Direct comparison of muscle force predictions using linear and nonlinear programming

Estimating forces in muscles and joints during locomotion requires formulations consistent with available methods of solving the indeterminate problem. Direct comparisons of results between differing optimization methods proposed in the literature have been difficult owing to widely varying model formulations, algorithms, input data, and other factors. We present an application of a new optimization program which includes linear and nonlinear techniques allowing a variety of cost functions and greater flexibility in problem formulation. Unified solution methods such as the one demonstrated here, offer direct evaluations of such factors as optimization criteria and constraints. This unified method demonstrates that nonlinear formulations (of the sort reported) allow more synergistic activity and in contrast to linear formulations, allow antagonistic activity. Concurrence of EMG activity and predicted forces is better with nonlinear predictions than linear predictions. The prediction of synergistic and antagonistic activity expectedly leads to higher joint force predictions. Relaxation of the requirement that muscles resolve the entire intersegmental moment maintains muscle synergism in the nonlinear formulation while relieving muscle antagonism and reducing the predicted joint contact force. Such unified methods allow more possibilities for exploring new optimization formulations, and in comparing the solutions to previously reported formulations.     

Potential of Agrotis ipsilon nucleopolyhedrovirus for suppression of the black cutworm (Lepidoptera: Noctuidae) and effect of an optical brightener on virus efficacy.

Studies were performed in the laboratory, greenhouse and field to assess the potential of Agrotis ipsilon multicapsid nucleopolyhedrovirus (AgipMNPV) and a viral enhancing agent, M2R, for suppression of Agrotis ipsilon (Hufnagel). In laboratory droplet feeding bioassays, AgipMNPV was shown to be highly active against third-instar A. ipsilon. The optical brightener M2R significantly reduced LD50 estimates by approximately 160-fold, but had no direct effect on survival time estimates. In greenhouse trials, spray and bait formulations of AgipMNPV significantly reduced feeding damage to corn seedlings caused by third-instar A. ipsilon. In two sets of replicated field trials, bait formulations of AgipMNPV significantly reduced feeding damage to corn seedlings by third-instar A. ipsilon. However, there were no beneficial effects attributable to the inclusion of M2R in AgipMNPV formulations under greenhouse or field conditions. It seems likely that in an appropriately designed pest management program AgipMNPV could be used to suppress field populations of early and mid-instar A. ipsilon.     

Integer programming approaches to haplotype inference by pure parsimony

In 2003, Gusfield introduced the haplotype inference by pure parsimony (HIPP) problem and presented an integer program (IP) that quickly solved many simulated instances of the problem. Although it solved well on small instances, Gusfield's IP can be of exponential size in the worst case. Several authors have presented polynomial-sized IPs for the problem. In this paper, we further the work on IP approaches to HIPP. We extend the existing polynomial-sized IPs by introducing several classes of valid cuts for the IP. We also present a new polynomial-sized IP formulation that is a hybrid between two existing IP formulations and inherits many of the strengths of both. Many problems that are too complex for the exponential-sized formulations can still be solved in our new formulation in a reasonable amount of time. We provide a detailed empirical comparison of these IP formulations on both simulated and real genotype sequences. Our formulation can also be extended in a variety of ways to allow errors in the input or model the structure of the population under consideration.     

Toxic effect of herbicides used for water hyacinth control on two insects released for its biological control in South Africa

The integrated control of water hyacinth, Eichhornia crassipes (Martius) Solms-Laubach (Pontederiaceae) has become necessary in South Africa, as biological control alone is perceived to be too slow in controlling the weed. In total, seven insect biological control agents have been released on water hyacinth in South Africa. At the same time, herbicides are applied by the water authorities in areas where the weed continues to be troublesome. This study investigated the assumption that the two control methods are compatible by testing the direct toxicity of a range of herbicide formulations and surfactants on two of the biological control agents released against water hyacinth, the weevil, Neochetina eichhorniae Warner (Coleoptera: Curculionidae) and the water hyacinth mirid, Eccritotarsus catarinensis (Carvalho) (Hemiptera: Miridae). A number of the formulations used resulted in significant mortality of the mirid and the weevil. Products containing 2,4-D amine and diquat as active ingredients caused higher mortality of both agents (up to 80% for the mirid) than formulations containing glyphosate. Furthermore, when surfactants were added to enhance herbicide efficiency, it resulted in increased toxicity to the insects. We recommend that glyphosate formulations should be used in integrated control programmes, and that surfactants be avoided in order to reduce the toxic nature of spray formulations to the insect biological control agents released against water hyacinth.     

