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Critical Parameter (critical + parameter)
Selected AbstractsEffect of chitosan crosslinking on bitterness of artemether using response surface methodologyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2008Punit P. Shah This work examines the influence of various process parameters on artemether entrapped in crosslinked chitosan microparticles for masking bitterness. A central composite design was used to optimize the experimental conditions for bitterness masking. Critical parameters such as the amounts of artemether, chitosan and crosslinking agent have been studied to evaluate how they affect responses such as incorporation efficiency, particle size and drug release at pH 6.8. The desirability function approach has been used to find the best compromise between the experimental results. The optimized microparticles were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Bitterness score was evaluated by human gustatory sensation test. Multiple linear regression analysis revealed that the crosslinking of chitosan significantly affects incorporation efficiency, particle size and drug release at pH 6.8. The bitterness score of microparticles was decreased to 0, compared with 3+ for pure artemether. The proposed method completed masked the bitter taste of artemether. [source] Solid-State Synthesis of Nanocrystalline BaTiO3: Reaction Kinetics and Powder PropertiesJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 9 2008Maria Teresa Buscaglia The formation of BaTiO3 nanoparticles by a solid-state reaction between nanocrystalline raw materials BaCO3 and TiO2 was studied as a function of temperature (400°,800°C), time (1,24 h), and titania particle size (15 and 30 nm). The reaction starts at 500°C and a high reaction rate is already observed at 600°C for the finest titania, with up to 90% conversion after 2 h. Two main reaction stages were observed at 600°,700°C. The first step is dominated by nucleation and growth of BaTiO3 at the TiO2,BaCO3 contact points and at the TiO2 surface. Surface diffusion of BaCO3 is, most likely, the prevailing mass transport mechanism responsible for the rapid formation of BaTiO3, even in the absence of a significant contribution from lattice diffusion. The second stage begins when the residual TiO2 cores are completely covered by the product phase. For longer times, the reaction can only proceed by the slower lattice diffusion, resulting in a strong decrease of the reaction rate. Single-phase BaTiO3 nanopowders with a specific surface area of 12,15 m2/g, an average particle size of 70,85 nm, a relative density of 96.5%,98.3%, and a tetragonality of 1.005 were obtained by calcination at 700°,800°C. Critical parameters in the preparation of ultrafine powders by solid-state reactions are the particle size of both raw materials, the absence of large hard agglomerates, and the homogeneity of the mixture. The use of fine raw materials and optimization of the reaction conditions make mechanical activation unnecessary. [source] Identification of Modal Combinations for Nonlinear Static Analysis of Building StructuresCOMPUTER-AIDED CIVIL AND INFRASTRUCTURE ENGINEERING, Issue 4 2004Sashi K. Kunnath An increasingly popular analytical method to establish these demand values is a "pushover" analysis in which a model of the building structure is subjected to an invariant distribution of lateral forces. Although such an approach takes into consideration the redistribution of forces following yielding of sections, it does not incorporate the effects of varying dynamic characteristics during the inelastic response. Simple modal combination schemes are investigated in this article to indirectly account for higher mode effects. Because the modes that contribute to deformations may be different from the modes that contribute to forces, it is necessary to identify unique modal combinations that provide reliable estimates of both force and deformation demands. The proposed procedure is applied to typical moment frame buildings to assess the effectiveness of the methodology. It is shown that the envelope of demands obtained from a series of nonlinear static analysis using the proposed modal-combination-based lateral load patterns results in better estimation of inter-story drift, a critical parameter in seismic evaluation and design. [source] Quantifying sediment storage in a high alpine valley (Turtmanntal, Switzerland)EARTH SURFACE PROCESSES AND LANDFORMS, Issue 13 2009Jan-Christoph Otto Abstract The determination of sediment storage is a critical parameter in sediment budget analyses. But, in many sediment budget studies the quantification of magnitude and time-scale of sediment storage is still the weakest part and often relies on crude estimations only, especially in large drainage basins (>100,km2). We present a new approach to storage quantification in a meso-scale alpine catchment of the Swiss Alps (Turtmann Valley, 110,km2). The quantification of depositional volumes was performed by combining geophysical surveys and geographic information system (GIS) modelling techniques. Mean thickness values of each landform type calculated from these data was used to estimate the sediment volume in the hanging valleys and the trough slopes. Sediment volume of the remaining subsystems was determined by modelling an assumed parabolic bedrock surface using digital elevation model (DEM) data. A total sediment volume of 781·3×106,1005·7×106,m3 is deposited in the Turtmann Valley. Over 60% of this volume is stored in the 13 hanging valleys. Moraine landforms contain over 60% of the deposits in the hanging valleys followed by sediment stored on slopes (20%) and rock glaciers (15%). For the first time, a detailed quantification of different storage types was achieved in a