Minor Changes In Parameters Research Articles

DEVELOPMENT AND VALIDATION OF ANALYTICAL METHOD FOR SIMULTANEOUS ESTIMATION OF TENELIGLIPTIN HYDROBROMIDE HYDRATE, PIOGLITAZONE HYDROCHLORIDE, AND METFORMIN HYDROCHLORIDE IN PHARMACEUTICAL DOSAGE FORM

A simple, precise, and accurate RP-HPLC method was developed and validated for the simultaneous estimation of TENE, PIO, and MET in pharmaceutical formulations as per ICH guidelines. The analytical wavelength utilized was 254.8 nm with linearity ranges of 1-6 μg/mL (TENE), 0.75-4.5 μg/mL (PIO), and 25-150 μg/mL (MET). Good linearity was demonstrated by the regression equations and correlation coefficients (r2 > 0.9985). Percentage recovery studies at 80%, 100%, and 120% levels showed mean recoveries within 99.5-102.3% (TENE), 99.4-102.2% (PIO), and 99.2-100.4% (MET) with relative standard deviation (RSD) < 1.4%, indicating accuracy. Precision was evaluated by intraday, interday, and repeatability studies, revealing RSD < 1.7% (TENE), < 0.9% (PIO), and < 1.1% (MET), suggesting good precision. Limits of detection were 0.242 μg/mL (TENE), 0.150 μg/mL (PIO), and 0.143 μg/mL (MET), while limits of quantitation were 0.732, 0.454, and0.434 μg/mL, respectively. The robustness of the RP-HPLC method was evaluated using a fractional factorial design by varying method parameters such as flow rate, mobile phase composition, and detection wavelength. The results demonstrated the method's resilience to minor parameter changes, indicating its robustness.

4D chaotic system-based secure data hiding method to improve robustness and embedding capacity of videos

Chaotic systems are used in various applications due to their high security and complexity. Because minor changes in parameters have a significant effect on the output values and the dynamic behavior of the system. Besides, security and robustness are the most important requirements of data hiding. Therefore, in this paper, it is proposed to use chaos-based data hiding for videos. The merits of the proposed method are selection of embedding location with robust system, increasing the secret data capacity, and keep the visual quality, which are in trade-off for existing methods. Because, in the existing methods the secret message is embedded into pixels of a consecutive, a selected or a random frame. Another deficiency of existing methods is embedding capacity. They embed fewer secret data to keep the visual quality of the stego object. However, compared to the drawback of existing literature, in the proposed method the secret message is embedded in entire video with 4D chaotic system, which is also an important novelty of this paper.The proposed method evaluated by objective criteria and achieved valuable results. The histogram analysis proves our method is undetectable. For different high ratios of embedding capacity, the visual quality of the stego videos is high where the average PSNR is about 55 dB, and MS-SSIM is closed to 1. The proposed method's results compared chaotic and non-chaotic video steganography methods. Our methods achieve 54.92 dB for embedding ratio 8.08% where the results are 53.57 dB and 5% for the best existing non-chaotic method and 49.99 dB and 0.001% for the best chaotic method, for similar capacity the proposed method gives superior visual performance over the chaotic literature. Finally, the robustness analysis with pixel value attack and lsb attack shows the proposed method appears to be resistant to these types of attacks.

Arnold’s potentials and quantum catastrophes

In the Thom’s approach to the classification of instabilities in one-dimensional classical systems every equilibrium is assigned a local minimum in one of the Arnold’s benchmark potentials V(k)(x)=xk+1+c1xk−1+…. We claim that in quantum theory, due to the tunneling, the genuine catastrophes (in fact, abrupt “relocalizations” caused by a minor change of parameters) can occur when the number N of the sufficiently high barriers in the Arnold’s potential becomes larger than one. A systematic classification of the catastrophes is then offered using the variable mass term ħ2∕(2μ), odd exponents k=2N+1 and symmetry assumption V(k)(x)=V(k)(−x). The goal is achieved via a symbolic-manipulation-based explicit reparametrization of the couplings cj. At the not too large N, a surprisingly user-friendly recipe for a systematic determination of parameters of the catastrophes is obtained and discussed.