Generation of density gradients. Approximations to equivolumetric gradients for zonal rotors

The use of a “density gradient generating function” allows the concentration profile of a density gradient to be written explicitly in terms of the required distribution of sedimentation coefficients in place of the previous implicit formulations. This function, which is easily implemented in a computer program, permits calculation of density gradients for a number of applications. This approach is applied to computation of a variety of equivolumetric gradients of sucrose for zonal rotors and yields a formula for the calibration of such gradients. An accurate approximation has been found which allows the generation of virtually all equivolumetric gradients of sucrose for a given rotor using a single program for the gradient generator employed; the adjustment for different particle densities and for different concentrations at the top of the gradient is made by varying only the initial and final concentrations of sucrose used.     

Determination of protection from serum nuclease activity by DNA-polyelectrolyte complexes using an electrophoretic method

Polyelectrolyte complexes between cationic polymers and DNA have emerged as potential nonviral vectors for DNA delivery. For successful in vivo delivery, methods for analyzing their ability to prevent digestion of the DNA payload by serum nucleases are essential. We report here a simple assay to determine degradation of DNA in these complexes using standard electrophoretic techniques. The assay is based on a high pH buffer which can dissociate the complexes under standard electrophoretic conditions. This assay can be used qualitatively to determine the time taken for degradation to occur. Alternatively, with a standard gel analysis program it can be used quantitatively to investigate rates of DNA degradation from complexes in the presence of serum nucleases. We have shown that it can distinguish between different formulations with the same polymer, and also to distinguish between the time taken to degradation and the rates of degradation of DNA in complexes formed with two structurally related, linear polyamidoamine polymers. The assay could also distinguish between the time to degradation using poly-l-lysine complexes, although these were less well dissociated by the electrophoresis buffer, and could not be analyzed quantitatively. This assay will be of value in investigating and developing polyelectrolyte formulations for parenteral administration.     

Delivery Considerations of Highly Viscous Polymeric Fluids Mimicking Concentrated Biopharmaceuticals: Assessment of Injectability <Emphasis Type="Italic">via</Emphasis> Measurement of Total Work Done “<Emphasis Type="Italic">W</Emphasis><Subscript>T</Subscript>”

An account is given of the recent development of the highly viscous complex biopharmaceuticals in relation to syringeability and injectability. The specific objective of this study is to establish a convenient method to examine problem of the injectability for the needle-syringe-formulation system when complex formulations with diverse viscosities are used. This work presents the inter-relationship between needle size, syringe volume, viscosity, and injectability of polymeric solutions having typical viscosities encountered in concentrated biologics, by applying a constant probe crosshead speed on the plunger-syringe needle assembly and continuously recording the force-distance profiles. A computerized texture analyzer was used to accurately capture, display, and store force, displacement, and time data. The force-distance curve and area under the curve are determined, and total work done for complete extrusion of the syringe content was calculated automatically by applying an established Matlab program. Various concentrations (i.e., 0.5–4% w/v of polymeric fluids/dispersions) of polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) with viscosity ranges of 5–100 cP mimicking concentrated monoclonal antibody solutions and complex biopharmaceutical formulations are investigated. Results indicate that calculated values of total work done to completely extrude the syringe content are the most appropriate parameter that describes viscosity-injection force of dispersed formulations. Additionally, the rheological properties of HPMC and PEO fluids in the context of syringeability and injectability are discussed.     

High-performance liquid chromatographic separation and electrochemical detection of cephalosporins

Pulsed amperometric detection (PAD) is useful for detection of cephalosporins following separation on a C₁₈ column using an acetate buffer solvent with a small percentage of organic modifier. Under these conditions, the indirect PAD mode worked better than direct PAD, with IPAD outperforming both. A gradient program was demonstrated that allowed separation and sensitive electrochemical detection of eleven different cephalosporins with widely differing side chain structures. The cephalosporins could be detected to sub-micromolar levels with this separation. Applications of the method for quantitation of pharmaceutical formulations and for monitoring cephalexin in porcine serum were demonstrated. To improve the detectability of cephalexin, an on-column concentration scheme using separate concentration and elution solvents was applied to porcine serum.     

