalcium phosphate resulted in about 25-30% decrease in the amount of metoprolol release after 12 h. The results of this study led to the choice of Methocel K100LV as the hydrophilic matrix polymer and fluid-bed granulation as the process of choice for further evaluation of critical and non-critical formulation and processing variables.

Comparative in vitro activity of a pharmacokinetically enhanced oral formulation of amoxicillin/clavulanic acid (2000/125 mg twice daily) against 9172 respiratory isolates collected worldwide in 2000.

PubMed

Koeth, Laura M; Jacobs, Michael R; Good, Caryn E; Bajaksouzian, Saralee; Windau, Anne; Jakielaszek, Charles; Saunders, Kay A

2004-11-01

A new, pharmacokinetically enhanced, oral formulation of amoxicillin/clavulanic acid has been developed to overcome resistance in the major bacterial respiratory pathogen Streptococcus pneumoniae, while maintaining excellent activity against Haemophilus influenzae and Moraxella catarrhalis, including beta-lactamase producing strains. This study was conducted to provide in vitro susceptibility data for amoxicillin/clavulanic acid and 16 comparator agents against the key respiratory tract pathogens. Susceptibility testing was performed on 9172 isolates collected from 95 centers in North America, Europe, Australia, and Hong Kong by broth microdilution MIC determination, according to NCCLS methods, using amoxicillin/clavulanic acid and 16 comparator antimicrobial agents. Results were interpreted according to NCCLS breakpoints and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints based on oral dosing regimens. Overall, 93.5% of Streptococcus pneumoniae isolates were susceptible to amoxicillin/clavulanic acid at the current susceptible breakpoint of < or =2 microg/mL and 97.3% at the PK/PD susceptible breakpoint of < or =4 microg/mL for the extended release formulation. Proportions of isolates that were penicillin intermediate and resistant were 13% and 16.5%, respectively, while 25% were macrolide resistant and 21.8% trimethoprim/sulfamethoxazole resistant. 21.9% of Haemophilus influenzae were beta-lactamase producers and 16.8% trimethoprim/sulfamethoxazole resistant, >99% of isolates were susceptible to amoxicillin/clavulanic acid, cefixime, ciprofloxacin and levofloxacin at NCCLS breakpoints. The most active agents against Moraxella catarrhalis were amoxicillin/clavulanic acid, macrolides, cefixime, fluoroquinolones, and doxycycline. Overall, 13% of Streptococcus pyogenes were resistant to macrolides. The extended release formulation of amoxicillin/clavulanic acid has potential for empiric use against many respiratory tract infections worldwide due to its activity against species resistant to many agents currently in use.

Understanding Developmental Reversals in False Memory: Reply to Ghetti (2008) and Howe (2008)

ERIC Educational Resources Information Center

Brainerd, C. J.; Reyna, V. F.; Ceci, S. J.; Holliday, R. E.

2008-01-01

S. Ghetti (2008) and M. L. Howe (2008) presented probative ideas for future research that will deepen scientific understanding of developmental reversals on false memory and establish boundary conditions for these counterintuitive patterns. Ghetti extended the purview of current theoretical principles by formulating hypotheses about how…

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

Manjunath, Naren; Samajdar, Rhine; Jain, Sudhir R., E-mail: srjain@barc.gov.in

Recently, the nodal domain counts of planar, integrable billiards with Dirichlet boundary conditions were shown to satisfy certain difference equations in Samajdar and Jain (2014). The exact solutions of these equations give the number of domains explicitly. For complete generality, we demonstrate this novel formulation for three additional separable systems and thus extend the statement to all integrable billiards.

Bridge Building for the Future of the Finnish Polytechnics

ERIC Educational Resources Information Center

Kettunen, Juha

2004-01-01

This study presents the strategy process of Finnish polytechnics using the balanced scorecard approach. The study extends the balanced scorecard from the communication and implementation of this strategy to the planning of the strategy. Stakeholders formulated a strategic managerial plan for the network of all polytechnics in Finland by applying…

Applying Theories of Deviance to Academic Cheating.

ERIC Educational Resources Information Center

Michaels, James W.; Miethe, Terance D.

1989-01-01

Reports on a study that extends social psychological theories of deviance to explain academic cheating. Uses self-report data from college students to examine the theories of deterrence, rational choice, social bond, and social learning formulations of cheating. Supports the claim that cheating is a serious problem in higher education. (SLM)

Utilitarian Aggregation of Beliefs and Tastes.

ERIC Educational Resources Information Center

Gilboa, Itzhak; Samet, Dov; Schmeidler, David

2004-01-01

Harsanyi's utilitarianism is extended here to Savage's framework. We formulate a Pareto condition that implies that both society's utility function and its probability measure are linear combinations of those of the individuals. An indiscriminate Pareto condition has been shown to contradict linear aggregation of beliefs and tastes. We argue that…

Bayesian Estimation of the DINA Model with Gibbs Sampling

ERIC Educational Resources Information Center

Culpepper, Steven Andrew

2015-01-01

A Bayesian model formulation of the deterministic inputs, noisy "and" gate (DINA) model is presented. Gibbs sampling is employed to simulate from the joint posterior distribution of item guessing and slipping parameters, subject attribute parameters, and latent class probabilities. The procedure extends concepts in Béguin and Glas,…

A Simple Blueprint for Automatic Boolean Query Processing.

ERIC Educational Resources Information Center

Salton, G.

1988-01-01

Describes a new Boolean retrieval environment in which an extended soft Boolean logic is used to automatically construct queries from original natural language formulations provided by users. Experimental results that compare the retrieval effectiveness of this method to conventional Boolean and vector processing are discussed. (27 references)…

Rearing sunshine bass using diets formulated for summer water temperatures

USDA-ARS?s Scientific Manuscript database

Elevated water temperatures are common in hybrid striped bass or Sunshine bass (HSB; Morone chrysops x M. saxatilis) production ponds during summer months in the southern US. Median daily water temperatures often exceed 30 C from June through September. This experiment was conducted to extend and re...

The Nature and Determinants of Intranet Discontinuance after Mandatory Adoption

ERIC Educational Resources Information Center

Cho, Inho

2008-01-01

This research examines post-adoption behavior (discontinuance versus continuance) with the context of Intranet use. Multiple theories are used as theoretical frameworks to extend information communication technology research to the case of post-adoption behavior. Three research questions and six sets of hypotheses are formulated to distinguish…

A variable-gain output feedback control design methodology

NASA Technical Reports Server (NTRS)

Halyo, Nesim; Moerder, Daniel D.; Broussard, John R.; Taylor, Deborah B.

1989-01-01

A digital control system design technique is developed in which the control system gain matrix varies with the plant operating point parameters. The design technique is obtained by formulating the problem as an optimal stochastic output feedback control law with variable gains. This approach provides a control theory framework within which the operating range of a control law can be significantly extended. Furthermore, the approach avoids the major shortcomings of the conventional gain-scheduling techniques. The optimal variable gain output feedback control problem is solved by embedding the Multi-Configuration Control (MCC) problem, previously solved at ICS. An algorithm to compute the optimal variable gain output feedback control gain matrices is developed. The algorithm is a modified version of the MCC algorithm improved so as to handle the large dimensionality which arises particularly in variable-gain control problems. The design methodology developed is applied to a reconfigurable aircraft control problem. A variable-gain output feedback control problem was formulated to design a flight control law for an AFTI F-16 aircraft which can automatically reconfigure its control strategy to accommodate failures in the horizontal tail control surface. Simulations of the closed-loop reconfigurable system show that the approach produces a control design which can accommodate such failures with relative ease. The technique can be applied to many other problems including sensor failure accommodation, mode switching control laws and super agility.

Emulsifier for intravenous cyclosporin inhibits neurite outgrowth, causes deficits in rapid axonal transport and leads to structural abnormalities in differentiating N1E.115 neuroblastoma.

PubMed

Brat, D J; Windebank, A J; Brimijoin, S

1992-05-01

The emulsifier for cyclosporin in clinical i.v. formulations, Cremophor EL, has recently come into question as a possible source of neurotoxic side effects in immunosuppressant therapy. To address this issue we tested Cremophor EL and cyclosporin on an in vitro neuronal model, the differentiating N1E.115 neuroblastoma cell. In terms of effects on elaboration of neurites by these cells, Cremophor accounted for nearly all the neurotoxicity of clinically formulated cyclosporin. At a concentration of 0.005% (v/v), Cremophor EL halved the number of cells that extended neurites after 48 hr in serum-free medium. Average neurite length was also reduced substantially. Inhibition of neurite outgrowth first became apparent 24 hr after exposure to Cremophor EL. Neurites that did grow in the presence of Cremophor were disfigured by a series of regularly spaced, gross dilatations (beads) filled with large (0.2-0.5 microns) lipid vesicles. Abnormalities of rapid axonal transport were documented in the beaded neurites by means of video-enhanced contrast, differential interference-contrast microscopy. Velocity of retrograde transport remained normal, but the velocity of anterograde transport and the total bidirectional flux of organelles were both reduced. It seems likely that the inhibition of neurite outgrowth, the swellings of the neurites and the abnormalities of transport are interrelated phenomena.

Controlled precipitation for enhanced dissolution rate of flurbiprofen: development of rapidly disintegrating tablets.

PubMed

Essa, Ebtessam A; Elmarakby, Amira O; Donia, Ahmed M A; El Maghraby, Gamal M

2017-09-01

The aim of this work was to investigate the potential of controlled precipitation of flurbiprofen on solid surface, in the presence or absence of hydrophilic polymers, as a tool for enhanced dissolution rate of the drug. The work was extended to develop rapidly disintegrated tablets. This strategy provides simple technique for dissolution enhancement of slowly dissolving drugs with high scaling up potential. Aerosil was dispersed in ethanolic solution of flurbiprofen in the presence and absence of hydrophilic polymers. Acidified water was added as antisolvent to produce controlled precipitation. The resultant particles were centrifuged and dried at ambient temperature before monitoring the dissolution pattern. The particles were also subjected to FTIR spectroscopic, X-ray diffraction and thermal analyses. The FTIR spectroscopy excluded any interaction between flurbiprofen and excipients. The thermal analysis reflected possible change in the crystalline structure and or crystal size of the drug after controlled precipitation in the presence of hydrophilic polymers. This was further confirmed by X-ray diffraction. The modulation in the crystalline structure and size was associated with a significant enhancement in the dissolution rate of flurbiprofen. Optimum formulations were successfully formulated as rapidly disintegrating tablet with subsequent fast dissolution. Precipitation on a large solid surface area is a promising strategy for enhanced dissolution rate with the presence of hydrophilic polymers during precipitation process improving the efficiency.

Finite Temperature Densities via the S-Function Method with Application to Electron Screening in Plasmas

NASA Astrophysics Data System (ADS)

Watrous, Mitchell James

1997-12-01

A new approach to the Green's-function method for the calculation of equilibrium densities within the finite temperature, Kohn-Sham formulation of density functional theory is presented, which extends the method to all temperatures. The contour of integration in the complex energy plane is chosen such that the density is given by a sum of Green's function differences evaluated at the Matsubara frequencies, rather than by the calculation and summation of Kohn-Sham single-particle wave functions. The Green's functions are written in terms of their spectral representation and are calculated as the solutions of their defining differential equations. These differential equations are boundary value problems as opposed to the standard eigenvalue problems. For large values of the complex energy, the differential equations are further simplified from second to first-order by writing the Green's functions in terms of logarithmic derivatives. An asymptotic expression for the Green's functions is derived, which allows the sum over Matsubara poles to be approximated. The method is applied to the screening of nuclei by electrons in finite temperature plasmas. To demonstrate the method's utility, and to illustrate its advantages, the results of previous wave function type calculations for protons and neon nuclei are reproduced. The method is also used to formulate a new screening model for fusion reactions in the solar core, and the predicted reaction rate enhancements factors are compared with existing models.

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.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation.

PubMed

Pachis, K; Blazaki, S; Tzatzarakis, M; Klepetsanis, P; Naoumidi, E; Tsilimbaris, M; Antimisiaris, S G

2017-11-15

A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Nucleation and crystal growth behavior of nepheline in simulated high-level waste glasses

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

Fox, K.; Amoroso, J.; Mcclane, D.

The Savannah River National Laboratory (SRNL) has been tasked with supporting glass formulation development and process control strategies in key technical areas, relevant to the Department of Energy’s Office of River Protection (DOE-ORP) and related to high-level waste (HLW) vitrification at the Waste Treatment and Immobilization Plant (WTP). Of specific interest is the development of predictive models for crystallization of nepheline (NaAlSiO4) in HLW glasses formulated at high alumina concentrations. This report summarizes recent progress by researchers at SRNL towards developing a predicative tool for quantifying nepheline crystallization in HLW glass canisters using laboratory experiments. In this work, differential scanningmore » calorimetry (DSC) was used to obtain the temperature regions over which nucleation and growth of nepheline occur in three simulated HLW glasses - two glasses representative of WTP projections and one glass representative of the Defense Waste Processing Facility (DWPF) product. The DWPF glass, which has been studied previously, was chosen as a reference composition and for comparison purposes. Complementary quantitative X-ray diffraction (XRD) and optical microscopy confirmed the validity of the methodology to determine nucleation and growth behavior as a function of temperature. The nepheline crystallization growth region was determined to generally extend from ~ 500 to >850 °C, with the maximum growth rates occurring between 600 and 700 °C. For select WTP glass compositions (high Al2O3 and B2O3), the nucleation range extended from ~ 450 to 600 °C, with the maximum nucleation rates occurring at ~ 530 °C. For the DWPF glass composition, the nucleation range extended from ~ 450 to 750 °C with the maximum nucleation rate occurring at ~ 640 °C. The nepheline growth at the peak temperature, as determined by XRD, was between 35 - 75 wt.% /hour. A maximum nepheline growth rate of ~ 0.1 mm/hour at 700 °C was measured for the DWPF composition using optical microscopy. This research establishes a viable alternative to more traditional techniques for evaluating nepheline crystallization in large numbers of glasses, which are prohibitively time consuming or otherwise impractical. The ultimate objective is to combine the nucleation and growth information obtained from DSC, like that presented in this report, with computer simulations of glass cooling within the canister to accurately predict nepheline crystallization in HLW during processing through WTP.« less

Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

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

Aradi, Bálint; Niklasson, Anders M. N.; Frauenheim, Thomas

A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born–Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materialsmore » science, chemistry, and biology.« less

Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

DOE PAGES

Aradi, Bálint; Niklasson, Anders M. N.; Frauenheim, Thomas

2015-06-26

A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born–Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materialsmore » science, chemistry, and biology.« less

Extended-release mesalamine granules for ulcerative colitis.

PubMed

Love, Bryan L; Miller, April D

2012-11-01

To evaluate the efficacy and safety of extended-release mesalamine granules in the maintenance of remission in ulcerative colitis (UC). Literature was obtained through searches of MEDLINE (1990-June 2012) using the terms mesalamine granules, ulcerative colitis, Apriso, and Salofalk. Bibliographies from retrieved articles were searched for additional citations. All English-language articles reporting on use of extended-release mesalamine granules in humans identified through the search were evaluated and included. The preferred initial treatment for induction and maintenance of remission in mild to moderate UC is agents from the 5-aminosalicylate class (balsalazide, mesalamine, olsalazine, sulfasalazine). Mesalamine granules are available as an encapsulated product in the US and as a nonencapsulated formulation in Europe. Data evaluating encapsulated mesalamine granules for induction of remission are lacking; however, the European mesalamine granule formulation has been evaluated for induction of remission. Patients receiving mesalamine granules for induction achieved clinical and endoscopic remission more frequently than those receiving placebo. Two pivotal, randomized, double-blind, placebo-controlled, multicenter studies have evaluated encapsulated mesalamine granules for maintenance in 562 adults in remission from UC. In both studies, the proportion of patients who remained relapse-free at 6 months was higher for those receiving encapsulated mesalamine granules than placebo. Mesalamine granules are well tolerated, with headache, nausea, and upper respiratory infections being the most frequently reported adverse effects. Current evidence supports the use of extended-release mesalamine granules for maintenance of remission in mild to moderate UC. Further studies are necessary to examine the ideal dose and regimen of encapsulated mesalamine granules for induction of remission in UC.

Stomach specific polymeric low density microballoons as a vector for extended delivery of rabeprazole and amoxicillin for treatment of peptic ulcer.

PubMed

Choudhary, Sandeep; Jain, Ashay; Amin, Mohd Cairul Iqbal Mohd; Mishra, Vijay; Agrawal, Govind P; Kesharwani, Prashant

2016-05-01

The study was intended to develop a new intra-gastric floating in situ microballoons system for controlled delivery of rabeprazole sodium and amoxicillin trihydrate for the treatment of peptic ulcer disease. Eudragit S-100 and hydroxypropyl methyl cellulose based low density microballoons systems were fabricated by employing varying concentrations of Eudragit S-100 and hydroxypropyl methyl cellulose, to which varying concentrations of drug was added, and formulated by stirring at various speed and time to optimize the process and formulation variable. The formulation variables like concentration and ratio of polymers significantly affected the in vitro drug release from the prepared floating device. The validation of the gastro-retentive potential of the prepared microballoons was carried out in rabbits by orally administration of microballoons formulation containing radio opaque material. The developed formulations showed improved buoyancy and lower ulcer index as compared to that seen with plain drugs. Ulcer protective efficacies were confirmed in ulcer-bearing mouse model. In conclusion, greater compatibility, higher gastro-retention and higher anti-ulcer activity of the presently fabricated formulations to improve potential of formulation for redefining ulcer treatment are presented here. These learning exposed a targeted and sustained drug delivery potential of prepared microballoons in gastric region for ulcer therapeutic intervention as corroborated by in vitro and in vivo findings and, thus, deserves further attention for improved ulcer treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

A study of the nonlinear aerodynamics of bodies in nonplanar motion. Ph.D. Thesis - Stanford Univ., Calif.; [numerical analysis of aerodynamic force and moment systems during large amplitude, arbitrary motions

NASA Technical Reports Server (NTRS)

Schiff, L. B.

1974-01-01

Concepts from the theory of functionals are used to develop nonlinear formulations of the aerodynamic force and moment systems acting on bodies in large-amplitude, arbitrary motions. The analysis, which proceeds formally once the functional dependence of the aerodynamic reactions upon the motion variables is established, ensures the inclusion, within the resulting formulation, of pertinent aerodynamic terms that normally are excluded in the classical treatment. Applied to the large-amplitude, slowly varying, nonplanar motion of a body, the formulation suggests that the aerodynamic moment can be compounded of the moments acting on the body in four basic motions: steady angle of attack, pitch oscillations, either roll or yaw oscillations, and coning motion. Coning, where the nose of the body describes a circle around the velocity vector, characterizes the nonplanar nature of the general motion.

Extended-release hydrocodone – gift or curse?

PubMed Central

Krashin, Daniel; Murinova, Natalia; Trescot, Andrea M

2013-01-01

Hydrocodone is a semisynthetic opioid, which has been used for decades as a short-acting analgesic combined with acetaminophen (or less commonly ibuprofen). Several long-acting, non-acetaminophen-containing hydrocodone formulations are undergoing trials in the US under the auspices of the US Food and Drug Administration, and may be available shortly. This article reviews some of the advantages (including drug familiarity and lack of acetaminophen toxicity) and potential disadvantages (including altered use patterns and high morphine equivalent dosing) of such a medication formulation. We also discuss the abuse potential of long-acting versus short-acting opioids in general and hydrocodone specifically, as well as the metabolism of hydrocodone. PMID:23358452

Statistical field theory of futures commodity prices

NASA Astrophysics Data System (ADS)

Baaquie, Belal E.; Yu, Miao

2018-02-01

The statistical theory of commodity prices has been formulated by Baaquie (2013). Further empirical studies of single (Baaquie et al., 2015) and multiple commodity prices (Baaquie et al., 2016) have provided strong evidence in support the primary assumptions of the statistical formulation. In this paper, the model for spot prices (Baaquie, 2013) is extended to model futures commodity prices using a statistical field theory of futures commodity prices. The futures prices are modeled as a two dimensional statistical field and a nonlinear Lagrangian is postulated. Empirical studies provide clear evidence in support of the model, with many nontrivial features of the model finding unexpected support from market data.

Consistency of the free-volume approach to the homogeneous deformation of metallic glasses

NASA Astrophysics Data System (ADS)

Blétry, Marc; Thai, Minh Thanh; Champion, Yannick; Perrière, Loïc; Ochin, Patrick

2014-05-01

One of the most widely used approaches to model metallic-glasses high-temperature homogeneous deformation is the free-volume theory, developed by Cohen and Turnbull and extended by Spaepen. A simple elastoviscoplastic formulation has been proposed that allows one to determine various parameters of such a model. This approach is applied here to the results obtained by de Hey et al. on a Pd-based metallic glass. In their study, de Hey et al. were able to determine some of the parameters used in the elastoviscoplastic formulation through DSC modeling coupled with mechanical tests, and the consistency of the two viewpoints was assessed.

An Eigensystem Realization Algorithm (ERA) for modal parameter identification and model reduction

NASA Technical Reports Server (NTRS)

Juang, J. N.; Pappa, R. S.