catchment of this size. Sediment volumes have been used to calculate mean denudation rates for the different processes ranging from 0·1 to 2·6,mm/a based on a time span of 10,ka. As the quantification approach includes a number of assumptions and various sources of error the values given represent the order of magnitude of sediment storage that has to be expected in a catchment of this size. Copyright © 2009 John Wiley & Sons, Ltd. [source] Redox Cycling of Ni-Based Solid Oxide Fuel Cell Anodes: A ReviewFUEL CELLS, Issue 3 2007D. Sarantaridis Abstract The published literature relating to damage to SOFCs caused by redox cycling of Ni-based anodes is reviewed. The review covers the kinetics of Ni oxidation and NiO reduction (as single phases and as constituents of composites with yttria-stabilised zirconia, YSZ), the dimensional changes associated with redox cycling and the effect of this on the mechanical integrity and electrical performance of cells and stacks. A critical parameter is the expansion strain that is caused by oxidation. Several studies report that the first complete oxidation of a Ni/YSZ composite causes a linear expansion of the order of 1%, but the actual values vary substantially between different investigations. The oxidation strain is the result of microstructural irreversibility during the redox process and leads to strain accumulation over several redox cycles. This can cause mechanical disruption to an anode, anode support or other cell components attached to the anode. A simplified mechanical model of the stress and damage that are likely to be caused by anode expansion is proposed and applied to anode-supported, electrolyte-supported and inert substrate-supported cell configurations. This allows the maximum oxidation strain to avoid damage in each configuration to be estimated. [source] Estimates of maximum annual population growth rates (rm) of mammals and their application in wildlife managementJOURNAL OF APPLIED ECOLOGY, Issue 3 2010Jim Hone Summary 1.,The maximum annual population growth rate (rm) is a critical parameter in many models of wildlife dynamics and management. An important application of rm is the estimation of the maximum proportion of a population that can be removed to stop population growth (p). 2.,When rm cannot be estimated in the field, one option is to estimate it from demographic data. We evaluate the use of the relationship between rm and female age at first reproduction (,), which is independent of phylogeny, to estimate rm. We first demonstrate that the relationship between field and demographic estimates of rm is unbiased. We then show that the relationship provides an unbiased and simple method to estimate rm using data for 64 mammal species. We also show that p declines exponentially as , increases. 3.,We use the fitted relationship to estimate annual rm and p for 55 mammal species in Australia and New Zealand for which there are no field estimates of rm. The estimates differ by species but have low precision (wide 95% credible intervals CIs). Our estimate of rm for the Tasmanian devil Sarcophilus harrisii is high (0·6, 95% CI: 0·05,2·39) and suggests devils would become extinct if >0·34 of the population is removed annually (e.g. by facial tumour disease). Our estimate of rm (0·77, 95% CI: 0·71,1·05) for brushtail possum Trichosurus vulpecula is much greater than published estimates and highlights the need for further field estimates of rm for the species in New Zealand. 4.,Synthesis and applications. Since rm has not been estimated in the field for the majority of mammal species, our approach enables estimates with credible intervals for this important parameter to be obtained for any species for which female age at first reproduction is known. However, the estimates have wide 95% CIs. The estimated rm, and associated uncertainty can then be used in population and management models, perhaps most importantly to estimate the proportion that if removed annually would drive the population to extinction. Our approach can be used for taxa other than mammals. [source] Transthoracic Tissue Doppler Imaging of the Atria: A Novel Method to Determine the Atrial Fibrillation Cycle LengthJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2006MATTIAS DUYTSCHAEVER M.D., Ph.D. Background: The atrial fibrillation cycle length (AFCL) is a critical parameter for the perpetuation and termination of AF. In the present study, we evaluated a new method to measure the AFCL based on transthoracic tissue Doppler imaging (TDI) of the right atrium (RA) and left atrium (LA). Methods: Twenty patients with AF (6 acute AF, 14 persistent or permanent AF) were studied. A quadripolar catheter was positioned at RA or LA to measure AFCL (AFCLEGM, gold standard). Transthoracic echocardiography (apical 4-chamber view) was used to perform pulsed wave TDI at the free wall of RA or LA. AFCLTDI was defined as the time interval between two consecutive positive to negative crossings of the baseline of the atrial time velocity curves. AFCLEGM and AFCLTDI were measured at baseline and during a 10-minute infusion of flecainide (1.5 mg/kg). Results: Measurement of AFCLTDI was feasible in all but one patient. At baseline, AFCLEGM was 170 ± 22 ms, AFCLTDI 172 ± 22 ms (difference 2 ± 5 ms). AFCLTDI correlated significantly with AFCLEGM (R = 0.91, P < 0.0001). Bland-Altman analysis showed a bias of ,2 ms with a 95% limit of agreement between ,26 ms and +22 ms. During flecainide, the AFCLTDI method yielded an AFCL prolongation from 176 ± 23 ms at baseline to 279 ± 68 ms (P < 0.01) after 10 minutes of infusion (57 ± 26%). Conclusions: (1) Tissue Doppler imaging of the atria during transthoracic echocardiography can be used to reliably determine the AFCL during both acute and persistent or permanent AF. (2) Continuous