Maximum Initial Slope Research Articles

Supercritical Fluid Extraction Kinetics of Cherry Seed Oil: Kinetics Modeling and ANN Optimization.

This study was primarily focused on the supercritical fluid extraction (SFE) of cherry seed oil and the optimization of the process using sequential extraction kinetics modeling and artificial neural networks (ANN). The SFE study was organized according to Box-Behnken design of experiment, with additional runs. Pressure, temperature and flow rate were chosen as independent variables. Five well known empirical kinetic models and three mass-transfer kinetics models based on the Sovová’s solution of SFE equations were successfully applied for kinetics modeling. The developed mass-transfer models exhibited better fit of experimental data, according to the calculated statistical tests (R2, SSE and AARD). The initial slope of the SFE curve was evaluated as an output variable in the ANN optimization. The obtained results suggested that it is advisable to lead SFE process at an increased pressure and CO2 flow rate with lower temperature and particle size values to reach a maximal initial slope.

Extraction kinetics modeling of wheat germ oil supercritical fluid extraction

The aim of this study was the optimization of supercritical fluid extraction (SFE) of wheat germ oil obtained as by-product from industrial mill. Extraction kinetics modeling and response surface methodology (RSM) were used for that purpose. SFE was performed with broadening Box-Behnken experimental design, where pressure (250–350 bar), temperature (40–60°C), and CO2 flow rate (0.2–0.4 kg/hr) were used as independent variables. Five empirical kinetic equations were successfully utilized for modeling of SFE. Model IV (Kandiah and Spiro model) provided the best fit with experimental data, according to statistical parameters (R2, sum of squared errors and average absolute relative deviation). Furthermore, initial slope calculated from this model was used as a response variable for RSM optimization. It could be concluded that SFE should be performed at elevated pressure (350 bar) and CO2 flow rate (0.4 kg/hr), while temperature should be held at a lower level (40°C) in order to achieve a maximal initial slope. Practical applications Optimization and modeling of industrial processes are crucial factors that will determine its efficiency and profitability. This research provided information about modeling of green and environmentally friendly extraction technique, that is, SFE, which could be successfully utilized for recovery of valuable oil from food industry by-product, that is, wheat germ. Commonly used empirical models were successfully applied for modeling of extraction process and influence of SFE factors on model parameters was determined providing information about mass transfer phenomena during extraction. Further investigation provided determination of the highest initial extraction rate constant which could be applicable for optimization of industrial scale processes.

Construct validity of pixel-by-pixel DCE-MRI: Correlation with conventional MRI scores in juvenile idiopathic arthritis

ObjectivesTo assess the capability of the pixel-by-pixel DCE-MRI time intensity curve (TIC)-shape analysis method in the evaluation of juvenile idiopathic arthritis (JIA) disease activity by correlating DCE-MRI parameters with semi-quantitative conventional-MRI scores of synovitis. MethodsClinical, laboratory, and (DCE)-MRI datasets of 85 JIA patients were prospectively obtained. TIC-shapes of each voxel were classified into one of seven predefined color-coded TIC shape categories. Spatial information on the relative amount of TIC-shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV) was calculated of the synovial membrane. The grade of synovitis was scored on conventional MR images by two readers using the validated JAMRIS system. The Bonferroni method was used to correct for multiple testing, therefore, a P value of <0.0056 is considered significant (0.05/9=0.0056). ResultsThe semi-quantitative JAMRIS synovitis score correlated substantially with the ME, EV, and iAUC (Rs=0.658, P<0.001; Rs=0.618, P<0.001; Rs=0.639, P<0.001), and moderately with MIS (Rs=0.453, P<0.001). A poor correlation was observed between the relative number of TIC-shapes 2–5 and the JAMRIS synovitis score (Rs=0.209, P=0.054; Rs=0.328, P=0.002; Rs=0.241, P=0.023; Rs=−0.241, P=0.026). ConclusionIn this explorative study, both TIC shape and semi-quantitative DCE-MRI analysis methods showed moderate to substantial correlations with conventional MRI scores of disease activity, indicating that this methods are feasible. Further research is warranted whether DCE-MRI holds potential to become an objective and quantitative method for the evaluation of disease activity in JIA.

Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis: a promising imaging biomarker as an alternative to gadolinium-based contrast agents

ObjectivesTo compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA).MethodsRegions of interest (ROI) were drawn in the synovium of JIA patients on T1 DCE and T2 DWI, followed by extraction of the maximum enhancement (ME), maximum initial slope (MIS), time to peak (TTP), % of different time intensity curve shapes (TIC) and apparent diffusion coefficient (ADC) of the ROIs. Mann-Whitney-U test was used for comparing parameters between MRI-active and -inactive patients (defined by the juvenile arthritis MRI scoring system). Spearman’s rank was used to analyse the correlation between DCE and DWI.ResultsThirty-five JIA patients (18 MRI active and 17 MRI inactive) were included. Median age was 13.1 years and 71% were female. ME, MIS, TTP, % TIC 5 and ADC were significantly different in MRI-active versus MRI-inactive JIA with median ADC 1.49 × 10-3mm2/s in MRI-active and 1.25 × 10-3mm2/s in MRI-inactive JIA, p = 0.001, 95% confidence interval of difference in medians =0.11-0.53 × 10-3mm2/s. ADC correlated to ME, MIS and TIC 5 shapes (r = 0.62, r = 0.45, r = -0.51, respectively, all p < 0.05).ConclusionsSimilar to DCE parameters, DWI-derived ADC is significantly different in MRI-active JIA as compared to MRI-inactive JIA. The non-invasiveness of DWI combined with its possibility to detect synovial inflammation shows the potential of DWI.Key Points• MRI can quantify: dynamic contrast-enhanced and diffusion-weighted MRI can quantify synovitis• Both DWI and DCE can differentiate active from inactive JIA• The DWI-derived apparent diffusion coefficient (ADC) is higher in active JIA• DWI is non-invasive and thus safer and more patient-friendly• DWI is a potentially powerful and non-invasive imaging biomarker for JIA

Activation of arginine vasopressin receptor 1a facilitates the induction of long-term potentiation in the accessory olfactory bulb of male mice

Olfaction plays an important role in social recognition in most mammals. Central arginine vasopressin (AVP) plays a role in this olfaction-based recognition. The high level of expression of AVP receptors in the accessory olfactory bulb (AOB) at the first relay of the vomeronasal system highlights the importance of AVP signaling at this stage. We therefore analyzed the effects of AVP on the synaptic plasticity of glutamatergic transmission from mitral cells to granule cells in AOB slices from male mice. To monitor the strength of the glutamatergic transmission, we measured the maximal initial slope of the lateral olfactory tract-evoked field potential, which represents the granule cell response to mitral cell activation. AVP paired with 100-Hz stimulation that only produced short-term potentiation enhanced the induction of long-term potentiation (LTP) in a dose-dependent manner. AVP-paired LTP was blocked by the selective AVP receptor 1a (AVPR1a) antagonist, d(CH2)5[Tyr(Me)2]AVP (Manning compound), but not by the AVPR1b antagonist SSR149415, and it was mimicked by the selective AVPR1a agonist [Phe2, Ile3, Orn8]-vasopressin. We further examined the effect of AVP on the reciprocal transmission between mitral and granule cells by stimulating a mitral cell and recording the evoked inhibitory postsynaptic currents (IPSCs) from the same cell using conventional whole-cell patch-clamp techniques. AVP reduced the reciprocal IPSCs triggered by endogenous glutamate release from the excited mitral cell. These results suggest that AVP promotes the induction of LTP at the mitral-to-granule cell synapse via the activation of AVPR1a through an as-yet-to-be-determined mechanism in the AOB of male mice.

Application of the Christensen Failure Criterion to Intact Rock

The Christensen criterion, originally introduced in materials science, has a simple mathematical form and uniaxial tensile and compressive strength as the only parameters, making it an attractive candidate for rock engineering purposes. In this study, the applicability of the criterion to rock materials is examined. Explicit equations for application of the criterion under biaxial, triaxial compression, triaxial extension, and polyaxial states of stresses are derived. A comprehensive strength data set including the results of tests on synthetic rock, chert dyke, Carrara marble and Westerly granite is utilized to examine the accuracy of the Christensen criterion to the failure of rock material. The two surprising findings about the Christensen criterion are the zero values of tensile strength and the very low slopes of the failure envelope obtained from fitting analyses for chert dyke and Westerly granite. It is shown that the two problems are interrelated and the values of tensile strength tend to zero to produce higher slopes. It is then mathematically proven that the maximum initial slope of the Christensen failure envelope is limited to 4 in triaxial compression and 2.5 in triaxial extension which is considerably lower than the slope of experimental data. The accuracy of the Christensen criterion was found to be significantly lower than the well-established Hoek–Brown criterion. The circular π-plane representations and brittle-to-ductile transition limits from the Christensen criterion are also inconsistent with the observed behavior of rocks.