Static and dynamic optimization of a pose adjusting mechanism considering parameter changes during construction

Abstract Having potentially high stiffness and good dynamic response, a parallel pose adjusting mechanism was proposed for being an attachment to a big serial robot of a macro-micro robotic system. This paper addresses its design optimization problem mainly concerning arrangements of design variables and objectives. Parameter changes during construction are added to the design variables in order to prevent the negative effects to the physical prototype. These parameter changes are interpreted as parameter uncertainty and modeled by probabilistic theory. For the objectives, both static and dynamic performances are simultaneously optimized by Pareto-based method. The involved performance indices are instantaneous energy based stiffness index, first natural frequency and execution mass. The optimization procedure is implemented as: (1) carrying out performance modeling and defining performance indices, (2) reformulating statistical objectives and probabilistic constraints considering parameter uncertainty, (3) conducting Pareto-based optimization with the aid of response surface method (RSM) and particle swarm optimization (PSO), (4) selecting optimal solution by searching for cooperative equilibrium point (CEP). By addressing parameter uncertainty and the best compromise among multiple objectives, the presented optimization procedure provides more reliable optimal parameters that would not be affected by minor parameter changes during construction, and less biased optimum between static and dynamic performances comparing with the conventional optimization methods. The proposed optimization method can also be applied to the other similar mechanisms.

Methodology of the process design of gross product output of an enterprise

The methods for designing the process of gross product output of an enterprise, based on the stochastic method of dynamic programming for continuous deterministic systems was created. The selection of weight factors of quadratic quality functional was substantiated, the dependence between parameters of design and weight factors was established, and the region of optimum values of design parameters was determined, the optimal filter of the process of gross product output of an enterprise was obtained. Modeling of the process of gross product output with optimum values of coefficients of growth and retirement of basic production assets. Production capacity is determined by the output at the achieved level of organization and production technology. The shape of production capacity graphs changes noticeably even with minor changes in parameters, i.e., capacity is sensitive to changes in the state of a firm. Design parameters are determined by the matrix method of dynamic programming. Based on the concepts of observability and controllability, it has been established that the process of producing a gross product of an enterprise is subject to management. By modeling and calculations, it was proved that using the matrix method of dynamic programming, one can obtain analytical dependencies for growth and retirement coefficients, as well as calculate the regions of their optimal values, i.e. The production capacity of an enterprise can be the main indicator of the characteristics of the life cycle of an enterprise. The technique should be used when designing the process of producing a gross product of enterprises, its implementation will reduce the design time and ensure the stability of the process of producing a gross product.

Coulometric trace humidity measurement in technical gases.

Trace humidity was measured by using miniaturized planar coulometric sensors in technical gases such as hydrogen, nitrogen, helium, nitrous oxide, and synthetic air. Frost point temperatures in the gases ranged from -60 °C to -30 °C, which is equivalent to a vapour mole fraction from 10 μmol mol-1 to 376 μmol mol-1. In addition, the generated humidity was determined by using a precision dew point hygrometer as reference. Nonlinear calibration functions were calculated that correlated electric current (sensor signal) and reference humidity. Parameters of functions were tested with one-way analysis of variances (ANOVA) to prove if all used sensors had a similar behavior in the same gas during experiments. Results of ANOVA confirmed that averaged functions can be applied for trace humidity measurement in nitrogen, helium, nitrous oxide, and synthetic air. The calculated functions were negligibly different for nitrogen, helium, and synthetic air. In humidified nitrous oxide, a minor change of parameters was observed due to lower electrical currents. In total contrast to that, the measured sensor signals were significantly higher in humidified hydrogen and each sensor required its own calibration function. The reason was a recombination effect that favoured multiple measurements of water molecules. Nevertheless, it was possible to measure continuously trace humidity in all tested gases by using coulometric sensors with an expanded uncertainty below 2 K (k = 2).