measurement of AFCL with TDI can be used to monitor the effect of antiarrhythmic drugs on atrial rate during AF. (3) This novel method is attractive because of the ease of acquiring the data and its noninvasive character. [source] Optimization of in vitro expansion of macaque CD4+ T cells using anti-CD3 and co-stimulation for autotransfusion therapyJOURNAL OF MEDICAL PRIMATOLOGY, Issue 4-5 2006Nattawat Onlamoon Abstract Background, Our laboratory has previously shown that adoptive transfer of in vitro -expanded autologous purified polyclonal CD4+ T cells using anti-CD3/CD28-coated beads induced antiviral responses capable of controlling SIV replication in vivo. Methods, As CD4+ T cells comprise several phenotypic and functional lineages, studies were carried out to optimize the in vitro culture conditions for maximal CD4+ T-cell expansion, survival and delineate the phenotype of these expanded CD4+ T cells to be linked to maximal clinical benefit. Results and Conclusions, The results showed that whereas anti-monkey CD3,/, was able to induce T-cell proliferation and expansion in combination with antibodies against multiple co-stimulatory molecules, monkey CD3, cross reacting antibodies failed to induce proliferation of macaque CD4+ T cells. Among co-stimulatory signals, anti-CD28 stimulation was consistently superior to anti-4-1BB, CD27 or ICOS while the use of anti-CD154 failed to deliver a detectable proliferation signal. Increasing the relative anti-CD28 co-stimulatory signal relative to anti-CD3 provided a modest enhancement of expansion. Additional strategies for optimization included attempts to neutralize free radicals, enhancement of glucose uptake by T cells or addition of T-cell stimulatory cytokines. However, none of these strategies provided any detectable proliferative advantage. Addition of 10 autologous irradiated feeder cells/expanding T cell provided some enhancement of expansion; however, given the high numbers of T cell needed, this approach was deemed impractical and costly, and lower ratios of feeder to expanding T cells failed to provide such benefit. The most critical parameter for efficient expansion of purified CD4+ T cells from multiple monkeys was the optimization of space and culture conditions at culture inception. Finally, anti-CD3/28-expanded CD4+ T cells uniformly exhibited a central memory phenotype, absence of CCR5 expression, marked CXCR4 expression in vitro, low levels of caspase 3 but also of Bcl-2 expression. [source] Data mining of fractured experimental data using neurofuzzy logic,discovering and integrating knowledge hidden in multiple formulation databases for a fluid-bed granulation processJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2008Q. Shao Abstract In the pharmaceutical field, current practice in gaining process understanding by data analysis or knowledge discovery has generally focused on dealing with single experimental databases. This limits the level of knowledge extracted in the situation where data from a number of sources, so called fractured data, contain interrelated information. This situation is particularly relevant for complex processes involving a number of operating variables, such as a fluid-bed granulation. This study investigated three data mining strategies to discover and integrate knowledge "hidden" in a number of small experimental databases for a fluid-bed granulation process using neurofuzzy logic technology. Results showed that more comprehensive domain knowledge was discovered from multiple databases via an appropriate data mining strategy. This study also demonstrated that the textual information excluded in individual databases was a critical parameter and often acted as the precondition for integrating knowledge extracted from different databases. Consequently generic knowledge of the domain was discovered, leading to an improved understanding of the granulation process. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2091,2101, 2008 [source] Effect of agitation intensity on the exo-biopolymer production and mycelial morphology in Cordyceps militarisLETTERS IN APPLIED MICROBIOLOGY, Issue 6 2002J.P. Park Aims:,The influence of agitation intensity on Cordyceps militaris morphology and exo-biopolymer production was investigated in a 5 litre stirred vessel using a six-blade Rushton turbine impeller. Methods and Results:,The mycelial morphology of C. militaris was characterized by means of image analysis, which included mean diameter, circularity, roughness and compactness of the pellets. The morphological parameters of the pellets grown under different stirring conditions were significantly different, which correspondingly altered exo-biopolymer production yields. Conclusions:,The compactness of the pellets was found to be the most critical parameter affecting exo-biopolymer biosynthesis; more compact pellets were formed at 150 rev min,1 with maximum exo-biopolymer production (15 g l,1). Significance and Impact of the Study:,The results of this study suggest that morphological change of pellets is a good indicator for identifying the cell activity for exo-biopolymer production. [source] Parametric study and synthesis of 60-GHz Fabry,Perot resonatorsMICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 4 2002R. Sauleau Abstract The analysis and the synthesis of plane-parallel Fabry,Perot (FP) resonators, illuminated by a normally incident plane wave, are investigated theoretically and experimentally in the 60-GHz band. The reflecting mirrors are inductive metal meshes with square apertures. The frequency response of symmetrical and asymmetric FP cavities is studied (a) approximately with the transmission-line theory (TL), and (b) and rigorously with the Finite-difference,time-domain (FDTD) technique combined with periodic boundary conditions. Then, the inverse problem is solved with the use of an iterative procedure based on the FDTD method. In particular, it is shown theoretically and checked experimentally that the thickness of the cavity is the most critical parameter in the design, although the grid dimensions enable a precise adjustment of the module and of the phase of the internal reflection coefficients. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 34: 247,252, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10429 [source] A novel type of intermittency in a non-linear dynamo in a compressible flowMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2009Erico L. Rempel ABSTRACT The transition to an intermittent mean-field dynamo is studied using numerical simulations of magnetohydrodynamic turbulence driven by a helical forcing. The low-Prandtl number regime is investigated by keeping the kinematic viscosity fixed while the magnetic diffusivity is varied. Just below the critical parameter for the onset of dynamo action, a transient mean field with low magnetic energy is observed. After the transition to a sustained dynamo, the system is shown to evolve through different types of intermittency until a large-scale coherent field with small-scale turbulent fluctuations is formed. Prior to this coherent field stage, a new type of intermittency is detected, where the magnetic field randomly alternates between phases of coherent and incoherent large-scale spatial structures. The relevance of these findings to the understanding of the physics of mean-field dynamo and the physical mechanisms behind intermittent behaviour observed in stellar magnetic field variability are discussed. [source] Reinvestigating hyperpolarized 129Xe longitudinal relaxation time in the rat brain with noise considerationsNMR IN BIOMEDICINE, Issue 3 2008X. Zhou Abstract The longitudinal relaxation time of hyperpolarized (HP) 129Xe in the brain is a critical parameter for developing HP 129Xe brain imaging and spectroscopy and optimizing the pulse sequences, especially in the case of cerebral blood flow measurements. Various studies have produced widely varying estimates of HP 129Xe T1 in the rat brain. To make improved measurements of HP 129Xe T1 in the rat brain and investigate how low signal-to-noise ratio (SNR) contributes to these discrepancies, we developed a multi-pulse protocol during the washout of 129Xe from the brain. Afterwards, we applied an SNR threshold theory to both the multi-pulse protocol and an existing two-pulse protocol. The two protocols yielded mean,±,SD HP 129Xe T1 values in the rat brain of 15.3,±,1.2 and 16.2,±,0.9,s, suggesting that the low SNR might be a key reason for the wide range of T1 values published in the literature, a problem that might be easily alleviated by taking SNR levels into account. Copyright © 2007 John Wiley & Sons, Ltd. [source] Cross-site comparison of herbivore impact on nitrogen availability in grasslands: the role of plant nitrogen concentrationOIKOS, Issue 11 2009E. S. Bakker Herbivores may influence the nitrogen (N) recycling rates and consequently increase or decrease the productivity of grasslands. Plant N concentration emerged as a critical parameter to explain herbivore effects from several conceptual models, which predict that herbivores decrease soil N availability when plant N concentration is low whereas they increase it when plant N concentration is high (Hobbs 1996, Ritchie et al. 1998, Pastor et al. 2006). However, a broader cross-site comparison among published studies to test these predictions is hampered by the different methodologies used to measure soil N availability or a proxy thereof, and a lack of measurements of plant N concentration. Therefore it remains unclear whether these model predictions are generally valid across a range of grasslands. We tested whether there is a relationship between plant N concentration and herbivore impact on soil N availability (measured with resin bags) with a study of replicate 6,8,year old exclosures (with an unfenced control) of vertebrate herbivores (>1,kg) established at each of seven grassland sites in North America and Europe. Contrary to model predictions, we found a negative relationship between the effect of herbivores on resin bag soil N availability and plant N concentration. Our study confirms the importance of plant N concentration as a predictor of herbivore effect on soil N availability across grasslands, but contradicts the models. A possible explanation may be that the results represent a transient situation as the exclosures were relatively young whereas the models may refer to an equilibrium state. Simultaneous measurements of both plant N concentration and herbivore effect on soil N availability from more grassland sites, preferably with contrasting plant N concentrations and including exclosures of different ages, should resolve the contrast between model predictions and our field measurements. [source] Studies on the effect of movement during the cure on the mechanical properties of a silicone building joint sealant,POLYMER ENGINEERING & SCIENCE, Issue 1 2010C.C. White A novel sealant testing device was used to continuously monitor the mechanical properties of a one-part silicone sealant for movement cycles initiated from 10 to 168 h after sample creation. These cure times fall between the proposed RILEM TC-139 technical recommendation of 5 min and the ASTM C719 standard of 21 days. At 10 h of cure, enough crosslinking occurred before testing such that neither the overall movement history of the sample nor the deformation step shapes affected subsequent curing of the sealant. A critical parameter for sealant performance appears to be the extent of cure at the onset of movement. POLYM. ENG. SCI., 2010. © 2009 Society of Plastics Engineers [source] Bridging the gap: A GFP-based strategy for overexpression and purification of membrane proteins with intra and extracellular C-terminiPROTEIN SCIENCE, Issue 4 2010Jennifer M. Hsieh Abstract Low expression and instability during isolation are major obstacles preventing adequate structure-function characterization of membrane proteins (MPs). To increase the likelihood of generating large quantities of protein, C-terminally fused green fluorescent protein (GFP) is commonly used as a reporter for monitoring expression and evaluating purification. This technique has mainly been restricted to MPs with intracellular C-termini (Cin) due to GFP's inability to fluoresce in the Escherichia coli periplasm. With the aid of Glycophorin A, a single transmembrane spanning protein, we developed a method to convert MPs with extracellular C-termini (Cout) to Cin ones providing a conduit for implementing GFP reporting. We tested this method on eleven MPs with predicted Cout topology resulting in high level expression. For nine of the eleven MPs, a stable, monodisperse protein-detergent complex was identified using an extended fluorescence-detection size exclusion chromatography procedure that monitors protein stability over time, a critical parameter affecting the success of structure-function studies. Five MPs were successfully cleaved from the GFP tag by site-specific proteolysis and purified to homogeneity. To address the challenge of inefficient proteolysis, we explored expression and purification conditions in the absence of the fusion tag. Contrary to previous studies, optimal expression conditions established with the fusion were not directly transferable for overexpression in the absence of the GFP tag. These studies establish a broadly applicable method for GFP screening of MPs with Cout topology, yielding sufficient protein suitable for structure-function studies and are superior to expression and purification in the absence GFP fusion tagging. [source] Determination of physical behaviour of feed pellets in Mediterranean waterAQUACULTURE RESEARCH, Issue 2 2006Paolo Vassallo Abstract Settled uneaten feed causes the most intense impact under sea cages, and settling velocity of the feed pellets represents a key parameter for waste dispersion models. Even if some data about physical properties of feed pellets have been published in the framework of salmonid rearing, there is a complete lack of information related to the Mediterranean Sea, as regards typical values of temperature, salinity and feed composition for Gilthead Sea Bream (Sparus aurata L.) and Sea Bass (Dicentrarchus labrax L.). In this study we try to fill this lack, determining dimensions, water adsorption properties, floating times and settling velocities of a typical growing sequence of pellets for the species mentioned above, under defined laboratory conditions reproducing Mediterranean Sea water. The settling velocity increases with pellet size from 0.087, for the smallest pellet (3 mm), to 0.144 m s,1, for the 5 mm pellet. The biggest extruded pellet (6 mm) falls slower (0.088 m s,1). The floating time before pellet's fall is found to be a critical parameter in determining settling velocity. The latter depends on pellet's size, water temperature and salinity. The examined pellets reach a 42% of weight increase after 10 min of immersion, while no appreciable dimension change is observed. Our results are in part different from previous ones and could play a role in evaluating and modelling Mediterranean aquaculture environmental impact. [source] Evaluation of a critical process parameter: Oxygen limitation during cultivation has a fully reversible effect on gene expression of Bordetella pertussisBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009Mathieu Streefland Abstract Modern (bio)pharmaceutical process development requires thorough investigation of all process parameters that are critical to product quality. The impact of a disturbance of such a parameter during processing needs to be known so that a rational decision can be made about the release of the product. In cultivation processes the dissolved oxygen (DO) concentration is generally accepted as being a critical parameter. In this article the impact of a 90 min period of oxygen limitation during the cultivation of the strictly aerobic Bordetella pertussis bacterium is investigated. The cultivation is the most important process step for the manufacturing of a vaccine against whooping cough disease. Samples were taken immediately before and after oxygen limitation and at the end of cultivation of four oxygen limited and three control cultivations. DNA microarray analysis of the full transcriptome of the B. pertussis bacterium revealed that a 90 min period of oxygen limitation has a substantial effect on overall gene expression patterns. In total 104 genes were identified as a significant hit at any of the sample points, of which 58 were directly related to oxygen limitation. The other genes were mainly affected towards the end of cultivation. Of all genes involved in oxygen limitation none were identified to show a significant difference between the oxygen limited and control cultivations at the end of the batch. This indicates a fully reversible effect of oxygen limitation on gene expression. This finding has implications for the risk assessment of dissolved oxygen concentration as a critical process parameter. Biotechnol. Bioeng. 