1985-01-01

A method, called the Eigensystem Realization Algorithm (ERA), is developed for modal parameter identification and model reduction of dynamic systems from test data. A new approach is introduced in conjunction with the singular value decomposition technique to derive the basic formulation of minimum order realization which is an extended version of the Ho-Kalman algorithm. The basic formulation is then transformed into modal space for modal parameter identification. Two accuracy indicators are developed to quantitatively identify the system modes and noise modes. For illustration of the algorithm, examples are shown using simulation data and experimental data for a rectangular grid structure.

Effects of a sphingolipid-enriched dairy formulation on postprandial lipid concentrations.

PubMed

Ohlsson, L; Burling, H; Duan, R-D; Nilsson, A

2010-11-01

The digestion of sphingolipids (SL) is slow and is catalyzed by mucosal enzymes. Dietary SL was shown to inhibit cholesterol absorption and to lower plasma cholesterol, triglycerides (TG) and hepatic fat accumulation in animal models. A dairy formulation based on fractionation of buttermilk, which is enriched in milk polar lipids of which SL account for a large part is now available. In this study, we examined whether this formulation, when ingested with a standard breakfast, exerted a different influence on postprandial lipids than an equivalent control formulation lacking the polar milk lipids. A total of 18 healthy male volunteers aged 22-65 years ingested a high-fat (40 g) standard breakfast together with a milk-like formulation containing 975 mg of milk SL (A) or the control formulation (B). Postprandial levels of TG, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, apolipoprotein AI (ApoAI), ApoB, glucose and insulin were measured 1 to 7 h after the meal. No difference was seen between experimental and control groups in postprandial levels of TG, insulin, ApoA1 or ApoB. After 1 hour there was a trend of lower cholesterol concentrations in large TG-rich lipoproteins after formulation A. The SL-rich buttermilk drink may affect cholesterol concentrations in TG-rich lipoproteins, but has no effect on postprandial TG after a breakfast with butter fat as the major lipid.

Probabilistic finite elements for transient analysis in nonlinear continua

NASA Technical Reports Server (NTRS)

Liu, W. K.; Belytschko, T.; Mani, A.

1985-01-01

The probabilistic finite element method (PFEM), which is a combination of finite element methods and second-moment analysis, is formulated for linear and nonlinear continua with inhomogeneous random fields. Analogous to the discretization of the displacement field in finite element methods, the random field is also discretized. The formulation is simplified by transforming the correlated variables to a set of uncorrelated variables through an eigenvalue orthogonalization. Furthermore, it is shown that a reduced set of the uncorrelated variables is sufficient for the second-moment analysis. Based on the linear formulation of the PFEM, the method is then extended to transient analysis in nonlinear continua. The accuracy and efficiency of the method is demonstrated by application to a one-dimensional, elastic/plastic wave propagation problem. The moments calculated compare favorably with those obtained by Monte Carlo simulation. Also, the procedure is amenable to implementation in deterministic FEM based computer programs.

Oil-in-oil-emulsions with enhanced substantivity for the treatment of chronic skin diseases.

PubMed

Lunter, Dominique Jasmin; Rottke, Michael; Daniels, Rolf

2014-05-01

The therapy of chronic skin diseases often requires several applications of creams or ointments per day. This is inconvenient to the patients and frequently leads to poor acceptance and compliance. We therefore developed oil-in-oil-emulsions that deliver the active pharmaceutical ingredient (API) to the skin over a prolonged period of time. In this study, we compare the permeation of the API from a conventional formulation to its permeation from an oil-in-oil-emulsion under infinite and finite dosing. Furthermore, we evaluate the substantivity of the formulations. Our results show that the permeation from oil-in-oil-emulsions is constant over a prolonged time and that the emulsions show significantly higher substantivity than conventional formulations. Because of that, the treatment intervals can be extended substantially and compliance can be increased. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Clinical applications of oxymorphone.

PubMed

Vadivelu, Nalini; Maria, Monisa; Jolly, Suneil; Rosenbloom, Julia; Prasad, Arun; Kaye, Alan David

2013-01-01

Oxymorphone (14-hydroxydihydromorphinone), a pyridine ring unsubstituted pyridomorphinan, a semisynthetic opioid analgesic derived from thebaine, first developed in the year 1914 and has been available as oxymorphone hydrochloride parenteral forms in the United States since 1959, when the US Food and Drug Administration approved it. Over the years, it has been used for the alleviation of moderate-to-severe pain. Pharmacological considerations, new and traditional formulations, clinical indications, and recent study populations are examined in this review. Specific considerations for oxymorphone interactions are focused on as well as specific side effects and end organ considerations. Although discovered many decades ago and used as parenteral formulation, the newer oral preparations of oxymorphone (immediate release and extended release) that were approved in 2006 can provide additional options for customizing therapy to accommodate various patient needs. This newer oral formulation could make this powerful agent an important drug in the armamentarium of the healthcare provider caring for patients with pain.

A mortar formulation including viscoelastic layers for vibration analysis

NASA Astrophysics Data System (ADS)

Paolini, Alexander; Kollmannsberger, Stefan; Rank, Ernst; Horger, Thomas; Wohlmuth, Barbara

2018-05-01

In order to reduce the transfer of sound and vibrations in structures such as timber buildings, thin elastomer layers can be embedded between their components. The influence of these elastomers on the response of the structures in the low frequency range can be determined accurately by using conforming hexahedral finite elements. Three-dimensional mesh generation, however, is yet a non-trivial task and mesh refinements which may be necessary at the junctions can cause a high computational effort. One remedy is to mesh the components independently from each other and to couple them using the mortar method. Further, the hexahedral mesh for the thin elastomer layer itself can be avoided by integrating its elastic behavior into the mortar formulation. The present paper extends this mortar formulation to take damping into account such that frequency response analyses can be performed more accurately. Finally, the proposed method is verified by numerical examples.

Long-term efficacy, safety and tolerability of Remoxy for the management of chronic pain.

PubMed

Pergolizzi, Joseph V; Zampogna, Gianpietro; Taylor, Robert; Raffa, Robert B

2015-03-01

Historically, chronic pain generally went under-treated for a variety of objective and subjective reasons, including difficulty to objectively diagnose and manage over a long period of time, potential serious adverse effects of commonly available medications, and patient, healthcare and societal concerns over opioid medications. More recently, in an effort to redress the under-treatment of pain, the number of prescriptions of opioid analgesics has risen dramatically. However, paralleling the increased legitimate use has been a concomitant increase in opioid abuse, misuse and diversion. Pharmaceutical companies have responded by developing a variety of opioid formulations designed to deter abuse by making the products more difficult to tamper with. One such product is Remoxy(®), an extended-release formulation of the strong opioid oxycodone. We review the efficacy, safety and tolerability of this formulation based on the available published literature.

Formulation of D-brane Dynamics

NASA Astrophysics Data System (ADS)

Evans, Thomas

2012-03-01

It is the purpose of this paper (within the context of STS rules & guidelines ``research report'') to formulate a statistical-mechanical form of D-brane dynamics. We consider first the path integral formulation of quantum mechanics, and extend this to a path-integral formulation of D-brane mechanics, summing over all the possible path integral sectors of R-R, NS charged states. We then investigate this generalization utilizing a path-integral formulation summing over all the possible path integral sectors of R-R charged states, calculated from the mean probability tree-level amplitude of type I, IIA, and IIB strings, serving as a generalization of all strings described by D-branes. We utilize this generalization to study black holes in regimes where the initial D-brane system is legitimate, and further this generalization to look at information loss near regions of nonlocality on a non-ordinary event horizon. We see here that in these specific regimes, we can calculate a path integral formulation, as describing D0-brane mechanics, tracing the dissipation of entropy throughout the event horizon. This is used to study the information paradox, and to propose a resolution between the phenomena and the correct and expected quantum mechanical description. This is done as our path integral throughout entropy entering the event horizon effectively and correctly encodes the initial state in subtle correlations in the Hawking radiation.

Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics

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

Martínez, Enrique; Cawkwell, Marc J.; Voter, Arthur F.

Here, Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached atmore » each time step. Lastly, the thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.« less

Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics

DOE PAGES

Martínez, Enrique; Cawkwell, Marc J.; Voter, Arthur F.; ...

2015-04-21

Here, Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached atmore » each time step. Lastly, the thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.« less

Influence of gas compressibility on a burning accident in a mining passage

NASA Astrophysics Data System (ADS)

Demir, Sinan; Calavay, Anish Raman; Akkerman, V'yacheslav

2018-03-01

A recent predictive scenario of a methane/air/coal dust fire in a mining passage is extended by incorporating the effect of gas compressibility into the analysis. The compressible and incompressible formulations are compared, qualitatively and quantitatively, in both the two-dimensional planar and cylindrical-axisymmetric geometries, and a detailed parametric study accounting for coal-dust combustion is performed. It is shown that gas compression moderates flame acceleration, and its impact depends on the type of the fuel, its various thermal-chemical parameters as well as on the geometry of the problem. While the effect of gas compression is relatively minor for the lean and rich flames, providing 5-25% reduction in the burning velocity and thereby justifying the incompressible formulation in that case, such a reduction appears significant, up to 70% for near-stoichiometric methane-air combustion, and therefore it should be incorporated into a rigorous formulation. It is demonstrated that the flame tip velocity remains noticeably subsonic in all the cases considered, which is opposite to the prediction of the incompressible formulation, but qualitatively agrees with the experimental predictions from the literature.

Flux-Based Finite Volume representations for general thermal problems

NASA Technical Reports Server (NTRS)

Mohan, Ram V.; Tamma, Kumar K.

1993-01-01

Flux-Based Finite Volume (FV) element representations for general thermal problems are given in conjunction with a generalized trapezoidal gamma-T family of algorithms, formulated following the spirit of what we term as the Lax-Wendroff based FV formulations. The new flux-based representations introduced offer an improved physical interpretation of the problem along with computationally convenient and attractive features. The space and time discretization emanate from a conservation form of the governing equation for thermal problems, and in conjunction with the flux-based element representations give rise to a physically improved and locally conservative numerical formulations. The present representations seek to involve improved locally conservative properties, improved physical representations and computational features; these are based on a 2D, bilinear FV element and can be extended for other cases. Time discretization based on a gamma-T family of algorithms in the spirit of a Lax-Wendroff based FV formulations are employed. Numerical examples involving linear/nonlinear steady and transient situations are shown to demonstrate the applicability of the present representations for thermal analysis situations.

Turbofan forced mixer lobe flow modeling. 2: Three-dimensional inviscid mixer analysis (FLOMIX)

NASA Technical Reports Server (NTRS)

Barber, T.

1988-01-01

A three-dimensional potential analysis (FLOMIX) was formulated and applied to the inviscid flow over a turbofan foced mixer. The method uses a small disturbance formulation to analytically uncouple the circumferential flow from the radial and axial flow problem, thereby reducing the analysis to the solution of a series of axisymmetric problems. These equations are discretized using a flux volume formulation along a Cartesian grid. The method extends earlier applications of the Cartesian method to complex cambered geometries. The effects of power addition are also included within the potential formulation. Good agreement is obtained with an alternate small disturbance analysis for a high penetration symmetric mixer in a planar duct. In addition, calculations showing pressure distributions and induced secondary vorticity fields are presented for practical trubofan mixer configurations, and where possible, comparison was made with available experimental data. A detailed description of the required data input and coordinate definition is presented along with a sample data set for a practical forced mixer configuration. A brief description of the program structure and subroutines is also provided.

Gauge symmetries of the free supersymmetric string field theories

NASA Astrophysics Data System (ADS)

Neveu, A.; West, P. C.

1985-12-01

The gauge covariant local formulations of the free supersymmetric strings that contained a finite number of supplementary fields are extended so as to place all the generators of the Ramond-Neveu-Schwarz algebra on a more equal footing. Permanent address: King's College, Mathematics Department, London WC2R 2LS, UK.

Use of diets formulated for summer water temperatures in pond production of hybrid striped bass

USDA-ARS?s Scientific Manuscript database

Elevated water temperatures are common in hybrid striped bass or Sunshine bass (HSB; Morone chrysops x M. saxatilis) production ponds during summer months in the southern US. Median daily water temperatures often exceed 30 C from June through September. This experiment was conducted to extend and re...

Nothing Exceptional: Against Agamben

ERIC Educational Resources Information Center

Colatrella, Steven

2011-01-01

Giorgio Agamben's work has become widely influential as a guide to explaining the extra-constitutional powers assumed by governments under the rubric of the War on Terror. His formulations, such as Homo Sacer and State of Exception, have been extended to apply to a wide variety of experiences of repression of liberties or social control, including…

Approach to atmospheric laser-propagation theory based on the extended Huygens-Fresnel principle and a self-consistency concept.

PubMed

Bochove, Erik J; Rao Gudimetla, V S

2017-01-01

We propose a self-consistency condition based on the extended Huygens-Fresnel principle, which we apply to the propagation kernel of the mutual coherence function of a partially coherent laser beam propagating through a turbulent atmosphere. The assumption of statistical independence of turbulence in neighboring propagation segments leads to an integral equation in the propagation kernel. This integral equation is satisfied by a Gaussian function, with dependence on the transverse coordinates that is identical to the previous Gaussian formulation by Yura [Appl. Opt.11, 1399 (1972)APOPAI0003-693510.1364/AO.11.001399], but differs in the transverse coherence length's dependence on propagation distance, so that this established version violates our self-consistency principle. Our formulation has one free parameter, which in the context of Kolmogorov's theory is independent of turbulence strength and propagation distance. We determined its value by numerical fitting to the rigorous beam propagation theory of Yura and Hanson [J. Opt. Soc. Am. A6, 564 (1989)JOAOD60740-323210.1364/JOSAA.6.000564], demonstrating in addition a significant improvement over other Gaussian models.

Emerging Treatment Options in Mild to Moderate Ulcerative Colitis

PubMed Central

Lichtenstein, Gary R.; Hanauer, Stephen B.; Sandborn, William J.

2015-01-01

Ulcerative colitis (UC) is a chronic inflammatory condition associated with rectal bleeding and urgency, tenesmus, and diarrhea. Several medical therapies can be used in the treatment of UC. Aminosalicylates are widely used based on their efficacy in the induction and maintenance of remission. Although corticosteroids are effective in patients with more severe disease, systemic use is associated with significant safety concerns. The newer corticosteroid budesonide has lower systemic bioavailability and, consequently, a more favorable safety profile. A budesonide extended-release formulation allows once-daily dosing and delivers the agent locally throughout the colon. Biologic agents used for the treatment of moderate to severe UC include the tumor necrosis factor inhibitors infliximab, adalimumab, and golimumab, and the integrin inhibitor vedolizumab. Rectally administered therapy can also be useful in the treatment of UC. In October 2014, the US Food and Drug Administration approved a budesonide foam formulation for inducing remission in patients with active mild to moderate distal UC extending up to 40 cm from the anal verge. Budesonide foam rapidly distributes to the sigmoid colon and the rectum and avoids some of the drawbacks of suppositories and enemas. PMID:26491415

Composite starch-based coatings applied to strawberries (Fragaria ananassa).

PubMed

García, M A; Martino, M N; Zaritzky, N E

2001-08-01

Starch-based coatings were used to the extend storage life of strawberries (Fragaria ananassa) stored at 0 degree C and 84.8% relative humidity. Effects of coating formulation (including starch type, plasticizer, lipid and antimicrobial agent) were analysed with respect to fruit quality. Plasticizer addition was necessary for film and coating integrity to avoid pores and cracks. Plasticizer presence reduced weight losses and maintained surface colour of fruits. Amylomaize coatings showed lower water vapour and gas permeabilities and decreased weight losses for longer periods than corn starch ones. Coatings with sorbitol showed lower permeabilities than glycerol ones. Coatings with antimicrobial agents decreased microbial counts, extending storage life of coated fruits by 10 to 14 days in comparison to the control. The addition of 2 g/l sunflower oil to the formulations decreased the water vapour permeability of starch-based films, maintained the surface colour of coated fruits and controlled effectively fruit weight losses during storage. Lipid addition minimized the effects of starch and plasticizer types. Composite starch-based coatings showed selective gas permeability (CO2 higher than O2) which helps to delay senescence of fruits.

77 FR 37947 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-25

... Rule Change To Extend a Fee Discount Pilot Program for Large-Sized Foreign Currency Options June 19... proposing to extend for an additional year the fee discount for large-sized foreign currency (``FX'') option... change is to extend for an additional year the fee discount for large-sized FX option orders. The...

Determining the Intensity of a Point-Like Source Observed on the Background of AN Extended Source

NASA Astrophysics Data System (ADS)

Kornienko, Y. V.; Skuratovskiy, S. I.

2014-12-01

The problem of determining the time dependence of intensity of a point-like source in case of atmospheric blur is formulated and solved by using the Bayesian statistical approach. A pointlike source is supposed to be observed on the background of an extended source with constant in time though unknown brightness. The equation system for optimal statistical estimation of the sequence of intensity values in observation moments is obtained. The problem is particularly relevant for studying gravitational mirages which appear while observing a quasar through the gravitational field of a far galaxy.

Instability model for recurring large and great earthquakes in southern California

USGS Publications Warehouse

Stuart, W.D.

1985-01-01

The locked section of the San Andreas fault in southern California has experienced a number of large and great earthquakes in the past, and thus is expected to have more in the future. To estimate the location, time, and slip of the next few earthquakes, an earthquake instability model is formulated. The model is similar to one recently developed for moderate earthquakes on the San Andreas fault near Parkfield, California. In both models, unstable faulting (the earthquake analog) is caused by failure of all or part of a patch of brittle, strain-softening fault zone. In the present model the patch extends downward from the ground surface to about 12 km depth, and extends 500 km along strike from Parkfield to the Salton Sea. The variation of patch strength along strike is adjusted by trial until the computed sequence of instabilities matches the sequence of large and great earthquakes since a.d. 1080 reported by Sieh and others. The last earthquake was the M=8.3 Ft. Tejon event in 1857. The resulting strength variation has five contiguous sections of alternately low and high strength. From north to south, the approximate locations of the sections are: (1) Parkfield to Bitterwater Valley, (2) Bitterwater Valley to Lake Hughes, (3) Lake Hughes to San Bernardino, (4) San Bernardino to Palm Springs, and (5) Palm Springs to the Salton Sea. Sections 1, 3, and 5 have strengths between 53 and 88 bars; sections 2 and 4 have strengths between 164 and 193 bars. Patch section ends and unstable rupture ends usually coincide, although one or more adjacent patch sections may fail unstably at once. The model predicts that the next sections of the fault to slip unstably will be 1, 3, and 5; the order and dates depend on the assumed length of an earthquake rupture in about 1700. ?? 1985 Birkha??user Verlag.

LOWER COST METHODS FOR IMPROVED OIL RECOVERY (IOR) VIA SURFACTANT FLOODING

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

William A. Goddard III; Yongchun Tang; Patrick Shuler

2004-09-01

This report provides a summary of the work performed in this 3-year project sponsored by DOE. The overall objective of this project is to identify new, potentially more cost-effective surfactant formulations for improved oil recovery (IOR). The general approach is to use an integrated experimental and computational chemistry effort to improve our understanding of the link between surfactant structure and performance, and from this knowledge, develop improved IOR surfactant formulations. Accomplishments for the project include: (1) completion of a literature review to assemble current and new surfactant IOR ideas, (2) Development of new atomistic-level MD (molecular dynamic) modeling methodologies tomore » calculate IFT (interfacial tension) rigorously from first principles, (3) exploration of less computationally intensive mesoscale methods to estimate IFT, Quantitative Structure Property Relationship (QSPR), and cohesive energy density (CED) calculations, (4) experiments to screen many surfactant structures for desirable low IFT and solid adsorption behavior, and (5) further experimental characterization of the more promising new candidate formulations (based on alkyl polyglycosides (APG) and alkyl propoxy sulfate surfactants). Important findings from this project include: (1) the IFT between two pure substances may be calculated quantitatively from fundamental principles using Molecular Dynamics, the same approach can provide qualitative results for ternary systems containing a surfactant, (2) low concentrations of alkyl polyglycoside surfactants have potential for IOR (Improved Oil Recovery) applications from a technical standpoint (if formulated properly with a cosurfactant, they can create a low IFT at low concentration) and also are viable economically as they are available commercially, and (3) the alkylpropoxy sulfate surfactants have promising IFT performance also, plus these surfactants can have high optimal salinity and so may be attractive for use in higher salinity reservoirs. Alkylpropoxy sulfate surfactants are not yet available as large volume commercial products. The results presented herein can provide the needed industrial impetus for extending application (alkyl polyglycoside) or scaling up (alkylpropoxy sulfates) of these two promising surfactants for enhanced oil recovery. Furthermore, the advanced simulations tools presented here can be used to continue to uncover new types of surfactants with promising properties such as inherent low IFT and biodegradability.« less

Extended release local anesthetic agents in a postoperative arthritic pain model.