Pixel-by-pixel analysis of DCE-MRI curve shape patterns in knees of active and inactive juvenile idiopathic arthritis patients.

To compare DCE-MRI parameters and the relative number of time-intensity curve (TIC) shapes as derived from pixel-by-pixel DCE-MRI TIC shape analysis between knees of clinically active and inactive juvenile idiopathic arthritis (JIA) patients. DCE-MRI data sets were prospectively obtained. Patients were classified into two clinical groups: active disease (n = 43) and inactive disease (n = 34). Parametric maps, showing seven different TIC shape types, were created per slice. Statistical measures of different TIC shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV), volume transfer constant (K(trans)), extravascular space fractional volume (V(e)) and reverse volume transfer constant (k(ep)) of each voxel were calculated in a three-dimensional volume-of-interest of the synovial membrane. Imaging findings from 77 JIA patients were analysed. Significantly higher numbers of TIC shape 4 (P = 0.008), median ME (P = 0.015), MIS (P = 0.001) and iAUC (P = 0.002) were observed in clinically active compared with inactive patients. TIC shape 5 showed higher presence in the clinically inactive patients (P = 0.036). The pixel-by-pixel DCE-MRI TIC shape analysis method proved capable of differentiating clinically active from inactive JIA patients by the difference in the number of TIC shapes, as well as the descriptive parameters ME, MIS and iAUC. • The pixel-by-pixel TIC shape method differentiates clinically active and inactive JIA patients • Significantly higher numbers of TIC shape 4 were observed in clinically active patients • DCE-MRI parameters ME, MIS and iAUC differ between active and inactive patients • The pixel-by-pixel analysis method allows direct visualization of the heterogeneously distributed disease • The DCE-MRI TIC shape method may serve as a quantitative outcome measure.

Three dimensional simulation on binding efficiency of immunoassay for a biosensor with applying electrothermal effect

In this work, we perform three dimensional finite element simulations on the binding reaction kinetics of the commonly used analyte–ligand protein pairs, namely, C-reactive protein (CRP) and anti-CRP, in a reaction chamber (microchannel) of a biosensor. For the diffusion limited binding biomolecular pairs, due to the slower transport speed of the analyte and the faster reaction rate of analyte–ligand complex, diffusion boundary layers often develop on the reaction surface. To enhance the performance of a biosensor by accelerating the transport speed, a non-uniform AC electric field is applied to induce the electrothermal force to stir the flow field. The swirling flow in the fluid can accelerate the transport of the analyte to and from the reaction surface and hence enhance the association and dissociation of analyte–ligand complex. Four types of biosensors with different arrangements of the geometric locations of the electrode pair and the reaction surface are designed to study the effects of varying geometric configuration on the binding efficiency. The simulation results show that the performance of a biosensor can be better improved by placing the electrodes and the reaction surface on the same side of the microchannel against the opposite side. For the best case studied in this work, the maximum initial slope of the binding curve can be raised up to 6.94 times (with respect to the field-free value) in the association phase, under applying AC field of 15 Vrms and operating frequency of 100 kHz. Another important result with applying electrothermal effect is that it is feasible to use the slower sample flow in the microchannel to save a lot of sample consumption without sacrificing the performance of a biosensor. Several control factors not studied in our previous works such as the thermal boundary condition and the effect of electrical conductivity are also discussed.

Enhancement of On-chip Bioassay Efficiency With Electrothermal Effect

AbstractWe have performed the finite element simulations to study the binding reaction kinetics of the analyte-ligand protein pairs, C-reactive protein (CRP) and anti-CRP, in a reaction chamber of a biosensor. For diffusion limited reactions, diffusion boundary layers often develop on the reaction surface, thus hindering the reaction. To enhance the efficiency of a biosensor, a non-uniform AC electric field is applied to induce the electrothermal force which stirs the flow field. Biosensors with different arrangements of the electrode pairs and the reaction surface are designed to study the effects of geometric configurations on the binding efficiency. The maximum initial slope of the binding curve can be 6.94 times of the field-free value in the association phase, under an AC field of 15 rms and an operating frequency of 100 kHz. With the electrothermal effect, it is possible to use a slower flow and save much sample consumption without sacrificing the performance of a biosensor. Several design factors not studied in our previous works such as the thermal boundary conditions are discussed.