2009;102: 161,167. © 2008 Wiley Periodicals, Inc. [source] Framework for the Rapid Optimization of Soluble Protein Expression in Escherichia coli Combining Microscale Experiments and Statistical Experimental DesignBIOTECHNOLOGY PROGRESS, Issue 4 2007R. S. Islam A major bottleneck in drug discovery is the production of soluble human recombinant protein in sufficient quantities for analysis. This problem is compounded by the complex relationship between protein yield and the large number of variables which affect it. Here, we describe a generic framework for the rapid identification and optimization of factors affecting soluble protein yield in microwell plate fermentations as a prelude to the predictive and reliable scaleup of optimized culture conditions. Recombinant expression of firefly luciferase in Escherichia coli was used as a model system. Two rounds of statistical design of experiments (DoE) were employed to first screen (D-optimal design) and then optimize (central composite face design) the yield of soluble protein. Biological variables from the initial screening experiments included medium type and growth and induction conditions. To provide insight into the impact of the engineering environment on cell growth and expression, plate geometry, shaking speed, and liquid fill volume were included as factors since these strongly influence oxygen transfer into the wells. Compared to standard reference conditions, both the screening and optimization designs gave up to 3-fold increases in the soluble protein yield, i.e., a 9-fold increase overall. In general the highest protein yields were obtained when cells were induced at a relatively low biomass concentration and then allowed to grow slowly up to a high final biomass concentration, >8 g·L,1. Consideration and analysis of the model results showed 6 of the original 10 variables to be important at the screening stage and 3 after optimization. The latter included the microwell plate shaking speeds pre- and postinduction, indicating the importance of oxygen transfer into the microwells and identifying this as a critical parameter for subsequent scale translation studies. The optimization process, also known as response surface methodology (RSM), predicted there to be a distinct optimum set of conditions for protein expression which could be verified experimentally. This work provides a generic approach to protein expression optimization in which both biological and engineering variables are investigated from the initial screening stage. The application of DoE reduces the total number of experiments needed to be performed, while experimentation at the microwell scale increases experimental throughput and reduces cost. [source] Mitochondrial Membrane Potential Selects Hybridomas Yielding High Viability in Fed-Batch CulturesBIOTECHNOLOGY PROGRESS, Issue 1 2002Brian D. Follstad Prior research (Follstad, B. D.; Wang, D. I. C.; Stephanopoulos, G. Mitochondrial membrane potential differentiates cells resistant to apoptosis in hybridoma cultures. Eur. J. Biochem. 2000, 267, 6534,6540.) identified mitochondrial membrane potential (MMP) as a marker of hybridoma subpopulations resistant to apoptosis caused by a variety of apoptosis inducers. In this study, we investigated the viability of hybridoma cell cultures inoculated with cells of varying MMP in regular fed-batch operation. A hybridoma cell population was separated using FACS into subpopulations based on their mean mitochondrial membrane potential (MMP) as measured using the common mitochondrial stain, Rhodamine 123 (Rh123). These subpopulations showed dramatic differences in their apoptotic death kinetics. Fed-batches inoculated with a high MMP subpopulation reached higher viable cell concentrations and viabilities that were maintained for prolonged periods of time relative to fed-batches inoculated with low MMP subpopulations. These results underline the heterogeneous nature of hybridoma cell cultures and suggest that mitochondrial physiology is a critical parameter determining culture performance. [source] Structural, Dynamic Properties of Key Residues in A, Amyloidogenesis: Implications of an Important Role of Nanosecond Timescale DynamicsCHEMBIOCHEM, Issue 11 2007Kwang Hun Lim Prof. Dr. Flexibility exercise. NMR studies of the A,(1,40) and -(1,42) peptides demonstrated that structural, dynamic properties of soluble monomeric A, peptides are highly correlated to the amyloid fibril structure. In particular, fast-timescale dynamics were found to be an additional critical parameter in identifying the more crucial aggregation-prone segments of A, peptides (see figure). This method can be applied to investigate amyloidogenic and nonamyloidogenic properties of disordered states of proteins. [source] A General Approach to First Order Phase Transitions and the Anomalous Behavior of Coexisting Phases in the Magnetic CaseADVANCED FUNCTIONAL MATERIALS, Issue 6 2009Sergio Gama Abstract First order phase transitions for materials with exotic properties are usually believed to happen at fixed values of the intensive parameters (such as pressure, temperature, etc.) characterizing their properties. It is also considered that the extensive properties of the phases (such as entropy, volume, etc.) have discontinuities at the transition point, but that for each phase the intensive parameters remain constant during the transition. These features are a hallmark for systems described by two thermodynamic degrees of freedom. In this work it is shown that first order phase transitions must be understood in the broader framework of thermodynamic systems described by three or more degrees of freedom. This means that the transitions occur along intervals of the intensive parameters, that the properties of the phases coexisting during the transition may show peculiar behaviors characteristic of each system, and that a generalized Clausius,Clapeyron equation must be obeyed. These features for the magnetic case are confirmed, and it is shown that experimental calorimetric data agree well with the magnetic Clausius,Clapeyron equation for MnAs. An estimate for the point in the temperature-field plane where the first order magnetic