PubMed

Ickowicz, Diana E; Golovanevski, Ludmila; Haze, Amir; Domb, Abraham J; Weiniger, Carolyn F

2014-01-01

Local anesthetics play an important role in postoperative pain management in orthopedic joint procedures. The aim of this study was to determine the effect of an intraoperative extra-articular injection of poly(DL-lactic acid co castor oil 3:7), p(DLLA:CO) 3:7 loaded with 15% bupivacaine, for postoperative analgesia following knee arthroplasty. Prolonged release local anesthetic formulation was synthesized by mixing p(DLLA:CO) 3:7 with bupivacaine base. Under anesthesia, the knee joint of Sprague-Dawley rats was exposed, a hole drilled in the femoral trochlea. 0.2 mL of either 15% polymer-bupivacaine formulation or plain bupivacaine (control) was injected locally and compared with a nonsurgery control group. Mechanical hyperalgesia was determined by counting the vocalizations and leg withdrawal after joint squeezing. Behavioral assessments over a day postoperative period revealed a reduction in rearing and ambulation in an open-field apparatus in animals of both experimental groups compared with the nonsurgery control. The vocalizations during the hyperalgesia test increased compared with the control at 24 h. At 48 h, 3.667 ± 0.5138, p = 0.0076 vocalizations were recorded for the plain bupivacaine group versus 1.417 ± 0.5138, p < 0.0001 in the 15% polymer-bupivacaine formulation. Bupivacaine encapsulated in p(DLLA:CO) 3:7 extended the duration of the analgesia compared with plain drug in rats and could represent effective postoperative analgesic in orthopedic joint procedures. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Initial-value semiclassical propagators for the Wigner phase space representation: Formulation based on the interpretation of the Moyal equation as a Schrödinger equation.

PubMed

Koda, Shin-ichi

2015-12-28

We formulate various semiclassical propagators for the Wigner phase space representation from a unified point of view. As is shown in several studies, the Moyal equation, which is an equation of motion for the Wigner distribution function, can be regarded as the Schrödinger equation of an extended Hamiltonian system where its "position" and "momentum" correspond to the middle point of two points of the original phase space and the difference between them, respectively. Then we show that various phase-space semiclassical propagators can be formulated just by applying existing semiclassical propagators to the extended system. As a result, a phase space version of the Van Vleck propagator, the initial-value Van Vleck propagator, the Herman-Kluk propagator, and the thawed Gaussian approximation are obtained. In addition, we numerically compare the initial-value phase-space Van Vleck propagator, the phase-space Herman-Kluk propagator, and the classical mechanical propagation as approximation methods for the time propagation of the Wigner distribution function in terms of both accuracy and convergence speed. As a result, we find that the convergence speed of the Van Vleck propagator is far slower than others as is the case of the Hilbert space, and the Herman-Kluk propagator keeps its accuracy for a long period compared with the classical mechanical propagation while the convergence speed of the latter is faster than the former.

Wide-Temperature Electrolytes for Lithium-Ion Batteries

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

Li, Qiuyan; Jiao, Shuhong; Luo, Langli

2017-05-26

Formulating electrolytes with solvents of low freezing points and high dielectric constants is a direct approach to extend the service temperature range of lithium (Li)-ion batteries (LIBs), for which propylene carbonate (PC), ethyl methyl carbonate (EMC), diethyl carbonate (DEC), methyl butyrate (MB) are excellent candidates. In this work, we report such low temperature electrolyte formulations by optimizing the content of ethylene carbonate (EC) in the EC-PC-EMC ternary solvent system with LiPF6 salt and CsPF6 additive. An extended service temperature range from 40°C to 60°C was obtained in LIBs with lithium nickel cobalt aluminum mixed oxide (LiNi0.80Co0.15Al0.05O2, NCA) as cathode andmore » graphite as anode. The discharge capacities at low temperatures and the cycle life at room and elevated temperatures were systematically investigated in association with the ionic conductivity and phase transition behaviors. The most promising electrolyte formulation was identified as 1.0 M LiPF6 in EC-PC-EMC (1:1:8 by wt.) with 0.05 M CsPF6, which was demonstrated in both coin cells of graphite||NCA and 1 Ah pouch cells of graphite||LiNi1/3Mn1/3Co1/3O2. This optimized electrolyte enables excellent wide-temperature performances, as evidenced by the 68% capacity retention at 40C and C/5 rate, and nearly identical stable cycle life at room and elevated temperatures up to 60C.« less

Wide-Temperature Electrolytes for Lithium-Ion Batteries.

PubMed

Li, Qiuyan; Jiao, Shuhong; Luo, Langli; Ding, Michael S; Zheng, Jianming; Cartmell, Samuel S; Wang, Chong-Min; Xu, Kang; Zhang, Ji-Guang; Xu, Wu

2017-06-07

Formulating electrolytes with solvents of low freezing points and high dielectric constants is a direct approach to extend the service-temperature range of lithium (Li)-ion batteries (LIBs). In this study, we report such wide-temperature electrolyte formulations by optimizing the ethylene carbonate (EC) content in the ternary solvent system of EC, propylene carbonate (PC), and ethyl methyl carbonate (EMC) with LiPF 6 salt and CsPF 6 additive. An extended service-temperature range from -40 to 60 °C was obtained in LIBs with lithium nickel cobalt aluminum oxide (LiNi 0.80 Co 0.15 Al 0.05 O 2 , NCA) as cathode and graphite as anode. The discharge capacities at low temperatures and the cycle life at room temperature and elevated temperatures were systematically investigated together with the ionic conductivity and phase-transition behaviors. The most promising electrolyte formulation was identified as 1.0 M LiPF 6 in EC-PC-EMC (1:1:8 by wt) with 0.05 M CsPF 6 , which was demonstrated in both coin cells of graphite∥NCA and 1 Ah pouch cells of graphite∥LiNi 1/3 Mn 1/3 Co 1/3 O 2 . This optimized electrolyte enables excellent wide-temperature performances, as evidenced by the high capacity retention (68%) at -40 °C and C/5 rate, significantly higher than that (20%) of the conventional LIB electrolyte, and the nearly identical stable cycle life as the conventional LIB electrolyte at room temperature and elevated temperatures up to 60 °C.

Gastroretentive extended-release floating granules prepared using a novel fluidized hot melt granulation (FHMG) technique.

PubMed

Zhai, H; Jones, D S; McCoy, C P; Madi, A M; Tian, Y; Andrews, G P

2014-10-06

The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid of low melting point materials, using Compritol 888 ATO and Gelucire 50/13 as meltable binders, in place of conventional liquid binders. The physicochemical properties, morphology, floating properties, and drug release of the manufactured granules were investigated. Granules prepared by this method were spherical in shape and showed good flowability. The floating granules exhibited sustained release exceeding 10 h. Granule buoyancy (floating time and strength) and drug release properties were significantly influenced by formulation variables such as excipient type and concentration, and the physical characteristics (particle size, hydrophilicity) of the excipients. Drug release rate was increased by increasing the concentration of hydroxypropyl cellulose (HPC) and Gelucire 50/13, or by decreasing the particle size of HPC. Floating strength was improved through the incorporation of sodium bicarbonate and citric acid. Furthermore, floating strength was influenced by the concentration of HPC within the formulation. Granules prepared in this way show good physical characteristics, floating ability, and drug release properties when placed in simulated gastric fluid. Moreover, the drug release and floating properties can be controlled by modification of the ratio or physical characteristics of the excipients used in the formulation.

Linear complementarity formulation for 3D frictional sliding problems

USGS Publications Warehouse

Kaven, Joern; Hickman, Stephen H.; Davatzes, Nicholas C.; Mutlu, Ovunc

2012-01-01

Frictional sliding on quasi-statically deforming faults and fractures can be modeled efficiently using a linear complementarity formulation. We review the formulation in two dimensions and expand the formulation to three-dimensional problems including problems of orthotropic friction. This formulation accurately reproduces analytical solutions to static Coulomb friction sliding problems. The formulation accounts for opening displacements that can occur near regions of non-planarity even under large confining pressures. Such problems are difficult to solve owing to the coupling of relative displacements and tractions; thus, many geomechanical problems tend to neglect these effects. Simple test cases highlight the importance of including friction and allowing for opening when solving quasi-static fault mechanics models. These results also underscore the importance of considering the effects of non-planarity in modeling processes associated with crustal faulting.

A three-dimensional meso-macroscopic model for Li-Ion intercalation batteries

DOE PAGES

Allu, S.; Kalnaus, S.; Simunovic, S.; ...

2016-06-09

Through this study, we present a three-dimensional computational formulation for electrode-electrolyte-electrode system of Li-Ion batteries. The physical consistency between electrical, thermal and chemical equations is enforced at each time increment by driving the residual of the resulting coupled system of nonlinear equations to zero. The formulation utilizes a rigorous volume averaging approach typical of multiphase formulations used in other fields and recently extended to modeling of supercapacitors [1]. Unlike existing battery modeling methods which use segregated solution of conservation equations and idealized geometries, our unified approach can model arbitrary battery and electrode configurations. The consistency of multi-physics solution also allowsmore » for consideration of a wide array of initial conditions and load cases. The formulation accounts for spatio-temporal variations of material and state properties such as electrode/void volume fractions and anisotropic conductivities. The governing differential equations are discretized using the finite element method and solved using a nonlinearly consistent approach that provides robust stability and convergence. The new formulation was validated for standard Li-ion cells and compared against experiments. Finally, its scope and ability to capture spatio-temporal variations of potential and lithium distribution is demonstrated on a prototypical three-dimensional electrode problem.« less

Preparation and In Vitro/Ex Vivo Evaluation of Moxifloxacin-Loaded PLGA Nanosuspensions for Ophthalmic Application.

PubMed

Mudgil, Meetali; Pawar, Pravin K

2013-01-01

The aim of the present investigation was to prepare a colloidal ophthalmic formulation to improve the residence time of moxifloxacin. Moxifloxacin-loaded poly(dl-lactide-co-glycolide) (PLGA) nanosuspensions were prepared by using the solvent evaporation technique. The nanosuspensions were characterised physically by using different techniques like particle size, zeta potential, FTIR, DSC, and XRD analysis. In vitro and ex vivo studies of nanosuspensions were carried out using a modified USP dissolution apparatus and all-glass Franz diffusion cells, respectively. The antibacterial activities of the nanosuspension and marketed formulations were performed against S. aureus and P. aeroginosa. The moxifloxacin-loaded PLGA nanosuspensions showed uniform particle size, ranging between 164-490 nm with negative zeta potential for all batches. The percentage entrapment efficiency of the drug-loaded nano-suspension was found to be between 84.09 to 92.05%. In vitro drug release studies suggest that all of the formulations showed extended drug release profiles and follow Korsemeyer-Peppas release kinetics. In vitro corneal permeability was found to be comparable with that of the marketed formulation across isolated goat cornea, indicating the suitability of the nanosuspension formulation in the ophthalmic delivery of moxifloxacin. The optimised nano-suspension was found to be more active against S. aureus and P. aeruginosa compared to the marketed eye drops.

Factors Affecting the Design of Slow Release Formulations of Herbicides Based on Clay-Surfactant Systems. A Methodological Approach

PubMed Central

Galán-Jiménez, María del Carmen; Mishael, Yael-Golda; Nir, Shlomo; Morillo, Esmeralda; Undabeytia, Tomás

2013-01-01

A search for clay-surfactant based formulations with high percentage of the active ingredient, which can yield slow release of active molecules is described. The active ingredients were the herbicides metribuzin (MZ), mesotrione (MS) and flurtamone (FL), whose solubilities were examined in the presence of four commercial surfactants; (i) neutral: two berols (B048, B266) and an alkylpolyglucoside (AG6202); (ii) cationic: an ethoxylated amine (ET/15). Significant percent of active ingredient (a.i.) in the clay/surfactant/herbicide formulations could be achieved only when most of the surfactant was added as micelles. MZ and FL were well solubilized by berols, whereas MS by ET/15. Sorption of surfactants on the clay mineral sepiolite occurred mostly by sorption of micelles, and the loadings exceeded the CEC. Higher loadings were determined for B266 and ET/15. The sorption of surfactants was modeled by using the Langmuir-Scatchard equation which permitted the determination of binding coefficients that could be used for further predictions of the sorbed amounts of surfactants under a wide range of clay/surfactant ratios. A possibility was tested of designing clay-surfactant based formulations of certain herbicides by assuming the same ratio between herbicides and surfactants in the formulations as for herbicides incorporated in micelles in solution. Calculations indicated that satisfactory FL formulations could not be synthesized. The experimental fractions of herbicides in the formulations were in agreement with the predicted ones for MS and MZ. The validity of this approach was confirmed in in vitro release tests that showed a slowing down of the release of a.i. from the designed formulations relative to the technical products. Soil dissipation studies with MS formulations also showed improved bioactivity of the clay-surfactant formulation relative to the commercial one. This methodological approach can be extended to other clay-surfactant systems for encapsulation and slow release of target molecules of interest. PMID:23527087

Simulation of global oceanic upper layers forced at the surface by an optimal bulk formulation derived from multi-campaign measurements.

NASA Astrophysics Data System (ADS)

Garric, G.; Pirani, A.; Belamari, S.; Caniaux, G.

2006-12-01

order to improve the air/sea interface for the future MERCATOR global ocean operational system, we have implemented the new bulk formulation developed by METEO-FRANCE (French Meteo office) in the MERCATOR 2 degree global ocean-ice coupled model (ORCA2/LIM). A single bulk formulation for the drag, temperature and moisture exchange coefficients is derived from an extended consistent database gathering 10 years of measurements issued from five experiments dedicated to air-sea fluxes estimates (SEMAPHORE, CATCH, FETCH, EQUALANT99 and POMME) in various oceanic basins (from Northern to equatorial Atlantic). The available database (ALBATROS) cover the widest range of atmospheric and oceanic conditions, from very light (0.3 m/s) to very strong (up to 29 m/s) wind speeds, and from unstable to extremely stable atmospheric boundary layer stratification. We have defined a work strategy to test this new formulation in a global oceanic context, by using this multi- campaign bulk formulation to derive air-sea fluxes from base meteorological variables produces by the ECMWF (European Centre for Medium Range and Weather Forecast) atmospheric forecast model, in order to get surface boundary conditions for ORCA2/LIM. The simulated oceanic upper layers forced at the surface by the previous air/sea interface are compared to those forced by the optimal bulk formulation. Consecutively with generally weaker transfer coefficient, the latter formulation reduces the cold bias in the equatorial Pacific and increases the too weak summer sea ice extent in Antarctica. Compared to a recent mixed layer depth (MLD) climatology, the optimal bulk formulation reduces also the too deep simulated MLDs. Comparison with in situ temperature and salinity profiles in different areas allowed us to evaluate the impact of changing the air/sea interface in the vertical structure.

Two-dimensional interaction of a shear flow with a free surface in a stratified fluid and its solitary-wave solutions via mathematical methods

NASA Astrophysics Data System (ADS)

Seadawy, Aly R.

2017-12-01

In this study, we presented the problem formulations of models for internal solitary waves in a stratified shear flow with a free surface. The nonlinear higher order of extended KdV equations for the free surface displacement is generated. We derived the coefficients of the nonlinear higher-order extended KdV equation in terms of integrals of the modal function for the linear long-wave theory. The wave amplitude potential and the fluid pressure of the extended KdV equation in the form of solitary-wave solutions are deduced. We discussed and analyzed the stability of the obtained solutions and the movement role of the waves by making graphs of the exact solutions.

Extended Spectrum Beta-lactamases: Definition, Classification and Epidemiology.

PubMed

Ghafourian, Sobhan; Sadeghifard, Nourkhoda; Soheili, Sara; Sekawi, Zamberi

2015-01-01

Extended spectrum beta-lactamases (ESBLs) are defined as enzymes produced by certain bacteria that are able to hydrolyze extended spectrum cephalosporin. They are therefore effective against beta-lactam antibiotics such as ceftazidime, ceftriaxone, cefotaxime and oxyimino-monobactam. The objective of the current review is to provide a better understanding of ESBL and the epidemiology of ESBL producing organisms which are among those responsible for antibiotic resistant strains. Globally, ESBLs are considered to be problematic, particularly in hospitalized patients. There is an increasing frequency of ESBL in different parts of the world. The high risk patients are those contaminated with ESBL producer strains as it renders treatment to be ineffective in these patients. Thus, there an immediate needs to identify EBSL and formulate strategic policy initiatives to reduce their prevalence.

Effects of drug-carrier interactions on drug dissolution from binary and ternary matrices

NASA Astrophysics Data System (ADS)

Iqbal, Zafar

For nearly five decades, pharmaceutical researchers have studied solid solutions of drugs in polymers as a potential means to enhance the dissolution of drugs with poor aqueous solubility. This has become of greater importance in recent years because most new potential drug compounds (new chemical entities) exhibit poor water solubility and present great challenges to scientists who must design dosage forms from which the drugs are bioavailable. During the formulation of a solid solution, the drug undergoes physical but not chemical alterations that increase its chemical potential in the formulation relative to that of the pure drug in its stable form. This increased chemical potential is responsible for enhanced dissolution as well as physical instabilities, such as amorphous to crystalline conversions and precipitation within the solid state. The chemical potential is derived from the Gibbs free energy, so it is reasonable to explain the behavior of solid solution systems in terms of thermodynamics. Solid solutions and dispersions have been extensively studied by pharmaceutical scientists, both with regard to manufacturing aspects and the proposal of various models in attempts to explain the physical bases for how these systems work. Recently, Dave and Bellantone proposed a model based on the thermodynamic changes resulting from the formulation of binary solid solutions of a drug in the polymer PVP. Their model introduced a modification of the F-H theory, which was used to quantify the drug-polymer interaction energies and calculate the entropy of mixing of the drug and polymer. In this work, the model of Dave and Bellantone was extended to include three-component systems, consisting of one drug mixed in a carrier matrix consisting of mixture of two polymers or a polymer and a surfactant. For this research, solid solutions were formed using various drug weight fractions in the formulations. The study focused on the following points: (1) Prepare solid solution formulations and perform appropriate physical characterizations. (2) Characterize the increase in drug dissolution rates resulting from solid solution formulations. (3) Relate the initial dissolution rates to the drug solubility. (4) Explain the solubility enhancement from solid solution dosage in terms of the drug polymer interactions using the extended thermodynamic model. Two poorly water soluble drugs, levonorgestrel (LEVO) and ethinyl estradiol (EE) were formulated in seven solid solution preparations comprised of four carrier systems. Materials used as carriers included various combinations of the polymers PVP K-30, Copovidone (COP), Poloxamer 182, and the surfactant TweenRTM 20. Additionally, ibuprofen (IBU) was used in three formulations consisting of various combinations of PVP K-30, Copovidone and TweenRTM 20. Formulations with various drug weight fractions (0.5%--30%) were prepared using the solvent evaporation technique. Each formulation was tested for dissolution using intrinsic dissolution apparatus (USP). The solid solutions were compressed into tablets into the sample die that maintained a constant surface area during the dissolution process. DSC, XRD and NIRS scans identified that the crystalline peaks of the drug disappeared with the addition of the polymer for all ratios of EE, indicating the formation of solid solutions (to within the limits of detection of the equipment). This was also observed for the LEVO dispersions up to 10% drug loading. At higher drug loading, solutions were formed but some small degree crystallinity was also present. For each experiment, the initial dissolution rates were obtained from the slope of the mass dissolved vs. time plots taken at early times, and volume normalized initial dissolution rates RV were calculated by dividing the initial dissolution rate by the volume fraction of the drug in the formulation. Comparison of the RV values for the various formulations with a reference RV (typically that of the pure drug or of the formulation with the highest polymer content) allowed calculation of relative volume normalized dissolution rates (RNV). The various RNV were used in the thermodynamic model for data analyses and to determine the interactions between the drug and carrier molecules. It was generally seen that RNV increased with decreased drug fraction, and was adequately modeled by the equations derived from the extended thermodynamic model. It was concluded that the model proposed for the binary and ternary systems successfully represented the mechanism of drug-polymer interaction and the energy changes taken place within the dispersion systems. The dissolution data analysis and subsequent understanding of physical modifications in the dispersion systems characterized by XRD, NIRS and DSC further substantiated the findings. The understanding of the fundamental physical might help scientists to predict the effects of mixing various drugs and polymers, and the effects of varying ratios.

A comparison of long-baseline strain data and fault creep records obtained near Hollister, California

USGS Publications Warehouse

Slater, L.E.; Burford, R.O.

1979-01-01

A comparison of creepmeter records from nine sites along a 12-km segment of the Calaveras fault near Hollister, California and long-baseline strain changes for nine lines in the Hollister multiwavelength distance-measuring (MWDM) array has established that episodes of large-scale deformation both preceded and accompanied periods of creep activity monitored along the fault trace during 1976. A concept of episodic, deep-seated aseismic slip that contributes to loading and subsequent aseismic failure of shallow parts of the fault plane seems attractive, implying that the character of aseismic slip sensed along the surface trace may be restricted to a relatively shallow (~ 1-km) region on the fault plane. Preliminary results from simple dislocation models designed to test the concept demonstrate that extending the time-histories and amplitudes of creep events sensed along the fault trace to depths of up to 10 km on the fault plane cannot simulate adequately the character and amplitudes of large-scale episodic movements observed at points more than 1 km from the fault. Properties of a 2-3-km-thick layer of unconsolidated sediments present in Hollister Valley, combined with an essentially rigid-block behavior in buried basement blocks, might be employed in the formulation of more appropriate models that could predict patterns of shallow fault creep and large-scale displacements much more like those actually observed. ?? 1979.