Performance of copper naphthenate and its analogs as ground contact wood preservatives

For several years, an extensive research program investigating new preservative systems has been ongoing at Mississippi State University. This paper details our continuing experience with field testing of copper naphthenate and other copper carboxylate preservative systems. Results from field stake tests at an AWPA Zone 4 test site are presented. In general, copper carboxylates made with 'synthetic' acids yielded results equivalent to or only slightly lower than systems with straight naphthenic acids or nap acids amended with synthetic neodecanoic acid bottoms. Oil carrier formulations outperformed those in water or light organic solvents. All systems carried in oil would qualify as ground contact preservatives at the proper retention.     

Effectiveness of five antidandruff cosmetic formulations against planktonic cells and biofilms of dermatophytes

This study aimed to investigate the in vitro antifungal effectiveness of five different formulations against dandruff and ringworm dermatophytes. Candida albicans was also included in our assays. Fungal susceptibility tests were performed with planktonic cells and biofilms of reference strains. Microbiological and physicochemical quality parameters were assessed for all formulations. Our data indicated that the formulations were effective against the dermatophytes strains, and to our knowledge, the effectiveness of cosmetic formulations against fungal biofilms is shown for the first time. The formulations were considered effective against the explored dermatophytes and were considered safe given the adequate microbiological and physicochemical characteristics shown in the proposed assays.     

Replacement of phosphates in detergents

Summary Government policy in the Netherlands aims at reducing phosphate inputs into surface waters by (I) adding phosphate removal facilities to sewage treatment plants, and (II) simultaneously banning phosphates from detergents. Several reasons are given for the necessity of detergent phosphate banning: reasons of environmental requirements and cost, but also of public acceptance.Four alternatives to phosphate are discussed briefly: soap, Citrex-S5, NTA (nitrilo-triacetic acid), and zeolites. All four are available in the Netherlands, as are detergent formulations containing them. In a simplified comparative assessment of environmental properties of phosphate substitutes and phosphate itself, the substitutes appear relatively safe.In January 1980 the results of a detailed environmental assessment of phosphate substitutes have been published, together with the text of an agreement between government and detergent manufacturers on a phosphate reduction program for the next three years.     

Development of new formulations of Bacillus subtilis for management of tomato damping-off caused by Pythium aphanidermatum

Formulations of a strain of Bacillus subtilis AUBS-1 inhibitory to the growth of the damping-off pathogen, Pythium aphanidermatum, were developed for seed treatment. The formulations included a talc-based powder, lignite-based powder, lignite+fly ash-based powder, wettable powder, bentonite-paste, polyethylene glycol (PEG) paste and a water-dispersible tablet. Formulations were stored at room temperature for 2 years and frequently sampled to test their shelf life. Populations of bacteria in the formulations were stable for up to 2 years storage at room temperature (28°C). Viability of propagules in lignite, lignite+fly ash, bentonite paste, wettable powder and water dispersible tablet formulations was 100% for up to 1 year. However, the viability of propagules was significantly reduced in talc, wettable powder, PEG paste and tablet formulations beyond 1 year of storage. Seed treatment of tomato with these formulations resulted in effective control of damping-off caused by P. aphanidermatum, and also enhanced plant biomass under glasshouse and field conditions. Active rhizosphere colonization by the bacterium was observed on tomato plants grown from seeds treated with the above formulations.     

MIP formulations for an application of project scheduling in human resource management

In the literature, various discrete-time and continuous-time mixed-integer linear programming (MIP) formulations for project scheduling problems have been proposed. The performance of these formulations has been analyzed based on generic test instances. The objective of this study is to analyze the performance of discrete-time and continuous-time MIP formulations for a real-life application of project scheduling in human resource management. We consider the problem of scheduling assessment centers. In an assessment center, candidates for job positions perform different tasks while being observed and evaluated by assessors. Because these assessors are highly qualified and expensive personnel, the duration of the assessment center should be minimized. Complex rules for assigning assessors to candidates distinguish this problem from other scheduling problems discussed in the literature. We develop two discrete-time and three continuous-time MIP formulations, and we present problem-specific lower bounds. In a comparative study, we analyze the performance of the five MIP formulations on four real-life instances and a set of 240 instances derived from real-life data. The results indicate that good or optimal solutions are obtained for all instances within short computational time. In particular, one of the real-life instances is solved to optimality. Surprisingly, the continuous-time formulations outperform the discrete-time formulations in terms of solution quality.     