Large Amplitude Oscillatory Shear Rheology of Living Fibroblasts: Path-Dependent Steady States

Mechanical properties of biological cells play a role in cell locomotion, embryonic tissue formation, and tumor migration among many other processes. Cells exhibit a complex nonlinear response to mechanical cues that is not understood. Cells may stiffen as well as soften, depending on the exact type of stimulus. Here we apply large-amplitude oscillatory shear to a monolayer of separated fibroblast cells suspended between two plates. Although we apply identical steady-state excitations, in response we observe different typical regimes that exhibit cell softening or cell stiffening to varying degrees. This degeneracy of the cell response can be linked to the initial paths that the instrument takes to go from cell rest to steady state. A model of cross-linked, force-bearing filaments submitted to steady-state excitation renders the different observed regimes with minor changes in parameters if the filaments are permitted to self-organize and form different spatially organized structures. We suggest that rather than a complex viscoelastic or plastic response, the different observed regimes reflect the emergence of different steady-state cytoskeletal conformations. A high sensitivity of the cytoskeletal rheology and structure to minor changes in parameters or initial conditions enables a cell to respond to mechanical requirements quickly and in various ways with only minor biochemical intervention. Probing path-dependent rheological changes constitutes a possibly very sensitive assessment of the cell cytoskeleton as a possible tool for medical diagnosis. Our observations show that the memory of subtle differences in earlier deformation paths must be taken into account when deciphering the cell mechanical response to large-amplitude deformations.

Improving tablet coating robustness by selecting critical process parameters from retrospective data

Context: Although tablet coating processes are widely used in the pharmaceutical industry, they often lack adequate robustness. Up-scaling can be challenging as minor changes in parameters can lead to varying quality results.Objective: To select critical process parameters (CPP) using retrospective data of a commercial product and to establish a design of experiments (DoE) that would improve the robustness of the coating process.Materials and methods: A retrospective analysis of data from 36 commercial batches. Batches were selected based on the quality results generated during batch release, some of which revealed quality deviations concerning the appearance of the coated tablets. The product is already marketed and belongs to the portfolio of a multinational pharmaceutical company.Results: The Statgraphics 5.1 software was used for data processing to determine critical process parameters in order to propose new working ranges.Discussion and conclusions: This study confirms that it is possible to determine the critical process parameters and create design spaces based on retrospective data of commercial batches. This type of analysis is thus converted into a tool to optimize the robustness of existing processes. Our results show that a design space can be established with minimum investment in experiments, since current commercial batch data are processed statistically.

The Rate Equation for Oxygen Evolution by Decomposition of LixCoO2 at Elevated Temperatures

The oxygen evolution from Li0.5CoO2 cathodes at elevated temperatures was investigated by mass spectrometry coupled with thermogravimetry (TG-MS). The rate equation for the oxygen evolution from Li0.5CoO2 (particle diameters: 1−5 μm) was found to be dα/dt = 1.88 × 108 (exp(-114 × 1000/RT))(1- α)1.62, where α is the fractional degree of conversion of reactants; the values obtained using this equation showed a good agreement with the experimental ones for the dependency of the oxygen evolution speed on the temperature rising speed. With minor parameter changes of the rate equation, the equations could explain the dependence of the oxygen evolution speed on x in LixCoO2. Nano-sized Li0.5CoO2 (particle diameters: 200–400 nm) was prepared and the influence of the particle size on the oxygen evolution speed was investigated. The nano-sized Li0.5CoO2 showed a shift of the onset temperatures of O2 evolution from 240°C to 210°C. When the frequency factor is optimized, the values calculated using the modified equation were coincident with the experimental ones for the nano-sized Li0.5CoO2.