The Capability Portfolio Analysis Tool (CPAT): A Mixed Integer Linear Programming Formulation for Fleet Modernization Analysis (Version 2.0.2).

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

Waddell, Lucas; Muldoon, Frank; Henry, Stephen Michael

In order to effectively plan the management and modernization of their large and diverse fleets of vehicles, Program Executive Office Ground Combat Systems (PEO GCS) and Program Executive Office Combat Support and Combat Service Support (PEO CS&CSS) commis- sioned the development of a large-scale portfolio planning optimization tool. This software, the Capability Portfolio Analysis Tool (CPAT), creates a detailed schedule that optimally prioritizes the modernization or replacement of vehicles within the fleet - respecting numerous business rules associated with fleet structure, budgets, industrial base, research and testing, etc., while maximizing overall fleet performance through time. This paper contains a thor-more » ough documentation of the terminology, parameters, variables, and constraints that comprise the fleet management mixed integer linear programming (MILP) mathematical formulation. This paper, which is an update to the original CPAT formulation document published in 2015 (SAND2015-3487), covers the formulation of important new CPAT features.« less

Impact of abuse-deterrent OxyContin on prescription opioid utilization.

PubMed

Hwang, Catherine S; Chang, Hsien-Yen; Alexander, G Caleb

2015-02-01

We quantified the degree to which the August 2010 reformulation of abuse-deterrent OxyContin affected its use, as well as the use of alternative extended-release and immediate-release opioids. We used the IMS Health National Prescription Audit, a nationally representative source of prescription activity in the USA, to conduct a segmented time-series analysis of the use of OxyContin and other prescription opioids. Our primary time period of interest was 12 months prior to and following August 2010. We performed model checks and sensitivity analyses, such as adjusting for marketing and promotion, using alternative lag periods, and adding extra observation points. OxyContin sales were similar before and after the August 2010 reformulation, with approximately 550 000 monthly prescriptions. After adjusting for declines in the generic extended-release oxycodone market, the formulation change was associated with a reduction of approximately 18 000 OxyContin prescription sales per month (p = 0.02). This decline corresponded to a change in the annual growth rate of OxyContin use, from 4.9% prior to the reformulation to -23.8% during the year after the reformulation. There were no statistically significant changes associated with the sales of alternative extended-release (p = 0.42) or immediate-release (p = 0.70) opioids. Multiple sensitivity analyses supported these findings and their substantive interpretation. The market debut of abuse-deterrent OxyContin was associated with declines in its use after accounting for the simultaneous contraction of the generic extended-release oxycodone market. Further scrutiny into the effect of abuse-deterrent formulations on medication use and health outcomes is vital given their popularity in opioid drug development. Copyright © 2014 John Wiley & Sons, Ltd.

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.

Phase field modeling of brittle fracture for enhanced assumed strain shells at large deformations: formulation and finite element implementation

NASA Astrophysics Data System (ADS)

Reinoso, J.; Paggi, M.; Linder, C.

2017-06-01

Fracture of technological thin-walled components can notably limit the performance of their corresponding engineering systems. With the aim of achieving reliable fracture predictions of thin structures, this work presents a new phase field model of brittle fracture for large deformation analysis of shells relying on a mixed enhanced assumed strain (EAS) formulation. The kinematic description of the shell body is constructed according to the solid shell concept. This enables the use of fully three-dimensional constitutive models for the material. The proposed phase field formulation integrates the use of the (EAS) method to alleviate locking pathologies, especially Poisson thickness and volumetric locking. This technique is further combined with the assumed natural strain method to efficiently derive a locking-free solid shell element. On the computational side, a fully coupled monolithic framework is consistently formulated. Specific details regarding the corresponding finite element formulation and the main aspects associated with its implementation in the general purpose packages FEAP and ABAQUS are addressed. Finally, the applicability of the current strategy is demonstrated through several numerical examples involving different loading conditions, and including linear and nonlinear hyperelastic constitutive models.

Finite elements based on consistently assumed stresses and displacements

NASA Technical Reports Server (NTRS)

Pian, T. H. H.

1985-01-01

Finite element stiffness matrices are derived using an extended Hellinger-Reissner principle in which internal displacements are added to serve as Lagrange multipliers to introduce the equilibrium constraint in each element. In a consistent formulation the assumed stresses are initially unconstrained and complete polynomials and the total displacements are also complete such that the corresponding strains are complete in the same order as the stresses. Several examples indicate that resulting properties for elements constructed by this consistent formulation are ideal and are less sensitive to distortions of element geometries. The method has been used to find the optimal stress terms for plane elements, 3-D solids, axisymmetric solids, and plate bending elements.

Damage tolerant design using collapse techniques

NASA Technical Reports Server (NTRS)

Haftka, R. T.

1982-01-01

A new approach to the design of structures for improved global damage tolerance is presented. In its undamaged condition the structure is designed subject to strength, displacement and buckling constraints. In the damaged condition the only constraint is that the structure will not collapse. The collapse load calculation is formulated as a maximization problem and solved by an interior extended penalty function. The design for minimum weight subject to constraints on the undamaged structure and a specified level of the collapse load is a minimization problem which is also solved by a penalty function formulation. Thus the overall problem is of a nested or multilevel optimization. Examples are presented to demonstrate the difference between the present and more traditional approaches.

Analysis of continuously rotating quadrupole focusing channels using generalized Courant-Snyder theory

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

Chung, Moses; Qin, Hong; Gilson, Erik

2013-01-01

By extending the recently developed generalized Courant-Snyder theory for coupled transverse beam dynamics, we have constructed the Gaussian beam distribution and its projections with arbitrary mode emittance ratios. The new formulation has been applied to a continuously-rotating quadrupole focusing channel because the basic properties of this channel are known theoretically and could also be investigated experimentally in a compact setup such as the linear Paul trap configuration. The new formulation retains a remarkably similar mathematical structure to the original Courant-Snyder theory, and thus provides a powerful theoretical tool to investigate coupled transverse beam dynamics in general and more complex linearmore » focusing channels.« less

Analysis of continuously rotating quadrupole focusing channels using generalized Courant-Snyder theory

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

Chung, Moses; Qin, Hong; Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026

2013-08-15

By extending the recently developed generalized Courant-Snyder theory for coupled transverse beam dynamics, we have constructed the Gaussian beam distribution and its projections with arbitrary mode emittance ratios. The new formulation has been applied to a continuously rotating quadrupole focusing channel because the basic properties of this channel are known theoretically and could also be investigated experimentally in a compact setup such as the linear Paul trap configuration. The new formulation retains a remarkably similar mathematical structure to the original Courant-Snyder theory, and thus, provides a powerful theoretical tool to investigate coupled transverse beam dynamics in general and more complexmore » linear focusing channels.« less

Geodesic regression for image time-series.

PubMed

Niethammer, Marc; Huang, Yang; Vialard, François-Xavier

2011-01-01

Registration of image-time series has so far been accomplished (i) by concatenating registrations between image pairs, (ii) by solving a joint estimation problem resulting in piecewise geodesic paths between image pairs, (iii) by kernel based local averaging or (iv) by augmenting the joint estimation with additional temporal irregularity penalties. Here, we propose a generative model extending least squares linear regression to the space of images by using a second-order dynamic formulation for image registration. Unlike previous approaches, the formulation allows for a compact representation of an approximation to the full spatio-temporal trajectory through its initial values. The method also opens up possibilities to design image-based approximation algorithms. The resulting optimization problem is solved using an adjoint method.

New infinite-dimensional hidden symmetries for heterotic string theory

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

Gao Yajun

The symmetry structures of two-dimensional heterotic string theory are studied further. A (2d+n)x(2d+n) matrix complex H-potential is constructed and the field equations are extended into a complex matrix formulation. A pair of Hauser-Ernst-type linear systems are established. Based on these linear systems, explicit formulations of new hidden symmetry transformations for the considered theory are given and then these symmetry transformations are verified to constitute infinite-dimensional Lie algebras: the semidirect product of the Kac-Moody o(d,d+n-circumflex) and Virasoro algebras (without center charges). These results demonstrate that the heterotic string theory under consideration possesses more and richer symmetry structures than previously expected.

Non-predictor control of a class of feedforward nonlinear systems with unknown time-varying delays

NASA Astrophysics Data System (ADS)

Koo, Min-Sung; Choi, Ho-Lim

2016-08-01

This paper generalises the several recent results on the control of feedforward time-delay nonlinear systems. First, in view of system formulation, there are unknown time-varying delays in both states and main control input. Also, the considered nonlinear system has extended feedforward nonlinearities. Second, in view of control solution, our proposed controller is a non-predictor feedback controller whereas smith-predictor type controllers are used in the several existing results. Moreover, our controller does not need any information on the unknown delays except their upper bounds. Thus, our result has certain merits in both system formulation and control solution perspective. The analysis and example are given for clear illustration.

Robustness of Flexible Systems With Component-Level Uncertainties

NASA Technical Reports Server (NTRS)

Maghami, Peiman G.

2000-01-01

Robustness of flexible systems in the presence of model uncertainties at the component level is considered. Specifically, an approach for formulating robustness of flexible systems in the presence of frequency and damping uncertainties at the component level is presented. The synthesis of the components is based on a modifications of a controls-based algorithm for component mode synthesis. The formulation deals first with robustness of synthesized flexible systems. It is then extended to deal with global (non-synthesized ) dynamic models with component-level uncertainties by projecting uncertainties from component levels to system level. A numerical example involving a two-dimensional simulated docking problem is worked out to demonstrate the feasibility of the proposed approach.

Validation of food grade salts of organic acids as ingredients to control Listeria monocytogenes on pork scrapple during extended refrigerated storage

USDA-ARS?s Scientific Manuscript database

Pork scrapple was formulated, with or without citrate-diacetate (0.64%), by a commercial processor to contain various solutions/blends of the following antimicrobials to control L. monocytogenes on pork scrapple during refrigerated storage: i) lactate-diacetate (3.0 or 4.0%), ii) lactate-diacetate-p...

Allspice, garlic, and oregano plant essential oils in tomato films inactive the foodborne pathogens Escherichia coli O157:H7, Salmonella enterica, and Listeria monocytogenes

USDA-ARS?s Scientific Manuscript database

Edible films containing plant essential oils are gaining importance as potential antibacterial formulations to extend product shelf-life and reduce risk of pathogen growth on food surfaces. An evaluation of both antimicrobial and physicochemical properties of edible films is important for applicati...

Allspice, garlic and oregano plant essential oils in tomato films inactivate the foodborne pathogens, Escherichia coli O157:h7, Salmonella enterica and Listeria monocytogenes

USDA-ARS?s Scientific Manuscript database

Edible films containing plant essential oils arc gaining importance as potential antibacterial formulations to extend product shelf life and reduce risk of pathogen growth on food surfaces. An evaluation of both antimicrobial and physicochemical properties of edible films is important for applicatio...

Higher Order First Integrals of Motion in a Gauge Covariant Hamiltonian Framework

NASA Astrophysics Data System (ADS)

Visinescu, Mihai

The higher order symmetries are investigated in a covariant Hamiltonian formulation. The covariant phase-space approach is extended to include the presence of external gauge fields and scalar potentials. The special role of the Killing-Yano tensors is pointed out. Some nontrivial examples involving Runge-Lenz type conserved quantities are explicitly worked out.

p-Forms and diffeomorphisms: Hamiltonian formulation

NASA Astrophysics Data System (ADS)

Baulieu, Laurent; Henneaux, Marc

1987-07-01

The BRST charges corresponding to various (equivalent) ways of writing the action of the diffeomorphism group on p-form gauge fields are canonically related by a canonical transformation in the extended phase space which is explicitly constructed. The occurrence of higher order structure functions is pointed out. Also at: Centro de Estudios Cientificos de Santiago, Casilla 16443, Santiago 9, Chile.

Some Applications of Linguistic Concepts to the Teaching of Freshman Composition.

ERIC Educational Resources Information Center

Maimon, Elaine P.

The problems which freshmen exhibit in using the written language extend beyond difficulties with mechanics to handicaps in using words to formulate and develop concepts. A linguistic approach to teaching freshman composition involves recognizing every linguistic act as creative and a word as having a history as well as a variety of meanings. In…

A Randomized, Single-Blind, Substitution Study of OROS Methylphenidate (Concerta) in ADHD Adults Receiving Immediate Release Methylphenidate

ERIC Educational Resources Information Center

Spencer, Thomas J.; Mick, Eric; Surman, Craig B. H.; Hammerness, Paul; Doyle, Robert; Aleardi, Megan; Kotarski, Meghan; Williams, Courtney G.; Biederman, Joseph

2011-01-01

Objective: The main aim of this study was to examine the efficacy, tolerability, and compliance of an extended-release formulation of methylphenidate (OROS-MPH) in adults with ADHD receiving immediate-release methylphenidate (IR-MPH). Method: Participants were outpatient adults with ADHD who were stable on IR-MPH-administered TID. Participants…

Self-contained filtered density function

DOE PAGES

Nouri, Arash G.; Nik, Mehdi B.; Givi, Pope; ...

2017-09-18

The filtered density function (FDF) closure is extended to a “self-contained” format to include the subgrid-scale (SGS) statistics of all of the hydro-thermo-chemical variables in turbulent flows. These are the thermodynamic pressure, the specific internal energy, the velocity vector, and the composition field. In this format, the model is comprehensive and facilitates large-eddy simulation (LES) of flows at both low and high compressibility levels. A transport equation is developed for the joint pressure-energy-velocity-composition filtered mass density function (PEVC-FMDF). In this equation, the effect of convection appears in closed form. The coupling of the hydrodynamics and thermochemistry is modeled via amore » set of stochastic differential equation for each of the transport variables. This yields a self-contained SGS closure. We demonstrated how LES is conducted of a turbulent shear flow with transport of a passive scalar. Finally, the consistency of the PEVC-FMDF formulation is established, and its overall predictive capability is appraised via comparison with direct numerical simulation (DNS) data.« less

Asymptotic analysis to the effect of temperature gradient on the propagation of triple flames

NASA Astrophysics Data System (ADS)

Al-Malki, Faisal

2018-05-01

We study asymptotically in this paper the influence of the temperature gradient across the mixing layer on the propagation triple flames formed inside a porous wall channel. The study begins by formulating the problem mathematically using the thermo-diffusive model and then presents a thorough asymptotic analysis of the problem in the limit of large activation energy and thin flames. Analytical formulae for the local burning speed, the flame shape and the propagation speed in terms of the temperature gradient parameter have been derived. It was shown that varying the feed temperatures can significantly enhance the burning of the reactants up to a critical threshold, beyond which no solutions can be obtained. In addition, the study showed that increasing the temperature at the boundaries will modify the usual triple structure of the flame by inverting the upper premixed branch and extending it to the boundary, which may have great implications on the safety of the adopted combustion chambers.

Final Report of the Project "From the finite element method to the virtual element method"

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

Manzini, Gianmarco; Gyrya, Vitaliy

The Finite Element Method (FEM) is a powerful numerical tool that is being used in a large number of engineering applications. The FEM is constructed on triangular/tetrahedral and quadrilateral/hexahedral meshes. Extending the FEM to general polygonal/polyhedral meshes in straightforward way turns out to be extremely difficult and leads to very complex and computationally expensive schemes. The reason for this failure is that the construction of the basis functions on elements with a very general shape is a non-trivial and complex task. In this project we developed a new family of numerical methods, dubbed the Virtual Element Method (VEM) for themore » numerical approximation of partial differential equations (PDE) of elliptic type suitable to polygonal and polyhedral unstructured meshes. We successfully formulated, implemented and tested these methods and studied both theoretically and numerically their stability, robustness and accuracy for diffusion problems, convection-reaction-diffusion problems, the Stokes equations and the biharmonic equations.« less

Efficient and Extensible Quasi-Explicit Modular Nonlinear Multiscale Battery Model: GH-MSMD

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

Kim, Gi-Heon; Smith, Kandler; Lawrence-Simon, Jake

Complex physics and long computation time hinder the adoption of computer aided engineering models in the design of large-format battery cells and systems. A modular, efficient battery simulation model -- the multiscale multidomain (MSMD) model -- was previously introduced to aid the scale-up of Li-ion material and electrode designs to complete cell and pack designs, capturing electrochemical interplay with 3-D electronic current pathways and thermal response. Here, this paper enhances the computational efficiency of the MSMD model using a separation of time-scales principle to decompose model field variables. The decomposition provides a quasi-explicit linkage between the multiple length-scale domains andmore » thus reduces time-consuming nested iteration when solving model equations across multiple domains. In addition to particle-, electrode- and cell-length scales treated in the previous work, the present formulation extends to bus bar- and multi-cell module-length scales. We provide example simulations for several variants of GH electrode-domain models.« less

Efficient and Extensible Quasi-Explicit Modular Nonlinear Multiscale Battery Model: GH-MSMD

DOE PAGES

Kim, Gi-Heon; Smith, Kandler; Lawrence-Simon, Jake; ...

2017-03-24

Complex physics and long computation time hinder the adoption of computer aided engineering models in the design of large-format battery cells and systems. A modular, efficient battery simulation model -- the multiscale multidomain (MSMD) model -- was previously introduced to aid the scale-up of Li-ion material and electrode designs to complete cell and pack designs, capturing electrochemical interplay with 3-D electronic current pathways and thermal response. Here, this paper enhances the computational efficiency of the MSMD model using a separation of time-scales principle to decompose model field variables. The decomposition provides a quasi-explicit linkage between the multiple length-scale domains andmore » thus reduces time-consuming nested iteration when solving model equations across multiple domains. In addition to particle-, electrode- and cell-length scales treated in the previous work, the present formulation extends to bus bar- and multi-cell module-length scales. We provide example simulations for several variants of GH electrode-domain models.« less

Effective friction of granular flows made of non-spherical particles

NASA Astrophysics Data System (ADS)

Somfai, Ellák; Nagy, Dániel B.; Claudin, Philippe; Favier, Adeline; Kálmán, Dávid; Börzsönyi, Tamás

2017-06-01

Understanding the rheology of dense granular matter is a long standing problem and is important both from the fundamental and the applied point of view. As the basic building blocks of granular materials are macroscopic particles, the nature of both the response to deformations and the dissipation is very different from that of molecular materials. In the absence of large gradients, the best approach formulates the constitutive equation as an effective friction: for sheared granular matter the ratio of the off-diagonal and the diagonal elements of the stress tensor depends only on dynamical parameters, in particular the inertial number. In this work we employ numerical simulations to extend this formalism to granular packings made of frictionless elongated particles. We measured how the shape of the particles affects the effective friction, volume fraction and first normal stress difference, and compared it to the spherical particle case. We had to introduce polydispersity in particle size in order to keep the systems of the more elongated particles disordered.

Multi-Agent Patrolling under Uncertainty and Threats.

PubMed

Chen, Shaofei; Wu, Feng; Shen, Lincheng; Chen, Jing; Ramchurn, Sarvapali D

2015-01-01

We investigate a multi-agent patrolling problem where information is distributed alongside threats in environments with uncertainties. Specifically, the information and threat at each location are independently modelled as multi-state Markov chains, whose states are not observed until the location is visited by an agent. While agents will obtain information at a location, they may also suffer damage from the threat at that location. Therefore, the goal of the agents is to gather as much information as possible while mitigating the damage incurred. To address this challenge, we formulate the single-agent patrolling problem as a Partially Observable Markov Decision Process (POMDP) and propose a computationally efficient algorithm to solve this model. Building upon this, to compute patrols for multiple agents, the single-agent algorithm is extended for each agent with the aim of maximising its marginal contribution to the team. We empirically evaluate our algorithm on problems of multi-agent patrolling and show that it outperforms a baseline algorithm up to 44% for 10 agents and by 21% for 15 agents in large domains.

Long-term stable time integration scheme for dynamic analysis of planar geometrically exact Timoshenko beams

NASA Astrophysics Data System (ADS)

Nguyen, Tien Long; Sansour, Carlo; Hjiaj, Mohammed

2017-05-01

In this paper, an energy-momentum method for geometrically exact Timoshenko-type beam is proposed. The classical time integration schemes in dynamics are known to exhibit instability in the non-linear regime. The so-called Timoshenko-type beam with the use of rotational degree of freedom leads to simpler strain relations and simpler expressions of the inertial terms as compared to the well known Bernoulli-type model. The treatment of the Bernoulli-model has been recently addressed by the authors. In this present work, we extend our approach of using the strain rates to define the strain fields to in-plane geometrically exact Timoshenko-type beams. The large rotational degrees of freedom are exactly computed. The well-known enhanced strain method is used to avoid locking phenomena. Conservation of energy, momentum and angular momentum is proved formally and numerically. The excellent performance of the formulation will be demonstrated through a range of examples.

A curvilinear, fully implicit, conservative electromagnetic PIC algorithm in multiple dimensions

DOE PAGES

Chacon, L.; Chen, G.