Rat model of reperfused partial liver infarction: Characterization with multiparametric magnetic resonance imaging, microangiography, and histomorphology

Rat model of reperfused partial liver infarction (RPLI) has been increasingly used in studying new diagnostics and therapeutics. To characterize the RPLI model using magnetic resonance imaging (MRI), microangiography, and histopathology. RPLI was induced in eight rats by occluding hepatic inflow to the right liver lobe for 3 hours. MRI was performed at a 1.5 T clinical scanner 6 hours after reperfusion to obtain T2-weighted (T2WI), T1-weighted (T1WI), contrast-enhanced (CE) T1WI, diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps, T1-weighted dynamic contrast-enhanced (T1-DC) perfusion-weighted imaging (PWI), and T2*-weighted dynamic susceptibility contrast-enhanced (T2*-DSC) PWI images. Rats were sacrificed for microangiography and histomorphology. In vivo morphological and functional MRI parameters, including maximum initial slope (MIS), K value, relative blood flow (rBF), relative blood volume (rBV), time to peak (TTP), and mean transit time (MTT), were matched with postmortem findings. The infarcted lobe was conspicuous from normal liver with lower and higher signal intensity on T1WI (P=0.018) and T2WI (P=0.001), respectively. Contrast between infarcted and normal liver reversed on CE-T1WI after gadolinium injection. The infarction averaged 37.5% of total liver volume. DWI and ADC maps were able to detect subtle perfusion-related differences (P<0.05). With T1-DC-PWI, increased extravasation and vascular permeability were reflected by significantly greater MIS (P=0.034) and K value (P=0.014) in infarction. T2*-DSC-PWI showed lower rBF and rBV with shorter TTP and MTT in infarcted liver (P<0.05). In vivo MRI findings corresponded well with postmortem outcomes. RPLI in rats could be characterized by multiparametric MRI and postmortem assessments, with insight into the no-reflow phenomenon, which implies its further application for preclinical assessments of new pharmaceutics.

Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology

We sought to establish and characterize a mouse liver tumor model as a platform for preclinical assessment of new diagnostics and therapeutics. Radiation-induced fibrosarcoma (RIF-1) was intrahepatically implanted in 27 C3H/Km mice. Serial in vivo magnetic resonance imaging (MRI) with a clinical 1.5-T-magnet was performed using T1- (T1WI), T2- (T2WI), and diffusion-weighted sequences (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and contrast-enhanced T1WI, and validated with postmortem microangiography and histopathology. Implantation procedure succeeded in 25 mice with 2 deaths from overdosed anesthesia or hypothermia. RIF-1 grew in 21 mice with volume doubling time of 2.55+/-0.88 days and final size of 216.2+/-150.4 mm(3) at day 14. Three mice were found without tumor growth and one only with abdominal seeding. The intrahepatic RIF-1 was hypervascularized with negligible necrosis as shown on MRI, microangiography and histology. On DCE-MRI, maximal initial slope of contrast-time curve and volume transfer constant per unit volume of tissue, K, differed between the tumor and liver with only the former significantly lower in the tumor than in the liver (P<0.05). Liver implantation of RIF-1 in mice proves a feasible and reproducible model and appears promising for use to screen new diagnostics and therapeutics under noninvasive monitoring even with a clinical MRI system.

Modulation of isolatedN-methyl-d-aspartate receptor response under hyperbaric conditions

In humans, hyperbaric pressure induces the high-pressure neurological syndrome (HPNS). HPNS is characterized by tremor, sleep disorders, electroencephalographic changes, and impairment of cognitive and motor performances. In animals, higher pressures result in convulsions and death. An increased N-methyl-d-aspartate receptor (NMDAR) response has been implicated with HPNS. We studied high-pressure effects on pharmacologically isolated NMDAR field excitatory postsynaptic potentials (fEPSPs). Hippocampal coronal brain slices from male Sprague-Dawley rats were prepared, constantly superfused with physiological solutions, gas-saturated at normobaric pressure and compressed up to 10.1 MPa with helium. fEPSPs were recorded from the dendritic layer of CA1 pyramidal neurones. High pressure significantly increased the single fEPSP delay, maximal initial slope, amplitude, decay time and time integral (elevated Na(+) and Ca(2+) influx) despite the known general decrease in glutamatergic synaptic release. The estimated negative and positive activation volumes (DeltaV*) for various kinetic segments of the fEPSP suggest a complex response of the receptor to pressure. The NMDAR frequency response was tested by a train of five stimuli. At 50-100 Hz, high pressure did not increase the fEPSPs' frequency-dependent depression and the train's time integral remained unchanged. At 25 Hz, pressure induced a larger frequency-dependent depression and significantly increased the time integral. Our results provide, for the first time, direct information on the isolated brain NMDAR response under hyperbaric conditions. These observations may explain some increase in the excitability of single normal glutametergic fEPSPs and their frequency responses.