A Phase Transition in Energy-Filtered RNA Secondary Structures

In this article we study the effect of energy parameters on minimum free energy (mfe) RNA secondary structures. Employing a simplified combinatorial energy model that is only dependent on the diagram representation and is not sequence-specific, we prove the following dichotomy result. Mfe structures derived via the Turner energy parameters contain only finitely many complex irreducible substructures, and just minor parameter changes produce a class of mfe structures that contain a large number of small irreducibles. We localize the exact point at which the distribution of irreducibles experiences this phase transition from a discrete limit to a central limit distribution and, subsequently, put our result into the context of quantifying the effect of sparsification of the folding of these respective mfe structures. We show that the sparsification of realistic mfe structures leads to a constant time and space reduction, and that the sparsification of the folding of structures with modified parameters leads to a linear time and space reduction. We, furthermore, identify the limit distribution at the phase transition as a Rayleigh distribution.

Sensory Irritation Response in Rats II: Recovery and Dose-Dependence

Inhaled irritants can cause respiratory depression by simulating trigeminal nerves in the nasal cavity. This decrease in inhalation rate results in a decrease in the rate of the irritant gases flowing to the stimulated nerves, creating a complex feedback response. Previously, a model was created to describe how the presence of formaldehyde affects respiration in the rat. This ordinary differential equation model incorporated a model of the physiology of the upper respiratory tract of the rat and a model of the neurological control of the respiration rate due to signaling from the stimulated nerves in the nasal cavity. However, an optimal fit to data was not fully established. In the current study, the fit of the previously established model is reevaluated while incorporating the recovery of the ventilation rate after the end of exposure. Additionally, the dose-dependence of the adaptation time allowed by the previous model is more fully quantified, and the updated model predicts formaldehyde data well. Not only are the results of the previous study improved, the model is also shown to predict ventilation decrease in response to other irritants, specifically acrolein, ammonia, and sulfur dioxide. The model is expected to translate to predictions of other irritants with minor parameter changes.

Evaluation of Snow Albedo in Land Models for Weather and Climate Studies

Abstract Snow albedo plays an important role in land models for weather, climate, and hydrometeorological studies, but its treatment in various land models still contains significant deficiencies. Complementary to previous studies that evaluated the snow albedo as part of an overall land model study, the snow albedo formulations as used in four major weather forecasting and climate models [European Centre for Medium-Range Weather Forecasts (ECMWF), National Centers for Environmental Prediction (NCEP) “Noah” land model, National Center for Atmospheric Research (NCAR) Community Land Model (CLM3), and NCEP global model] were directly evaluated here using multiyear Boreal Ecosystem–Atmosphere Study (BOREAS) in situ data over grass and forest sites. First, four idealized cases over grass and forest sites were designed to understand better the different albedo formulations in these models. Then the BOREAS data were used to evaluate snow albedo and relevant formulations and to identify deficiencies of each model. Based on these analyses, suggestions that involve only minor changes in parameters or formulations were made to significantly reduce these deficiencies of each model. For the ECMWF land model, using the square root of snow water equivalent (SWE), rather than SWE itself, in the computation of snow fraction would significantly reduce the underestimation of albedo over grass. For the NCEP Noah land model, reducing (increasing) the critical SWE for full snow cover over short (tall) vegetation would reduce the underestimate (overestimate) of snow albedo over the grass (forest) site. For the NCAR CLM3, revising the coefficient used in the ground snow-fraction computation would substantially reduce the albedo underestimation over grass. For the albedo formulations in the NCEP global model, replacing the globally constant fresh snow albedo by the vegetation-type-dependent Moderate-Resolution Imaging Spectroradiometer (MODIS) maximum snow albedo would significantly improve the overestimation of model albedo over forest.

γ-Mn at the border between weak and strong correlations

We investigate the role of magnetic fluctuations in the spectral properties of paramagnetic gamma-Mn. Two methods are employed. The Local Density Approximation plus Dynamical Mean-Field Theory together with the numerically exact quantum Monte-Carlo solver is used as a reference for the spectral properties. Then the same scheme is used with the computationally less demanding perturbative spin-polarized fluctuation-exchange solver in combination with the Disordered Local Moment approach, and photoemission spectra are calculated within the one-step model. It is shown that the formation of local magnetic moments in gamma-Mn is very sensitive to the value of Hund's exchange parameter. Comparison with the experimental photoemission spectra demonstrates that gamma-Mn is a strongly correlated system, with the Hubbard band formation, which cannot be described by the perturbative approach. However, minor change of parameters would transform it into a weakly correlated system.