2016-04-19

Here, we extend a recently proposed fully implicit PIC algorithm for the Vlasov–Darwin model in multiple dimensions (Chen and Chacón (2015) [1]) to curvilinear geometry. As in the Cartesian case, the approach is based on a potential formulation (Φ, A), and overcomes many difficulties of traditional semi-implicit Darwin PIC algorithms. Conservation theorems for local charge and global energy are derived in curvilinear representation, and then enforced discretely by a careful choice of the discretization of field and particle equations. Additionally, the algorithm conserves canonical-momentum in any ignorable direction, and preserves the Coulomb gauge ∇ • A = 0 exactly. Anmore » asymptotically well-posed fluid preconditioner allows efficient use of large cell sizes, which are determined by accuracy considerations, not stability, and can be orders of magnitude larger than required in a standard explicit electromagnetic PIC simulation. We demonstrate the accuracy and efficiency properties of the algorithm with numerical experiments in mapped meshes in 1D-3V and 2D-3V.« less

Self-contained filtered density function

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

Nouri, Arash G.; Nik, Mehdi B.; Givi, Pope

The filtered density function (FDF) closure is extended to a “self-contained” format to include the subgrid-scale (SGS) statistics of all of the hydro-thermo-chemical variables in turbulent flows. These are the thermodynamic pressure, the specific internal energy, the velocity vector, and the composition field. In this format, the model is comprehensive and facilitates large-eddy simulation (LES) of flows at both low and high compressibility levels. A transport equation is developed for the joint pressure-energy-velocity-composition filtered mass density function (PEVC-FMDF). In this equation, the effect of convection appears in closed form. The coupling of the hydrodynamics and thermochemistry is modeled via amore » set of stochastic differential equation for each of the transport variables. This yields a self-contained SGS closure. We demonstrated how LES is conducted of a turbulent shear flow with transport of a passive scalar. Finally, the consistency of the PEVC-FMDF formulation is established, and its overall predictive capability is appraised via comparison with direct numerical simulation (DNS) data.« less

A curvilinear, fully implicit, conservative electromagnetic PIC algorithm in multiple dimensions

NASA Astrophysics Data System (ADS)

Chacón, L.; Chen, G.

2016-07-01

We extend a recently proposed fully implicit PIC algorithm for the Vlasov-Darwin model in multiple dimensions (Chen and Chacón (2015) [1]) to curvilinear geometry. As in the Cartesian case, the approach is based on a potential formulation (ϕ, A), and overcomes many difficulties of traditional semi-implicit Darwin PIC algorithms. Conservation theorems for local charge and global energy are derived in curvilinear representation, and then enforced discretely by a careful choice of the discretization of field and particle equations. Additionally, the algorithm conserves canonical-momentum in any ignorable direction, and preserves the Coulomb gauge ∇ ṡ A = 0 exactly. An asymptotically well-posed fluid preconditioner allows efficient use of large cell sizes, which are determined by accuracy considerations, not stability, and can be orders of magnitude larger than required in a standard explicit electromagnetic PIC simulation. We demonstrate the accuracy and efficiency properties of the algorithm with numerical experiments in mapped meshes in 1D-3V and 2D-3V.

Self-contained filtered density function

NASA Astrophysics Data System (ADS)

Nouri, A. G.; Nik, M. B.; Givi, P.; Livescu, D.; Pope, S. B.

2017-09-01

The filtered density function (FDF) closure is extended to a "self-contained" format to include the subgrid-scale (SGS) statistics of all of the hydro-thermo-chemical variables in turbulent flows. These are the thermodynamic pressure, the specific internal energy, the velocity vector, and the composition field. In this format, the model is comprehensive and facilitates large-eddy simulation (LES) of flows at both low and high compressibility levels. A transport equation is developed for the joint pressure-energy-velocity-composition filtered mass density function (PEVC-FMDF). In this equation, the effect of convection appears in closed form. The coupling of the hydrodynamics and thermochemistry is modeled via a set of stochastic differential equation for each of the transport variables. This yields a self-contained SGS closure. For demonstration, LES is conducted of a turbulent shear flow with transport of a passive scalar. The consistency of the PEVC-FMDF formulation is established, and its overall predictive capability is appraised via comparison with direct numerical simulation (DNS) data.

Mean Flow Augmented Acoustics in Rocket Systems

NASA Technical Reports Server (NTRS)

Fischbach, Sean

2014-01-01

Combustion instability in solid rocket motors and liquid engines has long been a subject of concern. Many rockets display violent fluctuations in pressure, velocity, and temperature originating from the complex interactions between the combustion process and gas dynamics. Recent advances in energy based modeling of combustion instabilities require accurate determination of acoustic frequencies and mode shapes. Of particular interest is the acoustic mean flow interactions within the converging section of a rocket nozzle, where gradients of pressure, density, and velocity become large. The expulsion of unsteady energy through the nozzle of a rocket is identified as the predominate source of acoustic damping for most rocket systems. Recently, an approach to address nozzle damping with mean flow effects was implemented by French [1]. This new approach extends the work originated by Sigman and Zinn [2] by solving the acoustic velocity potential equation (AVPE) formulated by perturbing the Euler equations [3]. The present study aims to implement the French model within the COMSOL Multiphysiscs framework and analyzes one of the author's presented test cases.

A class of high resolution explicit and implicit shock-capturing methods

NASA Technical Reports Server (NTRS)

Yee, H. C.

1989-01-01

An attempt is made to give a unified and generalized formulation of a class of high resolution, explicit and implicit shock capturing methods, and to illustrate their versatility in various steady and unsteady complex shock wave computations. Included is a systematic review of the basic design principle of the various related numerical methods. Special emphasis is on the construction of the basis nonlinear, spatially second and third order schemes for nonlinear scalar hyperbolic conservation laws and the methods of extending these nonlinear scalar schemes to nonlinear systems via the approximate Riemann solvers and the flux vector splitting approaches. Generalization of these methods to efficiently include equilibrium real gases and large systems of nonequilibrium flows are discussed. Some issues concerning the applicability of these methods that were designed for homogeneous hyperbolic conservation laws to problems containing stiff source terms and shock waves are also included. The performance of some of these schemes is illustrated by numerical examples for 1-, 2- and 3-dimensional gas dynamics problems.

A curvilinear, fully implicit, conservative electromagnetic PIC algorithm in multiple dimensions

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

Chacon, L.; Chen, G.

Here, we extend a recently proposed fully implicit PIC algorithm for the Vlasov–Darwin model in multiple dimensions (Chen and Chacón (2015) [1]) to curvilinear geometry. As in the Cartesian case, the approach is based on a potential formulation (Φ, A), and overcomes many difficulties of traditional semi-implicit Darwin PIC algorithms. Conservation theorems for local charge and global energy are derived in curvilinear representation, and then enforced discretely by a careful choice of the discretization of field and particle equations. Additionally, the algorithm conserves canonical-momentum in any ignorable direction, and preserves the Coulomb gauge ∇ • A = 0 exactly. Anmore » asymptotically well-posed fluid preconditioner allows efficient use of large cell sizes, which are determined by accuracy considerations, not stability, and can be orders of magnitude larger than required in a standard explicit electromagnetic PIC simulation. We demonstrate the accuracy and efficiency properties of the algorithm with numerical experiments in mapped meshes in 1D-3V and 2D-3V.« less

Output-feedback control of combined sewer networks through receding horizon control with moving horizon estimation

NASA Astrophysics Data System (ADS)

Joseph-Duran, Bernat; Ocampo-Martinez, Carlos; Cembrano, Gabriela

2015-10-01

An output-feedback control strategy for pollution mitigation in combined sewer networks is presented. The proposed strategy provides means to apply model-based predictive control to large-scale sewer networks, in-spite of the lack of measurements at most of the network sewers. In previous works, the authors presented a hybrid linear control-oriented model for sewer networks together with the formulation of Optimal Control Problems (OCP) and State Estimation Problems (SEP). By iteratively solving these problems, preliminary Receding Horizon Control with Moving Horizon Estimation (RHC/MHE) results, based on flow measurements, were also obtained. In this work, the RHC/MHE algorithm has been extended to take into account both flow and water level measurements and the resulting control loop has been extensively simulated to assess the system performance according different measurement availability scenarios and rain events. All simulations have been carried out using a detailed physically based model of a real case-study network as virtual reality.

Perturbative tests for a large-N reduced model of {N} = {4} super Yang-Mills theory

NASA Astrophysics Data System (ADS)

Ishiki, Goro; Shimasaki, Shinji; Tsuchiya, Asato

2011-11-01

We study a non-perturbative formulation of {N} = {4} super Yang-Mills theory (SYM) on R × S 3 in the planar limit proposed in arXiv:0807.2352. This formulation is based on the large- N reduction, and the theory can be described as a particular large- N limit of the plane wave matrix model (PWMM), which is obtained by dimensionally reducing the original theory over S 3. In this paper, we perform some tests for this proposal. We construct an operator in the PWMM that corresponds to the Wilson loop in SYM in the continuum limit and calculate the vacuum expectation value of the operator for the case of the circular contour. We find that our result indeed agrees with the well-known result first obtained by Erickson, Semenoff and Zarembo. We also compute the beta function at the 1-loop level based on this formulation and see that it is indeed vanishing.

Perturbative tests for a large-N reduced model of mathcal{N} = {4} super Yang-Mills theory

NASA Astrophysics Data System (ADS)

Ishiki, Goro; Shimasaki, Shinji; Tsuchiya, Asato

2012-02-01

We study a non-perturbative formulation of mathcal{N} = {4} super Yang-Mills theory (SYM) on R × S 3 in the planar limit proposed in arXiv:0807.2352. This formulation is based on the large- N reduction, and the theory can be described as a particular large- N limit of the plane wave matrix model (PWMM), which is obtained by dimensionally reducing the original theory over S 3. In this paper, we perform some tests for this proposal. We construct an operator in the PWMM that corresponds to the Wilson loop in SYM in the continuum limit and calculate the vacuum expectation value of the operator for the case of the circular contour. We find that our result indeed agrees with the well-known result first obtained by Erickson, Semenoff and Zarembo. We also compute the beta function at the 1-loop level based on this formulation and see that it is indeed vanishing.

u-w formulation for dynamic problems in large deformation regime solved through an implicit meshfree scheme

NASA Astrophysics Data System (ADS)

Navas, Pedro; Sanavia, Lorenzo; López-Querol, Susana; Yu, Rena C.

2017-12-01

Solving dynamic problems for fluid saturated porous media at large deformation regime is an interesting but complex issue. An implicit time integration scheme is herein developed within the framework of the u-w (solid displacement-relative fluid displacement) formulation for the Biot's equations. In particular, liquid water saturated porous media is considered and the linearization of the linear momentum equations taking into account all the inertia terms for both solid and fluid phases is for the first time presented. The spatial discretization is carried out through a meshfree method, in which the shape functions are based on the principle of local maximum entropy LME. The current methodology is firstly validated with the dynamic consolidation of a soil column and the plastic shear band formulation of a square domain loaded by a rigid footing. The feasibility of this new numerical approach for solving large deformation dynamic problems is finally demonstrated through the application to an embankment problem subjected to an earthquake.

Surface tension and long range corrections of cylindrical interfaces

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

Bourasseau, E.; Malfreyt, P.; Ghoufi, A., E-mail: aziz.ghoufi@univ-rennes1.fr

2015-12-21

The calculation of the surface tension of curved interfaces has been deeply investigated from molecular simulation during this last past decade. Recently, the thermodynamic Test-Area (TA) approach has been extended to the calculation of surface tension of curved interfaces. In the case of the cylindrical vapour-liquid interfaces of water and Lennard-Jones fluids, it was shown that the surface tension was independent of the curvature of the interface. In addition, the surface tension of the cylindrical interface is higher than that of the planar interface. Molecular simulations of cylindrical interfaces have been so far performed (i) by using a shifted potential,more » (ii) by means of large cutoff without periodic boundary conditions, or (iii) by ignoring the long range corrections to the surface tension due to the difficulty to estimate them. Indeed, unlike the planar interfaces there are no available operational expressions to consider the tail corrections to the surface tension of cylindrical interfaces. We propose here to develop the long range corrections of the surface tension for cylindrical interfaces by using the non-exponential TA (TA2) method. We also extend the formulation of the Mecke-Winkelmann corrections initially developed for planar surfaces to cylindrical interfaces. We complete this study by the calculation of the surface tension of cylindrical surfaces of liquid tin and copper using the embedded atom model potentials.« less

Roller compaction of hydrophilic extended release tablets-combined effects of processing variables and drug/matrix former particle size.

PubMed

Heiman, Johanna; Tajarobi, Farhad; Gururajan, Bindhumadhavan; Juppo, Anne; Abrahmsén-Alami, Susanna

2015-04-01

The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found to be related to differences in granule porosity and morphology. Using the large-sized HPMC grade did in some cases result in lower tensile strength tablets but had the advantage to improve the powder flow into the roller compactor. This work also indicates that when the HPMC level lies near the percolation threshold, significant changes can occur in the drug release rate due to changes in other factors (raw material characteristics and processing).

Stability of smectic phases in hard-rod mixtures

NASA Astrophysics Data System (ADS)

Martínez-Ratón, Yuri; Velasco, Enrique; Mederos, Luis

2005-09-01

Using density-functional theory, we have analyzed the phase behavior of binary mixtures of hard rods of different lengths and diameters. Previous studies have shown a strong tendency of smectic phases of these mixtures to segregate and, in some circumstances, to form microsegregated phases. Our focus in the present work is on the formation of columnar phases which some studies, under some approximations, have shown to become thermodynamically stable prior to crystallization. Specifically we focus on the relative stability between smectic and columnar phases, a question not fully addressed in previous work. Our analysis is based on two complementary perspectives: on the one hand, an extended Onsager theory, which includes the full orientational degrees of freedom but with spatial and orientational correlations being treated in an approximate manner; on the other hand, we formulate a Zwanzig approximation of fundamental-measure theory on hard parallelepipeds, whereby orientations are restricted to be only along three mutually orthogonal axes, but correlations are faithfully represented. In the latter case novel, complete phase diagrams containing regions of stability of liquid-crystalline phases are calculated. Our findings indicate that the restricted-orientation approximation enhances the stability of columnar phases so as to preempt smectic order completely while, in the framework of the extended Onsager model, with full orientational degrees of freedom taken into account, columnar phases may preempt a large region of smectic stability in some mixtures, but some smectic order still persists.

Early history of extended irreversible thermodynamics (1953-1983): An exploration beyond local equilibrium and classical transport theory

NASA Astrophysics Data System (ADS)

Lebon, G.; Jou, D.

2015-06-01

This paper gives a historical account of the early years (1953-1983) of extended irreversible thermodynamics (EIT). The salient features of this formalism are to upgrade the thermodynamic fluxes of mass, momentum, energy, and others, to the status of independent variables, and to explore the consistency between generalized transport equations and a generalized version of the second law of thermodynamics. This requires going beyond classical irreversible thermodynamics by redefining entropy and entropy flux. EIT provides deeper foundations, closer relations with microscopic formalisms, a wider spectrum of applications, and a more exciting conceptual appeal to non-equilibrium thermodynamics. We first recall the historical contributions by Maxwell, Cattaneo, and Grad on generalized transport equations. A thermodynamic theory wide enough to cope with such transport equations was independently proposed between 1953 and 1983 by several authors, each emphasizing different kinds of problems. In 1983, the first international meeting on this theory took place in Bellaterra (Barcelona). It provided the opportunity for the various authors to meet together for the first time and to discuss the common points and the specific differences of their previous formulations. From then on, a large amount of applications and theoretical confirmations have emerged. From the historical point of view, the emergence of EIT has been an opportunity to revisit the foundations and to open new avenues in thermodynamics, one of the most classical and well consolidated physical theories.

Tracking trade transactions in water resource systems: A node-arc optimization formulation

NASA Astrophysics Data System (ADS)

Erfani, Tohid; Huskova, Ivana; Harou, Julien J.

2013-05-01

We formulate and apply a multicommodity network flow node-arc optimization model capable of tracking trade transactions in complex water resource systems. The model uses a simple node to node network connectivity matrix and does not require preprocessing of all possible flow paths in the network. We compare the proposed node-arc formulation with an existing arc-path (flow path) formulation and explain the advantages and difficulties of both approaches. We verify the proposed formulation model on a hypothetical water distribution network. Results indicate the arc-path model solves the problem with fewer constraints, but the proposed formulation allows using a simple network connectivity matrix which simplifies modeling large or complex networks. The proposed algorithm allows converting existing node-arc hydroeconomic models that broadly represent water trading to ones that also track individual supplier-receiver relationships (trade transactions).

Anisotropic norm-oriented mesh adaptation for a Poisson problem

NASA Astrophysics Data System (ADS)

Brèthes, Gautier; Dervieux, Alain

2016-10-01

We present a novel formulation for the mesh adaptation of the approximation of a Partial Differential Equation (PDE). The discussion is restricted to a Poisson problem. The proposed norm-oriented formulation extends the goal-oriented formulation since it is equation-based and uses an adjoint. At the same time, the norm-oriented formulation somewhat supersedes the goal-oriented one since it is basically a solution-convergent method. Indeed, goal-oriented methods rely on the reduction of the error in evaluating a chosen scalar output with the consequence that, as mesh size is increased (more degrees of freedom), only this output is proven to tend to its continuous analog while the solution field itself may not converge. A remarkable quality of goal-oriented metric-based adaptation is the mathematical formulation of the mesh adaptation problem under the form of the optimization, in the well-identified set of metrics, of a well-defined functional. In the new proposed formulation, we amplify this advantage. We search, in the same well-identified set of metrics, the minimum of a norm of the approximation error. The norm is prescribed by the user and the method allows addressing the case of multi-objective adaptation like, for example in aerodynamics, adaptating the mesh for drag, lift and moment in one shot. In this work, we consider the basic linear finite-element approximation and restrict our study to L2 norm in order to enjoy second-order convergence. Numerical examples for the Poisson problem are computed.

Measurement of the Retention Time of Different Ophthalmic Formulations with Ultrahigh-Resolution Optical Coherence Tomography.

PubMed

Gagliano, Caterina; Papa, Vincenzo; Amato, Roberta; Malaguarnera, Giulia; Avitabile, Teresio

2018-04-01

Purpose/aim of the study: The purpose of this study was to measure the pre-corneal retention time of two marketed formulations (eye drops and eye gel) of a steroid-antibiotic fixed combination (FC) containing 0.1% dexamethasone and 0.3% netilmicin. Pre-corneal retention time was evaluated in 16 healthy subjects using an ultrahigh-resolution anterior segment spectral domain optical coherence tomography (OCT). All subjects randomly received both formulations of the FC (Netildex, SIFI, Italy). Central tear film thickness (CTFT) was measured before instillation (time 0) and then after 1, 10, 20, 30, 40 50, 60 and 120 min. The pre-corneal retention time was calculated by plotting CTFT as a function of time. Differences between time points and groups were analyzed by Student's t-test. CTFT increased significantly after the instillation of the eye gel formulation (p < 0.001). CTFT reached its maximum value 1 min after instillation and returned to baseline after 60 min. No effect on CTFT was observed after the instillation of eye drops. The difference between the two formulations was statistically significant at time 1 min (p < 0.0001), 10 min (p < 0.001) and 20 min (p < 0.01). The FC formulated as eye gel was retained on the ocular surface longer than the corresponding eye drop solution. Consequently, the use of the eye gel might extend the interval between instillations and decrease the frequency of administration.

MPDATA: Third-order accuracy for variable flows

NASA Astrophysics Data System (ADS)

Waruszewski, Maciej; Kühnlein, Christian; Pawlowska, Hanna; Smolarkiewicz, Piotr K.

2018-04-01

This paper extends the multidimensional positive definite advection transport algorithm (MPDATA) to third-order accuracy for temporally and spatially varying flows. This is accomplished by identifying the leading truncation error of the standard second-order MPDATA, performing the Cauchy-Kowalevski procedure to express it in a spatial form and compensating its discrete representation-much in the same way as the standard MPDATA corrects the first-order accurate upwind scheme. The procedure of deriving the spatial form of the truncation error was automated using a computer algebra system. This enables various options in MPDATA to be included straightforwardly in the third-order scheme, thereby minimising the implementation effort in existing code bases. Following the spirit of MPDATA, the error is compensated using the upwind scheme resulting in a sign-preserving algorithm, and the entire scheme can be formulated using only two upwind passes. Established MPDATA enhancements, such as formulation in generalised curvilinear coordinates, the nonoscillatory option or the infinite-gauge variant, carry over to the fully third-order accurate scheme. A manufactured 3D analytic solution is used to verify the theoretical development and its numerical implementation, whereas global tracer-transport benchmarks demonstrate benefits for chemistry-transport models fundamental to air quality monitoring, forecasting and control. A series of explicitly-inviscid implicit large-eddy simulations of a convective boundary layer and explicitly-viscid simulations of a double shear layer illustrate advantages of the fully third-order-accurate MPDATA for fluid dynamics applications.

An accurate discontinuous Galerkin method for solving point-source Eikonal equation in 2-D heterogeneous anisotropic media

NASA Astrophysics Data System (ADS)

Le Bouteiller, P.; Benjemaa, M.; Métivier, L.; Virieux, J.