The protective effect of lactose on lyophilization of CNK-20402

The goal of this research was to assess the feasibility of using lyophilization to stabilize an exploratory compound, CNK-20402, with a minimal amount of impurity (CNK-20193) formation. A mixed-level full factorial experimental design was used to screen excipients of glycine, mannitol, lactose monohydrate, and povidone K-12. Cryostage microscopy, powder X-ray diffraction, Karl Fischer titration, HPLC, and water vapor sorption were used to assess the formulations' physicochemical properties and stability. Initial physical characterization from powder X-ray diffraction revealed that the mannitol- and glycine-containing formulations were crystalline with the patterns of the pure excipient, whereas the remaining formulations were amorphous in structure. Chemically, the formulations stored at 50°C for 1 month had 2.36%, 1.05%, 0.81%, 0.79%, and 0.49% CNK-20193 for glycine, mannitol, drug alone, povidone K-12, and lactose formulations, respectively. The formulations containing drug-mannitol, drug alone, and druglactose were selected for accelerated stability study based on statistical analysis. Recovery of CNK-20193 in these formulations was 1.22%, 1.00%, and 0.55%, respectively, when stored at 40°C/75% relative humidity storage conditions for 3 months. Water vapor sorption analysis revealed weight gains of over 7%, 21%, and 24% for the mannitol, lactose, and drug alone formulations, respectively. Testing formulations with different concentrations of lactose by water vapor sorption indicated that CNK-20402 concentrations as low as 10% (wt/wt) could inhibit the recrystallization of lactose. The lactose-containing formulation exhibited the best stability among the formulations tested. The protective mechanism of lactose on the CNK-20402, based on water vapor sorption studies, is believed to be a result of (1) the drug-lactose interaction, and (2) competition between lactose and drug for the residual water in the formulation. Published: September 20, 2005     

Assessment of microencapsulated formulations for improved residual activity of Bacillus thuringiensis

Bacillus thuringiensis Berliner is a highly efficacious bioinsecticide used to control lepidopteran pests in the field. Unfortunately, it has limited residual activity on plants because sunlight inactivates spores and crystals and they can be washed off by rain. To minimize loss of activity, formulations must contain UV protectants, stickers, or both. We tested approximately 80 formulations and determined optimal combinations of ingredients and spray drying conditions for improving B. thuringiensis residual activity after simulated rain and simulated sunlight. B. thuringiensis stability, after simulated sunlight (xenon light/8 h) and rain (5 cm/50 min), was improved using formulations based on lignin, corn flours, or both, with up to 20% of the active ingredient, when compared with technical powder or Dipel 2x in laboratory assays. Two formulations, made with corn flours or lignin + pregelatinized corn flour (PCF), killed 51.6 and 75.3% of Ostrinia nubilalis (Hübner) neonates after rain, respectively, versus 27% for technical powder. When the insecticidal activity was tested after simulated sunlight, corn flour-based formulations killed 78.5% of test larvae, and the lignin + PCF formulation killed 70.4%, in contrast to technical powder which caused an average of 29% mortality. Formulations made with Dipel 2x rather than technical powder, caused 62.5% mortality (corn flour-based formulations), and 72.3% mortality (lignin + PCF), versus 53.4% for Dipel 2x after rain. When tested after simulated sunlight, formulations killed 95% of the larvae (average of both formulations) versus 82% for Dipel 2x. In a field test, formulations were applied to cabbage and insecticidal activity was determined against Trichoplusia ni (Hübner) neonates exposed to treated leaves. Insecticidal activity of the corn flour-based formulations was comparable to Dipel 2x for 4 d after treatment, but was significantly better than Dipel 2x 7 d after application. A lignin and PCF-based formulation showed significantly higher residual activity than Dipel 2x, 4 and 7 d after application.     

Storage stability of Anagrapha falcifera nucleopolyhedrovirus in spray-dried formulations