transition turns to a second order one is obtained (the critical parameters) for MnAs and Gd5Ge2Si2 compounds. Anomalous behavior of the volumes of the coexisting phases during the magnetic first order transition is measured, and it is shown that the anomalies for the individual phases are hidden in the behavior of the global properties as the volume. [source] EFFECTS OF APPLICATION PARAMETERS AND ADJUVANTS ON THE FOLIAR SURVIVAL AND PERSISTENCE OF ENTOMOPATHOGENIC NEMATODE STEINERNEMA CARPOCAPSAE ALL STRAIN ON CABBAGESINSECT SCIENCE, Issue 2 2004Yong-ling Jin Abstract, Effects of the critical parameters (spray pressure, the distance between a sprayer and the sprayed plant, the concentration of infective juveniles (Us), volumes of the sprayed suspension of IJs, the temperature and humidity combinations) and the addition of various adjuvants on the survival and persistence of entomopathogenic nematode Steinernema carpocapsae All strain on leaf surfaces of the Chinese cabbage Brassica pekingensis were determined. The results showed that (1) The pressure of a sprayer had negative influence on the persistence of IJs on the leaf. (2) The numbers of the living IJs collected on the leaf significantly increased with the IJ dosages applied on the leaf when the dosage was over 2 000 IJs per mL. (3) More IJs (from 10.1 IJs/cm2 to 45.5 IJs/cm2) were collected on the leaf when more volumes of IJ suspension (from 3.3 mL to 19.8 mL) were sprayed. However, when the highest volume of IJ suspension was used, the IJ numbers collected did not increase. (4) In general, the survival of the IJs on the leaf decreased with the exposure time. (5) The formulation of IJs by adding xanthan gum, a sticker and detergent surfactant enhanced the survival and persistence of IJs. The number of living IJs on the leaf with 0.3 % of xanthan gum was 150 times higher than that of the IJs with water alone. IJ suspensions with different concentrations of glycerin and with 0.5 % molasses and 0.01 % detergent surfactant showed similar effects. [source] Global flow instability in a lid-driven cavityINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 8 2010V. B. L. Boppana Abstract The stability of flow in a lid-driven cavity is investigated using an accurate numerical technique based on a hybrid scheme with spectral collocation and high-order finite differences. A global stability analysis is carried out and critical parameters are identified for various aspect ratios. It is found that while there is reasonable agreement with the literature for the critical parameters leading to loss of stability for the square cavity, there are significant discrepancies for cavities of aspect ratios 1.5 and 2. Simulations of the linearized unsteady equations confirm the results from the global stability analysis for aspect ratios A = 1, 1.5 and A = 2. Copyright © 2009 John Wiley & Sons, Ltd. [source] Energy consideration for designing supercharged ram jet enginesINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 2 2008Amro M. Al-QutubArticle first published online: 20 JUN 200 Abstract The present work investigates the energy considerations and performance characteristics of a newly proposed supercharged ram jet engine. Thermodynamics and fluid mechanics analyses were developed to predict specific thrust, thrust-specific fuel consumption (TSFC), overall efficiency, and thrust-to-weight ratio of the engine. Compressor pressure ratio and efficiency, combustor temperature, and pressure losses in the burner and nozzle are considered as primary variables in the engine performance analysis. Performance characteristics are calculated to illustrate the effect of each parameter independently at different flight speeds. This is done while maintaining other parameters at given typical operating values. A computer program was developed to perform the iterative calculations. Results indicate that the compressor pressure ratio and the combustion product temperature are the most critical parameters in determining the performance of the engine. At compressor pressure ratio of 1.15,1.2, the typical static thrust-to-weight ratio is at maximum. Increasing combustion product temperature increases the thrust-to-weight ratio as well as TSFC. Finally, newly developed high power-to-weight ratio IC engine makes it possible for the supercharged ram jet engine to achieve high performance, in terms of thrust-to-weight ratio and TSFC. Copyright © 2007 John Wiley & Sons, Ltd. [source] A fracture-mechanics-based approach to fracture control in biomedical devices manufactured from superelastic Nitinol tubeJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2008S. W. Robertson Abstract Several key fracture-mechanics parameters associated with the onset of subcritical and critical cracking, specifically the fracture toughness, crack-resistance curve, and fatigue threshold, have recently been reported for the superelastic alloy Nitinol, in the product form of the thin-walled tube that is used to manufacture several biomedical devices, most notably endovascular stents. In this study, we use these critical parameters to construct simple decision criteria for assessing the quantitative effect of crack-like defects in such Nitinol devices with respect to their resistance to failure by deformation or fracture. The criteria are based on the (equivalent) crack-initiation fracture toughness and fatigue threshold stress-intensity range, together with the general yield strength and fatigue endurance strength, and are used to construct a basis for design against single-event (overload) failures as well as for time-/cycle-delayed failures associated with fatigue. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2008 [source] One-Dimensional Rabbit Sinoatrial Node Models:JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2003Benefits, Limitations Introduction: Cardiac multicellular modeling has traditionally focused on ventricular electromechanics. More recently, models of the atria have started to emerge, and there is much interest in addressing sinoatrial node structure and function. Methods and Results: We implemented a variety of one-dimensional sinoatrial models consisting of descriptions of central, transitional, and peripheral sinoatrial node cells, as well as rabbit or human atrial cells. These one-dimensional models were implemented using CMISS on an SGI® Origin® 2000 supercomputer. Intercellular coupling parameters recorded in experimental studies on sinoatrial node and atrial cell-pairs under-represent the electrotonic interactions that any cardiomyocyte would have in a multidimensional setting. Unsurprisingly, cell-to-cell coupling had to be scaled-up (by a factor of 5) in order to obtain a stable leading pacemaker site in the sinoatrial node center. Further critical parameters include the gradual increase in intercellular coupling from sinoatrial node center to periphery, and the presence of electrotonic interaction with atrial cells. Interestingly, the electrotonic effect of the atrium on sinoatrial node periphery is best described as opposing depolarization, rather than necessarily hyperpolarizing, as often assumed. Conclusion: Multicellular one-dimensional models of sinoatrial node and atrium can provide useful insight into the origin and spread of normal cardiac excitation. They require larger than "physiologic" intercellular conductivities in order to make up for a lack of "anatomical" spatial scaling. Multicellular models for more in-depth quantitative studies will require more realistic anatomico-physiologic properties. (J Cardiovasc Electrophysiol, Vol. 14, pp. S121-S132, October 2003, Suppl.) [source] LETHALITY CONTRIBUTION FROM THE TUBULAR HEAT EXCHANGER DURING HIGH-TEMPERATURE SHORT-TIME PROCESSING OF A MODEL LIQUID FOODJOURNAL OF FOOD PROCESS ENGINEERING, Issue 4 2004G.B. AWUAH ABSTRACT Experiments were conducted using Bacillus stearothermophilus spores in 0.5% w/w carboxymethylcellulose suspension to evaluate come-up contributions from the tubular heat exchanger. A lab-scale UHT/HTST simulator that allowed samples to be collected at the exit of the heat exchanger and holding tube was used with operating temperatures up to 270F. The bulk mean residence time in the heat exchanger ranged from 30 to 89 sec, while that in the holding tube ranged from 4 to 14 sec. It was observed that between 40% and 51% of the cumulative lethality () at the exit of the holding tube, was contributed by come-up in the tubular heat exchanger. This come-up contribution was determined on the basis of having anof 8.5 min in the holding tube alone. It was evident that come-up lethality will depend on product initial temperature, residence time and temperature history in the heat exchanger, with higher temperatures obviously contributing more lethality. Therefore, the entire aseptic system becomes even more complex since several critical parameters need to be monitored, controlled and documented. Experimental data compared favorably with computer-simulated data using the AseptiCALÔ software, with the software package giving more conservative results. Ultimately, come-up credit (CUC) should be tested on a pilot scale or industrial setup by way of reduced residence time (i.e. increased fluid flow rate), reduced holding tube length or temperature in order to determine if CUC can be applied towards the lethality required for the product. Monitoring and control devices become critical to ensure consistency and reproducibility in product residence time and time,temperature history, in the tubular heat exchanger. [source] Optimum design of cyclone separatorAICHE JOURNAL, Issue 9 2009Prabhata K. Swamee Abstract Cyclone separators are one of the most widely used gas-solid separators. Although the optimal design of cyclone separators has been suggested earlier, the earlier works do not include all the critical parameters responsible for minimizing the pressure drop which is quite decisive to obtain a correct optimal design. In this article, the optimal design of the cyclone separator has been formulated as a geometric programming with a single degree of difficulty. The solution of the problem yields the optimum values of the number of cyclones to be used in parallel, and the inside diameter of cyclone shell and exit pipe, when a specified flow rate of gas is to be separated from solid particles, when the cut diameter is already specified. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Mechanics of column beds: II.AICHE JOURNAL, Issue 3 2003Modeling of coupled stress-strain-flow behavior The rheological behavior of a bed of packing material during its consolidation was investigated using an elastic-plastic model, the Frictional Material Model. This model takes into account the behavior of the packing material under compression stress, its consolidation, its internal friction, its friction against the column wall, and the dependence of the bed's permeability on the local void fraction. The complexity of the problem arises from the nonlinear behavior of the relationships between the critical parameters controlling the column bed behavior and the external stresses applied to this bed. Solutions of the model were calculated for combinations of axial compression and seepage stresses, the latter corresponding to the flow of the mobile-phase stream under typical conditions used in HPLC. The results demonstrate the importance of the internal angle of friction of the packing material used on the degree of radial and axial heterogeneity of the beds of chromatographic columns packed with this material. [source] | ||||||||||||||||||||||||||||||||||||||||