2018-03-01

Accurate numerical computation of wave traveltimes in heterogeneous media is of major interest for a large range of applications in seismics, such as phase identification, data windowing, traveltime tomography and seismic imaging. A high level of precision is needed for traveltimes and their derivatives in applications which require quantities such as amplitude or take-off angle. Even more challenging is the anisotropic case, where the general Eikonal equation is a quartic in the derivatives of traveltimes. Despite their efficiency on Cartesian meshes, finite-difference solvers are inappropriate when dealing with unstructured meshes and irregular topographies. Moreover, reaching high orders of accuracy generally requires wide stencils and high additional computational load. To go beyond these limitations, we propose a discontinuous-finite-element-based strategy which has the following advantages: (1) the Hamiltonian formalism is general enough for handling the full anisotropic Eikonal equations; (2) the scheme is suitable for any desired high-order formulation or mixing of orders (p-adaptivity); (3) the solver is explicit whatever Hamiltonian is used (no need to find the roots of the quartic); (4) the use of unstructured meshes provides the flexibility for handling complex boundary geometries such as topographies (h-adaptivity) and radiation boundary conditions for mimicking an infinite medium. The point-source factorization principles are extended to this discontinuous Galerkin formulation. Extensive tests in smooth analytical media demonstrate the high accuracy of the method. Simulations in strongly heterogeneous media illustrate the solver robustness to realistic Earth-sciences-oriented applications.

Image velocimetry for clouds with relaxation labeling based on deformation consistency

NASA Astrophysics Data System (ADS)

Horinouchi, Takeshi; Murakami, Shin-ya; Kouyama, Toru; Ogohara, Kazunori; Yamazaki, Atsushi; Yamada, Manabu; Watanabe, Shigeto

2017-08-01

Correlation-based cloud tracking has been extensively used to measure atmospheric winds, but still difficulty remains. In this study, aiming at developing a cloud tracking system for Akatsuki, an artificial satellite orbiting Venus, a formulation is developed for improving the relaxation labeling technique to select appropriate peaks of cross-correlation surfaces which tend to have multiple peaks. The formulation makes an explicit use of consistency inherent in the type of cross-correlation method where template sub-images are slid without deformation; if the resultant motion vectors indicate a too-large deformation, it is contradictory to the assumption of the method. The deformation consistency is exploited further to develop two post processes; one clusters the motion vectors into groups within each of which the consistency is perfect, and the other extends the groups using the original candidate lists. These processes are useful to eliminate erroneous vectors, distinguish motion vectors at different altitudes, and detect phase velocities of waves in fluids such as atmospheric gravity waves. As a basis of the relaxation labeling and the post processes as well as uncertainty estimation, the necessity to find isolated (well-separated) peaks of cross-correlation surfaces is argued, and an algorithm to realize it is presented. All the methods are implemented, and their effectiveness is demonstrated with initial images obtained by the ultraviolet imager onboard Akatsuki. Since the deformation consistency regards the logical consistency inherent in template matching methods, it should have broad application beyond cloud tracking.

Implementation of Free-Formulation-Based Flat Shell Elements into NASA Comet Code and Development of Nonlinear Shallow Shell Element

NASA Technical Reports Server (NTRS)

Barut, A.; Madenci, Erdogan; Tessler, A.

1997-01-01

This study presents a transient nonlinear finite element analysis within the realm of a multi-body dynamics formulation for determining the dynamic response of a moderately thick laminated shell undergoing a rapid and large rotational motion and nonlinear elastic deformations. Nonlinear strain measure and rotation, as well as 'the transverse shear deformation, are explicitly included in the formulation in order to capture the proper motion-induced stiffness of the laminate. The equations of motion are derived from the virtual work principle. The analysis utilizes a shear deformable shallow shell element along with the co-rotational form of the updated Lagrangian formulation. The shallow shell element formulation is based on the Reissner-Mindlin and Marguerre theory.

On the correct representation of bending and axial deformation in the absolute nodal coordinate formulation with an elastic line approach

NASA Astrophysics Data System (ADS)

Gerstmayr, Johannes; Irschik, Hans

2008-12-01

In finite element methods that are based on position and slope coordinates, a representation of axial and bending deformation by means of an elastic line approach has become popular. Such beam and plate formulations based on the so-called absolute nodal coordinate formulation have not yet been verified sufficiently enough with respect to analytical results or classical nonlinear rod theories. Examining the existing planar absolute nodal coordinate element, which uses a curvature proportional bending strain expression, it turns out that the deformation does not fully agree with the solution of the geometrically exact theory and, even more serious, the normal force is incorrect. A correction based on the classical ideas of the extensible elastica and geometrically exact theories is applied and a consistent strain energy and bending moment relations are derived. The strain energy of the solid finite element formulation of the absolute nodal coordinate beam is based on the St. Venant-Kirchhoff material: therefore, the strain energy is derived for the latter case and compared to classical nonlinear rod theories. The error in the original absolute nodal coordinate formulation is documented by numerical examples. The numerical example of a large deformation cantilever beam shows that the normal force is incorrect when using the previous approach, while a perfect agreement between the absolute nodal coordinate formulation and the extensible elastica can be gained when applying the proposed modifications. The numerical examples show a very good agreement of reference analytical and numerical solutions with the solutions of the proposed beam formulation for the case of large deformation pre-curved static and dynamic problems, including buckling and eigenvalue analysis. The resulting beam formulation does not employ rotational degrees of freedom and therefore has advantages compared to classical beam elements regarding energy-momentum conservation.

A nonlinear generalized continuum approach for electro-elasticity including scale effects

NASA Astrophysics Data System (ADS)

Skatulla, S.; Arockiarajan, A.; Sansour, C.

2009-01-01

Materials characterized by an electro-mechanically coupled behaviour fall into the category of so-called smart materials. In particular, electro-active polymers (EAP) recently attracted much interest, because, upon electrical loading, EAP exhibit a large amount of deformation while sustaining large forces. This property can be utilized for actuators in electro-mechanical systems, artificial muscles and so forth. When it comes to smaller structures, it is a well-known fact that the mechanical response deviates from the prediction of classical mechanics theory. These scale effects are due to the fact that the size of the microscopic material constituents of such structures cannot be considered to be negligible small anymore compared to the structure's overall dimensions. In this context so-called generalized continuum formulations have been proven to account for the micro-structural influence to the macroscopic material response. Here, we want to adopt a strain gradient approach based on a generalized continuum framework [Sansour, C., 1998. A unified concept of elastic-viscoplastic Cosserat and micromorphic continua. J. Phys. IV Proc. 8, 341-348; Sansour, C., Skatulla, S., 2007. A higher gradient formulation and meshfree-based computation for elastic rock. Geomech. Geoeng. 2, 3-15] and extend it to also encompass the electro-mechanically coupled behaviour of EAP. The approach introduces new strain and stress measures which lead to the formulation of a corresponding generalized variational principle. The theory is completed by Dirichlet boundary conditions for the displacement field and its derivatives normal to the boundary as well as the electric potential. The basic idea behind this generalized continuum theory is the consideration of a micro- and a macro-space which together span the generalized space. As all quantities are defined in this generalized space, also the constitutive law, which is in this work conventional electro-mechanically coupled nonlinear hyperelasticity, is embedded in the generalized continuum. In this way material information of the micro-space, which are here only the geometrical specifications of the micro-continuum, can naturally enter the constitutive law. Several applications with moving least square-based approximations (MLS) demonstrate the potential of the proposed method. This particular meshfree method is chosen, as it has been proven to be highly flexible with regard to continuity and consistency required by this generalized approach.

Branes in Extended Spacetime: Brane Worldvolume Theory Based on Duality Symmetry.

PubMed

Sakatani, Yuho; Uehara, Shozo

2016-11-04

We propose a novel approach to the brane worldvolume theory based on the geometry of extended field theories: double field theory and exceptional field theory. We demonstrate the effectiveness of this approach by showing that one can reproduce the conventional bosonic string and membrane actions, and the M5-brane action in the weak-field approximation. At a glance, the proposed 5-brane action without approximation looks different from the known M5-brane actions, but it is consistent with the known nonlinear self-duality relation, and it may provide a new formulation of a single M5-brane action. Actions for exotic branes are also discussed.

Generalized probabilistic scale space for image restoration.

PubMed

Wong, Alexander; Mishra, Akshaya K

2010-10-01

A novel generalized sampling-based probabilistic scale space theory is proposed for image restoration. We explore extending the definition of scale space to better account for both noise and observation models, which is important for producing accurately restored images. A new class of scale-space realizations based on sampling and probability theory is introduced to realize this extended definition in the context of image restoration. Experimental results using 2-D images show that generalized sampling-based probabilistic scale-space theory can be used to produce more accurate restored images when compared with state-of-the-art scale-space formulations, particularly under situations characterized by low signal-to-noise ratios and image degradation.

Extending high-order flux operators on spherical icosahedral grids and their application in a Shallow Water Model for transporting the Potential Vorticity

NASA Astrophysics Data System (ADS)

Zhang, Y.

2017-12-01

The unstructured formulation of the third/fourth-order flux operators used by the Advanced Research WRF is extended twofold on spherical icosahedral grids. First, the fifth- and sixth-order flux operators of WRF are further extended, and the nominally second- to sixth-order operators are then compared based on the solid body rotation and deformational flow tests. Results show that increasing the nominal order generally leads to smaller absolute errors. Overall, the fifth-order scheme generates the smallest errors in limited and unlimited tests, although it does not enhance the convergence rate. The fifth-order scheme also exhibits smaller sensitivity to the damping coefficient than the third-order scheme. Overall, the even-order schemes have higher limiter sensitivity than the odd-order schemes. Second, a triangular version of these high-order operators is repurposed for transporting the potential vorticity in a space-time-split shallow water framework. Results show that a class of nominally third-order upwind-biased operators generates better results than second- and fourth-order counterparts. The increase of the potential enstrophy over time is suppressed owing to the damping effect. The grid-scale noise in the vorticity is largely alleviated, and the total energy remains conserved. Moreover, models using high-order operators show smaller numerical errors in the vorticity field because of a more accurate representation of the nonlinear Coriolis term. This improvement is especially evident in the Rossby-Haurwitz wave test, in which the fluid is highly rotating. Overall, flux operators with higher damping coefficients, which essentially behaves like the Anticipated Potential Vorticity Method, present optimal results.

α versus non-α cluster decays of the excited compound nucleus *124Ce using various formulations of the nuclear proximity potential

NASA Astrophysics Data System (ADS)

Kaur, Arshdeep; Chopra, Sahila; Gupta, Raj K.

2015-06-01

The earlier study of *124Ce formed in the 32S+92Mo reaction at an above barrier beam energy of 150 MeV, using the pocket formula of Blocki et al. for the nuclear proximity potential in the dynamical cluster-decay model (DCM), is extended to the use of other nuclear interaction potentials derived from the Skyrme energy density functional (SEDF) based on the semiclassical extended Thomas Fermi (ETF) approach under the frozen density approximation. The Skyrme forces used are the old SII, SIII, SIV, SKa, SkM, and SLy4 and new GSkI and KDE0(v1), given for both normal and isospin-rich nuclei. It is found that the α -nucleus structure, over the non-α nucleus structure, is preferred for only two Skyrme forces, the SIII and KDE0(v1). An extended intermediate mass fragments (IMFs) window, along with the new decay region of heavy mass fragments (HMFs) and the near-symmetric and symmetric fission fragments which, on adding the complementary heavy fragments, corresponds to (A /2 )±12 mass region of the fusion-fission (ff) process, are predicted by considering cross sections of orders observed in the experiment under study. For the predicted (total) fusion cross section, the survival probability Psurv of the compound nucleus (CN) against fission is shown to be very small because of the very large predicted ff component. On the other hand, the CN formation probability PCN is found to be nearly equal to 1, and hence the decay under study is a pure CN decay for all the nuclear potentials considered, since the estimated noncompound nucleus (nCN) content is almost negligible. We have also applied the extended-Wong model of Gupta and collaborators, and find that the ℓmax values and total fusion cross sections are of the same order as for the DCM. Thus, the extended-Wong model, which describes only the total fusion cross section in terms of the barrier characteristics of the entrance channel nuclei, could be useful for initial experimental studies to be fully treated using the DCM for all the observed decay products.

Nystatin and lidocaine pastilles for the local treatment of oral mucositis.

PubMed

Silva, Filipa Cosme; Marto, Joana M; Salgado, Ana; Machado, Paula; Silva, Alexandra N; Almeida, António J

2017-03-01

Oral mucositis (OM) is a common adverse reaction to radiotherapy and chemotherapy in oncology. Its treatment requires oral formulations that enhance therapy compliance, improve administration and ensure drug effectiveness. Solid dosage forms that act by slow dissolution, such as pastilles, are an effective alternative to mouthwashes, for their versatility, ease of administration and extended residence time in the oral cavity. The present work describes the development and stability studies of an innovative formulation of nystatin and lidocaine pastilles for the treatment of oral mucositis. Full pharmaceutical quality testing was carried out, including disintegration and dissolution testing, texture profile analysis, grittiness and an antifungal activity testing. A soft pastille formulation containing 0.25% lidocaine and 78,000 IU nystatin was obtained, presenting suitable pharmaceutical characteristics, as a disintegration time of 17 ± 2 min, dissolution rate and microbiological and physicochemical for 30 days when stored at 2-8 °C under light protection. Palatability was also evaluated, being well accepted by a panel of 38 healthy volunteers. This formulation allows an accurate drug dosing by the prescriber, while enabling the patients to control the retention time of the drugs in the oral cavity and consequently manage their pain treatment.

Biochemical stabilization of glucagon at alkaline pH.

PubMed

Caputo, Nicholas; Jackson, Melanie A; Castle, Jessica R; El Youssef, Joseph; Bakhtiani, Parkash A; Bergstrom, Colin P; Carroll, Julie M; Breen, Matthew E; Leonard, Gerald L; David, Larry L; Roberts, Charles T; Ward, W Kenneth

2014-11-01

For patients with type 1 diabetes mellitus, a bihormonal artificial endocrine pancreas system utilizing glucagon and insulin has been found to stabilize glycemic control. However, commercially available formulations of glucagon cannot currently be used in such systems because of physical instability characterized by aggregation and chemical degradation. Storing glucagon at pH 10 blocks protein aggregation but results in chemical degradation. Reductions in pH minimize chemical degradation, but even small reductions increase protein aggregation. We hypothesized that common pharmaceutical excipients accompanied by a new excipient would inhibit glucagon aggregation at an alkaline pH. As measured by tryptophan intrinsic fluorescence shift and optical density at 630 nm, protein aggregation was indeed minimized when glucagon was formulated with curcumin and albumin. This formulation also reduced chemical degradation, measured by liquid chromatography with mass spectrometry. Biological activity was retained after aging for 7 days in an in vitro cell-based bioassay and also in Yorkshire swine. Based on these findings, a formulation of glucagon stabilized with curcumin, polysorbate-80, l-methionine, and albumin at alkaline pH in glycine buffer may be suitable for extended use in a portable pump in the setting of a bihormonal artificial endocrine pancreas.

Biochemical Stabilization of Glucagon at Alkaline pH

PubMed Central

Jackson, Melanie A.; Castle, Jessica R.; El Youssef, Joseph; Bakhtiani, Parkash A.; Bergstrom, Colin P.; Carroll, Julie M.; Breen, Matthew E.; Leonard, Gerald L.; David, Larry L.; Roberts, Charles T.; Ward, W. Kenneth

2014-01-01

Abstract Background: For patients with type 1 diabetes mellitus, a bihormonal artificial endocrine pancreas system utilizing glucagon and insulin has been found to stabilize glycemic control. However, commercially available formulations of glucagon cannot currently be used in such systems because of physical instability characterized by aggregation and chemical degradation. Storing glucagon at pH 10 blocks protein aggregation but results in chemical degradation. Reductions in pH minimize chemical degradation, but even small reductions increase protein aggregation. We hypothesized that common pharmaceutical excipients accompanied by a new excipient would inhibit glucagon aggregation at an alkaline pH. Methods and Results: As measured by tryptophan intrinsic fluorescence shift and optical density at 630 nm, protein aggregation was indeed minimized when glucagon was formulated with curcumin and albumin. This formulation also reduced chemical degradation, measured by liquid chromatography with mass spectrometry. Biological activity was retained after aging for 7 days in an in vitro cell-based bioassay and also in Yorkshire swine. Conclusions: Based on these findings, a formulation of glucagon stabilized with curcumin, polysorbate-80, l-methionine, and albumin at alkaline pH in glycine buffer may be suitable for extended use in a portable pump in the setting of a bihormonal artificial endocrine pancreas. PMID:24968220

A novel thermoresponsive hydrogel based on chitosan.

PubMed

Schuetz, Yannic B; Gurny, Robert; Jordan, Olivier

2008-01-01

Injectable thermosetting chitosan hydrogels are attractive systems for drug delivery and tissue engineering that combine biodegradability, biocompatibility and the ability to form in situ gel-like implants. Thermally-induced gelation relies advantageously on biopolymer secondary interactions, avoiding potentially toxic polymerization reactions that may occur with in situ polymerizing formulations. In view of a biomedical use, such formulations have to be sterilizable and storable on extended periods without losing their thermosetting properties. These two key features have been studied in the present paper. Chitosans from two different sources were added with several phosphate-free polyols or polyoses as gelling agents. Despite a reduction in chitosan molecular weight following autoclaving, the hydrogels prepared with autoclaved chitosan showed the desired thermosetting properties. Hence, chitosan steam sterilization combined with aseptic preparation of the hydrogel allows a sterile formulation to be obtained. Whereas thermosetting hydrogels were shown to be unstable when refrigerated, freezing was shown to be conceivable as a storage method. When trehalose or mannitol was used as stabilizing agent, the formulation reconstituted from a lyophilizate displayed thermosetting properties and was still injectable, paving the way to the development of a clinically utilizable, novel chitosan thermosetting hydrogel.

Evaluation of a water-soluble bioadhesive patch for photodynamic therapy of vulval lesions.

PubMed

McCarron, Paul A; Donnelly, Ryan F; Zawislak, Agnieszka; Woolfson, A David; Price, John H; McClelland, Raymond

2005-04-11

An innovative bioadhesive patch intended primarily as a vulval drug delivery system and, specifically, as a means to deliver photosensitisers, or their prodrugs, for photodynamic purposes is described. The patch was formulated with a copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA) as a bioadhesive matrix and poly(vinyl chloride) as a drug-impervious backing layer. Adhesive strength to neonate porcine skin, as a model substrate, was evaluated using peel and tensile testing measurements. Acceptabilities of non-drug loaded patches were appraised using human volunteers and visual-analogue scoring devices. An optimal formulation, with water uptake and peel strengths appropriate for vulval drug delivery, was cast from a 20% (w/w) PMVE/MA solution and adhered with a strength of approximately 1.7 Ncm(-2). Patient evaluation demonstrated comfort and firm attachment for up to 4h in mobile patients. Aminolevulinic acid, a commonly used photosensitiser, was formulated into the candidate formulation and applied to vulval intraepithelial neoplastic lesions. Fluorescence under ultraviolet illumination revealed protoporphyrin synthesis. The patch achieves the extended application times obligatory in topical photodynamic therapy of vulval lesions, thereby contributing to potential methods for the eradication of neoplastic lesions in the lower female reproductive tract.

Modeling of intragranular misorientation and grain fragmentation in polycrystalline materials using the viscoplastic self-consistent formulation

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

Zecevic, Miroslav; Lebensohn, Ricardo A.; McCabe, Rodney J.

In this paper, the recently established methodology to use known algorithmic expressions of the second moments of the stress field in the grains of a polycrystalline aggregate for calculating average fluctuations of lattice rotation rates and the associated average intragranular misorientation distributions using the mean-field viscoplastic self-consistent (VPSC) formulation is extended to solve the coupled problem of considering the effect of intragranular misorientations on stress and rotation rate fluctuations. In turn, these coupled expressions are used to formulate and implement a grain fragmentation (GF) model in VPSC. Case studies, including tension and plane-strain compression of face-centered cubic polycrystals are usedmore » to illustrate the capabilities of the new model. GF-VPSC predictions of intragranular misorientation distributions and texture evolution are compared with experiments and full-field numerical simulations, showing good agreement. In particular, the inclusion of misorientation spreads reduced the intensity of the deformed texture and thus improved the texture predictions. Finally and moreover, considering that intragranular misorientations act as driving forces for recrystallization, the new GF-VPSC formulation is shown to enable modeling of microstructure evolution during deformation and recrystallization, in a computationally efficient manner.« less

Projector Augmented-Wave formulation of response to strain and electric field perturbation within the density-functional perturbation theory

NASA Astrophysics Data System (ADS)

Martin, Alexandre; Torrent, Marc; Caracas, Razvan

2015-03-01

A formulation of the response of a system to strain and electric field perturbations in the pseudopotential-based density functional perturbation theory (DFPT) has been proposed by D.R Hamman and co-workers. It uses an elegant formalism based on the expression of DFT total energy in reduced coordinates, the key quantity being the metric tensor and its first and second derivatives. We propose to extend this formulation to the Projector Augmented-Wave approach (PAW). In this context, we express the full elastic tensor including the clamped-atom tensor, the atomic-relaxation contributions (internal stresses) and the response to electric field change (piezoelectric tensor and effective charges). With this we are able to compute the elastic tensor for all materials (metals and insulators) within a fully analytical formulation. The comparison with finite differences calculations on simple systems shows an excellent agreement. This formalism has been implemented in the plane-wave based DFT ABINIT code. We apply it to the computation of elastic properties and seismic-wave velocities of iron with impurity elements. By analogy with the materials contained in meteorites, tested impurities are light elements (H, O, C, S, Si).