A multiply embedded nucleopolyhedrovirus isolated from Anagrapha falcifera (Kirby) (AfMNPV) can lose insecticidal activity during months of dry storage in ambient room conditions. We tested the spray-dried AfMNPV formulations after storage for up to 1 year at room temperatures for insecticidal activity against neonate Trichoplusia ni (Hübner). Experimental formulations were made using combinations of corn flours, lignin, and sucrose, and were selected based on previous work which demonstrated that these formulations resisted solar degradation in field experiments. Twelve experimental formulations (organized in three groups of four formulations) compared the effect of (1) the ratio of formulation ingredients (lignin and corn flour) to virus concentration, (2) different sources of lignin, or (3) different corn flours and sugar. Based on a single-dose plant assay with these 12 formulations, none of the formulations lost significant activity due to the drying process, when compared with the unformulated wet AfMNPV. Samples of the 12 dried formulations were stored at room (22+/-3 degrees C) and refrigerated (4 degrees C) temperatures. Insecticidal activity (LC(50)) was determined with a dosage-response assay for neonates fed on treated cotton-leaf disks. After 6 (or 9) and 12 months storage, refrigerated samples maintained insecticidal activity better than corresponding samples stored at room temperatures with LC(50)s that averaged 2.0 x 10(6) polyhedral inclusion bodies per milliliter (pibs/ml) for refrigerated samples and 5.4 x 10(6) pibs/ml for samples stored at room temperatures. Compared with unformulated stock virus stored frozen, six formulations stored at room temperature and 10 formulations stored in the refrigerator did not lose significant insecticidal activity after 1 year based on overlapping 90% confidence intervals. Changing the ratio of virus to formulation ingredients did not provide a clear trend over the range of concentrations tested, and may be less important for shelf-life of virus activity compared with formulations made with different ingredients. Two of the four formulations made with different lignins were about 15 times less active after 1 year at room temperature compared with refrigerated samples, indicating that specific formulation ingredients can affect storage stability. Formulations that contained sugar generally maintained activity during storage better than formulations without sugar. Unformulated virus stock maintained insecticidal activity (ranged from 0.20 to 2.5 x 10(6) pibs/ml) better during storage than dried formulations with LC(50)s that ranged from 0.39 to 27 x 10(6) pibs/ml. Unformulated virus stock, which is essentially a suspension of virus occlusion bodies in homogenized insect cadavers, did not lose activity when stored at refrigerated or room temperature. We believe that stability of AfMNPV insecticidal activity during storage as dry formulations is related to the general composition of the formulation and that sugar may play a critical role in maintaining insecticidal activity.     

SMOES: a simulation model for the Oosterschelde ecosystem

The model SMOES integrates the results of the ecological research program conducted in the Oosterschelde estuary before and during the construction of a storm surge barrier. Its aim is to provide a quantitative summary of the research findings and to provide a tool for analysis and prediction of the ecosystem in response to human manipulations. This chapter describes model background and formulations. An uncertainty analysis is used to analyze the effect of uncertainties in model parameters on model outcome. The results of the sensitivity analysis are classified by distinguishing groups of model parameters with a qualitatively different effect on model results. Within these groups, a quantitative ranking of the parameters is possible. It appears that the most sensitive parameters represent processes that are relatively little studied in the Oosterschelde, which may provide guidelines for further research.     

Recent advances in formulation and application of entomopathogenic fungi for biocontrol of stored-grain insects

The recent advances in biocontrol of stored-grain insects using formulated and unformulated strains of entomopathogenic fungi (EPF) are reviewed and discussed. Several liquid and dry formulations of EPF strains were developed and used against these insects. However, a literature search revealed lack of any commercially registered product of these formulations. Therefore, in order to achieve an effective control of these insects, the following potential areas of future research have been identified and discussed: (i) screening for new effective strains of EPF, in addition to new effective formulations, (ii) applying the most effective strains and formulations selected in the previous step under storage conditions, (iii) optimising the proportions of ingredients in the selected formulations and (iv) integrating the products of the most effective formulations, after registration and commercialisation, in the integrated pest management programmes of stored-grain insects. Such products would constitute an appropriate alternative control means to synthetic insecticides and fumigants commonly used for control of these insects. The various obstacles pertaining to how the selected EPF products are planned to be used in ‘real world’ in stored-grain protection are also critically discussed.     

Bioavailability of oral drugs and the methods for its improvement

Recent studies in nanotechnology resulted in the development of novel formulations with improved bioavailability. This is especially important for oral administered drugs as the most convenient formulations for administration to patients. The review considers processes occurring in the gastro-intestinal (GI) tract during oral administration of drugs. The increase of bioavailability of the drug may be achieved through designing novel formulations according to the specific drug properties. These include capsules that release pharmaceutical agents at various parts of the GI tract, floating systems that prolong the presence of the drug in stomach, maximally dispersed forms containing surface-active soluble polymers or micelles that carry poor-soluble drugs inside their non-polar core, agents that facilitate tight junction opening, such as caprate and chitosan, and lipid-based formulations. The own data show the stimulating influence of phospholipid nanoparticles on peroral absorption of the drug, indomethacin, in rats and on passage of transport marker and drugs through Caco-2 cell monolayer in vitro. The review summarizes current understanding of factors that influence the bioavailability of the oral drug formulations, currently used models for pharmacokinetic studies, and various approaches to developing novel pharmaceutical formulations that increase the bioavailability of the drugs.