High- versus low-dose fluconazole therapy for empiric treatment of suspected invasive candidiasis among high-risk patients in the intensive care unit: a cost-effectiveness analysis

ABSTRACTBackground: High-dose fluconazole is an alternative for patients with candidemia caused by Candida glabrata or other Candida species with decreased fluconazole susceptibility. However, empiric high-dose fluconazole is not currently recommended and may result in higher drug costs and toxicity.Objective: To determine the cost-effectiveness of using empiric high-dose fluconazole in intensive care unit (ICU) with suspected invasive candidiasis.Design: Decision analytic model. Target population: ICU patients with suspected invasive candidiasis. Time horizon: Lifetime. Perspective: Societal.Interventions: Low-dose fluconazole (loading dose of 800 mg followed by 400 mg daily) vs. high-dose fluconazole (loading dose of 1600 mg followed by 800 mg daily). Generic fluconazole costs were used for the analysis. Outcome measures: Incremental life expectancy and incremental cost per discounted life year (DLY) saved.Result of base-case analysis: Based on current national levels of fluconazole resistance and ability to correctly identify patients with candidemia, high-dose fluconazole was the more effective but more expensive treatment strategy. Empiric high-dose fluconazole therapy decreased the mortality rate by 0.15% compared to low-dose strategy with a cost-effectiveness rate of $55 526 per DLY saved.Results of sensitivity analysis: Empirical high-dose fluconazole was an acceptable treatment strategy (using $100 000 per DLY saved as threshold) unless the physical age of an ICU survivor was 66 years or older. Empirical high-dose fluconazole was an acceptable treatment strategy using $50 000 per DLY saved with minor changes in parameters estimates.Limitations: The estimates of our model may not be applicable to all ICU patients. Other hospitals with differences in fluconazole resistance, prevalence of invasive candidiasis, or duration of fluconazole therapy may produce different results.Conclusion: These results suggest that empiric high-dose fluconazole therapy should reduce the mortality associated with invasive candidiasis at an acceptable cost.

Effects of dietary macronutrient content on glucose metabolism in children.

Effects of carbohydrate, fat, and fructose intake on substrate and hormone concentrations, glucose production, gluconeogenesis, and insulin sensitivity were determined in healthy, nonobese prepubertal children (n = 12) and adolescents (n = 24) using a cross-over design. In one group (12 prepubertal children and 12 adolescents), subjects were studied after 7 d of isocaloric, isonitrogenous diets providing either 60% carbohydrate and 25% fat [high carbohydrate (H(CHO))/low fat (L(F))] or 30% carbohydrate and 55% fat [low carbohydrate (L(CHO))/high fat (H(F))], and in a second group (12 adolescents) H(CHO)/L(F) diets containing either 40% or 10% fructose was used. All subjects adapted to changes in carbohydrate and fat intakes primarily by appropriately adjusting their substrate oxidation rates to match the intakes, with only minor changes in parameters of glucose metabolism. Changing from a L(CHO)/H(F) to H(CHO)/L(F) diet resulted in increased insulin sensitivity (stable labeled iv glucose tolerance test) in adolescents [from 3.2 +/- 0.7 x 10(-4) to 5.0 +/- 1.4 x 10(-4) (min(-1))/( micro U.ml(-1)) (mean +/- SE)] but not in prepubertal children [9.4 +/- 2.5 x 10(-4) to 9.9 +/- 1.5 x 10(-4) (min(-1))/( micro U.ml(-1))], whereas beta-cell sensitivity was unaffected in both groups. Insulin sensitivity was higher in prepubertal children than in adolescents (P < 0.05). The dietary fructose content did not affect any measured parameter. We conclude that in the short term, dramatic changes in fat and carbohydrate intakes (regardless of fructose content) did not adversely affect glucose and lipid metabolism in healthy nonobese children. In the adolescents, the high carbohydrate diet resulted in increased insulin sensitivity, thus facilitating insulin-mediated glucose uptake.