Supramolecular PEGylation of biopharmaceuticals

PubMed Central

Webber, Matthew J.; Vinciguerra, Brittany; Cortinas, Abel B.; Thapa, Lavanya S.; Jhunjhunwala, Siddharth; Isaacs, Lyle; Langer, Robert; Anderson, Daniel G.

2016-01-01

The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host–guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbit[7]uril (CB[7])–PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB[7] and an N-terminal aromatic residue on one specific protein drug, insulin, further results in altering of its pharmacological properties in vivo by extending activity in a manner dependent on molecular weight of the attached PEG chain. Supramolecular modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other molecules or polymers, for applications in formulation or therapy. PMID:27911829

Testing of viscous anti-HIV microbicides using Lactobacillus

PubMed Central

Moncla, B.J.; Pryke, K.; Rohan, L. C.; Yang, H.

2012-01-01

The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30 min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To demonstrate the toxicity of formulated products a new assay was developed for use with viscous and non-viscous samples that we have termed the Lactobacillus toxicity test. We found that the vortex mixing of vaginal Lactobacillus species can lead to reductions in bacterial viability. Lactobacillus can survive brief, about 2 sec, but viability declines with increased vortex mixing. The addition of heat inactivated serum or bovine serum albumin, but not glycerol, prevented the decrease in bacterial viability. Bacillus atrophaeus spores also demonstrated loss of viability upon extended mixing. We observed that many of the excipients used in film formulation and the films themselves also afford protection from the killing during vortex mixing. This method is of relevance for toxicity for cidal activities of viscous products. PMID:22226641

Modeling of intragranular misorientation and grain fragmentation in polycrystalline materials using the viscoplastic self-consistent formulation

DOE PAGES

Zecevic, Miroslav; Lebensohn, Ricardo A.; McCabe, Rodney J.; ...

2018-06-15

In this paper, the recently established methodology to use known algorithmic expressions of the second moments of the stress field in the grains of a polycrystalline aggregate for calculating average fluctuations of lattice rotation rates and the associated average intragranular misorientation distributions using the mean-field viscoplastic self-consistent (VPSC) formulation is extended to solve the coupled problem of considering the effect of intragranular misorientations on stress and rotation rate fluctuations. In turn, these coupled expressions are used to formulate and implement a grain fragmentation (GF) model in VPSC. Case studies, including tension and plane-strain compression of face-centered cubic polycrystals are usedmore » to illustrate the capabilities of the new model. GF-VPSC predictions of intragranular misorientation distributions and texture evolution are compared with experiments and full-field numerical simulations, showing good agreement. In particular, the inclusion of misorientation spreads reduced the intensity of the deformed texture and thus improved the texture predictions. Finally and moreover, considering that intragranular misorientations act as driving forces for recrystallization, the new GF-VPSC formulation is shown to enable modeling of microstructure evolution during deformation and recrystallization, in a computationally efficient manner.« less

A coupled-mode model for the hydroelastic analysis of large floating bodies over variable bathymetry regions

NASA Astrophysics Data System (ADS)

Belibassakis, K. A.; Athanassoulis, G. A.

2005-05-01

The consistent coupled-mode theory (Athanassoulis & Belibassakis, J. Fluid Mech. vol. 389, 1999, p. 275) is extended and applied to the hydroelastic analysis of large floating bodies of shallow draught or ice sheets of small and uniform thickness, lying over variable bathymetry regions. A parallel-contour bathymetry is assumed, characterized by a continuous depth function of the form h( {x,y}) {=} h( x ), attaining constant, but possibly different, values in the semi-infinite regions x {<} a and x {>} b. We consider the scattering problem of harmonic, obliquely incident, surface waves, under the combined effects of variable bathymetry and a floating elastic plate, extending from x {=} a to x {=} b and {-} infty {<} y{<}infty . Under the assumption of small-amplitude incident waves and small plate deflections, the hydroelastic problem is formulated within the context of linearized water-wave and thin-elastic-plate theory. The problem is reformulated as a transition problem in a bounded domain, for which an equivalent, Luke-type (unconstrained), variational principle is given. In order to consistently treat the wave field beneath the elastic floating plate, down to the sloping bottom boundary, a complete, local, hydroelastic-mode series expansion of the wave field is used, enhanced by an appropriate sloping-bottom mode. The latter enables the consistent satisfaction of the Neumann bottom-boundary condition on a general topography. By introducing this expansion into the variational principle, an equivalent coupled-mode system of horizontal equations in the plate region (a {≤} x {≤} b) is derived. Boundary conditions are also provided by the variational principle, ensuring the complete matching of the wave field at the vertical interfaces (x{=}a and x{=}b), and the requirements that the edges of the plate are free of moment and shear force. Numerical results concerning floating structures lying over flat, shoaling and corrugated seabeds are presented and compared, and the effects of wave direction, bottom slope and bottom corrugations on the hydroelastic response are presented and discussed. The present method can be easily extended to the fully three-dimensional hydroelastic problem, including bodies or structures characterized by variable thickness (draught), flexural rigidity and mass distributions.

Numerical solutions for heat flow in adhesive lap joints

NASA Technical Reports Server (NTRS)

Howell, P. A.; Winfree, William P.

1992-01-01

The present formulation for the modeling of heat transfer in thin, adhesively bonded lap joints precludes difficulties associated with large aspect ratio grids required by standard FEM formulations. This quasi-static formulation also reduces the problem dimensionality (by one), thereby minimizing computational requirements. The solutions obtained are found to be in good agreement with both analytical solutions and solutions from standard FEM programs. The approach is noted to yield a more accurate representation of heat-flux changes between layers due to a disbond.

An extended micromechanics method for probing interphase properties in polymer nanocomposites [An extended micromechanics method for overlapping geometries with application to polymer nanocomposites

DOE PAGES

Liu, Zeliang; Moore, John A.; Liu, Wing Kam

2016-05-03

Inclusions comprised on filler particles and interphase regions commonly form complex morphologies in polymer nanocomposites. Addressing these morphologies as systems of overlapping simple shapes allows for the study of dilute particles, clustered particles, and interacting interphases all in one general modeling framework. To account for the material properties in these overlapping geometries, weighted-mean and additive overlapping conditions are introduced and the corresponding inclusion-wise integral equations are formulated. An extended micromechanics method based on these overlapping conditions for linear elastic and viscoelastic heterogeneous material is then developed. An important feature of the proposed approach is that the effect of both themore » geometric overlapping (clustered particles) and physical overlapping (interacting interphases) on the effective properties can be distinguished. Lastly, we apply the extended micromechanics method to a viscoelastic polymer nanocomposite with interphase regions, and estimate the properties and thickness of the interphase region based on experimental data for carbon-black filled styrene butadiene rubbers.« less

An extended micromechanics method for probing interphase properties in polymer nanocomposites [An extended micromechanics method for overlapping geometries with application to polymer nanocomposites

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

Liu, Zeliang; Moore, John A.; Liu, Wing Kam

Inclusions comprised on filler particles and interphase regions commonly form complex morphologies in polymer nanocomposites. Addressing these morphologies as systems of overlapping simple shapes allows for the study of dilute particles, clustered particles, and interacting interphases all in one general modeling framework. To account for the material properties in these overlapping geometries, weighted-mean and additive overlapping conditions are introduced and the corresponding inclusion-wise integral equations are formulated. An extended micromechanics method based on these overlapping conditions for linear elastic and viscoelastic heterogeneous material is then developed. An important feature of the proposed approach is that the effect of both themore » geometric overlapping (clustered particles) and physical overlapping (interacting interphases) on the effective properties can be distinguished. Lastly, we apply the extended micromechanics method to a viscoelastic polymer nanocomposite with interphase regions, and estimate the properties and thickness of the interphase region based on experimental data for carbon-black filled styrene butadiene rubbers.« less

Developing dissolution testing methodologies for extended-release oral dosage forms with supersaturating properties. Case example: Solid dispersion matrix of indomethacin.

PubMed

Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Mimura, Hisahi; Ozaki, Yukihiro; Reppas, Christos; Kitamura, Satoshi

2015-07-25

The objective of this study was to develop an in vitro dissolution test method with discrimination ability for an extended-release solid dispersion matrix of a lipophilic drug using the United States Pharmacopeia (USP) Apparatus 4, flow-through cell apparatus. In the open-loop configuration, the sink condition was maintained by manipulating the flow rate of the dissolution medium. To evaluate the testing conditions, the drug release mechanism from an extended-release solid dispersion matrix containing hydrophobic and hydrophilic polymers was investigated. As the hydroxypropyl methylcellulose (HPMC) maintained concentrations of indomethacin higher than the solubility in a dissolution medium, the release of HPMC into the dissolution medium was also quantified using size-exclusion chromatography. We concluded that the USP Apparatus 4 is suitable for application to an in vitro dissolution method for orally administered extended-release solid dispersion matrix formulations containing poorly water-soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation of cosmic-ray solar daily variation and its seasonal variation, produced from generalized stationary anisotropy of solar origin

NASA Technical Reports Server (NTRS)

Tatsuoka, R.; Nagashima, K.

1985-01-01

In previous papers, a formulation was presented of cosmic ray daily variations produced from solar anisotropies stationary through a year, and also of their annual (or seasonal) modulation caused by the annual variation of the rotation axis of the Earth relative to that of the Sun. These anisotropies are symmetric for an arbitrary rotation around an axis. From observations of the tri-diurnal variation, it has been suggested that solar anisotropies also contain some axis-asymmetric term of the third order with respect to the IMF-axis. This suggestion has recently found support in a theoretical study by Munakata and Nagashima. According to their results, the terms of axis-asymmetry with respect to IMF-axis appear also in the 2nd order anisotropy, together with some different kinds of axis-symmetric terms. The contribution of these anisotropies to the daily variation is different from that of those discussed previously. The above mentioned formulation is extended to a case of a generalized anisotropy.

Thermophoretic force and velocity of nanoparticles in the free molecule regime.

PubMed

Li, Zhigang; Wang, Hai

2004-08-01

We extend our previous gas-kinetic theory analysis of drag force in a uniform temperature field [Li and Wang, Phys. Rev. E. 68, 061206 (2003); 68, 061207 (2003)] to particle transport in fluids with nonuniform temperature. Formulations for drag and thermophoretic forces are proposed for nanoparticle transport in low-density gases. We specifically consider the influence of nonrigid body collision due to van der Waals or other forces between the particle and gas molecules and find that these forces play a notable role for particles a few nanometers in size. It is shown that the present formulations can be easily reduced to the classical result of Waldmann [Z. Naturforsch. A 14a, 589 (1959)] by assuming rigid body collision. From the force formulations we also obtain the equation governing the thermophoretic velocity. This velocity is found to be highly sensitive to the potential energy of interactions between gas molecules and particle, and as such Waldmann's thermophoretic velocity is not expected to be accurate for nanosized particles.

Nonlinear elasticity in rocks: A comprehensive three-dimensional description

DOE PAGES

Lott, Martin; Remillieux, Marcel; Garnier, Vincent; ...

2017-07-17

Here we study theoretically and experimentally the mechanisms of nonlinear and nonequilibrium dynamics in geomaterials through dynamic acoustoelasticity testing. In the proposed theoretical formulation, the classical theory of nonlinear elasticity is extended to include the effects of conditioning. This formulation is adapted to the context of dynamic acoustoelasticity testing in which a low-frequency “pump” wave induces a strain field in the sample and modulates the propagation of a high-frequency “probe” wave. Experiments are conducted to validate the formulation in a long thin bar of Berea sandstone. Several configurations of the pump and probe are examined: the pump successively consists ofmore » the first longitudinal and first torsional mode of vibration of the sample while the probe is successively based on (pressure) $P$ and (shear) $S$ waves. The theoretical predictions reproduce many features of the elastic response observed experimentally, in particular, the coupling between nonlinear and nonequilibrium dynamics and the three-dimensional effects resulting from the tensorial nature of elasticity.« less

A new numerical formulation of gas leakage and spread into a residential space in terms of hazard analysis.

PubMed

Nagaosa, Ryuichi S

2014-04-30

This study proposes a new numerical formulation of the spread of a flammable gas leakage. A new numerical approach has been applied to establish fundamental data for a hazard assessment of flammable gas spread in an enclosed residential space. The approach employs an extended version of a two-compartment concept, and determines the leakage concentration of gas using a mass-balance based formulation. The study also introduces a computational fluid dynamics (CFD) technique for calculating three-dimensional details of the gas spread by resolving all the essential scales of fluid motions without a turbulent model. The present numerical technique promises numerical solutions with fewer uncertainties produced by the model equations while maintaining high accuracy. The study examines the effect of gas density on the concentration profiles of flammable gas spread. It also discusses the effect of gas leakage rate on gas concentration profiles. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Efficient Reformulation of HOTFGM: Heat Conduction with Variable Thermal Conductivity

NASA Technical Reports Server (NTRS)

Zhong, Yi; Pindera, Marek-Jerzy; Arnold, Steven M. (Technical Monitor)

2002-01-01

Functionally graded materials (FGMs) have become one of the major research topics in the mechanics of materials community during the past fifteen years. FGMs are heterogeneous materials, characterized by spatially variable microstructure, and thus spatially variable macroscopic properties, introduced to enhance material or structural performance. The spatially variable material properties make FGMs challenging to analyze. The review of the various techniques employed to analyze the thermodynamical response of FGMs reveals two distinct and fundamentally different computational strategies, called uncoupled macromechanical and coupled micromechanical approaches by some investigators. The uncoupled macromechanical approaches ignore the effect of microstructural gradation by employing specific spatial variations of material properties, which are either assumed or obtained by local homogenization, thereby resulting in erroneous results under certain circumstances. In contrast, the coupled approaches explicitly account for the micro-macrostructural interaction, albeit at a significantly higher computational cost. The higher-order theory for functionally graded materials (HOTFGM) developed by Aboudi et al. is representative of the coupled approach. However, despite its demonstrated utility in applications where micro-macrostructural coupling effects are important, the theory's full potential is yet to be realized because the original formulation of HOTFGM is computationally intensive. This, in turn, limits the size of problems that can be solved due to the large number of equations required to mimic realistic material microstructures. Therefore, a basis for an efficient reformulation of HOTFGM, referred to as user-friendly formulation, is developed herein, and subsequently employed in the construction of the efficient reformulation using the local/global conductivity matrix approach. In order to extend HOTFGM's range of applicability, spatially variable thermal conductivity capability at the local level is incorporated into the efficient reformulation. Analytical solutions to validate both the user-friendly and efficient reformulations am also developed. Volume discretization sensitivity and validation studies, as well as a practical application of the developed efficient reformulation are subsequently carried out. The presented results illustrate the accuracy and implementability of both the user-friendly formulation and the efficient reformulation of HOTFGM.

Normal order and extended Wick theorem for a multiconfiguration reference wave function

NASA Astrophysics Data System (ADS)

Kutzelnigg, Werner; Mukherjee, Debashis

1997-07-01

A generalization of normal ordering and of Wick's theorem with respect to an arbitrary reference function Φ as some generalized "physical vacuum" is formulated in a different (but essentially equivalent) way than that suggested previously by one of the present authors. Guiding principles are that normal order operators with respect to any reference state must be expressible as linear combinations of those with respect to the genuine vacuum, that the vacuum expectation value of a normal order operator must vanish (with respect to the vacuum to which it is in normal order), and that the well-known formalism for a single Slater determinant as physical vacuum must be contained as a special case. The derivation is largely based on the concepts of "Quantum Chemistry in Fock space," which means that particle-number-conserving operators (excitation operators) play a central role. Nevertheless, the contraction rules in the frame of a generalized Wick theorem are derived, that hold for non-particle-number-conserving operators as well. The contraction rules are formulated and illustrated in terms of diagrams. The contractions involve the "residual n-particle density matrices" λ, which are the irreducible (non-factorizable) parts of the conventional n-particle density matrices γ, in the sense of a cumulant expansion for the density. A spinfree formulation is presented as well. The expression of the Hamiltonian in normal order with respect to a multiconfiguration reference function leads to a natural definition of a generalized Fock operator. MC-SCF-theory is easily worked out in this context. The paper concludes with a discussion of the excited configurations and the first-order interacting space, that underlies a perturbative coupled cluster type correction to the MCSCF function for an arbitrary reference function, and with general implications of the new formalism, that is related to "internally contracted multireference configuration interaction." The present generalization of normal ordering is not only valid for arbitrary reference functions, but also if the reference state is an ensemble state.

Kinetics of homogeneous nucleation on many-component systems

NASA Technical Reports Server (NTRS)

Hirschfelder, J. O.

1974-01-01

Reiss's (1950) classical treatment of the kinetics of homogeneous nucleation in a system containing two chemical components is extended to many-component systems. The formulation is analogous to the pseudostationary-state theory of chemical reaction rates, with the free energy as a function of the composition of the embryo taking the place of the potential energy as a function of interatomic distances.

String junction as a baryonic constituent

NASA Astrophysics Data System (ADS)

Kalashnikova, Yu. S.; Nefediev, A. V.

1996-02-01

We extend the model for QCD string with quarks to consider the Mercedes Benz string configuration describing the three-quark baryon. Under the assumption of adiabatic separation of quark and string junction motion we formulate and solve the classical equation of motion for the junction. We dare to quantize the motion of the junction, and discuss the impact of these modes on the baryon spectra.

Kinetics of homogeneous nucleation in many component systems

NASA Technical Reports Server (NTRS)

Hirschfelder, J. O.

1974-01-01

Reiss's classical treatment of the kinetics of homogeneous nucleation in a system containing two chemical components is extended to many-component systems. The formulation is analogous to the pseudo-stationary state theory of chemical reaction rates with the free energy as a function of the composition of the embryo taking the place of the potential energy as a function of interatomic distances.

Optimization-based Approach to Cross-layer Resource Management in Wireless Networked Control Systems

DTIC Science & Technology

2013-05-01

interest from both academia and industry [37], finding applications in un- manned robotic vehicles, automated highways and factories, smart homes and...is stable when the scaler varies slowly. The algorithm is further extended to utilize the slack resource in the network, which leads to the...model . . . . . . . . . . . . . . . . 66 Optimal sampling rate allocation formulation . . . . . 67 Price-based algorithm

Embodying Markov blankets. Comment on "Answering Schrödinger's question: A free-energy formulation" by Maxwell James Désormeau Ramstead et al.

NASA Astrophysics Data System (ADS)

Pezzulo, Giovanni; Levin, Michael

2018-03-01

The free-energy principle (FEP) has been initially proposed as a theory of brain structure and function [1], but its scope is rapidly extending to explain biological phenomena at multiple levels of complexity, from simple life forms and their morphology [2] to complex societal and cultural dynamics [3].

Kinematic activity of gray wolf (Canis lupus) sperm in different extenders, added before or after centrifugation.

PubMed

Christensen, Bruce W; Asa, Cheryl S; Wang, Chong; Bauman, Karen; Agnew, Mary K; Lorton, Steven P; Callahan, Margaret

2013-04-01

We evaluated two approaches to improving in vitro wolf sperm survival. Both approaches aimed to reduce the exposure of sperm to prostatic fluid resulting from electroejaculation: (1) use of extender formulations recently developed for the domestic dog (the most closely related domestic species); and (2) dilution of ejaculate shortly after semen collection. Three commercial extenders were compared with the TRIS-based extender we had previously used. We also compared the effects on motility of adding extender immediately after collection to our previous protocol in which extender was added after centrifugation. Both subjective and objective (computer-assisted semen analysis program) kinematic measurements were made. Relatively minor differences were noted (and not in total or progressive motility) between the centrifugation protocols. Two of the commercial extenders resulted in significant improvement in motility over the TRIS-based extender and one of the other commercial extenders at 8 hours after collection (mean ± SEM; total motility was 68.3 ± 4.0% and 70.0 ± 4.0% compared with 53.3 ± 4.0% and 55.0 ± 4.0%, respectively; progressive motility 58.6 ± 5.4% and 57.1 ± 5.4% compared with 32.8 ± 5.4% and 39.3 ± 5.4%; P < 0.05). We inferred that components in two of the commercial dog extenders might provide more protection for wolf sperm, prolonging their motility. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Optimization of Melatonin Dissolution from Extended Release Matrices Using Artificial Neural Networking.

PubMed

Martarelli, D; Casettari, L; Shalaby, K S; Soliman, M E; Cespi, M; Bonacucina, G; Fagioli, L; Perinelli, D R; Lam, J K W; Palmieri, G F

2016-01-01

Efficacy of melatonin in treating sleep disorders has been demonstrated in numerous studies. Being with short half-life, melatonin needs to be formulated in extended-release tablets to prevent the fast drop of its plasma concentration. However, an attempt to mimic melatonin natural plasma levels during night time is challenging. In this work, Artificial Neural Networks (ANNs) were used to optimize melatonin release from hydrophilic polymer matrices. Twenty-seven different tablet formulations with different amounts of hydroxypropyl methylcellulose, xanthan gum and Carbopol®974P NF were prepared and subjected to drug release studies. Using dissolution test data as inputs for ANN designed by Visual Basic programming language, the ideal number of neurons in the hidden layer was determined trial and error methodology to guarantee the best performance of constructed ANN. Results showed that the ANN with nine neurons in the hidden layer had the best results. ANN was examined to check its predictability and then used to determine the best formula that can mimic the release of melatonin from a marketed brand using similarity fit factor. This work shows the possibility of using ANN to optimize the composition of prolonged-release melatonin tablets having dissolution profile desired.

Pharmacokinetic drug evaluation of extended release lorcaserin for the treatment of obesity.

PubMed

Hurren, Kathryn M; Dunham, Marissa W

2017-08-01

Lorcaserin is a serotonin 2C receptor antagonist that was FDA approved in 2012. Lorcaserin is recently available as an extended-release (ER) formulation for the treatment of obesity as an adjunct to lifestyle modification. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of lorcaserin ER will be reviewed. Expert opinion: Lorcaserin ER 20mg daily provides drug exposure bioequivalent to lorcaserin immediate release (IR) 10mg twice daily. Lorcaserin IR is associated with 3.3 and 3.0% placebo-subtracted weight loss in patients without and with diabetes, respectively. A1C was reduced by 0.9% in patients with diabetes. Common side effects include headache, dry mouth, constipation, dizziness, fatigue, and nausea. Lorcaserin provides potential advantages over other antiobesity medications in regards to tolerability and simplicity of medication initiation, but may not be as effective as other options. Lorcaserin ER offers improved ease of administration and anticipated adherence compared to the IR formulation. The place in therapy for lorcaserin ER and other antiobesity medications will be further clarified by results of pending clinical trials addressing cardiovascular outcomes as well as the role pharmacogenomics and comorbid disease states may play in choosing patient-specific therapy.

Methylphenidate Efficacy: Immediate versus Extended Release at Short Term in Mexican Children with ADHD Assessed by Conners Scale and EEG

PubMed Central

Alatorre-Miguel, Efren; Zambrano-Sánchez, Elizabeth; Reyes-Legorreta, Celia

2015-01-01

Attention deficit hyperactivity disorder (ADHD) affects 5-6% of school aged children worldwide. Pharmacological therapy is considered the first-line treatment and methylphenidate (MPH) is considered the first-choice medication. There are two formulations: immediate release (IR) MPH and long-acting (or extended release) formulation (MPH-ER). In this work, we measure the efficacy of treatment for both presentations in one month with Conners' scales and electroencephalography (EEG). Results. for IR group, in parents and teachers Conners test, all items showed significant differences, towards improvement, except for teachers in perfectionism and emotional instability. For ER group in parent's Conners test, the items in which there were no significant differences are psychosomatic and emotional instability. For teachers, there were no significant differences in: hyperactivity and perfectionism. Comparing the Conners questionnaires (parents versus teachers) we find significant differences before and after treatment in hyperactivity, perfectionism, psychosomatics, DSM-IV hyperactive-impulsive, and DSM-IV total. In the EEG the Wilcoxon test showed a significant difference (P < 0.0001). As we can see, both presentations are suitable for managing the ADHD and have the same effect on the symptomatology and in the EEG. PMID:25838946

Methylphenidate Efficacy: Immediate versus Extended Release at Short Term in Mexican Children with ADHD Assessed by Conners Scale and EEG.

PubMed

Durand-Rivera, Alfredo; Alatorre-Miguel, Efren; Zambrano-Sánchez, Elizabeth; Reyes-Legorreta, Celia

2015-01-01

Attention deficit hyperactivity disorder (ADHD) affects 5-6% of school aged children worldwide. Pharmacological therapy is considered the first-line treatment and methylphenidate (MPH) is considered the first-choice medication. There are two formulations: immediate release (IR) MPH and long-acting (or extended release) formulation (MPH-ER). In this work, we measure the efficacy of treatment for both presentations in one month with Conners' scales and electroencephalography (EEG). Results. for IR group, in parents and teachers Conners test, all items showed significant differences, towards improvement, except for teachers in perfectionism and emotional instability. For ER group in parent's Conners test, the items in which there were no significant differences are psychosomatic and emotional instability. For teachers, there were no significant differences in: hyperactivity and perfectionism. Comparing the Conners questionnaires (parents versus teachers) we find significant differences before and after treatment in hyperactivity, perfectionism, psychosomatics, DSM-IV hyperactive-impulsive, and DSM-IV total. In the EEG the Wilcoxon test showed a significant difference (P < 0.0001). As we can see, both presentations are suitable for managing the ADHD and have the same effect on the symptomatology and in the EEG.

Pharmacokinetics of an oral extended-release formulation of doxycycline hyclate containing acrylic acid and polymethacrylate in dogs.

PubMed

Ruiz, Sara Melisa Arciniegas; Olvera, Lilia Gutiérrez; Chacón, Sara del Carmen Caballero; Estrada, Dinorah Vargas

2015-04-01

To determine the pharmacokinetics of doxycycline hyclate administered orally in the form of experimental formulations with different proportions of acrylic acid-polymethacrylate-based matrices. 30 healthy adult dogs. In a crossover study, dogs were randomly assigned (in groups of 10) to receive a single oral dose (20 mg/kg) of doxycycline hyclate without excipients (control) or extended-release formulations (ERFs) containing doxycycline, acrylic acid polymer, and polymethacrylate in the following proportions: 1:0.5:0.0075 (ERF1) or 1:1:0.015 (ERF2). Serum concentrations of doxycycline were determined for pharmacokinetic analysis before and at several intervals after each treatment. Following oral administration to the study dogs, each ERF resulted in therapeutic serum doxycycline concentrations for 48 hours, whereas the control treatment resulted in therapeutic serum doxycycline concentrations for only 24 hours. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different; however, findings for ERF1 did not differ significantly from those for the control treatment. Results indicated that both ERFs containing doxycycline, acrylic acid polymer, and polymethacrylate had an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and a longer release time than doxycycline alone following oral administration in dogs. Given the minimum effective serum doxycycline concentration of 0.26 μg/mL, a dose interval of 48 hours can be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in important infections in dogs. Treatment of dogs with either ERF may have several benefits over treatment with doxycycline alone.

Stabilization of the Nitric Oxide (NO) Prodrugs and Anti-Cancer Leads, PABA/NO and Double JS-K through Incorporation into PEG-Protected Nanoparticles

PubMed Central

Kumar, Varun; Hong, Sam Y.; Maciag, Anna E.; Saavedra, Joseph E.; Adamson, Douglas H.; Prud'homme, Robert K.; Keefer, Larry K.; Chakrapani, Harinath

2009-01-01

Here we report the stabilization of the nitric oxide (NO) prodrugs and anti-cancer lead compounds, PABA/NO (O2-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate) and “Double JS-K” (1,5-bis{[1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diol-2-ato]-2,4-dinitrobenzene), through their incorporation into polymer-protected nanoparticles. The prodrugs were formulated in block copolymer-stabilized nanoparticles with sizes from 220 to 450 nm by a novel rapid precipitation process. The block copolymers, with polyethylene glycol (PEG) soluble blocks, provide a steric barrier against NO prodrug activation by glutathione. Too rapid activation and NO release has been a major barrier to effective administration of this class of compounds. The nanoparticle stabilized PABA/NO from attack by glutathione as evidenced by a significant increase in time taken for 50% decomposition from 15 min (unformulated) to 5 h (formulated); in the case of Double JS-K, the 50% decomposition time was extended from 4.5 min (unformulated) to 40 min (formulated). The more hydrophobic PABA/NO produced more stable nanoparticles and correspondingly more extended release times in comparison with Double JS-K. The hydrophobic blocks of the polymer were either polystyrene or polylactide. Both blocks produced nanoparticles of approximately the same size and release kinetics. This combination of PEG-protected nanoparticles with sizes appropriate for cancer targeting by enhanced permeation and retention (EPR) and delayed release of NO may afford enhanced therapeutic benefit. PMID:20000791

Stabilization of the nitric oxide (NO) prodrugs and anticancer leads, PABA/NO and Double JS-K, through incorporation into PEG-protected nanoparticles.

PubMed

Kumar, Varun; Hong, Sam Y; Maciag, Anna E; Saavedra, Joseph E; Adamson, Douglas H; Prud'homme, Robert K; Keefer, Larry K; Chakrapani, Harinath

2010-02-01

We report the stabilization of the nitric oxide (NO) prodrugs and anticancer lead compounds, PABA/NO (O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate) and "Double JS-K" 1,5-bis-{1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diol-2-ato}-2,4-dinitrobenzene, through their incorporation into polymer-protected nanoparticles. The prodrugs were formulated in block copolymer-stabilized nanoparticles with sizes from 220 to 450 nm by a novel rapid precipitation process. The block copolymers, with polyethylene glycol (PEG) soluble blocks, provide a steric barrier against NO prodrug activation by glutathione. Too rapid activation and NO release has been a major barrier to effective administration of this class of compounds. The nanoparticle stabilized PABA/NO are protected from attack by glutathione as evidenced by a significant increase in time taken for 50% decomposition from 15 min (unformulated) to 5 h (formulated); in the case of Double JS-K, the 50% decomposition time was extended from 4.5 min (unformulated) to 40 min (formulated). The more hydrophobic PABA/NO produced more stable nanoparticles and correspondingly more extended release times in comparison with Double JS-K. The hydrophobic blocks of the polymer were either polystyrene or polylactide. Both blocks produced nanoparticles of approximately the same size and release kinetics. This combination of PEG-protected nanoparticles with sizes appropriate for cancer targeting by enhanced permeation and retention (EPR) and delayed release of NO may afford enhanced therapeutic benefit.

Urinary excretion of ciprofloxacin after administration of extended release tablets in healthy volunteers. Swellable drug-polyelectrolyte matrix versus bilayer tablets.

PubMed

Guzmán, M L; Romañuk, C B; Sanchez, M F; Luciani Giacobbe, L C; Alarcón-Ramirez, L P; Battistini, F D; Alovero, F L; Jimenez-Kairuz, A F; Manzo, R H; Olivera, María Eugenia

2018-02-01

This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, t max , area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.

Preparation and In Vitro/Ex Vivo Evaluation of Moxifloxacin-Loaded PLGA Nanosuspensions for Ophthalmic Application

PubMed Central

Mudgil, Meetali; Pawar, Pravin K.

2013-01-01

The aim of the present investigation was to prepare a colloidal ophthalmic formulation to improve the residence time of moxifloxacin. Moxifloxacin-loaded poly(dl-lactide-co-glycolide) (PLGA) nanosuspensions were prepared by using the solvent evaporation technique. The nanosuspensions were characterised physically by using different techniques like particle size, zeta potential, FTIR, DSC, and XRD analysis. In vitro and ex vivo studies of nanosuspensions were carried out using a modified USP dissolution apparatus and all-glass Franz diffusion cells, respectively. The antibacterial activities of the nanosuspension and marketed formulations were performed against S. aureus and P. aeroginosa. The moxifloxacin-loaded PLGA nanosuspensions showed uniform particle size, ranging between 164–490 nm with negative zeta potential for all batches. The percentage entrapment efficiency of the drug-loaded nano-suspension was found to be between 84.09 to 92.05%. In vitro drug release studies suggest that all of the formulations showed extended drug release profiles and follow Korsemeyer-Peppas release kinetics. In vitro corneal permeability was found to be comparable with that of the marketed formulation across isolated goat cornea, indicating the suitability of the nanosuspension formulation in the ophthalmic delivery of moxifloxacin. The optimised nano-suspension was found to be more active against S. aureus and P. aeruginosa compared to the marketed eye drops. PMID:23833723

Parallel Finite Element Domain Decomposition for Structural/Acoustic Analysis

NASA Technical Reports Server (NTRS)

Nguyen, Duc T.; Tungkahotara, Siroj; Watson, Willie R.; Rajan, Subramaniam D.

2005-01-01

A domain decomposition (DD) formulation for solving sparse linear systems of equations resulting from finite element analysis is presented. The formulation incorporates mixed direct and iterative equation solving strategics and other novel algorithmic ideas that are optimized to take advantage of sparsity and exploit modern computer architecture, such as memory and parallel computing. The most time consuming part of the formulation is identified and the critical roles of direct sparse and iterative solvers within the framework of the formulation are discussed. Experiments on several computer platforms using several complex test matrices are conducted using software based on the formulation. Small-scale structural examples are used to validate thc steps in the formulation and large-scale (l,000,000+ unknowns) duct acoustic examples are used to evaluate the ORIGIN 2000 processors, and a duster of 6 PCs (running under the Windows environment). Statistics show that the formulation is efficient in both sequential and parallel computing environmental and that the formulation is significantly faster and consumes less memory than that based on one of the best available commercialized parallel sparse solvers.

PEGylated polylysine dendrimers increase lymphatic exposure to doxorubicin when compared to PEGylated liposomal and solution formulations of doxorubicin.

PubMed

Ryan, Gemma M; Kaminskas, Lisa M; Bulitta, Jürgen B; McIntosh, Michelle P; Owen, David J; Porter, Christopher J H

2013-11-28

Improved delivery of chemotherapeutic drugs to the lymphatic system has the potential to augment outcomes for cancer therapy by enhancing activity against lymph node metastases. Uptake of small molecule chemotherapeutics into the lymphatic system, however, is limited. Nano-sized drug carriers have the potential to promote access to the lymphatics, but to this point, this has not been examined in detail. The current study therefore evaluated the lymphatic exposure of doxorubicin after subcutaneous and intravenous administration as a simple solution formulation or when formulated as a doxorubicin loaded PEGylated poly-lysine dendrimer (hydrodynamic diameter 12 nm), a PEGylated liposome (100 nm) and various pluronic micellar formulations (~5 nm) to thoracic lymph duct cannulated rats. Plasma and lymph pharmacokinetics were analysed by compartmental pharmacokinetic modelling in S-ADAPT, and Berkeley Madonna software was used to predict the lymphatic exposure of doxorubicin over an extended period of time. The micelle formulations displayed poor in vivo stability, resulting in doxorubicin profiles that were similar to that observed after administration of the doxorubicin solution formulation. In contrast, the dendrimer formulation significantly increased the recovery of doxorubicin in the thoracic lymph after both intravenous and subcutaneous dosing when compared to the solution or micellar formulation. Dendrimer-doxorubicin also resulted in increases in lymphatic doxorubicin concentrations when compared to the liposome formulation, although liposomal doxorubicin did increase lymphatic transport when compared to the solution formulation. Specifically, the dendrimer formulation increased the recovery of doxorubicin in the lymph up to 30 h post dose by up to 685 fold and 3.7 fold when compared to the solution and liposomal formulations respectively. Using the compartmental model to predict lymphatic exposure to longer time periods suggested that doxorubicin exposure to the lymphatic system would ultimately be 9796 times and 6.1 times greater after administration of dendrimer doxorubicin when compared to the solution and liposome formulations respectively. The recovery of doxorubicin in the sentinel lymph nodes draining the subcutaneous injection site was also quantified directly, and consistent with the lymph pharmacokinetic data, lymph node recovery was greatest for the dendrimer formulation (12% of dosed doxorubicin/g node) when compared to the liposome (1.4%/g node) and solution (<1%/g node) formulations. The data suggest that dendrimer-based drug delivery systems have the potential to enhance drug exposure to lymph-based drug targets such as lymphatic metastases. © 2013.

Differential Geometry Based Multiscale Models

PubMed Central

Wei, Guo-Wei

2010-01-01

Large chemical and biological systems such as fuel cells, ion channels, molecular motors, and viruses are of great importance to the scientific community and public health. Typically, these complex systems in conjunction with their aquatic environment pose a fabulous challenge to theoretical description, simulation, and prediction. In this work, we propose a differential geometry based multiscale paradigm to model complex macromolecular systems, and to put macroscopic and microscopic descriptions on an equal footing. In our approach, the differential geometry theory of surfaces and geometric measure theory are employed as a natural means to couple the macroscopic continuum mechanical description of the aquatic environment with the microscopic discrete atom-istic description of the macromolecule. Multiscale free energy functionals, or multiscale action functionals are constructed as a unified framework to derive the governing equations for the dynamics of different scales and different descriptions. Two types of aqueous macromolecular complexes, ones that are near equilibrium and others that are far from equilibrium, are considered in our formulations. We show that generalized Navier–Stokes equations for the fluid dynamics, generalized Poisson equations or generalized Poisson–Boltzmann equations for electrostatic interactions, and Newton's equation for the molecular dynamics can be derived by the least action principle. These equations are coupled through the continuum-discrete interface whose dynamics is governed by potential driven geometric flows. Comparison is given to classical descriptions of the fluid and electrostatic interactions without geometric flow based micro-macro interfaces. The detailed balance of forces is emphasized in the present work. We further extend the proposed multiscale paradigm to micro-macro analysis of electrohydrodynamics, electrophoresis, fuel cells, and ion channels. We derive generalized Poisson–Nernst–Planck equations that are coupled to generalized Navier–Stokes equations for fluid dynamics, Newton's equation for molecular dynamics, and potential and surface driving geometric flows for the micro-macro interface. For excessively large aqueous macromolecular complexes in chemistry and biology, we further develop differential geometry based multiscale fluid-electro-elastic models to replace the expensive molecular dynamics description with an alternative elasticity formulation. PMID:20169418

Using an object-based grid system to evaluate a newly developed EP approach to formulate SVMs as applied to the classification of organophosphate nerve agents

NASA Astrophysics Data System (ADS)

Land, Walker H., Jr.; Lewis, Michael; Sadik, Omowunmi; Wong, Lut; Wanekaya, Adam; Gonzalez, Richard J.; Balan, Arun

2004-04-01

This paper extends the classification approaches described in reference [1] in the following way: (1.) developing and evaluating a new method for evolving organophosphate nerve agent Support Vector Machine (SVM) classifiers using Evolutionary Programming, (2.) conducting research experiments using a larger database of organophosphate nerve agents, and (3.) upgrading the architecture to an object-based grid system for evaluating the classification of EP derived SVMs. Due to the increased threats of chemical and biological weapons of mass destruction (WMD) by international terrorist organizations, a significant effort is underway to develop tools that can be used to detect and effectively combat biochemical warfare. This paper reports the integration of multi-array sensors with Support Vector Machines (SVMs) for the detection of organophosphates nerve agents using a grid computing system called Legion. Grid computing is the use of large collections of heterogeneous, distributed resources (including machines, databases, devices, and users) to support large-scale computations and wide-area data access. Finally, preliminary results using EP derived support vector machines designed to operate on distributed systems have provided accurate classification results. In addition, distributed training time architectures are 50 times faster when compared to standard iterative training time methods.

High energy scattering in QCD and in quantum gravity

NASA Astrophysics Data System (ADS)

Lipatov, L. N.

2014-06-01

The theory of the high energy scattering in QCD is based on the BFKL equation for the Pomeron wave function and on its generalization for composite multi-gluon states in the crossing channel. At a large number of colors the equations for the gluon composite states have remarkable mathematical properties including their Möbius invariance, holomorphic separability, duality symmetry and integrability. High energy QCD interactions local in the particle rapidities are formulated in the form of the gauge invariant effective action. In the maximally extended N = 4 super-symmetry the Pomeron turns out to be dual to the reggeized graviton in the 10-dimensional anti-de-Sitter space. As a result, the Gribov calculus for the Pomeron interactions should be reformulated here as a generally covariant effective field theory for the reggeized gravitons. We construct the corresponding effective action, which gives a possibility to calculate their trajectory and couplings. The graviton trajectory in the leading order contains an ultraviolet divergency meaning the presence of the double-logarithmic (DL) terms. We sum the DL contributions in all orders of the perturbation theory in the Einstein-Hilbert gravity and in its super-symmetric generalizations. In the N = 8 super gravity the ratio of the scattering amplitude in the DL approximation to the Born expression tends to zero at large energies.

Effect of kafirin protein coating on sensory quality and shelf-life of 'Packham's Triumph' pears during ripening.

PubMed

Buchner, Sonya; Kinnear, Marise; Crouch, Ian J; Taylor, Janet; Minnaar, Amanda

2011-12-01

Pears are exported in large quantities from South Africa, resulting in large revenues. Minimisation of quality losses once the fruit has reached the export destination is as important as following strict export and distribution protocols. Kafirin can form edible films. In this study an edible coating made from 20 g kg(-1) kafirin coating solution was applied as a postharvest treatment to retard quality deterioration of 'Packham's Triumph' pears during storage at the typical ripening temperature (20 °C). Changes in physicochemical and sensory quality were monitored over a period of 24 days. The kafirin coating was unable to retard the onset of ripening but decreased the respiration rate and retarded the progression of senescence. However, moisture loss was exacerbated in the kafirin-coated fruit during ripening at 20 °C, especially towards the end of the shelf-life. The kafirin coating extended the eat-ripe quality of the pears by 1-2 weeks. However, the appearance of the fruit was unacceptable after 14 days of storage in terms of wrinkled skin. Further work is needed to improve the water barrier properties of the kafirin coating by incorporating a wax or triglyceride into the coating formulation or more simply by applying a kafirin coating to waxed fruit. Copyright © 2011 Society of Chemical Industry.