Modelling of simultaneous mass and heat transfer with chemical reaction using the Maxwell-Stefan theory—II. Non-isothermal study

In Part I a general applicable model has been developed which calculates mass and heat transfer fluxes through a vapour/gas-liquid interface in case a reversible chemical reaction with associated heat effect takes place in the liquid phase. In this model the Maxwell-Stefan theory has been used to describe the mass transport. Also in Part I the isothermal absorption of a pure gas A in a solvent containing a reactive component B has been studied. In this paper the influence of thermal effects on the mass transfer rates is investigated, with special attention to the concentrated systems. The thermal effects arise as a consequence of enthalpy changes due to phase transitions and chemical reaction. Account is taken of the influence of temperature gradients on (i) the solubility of the gaseous component in the liquid phase, (ii) the chemical reaction rate and (iii) the mass transfer coefficients in the liquid phase. Numerical simulations show that, when compared to the corresponding isothermal case, the thermal effects can affect the mass transfer rates by as much as a factor of 30. In case of high Lewis numbers the numerically calculated mass transfer rates can very well be predicted from an approximate analytical expression, which has been presented in this paper. In most cases this is also a reasonable estimate of the mass transfer rate in case the Lewis number equals unity. In case of a second-order chemical reaction it was shown that thermal effects may change the maximum enhancement factor and consequently shift the absorption from the instantaneous regime to the pseudo-first-order regime. Further, it is concluded that there may exist non-isothermal gas-li1uid absorption systems where minor changes in parameters appearing in the heat balance, e.g. binary mass transfer coefficients, chemical reaction rate constant, Lé number or heat transfer coefficients, may result in drastically altered system behaviour. For situations in which thermal effects are significant, also the vaporization of the liquid mixture should be taken into account, especially when the calculated interface temperature is near or exceeds the boiling temperature of the liquid.

Spin-fluctuation-induced superconductivity and normal-state properties of YBa2Cu3O7.

We have carried out strong-coupling calculations using the Eliashberg formalism for ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7}$. We consider the influence of potential impurity scattering on ${\mathit{T}}_{\mathit{c}}$. We find that, as the strength of the impurity potential increases, the unitary limit is reached comparatively quickly. In this (unitary) limit, the influence of isotropic impurity scattering on ${\mathit{T}}_{\mathit{c}}$ is relatively weak. We show, with the aid of a simple model to describe the disruption of the local magnetic order brought about by the substitution of Zn, that the latter has a strong influence on ${\mathit{T}}_{\mathit{c}}$. We consider the competition between antiferromagnetic and superconducting instabilities and find that, for our model parameters, the instability to a superconducting state always comes first. Next, we examine the sensitivity of our results for ${\mathit{T}}_{\mathit{c}}$ to the details of the spin-fluctuation spectrum and hole concentration. When that spectrum is modified so that it is consistent with both NMR ${\mathit{T}}_{1}$ and ${\mathit{T}}_{2}$ measurements, a superconducting transition temperature of 90 K is obtained with a dimensionless coupling contant, \ensuremath{\lambda}1/2. Strong-coupling calculations of the normal state, using these latter parameters and including vertex corrections, yield an in-plane resistivity which varies linearly with temperature, with a magnitude at 100 K of 20 \ensuremath{\mu}\ensuremath{\Omega} cm, and, with minor changes in parameters, a frequency dependence of the optical conductivity in quantitative agreement with experiment for energies 50 meV. With an interlayer hopping ${\mathit{t}}_{\mathrm{\ensuremath{\perp}}}$ of 8 meV, the c-axis resistivity is found to be linear in temperature with a magnitude at 150 K of 2.5 m\ensuremath{\Omega} cm.